Potential antidote to botulism

Researchers have identified a compound that strongly inhibits botulinum neurotoxin, the most toxic compound known. That inhibiting compound, nitrophenyl psoralen (NPP), could be used as a treatment to reduce paralysis induced by botulism. Botulinum neurotoxin is considered a potential bioweapon because there is no FDA-approved antidote. In the study, researcher’s first step was to identify the enzyme within botulinum neurotoxin that damages neurons, causing paralysis. Researcher’s screened a library containing more than 300 natural compounds from extracts of Indian medicinal plants, searching for enzymes that could neutralize the neuron-damaging activity. The investigators then tested NPP's activity in vitro and in cell culture against botulinum neurotoxin type A, which is the most potent serotype among the seven serotypes of botulinum toxin. NPP type A had powerful anti-botulinum toxin activity, with low toxicity to human cells. Researcher said, NPP also showed activity to reverse the mouse muscle paralysis induced by botulinum neurotoxin type A. Although fewer than 200 botulism cases occur worldwide, annually. Botulism can be acquired through routes other than food poisoning, such as through wound contamination, and via colonization of the digestive tracts of children and infants. Psoralen derived drugs are already approved by the FDA in the United States. That would likely hasten the drug approval process for NPP, said by lead researcher.

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                                      Weight likely cause for one-fourth of asthma cases in kids with obesity

This could mean about 10 percent of all kids ages 2 to 17 with asthma almost 1 million children in the U.S. might have avoided the illness by maintaining a healthy weight. Asthma is the No. 1 chronic disease in children and some of the causes such as genetics and viral infections during childhood are things can't prevent, said by lead researcher. Obesity may be the only risk factor for childhood asthma that could be preventable. This is another piece of evidence that keeping kids active and at a healthy weight is important. Children classified as obese those with a body-mass index (BMI) in the 95th percentile or above for their age and sex had a 30-percent increased risk of developing asthma than peers of a healthy weight. Asthma did not affect just those with obesity. Children who were overweight but not obese (BMI in the 85-94th percentile) also had a 17-percent increased asthma risk compared to healthy-weight peers. The researchers calculated asthma risk using several models and adjusted for risk factors such as sex, age, socioeconomic status and allergies. The results remained similar. Researcher said, the study has several limitations, including that the data were collected during doctor's visits and not in a controlled clinical research setting & more experiments are needed to prove overweight and obesity directly cause changes that lead to asthma because scientists don't completely understand how or why this would occur. Still, these findings and others, such as how asthma often improves with weight loss, suggests obesity plays a key role or is directly to blame.

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                               Migraine linked to increased risk of cardiovascular problems

Migraine is associated with increased risks of cardiovascular problems including heart attacks, stroke, blood clots and an irregular heart rate, said by lead researchers. Although the absolute risks were low, the findings suggest that migraine should be considered a potent and persistent risk factor for most cardiovascular diseases in both men and women. Around one billion people worldwide are affected by migraine. Previous studies have suggested a link between migraine and stroke and heart attacks, particularly among women, but the link between migraine and other heart problems are less well known. The average age for migraine diagnosis was 35 years, and 71% of participants were women. Over a period of 19 years, the researchers found that migraine was positively associated with heart attack, stroke, blood clots and irregular heart rate. These associations persisted after taking account of body mass index and smoking. No meaningful association was found with peripheral artery disease or heart failure. This is an observational study, so no firm conclusions can be drawn about cause and effect, and the researcher cannot rule out the possibility that other unknown factors, such as physical activity, may have influenced the results. However, key strengths include the large sample size and long term follows up. It will be important to determine whether prevention strategies in patients with migraine can reduce the burden of cardiovascular disease.

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                                              Cancer stem cells get energy from protein

Cancer cells do things a little differently. First, most cancer cells continue to depend on glucose, but switch over from cellular respiration (which requires oxygen), to glycolysis (which can happen with or without oxygen). Researcher sticks with cellular respiration, but switch from metabolizing sugar to metabolizing protein, or more precisely amino acids, which are the building blocks of protein. Healthy cells don't need to metabolize protein. The current study shows that cancer stem cells do need to metabolize protein. And this difference is proving to be an Achilles' heel that allows researchers to target cancer stem cells without harming healthy cells the approach has already proven effective in clinical trials against acute myeloid leukemia (AML) and holds promise for other cancers including breast, pancreatic, and liver. Conventional chemotherapy is not effective for most patients with acute myeloid leukemia. The new results with venetoclax look very promising. The current study circles back to pinpoint why the clinical trial was so successful. Study showed that leukemia stem cells do not (or are perhaps unable) to switch from cellular respiration to glycolysis like more mature cancer cells. Instead, switch from metabolizing glucose to metabolizing amino acids in fact, researcher come to absolutely depend on metabolizing amino acids for energy, so much so that when the ability of leukemia stem cells to uptake amino acids is interrupted, these cells die. The drug venetoclax stops leukemia stem cells from being able to use amino acids for energy. In the lab and now in the clinic, when researchers treated AML patients with venetoclax, leukemia stem cells died. Importantly, because healthy cells do not depend on amino acid metabolism, venetoclax killed leukemia stem cells without harming healthy cells. The group's future work hopes to explore the possibility of inhibiting lipid metabolism along with amino acid metabolism for use with AML patients whose cancers have resisted or relapsed after previous therapies.

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                                              Sudden cardiac arrest: New findings

An Association Between Multiple Sclerosis and Sudden Cardiac Death, Investigators found patients with multiple sclerosis have a five-fold higher incidence of sudden cardiac arrest over the general U.S. population. This observational study evaluated clinical characteristics of individuals who suffered cardiac arrest in the community. While the reasons for this finding need to be investigated, the brain has established links with heart function and could be influencing electrical function of the heart. Enhancement of Sudden Death Risk Prediction in Patients With Left Ventricular Hypertrophy -- Patients with left ventricular hypertrophy (LVH) also have a higher risk of sudden cardiac arrest, but until now, researchers have been unable to identify which patients are at highest risk. Using a novel electrocardiography risk score researcher identify patients with intermediate or high-risk LVH. Researcher’s plan to test their findings in a larger group of patients. This research study aimed to find if a correlation exists between obesity and LVH, or if independent of one another. Next steps are to understand if being both obese and having LVH doubles the risk of sudden cardiac arrest. Although "sudden cardiac arrest" and "heart attack" often are used interchangeably, the terms are not synonymous. Unlike heart attacks (myocardial infarctions), which are typically caused by clogged coronary arteries reducing blood flow to the heart muscle, sudden cardiac arrest is the result of defective electrical activity of the heart. Patients may have little or no warning, and the disorder usually causes instantaneous death. Sudden cardiac arrest accounts for approximately 300,000 deaths each year in the U.S.

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