Research aims for insecticide that targets malaria mosquitoes

Acetylcholinesterase helps regulate nervous system activity by stopping electrical signaling in nerve cells. If the enzyme can't do its job, the mosquito begins convulsing and dies. The research team's goal is to develop compounds perfectly matched to the acetylcholinesterase molecules in malaria-transmitting mosquitoes, he said.

"A simple analogy would be that we're trying to make a key that fits perfectly into a lock," Bloomquist said. "We want to shut down the enzyme, but only in target species."

Bloomquist and colleagues at Virginia Tech, where the project is based, are trying to perfect mosquito-specific compounds that can be manufactured on a large scale and applied to mosquito netting and surfaces where the pests might land.

It will take at least four to five years before the team has developed and tested a compound enough that it's ready to be submitted for federal approval, Bloomquist said.

As per the claims by the researchers, conventional insecticides targeting acetylcholinesterase (AChE) typically show high mammalian toxicities and because there is resistance to these compounds in many insect species, alternatives to established AChE inhibitors used for pest control are needed. Here researchers  used a fluorescence method to monitor interactions between various AChE inhibitors and the AChE peripheral anionic site, which is a novel target for new insecticides acting on this enzyme. The assay uses thioflavin-T as a probe, which binds to the peripheral anionic site of AChE and yields an increase in fluorescent signal. Three types of AChE inhibitors were studied: catalytic site inhibitors (carbamate insecticides, edrophonium, and benzylpiperidine), peripheral site inhibitors (tubocurarine, ethidium bromide, and propidium iodide), and bivalent inhibitors (donepezil, BW284C51, and a series of bis(n)-tacrines). All were screened on murine AChE to compare and contrast changes of peripheral site conformation in the TFT assay with catalytic inhibition. All the inhibitors reduced thioflavin-T fluorescence in a concentration-dependent manner with potencies (IC₅₀) ranging from 8 nM for bis(6)-tacrine to 159 μM for benzylpiperidine. Potencies in the fluorescence assay were correlated well with their potencies for enzyme inhibition (R² = 0.884). Efficacies for reducing thioflavin-T fluorescence ranged from 23–36% for catalytic site inhibitors and tubocurarine to near 100% for ethidium bromide and propidium iodide. Maximal efficacies could be reconciled with known mechanisms of interaction of the inhibitors with AChE. When extended to pest species, we anticipate these findings will assist in the discovery and development of novel, selective bivalent insecticides acting on AChE....

 Ref : http://www.sciencedirect.com/science/article/pii/S0048357513000655#f0025

Research aims for insecticide that targets malaria mosquitoes

Fish Oil Pills Might Cut Diabetes Risk....

Supplements, also known as omega-3 fatty acids, increase levels of a hormone called adiponectin that's linked to insulin sensitivity, Harvard researchers found. Higher levels of this hormone in the bloodstream have also been linked to a lower risk for heart disease.

"While prior animal studies found fish oil increased circulating adiponectin, whether similar effects apply in humans is not established," the study's lead author, Jason Wu, from the Harvard School of Public Health, said in a news release from the Endocrine Society.

For their study, the researchers conducted a "meta-analysis" of 14 clinical trials. A meta-analysis reviews existing research and attempts to find a consistent pattern. In this case, the studies that were reviewed were all randomized, placebo-controlled trials, which is considered the gold standard in research.

"By reviewing evidence from existing randomized clinical trials, we found that fish oil supplementation caused modest increases in adiponectin in the blood of humans," Wu explained.

Overall, the new study looked at 682 people who took fish oil supplements, and 641 who were given placebos such as sunflower or olive oil.

Among the people treated with fish oil, adiponectin levels increased by 0.37 micrograms per milliliter of blood. This hormone plays a beneficial role in processes that affect metabolism, such as blood sugar regulation and inflammation.

Because the effects of fish oil varied significantly in the studies analyzed, the researchers suggested that omega-3 fatty acids could have a stronger effect in certain groups of people. The investigators concluded that more research is needed to determine which people would benefit most from fish oil supplements.

"Although higher levels of adiponectin in the bloodstream have been linked to lower risk of diabetes and coronary heart disease, whether fish oil influences glucose [blood sugar] metabolism and development of type 2 diabetes remains unclear," Wu said.

