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Hypogonadism: Types, Causes, & Symptoms – healthline.com

What Is Hypogonadism?

Hypogonadism occurs when your sex glands produce little or no sex hormones. The sex glands, also calledgonads, are primarily the testes in men and the ovaries in women. Sex hormones help control secondary sex characteristics, such as breast development in women, testicular development in men, and pubic hair growth. Sex hormones also play a role in the menstrual cycle and sperm production.

Hypogonadism may also be known asgonad deficiency. It may be calledlow serum testosteroneorandropause when it happens in males.

Most cases of this disorder respond well to appropriate medical treatment.

9 Warning Signs of Low Testosterone

Types

There two types of hypogonadism are primary and central hypogonadism.

Primary hypogonadism means that you dont have enough sex hormones in your body due to a problem in your gonads. Your gonads are still receiving the message to produce hormones from your brain, but they arent able to produce them.

In central hypogonadism, the problem lies in your brain. The hypothalamus and pituitary gland in your brain, which control your gonads, arent working properly.

Causes

The causes of primary hypogonadism include:

Central, or secondary, hypogonadism may be due to:

Symptoms

Symptoms that may affect females include:

Symptoms that may affect males include:

Diagnosis

Your doctor will conduct a physical exam to confirm that your sexual development is at the proper level for your age. They may examine your muscle mass, body hair, and your sexual organs.

If your doctor thinks you might have hypogonadism, the first round of testing will involve checking your sex hormone levels. Youll need a blood test to check your level of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Your pituitary gland makes these reproductive hormones.

Youll have your estrogen level tested if youre female. Youll have your testosterone level tested if youre male. These tests are usually drawn in the morning, which is when your hormone levels are highest. If youre male, your doctor may also order a semen analysis to check your sperm count. Hypogonadism can reduce your sperm count.

Your doctor may order more blood tests to help confirm the diagnosis of hypogonadism and rule out any underlying causes.

Iron levels can affect your sex hormones. For this reason, your doctor may test for anemia, or iron deficiency. Your doctor may also wish to measure your prolactin levels. Prolactin is a hormone that promotes breast development and breast milk production in women, but its present in both genders. Your doctor may also check your thyroid hormone levels because thyroid problems can cause symptoms similar to hypogonadism.

Imaging tests can also be useful in diagnosis. Anultrasoundof the ovaries uses sound waves to create an image of the ovaries and check for any problems, including ovarian cysts and polycystic ovarian syndrome (PCOS).Your doctor may order MRIscans or CTscans to check for tumors in your pituitary gland.

Treatments

Your treatment will involve increasing the amount of female sex hormones in your body if youre a woman.

Your first line of treatment will probably be estrogen therapy if youve had a hysterectomy. Either a patch or pill can administer the supplemental estrogen hormone.

Because increased estrogen levels can increase your risk of endometrial cancer, youll be given a combination of estrogen and progesterone if women who havent had a hysterectomy. Progesterone can lower your risk of endometrial cancer if youre taking estrogen.

Other treatments can target specific symptoms. If youre a woman and you have a decreased sex drive, you may receive low doses of testosterone. If you have menstrual irregularities or trouble conceiving, you may receive injections of the hormone human choriogonadotropin (hCG) or pills containing FSH to trigger ovulation.

Testosterone is a male sex hormone. Testosterone replacement therapy (TRT) is a widely used treatment for hypogonadism in males. You can get testosterone replacement therapy by:

Injections of a gonadotropin-releasing hormone may trigger puberty or increase your sperm production.

Treatment for males and females is similar if the hypogonadism is due to a tumor on the pituitary gland. Treatment may include radiation, medication, or surgery to shrink or remove the tumor.

Outlook

According to the Urology Care Foundation, hypogonadism is a chronic condition that requires lifelong treatment. Your sex hormone level will probably decrease if you stop treatment.

Seeking support through therapy or support groups can help you before, during, and after treatment.

Can Testosterone Supplements Improve Your Sex Drive?

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DMG Health – About Us

Martin Nwosu MD is the founder and medical director of Doctors Medical Group (DMG) Health and wellness center. Founded in 2010, DMG is the leading Anti-Aging and Functional Medicine specialty practices in Middle Tennessee and surrounding states. The practice reflects his passion to bring an integrative approach to patient care that combines the latest in scientifically validated treatment protocols with the best of conventional medical therapies.

Dr. Nwosu specializes in treating men and women with bio-identical hormone replacement, weight management, a functional approach to treating and preventing chronic disease, and therapies to reverse the symptoms of aging and enhance overall wellness and longevity. Dr. Nwosu is a diplomat in Geriatric medicine, a board-certified internal medicine, a member of the American Academy of Anti-Aging Medicine and a member of the American Association of Pain Management. His practice emphasizes a thorough competency in the areas of nutrition, fitness, stress reduction, bio-identical hormone replacement and spirituality as a necessary basis for optimal health

By utilizing bio-identical hormone products that restore hormones to optimal levels, strengthen the immune system, and increase energy levels, we are able to help you regain and prolong your quality of life. Our Center has many years of experience in treating hypothyroidism, adrenal fatigue and hormone imbalances using bioidentical hormones, desiccated thyroid supplementation and Dr. Nwosus 8-Point Treatment Regimen. Given our years of experience, level of expertise, and renowned treatment using bio-identical hormones, the DMG Health & Wellness Center is considered the Hormone center of choice.

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Melatonin – Impressive Health Benefits | Life Extension …

New research indicates that melatonin does much more than help some people sleep better. Exciting studies show that melatonins multifaceted effects may improve treatment outcomes in cancer patients and extend their lives. Additional applications of melatonin include guarding the nervous system against degenerative diseasessuch as Alzheimers disease and strokeand preventing debilitating migraines.

Melatonin is secreted from the pineal gland deep inside the brain. For more than a quarter-century, scientists have been intrigued by melatonins ability to coordinate the bodys physiological rhythms that help set the brains biological clock.

The principal factor affecting melatonin is light, which inhibits the secretion of this hormone. Darkness has the opposite effect from light, resulting in signaling to the pineal gland to increase melatonin secretion. The normal cycles of melatonin production are altered due to factors including aging, medications, and light exposure at night. While the long-term health effects of disrupted melatonin secretion are not yet fully known, some scientists have suggested that years of working nights could lead to adverse effectseven cancer.

Fortunately, melatonin supplements can safely and effectively restore balance to the bodys circadian rhythm of this important hormonehelping achieve a restful nights sleep and keeping your biological clock ticking throughout a long, healthy life span.

Melatonin is a powerful and versatile antioxidant produced within the body. Melatonin protects both lipids and proteins against damage, and can scavenge some of the most dangerous free radicals in the bodyincluding hydroxyl radicals and hydrogen peroxide. Unlike other antioxidants, melatonin easily diffuses into all cells, and even crosses the blood-brain barrier to protect the delicate brain.1

Unfortunately, levels of naturally produced melatonin decline with advancing age, leaving older adults with limited antioxidant protection against conditions associated with oxidative stress, particularly neurodegenerative diseases.1 Supplementing with melatonin may thus help older adults enhance their antioxidant protection against some of the most ravaging diseases of aging, such as Alzheimers disease, Parkinsons disease, and stroke.

Melatonin levels are particularly low in patients with Alzheimers disease. Nearly half of affected individuals suffer from sleep disturbances and sundowningincreased confusion, agitation, and other symptoms in the afternoon and evening.2 Not surprisingly, melatonin supplementation benefits patients with Alzheimers disease by improving sleep and reducing late-day aggravation of symptoms. Melatonin has also been found to decrease cognitive deterioration in individuals with Alzheimers disease, possibly by protecting brain cells from the toxic protein, beta-amyloid.2

Melatonin may likewise play an important role in assisting patients suffering from Parkinsons disease. Parkinsons disease is associated with disrupted melatonin secretion in the brain, and supplemental melatonin may help improve sleep efficiency in affected adults.3

The brain can suffer dramatic, irreparable damage when an individual suffers a stroke. Utilizing animal models of stroke, scientists have found that melatonin may offer important protection against stroke-related damage and deterioration. When administered at the time of stroke, melatonin limited the area of brain tissue damage, decreased brain cell death, lessened behavioral deficits, and reduced the rate of stroke-related death. These investigators believe that melatonins protective actions stem from its free-radical-scavenging and antioxidant activities, and suggest that melatonin may hold promise in improving stroke outcomes in humans.4

Melatonin may help manage one of the leading risk factors for strokeelevated blood pressure. While an earlier study reported that hypertensive men taking melatonin experienced reduced nighttime blood pressure, a newer study confirms the same benefit for women.5 In a randomized, double-blind study, 18 women

(aged 47 to 63) with either normal blood pressure or treated high blood pressure received a three-week course of slow-release melatonin (3 mg) or placebo, one hour before bedtime. Researchers recorded blood pressure readings for 41 hours at the end of the trial. While the daytime blood pressure readings remained unchanged com-pared to placebo, the melatonin treatment significantly decreased nighttime blood pressure, without modifying heart rate.6

One of melatonins most important applications is in fighting a wide array of cancers, including breast and liver cancers, non-small-cell lung cancer, and brain metastases from solid tumors.7

When women with metastatic breast cancer who had failed to respond to tamoxifen received melatonin supplements (20 mg every evening), they demonstrated an improved response to the chemotherapy drug. More than one quarter of the subjectswhose disease otherwise was expected to progress rapidlybegan responding to the chemotherapy treatment. Most of the women also experienced anxiety relief from the melatonin supplementation.8 Laboratory studies suggest that melatonin may help fight hormone-responsive breast cancers by inhibiting the aromatase enzyme, which is responsible for the local synthesis of estrogens.9,10

