Target Health Presenting at BIO
Target Health is pleased to announce that Dr. Jules T. Mitchel will be presenting at the 2013 BIO International Convention a panel entitled “Clinical Trials Modernization: The Promises and Challenges of Risk-Based Approaches to Monitoring. “ The panel will take in Chicago on Wednesday, April 24, 2013 between 10:30-11:30.
Please let us know if you will be at BIO
Session Summary: For many pharmaceutical and biotechnology companies, the predominant mechanism for monitoring the progress of clinical investigations involves frequent visits to each clinical investigator site to evaluate study conduct and review data for each enrolled subject. However, general guidelines for Good Clinical Practice (GCP), FDA regulation, and International Conference on Harmonization (ICH) guideline E6 provide substantial latitude regarding the extent and nature of monitoring. Implementation of a risk-based approach to clinical trial monitoring that leverages centralized data monitoring through electronic data capture systems can lead to significant efficiencies for clinical trial sponsors. This session will evaluate current thinking, including perceived barriers and emerging opportunities, from three stakeholder groups: industry sponsors of clinical research, clinical research organizations, and regulatory authorities.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com
Medicinal Mushrooms and Fungi
Dr. Paul E. Stamets, renowned mycologist, with Fomitopsis officinalis
Medicinal mushrooms and mushroom extracts are used worldwide to fight cancer and enhance and modulate 1) ___ response. Lentinula edodes (shiitake), Grifola frondosa (maitake), Ganoderma lucidum (mannentake), and Cordyceps have a history of medicinal use for millennia in parts of Asia. Research has indicated mushrooms have possible anti-cancer, antiviral, anti-inflammatory and liver protective activities. Following, are some of the most well-researched anti-cancer mushrooms rich in polysaccharides and beta glucans, the primary active immune-enhancing constituents.
Medicinal mushrooms are mushrooms used or studied as possible treatments for disease. Research indicates mushrooms have potential antiviral, antimicrobial, anticancer, antihyperglycemic, cardioprotective, and anti-inflammatory activities. The mushroom isolate pleuromutilin was used to create the antibiotic retapamulin. The Turkey tail mushroom isolates lentinan, PSK, and PSP, are licensed pharmaceuticals in certain countries. 2) ___ that do not produce mushrooms, are currently being used to manufacture paclitaxel, and were the original source of the first beta-lactam antibiotics, statins, immunosuppressants like ciclosporin, and antifungals like griseofulvin.
Mushroom extracts have antimicrobial, antiviral, and nematicidal, activities in vitro. Antibiotics retapamulin, tiamulin, and valnemulin, are derivatives of the mushroom isolate pleuromutilin. The immunosuppressants ciclosporin, mycophenolic acid, etc, the antibiotics penicillin, cephalosporins, fusafungine, etc and the antifungals griseofulvin, echinocandins, strobilurin, etc, were discovered in fungi that do not produce mushrooms. The fungal isolate codinaeopsin, has activity against malaria protozoa with an IC50 of 2.3µg/mL.
Red yeast rice is made by fermenting normal white rice with the mold Monascus purpureus
Cholesterol biosynthesis inhibitors: Several Pleurotus species create the statin lovastatin. A recent study found an unidentified statin in Agaricus bisporus. The pravastatin precursor mevastatin, was discovered in a Penicillium mold. The red yeast rice fungus Monascus purpureus creates lovastatin, mevastatin, and the simvastatin precursor, monacolin J.
Anticancer activities: Lentinan, PSK, and PSP, are registered anticancer immunologic adjuvants in certain countries, Japan in particular. Irofulven and acylfulvene are anticancer compounds derived from the mushroom isolate illudin S. Clavariadelphus truncatus creates the FTI clavaric acid.
BMS manufactures paclitaxel using Penicillium raistrickii and plant cell fermentation (PCF). Endophytic fungi can synthesize podophyllotoxin and camptothecin, precursors to etoposide, teniposide, topotecan, and irinotecan.
Reishi mushroom is a 3) ___ that some people describe as “tough” and “woody” with a bitter taste. The fruiting body (above-ground part) and mycelium (filaments connecting a group of mushrooms) are used as medicine.
