Health Research Report
WHITE PAPER /ROUGH COPY
168th Issue Date 16 NOV 2013
Compiled By Ralph Turchiano
In this Issue:
1. The most commonly prescribed treatment for Colds and Sore Throats offers no benefit and may actually make the illness worse
2. Japanese super food prevents flu infection
3. Study links intestinal bacteria to rheumatoid arthritis
4. New research shows clear association between ACE inhibitors and acute kidney injury
5. Scientists at the University of Granada have disproved the old idea that chocolate is fattening, in a study reported this week in Nutrition
6. Vitamin C could ease muscle fatigue in chronic obstructive pulmonary disease patients
7. Allergic to Gummy Bears? Be Cautious Getting the Flu Shot
8. Oral allergy syndrome and high blood pressure medications can create lethal cocktail
9. Acid levels in the diet could have profound effects on kidney health
10. How zinc starves lethal bacteria to stop infection
11. Study is the first to show higher dietary acid load increases risk of diabetes
12. Scientists report human dietary supplement cures lab animals infected with human intestinal parasite
13. Inflammatory skin damage in mice blocked by bleach solution, Stanford study finds
14. Can Certain Herbs Stave Off Alzheimer’s Disease?
The most commonly prescribed treatment for Colds and Sore Throats offers no benefit and may actually make the illness worse
Questions have been raised about the advice given to patients with a cold and sore throat, in research published in the British Medical Journal.
A study carried out by the University of Southampton showed that compared with paracetamol, ibuprofen or a combination of both ibuprofen and paracetamol provide no advantage for patients overall with respiratory tract infections (otherwise known as colds or sore throats).
Additionally steam inhalation, another common treatment method, has no clear benefit and around 2 per cent of people get mild scalding but not bad enough to see a doctor.
Professor Paul Little, who led the study, comments: “Paracetamol, ibuprofen or a combination of both are the most common courses of treatment for respiratory tract infections. Clinicians should probably not advise patients to use steam inhalation in daily practice as it does not provide symptomatic benefit for acute respiratory infections and a few individuals are likely to experience mild thermal injury. Similarly, routinely advising ibuprofen or ibuprofen and paracetamol together than just paracetamol is also not likely to be effective. However our research has shown that ibuprofen is likely to help children, and those with chest infections.”
The research also showed that patients were more likely to come back within a month with worsening symptoms or new symptoms if they were prescribed with ibuprofen or ibuprofen with paracetamol. Between 50 per cent and 70 per cent of participants in the study who were prescribed ibuprofen or ibuprofen with paracetamol came back.
Professor Little admitted this was a surprising result and suggests the treatment may contribute to the progression of the illness. He adds: “This may have something to do with the fact the ibuprofen is an anti-inflammatory. It is possible that the drug is interfering with an important part of the immune response and leads to prolonged symptoms or the progression of symptoms in some individuals. Although we have to be a bit cautious since these were surprise findings, for the moment I would personally not advise most patients to use ibuprofen for symptom control for coughs colds and sore throat.”
The randomised control trial recruited 899 patients who presented at their GP with respiratory tract infection symptoms. They received different treatment types; paracetamol, ibuprofen or a combination of both. Participants were then told to either take it as needed or at regular intervals (four times a day) and some were also told to take steam inhalation.
The study was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme.
Japanese superfood prevents flu infection
Scientists have discovered that bacteria found in a traditional Japanese pickle can prevent flu. Could this be the next superfood?
The research, which assesses the immune-boosting powers of Lactobacillus brevis from Suguki – a pickled turnip, popular in Japan – in mice that have been exposed to a flu virus, is published today (06 November) in the SfAM journal, Letters in Applied Microbiology.
Lead researcher, Ms Naoko Waki of KAGOME CO., LTD. in Japan said: “Our results show that when a particular strain of Lactobacillus brevis is eaten by mice, it has protective effects against influenza virus infection.”
Suguki enthusiasts have often cited its protective powers but it is not known yet whether the same effects will be seen in humans. Human clinical trials using a probiotic drink containing Lactobacillus brevis KB290 bacteria are underway and scientists are hopeful that, given a suitable quantity of bacteria, foods containing them may turn out to be the next superfood.
What it is about the bacteria that gives them this amazing property is not known, but it is remarkably tolerant to stomach juices, which are too acidic for many bacteria. This is largely due to a protective layer of sugars called exopolysaccharides.
“We know that exopolysaccharides have immune boosting effects in other similar bacteria, so we wonder if the exopolysaccharides of KB290 are responsible for the effects we see,” said Ms Waki. Further studies will be undertaken to investigate this.
The effect of the bacteria is to increase the production of immune system molecules in the body – IFN-α and flu-specific antibodies – and to enhance activity to eradicate virus infected cells. In this study these effects were sufficient to prevent infection by the H1N1 flu and the scientists think that there could also be protection against other viral infections, including the deadly H7N9 flu, which has recently emerged in China.
Study links intestinal bacteria to rheumatoid arthritis
Findings suggest bacterial disturbances in the gut may play a role in autoimmune attacks on the joints, point the way to novel treatments and diagnostics
Researchers have linked a species of intestinal bacteria known as Prevotella copri to the onset of rheumatoid arthritis, the first demonstration in humans that the chronic inflammatory joint disease may be mediated in part by specific intestinal bacteria. The new findings by laboratory scientists and clinical researchers in rheumatology at NYU School of Medicine add to the growing evidence that the trillions of microbes in our body play an important role in regulating our health.