Emerging research suggests that melatonin may help fight one of the most common malignancies in aging menprostate cancer. In the laboratory, scientists treated androgen-sensitive and androgen-insensitive prostate cancer cells with pharmacological concentrations of melatonin. Treatment with melatonin dramatically reduced the number of prostate cancer cells, while the remaining cells displayed signs of slowed replication and increased differentiationcharacteristics of healthy, non-cancerous cells. Melatonin may thus hold promise against prostate cancers, whether they are hormone-sensitive or hormone-insensitive.11

Scientists conducted a meta-analysis of 10 randomized, controlled trials examining melatonins effects (alone or as an adjuvant treatment) on patients with various types of cancer. Supplementation with melatonin reduced the relative risk of death at one year by an impressive 34%regardless of the type of cancer or the melatonin dosage. Importantly, no adverse effects were reported.12

In addition to its benefits for cancer survival, melatonin may also help counteract the toxicity of chemotherapy treatment. Two-hundred-fifty individuals undergoing chemotherapy for advanced cancers of the lung, breast, gastrointestinal tract, or head and neck received chemotherapy, either alone or in combination with melatonin (20 mg/day). After one year, the melatonin-supplemented individuals demonstrated a higher rate of survival, and were significantly protected against many of the side effects associated with chemotherapy, including decreased platelet count, neurotoxicity, heart damage, mouth sores, and fatigue.13

A promising study suggests that migraine sufferers may be able to reduce the frequency and severity of their headaches by using melatonin. Researchers gave 34 migraine sufferers (29 women and 5 men) a 3-mg dose of melatonin, 30 minutes before bedtime, for three months. Of the 32 patients who finished the study, more than two thirds experienced at least a 50% reduction in number of headaches per month. Additionally, the intensity and duration of headaches decreased. The scientists believe that melatonins anti-inflammatory effect and free-radical-scavenging effects contribute to its headache-relieving benefits.14

Obtaining sufficient amounts of quality sleep is an absolute necessity for good health, yet many of us experience sleep difficulties on occasion. Insomnia occurs due to a variety of factorsranging from long hours of work or travel to sleep-disruptive conditions, such as urinary frequency and stressful events. Elderly adults may be particularly susceptible to difficulty sleeping and nighttime awakenings, due to the decline in melatonin levels associated with aging.15 Melatonin can help promote healthy sleep patterns in some people, regardless of the cause of insomnia.

A large analysis revealed several of melatonins sleep-enhancing benefits. Reviewing 15 studies of sleep in healthy adults, scientists noted that melatonin administration significantly reduced sleep latency (the amount of time needed to fall asleep), while boosting sleep efficiency (the percentage of time in bed spent asleep) and increasing total sleep duration.16

Men with benign prostatic enlargement often experience poor sleep due to nighttime urinary frequency. Scientists from the United Kingdom found that melatonin may offer an effective solution. When 20 older men were treated with 2 mg of melatonin each day for one month, they experienced a significant decrease in nighttime urination, and reported that their condition was less bothersome than before treatment.15

Individuals who work the night shift are often chronically tired due to difficulty falling asleep during the daytime. Supplementing with melatonin has helped improve the length and quality of daytime sleep in these individuals. These findings demonstrate an important characteristic of melatonin: the hormone exerts its hypnotic (sleep-inducing) and sedative (anxiety-relieving) effects, regardless of dosage time.7

Traveling to different time zones often leads to the fatigue and insomnia known as jet lag. Supplementing with melatonin can help prevent or reduce jet lag, particularly when traveling across several time zones. Melatonin works by helping re-synchronize the bodys circadian rhythms, helping the traveler adapt to the local time.7

Melatonin is used in doses ranging from 0.3-5.0 mg to promote sleep, with doses of 1-3 mg most common.17 Studies examining melatonins effects on cancer have utilized doses of 3-50 mg/day.7

Melatonin has a sedating effect, which may be magnified by the use of benzodiazepines or other sedating drugs such as antihistamines or antidepressants. Similarly, the use of melatonin with valerian, 5-hydroxytryptophan, or alcohol may increase sedation.17

The bioavailability of oral melatonin is increased by co-administration of the antidepressant drug fluvoxamine (Luvox).17 Beta blockers, as well as aspirin and other non-steroidal anti-inflammatory drugs, may decrease melatonin production in the body.17

A factor in restorative sleep, melatonins benefits extend to neuroprotection and fighting cancer. Its powerful antioxidant effect offers important enhancements to the brain and nervous system, helping protect against age-related damage. Most exciting are melatonins benefits for cancer patientsrelieving anxiety and improving survival from an array of cancers. Finally, migraine sufferers using melatonin may enjoy a vast decline in the frequency and severity of their headachesleading to a tremendously improved quality of life.

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CRISPR Update CRISPR Updates, News and Articles

Sharifnia, T., et. al. (2017) Cell Chemical Biology. 24:1075-1091. https://www.ncbi.nlm.nih.gov/pubmed/28938087

Rare cancers have traditionally been difficult to study due to low incidence and limited sample availability. However, new technologies, such as sequencing, have allowed for a greater understanding of the underlying genetic causes. In tandem with sequencing technologies, CRISPR/Cas and small molecule screens have allowed researchers to rapidly screen rare cancers for possible mechanisms and treatments.

Sharon Begley, STAT, 25 September 2017, https://www.statnews.com/2017/09/25/nobel-prize-predictions/

The season of Nobel Prize awards has arrived, and with it comes a slew of predictions. This year, STAT has identified who they believe has the best chance of winning the Nobel Prize in Medicine; including the CRISPR crowd of Emmanuelle Charpentier, George Church, Jennifer Doudna, and Feng Zhang. The only problem being each Nobel Prize can only be awarded to three people.

Rachael Lallensack, Nature News, 18 September 2017, http://www.nature.com/news/crispr-reveals-genetic-master-switches-behind-butterfly-wing-patterns-1.22628

Two new studies in the Proceedings of the National Academy of Sciences (http://www.pnas.org/content/early/2017/08/29/1709058114, http://www.pnas.org/content/early/2017/08/29/1708149114) provide insight into butterfly wing color. The studies identified two genes, WntA is responsible for creation of the coloring pattern and borders, while optix fills the color within the borders. Understanding butterfly coloration could provide insights into adaptations such as mimicry.

Vella, M.R. et. al. (2017) Scientific Reports 7:11038. https://www.ncbi.nlm.nih.gov/pubmed/28887462

CRISPR/Cas gene drives could be used to eliminate vector-borne diseases such as malaria and Lyme disease. However, release of modified organisms is controversial in part due to unforeseen consequences. Developing strategies for gene drive reversal could prove useful if such problems arise. This paper develops models to evaluate the effectiveness of gene drive counter-measures in order to evaluate their potential use.

Bikard, D., Barrangou, R., (2017) Current Opinion in Microbiology, 37:155-160. https://www.ncbi.nlm.nih.gov/pubmed/28888103

Self-targeting bacteria with CRISPR usually proves fatal. This observation could lead to a new type of antimicrobial where the CRISPR/Cas system is introduced to fight infection. This review discusses how CRISPR/Cas could target bacterial infections, as well as how the system may be delivered to the infection site.

David Nield, Science Alert, 9 September 2017, https://www.sciencealert.com/now-scientists-are-using-crispr-to-change-the-colour-of-flowers

The Japanese morning glory plant has traditionally had violet flowers, however using CRISPR to disrupt a single gene, scientists have altered the flower color to white. White morning glories can be found; however, it took 850 years for the white version to appear. CRISPR accomplished the task in less than 12 months. This is the first time CRISPR has been used to alter flower color in higher plants.

Liu, X., et. al. (2017) Cell 170:1028-1043. https://www.ncbi.nlm.nih.gov/pubmed/28841410

Many genes are regulated by cis-regulatory elements, though the molecular composition of these elements remains unknown. In a new study published in Cell, Liu et. al. describe a new technique called CAPTURE (CRISPR affinity purification in situ of regulatory elements) that uses a biotin labeled dCas9 to isolate cis regulatory elements in an unbiased fashion, allowing for insights into genome structure and function.

Stanford Medicine News Center, 29 August 2017, http://med.stanford.edu/news/all-news/2017/08/online-game-challenges-players-to-design-on-off-switch-for-crispr.html

Researchers at Stanford University School of Medicine have created a new online computer game called Eterna where players design RNA molecules that could act as an on/off switch for Cas9. Molecular biologists at Stanford will then create the most promising molecules and test them in living cells. Researchers aim to have 100,000 players contribute 10 solutions each. As the research team tests the molecules in the lab, they will provide information to the players for further refinement.

Julia Franz and Katie Hiler, WUNC Science Friday, 27 August 2017, http://wunc.org/post/new-developments-human-gene-editing-face-ethical-and-regulatory-quagmire-us#stream/0

Despite the results of Augusts CRISPR edited embryo paper being called into question, its publication has resulted in an increase in the ethics debate. Scientists agree that CRISPR gene editing will continue to improve and society must grapple with the ethical problems. Ira Flatow sits down with the author of the August Nature article and with Kelly Ormond, genetics professor at Stanford University and member of the Stanford Center for Biomedical Ethics, to discuss the results and how to proceed.

Dieter et. al. (2017) BioRxiv, 181255. http://www.biorxiv.org/content/early/2017/08/28/181255

On 02 August 2017, a Nature article claimed a major breakthrough in CRISPR genome editing. Researchers from around the world, including the United States, announced that they had successfully corrected viable human embryos heterozygous for the MYBPC3 mutation that results in heart disease, without mosaicism. Recently, the results of this article have been called into question with the publishing of a BioRxiv article. The authors of the new paper identify other possible mechanisms that could have caused the observed results and suggest additional experiments to effectively prove CRISPR gene editing.