Reishi mushroom is used for 4) ___ the immune system; viral infections such as the flu (influenza), swine flu, and avian flu; lung conditions including asthma and bronchitis; heart disease and contributing conditions such as high blood pressure and high cholesterol; kidney disease; cancer; and liver disease. It is also used for HIV/AIDS, altitude sickness, chronic fatigue syndrome (CFS), trouble sleeping (insomnia), stomach ulcers, poisoning, and herpes pain. Other uses include reducing stress and preventing fatigue.
In combination with other herbs, reishi mushroom is used to treat prostate 5) ___. Reishi mushroom contains chemicals that seem to have a variety of potentially beneficial effects, including activity against tumors (cancer) and beneficial effects on the immune system. Be sure to follow relevant directions on product labels and consult your pharmacist or physician or other healthcare professional before using.
Dr. Paul E. Stamets has been a dedicated 6) ___ for over thirty years. His newest book is Mycelium Running: How Mushrooms Can Help Save The World. Dr. Stamets sees the ancient Old Growth forests of the Pacific Northwest as a resource of incalculable value, especially in terms of its fungal genome. The mushroom genome is becoming increasingly threatened, by climate change and lack of human care in preserving these irreplaceable areas. At the current rates of extinctions, this last refuge of the mushroom 7) ___ should be at the top of the list of priorities for mycologists, environmentalists and government.
George Hudler, a professor in Cornell University’s Department of Plant Pathology and Plant-Microbe Biology, thinks there’s a lot of potential for mushrooms’ healing properties. “In the next 10 years, we’ll just see an incredible expansion of our awareness of chemicals in mushrooms, hopefully even their use in conventional 8) ___,” says Hudler. In Hudler’s view, Shiitake mushrooms have the longest track record of research in health benefits. Chemicals in them may stimulate the immune system and lower 9) ___. White button mushrooms found in salad are also high in vitamin B complex, and the antioxidant properties of mushrooms could protect against heart disease and cancer.
Last year (2012) the Medical School at the University of Minnesota, conducted a Phase 1 Clinical Trial of Trametes versicolor (Tv) in Women with Breast Cancer, which was published in the ISRN Oncology Journal. The study showed that Turkey tail mushrooms can augment conventional therapies for treating 10) ___ cancer by increasing NK and CD8+T cell activity. The authors concluded: The phase I data suggest that Tv is a safe immunotherapy for breast cancer patients that may correct radiotherapy-related immune defects. Based on these findings, Tv mushroom therapy orally administered in the postradiotherapy setting may enhance lymphocyte numbers and NK cell tumoricidal activity.
Turkey Tail Mushroom
Due to its long history of therapeutic use, however, turkey tail prepared and packaged as an immune therapy drug is unlikely to be patentable, deterring big pharmas from conducting costly 11) ___ studies. Typically, the longer the historical use of natural medicines for treating an ailment, the less likely derivatized drugs from these natural products will be patentable. To fill this research gap, the NIH established The National Center for Complementary and Alternative Medicine (www.nccam.nih.gov), which funded and oversaw this study. NIH’s interest is not surprising — more than 70% of new drugs are estimated to originate from natural sources.
The natural killer cells promoted by ingesting Turkey tails also target virally-infected cells. Moreover, Turkey tail mycelium excretes strong antiviral compounds, specifically active against Human papillomavirus (HPV), which causes cervical cancer, and hepatitis C virus (HEP-C), which causes 12) ___ cancer. Viruses that induce cancer are called “oncoviruses.” The virus-to-cancer connection is where medicinal mushrooms offer unique opportunities for medical research. The current thinking amongst many researchers is that Turkey tails and other medicinal mushrooms lessen the odds of getting cancer by reducing causal co-factors such as oncoviruses.
Turkey tail is renowned in Asia as a source for cancer therapy. The Japanese company Kureha first screened many polypore mushrooms and found that Turkey tails produced a profound immune 13) ___, a discovery confirmed by many other subsequent studies. The extraction method led to marketing “PSK” (polysaccharide Krestin®) and later “PSP,” both protein-bound polysaccharides. PSK became recognized as a cancer drug in Japan and approved under somewhat controversial conditions.
Since this Turkey tail mycelium is presented in its unaltered form, it qualifies as a FDA approved “nutraceutical” ingredient. In this form, it can be advertised in the United States and Canada as a supplement to “support the immune system.” Getting this 14) ___ on the shelves of health food stores lets physicians and patients access another tool to battle cancer. Enhancing the population and activity of NK cells and other lymphocytes and ensuring antioxidant effects against free radicals can both limit damage to healthy cells and reduce inflammation. These are some of the distinct advantages to using mushrooms in cancer therapy. Nature is a numbers game, and Turkey tail helps tilt the balance in the complex battle to overcome cancer.
