Vitamin A Compound Might Aid in Colon Cancer Fight

In continuation of my update on Retinoic acid

Retinoic acid, a compound derived in the body from vitamin A, might have a role in suppressing colon cancer, new animal research suggests.

"Retinoic acid has been known for years to be involved in suppressing inflammation in the intestine," said study senior author Dr. Edgar Engleman, professor of pathology and medicine at Stanford University School of Medicine in Palo Alto, Calif.

Meanwhile, the development of colon cancer has been linked to inflammation. For example, inflammatory bowel disease, such as ulcerative colitis, has been associated with colon cancer, he said in a university news release.

"We wanted to connect the dots and learn whether and how retinoic acid levels directly affect cancer development," Engleman added.

When the researchers looked at mice with colon cancer, they saw lower levels of retinoic acid in the intestines of the mice.

The researchers also found that boosting levels of retinoic acid in the intestines of mice with colon cancer slowed progression of the disease.

In humans, colon cancer patients who had high levels of a protein that degrades retinoic acid in their intestinal tissue tended to have worse outcomes than other patients, the study authors noted.

The findings suggest new ways to prevent or treat colon cancer. However, it's important to note that animal research doesn't always produce the same results in humans.

"The intestine is constantly bombarded by foreign organisms. As a result, its immune system is very complex," Engleman said.

"We found that bacteria, or molecules produced by bacteria, can cause a massive inflammatory reaction in the gut that directly affects retinoic acid metabolism," he said.

He said that retinoic acid levels are normally regulated very tightly.

"Now that we've shown a role for retinoic acid deficiency in colorectal cancer, we'd like to identify the specific microorganisms that initiate these changes in humans. Ultimately we hope to determine whether our findings could be useful for the prevention or treatment of colorectal cancer," he concluded.

The study was published online Aug. 30 in the journal Immunity.

Antidepressant, TCP (Trabylcypromine) could help the workings of anticancer drug used in leukemia...

A new study shows that an antidepressant could be crucial in helping cancer treatment drugs reach their full potential.

The study by scientists at the Institute of Cancer Research found that tranylcypromine (TCP - cis and trans iosmers - below structures) – which can be used to treat psychotic depressive states - can make cancer cells vulnerable to the effects of a vitamin A- derivative drug called ATRA (above structure).

Retinoids are a class of chemical compounds related chemically to vitamin A. ATRA is already used successfully to treat a rare form of acute myeloid leukemia (AML), but up until now, has not been effective against other types of the disease. ATRA works by encouraging leukemia cells to mature and die naturally, but the researchers lead by Ar. Arthur Zelent say that the reason many AML patients do not respond to the treatment is because the genes that ATRA normally attacks are switched off by an enzyme called LSD1. The scientists discovered that using TCP to block this 'off switch' could reactivate these genes, making the cancer cells susceptible to ATRA.

The team has already joined forces with the University of Munster in Germany to start a Phase II clinical trial of the drug combination in AML patients. The authors also commented that both the retinoid ATRA and the antidepressant TCP are already available in the UK and off-patent, so these drugs should not be expensive for the health service. 

Ref : http://www.icr.ac.uk/research/new_research_highlights/research_highlights/22625.shtml

ProstaCaid (33-ingredient comprehensive polyherbal preparation) against prostate cancer......

We have seen  many benefits of natural products rich in  Quercetin,   Epigallocatechin gallate (EGCG) and many other polyphenol antioxidant from natural products like green tea, broccoli peaches and plums. Interestingly, now researchers from  Columbia University have come up with an interesting finding, i.e., ProstaCaid is a 33-ingredient comprehensive polyherbal preparation with supplements of vitamin C, vitamin D3, zinc, selenium, quercitin, 3,3′-diinodolymethane (DIM), and lycopene was able to stop abnormal cell growth and induce apoptosis (programmed cell death) in both hormone sensitive and hormone resistant prostate cancer cell lines at unusually low concentrations, which makes the findings more significant...

Herbal extracts include the extracts from turmeric root, saw palmetto berry, grape skin, pomegranate, pumpkin seed, pygeum bark, sarsaparilla root, green tea, and Japanese knotweed. Hence, it is rich in natural polyphenols, including quercetin, resveratrol, epigallocatechin gallate (EGCG), and ellagic acid, which have previously demonstrated anticancer potential. The unique formula contains 3 medicinal mushrooms grown on an herbal-enhanced medium. The mushrooms included are Phellinus linteus, Ganoderma lucidum, and Coriolus versicolor, each with known anticancer properties.

