Health Technology Research Synopsis
128th Issue Date 04 MAY 2012
Compiled By Ralph Turchiano
Editors Top Five:
1. Component of pizza seasoning herb oregano kills prostate cancer cells 2. Evidence shows that anti-depressants likely do more harm than good, researchers find 3. Garlic compound fights source of food-borne illness better than antibiotics 4. Protein heals wounds, boosts immunity and protects from cancer 5. Unmasking black pepper's secrets as a fat fighter
In this Issue:
1. Avocado oil: The ‘olive oil of the Americas’?
3. Link between common environmental contaminant and rapid breast cancer growth
4. Rutgers Study: Vitamin E in Diet Protects Against Many Cancers
5. Beyond apples: A serving a day of dark chocolate might keep the doctor away
6. Component of pizza seasoning herb oregano kills prostate cancer cells
7. Chronic cocaine use may speed up aging of brain
8. Egg nutrition research reveals positive impact on metabolic syndrome and satiety
9. Evidence shows that anti-depressants likely do more harm than good, researchers find
10. Research shows how PCBs promote dendrite growth, may increase autism risk
11. Berries keep your brain sharp
12. How probiotic bacteria protect against inflammatory bowel diseases
13. Vitamin D supplements may protect against viral infections during the winter
14. Protein heals wounds, boosts immunity and protects from cancer
15. Garlic compound fights source of food-borne illness better than antibiotics
16. Large-scale analysis finds majority of clinical trials don’t provide meaningful evidence
17. Everyday fish oil capsule may provide kidney-related benefits
18. Eating fish, chicken, nuts may lower risk of Alzheimer’s disease
19. NSAIDs and cardiovascular risk explained
20. Increased fructose consumption may deplete cellular energy in patients with obesity and diabetes
21. Unmasking black pepper’s secrets as a fat fighter
22. Low oxygen levels could drive cancer growth
23. Beehive extract shows potential as prostate cancer treatment
24. Scientific Evidence Proves why Healers See the “Aura” of People
Avocado oil: The ‘olive oil of the Americas’?
Mexican study indicates it could fight harmful free radicals tied to aging and cancer
SAN DIEGO, April 22, 2012 – Atmospheric oxygen facilitated the evolution and complexity of terrestrial organisms, including human beings, because it allowed nutrients to be used more efficiently by those organisms, which in turn were able to generate more energy. However, as we find out more about how oxygen molecules work inside the body, more attention is being paid to their not-so-good effects, and researchers are seeking ways to thwart them.
A number of environmental factors — such as pollution, cigarette smoke and radiation — can turn the oxygen molecules found in mitochondria, the power plants of cells, into free radicals. These unstable molecules destroy virtually all the normal molecules forming cells, such as lipids, proteins and even DNA, by turning them into free radicals, too. This destructive phenomenon is associated with aging and occurs in a variety of diseases, including hypertension and diabetes, which represent major challenges for health systems due to their great social and economic costs. Those costs have motivated scientists worldwide to undertake intensive searches for substances that bolster cell resistance to the harmful effects of free radicals.
Many studies of antioxidants in vegetables and fruits, such as carrots and tomatoes, have been completed with few encouraging results, says Christian Cortés-Rojo, a researcher at Universidad Michoacana de San Nicolás de Hidalgo in Morelia, Michoacán, México. “The problem is that the antioxidants in those substances are unable to enter mitochondria. So free radicals go on damaging mitochondria, causing energy production to stop and the cell to collapse and die. An analogy would be that, during an oil spill, if we cleaned only the spilled oil instead of fixing the perforation where oil is escaping, then the oil would go on spilling, and fish would die anyway.”
But Cortés-Rojo is prepared to reveal next week the first research results showing the protective effects of avocado oil against free radicals in mitochondria. At 12:25 p.m. Sunday, April 22, Cortés-Rojo will present his group’s work at the annual meeting of the American Society for Biochemistry and Molecular Biology, held in conjunction with the Experimental Biology 2012 conference in San Diego.
The research team used yeast cells – those used in wine and beer production – to examine avocado oil’s properties.
“The reason why we have chosen yeast,” explains Cortés-Rojo, “is that (a) this microorganism is easier to study than other biological models due to its relative simplicity and (b) because studies our group published in 2009 and 2011 found that yeast mitochondria are very resistant to free radicals due to the sort of fat that forms its envelope, which is highly resistant to oxidation. The same kind of fat can be found in avocado oil; but, in addition, avocados also contain some plant pigments that inhibit oxidation. That is why we decided to test whether these avocado properties could increase even more the yeast’s resistance to mitochondrial oxidation.”
The results of this research, he says, show that avocado oil allowed the yeast cells to survive exposure to high concentrations of iron, which produces a huge amount of free radicals, “even to higher levels to those found in some human diseases.”
He continues: “These results could be attributed to the fact that avocado oil caused accelerated respiration in mitochondria, which indicate that the use of nutrients for producing energy for cell functions remains effective even in cells attacked by free radicals and that mitochondria itself could produce little amounts of damaging free radicals.”
Cortés-Rojo emphasized that these findings reinforce the good reputation the avocado has when it comes to health maintenance. He points to pioneering research by Mario Alvizouri-Muñoz, a doctor at the Morelia General Hospital, who demonstrated that avocado lowers the blood concentration of cholesterol and certain fats that are increased in diabetic patients and that may lead to stroke or heart attack.
“Our results are promising because they indicate that avocado consumption could improve the health status of diabetic and other patients through an additional mechanism to the improvement of blood lipids,” he says. “We’ll need to confirm that what has been observed in yeasts could occur in higher organisms, such as humans. We hope this will be the case, because there are many vital processes conserved in organisms that seem very dissimilar to humans.”
Moreover, Cortés-Rojo says, the findings, and the fact that México is the largest producer of avocados in the world, could promote the use of avocado oil or some of its components to reduce the socioeconomic impact of chronic degenerative diseases. “In some Mediterranean countries, low or almost no appearance of these kinds of diseases has been associated with the high olive oil consumption,” he explains. “Olive oil has a fat composition similar to that found in avocado oil. Therefore, avocado oil could eventually be referred to as the olive oil of the Americas.”
University of Illinois study shows soy protein alleviates symptoms of fatty liver disease
It could reduce fat accumulation and triglycerides in obese patients by partially restoring function of key signaling pathway
University of Illinois researchers will report this week that new research shows how soy protein could significantly reduce fat accumulation and triglycerides in the livers of obese patients by partially restoring the function of a key signaling pathway in the organ.
Hong Chen, an assistant professor of food science and human nutrition at the University of Illinois, will present her team’s findings at 1:05 p.m. Sunday, April 22, at the annual meeting of the American Society for Biochemistry and Molecular Biology, held in conjunction with the Experimental Biology 2012 meeting in San Diego.
“Almost a third of American adults have fatty liver disease, many of them without symptoms,” Chen explained. “Obesity is a key risk factor for this condition, which can lead to liver failure.”
Fat is metabolized in the liver, and in those who are obese the transport of fat to adipose tissue can slow down to the point at which the liver becomes a dumping ground for excess fat, she said.
“When fat accumulates in an organ that’s not supposed to store fat — like the liver, that organ’s vital function can be dangerously compromised,” she noted.
Eating soy protein, from such sources as tofu and yogurt, appears to alleviate some of the stress on fatty livers, Chen said. For her study, Chen compared fat accumulation in the livers of lean and obese rats, which were assigned to either a diet containing casein, a milk-based protein, or a diet containing soy protein, for 17 weeks after weaning.
While diet had no effect on the liver profiles of lean animals, the obese rats that were fed soy showed a 20 percent reduction in triglycerides and overall fat accumulation in the liver, leading Chen to believe that soy protein could be used to alleviate the symptoms of fatty liver disease.
Furthermore, the scientists discovered that soy protein isolate partially restored the Wnt/β-catenin signaling pathway, a crucial player in fat metabolism. “In many obese persons, there’s a sort of traffic problem, and when more fat can make its way out of the liver, there is less pressure on that organ,” Chen said.
Link between common environmental contaminant and rapid breast cancer growth
Breast cancer cells are more aggressive the longer they’re exposed to cadmium
Studies by researchers at Dominican University of California show that breast cancer cells become increasingly aggressive the longer they are exposed to small concentrations of cadmium, a heavy metal commonly found in cosmetics, food, water and air particles.
The study by Maggie Louie, associate professor of biochemistry, shows exposure to cadmium for prolonged periods of time can cause the progression of breast cancer to become more aggressive. Her findings will be presented Monday, April 23, at the annual meeting of the American Society for Biochemistry and Molecular Biology, held in conjunction with the Experimental Biology 2012 conference in San Diego.
