OREGON STATE UNIVERSITY

college of pharmacy

Proteins discovered in gonorrhea may offer new approach to treatment

CORVALLIS, Ore. – Researchers at Oregon State University have discovered novel proteins in, or on the surface of the bacteria that causes gonorrhea, which offer a promising new avenue of attack against a venereal disease that is showing increased resistance to the antibiotics used to treat it.

Only a single, third-generation cephalosporin antibiotic still shows good efficacy against gonorrhea, creating a race against time to find some alternative way to treat this disease that can have serious health effects. It’s the second most commonly reported infectious disease in the United States.

Investigations based on these proteins might lead to new ways to combat the disease, including a vaccine, new types of drugs to block the growth of the bacteria, or even restoring the efficacy of some older antibiotics that have lost their usefulness, said Aleksandra Sikora, an assistant professor in the OSU College of Pharmacy.

“This could be a milestone in finding new ways to treat a global problem,” Sikora said. “It appears that one or more of these proteins, either within the bacterial cell envelope or on its surface, are essential to its growth and survival. Now we have a new target to aim at.”

World health officials have raised alarms that the growing resistance of gonorrhea to antibiotics could cause it to become untreatable. There are more than 60 million cases of this venereal disease treated around the world every year – and 300,000 just in the U.S. – in people who experience clear symptoms. But some of the worst damage is done among millions of other cases that are very mild or asymptomatic.

Such symptomless infections, most common in women, can cause pelvic inflammatory disease, ectopic pregnancy and infertility, as well as increase the transmission of the HIV virus. Gonorrhea can also affect joints and heart valves, and cause blindness in infants infected during birth.

The new findings were just published in Molecular and Cellular Proteomics, by researchers from OSU and the Fred Hutchinson Cancer Research Center. The research has been supported by OSU and the Medical Research Foundation of Oregon.

Using the evolving science of proteomics - which is the large-scale, high-throughput study of proteins and their functions - researchers identified a plethora of proteins that reside in a space in the gonorrhea bacteria, an “envelope” and its small outpouchings, or membrane vesicles.

This cell envelope shields the interior of gonorrhea from the environment and is essential for survival of the microbes, as well as their ability to cause disease. The proteins localized there help acquire nutrients, provide a permeability barrier, suppress the immune response and keep the bacteria fit.

Other proteins on the bacteria surface also help it attach to the host. The membrane vesicles are spherical structures that contain proteins and DNA, and are involved in antibiotic resistance, microbe communication and delivery of factors important for infection.

Any or all of these proteins may now offer a way to attack the survival and spread of the gonorrhea bacteria, Sikora said. None of them have yet been used for that purpose.

“Some past approaches to create a gonorrhea vaccine failed because they were focused on proteins essential to infection, which were quite unstable,” she said. “Because they were changing so constantly they were unsuitable for a vaccine. The proteins we’ve now identified offer a much more stable and vulnerable target.”

Researchers have already quantified their abundance of these cell envelope proteins and are learning their basic function, and in continued studies will screen compounds for activity against some of them.

“With this information, the chance to create either a vaccine or new drug treatments is very promising,” Sikora said.

The gonorrhea bacteria, Neisseria gonorrhoeae, is a pathogen specific to humans and no other animals. It dates to antiquity and it’s uncertain when it first developed. Many epidemics have been reported in world history.

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Aleksandra Sikora, 541-737-5811

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One in five older Americans take medications that work against each other

PORTLAND, Ore. – About three out of four older Americans have multiple chronic health conditions, and more than 20 percent of them are being treated with drugs that work at odds with each other – the medication being used for one condition can actually make the other condition worse.

This approach of treating conditions “one at a time” even if the treatments might conflict with one another is common in medicine, experts say, in part because little information exists to guide practitioners in how to consider this problem, weigh alternatives and identify different options.

One of the first studies to examine the prevalence of this issue, however, found that 22.6 percent of study participants received at least one medication that could worsen a coexisting condition. The work was done by researchers in Connecticut and Oregon, and published in PLOS One.