Using sophisticated DNA analysis to compare gut bacteria from fecal samples of patients with rheumatoid arthritis and healthy individuals, the researchers found that P. copri was more abundant in patients newly diagnosed with rheumatoid arthritis than in healthy individuals or patients with chronic, treated rheumatoid arthritis. Moreover, the overgrowth of P. copri was associated with fewer beneficial gut bacteria belonging to the genera Bacteroides.
“Studies in rodent models have clearly shown that the intestinal microbiota contribute significantly to the causation of systemic autoimmune diseases,” says Dan R. Littman, MD, PhD, the Helen L. and Martin S. Kimmel Professor of Pathology and Microbiology and a Howard Hughes Medical Institute investigator.
“Our own results in mouse studies encouraged us to take a closer look at patients with rheumatoid arthritis, and we found this remarkable and surprising association,” says Dr. Littman, whose basic science laboratory at NYU School of Medicine’s Skirball Institute of Biomolecular Medicine collaborated with clinical investigators led by Steven Abramson, MD, senior vice president and vice dean for education, faculty, and academic affairs; the Frederick H. King Professor of Internal Medicine; chair of the Department of Medicine; and professor of medicine and pathology at NYU School of Medicine.
“At this stage, however, we cannot conclude that there is a causal link between the abundance of P. copri and the onset of rheumatoid arthritis,” Dr. Littman says. “We are developing new tools that will hopefully allow us to ask if this is indeed the case.”
The new findings, reported today in the open-access journal eLife, were inspired by previous research in Dr. Littman’s laboratory, collaborating with Harvard Medical School investigators, using mice genetically predisposed to rheumatoid arthritis, which resist the disease if kept in sterile environments, but show signs of joint inflammation when exposed to otherwise benign gut bacteria known as segmented filamentous bacteria.
Rheumatoid arthritis, an autoimmune disease that attacks joint tissue and causes painful, often debilitating stiffness and swelling, affects 1.3 million Americans. It strikes twice as many women as men and its cause remains unknown although genetic and environmental factors are thought to play a role.
The human gut is home to hundreds of species of beneficial bacteria, including P. copri, which ferment undigested carbohydrates to fuel the body and keep harmful bacteria in check. The immune system, primed to attack foreign microbes, possesses the extraordinary ability to distinguish benign or beneficial bacteria from pathogenic bacteria. This ability may be compromised, however, when the gut’s microbial ecosystem is thrown off balance.
“Expansion of P. copri in the intestinal microbiota exacerbates colonic inflammation in mouse models and may offer insight into the systemic autoimmune response seen in rheumatoid arthritis,” says Randy S. Longman, MD, PhD, a post-doctoral fellow in Dr. Littman’s laboratory and a gastroenterologist at Weill-Cornell, and an author on the new study. Exactly how this expansion relates to disease remains unclear even in animal models, he says.
Why P. copri growth seems to take off in newly diagnosed patients with rheumatoid arthritis is also unclear, the researchers say. Both environmental influences, such as diet and genetic factors can shift bacterial populations within the gut, which may set off a systemic autoimmune attack. Adding to the mystery, P. copri extracted from stool samples of newly diagnosed patients appears genetically distinct from P. copri found in healthy individuals, the researchers found.
To determine if particular bacterial species correlate with rheumatoid arthritis, the researchers sequenced the so-called 16S gene on 44 fecal DNA samples from newly diagnosed patients with rheumatoid arthritis prior to immune-suppressive treatment; 26 samples from patients with chronic, treated rheumatoid arthritis; 16 samples from patients with psoriatic arthritis (characterized by red, flaky skin in conjunction with joint inflammation); and 28 samples from healthy individuals.
Seventy-five percent of stool samples from patients newly diagnosed with rheumatoid arthritis carried P. copri compared to 21.4% of samples from healthy individuals; 11.5% from chronic, treated patients; and 37.5% from patients with psoriatic arthritis.
Rheumatoid arthritis is treated with an assortment of medications, including antibiotics, anti-inflammatory drugs like steroids, and immunosuppressive therapies that tame immune reactions. Little is understood about how these medications affect gut bacteria. This latest research offers an important clue, showing that treated patients with chronic rheumatoid arthritis carry smaller populations of P. copri. “It could be that certain treatments help stabilize the balance of bacteria in the gut,” says Jose U. Scher, MD, director of the Microbiome Center for Rheumatology and Autoimmunity at NYU Langone Medical Center’s Hospital for Joint Diseases, and an author on the new study. “Or it could be that certain gut bacteria favor inflammation.”
The researchers plan to validate their results in regions beyond New York, since gut flora can vary across geographical regions, and investigate whether the gut flora can be used as a biological marker to guide treatment. “We want to know if people with certain populations of gut bacteria respond better to certain treatment than others,” says Dr. Scher. Finally, they hope to study people before they develop rheumatoid arthritis to see whether overgrowth of P. copri is a cause or result of autoimmune attacks.
New research shows clear association between ACE inhibitors and acute kidney injury
These and similar drugs are the second most prescribed on the NHS
Cambridge scientists have found an association between ACE inhibitors (and similar drugs) and acute kidney injury – a sudden deterioration in kidney function. The research is published today, 06 November, in the journal PLOS ONE.
