ScienceDaily Apr. 21, 2010

Natural compounds in cranberries are linked to the prevention of urinary tract infections (UTIs) but inconsistencies in methods currently used commercially to measure levels can result in the over- or under-estimation of potency levels, leaving product manufacturers and consumers without good data. A study recently published in the Journal of the Science of Food and Agriculture outlines a new, commercially viable method of measuring these compounds.

UTIs are caused by bacterial adhesion (bacteria growth) on cells in the bladder. To maintain urinary tract health, especially for those prone to UTIs, daily consumption of 36mg of cranberry proanthocyanidins (PACs) has shown effectiveness in inhibiting bacteria from adhering to bladder cells, multiplying and consequently causing infection. This amount of PACs can be easily consumed in a 9-10 oz (266-296 ml) serving of 27% cranberry juice cocktail.

PACs are small molecules (catechin or epicatechin) linked together to form larger polymers. The PACs in cranberries contain a high proportion of what are called “A-type double linkages” between the catechin or epicatechin molecules. Other food sources of PACs that do not contain these linkages (chocolate, grapes, apples and green tea) do not elicit the bacterial anti-adhesion activity.

With some cranberry product testing methods, overestimation of up to five times the PAC level have been reported. This study uses the new BL-DMAC method of quantifying PAC levels in cranberry products which the authors claim can now serve as the standard industry method, allowing product manufacturers to provide accurate PAC levels.

To evaluate this method, 11 samples of cranberry products were obtained (five from U.S. sources and six from European sources) for PAC quantitation analysis. Powdered samples were coded and sent blinded to five different analytical laboratories (three in the U.S., one in China and one in Europe) for analysis by the BL-DMAC method. Each laboratory reported statistically consistent results of PAC levels.

“It is important to have an accurate, standard method for cranberry PAC quantitation that can be performed quickly and inexpensively in any commercial lab,” said Ronald L. Prior, Ph.D, lead author of the study. “In our study, we have shown that the BL-DMAC method is validated for this use. It utilizes a commercially available standard, which is vital to obtaining accurate results among different laboratories.”

“Universal adoption of this standard worldwide by the cranberry industry will allow producers to use one standard method to ensure accurate labelling of PAC levels in products, and aid consumers in selecting products with sufficient PAC levels to obtain bacterial anti-adhesion activity,” added Prior.

Adults who are obese or have less-than-ideal lifestyle habits may be more likely to have multiple, and more severe, urinary problems, new research suggests.

In a study of more than 5,500 men and women ages 30 to 79, researchers found that three-quarters of women and two-thirds of men reported at least one urinary tract symptoms — such as frequent trips to the bathroom overnight, difficulty emptying the bladder and urinary incontinence.

Obese adults were more likely than their normal-weight counterparts to have multiple, more severe symptoms. Smoking, lack of exercise and heavy drinking were also linked to more serious urinary problems.

The researchers, led by Dr. John B. McKinlay of the New England Research Institutes in Watertown, Massachusetts, report the findings in the medical journal BJU International.

The results are based on 5,506 Boston residents who were surveyed about 14 different urological symptoms, as well as their overall health. The researchers were able to identify four “clusters” of urinary symptoms among women, and five among men.

For example, just over half of women with urinary problems fell into the first cluster, which had the mildest symptoms; these women largely complained of frequent urination and having to get out of bed at least twice a night to go to the bathroom.

Women in the fourth cluster — 8 percent of those with urinary symptoms — suffered from nearly all of the symptoms assessed, including urine leakage and incontinence. Two-thirds of these women were obese, and often had the disorders associated with obesity, including diabetes and high blood pressure.

Smokers were more likely than non-smokers to have any urinary symptoms, and women in the cluster with the most severe symptoms had the highest smoking rate. Physical inactivity and heavy drinking were also most common among women with the most severe urinary problems.

Similar patterns emerged among men, with obesity and sedentary living being more common among those with the most severe urinary symptoms.

The findings highlight the importance of asking such high-risk patients about urinary problems, according to Dr. Raymond C. Rosen, who was involved in the research.

“These results will hopefully aid our understanding of why urological problems occur and how we can manage these conditions more effectively,” he said in a statement.

