Monday, May 8, 2017

FDA Approves Flonase Sensimist Allergy Relief

Fluticasone furoate.svg
In continuation of my update on fluticasone

GSK Consumer Healthcare announced today that the U.S. Food and Drug Administration (FDA) has approved Flonase® Sensimist™ Allergy Relief (fluticasone furoate, 27.5 mcg spray) as an over-the-counter (OTC) treatment for symptoms associated with seasonal and perennial allergies. Previously available by prescription as Veramyst®, Flonase Sensimist is the latest Rx-to-OTC switch from GSK.
Flonase Sensimist helps block six allergic substances*, providing non-drowsy, 24-hour relief of both nose- and eye-related allergy symptoms like itchy, watery eyes**, nasal congestion, runny nose, itchy nose and sneezing.
“There are roughly 50 million people in the United States who suffer from allergies,2 and, as a category leader, GSK continues to innovate to satisfy the needs of all allergy sufferers,” said Amardeep Kahlon, Director of Marketing. “In the case of Flonase Sensimist, GSK is proud to offer an additional treatment option that not only provides more complete allergy symptom relief1 but also suits specific consumer preferences.”
Additional key features of Flonase Sensimist include:
  • Nasal allergy relief indicated for adults and children ages 2 and older**
  • Scent-free
  • Alcohol-free
  • Little or no drip
Flonase Sensimist will be nationally available OTC in early 2017.

About Flonase Sensimist

Flonase Sensimist (fluticasone furoate, 27.5 mcg spray) is an approved over-the-counter treatment for symptoms associated with seasonal and perennial allergic rhinitis including sneezing, runny nose, itchy nose, congestion, and itchy, watery eyes.**

FDA Approves Qbrelis (lisinopril) Oral Solution for Pediatric Patients 6 Years of Age and Older

We know that,  Lisinopril is a drug of the angiotensin-converting enzyme (ACE) inhibitor class used primarily in treatment of high blood pressure, heart failure, and after heart attacks. It is also used for preventing kidney and eye complications in people with diabetes. Its indications,contraindications, and side effects are as those for all ACE inhibitors.
Lisinopril was the third ACE inhibitor (after captopril and enalapril) and was introduced into therapy in the early 1990s. A number of properties distinguish it from other ACE inhibitors: It ishydrophilic, has a long half-life and tissue penetration, and is not metabolized by the liver.

Structural formula of lisinopril

Now Silvergate Pharmaceuticals, Inc., leader in the development and commercialization of innovative and safe medicines for children, today announced that the United States Food and Drug Administration (FDA) approved Qbrelis (Lisinopril) Oral Solution, the first and only FDA-approved Lisinopril oral solution. Qbrelis is indicated for the treatment of hypertension (high blood pressure) in adult patients and pediatric patients 6 years of age and older, adjunct therapy for heart failure, and treatment of acute myocardial infarction in adults. 

“We are excited to launch our second product focused on pediatric patients and pediatric hypertension” said Frank Segrave, President & CEO, Silvergate Pharmaceuticals, Inc. “Qbrelis provides a ready-to-use oral solution for these children with the additional assurance of an FDA approved medication. As a company, we continue to focus on pediatric medications that are safe, effective, and readily available.”
Qbrelis enables weight-based dosing for children 6 years of age and older who until now have relied on an adjusted adult dose. Qbrelis will be available through an extensive network of pharmacies and a qualified mail order service. For additional information on how to obtain Qbrelis, please call 1-855-379-0382.

About Qbrelis

Qbrelis delivers the trusted efficacy of lisinopril (an ACE inhibitor), the effectiveness of which has been well established in clinical trials.1 As a unique formulation of an oral solution, Qbrelis provides consistent potency and stability in each dose1, in addition to the quality of a product made in accordance with FDA regulations and requirements. People who have trouble swallowing lisinopril tablets may also benefit from Qbrelis.
Qbrelis reduces blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Control of high blood pressure should be part of a comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake.
More info @ https://www.drugs.com/history/qbrelis.html

Thursday, May 4, 2017

Lisinopril oral solution approved for treatment of hypertension in children and adults

Silvergate Pharmaceuticals, Inc.  leader in the development and commercialization of innovative and safe medicines for children, today announced that the United States Food and Drug Administration (FDA) approved Qbrelis™ (Lisinopril) Oral Solution, the first and only FDA-approved Lisinopril oral solution. Qbrelis™ is indicated for the treatment of hypertension (high blood pressure) in adult patients and pediatric patients 6 years of age and older, adjunct therapy for heart failure, and treatment of acute myocardial infarction in adults.