Breast cancer results from the abnormal growth of the cells in the mammary gland. The normal growth of mammary gland epithelial cells is modulated by the circulating levels of estrogen, a hormone produced by the ovaries. The activity of estrogen is stimulated by the estrogen receptor (ER). Heavy metals such as cadmium can act as endocrine disruptors and mimic estrogen, thereby disrupting the hormone dependent pathways.
While other studies have shown links between acute cadmium exposure and activation of the ER, Louie’s study is one of few to focus on chronic cadmium exposure. “The relationship between cancer and chronic exposures at low levels is important to understand because most people are not exposed to high levels of heavy metals, unless they work in manufacturing plants that deal with such metals,” Louie said.
She continued: “Unfortunately, cadmium is all around us – it is in our food, our water, our makeup and our air. Understanding the role that cadmium plays in the progression of breast cancer is extremely important in order to find better ways to prevent the disease from advancing. Ninety percent of cancer deaths are associated with the cancer spreading to other parts of the body. If we can prevent the tumor from spreading, we have a better chance of treating cancer.”
Taken together, the findings of Louie’s new study and a handful of others published in recent years show that cadmium plays a significant role in the development of breast cancer. However, Louie’s research is unique in that it focuses on prolonged exposure rather than acute exposure at the cellular level. The study indicates that chronic exposure to cadmium can contribute to the development of more malignant characteristics in breast cancer cells.
“Many of us are exposed to very low levels of cadmium from the environment on a daily basis, and our research shows that even small concentrations of this metal at prolonged exposures can cause breast cancer cell growth.”
Cadmium is produced mainly as a byproduct from mining, smelting and refining sulfidic ores of zinc, lead and copper. Rocks mined to produce phosphate fertilizers also contain varying amounts of cadmium. Cadmium also is found in rechargeable batteries and cigarette smoke. Cadmium enters the body through consumption of contaminated food, water or inhalation of cigarette smoke.
Louie’s preliminary data show an increase in the ability of breast cancer cells to migrate and invade through the extracellular matrix with prolonged cadmium exposure. The extracellular matrix is the outer barrier of an organ or tissue. Increased invasive and migration abilities are characteristic of cancer cells’ ability to spread. Louie discovered that MCF-7 cells chronically exposed to cadmium express higher levels of SDF-1, a protein associated with tumor invasion and metastasis.
How specific proteins, including SDF-1, contribute to the aggressive characteristics of the cadmium exposed cells requires further research, and understanding their role in cadmium-induced carcinogenesis will provide further insights to how heavy metals contribute to breast cancer progression.
Rutgers Study: Vitamin E in Diet Protects Against Many Cancers
Researchers find form commonly used in supplements has no such benefit
April 23, 2012
Professor Yang can be contacted at 732-445-3400, ext. 248 or at firstname.lastname@example.org
Credit: Skin Care By Louisa
Vitamin E in vegetable oils and nuts prevents cancer, according to research done at Rutgers University and the Cancer Institute of New Jersey.
Next time you need to choose between vegetable oil and margarine in that favorite recipe, think about your health and reach for the oil.
While the question of whether vitamin E prevents or promotes cancer has been widely debated in scientific journals and in the news media, scientists at the Center for Cancer Prevention Research, at Rutgers Ernest Mario School of Pharmacy, and the Cancer Institute of New Jersey, believe that two forms of vitamin E – gamma and delta-tocopherols – found in soybean, canola and corn oils as well as nuts do prevent colon, lung, breast and prostate cancers.
“There are studies suggesting that vitamin E actually increases the risk of cancer and decreases bone density,” says Chung S. Yang, director of the center. “Our message is that the vitamin E form of gamma-tocopherols, the most abundant form of vitamin E in the American diet, and delta-tocopherols, also found in vegetable oils, are beneficial in preventing cancers while the form of vitamin E, alpha- tocopherol, the most commonly used in vitamin E supplements, has no such benefit.”
Credit: Courtesy Chung S. Yang
Director of the Center for Cancer Prevention Research at Rutgers Ernest Mario School of Pharmacy
Yang and colleagues, Nanjoo Suh and Ah-Ng Tony Kong, summarized their findings recently in Cancer Prevention Research, a journal of the American Association for Cancer Research. In a Commentary, “Does Vitamin E Prevent or Promote Cancer?” the Rutgers scientists discuss animal studies done at Rutgers as well as human epidemiological studies that have examined the connection between vitamin E and cancer.
Yang says Rutgers scientists conducting animal studies for colon, lung, breast and prostate cancer found that the forms of vitamin E in vegetable oils, gamma and delta-tocopherols, prevent cancer formation and growth in animal models.
“When animals are exposed to cancer-causing substances, the group that was fed these tocopherols in their diet had fewer and smaller tumors,” Yang says. “When cancer cells were injected into mice these tocopherols also slowed down the development of tumors.”
In researching colon cancer, Yang pointed to another recently published paper in Cancer Prevention Research indicating that the delta-tocopherol form of vitamin E was more effective than other forms of vitamin E in suppressing the development of colon cancer in rats.
This is good news for cancer research. Recently, in one of the largest prostate cancer clinical trials in the United States and Canada, scientists found that the most commonly used form of vitamin E supplements, alpha-tocopherol, not only did not prevent prostate cancer, but its use significantly increased the risk of this disease among healthy men.
This is why, Yang says, it is important to distinguish between the different forms of vitamin E and conduct more research on its cancer preventive and other biological effects.
“For people who think that they need to take vitamin E supplements,” Yang says, “taking a mixture of vitamin E that resembles what is in our diet would be the most prudent supplement to take.”
Beyond apples: A serving a day of dark chocolate might keep the doctor away
San Diego, CA— Chocolate, considered by some to be the “food of the gods,” has been part of the human diet for at least 4,000 years; its origin thought to be in the region surrounding the Amazon basin. Introduced to the Western world by Christopher Columbus after his fourth voyage to the New World in 1502, chocolate is now enjoyed worldwide. Researchers estimate that the typical American consumes over 10 pounds of chocolate annually, with those living on the west coast eating the most. Wouldn’t it be great if only chocolate were considered healthy?
In fact, chocolate is a great source of myriad substances that scientists think might impart important health benefits. For instance, it contains compounds called “flavanols” that appear to play a variety of bodily roles including those related to their potent antioxidant and anti-inflammatory actions. Many large-scale human studies have documented a statistical correlation between flavanol intake and risk for cardiovascular disease. And animal studies suggest that this relationship may be due to the physiologic effects that flavanols have on chronic inflammation, blood vessel health, and circulating lipid levels. However, few controlled human intervention studies have been conducted to test the direct effect of chocolate consumption on these variables.
To help fill this knowledge gap, researchers at San Diego State University tested their hypothesis that chocolate, in particular dark chocolate which contains higher levels of flavanols than milk chocolate, may protect against the risk of cardiovascular disease by lowering blood pressure, blood flow, and improving blood lipid levels.
In this prospective, controlled human intervention study, 31 fortunate subjects were assigned randomly to consume either a daily serving (50 grams) of either regular dark chocolate (70% cocoa), dark chocolate (70% cocoa) that had been overheated or “bloomed,” or white chocolate (0% cocoa). The subjects were asked to consume the chocolate for 15 days. Blood pressure, forearm skin blood flow, circulating lipid profiles, and blood glucose levels were recorded at the beginning and end of the study.
When compared to participants assigned to the white chocolate group, those consuming either form of dark chocolate had lower blood glucose and low-density lipoprotein cholesterol (LDL, the “bad” form) levels coupled with higher high-density lipoprotein cholesterol (HDL, the “good” form).
The researchers concluded that dark chocolate may reduce the risk of cardiovascular disease by improving glucose levels and lipid profiles. However, they cautioned that—although habitual dark chocolate consumption may benefit one’s health by reducing the risk of cardiovascular disease—it must be eaten in moderation because it can easily increase daily amounts of saturated fat and calories. Indeed, the authors commented, “We had great compliance with our study subjects because everybody wanted to eat chocolate. We actually had to tell them not to eat more than 50 grams a day.”
The group reports that it is planning follow-up studies involving more subjects and a longer duration of chocolate consumption.
Results from this study will be presented April 24, 2012 at the Experimental Biology 2012 meeting in San Diego, CA.
Component of pizza seasoning herb oregano kills prostate cancer cells
San Diego, CA — Oregano, the common pizza and pasta seasoning herb, has long been known to possess a variety of beneficial health effects, but a new study by researchers at Long Island University (LIU) indicates that an ingredient of this spice could potentially be used to treat prostate cancer, the second leading cause of cancer death in American men.
Prostate cancer is a type of cancer that starts in the prostate gland and usually occurs in older men. Recent data shows that about 1 in 36 men will die of prostate cancer. Estimated new cases and deaths from this disease condition in the US in 2012 alone are 241,740 and 28,170, respectively. Current treatment options for patients include surgery, radiation therapy, hormone therapy, chemotherapy, and immune therapy. Unfortunately, these are associated with considerable complications and/or severe side effects.
