tag:blogger.com,1999:blog-77214173452461659062024-03-13T21:14:49.100-07:00Joe's Science CornerAn understanding of science in this the 21st century is an essential ingredient for leading a productive and rewarding life.Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.comBlogger222125tag:blogger.com,1999:blog-7721417345246165906.post-14534069904618681752023-12-13T23:19:00.000-08:002023-12-13T23:19:26.307-08:00Exciting New Results in the Development of an Anti-Malaria Vaccine<p> </p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgQ8r_o89QUeEvqqyVeLFwPfE15COHAD_phoEPqjZk_z4qgslMGLTg-6ng7eTaSx2bmqrNKTbuyKabtC8Rt3ragGSsBF65zfZ8vi5ERgtUB-iz_kAECOn0QC0V0P-eVJNzEZwgj7_pMiwukL7aPQdwbW3SO84Vj470wlntGmpb61kWyugtOf6HwCic3PQ22/s375/mechanism%20of%20action%20of%20anti-malaria%20vaccine.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="375" data-original-width="375" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgQ8r_o89QUeEvqqyVeLFwPfE15COHAD_phoEPqjZk_z4qgslMGLTg-6ng7eTaSx2bmqrNKTbuyKabtC8Rt3ragGSsBF65zfZ8vi5ERgtUB-iz_kAECOn0QC0V0P-eVJNzEZwgj7_pMiwukL7aPQdwbW3SO84Vj470wlntGmpb61kWyugtOf6HwCic3PQ22/s320/mechanism%20of%20action%20of%20anti-malaria%20vaccine.jpg" width="320" /></a></div><br /><p></p>An exciting recent development has been reported in the prestigious journal Science regarding the development of a anti-malaria vaccine that has been shown to substantially reduce childhood victims of this disease. This vaccine is referred to as RTS, S. or Mosquirix and made by GSK. <br /><br />Analysis of the efficacy of this vaccine approved to combat the death of the young children demonstrated a 13% drop in mortality during a nearly 4 year duration. This result was reported by the World Health Organization (WHO). In addition it was also found that there was a 22% reduction in the incidence of severe malaria in children young enough to receive a three-shot series. <br /><br />According to John Tanko Bawa, director of the malaria vaccine implementation at the Program for Appropriate Technology in Health (PATH) stated, “The RTS,S malaria vaccine is already saving lives.” Furthermore he noted that, “What we have seen is a considerable impact of a vaccine described as having modest efficacy.” <br /><br />The results of this analysis is so impressive that it has been estimated that the mortality decline could ultimately save tens of thousands of lives if RTS,S, is more broadly utilized. <br /><br />In regard to the actual mode of action of RTS,S vaccine, it binds to the circumsporozoite protein on the surface of P. falciparum parasite before it infects liver cells disrupting its life cycle so that it is unable to infect circulating red bloods where it exerts its deadly effect – a pre-erythrocytic vaccine. <br /><br />This is a profoundly important development in regard to the control of the spread of malaria among susceptible human populations.Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-77596528637427584912023-03-03T18:48:00.002-08:002023-03-03T18:51:11.935-08:00Breast Cancer Overview - 2023<p> </p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhdYrwO8ZFuSsNjoIF25l97kpYHE1BmaXoog5nkHdItwapi5WrEEXZFOc9ezhwBMd2ezsJxQDWyrlh8aRMRmwgkaNeLIACf5wfIOuKD1yNK8U_PtsbWUfFFwFMPJQuf1au5Cbzd8zU1zh1tZl0o6DaPrwl6MoelzuPeHQY-qGbTT28RkHXXPp_vfQVxRw/s885/er+%20breast%20cancer%20cells.jpg" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="664" data-original-width="885" height="332" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhdYrwO8ZFuSsNjoIF25l97kpYHE1BmaXoog5nkHdItwapi5WrEEXZFOc9ezhwBMd2ezsJxQDWyrlh8aRMRmwgkaNeLIACf5wfIOuKD1yNK8U_PtsbWUfFFwFMPJQuf1au5Cbzd8zU1zh1tZl0o6DaPrwl6MoelzuPeHQY-qGbTT28RkHXXPp_vfQVxRw/w442-h332/er+%20breast%20cancer%20cells.jpg" width="442" /></a></div><p class="MsoNormal" style="text-align: justify;"><u><span style="font-family: "Times New Roman",serif; font-size: 14pt; line-height: 19.9733px;">Introduction<o:p></o:p></span></u></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">It is currently estimated that one in eight women (12.5%) in the United States will be diagnosed with breast cancer.<span style="mso-spacerun: yes;"> </span>For example, In the year 2014 232,670 new breast cancer cases and 40,000 deaths were reported for women living in the United Sates. Age is the strongest risk factor for breast cancer. Surprisingly, breast cancer begins to rise in the third decade of life. <span style="mso-spacerun: yes;"> </span>This unusual aspect of breast cancer, is postulated to be related to the effects of ovarian hormones – especially estrogen and progesterone - on breast tissue. More than 2/3 of all new cases occur after the age of 55 and women older than 65 have a relative risk greater than 4.0 when compared with those younger than 65.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">For this reason, it is imperative that causative agents responsible for the transformation of normal breast tissue cells to a cancerous state be more fully understood; that women be encouraged to undergo the appropriate screening and health checkups; and that more anti-breast cancer therapies be developed to combat this disease.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><u><span style="font-family: "Times New Roman",serif; font-size: 14pt; line-height: 19.9733px;">Additional Risk Factors</span></u></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">In addition to the endogenous ovarian hormones as cited earlier, there are the following factors that may play a significant role in the etiology of breast cancer –<o:p></o:p></span></p><ul style="margin-top: 0in;" type="disc"><li class="MsoNormal" style="mso-list: l0 level1 lfo1; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Genetic factors such as the BRCA1 and BRCA2 genetic mutations and family history of the disease pointing to genetic factors that are poorly understood.<o:p></o:p></span></li><li class="MsoNormal" style="mso-list: l0 level1 lfo1; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">High levels of HER2 (HER2+) – an epidermal growth factor –can trigger uncontrolled cell division in breast tissue.<span style="mso-spacerun: yes;"> </span>TCHP is a combination drug treatment that includes docetaxel, carboplatin, trastuzumab, and pertuzumab. These are drugs that people take intravenously to kill cancer cells if they have early-stage HER2+ breast cancer.<o:p></o:p></span></li><li class="MsoNormal" style="mso-list: l0 level1 lfo1; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Reproductive history<o:p></o:p></span></li><li class="MsoNormal" style="mso-list: l0 level1 lfo1; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">High dose radiation to the chest<o:p></o:p></span></li><li class="MsoNormal" style="mso-list: l0 level1 lfo1; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">High dose hormone therapy<o:p></o:p></span></li><li class="MsoNormal" style="mso-list: l0 level1 lfo1; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Obesity<o:p></o:p></span></li><li class="MsoNormal" style="mso-list: l0 level1 lfo1; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Alcohol Consumption<o:p></o:p></span></li><li class="MsoNormal" style="mso-list: l0 level1 lfo1; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Environmental factors related to the abundance of carcinogenic compounds that permeate the environment.<o:p></o:p></span></li></ul><p class="MsoNormal" style="text-align: justify;"><u><span style="font-family: "Times New Roman",serif; font-size: 14pt; line-height: 19.9733px;">Endogenous Estrogen Levels and the Etiology of Breast Cancer<o:p></o:p></span></u></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">The Data accumulated in the past few decades indicate that endogenous estrogens play a very important role in regard to the etiology of breast cancer.<span style="mso-spacerun: yes;"> </span>For this reason it is important to understand how estrogens are produced and metabolized in the body.<span style="mso-spacerun: yes;"> </span>Estrogen and Progesterone are steroid hormones, and the first step involving steroidogenesis in the human ovary is the transport of their precursor, cholesterol into the mitochondria.<span style="mso-spacerun: yes;"> </span>This is followed by a number of enzyme-mediated steps that lead to the formation of Pregnenolone that is the precursor for all steroid hormones, and eventually to estrogen.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">In premenopausal women, estradiol synthesized in the ovaries is the most predominant form; whereas in postmenopausal women, estrone is the most prevalent and is synthesized in the peripheral tissue.<span style="mso-spacerun: yes;"> </span>Estrone is reversibly converted to estradiol through an enzyme-mediated reaction.<span style="mso-spacerun: yes;"> </span>Testosterone, in turn, is converted to estradiol by the action of aromatase enzyme in the peripheral tissues.<span style="mso-spacerun: yes;"> </span>Aromatase is the enzyme that mediates the rate-limiting step in the conversion of androgens like testosterone into estrogens.<span style="mso-spacerun: yes;"> </span>On account of the paramount importance of this metabolic step, pharmaceuticals that can effectively block aromatase activity have proven to be important aspect of the treatment of estrogen-dependent diseases such as breast cancer, endometriosis, and endometrial cancer.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">It has been well established that active genes within the DNA serve as molecular blueprints for the production of unique proteins.<span style="mso-spacerun: yes;"> </span>The steps in chemical metabolism within all the cells in the human body are mediated by specific enzymes that act as highly specialized chemical catalysts.<span style="mso-spacerun: yes;"> </span>Enzymes are proteins.<span style="mso-spacerun: yes;"> </span>Without enzymes life on earth would not be possible.<span style="mso-spacerun: yes;"> </span>The dictum, “one gene one enzyme” can be applied universally throughout life.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">It is important to keep in mind that by the very nature of their integration into DNA, genes are inheritable.<span style="mso-spacerun: yes;"> </span>It is not uncommon to find polymorphisms within genes that are slight variations in the structure of those genes and what is referred to as single nucleotide polymorphisms (SNPs) that represent a singular change in the gene.<span style="mso-spacerun: yes;"> </span>These variations in genetic structure produce corresponding variations in the proteins that are encoded in the genes that are the blueprints for these proteins.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Given this overall view, genetic research in regards to breast cancer is guided by an investigation of the genes that encode the structure of the enzymes involved in estrogen production.<span style="mso-spacerun: yes;"> </span>The driving motivation of some of this work is to find the answer to the following question – Could the polymorphisms and SNPs in the genes responsible for the production of estrogens that are found in breast cancer patients result in an over-production of estrogens?<span style="mso-spacerun: yes;"> </span>Secondly, could this over-production trigger the onset of breast cancer?<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Clinical data that reinforces the primacy of estrogens in the onset of breast cancer are the following:<o:p></o:p></span></p><ul style="margin-top: 0in;" type="disc"><li class="MsoNormal" style="mso-list: l8 level1 lfo2; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Bilateral oophorectomy (ovary removal) significantly reduces breast-cancer risk, and that risk reduction is greater if the ovaries are removed earlier in life.<o:p></o:p></span></li><li class="MsoNormal" style="mso-list: l8 level1 lfo2; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">In addition, some of the well-established risk factors for breast cancer, including early onset of menarche (menstruation) (<12 years), late menopause (>55 years), nulliparity or having child late in life, are related to lifetime exposure of breast tissue to sex hormones.<o:p></o:p></span></li><li class="MsoNormal" style="mso-list: l8 level1 lfo2; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Approximately 2/3 of breast tumors are estrogen receptor (ER) positive (ER+) and responsive to circulating estrogens, and that almost all ER negative (ER−) cases are resistant to endocrine therapy, it is important to elucidate the specific mechanisms by which estrogens are related to elevated breast cancer risk.<o:p></o:p></span></li></ul><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">In fact, circulating primary hormones in postmenopausal women, increased circulating concentrations of estradiol, estrone, estrone-sulfate, and androstendione have been shown to correlate with higher breast cancer risk. A thorough analysis of 663 women who developed breast cancer and had not received any hormonal-based therapy, demonstrated that the risk of breast cancer significantly increased with higher endogenous levels of total estradiol, free estradiol, estrone, estrone-sulfate, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and testosterone. Since this analysis was published, a few more prospective and case-control studies have been reported that have found similar results. It should be noted that the majority of populations studied were general populations with average breast cancer risk who were not taking any exogenous sex hormones.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">In addition the levels of endogenous estrogens were studied in those patients that had a number of breast cancer risk factors including obesity, reproductive, demographic, and life style factors has been investigated by the Endogenous Hormones and Breast Cancer Collaborative Group in several studies. The results of these studies did not a show a statistical significance for the association between BMI (a metric whose value can be indicative of obesity) and breast cancer risk. However, in another cross-sectional analysis of 13 prospective studies by the same group, “estrogen and androgen levels were positively associated with obesity, smoking (15+ cigarettes daily) and alcohol consumption (20+g alcohol daily), and inversely linked with age.”<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Although this summary does not include any data regarding the role of the level of endogenous androgens or progesterone in regard to the onset of breast cancer, the role of estrogens in the biology of breast cancer is very significant, and has led to the development of hormonal therapy medications as a way to limit the exposure of breast tissue to circulating estrogens. What follows is a more detailed look at these therapeutic approaches.</span></p><p class="MsoNormal" style="text-align: justify;"><u><span style="font-family: "Times New Roman",serif; font-size: 14pt; line-height: 19.9733px;">“Hormonal therapy medicines are used in four ways</span></u><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">: (Jenni Sheng, MD</span><span style="font-family: "Times New Roman", serif; font-size: 12pt;">Johns Hopkins University School of Medicine, Baltimore, MD)</span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“If the breast cancer is large and hormone receptor-positive, your doctor may recommend hormonal therapy before surgery to shrink the cancer. Treatments given before surgery are called neoadjuvant treatments, so hormonal therapy given this way is called neoadjuvant hormonal therapy.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“To reduce recurrence risk: If you’ve been diagnosed with early-stage hormone receptor-positive breast cancer, your treatment plan will include hormonal therapy after surgery and possibly other treatments to reduce the risk of the cancer coming back (recurrence). Treatments given after surgery are called adjuvant treatments, so hormonal therapy given this way is called adjuvant hormonal therapy.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“To stop advanced-stage cancer from growing: If you’ve been diagnosed with advanced-stage, hormone receptor-positive breast cancer, hormonal therapy can be used to help stop the cancer from growing.