More - Read at

Fish Oil Pills Might Cut Diabetes Risk, Researchers Say - Drugs.com MedNews

Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction : Nature Communications : Nature Publishing Group

In a striking, unexpected discovery, researchers at Albert Einstein College of Medicine of Yeshiva University have determined that vitamin C kills drug-resistant tuberculosis (TB) bacteria in laboratory culture. The finding suggests that vitamin C added to existing TB drugs could shorten TB therapy, and it highlights a new area for drug design.

Dr. Jacobs and his colleagues observed that isoniazid-resistant TB bacteria were deficient in a molecule called mycothiol. "We hypothesized that TB bacteria that can't make mycothiol might contain more cysteine, an amino acid," said Dr. Jacobs. 

"So, we predicted that if we added isoniazid and cysteine to isoniazid-sensitive M. tuberculosis in culture, the bacteria would develop resistance. Instead, we ended up killing off the culture  something totally unexpected."

The Einstein team suspected that cysteine was helping to kill TB bacteria by acting as a "reducing agent" that triggers the production of reactive oxygen species (sometimes called free radicals), which can damage DNA.

"To test this hypothesis, we repeated the experiment using isoniazid and a different reducing agent vitamin C," said Dr. Jacobs. "The combination of isoniazid and vitamin C sterilized the M. tuberculosis culture. We were then amazed to discover that vitamin C by itself not only sterilized the drug-susceptible TB, but also sterilized MDR-TB and XDR-TB strains."

To justify testing vitamin C in a clinical trial, Dr. Jacobs needed to find the molecular mechanism by which vitamin C exerted its lethal effect. More research produced the answer: Vitamin C induced what is known as a Fenton reaction, causing iron to react with other molecules to create reactive oxygen species that kill the TB bacteria.

"We don't know whether vitamin C will work in humans, but we now have a rational basis for doing a clinical trial," said Dr. Jacobs. "It also helps that we know vitamin C is inexpensive, widely available and very safe to use. At the very least, this work shows us a new mechanism that we can exploit to attack TB.".....

Ref : http://www.einstein.yu.edu/news/releases/907/study-finds-vitamin-c-can-kill-drug-resistant-tb/


Mycobacterium tuberculosis is extraordinarily sensitive to killing by a vitamin C-induced Fenton reaction : Nature Communications : Nature Publishing Group

New tumor-killer shows great promise in suppressing cancers

A molecule  based on a natural protein present in human breast milk, which has been found to have strong and wide-ranging tumour killing properties when bound to certain lipids. Lipids are organic molecules like amino acids and carbohydrates, made up of carbon and hydrogen, and help to store energy and to form biological membranes.

The protein-lipid molecule complex, is known as HAMLET, which stands for Human Alpha-lactabumin Made Lethal to Tumour cells. It has been proven to be safe and effective as it only targets tumour cells, leaving healthy human cells intact.

HAMLET has most recently been shown to successfully suppress colon cancer in laboratory mice.

The scientists have also successfully identified and isolated specific components of HAMLET called peptide-oleate bound forms, which have the tumour-killing effect. Peptides are short chain amino acids commonly found in the human body.

These latest breakthroughs are led by Professor Catharina Svanborg and Dr Manoj Puthia from Lund University, Sweden, and Professor Gerhard Grüber from NTU's School of Biological Sciences. The HAMLET complex was first discovered by Professor Svanborg's research group.

The findings were published recently in Gut and in PLoS ONE. The researchers found that laboratory mice genetically modified to develop colon cancer, were protected to a large extent when fed with HAMLET- laced water. This suggested that HAMLET was killing emerging tumour cells faster than these cells could grow and proliferate.

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0053051

New tumor-killer shows great promise in suppressing cancers

Most Commonly Used Glaucoma Drug Can Cause Droopy Eyelids | Massachusetts Eye and Ear Infirmary

Prostaglandin analogues (PGAs), drugs which lower intraocular pressure, are often the first line of treatment for people with glaucoma, but their use is not without risks. PGAs have long been associated with blurred vision, dryness, changes in eye color and other side effects. Now a new study has found that these drugs also cause upper and lower eyelid drooping and other issues that can interfere with vision.