Always consult your doctor before using mushrooms for health (strengthening the immune system) or medical purposes
ANSWERS: 1) immune; 2) Fungi; 3) fungus; 4) boosting; 5) cancer; 6) mycologist; 7) genome; 8) medicine; 9) cholesterol; 10) breast; 11) clinical; 12) liver; 13) response; 14) nutraceutical
Paul Stamets On Mushrooms
Paul Stamets Gives TEDMED Talk
Paul Stamets Q & A at TEDMED
Paul Stamets Mushrooms Can Help Save the World
Medicinal Mushrooms and Fungi
Mushrooms, fermentation molds, mycelia, and lichens, have a history of medicinal use spanning millennia. The mushroom with the longest record of medicinal use in China, Ganoderma lucidum, is known in Chinese as ling zhi ( “spirit plant “), and in Japanese as mannentake ( “10,000 year mushroom “). In ancient Japan, Grifola frondosa was worth its weight in silver. Inonotus obliquus was used in Russia as early as the 16th century, and its medicinal properties were described by Nobel laureate Alexandr Solzhenitsyn. Ancient Egyptians considered mushrooms food for royalty. The Hadith states, “Truffles (Terfeziaceae) are manna which Allah sent to the people of Israel through Moses, and its juice is a medicine for the eyes. “
Traditionally, our ancestors boiled mushrooms in water to make a soothing tea. Boiling served several purposes: killing contaminants, softening the flesh, and extracting the rich soluble polysaccharides. The mushrooms — called fruiting bodies by mycologists — are made of densely-compacted cobwebby cells called mycelium. With modern laboratory methods of cell tissue culture, the large-scale production of mycelium brought to light a whole new array of medicinal preparations. In this article, the history of a few of the best known medicinal mushrooms/fungi will be mentioned.
The Shitake (Lentinula edodes) Black Forest Tree Mushroom or Xiang Gu (Fragrant Mushroom) is a tender and tasty mushroom found in many Asian cuisines. (see first photo, above) It is considered both a delicacy and a medicinal mushroom. Shitake contains a glucan called AHCC (Active Hexose Correlated Compound) and is widely used in alternative and complementary treatment of cancer in Japan due to its immune-enhancing functions. Lentinan, a compound found in Shitake, is used as an intravenous anti-cancer drug with antitumor properties. Clinical studies have associated lentinan with a higher survival rate, higher quality of life and lower recurrence of cancer.
Otzi the Iceman
Otzi the Iceman, a well-preserved natural mummy of a Chalcolithic (Copper Age) man from about 3300 BCE, was found in 1991 in the Schnalstal glacier in the Otztal Alps, near Hauslabjoch on the border between Austria and Italy. On his body was found a sack containing various items, among them two tree mushroom varieties, Fomes fomentarius and Piptoporus betulinus (photos below), known to have antibacterial properties.
Carried by Otzi the Iceman, Fomes fomentarius extracts have immunomodulatory activity in vivo, and anticancer activity in vitro.
Piptoporus betulinus (Birch polypore)
Carried by Otzi the Iceman, a hydroquinone isolated from Piptoporus betulinus inhibits a matrix metalloproteinase (MMP).
Coriolus versicolor (Trametes versicolor) “Turkey tail Mushroon “ Yun Zhi
Coriolus versicolor is one of the most well-researched medicinal mushrooms in the world. It is a biological response modifier. Turkey tail mushrooms have been used to treat various maladies for hundreds of years in Asia, Europe, and by indigenous peoples in North America. Studies show that it improves survival rates and acts an immune modulator with immune stimulating and anti-tumor properties. Some studies show that it can enhance the effects of chemotherapy cancer treatment and reduce the side effects of radiation therapy.
Records of turkey tail brewed as medicinal tea date from the early 15th century, during the Ming Dynasty in China. Our ancestors certainly encountered them and most likely explored their uses long before written history. Since the late 1960s, researchers in Japan have focused on how turkey tail benefits human health and how extracts of turkey tail can boost the immune system. In many Asian cultures, turkey tails’ incurving cloud forms symbolize longevity and health, spiritual attunement and infinity.