ACE inhibitors and related drugs known as angiotensin receptor antagonists (ARAs or ‘sartans’) are the second most frequently prescribed medicines in UK clinical practice, and are used to treat common conditions such as high blood pressure, heart disease and kidney problems, especially in people with diabetes. Although concerns about a link between these drugs and kidney function have been raised in the past, the size of the problem had previously been unknown.
The researchers therefore examined the issue using data from the whole of England. They compared the admission rates for acute kidney injury to English hospitals with the prescribing rates of ACE inhibitors and ARAs. From 2007/8 to 2010/11, there was a 52 per cent increase in acute kidney injury admissions. During this same period of time, there was an increase in the number of prescriptions for ACE inhibitors and ARAs issued by GP surgeries by 16 per cent.
The results show a clear association between the increase in prescriptions and the increase in hospital admissions. The researchers estimate that 1636 hospital admissions with acute kidney injury – which has a mortality rate in the UK of around 25-30 per cent of patients – could potentially have been avoided if the prescribing rate had remained at the 2007/8 levels. They estimate that one in seven cases of acute kidney injury could be due to increased prescriptions for these drugs.
This is the first time that a study has been able to assess the extent to which these medications are linked to acute kidney injury. However, the researchers emphasise that we cannot assume that the medication was a direct cause of the acute kidney injury in this study, and no one should stop taking these medications unless advised by their doctor to do so.
Dr Rupert Payne, senior author of the study from the University of Cambridge’s Institute of Public Health, said: “There has been lots of anecdotal evidence suggesting these drugs may be a contributory factor in patients developing acute kidney injury, and this work gives us an opportunity to estimate the size of the problem, as well as making clinicians and patients more aware of the importance of using these drugs in accordance with current clinical guidelines.
“As both a GP and clinical pharmacologist, it also highlights to me the importance of improving our understanding of the risks and benefits of drugs more generally in the real world of clinical practice, away from the artificial setting of clinical trials.”
Dr Laurie Tomlinson, co-author of the study, added: “As a kidney doctor I have looked after many patients with acute kidney injury who were taking these medications prior to becoming unwell and have often worried that the drugs were doing more harm than good. These results are the first to estimate to what extent these drugs may be contributing to the growing incidence of acute kidney injury. Therefore, they represent the first step of research needed to better define when they can be prescribed safely, which should reduce the growing burden of acute kidney injury and save NHS costs and ultimately lives.”
The researchers will next use large primary care databases to examine the association between the drugs and acute kidney injury for individual patients and, in particular, the role of other medication, patient factors (such as the existence of chronic kidney disease) and infections in causing acute kidney injury.
Scientists at the University of Granada have disproved the old idea that chocolate is fattening, in a study reported this week in Nutrition
Higher chocolate consumption associated with lower levels of total fat—fat deposits all over the body—and central—abdominal—fat, independently of whether or not subjects are physically active, and of their diet
The study—possibly the most comprehensive to date—included 1458 European adolescents aged between 12 and 17 years
University of Granada researchers from the Faculty of Medicine and the Faculty of Physical Activity and Sports Sciences have scientifically disproven the old belief that eating chocolate is fattening. In an article published this week in the journal Nutrition, the authors have shown that higher consumption of chocolate is associated with lower levels of total fat (fat deposited all over the body) and central fat (abdominal), independently of whether or not the individual participates in regular physical activity and of diet, among other factors.
The researchers determined whether greater chocolate consumption associated with higher body mass index and other indicators of total and central body fat in adolescents participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study. This project, financed by the European Union, studies eating habits and lifestyle in young people in 9 European countries, including Spain.
Independent of diet and physical activity
The study involved 1458 adolescents aged between 12 and 17 years and results showed that a higher level of chocolate consumption associated with lower levels of total and central fat when these were estimated through body mass index, body fat percentage—measured by both skinfolds and bioelectrical impedance analysis—and waist circumference. These results were independent of the participant’s sex, age, sexual maturation, total energy intake, intake of saturated fats, fruit and vegetables, consumption of tea and coffee, and physical activity.
As the principle author Magdalena Cuenca-García explains, although chocolate is considered a high energy content food—it is rich in sugars and saturated fats—“recent studies in adults suggest chocolate consumption is associated with a lower risk of cardiometabolic disorders”.
In fact, chocolate is rich in flavonoids—especially catechins—which have many healthy properties: “they have important antioxidant, antithrombotic, anti-inflammatory and antihypertensive effects and can help prevent ischemic heart disease”.
Recently, another cross-sectional study in adults conducted by University of California researchers found that more frequent chocolate consumption also associated with a lower body mass index. What’s more, these results were confirmed in a longitudinal study in women who followed a catechin-rich diet.
The effect could be partly due to the influence of catechins on cortisol production and on insulin sensitivity, both of which are related with overweight and obesity.
Calorie impact is not the only thing that matters
The University of Granada researchers have sought to go further and analyse the effect of chocolate consumption at a critical age like adolescence by also controlling other factors that could influence the accumulation of fat. The research, which is both novel and, perhaps, the largest and best-controlled study to date, is the first to focus on the adolescent population. It includes a large number of body measures, objective measurement of physical activity, detailed dietary recall with 2 non-consecutive 24-hour registers using image-based software, and controls for the possible effect of a group of key variables.