Structural formula of lisinopril

"We are excited to launch our second product focused on pediatric patients and pediatric hypertension" said Frank Segrave, President & CEO, Silvergate Pharmaceuticals, Inc. "Qbrelis provides a ready-to-use oral solution for these children with the additional assurance of an FDA approved medication. As a company, we continue to focus on pediatric medications that are safe, effective, and readily available."

Qbrelis enables weight-based dosing for children 6 years of age and older who until now have relied on an adjusted adult dose. Qbrelis will be available through an extensive network of pharmacies and a qualified mail order service.

Lisinopril oral solution approved for treatment of hypertension in children and adults

Silvergate Pharmaceuticals, Inc.  leader in the development and commercialization of innovative and safe medicines for children, today announced that the United States Food and Drug Administration (FDA) approved Qbrelis™ (Lisinopril) Oral Solution, the first and only FDA-approved Lisinopril oral solution. Qbrelis™ is indicated for the treatment of hypertension (high blood pressure) in adult patients and pediatric patients 6 years of age and older, adjunct therapy for heart failure, and treatment of acute myocardial infarction in adults.

Structural formula of lisinopril

"We are excited to launch our second product focused on pediatric patients and pediatric hypertension" said Frank Segrave, President & CEO, Silvergate Pharmaceuticals, Inc. "Qbrelis provides a ready-to-use oral solution for these children with the additional assurance of an FDA approved medication. As a company, we continue to focus on pediatric medications that are safe, effective, and readily available."

Qbrelis enables weight-based dosing for children 6 years of age and older who until now have relied on an adjusted adult dose. Qbrelis will be available through an extensive network of pharmacies and a qualified mail order service.

Wednesday, May 3, 2017

FDA Expands Indication For Type 2 Diabetes Treatment Synjardy (Empagliflozin/Metformin Hydrochloride) To Include Treatment-Naïve Adults


In continuation of my update on empagliflozin and metformin
The U.S. Food and Drug Administration has approved an expanded indication for Synjardy (empagliflozin and metformin hydrochloride) tablets to include treatment-naïve adults with type 2 diabetes (T2D). Synjardy, from Boehringer Ingelheim and Eli Lilly and Company (NYSE: LLY), is indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D when treatment with both empagliflozin and metformin is appropriate.
Empagliflozin.svgempagliflozin Metformin.svgMetformin

Synjardy is a combination of empagliflozin (Jardiance) and metformin — two medicines with complementary mechanisms of action — to help control blood glucose in adults with T2D. Empagliflozin, a sodium glucose co-transporter-2 inhibitor, removes excess glucose through the urine by blocking glucose re-absorption in the kidney. Metformin, a commonly prescribed initial treatment for T2D, lowers glucose production by the liver and its absorption in the intestine.
"Type 2 diabetes is a complex condition, which often requires that people take more than one treatment to manage their blood sugar," said Paul Fonteyne, president and CEO, Boehringer Ingelheim Pharmaceuticals, Inc. "The expanded indication for Synjardy further validates the potential of this combination therapy to help adults with type 2 diabetes who are not at goal, including those already being treated and, now, those at the beginning of their treatment journey."
The Synjardy label was updated to include results from a phase III, double-blind, randomized, active-controlled study that evaluated the efficacy and safety of empagliflozin in combination with metformin as initial therapy compared with the individual components. In the study, at 24 weeks, the combination of empagliflozin 10 mg or 25 mg with metformin 1000 mg or 2000 mg resulted in significant reductions in A1C (a measure of average blood glucose over the past two to three months) compared with the corresponding dose of either component alone.
Synjardy can cause serious side effects, including Lactic Acidosis (a buildup of lactic acid in the blood). Metformin, one of the medicines in Synjardy, can cause lactic acidosis, a rare, but serious condition that can cause death. Lactic acidosis is a medical emergency and must be treated in a hospital. Synjardy is not for the treatment of type 1 diabetes or diabetic ketoacidosis.