"We identified important side effects of PGAs, namely the loss of periorbital fat in the upper and lower lid and the presence of ptosis," said senior author Louis R. Pasquale, M.D., F.A.R.V.O., director of the Glaucoma Service at Mass. Eye and Ear and associate professor of ophthalmology at Harvard Medical School. "The loss of periorbital fat was previously described by us in a small series of unilateral PGA users. In fact, those observations did ultimately lead to a change in drug labeling. These new findings could change labeling for the PGAs, as the upper lid ptosis could aggravate pre-existing visual field loss."

Researchers performed this study to confirm whether prostaglandin-associated periorbitopathy (PAP) is clearly associated with PGA application among bilateral users using a validated grading scheme applied by masked observers and confirmed by clinical examination. They performed multivariable analyses to assess whether PAP was independently associated with PGA use or if it was the result of confounding features such as age, ethnicity, BMI or use of other classes of glaucoma medications. They studied 343 patients (186 females and 157 males) over the course of seven months in 2011.

The study showed associations between current bilateral PGA use and deepened upper eyelid sulci, hollowing of the inferior periorbital fat pads, upper eyelid ptosis with levator muscle dysfunction, and lower lid retraction. Their work demonstrated that PAP is fairly common and consists of findings that extend beyond deepening of the upper eyelid sulcus.

Most Commonly Used Glaucoma Drug Can Cause Droopy Eyelids | Massachusetts Eye and Ear Infirmary

Ref : http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0061638

Scientists Uncover How Grapefruits Provide a Secret Weapon in Medical Drug Delivery...

Lipids (right panel first three tubes) derived from grapefruit. GNVs can efficiently deliver a variety of therapeutic agents, including DNA, RNA (DIR-GNVs), proteins and anti-cancer drugs (GNVs-Drugs) as demonstrated in this study. University of Louisville researchers have uncovered how to create nanoparticles using natural lipids derived from grapefruit, and have discovered how to use them as drug delivery vehicles.

"These nanoparticles, which we've named grapefruit-derived nanovectors (GNVs), are derived from an edible plant, and we believe they are less toxic for patients, result in less biohazardous waste for the environment, and are much cheaper to produce at large scale than nanoparticles made from synthetic materials," Zhang said.

The researchers demonstrated that GNVs can transport various therapeutic agents, including anti-cancer drugs, DNA/RNA and proteins such as antibodies. Treatment of animals with GNVs seemed to cause less adverse effects than treatment with drugs encapsulated in synthetic lipids.

"Our GNVs can be modified to target specific cells -- we can use them like missiles to carry a variety of therapeutic agents for the purpose of destroying diseased cells," he said. "Furthermore, we can do this at an affordable price."

The therapeutic potential of grapefruit derived nanoparticles was further validated through a Phase 1 clinical trial for treatment of colon cancer patients. So far, researchers have observed no toxicity in the patients who orally took the anti-inflammatory agent curcumin encapsulated in grapefruit nanoparticles.

Ref : http://www.nature.com/ncomms/journal/v4/n5/full/ncomms2886.html

Experimental drug beneficial in trial to treat a rare sarcoma

We know that, Cediranib (tentative trade name Recentin), also known as AZD2171, is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases. It is being developed by AstraZeneca as a possible anti-cancer chemotherapeutic agent for oral administration. Beginning in 2007, it is undergoing Phase I clinical trials for the treatment of non-small cell lung cancer, kidney cancer, and colorectal cancer in adults, as well as tumors of the central nervous system in children. Phase I trials of interactions with other drugs used in cancer treatment are also underway.\

On February 27, 2008, AstraZeneca announced that the use of Recentin in non-small cell lung cancer will not progress into phase III after failing to meet its main goal. On 8th March 2010, AstraZeneca issued a press-release stating that Recentin had failed Phase III clinical trials for use in first-line metastatic colorectal cancer when it was compared clinically with the market-leader bevacizumab. 

As of November 2012, it is currently in double-blind studies for the treatment of methylated Glioblastoma Multiforme at the University of Washington Medical Center at a 20mg daily dose.

Now...