In Nutrition, the authors stress that the biological impact of foods should not be evaluated solely in terms of calories. “The most recent epidemiologic research focuses on studying the relation between specific foods—both for their calorie content and for their components—and the risk factors for developing chronic illnesses, including overweight and obesity”.
Despite their results, the authors insist that chocolate consumption should always be moderate. “In moderate quantities, chocolate can be good for you, as our study has shown. But, undoubtedly, excessive consumption is prejudicial. As they say: you can have too much of a good thing”.
The University of Granada researchers stress that their findings “are also important from a clinical perspective since they contribute to our understanding of the factors underlying the control and maintenance of optimal weight”.
Vitamin C could ease muscle fatigue in chronic obstructive pulmonary disease patients
Bethesda, Md. (Nov. 7, 2013)—Chronic obstructive pulmonary disease—a health problem in which the lungs lose their inherent springiness, making it progressively harder to breathe—can have a dramatic effect on the ability to exercise and even perform simple activities of daily life because of the disease’s fallout effects on skeletal muscles. Several factors have been implicated in these muscle problems. These include loss of fitness from inactivity, problems with the part of cells that convert fuel to energy caused by the COPD itself, and oxidative stress, a phenomenon in which cells and tissues become damaged by unstable molecules called free radicals that harm other molecules in domino-like chain reactions. Some research suggests that easing oxidative stress could improve skeletal muscle function.
To test this idea, researchers led by Matthew J. Rossman of the George E. Whalen VA Medical Center and the University of Utah gave COPD patients intravenous (IV) infusions of vitamin C, a powerful antioxidant that can combat oxidative stress, or saline as a placebo before the patients performed knee extension exercises and underwent neuromuscular function tests. Their findings show that IV infusions of vitamin C can improve skeletal muscle fatigue in COPD patients, further implicating the role of oxidative stress in the skeletal muscle problems that accompany this disease.
The article is entitled “Ascorbate Infusion Increases Skeletal Muscle Fatigue Resistance in Patients with Chronic Obstructive Pulmonary Disease“. It appears in the online edition of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, published by the American Physiological Society.
The researchers worked with 10 COPD patients. Each patient performed a set of knee extension exercises, receiving either an IV infusion of saline or an IV infusion of vitamin C before the set, but both the study volunteers and the researchers monitoring the exercises didn’t know which infusion the volunteers received. Two to three days later, the volunteers performed a second set of knee exercises after receiving the other type of infusion. Before and after they performed these exercises, the study subjects had blood drawn to test for antioxidant levels. Immediately after the exercises, the researchers measured a variety of other factors, including the volunteers’ breathing and heart rate, blood pressure, feelings of exertion of breathlessness, and blood flow.
The researchers found that during exercises, patients had significantly less muscle fatigue after receiving vitamin C and breathed better and slower. After vitamin C infusions, the volunteers also had significantly higher blood antioxidant activity than when they received only saline. Additionally, vitamin C infusions lowered their resting blood pressure and blood flow.
Importance of the Findings
These findings suggest that IV infusions of antioxidants, such as vitamin C, can curb the skeletal muscle fatigue that plagues COPD patients. They also provide further evidence that oxidative stress plays a critical role in the skeletal muscle dysfunction that many COPD patients experience. They suggest that antioxidants could eventually be used as a treatment for these problems.
“Targeting oxidative stress with some form of antioxidant therapy in a clinical setting may represent an important therapeutic avenue for patients with COPD,” they write.
Allergic to Gummy Bears? Be Cautious Getting the Flu Shot
Those with gelatin allergy can have reaction from flu vaccinations
BALTIMORE, MD. (November 8, 2013) – Do marshmallows make your tongue swell? Gummy bears make you itchy? If you’ve answered yes and are allergic to gelatin, you will want to take some precautions when getting the flu shot. While the vaccine is recommended for those six months of age and older, a case report being presented at the American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting notes that individuals with a gelatin allergy can have a mild to severe reaction from the shot.
“Gelatin is used in the flu shot, as well as other vaccines, as a stabilizer,” said Stephanie Albin, MD, an allergist and ACAAI member. “Because it is found in the vaccine, those with a known allergy to gelatin can experience allergic reactions, such as hives, sneezing and difficulty breathing.”
There is a misconception about allergies and the flu shot, with many believing those with an egg allergy should not receive the vaccination. But last month, ACAAI published an update that found even those with a severe egg allergy can receive the vaccine without special precautions.
“Gelatin reactions can cause hives, swelling, itchiness, shortness of breath and a severe life-threatening reaction known as anaphylaxis,” explained Dr. Albin. “Because of this, precautions should be taken, such as having a board-certified allergist administer the vaccine in a person with known gelatin allergy in case a reaction occurs.”
Gelatin can contain proteins derived from cow, pig or fish. Gelatin can be found in a variety of foods and pharmaceuticals, including gummy vitamins, marshmallows and candy.
“Gelatin allergy is very rare,” said allergist Richard Weber, M.D., ACAAI president. “Many food intolerances can be mistaken as allergies. Those who believe they might have an allergy should be tested and diagnosed by an allergist before taking extreme avoidance measures or skipping vaccinations. The flu shot is an important vaccine and can even be life-saving for individuals that are at an increased risk for severe side effects associated with the flu.”
