Vinegar kills tuberculosis, other mycobacteria

The active ingredient in vinegar, acetic acid, can effectively kill mycobacteria, even highly drug-resistant Mycobacterium tuberculosis, an international team of researchers from Venezuela, France, and the US reports in mBio, the online open-access journal of the American Society for Microbiology.Acetic acid might be used as an inexpensive and non-toxic disinfectant against drug-resistant tuberculosis (TB) bacteria as well as other stubborn, disinfectant-resistant mycobacteria.Work with drug-resistant tuberculosis bacteria carries serious biohazard risks. Chlorine bleach is often used to disinfect TB cultures and clinical samples, but bleach is toxic and corrosive. Other effective commercial disinfectants can be too expensive for TB labs in the resource-poor countries where the majority of TB occurs.”Mycobacteria are known to cause tuberculosis and leprosy, but non-TB mycobacteria are common in the environment, even in tap water, and are resistant to commonly used disinfectants. When they contaminate the sites of surgery or cosmetic procedures, they cause serious infections. Innately resistant to most antibiotics, they require months of therapy and can leave deforming scars.” says Howard Takiff, senior author on the study and head of the Laboratory of Molecular Genetics at the Venezuelan Institute of Scientific Investigation (IVIC) in Caracas.”Many cosmetic procedures are performed outside of hospital settings in developing countries, where effective disinfectants are not available.” Takiff says, “These bacteria are emerging pathogens. How do you get rid of them?”While investigating the ability of non-TB mycobacteria to resist disinfectants and antibiotics, Takiff’s postdoctoral fellow, Claudia Cortesia stumbled upon vinegar’s ability to kill mycobacteria. Testing a drug that needed to be dissolved in acetic acid, Cortesia found that the control, with acetic acid alone, killed the mycobacteria she wanted to study.”After Claudia’s initial observation, we tested for the minimal concentrations and exposure times that would kill different mycobacteria,” says Takiff. Since the Venezuelan lab does not work with clinical TB, collaborators Catherine Vilchze and William Jacobs, Jr. at the Albert Einstein College of Medicine in New York tested TB strains and found that exposure to a 6% solution of acetic acid for 30 minutes effectively kills tuberculosis, even strains resistant to almost all antibiotics.Said another way, exposure to 6% acetic acid, just slightly more concentrated than supermarket vinegar, for 30 minutes, reduced the numbers of TB mycobacteria from around 100 million to undetectable levels.During a sabbatical in Laurent Kremer’s laboratory at the University of Montpellier 2 in France, Takiff tested how effective acetic acid was against M. abscessus, one of the most resistant and pathogenic of the non-TB mycobacteria.M. …

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Addicts and Disease

Commentary.Former National Institute on Drug Abuse (NIDA) director Alan Leshner has been vilified by many for referring to addiction as a chronic, relapsing “brain disease.” What often goes unmentioned is Leshner’s far more interesting characterization of addiction as the “quintessential biobehavioral disorder.”Multifactorial illnesses present special challenges to our way of thinking about disease. Addiction and other biopsychosocial disorders often show symptoms at odds with disease, as people generally understand it. For patients and medical professionals alike, questions about the disease aspect of addiction tie into larger fears about the medicalization of human behavior.These confusions are mostly understandable. Everybody knows what cancer is—a disease of the cells. Schizophrenia? Some kind of brain illness. But addiction? Addiction strikes many people as too much a part …

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Growing impact of lethal ‘legal highs:’ U.K. Deaths report