In cases where this “therapeutic competition” exists, the study found that it changed drug treatments in only 16 percent of the cases. The rest of the time, the competing drugs were still prescribed.

“Many physicians are aware of these concerns but there isn’t much information available on what to do about it,” said David Lee, an assistant professor in the Oregon State University/Oregon Health & Science University College of Pharmacy.

“Drugs tend to focus on one disease at a time, and most physicians treat patients the same way,” Lee said. “As a result, right now we’re probably treating too many conditions with too many medications. There may be times it’s best to just focus on the most serious health problem, rather than use a drug to treat a different condition that could make the more serious health problem even worse.”

More research in this field and more awareness of the scope of the problem are needed, the scientists said. It may be possible to make better value judgments about which health issue is of most concern, whether all the conditions should be treated, or whether this “competition” between drug treatments means one concern should go untreated. It may also be possible in some cases to identify ways to treat both conditions in ways that don’t conflict with one another.

A common issue, for example, is patients who have both coronary heart disease and chronic obstructive pulmonary disease, or COPD. Beta blockers are often prescribed to treat the heart disease, but those same drugs can cause airway resistance that worsens the COPD.

“There are several types of beta blocker that don’t cause this negative interaction, but many of the other types are still prescribed anyway,” Lee said. “It’s this type of information that would be of value in addressing these issues if it were more widely known and used.”

The chronic conditions in which competing therapies come into play include many common health concerns – coronary artery disease, diabetes, COPD, dementia, heart failure, hypertension, high cholesterol, osteoarthritis and others.

This study was done by researchers from OSU and the Yale University School of Medicine, with 5,815 community-living adults between the years 2007-09. The lead author of the study was Dr. Mary E. Tinetti at Yale University, and it was supported by the National Institutes of Health. The analysis included a nationally representative sample of older adults, and both men and women.

The research identified some of the most common competing chronic conditions, in which medications for one condition may exacerbate the other. They included hypertension and osteoarthritis; hypertension and diabetes; hypertension and COPD; diabetes and coronary artery disease; and hypertension and depression. These issues affect millions of older Americans.

“More than 9 million older adults in the U.S. are being prescribed medications that may be causing them more harm than benefit,” said Jonathan Lorgunpai, a medical student at the Yale School of Medicine and co-author of the study. “Not only is this potentially harmful for individual patients, it is also very wasteful for our health care system.”

Direct competition between medications is just one of the concerns, the report noted. Use of multiple medications can also lead to increased numbers of falls and delirium, dizziness, fatigue and anorexia.

The researchers pointed out that the presence of competing conditions does not necessarily contraindicate the use of needed medications, but rather the need for this competition to be more seriously considered in treatment.

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David Lee, 503-494-2258

Low birth weight reduces ability to metabolize drugs

PORTLAND, Ore. – Researchers have identified another concern related to low birth weight – a difference in how the body reacts to drugs, which may last a person’s entire life and further complicate treatment of illnesses or diseases that are managed with medications.

The findings add to the list of health problems that are already known to correspond to low birth weight, such as a predisposition for adult-onset diabetes, hypertension, and obesity. The implication, researchers say, is that low birth weight may not only cause increased disease, but it may also lessen the effectiveness of the drugs used to treat those diseases.

The research is among the first of its type to implicate low birth weight as a permanent factor in drug response. It was published in the European Journal of Pharmacology, by researchers from Oregon State University and Oregon Health & Science University. Funding was provided by both universities and the National Institutes of Health.

When more fully understood, low birth weight may be added to the list of factors already being considered in medication dosages, such as age, weight, gender and ethnicity. Some of that is already being done in infants. But right now it’s not one of the factors considered in adults, scientists say, and more work needs to be done before such consideration is warranted.

“Low birth weight affects the development of organs, as the fetus tries to finish development of the brain and, in a sense, sacrifice as necessary the ordinary development of organs such as the kidney,” said Ganesh Cherala, an assistant professor in the OSU/OHSU College of Pharmacy.  “But the kidney is one of the primary filtering agents in the body, and is directly involved in drug elimination.”