The Centers for Disease Control and Prevention (CDC) recommends receiving an annual flu shot, especially for high risk age groups as children and the elderly. The vaccination can be given either as a shot or a nasal spray, both of which can contain gelatin.
For more information about allergies and to locate an allergist in your area, visit AllergyandAsthmaRelief.org. The ACAAI Annual Meeting is being held Nov. 7-11 at the Baltimore Convention Center in Baltimore. For more news and research being presented at the meeting, follow the conversation on Twitter #ACAAI.
Oral allergy syndrome and high blood pressure medications can create lethal cocktail
Some allergy suffers with hypertension may be at increased risk for severe reaction
BALTIMORE, MD. (November 8, 2013) – Oral allergy syndrome sufferers that take high blood pressure medications may experience extreme facial swelling and difficulty breathing the next time they bite into a juicy apple. When patients with oral allergy syndrome take angiotensin-converting enzyme (ACE) inhibitors for hypertension and congestive heart failure, they are at an increased risk for a life-threatening allergic reaction known as anaphylaxis, according to new research.
The case studies, being presented at the Annual Scientific Meeting of the American College of Allergy, Asthma and Immunology (ACAAI), found use of ACE inhibitors can cause what is known as a “priming effect” in oral allergy syndrome sufferers.
“When a sufferer’s allergies are primed and they come in contact with a particular allergen, they experience a more severe than normal reaction,” said allergist Denisa Ferastraoaru, MD, ACAAI member and lead study author. “Symptoms can include extreme facial swelling (angioedema) and difficulty breathing, which can lead to death in some cases.”
Hay fever sufferers that experience an itchy mouth or scratchy throat after eating certain raw fruits or vegetables and some tree nuts, may have oral allergy syndrome. It is also known as pollen-food syndrome, since it is caused by cross-reacting allergens found in both pollen and raw produce.
“Sufferers can often mistake oral allergy syndrome symptoms for food allergy,” said allergist David Rosenstreich, MD, ACAAI fellow and study author. “But it isn’t a food allergy, and often patients can eat that food when it is cooked. For example, an individual may have a reaction to a raw apple but not to apples baked in a pie.”
When allergists advised patients to avoid raw produce and switched from ACE inhibitors to angiotensin II receptor blocker (ARB) therapy, no further oral allergy symptoms occurred.
Not everyone with a pollen allergy will experience oral allergy syndrome when eating raw produce and tree nuts. However, the syndrome is commonly associated with these allergens:
- Birch Pollen: apple, almond, carrot, celery, cherry, hazelnut, kiwi, peach, pear, plum
- Grass Pollen: celery, melons, oranges, peaches, tomato
- Ragweed Pollen: banana, cucumber, melons, sunflower seeds, zucchini
While oral allergy symptoms are typically mild, including mouth and throat discomfort, swelling and itching, it is important sufferers discuss these symptoms with their allergist because anaphylaxis can sometimes occur.
Acid levels in the diet could have profound effects on kidney health
Atlanta, GA (November 9, 2013)—Three new studies suggest that controlling dietary acid intake could help improve kidney health. Results of these studies will be presented at ASN Kidney Week 2013 November 5-10 at the Georgia World Congress Center in Atlanta, GA.
A diet rich in wheat flour and animal protein produces an acidic environment in the body that worsens with age as kidney function declines. This acid load can be detrimental to a variety of tissues and processes. Research suggests that consuming more fruits and vegetables—which are highly alkaline—may help counteract these effects.
In a new study, a team led by Nimrit Goraya, MD (Texas A&M College of Medicine) investigated whether consuming fruits and vegetables can protect the kidney health of individuals with hypertensive nephropathy, a condition in which damage to the kidneys occurs due to high blood pressure. In this study, 23 hypertensive patients received extra dietary fruits and vegetables, 23 patients received an oral alkaline medication, and 25 patients received nothing. One year later, kidney injury progressed in patients who received no intervention, but kidney health was preserved in those receiving fruits and vegetables or oral alkaline medication.
In another study, Eiichiro Kanda, MD, PhD (Tokyo Kyosai Hospital) and his colleagues investigated the role of dietary acid levels in chronic kidney disease (CKD) progression. The retrospective study analyzed data from 249 CKD patients in Japan. High acid levels were linked with accelerated kidney function decline, and patients with elevated acid levels had an increased risk of CKD progression compared with patients with low acid levels. The findings suggest that monitoring and control of dietary acid levels are necessary for the prevention of CKD progression.
Another study led by Deidra Crews, MD, FASN (Johns Hopkins University School of Medicine) looked to see whether the effect of dietary acid on risk of kidney failure differed by race in a group of 159 non-Hispanic black and 760 non-Hispanic white CKD patients who had an annual household income below 300% of the federal poverty guideline. Participants were taking part in the 1999-2004 National Health and Nutrition Examination Survey. Overall, 12.4% of participants (38.3% whites and 61.7% blacks) developed kidney failure during an average of 6.4 years of follow up. Blacks had higher acid levels than whites. They also had a 3-fold higher risk of developing kidney failure compared with whites after adjusting for factors such as age, sex, and caloric intake. Increased acid levels were more strongly associated with kidney failure among blacks than among whites. The findings indicate that among CKD patients with low socioeconomic status, the detrimental effect of high dietary acid levels on progression to kidney failure appears to be greater for blacks than for whites.
