segunda-feira, 20 de novembro de 2017

Gene Therapy Could Help People Overcome Meth Addiction









Gene therapy, which modifies a person’s DNA, has long been thought of as a way to treat genetic diseases—and, more recently, cancer. But a team at the University of Arkansas for Medical Sciences thinks it can use this same idea to treat addiction by counteracting the high that methamphetamine produces.

Eric Peterson, associate professor of pharmacology and toxicology, and his colleagues have packaged a gene that codes for an anti-meth antibody into an engineered virus. When injected, the therapy makes the body generate antibodies against meth. The antibodies bind to and trap methamphetamine molecules that are circulating in the bloodstream, preventing them from traveling to the brain and triggering pleasurable feelings. In mice, researchers showed that the therapy lasted for over eight months, reducing the amount of meth in the brain and the stimulant effects caused by the drug.

The hope, Peterson says, is that a drug based on the approach could be used with behavior therapies to treat people addicted to meth. If people tried to use meth after they had received the gene therapy, they wouldn’t feel the high they expected.
An estimated 897,000 people aged 12 or older were users of methamphetamine in 2015, according to the most recent National Survey on Drug Use and Health. Most of those have a substance abuse disorder, a condition in which the repeated use of the drug interferes with a person’s health, work, school, or home life.

Yngvild Olsen, a secretary of the American Society of Addiction Medicine and the medical director of the Baltimore-based Institutes for Behavior Resources, says she’s enthusiastic about the research because treatments for meth addiction are needed. But she adds it’s too early to tell how effective this would be in people.

Over the years, there have been attempts to use similar therapeutic approaches for other stimulants—like a vaccine for cocaine. Olsen says these efforts have struggled to make it from animal tests into humans, and a handful of medicines that have been tested in clinical trials haven’t been as effective as they were in mice.
There’s also the potential that people who have received the gene therapy could take more meth to try to feel the high they used to get. That is something researchers running a future clinical trial would have to keep in mind, Olsen says.

domingo, 19 de novembro de 2017

Age, gut bacteria contribute to MS disease progression, according to study




Researchers at Rutgers Robert Wood Johnson Medical School published a study suggesting that gut bacteria at young age can contribute to Multiple sclerosis (MS) disease onset and progression.
In this study, published in the October 31 issue of the Proceedings of the National Academy of Sciences, Sudhir Yadav PhD, a neuroimmunology post-doctoral fellow in the laboratories of Drs. Kouichi Ito, associate professor of neurology, and Suhayl Dhib-Jalbut, professor and chair of neurology, tested mice that were engineered to have a pre-disposition for MS. Because mice would not normally develop MS, researchers used MS-associated risk genes from real patients to genetically engineer mice for this study. Dr. Ito created this unique model of genetically engineered mice to specifically study the cause of MS.

At first, when the genetically modified mice were put in a sterile, germ-free environment, they did not develop MS. When exposed to a normal environment that would normally contain bacteria, the mice did develop MS-like disease and inflammation in their bowels, suggesting gut bacteria is a risk factor that triggers MS disease development.

The study showed a link between gut bacteria and MS-like disease incidence, which was more prominent at a younger age, when MS is also more prevalent. The younger mice were more prone to develop MS than the older mice. Together, age, gut bacteria, and MS-risk genes collaboratively seem to trigger disease. This study is also the first to identify mechanisms by which gut bacteria triggers changes in the immune system that underlie MS progression.

"The findings could have therapeutic implications on slowing down MS progression by manipulating gut bacteria," says Suhayl Dhib-Jalbut, Director of Rutgers-Robert Wood Johnson Center for Multiple Sclerosis. Future research could lead to the elimination of harmful types of gut bacteria that wereshown to cause MS progression, or conversely enhance beneficial bacteria that protects from disease progression. The investigators recently received NIH funding to examine their findings in MS patients.

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sábado, 18 de novembro de 2017

Link between obesity and cancer is not widely recognized




A new study published in the Journal of Public Health has shown that the majority of people in the United Kingdom do not understand the connection between weight issues and cancer. Obesity is associated with thirteen types of cancer, including those of the breast, kidney, bowel, and womb. However, after surveying 3293 adults, taken as representative of the UK population, researchers found that only a quarter of respondents were aware of the link between obesity and cancer.
Obesity is the second biggest preventable cause of cancer after smoking, leading to approximately 3.4 million deaths worldwide. Despite the fact that 63% of the English and 67% of the Scottish adult population is overweight, only 25.4% of this population listed cancer as a health issue related to being overweight when asked an unprompted question.