The kidneys of low birth weight individuals have a significantly impaired ability to filter and excrete foreign compounds, Cherala said. Since the biologic impact of a medication is affected by its absorption, metabolism and excretion, low birth weight individuals might be less able to excrete drugs.

However, the biologic processes are not that simple, Cherala said. Because of liver metabolism and other issues, in many cases low birth weight individuals end up having less response to a drug, instead of more.

“A pain killer, for instance, might end up being metabolized in the liver instead of making its way to the brain where it is supposed to function,” Cherala said. “You might need more of that same drug in a low birth weight individual to have the same effect.”

The complexities of these processes need additional study before recommendations could be made to alter drug dosages based on low birth weight status, Cherala said. But this issue could be important and should be further explored, he said.

In developed countries about 8-10 percent of individuals are born with low birth weight, but the issue is of higher concern in some developing nations where 20-25 percent of babies are born with this condition. Low birth weight is generally caused by poor nutrition during pregnancy.

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Ganesh Cherala, 503-418-0447

Genetic function discovered that could offer new avenue to cancer therapies

The study this story is based on is available online: http://rsc.li/1fcWMim

 

CORVALLIS, Ore. – Researchers at Oregon State University have discovered a genetic function that helps one of the most important “tumor suppressor” genes to do its job and prevent cancer.

Finding ways to maintain or increase the effectiveness of this gene – called Grp1-associated scaffold protein, or Grasp – could offer an important new avenue for human cancer therapies, scientists said.

The findings were just published in Photochemical and Photobiological Sciences, a journal of the Royal Society of Chemistry, by researchers from OSU and Oregon Health & Science University. The work was supported by the National Institute of Environmental Health Sciences.

The Grasp gene was studied in the skin of mice in this research, but is actually expressed at the highest levels in the brain, heart and lung, studies have shown. It appears to play a fundamental role in the operation of the p53 tumor suppressor gene, which is a focus of much modern cancer research.

The p53 gene is involved in repair of DNA damage and, if the damage is too great, causing a mutated cell to die before it can cause further problems, up to and including cancer. Dysfunction of p53 genetic pathways have been linked to more than half of all known cancers - particularly skin, esophageal, colon, pancreatic, lung, ovarian, and head and neck cancers.

“DNA mutations occur constantly in our bodies just by ordinary stresses, something as simple as exposure to sunlight for a few seconds,” said Mark Leid, professor of pharmacology and associate dean for research in the OSU College of Pharmacy, and one of the lead authors on this study.

“Just as constantly, the p53 gene and other tumor suppressors are activated to repair that damage,” Leid said. “And in cases where the damage is too severe to be repaired, p53 will cause the apoptosis, or death of the mutated cell. Almost all of the time, when they are working right, these processes prevent the formation of cancers.”

But the activity and function of p53 can sometimes decline or fail, Leid said, and allow development of cancer. Promising approaches to cancer therapy are now based on activating or stimulating the p53 protein to do its job.

The new study has found that the Grasp gene is significantly involved in maintaining the proper function of p53. When “Grasp” is not being adequately expressed, the p53 protein that has entered the cell nucleus to either repair or destroy the cell comes back out of the nucleus before its work is finished.

“It appears that a primary function of Grasp is to form sort of a halo around the nucleus of a damaged skin cell, and act as kind of a plug to keep the p53 cell inside the nucleus until its work is done,” Leid said. “A drug that could enhance Grasp function might also help enhance the p53 function, and give us a different way to keep this important tumor suppressor working the way that it is supposed to.

“This could be important,” he said.

OSU experts created laboratory mice that lacked the Grasp gene, and so long as the mice were reared in a perfect environment, they developed normally. But when they were exposed to even a mild environmental stress – ultraviolet light similar to moderate sun exposure – they began to develop cellular abnormalities much more rapidly than ordinary mice. Most significantly, mutated skin cells did not die as they should have.

In normal mice, the same moderate light exposure caused a rapid increase in expression of the Grasp gene, allowing the p53 protein to stay in the nucleus and normal protective mechanisms to do their work.

Most current cancer therapies related to the p53 tumor suppression process are directed toward activating the p53 protein, Leid said. A therapy directed toward improving the Grasp gene function would be a different approach toward the same goal, he said, and might improve the efficacy of treatment.