- In patients with hypertensive nephropathy, kidney health was preserved in those consuming extra fruits and vegetables, which are highly alkaline.
- In patients with chronic kidney disease, those with high dietary acid levels experienced accelerated kidney function decline.
- In chronic kidney disease patients with low socioeconomic status, the detrimental effect of high dietary acid levels on progression to kidney failure was greater for blacks than for whites.
“Fruits and Vegetables or Oral NaHCO3 Prevent Progression of Kidney Injury in Stage 1 CKD Due to Hypertensive Nephropathy.” (Abstract FR-PO816)
“Dietary Acid Load Is Associated with Chronic Kidney Disease Progression in Elderly Patients.” (Abstract TH-PO243)
How zinc starves lethal bacteria to stop infection
Australian researchers have found that zinc can ‘starve’ one of the world’s most deadly bacteria by preventing its uptake of an essential metal.
The finding, by infectious disease researchers at the University of Adelaide and The University of Queensland, opens the way for further work to design antibacterial agents in the fight against Streptococcus pneumoniae.
Streptococcus pneumoniae is responsible for more than one million deaths a year, killing children, the elderly and other vulnerable people by causing pneumonia, meningitis, and other serious infectious diseases.
Published today in the journal Nature Chemical Biology, the researchers describe how zinc “jams shut” a protein transporter in the bacteria so that it cannot take up manganese, an essential metal that Streptococcus pneumoniae needs to be able to invade and cause disease in humans.
“It’s long been known that zinc plays an important role in the body’s ability to protect against bacterial infection, but this is the first time anyone has been able to show how zinc actually blocks an essential pathway causing the bacteria to starve,” says project leader Dr Christopher McDevitt, Research Fellow in the University of Adelaide’s Research Centre for Infectious Diseases.
“This work spans fields from chemistry and biochemistry to microbiology and immunology to see, at an atomic level of detail, how this transport protein is responsible for keeping the bacteria alive by scavenging one essential metal (manganese), but at the same time also makes the bacteria vulnerable to being killed by another metal (zinc),” says Professor Bostjan Kobe, Professor of Structural Biology at The University of Queensland.
The study reveals that the bacterial transporter (PsaBCA) uses a ‘spring-hammer’ mechanism to bind the metals. The difference in size between the two metals, manganese and zinc, causes the transporter to bind them in different ways. The smaller size of zinc means that when it binds to the transporter, the mechanism closes too tightly around the zinc, causing an essential spring in the protein to unwind too far, jamming it shut and blocking the transporter from being able to take up manganese.
“Without manganese, these bacteria can easily be cleared by the immune system,” says Dr McDevitt. “For the first time, we understand how these types of transporters function. With this new information we can start to design the next generation of antibacterial agents to target and block these essential transporters.”
Study is the first to show higher dietary acid load increases risk of diabetes
A study of more than 60 000 women has shown that higher overall acidity of the diet, regardless of the individual foods making up that diet, increases the risk of type 2 diabetes. The study, the first large prospective study to demonstrate these findings, is published in Diabetologia, the journal of the European Association for the Study of Diabetes (EASD), and is by Dr Guy Fagherazzi and Dr Françoise Clavel-Chapelon, Center for Research in Epidemiology and Population Health, INSERM, Paris, France, and colleagues.
A western diet rich in animal products and other acidogenic foods can induce an acid load that is not compensated for by fruit and vegetables; this can cause chronic metabolic acidosis and lead to metabolic complications. Most importantly from a blood-sugar control perspective, increasing acidosis can reduce the ability of insulin to bind at appropriate receptors in the body, and reduce insulin sensitivity. With this in mind, the authors decided to analyse whether increased acidosis caused by dietary acid loads increased the risk of type 2 diabetes.
A total of 66,485 women from the E3N study (the French Centre of the European Prospective Investigation into Cancer and Nutrition, a well-known ongoing epidemiological study) were followed for new diabetes cases over 14 years. Their dietary acid load was calculated from their potential renal acid load (PRAL) and their net endogenous acid production (NEAP) scores, both standard techniques for assessing dietary acid consumption from nutrient intake.
During follow-up, 1,372 new cases of incident type 2 diabetes occurred. In the overall population, those in the top 25% (quartile) for PRAL had a 56% increased risk of developing type 2 diabetes compared with the bottom quartile. Women of normal weight (BMI of 25 and under) had the highest increased risk (96% for top quartile versus bottom) while overweight women (BMI 25 and over) had only a 28% increased risk (top quartile versus bottom). NEAP scores showed a similar increased risk for higher acid load.
The authors say: “A diet rich in animal protein may favour net acid intake, while most fruits and vegetables form alkaline precursors that neutralise the acidity. Contrary to what is generally believed, most fruits such as peaches, apples, pears, bananas and even lemons and oranges actually reduce dietary acid load once the body has processed them. In our study, the fact that the association between both PRAL and NEAP scores and the risk of incident type 2 diabetes persisted after adjustment for dietary patterns, meat consumption and intake of fruit, vegetables, coffee and sweetened beverages suggests that dietary acids may play a specific role in promoting the development of type 2 diabetes, irrespective of the foods or drinks that provide the acidic or alkaline components.”