Researchers claim that, ProstaCaid was designed based on constituents that exhibit antiprolifetaive, antioxidant, and apoptotic activities; however, its efficacy and the mechanisms of action are yet to be examined. Researchers looked at the effectiveness of the preparation in suppressing several types of prostate cancer cell lines in culture and attempt to delineate the mechanism of action for justification in pursuing animal to determine efficicacy invivo.

Researchers conclude that, the anticancer activity of ProstaCaid may be ascribed to its polyphenolic flavonoids and curcuminoids derived from various herbs as well as other supplements, such as DIM. The preparation contains supplements such as quercetin (15%), Curcuma longa root extract complex with enhanced bioavailability (BCM-95; 20%), DIM (3%), and resveratrol (0.2%). Some of these components have shown a strong doseand time-dependent growth inhibition and apoptotic death in prostate cancer cells; 25 mM of quercetin inhibited about 50% PC3 cell growth for 72 hours. At 24 hours, 50 mM and 100 mM quercetin induced G2/M arrest and apoptosis, manifested by the decrease in G2/M-related protiens.

Researchers summarise  that,    ProstaCaid has anti-cancer activities in both AD and AI prostate cancer cells at very low concentrations (25 mg/mL). It also suggests that ProstaCaid inhibits cell growth and survival, at least through the inhibition of AKT and MAPK signaling. The effect on AI cell lines is especially of importance as there is presently no curative therapy for hormone refractory prostate cancer.

Researchers postulate that ProstaCaid may affect activity of Cdc2/cyclin B1 kinase by reducing this complex formation. Cdc2 could be dephosphorylated by Cdc25C and become inactive or be phosphorylated by protein kinase, such as Wee1, and then converted into an inactive form. They also suggest that more studies are needed in the future to test it and to define its upstream events in PC3 cells.

Ref : Jun Yan and Aaron E. Katz, Integr Cancer Ther 2010 9: 186

Benefits of calcium and vitamin D in preventing fractures confirmed

Benefits of calcium and vitamin D in preventing fractures confirmed

Folinic acid treatment could help improve language and communication skills of children with ASD

In continuation of my update on Folinic acid

Prescription doses of folinic acid, which is a reduced form of a B vitamin known as folate, could help improve the language and communication skills of children with autism spectrum disorder (ASD). These are the preliminary findings from a placebo-controlled trial in which children were randomized to receive either high-dose folinic acid or a placebo, says lead author Richard Frye of Arkansas Children's Research Institute in the US. The study, which is published in Springer Nature's journal Molecular Psychiatry, also identified a specific blood marker that can be used to predict which patients have the best chance to respond to the treatment.

Up to two percent of American children are said to experience symptoms that place them on the autism spectrum. Many of these children have difficulty communicating and interacting with others, especially within a social setting. Researchers do not yet fully understand all the reasons behind the development of ASD and, importantly, there are currently no approved treatments that address the core symptoms of this disorder.

"The only currently approved medications for autism are both antipsychotic medications that address non-core symptoms and can lead to unwanted side effects," says John Slattery, a co-author of the study.

Scientific research has linked this disorder to abnormalities in the metabolism of folate as well as genes that are involved in folate metabolism. Certain studies have also shown that the offspring of women who took folate supplements before conception and during pregnancy had a lower risk of having a child with ASD.

About ten years ago a condition, known as cerebral folate deficiency (CFD), was described in which the concentration of folate is below normal in the central nervous system but not in the blood. Many children with CFD had ASD symptoms and responded well to treatment with high-dose folinic acid.

Previously Frye's team could show that folate receptor autoantibodies were found with a high prevalence in children with ASD. In the current study, these researchers found that participants with folate receptor autoantibodies had a more favourable response to the folinic acid treatment. This leads the way to a test that might be useful for clinicians to determine if high-dose folinic acid might be a treatment for a particular child with ASD. The deleterious effects of folate receptor antibodies on brain development and function are now confirmed in a laboratory rat model.

"Improvement in verbal communication was significantly greater in participants receiving folinic acid as compared with those receiving the placebo," says Frye. He adds that the findings should be considered preliminary until the treatment has been assessed further in larger long-term studies.

The researchers indicated they were very pleased with the positive findings of this study, but caution that more research is needed in order to replicate the findings in a larger population.

Cancer Fighting Foods.............