There were also several misconceptions about cancer types linked to obesity. Researchers found greater levels of awareness about cancers of the digestive system organs, such as bowel and kidney, than for those of the reproductive organs, such as womb or breast.

The study's authors also examined the impact of respondents' socio-economic background and found that those in a lower income group were more likely to be overweight or obese and were less aware of the link between weight issues and cancer. Modelled projections show obesity trends will increase by 2035 and the gap between the highest and lowest income groups will widen further.

Although there are currently several healthcare initiatives to address obesity issues, the study found that not all participants had seen a healthcare professional in the last 12 months. Of those who had, only 17.4% had received advice about their weight, despite 48.4% being overweight.

Those who received advice were mainly instructed on how to lose weight, rather than given information about the range of health issues associated with being overweight or obese.
Dr Jyotsna Vohra, from Cancer Research UK and study co-author, said: "We're very concerned that most people simply don't connect cancer with obesity. This study shows that only one in four know that excess weight increases the risk of cancer so we need to make the link very clear. This may go some way towards tackling the obesity epidemic which all too often begins in childhood."

"Our study also showed that GPs aren't discussing weight with patients who are too heavy as often as they might, Dr Vohra said "GPs have very little time during their appointments and should have more support to introduce sensitive issues such as obesity, with patients."

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quinta-feira, 16 de novembro de 2017

FDA warns of heart attack and stroke risks from Ibuprofen, NSAIDs


businessinsider.com


Lydia Ramsey

ibuprofen 
  • The use of prescription and over-the-counter painkillers like ibuprofen and naproxone is associated with an increased risk of heart attack and stroke.
  • The FDA updated its warnings for the category of drugs, NSAIDs, based on more evidence of the increased risk. 

Some of the most common painkillers available carry a warning: their use can increase the risk of heart attack and stroke. 
That warning was strengthened by the FDA on Thursday, after more evidence connected those risks to a category of medication known as non-aspirin nonsteroidal anti-inflammatory drugs, also known as NSAIDs. 
The over-the-counter and prescription versions of the medications relieves the symptoms of  fever, headaches, colds and cramping. Ibuprofen (Advil or Motrin) and naproxone (Aleve) are the most common forms of NSAIDs. 
"Based on our comprehensive review of new safety information, we are requiring updates to the drug labels of all prescription NSAIDs," the FDA said on its website.
Here's what to know: 
  • People with heart disease have a greater chance of having a heart attack or stroke after using NSAIDs. 
  • There's also an increased risk of heart failure associated with NSAID use. 
  • The risk of heart attack and stroke associated with NSAID medications has been known since 2005, so this is an update to those warnings. 
  • This change is specific to prescription NSAIDs, though the FDA did say it plans to request changes to the over-the-counter labels as well. 
  • The risk of heart attack and stroke is greater when people use higher doses, and can increase the longer the drugs are used. 
  • Some NSAIDs likely increase the risk of heart attack and stroke more than others, though the FDA couldn't definitively say which ones are higher-risk. 
  • The warning does not apply to aspirin, which is actually often recommended for people with a high risk of heart attack

quarta-feira, 15 de novembro de 2017

Promising autism drug shows early success in animal tests





In mice experiments, a new autism drug is proving promising(Credit: chrupka/Depositphotos)

There is currently no single drug treatment for autism. Many doctors treat autistic patients with a variety of psychotropic drugs geared at managing their perceived antisocial symptoms, but this is reasonably controversial, especially in children. A new drug targeted at restoring an electrical signaling imbalance in the brain is showing exciting success in mice and researchers hope to move into human clinical trials soon.

Autism spectrum disorder (ASD) is an extremely complex brain disorder affecting, in the United States, an estimated 1 out of every 68 children. The new research centers on a form of autism called MHS (MEF2C Haploinsufficiency Syndrome).
Back in the 1990s, scientists discovered that when there was a mutation in a gene called MEF2C a child went on to display significant autism symptoms. In mouse models the researchers identified the mutated gene as causing an excess of excitatory brain signaling, and this was thought to explain many of the cognitive and behavioral features of autism.