The deadly risk of so-called ‘legal highs’ and other designer drugs, such as the notorious ‘meow meow’, has been confirmed by a huge leap in their links to drug-related deaths in the UK. One expert described experimentation with such drugs as ‘dancing in a minefield.”Meow meow’, officially known as mephedrone and now illegal, is just one of a group of drugs called Novel Psychoactive Substances (NPS), which also includes the amphetamine-like substances Benzo Fury and PMA, amongst others.According to data published in the National Programme on Substance Abuse Deaths (NPSAD) report, compiled by experts at St George’s, University of London, NPS are now linked to more drug-related deaths than ever before.The prevalence of these drugs in the post mortem toxicology tests submitted to the report has increased 800% in three years, from 12 in 2009 to 97 in 2012.The number of cases where NPS were identified as the cause of death rose by almost 600% during the same period — from 10 deaths in 2009 to 68 in 2012.In many cases traces of multiple NPS were found, suggesting that drug users are experimenting with combinations of these drugs, as well as alcohol in some cases.These drugs have undergone little or no human testing so their health effects are virtually unknown.Professor Fabrizio Schifano, a spokesman for NPSAD, said: “We have observed an increase in the number and range of these drugs in the post mortem toxicology results and in the cause of death of cases notified to us.”These include amphetamine-type substances, dietary supplements, ketamine derivatives, among a host of others.”The worrying trend is that these type of drugs are showing up more than ever before. Clearly this is a major public health concern and we must continue to monitor this worrying development.”Those experimenting with such substances are effectively dancing in a minefield.”The report also indicates an increase in the proportion of deaths involving stimulants such as cocaine and ecstasy-type drugs, following a decline in 2009 and stabilisation in 2010.In total, the number of drug-related deaths reported to the NPSAD during 2012 was 1,613.Opiates/opioids such as heroin and morphine, alone or in combination with other drugs continued to account for the highest proportion (36%) of reported drug-related deaths in 2012, a 4% increase compared to 2011 — a reversal of the decline in such deaths observed in recent years.Regional Highlights:Hammersmith one of worst areas in UK for drug-related deaths, says reportNew figures reveal that Hammersmith and Fulham recorded one of the highest drug-related death rates across the country in 2012 with 11.34 deaths per 100,000 population.Only Liverpool (12.57) and Blackburn with Darwen (11.45) were higher.The type of drugs related to deaths in London also drew a strong contrast to some other parts of England. As in 2011, London had the highest proportion of cocaine-related deaths in the country (15.2%), contrasting greatly with other regions, such as the Midlands and East of England where cocaine was implicated in just 3.4% of drug-related deaths.However, it is important to note that when taking into account absolute figures, Liverpool alone had more deaths involving cocaine, which was 20, than the whole of the following regions: Midlands and East of England; London; and the South of England.Liverpool overtakes Manchester with highest rates of drug-related deaths in the North West, reveals new reportThe number of drugs-related deaths in Liverpool has risen above those in Manchester for the first time since 2006 according to a new study.For the first time in over five years there were more drug-related deaths in Liverpool, which saw 49 such cases, compared to Manchester with 36.The report, compiled by researchers at St George’s, University of London, also found that Liverpool alone had more deaths linked to cocaine than the whole of the Midlands and East of England region, London and the South of England.Drugs deaths in Northern Ireland buck wider UK trend of lethal heroin useDeaths related to drugs in Northern Ireland show a marked difference from the rest of the UK as fatalities are mostly linked to prescription drugs, says a new report.Whereas the vast majority of drug-related deaths in the UK are linked to opiates such as heroin and morphine, in the province most relate to other drugs.The new research from St George’s, University of London, also shows a small decrease in the overall number of drug-related deaths in Northern Ireland. There were 78 such deaths in 2012 as opposed to 82 in 2011.Northern Ireland contrasts the rest of the UK with higher proportions of deaths attributed to drugs such as tramadol, benzodiazepines and anti-depressants. Northern Ireland also displayed a substantially lower proportion of deaths attributed to heroin/morphine and methadone than other regions of the UK, such as the South of England, the midlands and London.

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Illicit Behavior and Super Bowl Sunday

Photo Via Today is Super Bowl Sunday when many parties abound that lead to overindulgence in eating, drinking and other self-defeating behaviors.Many who are newly sober find this day difficult because beer and watching football are portrayed by the media to go perfectly hand in hand. In fact, beer manufacturers like Budweiser spend millions on their commercials leading up to and on Super Bowl Sunday.Given that the game is in New York City this weekend, scandals and stories related to Super Bowl weekend partying were inevitable. On Thursday New York City police arrested 18 people for selling “party packs” and high end prostitutes to wealthy clients in town for the festivities.The arrests came after a nearly year long investigation organized by DHS, NYPD and…

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Could Anti-Balding Drug Help Alcoholics Fight Cravings in Recovery?

Could Anti-Balding Drug Help Alcoholics Fight Cravings in Recovery? – Rehab Info Rehab InfoThe Most Trusted Rehab Referrals. Home»Blog›Could Anti-Balding Drug Help Alcoholics Fight Cravings in Recovery?Could Anti-Balding Drug Help Alcoholics Fight Cravings in Recovery?September 24th 2013 | By: Staff | Posted In: Drugs and Alcohol, Studies and ResearchA recent study completed by the researchers at George Washington University School of Medicine and Health Sciences discovered that 65 percent of male participants who took the drug Finasteride for baldness also reported that they drank less alcohol while on the drug. Finasteride disrupts particular hormones in the brain that are reportedly linked to the brain’s reaction to alcohol. This intriguing piece of information will likely lead to other studies that will investigate the success of Finasteride …