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CRISPR Update CRISPR Updates, News and Articles

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About Stem Cells

Stem cells are found in the early embryo, the foetus, amniotic fluid, the placenta and umbilical cord blood. After birth and for the rest of life, stem cells continue to reside in many sites of the body, including skin, hair follicles, bone marrow and blood, brain and spinal cord, the lining of the nose, gut, lung, joint fluid, muscle, fat, and menstrual blood, to name a few.In the growing body, stem cells are responsible for generating new tissues, and once growth is complete, stem cells are responsible for repair and regeneration of damaged and ageing tissues. The question that intrigues medical researchers is whether you can harness the regenerative potential of stem cells and be able to grow new cells for treatments to replace diseased or damaged tissue in the body.

To find out more about how stem cells are used in research and in the development of new treatments download a copy of The Australian Stem Cell Handbook or visit Stem Cell Clinical Trials to find out more about the latest clinical research using stem cells.

Stem cells can be divided into two broad groups:tissue specific stem cells(also known as adult stem cells) andpluripotent stem cells(including embryonic stem cells and iPS cells).

To learn more about the different types of stem cells visit our frequently asked questions page.

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About Stem Cells

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CRISPR breakthrough could drop miscarriage rates | TechCrunch

Gene-editing technology CRISPR has revealed a clue in how human embryos begin to develop, possibly reducing the risk of miscarriage in those crucial first few weeks of pregnancy.

CRISPR Cas9 can modify or snip out genetic defects thought to contribute to miscarriage, but until now it wasnt clear why some embryos continued to form into a fetus and others did not. However,findings, published Wednesday in the journal Nature, hold genetic clues.

British scientists conducting the study found that a certain human genetic marker called OTC4 played an important role in the formation and development in the early stages of embryonic development. The scientists used CRISPR Cas9 to knock out this important gene in days-old human embryos and found that without it, these embryos ceased to attach or grow properly.

The findings could not only help us better understand why some women suffer more miscarriages than others, but it could also potentially greatly increase the rate of successful in vitro fertilization (IVF) procedures.

IVF is sometimes the only way a couple can make a baby using their own genes, but even with technological improvements over the years, the rates of success are still poor.Only about 36 percent of IVF cycles result in a viable pregnancy, and a mere 24 percent produce a baby, according to the Centers for Disease Control.

Of course, this is not the first time scientists have tested on human embryos. The practice has sparked a fierce international debate, but earlier this year, U.S. scientists used CRISPR technology to cut out a gene known to cause heart defects in three-day old human embryos.

None of the embryos in that study or this latest one were meant to go on to become human beings and were discarded after the study was finished. However, both studies hint at the potential CRISPR could have in the formation of human life in the future.

It will likely take years before putting this breakthrough into practice on viable embryos meant to develop beyond a few days, and theres likely still much more research needed, but it does give hope for those whove suffered a miscarriage and wanting to ensure they can one day carry a healthy baby to full term.

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CRISPR breakthrough could drop miscarriage rates | TechCrunch

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CRISPR gene-editing could result in more successful birth rates

Usually, this type of study is conducted on mice, which are easier to come by and carry less ethical considerations. But, in this case, scientists knocked out the gene in 41 human embryos donated by couples who had undergone in-vitro fertilization (IVF). The researchers claim the switch allowed them to highlight key differences between the role of OCT4 in human and mouse models. The team are hoping their findings can help scientists better grasp why some women suffer more miscarriages than others. Additionally, the study could also increase the rate of successful IVF procedures.

This isn't the first time scientists have used human embryos. Earlier this year, a team of researchers from Oregon became the first to use CRISPR tech to cut out genes that cause inherited diseases in humans. Before that, scientists in China utilized the technique to repair a gene that can bring about a fatal blood disorder.

The new study is being hailed as a compelling first step. "We were surprised to see just how crucial this gene is for human embryo development, but we need to continue our work to confirm its role," Norah Fogarty of the Francis Crick Institute told CNN. "Other research methods, including studies in mice, suggested a later and more focused role for OCT4, so our results highlight the need for human embryo research."

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Clinic North Vancouver | Bioidentical Hormone Treatments

Our goal is to help you to improve your health and quality of life, while identifying the possible cause of your symptoms. We strive to offer you the best care possible in a professional, spa-like space and support you through the latest Naturopathic Medical practices.

Are you suffering for a health condition you need help treating? Are you generally healthy but have noticed increasing difficulty with your weight, mood, energy, focus or hormones? Thepractitioners at Marine Drive Naturopathic Clinic offer programs and treatments to help you not only to feel better, but examine the cause of your symptoms or conditions.

Our team includes Naturopathic Physicians Dr. Cathryn Coe,Dr. Cameron McIntyre, Dr. Elizabeth Miller, Dr. Lynn Klassen, and Dr. Sarah Wulkan.

Weight gain? Hot flashes? Poor sleep? We offer comprehensive thyroid and hormone testing to identify hormonal imbalances, correcting them using bioidentical hormone treatments or herbal support

Are you or your child affected by learning difficulties or cognitive problems? We offer testing and treatment for conditions such as autism spectrum disorders, Alzheimers disease and dementia, and ADD/ADHD. Our Clinical Counsellor also offers support forparents of children with autism and spectrum disorders

The clinic is conveniently located along Marine Drive in North Vancouver with plenty of free parking and direct access to public transit. Come in, relax, enjoy a cup of tea and read a magazine in our spa-like environment. At Marine Drive Naturopathic Clinic, your treatment begins the minute you walk in the door

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Clinic North Vancouver | Bioidentical Hormone Treatments

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What Is a Hormone Doctor? | Career Trend

A hormone doctor, or an endocrinologist, is a physician who treats diseases related to the endocrine system. While primary care physicians (family practitioners and internal medicine physicians) can treat many hormonal disorders without a need for specialized training, a physician may also receive advanced training and specialize in endocrinology. A primary care physician can determine whether he or she can treat a patient or whether the patient should be referred to a specialist treating only disorders of the endocrine system.

The endocrine system is composed of many glands, including the pituitary, thyroid, parathyroids, adrenals, hypothalamus, pineal body, ovaries and testicles. The islet cells of the pancreas are also part of the endocrine system. These glands secrete hormones (chemical messengers) that regulate the bodys metabolism, growth, sexual development and sexual function, by complex feedback systems comparable to a thermostat regulating room temperature.

A hormone doctor can specialize in diseases of one or two glands or treat patients in all areas of endocrinology. A large part of a typical practice could involve treating diabetes and related complications. The physician may also treat thyroid disorders, inborn metabolic disorders, over- and underproduction of hormones, osteoporosis, menopause, cholesterol disorders, hypertension, and short or tall stature. Patients with endocrine cancer are usually referred to an oncologist.

To treat non-reproductive hormonal disorders, a physician generally completes four years of medical or osteopath school and a three-year residency in either family medicine or internal medicine. He or she must pass a board examination to become board certified in family or internal medicine. To become board certified as an endocrine specialist, the physician completes a three-year endocrinology fellowship program and passes a board certification examination.

Reproductive endocrinologists complete four years of residency training in obstetrics and gynecology, rather than training in family medicine or internal medicine. They must complete two or three years of fellowship training in reproductive endocrinology and infertility and pass the board certification examination. These specialists treat infertility by using in vitro fertilization, embryo and sperm freezing, assisted embryo hatching, pre-implantation genetic diagnosis and other emerging technologies. Reproductive endocrinologists also treat a wide range of reproductive disorders, including endometriosis, polycystic ovary syndrome, gonadal dysgenesis, galactorrhea, repeat pregnancy loss, ectopic pregnancy and excess hair in women, to name just a few.

A hormone doctor may work in academic medical centers, community hospitals, private group practices or private solo practices. Each situation can involve different work hours, a different patient base, and different lifestyles. Unlike surgical specialties, hormone doctors generally do not take call hours, but they may be called on an emergency basis to see a patient in a hospital when the physician on staff cannot appropriately treat the patient.

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What Is a Hormone Doctor? | Career Trend

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Gene therapy | Cancer in general | Cancer Research UK

Gene therapy is a type ofbiological therapy for cancer that is still in the early stages of research.

Genes are coded messages that tell cells how to make proteins. Proteins are the molecules that control the way cells behave. Our genes decide what we look like and how our body works.We have many thousands of separate genes.

Genes are made ofDNAand they are in the nucleus of the cell. The nucleus is the cell's control centre.Genes are grouped together to make chromosomes. We inherit half our chromosomes from our mother and half from our father.

Cancer cells are different from normal cells. They have changes (called faults or mutations) in several of their genes which make them divide too often and form a tumour. The genes that are damaged mightbe:

Many gene changes that may make a cell become cancerous are caused by environmental or lifestyle factors, such as smoking.

Some people have inherited faulty genes that increase their risk of particular types of cancer. Inherited damaged genes cause between 2 and 3 in every 100 (2% to 3%) of cancers.

Gene therapy is a type of treatment which uses genes to treat illnesses. Researchers have been developing differenttypes of gene therapyto treat cancer.

The ideas for these new treatments have come about because we are beginning to understand how cancer cells are different from normal cells. It is stillearly days for this type of treatment. Some of these treatments are being looked at in clinical trials. Otherscan now be used for some people with types of cancer such as melanoma skin cancer.

Getting genes into cancer cells is one of the most difficult aspects of gene therapy. Researchers are working on finding new and better ways of doing this. The gene is usually taken into the cancer cell by a carrier called a vector.

The most common types of carrier used in gene therapy are viruses because they can enter cells and deliver genetic material. The viruses have been changed so that they cannot cause serious disease but they may still cause mild, flu like symptoms.

Some viruses have been changed in the laboratory so that they target cancer cells and not healthy cells. So they only carry the gene into cancer cells.