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Mark Leid, 541-737-5809

Drug interactions causing a significant impact on statin use

CORVALLIS, Ore. – A new study has found that many people who stopped taking cholesterol-lowering statin drugs were also taking an average of three other drugs that interfered with the normal metabolism of the statins.

The other drugs can contribute to a common side effect of taking statins - muscle pain – and often led people to discontinue use of a medication that could otherwise help save their life, researchers learned.

The interactions of many drugs with statins have been known of for some time, researchers said, but are not being adequately managed by physicians and pharmacists, who could often choose different medications or adjust dosages to retain the value of statin drugs without causing this side effect.

The research, done as part of a survey of more than 10,000 current and former statin users, found that use of medications which interfere with statin metabolism almost doubles the chance that a person will discontinue statin use due to muscle pain.

The issue is of growing importance because statin drugs are some of the most widely used medications in the world, proven to lower LDL, or “bad” cholesterol, and decrease the risk of heart attacks, heart disease, strokes and death. About 20 million people in the U.S. now take statins, and new guidelines have just been issued to further expand the types of health conditions for which statins may be of benefit. Based on those guidelines, the number of statin users could increase to more than 30 million.

The findings were published in the Journal of Clinical Lipidology by scientists from Oregon State University and four other universities or research institutes.

“We’ve known for some time of many medications that can interact with statins, but only now is it becoming clear that this is a significant contributor to the side effects, and often the reason some patients stop taking statins,” said Matt Ito, a professor in the OSU College of Pharmacy and president of the National Lipid Association, which funded this study.

“This issue is something physicians, pharmacists and patients all need to be more aware of,” Ito said. “There’s a lot we can do besides discontinue use of these valuable medications. You can change dosages, use drugs that don’t cause interactions, use different types of statins. Patients need to be proactive in understanding this issue and working with their health care providers to address it.”

Persons who have problems taking statins should discuss options with their physicians or pharmacists, Ito said, and not assume the drug has be to discontinued. A Medscape web site at http://reference.medscape.com/drug-interactionchecker also can help individuals learn more about possible interactions between statins and the full range of medications they may be taking.

Statins are usually well-tolerated, but in the recent survey, a muscle-related side effect was reported by 29 percent of participants. In former statin users, 62 percent of the people said that side effects, mostly muscle pain, were the reason they stopped taking the drugs.

There are many drugs that can interfere with statin metabolism, increase systemic exposure to the statin and raise the risk of this muscle pain, the researchers said in their report. This can include some common antibiotics, cardiovascular drugs, and others taken for treatment of cancer, mental health, HIV treatment and other conditions.

These interactions are not always adequately considered by physicians and pharmacists, however. One recent report found that as many as 20 percent of significant statin-drug interactions were missed in 64 pharmacies.

Besides drug interactions, statin side effects are also more common in women and associated with increasing age, history of cardiovascular disease, and some other conditions. Statin discontinuation has been associated with increased cardiovascular morbidity and death.

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Matt Ito, 503-494-3657

Problems continue with inappropriate prescription of antipsychotic drugs

PORTLAND, Ore. – Low-dose, antipsychotic medications are continuing to be widely prescribed, a new analysis suggests, even though it’s likely many of the prescriptions are for conditions where there’s weak evidence of their effectiveness and serious risks remain.

The problem is less severe than it used to be, due to changes in marketing of the drugs, researchers said. A $520 million settlement against the manufacturer of the medication of largest concern, quetiapine, reduced “off-label” promotion of the drug for conditions not approved by the FDA, and may have led to declines in this type of sub-therapeutic use.

However, an analysis of Medicaid patients from 2004-08 shows that many of these powerful medications – which are meant to be used for severe mental illness such as schizophrenia and bipolar disorder – are still being prescribed at lower doses, possibly for conditions such as anxiety, attention deficit disorder and even insomnia.

The findings were made by researchers from Oregon State University, Oregon Health and Science University, the University of Colorado and Dartmouth Institute for Health Policy and Clinical Practice. They were published in Pharmacoepidemiology and Drug Safety, in work supported by the National Institutes of Health.