The latest study deployed a new drug called NitroSynapsin to reduce this excess brain signaling. The drug was tested on MHS mouse models for three months and the results were incredibly encouraging. The previously identified electrical signaling imbalance was improved and abnormal autism-like behaviors in the mice were reduced.

Signs of anxiety, abnormal repetitive movements, and impaired spatial memory, were all characteristics that were somewhat repaired in the mouse model experiments. Despite MHS specifically only accounting for a minor volume of overall autism cases, the researchers are confident these results should translate to a broad spectrum of autism disorders.

"Because MEF2C is important in driving so many autism-linked genes, we're hopeful that a treatment that works for this MEF2C-haploinsufficiency syndrome will also be effective against other forms of autism, and in fact we already have preliminary evidence for this," says senior investigator on the study, Stuart Lipton.

The drug is currently being tested in mice models for other autism disorders and in vitro testing on human cells are showing positive results. The next step for the team is to start paving the way for human clinical trials, so the reality of a drug treatment for autism may still be some time in the future, but the path might suddenly have become a lot clearer.

The study was published in the journal Nature Communications.


Stop Alzheimer’s before it starts




Katherine Frey/The Washington Post

The number of people living with Alzheimer's is on the rise — one in ten people aged 65 or over now has the disease.
In 2015, the global cost of Alzheimer’s disease was US$818 billion. That’s similar to the gross domestic product of the world’s 18th-largest economy. By 2030, the number of people with the disease is expected to rise to more than 70 million worldwide (see ‘Staying ahead’).

Unless there is a breakthrough in treatment, nearly one in every 2–3 people over 85 will have Alzheimer’s. Even those who escape the disease will have at least one close friend or relative who can no longer converse with them, has no recollection of what happened minutes before and is reliant on round-the-clock care.
Clinical trials have predominantly focused on therapies aimed at treating people who have developed symptoms (memory loss, confusion and difficulties communicating) and begun to lose independence. In the past five years, investigators have started trials at an earlier stage — when memory loss is mild or absent but brain scans reveal the hallmark pathology of amyloid-β protein plaques. However, we think that the clock should be turned back even further — to when the signature brain pathology hasn’t yet appeared.

An important precedent for such ‘primary prevention’ is statins. In the early 1980s, these now-widespread medications were shown to lower blood cholesterol in people with a rare genetic disorder that severely elevates it. People with the condition (around 0.005% of the population) typically develop cardiovascular symptoms as adolescents or young adults. Without treatment, they typically die in their 30s1. But when statins are given to such people in childhood, the onset of heart disease and stroke is delayed by decades, and lifespan prolonged by between 15 and 30 years.
The search for an Alzheimer’s ‘statin’ is an imperative next step thanks to recent advances in our understanding of Alzheimer’s pathology and the establishment of a committed group of people who are keen to take part in clinical trials. All that remains is for pharmaceutical companies, along with public and private agencies, to provide the necessary resources, including funding.

The right time

In the 1980s, recognizing the imminent threat of an Alzheimer’s catastrophe, the US National Institutes of Health began funding Alzheimer’s Disease Centers throughout the United States. Other countries, such as the United Kingdom, made similar investments. As our understanding of Alzheimer’s grew, academic researchers and the pharmaceutical industry increased their efforts to identify drugs to treat the symptoms of the disease.



Sources: Alzheimer's Association. Alzheimers Dement. 13, 325–373 (2017)/World Alzheimer Report 2015

Many early efforts sought to relieve memory loss by blocking the degradation of the neurotransmitter acetylcholine. Autopsies had revealed that neurons dependent on it were severely depleted in the brains of people with Alzheimer’s. In the late 1990s, researchers shifted their focus to the amyloid-β plaques and tau tangles that are thought to damage the brain. Hundreds of drug trials have targeted different forms of amyloid-β with the aim of removing plaques or stopping them from developing.
But these efforts involved people who were 20 years or more into the pathological process. By then, neurons have begun to die and the brain has started to shrink. Of the four drugs that have been approved (three based on acetylcholine), none alters the course of the disease or treats the symptoms to a degree that’s detectable in individuals. Scores of other drug candidates have had no effect on amyloid-β plaques in humans. Some have even had serious adverse effects; an experimental amyloid-β vaccine caused inflammation in the brain of several patients. Just a few recent exceptions have robustly removed amyloid plaques or dramatically lowered the levels of a plaque precursor in clinical trials23.