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“To reduce the risk of a first diagnosis: Hormonal therapy also can be used to reduce breast cancer risk in certain women who haven’t been diagnosed. Women with a much higher than average risk of breast cancer may take a hormonal therapy medicine preventively to reduce the risk of hormone receptor-positive breast cancer developing.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“How does hormonal therapy treat breast cancer?<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Hormonal therapy medicines work in two ways:<o:p></o:p></span></p><ul style="margin-top: 0in;" type="disc"><li class="MsoNormal" style="margin-bottom: 0in; mso-list: l9 level1 lfo3; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">by blocking estrogen production in the body<o:p></o:p></span></li></ul><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><ul style="margin-top: 0in;" type="disc"><li class="MsoNormal" style="margin-bottom: 0in; mso-list: l9 level1 lfo3; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">by blocking the effects of estrogen on breast cancer cells<o:p></o:p></span></li></ul><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman", serif; font-size: 12pt;">“Hormonal therapy is not a treatment option for hormone receptor-negative breast cancer.</span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“It's important to know that hormonal therapy for breast cancer is different than hormone replacement therapy (HRT) for treating symptoms of menopause. HRT isn't used to treat breast cancer. HRT is taken by some women to treat troublesome menopausal side effects such as hot flashes and mood swings. HRT is used to raise estrogen levels that drop after menopause. HRT contains estrogen and can contain progesterone and other hormones. Hormonal therapy for breast cancer is exactly the opposite — it blocks or lowers estrogen levels in the body.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“Types of hormonal therapy to treat breast cancer<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“There are three main types of hormonal therapy medicines used to treat breast cancer:<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l2 level1 lfo4; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Aromatase inhibitors stop the body from making estrogen.<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l2 level1 lfo4; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Selective estrogen receptor modulators (SERMs) block the action of estrogen on certain cells.<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l2 level1 lfo4; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Selective estrogen receptor downregulators (ERDs) block the action of estrogen on certain cells.<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l2 level1 lfo4; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Aromatase inhibitors<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><u><span style="font-family: "Times New Roman",serif; font-size: 14pt; line-height: 19.9733px;">“Aromatase inhibitors</span></u><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> lower estrogen levels by stopping the enzyme aromatase from changing other hormones into estrogen. In estrogen receptor-positive breast cancer, the hormone estrogen can stimulate the growth of breast cancer cells.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“There are three aromatase inhibitors used to treat breast cancer:<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l4 level1 lfo5; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Arimidex (chemical name: anastrozole)<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l4 level1 lfo5; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Aromasin (chemical name: exemestane)<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l4 level1 lfo5; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Femara (chemical name: letrozole)<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="text-align: justify;"><u><span style="font-family: "Times New Roman",serif; font-size: 14pt; line-height: 19.9733px;">“Selective estrogen receptor modulators (SERMs)<o:p></o:p></span></u></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“Selective estrogen receptor modulators (SERMs) block the effects of estrogen on breast cancer cells by sitting in the estrogen receptors. If a SERM is in the estrogen receptor, estrogen can’t attach to the cancer cell and the cell doesn’t receive estrogen’s signals to grow and multiply.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“There are three SERMs used to treat breast cancer:<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l5 level1 lfo6; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Tamoxifen in pill form, also called tamoxifen citrate (brand name Nolvadex), and in liquid form (brand name: Soltamox)<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l5 level1 lfo6; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Evista (chemical name: raloxifene)<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l5 level1 lfo6; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Fareston (chemical name: toremifene)<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="text-align: justify;"><u><span style="font-family: "Times New Roman",serif; font-size: 14pt; line-height: 19.9733px;">“Selective estrogen receptor downregulators (SERDs)<o:p></o:p></span></u></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“Selective estrogen receptor downregulators (SERDs), much like SERMs, block the effects of estrogen on breast cancer cells by sitting in the estrogen receptors. SERDs also lower the number of estrogen receptors and change the shape of breast cell estrogen receptors so they don’t work as well. There are two SERDs used to treat breast cancer:<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l3 level1 lfo7; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Faslodex (chemical name: fulvestrant)<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l3 level1 lfo7; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Orserdu (chemical name: elacestrant)<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"><span style="mso-spacerun: yes;"> </span><o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><u><span style="font-family: "Times New Roman",serif; font-size: 14pt; line-height: 19.9733px;">“Hormonal therapy side effects<o:p></o:p></span></u></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Each hormonal therapy medicine may cause different side effects.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">The most common side effects of the aromatase inhibitors are:<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l1 level1 lfo8; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">joint and bone pain<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l1 level1 lfo8; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">hot flashes<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l1 level1 lfo8; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">fatigue<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l1 level1 lfo8; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">weakness<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> <o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“The most common side effects of the SERMs are:<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l6 level1 lfo9; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">hot flashes<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l6 level1 lfo9; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">vaginal discharge<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l6 level1 lfo9; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">mood swings<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l6 level1 lfo9; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">fatigue<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“The most common side effects of the SERDs are:<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l7 level1 lfo10; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">nausea<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l7 level1 lfo10; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">bone pain<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l7 level1 lfo10; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">fatigue<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l7 level1 lfo10; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">hot flashes<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l7 level1 lfo10; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">injection site pain (for Faslodex only)<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“For many years, women took hormonal therapy for five years after surgery for early-stage, hormone receptor-positive breast cancer. In most cases, the standard of care is five years of tamoxifen, or two to three years of tamoxifen followed by two to three years of an aromatase inhibitor, depending on menopausal status.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“Recent research has found that in certain cases, taking tamoxifen for 10 years instead of five years after surgery lowered a woman’s risk of recurrence and improved survival.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“In most cases, a post-menopausal woman diagnosed with early-stage, hormone receptor-positive breast cancer would take an aromatase inhibitor for five years after surgery to reduce the risk of recurrence. After that, if breast cancer had been found in the lymph nodes, called node-positive disease, a woman would take an aromatase inhibitor for an additional five years, for a total of 10 years of hormonal therapy treatment.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“Doctors call taking hormonal therapy for 10 years after surgery extended adjuvant hormonal therapy.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><u><span style="font-family: "Times New Roman",serif; font-size: 14pt; line-height: 19.9733px;">“Ovarian suppression or removal<o:p></o:p></span></u></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“In pre-menopausal women, most of the estrogen in the body is made by the ovaries. In some cases, medicine may be used to stop the ovaries from functioning temporarily, called ovarian suppression or ovarian shutdown. Two medicines commonly used are:<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l10 level1 lfo11; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Zoladex (chemical name: goserelin)<o:p></o:p></span></p><p class="MsoNormal" style="margin-bottom: 0in; text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span></p><p class="MsoNormal" style="margin-bottom: 0in; margin-left: .75in; margin-right: 0in; margin-top: 0in; margin: 0in 0in 0in 0.75in; mso-list: l10 level1 lfo11; text-align: justify; text-indent: -0.5in;"><!--[if !supportLists]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px; mso-fareast-font-family: "Times New Roman";"><span style="mso-list: Ignore;">•<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; font-variant-east-asian: normal; font-variant-numeric: normal; line-height: normal;"> </span></span></span><!--[endif]--><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">Lupron (chemical name: leuprolide)<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"> </span><span style="font-family: "Times New Roman", serif; font-size: 12pt;">“These medicines are given as injections once a month for several months or every few months. They can be used alone or in combination with other hormonal therapy medicines to treat pre-menopausal women.</span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“Once you stop receiving the medicine, your ovaries usually begin functioning again. The time it takes for the ovaries to recover varies from woman to woman.<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">“Some women with a much higher than average risk of breast cancer may choose to have their ovaries removed, called prophylactic or preventive ovary removal, either before or after being diagnosed with breast cancer.”<o:p></o:p></span></p><p class="MsoNormal" style="text-align: justify;"><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;">This article is designed to summarize the known relationship between estrogen levels and the majority of breast cancers (ER+).<span style="mso-spacerun: yes;"> </span>It is important to keep in mind that this area of scientific, medical and clinically-based research is constantly generating new data, and the findings presented above do not represent the last word on the understanding of this devastating illness.<o:p></o:p></span></p><div><span style="font-family: "Times New Roman",serif; font-size: 12pt; line-height: 17.12px;"><br /></span></div><p></p>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-588975162373927572023-01-19T09:14:00.001-08:002023-01-19T09:14:15.298-08:00An approach to Cancer Treatment Combining Immunotherapy and Chemotherapy<br />Immunotherapy is an approach that focuses on and improving the body’s inherent capacity to attack tissue cells that have been transformed into cancerous cells. However, the current drawback of this approach is its inability to effectively distinguish the target cell from neighboring healthy cells. This is especially true for cancers that are derived from oncogene expression. Chemotherapy that has long been the mainstay of cancer treatment has a serious limitation of its own – actively growing cancer cells often develop a resistance to this kind of drug treatment.<br />Takmitsu Hattori and his colleagues at the Laura and Issac Perlmutter Cancer Center at New York University have attempted to overcome this impasse by developing a methodology that combines these two methodologies. Their approach is to effectively create a neoantigen, a hapten-peptide conjugate, which can preferentially combine with cancer cells and serve as a target for selective elimination. <br /><br />These research scientists treated lung cancer with sotorasib – a drug that specifically targets KRAS – an oncogene that is involved in cell signaling pathways that are in involved in the control of cellular proliferation, cell development and cell death. Subsequently, they administered synthetically created antibodies designed to recognize the neoantigens that were the product of KRAS generated protein that had been bound to sotorasib. These administered antibodies were shown to have selectively killed even the sotorasib-resistant cells while leaving normal cells intact.<br /> <br /><div style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEghSdpAskY4wHaMp5qEB8dnFFyekvvsncgbmZ6heBMJ3epx9l7syjgj-KjhL3Lh6myZ-DIyoF_c5ZazsFKCI9N5uLJx1AuFVt0wp2GT7qJ8GWWiFEMEr6FZgUPpsi-mud8Xkq3SLUiZO9BgsGBBW14xOcGLI1YVsjua9g5Wm6ZvcL0hzSJJHb2uWA5ilg/s208/sotorasib.jpeg"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEghSdpAskY4wHaMp5qEB8dnFFyekvvsncgbmZ6heBMJ3epx9l7syjgj-KjhL3Lh6myZ-DIyoF_c5ZazsFKCI9N5uLJx1AuFVt0wp2GT7qJ8GWWiFEMEr6FZgUPpsi-mud8Xkq3SLUiZO9BgsGBBW14xOcGLI1YVsjua9g5Wm6ZvcL0hzSJJHb2uWA5ilg/s1600/sotorasib.jpeg" /></a></div><br /><div style="text-align: center;">Sturcture of Sotorasib</div><br />These results show a great deal of promise in regard to adding to the repertoire of cancer treatment modalities.<div><p class="MsoNormal"><o:p> </o:p></p></div>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-68506124940156247172023-01-17T08:21:00.003-08:002023-01-17T08:23:50.642-08:00A Vaccine for Respiratory Syncytial Virus (RSV) Virus May Soon be Available<div class="separator">This fall the general population has been plagued by an increased incidence of illnesses caused by three distinct viruses - COVID 19 (Coronavirus), Respiratory Syncytial Virus (RSV) and the Influenza Virus.