Dr. Supriya Bavadekar, PhD, RPh, Assistant Professor of Pharmacology at LIU’s Arnold & Marie Schwartz College of Pharmacy and Health Sciences, is currently testing carvacrol, a constituent of oregano, on prostate cancer cells. The results of her study demonstrate that the compound induces apoptosis in these cells. Apoptosis, Dr. Bavadekar explains, is programmed cell death, or simply “cell suicide.” Dr. Bavadekar and her group are presently trying to determine the signaling pathways that the compound employs to bring about cancer cell suicide.
“We know that oregano possesses anti-bacterial as well as anti-inflammatory properties, but its effects on cancer cells really elevate the spice to the level of a super-spice like turmeric,” said Dr. Bavadekar. Though the study is at its preliminary stage, she believes that the initial data indicates a huge potential in terms of carvacrol’s use as an anti-cancer agent. “A significant advantage is that oregano is commonly used in food and has a ‘Generally Recognized As Safe’ status in the US. We expect this to translate into a decreased risk of severe toxic effects.”
“Some researchers have previously shown that eating pizza may cut down cancer risk. This effect has been mostly attributed to lycopene, a substance found in tomato sauce, but we now feel that even the oregano seasoning may play a role,” stated Dr. Bavadekar. “If the study continues to yield positive results, this super-spice may represent a very promising therapy for patients with prostate cancer.” The results of the study will be presented at the Experimental Biology 2012 poster session on Tuesday, April 24.
Chronic cocaine use may speed up aging of brain
Research shows chronic users’ brains age dramatically faster than their non-drug-using peers
New research by scientists at the University of Cambridge suggests that chronic cocaine abuse accelerates the process of brain ageing. The study, published today 25 April in Molecular Psychiatry, found that age-related loss of grey matter in the brain is greater in people who are dependent on cocaine than in the healthy population.
For the study, the researchers scanned the brains of 120 people with similar age, gender and verbal IQ. Half of the individuals had a dependence on cocaine while the other 60 had no history of substance abuse disorders.
The researchers found that the rate of age-related grey matter volume loss in cocaine-dependent individuals was significantly greater than in healthy volunteers. The cocaine users lost about 3.08 ml brain volume per year, which is almost twice the rate of healthy volunteers (who only lost about 1.69 ml per year). The accelerated age-related decline in brain volume was most prominent in the prefrontal and temporal cortex, important regions of the brain which are associated with attention, decision-making, and self-regulation as well as memory.
Previous studies have shown that psychological and physiological changes typically associated with old age such as cognitive decline, brain atrophy and immunodeficiency are also seen in middle-aged cocaine-dependent individuals. However, this is the first time that premature ageing of the brain has been associated with chronic cocaine abuse.
Dr Karen Ersche, of the Behavioural and Clinical Neuroscience Institute (BCNI) at the University of Cambridge, said: “As we age, we all lose grey matter. However, what we have seen is that chronic cocaine users lose grey matter at a significantly faster rate ,which could be a sign of premature ageing. Our findings therefore provide new insight into why the cognitive deficits typically seen in old age have frequently been observed in middle aged chronic users of cocaine.”
The scientists also highlight concerns that premature ageing in chronic cocaine users is an emerging public health concern. The United Nations Office on Drugs and Crime estimates that cocaine is used by up to 21 million individuals worldwide, with approximately 1 per cent of these individuals becoming dependent.
Dr Ersche said: “Our findings clearly highlight the need for preventative strategies to address the risk of premature ageing associated with cocaine abuse. Young people taking cocaine today need to be educated about the long-term risk of ageing prematurely.”
The concern of accelerated ageing is not limited to young people but also affects older adults who have been abusing drugs such as cocaine since early adulthood.
Dr Ersche added: “Our findings shed light on the largely neglected problem of the growing number of older drug users, whose needs are not so well catered for in drug treatment services. It is timely for heath care providers to understand and recognise the needs of older drug users in order to design and administer age-appropriate treatments.”
Egg nutrition research reveals positive impact on metabolic syndrome and satiety
Lessons from Experimental Biology 2012
Park Ridge, IL (April 24, 2012) – This week at Experimental Biology (EB) 2012 in San Diego, experts are convening to discuss the latest science in a variety of health and disease-related areas, including nutrition. Research on whole egg consumption in individuals with metabolic syndrome as well as the positive effects of a higher-protein breakfast is further revealing the potential benefits of including eggs in the diet.
Whole Egg Consumption May Improve Markers of Metabolic Syndrome
A University of Connecticut study presented this week suggests that eating eggs may actually have favorable effects on HDL metabolism in men and women with metabolic syndrome.(i) Participants in the study followed a carbohydrate-restricted diet with some individuals eating three whole eggs per day and others eating an equivalent amount of egg substitute. After 12 weeks, the group eating whole eggs experienced an improvement in HDL measures showing significantly greater increases in the number and size of HDL particles. HDL or “good” cholesterol scavenges for fat throughout the bloodstream and returns it to the liver, making it less likely that fatty deposits will build up in the blood vessels and lead to atherosclerosis.
Related findings were also presented in separate sessions that suggest that consuming whole eggs as part of a carbohydrate-restricted diet may help to further improve markers indicative of inflammation, such as tumor necrosis factor-alpha, in individuals with metabolic syndrome.(ii)
Higher-Protein Breakfast Reduces High-Fat Snacking
A study by researchers at the University of Missouri found that teen girls reported greater feelings of satiety and experienced improved hormone responses related to hunger and satiety after consuming a higher-protein breakfast, containing about 35 grams of protein from egg or beef-based foods. Teen girls who consumed a high-protein breakfast also ate fewer snacks, especially those higher in fat, later in the day.(iii) These findings build on past research showing the benefits of high-quality protein on satiety, further supporting the science behind what makes eggs such a satisfying breakfast choice.(iv)
Clarifying Cholesterol Confusion
Many Americans avoid the dietary cholesterol found in eggs for fear of raising their risk of heart disease, but more than 40 years of research has shown that healthy adults can enjoy eggs without concern for increasing their risk for heart disease. Additionally, an analysis from the United States Department of Agriculture’s Agricultural Research Service showed that eggs have 14 percent less cholesterol (down from 215 mg to 185 mg) than previously measured.(v) Established research also has shown that saturated fat intake may be more likely to raise a person’s blood cholesterol than dietary cholesterol intake and eggs contain relatively little saturated fat.(vi) The findings presented at this week’s meeting in combination with the decades of science demonstrating the health benefits of eating eggs further support the role of eggs in a nutritious diet.
Evidence shows that anti-depressants likely do more harm than good, researchers find
HAMILTON, ON, April 24, 2012 — Commonly prescribed anti-depressants appear to be doing patients more harm than good, say researchers who have published a paper examining the impact of the medications on the entire body.
“We need to be much more cautious about the widespread use of these drugs,” says Paul Andrews, an evolutionary biologist at McMaster University and lead author of the article, published today in the online journal Frontiers in Psychology.
“It’s important because millions of people are prescribed anti-depressants each year, and the conventional wisdom about these drugs is that they’re safe and effective.”
Andrews and his colleagues examined previous patient studies into the effects of anti-depressants and determined that the benefits of most anti-depressants, even taken at their best, compare poorly to the risks, which include premature death in elderly patients.
Anti-depressants are designed to relieve the symptoms of depression by increasing the levels of serotonin in the brain, where it regulates mood. The vast majority of serotonin that the body produces, though, is used for other purposes, including digestion, forming blood clots at wound sites, reproduction and development.
What the researchers found is that anti-depressants have negative health effects on all processes normally regulated by serotonin.
The findings include these elevated risks:
- · developmental problems in infants
- · problems with sexual stimulation and function and sperm development in adults
- · digestive problems such as diarrhea, constipation, indigestion and bloating
- · abnormal bleeding and stroke in the elderly
The authors reviewed three recent studies showing that elderly anti-depressant users are more likely to die than non-users, even after taking other important variables into account. The higher death rates indicate that the overall effect of these drugs on the body is more harmful than beneficial.
“Serotonin is an ancient chemical. It’s intimately regulating many different processes, and when you interfere with these things you can expect, from an evolutionary perspective, that it’s going to cause some harm,” Andrews says.
Millions of people are prescribed anti-depressants every year, and while the conclusions may seem surprising, Andrews says much of the evidence has long been apparent and available.
“The thing that’s been missing in the debates about anti-depressants is an overall assessment of all these negative effects relative to their potential beneficial effects,” he says. “Most of this evidence has been out there for years and nobody has been looking at this basic issue.”
In previous research, Andrews and his colleagues had questioned the effectiveness of anti-depressants even for their prescribed function, finding that patients were more likely to suffer relapse after going off their medications as their brains worked to re-establish equilibrium.
With even the intended function of anti-depressants in question, Andrews says it is important to look critically at their continuing use.