They conclude: “We have demonstrated for the first time in a large prospective study that dietary acid load was positively associated with type 2 diabetes risk, independently of other known risk factors for diabetes. Our results need to be validated in other populations, and may lead to promotion of diets with a low acid load for the prevention of diabetes. Further research is required on the underlying mechanisms.”
Scientists report human dietary supplement cures lab animals infected with human intestinal parasite
Preliminary success using ‘probiotics’ against hookworms raises hope for treating afflictions that burden 1.5 billion and cause stunting, development delays in children
WASHINGTON, D.C. (November 15, 2013) — Laboratory animals fed a modified version of a common human dietary supplement were completely cured of intestinal worms that belong to a family of parasites that currently infect 1.5 billion people, or almost one quarter of the world’s population, according to new research presented today at the annual meeting of the American Society of Tropical Medicine and Hygiene (ASTMH).
“We need to replicate the results in other animals and also in humans, but this is an important development in our effort to find a safe, affordable and effective way to confront a major global health problem,” said Raffi Aroian, PhD, principal investigator of a team of scientists at the University of California, San Diego who are seeking new treatments for a variety of parasitic worms known as “soil-transmitted helminths” or STHs.
While rarely fatal, STHs and other intestinal worms are leading contributors to disease in school-age children in low-income countries and are viewed by many experts as among the most burdensome of the world’s “neglected tropical diseases” or NTDs.
The study conducted by Aroian’s team focused on hookworms, common STHs that are found in soil that has been contaminated with human feces. Hookworms can linger in the intestines for years, where they feed on blood and tissue, robbing their hosts of iron and protein and interfering with absorption of critical nutrients. They frequently cause stunting and cognitive delays in infected children. They also can have long-term effects on educational achievement and productivity.
Currently, the only drugs available to treat hookworms in humans were originally developed to combat parasites that infect farm animals. Aroian said they are only partially effective against the range of intestinal parasites that infect humans. There is also evidence of reinfections occurring rapidly after treatment and low levels of efficacy in some places.
At the ASTMH meeting, Aroian’s colleague Yan Hu, PhD reported findings from a study in which hamsters were deliberately infected with hookworms. The hamsters were later divided into two groups. One group received a common strain of the bacteria Bacillus subtilis, which is often marketed as a “probiotic”—a dietary supplement consumed as a pill or added to food that is intended to promote digestive health. It also is the key ingredient in a popular Japanese fermented soybean dish called Natto. The other group received the same probiotic, except the researchers modified it to express a protein derived from a closely related bacterium, Bacillus thuringiensis or Bt, which is known to be safe in humans but potentially lethal to intestinal worms.
“Five days after we administered the bacteria, we examined the animals’ intestines,” Hu said. “We found no worms in the animals that received the modified probiotic, while those that did not receive the modified probiotic remained infected.”
Hu said the next step will be to conduct tests in different types of animals and against different types of STHs. If the probiotic continues to perform well against multiple intestinal parasites and is shown to be safe, then researchers would consider testing in humans, she said.
The research is supported by grants from the Bill & Melinda Gates Foundation and the National Institutes of Health.
“While the research has yet to move beyond tests in animals, the human health burden is so immense and the solutions so few that it’s gratifying to see progress being made toward finding new treatments for intestinal worm diseases,” said ASTMH President David H. Walker, MD. “It shows that new investments in neglected tropical diseases are inspiring creative solutions for the more than a billion people in need.”
Aroian said the overall goal of the work is to produce a treatment for intestinal worms that is safe, effective and affordable in the world’s poorest countries, where hookworms and other STHs do the most damage. “This probiotic is a food-grade bacterial product that can be easily produced in large quantities in a simple fermenter, and it can be manufactured in a form that has a long shelf-life,” he said. “It could be well-suited to providing the cheap, mass treatment we need to substantially reduce the burden of this disease.”
Aroian said Bt is attractive because it is a well-understood, natural substance for controlling plant pests that is believed to be safe for animals and humans. It is frequently sprayed on organic crops and is mainly lethal to insects in their larva stage. Bt also is a bacteria used in genetically engineered corn and soybean to endow the crops with resistance to plant pests.
Aroian said that while the modified probiotic under development in his lab should be safe to consume, if it proves to be an effective intervention for intestinal worms it would be marketed as a treatment, not as a dietary supplement.
Inflammatory skin damage in mice blocked by bleach solution, Stanford study finds
STANFORD, Calif. — Processes that age and damage skin are impeded by dilute bleach solution, according to a new study by researchers at the Stanford University School of Medicine.
The study was conducted on mice. But if shown to work similarly in humans, the inexpensive, widely available household chemical could provide a new way to treat skin damage caused by radiation therapy, excess sun exposure or aging.
Dilute bleach baths have been used for decades to treat moderate to severe eczema in humans, but it has not been clear until now why they work. “Originally it was thought that bleach may serve an antimicrobial function, killing bacteria and viruses on the skin,” said Thomas Leung, MD, PhD, an instructor in dermatology at Stanford and a pediatric dermatologist at Lucile Packard Children’s Hospital. “But the concentrations used in clinic are not high enough for this to be the sole reason. So we wondered if there could be something else going on.”
Leung is the lead author of the study, which will be published online Nov. 15 in the Journal of Clinical Investigation. Seung Kim, MD, PhD, professor of developmental biology and a Howard Hughes Medical Institute investigator, is the study’s senior author.