</div><br />Infants and the elderly can be particularly impacted by severe illness with RSV. RSV is a negative-strand RNA virus. The term syncytial comes from the fact that host cells infected by the virus fuse and form large cells, syncytia. Although RSV infection is quite common and the respiratory issues it produces are usually not severe and of short durations, for infants and the elderly, it can produce severe and dangerous symptoms that may include difficulty breathing, abnormal respiratory sounds and coughing and wheezing that does not stop. <br /><div><br /></div><div><br /></div><div><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjtFNweVrr_76ZXjA2BClHywoE_FibRDXb6DIingMCve8ZmIe7bF8jQpiqDHvRR9GrN6hRGl3WWZCQlus5JoWjnqkyj_R_lNOmx3CDm6eVnERBMMSG25B-H1WZeH8T5-pudVTNnuwRwNAjREkVYA3Uepv9Xe0sOwJbqGSmiuE1jj5L2pC5MmpeDNE2FsQ/s800/rsv.jpg" style="margin-left: 1em; margin-right: 1em; text-align: center;"><img border="0" data-original-height="533" data-original-width="800" height="213" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjtFNweVrr_76ZXjA2BClHywoE_FibRDXb6DIingMCve8ZmIe7bF8jQpiqDHvRR9GrN6hRGl3WWZCQlus5JoWjnqkyj_R_lNOmx3CDm6eVnERBMMSG25B-H1WZeH8T5-pudVTNnuwRwNAjREkVYA3Uepv9Xe0sOwJbqGSmiuE1jj5L2pC5MmpeDNE2FsQ/s320/rsv.jpg" width="320" /></a></div><div><br /></div><div><br /></div><div>This fall, hospitalization of infants and the elderly with RSV has been particularly devastating. This reality has accelerated the development of a safe and effective vaccine against this virus. It has recently be reported in the prestigious journal, Science that two large trials have proven the efficacy of two vaccines against RSV infection. The data demonstrate that either vaccine can protect both infants and individuals over the age of 60. One of these vaccines also was found to protect infants for up to six months when given to women in the latter stage of pregnancy who could pass the antibodies induced by the vaccine to the fetus.</div><div><br />Some fifty years ago an initial attempt to develop a vaccine against RSV proved unsuccessful; a chemically inactivated intact virus was used in this particular vaccine. Not only did the vaccine fail to elicit a robust response to RSV infection, it also led to some fatalities and even worsened the symptoms of those treated from subsequent RSV infection. <br /><br />It was reported that, “The new vaccines avoid this problem by relying on a key advance made by Barney Graham and co-workers at the National Institute of Allergy and Infectious Diseases in 2013” <br /><br />They discovered that a key viral protein located on the surface of the viral membrane interacts with a particular receptor on the cell membrane of the target tissue and changes its shape allowing it to gain entry into the host cell. The team working on vaccine development led by Doctor Graham currently at the Morehouse School of Medicine (Atlanta, Georgia) used this knowledge to modify the viral protein so it remains fixed in this modified state. Once this modified antigen was introduced into the vaccine, it resulted in the production of higher levels of effective antibodies. This good news was established as a result of clinical trials run by GSK and Pfizer. This result illustrates how the knowledge gained from the study of viral biology can prove efficacious in the development of treatments against infection.<div class="separator" style="clear: both; text-align: center;"><br /></div><br /><div class="separator" style="clear: both; text-align: center;"><br /></div></div><br />Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-18415419093076122022-11-11T14:43:00.005-08:002022-11-11T16:01:24.194-08:00The Role of Microbial Metabolites in the Etiology of Colon Cancer<p> It has been shown that a number cancers are caused by
pathogens as the table below demonstrates</p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal"><br /></p>
<table border="1" cellpadding="0" cellspacing="0" class="MsoTableGrid" style="border-collapse: collapse; border: none; mso-border-alt: solid windowtext .5pt; mso-padding-alt: 0in 5.4pt 0in 5.4pt; mso-yfti-tbllook: 1184;">
<tbody><tr style="mso-yfti-firstrow: yes; mso-yfti-irow: 0;">
<td style="border: 1pt solid windowtext; mso-border-alt: solid windowtext .5pt; padding: 0in 5.4pt; width: 148.25pt;" valign="top" width="198">
<p class="MsoNormal"><b><span style="font-size: 14pt;">Disease<o:p></o:p></span></b></p>
</td>
<td style="border-left: none; border: 1pt solid windowtext; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; padding: 0in 5.4pt; width: 319.25pt;" valign="top" width="426">
<p class="MsoNormal"><b><span style="font-size: 14pt;">Causative Agent<o:p></o:p></span></b></p>
<p class="MsoNormal"><b><span style="font-size: 14pt;"><o:p> </o:p></span></b></p>
</td>
</tr>
<tr style="mso-yfti-irow: 1;">
<td style="border-top: none; border: 1pt solid windowtext; mso-border-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt; width: 148.25pt;" valign="top" width="198">
<p class="MsoNormal">T-cell Leukemia<o:p></o:p></p>
</td>
<td style="border-bottom: 1pt solid windowtext; border-left: none; border-right: 1pt solid windowtext; border-top: none; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt; width: 319.25pt;" valign="top" width="426">
<p class="MsoNormal">HTLV-1 Human Retrovirus<o:p></o:p></p>
</td>
</tr>
<tr style="mso-yfti-irow: 2;">
<td style="border-top: none; border: 1pt solid windowtext; mso-border-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt; width: 148.25pt;" valign="top" width="198">
<p class="MsoNormal">Cervical Cancer<o:p></o:p></p>
</td>
<td style="border-bottom: 1pt solid windowtext; border-left: none; border-right: 1pt solid windowtext; border-top: none; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt; width: 319.25pt;" valign="top" width="426">
<p class="MsoNormal">Human Papilloma Virus (HPV)<span style="mso-spacerun: yes;"> </span><o:p></o:p></p>
</td>
</tr>
<tr style="mso-yfti-irow: 3;">
<td style="border-top: none; border: 1pt solid windowtext; mso-border-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt; width: 148.25pt;" valign="top" width="198">
<p class="MsoNormal">Liver Cancer<o:p></o:p></p>
</td>
<td style="border-bottom: 1pt solid windowtext; border-left: none; border-right: 1pt solid windowtext; border-top: none; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt; width: 319.25pt;" valign="top" width="426">
<p class="MsoNormal">Hepatitis B and Hepatitis C Virus (HBV and HCV)<o:p></o:p></p>
</td>
</tr>
<tr style="mso-yfti-irow: 4; mso-yfti-lastrow: yes;">
<td style="border-top: none; border: 1pt solid windowtext; mso-border-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt; width: 148.25pt;" valign="top" width="198">
<p class="MsoNormal">Stomach Cancer<o:p></o:p></p>
</td>
<td style="border-bottom: 1pt solid windowtext; border-left: none; border-right: 1pt solid windowtext; border-top: none; mso-border-alt: solid windowtext .5pt; mso-border-left-alt: solid windowtext .5pt; mso-border-top-alt: solid windowtext .5pt; padding: 0in 5.4pt; width: 319.25pt;" valign="top" width="426">
<p class="MsoNormal">H.pylori – a Bacteria<o:p></o:p></p>
</td>
</tr>
</tbody></table>
<p class="MsoNormal"><o:p> </o:p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjcbwhKCalmMCJ0s-9_nMJuvJIkL-G1_6cfPT_Pj670h2-NRjFSZLVQJ1r0XDJ5qWdXVUMQWej7f69GrDyu5rYgFpCMdVqJ7A3YbhPf2cIFVJA6brWqjhxtKTFRyco2RFJ723ytvjdcWWWxK-VYWFtmXV7DURvebYZMkOz4bxjdLJk66mQWOHqTrt4wpA/s800/human%20gut%20microbiome.jpg" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="762" data-original-width="800" height="305" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjcbwhKCalmMCJ0s-9_nMJuvJIkL-G1_6cfPT_Pj670h2-NRjFSZLVQJ1r0XDJ5qWdXVUMQWej7f69GrDyu5rYgFpCMdVqJ7A3YbhPf2cIFVJA6brWqjhxtKTFRyco2RFJ723ytvjdcWWWxK-VYWFtmXV7DURvebYZMkOz4bxjdLJk66mQWOHqTrt4wpA/s320/human%20gut%20microbiome.jpg" width="320" /></a></div><br /><p></p><p class="MsoNormal">This growing evidence involving the role of pathogens in the
etiology of various cancers has led to numerous studies that look at a possible
role of enteric microorganisms that naturally inhabit the human gut in the
etiology of colon cancer. The result of
this kind of investigation has revealed that so-called genotoxic gut bacteria, whose
metabolic product(s) can damage or mutate human DNA, may well be drivers of
colorectal cancer (CRC) parthenogenesis.</p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal">Moreover, it has been recently reported in the prestigious
journal, <i>Science, </i>by Dr. Cao and his colleagues that patients presenting
with inflammatory bowel disease (IBD) – a condition that can lead to CRC – show
the evidence of diverse populations of bacterial strains that can exert genotoxic
activity.</p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal"><o:p> </o:p>In this study, a particular bacterium, Monganella morganii,
proved pf particular interest. This
organism is a Gramnegative bacterium that was discovered as an enriched
population among individuals suffering from IBD and CRC. The organisms of this type was identified as belonging
to a class of bacteria that produce indolimines. This is of special importance since
indolimines have been found to promote tumor growth in mice.</p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal"><o:p> </o:p>In addition to these findings, “Among the most
well-described genotoxic bacteria are enterotoxigenic Bacteroides fragilis
(ETBF) (3) that produce Bacteroides fragilis toxin (BFT), strains of
Escherichia coli or other bacteria that produce colibactin (4), and
Campylobacter jejuni strains that express cytolethal distending toxin (CDT)
(5). The DNA-damaging properties of these strains and their toxins vary
considerably, ranging from alkylating DNA interstrand cross-links for
colibactin to deoxyribonuclease (DNase) activity for CDT (1, 4, 5).
Intriguingly, ETBF and E. coli producing colibactin have been linked to IBD and
CRC development using in vitro and in vivo models.”</p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal">The contribution of Dr. Chao and his colleagues made as cited
in their study was the successful elucidation and characterization of the
existence of some 18 strains of strains of enteric bacteria that actively
produce genotoxins out of the 122 strains that were isolated for examination.</p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal">In the final analysis, the correlation between genotoxins
found in the gut and the onset of IBD and CRC is of immense value and points to
an avenue for future studies that may be of profound importance in regard to the
ultimate prevention and treatment of these diseases.</p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal"><o:p> </o:p></p>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-62677300986047556442022-10-01T18:26:00.000-07:002022-10-01T18:26:15.139-07:00Immunotherapeutic Methodology Designed to Treat LupusLupus is a disease in which the patient manifests certain symptoms that are a result of an autoimmune disease in which the patient’s immune system is producing antibodies against the individual’s own tissue(s). <br /><br />The following is an overview of this condition as described on the website of the Mayo Clinic – (https://www.mayoclinic.org/diseases-conditions/lupus/symptoms-causes/syc-20365789) <br /><br />“Lupus is a disease that occurs when your body's immune system attacks your own tissues and organs (autoimmune disease). Inflammation caused by lupus can affect many different body systems — including your joints, skin, kidneys, blood cells, brain, heart and lungs. <br /><br />“Lupus can be difficult to diagnose because its signs and symptoms often mimic those of other ailments. The most distinctive sign of lupus — a facial rash that resembles the wings of a butterfly unfolding across both cheeks — occurs in many but not all cases of lupus. <br /><br />“Some people are born with a tendency toward developing lupus, which may be triggered by infections, certain drugs or even sunlight. While there's no cure for lupus, treatments can help control symptoms. <br /><br />Symptoms <br /><br />Red, butterfly-shaped rash on nose and cheeks<div><br /></div><div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjRWu0FXSNobj3TSVj2Ij9_MKYe4e0doxRc8hBPZGHJXMunQwTDyRZNJVRT9HoPlT2cFg28Oo-91qwsQcfHlMr-HW4L92XGlPLK02ks3fts5_to2f0J47cSx6jesXLH28uorskySeS7E-O3EsrPP2bHkRYZRQMR3waM_kgUT6EuTddorA5Lj4JiypM5xg/s800/lupus.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="800" data-original-width="632" height="220" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjRWu0FXSNobj3TSVj2Ij9_MKYe4e0doxRc8hBPZGHJXMunQwTDyRZNJVRT9HoPlT2cFg28Oo-91qwsQcfHlMr-HW4L92XGlPLK02ks3fts5_to2f0J47cSx6jesXLH28uorskySeS7E-O3EsrPP2bHkRYZRQMR3waM_kgUT6EuTddorA5Lj4JiypM5xg/w174-h220/lupus.jpg" width="174" /></a></div><br /> No two cases of lupus are exactly alike. Signs and symptoms may come on suddenly or develop slowly, may be mild or severe, and may be temporary or permanent. Most people with lupus have mild disease characterized by episodes — called flares — when signs and symptoms get worse for a while, then improve or even disappear completely for a time. <br /><br />The signs and symptoms of lupus that you experience will depend on which body systems are affected by the disease. The most common signs and symptoms include: <br /><br />Fatigue <br /><br />Fever <br /><br />Joint pain, stiffness and swelling <br /><br />Butterfly-shaped rash on the face that covers the cheeks and bridge of the nose or rashes elsewhere on the body <br /><br />Skin lesions that appear or worsen with sun exposure <br /><br />Fingers and toes that turn white or blue when exposed to cold or during stressful periods <br /><br />Shortness of breath <br /><br />Chest pain <br /><br />Dry eyes <br /><br />Headaches, confusion and memory loss” <br /><br /> <br /><br />Autoimmune diseases as a class of ailments have been historically exceedingly difficult to treat. However, impressive inroads have been made in recent years using the rapidly advancing techniques embodies in immunotherapy. It has been reported in a recent issue of the prestigious scientific publication, Nature Medicine, from a medical team in Germany that five patients, four women and a man, have been successfully treated with their own immune cells that have been genetically engineered. <br /><br />This technique involves isolating the patient’s own T cells – a subset of the immune system’s cellular repertoire – and genetically modifying them so that they would recognize those B cells that are involved in the autoimmune response unique to lupus and attack them by binding to a specific cell surface protein (antigen). This kind approach is referred to as T cell (CAR-T) therapy. <br /><br />In this case, all five patients tolerated the therapy and their lupus-caused impaired organ function either improved or was resolved. As a result, these patients were no longer required to take immune-suppressive medication. <br /><br />These results are quite encouraging and certainly are promising in regard to the treatment of lupus. </div>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-22544852894103478652022-05-27T18:31:00.008-07:002023-03-13T08:50:24.145-07:00The Beginning of Cellular Life on Planet Earth - An Hypothesis<p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgnL-c-SDIKZZDFcMIIIH7ClyevB78ywHtWc0tsEfR18TmUlOSYr87nRl1RgzWJPkP5RMExsG9eJIv8J5m3BGZXjv75FrCefuB0sGgevoTe1ACKtX1KGse_RmXDcZD8TlipxrFIfAhOGyWCPtmpqTGvwZBId5EXL1BRs0OdCcUG2YQUZ4jj4W_ea-7K9A/s259/first%20cells.jpg" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="194" data-original-width="259" height="194" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgnL-c-SDIKZZDFcMIIIH7ClyevB78ywHtWc0tsEfR18TmUlOSYr87nRl1RgzWJPkP5RMExsG9eJIv8J5m3BGZXjv75FrCefuB0sGgevoTe1ACKtX1KGse_RmXDcZD8TlipxrFIfAhOGyWCPtmpqTGvwZBId5EXL1BRs0OdCcUG2YQUZ4jj4W_ea-7K9A/s1600/first%20cells.jpg" width="259" /></a></div><p></p><p style="text-align: center;">A Possible Structure for a Primitive Cell- Biology Libre Texts</p><p>A necessary first step in examining the evolution of cellular-based life from the pre-biotic world is to discern what constitutes the makeup of cells in the broadest possible terms. In deconstructing cell structure from the viewpoint of prokaryotes, I propose the following necessary prerequisites for a living cell:</p>· Cell Membrane to delineate the cell and protect it from the local environment <br /><br />· Cell infrastructure composed of the most basic structural components including actin, myosin, etc. <br /><br />· Source of readily available energy <br /><br />· Proteins especially enzymes involved in catabolic and anabolic activities <br /><br />· Signal transduction pathways that allow for both intracellular and extra-cellular communication. <br /><br />· Nucleic Acids: DNA and RNA to serve as information stores for the cell. <br /><br />· Mechanisms for DNA and cellular replication. <br /><br />Any attempt to propose a mechanism by which primordial cell-like structures evolved into the complex cells that exist today, strongly suggests a gradual stepwise process that took eons to accomplish. It also suggests, in my mind, that the process would involve steps in which cellular organization would grow in complexity from the level of simple molecules (substrates) through proteins and nucleic acids and finally through protein-nucleic acid interaction to the encoding of the genetic material. In this way, selection pressures and processes would enhance each succeeding step. <br /><br /><i>Taking all this into account, I propose the following model for the evolution of cellular life from primordial beginnings. </i><br /><br /><b><u>Elements of the Hypothesis: </u></b><br /><br />There existed an aqueous environment (possibly shallow ponds or along coastal regions or possibly the sea floor) where there was an abundance of nucleotides, fatty acids, amino acids, peptides and polypeptides. It is possible that some of this organic material may have been seeded by meteorites. <br />In these organic-enriched regions, conditions were appropriate for the spontaneous formation of cell-like structures.