Saturday, April 26, 2014

Scientists at Johns Hopkins Come Closer to Eliminating Heart Disease

A world without heart disease seems impossible. But researchers at Johns Hopkins just got one step closer.
Scientists at Johns Hopkins University may be one step closer to eradicating debilitating heart diseases in humans, particularly those caused by excessive buildup of cholesterol.
A new study published in the journalCirculation shows that a synthesized drug reduces, and may even eradicate, the effects of high-fat and high-cholesterol diets. And though the drug is prosperous for the heart and brain most specifically, the entire body may benefit from this development.  
“It’s the entire cardiovascular system that’s affected,” Ekaterina Pesheva, a representative for Johns Hopkins, told The Daily Beast. “The reason we’re worried about the heart and the brain is because those are the centers that end up being the most debilitating to human life when affected by fatty buildups.”
The study shows that the new drug under examination, known now as D-PDMP, changes the way fat metabolism works, and eliminates the risk of heart attack and heart disease. The drug halts the development of atherosclerosis, a word referring to the hardening of the arteries. Atherosclerosis is based on a buildup of fat and cholesterol in blood vessels, and happens to be the main cause of heart attacks in humans. Most notably, atherosclerosis is the No. 1 cause of death in humans (perhaps a little-known fact in a world rampant with famine, war, and crime).
Atherosclerotic heart disease is the most common type of heart disease, which develops when fat builds inside the blood vessels over time, rendering them stiff, narrowed, and hardened. This, in turn, reduces blood flow to the heart and brain.
Other kinds of heart disease include structural heart disease—people born with malformations of their heart, which is rare, and heart failure (mostly a result of poorly functioning heart muscle, which can be due to a number of causes, including atherosclerosis. It can also be caused by other conditions such as viral infections of the heart) will also benefit from this development.
Perhaps the most remarkable aspect of these new developments is that the compound used to control the atherosclerosis is a widely available, man-made compound.
Dr. Subroto Chatterjee, Ph.D, a cardio-metabolic expert at Johns Hopkins Medicine, spearheaded the research and development of this project. “Atherosclerotic, in most colloquial terms, means clogged vessels, or vessels thickened by buildup of fat inside the vessel,” Chatterjee told The Daily Beast. “And this research was quite challenging,” he said, “but we feel like we got quite lucky with the development here.”
Chatterjee and his team found that D-PDMP almost totally eliminated the buildup of cholesterol in vital regions of the body. Perhaps the most remarkable aspect of these new developments is that the compound used to control the atherosclerosis is a widely available, man-made compound.
The researchers tested the drug in mice and rabbits, Chatterjee told The Daily Beast. The mice were known to already have heart problems and the rabbits were known to have healthy hearts. That complicates the study, if only because the control group of the species isn’t specific to one cardiovascular system. Researchers fed both species a high-fat and high-cholesterol diet.
“Indeed, this diet nearly guarantees arteriosclerosis in these transgenic/mutant mice as they fail to handle LDL [low-density liver] cholesterol,” Chatterjee said. “In these animals on this diet, the risk of this disease is nearly 100%. There is one chance in four that your child may have blood cholesterol that is too high. Healthy individuals have a one in two chance of abnormally elevated blood cholesterol,” he said. “More than 70 million Americans have high cholesterol, according to the CDC.”
Cholesterol control is a contentious field in medical research, because the side effects of drugs used to treat the issue can be dangerous. The Daily Beast spoke with John McEvoy, a cardiology fellow in preventive cardiology physician, at Johns Hopkins, who was not involved with this particular study.
“It’s always very important when a new mechanism for treating high cholesterol and heart disease comes about,” McEvoy said. “This pathway and new treatment are very exciting in that regard. However, the next step for these researchers will be making sure there are no side effects of the drug that are harmful to humans.”
Chatterjee said that the actual development of the drug is about five years away. He put its science in simple terms 
“Imagine you have clogged up plumbing due to debris,” Chatterjee said. “Similar clogging in our blood vessels occurs due to fat and cholesterol building up over time. Our drug, we hope, will prevent [or] delay the rise in cholesterol and fat and thus prevent thickening/hardening of the blood vessel. This is like the use of Drano to clean up our plumbing at home.”

Tuesday, March 11, 2014

Unique individual with lupus and HIV demonstrates desired immune response to HIV

Date:
Source:
Duke Medicine
Summary:
One person’s unique ability to fight HIV has provided key insights into an immune response that researchers now hope to trigger with a vaccine, according to new findings. The person had a rare combination of both lupus and HIV. Lupus, specifically systemic lupus erythematosus, or SLE, is a disease in which the immune system attacks the body's cells and tissue.