In the past five years, clinical trials have begun an attempt to reduce the progression of brain pathology before symptoms develop. Of the more than 11 such trials now under way or planned, all enrol people with increased risk of Alzheimer’s disease, as indicated by their genetics or brain scans showing plaques4. These trials hold great promise.

But in our view, recent developments on four fronts make now the moment to start clinical trials for drugs to prevent brain pathology.
Scientific evidence There are various indications that addressing the disease at its earliest stages will increase the likelihood of a single drug with a single target being effective. Studies in mice genetically altered to develop amyloid-β plaques have shown that therapies that lower amyloid-β production are most effective when administered before the plaques have developed56. Other studies indicate that Alzheimer’s progression may become a runaway process after a certain point — one that is not linked to a specific pathology. For example, the spread of tau tangles seems to be triggered by the presence of amyloid-β plaques78. Once started, the establishment of the tangles seems to continue unabated, even after amyloid-β has been removed. Thus, anti-amyloid drugs may have limited effectiveness after a certain point.
“The best way to test the role of amyloid-β pathology is to stop it from taking hold in the first place.”
Researchers now have detailed knowledge about the sequence of changes in the brain that occur during the asymptomatic phase of Alzheimer’s disease. Plaques are followed by changes in brain metabolism; these are followed by alterations in tau deposition and inflammation. These insights have come largely from observational studies. The Dominantly Inherited Alzheimer Network (DIAN), for instance, has tracked more than four decades of disease stages — from before any symptoms show to advanced dementia — in hundreds of people who carry genetic mutations that cause Alzheimer’s disease.

Such knowledge provides researchers with a suite of biomarkers to test the efficacy of treatments after three to five years. That’s a time frame that is likely to be palatable to those funding trials such as pharmaceutical companies. Better diagnostic tools, involving brain-imaging techniques and the analysis of cerebrospinal fluid, are also now available to measure disease progression.

Trial population Less than 1% of all those diagnosed with Alzheimer’s have dominantly inherited Alzheimer’s disease (DIAD). People with this form develop amyloid-β plaques in their brains in their 20s and 30s, and their children have a 50% chance of inheriting the condition. Crucial to the success of primary prevention trials is the increased involvement in research of families affected by DIAD.

With the knowledge that symptoms will appear at a predictable time in people carrying the mutations that cause DIAD9, researchers can track changes in brain pathology, starting many years before symptoms are expected to appear. DIAD mutations all affect the amyloid-β production pathway. So, even for people with different mutations (230 are known), amyloid plaques are a common target to focus on — one that is shared with the much more common late-onset Alzheimer’s disease.



Zephyr/Spl
Magnetic resonance imaging scan showing damage (orange) in the brain of a person with Alzheimer's.

Of course, how exactly the results from a rare genetic form of Alzheimer’s disease will translate to the more common form is uncertain. But there is strong evidence that the fundamental processes that lead to dementia are very similar. Trying to identify who in the general population will get Alzheimer’s, and predicting when they will develop amyloid-β pathology, would require trials involving many thousands of people.

Those who carry DIAD mutations would almost certainly enrol in primary prevention trials — even though it may take ten years or more to demonstrate the effects of a drug on cognition. Ongoing trials such as the DIAN Trials Unit (DIAN-TU), have demonstrated that it is possible to enrol appropriate numbers of families (several hundred people) with dominantly inherited mutations. In fact, the DIAN-TU trial has one of the best rates of enrolment, retention and completion of any trials in Alzheimer’s disease, owing to highly committed family members. When we surveyed people at risk of familial Alzheimer’s disease using our DIAN Expanded Registry (www.DIANexr.org) more than 90% of the 80 respondents said that they would be willing to stay in trials for “as long as the study requires to arrive at an answer about the drug’s efficacy”.

Effective and safe therapies Amyloid-β is an ideal target for primary prevention; numerous findings indicate that its abnormal metabolism is the cause of DIAD.
There is now strong evidence that a rare mutation protects some populations from developing plaques in their brains. In Iceland, for example, the chance of carriers of this mutation (which reduces the production of amyloid-β) developing dementia is one-fifth that of the general population10. Over the past few years, this genetic effect has been mimicked with various medications3. Around a dozen therapies that target enzymes involved in the production of amyloid-β in various phases of clinical trial reduce the production of the protein3 by as much as 70–80%. Moreover, drugs that target enzymes such as BACE and gamma secretase can be taken orally (other drugs that target amyloid-β have to be given by injection), and newer generations of these classes of compounds seem to have few serious side effects.