Grifola frondosa (Maitake)
Grifola frondosa studies indicate potential anticancer and antihyperglycemic activities. D-fraction, MD-fraction, SX-fraction, and grifolan, are isolates of Grifola frondosa. Maitake Grifola frondosa (Cloud Mushroom Hui Shu Hua) is used in traditional Chinese and Japanese medicine to enhance the immune system. It is one of the major mushrooms in Japanese cooking. Studies have shown that it can enhance both the innate immune response to fight infections as well as adaptive immune response conferring long-term immune enhancement. Maitake also protects cells with its antioxidant properties and decreases the inflammatory factor COX2 enzyme so common in cancer physiology. Studies have also shown that Maitake has potential anti-metastatic properties inhibiting the proliferation and spread of cancer.
Inonotus obliquus is the medicinal mushroom promoted by Alexandr Solzhenitsyn and used in Russia from as far back as the 16th Century to present.
Chaga Inonotus obliquus (Black Tree Fungus) has been recorded as a folk medicine and the botanical medicine of the Eastern European countries as a remedy for cancer, gastritis,ulcers, and tuberculosis of the bones. As early as in the 16th century, chaga was used as an effective folk medicine in Russia and Northern Europe to treat several human malicious tumors and other diseases in the absence of any unacceptable toxic side effects.
Chaga has been studied as a potential anti-cancer agent, which contains betulin, a precursor to betulinic acid, which has been shown to inhibit the cancer-promoting enzyme topoisomerase. Betulinic acid has been found to be active against skin, brain, ovarian and head and neck cancers by promoting apoptosis, or the natural progression of programmed cell death. Cancer cells do not go through this natural life cycle and become immortalized and do not die. Today, there are ongoing clinical trials in Eastern Europe to determine the uses for the chaga mushroom.
The Hadith states, “Truffles (Terfeziaceae) are manna which Allah sent to the people of Israel through Moses, and its juice is a medicine for the eyes. “ Interestingly, “hadith “ is an Arabic noun which means an interesting piece of information conveyed either in a small quantity or large.
Ganoderma lucidum (Ling zhi, mannentake, reishi)
Ganoderma lucidum is the mushroom with the longest record of medicinal use. Ganoderma lucidum is thought to be useful against a variety of ailments. Over 100 lanostane-type triterpenoids, including ganoderic acids, have been isolated from Ganoderma lucidum. Ganoderma Reishi Mushroom Ling Zhi, Mannentake, “The Mushroom of Immortality “ is one of the great longevity tonics of Chinese Medicine used in cancer treatment in Traditional and Modern Chinese Medicine to improve vitality, strength and stamina and to prolong life. Reishi enhances immune response, alleviates chemotherapy side effects such as nausea and kidney damage and protects cellular DNA by raising antioxidant capacity.
Ophiocordyceps sinensis (left) growing out of the head of a dead caterpillar
Cordyceps sinensis Chinese Caterpillar Fungus Dong Chong Xia Cao
Cordyceps acts an immune stimulator by raising cancer- and virus-fighting T Cells and Natural Killer Cells and prolongs the life of white blood cells, improving resolution of infections. It has demonstrated anti-tumor properties and also protects the kidneys from chemotherapy side effects. It is one of the most widely used tonics in anti-cancer formulas in Chinese Medicine. Ophiocordyceps sinensis is a fungus that parasitizes larvae of ghost moths and produces a fruiting body valued as an herbal remedy. The fungus germinates in the living larva, kills and mummifies it, and then the stalk-like fruiting body emerges from the corpse. It is known in English colloquially as caterpillar fungus, or by its more prominent foreign names: yartsa gunbu or yatsa gunbu (Tibetan), or Dong chong xia cao (literally “winter worm, summer grass “). O. sinensis is known in the West as a medicinal mushroom, and its use has a long history in Traditional Chinese medicine as well as Traditional Tibetan medicine. The hand-collected fungus-caterpillar combination is valued by herbalists and as a status symbol, it is used as an aphrodisiac and treatment for ailments such as fatigue and cancer, although such use is mainly based on traditional Chinese medicine and anecdote. Recent research however seems to indicate a variety of beneficial effects in animal testing, including increased physical endurance through heightened ATP production in rats.