<div> <br />These cell-like structures developed semi-permeable membranes formed from the spontaneous assembly of proteins and lipids (probably a more primitive structure than found in present day cells) and highly permeable to dissolved organic matter in the local environment.</div><div> <br />The local environment was such that amino acids, nucleotides, fatty acids and carbohydrates could readily penetrate the cell membranes of these primordial cells and concentrate there.</div><div> <br />Ambient conditions including oxygen concentration, temperature, abundance of ammonia and methane made the spontaneous synthesis of proteins and nucleic acids not only possible but highly likely. <br />Assuming that spontaneous formation of tRNAs were a likely scenario, these tRNAs could bind to their appropriate amino acids. These amino acid carriers collided with each other and resulted in the formation of random polypeptide chains. Subsequently, polypeptides that were capable of binding to carbon sources such as glucose stabilized these small proteins and gave them a competitive advantage over more non-specific proteins. Since the metabolic pathway for glucose metabolism is universal to all life, one must assume that glucose was abundant in pre-biotic times. This same argument can be applied to the presence of ADP/ATP, since this molecule is the essential ingredient for all energy sustaining life activities.</div><div> <br />Some of these selected proteins also possessed catalytic capabilities and were able to breakdown carbon rich substrates and ultimately capture energy in ATP molecules. This energy may have been used in accelerating the synthesis of more complex molecules and intra-cellular structures, the precursors of cellular organelles. </div><div> <br />There is mounting evidence that strongly suggests that RNA may have played a pivotal role in information storage in the early evolution of cellular life. As I have postulated above, tRNAs may have been abundant. Additionally, evidence for the role of RNA in information storage includes:</div><div> <br /><ul style="text-align: left;"><li>The discovery of RNA that possesses catalytic activity referred to as ribozymes. There is a ribozyme that has been found in the core of ribosomes. </li><li>The discovery of small pieces of RNA that can readily bind to a variety of organic molecules and that are found on the ends of mRNA in prokaryotes. These pieces function as switches that can turn translation on or off and are referred to as riboswitches. </li><li>Double-stranded RNA that can silence gene transcription in a complex referred to as RISC. </li><li>What is now referred to as the anti-codon region of tRNA may have been used to make mRNA possibly happening spontaneously utilizing an environment rich in small pieces of RNA or assisted by a ribozyme. These nascent mRNAs served as templates for the further synthesis of specific and biologically valuable proteins. Whether or not such associations are possible today in conditions that simulate the pre-biotic environment would need to be tested. It is possible that “ancient” RNA had a different structure than the current form. This early mechanism was probably inefficient and prone to error.</li></ul></div><div> <br />These early cells were infiltrated by a competing entity that gradually assumed a symbiotic relationship and was to become what is now referred to as ribosomes. These structures contributed a much more efficient mechanism for the synthesis of proteins. In addition, the mitochondria found in eukaryotic cells and the chloroplasts found uniquely in plant cells have their own nucleic acid and most probably were once independent organisms that also assumed a symbiotic relationship with their host cells.</div><div> <br />Messenger RNAs were no longer able to sustain the growing complexity of cell life as embodied in metabolism and energy transfer mechanisms. A more highly conserved store of information was required. The appearance of an enzyme capable of using mRNA as a template to make highly stable double-stranded DNA encouraged the further development of cellular complexity and evolution. This transition was necessitated by the fact that the extra-cellular environment was no longer as rich in nutrients and building materials as was previously the case. It has become clear that large portions of the genome of humans and other complex organisms are made up of retrotransposons. There are relatively small pieces of DNA that code for reverse transcriptases that allow for copying of these segments and ultimately inserting them in other places in the genome. These were originally discovered by McClintock and referred to as so-called “jumping genes.” Integration of these pieces in the promoter or structural regions of active genes can have profound impacts on gene expression. Certain diseases have been associated with this process. Furthermore, there are retrotransposons that have been conserved among and between organisms. This suggests that the increasing complexity of the genome as seen in evolution may be in large due to retrotransposons. In addition, retrotransposons have many characteristics similar to retroviruses suggesting that retroviruses may have played a significant role in delivering novel genetic material to the genome.<ul style="margin-top: 0in;" type="disc">
</ul></div><div>In conclusion, the particular scenario I have outlined represents one possible pathway that may have taken place that was responsible for the evolution of cellular life as we know it from prebiotic conditions that existed on planet Earth billions of years ago.</div>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-71046421231868606962022-05-18T14:57:00.001-07:002022-05-18T16:35:55.239-07:00The Impact of Sunscreen Products Upon the Viability of CoralIt has been reported that the compound oxybenzone (shown below) that is the active ingredient in sunscreen preparations exhibits a toxicity to corals. The mechanism of this toxicity has not been fully understood. <br /><br /> <a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgqBzRRE0Ii8exeLiDk4Yc9aNK_vSg65sykdwvaRGnx7OzGn6PtOaHx7nXuZCJi4NUO8uyoX64XDiVz3wD_7ZwgosW1iOnFi-tgmwOL2Lxsg3Bj39J84pyz9XJ-YMZ_ONY9HUv_qj0AGlsIGITQbvkjJyW41m_73AqrO3xpRxsFkTSJp99WQJS-MZmXqA/s282/oxybenzone.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em; text-align: center;"><img border="0" data-original-height="157" data-original-width="282" height="180" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgqBzRRE0Ii8exeLiDk4Yc9aNK_vSg65sykdwvaRGnx7OzGn6PtOaHx7nXuZCJi4NUO8uyoX64XDiVz3wD_7ZwgosW1iOnFi-tgmwOL2Lxsg3Bj39J84pyz9XJ-YMZ_ONY9HUv_qj0AGlsIGITQbvkjJyW41m_73AqrO3xpRxsFkTSJp99WQJS-MZmXqA/w323-h180/oxybenzone.jpg" width="323" /></a><br /><h2 style="text-align: left;"><b>Oxybenzone</b></h2>William Mitch and his colleagues at Civil and Engineering at Stanford University, California have successfully delineated the mechanisms involved in regard to this toxicity. They have established that oxybenzone caused increased mortality of a sea anemone under conditions that simulated the natural (UV) radiation (290 to 370 nanometers). Furthermore they found that both the anemone and a mushroom coral formed oxybenzone–glucoside conjugates (see image below) that were powerful auto-oxidants. Corals are composed of layers, of calcium carbonate secreted by soft bodied animals called coral polyps. These polyps live in a symbiotic relationship with a host zooxanthellae such as algae that gives the coral its color. Corals devoid of algae are bleached as a consequence of climate change. <br /><br /> <br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjzgH5RdlAxUwPB0WAedJx0jcgRg3GJG1h6huJERTugwowGACirsQUMJDrNMFUfyRPOi5TjECN2bU7NNRIxfSFZTP9tO2Wdo5mTosjANYtRyJWIBPl7VJ3HgOrTtrwFqTZyVc0lkwZzIX9upigKTsaY4cTbdFlChMDlFmub4P6Y7BhdeTl5oBJ4kbTP6A/s367/oxybenzone%20glucoside%20conjugate.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em; text-align: center;"><img border="0" data-original-height="367" data-original-width="367" height="320" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjzgH5RdlAxUwPB0WAedJx0jcgRg3GJG1h6huJERTugwowGACirsQUMJDrNMFUfyRPOi5TjECN2bU7NNRIxfSFZTP9tO2Wdo5mTosjANYtRyJWIBPl7VJ3HgOrTtrwFqTZyVc0lkwZzIX9upigKTsaY4cTbdFlChMDlFmub4P6Y7BhdeTl5oBJ4kbTP6A/s320/oxybenzone%20glucoside%20conjugate.jpg" width="320" /></a><br /><br /><div>Algal symbionts took up these conjugates, and their mortality correlated well with the corresponding concentration of oxybenzone glucosides within the animal cells. Since many commercial sunscreens preparations contain compounds structurally analogous to oxybenzone, an understanding of the mechanism of this toxicity should enable the synthesis of more eco-friendly sunscreen products.</div><div><br />According to the authors of a paper published in a recent article in the prestigious journal, Science, “Research in the US Virgin Islands found no substantial settlement of coral larvae, survival of juvenile corals, or regeneration of adult tissue in induced lesions over a 5-year period in Trunk Bay, where high levels of recreational swimming resulted in up to 1.4 mg of oxybenzone per liter of seawater. Meanwhile, a thriving coral community was found at neighboring Caneel Bay, with lower recreational use but presumably the same impacts from global stressors. Exacerbation of coral declines by sunscreens washed off tourists would be ironic and particularly pernicious, given the promotion of ecotourism in the interest of protecting coral reefs.” <br /><br />Finally, the authors go on to say that, “With recent moves by regulatory authorities in Hawaii and elsewhere to ban oxybenzone, understanding the mechanism(s) of its phototoxicity is important to ensure that the sunscreen components that are selected as alternatives are truly safer for corals.” <br /><br />The ecological factors that promote and sustain the delicate balance in the natural world can easily be disrupted by human encroachment. It is vitally important to support the kind of scientific investigations that uncover these human factors and find ways to mitigate their impact.<div class="separator" style="clear: both; text-align: center;"><br /></div><br /><div class="separator" style="clear: both; text-align: center;"><br /></div><br /></div>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-35112048476069567082022-05-15T07:47:00.006-07:002022-05-18T20:30:04.316-07:00The FilovirusOne of the suspected and postulated origins of COVID-19 virus in human populations is the transfer of the virus across the species barrier i.e. from bats. This capacity to “jump” across species is of added concern given the severity of illness originating from human infection by a family of viruses referred to as filoviruses. A filovirus is a filamentous RNA virus (see image below).<div><br /></div><div><div class="separator" style="clear: both; text-align: center;"><br /></div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgMbOaIvCcym6Cmp-5rsY9KfcWmzufLVtryEPHh6p_oQHRTpMa9tKKyhShqFuxJ6ZWu-3fV7iTKm1XJ_-nBgufv6c6wugFwEybtIqnz4CbFBxz1sbN598dhp929XSAv6VVQkyexwi3YM00AKUePm5SltTXwQQ0H4s71WSo8oFbFxTl4O0dYP0F0eDaqkg/s268/filovirus.jpg" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="188" data-original-width="268" height="188" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgMbOaIvCcym6Cmp-5rsY9KfcWmzufLVtryEPHh6p_oQHRTpMa9tKKyhShqFuxJ6ZWu-3fV7iTKm1XJ_-nBgufv6c6wugFwEybtIqnz4CbFBxz1sbN598dhp929XSAv6VVQkyexwi3YM00AKUePm5SltTXwQQ0H4s71WSo8oFbFxTl4O0dYP0F0eDaqkg/s1600/filovirus.jpg" width="268" /></a></div><br /> <br /><br />Infection by this virus is the causative agent of so-called “hemorrhagic fevers” in humans and primates, that includes the Ebola and Marburg viruses. These viruses can result in multiple organ system involvement. The Marburg virus, for example, can produce nausea, vomiting, chest pain, a sore throat, abdominal pain, and diarrhea may appear. Symptoms become increasingly severe and can include jaundice, inflammation of the pancreas, severe weight loss, delirium, shock, liver failure, massive hemorrhaging, and multi-organ dysfunction. These diseases are most prevalent in sub-Saharan Africa.</div><div><br /></div><br /><div><br /><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiNnEqI9HBCxwNkmcdtf8B5-vkYVIfY7N3E5fqsE0GEd_7-KrMl6KK9XZl_W5BCYISLjQrLJ1ma_yiv42EjLN1QM0szMsqqnHFuPOZZDZUXB1S-Yivh2OogDRbY-eyGMH8FQ8pw3abCui-10ohXI7n479NChEAU3GpDQ_9Gdrr4bPqrk30rnVeNjWOlsA/s283/scheiber%20bat.jpg" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="178" data-original-width="283" height="178" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiNnEqI9HBCxwNkmcdtf8B5-vkYVIfY7N3E5fqsE0GEd_7-KrMl6KK9XZl_W5BCYISLjQrLJ1ma_yiv42EjLN1QM0szMsqqnHFuPOZZDZUXB1S-Yivh2OogDRbY-eyGMH8FQ8pw3abCui-10ohXI7n479NChEAU3GpDQ_9Gdrr4bPqrk30rnVeNjWOlsA/s1600/scheiber%20bat.jpg" width="283" /></a></div></div><div> <br /><br />In 2002, the Lloviu filovirus was found in Schreiber bats (Miniopterus schreibersii) in northern Spain. This infection resulted in a massive die-off of these animals. Gabor Kemenesi and his colleagues from the National Laboratory of Virology at Szentagothai Research Center at the University of Pecs, Hungary successfully isolated and sequenced the Lloviu filovirus from Schreiber bats in Hungary. During a active surveillance of these bats, they found the Lloviu virus resident in these dead and living cave-dwelling bats. <br /><br />Furthermore, antibody testing detected nine seropositive bats out of 74 live bats and four positives among 351 live bats sampled. The Lloviu virus is known to infect human cells in culture, but unlike the Ebola virus appears to be nonpathogenic to humans, at least for the time being.</div><div><br /></div><br />Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-50218621424664288312022-01-23T18:37:00.001-08:002022-01-23T18:37:04.074-08:00Epstein Barr Virus Infection May be Associated with the Onset of Multiple Sclerosis<p>Multiple Sclerosis (MS) is a chronic and debilitating
disease that is a result of the destruction of the myelin sheath that serves as
insulation for the peripheral nerves within the central nervous system (CNS). The loss of myelin has serious implications
for the patient suffering from this syndrome – it results in a gradual
deterioration of motor function. </p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal">To date the etiology of this disease has been unclear.<span style="mso-spacerun: yes;"> </span>It has long been suggested that Infection
with the Epstein-Barr virus (EBV) may be responsible for triggering the onset
of MS.<span style="mso-spacerun: yes;"> </span>In a recent issue of the
prestigious publication <i>Science</i> (January, 2022), Kjetil Bjornevik, from
the Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston,
MA, has provided compelling statistical evidence that EBV infection triggers
the onset of MS.<span style="mso-spacerun: yes;"> </span>According to the
author, “analyzed EBV antibodies in serum from 801 individuals who developed MS
among a cohort of >10 million people active in the US military over a
20-year period (1993–2013). Thirty-five of the 801 MS cases were initially EBV
seronegative, and 34 became infected with EBV before the onset of MS. EBV
seropositivity was nearly ubiquitous at the time of MS development, with only
one of 801 MS cases being EBV seronegative at the time of MS onset. These
findings provide compelling data that implicate EBV as the trigger for the
development of MS.”<span style="mso-spacerun: yes;"> </span><o:p></o:p></p>
<p class="MsoNormal">EBV (see diagram below) preferentially attacks B cells; B cells are the part of