“It could change the way we think about such major pharmaceutical drugs,” he says. “You’ve got a minimal benefit, a laundry list of negative effects – some small, some rare and some not so rare. The issue is: does the list of negative effects outweigh the minimal benefit?”
Research shows how PCBs promote dendrite growth, may increase autism risk
April 24, 2012
(SACRAMENTO, Calif.) —
New research from UC Davis and Washington State University shows that PCBs, or polychlorinated biphenyls, launch a cellular chain of events that leads to an overabundance of dendrites — the filament-like projections that conduct electrochemical signals between neurons — and disrupts normal patterns of neuronal connections in the brain.
Isaac Pessah © 2012 UC Regents
“Dendrite growth and branching during early development is a finely orchestrated process, and the presence of certain PCBs confuses the conductor of that process,” said Pamela Lein, a developmental neurobiologist and professor of molecular biosciences in the UC Davis School of Veterinary Medicine. “Impaired neuronal connectivity is a common feature of a number of conditions, including autism spectrum disorders.”
Reported today in two related studies in the journal Environmental Health Perspectives, the findings underscore the developing brain’s vulnerability to environmental exposures and demonstrate how PCBs could add to autism risk.
“We don’t think PCB exposure causes autism,” Lein said, “but it may increase the likelihood of autism in children whose genetic makeup already compromises the processes by which neurons form connections.”
The senior authors of the studies were Lein and Isaac Pessah, chair of molecular biosciences in the School of Veterinary Medicine and director of the Center for Children’s Environmental Health at UC Davis. Both are researchers with the UC Davis MIND Institute, which is dedicated to finding answers to autism and other neurodevelopmental disorders. The lead author was Gary Wayman of Washington State University’s Program in Neuroscience, who first described the molecular pathway that controls the calcium signaling in the brain that guides normal dendrite growth.
Wayman found that key cellular players, called calcium and calmodulin kinases, are activated by increased calcium levels. Activated calmodulin kinase then turns on the protein known as CREB that regulates genes that produce Wnt2, a potent molecule and the final arbiter of whether and how dendrites grow. Wnt2 directs structural proteins to construct scaffolding that supports dendrite growth and branching.
“Orderly choreography of the calmodulin kinase-to-Wnt2 pathway translates normal increases in calcium levels into normal levels of dendrite production,” said Wayman. “The wiring of billions of neurons is dependent on the health of this cellular process and is crucial to proper development of virtually all complex behaviors, learning, memories and language.”
For the current studies, the team set out to determine if that pathway was altered by exposure to PCBs, focusing on neurons of the hippocampus — the brain region linked with learning and memory and known to suffer impaired connectivity in many neurodevelopmental disorders.
The scientists also focused on the effects of an understudied PCB subset known as non-dioxin-like PCBs, which have been shown to increase calcium levels in neurons. Both non-dioxin-like PCBs and the more familiar dioxin-like subset were widely used in electrical equipment in the 1950s and 1960s. Banned in the 1970s because of the potential for dioxin-like PCBs to cause cancer, all PCBs are stable compounds that persist throughout the environment today.
One of the current UC Davis studies examined dendrite growth in rat pups born to and nursed by PCB-exposed mothers. Another study analyzed how PCBs affect rat neurons in cell cultures at developmental stages similar to those in the third trimester of pregnancy in humans. In both studies, PCB exposure levels were similar to those found in the human diet and in human tissues, including the placenta and breast milk.
Evaluation of the brains of the rats exposed to PCBs early in life showed significant overproduction of dendrites. The cellular studies showed that PCBs triggered the calcium pathway that led to the aberrant brain architecture, and that dendrite production was normal when that cellular pathway was blocked.
“We are the first to show that non-dioxin-like PCBs alter how the developing brain gets wired by hijacking the calcium signaling pathway and greatly expanding dendrite growth,” said Lein.
The experiments also helped identify for the first time the specific trigger for this cellular chain of events as the ryanodine receptor (RyR) calcium channel. Pessah, a recognized leader in calcium-channel dysfunction and neurodevelopment, previously showed that RyR is selectively activated by non-dioxin-like PCBs. The new studies prove that RyR is a necessary component in the pathway that controls dendritic growth. “These same calcium pathways are implicated in some forms of autism and, while environmental exposures alone do not cause autism, these new findings provide good evidence that PCBs could add to autism risk in genetically predisposed children,” said Pessah. “Understanding the fundamental mechanisms by which PCBs alter neural networks sets the stage for research on environmental contaminants that are structurally related to PCBs, including flame retardants, and their risks to susceptible populations.”
In addition to Lein, Pessah and Wayman, coauthors on the papers were Dongren Yang, Diptiman Bose and Donald Bruun of UC Davis; Adam Lesiak of Washington State University; and Soren Impey and Veronica Ledoux of the Oregon Health & Science University.
Berries keep your brain sharp
A new study from Brigham and Women’s Hospital found that certain berries may delay memory decline in older women
Boston, MA—Berries are good for you, that’s no secret. But can strawberries and blueberries actually keep your brain sharp in old age? A new study by researchers at Brigham and Women’s Hospital (BWH) finds that a high intake of flavonoid rich berries, such as strawberries and blueberries, over time, can delay memory decline in older women by 2.5 years. This study is published by Annals of Neurology, a journal of the American Neurological Association and Child Neurology Society, on April 26, 2012.
“What makes our study unique is the amount of data we analyzed over such a long period of time. No other berry study has been conducted on such a large scale,” explained Elizabeth Devore, a researcher in the Channing Laboratory at BWH, who is the lead author on this study. “Among women who consumed 2 or more servings of strawberries and blueberries each week we saw a modest reduction in memory decline. This effect appears to be attainable with relatively simple dietary modifications.”
The research team used data from the Nurses’ Health Study—a cohort of 121,700 female, registered nurses between the ages of 30 and 55—who completed health and lifestyle questionnaires beginning in 1976. Since 1980, participants were surveyed every four years regarding their frequency of food consumption. Between 1995 and 2001, memory was measured in 16,010 subjects over the age of 70 years, at 2-year intervals. Women included in the present study had a mean age of 74 and mean body mass index of 26.
Findings show that increased consumption of blueberries and strawberries was associated with a slower rate of memory decline in older women. A greater intake of anthocyanidins and total flavonoids was also associated with reduced memory decline. Researchers observed that women who had higher berry intake had delayed memory decline by up to 2.5 years.
“We provide the first epidemiologic evidence that berries appear to slow progression of memory decline in elderly women,” notes Dr. Devore. “Our findings have significant public health implications as increasing berry intake is a fairly simple dietary modification to reduce memory decline in older adults.”
How probiotic bacteria protect against inflammatory bowel diseases
A glimpse through the laser microscope – green indicates the presence of inflammatory messenger substances (chemokines) in the bowel tissue. Picture: TUM
25.04.2012, Press releases
Some lactic acid bacteria can alleviate inflammation and therefore prevent intestinal disorders. Scientists have now decoded the biochemical mechanism that lies behind the protective effect of the bacteria. In experiments with mice, the researchers succeeded in demonstrating that lactocepin – an enzyme produced by certain lactic acid bacteria – selectively degrades inflammatory mediators in diseased tissue. This new evidence might lead to new approaches for the treatment of inflammatory bowel diseases.
Yoghurt has been valued for centuries for its health-promoting effects. These effects are thought to be mediated by the lactic acid bacteria typically contained in yoghurt. Evidence from recent scientific studies show that some bacterial strains actually have a probiotic effect and can thus prevent disease. A team of biologists and nutrition scientists working with Prof. Dirk Haller from the Technische Universitaet Muenchen (TUM) has now discovered the mechanisms at work behind this protective effect (Cell Host & Microbe). In experiments with mice, the scientists observed that lactocepin – an enzyme produced from the lactic acid bacterium Lactobacillus paracasei – can selectively interrupt inflammatory processes. As the scientists observed, lactocepin degrades messengers from the immune system, known as chemokines, in the diseased tissue. As a part of the “normal” immune response, chemokines are needed to guide defense cells to the source of the infection. In chronic intestinal disorders like Crohn’s disease and ulcerative colitis, the otherwise highly effective defense mechanism against infectious agents is malfunctioning. Chemokines such as “IP-10” then contribute to the tissue damage due to chronic inflammatory processes, preventing the tissue from healing. “Lactocepin is a familiar element in food technology research,” says Prof. Dirk Haller, who holds the Chair for Biofunctionality of Food at the TUM. “What is surprising, however, is its biomedical effect, namely the force with which the enzyme attacks and degrades very specific inflammatory mediators.” Haller is certain that, based on this mechanism, it will be possible to develop new approaches to the targeted prevention and treatment of chronic bowel diseases as well as skin disorders: “The anti-inflammatory effect of lactocepin is limited to specific areas and up to now it has no known side effects.” The scientist therefore plans to carry out clinical studies in order to test the possible pharmaceutical application of the enzyme. Questions also remain to be answered in relation to the “production” of lactocepin by lactic acid bacteria. Some bacterial strains, such as Lactobacillus paracasei, produce highly potent lactocepins; however, the effectiveness of other microorganisms has not yet been proven. Dirk Haller therefore warns against false promises: “Not every product labeled as ‘probiotic’ actually earns this name.”