“Dr. Leung relentlessly followed his hunch that an antimicrobial effect of dilute bleach wasn’t the whole story,” Kim said. “And his work has revealed new mechanisms for targeting inflammatory pathways with this versatile small molecule. It has also identified new possible clinical applications.”
Leung and his colleagues knew that many skin disorders, including eczema and radiation dermatitis, have an inflammatory component. When the skin is damaged, immune cells rush to the site of the injury to protect against infection. Because inflammation itself can be harmful if it spirals out of control, the researchers wondered if the bleach (sodium hypochlorite) solution somehow played a role in blocking this response.
To find out, they homed in on a molecule called nuclear factor kappa-light-chain-enhancer of activated B cells, or NF-kB, which is known to play a critical role in inflammation, aging and response to radiation. When activated by signaling molecules, it enters the cell’s nucleus and binds to DNA to control gene expression. When inactive, it is sequestered in the cytoplasm, away from the DNA.
Leung wondered if there could be a link between the effect of the dilute bleach solution and NF-kB’s role in skin. He exposed human keratinocytes, or skin cells, to 0.005 percent bleach for one hour before treating them with a signaling molecule that normally activates NF-kB function. He found that exposure to the solution blocked the expression of two genes known to be regulated by NF-kB. The effect was reversible, however — waiting 24 hours after the bleach treatment restored NF-kB’s ability to activate expression of the target genes.
Further investigation divulged how this happens.
“We found that the bleach solution oxidizes and inhibits an activator necessary for NF-kB to enter the nucleus, essentially blocking NF-kB’s effect,” Leung said. When the researchers mutated the activator to be oxidation-resistant, NF-kB’s gene targeting activity was unhindered.
Next, the researchers turned to potential clinical applications. Radiation dermatitis is a common side effect of radiation therapy for cancer. While radiation therapy is directed at cancer cells inside the body, the normal skin in the radiation therapy field is also affected. Radiation therapy often causes a sunburn-like skin reaction. In some cases, these reactions can be quite painful and can require interrupting the radiation therapy course to allow the skin to heal before resuming treatment. However, prolonged treatment interruptions are undesirable.
“An effective way to prevent and treat radiation dermatitis would be of tremendous benefit to many patients receiving radiation therapy,” said Susan Knox, MD, PhD, associate professor of radiation oncology and study co-author.
Leung and his colleagues tested the effect of daily, 30-minute baths in bleach solution on laboratory mice with radiation dermatitis. They found that the animals bathed in the bleach solution experienced less severe skin damage and better healing and hair regrowth than animals bathed in water.
They then turned their attention to old — but healthy — laboratory mice.
“Multiple research studies have linked increased NF-kB activity with aging,” Leung said. “We found that if we blocked NF-kB activity in elderly laboratory mice by bathing them in the bleach solution, the animals’ skin began to look younger. It went from old and fragile to thicker, with increased cell proliferation.” The effect diminished soon after the dilute-bleach baths were stopped, indicating that regular exposure is necessary to maintain skin thickness.
The researchers are now considering clinical trials in humans, and they are also looking at other diseases that could be treated by dilute-bleach baths. “It’s possible that, in addition to being beneficial to radiation dermatitis, it could also aid in healing wounds like diabetic ulcers,” Leung said. “This is exciting because there are so few side effects to dilute bleach. We may have identified other ways to use hypochlorite to really help patients. It could be easy, safe and inexpensive.”
Can Certain Herbs Stave Off Alzheimer’s Disease?
ST. LOUIS — Enhanced extracts made from special antioxidants in spearmint and rosemary improve learning and memory, a study in an animal model at Saint Louis University found.
“We found that these proprietary compounds reduce deficits caused by mild cognitive impairment, which can be a precursor to Alzheimer’s disease,” said Susan Farr, Ph.D., research professor geriatrics at Saint Louis University School of Medicine.
Farr added, “This probably means eating spearmint and rosemary is good for you. However, our experiments were in an animal model and I don’t know how much — or if any amount — of these herbs people would have to consume for learning and memory to improve. In other words, I’m not suggesting that people chew more gum at this point.”
Farr presented the early findings at Neuroscience 2013, a meeting of 32,000 on Monday, Nov. 11. She tested a novel antioxidant-based ingredient made from spearmint extract and two different doses of a similar antioxidant made from rosemary extract on mice that have age-related cognitive decline.
She found that the higher dose rosemary extract compound was the most powerful in improving memory and learning in three tested behaviors. The lower dose rosemary extract improved memory in two of the behavioral tests, as did the compound made from spearmint extract.
Further, there were signs of reduced oxidative stress, which is considered a hallmark of age-related decline, in the part of the brain that controls learning and memory.
“Our research suggests these extracts made from herbs might have beneficial effects on altering the course of age-associated cognitive decline,” Farr said. “It’s worth additional study.”
The research, which was supported by the VA Medical Center in St. Louis, was conducted in conjunction with Kemin Industries, which manufactures specialty ingredients for vitamin/dietary supplements or that can be added to food to enhance its nutritional and health benefits.
Established in 1836, the School of Medicine has the distinction of awarding the first medical degree west of the Mississippi River. The school educates physicians and biomedical scientists, conducts medical research, and provides health care on a local, national and international level. Research at the school seeks new cures and treatments in five key areas: infectious disease, liver disease, aging and brain disease, cancer and heart/lung disease.
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