People With Serious Mental Illnesses Can Lose Weight
Over 80% of people with serious mental illnesses are overweight or obese, which contributes to them dying at three times the rate of the overall population. They succumb mostly to the same things the rest of the population experiences-cardiovascular disease, diabetes and cancer. Although antipsychotic medications increase appetite and cause weight gain in these patients, it is not the only culprit. Like the general population, sedentary lifestyle and poor diet also play a part. Lifestyle modifications such as diet and exercise should work for these patients, yet they are often left out of weight loss studies. Other factors that preclude people with serious mental illnesses from losing weight include memory impairments or residual psychiatric symptoms that impede learning and adopting new behaviors such as counting calories. Socioeconomics are also a factor as many can’t afford or can’t get to physical activity programs like fitness gyms. Some patients additionally suffer from social phobia or have poor social interactions, and are simply afraid to work out in a public area.
According to an article published online in The New England Journal of Medicine (21 March 2013), it was shown that people with serious mental illnesses such as schizophrenia, bipolar disorder and major depression can lose weight and keep it off through a modified lifestyle intervention program. As a result, this study could usher in new forms of weight loss treatment for people with serious mental illness.
The study attempted to solve these issues by bringing the gyms and nutritionists to places most of these patients frequent — psychiatric rehabilitation outpatient programs. Under the trial name ACHIEVE, 291 participants in 10 rehab centers around Maryland were randomized to receive the usual care , consisting of nutrition and physical activity information, or six months of intensive intervention consisting of exercise classes three times a week along with individual or group weight loss classes once a week. Both groups were followed for an additional year, during which the weight loss classes of the intervention arm tapered down but the exercise classes remained constant. The intervention arm included goals such as reducing caloric intake by avoiding sugar-sweetened beverages and junk food; eating five servings of fruits and vegetables daily; choosing smaller portions and healthy snacks; and moderate intensity aerobic exercise.
Results showed that participants in the specially tailored weight loss program lost seven pounds more than the controls — and continued to lose weight and did not regain, despite the reduced frequency of classes and counseling sessions. In contrast, the general population tends to experience peak weight loss in the first six months and then rebound and gain part or all of their weight back.
On average, each participant was on three psychotropic medications, with half on lithium or mood stabilizers, all known to cause weight gain. But no matter what they were on, they lost the weight.
Delay in Shifting Gaze Linked To Early Brain Development in Autism
Efficiently shifting attention early in infancy is thought to be important for later social and cognitive development. Split-second delays, the researchers suggested, could be a precursor to such well known symptoms of autism as difficulty making eye contact or following a parent’s pointing finger, problems that generally emerge after a child turns 1. Typically, autism spectrum disorder (ASD) is not diagnosed until after 3 or 4 years of age.
According to a study published online in American Journal of Psychiatry (20 March 2013), at 7 months of age, children who are later diagnosed with autism take a split second longer to shift their gaze during a task measuring eye movements and visual attention than do typically developing infants of the same age. The difference between the groups’ test results was 25 to 50 milliseconds on average, too brief to be detected in social interactions with an infant. However, the study showed that this measurable delay could be accounted for by differences in the structure and organization of actively developing neurological circuits of a child’s brain.
According to the authors, this study ties a difference in reaction times to differences in the developing brain, which may shape the way babies take in and respond to their environment in more noticeable ways over time. The authors added that the brain’s pathways for communication are forming rapidly in early infancy, and small differences at this stage could foretell greater difference at a later age. “
To measure shifts in gaze and visual attention, the study used sophisticated eye tracking equipment to capture the precise timing of eye movements. The infants sat on their parent’s laps and watched images appear on a computer monitor. The test procedure used in the study is known as the gap/overlap task. In one part of the test, an image would appear in the center of the screen to attract the infant’s gaze, and would then disappear. After a brief delay, or gap, another image would appear at the edge of the screen. In another part of the test, the central image remained on the screen, and an image appeared at the periphery of the screen. The authors measured the time it took infants to initiate an eye movement to the image in the periphery. In addition to the eye tracking task, the 7-month-old infants took part in a type of magnetic resonance brain imaging called diffusion weighted imaging, which measures the organization of neural circuits in the brain.