At a press briefing, Dr. Steven A. Kaplan from Weill Cornell Medical College, New York, noted that waist size is one component of the so-called metabolic syndrome, which signifies an elevated risk of heart disease and diabetes. “It is becoming very clear that when you have multiple components of the metabolic syndrome you can bet that you will have components of pelvic dysfunction, which we would define as sexual dysfunction and voiding dysfunction,” Kaplan said.

He and his colleagues tested the idea that waist circumference may be a useful predictor of prostate volume and the severity of pelvic dysfunction.

They grouped 88 men (average age, 62 years) with moderate or severe untreated voiding symptoms by waist circumference: 30-36 inches, 36-40 inches, and more than 40 inches.

Increasing waist circumference was significantly associated with “every parameter we looked at,” Kaplan said. Prostate volume, PSA level, voiding symptom score, erectile dysfunction, and ejaculatory dysfunction all increased as waist size increased, he explained.

“The results were simply remarkable. They even surprised us,” he commented. “We have no doubt, at least from this cohort of patients, that increasing waist circumference is associated with worsening male health — voiding and sexual function.”

This study, Kaplan concluded, shows that obese men are at increased risk of pelvic dysfunction and can be “easily diagnosed” by measuring waist circumference.

WEDNESDAY, May 24 (HealthDay News) — The herbal supplement St. John’s wort may help control pain linked to hypersensitive bladder disorders such as interstitial cystitis (IC), according to a new study involving rats.

Bladder hyperactivity — characterized by frequent contractions — is a significant cause of bladder irritation and pain.

In the study, researchers at the University of Pittsburgh Medical Center injected a formulation of St. John’s wort called DP015 into the abdomens of rats with bladder inflammation.

They found that the treatment resulted in longer intervals between bladder contractions. The findings were expected to be presented Tuesday at the American Urological Association annual meeting, in Atlanta.

Prior research found that neural control of the lower urinary tract is controlled by serotonin- and norepinephrine-emitting neurons. These are similar to neurons that play a role in anxiety and depression.

“St. John’s Wort is an herbal supplement that has been used for years to treat symptoms of mild depression, while urologists often use antidepressants to treat interstitial cysts,” researcher Dr. Michael B. Chancellor, a professor of urology and gynecology, said in a prepared statement.

“Given that the supplement and the drug work on the same systems, it makes sense that St. John’s wort could help treat this painful disease,” Chancellor said.

IC affects an estimated 700,000 Americans (90 percent of them women), according to the U.S. National Institute of Diabetes and Digestive and Kidney Diseases.

FRIDAY, Nov. 9 (HealthDay News) — As many as 25 percent of men over age 45 admitted to hospital with acute urinary retention (AUR) die within a year, a death risk comparable to that of patients with a broken hip, a new study says.

AUR, the sudden inability to pass urine, is a medical emergency. The condition is often a progression of benign prostatic hyperplasia, an enlargement of the prostate that can interfere with normal urine flow. AUR may also be linked to the presence of other disorders such as diabetes and high blood pressure, according to background information in the study, which was published Nov. 9 by BMJ Online First.

The study authors, from the University College London and London School of Hygiene and Tropical Medicine, analyzed data on more than 176,000 English men over the age of 45 who were hospitalized for treatment of a first episode of AUR between 1998 and 2005.

The researchers found that one in seven of the men with spontaneous AUR (no evidence of precipitating factors other than benign prostatic hyperplasia), and one in four with precipitated AUR, died within one year.

The risk of death increased with age and the presence of other health problems (comorbidity). About half the AUR patients over age 85 with comorbid conditions died within a year after being hospitalized.

The researchers calculated that the overall one-year death risk for men admitted to hospital with AUR was two to three times higher than for the general male population. Among AUR patients ages 45 to 54, the death risk was nearly 24 times higher.

AUR patients may benefit from urgent multidisciplinary care to identify and treat comorbid conditions early, the researchers concluded.

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NEW YORK (Reuters Health) – Elderly men with moderate or severe bladder problems are at increased risk of suffering a fall, new research suggests.

Understanding the links bladder problems and falls in men is “a salient public health issue,” Dr. J. Kellogg Parsons, at the University of California, San Diego Medical Center, and co-authors note in the medical journal BJU International.