One person's unique ability to fight HIV has provided key insights into an immune response that researchers now hope to trigger with a vaccine, according to findings reported by a team that includes Duke Medicine scientists.
The person had a rare combination of both lupus and HIV. Lupus, specifically systemic lupus erythematosus, or SLE, is a disease in which the immune system attacks the body's cells and tissue.
In an analysis published March 10, 2014, in the Journal of Clinical Investigation, the Duke-led research team detailed how the individual's immune system made a desired type of neutralizing antibodies that is considered essential to an effective vaccine response.
"Over the years we have searched for and now have found one person with SLE who was also chronically infected with HIV to determine if this person could make broad neutralizing antibodies," said Barton F. Haynes, M.D., director of the Duke Human Vaccine Institute and senior author of the study. "We found that the patient did indeed make these important antibodies, and by determining how this immune response occurred, we have enhanced our understanding of the process involved."
Haynes said a huge barrier to creating an effective HIV vaccine has been the difficulty in eliciting the broad neutralizing antibody response. These antibodies arise in a few people infected with HIV, but it takes at least two years.
In 2005, Haynes found that some broad neutralizing antibodies to HIV cross-reacted with the body's tissues in a process termed autoreactivity. Autoreactive antibodies are kept in check by the body's immune tolerance controls, which sense antibodies that react with the body and prevent them from being made.
Haynes's hypothesis has been that these autoreactive broad neutralizing antibodies are not routinely made because the immune system targets them as harmful and keeps them in check. In essence, the virus has found a unique escape mechanism from neutralizing antibodies by adapting itself to look like the body's tissues.
In an autoimmune disease such as lupus, the immune tolerance controls are defective, so the broad neutralizing antibodies should be produced, the Duke team reasoned.
Haynes and colleagues, including lead author Mattia Bonsignori, M.D., assistant professor of medicine at Duke, identified an individual with both lupus and HIV and found that, after several years, the person made the desired broad neutralizing antibodies.
Remarkably, the broad neutralizing antibody found in the lupus individual was autoreactive, and reacted with similar molecules in the body called double stranded DNA, or dsDNA, that are made in individuals with lupus who do not have HIV.
"The cross-reactivity of the broad neutralizing antibody with dsDNA was very surprising and provided support for the hypothesis that broad neutralizing antibodies are similar to the autoantibodies that arise in lupus patients who are not infected with HIV," Bonsignori said.
The findings in no way suggest that individuals with lupus are immune to HIV, and they, like all individuals, should protect themselves from contracting the virus. Rather, it suggests that when individuals with lupus do become infected with HIV, they can eventually make broad neutralizing antibodies, although unfortunately too late to help them fight off the infection.
"Our study of this person with SLE and HIV has been critically instrumental in our understanding of the unusual biology of the remarkable host control of antibody responses to the conserved broad neutralizing sites of the HIV envelope," Bonsignori said. "We are hopeful that these insights in lupus will aid in our implementation of strategies for designing experimental vaccines capable of overcoming the host tolerance control of broad neutralizing antibodies."
In addition to Haynes and Bonsignori, study authors from Duke include Kevin Wiehe, Guang Yang, Daniel M. Kozink, Florence Perrin, Abby J. Cooper, Kwan-Ki Hwang, Xi Chen, Mengfei Liu, Robert J. Parks, Joshua Eudailey, Minyue Wang, Megan Clowse, Lisa G. Criscione-Schreiber, M. Anthony Moody, Feng Gao, Garnett Kelsoe, Laurent Verkoczy, Georgia D. Tomaras, Hua-Xin Liao, and David C. Montefiori. Other authors include Sabastian K. Grimm and Margaret E. Ackerman from Dartmouth College; Rebecca Lynch, Krisha McKee and John R. Mascola from the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases; and Scott D. Boyd of Stanford University.
The National Institute of Allergy and Infectious Diseases funded the study (AI067854 and AI100645).

Story Source:
The above story is based on materials provided by Duke Medicine. Note: Materials may be edited for content and length.

Journal Reference:
  1. Mattia Bonsignori, Kevin Wiehe, Sebastian K. Grimm, Rebecca Lynch, Guang Yang, Daniel M. Kozink, Florence Perrin, Abby J. Cooper, Kwan-Ki Hwang, Xi Chen, Mengfei Liu, Krisha McKee, Robert J. Parks, Joshua Eudailey, Minyue Wang, Megan Clowse, Lisa G. Criscione-Schreiber, M. Anthony Moody, Margaret E. Ackerman, Scott D. Boyd, Feng Gao, Garnett Kelsoe, Laurent Verkoczy, Georgia D. Tomaras, Hua-Xin Liao, Thomas B. Kepler, David C. Montefiori, John R. Mascola, Barton F. Haynes. An autoreactive antibody from an SLE/HIV-1 individual broadly neutralizes HIV-1. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI73441

Cite This Page:
Duke Medicine. "Unique individual with lupus and HIV demonstrates desired immune response to HIV." ScienceDaily. ScienceDaily, 10 March 2014. <www.sciencedaily.com/releases/2014/03/140310182542.htm>.