Cancer Fighting Foods:

How can food fight cancer, you ask? In many, many ways! Certain healthy foods can lower your risk for cancer by repairing damaged cells and protect sensitive skin. Incorporating more plant-based foods into your diet is a relatively small lifestyle change that can really reduce your cancer risk.

Orange Juice:

Oranges are high in folate, and recent research suggests that people with low levels of folate are more likely have mutations occur in their DNA, which can lead to mutated cancer cells.  Leafy greens, like spinach and Brussels sprouts, are also high in folate. In recent research, men who consumed their daily suggested intake of folate were able to decrease their risk for pancreatic cancer by 50-percent.

Milk:

We’ve all heard that calcium is important for healthy bones, but milk is also high in vitamin D, another nutrient that is linked to combating cancer—researchers suggest that vitamin D helps stop the growth of cancerous cells. In fact, it has been shown to significantly decrease the risk of breast cancer.

Beans:

The more you eat, the more you—well, the more you decrease your risk for cancer.  Beans, in addition to being high in protein and fiber (great for vegetarian diet), are also high in antioxidants that are key in the fight against cancer.  Antioxidants protect your cells against free radicals—free radicals, which can come from activities like smoking, cause damage to cells, leading to cancer and other complications.

Other foods that are high in antioxidants: Berries, cruciferous vegetables (think broccoli and cabbage), potatoes and nuts. A good general rule of thumb is to eat fruits and veggies that have a lot of color to them, as they usually contain the highest amount antioxidants.

Salad :

Your mom was right—you really should eat up all of your leafy greens .  Leafy greens (like spinach and kale) contain a substance called chlorophyllin, which can help fight cancer—it works by blocking toxins. People who consume more leafy greens show lower rates of stomach cancer.

And A Glass of Wine!

Grapes and wine contain resveratrol, which is another substance that slows the growth of cancerous cells. It does so by limiting growth and acts as a catalyst for apoptosis (a cancer cell death).  In addition to it’s anti-carcinogenic properties, it also helps prevent Alzheimer’s and diabetes. More importantly (ha-ha), it’s also been linked to anti-aging properties: it helps stimulate the production of SIRT1, a serum that helps slow the aging process.

So, there you have it; your first steps to prevent cancer (along with SPF and quitting smoking) are right here.  A healthier diet with more fruits and veggies will do more than lower your risk of cancer; it will change your quality of life. And, if eating healthy is not your thing, start with small changes, and build from there!

Virginia Cunningham is a freelance writer from Los Angeles whose writing covers a range of health topics, including holistic alternatives, healthy cooking and personal fitness. She not only includes these cancer-fighting foods into her diet, but she enjoys them as well!

Pomegranates May Prevent Growth of Breast cancer cells.....

We know that Pomegranate aril juice provides about 16% of an adult's daily vitamin C requirement per 100 ml serving, and is a good source of vitamin B₅ (pantothenic acid), potassium and antioxidant polyphenols.  The most abundant polyphenols in pomegranate juice are the hydrolyzable tannins called punicalagins which have free-radical scavenging properties in laboratory experiments. Punicalagins are absorbed into the human body and may have dietary value as antioxidants. Other phytochemicals include polyphenols catechins, gallocatechins, and anthocyanins such as prodelphinidins, delphinidin, cyanidin, and pelargonidin.   Many food and dietary supplement makers have found advantages of using pomegranate phenolic extracts as ingredients in their products instead of the juice. One of these extracts is ellagic acid which may become bioavailable only after parent molecule punicalagins are metabolized. However, ingested ellagic acid from pomegranate juice does not accumulate in the blood in significant quantities and is rapidly excreted. Accordingly, ellagic acid from pomegranate juice does not appear to be biologically important in vivo.

Now researchers lead by Dr Shiuan Chen, director of the Division of Tumour Cell Biology, and Dr Lynn Adams, a research fellow at the centre's Beckman Research Institute have found that Pomegranates contain a group of compounds called ellagitannins ( glucosidesof elligacic acid) may prevent the growth of breast cancer cells. Researchers tried to determine whether chemicals in pomegranates could block the action of an enzyme called aromatase. Aromatase plays a key role in driving the growth of some forms of breast cancer by helping the body produce the female sex hormone oestrogen. Breast cancer drugs like anastrozole are designed to block its action.

The researchers screened ten ellagitannin-like compounds and found that one in particular, Urolithin B, (see above structure) significantly inhibited breast cancer cell growth in the laboratory. Its interesting to note that phytochemicals in pomegranates to exhibit this property (earlier the same authors have reported the inhibition of aromatase by grapes (phytochemicals).