the immune system repertoire responsible for the production of antibodies.<span style="mso-spacerun: yes;"> </span><span style="mso-spacerun: yes;"> </span>In MS
the myelin sheath is degraded through an inflammatory response.<span style="mso-spacerun: yes;"> </span>It has been shown that in MS the B cells responsible
for this inflammatory are derived from plasmablasts that are generated in the
marrow and take residence inside the brain and its internal lining.<span style="mso-spacerun: yes;"> </span>These plasmablasts divide and produce
clusters of daughter cells that produce immunoglobulins.<span style="mso-spacerun: yes;"> </span>These immunoglobulins contain specific antibodies
that target myelin-producing glial cells within the central nervous system
(CNS).<o:p></o:p></p>
<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/a/AVvXsEhA1WxXmwrAomsqEv53uXK_cA77MtvJU4skCw4YBSwz8WZe_4zY8hNhq447BcoEyIKH2hwMd89uEzhDtIv4WS5hc80QBRBjaIvTLLkIYFbJ6ML_G8Lt8-yyHnuCDzFECkr--pDZgyLvHoRW75d2CNsN-pcatechSw0I344kpaNXaxxQbK3zxkw_zD5lYQ=s279" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="181" data-original-width="279" height="181" src="https://blogger.googleusercontent.com/img/a/AVvXsEhA1WxXmwrAomsqEv53uXK_cA77MtvJU4skCw4YBSwz8WZe_4zY8hNhq447BcoEyIKH2hwMd89uEzhDtIv4WS5hc80QBRBjaIvTLLkIYFbJ6ML_G8Lt8-yyHnuCDzFECkr--pDZgyLvHoRW75d2CNsN-pcatechSw0I344kpaNXaxxQbK3zxkw_zD5lYQ" width="279" /></a></div><p class="MsoNormal" style="text-align: center;">EBV Virus</p><p class="MsoNormal"><br /></p><p class="MsoNormal">One of the accepted therapies that attempt to take advantage
of this etiology is the use of monoclonal antibodies that target CD20 - a protein
preferentially found on the surface of B cells.<span style="mso-spacerun: yes;">
</span>However, it has significant drawbacks in so far as these monoclonals do
not readily pass through the blood brain barrier (BBB) and they are unable to
bind to plasmablasts.<o:p></o:p></p>
<p class="MsoNormal">What remains unclear, however, is the mechanism through
which EBV triggers this sequence of events in MS patients.<span style="mso-spacerun: yes;"> </span>One possibility involves what is referred to
as molecular mimicry in which some EBV proteins may be similar enough in
structure to myelin that the immune system is induced to produce antibodies against
the infected individual’s myelin and CNS antigens – this would represent an
autoimmune response.<span style="mso-spacerun: yes;"> </span>In addition, EBV
encodes an interleukin-10–like protein, which activates B cells. <span style="mso-spacerun: yes;"> </span>The author of this study, reports that recent
evidence seems to suggest that molecular mimicry may be the actual mechanism
underlying the association between EBV infection and MS.<o:p></o:p></p>
<p class="MsoNormal">The results of these kind intensive studies of the etiology
of MS are extremely important in that the product of this work may finally
produce effective therapies for MS patients.<o:p></o:p></p>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-59995571994162181802021-10-28T12:58:00.003-07:002022-05-15T06:44:12.387-07:00What drives Cancer?<p>In a recent article in the Science, a prestigious scientific
journal published by the American Association for the Advancement of Science (AAAS), Dr. Arianna Baggiolini and her colleagues, from the Memorial
Sloan Kettering Cancer Center In New York, NY, proposed a model to explain why some
melanocytes preferentially transform into the cancerous state while other melanocytes
do not.</p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal">Melanoma is a cancer that preferentially arises from cells
of the melanocyte lineage.<span style="mso-spacerun: yes;"> </span>Melanocytes (see image below) are
responsible for <span style="mso-spacerun: yes;"> </span>skin pigmentation
through the production of melanin so that skin cells, especially keratinocytes,
are protected from UV-induced DNA damage.<span style="mso-spacerun: yes;">
</span>Melanoma typically resides in the skin.<span style="mso-spacerun: yes;">
</span>It has been well established that a so-called “founder mutation” is required
to initiate uncontrolled proliferation of cells – a phenomenon that is
characteristic of all cancers.<span style="mso-spacerun: yes;"> </span>Interestingly,
these mutations, also referred to as driver mutations (oncogenes), are also found
in healthy skin.<span style="mso-spacerun: yes;"> </span>The question arises –
why is it that oncogenesis preferentially arises in in some melanocytes and not
others.<o:p></o:p></p>
<div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhGmszLxdFr8cpADnzI2Bx2HYKF6xez4q0MKNMKtvNq7NT2BvLmVeyCud95bpEK-C6oOZ6YpGgm2ledeabDx9OLC8rLkU_EuFXYR7ynBYGp-BhZGr668uXQKiIIIuBd1KQo8uY7B__BGMWj/s280/melanocyte.jpg" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="280" data-original-width="260" height="280" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhGmszLxdFr8cpADnzI2Bx2HYKF6xez4q0MKNMKtvNq7NT2BvLmVeyCud95bpEK-C6oOZ6YpGgm2ledeabDx9OLC8rLkU_EuFXYR7ynBYGp-BhZGr668uXQKiIIIuBd1KQo8uY7B__BGMWj/s0/melanocyte.jpg" width="260" /></a></div><br /><p class="MsoNormal">Dr. Baggliolini and her group of investigators conducted an
experimental study in an attempt to explain this behavior.<span style="mso-spacerun: yes;"> </span>The animal they chose for their studies was genetically
modified zebra fish deficient for the tumor suppressor p53 to drive expression
of the BRAFV600E oncoprotein in each stage of melanocyte differentiation.<span style="mso-spacerun: yes;"> </span>The evidence they obtained led to a concept
they refer to as oncogenic competence – an additional variable is present that
renders the melanocytes more susceptible to transformation to tumor cells.</p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal">In regard to Melanoma, to give rise to cancer, melanocytes
require a driver mutation. For melanoma, such mutations frequently occur in
proteins of the mitogen-activated protein kinase (MAPK) pathway, with the
BRAFV600E mutation (in which Val600 is replaced with Glu) being most prevalent.<span style="mso-spacerun: yes;"> </span>Furthermore in normal human skin, individual melanoblasts
and neural crest cells also possess this driver mutation.<o:p></o:p></p>
<p class="MsoNormal">Human skin contains many individual melanocytes harboring
potentially oncogenic driver mutations. However, what determines which of those
cells can evolve to produce melanoma has not been unambiguously determined.
Baggiolini and her experimental team found that both neural crest cells and
melanoblasts were capable of giving rise to melanomas but, surprisingly, that
melanocytes were somewhat resistant. These findings from zebrafish were confirmed
in a parallel study using human pluripotent stem cells (hPSCs) rendered
deficient for the tumor suppressors retinoblastoma (RB), p53, and p16 and in
which the precursor cell line was induced at various stages of melanocytic
differentiation.<span style="mso-spacerun: yes;"> </span>The results show that melanocytes,
but not neural crest cells or melanoblasts, were largely incapable of forming
tumors when subcutaneously transplanted into immunodeficient mice.<o:p></o:p></p>
<p class="MsoNormal">The result of these experimental studies has clearly shown
that the additional factor required to explain why some melanocytes do go on to
produce cancer while other melanocytes with the driver mutation do not, is the
enzyme ATAD2.<span style="mso-spacerun: yes;"> </span>This enzyme is responsible
for chromatin reorganization.<span style="mso-spacerun: yes;"> </span>In those melanocytes
in which this enzyme is expressed at lower levels, the likelihood of
transformation of melanocytes into the cancerous state is increased.<o:p></o:p></p>
<p class="MsoNormal">This is a very interesting finding for it establishes a link
between tumorigenesis and chromatin organization.<o:p></o:p></p>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-2396538416732874002021-06-11T07:46:00.002-07:002021-06-11T07:47:12.217-07:00Biology of a Virus<p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhe0kQD0lOKswFnNVV3rC0JNPkktcI0KK8zM2ZaoXKy_IFjNyki6hXOhID6ExMn2_1NsZd2VEZPvlMJ2vTP3AgjUWM56H3c3c0k02uv8L6aTY6Rk0KI2d0jxXvd2v9oRlkHT8-I_j6ez42V/s275/artist+conception+of+HIVAIDS+atacking+target+cell.jpeg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="183" data-original-width="275" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhe0kQD0lOKswFnNVV3rC0JNPkktcI0KK8zM2ZaoXKy_IFjNyki6hXOhID6ExMn2_1NsZd2VEZPvlMJ2vTP3AgjUWM56H3c3c0k02uv8L6aTY6Rk0KI2d0jxXvd2v9oRlkHT8-I_j6ez42V/s0/artist+conception+of+HIVAIDS+atacking+target+cell.jpeg" /></a></div><br /> <p></p><p>It has been over a year since the world population has been dealing with the COVID-19 pandemic. As a result of intense scientific investigation and study, effective vaccines have been developed and are being distributed worldwide. </p><p>Given this reality, it would be of value to more fully understand what viruses are and how they function.</p><p>The following <a href="https://1drv.ms/b/s!AhLgmI2tjfZRioQ6XvTu7sqJsUX2DA?e=B9BFuA">document </a>may be of some help in this regard.</p>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-63092650709306607602021-02-07T16:42:00.007-08:002021-02-10T15:48:19.365-08:00The Basis of Antiviral Immunity<p></p><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh0TyhqDWOSOsryM15OOVGQrfI5JQYOFrL6-wu50ycO79NuukTaCN_OrH_n9BIxl0aJhdSJZmNdYxHz5yitPdEXs8S9stWS-HTcimOU56xLdVe7pi2JrY3wvtZkIFiXiSGmvS_X059ySA6c/s873/corona+virus+and+corona+virus+spike+protein.jpg" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="655" data-original-width="873" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEh0TyhqDWOSOsryM15OOVGQrfI5JQYOFrL6-wu50ycO79NuukTaCN_OrH_n9BIxl0aJhdSJZmNdYxHz5yitPdEXs8S9stWS-HTcimOU56xLdVe7pi2JrY3wvtZkIFiXiSGmvS_X059ySA6c/s320/corona+virus+and+corona+virus+spike+protein.jpg" width="320" /></a></div><div style="text-align: center;"> Models of COVID-19 and the Spike Protein</div><div style="text-align: center;"><br /></div><p></p><p>The human immune system is a highly sophisticated and powerful system that the body utilizes on an ongoing basis in order to ensure the continued survival of the individual in a hostile environment. It is comprised of a heterogeneous population of cells, factors and organs that function together to maintain the general health of the individual. The immune system is, in fact, a product of millions of years of evolution. Rudimentary immune systems and processes can be found in many more primitive forms of life including single-celled organisms.</p>Immunologists have delineated two arms of the human immune system – innate and adaptive. The innate branch of the immune system possesses pattern recognition mechanisms designed to recognize any non-self antigen – an antigen is any substance, usually protein, that can elicit an immune response. When an antigen is recognized as foreign, the innate immune system is designed to mobilize quickly to neutralize the foreign organism that carries this antigen. <br /><br />The other part of the immune system is referred to as the adaptive immune system. As the name infers, the adaptive immune system can adapt to new foreign invasive bacteria and viruses that find their way into the host. It is precisely this arm of the human immune system that responds to SARS-COV-2 (COVID-19). It is this system that neutralizes virally-infected cells and can induce the production of so-called, “memory cells.” It is this capability that is exploited and enhanced by vaccination strategies. <br /><br />Both T-cells and B cells represent the primary cellular arsenal for the adaptive immune system essential for the eradication of invading viruses. The progenitors of the cellular components of the human immune system originate in the bone marrow. The COVID-19 pandemic has revealed the wide variability of the immune response to the COVID-19 virus ranging from an asymptomatic response to an acute and sometimes life threatening severe acute respiratory syndrome. This apparent variability has raised questions regarding the mechanisms through which antiviral responses are employed and the nature of the longevity of immunological memory. <br /><br />As we are well aware, viral infections often lead to disease states within the impacted host. Viruses occupy a special place in regard to life on planet earth. They are essentially inert when outside a living cell showing no properties that are ordinarily assigned to living things. However, once they gain entry into a host cell, they subvert the cellular machinery, effectively diverting ordinary cell processes to a singular goal – the production of viral particles. This usually leads to the death of the host cell facilitating the release of new viral particles that go ahead and infect neighboring cells within the target tissue – in the case of COVID-19 its target tissue is found in the lungs. <br /><br />The dynamics of the human body’s response to an invasion by a virus is intricate, immediate, and multi-faceted. The current understanding of this process is that it involves the integration of the two arms of the immune system we have previously referred to i.e. the innate and the adaptive. The first and rapid response is that of the innate system. The innate immune responses result in the production of factors that lead to inflammation at the site of entry – this is the so-called “inflammatory response.” This response leads to the activation of the adaptive immune system. <br /><br />Viral particles are essentially composed of an inner core of either DNA or RNA and an outer shell of protein. It is the proteins on the viral surface that are potential antigens. Viral proteins and particles are subsequently taken up by specialized cells in the immune repertoire that are called dendritic cells (DCs) These cells transport the ingested antigen(s) to the lymphoid organs (lymph nodes and spleen for example), where they are specifically recognized by T and B cells. The T cells constitute the cellular branch of the adaptive system and the B cells represent the humoral branch responsible for the production of specific antibodies against the viral intruder. It is the cellular (T cell) and humoral (B cell) branches of adaptive immunity that collaborate to enable highly specific defenses against diverse viruses. <br /><br />According to Dr. Linda Bradley from the Tumor and Microenvironment and Cancer Immunology Program at Sanford Burnham Prebys Medical Discovery Institute at La Jolla in a recent report in the prestigious journal, Science, “The magnitudes of the T and B cell responses are determined by such factors as the pathogenicity of the virus, the extent of inflammation, the frequencies of virus-specific T and B cells, and the kinetics of viral replication. CD8+ T cells differentiate into effector cells that limit viral replication through production of cytokines and direct killing of infected cells."<br /><br />Furthermore, in regard to immune responses to COVID-19, this report goes on to state that, “Viral recognition elicits cytokine-producing effector cells, such as T helper 1 (TH1) cells, which inhibit viral replication and support CD8+ T cell as well as B cell differentiation. Effector T cells can enter the circulation and relocate to tissue sites of infection, where they mediate local antiviral responses. CD4+ T cells also differentiate into T follicular helper (TFH) cells that are crucial for the development of antibody-producing B cells (plasma cells) in lymphoid tissues and support memory B cell development. Antibodies can neutralize viruses by preventing host cell entry or promoting the lysis of infected cells. As a result of the coordinated interplay of innate and adaptive responses, the peak T and B cell responses lead to decreasing viral load and subsiding inflammation, often within 1 week of infection."<br /><br />It is an understanding of the mode of action of a particular virus and the immune system’s responses to it, as outlined above, that plays a critical role in developing a vaccine that can effectively augment the natural immunity. For a virus to successfully infect a host it must gain entry to the host, successfully evade the immune response, gain entry into the host cell, and successfully commandeer the host cells machinery to make more viral particle and spread the infection. Any vaccine that successfully interdicts any of these mechanisms will necessarily prove efficacious.