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New Harm Reduction Measure: Medication to Fight HIV Transmission in IDUs

New Harm Reduction Measure: Medication to Fight HIV Transmission in IDUsOctober 2nd 2013 | By: Staff | Posted In: Drugs and Alcohol, Recent NewsA treatment called pre-exposure prophylaxis (PrEP) has proven to be a significant assistance in protecting those individuals who use needles to inject drugs, also known as intravenous drug users, or IDUs. Addicts who utilize needles are at continual risk for a myriad of diseases, including HIV.A study conducted with 2,400 drug users in Bangkok, Thailand concluded that those individuals who ingested tenofovir pills or the PrEP treatment on a daily basis decreased their chance of acquiring the HIV virus by 74 percent. The exciting findings from this study will likely lead to other studies on the safety and validity of the PrEP treatment in acting …

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Beware: Flesh Rotting Street Drug "Krokodil"

Krokodil Drug – May Have Come From Russia to the US Over a year ago the nation was shocked by the synthetic drug known as bath salts that was suspected in a horrific act of violence in Miami, Florida. Since then there have been national crackdowns on head shops and gas stations that sold the synthetic drug and news reports of it have dwindled. Last week a new drug, that proves just as, if not more, horrifying than bath salts may have hit the streets in the US.The drug is called “krokodil” because it causes users to break out in scaly sores like a crocodile. These sores aren’t a result of picking, as with meth addicts but from contaminants in the drug that cause human flesh to…

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Spiced: Synthetic Cannabis Keeps Getting Stronger

Case reports of seizures in Germany from 2008 to 2011.I wish I could stop writing blog posts about Spice, as the family of synthetic cannabinoids has become known. I wish young people would stop taking these drugs, and stick to genuine marijuana, which is far safer. I wish that politicians and proponents of the Drug War would lean in a bit and help, by knocking off the testing for marijuana in most circumstances, so the difficulty of detecting Spice products isn’t a significant factor in their favor. I wish synthetic cannabinoids weren’t research chemicals, untested for safety in humans, so that I could avoid having to sound like an alarmist geek on the topic. I wish I didn’t have to discuss the clinical toxicity of more powerful synthetic …

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Lung cancer drug could aid plight of ectopic pregnancy patients

Sep. 9, 2013 — Women with ectopic pregnancies could be spared surgery if they are treated with a lung cancer drug, a study suggests.Researchers treated ectopic pregnancies — where an embryo implants inside the Fallopian tube — by combining an existing treatment with a lung cancer therapy.They found that prescribing both drugs together was more effective at helping cure an ectopic pregnancy than the conventional drug alone.Lung cancer drugThe lung cancer drug — called gefitinib — helps by blocking a protein that is known to encourage cell growth, and which was found to be present in high levels at the site of ectopic pregnancies.Combining gefitinib with the conventional treatment, which is called methotrexate, could reduce the need to remove the Fallopian tube in a significant number of cases.This would help the patient’s level of fertility — say researchers led by Dr Andrew Horne at the University of Edinburgh and Dr Stephen Tong at the University in Melbourne.Ectopic pregnanciesEctopic pregnancy can be treated with drugs in the early stages of development, but surgery is needed when it is more developed.Researchers also found that the drug combination was able to shorten the time it took to successfully treat ectopic pregnancies in women who did not need surgery.Around 12,000 women undergo an ectopic pregnancy in the UK each year, and the condition is responsible for up to eight per cent of pregnancy-related deaths.The study, published in the journal Obstetrics and Gynaecology, involved a trial of 12 women with ectopic pregnancies. Researchers now plan to run a larger trial.

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Scientists fish for new epilepsy model and reel in potential drug

Sep. 3, 2013 — According to new research on epilepsy, zebrafish have certainly earned their stripes. Results of a study in Nature Communications suggest that zebrafish carrying a specific mutation may help researchers discover treatments for Dravet syndrome (DS), a severe form of pediatric epilepsy that results in drug-resistant seizures and developmental delays.Scott C. Baraban, Ph.D., and his colleagues at the University of California, San Francisco (UCSF), carefully assessed whether the mutated zebrafish could serve as a model for DS, and then developed a new screening method to quickly identify potential treatments for DS using these fish. This study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health and builds on pioneering epilepsy zebrafish models first described by the Baraban laboratory in 2005.Dravet syndrome is commonly caused by a mutation in the Scn1a gene, which encodes for Nav1.1, a specific sodium ion channel found in the brain. Sodium ion channels are critical for communication between brain cells and proper brain functioning.The researchers found that the zebrafish that were engineered to have the Scn1a mutation that causes DS in humans exhibited some of the same characteristics, such as spontaneous seizures, commonly seen in children with DS. Unprovoked seizure activity in the mutant fish resulted in hyperactivity and whole-body convulsions associated with very fast swimming. These types of behaviors are not seen in normal healthy zebrafish.”We were also surprised at how similar the mutant zebrafish drug profile was to that of Dravet patients,” said Dr. Baraban. “Antiepileptic drugs shown to have some benefits in patients (such as benzodiazepines or stiripentol) also exhibited some antiepileptic activity in these mutants. …