Though further studies like in vivo are essential to further substantiate the in vitro studies (relatively high levels of ellagitannin compounds were required to demonstrate an anti-proliferative effect on cultured breast cancer cells) are essential (because of the fact that  the ellagitannins are not well absorbed into blood when provided in the diet), still in my opinion its a good finding......

^{Ref : http://cancerpreventionresearch.aacrjournals.org/cgi/content/abstract/3/1/108}

Beta carotene may protect people with common genetic risk factor for type-2 diabetes

Stanford University School of Medicine investigators have found that for people harboring a genetic predisposition that is prevalent among Americans, beta carotene, which the body converts to a close cousin of vitamin A, may lower the risk for the most common form of diabetes, while gamma tocopherol, the major form of vitamin E in the American diet, may increase risk for the disease. 

Beta carotene may protect people with common genetic risk factor for type-2 diabetes

Researchers identifiy elusive anti-cancer property of vitamin E

Researchers identifiy elusive anti-cancer property of vitamin E

When Having the Blues is a Good Thing: Blueberries & Cancer Prevention

In continuation of my up date on the usefulness of blue berries.

Now researchers from the Department of Nutrition Sciences at the University of Alabama at Birmingham, lead by Laura Newton have come up with another interesting finding about blue berries, i.e., as little as a cup a day can help prevent cell damage linked to cancer.

As per the claim by the researchers, free radicals, atoms that contain an odd number of electrons and are highly reactive, can cause cellular damage, one of the factors in the development of cancer; many believe a diet filled with fruits and vegetables may help reduce the risk. 

Lead researcher says

"Studies suggest that antioxidants may help prevent the free-radical damage associated with cancer"

Researchers add that, Blueberries also are rich in vitamin C, which helps the immune system and can help the body to absorb iron. "Vitamin C also helps to keep blood vessels firm, offering protection from bruising. Blueberry juice and other products may be nutritious but often contain less fiber than the whole fruit, and added sugar or corn syrup may decrease their nutritional value. Consuming fresh, raw blueberries provides the most benefits; the average serving size of raw blueberries is one cup, which contains about 80 calories...

More...

Revolutionary drug explained by scientists: Scientists figured out how the world's first drug that protects the cell mitochondria from damage by aggressive oxygen can work

Recently, Russian researchers, led by Prof. Vladimir P. Skulachev, managed to create an antioxidant drug that selectively accumulates within mitochondria and protects them from oxidative damage. Under the trade name "Visomitin" the drug was approved for treatment of such eye diseases as cataracts and dry eye. Prof. Armen Mulkidjanian of the Faculty of Bioengineering and Bioinformatics of the Lomonosov Moscow State University and the University of Osnabrück, Germany, and his colleagues have explained why very small doses of synthetic antioxidants such as "Visomitin" could give a pronounced therapeutic effect, despite the presence of large quantities of natural mitochondrial antioxidants.

 Visomitin

Mitochondria are intracellular structures that conduct respiration. Respiration, however, is accompanied by formation of reactive oxygen species (ROS) as by-products. The ROS are capable of damaging the mitochondria. Damaged mitochondria produce even more ROS, which can destroy cells and tissues, so that nature has special mechanisms, such as mitophagy and apoptosis, for elimination of damaged mitochondria and cells. These mechanisms are triggered after a signal of a disorder passes through the double membrane surrounding the mitochondria. Several laboratories have shown that it is possible to avoid the decay of cells and tissues by preventing the oxidation of a particular component of the mitochondrial membrane -- cardiolipin, because the oxidized molecules of cardiolipin are exactly the triggers of the signal chain.

The group of Prof. Vladimir Skulachev, the Dean of the Faculty of Bioengineering and Bioinformatics and the Director of the Belozersky Institute of Physical and Chemical Biology, (the Lomonosov Moscow State University), has developed a line of mitochondria-targeted antioxidants, the so-called SkQ-ions, specifically protecting the molecules of mitochondrial cardiolipin from oxidation. In animal trials, the SkQ-ions cured inflammatory eye diseases, helped to overcome the ischemia-simulating conditions, and even reduced the manifestation of senescence. Although similarly acting drugs have been developed and studied in the US and UK laboratories, the Russian group was the first to get an approval for their drug -- as eye drops. The researchers hope that SkQ-based drugs, in the form of pills and injections, after their certification, would help to attenuate the pathological symptoms that accompany strokes, heart attacks and serious traumas.