Scientists describe deadly immune “storm” caused by emergent flu infections

Scientists describe deadly immune “storm” caused by emergent flu infections

Fri, 02/28/2014 - 7:53am
Scientists at The Scripps Research Institute (TSRI) have mapped key elements of a severe immune overreaction—a “cytokine storm”—that can both sicken and kill patients who are infected with certain strains of flu virus.
Their findings, published online in the Proceedings of the National Academy of Sciences, also clarify the workings of a potent new class of anti-inflammatory compounds that prevent this immune overreaction in animal models.
“We show that with this type of drug, we can quiet the storm enough to interfere with the virus-induced disease and lung injury, while still allowing the infected host to mount a sufficient immune response to eliminate the virus,” said John R. Teijaro, an asst. prof. in TSRI’s Dept. of Immunology and Microbial Science and first author of the study.
“This study provides insights into mechanisms that are chemically tractable and can modulate these cytokine storms,” said Hugh Rosen, prof. in TSRI’s Dept. of Chemical Physiology and senior author of the study with Michael B. A. Oldstone, prof. in TSRI’s Dept. of Immunology and Microbial Science.
Calming the storm
A cytokine storm is an overproduction of immune cells and their activating compounds (cytokines), which, in a flu infection, is often associated with a surge of activated immune cells into the lungs. The resulting lung inflammation and fluid buildup can lead to respiratory distress and can be contaminated by a secondary bacterial pneumonia—often enhancing the mortality in patients.
This little-understood phenomenon is thought to occur in at least several types of infections and autoimmune conditions, but it appears to be particularly relevant in outbreaks of new flu variants. Cytokine storm is now seen as a likely major cause of mortality in the 1918-20 “Spanish flu”—which killed more than 50 million people worldwide—and the H1N1 “swine flu” and H5N1 “bird flu” of recent years. In these epidemics, the patients most likely to die were relatively young adults with apparently strong immune reactions to the infection—whereas ordinary seasonal flu epidemics disproportionately affect the very young and the elderly.
For the past eight years, Rosen’s and Oldstone’s laboratories have collaborated in analyzing the cytokine storm and finding treatments for it. In 2011, led by Teijaro, who was then a research associate in the Oldstone Laboratory, the TSRI team identified endothelial cells lining blood vessels in the lungs as the central orchestrators of the cytokine storm and immune cell infiltration during H1N1 flu infection.
In a separate study, the TSRI researchers found that they could quiet this harmful reaction in flu-infected mice and ferrets by using a candidate drug compound to activate immune-damping receptors (S1P1 receptors) on the same endothelial cells. This prevented most of the usual mortality from H1N1 infection—and did so much more effectively than the existing antiviral drug oseltamivir, although the combination of both therapies worked even better. “That was really the first demonstration that inhibiting the cytokine storm is protective,” said Teijaro.
Mapping a path forward
For the new study, Teijaro and his colleagues set out to map the major elements of the cytokine storm in H1N1 infection. To do so, they used gene knock-out techniques to breed mice that lack one or more molecular sensors of influenza virus infection and then observed the response to infection by H1N1 influenza virus.
The experiments showed that knocking out any one infection-sensing pathway has relatively modest effects on damping the cytokine and immune cell lung-infiltration response. In each case, an experimental drug compound (CYM5442) that activates S1P1 receptors knocked it down much more.
“What this shows is that our drug is working not through one selective pathway but much more broadly,” said Teijaro. “Many different cytokines are induced in this reaction, so just blocking one is surely not enough to reduce the lung disease.”
While CYM5442’s effect is broad, its action is selective on cells that bear the sphingosine-1-phosphate 1 receptor (S1P1R). Teijaro pointed out that it is also milder than those of steroids, which act indiscriminately on all lymphoid cells, and other strong immunosuppressant drugs, which may block the immune response so completely that an infecting virus ends up replicating out of control.
An optimized version of CYM5442, initially developed by Rosen and fellow TSRI chemist Ed Roberts, has been licensed to the pharmaceutical company Receptos. It is now in Phase 3 clinical trials for treating relapsing-remitting multiple sclerosis and Phase 2 trials for ulcerative colitis. Other S1P1 receptor agonists are in development for inflammatory conditions. A less-specific S1P receptor agonist—which hits S1P1, but also hits S1P3, S1P4 and S1P5, with potential off-target effects—is already approved for treating multiple sclerosis.
“We’d like to understand all the pathways through which S1P1 agonists work and, by pinpointing specific stop/start points, figure out how best to target those pathways with future drugs,” said Teijaro, who plans further studies with his colleagues to determine what other cell types are involved in orchestrating and possibly quieting the cytokine storm. “I’m hoping our work can further contribute to TSRI’s long track record of success in employing small molecule probes coupled to genetic and biochemical tools to provide biological insight into pathological disease processes