Tuesday, May 2, 2017

Sanofi Receives FDA Approval of Adlyxin (lixisenatide) for Treatment of Adults With Type 2 Diabetes

Sanofi announced today that the U.S. Food and Drug Administration (FDA) approved Adlyxin (lixisenatide), a once-daily mealtime GLP-1 receptor agonist injection indicated as an adjunct to diet and exercise for the treatment of adults with type 2 diabetes.
"The approval of Adlyxin reaffirms our continued commitment to addressing the challenges faced by people living with diabetes when trying to reach and maintain their individual blood glucose (HbA1c) targets," said Peter Guenter, Executive Vice President, Head, Global Diabetes & Cardiovascular Business Unit, Sanofi. "We are pleased with this approval, as it offers us the opportunity to continue helping patients treated with basal insulin who remain uncontrolled."
The approval of Adlyxin was based on FDA review of results from the GetGoal clinical program and findings from the ELIXA trial, which successfully addressed the FDA's request to demonstrate CV safety. The GetGoal clinical program, which included 13 clinical trials involving more than 5,000 adults with type 2 diabetes worldwide, evaluated the safety and efficacy of lixisenatide in adults with type 2 diabetes. All studies of the GetGoal program successfully met the primary efficacy endpoint of HbA1c reduction. The most common adverse events reported for Adlyxin included nausea, hypoglycemia and vomiting.
Adlyxin will be available in a disposable pre-filled pen in a single dose of 20 micrograms. Patients will also receive a disposable pre-filled pen in a single dose of 10 micrograms that they should initiate once daily for 14 days. On Day 15, patients will increase dosage to 20 micrograms once daily.
Adlyxin is approved under the proprietary name, Lyxumia® in more than 60 countries and marketed in over 40. Commercial launches include most EU countries, Japan, Brazil, Mexico and India. Adlyxin was in-licensed from Zealand Pharma A/S (NASDAQ OMX Copenhagen: ZEAL), www.zealandpharma.com.

About Adlyxin

Adlyxin is a once-daily glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of adult patients with type 2 diabetes mellitus as an adjunct to diet and exercise. GLP-1 is a peptide hormone that is released within minutes after eating a meal. It is known to suppress glucagon secretion from pancreatic alpha cells and stimulate glucose-dependent insulin secretion by pancreatic beta cells. Adlyxin increases glucose-dependent insulin release, decreased glucagon secretion, and slows gastric emptying.

AbbVie Receives U.S. FDA Approval of Once-Daily Viekira XR (dasabuvir, ombitasvir, paritaprevir and ritonavir) for the Treatment of Genotype 1 Chronic Hepatitis C


In continuation of my update on Dasabuvir ombitasvir, paritaprevir and ritonavir
 AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that the U.S. Food and Drug Administration (FDA) has approved a New Drug Application (NDA) for Viekira XR (dasabuvir, ombitasvir, paritaprevir and ritonavir) extended-release tablets. Viekira XR is a once-daily, extended-release co-formulation of the active ingredients in Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) and is for the treatment of patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with compensated cirrhosis (Child-Pugh A). Viekira XR is not for people with decompensated cirrhosis.
Dasabuvir.svg dasabuvir  Ombitasvir.svg  ombitasvir

Paritaprevir structure 2.svgParitaprevir  Ritonavir structure.svgritonavir


Viekira XR is the first co-formulated three direct-acting antiviral (DAA) treatment for adult patients with GT1 HCV. Viekira XR is given once-daily as three oral tablets and must be taken with a meal. It is used without ribavirin (RBV) in GT1b patients and in combination with twice daily RBV in GT1a patients. The approval is supported by Phase 3 clinical trials for Viekira Pak which include data that demonstrated 100 percent sustained virologic response 12 weeks following treatment (SVR12) in GT1b patients with 12 weeks of therapy without ribavirin and 95 percent SVR12 in GT1a patients when used with ribavirin for 12 or 24 weeks of therapy.
"AbbVie's work continues to contribute to the transformation of hepatitis C care through our focus on evolving our current therapies as part of our ongoing commitment to patients," said Rob Scott, M.D., vice president, development and chief medical officer, AbbVie. "The approval of Viekira XR provides a new treatment option for genotype 1 hepatitis C patients in the U.S. with clinical trial data using the components of Viekira XR demonstrating 100 percent cure rates in genotype 1b patients."
There are six major HCV genotypes (GT1-6) and GT1 is the most prevalent form of HCV in the U.S., accounting for approximately 74 percent of all cases.1 Hepatitis C continues to be an important public health issue, with the Centers for Disease Control and Prevention (CDC) estimating that in the U.S. approximately 2.7 million people are chronically infected with HCV.2
The approval of Viekira XR is supported by data from seven Phase 3 clinical trials in more than 2,300 patients who received Viekira Pak with or without RBV for 12 or 24 weeks and two bioavailability studies comparing the formulations.