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New strategy against high-risk leukemia

Aug. 29, 2013 — After identifying a protein that blocks death of high-risk acute lymphoblastic leukemia (ALL) cells, scientists use two-drug combination therapy to offer hope to children and adults with the disease.St. Jude Children’s Research Hospital scientists have identified a protein that certain high-risk acute lymphoblastic leukemia (ALL) cells need to survive and have used that knowledge to fashion a more effective method of killing tumor cells. The findings appear in the August 29 edition of the journal Blood.The work focused on Philadelphia chromosome-positive ALL (Ph-positive ALL), a high-risk cancer that accounts for about 40 percent of ALL in adults and about 5 percent in children. The disease is named for a chromosomal rearrangement that brings together pieces of the BCR and ABL genes. That leads to production of the BCR-ABL protein, which fuels the unchecked cell growth that is a hallmark of cancer.In this study, researchers identified the protein MCL1 as the partner in crime of BCR-ABL. MCL1 is one of several proteins that can block the process of programmed cell death known as apoptosis. The body uses apoptosis to eliminate damaged, dangerous or unneeded cells. The research demonstrates that MCL1 is essential for preventing apoptosis of leukemia cells.Investigators combined drugs that reduce MCL1 levels in leukemia cells with a second drug that targets another protein that inhibits cell death. The pairing increased apoptosis in human leukemia cells growing in the laboratory.”These findings suggest that disrupting the ability of leukemia cells to produce MCL1 renders those cells vulnerable to other drugs,” said corresponding author Joseph Opferman, Ph.D., an associate member of the St. …

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Promising new angle for drugs to prevent stroke and heart attack

Aug. 30, 2013 — Platelets, which allow blood to clot, are at the heart of numerous cardiovascular problems, including heart attacks and stroke. New research has uncovered a key platelet protein that could offer a new angle for developing drugs to prevent thrombosis, or dangerous blood clots, in patients who are at high risk such as those with atherosclerosis or a history of heart problems.”I think we’re at the start of an exciting journey of drug discovery for a new class of antithrombotic therapies,” said lead study author Stephen Holly, PhD, assistant professor of biochemistry and biophysics at the University of North Carolina School of Medicine. This work was performed in collaboration with senior authors Leslie Parise, PhD, at UNC and Benjamin Cravatt, PhD, at The Scripps Research Institute.The study was published online August 29 ahead of print in the journal Chemistry & Biology and funded by grants from the American Heart Association and the National Institutes of Health.In the human circulatory system, platelets are something of a double-edged sword. Without their clotting abilities, even a minor injury could result in potentially fatal bleeding. But during a heart attack or stroke, platelets form a clot that can potentially block blood flow through our veins and arteries, a dangerous condition called thrombosis, which can deprive tissues of oxygen and lead to death.Several antithrombotic drugs are available, but some have been found to cause bleeding — a side effect that is particularly troublesome when these drugs are used to prevent thrombosis in people undergoing heart surgery. “There’s still room for improvement, in terms of making an ideal drug that can block platelet function without initiating bleeding,” said Dr. Holly.Dr. Holly and his colleagues uncovered several potential drug targets using a screening technique that has never before been applied to the cardiovascular system. The technique, called activity-based protein profiling, has been used in cancer research and allows researchers to track the actual activities of proteins operating within a cell. …

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Shutting off neurons helps bullied mice overcome symptoms of depression