Vitamin D supplements may protect against viral infections during the winter
New research published in the Journal of Leukocyte Biology suggests that the older population could benefit from vitamin D supplementation in autumn and winter to protect against viral infections
Vitamin D may be known as the sunshine vitamin, but a new research report appearing in the Journal of Leukocyte Biology shows that it is more than that. According to the report, insufficient levels of vitamin D are related to a deficiency in our innate immune defenses that protect us from infections, neoplasias or autoimmune diseases. Since vitamin D levels decrease during autumn and winter when days are shorter and sunlight is relatively weak, this may explain why people are more prone to viral infection during these times. It also suggests that vitamin D supplementation, especially in older populations, could strengthen people’s innate immunity against viral infections.
“There are numerous studies showing the benefits of maintaining adequate Vitamin D levels. As more and more research into Vitamin D is conducted, we are learning that it is extremely important for human health. Our study is no different, and vitamin D supplements should be considered one of many tools that might help when conventional therapies are not enough,” said Victor Manuel Martinez-Taboada, M.D., a researcher involved in the work from the Division of Rheumatology at the Hospital Universitario “Marque’s de Valdecilla,” Facultad de Medicina at the Unversidad de Cantabria, in Santander, Spain.
To make this discovery, the researchers compared the changes in the blood levels of vitamin D among three groups of healthy subjects: young (age range: 20-30), middle (age range: 31-59), and elderly (age range: 60-86). They found decreased levels of vitamin D with aging, prompting researchers to compare whether such changes kept any relationship with toll-like receptor (TLR) expression measured on lymphocytes and monocytes and function after in vitro stimulation with specific ligands for each of the nine human TLRs and measurement of effector molecules, such as proinflammatory cytokines. Specifically, they found that the TRL most affected by a vitamin D insufficiency is TLR7, which regulates the immune response against viruses. Finally, scientists studied whether there was any difference in the three age groups depending on the season of the year since it is well known that a limited sun exposure during darker winter months is related with vitamin D deficiency.
“Any school teacher will tell you that people tend to be sicker during the winter than any other time of the year,” said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. “There have been numerous studies showing several environmental factors during winter months may allow viruses to spread easier. This study shows that sunlight, or more precisely the lack of vitamin D, could have a role in the seasonally higher rates of infection. More extensive studies must be conducted for this link to be conclusive, but since vitamin D supplements are inexpensive and generally safe, this is a really exciting discovery.”
Protein heals wounds, boosts immunity and protects from cancer
University of Calgary researcher edits special issue on disease fighting properties of lactoferrin
Hans Vogel, a professor in the biological sciences department, is the guest editor of a special issue of the journal Biochemistry and Cell Biology that focuses on lactoferrin, an important iron-binding protein with many health benefits.
“Some people describe this protein as the ‘Swiss army knife’ of the human host defense system,” says Vogel. “We now know that lactoferrin has many functions in innate immunity and that it plays a role in protecting us from bacterial, viral, fungal, and protozoal infections. It can even protect us from some forms of cancer.”
Lactoferrin—which is secreted into human milk, blood and other biofluids—has attracted a lot of interest from academics and industry. Furthermore, Vogel says it’s likely the only protein that garners its own regular scientific conference. Researchers are starting to use lactoferrin as a potential therapeutic protein, one that can be taken orally instead of injected like other proteins.
“Lactoferrin is quite an unusual protein that has many effects on health,” Vogel says. “It is also used as a general health-promoting substance, and in Japan it is added to infant formula.”
The June issue of the journal includes 27 peer reviewed papers from leading international researchers on topics including the role of lactoferrin on small intestinal growth and development during early life, use of bovine lactoferrin to inhibit influenza and how the protein may prevent some preterm deliveries.
The protein may also have an important role in wound healing, says Vogel. “We’ve been working in this area for about 15 years and it’s cool to see how the whole field slowly progresses, and you start to see more and more interesting applications. It is particularly exiting to see that clinical trials are now going on in the infectious disease area and in cancer.”
Vogel says being a guest editor was a lot of work and a lot of fun. He also wrote an introductory article for the special issue that provides an overview of the current status of research into the protein. Read the open access article: http://www.nrcresearchpress.com/doi/full/10.1139/o2012-016
Garlic compound fights source of food-borne illness better than antibiotics
Discovery could play role in treatments for food and prep areas
PULLMAN, Wash.—Researchers at Washington State University have found that a compound in garlic is 100 times more effective than two popular antibiotics at fighting the Campylobacter bacterium, one of the most common causes of intestinal illness. Their work was recently published in the Journal of Antimicrobial Chemotherapy.
The discovery opens the door to new treatments for raw and processed meats and food preparation surfaces.
“This work is very exciting to me because it shows that this compound has the potential to reduce disease-causing bacteria in the environment and in our food supply,” says Dr. Xiaonan Lu, a postdoctoral researcher and lead author of the paper.
“This is the first step in developing or thinking about new intervention strategies,” says Michael Konkel, a co-author who has been researching Campylobacter jejuni for 25 years.
“Campylobacter“, says Konkel, “is simply the most common bacterial cause of food-borne illness in the United States and probably the world.” Some 2.4 million Americans are affected every year, according to the Centers for Disease Control and Prevention, with symptoms including diarrhea, cramping, abdominal pain and fever. The bacteria are also responsible for triggering nearly one-third of the cases of a rare paralyzing disorder known as Guillain-Barré syndrome.
Most infections stem from eating raw or undercooked poultry or foods that have been cross-contaminated via surfaces or utensils used to prepare poultry.
Lu and his colleagues looked at the ability of the garlic-derived compound, diallyl sulfide, to kill the bacterium when it is protected by a slimy biofilm that makes it 1,000 times more resistant to antibiotics than the free floating bacterial cell. They found the compound can easily penetrate the protective biofilm and kill bacterial cells by combining with a sulfur-containing enzyme, subsequently changing the enzyme’s function and effectively shutting down cell metabolism.
The researchers found the diallyl sulfide was as effective as 100 times as much of the antibiotics erythromycin and ciprofloxacin and would often work in a fraction of the time.
Two previous works published last year by Lu and WSU colleagues in Applied and Environmental Microbiology and Analytical Chemistry found diallyl sulfide and other organosulfur compounds effectively kill important foodborne pathogens, such as Listeria monocytogenes and Escherichia coli O157:H7.
Konkel cautions that the recent work is still at the basic stage, well removed from an actual application. While eating garlic is a generally healthy practice, it is unlikely to prevent Campylobacter-related food poisoning. However, “diallyl sulfide may be useful in reducing the levels of the Campylobacter in the environment and to clean industrial food processing equipment, as the bacterium is found in a biofilm in both settings.”
“Diallyl sulfide could make many foods safer to eat”, says Barbara Rasco, a co-author on all three recent papers and Lu’s advisor for his doctorate in food science. “It can be used to clean food preparation surfaces and as a preservative in packaged foods like potato and pasta salads, coleslaw and deli meats”.
“This would not only extend shelf life but it would also reduce the growth of potentially bad bacteria,” she says.
Large-scale analysis finds majority of clinical trials don’t provide meaningful evidence
DURHAM, N.C.— The largest comprehensive analysis of ClinicalTrials.gov finds that clinical trials are falling short of producing high-quality evidence needed to guide medical decision-making. The analysis, published today in JAMA, found the majority of clinical trials is small, and there are significant differences among methodical approaches, including randomizing, blinding and the use of data monitoring committees.
“Our analysis raises questions about the best methods for generating evidence, as well as the capacity of the clinical trials enterprise to supply sufficient amounts of high quality evidence to ensure confidence in guideline recommendations,” said Robert Califf, M.D., first author of the paper, vice chancellor for clinical research at Duke University Medical Center, and director of the Duke Translational Medicine Institute.
The analysis was conducted by the Clinical Trials Transformation Initiative (CTTI), a public private partnership founded by the Food and Drug Administration (FDA) and Duke. It extends the usability of the data in ClinicalTrials.gov for research by placing the data through September 27, 2010 into a database structured to facilitate aggregate analysis. This publically accessible database facilitates the assessment of the clinical trials enterprise in a more comprehensive manner than ever before and enables the identification of trends by study type.
The National Library of Medicine (NLM), a part of the National Institutes of Health, developed and manages ClinicalTrials.gov. This site maintains a registry of past, current, and planned clinical research studies.