Researchers are testing other types of carrier such as inactivated bacteria.

Researchers are looking at different ways of using gene therapy:

Some types of gene therapy aim to boost the body's natural ability to attack cancer cells. Ourimmune systemhas cells that recognise and kill harmful things that can cause disease, such as cancer cells.

There are many different types of immune cell. Some of them produce proteins that encourage other immune cells to destroy cancer cells. Some types of therapy add genes to a patient's immune cells. Thismakes them better at finding or destroying particular types of cancer.

There are a few trials using this type of gene therapy in the UK.

Some gene therapies put genes into cancer cells to make the cells more sensitive to particular treatments. The aim is to make treatments,such as chemotherapy or radiotherapy, work better.

Some types of gene therapy deliver genes into the cancer cells that allow the cells to change drugs from an inactive form to an active form. The inactive form of the drug is called a pro drug.

First of all you have treatment with the the carrier containing the gene, then you havethe pro drug.The pro drug circulates in the body and doesn't harm normal cells. But when it reaches the cancer cells, it is activated by the gene and the drug kills the cancer cells.

Some gene therapies block processes that cancer cells use to survive. For example, most cells in the body are programmed to die if their DNA is damaged beyond repair. This is called programmed cell death or apoptosis. Cancer cells block this process so they don't die even when they are supposed to.

Some gene therapy strategies aim to reverse this blockage. Doctors hope these new types of treatment will make the cancer cells die.

Some viruses infect and kill cells. Researchers are working on ways to change these viruses so they only target and kill cancer cells, leaving healthy cells alone.

This sort of treatment uses the viruses to kill cancer cells directly rather than to deliver genes. So it is not cancer gene therapy in the true sense of the word. But doctors sometimes refer to it as gene therapy.

A drug called T-VEC (talimogene laherparepvec)isnowavailable as a treatmentfor melanoma skin cancer. It isalso calledImlygic. It is also being looked at in trials for other types of cancer, such as head and neck cancer.

T-VEC uses a strain of the cold sore virus (herpes simplex virus)that been changed by altering the genes that tell the virus how to behave. It tells the virus to destroy the cancer cells and ignore the healthy cells.

T-VEC can beused to treatsome people with melanoma skin cancer whose cancer cannot be removed with surgery. You have T-VEC as an injectiondirectly into yourmelanoma.

Use the tabs along the top to look at recruiting,closed and results.

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Gene therapy | Cancer in general | Cancer Research UK

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Relief of Overactive Bladder – page 1 | Life Extension …

A common and frustrating complaint we at Life Extension hear is how to stop urinary incontinence.

Our frustration has been that despite aggressive research, we could not identify a safe solution to this problem that plagues so many aging women (and men to a lesser extent).

Even more numerous are inquiries we receive from people seeking relief from frequent daytime and nighttime urinary urges.

In a breakthrough discovered by Japanese scientists, a natural plant extract combination has been shown to reduce incontinent episodes by up to 79%,1 daytime urination by up to 39%,2 and nighttime urination by up to 68%.3

This article will discuss the research findings on maturing women who found significant relief after taking this novel supplement for only six to eight weeks.

Additionally, this article will discuss more limited data obtained when men suffering from nighttime urinary urgencies were given this same plant extract.

Urinary frequency becomes more common with advancing age, with nearly half of people over 60 reporting to suffer from nocturia (two or more episodes of urination during the night).

Urinary incontinence is defined as an involuntary loss of urine. It represents a major social and hygiene problem in the aging population. About 48% of women and 17% of men over age 70 suffer urinary incontinence.4

Overactive bladder affects one in six adults over age 40, and is defined as having an urgent need to empty the bladder during the day-night, along with incontinence. Those afflicted with an overactive bladder have to go to the bathroom frequently, leak urine into their clothes, and report feeling depressed, stressed, and sleep-deprived.

In women, stress incontinence (involuntary loss of urine during physical activity such as sneezing or exercise) is usually caused by a weakening of the bladder sphincter and pelvic floor muscles. Shrinkage (atrophy) of tissues where the bladder and urethra meet also contributes to the problem. Hormonal changes occurring after menopause are thought to be an underlying cause of these anatomical changes in the bladder sphincter that lead to urinary incontinence.

In postmenopausal women, decreased androgen (testosterone) levels weaken the pelvic floor and sphincter muscles, while an estrogen deficit induces atrophy of the urethra.

Mainstream medicine offers only mediocre therapies to address urinary incontinence. Drugs commonly used for this condition are expensive and side-effect-prone. Only a small proportion of the affected population seeks treatment because most people consider their urinary symptoms a consequence of normal aging.

Fortunately, a safe, natural, and low-cost approach has been developed that has demonstrated remarkable benefits in human clinical trials.

Pumpkin seeds were traditionally used by Native American tribes to facilitate passage of urine. A European herbal encyclopedia first mentioned the use of pumpkins seeds to treat urinary problems in the year 1578. The German health regulators approve pumpkin seed as a treatment for irritable bladder.

Pumpkin seed oil has been included in products used to alleviate urinary difficulties. While some effects have been shown when using the fat-soluble (oil) fraction of the pumpkin seed, it is the water-soluble portion that demonstrated impressive symptomatic effects in recent studies.

Japanese scientists have patented a method to obtain the water-soluble constituents of the pumpkin seed, which are absorbed far more efficiently into the bloodstream.

Urinary incontinence worsens after menopause. While menopausal problems are usually associated with estrogen deficit, low levels of testosterone and progesterone are also underlying culprits.

Water-soluble pumpkin seed extract exerts an anabolic (tissue-building) effect on the pelvic floor muscles via several mechanisms. By inhibiting the aromatase enzyme, it may make more testosterone available to strengthen the pelvic muscles.5

Secondly, this water-soluble pumpkin seed fraction binds to the androgen receptor on pelvic muscle cells, thus inducing a strengthening effect. This is important because androgen receptors are expressed in the pelvic floor and lower urinary tract in humans.6 By promoting androgenic activity, water-soluble pumpkin seed extract may play an important role in female pelvic floor structural integrity and lower urinary tract disorders.5

Nitric oxide is a molecule critically involved in lower urinary tract functions. For the urination muscles to relax when the bladder is full, nitric oxide is required. When nitric oxide synthesis is inhibited, the result is bladder hyperactivity and reduced bladder volume.

The dual mechanisms of strengthening pelvic floor muscles, while increasing nitric oxide synthesis,5 help explain how water-soluble pumpkin seed extract alleviated urinary incontinence in three separate studies on aging women.1-3

Soy extracts provide standardized phyoestrogens that are potentially effective in ameliorating geriatric symptoms relating to estrogen deficit.

The ingestion of standardized soy extract has been hypothesized to decrease the atrophy of tissues where the bladder and urethra meet and thus alleviate frequent urinary urges and incontinence.

A study was done to evaluate the effects of water-soluble pumpkin seed extract in anesthetized rats to determine bladder functionality.7

As measured by a cystometrogram, bladder parameters showed a dramatic 54.5% improvement in rats receiving water-soluble pumpkin extract compared to other agents.

When the excretion frequency was measured, a 60% reduction in urine excretion frequency occurred after administration of water-soluble pumpkin seed extract. No improvement was seen in the group given inactive solvent.

Conclusions from the study showed that water-soluble pumpkin extract significantly increases maximum bladder capacity while decreasing urination frequency.

A study of 39 incontinent females (aged 55-79 years) using water-soluble pumpkin seed and soy isoflavone extracts was conducted over a six-week period.1 The objective was to evaluate the effects on frequency of daytime and nighttime urinations and number of incontinent episodes.

After six weeks, the number of nighttime urinations was reduced from 3.3 to 2.0 a 39% improvement. Daytime urinations went from 8.0 to 6.7 after six weeks a modest 16% improvement.

The number of incontinent episodes, however, plunged to a remarkably low number. Prior to receiving the water-soluble pumpkin seed-soy extract, these women experienced an average of 7.3 incontinent episodes a day. After six weeks of using this supplement, daily incontinent episodes averaged only 1.5 an astounding 79% decrease in urinary incontinence!

When these women were questioned about the effects they noticed in response to taking water-soluble pumpkin seed-soy extract, there was a 73% subjective improvement in the highest fulfilled category. When the global improvement ratio was evaluated, which included degree of satisfaction after sleeping, 81.8% of women with two to four episodes of nightly urinations reported that they were markedly improved.

A study of 50 incontinent women (aged 35-84 years) was conducted using the same water-soluble pumpkin seed-soy extract supplement to evaluate the effect on stress incontinence episodes.3

Before the pumpkin seed-soy supplement was given, these women averaged 2.1 incontinent events each day. After taking the supplement for six weeks, incontinent events fell to an average of only 0.7 a day a remarkable 67% decrease in stress-induced incontinent episodes!

A consumer test of 10 women (aged 45-65 years) was conducted using the same water-soluble pumpkin seed and soy extract supplement.2

After eight weeks, daytime urinations went from 9.3 to 5.6 a 39% reduction. Nighttime urinations went from 2.0 to 0.8 a 60% reduction.

Prior to initiating the pumpkin seed-soy supplement, there was an average of 2.3 incontinent episodes each day. After eight weeks, the frequency of incontinent episodes declined to only 1.0 per day a 57% reduction!

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Relief of Overactive Bladder - page 1 | Life Extension ...

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CRISPR: A game-changing genetic engineering technique …

Have you heard? A revolution has seized the scientific community. Within only a few years, research labs worldwide have adopted a new technology that facilitates making specific changes in the DNA of humans, other animals, and plants. Compared to previous techniques for modifying DNA, this new approach is much faster and easier. This technology is referred to as CRISPR, and it has changed not only the way basic research is conducted, but also the way we can now think about treating diseases [1,2].

CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeat. This name refers to the unique organization of short, partially palindromic repeated DNA sequences found in the genomes of bacteria and other microorganisms. While seemingly innocuous, CRISPR sequences are a crucial component of the immune systems [3] of these simple life forms. The immune system is responsible for protecting an organisms health and well-being. Just like us, bacterial cells can be invaded by viruses, which are small, infectious agents. If a viral infection threatens a bacterial cell, the CRISPR immune system can thwart the attack by destroying the genome of the invading virus [4]. The genome of the virus includes genetic material that is necessary for the virus to continue replicating. Thus, by destroying the viral genome, the CRISPR immune system protects bacteria from ongoing viral infection.

Figure 1 ~ The steps of CRISPR-mediated immunity. CRISPRs are regions in the bacterial genome that help defend against invading viruses. These regions are composed of short DNA repeats (black diamonds) and spacers (colored boxes). When a previously unseen virus infects a bacterium, a new spacer derived from the virus is incorporated amongst existing spacers. The CRISPR sequence is transcribed and processed to generate short CRISPR RNA molecules. The CRISPR RNA associates with and guides bacterial molecular machinery to a matching target sequence in the invading virus. The molecular machinery cuts up and destroys the invading viral genome. Figure adapted from Molecular Cell 54, April 24, 2014 [5].

Interspersed between the short DNA repeats of bacterial CRISPRs are similarly short variable sequences called spacers (FIGURE 1). These spacers are derived from DNA of viruses that have previously attacked the host bacterium [3]. Hence, spacers serve as a genetic memory of previous infections. If another infection by the same virus should occur, the CRISPR defense system will cut up any viral DNA sequence matching the spacer sequence and thus protect the bacterium from viral attack. If a previously unseen virus attacks, a new spacer is made and added to the chain of spacers and repeats.

The CRISPR immune system works to protect bacteria from repeated viral attack via three basic steps [5]:

Step 1) Adaptation DNA from an invading virus is processed into short segments that are inserted into the CRISPR sequence as new spacers.

Step 2) Production of CRISPR RNA CRISPR repeats and spacers in the bacterial DNA undergo transcription, the process of copying DNA into RNA (ribonucleic acid). Unlike the double-chain helix structure of DNA, the resulting RNA is a single-chain molecule. This RNA chain is cut into short pieces called CRISPR RNAs.

Step 3) Targeting CRISPR RNAs guide bacterial molecular machinery to destroy the viral material. Because CRISPR RNA sequences are copied from the viral DNA sequences acquired during adaptation, they are exact matches to the viral genome and thus serve as excellent guides.

The specificity of CRISPR-based immunity in recognizing and destroying invading viruses is not just useful for bacteria. Creative applications of this primitive yet elegant defense system have emerged in disciplines as diverse as industry, basic research, and medicine.

In Industry

The inherent functions of the CRISPR system are advantageous for industrial processes that utilize bacterial cultures. CRISPR-based immunity can be employed to make these cultures more resistant to viral attack, which would otherwise impede productivity. In fact, the original discovery of CRISPR immunity came from researchers at Danisco, a company in the food production industry [2,3]. Danisco scientists were studying a bacterium called Streptococcus thermophilus, which is used to make yogurts and cheeses. Certain viruses can infect this bacterium and damage the quality or quantity of the food. It was discovered that CRISPR sequences equipped S. thermophilus with immunity against such viral attack. Expanding beyond S. thermophilus to other useful bacteria, manufacturers can apply the same principles to improve culture sustainability and lifespan.

In the Lab

Beyond applications encompassing bacterial immune defenses, scientists have learned how to harness CRISPR technology in the lab [6] to make precise changes in the genes of organisms as diverse as fruit flies, fish, mice, plants and even human cells. Genes are defined by their specific sequences, which provide instructions on how to build and maintain an organisms cells. A change in the sequence of even one gene can significantly affect the biology of the cell and in turn may affect the health of an organism. CRISPR techniques allow scientists to modify specific genes while sparing all others, thus clarifying the association between a given gene and its consequence to the organism.

Rather than relying on bacteria to generate CRISPR RNAs, scientists first design and synthesize short RNA molecules that match a specific DNA sequencefor example, in a human cell. Then, like in the targeting step of the bacterial system, this guide RNA shuttles molecular machinery to the intended DNA target. Once localized to the DNA region of interest, the molecular machinery can silence a gene or even change the sequence of a gene (Figure 2)! This type of gene editing can be likened to editing a sentence with a word processor to delete words or correct spelling mistakes. One important application of such technology is to facilitate making animal models with precise genetic changes to study the progress and treatment of human diseases.

Figure 2 ~ Gene silencing and editing with CRISPR. Guide RNA designed to match the DNA region of interest directs molecular machinery to cut both strands of the targeted DNA. During gene silencing, the cell attempts to repair the broken DNA, but often does so with errors that disrupt the geneeffectively silencing it. For gene editing, a repair template with a specified change in sequence is added to the cell and incorporated into the DNA during the repair process. The targeted DNA is now altered to carry this new sequence.

In Medicine

With early successes in the lab, many are looking toward medical applications of CRISPR technology. One application is for the treatment of genetic diseases. The first evidence that CRISPR can be used to correct a mutant gene and reverse disease symptoms in a living animal was published earlier this year [7]. By replacing the mutant form of a gene with its correct sequence in adult mice, researchers demonstrated a cure for a rare liver disorder that could be achieved with a single treatment. In addition to treating heritable diseases, CRISPR can be used in the realm of infectious diseases, possibly providing a way to make more specific antibiotics that target only disease-causing bacterial strains while sparing beneficial bacteria [8]. A recent SITN Waves article discusses how this technique was also used to make white blood cells resistant to HIV infection [9].

Of course, any new technology takes some time to understand and perfect. It will be important to verify that a particular guide RNA is specific for its target gene, so that the CRISPR system does not mistakenly attack other genes. It will also be important to find a way to deliver CRISPR therapies into the body before they can become widely used in medicine. Although a lot remains to be discovered, there is no doubt that CRISPR has become a valuable tool in research. In fact, there is enough excitement in the field to warrant the launch of several Biotech start-ups that hope to use CRISPR-inspired technology to treat human diseases [8].

Ekaterina Pak is a Ph.D. student in the Biological and Biomedical Sciences program at Harvard Medical School.

1. Palca, J. A CRISPR way to fix faulty genes. (26 June 2014) NPR < http://www.npr.org/blogs/health/2014/06/26/325213397/a-crispr-way-to-fix-faulty-genes> [29 June 2014]

2. Pennisi, E. The CRISPR Craze. (2013) Science, 341 (6148): 833-836.

3. Barrangou, R., Fremaux, C., Deveau, H., Richards, M., Boyaval, P., Moineau, S., Romero, D.A., and Horvath, P. (2007). CRISPR provides acquired resistance against viruses in prokaryotes. Science 315, 17091712.

4. Brouns, S.J., Jore, M.M., Lundgren, M., Westra, E.R., Slijkhuis, R.J., Snijders, A.P., Dickman, M.J., Makarova, K.S., Koonin, E.V., and van der Oost, J. (2008). Small CRISPR RNAs guide antiviral defense in prokaryotes. Science 321, 960964.

5. Barrangou, R. and Marraffini, L. CRISPR-Cas Systems: Prokaryotes Upgrade to Adaptive Immunity (2014). Molecular Cell 54, 234-244.

6. Jinkek, M. et al. A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. (2012) 337(6096):816-21.

7. CRISPR reverses disease symptoms in living animals for first time. (31 March 2014). Genetic Engineering and Biotechnology News. <http://www.genengnews.com/gen-news-highlights/crispr-reverses-disease-symptoms-in-living-animals-for-first-time/81249682/> [27 July 2014]

8. Pollack, A. A powerful new way to edit DNA. (3 March 2014). NYTimes < http://www.nytimes.com/2014/03/04/health/a-powerful-new-way-to-edit-dna.html?_r=0> [16 July 2014]

9. Gene editing technique allows for HIV resistance? <http://sitn.hms.harvard.edu/flash/waves/2014/gene-editing-technique-allows-for-hiv-resistance/> [13 June 2014]

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CRISPR: A game-changing genetic engineering technique ...

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Thanks to CRISPR, gene-edited pigs could be organ donors for …

Why it matters to you

Pigs could be a solution to the shortage of transplant organs. CRISPR gene editing makes them safer candidates.

There is a massive shortage of transplant organs worldwide, and scientists are desperate to come up with a solution whether that be boosting patients immune systems to let them accept otherwise incompatible organs, or creating technology for preserving organs after they are harvested. A new international research initiative has another approach: Using CRISPR gene editing on pigs to make them into safe organ donor candidates for humans.

The reason pigs are desirable as possible sources of organs is that their organs are similar to humans in both size and anatomy. Unfortunately, they also carry viruses known as porcine endogenous retroviruses (PERVs) embedded in their DNA. As this research demonstrated, this can be passed on to humans, although gene editing can be used to eradicate it.

Currently, the major problem of human transplants is the great shortage of transplantable human organs, Lin Lin, a researcher in the department of biomedicine at Denmarks Aarhus University, told Digital Trends. While using pig organs, we can in principle use as many as we need. Eradicating PERVs makes porcine organs safer for human transplants. However, there are still several other barriers that we have to cross in order to make pig organs better for human transplants. This is now achievable with the great development in CRISPR gene editing.

Using an optimized CRISPR-Cas9 gene editing technology and porcine somatic cell nuclear transfer, this work successfully generated viable pigs that are 100 percent PERV-inactivated.Thirty-seven PERV-inactive piglets have so far been born, with 15 remaining alive. The oldest of these is four months old, which means it will need to be monitored for a longer period of time to make sure it suffers no ill-effects.