About Clinical Studies

The components of Viekira XR (administered twice daily with a meal) have been studied in seven Phase 3 clinical trials where 1076 subjects (including 181 with compensated cirrhosis) received the recommended regimen of Viekira +/? RBV for 12 weeks, or for 24 weeks in GT1a patients with compensated cirrhosis. Ninety-five to 100 percent achieved SVR12, which means the hepatitis C virus is not detectable in the blood three months after treatment ends. Cure rates varied by the subtype of hepatitis C and whether or not the person had cirrhosis. Individual results may vary.
USE
Viekira XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) extended-release tablets/Viekira Pak (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets) (Viekira) are prescription medicines used with or without ribavirin to treat adults with genotype 1 chronic (lasting a long time) hepatitis C (hep C) virus infection.
Viekira can be used in people who have compensated cirrhosis.
Viekira is not for people with advanced cirrhosis (decompensated). If people have cirrhosis, they should talk to a doctor before taking Viekira.

About Viekira XR

The components of Viekira XR* have been studied in a broad range of genotype 1 (GT1) patients with chronic hepatitis C virus (HCV) infection, ranging from treatment-naïve to difficult to treat patients, such as those with compensated (mild, Child-Pugh A) cirrhosis of the liver, HCV/HIV-1 co-infection, liver transplant recipients with normal hepatic function and mild fibrosis, and those who have failed previous treatment with pegylated interferon (pegIFN) and ribavirin (RBV).
The extended-release co-formulation of these components, Viekira XR, consists of 200 mg of dasabuvir, 8.33 mg of ombitasvir, 50 mg of paritaprevir, and 33.33 mg of ritonavir per tablet, and is dosed three tablets once daily. Viekira XR must be taken with a meal, and tablets should be swallowed whole. People should not drink alcohol within four hours of taking Viekira XR. Viekira XR is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B and C) due to risk of potential toxicity. Viekira XR is taken for 12 weeks, except in GT1a patients with cirrhosis and all liver transplant recipients with normal hepatic function and mild fibrosis, who should take it for 24 weeks. Ribavirin should be co-administered in GT1a patients and in all patients who have received a liver transplant.
Paritaprevir was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. Paritaprevir is used in combination with AbbVie's ombitasvir with or without dasabuvir for the treatment of hepatitis C.
*Given as a fixed-dose combination of ombitasvir 25mg (an NS5A inhibitor), paritaprevir 150mg (an NS3/4A protease inhibitor), and ritonavir 100mg (an HIV-1 protease inhibitor), dosed once daily with a meal, and dasabuvir 250mg (a non-nucleoside NS5B palm polymerase inhibitor), dosed twice daily with a meal.

Monday, May 1, 2017

Eisai Inc. and Arena Pharmaceuticals Announce FDA Approval of Belviq XR (lorcaserin HCl) Extended-Release Tablets

In continuation of my update on Lorcaserin
Eisai Inc. and Arena Pharmaceuticals, Inc.   announced   the approval by  U.S. Food and Drug Administration (FDA)  the New Drug Application (NDA) for Belviq XR (lorcaserin HCl) CIV extended-release 20 mg tablets. The new formulation of lorcaserin will offer patients a once-a-day dosing option that may help them achieve and maintain weight loss. Belviq XR is expected to be available in the fall of 2016. In connection with the approval, Arena will receive a $10 million milestone payment.
Lorcaserin.svg
Belviq XR is proven to be slowly absorbed in the body and lasts throughout the day. Both the original 10 mg twice-daily formulation of Belviq and newly-approved 20 mg once-daily extended release formulation are approved for use with a reduced-calorie diet and increased physical activity for chronic weight management in adults who have a body mass index (BMI) of 30 kg/m2 or greater (obese), or BMI of 27 kg/m2 or greater (overweight) with at least one weight-related medical condition, such as high blood pressure, high cholesterol, or type 2 diabetes. It is not known if Belviq or Belviq XR, when taken with other prescription, over-the-counter, or herbal weight-loss products, is safe and effective. It is not known if Belviq or Belviq XR changes your risk of heart problems, stroke, or death due to heart problems or stroke.
"With approximately two-thirds of the U.S. population living with extra weight or obesity, there is a significant and growing need to address chronic weight management," said Louis J. Aronne, M.D., Director of the Comprehensive Weight Control Center at Weill Cornell Medicine, physician at NewYork-Presbyterian/Weill Cornell Medical Center and Principal Investigator of the BELVIQ clinical trials. "Having a once-daily treatment may offer an option for patients to stay on track to meet their weight loss goals."
The bioequivalence and bioavailability of once-daily Belviq XR 20 mg compared with twice-daily Belviq 10 mg was based on two Phase 1 registrational clinical trials among healthy adult subjects. The most common treatment-emergent adverse events were similar to those seen in the Phase 3 clinical trials of Belviq 10 mg twice-daily.
"We're excited to offer this once-a-day option of lorcaserin," said Andrew Satlin, M.D., Executive Vice President, Neurology Business Group, Eisai Inc. "This option may provide another choice for patients who are overweight or obese and find it difficult to lose weight through diet and exercise alone. The development of this new formulation further underscores Eisai's ongoing commitment to help address the health care needs of this underserved population."
"We are pleased that once-daily Belviq XR has been approved by the FDA and will provide patients another option for weight loss," said Amit D. Munshi, Arena's President and Chief Executive Officer. "The approval of this new formulation is another example of Arena's success in supporting our collaborators."