Since 57 infants had an older sibling diagnosed with autism, they were considered at higher risk for developing autism themselves. The study also included 40 infants who did not have an older sibling with autism and so were considered at low risk for developing autism. All of the children returned to the study facility after their second birthdays for clinical assessments. By this time, 16 of the high-risk children were classified as having ASD. Based on the classification during the clinical assessment visit, the authors compared the brain imaging data and the eye tracking data collected at 7 months across three groups:
1. Children with an older sibling with ASD who themselves were classified with ASD (high-risk positive)
2. Children with an older sibling with ASD who were not classified with ASD (high-risk negative)
3. Children who did not have an older sibling with ASD (low risk)
During the overlap condition of the eye tracking task, in which presentation of the central image overlapped with the appearance of the image at the edge of the screen, the study found a notable difference in the time it took for the high-risk positive infants to shift their gaze, compared to the other groups of infants. Evidence was uncovered evidence that the functioning of a key brain structure may account for the differences in gaze shifting between the groups. The brain structure is called the splenium of the corpus callosum and is considered to be an important neural connection between the two hemispheres of the brain.
In the low-risk infants, it was found that the speed with which the infants shifted their gaze was closely associated with the size of the splenium. The greater the size of the splenium, the more rapidly the infants were able to switch their gaze. However, in the infants who later were found to have autism, no correlation was found between splenium size and the speed at which an infant shifted gaze. The authors theorized that the differences in gaze shifting between the two groups may not be due directly to differences in the splenium between the groups, but to differences in a brain circuit that connects the splenium to visual areas of the brain.
According to the authors, ultimately, differences in gaze detected at 7 months of age might help doctors identify children likely to develop autism later on and by refining the gaze test and coupling it with other assessments, there may be the ability to improve the identification of ASD in the first year of life.
An image depicting the splenium of the corpus callosum is available online.
Effects of Enobosarm on Muscle Wasting and Physical Function in Cancer
Muscle wasting is a common cancer related symptom which can begin early in the course of a patient’s malignancy resulting in decline in physical function and other detrimental clinical consequences. Muscle wasting and muscle weakness are also side effects of many chemotherapy drugs. There are no drugs approved for the prevention and treatment of muscle wasting in patients with cancer. At diagnosis, approximately 50% of advanced non-small cell lung cancer (NSCLC) patients have severe muscle loss, and approximately 70% of these patients will lose muscle before death. Muscle weakness and functional limitations are highly prevalent, with 88% of NSCLC patients reporting difficulty climbing stairs, lifting and carrying 10 lbs, walking a quarter mile, or stooping, crouching or kneeling. Muscle loss is a predictor of performance status, tolerability to cancer treatment, progression free survival and overall survival. Limitations in physical function predict the ability of a NSCLC patient to tolerate chemotherapy, and patients with functional limitations are less likely to be offered treatment. Functional status is also a predictor of survival.
The following describes the results of a randomized clinical trial of Enobosarm (Ostarine®; GTx-024), an oral selective androgen receptor modulator that GTx is developing for the prevention and treatment of muscle wasting in patients with non-small cell lung cancer. The study was published online in The Lancet Oncology (14 March 2013).
The study enrolled male (>45 years) and female (postmenopausal) patients with cancer who were not obese and who had at least 2% weight loss in the previous 6 months. Participants were randomly assigned (1:1:1 ratio, by computer generated list, block size three, stratified by cancer type) to receive once-daily oral enobosarm 1 mg, 3 mg, or placebo for up to 113 days. The primary endpoint was change in total lean body mass from baseline, assessed by dual-energy x-ray absorptiometry.
Enrolment started on July 3, 2007, and the last patient completed the trial on Aug 1, 2008. 159 patients were analysed for safety (placebo, n=52; enobosarm 1 mg, n=53; enobosarm 3 mg, n=54). The evaluable efficacy population included 100 participants (placebo, n=34; enobosarm 1 mg, n=32; enobosarm 3 mg, n=34). Compared with baseline, significant increases in total lean body mass by day 113 or end of study were noted in both enobosarm groups (enobosarm 1 mg median 1.5 kg; p=0·0012); enodosarm 3 mg 1.0 kg; p=0·046). Change in total lean body mass within the placebo group (median 0·02 kg) was not significant (p=0.88).