Aug. 29, 2013 — A new drug target to treat depression and other mood disorders may lie in a group of GABA neurons (gamma-aminobutyric acid -the neurotransmitters which inhibit other cells) shown to contribute to symptoms like social withdrawal and increased anxiety, Penn Medicine researchers report in a new study in the Journal of Neuroscience.Experts know that people suffering from depression and other mood disorders often react to rejection or bullying by withdrawing themselves socially more than the average person who takes it in strides, yet the biological processes behind these responses have remained unclear.Now, a preclinical study, from the lab of Olivier Berton, PhD, an assistant professor in the department of Psychiatry, in collaboration with Sheryl Beck, PhD, a professor in the department of Anesthesiology at Children’s Hospital of Philadelphia, found that bullying and other social stresses triggered symptoms of depression in mice by activating GABA neurons, in a never-before-seen direct relationship between social stimuli and this neural circuitry. Activation of those neurons, they found, directly inhibited levels of serotonin, long known to play a vital role in behavioral responses — without it, a depressed person is more likely to socially withdrawal.Conversely, when the researchers successfully put the brake on the GABA neurons, mice became more resilient to bullying and didn’t avoid once -perceived threats.”This is the first time that GABA neuron activity — found deep in the brainstem — has been shown to play a key role in the cognitive processes associated with social approach or avoidance behavior in mammals,” said Dr. Berton. “The results help us to understand why current antidepressants may not work for everyone and how to make them work better — by targeting GABA neurons that put the brake on serotonin cells.”Less serotonin elicits socially defensive responses such as avoidance or submission, where enhancement — the main goal of antidepressants — induces a positive shift in the perception of socio-affective stimuli, promoting affiliation and dominance. However, current antidepressants targeting serotonin, like SSRIs, are only effective in about 50 percent of patients.These new findings point to GABA neurons as a new, neural drug target that could help treat the other patients who don’t respond to today’s treatment.For the study, “avoidant” mice were exposed to brief bouts of aggression from trained “bully” mice. By comparing gene expression in the brains of resilient and avoidant mice, Berton and colleagues discovered that bullying in avoidant mice puts GABA neurons in a state where they become more excitable and the mice exhibit signs of social defeat. Resilient mice, however, had no change in neuron levels and behavior.To better understand the link between GABA and the development of stress resilience, Berton, Beck, and colleagues also devised an optogenetics-based approach to directly manipulate levels: Lifting GABA inhibition of serotonin neurons reduced social and anxiety symptoms in mice exposed to bullies and also fully prevented neurobiological changes due to stress.”Our paper provides a novel cellular understanding of how social defensiveness and social withdrawal develop in mice and gives us a stepping stone to better understand the basis of similar social symptoms in humans,” said Berton. “This has important implications for the understanding and treatment of mood disorders.”This work was funded by the National Institute of Mental Health grants MH087581, MH0754047 and MH089800 and grants from the International Mental Health Research Organization, the National Alliance for Research on Schizophrenia and Depression and the National Institute on Drug Abuse.Co-authors on the study include Collin Challis, Janette Boulden, Avin Veerakumar, Julie Espallergues, and R. Christopher Pierce from Penn’s department of Psychiatry.

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Adding blood pressure drug to standard antibiotics speeds up TB treatment

Aug. 29, 2013 — Infectious disease experts at Johns Hopkins have found, in studies in mice, that a drug better known as a treatment for high blood pressure and headaches effectively speeds up treatment of TB when added to the standard, daily antibiotic regimen. Test animals were cured in four months instead of the usual six.Researchers say that if clinical trials starting later this year in India, a country heavily burdened by the highly contagious lung disease, prove successful, then the shortened treatment time with verapamil, a so-called calcium channel blocker, used in combination with antibiotics isoniazid and rifampin, could make it easier for infected people to complete their drug therapy as prescribed. The experts note that antibiotics for TB do not work if treatment is interrupted or if people stop taking their medication. Improved drug adherence, they say, could also prevent the buildup of drug-resistant strains of TB, caused by Mycobacterium tuberculosis, which is now estimated to kill a million people each year, mostly in the developing world.”Our results show that verapamil is a good drug candidate as an add-on therapy with antibiotics for TB, a global disease in urgent need of new treatment options,” says study senior investigator and infectious disease specialist William Bishai, M.D., Ph.D. Bishai’s team’s latest findings are set to be published in the Sept. 1 edition of the American Journal of Respiratory and Critical Care Medicine.Bishai, a professor at the Johns Hopkins University School of Medicine and its Center for Tuberculosis Research, says that drug treatment options for TB are “too few,” and limited to about a dozen older antibiotics, some with serious side effects. Bishai, who also is a Howard Hughes Medical Institute Lab Head at Johns Hopkins, says verapamil has been around for some 40 years, so its side effects — such as too-low blood pressure — are well-known. He says the clinical trial in India, primarily a safety study to determine a minimum effective dose, will be pivotal in clarifying the drug’s “true potential” as an add-on therapy in TB.Lead study investigator and immunologist Shashank Gupta, Ph.D., says the study results also suggest that verapamil, commonly sold under the brand names Isoptin, Verelan, Calan, Bosoptin and Covera, could be a good drug candidate for combination therapy studies with multidrug-resistant forms of TB.Gupta, a postdoctoral fellow at Johns Hopkins, says verapamil is known to work as an efflux pump inhibitor, making bacteria more susceptible to antibiotics and killing by immune cell macrophages, but whose precise workings remain unknown. He says the research team investigated verapamil’s potential as a TB therapy after another study showed that increased efflux pump action promoted drug tolerance to TB, minimizing antibiotics’ effectiveness.Among the latest study’s other key findings were that verapamil accelerated killing of TB bacteria 10-fold after two months of treatment. …