Thursday, January 30, 2014

Immune cells in the gut may improve control of HIV growth
Date:
June 11, 2012
Source:
University of North Carolina School of Medicine
The study was led by researchers at the University of California, San Francisco and included Kristina Abel, Ph.D., an assistant professor in the department of microbiology and immunology at UNC, at the time of the study a faculty member at the University of California, Davis.
Credit: UNC School of Medicine
The findings of a new study in monkeys may help clarify why some people infected with HIV are better able to control the virus. They also may pinpoint a target for treatment during early HIV infection aimed at increasing the supply of certain immune cells in the gut, which the study shows could be an important factor in limiting HIV growth in cells throughout the body.
The study was led by researchers at the University of California, San Francisco (UCSF) and included Kristina Abel, PhD, an assistant professor in the department of microbiology & immunology at UNC, at the time of the study a faculty member at the University of California, Davis (UCD). "The research involved a rhesus macaque model of HIV, monkeys who were infected with simian immunodeficiency virus, SIV" Abel said. "The course of SIV infection in these monkeys is quite similar to that of HIV in humans."
Both HIV and SIV infections cause severe CD4 T cell loss in the gut during early infection. As a result, the intestinal mucosal barrier, which is like the body's second skin or front line of defense against pathogens, is compromised. The "leaky gut" causes bacteria that are normally located in the gut (the normal flora) to migrate out and activate the immune system throughout the body with disastrous health consequences. "The immune activation contributes to higher replication of the virus. And so the question is, why do some patients progress from infection to AIDS faster than others?" Abel asks.
This new study looked at the balance between certain immune cell populations that might influence disease outcome. The study shows the presence of a subtype of CD4-positive immune cells called Th17 (T helper 17) cells in the gut "could influence disease outcome."
A report of the research appeared in the May 30, 2012 online issue of Science Translational Medicine.
Th17 cells are commonly found at mucosal surfaces and activate epithelial or outer layer barrier cells to secrete antimicrobial molecules, thus blocking disease-causing bacteria from entering. Abel points out that they also stimulate the production of "tight junction" proteins that keep all the cells that make up the intestinal barrier in close contact, "so that bacteria of the normal flora or their products cannot leak out."
The researchers wondered if there are more Th17 cells in the gut, would infection with the AIDS virus still have that early massive effect on gut permeability? And if you could keep the intestinal barrier intact during early infection with HIV, would it have an impact on the severity of disease progression, on having less severe disease in the long run?
Results of the study suggest that the answers may be yes. Rhesus macaques with higher numbers of Th17 cells in blood and intestinal tissue before they are infected with SIV subsequently have lower SIV viral loads. "It appears they're more able to control the infection," Abel said.
The study also found that among animals given a drug that increases regulatory T cells and thereby suppresses Th17 cell development, disease progression occurred more rapidly, and they had higher levels of SIV virus six months after infection.
"The main message of the study is that the frequencies of certain immune cell populations in the normal, still uninfected individual are important in subsequent disease progression and outcome," Abel said. "The paper also suggests that treatment aimed at increasing Th17 cells may improve the control of HIV growth by promoting an environment in which T cells having more anti-viral capabilities are produced."
The study's principal investigator was Dennis J. Hartigan-O'Connor, MD, PhD, from UCSF (now at UCD). Other investigators are Koen K.A. Rompay, from UCD; Bitoo Kanwar, from UCSF; and study senior author Joseph M. McCune, MD, PhD, from UCSF.
Support for the research came from the National Institutes of Health, the Bill and Melinda Gates Foundation, the California National Primate Research Center, the National Center for Research Resources, and the Harvey V. Berneking Living Trust.
Story Source:
The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.

Wednesday, January 29, 2014

11 Ways to Rev Up Your Metabolism


Speed Up Your MetabolismSure, your metabolism slows as you get older. But who says you have to take that sitting down? New research shows the best ways to burn more calories - faster!
Traditional wisdom holds that a sluggish metabolism is a curse of midlife, like needing reading glasses to use a smartphone or starting to worry about your retirement plan. So we fight the slowdown, eating like parakeets for a few days or launching into an intense exercise routine. When a week goes by with no miracles, we give up and resume the same bad habits - sloppy portions, half-hearted workouts, and non-petite servings of imported cheese.
Ok, put away the Brie and consider this: About 30% of your metabolism is under your control(the rest, devoted to such mundane but essential functions as digesting food and repairing cells, isn't). And as researchers get deeper into the physiology of weight regulation, they're fine-tuning their understanding of what it takes to ramp up that 30% and drop pounds. Happily, it starts with what you consume - the right foods at the right times. 

Related:
 10 Healthy Tips to Steal from Popular Diets
1. Measure Your Meals 
If simply cutting back isn't budging the scale, it's helpful to know how many calories you need each day to maintain your weight. Then, to lose pounds, you can subtract from that maintenance number. Since a woman's metabolic rate falls roughly 2% to 3% each decade, this number - alas - goes down with age. A moderately active woman in her 20s requires a daily average of 2,000 to 2,200 calories to maintain her weight. In her 30s and 40s, it drops a little to just about 2,000. After 50, it falls to 1,800.
And you? Check out the Metabolism Calculator at webmd.com. By plugging in your gender, age, height, weight and activity level (there's a five-point range on the site, from "inactive" to "extremely active"), you'll learn what it takes to keep the status quo. For example, a 45-year-old woman who is 5'4", 158 pounds, and moderately active will maintain her weight on 2,093 calories a day. There's been some refinement of thinking on this, but in general, to lose a pound a week, she will need to consume 500 fewer calories each day (because a pound equals about 3,500 calories), or 1,593 calories.
Try to stick to your Metabolism Calculator calories for a week without changing your exercise routine. If a pound disappears, that's a calorie-needs bull's-eye. If not, adjust accordingly.
But don't be tempted to subtract too many calories. As counterintuitive as it may seem, eating too little can slow your metabolism - by as much as 20%. "If your body thinks you're trying to starve it, it fights back by burning fewer calories," says Domenica Rubino, M.D., an endocrinologist and a spokesperson for the Obesity Society.
2. Reset Your Eating Clock 
For years, experts have said that working on smaller, more frequent meals is essential to a faster metabolism. But recent studies suggest that's no better - diet-wise - than eating three larger meals a day. There's no cut-and-dried approach, says Dr. Rubino. "The research is certainly clear that breakfast is beneficial," she says. "But beyond that, you need to find what works for you." Some people do best with six small meals a day, while others consume way too much on that schedule. Some do better with three square meals, but that can make others so hungry that they set themselves up to overeat.
Whichever plan you choose - and you may want to experiment if you've been frustrated in your past dieting efforts - be sure to keep an eye on calories and track your hunger throughout the day. And once you do decide on the best approach, start a diet log: Note meals, snacks, and your mood before you eat. "It's the number one way to be conscious of what you're taking in and what is (and isn't) working for you," says Dr. Rubino. 