According to the authors, cancer cachexia is an unmet medical need and the data suggest that use of enobosarm might lead to improvements in lean body mass, without the toxic effects associated with androgens and progestational agents.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area
FDA Approves First Botulism Antitoxin for Use in Neutralizing All Seven Known Botulinum Nerve Toxin Serotypes
Botulism is a rare but serious illness caused by ingesting or inhaling a botulinum nerve toxin, or by exposure arising from toxin secreted by Clostridium bacteria in a wound or the intestine. Patients with botulism develop severe muscle weakness that progresses from the head to the rest of the body. If untreated, the illness may progress to total loss of muscle function and inability to breathe. This heptavalent antitoxin is the only product available for the treatment of botulism in adults, and for cases of infant botulism caused by nerve toxins other than types A and B.
The FDA has approved Botulism Antitoxin Heptavalent (A, B, C, D, E, F, G)-(Equine) to treat patients showing signs of botulism following documented or suspected exposure to botulinum neurotoxin. The product is derived from horse plasma and contains a mixture of antibody fragments that neutralize all of the seven botulinum nerve toxin serotypes known to cause botulism. The product to be stored in the Strategic National Stockpile for emergency preparedness and responses
The effectiveness of the product was studied in animals because it was not feasible or ethical to conduct efficacy studies in humans. These results provided substantial evidence that the antitoxin is reasonably likely to benefit humans with botulism. Under the FDA’s Animal Rule, the agency may approve a biological product when the results of well-controlled animal studies demonstrate that the product is reasonably likely to be effective, in addition to establishing safety in humans. This is the first approval of a plasma derivative using the Animal Rule.
The safety of the product was tested in 40 healthy human volunteers and also monitored in 228 patients who received the antitoxin experimentally under a botulism treatment program administered by the Centers for Disease Control and Prevention (CDC). The most commonly observed side effects were headache, fever, chills, rash, itching and nausea. Since the product is manufactured from horse plasma it may cause allergic reactions and a delayed hypersensitivity reaction (serum sickness) in people sensitive to horse proteins.
The product is manufactured by Cangene Corporation, based in Winnipeg, Canada. It was developed with support from the Biomedical Advanced Research and Development Authority within the U.S. Department of Health and Human Services’ Office of the Assistant Secretary for Preparedness and Response. The antitoxin will be maintained in the Strategic National Stockpile and distributed through the CDC’s Drug Service.
Glen Park’s Wild Mushroom Roast en Croute
1 medium onion (~1 1/4 Cup) diced
2 medium carrots diced (~1 Cup)
1 med-large bulb of fennel diced (~2 Cup)
3 large cloves of garlic, crushed or minced
Water for sautéing
2 Cups thinly sliced crimini mushrooms
2 Cups chopped shiitake mushrooms
1 oz dry wild mushrooms, preferably chanterelle and porcini, rehydrated according to package
2 Cups panko bread crumbs
1 Cups roasted cashews, ground finely in the food processor (but not too finely – you do want a little texture)
2 Tablespoon minced fresh sage
2 Tablespoon minced fresh thyme
1 teaspoon garlic powder
¾ teaspoon hot paprika
2 teaspoons salt & pepper to taste
1/2 Cup vegetable broth
1 Tablespoon soy sauce
1/2 Cup dry sherry (or another 1/2 Cup vegetable broth)
1 Tablespoon tomato paste
1 thawed puff pastry sheet – keep refrigerated until use
Extra virgin olive oil – just enough to brush on top of the puff pastry
Sesame seeds for sprinkling
Coarse salt for sprinkling (optional)
Fennel pollen for sprinkling (optional, but insanely delicious and highly recommended!)
Preheat oven to 400 °F. Get out a baking sheet and cover it with a piece of parchment paper.
Combine the mushrooms and sauté over medium-high heat in a nonstick skillet until soft. Make sure the heat is high enough that most of the liquid evaporates (but not all – you don’t want them to burn or dry out). Pour mushroom mixture into a large mixing bowl and set aside.
Sauté onion, carrot and fennel (in the same nonstick skillet that you used for the mushrooms) in 2 Tbsp water for 15-20 minutes until the onion is soft and the carrot and fennel are cooked but still sort of firm. After 10 min, add the garlic. Stir frequently so that the garlic does not burn. After the veggies are done, pour them into the large mixing bowl with the mushrooms. Note: You can cook the mushrooms and veggies together if you are crunched for time. I like to cook them separately.