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Botox not just for wrinkles

Aug. 27, 2013 — Botox is best known as a cosmetic treatment for frown lines, but the drug also effectively treats the after effects of Bell’s palsy and other serious facial nerve problems.Bell’s palsy results from damage to the facial nerve that controls muscles on one side of the face. Ear-nose-throat surgeon Dr. Matthew Kircher of Loyola University Medical Center is giving patients Botox injections to treat facial nerve disorders that sometimes occur after Bell’s palsy, including unwanted facial movements known as synkinesis.Botox injections work by weakening or paralyzing certain muscles or by temporarily blocking the nerve input into the muscles.Facial synkinesis is the involuntary movement of one set of muscles when the patient tries to move another set of muscles. For example, when the patient blinks, the mouth smiles or grimaces.Botox can improve the symmetry of the face and reduce muscle contractures and spasms. Botox also is effective for platysmal banding — verticle lines that develop in the neck as a result of muscle contractions.Kircher said he starts out conservatively, treating patients with dilute doses. After seeing how well the patient does, Kircher adjusts the dose if necessary.Botox is not a cure. The drug wears off after three or four months, so patients need repeat injections.”While we can never make the face perfect, we have found Botox to be extremely effective,” Kircher said. “It can make a huge difference in patients’ lives.”Kircher is an assistant professor in the Department of Otolaryngology of Loyola University Chicago Stritch School of Medicine.

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Drug blocks light sensors in eye that may trigger migraine attacks

Aug. 27, 2013 — For many migraine sufferers, bright lights are a surefire way to exacerbate their headaches. And for some night-shift workers, just a stroll through a brightly lit parking lot during the morning commute home can be enough to throw off their body’s daily rhythms and make daytime sleep nearly impossible. But a new molecule that selectively blocks specialized light-sensitive receptors in the eyes could help both these groups of people, without affecting normal vision.”It took almost ten years to find and test a molecule that fit all the properties and acted in vivo as we wanted,” says senior study author Satchidananda Panda , an associate professor in Salk’s Regulatory Biology Laboratory.Scientists have known for nearly a century that humans and animals can sense light even when they can’t see. Before they’ve opened their eyes, and even before cells that allow vision have matured, newborn mice still scurry away from bright lights, and set their sleep-wake cycles based on the patterns of light and dark throughout the day. The same is true of many blind people-though they can’t see what’s in front of them, their bodies still follow daily circadian rhythms, and the pupils of their eyes constrict in response to light.More than ten years ago, Panda’s lab group discovered that melanopsin, a receptor found in neurons connecting the eyes and brain, is responsible for sensing light independently of normal vision. Since then, researchers have determined that the receptor is vital for maintaining sleep cycles and other circadian rhythms in those with healthy vision, constricting the pupil of the eye in bright light, and potentially exacerbating the light-sensitivity associated with migraine headaches. While melanopsin senses light for these non-vision purposes in the body, closely related receptors-rhodopsin and cone opsins-provide vision-forming information to the brain.Panda figured that if he could find a compound that blocked melanopsin, but not rhodopsin or cone opsins, it could pave the way toward treating migraines or circadian rhythm imbalances. Scientists already know of one class of compounds, retinoids, which interact with opsins, but they’re non-specific and so bind to melanopsin, rhodopsin, cone opsins, and a whole handful of other receptors in the body, causing widespread side effects. Panda wanted something more specific. …

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Perception of marijuana as a ‘safe drug’ is scientifically inaccurate, finds review of teen brain studies