The high prevalence of lower urinary tract symptoms, or LUTS, in older men “underscores the relevance of this problem, particularly in an era of rapidly increasing male longevity,” they point out.

Among 5872 men aged 65 and older, Parsons and colleagues determined that 54% had mild LUTS, 39% had moderate LUTS, and 7% had severe bladder symptoms.

Over the course of 1 year, 25% of men reported falling at least once and 12% reported two or more falls.

Men with moderate or severe bladder problems, the investigators found, were far more likely to fall than men with mild bladder woes, after adjusting for factors that might influence the results, like history of falls, dizziness, relevant medications, and physical limitations.

The urinary symptoms most strongly associated with falls were urinary “urgency,” difficulty initiating urination, and having to urinate frequently at night.

Parsons’ team speculates that urgency might prompt impulsive, risk-generating motions toward the toilet.

Men with difficulty urinating may try to find relief with the so-called Valsalva maneuver — where a person exhales forcefully while closing off the top of the throat, not allowing the air out. This maneuver may increase the risk of fainting.

Frequent nighttime urination, they suggest, could disrupt normal sleep patterns, induce sleep deprivation, and cause men to repeatedly navigate darkened environments.

“Because of the serious consequences of falls,” Parsons and colleagues say, doctors should consider asking older men about bladder problems.

SOURCE: BJU International, July 2009.

NEW YORK (Reuters Health) – Electrical stimulation of a nerve in the lower leg for 30 minutes twice weekly benefits some people suffering from interstitial cystitis, doctors have shown.

Interstitial cystitis is an inflammation and irritation of the wall of the bladder, more often afflicting women than men. It can be painful and causes frequent and urgent urination.

The procedure described in the medical journal Urology is called posterior tibial nerve stimulation or PTNS.

“I think PTNS is simple and easy to use with no complications,” Dr. Jimao Zhao from Beijing Friendship Hospital in the People’s Republic of China told Reuters Health. “Our experiences have shown that it can improve some symptoms in patients with interstitial cystitis.”

Zhao and colleagues evaluated the efficacy of PTNS for relieving pelvic pain and frequency/urgency symptoms in 18 Chinese women with cystitis that had not responded to other therapies.

Pain scores did not change significantly after PTNS treatment, the investigators report.

There were, however, significant improvements after PTNS in standardize scores assessing interstitial cystitis problems and symptoms, as well as health status scores, the report indicates.

“These results, together with the … convenience of this method, make it an effective alternative in the treatment of symptoms of lower urinary tract dysfunction,” the report concludes.

“We plan to study the effect of intensity and the frequency of PTNS in these patients,” Zhao said. “Longer or more numerous sessions may be used in the next study.”

SOURCE: Urology, June 2008.

SUNDAY, May 20 (HealthDay News) — Green tea may help protect against bladder inflammation, a new study says.

“We discovered that catechins found in green tea protected both normal and cancerous bladder cells from inflammation when we exposed the cells to hydrogen peroxide,” Dr. Michael B. Chancellor, professor of urology and gynecology at the University of Pittsburgh School of Medicine, said in a prepared statement.

“Although further studies are needed, the results indicate herbal supplements from green tea could be a treatment option for various bladder conditions that are caused by injury or inflammation,” he said.

In their laboratory study, Chancellor and his colleagues exposed normal and cancerous bladder cells to two major catechin components of green tea — epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) — and then exposed the cells to hydrogen peroxide.

Hydrogen peroxide normally damages or kills cells, but EGCG and ECG offered significant protection to the cells. The concentrations of the two kinds of catechins were at levels that can be obtained through normal dietary intake, the researchers said.

The study was to presented Sunday at the annual meeting of the American Urological Association, in Anaheim, Calif.

The chemical, called epigallocatechin-3-gallate (EGCG), has never been studied as an anti-cancer agent injected directly into the bladder, lead author Dr. J. Karl Kemberling and colleagues, from the Medical College of Ohio in Toledo, note.

Although EGCG has been shown to have anticancer properties, studies examining green tea use have yielded conflicting results. In one study, green tea consumption was actually tied to an increased risk of bladder cancer (see Reuters Health report November 26, 1999). However, in another study, drinking more than five cups per day seemed to protect against the malignancy.