“The reduction in low-dose prescribing suggests there has been a decline in off-label use of quetiapine, but it’s still a problem that people should be aware of,” said Daniel Hartung, an associate professor in the OSU College of Pharmacy.

“In far too many cases, these drugs are being prescribed for conditions in which there’s less-clear evidence of efficacy and safety,” Hartung said. “Other medications are available that have been shown to work and usually cost less. And the side effects of these antipsychotic drugs include serious concerns such as increases in blood sugar, cholesterol, weight gain and an increased risk of diabetes.”

The drugs at first were used mostly by psychiatrists treating serious mental illness, but in recent years have been much more widely administered by general practitioners. Too often that was done without careful screening of blood sugar and cholesterol, a past study found, since use of the drugs can increase the risk of diabetes in a patient population already more prone to that condition.

Quetiapine, sold under the trade name Seroquel, was one serious concern. It was promoted by its manufacturer for a range of uses not approved by the Food and Drug Administration, and widely prescribed at lower doses for dementia, post-traumatic stress, anxiety, attention deficit and insomnia. It and some other drugs have since gained approval for use in treatment-resistant depression, but in many cases the inappropriate prescription of these medications is continuing.

The investigation of this problem was prompted by state Medicaid agencies, researchers said, because of an explosion in the use of costly antipsychotic drugs from 1997 to 2007. During that period, the market more than quadrupled from $1.7 billion to $7.4 billion.

One estimate indicated that second-generation antipsychotic medications accounted for more than 16 percent of total Medicaid pharmacy spending.At least five state Medicaid programs are exploring policy options to curtail the use of sub-therapeutic doses of quetiapine, the researchers said in their report.

States concerned about these issues may wish to first evaluate policies that restrict potentially safer options, such as other drugs that could be used off-label as a sedative, the scientists recommended. This might avoid driving physicians toward prescribing the antipsychotic medications.

“These issues have been reported nationally and policy discussions have taken place,” Hartung said. “But changes in the prescribing practices of the medical profession are sometimes slow to come.”

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Daniel Hartung, 503-494-4720

Nanotech system, cellular heating may improve treatment of ovarian cancer

The study this story is based on is available online: http://bit.ly/18PLoY4

 

CORVALLIS, Ore. – The combination of heat, chemotherapeutic drugs and an innovative delivery system based on nanotechnology may significantly improve the treatment of ovarian cancer while reducing side effects from toxic drugs, researchers at Oregon State University report in a new study.

The findings, so far done only in a laboratory setting, show that this one-two punch of mild hyperthermia and chemotherapy can kill 95 percent of ovarian cancer cells, and scientists say they expect to improve on those results in continued research.

The work is important, they say, because ovarian cancer – one of the leading causes of cancer-related deaths in women – often develops resistance to chemotherapeutic drugs if it returns after an initial remission. It kills more than 150,000 women around the world every year.

“Ovarian cancer is rarely detected early, and because of that chemotherapy is often needed in addition to surgery,” said Oleh Taratula, an assistant professor in the OSU College of Pharmacy. “It’s essential for the chemotherapy to be as effective as possible the first time it’s used, and we believe this new approach should help with that.”

It’s known that elevated temperatures can help kill cancer cells, but heating just the cancer cells is problematic. The new system incorporates the use of iron oxide nanoparticles that can be coated with a cancer-killing drug and then heated once they are imbedded in the cancer cell.

Other features have also been developed to optimize the new system, in an unusual collaboration between engineers, material science experts and pharmaceutical researchers.

A peptide is used that helps guide the nanoparticle specifically to cancer cells, and the nanoparticle is just the right size – neither too big nor too small – so the immune system will not reject it. A special polyethylene glycol coating further adds to the “stealth” effect of the nanoparticles and keeps them from clumping up. And the interaction between the cancer drug and a polymer on the nanoparticles gets weaker in the acidic environment of cancer cells, aiding release of the drug at the right place.