What are Belviq and Belviq XR?

Belviq and Belviq XR are FDA-approved prescription weight-loss medications that, when used with diet and exercise, can help some overweight (Body Mass Index [BMI] ≥27 kg/m2) adults with a weight-related medical problem, or obese (BMI ≥30 kg/m²) adults, lose weight and keep it off.
It is not known if Belviq or Belviq XR when taken with other prescription, over-the-counter, or herbal weight-loss products is safe and effective. It is not known if Belviq or Belviq XR changes your risk of heart problems, stroke, or death due to heart problems or stroke.

Sunday, April 30, 2017

New wonder compound offers strong protection against harmful effects of UVA rays

A new wonder compound developed by University of Bath scientists in collaboration with King's College London offers unprecedented protection against the harmful effects of UVA radiation in sunlight, which include photo-ageing, cell damage and cancer.

Most sunscreens on the market protect well against solar UVB radiation but have limited effectiveness against UVA-induced damage, relying on the reflective properties of creams to defend against dangerous UVA rays.

However this compound, called the 'mitoiron claw' by the team, offers strong protection within our cells precisely where the greatest damage from UVA occurs, and doesn't interfere with rest of the cell.
The researchers from the University of Bath, working with colleagues at Kings College London, hope to see the mitoiron claw compound added to sunscreens and skin care products within 3-4 years.

Free iron concentration is particularly high within mitochondria, the batteries of the cell, where it is needed for several vital functions. However upon exposure to UVA in sunlight, excess free iron acts as a catalyst for the production of toxic reactive oxygen species (ROS), damaging cell components such as DNA, fat and proteins thereby increasing the risk of cell death and cancer.

However this custom-designed iron chelator (a molecule that binds to an iron atom like a claw) moves directly to mitochondria where it safely binds the excess free iron, preventing it from reacting upon exposure to UVA rays.

Tests with human skin fibroblast cells exposed to UVA radiation equivalent to 140 min of uninterrupted sun exposure at sea level, showed cells treated with the mitoiron claw were completely protected against cell death. Untreated cells suffered significant cell death.

The research is published in the Journal of Investigative Dermatology.

Dr Charareh Pourzand, from the Department of Pharmacy and Pharmacology at the University of Bath, said: "The role of iron-mediated damage induced upon exposure of skin cells to UVA has been underestimated for many years. For efficient protection against UVA-induced iron damage of skin strong chelators are needed, but until now these risked toxic effects caused by non-targeted iron starvation of cells.

"Our mitochondria-targeted compound provides a solution to this problem and can address an unmet need in the skincare and sunscreen fields. This mitoiron claw is a highly effective compound, offering unprecedented protection against UVA-induced mitochondrial damage."

Now that the protective effects of the compound have been demonstrated the team, Dr Charareh Pourzand and Dr Olivier Reelfs from University of Bath and Prof Robert Hider and Dr Vincenzo Abbate at Kings College London, plans further work to explore the potential of this new type of compound.

This includes the possibility of developing therapies for diseases involving mitochondrial iron overload, such as Friedreich's ataxia.