In the new study, Kemberling’s team examined the anti-cancer effects of EGCG in the test tube and in rats with bladder tumors.

An EGCG dose was identified that could kill 100% of cancer cells after two hours of incubation.

The authors then tested EGCG on rats implanted with tumor cells. Thirty minutes after tumor cell injection, some of the animals were treated with EGCG, whereas others were not.

Eighteen of 28 animals (64 percent) treated with EGCG were tumor free three weeks later, the researchers note. In contrast, all 12 untreated animals showed tumor growth.

The results suggest that EGCG could be a useful treatment for bladder cancer. Moreover, “it is readily available and easily processed from green tea leaves,” the authors state.

WASHINGTON – An herbal extract that is sold in health food stores and promoted as an allergy and fat loss aid may improve treatment of bladder infections when it is taken with antibiotics, research suggests.

Some 90 percent of bladder infections are caused by E. coli bacteria. They affect women four times more often than men, sometimes recurring over and over.

The bladder is lined with small pouches that allow it to stretch as it fills. Researchers at Duke University reported in Sunday’s online edition of Nature Medicine that some bacteria were able to hide in those pouches, escaping the antibiotics used to treat the infection.

In tests in mice, the extract forskolin can cause the pouches to kick out the bacteria, allowing antibiotics to kill them, said the lead researcher, microbiologist Soman N. Abraham. Forskolin is derived from the Indian coleus plant.

“If we combine this with antibiotics we would be in a very good position to eradicate urinary tract infection,” he said in a telephone interview.

In the experiments, forskolin was injected into some mice and placed directly into the bladders in others, Abraham said.

The extract is available in health food stores and some people take it by mouth as a supplement, he said. It is promoted as a treatment for allergies, breathing problems and even fat loss.

That availability does “absolutely not” mean people should attempt to treat themselves for bladder infections, Abraham said.

Urinary tract infections must be treated with antibiotics because they can quickly spread to the kidneys, so infected people needed to see their doctor, he said. But the fact that forskolin is being used by some people does help indicate it is safe, he said.

Abraham said the next step for the researchers is to experiment in larger animals to see if they can completely eliminate a bladder infection.

“If we can show an impact in combination with antibiotics it should not be too long before we can go to clinical trials” in people, he said.

Extracts from the Indian coleus were used in ancient Asia to treat a variety of diseases including urinary tract infections, Abraham said. “So, we have come full circle,” he said.

Walter Hopkins, a scientist in the Division of Urology at the University of Wisconsin School of Medicine and Public Health, said the research shows “forskolin may provide a means to interrupt the infection-reinfection cycle” and lead to a quicker resolution of the illness.

“If these results could be duplicated in human studies, forskolin could offer a new treatment option for recurrent” urinary tract infection said Hopkins, who was not part of the research team.

Dr. Gregor Reid of the Lawson Health Research Institute in London, Ontario, said the research was interesting.

“In some patients, such augmentation may be beneficial. Once human studies are done, we’ll have a better idea,” he said. “For now, this concept is a long way from being used in patients,” said Reid, who was not part of the research team.

The research was funded by the National Institutes of Health.

The study, published in the journal Colloids and Surfaces: B, was conducted by Terri Camesano, associate professor of chemical engineering at WPI, and a team of graduate students, including PhD candidate Yatao Liu. They exposed two varieties of E. coli bacteria, one with hair-like projections known as fimbriae and one without, to different concentrations of cranberry juice. Fimbriae are present on a number of virulent bacteria, including those that cause urinary tract infections, and are believed to be used by bacteria to form strong bonds with cells.

For the fimbriaed bacteria, they found that even at low concentrations, cranberry juice altered two properties that serve as indicators of the ability of bacteria to attach to cells. The first factor is called Gibbs free energy of attachment, which is a measure of the amount of energy that must be expended before a bacterium can attach to a cell. Without cranberry juice, this value was a negative number, indicating that energy would be released and attachment was highly likely. With cranberry juice the number was positive and it grew steadily as the concentration of juice increased, making attachment to urinary tract cells increasingly unlikely.