Aug. 27, 2013 — The nature of the teenage brain makes users of cannabis amongst this population particularly at risk of developing addictive behaviors and suffering other long-term negative effects, according to researchers at the University of Montreal and New York’s Icahn School of Medicine at Mount Sinai.”Of the illicit drugs, cannabis is most used by teenagers since it is perceived by many to be of little harm. This perception has led to a growing number of states approving its legalization and increased accessibility. Most of the debates and ensuing policies regarding cannabis were done without consideration of its impact on one of the most vulnerable population, namely teens, or without consideration of scientific data,” wrote Professor Didier Jutras-Aswad of the University of Montreal and Yasmin Hurd, MD, PhD, of Mount Sinai. “While it is clear that more systematic scientific studies are needed to understand the long-term impact of adolescent cannabis exposure on brain and behavior, the current evidence suggests that it has a far-reaching influence on adult addictive behaviors particularly for certain subsets of vulnerable individuals.”The researchers reviewed over 120 studies that looked at different aspects of the relationship between cannabis and the adolescent brain, including the biology of the brain, chemical reaction that occurs in the brain when the drug is used, the influence of genetics and environmental factors, in addition to studies into the “gateway drug” phenomenon. “Data from epidemiological studies have repeatedly shown an association between cannabis use and subsequent addiction to heavy drugs and psychosis (i.e. schizophrenia). Interestingly, the risk to develop such disorders after cannabis exposure is not the same for all individuals and is correlated with genetic factors, the intensity of cannabis use and the age at which it occurs. When the first exposure occurs in younger versus older adolescents, the impact of cannabis seems to be worse in regard to many outcomes such as mental health, education attainment, delinquency and ability to conform to adult role,” Dr Jutras-Aswad said.Although it is difficult to confirm in all certainty a causal link between drug consumption and the resulting behavior, the researchers note that rat models enable scientists to explore and directly observe the same chemical reactions that happen in human brains. Cannabis interacts with our brain through chemical receptors (namely cannabinoid receptors such as CB1 and CB2.) These receptors are situated in the areas of our brain that govern our learning and management of rewards, motivated behavior, decision-making, habit formation and motor function. …

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Cocaine use linked to new brain structures: Possible mechanism for drug-seeking behavior in humans identified

Aug. 25, 2013 — Mice given cocaine showed rapid growth in new brain structures associated with learning and memory, according to a research team from the Ernest Gallo Clinic and Research Center at UC San Francisco. The findings suggest a way in which drug use may lead to drug-seeking behavior that fosters continued drug use, according to the scientists.The researchers used a microscope that allowed them to peer directly into nerve cells within the brains of living mice, and within two hours of giving a drug they found significant increases in the density of dendritic spines — structures that bear synapses required for signaling — in the animals’ frontal cortex. In contrast, mice given saline solution showed no such increase.The researchers also found a relationship between the growth of new dendritic spines and drug-associated learning. Specifically, mice that grew the most new spines were those that developed the strongest preference for being in the enclosure where they received cocaine rather than in the enclosure where they received saline. The team published its findings online in Nature Neuroscience on August 25, 2013.”This gives us a possible mechanism for how drug use fuels further drug-seeking behavior,” said principal investigator Linda Wilbrecht, PhD, a Gallo investigator now at UC Berkeley, but who led the research while she was on the UCSF faculty.”It’s been observed that long-term drug users show decreased function in the frontal cortex in connection with mundane cues or tasks, and increased function in response to drug-related activity or information,” Wilbrecht said. “This research suggests how the brains of drug users might shift toward those drug-related associations.”In all living brains there is a baseline level of creation of new spines in response to, or in anticipation of, day-to-day learning, Wilbrecht said. By enhancing this growth, cocaine might be a super-learning stimulus that reinforces learning about the cocaine experience, she said.The frontal cortex, which Wilbrecht called the “steering wheel” of the brain, controls functions such as long-term planning, decision-making and other behaviors involving higher reasoning and discipline.The brain cells in the frontal cortex that Wilbrecht and her team studied regulate the output of this brain region, and may play a key role in decision-making. “These neurons, which are directly affected by cocaine use, have the potential to bias decision-making,” she said.Wilbrecht said the findings could potentially advance research in human addiction “by helping us identify what is going awry in the frontal cortexes of drug-addicted humans, and by explaining how drug-related cues come to dominate the brain’s decision-making processes.”In the first of a series of experiments, the scientists gave cocaine injections to one group of mice and saline injections to another. The next day, they observed the animals’ brain cells using a 2-photon laser scanning microscope. …

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Drug used for blood cancers may stop spread of breast cancer cells