“Since 2007, the Food and Drug Administration Amendment Act has required registration of clinical trials, and the expanded scope and rigor of trial registration policies internationally is producing more complete data from around the world,” stated Deborah Zarin, MD, director, ClinicalTrials.gov, and assistant director for clinical research projects, NLM. “We have amassed over 120,000 registered clinical trials. This rich repository of data has a lot to say about the national and international research portfolio.”
This CTTI project was a collaborative effort by informaticians, statisticians and project managers from NLM, FDA and Duke. CTTI comprises more than 60 member organizations with the goal of identifying practices that will improve the quality and efficiency of clinical trials.
“Since the ClinicalTrials.gov registry contains studies sponsored by multiple entities, including government, industry, foundations and universities, CTTI leaders recognized that it might be a valuable source for benchmarking the state of the clinical trials enterprise,” stated Judith Kramer, MD, executive director of CTTI.
The project goal was to produce an easily accessible database incorporating advances in informatics to permit a detailed characterization of the body of clinical research and facilitate analysis of groups of studies by therapeutic areas, by type of sponsor, by number of participants and by many other parameters.
“Analysis of the entire portfolio will enable the many entities in the clinical trials enterprise to examine their practices in comparison with others,” says Califf. “For example, 96% of clinical trials have ≤1000 participants, and 62% have ≤ 100. While there are many excellent small clinical trials, these studies will not be able to inform patients, doctors and consumers about the choices they must make to prevent and treat disease.”
The analysis showed heterogeneity in median trial size, with cardiovascular trials tending to be twice as large as those in oncology and trials in mental health falling in the middle. It also showed major differences in the use of randomization, blinding, and data monitoring committees, critical issues often used to judge the quality of evidence for medical decisions in clinical practice guidelines and systematic overviews.
“These results reinforce the importance of exploration, analysis and inspection of our clinical trials enterprise,” said Rachel Behrman Sherman, MD, associate director for the Office of Medical Policy at the FDA’s Center for Drug Evaluation and Research. “Generation of this evidence will contribute to our understanding of the number of studies in different phases of research, the therapeutic areas, and ways we can improve data collection about clinical trials, eventually improving the quality of clinical trials.”
Everyday fish oil capsule may provide kidney-related benefits
Lawson research suggests significant improvements to hemodialysis patient outcomes
LONDON, ON – Over the past decade, there has been a steady stream of information promoting the health benefits of fish oil capsules. According to Dr. Louise Moist, a Scientist at Lawson Health Research Institute, fish oil may also improve outcomes for kidney patients undergoing hemodialysis.
Hemodialysis can be delivered through arteriovenous (AV) grafts, artificial vessels created to join an artery to a vein. Unfortunately, AV grafts are prone to congestion and clotting, causing disruptions to treatment and a need for surgical correction.
Research suggests fish oil could prevent AV grafts from clotting and reduce related cardiovascular events. In a new multi-centre, randomized clinical trial, Dr. Moist and her colleagues followed patients undergoing hemodialysis using new AV grafts for 12 months after creation. Patients were assigned to daily doses of either four fish oil capsules, or four placebo capsules.
Results show those patients taking fish oil experienced a lower rate of graft failure, with half as many grafts lost to clotting. The amount of time until clotting occurred increased, and fewer corrective interventions were required. In addition, those taking fish oil had lower blood pressure, and lower rates of heart attacks, heart failure and other cardiac-related events.
“This study provides very exciting results,” Dr. Moist says. “Fish oil did not fix all the problems with grafts but it reduced the number of costly, time consuming procedures for patients already receiving a very burdensome treatment with dialysis. It is not often we have such encouraging results that benefit patients’ quality of life and reduce health care costs. “
Moving forward Dr. Moist and her colleagues are planning a second study focusing more intensely on blood pressure and cardiovascular events as related to fish oil. Dr. Moist is hopeful these results could provide a safer way to avoid cardiovascular complications and extend the patency of the graft during hemodialysis.
The trial was led by Dr. Charmaine Lok at Toronto General Hospital, and funded by the Canadian Institutes of Health Research (CIHR) and the Physicians Services Incorporated (PSI) Foundation. The full study will be released today in the Journal of the American Medical Association.
Eating fish, chicken, nuts may lower risk of Alzheimer’s disease
MINNEAPOLIS – A new study suggests that eating foods that contain omega-3 fatty acids, such as fish, chicken, salad dressing and nuts, may be associated with lower blood levels of a protein related to Alzheimer’s disease and memory problems. The research is published in the May 2, 2012, online issue of Neurology®, the medical journal of the American Academy of Neurology.
“While it’s not easy to measure the level of beta-amyloid deposits in the brain in this type of study, it is relatively easy to measure the levels of beta-amyloid in the blood, which, to a certain degree, relates to the level in the brain,” said study author Nikolaos Scarmeas, MD, MS, with Columbia University Medical Center in New York and a member of the American Academy of Neurology.
For the study, 1,219 people older than age 65, free of dementia, provided information about their diet for an average of 1.2 years before their blood was tested for the beta-amyloid. Researchers looked specifically at 10 nutrients, including saturated fatty acids, omega-3 and omega-6 polyunsaturated fatty acids, mono-unsaturated fatty acid, vitamin E, vitamin C, beta-carotene, vitamin B12, folate and vitamin D.
The study found that the more omega-3 fatty acids a person took in, the lower their blood beta-amyloid levels. Consuming one gram of omega-3 per day (equal to approximately half a fillet of salmon per week) more than the average omega-3 consumed by people in the study is associated with 20 to 30 percent lower blood beta-amyloid levels.
Other nutrients were not associated with plasma beta-amyloid levels. The results stayed the same after adjusting for age, education, gender, ethnicity, amount of calories consumed and whether a participant had the APOE gene, a risk factor for Alzheimer’s disease.
“Determining through further research whether omega-3 fatty acids or other nutrients relate to spinal fluid or brain beta-amyloid levels or levels of other Alzheimer’s disease related proteins can strengthen our confidence on beneficial effects of parts of our diet in preventing dementia,” said Scarmeas.
NSAIDs and cardiovascular risk explained
PHILADELPHIA – After nearly 13 years of study and intense debate, a pair of new papers from the Perelman School of Medicine, at the University of Pennsylvania have confirmed exactly how a once-popular class of anti-inflammatory drugs leads to cardiovascular risk for people taking it.
It has been almost eight years since Vioxx® was withdrawn by Merck from the market, provoking an intense controversy about the role inhibitors of the enzyme COX-2 play in causing heart attacks and strokes. Since then, other drugs in the class from Pfizer, Novartis, and Merck have been withdrawn (Bextra®); have failed to be approved (Arcoxia®, Prexige®); or have been retained on the market in the US with a “black box” warning on the label (Celebrex®).
COX-2 is one of two similar enzymes that churn out short-lived fats called prostaglandins. The other, COX-1, works in platelets — cells in the blood that stick together in the first stages of clotting. COX-2 is active in the cells that line blood vessels. These enzymes have diverse, potent, and often contrasting effects in the body. For example, low-dose aspirin protects against heart attacks and strokes by blocking COX-1 from forming a prostaglandin called thromboxane A2 in platelets. On the other hand, COX-2 is the more important source of prostaglandins, particularly one called prostocyclin, which causes pain and inflammation.
COX-2 inhibitors are a subclass of nonsteroidal anti-inflammatory drugs (NSAIDs), among the most common drugs consumed on the planet. Older NSAIDs include drugs like Naprosyn, which inhibits mostly COX-1; Advil®, which inhibits COX-1 and COX-2; and Voltaren® and Mobic®, which mostly inhibit COX-2. The newer drugs were developed because targeting COX-2 reduced serious gastrointestinal side effects like bleeding ulcers. However, aggressive direct-to-consumer advertising meant that drugs like Vioxx and Celebrex were taken mostly by patients who had never had the GI problems with the older, cheaper NSAIDs.
Just before Celebrex and Vioxx were approved and launched, a group led by Garret FitzGerald, MD, chair of the department of Pharmacology, and director of the Institute for Translational Medicine and Therapeutics at Penn, observed that both drugs suppressed prostacyclin in humans, as reflected by its major metabolite in urine, PGI-M. Based on the potentially cardioprotective properties of prostacyclin, which relaxes blood vessels and unglues platelets in test tube experiments, the team predicted that shutting down this protection with inhibitors would cause heart attacks and strokes.
More than 10 years later, it is now clear what the COX inhibitors do in the body. Eight placebo-controlled, randomized trials, performed to find new uses of these drugs, showed that they posed a cardiovascular hazard, similar in magnitude to that resulting from being a smoker or a diabetic, notes FitzGerald. “Despite this, controversy has continued about how all this came about, until now.”
Arguments against the proposed mechanism were threefold. First, it was proposed that COX-2 didn’t exist under normal circumstances in the blood-vessel lining and PGI-M came from some other source. The kidneys were suggested as the source by some researchers. Second, even if blood-vessel prostacyclin was blocked, other protective mechanisms, especially formation of nitric oxide (NO) would take over. And third, although NSAIDs elevate blood pressure, it was proposed that this observation was unrelated to COX-2 and treating high blood pressure would deal with the problem.