Armen Mulkidjanian and his collaborators have managed to suggest answers to some intriguing questions. Specifically, it was not clear why cardiolipin, of all the components of the membrane, it specifically oxidized. Molecules of cardiolipin, while making only 10-20% of total membrane lipids, are specifically targeted by ROS and, after getting oxidized, trigger the self-destruction of cells. Secondly, it was not clear why the natural antioxidants, namely coenzyme Q (ubiquinol) and vitamin E (alpha-tocopherol), which are present in mitochondrial membranes in large quantities, fail in the case of cardiolipin. It remained a mystery why these substances could not protect cardiolipin from oxidation, whereas artificial, mitochondria-targeted antioxidants, designed either by the Skulachev's group in Moscow, or by their counterparts in the US and the UK, perfectly coped with this task, in spite of very small doses of the administered drugs.

Armen Mulkidjanian says that the goal of the study was set by Prof. Skulachev.

'Prof. Skulachev asked our group in Germany to tackle these puzzles,' says Armen Mulkidjanian. 'Most of the work was carried out by the post-graduate students and the employees of the Moscow University, who worked in Russia and in Germany, so that their contribution was decisive. As to the research, we have developed an experimental system to investigate quantitatively the oxidation of the cardiolipin membranes and the ability of various antioxidants to prevent it. It turned out that the SkQ-ions and the molecules of coenzyme Q protected the cardiolipin membranes from oxidation equally well, whereas vitamin E performed much worse'.

To understand why cardiolipin molecules are the main target of the ROS, the researchers compared the experimental data with their previous results and the structures of respiratory enzymes. A fraction of cardiolipin molecules is occluded within respiratory protein complexes, just those that generate ROS. 'These molecules should be the first to be oxidized,' Mulkidjanian says.

The bulky, water-insoluble molecule of coenzyme Q cannot get to these "hidden" cardiolipin molecules, as opposed to small, agile molecules of artificial antioxidants, which, as shown in the study, are capable of protecting cardiolipin molecules from oxidation by accessing them both from the membrane and from the aqueous phase.

"The essence of our work is that we have proposed a mechanism that explains how very low doses of mitochondria-targeted antioxidants could provide a distinct therapeutic effect, even being applied over large amounts of natural antioxidants, which were ineffective in this case. The mechanism should be valid for the whole class of similar drugs. We hope that our findings would help to develop new drugs,' says Armen Mulkidjanian.

Revolutionary drug explained by scientists: Scientists figured out how the world's first drug that protects the cell mitochondria from damage by aggressive oxygen can work: An international team now clarifies the molecular mechanism of a drug created in Russia and designed to prevent the damaging of cell mitochondria by reactive oxygen species.

FDA Approves Sorilux for Adolescent Plaque Psoriasis

In continuation of my update on Sorilux(calcipotriene) 

 

Mayne Pharma Group Limited, announced that the US Food and Drug Administration (FDA) has approved Sorilux(calcipotriene) Foam, 0.005% in adolescents.

Sorilux is now approved for treating plaque psoriasis of the scalp and body in patients aged 12 years and older.

The FDA approved Sorilux in 2010 based on evidence from two 8-week placebo controlled clinical trials in patients with mild to moderate plaque psoriasis of the body and one 8-week placebo controlled clinical trial in patients with moderate plaque psoriasis of the scalp. Further data was obtained in a follow-on open label study in patients aged 12 to 17 years of age with psoriasis.

Sorilux Foam contains calcipotriene, a synthetic vitamin D analog that has a similar receptor binding affinity as natural vitamin D. The exact mechanism of action contributing to the clinical efficacy is unknown.

Psoriasis is a chronic disease of the immune system affecting approximately 7.5 million Americans each year[1]. The most common form, plaque psoriasis affects roughly 80 percent of people who have the condition.

Mayne Pharma's CEO, Mr Scott Richards, said "Sorilux is an elegant foam formulation that is marketed by Mayne Pharma's Specialty Brands sales team alongside recently launched LEXETTE™ (halobetasol propionate) Foam, a potent topical corticosteroid also used to treat plaque psoriasis in adult patients. Topical products are the mainstay of treatment for plaque psoriasis patients and the foam delivery platform has a well-established reputation with dermatologists due to ease of application and lack of greasiness and stickiness, especially in hair-bearing areas and under clothing."