Funding and regulation It could take ten years or more of primary prevention trials based on cognitive or clinical outcomes for regulatory agencies to approve drugs for prevention. Few pharmaceutical companies are willing to pay for the majority of expenses in such long trials. Recognizing the urgency of the problem, governments, particularly those of the United States and Europe, are increasingly supporting the development of prevention initiatives (see go.nature.com/2ubyv5k and go.nature.com/2tdrn4f).

Another encouraging development within the past four years is that guidelines for the approval of Alzheimer’s drugs from the US Food and Drug Administration and European Medicines Agency now include the consideration of the effects of compounds on surrogate biomarkers, such as amyloid-β plaques, in addition to tests of memory. (So far, there has been no case of a drug for Alzheimer’s being approved only on the basis of a biomarker.)

High Stakes

Some researchers may object to our proposal to make amyloid-β the target of primary prevention trials. Around ten large trials that target amyloid-β plaques have failed over the past five years or so. In our view, the various explanations for these failures11 can be summarized as ‘too little, too late’. The best way to test the role of amyloid-β pathology in Alzheimer’s disease is to stop it from taking hold in the first place.

Some scientists are also concerned that a single drug is unlikely to be sufficient to treat such a complex, chronic disorder. But, as demonstrated in familial hypercholesterolaemia, one drug can be extremely effective when used for prevention. What is needed now is engagement from all stakeholders — including public and private funders — who need to commit hundreds of millions of dollars.
The stakes are extraordinarily high. If successful, a primary prevention treatment could avert the loss of memories, thoughts and independence for a significant proportion of the world’s older population.

terça-feira, 14 de novembro de 2017

Study suggests ways to block hypertension in those with sleep apnea




Obstructive sleep apnea -- a disorder that affects nearly one out of four people between the ages of 30 and 70 -- is a common cause of high blood pressure. In the Aug. 17, 2016, issue of the journal Science Signaling, researchers based primarily at the University of Chicago describe the signaling cascade that leads to this form of hypertension and suggest ways to disrupt those signals and prevent elevated blood pressures.

"Our results, using a rodent model, establish a mechanism that is the cause of apnea-associated hypertension," said study leader Nanduri Prabhakar, PhD, director of the Institute for Integrative Physiology and Center for Systems Biology of Oxygen Sensing at the University of Chicago. "They also offer a novel way to block the process, preventing this form of hypertension and restoring normal blood pressures."

The connection between sleep apnea and high blood pressure begins in the carotid body, a small cluster of cells located in the carotid arteries, which pass through the right and left sides of the neck. Chemosensory cells in the carotid bodies constantly measure oxygen levels in the blood and use that information to regulate breathing.
When people with sleep apnea periodically slow or stop their breathing during sleep, their blood-oxygen levels plummet. The carotid bodies recognize this deficit and quickly release signals to increase breathing and bring oxygen levels back to normal. These signals, however, can also increase blood pressure, which can lead to strokes during sleep.

"In both central and obstructive sleep apnea, the acute elevations in blood pressure associated with apneic episodes may predispose patients to hemorrhagic stroke, while chronic hypertension increases the risk of heart failure," the authors wrote. "Thus, controlling hypertension in sleep apnea patients is a major clinical problem."
So the researchers carefully mapped out the chain of signaling events that began with sleep-disordered breathing and led to the onset of hypertension.
When an episode of apnea causes low blood oxygen levels, the carotid bodies quickly detect the decrease and begin to generate reactive oxygen species (a natural byproduct of the normal metabolism of oxygen). These inactivate heme oxygenase-2, an enzyme that generates carbon monoxide (CO). This leads to an increase in hydrogen sulfide, which stimulates the carotid bodies to send out chemical signals to take in more oxygen.