The next major step is to solve the problem of vigorous immune responses, such as complement activation, coagulation and thrombosis, triggered by xenotransplantation, Lin said. Many previous works have demonstrated that the immunological incapability can be alleviated through tailoring the pig genome. Thus, a serial of very sophisticated gene editing and modifications will be further introduced into the PERV-inactivated pigs and tested in higher primates.

A paper describing the research was recently published in the journal Science.

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Thanks to CRISPR, gene-edited pigs could be organ donors for ...

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CRISPR – CRISPR-Cas9 | Gene Editing

CRISPR or CRISPR Cas9 is commonly used to refer to a revolutionary genome editing technology that enables efficient and precise genomic modifications in a wide variety of organisms and tissues.

Definition: Clustered Regularly Interspaced Short Palindromic Repeat or CRISPR (pronounced 'crisper') was identified in a prokaryotic defence system. CRISPR are sections of genetic code containing short repetitions of base sequences followed by spacer DNA segments

Identified in archaea and bacteria, short nucleic acid sequences are captured from invading pathogens and integrated in the CRISPR loci amidst the repeats. Small RNAs, produced by transcription of these loci, can then guide a set of endonucleases to cleave the genomes of future invading pathogens, thereby disabling their attacks.

Definition: CRISPR ASsociated protein 9 (Cas 9) is an endonuclease used in an RNA-guided gene editing platform. It uses a synthetic guide RNA to introduce a double strand break at a specific location within a strand of DNA

Cas9 was the first of several restriction nucleases (or molecular scissors) discovered that enable CRISPR genome editing. The CRISPR Cas9 mechanism has since been adapted into a powerful tool that puts genome editing into the mainstream.

In the laboratory, CRISPR Cas9 genome editing is achieved by transfecting a cell with the Cas9 protein along with a specially designed guide RNA (gRNA) that directs the cut through hybridization with its matching genomic sequence. When the cell repairs that break, errors can occur to generate a gene knockout or additional genetic modifications can be introduced. Our CRISPR gene editing technology is particularly good for the efficient generation of complete knockout of genes on multiple alleles.

Use of wild-type Cas 9 has been shown to lead to off-target cleavage, but a modified version introduces only single strand nicks to the DNA, which in pairs still stimulate the repair mechanisms while significantly decreasing the risk of off-target cutting.

Horizon has licensed gene editing IP from Harvard University, the Broad Institute and ERS Genomics with the goal of being able to ensure that we will be able to offer uninterrupted use of CRISPR tools to our customers. Our scientists have extensive knowledge of CRISPR technology including the benefits of using each Cas9 structure.

Other Gene Editing Systems

Genome editing can be achieved using the widely used S. Pyogenes (spCas9), and also utilising CRISPR Cas 9 protocol for S. Aureus (scCas9), Cpf1, HiFi Cas9, Nickase Cas9, Nuclease Cas9, NgAgo gDNA and even synthetic spCas9 with alternative PAM sites.

Our genome editing knowledge also includes rAAV and ZFNs.

Continue your CRIPSR/Cas9 research with ourpopular education and training webinars:

Find out more about our exciting upcoming eventwhere the future of CRISPR will be discussed:

The CRISPR Forum 2017

Barrangou R, Fremaux C, Deveau H, Richards M, Boyaval P, Moineau S, Romero DA, Horvath P. 2007.CRISPR provides acquired resistance against viruses in prokaryotes. Science 315(5819): 1709-1712.

Jinek M, Chylinski K, Fonfara I, Hauer M, Doudna JA, Charpentier E. 2012.A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337(6096): 816-821.

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CRISPR - CRISPR-Cas9 | Gene Editing

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Birth of CRISPR’d pigs advances hopes for turning pigs into …

B

ioengineer Luhan Yang swiped through the photos on her phone until she got to one that made her beam: It showed her crouching down by a pudgy, wide-eyed newborn she calls my baby.

This newborn is a pig, and its the first to be born with dozens of genetic changes that could enable scientists to turn swine into a source of organs for human transplants, Yang and her colleaguesreported on Thursday in Science.

Theynamed the piglet Laika, after the first dog to orbit Earth in 1957. The new Laika, born this year in China after numerous miscarriages and other setbacks, could be a pioneer in her own right. Using the genome-editing technology CRISPR-Cas9, Yang and her team at the biotech startup eGenesis knocked out pig DNA that has long been considered a deal-breaker for efforts to use pigs as organ donors. Laika and 36 other designer piglets are completely free of it.

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There are additional Olympic-level hurdles to overcome before people facing death from organ failure get replacement kidneys, hearts, livers, or lungs from the species that provides their bacon and pork chops.Other genetic changes will be necessary. And regulators require stringent tests in lab primates before a single patient could get a CRISPRd pig organ; that will take years.

But after decades of dashed hopes, experts say, xenotransplantation might actually be in the offing.

Its an elegant tour de force of genetic engineering, so my hat is off to them, said Dr. A. Joseph Tector, of the University of Alabama, Birmingham, who has also made genetically modified pigs aimed at producing transplantable organs. But if you want to move xenotransplantation to the hospital, there are many more things youll have to do.

Doctors wont have to do much persuasion, however, to get patients to accept organs from another species. There is so much desperation among people on transplant lists, and 20 a day are dying as they wait, said Dr. Adam Griesemer, a xenotransplantation researcher and transplant surgeon at Columbia University Medical Center. This could be a path to a transplant for them. Colleagues keep asking me when were going to do it.

Pigs are scientists first choice because their organs and physiology are pretty close matches to humans, and they come with less ethical baggage than, say, chimps or baboons. But for years, the path to xenotransplantation has been paved with disappointment. Pig organs with genetic changes, transplanted into baboons and other lab animals,kept failing within weeks, even though the recipients received immune-suppressing drugs to prevent organ rejection.

Yang believes that CRISPR can accomplish what previous approaches have not: make multiple, simultaneous changes in pig DNA so that the animals organs work, and work safely, in people.

The team at Massachusetts-based eGenesis, working with scientists in China, used the Dolly recipe to clone pigs. They started with cells from adult pigs, and used an electrical jolt to fuse them with pig ova whose DNA had been removed. They grew the resulting embryos in lab dishes and then transferred healthy ones to sows, hoping for pregnancies.

The adult cells were not as nature made them, however. In a key step, the scientists used the genome-editor CRISPR to cripple all 25 copies of PERV genes DNA in the pig genome that makes potentially dangerous viruses that could infect anyone who receives a pig organ. (PERV stands for porcine endogenous retroviruses.) Initially, in about one-third of the CRISPRd pig cells, the PERV genes were almost all gone. In most of the rest, CRISPR missed its mark. That wasnt unexpected; for all the hype around CRISPR, it isnt perfect.

The unwelcome surprise was that cells that were effectively CRISPRd the ones the scientists needed to clone designer pigs were dying like orchids in the tundra. Apparently, in its zeal to attack so many PERV genes, CRISPR had shredded the cells genomes fatally.

Its quite a problem, when you move to so many targets, said Yang, the chief scientific officer at eGenesis. If there are multiple cuts in the genome at the same time, chromosomes rearrange themselves. That can happen when you make two or three [CRISPR edits], and were dealing with 25.

The eGenesis scientists, many of them alums of George Churchs lab at Harvard Medical School, scrambled for a solution. They eventually stumbled on a cocktail of molecules that both increased the number of PERV targets that CRISPR hit and, even better, kept the well-CRISPRd cells alive. We were able to get cells to grow even with very aggressive gene editing, Yang said: 100 percent of the cells doused with the chemical cocktail were 100 percent PERV-free.

As is typical with cloning, very few of the cloned embryos were healthy enough to implant into sows, and few implanted embryos resulted in births. Crucially, however, of the 37 piglets born from 17 sows, all were PERV-free. And CRISPR did not change any DNA it wasnt supposed to; there were no off-target effects.

The oldest pigs are nearly 5 months old, or adolescents; 15 remain alive. The rest were killed so the scientists could see whether their organs were developing normally.

So far, so good, Yang said, showing that pigs dont need PERVs to live: Weve shown you can produce PERV-free pigs which could serve as a source for future xenotransplants.

Among eGenesiss next experiments: see if the pigs are fertile and, if so, whether their CRISPRd genetic changes, including inactivating PERVs, are inherited. That could provide an easier source of transplantable organs than cloning.

Other scientists have also used CRISPR to produce pigs with altered genomes, including pigs in which a genethat triggers organ rejection was eliminated. Last year, scientists announcedthat hearts from genetically-modified pigs survived in baboons for up to 945 days, a record.

UABs Tector and his colleagues, with financial backing from United Therapeutics Corp., are using CRISPR not on PERVs but on other pig genes. Knocking out threein particular could protect pig organs from being attacked by the human immune system, he said; lab macaques that received kidneys from the pigs have survived as long as 499 days. We have a pig we are very confident we can make work for kidney transplants, Tector said.

There is disagreement about whether pig organs would have to be PERV-free to be successfully transplanted into people. Tector said transplant patients could take anti-retroviral drugs, just as they take immune-suppressing drugs, to kill the viruses.

Nevertheless, eGenesis scientists achievement with their 25 DNA edits, the eGenesis pigs set the record for genome modifications suggests that however many edits are needed to make pigs into organ donors might be feasible. The challenge is to identify which pig genes are necessary and sufficient to change so that the animals organs have a shot at working in people.

Senior Writer, Science and Discovery

Sharon covers science and discovery.

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Medical Weight Loss – Hormone Replacement Therapy and HCG …

Medical Weight Loss Programs

If you consider yourself overweight, odds are that you have tried diet and exercise routines but have, at some point, found them lacking in terms of results.