Mayne Pharma directly markets more than 60 products in the US including four branded dermatology products FABIOR® (tazarotene) Foam, Sorilux Foam, DORYX® MPC (doxycycline hyclate) delayed-release tablets and LEXETTE Foam. The Company also markets TOLSURA® (SUBA®-itraconazole) capsules used to treat certain fungal infections which was recently approved and launched this year.

https://en.wikipedia.org/wiki/Calcipotriol

Carnitine supplement may improve survival rates of children with heart defects

We know that, Carnitine is a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine. In living cells, it is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids (fats) for the generation of metabolic energy. It is widely available as a nutritional supplement. Carnitine was originally found as a growth factor for mealworms and labeled vitamin B_T, although carnitine is not a proper vitamin. Carnitine exists in two stereoisomers: Its biologically active form is L-carnitine, whereas its enantiomer, D-carnitine, is biologically inactive.

New research shows it appears to normalize the blood vessel dysfunction that can accompany congenital heart defects and linger even after corrective surgery, said Dr. Stephen M. Black, cell and molecular physiologist at the Vascular Biology Center at the Medical College of Georgia at Georgia Regents University.

"My hope is this is going to have a major, major impact on survival of babies," Black said. About half the babies born with heart defects have excessive, continuous high pressure on their lungs from misdirected blood flow. Early surgery can prevent full-blown pulmonary vascular disease, but scientists are finding more subtle disruptions in the signaling inside blood vessels walls that can be problematic -- even deadly -- up to 72 hours after surgery.

The good news is the changes are reversible and that carnitine speeds recovery and can even prevent the damage in a lamb model of these human heart defects, according to studies published in the journal Pediatric Research.

Carnitine supplement may improve survival rates of children with heart defects

New oral blood thinners can decrease stroke risk in atrial fibrillation patients without frequent monitoring

In continuation of my update on dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa).

A new generation of blood thinners can reduce the risk of stroke in patients with atrial fibrillation, without requiring frequent monitoring and dietary restrictions.

But special attention must be given to the patient's age, kidney function and other factors before prescribing the new medications, according to a review article by neurologists at Loyola Medicine and Loyola University Chicago Stritch School of Medicine.

The report by Rochelle Sweis, DO and José Biller, MD, is published in the journal Current Treatment Options in Cardiovascular Medicine.

Atrial fibrillation (AFib) is the most common type of irregular heartbeat, and the prevalence is increasing as the population ages. In AFib, electrical signals that regulate the heartbeat become erratic. Instead of beating regularly, the upper chambers of the heart quiver and blood doesn't flow well. Blood clots can form, migrate to the brain and cause strokes. AFib is associated with a fivefold increase in the risk of stroke.

Blood thinning medications decrease the stroke risk by approximately 70 percent. For 60 years physicians have prescribed warfarin (Coumadin) and other blood thinners known as vitamin K antagonists. These medications have been proven to be effective in reducing the risk of blood clots and strokes. But they require continual monitoring and dose adjustments to ensure the drugs thin the blood enough to prevent clots, but not enough to increase the risk of major bleeding. Patients also must restrict their consumption of foods rich in vitamin K, such as spinach, Brussels sprouts, kale, parsley and green tea.

 

Warfarin

The new blood thinners include dabigatran (Pradaxa), rivaroxaban (Xarelto), apixaban (Eliquis) and edoxaban (Savaysa). In the right patient population, the new drugs are a safe and effective option for treating atrial fibrillation, Drs. Sweis and Biller write.

Dabigatran         Rivaroxaban (BAY 59-7939)

Apixaban Edoxaban

New oral blood thinners can decrease stroke risk in atrial fibrillation patients without frequent monitoring: A new generation of blood thinners can reduce the risk of stroke in patients with atrial fibrillation, without requiring frequent monitoring and dietary restrictions.

FDA Approves Onpattro (patisiran) Targeted RNA-based Therapy for Polyneuropathy Caused by hATTR

The U.S. Food and Drug Administration today approved Onpattro (patisiran) infusion for the treatment of peripheral nerve disease (polyneuropathy) caused by hereditary transthyretin-mediated amyloidosis (hATTR) in adult patients. This is the first FDA-approved treatment for patients with polyneuropathy caused by hATTR, a rare, debilitating and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart and other organs. It is also the first FDA approval of a new class of drugs called small interfering ribonucleic acid (siRNA) treatment.