Unfortunately, those signals also stimulate the sympathetic nervous system and cause blood vessels to constrict, boosting blood pressure. The standard therapies for hypertension caused by constricted vessels "do not work in this form of hypertension," Prabhakar said.
In the 1960s, when the relationship between the carotid bodies and asthma was being first investigated, researchers tried to treat the disease by surgical removal of the carotid bodies. However, some of those patients developed sleep apnea. Although carotid body resection prevented hypertension, that approach came with serious side effects. Because they lacked the urge to breathe more during exertion, patients were unable to exercise safely, Prabhakar said, adding that "some died in their sleep from extended apneic episodes."

The authors suggest instead that drugs designed to inhibit the enzyme cystathionine-y-lyase -- required for the production of hydrogen sulfide, the signal to increase oxygen intake -- could be used to disrupt the cascade of signals leading to apnea-related hypertension.
"A major finding of the present study is that blockade of hydrogen sulfide synthesis is sufficient to prevent carotid body activation and hypertension in intermittent hypoxia-exposed rodents," the authors note. Treating rats with a cystathionine-y-lyase inhibitor L-propargylglycine (L-PAG) "restored normal carotid body function, sympathetic nerve activity and blood pressure, and blocked hypertensive responses to simulated apneas."

"Our results," they conclude, "suggest that inhibiting cystathionine-y-lyase to reduce hydrogen sulfide signaling in the carotid body with more potent inhibitors than L-PAG may be a novel approach to treat hypertension in patients with sleep apnea."

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Landmark gene therapy for hereditary blindness closes in on FDA approval




A breakthrough gene therapy for a rare form of hereditary blindness is close to FDA approval

A breakthrough gene therapy for a rare form of hereditary blindness is close to FDA approval(Credit: Pirotehnik/Depositphotos)


Back in August, the FDA approved the first gene therapy for general use in the United States. That particular treatment, for cancer, was beset by controversy due to its exorbitant price tag and potential side effects. Now another gene therapy is on the cusp of approval, this time to treat a form of hereditary blindness. If given the tick by the FDA, this therapy could pave the way for a whole host of treatments for genetically-based vision problems.

The gene therapy focuses on a rare inherited retinal disease called Leber congenital amaurosis (LCA), which is caused by a mutation in one of 19 particular genes. The therapy focuses in one specific gene called RPE65. A healthy version of that gene is attached to a genetically modified harmless virus and injected into a patient's eyes.
The treatment is currently undergoing final phase 3 clinical trials after nearly a decade of research and the early results have been excitingly positive. Data from the first phase 3 trial showed 93 percent of subjects (27 out of 29) displayed "meaningful improvements in their vision."

"These are kids who could not walk through a room in normal light, and who were absolutely paralyzed in dim light," says study leader Stephen Russell. "Now they're walking around markedly better."
The final FDA approval decision is hoped to come by January 2018, and back in October an advisory panel unanimously endorsed the efficacy of the treatment. The FDA doesn't have to follow the advice of this expert panel, but it traditionally does.

The gene therapy focuses on a rare inherited retinal disease called Leber congenital amaurosis

While this particular therapy is not a complete cure, and it is targeted at a rare genetic disease, many hope it is the first in a new wave of gene therapies directed at a wide variety of occular diseases. There are over 225 known genetic mutations that cause blindness, and the genetically modified virus used in this particular treatment can likely be used as a delivery mechanism in treatments for a great majority of those conditions.
If this therapy is ultimately approved it will certainly be a landmark for modern gene therapy. Unlike theprior cancer therapy approved in August, which concentrates on genetically modifying immune cells, this treatment will be the first to replace, or essentially fix, specific missing and mutated genes that directly cause disease.
The early trial results were published in the journal The Lancet.



sexta-feira, 10 de novembro de 2017

Blueberries, canary seed, ginger, olive oil and green tea are just some of the foods recommended for managing rheumatoid arthritis





A list of food items with proven beneficial effects on the progression and symptoms of rheumatoid arthritis is provided in a new study published today in Frontiers in Nutrition. The authors suggest incorporating these foods into the diet to support the management of this debilitating autoimmune disease.
"Regular consumption of specific dietary fibers, vegetables, fruits and spices, as well as the elimination of components that cause inflammation and damage, can help patients to manage the effects of rheumatoid arthritis," says Dr. Bhawna Gupta, who completed this study together with Ms. Shweta Khanna and Mr. Kumar Sagar Jaiswal at the Disease Biology Lab, School of Biotechnology, KIIT University, India. 