Add the panko, cashews, sage, thyme, garlic powder, hot paprika or cayenne, salt and pepper to the bowl containing the mushrooms and veggies. Mix well.
Whisk together the broth, sherry, and tomato paste in a small bowl. Pour into the large mixing bowl with the rest of the ingredients.
Get the puff pastry sheet out of the refrigerator. Unwrap and unfold the sheet out onto a lightly floured counter. Sprinkle the sheet with flour and roll it out a little with a rolling pin, to make it slightly larger. You have a lot of stuffing to put in there! Be gentle with the pastry though – you don’t want to tear it. Lay the pastry sheet on the parchment paper that is on the baking sheet. Start piling in the stuffing along the center section (lengthwise) until you’ve got it all in there. Form the stuffing into a cylinder shape with your hands and wrap the puff pastry sheet all around it. With a pastry brush, brush olive oil over the outside of the pastry sheet and sprinkle sesame seeds and coarse or flake salt on top (and fennel pollen if you are lucky enough to have it).
Bake at 4000F for 20 minutes and then turn down the heat and bake for 30 more minutes at 3500F, or until golden brown and it smells so good that you can’t wait any longer to eat it!
Also on the plate (photo) is a nice veggie slaw.
With your mandolin, slice match-size pieces of favorite veggies add some lemon, olive oil and seasoning and you have a delicious colorful accompaniment for the Mushroom Roast en Croute. Add baked (with agave) sweet potato and you have a really winning meal. If you want a mushroom puree or gravy to serve over the Mushroom Roast en Croute, take a look at the recipes given. We’re partial to icy Sauvignon Blanc with all of these delicious vegetable creations.
Sherry Mushrooms & Mushroom Puree
Cremini, Shiitake, Oyster and Porcini Mushrooms are Healthy & Have Great Flavor. The photo shows Cremini Mushrooms, which were used in both recipes, below
3 pounds cremini or shitaki mushrooms, trimmed
1 Onion, chopped well
1 Tablespoon extra-virgin olive oil
1 cup cream sherry
8 cloves garlic, minced
2 Tablespoons lemon juice
1/2 teaspoon kosher salt (optional)
2 Tablespoons minced fresh parsley
Freshly ground pepper, to taste
2/3 cup fresh cilantro, chopped
1. Clean mushrooms (do not wash) by wiping with clean cloth and cut in half (or quarters if large).
2. Heat oil in a large skillet or Dutch oven over medium-high heat. Add mushrooms, garlic, parsley, cilantro and onions and cook, stirring, for 10 minutes.
3. Stir in sherry and continue cooking, stirring occasionally, for no more than10 to 14 minutes. Stir in lemon juice and season with salt (optional) and pepper to your taste. Save some chopped greens for garnish.
4. Serve on jasmine rice
Simply prepare the above recipe and put into food processor and pulse the mushrooms until they are smooth and pureed. Depending on the size of your food processor, you may have to pulse the mushrooms in stages. These pureed mushrooms can be used as a sauce over rice, or use for other recipes calling for pureed mushrooms, like the Mushroom Gravy recipe, below.
Smooth Mushroom Gravy
2 tablespoons Canola oil
1 Onion, chopped fine
2 garlic cloves, juiced
Pinch Kosher salt
Pinch black pepper (or grind to your taste)
1 pint of no-fat sour cream
1/2 cup Cream Sherry wine
2 cups chicken stock or veggie broth
2 Tablespoons almond flour
1 or 2 cups mushroom puree
1 or 2 drops of Worchester sauce
1. Add the Canola oil in a large frying pan over medium heat. Add the onions, season with salt and pepper, just a few drops of Worchester sauce and cook.
2. Add the almond flour and whisk constantly, for about 1 minute. Increase the heat to medium high, add the garlic juice, and cook until the mixture thickens, about 1 minute.
3. Add the Cream sherry and stir it in well.
4. Add the mushroom puree and stir it in well.
5. Whisk in the chicken stock or broth and no-fat sour cream and bring to a simmer. Reduce the heat to medium and simmer, stirring occasionally, until slightly reduced and thick enough to coat the back of a spoon, about 10 minutes. If your gravy isn’t thick enough, add 1 teaspoon slowly, while mixing, of agar-agar. Let it stand for a while. The gravy will thicken. If you need thinner gravy, simply add a tiny bit at a time, while stirring the whole time, some chicken broth.