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...

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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

Mouse study finds black raspberries can prevent colorectal cancer

We know that, The blackberries, as well as various other Rubus species with mounding or rambling growth habits, are often called brambles. However, this name is not used for those like the raspberry that grow as upright canes, or for trailing or prostrate species such as most dewberries, or various low-growing boreal, arctic, or alpine species. Black raspberries have been also reported to possess antioxidant, anti-cancer, anti-neurodegenerative and anti-inflammatory properties, now the researchers from UIC College of Medicine have looked at the fruit's ability to prevent colon cancer.

The researchers used two strains of mice, Apc1638 and Muc2, which each have a specific gene knocked out, causing the mice to develop either intestinal tumors (in the case of Apc1638) or colitis in the case of Muc2. Colitis is an inflammation of the large intestine that can contribute to the development of colorectal cancer.

Both mouse strains were randomized to be fed either a Western-style, high-risk diet (high in fat and low in calcium and vitamin D) or the same diet supplemented with 10 percent freeze-dried black raspberry powder for 12 weeks.

The researchers found that in both mouse strains the black raspberry-supplemented diet produced a broad range of protective effects in the intestine, colon and rectum and inhibited tumor formation.

In the Apc1638 mice, tumor incidence was reduced by 45 percent and the number of tumors by 60 percent. The researchers found that black raspberries inhibited tumor development by suppressing a protein, known as beta-catenin, which binds to the APC gene.

In the Muc2 mice, tumor incidence and the number of tumors were both reduced by 50 percent, and black raspberries inhibited tumor development by reducing chronic inflammation associated with colitis.

The researchers now hope to obtain funding to begin clinical trials in humans. Because black raspberries not only prevent cancer but also inflammation, they may also protect against other diseases, such as heart disease.

I read an article in the same lines, wherein the researchers attribute the colorectal anticancer activity due to the anthocyanins present

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