<p class="MsoNormal" style="line-height: 15.6pt; margin-bottom: 0in;"><span face=""Open Sans",sans-serif" style="color: #666666; font-size: 15pt; mso-fareast-font-family: "Times New Roman";"><o:p> </o:p></span></p>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-51970645855394037622020-12-23T10:46:00.007-08:002020-12-23T10:46:57.848-08:00Holiday Message for the Coming Year - 2021<p>The year 2020 has been in many ways disturbing and
unsettling. What, of course, comes to
mind almost immediately is the COVID 19 pandemic that has claimed so many lives
and has been so economically devastating to many facets of the national economy,
and especially for those who have lost their livelihoods and businesses. Added to this national burden are the deep
fractures that have been exposed in regard to a national sense of unity, shared-mission
and purpose.</p><p class="MsoNormal"><o:p></o:p></p>
<p class="MsoNormal">Along with this overwhelming sense of loss, however, is the
untold bravery, courage and unwavering energy displayed by so many who have
risked their own lives and safety to come to the aid of all of us for the
unselfish commitment to the greater good.<span style="mso-spacerun: yes;">
</span>These individuals have come from many diverse positions - as doctors,
nurses, emergency response teams, members of the police and fire departments
and first responders of all kinds.<span style="mso-spacerun: yes;"> </span>To
this list, we should include all those responsible for providing food; for
delivering the mail; for the taxi and bus drivers, train operators and pilots;
for the teachers; for all those who care for the elderly and for all those who
provide the essential services that we all too often take for granted.<o:p></o:p></p>
<p class="MsoNormal">My wish for the New Year (2021) is that we grow wiser from
the events that have befallen us and see the future as a time for healing and
learning from our collective missteps.<span style="mso-spacerun: yes;">
</span>My hope is that the new year will be a time of new beginnings. <span style="mso-spacerun: yes;"> </span>My dream is that we will finally come to
recognize that regardless of our national origin, religious affiliation, skin
color or sexual orientation we are all members of the same species with the
same physical bodies, the same architecture of the brain, the same genetic
makeup, the same constellation of feelings, of hopes and of dreams.<span style="mso-spacerun: yes;"> </span>Each of us is worthy of the same
opportunities to grow and develop as sentient beings on this most remarkable
planet that also needs our kindness, care, and attention.<span style="mso-spacerun: yes;"> </span>Earth is, after all, our only home.<o:p></o:p></p>
<p class="MsoNormal">Best Wishes to All<o:p></o:p></p>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-51709360260613809702020-12-23T09:38:00.004-08:002020-12-23T09:38:53.117-08:00CRISPR and Other Tools May Radically Change the Treatment of Intractable Genetic Disorders<p class="MsoNormal">Genetic diseases such as Sickle Cell Anemia and others have posed
a serious and seemingly intractable problem for the science of medicine since
any cure would require the repair of the damaged gene(s) involved. However a number of significant technological
breakthroughs in recent years have begun to change that bleak impasse. In 2003, the complete mapping of the human
genome was accomplished. This technology
and the information provided with its use have led to discoveries that have
pinpointed the genetic origin of many diseases and continues to do so. In 2012 a new tool was fashioned – the genomic
editor referred to as CRISPR. This
remarkable tool can precisely edit particular sequences within the introns of
targeted genes. The designers of this
capability, Jennifer Doudna and Emmanuelle Charpentier were awarded the Nobel
Prize in Chemistry in 2020. These two
advances are changing the prospects for the treatment of genetic diseases. CRISPR and an additional methodology
(described below) have demonstrated great promise.<o:p></o:p></p>
<p class="MsoNormal">It has recently been reported in the prestigious scientific
journal <i>Science</i> that, “Two strategies for directly fixing malfunctioning
blood cells have dramatically improved the health of a handful of people with
these genetic diseases. One relies on
CRISPR, marking the first inherited disease clearly helped by the powerful tool
created just 8 years ago. And both treatments are among a wave of genetic
strategies poised to expand who can get durable relief from the blood
disorders. The only current cure, a bone marrow transplant, is risky, and
matched donors are often scarce.”<o:p></o:p></p>
<p class="MsoNormal">The two genetic diseases referred to are so-called, “blood
disorders.” One is Sickle Cell Anemia,
and the other is Beta Thalassemia. Sickle
Cell Anemia is a disease in which the red blood cells are mishappen and their ability
to carry oxygen to the tissues is seriously compromised. The origin of this disease is genetic -the
alteration of both alleles that carry the blueprint for hemoglobin protein, the
protein responsible for binding oxygen.
This disease particularly impacts the African-American population. In Beta Thalassemia, the patient makes little
or no functional hemoglobin. The result,
for the patient, is a dangerous and debilitating anemia since the body’s tissue
cannot receive enough oxygen to effectively function. <o:p></o:p></p>
<p class="MsoNormal">The treatment devised that has been applied to both Sickle
Cell Anemia and Beta Thalassemia involve modifying the genes that carry the information
for the structure of hemoglobin in the following way. The stem cells responsible for producing red
blood cells resident in the bone marrow are harvested from the patient, and the
BCL11A gene responsible for shutting off the fetal form of hemoglobin is
disabled thereby allowing it to be produced.
The research tool utilized for this kind of genetic modification is
CRISPR. The patient then receives
chemotherapy to destroy any resident diseased cells and the modified stem cells
are then reintroduced into the patient.
If successful, the patient will then produce red blood cells with the completely
functional fetal hemoglobin.<o:p></o:p></p>
<p class="MsoNormal">In addition, Dr. David Williams from Boston Children’s
Hospital has achieved the same result using a novel technique - a specially genetically
engineered virus is utilized to introduce a fragment of DNA encoded RNA into
the harvested stem cells that effectively silences the BCL11A gene (referred to
earlier).<o:p></o:p></p>
<p class="MsoNormal">It has been reported that, “Patients treated in both trials
have begun to make sufficiently high levels of fetal hemoglobin and no longer
have sickle cell crises or, except in one case, a need for transfusions.” The Boston team described a particular case in
of a teenager, “who can now swim without pain, and a young man who once needed
transfusions but has gone without them for nearly 2.5 years.”<span style="color: #333333; font-family: Roboto; font-size: 13.5pt; line-height: 107%; mso-bidi-font-family: Helvetica; mso-fareast-font-family: "Times New Roman";"><o:p></o:p></span></p>
<p class="MsoNormal"><o:p></o:p></p><p>These are, indeed, exciting developments, but represent only
the beginnings of what could be an amazing era in the approach to many other
diseases of this kind. </p>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-84990602068874303782020-10-21T06:02:00.000-07:002020-10-21T06:02:05.738-07:00The Role of Microglia in Alzheimer's and Parkinson's Diseases<p> </p>Alzheimer’s and Parkinson’s are diseases that directly impact and impair brain functions. They are degenerative and devastating illnesses that result in severe dementia in the case of Alzheimer’s and a serious degradation of motor control in the case of Parkinson’s disease. There is no cure in either case and no known biomarkers that could predict onset of these conditions. There is a type of cell resident in the brain referred to as microglia that function as amyloid phagocytes – they are cells capable of monitoring the local environment and can ingest and clear amyloid protein. <br /><br />It seems that in addition to this known role, microglia may play an additional and essential role in maintaining neuronal function and homeostasis. In fact, the build up of amyloid protein in brain tissue may not be the primary cause of dementia that is the result of neuronal dysfunction and cognitive decline in neurodegenerative disease – some centenarians have been found to display good cognitive health and a build up of amyloid proteins in their brain tissue. It seems that accumulated patient data demonstrate that some aging individuals with accumulated amyloid protein show cognitive dysfunction while others do not. It is important from a therapeutic standpoint to understand the nature of this difference. <br /><br />Several genetic studies indicate that microglia may provide the answer to this difference in health outcomes. According to Soyon Hong from the UK Dimentia Research Institute at University College, London, “Emerging data in developing, adult, and diseased brains collectively suggest that microglia are critical to neuronal homeostasis and health. These observations raise the question of whether, and which, microglia-neuron interactions may be impaired in Alzheimer’s disease (AD) and Parkinson’s disease (PD) to confer neurodegeneration. Insight into this question will enable the development of methods to assess and modulate microglia-neuron interactions in the aging brain and allow for a desperately needed expansion of focus from clearing amyloids alone to monitoring neuronal health in biomarker and target engagement efforts.” <br /><br />It seems that in addition to their role in clearing pathogens and amyloid protein and responding to the presence of injury and dying neurons present in the environment of the brain, microglia are involved in monitoring changes in neuronal activity and the modulation of such distinct functions as memory and learning. In AD, for example, synaptic loss and dysfunction have been shown to be associated with the disruption of cognitive ability in patients. It is, therefore, of great importance to understand the underlying mechanisms that are responsible for this degenerative process and the role that microglia play in maintaining synaptic integrity.Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-85638210959479553152020-07-02T20:25:00.001-07:002020-07-02T20:25:57.809-07:00Evidence for the Role of Dramatically Increased Numbers of Megakaryocytes Associated with Blood Clots in COVID-19 <div class="separator">Disturbing new evidence is emerging from the post-mortems of patients who have died from COVID-19 disease that demonstrates the presence of blood clots (thrombi). These thrombi have been shown in this extensive study to be present in major organs and systems including the lungs, heart, kidney, and brain. </div><br />In addition, a particular cell type referred to as a megakaryocyte has also been found associated with these thrombi. Platelets (thrombocytes) are often associated with thrombi. Platelets, themselves, are generated from so-called progenitor, promegakaryocytes that reside and multiply within the bone marrow. Megakaryocytes are formed from promegakaryocytes and from these megakaryocytes are formed that ultimately break up to produce platelets (see diagram below) that are released into the blood and tissues. The fact that megakaryocytes are evidenced in higher than usual numbers in tissues such as lung, heart, kidney, and brain in patients with COVID-19 disease is a cause for concern. <br /><br /><br /> <a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgVZ3P42uBS4vsWAvj_f6F_4gTGv6yMnFIEByRJ9gI5lLuhXY2vwQXED2U-TmLfxPc8UAAUA_iXourebtR7ghMf8X_PyE17UBQh3hyphenhyphenF_a5HsfrDmJvtPJIlU8wNzSUkmu8Rwh1y_boSg6O1/s1000/platelet+formation.jpg" style="margin-left: 1em; margin-right: 1em; text-align: center;"><img border="0" data-original-height="656" data-original-width="1000" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgVZ3P42uBS4vsWAvj_f6F_4gTGv6yMnFIEByRJ9gI5lLuhXY2vwQXED2U-TmLfxPc8UAAUA_iXourebtR7ghMf8X_PyE17UBQh3hyphenhyphenF_a5HsfrDmJvtPJIlU8wNzSUkmu8Rwh1y_boSg6O1/s320/platelet+formation.jpg" width="320" /></a><br /><br /><br />According to an abstract published by Lancet – a prestigious medical publication – and authored by Amy V. Rapkiewicz, “In seven patients (four female), regardless of anticoagulation status, all autopsies demonstrated platelet-rich thrombi in the pulmonary, hepatic, renal, and cardiac microvasculature. Megakaryocytes were seen in higher than usual numbers in the lungs and heart. Two cases had thrombi in the large pulmonary arteries, where casts conformed to the anatomic location. Thrombi in the IVC were not found, but the deep leg veins were not dissected. Two cases had cardiac venous thrombosis with one case exhibiting septal myocardial infarction associated with intramyocardial venous thrombosis, without atherosclerosis.” In addition, The presence of circulating megakaryocytes on autopsy in various organs was also found and thoroughly studied. <br /><br />The fact that thrombi have been found in the post-mortems of a significant number of patients who died of COVID-19 disease can account for systemic organ failure in vital organs such as lung, kidneys and heart and such a set of conditions could easily lead to subsequent death. <br /><br />These data are exceedingly troubling and leaves researchers with a profound question – how does COVID-19 infection trigger such a disastrous response?<div class="separator" style="clear: both; text-align: center;"><br /></div>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-47610168936575825572020-07-02T12:08:00.000-07:002020-07-02T12:08:05.071-07:00The Apparent Efficacy of the Steroid Drug Dexamethasone as Therapy for COVID-19 PatientsAs medical professionals, epidemiologists, immunologists, and molecular biologists work in the midst of the COVID-19 pandemic, many aspects of the biology of this virus are being studied and as a result, new understandings are emerging. <br /><br />It seems that patients with advanced disease that require intervention using a ventilator may be suffering from a hyper-active immune response. In such cases, the use of steroid-based anti-inflammatory drugs may prove efficacious. <br /><br />An extremely encouraging report from the highly respected Science journal, Nature, has shown the results of a trial study using the proven steroid drug Dexamethasone. <br /><br />According to the report, the results have indicated that, “An inexpensive and commonly used steroid can save the lives of people seriously ill with COVID-19, a randomized, controlled clinical trial in the United Kingdom has found. The drug, called dexamethasone, is the first shown to reduce deaths from the coronavirus that has killed more than 440,000 people globally. In the trial, it cut deaths by about one-third in patients who were on ventilators because of coronavirus infection.” <br /><br />This study was expansive involving 2100 participants who received the drug at what is considered a low to moderate dose – 6 milligrams (mg.) per day for 10 consecutive days. The results from the patients were then compared to the results from 4300 patients who received standard care for COVID-19 infection. <br /><br />Although the drug had no noticeable impact on patients showing no severe symptoms, the positive effect was most striking on patients on ventilators and even on those undergoing just oxygen therapy (not on ventilators) where the rate of death was reduced by 20%. <br /><br />These are, indeed, encouraging results.<br />Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-23667865706685182532020-06-09T08:08:00.002-07:002020-06-09T08:09:43.379-07:00The Respiratory Syncytial Virus (RSV) and Pulmonary DiseaseRespiratory Syncytial Virus Infection (RSV)According to the Center for Disease Control (CDC), “Respiratory syncytial virus, or RSV (see image below), is a common respiratory virus that usually causes mild, cold-like symptoms. RSV is an RNA virus and a member of the pneumoviridae family of viruses belonging to the genus orthopneumovirus. Most people recover in a week or two, but RSV can be serious, especially for infants and older adults.” <br /><br />According the National Institutes of Health (NIH), “It is one of the most commons causes of infant viral death worldwide. In fact, RSV is the most common cause of bronchiolitis (inflammation of the small airways in the lung) and pneumonia (infection of the lungs) in children younger than 1 year of age in the United States. It is also a significant cause of respiratory illness in older adults.”