FitzGerald’s group has now “closed the loop” with its earlier clinical studies and answered these questions in a paper just published in Science Translational Medicine. In it, they confirm that COX-2 is expressed in cells lining blood vessels and that selectively removing it predisposes mice to blood clotting and high blood pressure. These mice, just like humans taking COX-2 inhibitors, also see a fall in PGI-M. What’s more, the Penn group discovered that COX-2 in lining cells controls the expression of eNOS, the enzyme that makes NO in the body. “So, rather than replacing the missing prostacyclin, as others have proposed, NO is lost and amplifies the effects of COX-2 inhibition on the cardiovascular system,” says FitzGerald.
Indeed, the lost NO may not be the only step that magnifies the effects of losing prostacyclin. In a second paper, published in April 2012, in the Proceedings of the National Academy of Sciences, FitzGerald’s group shows that arachidonic acid, the fat broken down by COX-2 to make prostacyclin, can be shunted down another pathway to make a new series of dangerous fats called leukotrienes when COX-2 is disrupted.
Clinical studies have shown that those most at risk from COX-2 inhibitors are patients who already have heart disease. However, the Penn group now suggests broader implications. Here, the group resolves one aspect of the controversy, showing that COX-2 disruption causes hardening of the arteries in mice. This result is provocative because randomized trials of Vioxx and Celebrex in patients at low risk of heart disease detected an increase in heart attacks after patients had been taking the drugs for more than a year. These current Penn studies raise the disturbing prospect that heart-healthy patients taking NSAIDs for prolonged periods might be gradually increasing their risk of heart attacks and strokes by progressively hardening their arteries.
“However, it’s not all bad news,” says FitzGerald. This risk of hardening of the arteries was diminished in mice by reducing leukotriene formation, via blocking a critical protein called the 5-lipoxygenase activating protein, or FLAP. Inhibitors of FLAP are already in trials in humans to see if they work in asthma. Perhaps, FitzGerald concludes, they can now find an additional use — protecting the heart from NSAIDs.
Increased fructose consumption may deplete cellular energy in patients with obesity and diabetes
DURHAM, N.C. — Obese people who consume increased amounts of fructose, a type of sugar that is found in particular in soft drinks and fruit juices, are at risk for nonalcoholic fatty liver disease (NFALD) and more its more severe forms, fatty inflammation and scarring.
Now researchers at Duke University Medical Center believe they better understand what mechanism may account for fructose-related liver injury.
Chronic fructose consumption in a diet puts people at risk for depleting their store of critically important molecules called ATP, which provide liver cells (and other body cells) energy for important cellular processes, including metabolism.
“The stores of liver ATP are decreased in obese and/or diabetic individuals who chronically consume increased amounts of fructose-containing beverages,” said lead author Manal Abdelmalek, M.D., MPH, Associate Professor of Gastroenterology & Hepatology at Duke.
The study was published online at the Hepatology journal site on May 2.
Nonalcoholic fatty liver disease is currently the leading cause of chronic liver disease in the United States. This condition can lead to elevated liver enzymes, inflammation and rarely even advanced scarring (cirrhosis) in individuals who do not drink alcohol. In obesity and/or diabetes, the ability of the cells to optimally make ATP may already be impaired.
Unlike other simple sugars, fructose requires ATP for its metabolism. The inability to optimally generate cellular energy as well and the continued consumption of ATP from chronic fructose ingestion can result in the liver’s depletion of energy. ATP depletion may increase risk for inflammation and scarring in the liver.
“The state of being insulin resistant impairs the ability of a vital enzyme, AMP kinase, to make new ATP molecules,” Abdelmalek explained. “Increased fructose consumption, and excess utilization of ATP favors the increase in molecules that lead to increased fatty acid synthesis as well as increased uric acid.”
The researchers also noted that more uric acid is produced in the body when excess fructose is consumed. Too much uric acid is associated with conditions that include gout, high blood pressure, cardiovascular disease, type 2 diabetes, metabolic syndrome and uric acid stones, a form of kidney stones.
The silver lining is that measuring the amount of uric acid in these individuals may help doctors predict the presence and monitor the severity of nonalcoholic fatty liver disease, Abdelmalek said.
Research Abdelmalek published in the Journal of Hepatology in 2008 showed that, within a small subset of patients, fructose-containing beverages were associated with NAFLD compared to patients with comparable weight, age, and gender. Her 2010 research, published in Hepatology, went further and linked fructose with the liver injury and scarring (fibrosis).
The current study evaluated adults enrolled in the NIH-sponsored Look Ahead Fatty Liver Disease Ancillary Study headed by senior author Jeanne M.Clark, M.D., MPH, at Johns Hopkins University. The researchers analyzed dietary questionnaires collected in patients who underwent a magnetic resonance imaging to measure liver fat as well as an intravenous fructose challenge to evaluate the liver’s ATP stores and response to ATP depletion.
Patients enrolled in the Look Ahead study had been counseled on lower dietary sugar consumption for the management of diabetes. Despite the overall lower levels of fructose use in this study population, the researchers found evidence of liver ATP depletion in those who consumed more fructose.
“The fact we found a difference in liver ATP stores at lower levels of dietary fructose intake does suggest that higher fructose consumption (as would occur with the consumption of processed food and sweetened beverages) could deplete the liver of energy and thus risk causing worse metabolic problems and potentially even liver injury,” Abdelmalek said. In the past 30 years, Abdelmalek and authors wrote, fructose consumption has more than doubled.
Unmasking black pepper’s secrets as a fat fighter
A new study provides a long-sought explanation for the beneficial fat-fighting effects of black pepper. The research, published in ACS’ Journal of Agricultural and Food Chemistry, pinpoints piperine — the pungent-tasting substance that gives black pepper its characteristic taste, concluding that piperine also can block the formation of new fat cells.
Soo-Jong Um, Ji-Cheon Jeong and colleagues describe previous studies indicating that piperine reduces fat levels in the bloodstream and has other beneficial health effects. Black pepper and the black pepper plant, they note, have been used for centuries in traditional Eastern medicine to treat gastrointestinal distress, pain, inflammation and other disorders. Despite that long medicinal history, scientists know little about how piperine works on the innermost molecular level. The scientists set out to get that information about piperine’s anti-fat effects.
Their laboratory studies and computer models found that piperine interferes with the activity of genes that control the formation of new fat cells. In doing so, piperine may also set off a metabolic chain reaction that helps keep fat in check in other ways. The group suggests that the finding may lead to wider use of piperine or black-pepper extracts in fighting obesity and related diseases
Low oxygen levels could drive cancer growth
Athens, Ga. – Low oxygen levels in cells may be a primary cause of uncontrollable tumor growth in some cancers, according to a new University of Georgia study. The authors’ findings run counter to widely accepted beliefs that genetic mutations are responsible for cancer growth.
If hypoxia, or low oxygen levels in cells, is proven to be a key driver of certain types of cancer, treatment plans for curing the malignant growth could change in significant ways, said Ying Xu, Regents-Georgia Research Alliance Eminent Scholar and professor of bioinformatics and computational biology in the Franklin College of Arts and Sciences.
The research team analyzed samples of messenger RNA data—also called transcriptomic data—from seven different cancer types in a publicly available database. They found that long-term lack of oxygen in cells may be a key driver of cancer growth. The study was published in the early online edition of the Journal of Molecular Cell Biology.
Previous studies have linked low oxygen levels in cells as a contributing factor in cancer development, but not as the driving force for cancer growth. High incidence rates of cancer around the world cannot be explained by chance genetic mutations alone, Xu said. He added that bioinformatics, which melds biology and computational science, has allowed researchers to see cancer in a new light. Gene-level mutations may give cancer cells a competitive edge over healthy cells, but the proposed new cancer growth model does not require the presence of common malfunctions such as a sudden proliferation of oncogenes, precursors to cancer cells.
“Cancer drugs try to get to the root—at the molecular level—of a particular mutation, but the cancer often bypasses it,” Xu said. “So we think that possibly genetic mutations may not be the main driver of cancer.”
Much of cancer research so far has focused on designing drug treatments that counteract genetic mutations associated with a particular type of cancer. In their study, the researchers analyzed data downloaded from the Stanford Microarray Database via a software program to detect abnormal gene expression patterns in seven cancers: breast, kidney, liver, lung, ovary, pancreatic and stomach. The online database allows scientists to examine information from microarray chips, which are small glass slides containing large amounts of gene material.
Xu relied on the gene HIF1A as a biomarker of the amount of molecular oxygen in a cell. All seven cancers showed increasing amounts of HIF1A, indicating decreasing oxygen levels in the cancer cells.