Aug. 22, 2013 — A drug used to treat blood cancers may also stop the spread of invasive breast cancer, researchers at Mayo Clinic in Florida have discovered. Their study, published online in Breast Cancer Research, found that in the lab and in animals, the drug decitabine turns on a gene coding for protein kinase D1 (PRKD1) that halts the ability of cancer cells to separate from a tumor and spread to distant organs.”Treatment with low doses of decitabine in an animal model of breast cancer restored PRKD1 expression, reduced tumor size, and blocked metastasis to the lung,” says the study’s senior investigator, Peter Storz, Ph.D., a biochemist and molecular biologist at Mayo Clinic in Florida.”The outcome of patients with invasive breast cancer is less than optimal despite many attempts to improve treatment, including advanced chemotherapy and hormonal therapy,” says Dr. Storz. “We hope this study offers a new avenue to prevent breast cancer from becoming aggressive and untreatable.”The research team, which includes first author Sahra Borges, Ph.D., a postdoctoral researcher in Dr. Storz’s lab, found that the gene coding for PRKD1 was silenced in all but one subtype of invasive breast cancer, including aggressive triple negative breast cancer. That subtype is invasive lobular carcinoma.Dr. Borges also developed an assay that can be used to measure the amount of PRKD1 that is silenced in patients’ breast tumors.”Because we found that PRKD1 is increasingly silenced as breast cancer becomes aggressive and spreads, the hope is that this test can be further developed and used to predict which patients are at risk for cancer metastasis, and thus may benefit from decitabine,” Dr. Borges says.Decitabine, approved by the U.S. Food and Drug Administration for use in some blood cancers, is a demethylating agent, meaning that it can switch on beneficial genes such as PRKD1 that cancer has silenced in order to grow.Treating genes that are silenced is much easier than trying to restore function of a mutated gene, Dr. …

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Study examines risk of severe blood sugar swings among diabetics taking fluoroquinolones

Aug. 15, 2013 — Diabetic patients taking oral fluoroquinolones, a frequently prescribed class of antibiotics, were found to have a higher risk of severe blood sugar-related problems than diabetic patients taking other kinds of antibiotics, according to a recent study from Taiwan published in Clinical Infectious Diseases. The increased risk was low — hyperglycemia (high blood sugar) or hypoglycemia (low blood sugar) related to the drugs occurred in fewer than one in 100 patients studied — but clinicians should consider the higher risk when treating diabetic patients with fluoroquinolones, especially moxifloxacin, and prescribe them cautiously, the study’s authors concluded.Increased use of these drugs, commonly used to treat such illnesses as urinary tract infections and community-acquired pneumonia, has raised concerns about rare but severe adverse effects, including tendon rupture and heart arrhythmia. Previous studies have also indicated a relationship between fluoroquinolones and severe glucose-related abnormalities, known as dysglycemia, which includes hyperglycemia or hypoglycemia. Severe blood sugar swings can lead to serious health problems, including irreversible brain damage or even death. In 2006, one drug from the fluoroquinolone class, gatifloxacin, was withdrawn from the U.S. market due to the risk of blood sugar abnormalities.To assess the risk of blood sugar swings in diabetic patients using specific fluoroquinolones, a team of researchers, led by Mei-Shu Lai, MD, PhD, at National Taiwan University in Taipei, conducted a population-based cohort study of approximately 78,000 people with diabetes in Taiwan from January 2006 to November 2007.Using the claims database for Taiwan’s national insurance program, the researchers analyzed data for diabetic outpatients who had received a new prescription for an antibiotic from one of three different classes of antibiotics: fluoroquinolones (levofloxacin, ciprofloxacin, or moxifloxacin); second-generation cephalosporins (cefuroxime, cefaclor, or cefprozil); or macrolides (clarithromycin or azithromycin). The study’s authors then looked for any emergency department visits or hospitalizations for dysglycemia among these patients within 30 days of the start of their antibiotic therapy.Diabetics using oral fluoroquinolones faced greater risk of severe blood sugar swings than diabetic patients using antibiotics in other classes, the researchers found. The risks varied according to the specific fluoroquinolone the patients were using: The absolute risk, or incidence, of hyperglycemia per 1,000 people studied was 6.9 for moxifloxacin, 3.9 for levofloxacin, and 4.0 for ciprofloxacin. The absolute risk of hypoglycemia was 10.0 for moxifloxacin, 9.3 for levofloxacin, and 7.9 for ciprofloxacin.(By comparison, among diabetic patients taking antibiotics in the macrolides class, the absolute risk of hyperglycemia was lower, at 1.6 per 1,000, and 2.1 per 1,000 among those taking antibiotics in the cephalosporin class; for hypoglycemia, the absolute risk per 1,000 was 3.7 for macrolides and 3.2 for cephalosporins, respectively.)”Our results identified moxifloxacin as the drug associated with the highest risk of hypoglycemia, followed by levofloxacin and ciprofloxacin,” the study’s authors wrote. …

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