<div> <br /><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjhI0TGQn32c53aDnsyOUm5EQG1GWxIzK2B-Uz8FU02VNcdb7tzuvkKnZ3PA73lnVsvK1Kfja3hAAvwyTjTO-Sd38mUv5FBZY1zyVYqmAlXkANi3Gv2h6bePiFrLysMjdhi8varRAGcq_SF/s800/rsv.jpg"><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjhI0TGQn32c53aDnsyOUm5EQG1GWxIzK2B-Uz8FU02VNcdb7tzuvkKnZ3PA73lnVsvK1Kfja3hAAvwyTjTO-Sd38mUv5FBZY1zyVYqmAlXkANi3Gv2h6bePiFrLysMjdhi8varRAGcq_SF/s320/rsv.jpg" /></a><br /><br />RSV infects cells of the mucosal lining of the respiratory tract resulting in the fusion of the infected cells to form a syncytium – a cytoplasmic mass containing a multiplicity of nuclei. It is a major cause of lower respiratory tract infections and hospital visits during infancy and childhood. <br /><br />A further characterization of the virus is described by an article from the NIH, “The RNA of RSV contains 10 genes encoding 11 proteins. The envelope of the virus is formed by four proteins associated with the lipid bilayer: the matrix (M) protein, the small hydrophobic (SH) protein, and the two glycosylated surface proteins: the fusion (F) and the attachment glycoprotein (G). F and G proteins are crucial for virus infectivity and pathogenesis since the G protein is responsible for the attachment of the virus to respiratory epithelial cells, while the F protein determines the entry of the virus, by fusing viral and cellular membranes, as well as the subsequent insertion of the viral RNA into the host cell inducing the formation of the characteristic syncytia. Moreover, the F and G proteins stimulate the neutralizing antibody immune response by the host.<br /><br />"The G protein is a type II glycoprotein synthesized as a polypeptide composed by 300 amino acids (depending on the viral strain) with a single C-terminal hydrophobic domain and a large number of glycan added [20]. Three types of epitopes have been identified in the G protein by murine monoclonal antibodies: (I) conserved epitopes, detectable in all viral strains; (II) group-specific epitopes, expressed only by to the same antigenic group and (III) strain-specific epitopes, that are present only in specific strains of the same antigenic group and expressed in the C-terminal hypervariable region of the G protein ectodomain [21]. <br /><br />"The F protein is a type I glycoprotein which has a structure comparable to the F proteins of other Pneumoviridae (e.g., metapneumovirus) and Paramyxoviridae (e.g., parainfluenza virus type 5) viruses. The F glycoprotein derives from an inactive precursor containing three hydrophobic peptides: (I) the N-terminal signal peptide, which mediates translocation of the nascent polypeptide into the lumen of the endoplasmic reticulum; (II) the transmembrane region near the C-terminus, which links F protein to the cell and viral membranes; and (III) the so-called fusion peptide, which inserts into the target cell membrane and determines the fusion process. The binding of prefusion F protein to the cell surface is followed by its activation and conformational changes, which leads to the fusion of the virion membrane with the host cell membrane.” <br /><br />These details regarding the molecular biology of RSV is vitally important in establishing the mode of infection and suggests approaches to the development of suitable therapies and the creation of an effective vaccine. For example, a detailed understanding of the molecular structure of the attachment glycoprotein G as described above is of immense importance in regards to establishing methodologies to prevent attachment of the virus to host cells and thereby curtailing infection including the potential for the production of a vaccine for this purpose.</div>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-44681320630393366152020-06-01T08:53:00.005-07:002020-06-01T08:56:20.115-07:00Promising News Regarding Cellular Immunity and COVID-19As medical professionals, epidemiologists, immunologists, and molecular biologists work in the midst of the COVID-19 pandemic, many aspects of the biology of this virus are being studied and as a result, a new understanding is emerging.<br /><br />As a result of these efforts some promising aspects of the immunological response have been revealed. Primary among the results of these accumulated data is the fact that individuals infected with this virus harbor T-cells – an important subset of circulating lymphocytes that play a critical role in the human immunological response – that actively target the virus and may assist in recovery. In addition, it seems that some individuals who have never been infected with COVID-19, have these cellular defenses – suggesting that this potential immunological defense arose; because they were previously infected with other coronaviruses that cause the common cold. <div><br /></div><div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiXNc1CBor64zZMUfyBajIJmn6ahDUeiRZu0pNw0YTyevWaH9Lco8P0Au9hRexCsFfV9qCJNC5JJ90N1WZpr-0mIijui6XLmwXX7FYtNerF-wS0RHb7YqQ2XA79tqFY2jcSXGvrk1bzfyzU/" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="203" data-original-width="248" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiXNc1CBor64zZMUfyBajIJmn6ahDUeiRZu0pNw0YTyevWaH9Lco8P0Au9hRexCsFfV9qCJNC5JJ90N1WZpr-0mIijui6XLmwXX7FYtNerF-wS0RHb7YqQ2XA79tqFY2jcSXGvrk1bzfyzU/d/helper+T+cells.jpg" title="Helper T Cells" /></a></div><div><div style="text-align: center;"><br /></div><div style="text-align: center;">Helper T Cells</div><br />These findings provide suggestive evidence that the potent T cell responses that were shown to exist may play an important role in long-term protective immunity. In addition, a more complete understanding of how the human body responds to this particular virus will undoubtedly enhance the search for an effective prophylactic vaccine. <br /><br />There are more than 100 COVID-19 vaccines in various stages of development focusing on a wide rage of modalities. Within the arsenal of the so-called “adaptive” arm of the human immune system are circulating B and T lymphocytes. The B cells are responsible for the production of antibodies against particular targets. The mechanism that the immune system employs in this regard is that the B cell produced in response to exposure to the virus is to attach itself to the viral particle and prevent it from entering healthy tissue cells. This role can be exploited in the development of a vaccine. In addition, to this part of the natural arsenal against infection, there are circulating T cells that can activate and enhance B cell response. In addition to these players, there are killer T cells that actually target and destroy tissue cells that have been infected. Given the interrelationship of these defense mechanisms, there is a correlation between the severity of the disease and the strength of the T cell responses. <br /><br />Shane Crotty and Alessandro Sette – immunologists from the La Jolla Institute of Immunology – determined what proteins from the surface of COVID-19 particles were most likely to stimulate immune response and subsequently exposed cells grown in culture (in-vitro) from 10 patients who had recovered from mild cases of COVID-19 to these virally-derived protein pieces. In all the samples studied, the patients carried helper T cells that were specific for the COVID-19 spike protein – the predominant protein of the viral surface that is involved in targeting tissue cells. In addition, 70% of the patients studied showed the presence of virus-specific killer T cells. Whether these patients also acquired long term immunity is not completely clear. These data, however, are very encouraging. <br /><br />Although not unambiguous, these results are of great interest and suggest that an effective vaccine against COVID-19 infection needs to stimulate the production of helper T cells.<br /></div>Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-38351171769960001742020-05-02T11:54:00.002-07:002020-05-02T11:56:52.996-07:00The Mode of Action of the Anti-viral Drug Remdesivir<div class="separator" style="clear: both; text-align: left;">
Currently, the United States along with many parts of the world is being severely impacted by the COVID-19 pandemic. As discussed in more detail in previous reports, COVID-19 is an RNA virus that was previously resident in another mammalian species and underwent a genetic modification that allowed it to cross species to humans – a not uncommon event among viral pathogens. The current genetic evidence is strongly suggestive that the mammalian species from where the virus originated was the bat. </div>
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Recent clinical trials have demonstrated that the anti-viral drug remdesivir has some efficacy in the treatment of the illness brought about by COVID-19 infection. Remdesivir is a nucleoside analog (structure shown below)<br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvAytDRs5LqGnKyWI0MoixeIVQTba_j5aMOz7AF17hQSE7gXkqGZNgDWK8C2fHNUxxAZ1koMRqFjE3M9pZyp1ZdJtYiaZSXGQUYBmr-KXcHs4N_0XbFMb9dmlr2yMwh6aqv6MO3z1R9eng/s1600/remdisivir.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto; text-align: center;"><img border="0" data-original-height="172" data-original-width="292" height="235" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEjvAytDRs5LqGnKyWI0MoixeIVQTba_j5aMOz7AF17hQSE7gXkqGZNgDWK8C2fHNUxxAZ1koMRqFjE3M9pZyp1ZdJtYiaZSXGQUYBmr-KXcHs4N_0XbFMb9dmlr2yMwh6aqv6MO3z1R9eng/s400/remdisivir.jpg" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Structure of Remdesivir</td></tr>
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Inside the target host cell – lung tissue as an example – this substance functions as an inhibitor of the process that is involved in viral replication. The drug’s specific target tin RdRp (see diagram below) – the protein complex that the coronavirus uses to replicate its RNA genome. <br />
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<tr><td style="text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiC3VPYtFMDg6RRThJmW3NsczqTxc3kJx_1TZm9xqImcbd4uBOhdhjuctdBl3OyrbakKg8kLeoeufU0jcAvkK4-ZUHM9XcFT0CvzRfDFZuilFGbdKz0NeFupVCyTuYapimYQfucvP5Y7T3f/s1600/coronavirusrdrp.jpg" imageanchor="1" style="margin-left: auto; margin-right: auto; text-align: center;"><img border="0" data-original-height="715" data-original-width="1403" height="203" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiC3VPYtFMDg6RRThJmW3NsczqTxc3kJx_1TZm9xqImcbd4uBOhdhjuctdBl3OyrbakKg8kLeoeufU0jcAvkK4-ZUHM9XcFT0CvzRfDFZuilFGbdKz0NeFupVCyTuYapimYQfucvP5Y7T3f/s400/coronavirusrdrp.jpg" width="400" /></a></td></tr>
<tr><td class="tr-caption" style="text-align: center;">Structure of RdRp</td></tr>
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According to a report presented by E.S. Amirian, “After the host metabolizes remdesivir into active nucleoside triphosphate (NTP), the metabolite competes with adenosine triphosphate (ATP; the natural nucleotide normally used in this process) for incorporation into the nascent RNA strand – effectively substituting the drug metabolite for ATP. The incorporation of this substitute into the new strand results in premature termination of RNA synthesis, halting the growth of the RNA strand after a few more nucleotides are added. Although coronaviruses (CoVs) have a proofreading process that is able to detect and remove other nucleoside analogs, rendering them resistant to many of these drugs, remdesivir seems to outpace this viral proofreading activity, thus maintaining antiviral activity. Unsurprisingly, Agostini et al. reported that a mutant murine hepatitis virus (MHV) devoid of proofreading ability was more sensitive to remdesivir.”<br />
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Since viruses are prone to mutations, it is also possible that that mutations could spontaneously occur that would effectively improve proofreading and result in remdesivir resistance. In addition, it also quite possible that the effectiveness of this anti-viral drug could be due to additional factors that are currently unknown. <br />
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At the present time, in-vitro and clinical trials have yielded strong suggestive evidence that remdesivir may provide a clinical route to a therapy that could be applied to COVID-19 patients. Ongoing studies are also investigating the possibility of finding additional drugs that could provide a synergistic effect to further improve positive outcomes. <br />
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This line of investigation together with a fast-track search for an effective vaccine may ultimately safe countless lives worldwide. These scientific investigations highlight the intrinsic and inestimable value that the ongoing scientific studies contribute to humanity and its future.Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-12995049712872032952020-04-11T12:09:00.001-07:002020-05-02T12:07:54.502-07:00NIH Clinical Trial of Investigational Vaccine for COVID-19 Begins<div class="separator" style="clear: both; text-align: center;">
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"The following article has been take from the National Institutes of Health (NIH) website: http://www.nih.gov describing a study enrolling Seattle-based healthy adult volunteers. </div>
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The image below shows a spike protein of SARS-CoV-2—also known as 2019-nCoV (COVID-19). The spike protein enables the virus to enter and infect human cells. On the virus model, the virus surface is covered with spike proteins that enable the virus to enter and infect human cells. For more information, visit NIH <br />
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<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgqE2HYxrWJP2lyXmpjZJcYGJ_AbPzGPTj-7yIoBdDEAiA8_dW8KQR4OxQjN7pCfim0-yy_-g_RI3KTHtsnwWjNjICuSKCmw4aGeSUugXr0U9oGFf6wxyWI9RJd6o_3egh8H41xj9vDIItQ/s1600/spike+protein.jpg" imageanchor="1" style="margin-left: 1em; margin-right: 1em;"><img border="0" data-original-height="266" data-original-width="189" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgqE2HYxrWJP2lyXmpjZJcYGJ_AbPzGPTj-7yIoBdDEAiA8_dW8KQR4OxQjN7pCfim0-yy_-g_RI3KTHtsnwWjNjICuSKCmw4aGeSUugXr0U9oGFf6wxyWI9RJd6o_3egh8H41xj9vDIItQ/s1600/spike+protein.jpg" /></a></div>
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"A Phase 1 clinical trial evaluating an investigational vaccine designed to protect against coronavirus disease 2019 (COVID-19) has begun at Kaiser Permanente Washington Health Research Institute (KPWHRI) in Seattle. The <a href="https://www.niaid.nih.gov/diseases-conditions/coronaviruses">National Institute of Allergy and Infectious Diseases (NIAID)</a>, part of the National Institutes of Health, is funding the trial. KPWHRI is part of NIAID’s <a href="https://www.niaid.nih.gov/news-events/infectious-diseases-clinical-research-consortium-awards-announced">Infectious Diseases Clinical Research Consortium</a>. The open-label trial will enroll 45 healthy adult volunteers ages 18 to 55 years over approximately 6 weeks. The first participant received the investigational vaccine today. <br />
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"The study is evaluating different doses of the experimental vaccine for safety and its ability to induce an immune response in participants. This is the first of multiple steps in the clinical trial process for evaluating the potential benefit of the vaccine. <br />
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"The vaccine is called mRNA-1273 and was developed by NIAID scientists and their collaborators at the biotechnology company Moderna, Inc., based in Cambridge, Massachusetts. The Coalition for Epidemic Preparedness Innovations (CEPI) supported the manufacturing of the vaccine candidate for the Phase 1 clinical trial. <br />
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'Finding a safe and effective vaccine to prevent infection with SARS-CoV-2 is an urgent public health priority,' said NIAID Director Anthony S. Fauci, M.D. 'This Phase 1 study, launched in record speed, is an important first step toward achieving that goal.'<br />
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"Infection with SARS-CoV-2, the virus that causes COVID-19, can cause a mild to severe respiratory illness and include symptoms of fever, cough and shortness of breath. COVID-19 cases were first identified in December 2019 in Wuhan, Hubei Province, China. As of March 15, 2020, the <a href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports">World Health Organization (WHO)</a> has reported 153,517 cases of COVID-19 and 5,735 deaths worldwide. More than 2,800 confirmed COVID-19 cases and 58 deaths have been reported in the United States as of March 15, according to the <a href="https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html">Centers for Disease Control and Prevention (CDC)</a>. <br />
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"Currently, no approved vaccines exist to prevent infection with SARS-CoV-2. <br />