Ref:

1. http://www.bath.ac.uk/news/2016/07/20/sun-cream-uva/

2. http://www.jidonline.org/article/S0022-202X(16)31053-3/fulltext

Saturday, April 29, 2017

Combinations of three antibiotics could help combat drug-resistant bacterial infections

Amoxicillin.svg

Each year, approximately 700,000 people die from drug-resistant bacterial infections. A study by UCLA life scientists could be a major step toward combating drug-resistant infections.

The research, reported in the journal Royal Society Interface, found that combinations of three different antibiotics can often overcome bacteria's resistance to antibiotics, even when none of the three antibiotics on their own -- or even two of the three together -- is effective.

The researchers grew E. coli bacteria in a laboratory and treated the samples with combinations of one, two and three antibiotics from a group of 14 drugs. The biologists studied how effectively every single possible combination of drugs worked to kill the bacteria.

Some combinations killed 100 percent of the bacteria, including 94 of the 364 three-drug groupings the researchers tested. According to said Pamela Yeh, the paper's senior author and a UCLA assistant professor of ecology and evolutionary biology, the success rate might have been even greater if the researchers tested higher doses of the drugs.

Elif Tekin, the paper's lead author and a UCLA graduate student, helped create a sophisticated framework that enabled the scientists to determine when adding a third antibiotic was producing new effects that combinations of just two drugs couldn't achieve.

"Three antibiotics can change the dynamic," she said. "Not many scientists realize that three-drug combinations can have really beneficial effects that they would not have predicted even by studying all pairs of the antibiotics together."

Different classes of antibiotics use different mechanisms to fight bacteria. One class, which includes amoxicillin, kill bacteria by preventing them from making cell walls. Another disrupts their tightly coiled DNA. A third inhibits their ability to make proteins. But there had been little previous research indicating that combinations of three antibiotics might be more potent together than any two of them.
"People tend to think that you don't need to understand interactions beyond pairs," said Van Savage, a co-author of the paper and a UCLA associate professor of ecology and evolutionary biology and of biomathematics. "We found that isn't always so."

The researchers combined techniques from biology and mathematics to determine which groups of antibiotics would be most effective.

"The three antibiotics must be chosen systematically and rationally," Yeh said.

In addition to identifying certain combinations that were more potent than the researchers expected, the analysis revealed that adding a third antibiotic sometimes made the drug combination less potent -- sometimes much less so, she said.

Yeh said the findings could be one weapon to fight what has become a major public health risk, but overcoming drug resistance will require a full arsenal.

"We need sound policy to stop the overuse of antibiotics, doctors to prescribe antibiotics wisely, agriculture to stop overusing antibiotics and researchers to develop new antibiotics," she said. "We need to attack this problem from all sides. We think our contribution will buy time for researchers to better leverage existing drugs and for policymakers to develop better policy about the use of antibiotics."

Another benefit of three-drug combinations is that they could allow doctors to prescribe lower doses of each antibiotic, which could reduce side effects.

The researchers plan to make available open-access software that would let other scientists and clinicians decide which combinations of antibiotics will be most effective.

Yeh said the team's approach could also be used to study how four or more pharmaceuticals interact, and a similar mathematical framework could be used to better understand climate change (for example, to understand how temperature, rainfall, humidity and acidity of the oceans interact) and other scientific questions that have three or more key factors.

Ref : http://rsif.royalsocietypublishing.org/content/13/119/20160332

Friday, April 28, 2017

Combination of two plant compounds holds promise in treating colon cancer

In combination of my update on curcumin

The combination of two plant compounds that have medicinal properties - curcumin and silymarin - holds promise in treating colon cancer, according Saint Louis University research published in the June 23 issue of the Journal of Cancer.


Skeletal formula Skeletal formula  curcumin


Silibinin skeletal.svg silymarin

Curcumin is the active ingredient in the spice turmeric, which is present in spicy curry dishes, and silymarin is a component of milk thistle, which has been used to treat liver disease.

The researchers and their students studied a line of colon cancer cells in a laboratory model. They found treating the cells initially with curcumin, then with silymarin was more effective in fighting cancer than treating the cells with either phytochemical alone, said Uthayashanker Ezekiel, Ph.D., corresponding author and associate professor of biomedical laboratory science at Saint Louis University.

"The combination of phytochemicals inhibited colon cancer cells from multiplying and spreading. In addition, when the colon cancer cells were pre-exposed to curcumin and then treated with silymarin, the cells underwent a high amount of cell death," Ezekiel said.