Low oxygen levels in a cell interrupt the activity of oxidative phosphorylation, a term for the highly efficient way that cells normally use to convert food to energy. As oxygen decreases, the cells switch to glycolysis to produce their energy units, called ATP. Glycolysis is a drastically less efficient way to obtain energy, and so the cancer cells must work even harder to obtain even more food, specifically glucose, to survive. When oxygen levels dip dangerously low, angiogenesis, or the process of creating new blood vessels, begins. The new blood vessels provide fresh oxygen, thus improving oxygen levels in the cell and tumor and slowing the cancer growth—but only temporarily.
“When a cancer cell gets more food, it grows; this makes the tumor biomass bigger and even more hypoxic. In turn, the energy-conversion efficiency goes further down, making the cells even more hungry and triggering the cells to get more food from blood circulation, creating a vicious cycle. This could be a key driver of cancer,” Xu said.
Xu explained that this new cancer-growth model could help explain why many cancers become drug resistant so quickly—often within three to six months. He stressed the importance of testing the new model through future experimental cancer research. If the model holds, researchers will need to search for methods to prevent hypoxia in cells in the first place, which could result in a sea change in cancer treatment.
Beehive extract shows potential as prostate cancer treatment
Proteomics reveals how ancient remedy slows prostate tumor cell proliferation
An over-the-counter natural remedy derived from honeybee hives arrests the growth of prostate cancer cells and tumors in mice, according to a new paper from researchers at the University of Chicago Medicine.
Caffeic acid phenethyl ester, or CAPE, is a compound isolated from honeybee hive propolis, the resin used by bees to patch up holes in hives. Propolis has been used for centuries as a natural remedy for conditions ranging from sore throats and allergies to burns and cancer. But the compound has not gained acceptance in the clinic due to scientific questions about its effect on cells.
In a paper published in Cancer Prevention Research, researchers combined traditional cancer research methods with cutting-edge proteomics to find that CAPE arrests early-stage prostate cancer by shutting down the tumor cells’ system for detecting sources of nutrition.
“If you feed CAPE to mice daily, their tumors will stop growing. After several weeks, if you stop the treatment, the tumors will begin to grow again at their original pace,” said Richard B. Jones, PhD, assistant professor in the Ben May Department for Cancer Research and Institute for Genomics and Systems Biology and senior author of the study. “So it doesn’t kill the cancer, but it basically will indefinitely stop prostate cancer proliferation.”
Natural remedies isolated from plant and animal products are often marketed as cure-alls for a variety of maladies, usually based on vague antioxidant and anti-inflammatory claims. While substances such as ginseng or green tea have been occasionally tested in laboratories for their medicinal properties, scientific evidence is commonly lacking on the full biological effects of these over-the-counter compounds.
“It’s only recently that people have examined the mechanism by which some of these herbal remedies work,” Jones said. “Our knowledge about what these things are actually doing is a bit of a disconnected hodge-podge of tests and labs and conditions. In the end, you’re left with a broad, disconnected story about what exactly these things are doing and whether or not they would be useful for treating disease.”
To study the purported anti-cancer properties of CAPE, first author Chih-Pin Chuu (now at the National Health Research Institutes in Taiwan) tested the compound on a series of cancer cell lines. Even at the low concentrations expected after oral administration, CAPE successfully slowed the proliferation of cultured cells isolated from human prostate tumors.
CAPE was also effective at slowing the growth of human prostate tumors grafted into mice. Six weeks of treatment with the compound decreased tumor volume growth rate by half, but when CAPE treatment was stopped, tumor growth resumed its prior rate. The results suggested that CAPE stopped cell division rather than killing cancerous cells.
To determine the cellular changes that mediated this effect, the researchers then used an innovative proteomics technique invented by Jones and colleagues called the “micro-western array.” Western blots are a common laboratory tool used to measure the changes in protein levels and activity under different conditions. But whereas only one or a few proteins at a time can be monitored with Western blots, micro-western arrays allow researchers to survey hundreds of proteins at once from many samples.
Chuu, Jones and their colleagues ran micro-western arrays to assess the impact of CAPE treatment on the proteins of cellular pathways involved in cell growth – experiments that would have been prohibitively expensive without the new technique.
“What this allowed us to do is screen about a hundred different proteins across a broad spectrum of signaling pathways that are associated with all sorts of different outcomes. You can pick up all the pathways that are affected and get a global landscape view, and that’s never been possible before,” Jones said. “It would have taken hundreds of Westerns, hundreds of technicians, and a very large amount of money for antibodies.”
The micro-western array results allowed researchers to quickly build a new model of CAPE’s cellular effects, significantly expanding on previous work that studied the compound’s mechanisms. Treatment with CAPE at the concentrations that arrested cancer cell growth suppressed the activity of proteins in the p70S6 kinase and Akt pathways, which are important sensors of sufficient nutrition that can trigger cell proliferation.
“It appears that CAPE basically stops the ability of prostate cancer cells to sense that there’s nutrition available,” Jones said. “They stop all of the molecular signatures that would suggest that nutrition exists, and the cells no longer have that proliferative response to nutrition.”
The ability of CAPE to freeze cancer cell proliferation could make it a promising co-treatment alongside chemotherapies intended to kill tumor cells. Jones cautioned that clinical trials would be necessary before CAPE could be proven effective and safe for this purpose in humans. But the CAPE experiments offer a precedent to unlock the biological mechanisms of other natural remedies as well, perhaps allowing these compounds to cross over to the clinic.
“A typical problem in bringing some of these herbal remedies into the clinic is that nobody knows how they act, nobody knows the mechanism, and therefore researchers are typically very hesitant to add them to any pharmaceutical treatment strategy,” Jones said. “Now we’ll actually be able to systematically demonstrate the parts of cell physiology that are affected by these compounds.”
Scientific Evidence Proves why Healers See the “Aura” of People
• University of Granada researchers affirm that healers present synesthesia, a neuropsychological phenomenon involving a “mingling” of the senses.
• The results of this study have been published in the prestigious journal Consciousness and Cognition.
• The authors remark the significant “placebo effect” that healers have on ill people.
Researchers in Spain have found that many of the individuals claiming to see the aura of people –traditionally called “healers” or “quacks”– actually present the neuropsychological phenomenon known as “synesthesia” (specifically, “emotional synesthesia”). This might be a scientific explanation of their alleged “virtue”. In synesthetes, the brain regions responsible for the processing of each type of sensory stimuli are intensely interconnected. This way, synesthetes can see or taste a sound, feel a taste, or associate people with a particular color.
The study was conducted by the University of Granada Department of Experimental Psychology Óscar Iborra, Luis Pastor and Emilio Gómez Milán, and has been published in the prestigious journal Consciousness and Cognition. This is the first time that a scientific explanation is provided on the esoteric phenomenon of the aura, a supposed energy field of luminous radiation surrounding a person as a halo, which is imperceptible to most human beings.
In neurological terms, synesthesia is due to cross-wiring in the brain of some people (synesthetes); in other words, synesthetes present more synaptic connections than “normal” people. “These extra connections cause them to automatically establish associations between brain areas that are not normally interconnected”, professor Gómez Milán explains. Many healers claiming to see the aura of people might have this condition.
The case of the “Santón de Baza”
The University of Granada researchers remark that “not all healers are synesthetes, but there is a higher prevalence of this phenomenon among them. The same occurs among painters and artists, for example”. To carry out this study, the researchers interviewed some synesthetes as the healer from Granada “Esteban Sánchez Casas”, known as “El Santón de Baza”.
Many people attribute “paranormal powers” to El Santón, such as his ability to see the aura of people “but, in fact, it is a clear case of synesthesia”, the researchers explain. El Santón presents face-color synesthesia (the brain region responsible for face recognition is associated with the color-processing region); touch-mirror synesthesia (when the synesthete observes a person who is being touched or is experiencing pain, s/he experiences the same); high empathy (the ability to feel what other person is feeling), and schizotypy (certain personality traits in healthy people involving slight paranoia and delusions). “These capacities make synesthetes have the ability to make people feel understood, and provide them with special emotion and pain reading skills”, the researchers explain.
In the light of the results obtained, the researchers remark the significant “placebo effect” that healers have on people, “though some healers really have the ability to see people’s auras and feel the pain in others due to synesthesia”. Some healers “have abilities and attitudes that make them believe in their ability to heal other people, but it is actually a case of self-deception, as synesthesia is not an extrasensory power, but a subjective and ‘adorned’ perception of reality”, the researchers state.
• Auras in mysticism and synaesthesia: a comparison. Consciousness and cognition, 2012, 21(1), 258-268 de Milán, Iborra, Pastor y otros. Avalaible at: http://www.sciencedirect.com/science/article/pii/S1053810011002868
These reports are done with the appreciation of all the Doctors, Scientist, and other
Medical Researchers who sacrificed their time and effort. In order to give people the
ability to empower themselves. Without the base aspirations for fame, or fortune. Just honorable people, doing honorable things.