Related: 15 Slimming Superfoods That Magically Help You Lose 

3. Pack on the Protein 
You need it to build muscles - the metabolic powerhouses in your body. Indeed, every pound of muscle zaps six calories a day just doing nothing, while a pound of fat burns a measly two. A 2012 review from the Netherlands found that eating a healthy amount of protein helps you drop pounds and keep them off. What's "a healthy amount"? The study authors suggest 1.2 grams of protein for each kilogram you weigh. So our 158-pound (72-kilogram) woman might eat 86 grams of protein a day - that's one egg at breakfast (6 grams), a tuna salad sandwich at lunch (16 grams), 4 ounces of fat-free cottage cheese for a snack (12 grams), and a 6-ounce chicken breast at dinner (52 grams). If she starts by loading up at breakfast, she not only will feel more satisfied throughout the day, a new study of overweight women reports, but will also snack less at night. Remember, though, "Protein doesn't have any superpowers," says Felicia D. Stoler, D.C.N., a doctor of clinical nutrition and an exercise physiologist. "Excess calories from protein will just get stored as fat."
4. Say "Yo!" to Yogurt 
This favorite snack has been associated with maintenance of a healthy weight. Now researchers believe this may be because of yogurt's bacteria. "Scientists have found that obese people have more of a certain type of bacteria that is more efficient at extracting energy from food," says Gerard Mullin, M.D., a gastroenterologist at Johns Hopkins Hospital. "It's possible that the 'good' bacteria in yogurt help counter these 'bad,' weight-gain-causing bacteria."
5. Sprinkle on Spicy Extras 
Chili peppers, ginger, and turmeric have all been found to have a beneficial, albeit small, effect on metabolism. Use them often-beyond the boost, "You'll be getting phytonutrients, and they make meals more flavorful," Stoler says. 

Related: Little Every Day Tricks To Burn Extra Calories
6. Be Cardio Smart 
Aerobic exercise is like one of those store sales at which you buy one item at full price and get a second item for 50% off: There are the calories you burn while working out and, because your metabolic rate stays elevated, the extra calories you continue to burn while lounging on the chaise. Researchers found that about five sessions of moderate cardio per week - each lasting between 20 and 45 minutes - increased daily metabolism by an average of 109 calories in women. So even on the days the women weren't exercising, they enjoyed an afterburn.
Need more motivation? Even without dieting, cardio can lead to weight loss: In recent research from the University of Kansas, overweight women doing moderate cardio five days a week dropped 5% of their body weight in 10 months - without changing a thing about their diets.
To make sure your own workout is sufficiently strenuous, try to talk during it - having a short conversation should be possible, but not easy. Or, you can find your target heart rate here. For each age group, the rate is given as a range, so you may want to start with the lower number (especially if you're new to exercise or haven't done it in a while) and work your way up.
Try to get your workout to 30 minutes a day, and don't worry - it'll pay off: In a Danish study, previously sedentary volunteers instructed to exercise for half an hour lost just as much weight as those who worked out for an hour. (The researchers speculate that 30 minutes likely felt so doable and rewarding to those participants that they went on to do more physical activity in other ways not connected to the study.)
7. "HIIT" It 
High-intensity interval training has become the rage for a very good reason: Sprinkling just five 30-second extra-hard intervals into your normal cardio routine can torch as many as 200 additional calories in your workout. (You can do anything for 2 minutes!)
Or you can alternate intensities, going faster for one minute and then slower for the next. There's an unexpected perk to this approach, says Wayne L. Westcott, Ph.D., a professor of exercise science at Quincy College in Quincy, MA: The recovery minute feels so good to people that "time becomes their friend for that minute. It becomes more like a game and less like a workout." Research backs this up: A study from Liverpool John Moores University reports that recreational exercisers who ran using HIIT found it significantly more fun than just slogging along.
8. Get Muscular 
At around age 30, we start morphing into marshmallows as we lose about 5% of our muscle mass per decade. But maintaining and building muscle revs our metabolism. Even a simple weight-training program of three 25-minute sessions a week can keep your muscles toned - and burn 100 calories per session. The happy result: You could blast a third of a pound of pure fat in a month or 4 pounds a year.
There's no need to go to the gym. Exercises that rely on body weight, such as push-ups, tricep dips, wall sits, squats, and lunges, can be just as effective as those that use weights or machines. For how-tos, check out the exercise library at the American Council on Exercise.
9. Cure Sitting Sickness 
If you make phone calls for one hour at your desk, you'll burn 15 calories, but if you do it while standing up and pacing, you'll blast 100 calories. It's called NEAT - Non-Exercise Activity Thermogenesis - and ongoing research at the Mayo Clinic has found that we can burn up to an additional 800 calories a day simply by getting off our keisters and moving around more. Not only does NEAT help drop pounds, but it also may have a greater impact on longevity than standard exercise. A large study from the American Cancer Society found that women who sat for more than six hours a day were 37% more likely to die during the course of the 14 years of research than those who were sedentary fewer than three hours a day. This association remained virtually unchanged even when the sitters were devoted exercisers.
Some of the ways to incorporate more activity into your day are well known - taking the stairs instead of elevators, walking to colleagues' desks rather than e-mailing them. But you can also seed mini workouts into your daily life. "Do squats or lunges while waiting for the copier to warm up," suggests Stoler. At home, get in some tricep dips while the dryer is finishing its cycle or the coffee is brewing.
10. Call "Om" 
Add a bigger belly to the list of miseries chronic stress can inflict. Even if you're not eating more, changes in the way your body stores fat may cause thickening. In a just-completed study, for example, researchers found that a woman caring for a loved one with dementia had a bigger waistline than her less stressed counterpart, although both were eating the same large amounts of high-fat, high-sugar comfort foods.
It's the stress hormones and peptides at play here, which become elevated when we're under pressure. But several studies have shown that practicing yoga can tame anxiety - and also lower levels of these chemicals.
11. Melt Fat Mindfully 
A study in which women practiced mindfulness techniques (meditation, yoga, and more) for four months found those who showed greatest improvement in awareness of thoughts and feelings reduced their abdominal fat the most. And such focus, experts say, may be just what you need to embark on a bigger metabolism-revving program.