"Phytochemicals may offer alternate therapeutic approaches to cancer treatments and avoid toxicity problems and side effects that chemotherapy can cause."

Ezekiel noted the research is a preliminary cell study, with more research ahead before scientists know if the compounds are an effective treatment for people who have colon cancer. He saw promise in using the phytochemicals to help prevent colon cancer, which frequently is caused by lifestyle factors, such as diet.

Scientists next would need to study how the curcumin and silymarin impact the actions of molecules, such as genetic transcription and expression, that cause cells to change, Ezekiel said. Then the compounds would be studied in an animal model, then in humans.

"Concentrations of curcumin and silymarin that are too high could be harmful to people," he said. "We still have much to learn, and for now, it's so much safer to add a little spice to your diet and get your curcumin from foods that contain turmeric, such as curry, rather than taking high doses of the compound."

Thursday, April 27, 2017

Cinnamon treatment turns poor-learning mice into good ones, research shows

If Dr. Kalipada Pahan's research pans out, the standard advice for failing students might one day be: Study harder and eat your cinnamon!

Image result for cinnamon Image result for sodium benzoate (sodium benzoate)

Pahan a researcher at Rush University and the Jesse Brown Veterans Affairs Medical Center in Chicago, has found that cinnamon turns poor learners into good ones--among mice, that is. He hopes the same will hold true for people.

His group published their latest findings online June 24, 2016, in the Journal of Neuroimmune Pharmacology.

"The increase in learning in poor-learning mice after cinnamon treatment was significant," says Pahan. "For example, poor-learning mice took about 150 seconds to find the right hole in the Barnes maze test. On the other hand, after one month of cinnamon treatment, poor-learning mice were finding the right hole within 60 seconds."

Pahan's research shows that the effect appears to be due mainly to sodium benzoate--a chemical produced as cinnamon is broken down in the body.

If that chemical sounds familiar, you may have noticed it on the ingredient labels of many processed foods. Food makers use a synthetic form of it as a preservative. It is also an FDA-approved drug used to treat hyperammonemia--too much ammonia in the blood.

Though some health concerns exist regarding sodium benzoate, most experts agree it's perfectly safe in the amounts generally consumed. One reassuring point is that it's water-soluble and easily excreted in the urine.

Cinnamon acts as a slow-release form of sodium benzoate, says Pahan. His lab studies show that different compounds within cinnamon--including cinnamaldehyde, which gives the spice is distinctive flavor and aroma--are "metabolized into sodium benzoate in the liver. Sodium benzoate then becomes the active compound, which readily enters the brain and stimulates hippocampal plasticity."

Those changes in the hippocampus--the brain's main memory center--appear to be the mechanism by which cinnamon and sodium benzoate exert their benefits.

In their study, Pahan's group first tested mice in mazes to separate the good and poor learners. Good learners made fewer wrong turns and took less time to find food.

In analyzing baseline disparities between the good and poor learners, Pahan's team found differences in two brain proteins. The gap was all but erased when cinnamon was given.

"Little is known about the changes that occur in the brains of poor learners," says Pahan. "We saw increases in GABRA5 and a decrease in CREB in the hippocampus of poor learners. Interestingly, these particular changes were reversed by one month of cinnamon treatment."

The researchers also examined brain cells taken from the mice. They found that sodium benzoate enhanced the structural integrity of the cells--namely in the dendrites, the tree-like extensions of neurons that enable them to communicate with other brain cells.

Cinnamon, like many spices, has antioxidant and anti-inflammatory properties. So it could be expected to exert a range of health-boosting actions, and it does have a centuries-long history of medicinal use around the world.

But the U.S. National Center for Complementary and Integrative Health says that "high-quality clinical evidence to support the use of cinnamon for any medical condition is generally lacking." Most of the clinical trials that have taken place have focused on the spice's possible effect on blood sugar for people with diabetes. Little if any clinical research has been done on the spice's possible brain-boosting properties.

Pahan hopes to change that. Based on the promising results from his group's preclinical studies, he believes that "besides general memory improvement, cinnamon may target Alzheimer's disease, mild cognitive impairment [a precursor to Alzheimer's], and Parkinson's disease as well." He is now talking with neurologists about planning a clinical trial on Alzheimer's.

Before you start heaping cinnamon on your oatmeal, keep a few caveats in mind.

First, most cinnamon found in the store is the Chinese variety, which contains a compound called coumarin that may be toxic to the liver in high amounts. A person would likely have to eat tons of cinnamon to run into a problem, but just the same, Pahan recommends the Ceylon or Sri Lanka type, which is coumarin-free.