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The thyroid is the master gland in the body, and it can significantly impact weight gain, as well as the immune system, fertility, motivation and other important aspects

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Insulin is a hormone made in the pancreas, an organ located behind the stomach. The pancreas contains clusters of cells called islets. Beta cells within the islets make insulin and release it into the blood.

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PCOS is a weight gaining condition that can manifest in numerous ways. As such, the females who experience this condition almost never have the same combination

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Migraine headaches in women usually go hand in hand with other female problems like PMS, uterine fibroids, ovarian cysts, irregular and painful periods cystic acne, facial hair, infertility, post-partum depression and various cancers

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Does the HCG really work for weight loss ? absolutely it does. But with new web sites appearing daily offering a wide range of HCG diet products, from prescription shots to homeopathic supplements

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Hormone replacement therapy is not a necessity for everyone, though. The professionals at Medical Weight Loss certainly offer this treatment to all clients who would benefit from it.

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Buy Serum Stem Cells Skin Care Products | CHOLLEY

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Frozen Dead Guy

Frozen Dead GuyHome of The Frozen Dead Guy (AKA Bredo Morstoel)The Iceman's Chronicle...Contact the Iceman for information on where to get your copy...and for booksignings and special events.Get information on events for 2013 FDGDays>>>>Get Twitter Tweets from Botheiceman@Twitter.com!!!What's the Frozen Dead Guy all about?It has a lot to do with Cryonics, which is pretty much freezing people who are about to die, in hopes that future technology will be able to "re-animate" them and cure what ailed them.It had a lot to do with the Town of Nederland and the Nederland Chamber of Commerce....and there's a year round Information Center in Ned for souvenirs of the Frozen Dead Guy Days festival (see below). The Chamber's site had all the information on upcoming FDGDaze.....but in 2011 they sold the festival to a private group who now has the only site with information on the upcoming festival. Frozen Dead Guy Days is their link.It has a big connection to Norway, as the Grandson of the FDG, Trygve, lives there with his Mother, Aud (FDG's Daughter). They are the ones responsible for maintaining the financials and micro-managing from afar. Trygve was deported in 1994 and has not set foot in the US since. Aud has visited...once. THere are long and curious tales about both of these situations, but suffice to say, neither is allowed back in the country at this time.There's some of that old history......Psychics and all, found in the Historical Archives of the Planetary Ecologists at....There's some history regarding the Great Unappearance on the Jay Leno Tonight Show..Here's some archived video of the days when Grandpa was persona non grata.....Although there is a wild and entertaining side to this story.....there is also a serious and scientific side, too.There's been some Press.......and some websites, like Dark DestinationsEven a local company who went National has played a part....Tuff Shed has made it all possible from a practical point of view.We celebrated Grandpa Bredo's 107th Birthday with an Ice Run Party at the old International Cryonics Institute, before it was dismantled.********Update.....September 2012******* In September of 2012, a labor dispute broke out and when overseas management and local labor couldn't agree on terms, a walkout ensued. The International Cryonics Institute was kicked out of it's offices and had to remove all their equipment. Scabs were hired and the fate of Grandpa Bredo now rests in the hands of some guy and a truck. The coming winter is predicted to be snowy and cold. Stay tuned for further info.... The Iceman's last day on the job...Here's a wordle from the book "Chronicles of the Colorado Iceman"....And then there's the Frozen Dead Guy Days Festival.....Frozen Dead Guy Days 2006 Frozen Dead Guy Daze of 2007.....a festival to remember!Frozen Dead guy Days of 2008...A picture GalleryFrozen Dead Guy Daze 2009...Frozen Dead Guy Daze 2010...Re-animated Tours!If, after perusing this evolving site, you have any questions or still just can't seem to figure out what the FDG is all about...Feel free to Send your query to The IcemanThis Page is deep in the throes of Creative Endeavour.......please be advised

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Frozen Dead Guy

Recommendation and review posted by Bethany Smith

Skin Stem Cells – Methods and Protocols | Kursad Turksen …

During the last decade, an increased interest in somatic stem cells has led to a flurry of research on one of the most accessible tissues of the body: skin. Much effort has focused on such topics as understanding the heterogeneity of stem cell pools within the epidermis and dermis, and their comparative utility in regenerative medicine applications. In Skin Stem Cells: Methods and Protocols, expert researchers in the field detail many of the methods which are now commonly used to study skin stem cells. These include methods and techniques for the isolation, maintenance and characterization of stem cell populations from skin. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls.

Authoritative and practical, Skin Stem Cells: Methods and Protocols seeks to aid scientists in the further understanding of these diverse cell types and the translation of their biological potential to the in vivo setting.

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Skin Stem Cells - Methods and Protocols | Kursad Turksen ...

Recommendation and review posted by simmons

Home – Cell & Gene Therapy World 2018 – Meet the Future of …

"The event reflected the fantastic growing enthusiasm around cell and gene therapy, including small and large companies, investors and regulators. It was great to see everyone so engaged and so positive. The event really gives you the pulse of what is happening right now in cell and gene therapy."

Vice President, Regulatory Science, Bluebird Bio, Inc

Great program, great people, great venue.

Managing Director, EUFETS GmbH

Dynamic, interesting and highly interactive event that promotes exchange and networking in highly specialized field of gene therapy.

Associate Director, Powell Gene Therapy Center, University of Florida

"Phacilitate provides a unique forum, bringing together research, process development, and commercial leaders on the cutting edge of cell, gene, and immunotherapy. A great conference for anyone wanting a comprehensive view of the field."

Vice President, Research & Product Development, Dendreon

"It was all business. Ive never been to an event where over 80% of the conversations I had were constructive to my business objectives."

Acquisition & Business Development Manager, BioMedical Materials, Chemelot Campus B.V.

Great way to expand network with global experts in cell and gene therapy who are facing similar challenges.

Director, Strategy and Engagement, GSK

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Home - Cell & Gene Therapy World 2018 - Meet the Future of ...

Recommendation and review posted by simmons

Severe hyponatremia due to hypopituitarism with adrenal …

Objective: Adrenal insufficiency due to hypopituitarism can lead to severe hyponatremia with potentially fatal consequences. Prompt diagnosis and adequate hormonal replacement therapy are essential to block an otherwise unfavorable course and to re-establish a healthy life. Unfortunately, this condition is often misdiagnosed. Design: Case report. Setting: Intensive Care Unit of a teaching hospital. Patient: A 76-yr-old man with refractory hypotension, acute myocardial infarction, and left ventricular dysfunction, secondary to severe chronic pan-hypopituitarism, associated with severe hyponatremia. Methods and main results: The patient underwent mechanical ventilation and continuous venous-venous hemodiafiltration, for severe respiratory and renal insufficiency. A hormonal replacement therapy with T4, hydrocortisone, and nandrolone was started and the patient was discharged to a rehabilitation facility after 31 days of hospitalization. Conclusions: Hypopituitarism with secondary adrenal insufficiency is often misdiagnosed at an early stage and a high degree of suspicion is necessary for early diagnosis. Determination of plasma cortisol level in patients with hyponatremia not explained by other causes should always be obtained.

Key-wordsHyponatremiapan-hypopituitarismadrenal insufficiencymyocardial infarctionhypothyroidism

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Yatagai T, Kusaka I, Nakamura T, et al. Close association of severe hyponatremia with exaggerated release of arginine vasopressin in elderly subjects with secondary adrenal insufficiency. Eur J Endocrinol 2003, 148: 2216.

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Ishikawa SE, Saito T, Fukagawa A, et al. Close association of urinary excretion of aquaporin-2 with appropriate and inappropriate arginine vasopressin-dependent antidiuresis in hyponatremia in elderly subjects. J Clin Endocrinol Metab 2001, 86: 166571.

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Heneghan C, Goldrick P, Pham H. Management of acute symptomatic hyponatremia. BMJ 1994, 308: 203.

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Goldstein CS, Braunstein S, Goldfarb S. Idiopathic syndrome of inappropriate antidiuretic hormone secretion possibly related to advanced age. Ann Intern Med 1983, 99: 1858.

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Smith JC, Siddique H, Corrall RJM. Misinterpretation of serum cortisol in a patient with hyponatremia. BMJ 2004, 328: 2156.

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Surawicz B, Mangiardi ML. Electrocardiogram in endocrine and metabolic disorders. Cardiovasc Clin 1977, 8: 24366.

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Biondi B, Palmieri EA, Lombardi G, Fazio S. Effects of subclinical thyroid dysfunction on the heart. Ann Intern Med 2002, 137: 90414.

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Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001, 344: 5019.

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Hazouard E, Piquemal R, Dequin PF, Tayoro J, Valat C, Legras A. Severe non-infectious circulatory shock related to hypopituitarism. Intensive Care Med 1999, 25: 8658.

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Al Jarallah AS. Reversible cardiomyopathy caused by an uncommon form of congenital adrenal hyperplasia. Pediatr Cardiol 2004, 25: 6756.

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Francque SM, Schwagten VM, Ysebaert DK, Van Marck EA, Beaucourt LA. Bilateral adrenal haemorrhage and acute adrenal insufficiency in a blunt abdominal trauma: a case-report and literature review. Eur J Emerg Med 2004, 11: 1647.

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Yanagi N, Maruyama T, Arita M, Kaji Y, Niho Y. Alterations in electrical and mechanical activity in Langendorff-perfused guinea pig hearts exposed to decreased external sodium concentration with or without hypotonic insult. Pathophysiology 2001, 7: 25161.

Italian Society of Endocrinology (SIE)2007

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Recommendation and review posted by Bethany Smith

Stem Cell Basics I. | stemcells.nih.gov

Stem cells have the remarkable potential to develop into many different cell types in the body during early life and growth. In addition, in many tissues they serve as a sort of internal repair system, dividing essentially without limit to replenish other cells as long as the person or animal is still alive. When a stem cell divides, each new cell has the potential either to remain a stem cell or become another type of cell with a more specialized function, such as a muscle cell, a red blood cell, or a brain cell.