“This approval is part of a broader wave of advances that allow us to treat disease by actually targeting the root cause, enabling us to arrest or reverse a condition, rather than only being able to slow its progression or treat its symptoms. In this case, the effects of the disease cause a degeneration of the nerves, which can manifest in pain, weakness and loss of mobility,” said FDA Commissioner Scott Gottlieb, M.D. “New technologies like RNA inhibitors, that alter the genetic drivers of a disease, have the potential to transform medicine, so we can better confront and even cure debilitating illnesses. We’re committed to advancing scientific principles that enable the efficient development and review of safe, effective and groundbreaking treatments that have the potential to change patients’ lives.”

RNA acts as a messenger within the body’s cells, carrying instructions from DNA for controlling the synthesis of proteins. RNA interference is a process that occurs naturally within our cells to block how certain genes are expressed. Since its discovery in 1998, scientists have used RNA interference as a tool to investigate gene function and its involvement in health and disease. Researchers at the National Institutes of Health, for example, have used robotic technologies to introduce siRNAs into human cells to individually turn off nearly 22,000 genes.

This new class of drugs, called siRNAs, work by silencing a portion of RNA involved in causing the disease. More specifically, Onpattro encases the siRNA into a lipid nanoparticle to deliver the drug directly into the liver, in an infusion treatment, to alter or halt the production of disease-causing proteins.

Affecting about 50,000 people worldwide, hATTR is a rare condition. It is characterized by the buildup of abnormal deposits of protein fibers called amyloid in the body's organs and tissues, interfering with their normal functioning. These protein deposits most frequently occur in the peripheral nervous system, which can result in a loss of sensation, pain, or immobility in the arms, legs, hands and feet. Amyloid deposits can also affect the functioning of the heart, kidneys, eyes and gastrointestinal tract. Treatment options have generally focused on symptom management.

Onpattro is designed to interfere with RNA production of an abnormal form of the protein transthyretin (TTR). By preventing the production of TTR, the drug can help reduce the accumulation of amyloid deposits in peripheral nerves, improving symptoms and helping patients better manage the condition.

“There has been a long-standing need for a treatment for hereditary transthyretin-mediated amyloidosis polyneuropathy. This unique targeted therapy offers these patients an innovative treatment for their symptoms that directly affects the underlying basis of this disease,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research.

The efficacy of Onpattro was shown in a clinical trial involving 225 patients, 148 of whom were randomly assigned to receive an Onpattro infusion once every three weeks for 18 months, and 77 of whom were randomly assigned to receive a placebo infusion at the same frequency. The patients who received Onpattro had better outcomes on measures of polyneuropathy including muscle strength, sensation (pain, temperature, numbness), reflexes and autonomic symptoms (blood pressure, heart rate, digestion) compared to those receiving the placebo infusions. Onpattro-treated patients also scored better on assessments of walking, nutritional status and the ability to perform activities of daily living.

The most common adverse reactions reported by patients treated with Onpattro are infusion-related reactions including flushing, back pain, nausea, abdominal pain, dyspnea (difficulty breathing) and headache. All patients who participated in the clinical trials received premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) to reduce the occurrence of infusion-related reactions. Patients may also experience vision problems including dry eyes, blurred vision and eye floaters (vitreous floaters). Onpattro leads to a decrease in serum vitamin A levels, so patients should take a daily Vitamin A supplement at the recommended daily allowance.

The FDA granted this application Fast Track, Priority Review and Breakthrough Therapy designations. Onpattro also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

https://en.wikipedia.org/wiki/Patisiran

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FDA Approves Onpattro (patisiran) Targeted RNA-based Therapy for Polyneuropathy Caused by hATTR

Bitter gourd(Karela) leaves Medicinal uses

In continuation of my update on bitter gourd

Phytochemical constituents of Bitter gourd Leaves

Alkaloid, Flavonoids, Sterols, Terpenoids, Anthraquinones, Proteins and Phenols, glycosides including momordin, charantosides, glycosides, momordicosides, goyaglycosides and other terpenoid compounds that include momordicin-28, momordicinin, momordicilin, momordenol, and momordol.

Medicinal Uses of Bitter gourd Leaves

Bitter gourd leaves are used to treat variety of diseases such as diabetes, piles, respiratory ailments, cholera, viral diseases and skin eruptions. Below is listed few such time-tested home remedies. These are simple, reliable and inexpensive. Even modern studies also support these traditional treatments.

Diabetes

Take about six tablespoon of the chopped bitter gourd leaves and two glass of water. Boil leaves in water for approximately 15 minutes. Do not cover the vessel.