Tuesday, December 24, 2013


Are you having trouble remembering things? One of these meds may be the problem

En español l For a long time doctors dismissed forgetfulness and mental confusion as a normal part of aging. But scientists now know that memory loss as you get older is by no means inevitable. Indeed, the brain can grow new brain cells and reshape their connections throughout life.

Most people are familiar with at least some of the things that can impair memory, including alcohol and drug abuse, heavy cigarette smoking, head injuries, stroke, sleep deprivation, severe stress, vitamin B12 deficiency, and illnesses such as Alzheimer's disease and depression.
Woman rubbing temples, Medications that cause memory loss
Forgetful? Your prescription meds could be interfering with your memory. — Larry Williams/Corbis
But what many people don't realize is that many commonly prescribed drugs also can interfere with memory. Here are 10 of the top types of offenders.

1. Antianxiety drugs (Benzodiazepines)

Why they are prescribed: Benzodiazepines are used to treat a variety of anxiety disorders, agitation, delirium and muscle spasms, and to prevent seizures. Because benzodiazepines have a sedative effect, they are sometimes used to treat insomnia and the anxiety that can accompany depression.
Examples: Alprazolam (Xanax), chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Valium), flurazepam (Dalmane), lorazepam (Ativan), midazolam (Versed), quazepam (Doral), temazepam (Restoril) and triazolam (Halcion).
How they can cause memory loss: Benzodiazepines dampen activity in key parts of the brain, including those involved in the transfer of events from short-term to long-term memory. Indeed, benzodiazepines are used in anesthesia for this very reason. When they're added to the anesthesiologist's cocktail of meds, patients rarely remember any unpleasantness from a procedure. Midazolam (Versed) has particularly marked amnesic properties.
Alternatives: Benzodiazepines should be prescribed only rarely in older adults, in my judgment, and then only for short periods of time. It takes older people much longer than younger people to flush these drugs out of their bodies, and the ensuing buildup puts older adults at higher risk for not just memory loss, but delirium, falls, fractures and motor vehicle accidents.
If you take one of these meds for insomnia, mild anxiety or agitation, talk with your doctor or other health care professional about treating your condition with other types of drugs or nondrug treatments. If you have insomnia, for instance, melatonin might help. Taken before bedtime in doses from 3 to 10 mg, melatonin can help to reestablish healthy sleep patterns.
Be sure to consult your health care professional before stopping or reducing the dosage of any benzodiazepine. Sudden withdrawal can trigger serious side effects, so a health professional should always monitor the process.

2. Cholesterol-lowering drugs (Statins)

Why they are prescribed: Statins are used to treat high cholesterol.
Examples: Atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), rosuvastatin (Crestor) and simvastatin (Zocor).
How they can cause memory loss: Drugs that lower blood levels of cholesterol may impair memory and other mental processes by depleting brain levels of cholesterol as well. In the brain, these lipids are vital to the formation of connections between nerve cells — the links underlying memory and learning. (The brain, in fact, contains a quarter of the body's cholesterol.)
A study published in the journal Pharmacotherapy in 2009 found that three out of four people using these drugs experienced adverse cognitive effects "probably or definitely related to" the drug. The researchers also found that 90 percent of the patients who stopped statin therapy reported improvements in cognition, sometimes within days. In February 2012, the Food and Drug Administration ordered drug companies to add a new warning label about possible memory problems to the prescribing information for statins.
Alternatives: If you're among the many older Americans without known coronary disease who are taking these drugs to treat your slightly elevated LDL ("bad") cholesterol and low HDL ("good") cholesterol), ask your doctor or other health care provider about instead taking a combination of sublingual (under-the-tongue) vitamin B12 (1,000 mcg daily), folic acid (800 mcg daily) and vitamin B6 (200 mg daily).