Stem cells are distinguished from other cell types by two important characteristics. First, they are unspecialized cells capable of renewing themselves through cell division, sometimes after long periods of inactivity. Second, under certain physiologic or experimental conditions, they can be induced to become tissue- or organ-specific cells with special functions. In some organs, such as the gut and bone marrow, stem cells regularly divide to repair and replace worn out or damaged tissues. In other organs, however, such as the pancreas and the heart, stem cells only divide under special conditions.

Until recently, scientists primarily worked with two kinds of stem cells from animals and humans: embryonic stem cells and non-embryonic "somatic" or "adult" stem cells. The functions and characteristics of these cells will be explained in this document. Scientists discovered ways to derive embryonic stem cells from early mouse embryos more than 30 years ago, in 1981. The detailed study of the biology of mouse stem cells led to the discovery, in 1998, of a method to derive stem cells from human embryos and grow the cells in the laboratory. These cells are called human embryonic stem cells. The embryos used in these studies were created for reproductive purposes through in vitro fertilization procedures. When they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. In 2006, researchers made another breakthrough by identifying conditions that would allow some specialized adult cells to be "reprogrammed" genetically to assume a stem cell-like state. This new type of stem cell, called induced pluripotent stem cells (iPSCs), will be discussed in a later section of this document.

Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, the inner cells give rise to the entire body of the organism, including all of the many specialized cell types and organs such as the heart, lungs, skin, sperm, eggs and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease.

Given their unique regenerative abilities, stem cells offer new potentials for treating diseases such as diabetes, and heart disease. However, much work remains to be done in the laboratory and the clinic to understand how to use these cells for cell-based therapies to treat disease, which is also referred to as regenerative or reparative medicine.

Laboratory studies of stem cells enable scientists to learn about the cells essential properties and what makes them different from specialized cell types. Scientists are already using stem cells in the laboratory to screen new drugs and to develop model systems to study normal growth and identify the causes of birth defects.

Research on stem cells continues to advance knowledge about how an organism develops from a single cell and how healthy cells replace damaged cells in adult organisms. Stem cell research is one of the most fascinating areas of contemporary biology, but, as with many expanding fields of scientific inquiry, research on stem cells raises scientific questions as rapidly as it generates new discoveries.

I.Introduction|Next

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Stem Cell Basics I. | stemcells.nih.gov

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Drug may reduce female cancer patient infertility risk, according to study – Life Science Daily

Researchers recently determined that an existing drug may protect premenopausal women from infertility following cancer treatments.

A study funded by the National Institutes of Health with findings published in Genetics revealed the benefits of checkpoint protein (CHK2) in mice.

Officials said women treated for cancer with radiation or certain chemotherapy drugs are commonly rendered sterile adding women are born with a lifetime reserve of oocytes or immature eggs but those oocytes are among the most sensitive cells in the body and may be wiped out by cancer treatments.

Investigators said CHK2 functions in a pathway that eliminates oocytes with DNA damage, a natural function to protect against giving birth to offspring bearing new mutations. When they irradiated mice lacking the CHK2 gene, the oocytes survived and eventually repaired the DNA damage, with the mice birthing healthy pups.

It turns out there were pre-existing CHK2 inhibitor drugs that were developed, ironically enough, for cancer treatment, but they turned out not to be very useful for treating cancer, said John Schimenti, the papers senior author and Cornell University professor in the Departments of Biomedical Sciences and Molecular Biology and Genetics. The one major concern is that even though these irradiated oocytes led to the birth of healthy mouse pups, its conceivable that they harbor mutations that will become manifested in a generation or two because we are circumventing an evolutionarily important mechanism of genetic quality control. This needs to be investigated by genome sequencing.

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Drug may reduce female cancer patient infertility risk, according to study - Life Science Daily

Recommendation and review posted by sam

What’s Up with All the Zoo Babies? – Memphis Flyer (blog)

On Monday, the Memphis Zoo tweeted about their new baby flamingos the most recent in a long line of zoo babies we've met through the spring and summer.

Let's see ... there's been Winnie the hippo, two giraffes, a sloth, an orangutan, rare Louisiana pine snakes, a Yellow-backed Duiker, aFrancois langur, and a Spot-nosed Guenon named Grommet.

So what is going on? Has there been extra-sexy time at the zoo? Do we need to have a birds-and-the-bees talk with them? Is this all a PR stunt?

Matt Thompson, director of the zoo's Animal Programs, says that while springtime is a time for babies, reproduction at the zoo has been higher than average, and the push to get the public involved has also been higher than average.

The birth rate is all part of a bigger plan, bigger than the Memphis Zoo.

"Theres different programs for different species of animals Species Survival Plan (SSP)," Thompson explains. "For instance, there is a sloth SSP, and a hippo SSP and a giraffe SSP. What that is is a collection of zoo professionals, very smart people who analyze and look at the genetics of different lines of animals, so if the Memphis Zoo, for example, has a certain genetic line and a certain female that would really work well at the Indianapolis Zoo, they might put out a recommendation.They work their hardest to keep the gene pool healthy to prevent inbreeding and that kind of thing."

A prime example of the SSP at work is one little hippo named Winnie.

"Her mother and father both came to us from Disneys Animal Kingdom and they came as a result of an SSP recommendation. It was kind of win-win because Disney was getting a little full with hippos as you can imagine, hippos take up a lot of room," Thompson says. "We were building a new hippo exhibit and we needed a hippo or two, so we reached out to the SSP and they made recommendations based on genetics and thats how we wound up with these animals."

As for birth control, Thompson says it ranges from oral contraceptives to physically pulling the animals apart. And there are accidents. "Sure, just like with people, there are surprises. Not many, but every now and then," says Thompson.

Thompson says there are over 500 SSPs that cover all sorts of animals from pandas to lizards. The coordinator for the SSP for Louisiana Pine snakes, a rare species, is based at the Memphis Zoo.

Some of the toughest animals to breed are amphibians, and, yep, pandas.

"Its not for lack of trying," Thompson says. "Pandas are challenging because they ovulate about once a year and you have about a three-day window for them to get pregnant. Theyve got to tell you when they are ready [and] thats very challenging."

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What's Up with All the Zoo Babies? - Memphis Flyer (blog)

Recommendation and review posted by simmons

Drug may curb female infertility from cancer treatments – Medical Xpress

A mouse ovary with proteins specific to oocytes labelled in red and yellow. The study reports that culturing such ovaries in the presence of a drug that inhibits DNA damage checkpoint enzymes protects the oocytes from lethal levels of radiation that would normally kill the entire oocyte reserve (small oocytes in picture). Credit: Schimenti Lab, Cornell University

An existing drug may one day protect premenopausal women from life-altering infertility that commonly follows cancer treatments, according to a new study.

Women who are treated for cancer with radiation or certain chemotherapy drugs are commonly rendered sterile. According to a 2006 study from Weill Cornell Medicine, nearly 40 percent of all female breast cancer survivors experience premature ovarian failure, in which they lose normal function of their ovaries and often become infertile.

Women are born with a lifetime reserve of oocytes, or immature eggs, but those oocytes are among the most sensitive cells in the body and may be wiped out by such cancer treatments.

The current study, published in the journal Genetics, was led by John Schimenti, Cornell University professor in the Departments of Biomedical Sciences and Molecular Biology and Genetics. The study builds on his 2014 research that identified a so-called checkpoint protein (CHK2) that becomes activated when oocytes are damaged by radiation.

CHK2 functions in a pathway that eliminates oocytes with DNA damage, a natural function to protect against giving birth to offspring bearing new mutations. When the researchers irradiated mice lacking the CHK2 gene, the oocytes survived, eventually repaired the DNA damage, and the mice gave birth to healthy pups.

The new study explored whether the checkpoint 2 pathway could be chemically inhibited.

"It turns out there were pre-existing CHK2 inhibitor drugs that were developed, ironically enough, for cancer treatment, but they turned out not to be very useful for treating cancer," said Schimenti, the paper's senior author. Vera Rinaldi, a graduate student in Schimenti's lab, is the paper's first author. "By giving mice the inhibitor drug, a small molecule, it essentially mimicked the knockout of the checkpoint gene," Rinaldi said.

By inhibiting the checkpoint pathway, the oocytes were not killed by radiation and remained fertile, enabling birth of normal pups.

"The one major concern," Schimenti said, "is that even though these irradiated oocytes led to the birth of healthy mouse pups, it's conceivable that they harbor mutations that will become manifested in a generation or two, because we are circumventing an evolutionarily important mechanism of genetic quality control. This needs to be investigated by genome sequencing."

When doctors recognize the need for oocyte-damaging cancer treatments, women may have their oocytes or even ovarian tissue removed and frozen, but this practice delays treatment. Also, when women run out of oocytes, women's bodies naturally undergo menopause, as their hormonal systems shift.

"That is a serious dilemma and emotional issue," Schimenti said, "when you layer a cancer diagnosis on top of the prospect of having permanent life-altering effects as a result of chemotherapy, and must face the urgent decision of delaying treatment to freeze oocytes at the risk of one's own life."

The study sets a precedent for co-administering this or related drugs and starting cancer therapy simultaneously, though such interventions would first require lengthy human trials.

"While humans and mice have different physiologies, and there is much work to be done to determine safe and effective dosages for people, it is clear that we have the proof of principle for this approach," Schimenti said.

Explore further: Protein that culls damaged eggs identified, infertility reversed

Journal reference: Genetics

Provided by: Cornell University

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Drug may curb female infertility from cancer treatments - Medical Xpress

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