Allow it to cool and then strain. Drink 1/3 cup of it thrice a day.

This leaf decoction is found to be very effective in the management of diabetes type 2. On regular intake, this keeps blood sugar in control.

Piles

Common home remedy is to extract three teaspoonful juice from clean bitter melon leaves and mix this with a glassful of buttermilk. This should be taken every morning for about a month on empty stomach. Topically leaves paste can be applied over the haemorrhoids.

Cholera, diarrhoea

Intake of 10-15 ml juice of Karela leaves is useful in diarrhoea and early stage of cholera.

Asthma, bronchitis, common colds, pharyngitis

Bitter melon leaves paste is mixed with equal amounts of the paste of tulsi/Basil leaves.

This should be taken with honey each morning. This can also be taken as preventive medicine for respiratory problems.

Arthritis

1. Drinking 10-15 ml juice of Karela leaves is beneficial in arthritis.
2. Ascite (gastroenterological term for an accumulation of fluid in the peritoneal cavity)
3. Extract 10-15 ml juice of leaves and add some honey and drink.

Hepatitis

In Hepatitis, the leaves juice of bitter gourd is useful. Extract 10-15 ml juice of bitter gourd leaves and mix some big chebulic myroblan powder and drink.

Intestinal parasites, pox, measles, Pneumonia

Drinking 10-15 ml juice of Karela leaves is useful.

Boils, burns and other skin eruptions

The dried and powdered bitter gourd leaves can be applied topically on affected areas.

Burning sensation in hands and feet

Bitter gourd juice is applied topically in burning sensation in hands and feet.

Nutrition

Bitter melon leaves are good source of vitamins and minerals such as iron, calcium, phosphorus and vitamin B.

Bitter gourd(Karela) leaves Medicinal uses

First drug to significantly improve heart failure mortality in over a decade

We know that, Coenzyme Q₁₀, also known as ubiquinone, ubidecarenone, coenzyme Q, and abbreviated at times to CoQ₁₀, CoQ, or Q₁₀ is a 1,4-benzoquinone, where Q refers to the quinone chemical group, and 10 refers to the number of isoprenyl chemical subunits in its tail.

This oil-soluble, vitamin-like substance is present in most eukaryotic cells, primarily in the mitochondria. It is a component of the electron transport chain and participates in aerobic cellular respiration, generating energy in the form of ATP. Ninety-five percent of the human body’s energy is generated this way.  Therefore, those organs with the highest energy requirements—such as the heart, liver and kidney—have the highest CoQ₁₀ concentrations.There are three redox states of CoQ₁₀: fully oxidized (ubiquinone), semiquinone (ubisemiquinone), and fully reduced (ubiquinol). The capacity of this molecule to exist in a completely oxidized form and a completely reduced form enables it to perform its functions in the electron transport chain and as an antioxidant respectively.

Now double blind controlled trials have shown that CoQ10 improves symptoms, functional capacity and quality of life in patients with heart failure with no side effects. But until now, no trials have been statistically powered to address effects on survival.

The Q-SYMBIO study (2) randomised 420 patients with severe heart failure (New York Heart Association (NYHA) Class III or IV) to CoQ10 or placebo and followed them for 2 years. The primary endpoint was time to first major adverse cardiovascular event (MACE) which included unplanned hospitalisation due to worsening of heart failure, cardiovascular death, urgent cardiac transplantation and mechanical circulatory support. Participating centres were in Denmark, Sweden, Austria, Slovakia, Poland, Hungary, India, Malaysia and Australia.

CoQ10 halved the risk of MACE, with 29 (14%) patients in the CoQ10 group reaching the primary endpoint compared to 55 (25%) patients in the placebo group (hazard ratio=2; p=0.003). CoQ10 also halved the risk of dying from all causes, which occurred in 18 (9%) patients in the CoQ10 group compared to 36 (17%) patients in the placebo group (hazard ratio=2.1; p=0.01).

CoQ10 treated patients had significantly lower cardiovascular mortality (p=0,02) and lower occurrence of hospitalisations for heart failure (p=0.05). There were fewer adverse events in the CoQ10 group compared to the placebo group (p=0.073).

Professor Mortensen said: "CoQ10 is the first medication to improve survival in chronic heart failure since ACE inhibitors and beta blockers more than a decade ago and should be added to standard heart failure therapy."

First drug to significantly improve heart failure mortality in over a decade