Surface free energy also rose, suggesting that the presence of cranberry juice creates an energy barrier that repels the bacteria. The researchers also placed the bacteria and urinary tract cells together in solution. Without cranberry juice, the fimbriaed bacteria attached readily to the cells. As increasing concentrations of cranberry juice were added to the solution, fewer and fewer attachments were observed.

Cranberry juice had no discernible effect on E. coli bacteria without fimbriae, suggesting that compounds in the juice may act directly on the molecular structure of the fimbriae themselves. This reinforces previous work by the WPI team that showed that exposure to cranberry juice alters the shape of the fimbriae, causing them to become compressed. Using an atomic force microscope as a minute strain gauge, the team also showed that the adhesive force exerted by bacteria on urinary tract cells declined in direct proportion to the concentration of cranberry juice in the solution.

“Our results show that, at least for urinary tract infections, cranberry juice targets the right bacteria—those that cause disease—but has no effect on non-pathogenic organisms, suggesting that cranberry juice will not disrupt bacteria that are part of the normal flora in the gut,” Camesano says. “We have also shown that this effect occurs at concentrations of cranberry juice that are comparable to levels we would expect to find in the urinary tract.”

Camesano notes that unpublished work has shown that while cranberry juice has potent effects on disease-causing bacteria, those effects are transitory. “When we takes E. coli. bacteria that have been treated with cranberry juice and place them in normal growth media, they regain the ability to adhere to urinary tract cells,” she says. “This suggests that to realize the antibacterial benefits of cranberry, one must consume cranberry juice regularly—perhaps daily.”

For those watching calories, Camesano says other recent work in her lab has shown that the effects of regular cranberry juice cocktail and diet (sugar-free) cranberry juice are identical. “That’s good news for people who do not like to consume a lot of sugary juice,” she says.

A daily dose of sodium bicarbonate — baking soda, already used for baking, cleaning, acid indigestion, sunburn, and more — slows the decline of kidney function in some patients with advanced chronic kidney disease (CKD), reports an upcoming study in the Journal of the American Society of Nephrology (JASN). “This cheap and simple strategy also improves patients’ nutritional status, and has the potential of translating into significant economic, quality of life, and clinical outcome benefits,” comments Magdi Yaqoob, MD (Royal London Hospital).

The study included 134 patients with advanced CKD and low bicarbonate levels, also called metabolic acidosis. One group received a small daily dose of sodium bicarbonate in tablet form, in addition to their usual care. For this group, the rate of decline in kidney function was greatly reduced—about two-thirds slower than in patients. “In fact, in patients taking sodium bicarbonate, the rate of decline in kidney function was similar to the normal age-related decline,” says Yaqoob.

Rapid progression of kidney disease occurred in just nine percent of patients taking sodium bicarbonate, compared to 45 percent of the other group. Patients taking sodium bicarbonate were also less likely to develop end-stage renal disease (ESRD) requiring dialysis.

Patients taking sodium bicarbonate also had improvement in several measures of nutrition. Although their sodium levels went up, this didn’t lead to any problems with increased blood pressure.

Low bicarbonate levels are common in patients with CKD and can lead to a wide range of other problems. “This is the first randomized controlled study of its kind,” says Yaqoob. “A simple remedy like sodium bicarbonate (baking soda), when used appropriately, can be very effective.”

The researchers note some important limitations of their study—there was no placebo group and the researchers were aware of which patients were receiving sodium bicarbonate. “Our results will need validation in a multicenter study,” says Yaqoob.

The study entitled, Bicarbonate Supplementation Slows Progression of CKD and Improves Nutritional Status will appear online.

Source: American Society of Nephrology

Allergy testing and treatment may offer a new therapeutic option for many patients with interstitial cystitis (IC). IC is a severely painful bladder condition affecting as many as 8 million women and 1.5 million men in the United States. Patients and the providers who treat them have long noticed a correlation between allergies and IC. Recently, a urologist and allergist in Louisville, Kentucky, began to explore the link between these two chronic ailments to provide patients with more effective treatment. The story of their discoveries is featured in the ICA Update, the quarterly magazine of the Interstitial Cystitis Association (ICA).