Patients with advanced alveolar soft part sarcoma (ASPS), a rare cancer, achieved some control of their disease using an experimental anti-cancer drug called cediranib. The results from this largest clinical trial on ASPS to date were published online ahead of print on April 29, 2013, in the Journal of Clinical Oncology.

Ref : http://jco.ascopubs.org/content/early/2013/04/29/JCO.2012.47.4288

Experimental drug beneficial in trial to treat a rare sarcoma

Nearly five million asthmatics worldwide could benefit from antifungal therapy

Clinical studies have shown that oral antifungal drugs significantly improve symptoms and asthma control in asthmatics with ABPA, treatment endorsed by the Cochrane Collaboration. This is the first time that a global estimate of ABPA numbers has been made.

In national league tables of asthma rates in adults, only Australia and Sweden have a higher prevalence than the UK. In global league tables of ABPA occurrence, New Zealand tops the list with a 3.5% rate in new patients attending chest clinics at hospitals. The rates were 2.6% in Cape Town, 2.3% in Saudi Arabia, 2.5% in China and 0.7% in an older study from Ireland. No population-based studies have been done.

Itraconazole

Posaconazole

Voriconazole

In addition to standard asthma therapy, the antifungal therapy used is itraconazole  now a generic, inexpensive antifungal  with a response rate of 60%. The researchers also found that antifungal therapy also benefits patients with severe asthma sensitized to fungi, called SAFS.

Alternatives include voriconazole and posaconazole, which have 75-80% response rates. In a recent assessment of voriconazole and posaconazole for both ABPA and SAFS, 75% of patients were able to stop taking oral corticosteroids, a major benefit, and 38% of patients had their asthma severity downgraded on antifungal therapy.

Professor David Denning, professor of medicine and medical mycology at the University of Manchester and Director of the University Hospital of South Manchester's National Aspergillosis Centre, led the study into the total number of asthmatics worldwide. He said the study results implied that asthma admissions and deaths could be avoided with more extensive use of antifungal therapy.

"We were surprised by the number of patients with ABPA, and by the lack of community based studies done," he said. "Our National Aspergillosis Centre treats hundreds of these patients each year, generally with major improvement, and so a conscious program to seek out ABPA from all asthmatics is required."

Professor Donald Cole of the Dalla Lana School of Public Health at the University of Toronto was the senior author of the study and contributed his expert epidemiological knowledge to the development of the model and provided a 'reality' check of the model's estimates.

Nearly five million asthmatics worldwide could benefit from antifungal therapy

Popular diabetes drug does not improve survival rates after cancer

In continuation of my update on metformin

Despite previous scientific studies that suggest diabetes drug metformin has anti-cancer properties, a new, first-of-its-kind study from Women's College Hospital has found the drug may not actually improve survival rates after breast cancer in certain patients.

The study, published in the journal Diabetes Care, failed to show an improved survival rate in older breast cancer patients with diabetes taking the drug metformin, a first-line treatment for diabetes. However, the authors caution further research is necessary to validate the study's findings.

"Metformin is a drug commonly used by diabetic patients to control the amount of glucose in their blood," said the study's lead author Dr. Iliana Lega, a research fellow at Women's College Research Institute. "Although existing scientific literature suggests that drug may prevent new cancers and death from breast cancer, our study found the drug did not significantly impact survival rates in our patients."

Scientific research has found metformin is associated with an up to 30 per cent reduction in new cancers and a reduction in tumour growth in non-diabetic breast cancer patients treated with the drug, Dr. Lega notes in the study.

To test the drug's anti-cancer properties, the authors examined 2,361 women, aged 66 or older who were treated with the drug and diagnosed with breast cancer between April 1, 1997 and March 31, 2008. The women were followed from their date of breast cancer diagnosis until their death or until March 30, 2010. The researchers found no significant statistical correlation between cumulative use of metformin and death from all causes or a significant reduction in deaths due to breast cancer.

"What makes our study so unique is that while the effects of metformin have been well documented, previous research has not examined the cumulative effects of the drug on patients, particularly breast cancer patients with diabetes," Dr. Lega said. "This is important given that diabetic patients may switch drugs over the course of their treatment."

The authors note a lack of data on body mass index, breast cancer stage and a short followup period for breast-cancer specific deaths, limit interpretation of their findings. Further research is necessary in a younger population of patients with breast cancer and diabetes.