“The hyperthermia, or heating of cells, is done by subjecting the magnetic nanoparticles to an oscillating, or alternating magnetic field,” said Pallavi Dhagat, an associate professor in the OSU School of Electrical Engineering and Computer Science, and co-author on the study. “The nanoparticles absorb energy from the oscillating field and heat up.”

The result, in laboratory tests with ovarian cancer cells, was that a modest dose of the chemotherapeutic drug, combined with heating the cells to about 104 degrees, killed almost all the cells and was far more effective than either the drug or heat treatment would have been by itself.

Doxorubicin, the cancer drug, by itself at the level used in these experiments would leave about 70 percent of the cancer cells alive. With the new approach, only 5 percent were still viable.

The work was published in the International Journal of Pharmaceutics, as a collaboration of researchers in the OSU College of Pharmacy, College of Engineering, and Ocean NanoTech of Springdale, Ark. It was supported by the Medical Research Foundation of Oregon, the PhRMA Foundation and the OSU College of Pharmacy.

“I’m very excited about this delivery system,” Taratula said. “Cancer is always difficult to treat, and this should allow us to use lower levels of the toxic chemotherapeutic drugs, minimize side effects and the development of drug resistance, and still improve the efficacy of the treatment. We’re not trying to kill the cell with heat, but using it to improve the function of the drug.”

Iron oxide particles had been used before in some medical treatments, researchers said, but not with the complete system developed at OSU. Animal tests, and ultimately human trials, will be necessary before the new system is available for use.

Drug delivery systems such as this may later be applied to other forms of cancer, such as prostate or pancreatic cancer, to help improve the efficacy of chemotherapy in those conditions, Taratula said.

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Oleh Taratula, 541-737-5785

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Gut microbes closely linked to range of health issues

CORVALLIS, Ore. –A new understanding of the essential role of gut microbes in the immune system may hold the key to dealing with some of the more significant health problems facing people in the world today, Oregon State University researchers say in a new analysis.

Problems ranging from autoimmune disease to clinical depression and simple obesity may in fact be linked to immune dysfunction that begins with a “failure to communicate” in the human gut, the scientists say. Health care of the future may include personalized diagnosis of an individual’s “microbiome” to determine what prebiotics or probiotics are needed to provide balance.

Appropriate sanitation such as clean water and sewers are good. But some erroneous lessons in health care may need to be unlearned – leaving behind the fear of dirt, the love of antimicrobial cleansers, and the outdated notion that an antibiotic is always a good idea. We live in a world of “germs” and many of them are good for us.

“Asked about their immune system, most people might think of white blood cells, lymph glands or vaccines,” said Dr. Natalia Shulzhenko, author of a new report in Clinical Reviews in Allergy and Immunology, and assistant professor and physician in the OSU Department of Biomedical Sciences. “They would be surprised that’s not where most of the action is. Our intestines contain more immune cells than the entire rest of our body.

“The human gut plays a huge role in immune function,” Shulzhenko said. “This is little appreciated by people who think its only role is digestion. The combined number of genes in the microbiota genome is 150 times larger than the person in which they reside. They do help us digest food, but they do a lot more than that.”

An emerging theory of disease, Shulzhenko said, is a disruption in the “crosstalk” between the microbes in the human gut and other cells involved in the immune system and metabolic processes.

“In a healthy person, these microbes in the gut stimulate the immune system as needed, and it in turn talks back,” Shulzhenko said. “There’s an increasing disruption of these microbes from modern lifestyle, diet, overuse of antibiotics and other issues. With that disruption, the conversation is breaking down.”

An explosion of research in the field of genomic sequencing is for the first time allowing researchers to understand some of this conversation and appreciate its significance, Shulzhenko said. The results are surprising, with links that lead to a range of diseases, including celiac disease and inflammatory bowel disease. Obesity may be related. And some studies have found relevance to depression, late-onset autism, allergies, asthma and cancer.

In the new review, researchers analyzed how microbe dysfunction can sometimes result in malabsorption and diarrhea, which affects tens of millions of children worldwide and is often not cured merely by better nutrition. In contrast, a high-fat diet may cause the gut microbes to quickly adapt to and prefer these foods, leading to increased lipid absorption and weight gain.