Next page: Antiseizure drugs, antidepressants, narcotic painkillers »

3. Antiseizure drugs

Why they are prescribed: Long used to treat seizures, these medications are increasingly prescribed for nerve pain, bipolar disorder, mood disorders and mania.
Examples: Acetazolamide (Diamox), carbamazepine (Tegretol), ezogabine (Potiga), gabapentin (Neurontin), lamotrigine (Lamictal), levetiracetam (Keppra), oxcarbazepine (Trileptal), pregabalin (Lyrica), rufinamide (Banzel), topiramate (Topamax), valproic acid (Depakote) and zonisamide (Zonegran).
How they can cause memory loss: Anticonvulsants are believed to limit seizures by dampening the flow of signals within the central nervous system (CNS). All drugs that depress signaling in the CNS can cause memory loss.
Alternatives: Many patients with seizures do well on phenytoin (Dilantin), which has little if any impact on memory. Many patients with chronic nerve pain find that venlafaxine (Effexor) — which also spares memory — alleviates their pain.

4. Antidepressant drugs (Tricyclic antidepressants)

Why they are prescribed: TCAs are prescribed for depression and, increasingly, anxiety disorders, eating disorders, obsessive-compulsive disorder, chronic pain, smoking cessation and some hormone-mediated disorders, such as severe menstrual cramps and hot flashes.
Examples: Amitriptyline (Elavil), clomipramine (Anafranil), desipramine (Norpramin), doxepin (Sinequan), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil) and trimipramine (Surmontil).
How they can cause memory loss: About 35 percent of adults taking TCAs report some degree of memory impairment and about 54 percent report having difficulty concentrating. TCAs are thought to cause memory problems by blocking the action of serotonin and norepinephrine — two of the brain's key chemical messengers.
Alternatives: Talk with your health care provider about whether nondrug therapies might work just as well or better for you than a drug. You might also want to explore lowering your dose (the side effects of antidepressants are often dose-related) or switching to a selective serotonin/norepinephrine reuptake inhibitor (SSRI/SNRI). Of the drugs in this category, I find venlafaxine (Effexor) to have the fewest adverse side effects in older patients.

5. Narcotic painkillers

Why they are prescribed: Also called opioid analgesics, these medications are used to relieve moderate to severe chronic pain, such as the pain caused by rheumatoid arthritis.
Examples: Fentanyl (Duragesic), hydrocodone (Norco, Vicodin), hydromorphone (Dilaudid, Exalgo), morphine (Astramorph, Avinza) and oxycodone (OxyContin, Percocet). These drugs come in many different forms, including tablets, solutions for injection, transdermal patches and suppositories.
How they can cause memory loss: These drugs work by stemming the flow of pain signals within the central nervous system and by blunting one's emotional reaction to pain. Both these actions are mediated by chemical messengers that are also involved in many aspects of cognition. So use of these drugs can interfere with long- and short-term memory, especially when used for extended periods of time.
Alternatives: In patients under the age of 50 years, nonsteroidal anti-inflammatory drugs (NSAIDs) are the frontline therapy for pain. Unfortunately, NSAID therapy is less appropriate for older patients, who have a much higher risk of dangerous gastrointestinal bleeding. Research shows the risk goes up with the dosage and duration of treatment.
Talk with your doctor or other health care provider about whether tramadol (Ultram), a nonnarcotic painkiller, might be a good choice for you. In my practice, I often recommend supplementing each 50 mg dose with a 325 mg tablet of acetaminophen (Tylenol). While there are prescription drugs that combine tramadol and acetaminophen, these products have only 37.5 mg of tramadol, and in my practice I've found that patients generally need the larger dose.

Next page: Parkinson's drugs, hypertension drugs, and sleeping aids »

6. Parkinson's drugs (Dopamine agonists)

Why they are prescribed: These drugs are used to treat Parkinson's disease, certain pituitary tumors and, increasingly, restless legs syndrome (RLS).
Examples: Apomorphine (Apokyn), pramipexole (Mirapex) and ropinirole (Requip).

How they can cause memory loss: These meds activate signaling pathways for dopamine, a chemical messenger involved in many brain functions, including motivation, the experience of pleasure, fine motor control, learning and memory. As a result, major side effects can include memory loss, confusion, delusions, hallucinations, drowsiness and compulsive behaviors such as overeating and gambling.
Alternatives: If you are being treated for RLS, ask your doctor or pharmacist whether one of your prescription or over-the-counter medications may be the trigger. Potential culprits include many antinausea and antiseizure medications, antipsychotic drugs with tranquilizing effects, some antidepressants, and some cold and allergy medications. In this case, your RLS — and memory problems — could potentially be resolved by simply replacing the offending medication with another drug.