"Understanding the effects of metformin on breast cancer patients is critical in helping address the gap in cancer outcomes in patients with and without diabetes," she added. "The findings will help physicians inform treatment plans for patients with diabetes."

Ref : http://care.diabetesjournals.org/content/early/2013/04/30/dc12-2535

Popular diabetes drug does not improve survival rates after cancer

Soy and tomato may be effective in preventing prostate cancer

Tomatoes and soy foods may be more effective in preventing prostate cancer when they are eaten together than when either is eaten alone, said a University of Illinois study.

"Eating tomato, soy, and the combination all significantly reduced prostate cancer incidence. But the combination gave us the best results. Only 45 percent of mice fed both foods developed the disease compared to 61 percent in the tomato group, and 66 percent in the soy group," he said.

Prostate cancer is the most frequently diagnosed cancer in men, but the disease has nearly a 100 percent survival rate if it's caught early. In older men, it is often a slow-growing cancer, and these men often choose watchful waiting over radiation and surgical treatments that have unwelcome side effects, said Krystle Zuniga, co-author of the paper.

Soy isoflavone serum and prostate levels in the mice are similar to those found in Asian men who consume one to two servings of soy daily. In countries where soy is eaten regularly, prostate cancer occurs at significantly lower levels, Erdman noted.

How much soy and tomato should a 55-year-old man concerned about prostate health eat in order to receive these benefits?

"The results of the mouse study suggest that three to four servings of tomato products per week and one to two servings of soy foods daily could protect against prostate cancer," Zuniga said.

According to the scientists, these findings reinforce the recommendation that we should all eat a wide variety of whole fruits and vegetables.

"It's better to eat a whole tomato than to take a lycopene supplement. It's better to drink soy milk than to take soy isoflavones. When you eat whole foods, you expose yourself to the entire array of cancer-fighting, bioactive components in these foods," Erdman said.

The researcher's whole-food recommendation is bolstered by the way soy germ performed in this study. He noted that soy germ has a very different isoflavone profile than the rest of the soybean.

"Of the isoflavones, genistein gets most of the attention. But soy germ is very high in the other isoflavones, daidzein and glycitein, and low in genistein," he said...

Ref : http://cancerpreventionresearch.aacrjournals.org/content/early/2013/04/16/1940-6207.CAPR-12-0443

Soy and tomato may be effective in preventing prostate cancer

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

Cancer drug prevents build-up of toxic brain protein

In continuation of my update on Nilotinib

We know that, Nilotinib (AMN107, trade name Tasigna), in the form of the hydrochloride monohydrate salt, is a tyrosine kinase inhibitor approved for the treatment of chronic myelogenous leukemia

Now, researchers at Georgetown University Medical Center have used tiny doses of a leukemia drug nilotinib,  to halt accumulation of toxic proteins linked to Parkinson's disease in the brains of mice. This finding provides the basis to plan a clinical trial in humans to study the effects.....More...

Cancer drug prevents build-up of toxic brain protein

Ref : http://hmg.oxfordjournals.org/content/early/2013/05/09/hmg.ddt192

Eating Peppers Tied to Lower Parkinson's Risk, Study Finds - Drugs.com MedNews

Eating vegetables that naturally contain nicotine, such as peppers and tomatoes, may reduce your risk of developing Parkinson's disease, according to a new study....

Eating Peppers Tied to Lower Parkinson's Risk, Study Finds - Drugs.com MedNews

FDA Approves Merck’s Liptruzet (ezetimibe and atorvastatin), a New Product That Can Help Lower LDL Cholesterol

In continuation of my update on ezetimibe and atorvastatin
FDA Approves Merck’s Liptruzet (ezetimibe and atorvastatin), a New Product That Can Help Lower LDL Cholesterol

FDA Approves Breo Ellipta to Treat Chronic Obstructive Pulmonary Disease (COPD)

  The U.S. Food and Drug Administration today approved Breo Ellipta (fluticasone furoate above structure) and vilanterol (below structure)  inhalation powder) for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. It is also approved to reduce exacerbations of COPD in patients with a history of exacerbations......

FDA Approves Breo Ellipta to Treat Chronic Obstructive Pulmonary Disease (COPD)