"Incorporating probiotics into the diet can also reduce the progression and symptoms of this disease."
She continues, "Patients suffering from rheumatoid arthritis should switch from omnivorous diets, drinking alcohol and smoking to Mediterranean, vegan, elemental or elimination diets, as advised by their doctor or dietician."
Rheumatoid arthritis causes pain, swelling and stiffness in the joints, severely impacting quality of life. It is difficult to detect the early onset of the disease and if undetected or misdiagnosed has a rapid rate of progression in the first few years. The first line of treatment includes disease-modifying anti-rheumatic drugs, but these can be expensive.

"Supporting disease management through food and diet does not pose any harmful side effects and is relatively cheap and easy," Dr. Gupta explains. "Doctors, physicians and dieticians can use our study to summarize current proven knowledge on the links between certain foods and rheumatoid arthritis. Knowing the nutritional and medicinal requirements of their patients they can then tailor this information for the betterment of their health."

Various dietary plans for rheumatoid arthritis, such as vegan, 7-10 days fasting and Mediterranean, have long been recommended. This study -- only the second overall assessment of diet and food on this disease -- provides a very thorough evaluation of current scientific knowledge and makes a point of only reporting dietary interventions and specific foods that clearly show proven long-term effects.

Foods highlighted as reducing the progression and symptoms of rheumatoid arthritis range from fruits such as dried plums, blueberries and pomegranates, to whole grains, the spices ginger and turmeric, as well as specific oils and teas. They can provide a range of beneficial effects, such as lowering inflammatory cytokines (chemicals released by the immune system that can cause problems in rheumatoid arthritis patients), reducing joint stiffness and pain, as well as lowering oxidative stress -- the ability of the body to counteract or detoxify harmful chemicals.
The authors hope the study can also be used as a reference for the development of new medicines.

"Our review focused on specific dietary components and phytochemicals from foods that have a proven beneficial effect on rheumatoid arthritis," says Dr. Gupta. "Pharmaceutical companies may use this information to formulate 'nutraceuticals'. Nutraceuticals have an advantage over chemically-tailored medicines as they are not associated with any side effects, originate from natural sources and are cheaper."
Dr. Gupta concludes by offering some advice for those hoping to use the findings of their study.

"We reviewed research from several laboratory experiments under different conditions. Dietary components vary according to geography and weather conditions, so patients should be aware of their nutritional requirements, allergies and any other food-related disease history. We strongly suggest the general public consult doctors and dieticians before following any diet program or food compounds discussed in the study."

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Study in mice shows benefits from calorie-restricted diet



Caloric restriction diets have been associated with various health benefits, but their effects on the skin have not been previously demonstrated. Research conducted at the University of São Paulo (USP) in Brazil shows that controlling calories helps mice live longer, although it reduces the reserves of fat in adipose tissue needed to keep the body warm.
To offset this effect of the diet, the skin of the mice stimulated fur growth and increased blood flow to warm the skin.

The authors also observed changes in cell metabolism. The mice displayed an adaptive response to remain warm -- and alive -- under conditions of limited food.
The research was conducted during Maria Fernanda Forni's postdoctoral fellowship at USP's Chemistry Institute with support from FAPESP and supervision by Alicia Kowaltowski. This research was part of the Thematic Project "Mitochondrial bioenergetics, ion transport, redox state and DNA metabolism" for which Kowaltowski was the principal investigator.
The results of the study were published in September in the journal Cell Reports. "The changes in fur and skin were highly perceptible," Kowaltowski said. "These changes are interesting because they appeared after only a few months when the animals were not yet old."

The experiment involved two groups of mice and lasted six months. In one of the groups, the mice were allowed to eat as much as they wanted at all times and became obese. The others were fed a diet with only 60% of the calories consumed by the other group on average.
After six months, the body mass of the mice fed a caloric restriction (CR) diet was 40% lower than that of the mice fed an unrestricted diet. This change was not due to the mice losing weight; the mice fed a CR diet did not gain as much weight as the mice that could eat ad libitum. As the fat that helps keep the body warm diminished in CR mice, the adaptive response of their skin was to stimulate fur growth, and after six months, their fur was more uniform, thicker and longer.