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"The investigational vaccine was developed using a genetic platform called mRNA (messenger RNA). The investigational vaccine directs the body’s cells to express a virus protein that it is hoped will elicit a robust immune response. The mRNA-1273 vaccine has shown promise in animal models, and this is the first trial to examine it in humans. <br />
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"Scientists at NIAID’s Vaccine Research Center (VRC) and Moderna were able to quickly develop mRNA-1273 because of prior studies of related coronaviruses that cause severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). Coronaviruses are spherical and have spikes protruding from their surface, giving the particles a crown-like appearance. The spike binds to human cells, allowing the virus to gain entry. VRC and Moderna scientists already were working on an investigational MERS vaccine targeting the spike, which provided a head start for developing a vaccine candidate to protect against COVID-19. Once the genetic information of SARS-CoV-2 became available, the scientists quickly selected a sequence to express the stabilized spike protein of the virus in the existing mRNA platform. <br />
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"The Phase 1 trial is led by Lisa A. Jackson, M.D., senior investigator at KPWHRI. Study participants will receive two doses of the vaccine via intramuscular injection in the upper arm approximately 28 days apart. Each participant will be assigned to receive a 25 microgram (mcg), 100 mcg or 250 mcg dose at both vaccinations, with 15 people in each dose cohort. The first four participants will receive one injection with the low dose, and the next four participants will receive the 100 mcg dose. Investigators will review safety data before vaccinating the remaining participants in the 25 and 100 mcg dose groups and before participants receive their second vaccinations. Another safety review will be done before participants are enrolled in the 250 mcg cohort. <br />
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"Participants will be asked to return to the clinic for follow-up visits between vaccinations and for additional visits across the span of a year after the second shot. Clinicians will monitor participants for common vaccination symptoms, such as soreness at the injection site or fever as well as any other medical issues. A protocol team will meet regularly to review safety data, and a safety monitoring committee will also periodically review trial data and advise NIAID. Participants also will be asked to provide blood samples at specified time points, which investigators will test in the laboratory to detect and measure the immune response to the experimental vaccine. <br />
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“This work is critical to national efforts to respond to the threat of this emerging virus,” Dr. Jackson said. “We are prepared to conduct this important trial because of our experience as an NIH clinical trials center since 2007.” <br />
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"Adults in the Seattle area who are interested in joining this study should visit <a href="https://corona.kpwashingtonresearch.org/">https://corona.kpwashingtonresearch.org</a>. For more information about the study, visit ClinicalTrials.gov and search identifier <a href="https://clinicaltrials.gov/ct2/show/NCT04283461?term=mrna-1273&draw=2&rank=1">NCT04283461</a>. <br />
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"NIAID conducts and supports research — at NIH, throughout the United States, and worldwide — to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the <a href="https://www.niaid.nih.gov/">NIAID website</a>. <br />
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"About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit <a href="https://www.nih.gov/">www.nih.gov</a>. <br />
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"Adults in the Seattle area who are interested in joining this study should visit <a href="https://corona.kpwashingtonresearch.org/">https://corona.kpwashingtonresearch.org/</a>. People who live outside of this region will not be eligible to participate in this trial."<br />
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The mode of action of mRNA vaccines is to introduce a messenger RNA (mRNA) into the individual recipient that codes for the production of a unique protein that is part of the structure of the pathogen being targeted. In this case the pathogen is COVID-19 and the protein is referred to as spike (see image above). Once spike is made by the individual vaccinated, that should alert the immune system to recognize an essential protein on COVID 19 and prepares the body if and when it is actually exposed to the virus. This methodology would obviate the need to introduce a weakened (attenuated) form of COVID-19 as part of a vaccine. This kind of approach holds a lot of promise.Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-62151416506977896632020-03-13T15:55:00.001-07:002020-03-13T15:55:49.160-07:00An Appreciation of the CommonsWe are now in the midst of what might be regarded as a raging pandemic in relation to the spreading impact of the corona virus on human populations throughout the world. To me, this new reality is a not so subtle reminder of the precarious nature of civilization and the inescapable reality that our species in general and our place in the so-called “developed” world in particular does not grant us any immunity to the nature of our individual and collective frailty as living beings on our planetary home. We are all subject to the physical and biological forces that constitute our everyday existence for better or worse. <br /><br />From a biological perspective, viruses portray unusual properties in that outside of living cells they are quite incapable of independent existence. They are specifically engineered to “infect” living cells and have the capacity to commandeer the cellular machinery that ordinarily sustains the life of the cell and appropriate cellular processes to a singular role – the production of more viral particles. They are so successful at this that the infected cell usually succumbs, and the viral progenies go on to invade neighboring cells that in the case of the corona virus are the cells that constitute lung tissue. As entities, viruses have been among the living for billions of years. As a matter of fact, portions of human DNA contain the remnants of an array of viral DNA from many sources. In this regard, viruses have apparently played an important role in the evolution of life, including human life, on the planet. For this reason, viruses will always be with us. <br /><br />Thanks to the multitude of scientific discoveries and the cumulative efforts embodied in scientific research, we are extremely knowledgeable regarding the biology of many viruses including the corona virus and its mode of infection. One possible outcome of the acceptance of this basic reality, may hopefully be a renewed appreciation of the Commons – those aspects of civilization that are fundamental to the sustainability and viability of communal life. Examples of the these would be public health, clean air, drinkable water, adequate shelter and nutrition, etc. <br /><br />It has become a patent reality that in the United States the wholesale neglect of the Commons has made us particularly vulnerable to this pandemic and its ineluctable impact on societal institutions. It also has placed particular emphasis on the essential importance of smart government leadership that places appropriate reliance on the important role that science and professional expertise can play in dealing with a national crisis such as this one. <br /><br />It is my hope that the lessons from this throughout the world will find direct application in preparing for future calamities including climate change to help ensure the future viability of the species.Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-83693508539122823282020-02-04T23:53:00.001-08:002020-02-07T06:57:00.926-08:00The Biology of the Coronavirus<br />
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The global spread of viral pneumonia associated with the so-called “Wuhan coronavirus” appears to be reaching pandemic proportions. Given this distressing reality, it is important to more fully understand the biology of this virus. <br />
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Viruses represent a class of infectious agents that pose interesting challenges as witnessed by the HIV/AIDS virus that is the causative agent of the devastating acquired immunodeficiency syndrome (AIDS) that targets a particularly important cell type in the human adaptive immune system – the so-called, “T-helper cells (CD4).” Viruses possess the unusual property of being inert when outside a living cell. However, once they gain access to a living cell, the infective agent – either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) - commandeers the host cellular machinery to make copies of itself. This process can lead either to the ultimate death of the target cell or can result in a transformation of the host DNA that in some instances can lead to cancer – T-cell leukemia (HTLV-1 virus) and Cervical cancer (Human Papilloma virus – HPV) being some important examples. <br />
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Coronaviruses are a family of enveloped, single-stranded, positive-strand RNA viruses that are classified within the Nidovirales order. The name coronavirus was coined on account of the corona-like appearance of this virus as viewed under the electron microscope (See accompanying image). The existence of this type of virus was first reported in 1949 and the molecular mechanisms of both replication and disease formation was well-studied in the 1970s. The coronavirus family comprises pathogens that infect many animal species. Coronaviruses have been shown to be the causative agents for acute and chronic respiratory, enteric and central nervous system (CNS) diseases. This family of viruses have been associated with infectious disease in mouse (murine), a pig (porcine) transmissible gastroenteritis (TGEV), cow (bovine) and a bird (avian) bronchitis (BCoV). The first example of a potentially life-threatening human emerging coronavirus was the acute respiratory syndrome coronavirus (SARS-CoV). <br />
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Until 2003 the human coronavirus was only known to produce cold-like symptoms. This changed with the onset of severe acute respiratory syndrome (SARS) and now the Wuhan coronavirus that is apparently spread readily from human to human. These kinds of changes in infectivity are not unusual in the evolution of a virus; since, the infective material is prone to mutation. It is for this reason that it has proven exceedingly difficult to come up with an effective vaccine against HIV/AIDS. <br />
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Structurally, a virus particle consists of a protein outer coat that interacts and fuses with the cell membrane of the host cell. This is generally followed by the transfer of the infective agent – in this case the RNA of the coronavirus. Once this RNA enters the host cell, it directs the replication of its viral RNA and interferes with host cell processes. These tasks are accomplished through the transcription of viral RNA into proteins that exploit the cell’s protein synthesis “machinery.” It seems that coronavirus contains 7 genes – each gene having the blueprints for the production of a unique protein. One of the products of these genes is the so-called “spike” protein that plays a role in attaching to the host cell and has been shown to play a major part in the virus’ pathogenicity. The end result of this process is the formation of multiple copies of the virus followed by the death of the host cell and subsequent release of the new viruses into the extra-cellular environment. <br />
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The global nature of this threat can be circumvented by a number of different approaches - the first being isolating infected individuals and thereby thwarting the spread of the disease to others. It is likely that the virus is spread through aerosols as a result of coughing from infected individuals. This standard epidemiological approach is made particularly difficult given the reality of the constant movement of people to all areas of the globe. <br />
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However, it is also imperative that research efforts be directed towards developing a vaccine in order to assist the human immune system in its attempt to destroy the coronavirus once it has gained entry into the host. In regard to SARS, several studies were directed towards the development of active immunization strategies. These included Inactivated virions, recombinant antigen, DNA vaccines, and adenoviral vectors as well as other avenues of research. Undoubtedly, these kinds of studies will continue with added urgency.<br />
<br />Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0tag:blogger.com,1999:blog-7721417345246165906.post-74034647888810215432020-01-20T11:32:00.003-08:002020-01-20T11:33:11.164-08:00Resistance to the anti-malarial drug Artemisinin in Malaria Parasites<div class="separator" style="clear: both; text-align: center;">
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<b>Image showing human red blood cells infected with Plasmodium falciparum</b></div>
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Resistance of the anti-malarial drug Artemisinin in Malaria ParasitesMalaria continues to be a scourge in many parts of the world. The problem is particularly acute in Africa. Malaria is a pervasive illness characterized by high fevers, shaking chills, flu-like symptoms, and anemia. It is caused by a parasite referred to as Plasmodium falciparum. Plasmodium is carried by the Anopheles mosquito prevalent in the tropics.<br />
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The drug, Artemisinin (ART) has proven to be an effective drug against the malarial parasite – plasmodium falciparum. However, the parasite has apparently developed an immunity to this efficacious drug. It is, therefore, imperative that the mechanism of this resistance be more fully understood if an effective remedy is to be found. The collaborative efforts from research investigators at the Bernhard Nocht Institute of Tropical Medicine in Hamburg, Germany and the Department of Molecular Biology at Radbound University in the Netherlands have helped elucidate this mechanism. <br />
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The life-threatening aspect of infection by the Plasmodium falciparum parasite is the capacity of this parasite to continuously multiply within human red blood cells. Residing within human red blood cells, these parasites actively breakdown hemoglobin thereby obviating its capacity to deliver oxygen to the body’s tissues. Artemisinin has been long regarded as a first-line drug. However, ART resistance has manifested itself as a decreased susceptibility of young ring-stage parasites to a short pulse of this drug. <br />
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ART resistance has been shown to be associated with point mutations in the parasite’s so-called, Kelch propeller protein (Kelch13). However, the precise mechanism of this resistance to ART was essentially unknown. Although cellular stress, reduced protein translation and altered DNA replication had been implicated, the role of Kelch13 within the parasitic cell remained enigmatic. Here, the authors report an entire pathway in ART resistance and the Kelch13-dependent mechanism that effectively describes the reduced susceptibility to ART in resistant parasites. <br />
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The investigators in this extensive study, “show that Kelch13 defines an endocytosis pathway required for the uptake of host cell hemoglobin and its subsequent breakdown and that this pathway is critical for ART resistance. Their data indicate that Kelch13 and its compartment proteins mediate resistance upstream of both, drug activation and action. They have proposed a model where Kelch13 and its compartment proteins control endocytosis levels, thereby influencing the amount of hemoglobin available for degradation and hence the concentration of active drug.” <br />
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As a result of these findings that help elucidate the mechanism of ART resistance in malarial parasites, the authors conclude that, “We envisage that the mechanism of ART resistance indicated by this work will aid in finding ways to antagonize it. It may also inform the choice of ART partner drugs, particularly as hemoglobin digestive processes are the target of existing drugs.”Joseph Aprilehttp://www.blogger.com/profile/09146849288862816584noreply@blogger.com0