The chronic inflammation linked to most of the diseases that kill people in the developed world today – heart disease, cancer, diabetes – may begin with dysfunctional gut microbiota.

Understanding these processes is a first step to addressing them, Shulzhenko said. Once researchers have a better idea of what constitutes healthy microbiota in the gut, they may be able to personalize therapies to restore that balance. It should also be possible to identify and use new types of probiotics to mitigate the impact of antibiotics, when such drugs are necessary and must be used.

Such approaches are “an exciting target for therapeutic interventions” to treat health problems in the future, the researchers concluded.

The study, supported by OSU, included researchers from both the College of Veterinary Medicine and the College of Pharmacy.

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Dr. Natalia Shulzhenko, 541-737-1051

Statins being overprescribed for growing number of kidney disease patients

PORTLAND, Ore. – A new analysis concludes that large numbers of patients in advanced stages of kidney disease are inappropriately being prescribed statins to lower their cholesterol – drugs that offer them no benefit and may increase other health risks such as diabetes, dementia or muscle pain.

The findings, which were published in the American Journal of Cardiovascular Drugs as a review of multiple studies, raise serious questions about the value of cholesterol-lowering therapies in kidney disease.

The issue is important, the researchers say, because the incidence of chronic kidney disease is rising in the United States at what they called “an alarming rate.” Also, kidney disease patients are 23 times more likely to get cardiovascular disease, and for them it’s the leading cause of death.

But for these patients, the frequent decision to prescribe statin drugs to lower cholesterol in order to reduce the risk of cardiovascular disease is not supported by the wider body of research, experts say.

“There is very little benefit to statin drugs for patients in the early stages of kidney disease, and no benefit or possible toxicity for patients in later stages,” said Ali Olyaei, a professor of pharmacotherapy in the College of Pharmacy at Oregon State University, and lead author on the new report.

“I believe the evidence shows that the majority of people with chronic kidney disease are taking statins inappropriately,” Olyaei said. “They may help a little in early-stage disease, but those people are not the ones who generally die from cardiovascular diseases. And by the end stages the risks outweigh any benefit. More drugs are not always better.”

Some of the particular risks posed by statin use, especially at higher doses, include severe muscle pain known as rhabdomyolysis, an increase in dementia and a significant increase in the risk of developing diabetes. The body of research also shows that statins do nothing to slow the progression of kidney disease, contrary to some reports that it might.

The impetus to use statin drugs – some of the most widely prescribed medications in the world to lower cholesterol – is obvious in end-stage kidney disease, because those patients have a mortality rate from coronary heart disease 15 times that of the general population. Unfortunately, evidence shows the drugs do not help prevent mortality in that situation. There is also no proven efficacy of the value of statins in patients using dialysis, researchers said.

If statins are prescribed in early-stage kidney disease, the study concluded that low dosages are more appropriate.

Collaborators on this report, which was supported by OSU, included researchers from the Oregon Health and Science University and the University of Illinois at Chicago.

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Ali Olyaei, 503-494-1308

Science of skin to be presented at Corvallis Science Pub

CORVALLIS, Ore. – Americans spend billions to beautify their outermost organ – to make it softer and younger, to erase wrinkles, conceal freckles, fake a tan, or flaunt a tattoo.

At the March 10 Corvallis Science Pub, Arup Indra of the Oregon State University College of Pharmacy will discuss what scientists know about skin development and what happens when things go awry. The Science Pub presentation, which is free and open to the public, begins at 6 p.m. in the Old World Deli located at 341 S.W. Second St. in Corvallis.

Indra and his wife, Gitali Indra, collaborate in studies of skin cell development. Their goal is to identify treatment options to help protect against diseases such as skin cancer and eczema. More cases of skin cancer are diagnosed in the United States every year than of breast, prostate, lung and colon cancer combined. 

And while skin cancer rates vary geographically, the nation’s highest are in the Pacific Northwest.

Sponsors of Science Pub include Terra magazine at OSU, the Downtown Corvallis Association and the Oregon Museum of Science and Industry.

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Arup Indra, 541-737-5775