7. Hypertension drugs (Beta-blockers)

Why they are prescribed: Beta-blockers slow the heart rate and lower blood pressure and typically are prescribed for high blood pressure, congestive heart failure and abnormal heart rhythms. They're also used to treat chest pain (angina), migraines, tremors and, in eyedrop form, certain types of glaucoma.
Examples: Atenolol (Tenormin), carvedilol (Coreg), metoprolol (Lopressor, Toprol), propranolol (Inderal), sotalol (Betapace), timolol (Timoptic) and some other drugs whose chemical names end with "-olol."
How they can cause memory loss: Beta-blockers are thought to cause memory problems by interfering with ("blocking") the action of key chemical messengers in the brain, including norepinephrine and epinephrine.
Alternatives: For older people, benzothiazepine calcium channel blockers, another type of blood pressure medication, are often safer and more effective than beta-blockers. If the beta-blocker is being used to treat glaucoma, I recommend talking with your health care professional about potentially using a carbonic anhydrase inhibitor, such as dorzolamide (Trusopt), instead.

8. Sleeping aids (Nonbenzodiazepine sedative-hypnotics)

Why they are prescribed: Sometimes called the "Z" drugs, these medications are used to treat insomnia and other sleep problems. They also are prescribed for mild anxiety.
Examples: Eszopiclone (Lunesta), zaleplon (Sonata) and zolpidem (Ambien).
How they can cause memory loss: Although these are molecularly distinct from benzodiazepines (see No. 1 above), they act on many of the same brain pathways and chemical messengers, producing similar side effects and problems with addiction and withdrawal.
The "Z" drugs also can cause amnesia and sometimes trigger dangerous or strange behaviors, such as cooking a meal or driving a car — with no recollection of the event upon awakening.
Alternatives: There are alternative drug and nondrug treatments for insomnia and anxiety, so talk with your health care professional about options. Melatonin, in doses from 3 to 10 mg before bedtime, for instance, sometimes helps to reestablish healthy sleep patterns.
Before stopping or reducing the dosage of these sleeping aids, be sure to consult your health care professional. Sudden withdrawal can cause serious side effects, so a health professional should always monitor the process.

9. Incontinence drugs (Anticholinergics)

Why they are prescribed: These medications are used to relieve symptoms of overactive bladder and reduce episodes of urge incontinence, an urge to urinate so sudden and strong that you often can't get to a bathroom in time.
Examples: Darifenacin (Enablex), oxybutynin (Ditropan XL, Gelnique, Oxytrol), solifenacin (Vesicare), tolterodine (Detrol) and trospium (Sanctura). Another oxybutynin product, Oxytrol for Women, is sold over the counter.

How they can cause memory loss: These drugs block the action of acetylcholine, a chemical messenger that mediates all sorts of functions in the body. In the bladder, anticholinergics prevent involuntary contractions of the muscles that control urine flow. In the brain, they inhibit activity in the memory and learning centers. The risk of memory loss is heightened when the drugs are taken for more than a short time or used with other anticholinergic drugs.
A 2006 study of oxybutynin ER, for example, found its effect on memory to be comparable to about 10 years of cognitive aging. ("In other words," as the study's lead author put it, "we transformed these people from functioning like 67-year-olds to 77-year-olds.")
Older people are particularly vulnerable to the other adverse effects of anticholinergic drugs, including constipation (which, in turn, can cause urinary incontinence), blurred vision, dizziness, anxiety, depression and hallucinations.
Alternatives: As a first step, it's important to make sure that you have been properly diagnosed. Check with your doctor or other health professional to see if your urinary incontinence symptoms might stem from another condition (such as a bladder infection or another form of incontinence) or a medication (such as a blood pressure drug, diuretic or muscle relaxant).
Once these are ruled out, I'd recommend trying some simple lifestyle changes, such as cutting back on caffeinated and alcoholic beverages, drinking less before bedtime, and doing Kegel exercises to strengthen the pelvic muscles that help control urination.
If these approaches don't work out, consider trying adult diapers, pads or panty liners, which can be purchased just about anywhere. They can be worn comfortably (and invisibly) under everyday clothing and virtually eliminate the risk of embarrassing accidents. In my experience, many patients are reluctant to try this approach, but once over the initial hurdle, come to prefer it for security and peace of mind.
Correction: An earlier version of this article mistakenly implied that mirabegron (Myrbetriq), which the FDA approved last year for the treatment of overactive bladder, is an anticholinergic drug; in fact, it is in a new class of medications called beta-3 adrenergic agonists and is not expected  to cause memory loss seen with anticholinergic medications. There currently are no data describing the effect of Myrbetriq on cognition.

10. Antihistamines (First-generation)

Why they are prescribed: These medications are used to relieve or prevent allergy symptoms or those of the common cold. Some antihistamines are also used to prevent motion sickness, nausea, vomiting and dizziness, and to treat anxiety or insomnia.
Examples: Brompheniramine (Dimetane), carbinoxamine (Clistin), chlorpheniramine (Chlor-Trimeton), clemastine (Tavist), diphenhydramine (Benadryl) and hydroxyzine (Vistaril).
How they can cause memory loss: These medications (prescription and over-the-counter) inhibit the action of acetylcholine, a chemical messenger that mediates a wide range of functions in the body. In the brain, they inhibit activity in the memory and learning centers, which can lead to memory loss.
Alternatives: Newer-generation antihistamines such as loratadine (Claritin) and cetirizine (Zyrtec) are better tolerated by older patients and do not present the same risks to memory and cognition.
Ask the Pharmacist is written by Armon B. Neel Jr., PharmD, CGP, in collaboration with journalist Bill Hogan. They are coauthors of Are Your Prescriptions Killing You? (Atria Books).