"Fur has properties that insulate animals to retain warmth," Kowaltowski said. "We believe this is an adaptation present in mammals. Those that eat less have less fat, and they need more fur or body hair as thermal insulation."
Skin vascularization also changed. Compared with the obese group, the CR group had three times more blood vessels in their skin. This change increased blood flow to skin cells. Moreover, skin cell metabolism exhibited differences between the groups.

Conversely, signs of premature skin aging appeared in the overweight mice. "The change in vasoconstriction helped the slimmer mice stay warm, and their skin also remained young," Kowaltowski said.
In the second stage of the experiment, parts of the skin were shaved in both groups to confirm that the extra fur was helping CR mice keep warm. "We shaved the mice and observed their evolution for a month," Kowaltowski said.

The researchers measured the loss of body heat and found that thicker fur did indeed help the mice retain warmth.
"CR mice lost muscle mass and became lethargic," Kowaltowski said. "This metabolic change directly resulted from the loss of body heat to the environment. The mice were unable to live well without fur."
Finally, the skin of the mice was dyed blue to investigate whether there was a difference between CR mice and overweight mice in terms of fur thickness. The result showed that CR mice had thicker fur than did overweight mice. "They lost less fur, and their fur remained thick for longer. This could be an adaptation to avoid energy expenditure on growing fur," Kowaltowski said.

"These discoveries are particularly significant since they reveal not just a pronounced effect of the CR diet on skin but also an adaptive mechanism to deal with the reduced insulation due to skin changes under conditions of lower caloric intake."
Liver protection
In another study published in Free Radical Biology and Medicine, Kowaltowski's group showed that a CR diet protected the liver from damage due to temporary interruption of blood flow to the organ.

"When we compared mice fed ad libitum with mice fed a CR diet, we found a huge difference," Kowaltowski said. "Approximately 25% of the liver was damaged in the former group, and only 1% was damaged in the latter."
The ischemia/reperfusion model used in the experiment consists of interrupting approximately 70% of blood flow to the liver for 40 minutes, simulating a heart attack. Data in the scientific literature suggest that this procedure induces a pathological increase in tissue calcium, which causes a breakdown in the function of mitochondria (organelles that produce energy for cells) and leads to the death of some liver cells.

"Calcium is important to regulate mitochondrial metabolism and increase ATP [adenosine triphosphate, the molecule that stores energy] production. However, an excessive amount of calcium causes the organelles to stop working properly. Therefore, our hypothesis was that the observed benefit of the diet was related to an increase in the capacity of the mitochondria to capture calcium from the intracellular medium without ceasing to produce energy," said Sergio Menezes-Filho, a researcher at IQ-USP and first author of the article.

In vitro experiments were performed to test the hypothesis and better understand the mechanisms involved. To accomplish this, the researchers isolated mitochondria from both groups of mice, the control group allowed to feed ad libitum and the group fed a CR diet (60% of the control group's caloric intake).
The mitochondria were placed in incubation medium with a fluorescent probe that shone more brightly as the level of calcium increased.

"We added a small amount of calcium to the medium, and the fluorescence intensified. As the mitochondria captured the calcium, the brightness diminished. We added a little more. When the mitochondria reached maximum calcium uptake capacity, calcium began returning to the incubation medium, and fluorescence increased even without the addition of more calcium," Menezes-Filho explained.
In this experiment, the group observed that CR mouse mitochondria were able to absorb approximately 70% more calcium than were control mouse mitochondria without functional impairment.

Using mass spectrometry, the group found that there were more ATP molecules in the mitochondria extracted from the CR group than in those extracted from the control group. Marisa Medeiros, a professor at IQ-USP, collaborated in this part of the study.
"We do not yet know why the mitochondria of the mice fed ad libitum have less ATP, but this difference is certainly associated with their calcium uptake capacity," Kowaltowski said. "When we artificially matched the ATP levels in both groups by adding ATP to control mitochondria or reducing it in CR mitochondria, calcium uptake also became equal."

Multiple benefits

The two recently published articles are part of a series of studies led by Kowaltowski under the aegis of the Center for Research on Redox Processes in Biomedicine (Redoxome), one of the Research, Innovation & Diffusion Centers (RIDCs) funded by FAPESP. The aim is to investigate the effects of caloric restriction on different tissues.
"Simply telling people to eat less is not working. Obesity has become a global epidemic. We are trying to understand how CR acts in the organism and which molecules are involved to identify targets for preventing or treating diseases associated with weight gain and age," Kowaltowski said.