Even then, don't overdo it. "Anything in excess is toxic," says Pahan.

What about simply inhaling the pleasant-smelling spice? Will that benefit the brain?

"Simply smelling the spice may not help because cinnamaldehyde should be metabolized into cinnamic acid and then sodium benzoate," explains Pahan. "For metabolism [to occur], cinnamaldehyde should be within the cell."

As for himself, Pahan isn't waiting for clinical trials. He takes about a teaspoonful--about 3.5 grams--of cinnamon powder mixed with honey as a supplement every night.

Should the research on cinnamon continue to move forward, he envisions a similar remedy being adopted by struggling students worldwide.

"Individual differences in learning and educational performance is a global issue, he says. "In many cases, we find two students of the same background studying in the same class, and one turns out to be a poor learner and does worse than the other academically. Now we need to find a way to test this approach in poor learners. If these results are replicated in poor-learning students, it would be a remarkable advance. At present, we are not using any other spice or natural substance."

Wednesday, April 26, 2017

Rare antibiotic compound detected in fungi for first time

In continuation of my update on valproic acid

Besides mushrooms such as truffles or morels, also many yeast and mould fungi, as well as other filamentous fungi belong to the Ascomycota phylum. They produce metabolic products which can act as natural antibiotics to combat bacteria and other pathogens. Penicillin, one of the oldest antibiotic agents, is probably the best known example. Since then, fungi have been regarded as a promising biological source of antibiotic compounds. Researchers expect that there is also remedy for resistant pathogens among these metabolites.

It depends on the stimulus

However, agents like penicillin are only produced when necessary, not permanently. "Fungi can even deactivate the respective parts of their genome if a metabolite is not needed anymore. These compounds can't be detected any longer and are classified as cryptic compounds," explained Christoph Zutz from the Institute for Milk Hygiene, Milk Technology and Food Science of the Vetmeduni Vienna.

The right stimulus can reinduce the production of antibiotic compounds. The researchers used valproic acid which can induce the activation of such deactivated genes in fungi. In the fungus Doratomyces microsporus, valproic acid even induced the production of several antimicrobial compounds.

ChemSpider 2D Image | cyclo-(L-proline-L-methionine) | C10H16N2O2S
Valproic acid.svg 1.valproic acid  



2. cyclo-(L-proline-L-methionine)
Rare compound detected in fungi for the first time

The gained metabolites were effective against a "normal", as well as resistantStaphylococcus aureus pathogens. The team succeeded in filtering out the six most active compounds from all metabolites. These six compounds have been regarded as "cryptic" so far. One compound, cyclo-(L-proline-L-methionine) or cPM, could be detected even for the first time in a fungus. The only source of this compound so far has been a bacterium living in an Antarctic sponge.

Boosting effect as an asset in the fight against resistance

The as yet "cryptic" compound cPM has a special function. It boosts the activity of other antimicrobial compounds. The team assumes that particularly this boosting effect constitutes the effect these compounds have on the tested pathogens.

Therefore, the researchers went a step further and tested the newly detected compound cPM together with ampicillin in two ampicillin-resistant bacteria. The combination has proved successful. "The resistance was demonstrably reduced, even at a lower dose of ampicillin than usually," said co-author and corresponding group leader Kathrin Rychli.

New research platform is looking at the big picture

The team is now going to search for novel antibiotic compounds from other microorganisms by applying similar methods. The new research platform "Bioactive Microbial Metabolites" (BiMM) in Tulln (Lower Austria) provides the facility. BiMM represents the detection of bioactive compounds - metabolites - in microorganisms. "Valproic acid is not the only way to gain active compounds from fungi or other microorganisms. You can also make bacteria and fungi grow together. This also leads to a natural stimulus," explained Joseph Strauss from the University of Natural Resources and Life Sciences, Vienna, who heads the platform. For this purpose, researchers from the University of Veterinary Medicine, Vienna and the University of Natural Resources and Life Sciences, Vienna founded this new research core facility.

Christoph Zutz identified a significant advantage of this inter-university research platform. "Unlike industrial enterprises, we investigate all promising metabolites in microorganisms, not only single chemical compounds. Thus, we consider known and cryptic compounds in our analyses."

Ref : http://www.vetmeduni.ac.at/en/infoservice/news/detail/artikel/2016/07/15/fungi/