“Until now, the evidence linking IC and allergies has been circumstantial,” said Barbara Gordon, executive director of the ICA, an organization providing advocacy, research funding, and education to ensure early diagnosis and optimal care with dignity for people affected by IC. “Epidemiologic studies show the prevalence of allergies in IC patients to be higher than in people in general. Anti-allergy medications seem to ease IC symptoms, especially when patients have seasonal allergies. And during allergy seasons, doctors report an upswing in IC-related calls and patient visits.”

That suggests that there is a correlation between allergies and IC, but can allergies cause bladder symptoms? A clearer answer comes from actual allergy testing and treatment of patients. After holding several discussions on this subject, John Hubbard, M.D., a urologist, and C. Steven Smith, M.D., an allergist/immunologist, partnered to study this phenomenon in a more formal way.

These doctors found they were referring patients to each other. Hubbard was sending IC patients with seasonal allergies to Smith, and Smith had allergy patients who also had bladder symptoms. Then, they found that Smith’s allergy testing and treatment was helping to resolve IC symptoms, sometimes dramatically.

Foods Fingered

Although IC patients’ seasonal allergy miseries are what gave the clue to the connection, Smith is finding that food allergies are common in IC patients. He estimates that 35 to 40 percent of the IC patients he sees have bona fide allergies to foods, based on the results of their skin prick tests and elimination-challenge diets, and that their IC gets better when they remove those foods from their diet. “We’ve been able to identify a lot of food allergies that IC patients didn’t even know they had,” noted Heather Lange, ARNP, the nurse practitioner who works with urologist Hubbard’s IC patients.

Stimulants, such as coffee and tea, and the acid and spicy foods that have long been known to cause problems for IC patients may be bladder irritants even without allergy. “Put those on already irritated bladder tissue, and you probably are going to see a response,” Smith said. But he’s also finding allergic reactions to some of these items in IC patients. Positive skin prick tests for cayenne (a hot pepper) seem to be common.

The effect on IC of treating environmental allergies with shots or medications is less obvious, said Smith, but still seems to be beneficial. About half to a third of the IC patients he sees have proven environmental allergies or symptoms, such as hay fever, asthma, recurrent ear infections, or chronic urticaria (hives).

Hubbard and Smith are collaborating on a more formal study of the link. One goal is to find a marker that will help urologists decide which patients may benefit from allergy testing and treatment. Like many urologists, Hubbard uses cystoscopy and hydrodistention under anesthesia as part of his workup to exclude other conditions that may cause IC-like symptoms. But he is reviving an older practice of taking a biopsy specimen during the procedure and sending it to a pathologist to look for mast cells because, when mast cells reach a certain density, patients seem to benefit from allergy testing and treatment. Mast cells elsewhere in the body are key players in allergic reactions, but their role in the bladder tissue of IC patients has not been clear.

Dr. Smith and Dr. Hubbard plan to conduct more research and hope to spark the interest of additional IC and allergy researchers. Meanwhile, these doctors are continuing to help IC patients get better. Not everyone responds, said Smith, “But for the high percentage who do improve with allergy management, it’s well worth the effort. It’s one of the most rewarding patient care experiences I have ever had.”

Diet and IC

Future research will reveal more about the role of food allergy in IC patients’ symptoms. Meanwhile, whether patients have “true” allergies or sensitivity to foods, the treatment is the same — an elimination challenge diet. Elimination diets remove the potential problem foods from the patient’s diet and add them back one at a time to see if the food really causes a problem.

ICA offers the following advice to patients when modifying their diets: — The effect of food and drinks on IC symptoms varies greatly from individual to individual. It’s important to note the type of food or beverage, as well as how much, how often and the specific combination of food and beverages ingested. Give yourself plenty of time to discover your ideal diet. It may require several weeks of trial and error.

– Eat a healthy, varied, balanced diet — most patients can do this if they work to identify problem items first.

The study, published in Obstetrics & Gynecology, followed 85 women with overactive bladder and urge incontinence. The women were randomly assigned to one of two groups, with approximately half receiving acupuncture that targeted bladder control and the other half receiving acupuncture treatments for relaxation.

The women who received acupuncture for bladder control were treated specifically on the lower back and abdomen, and those treated for relaxation were given acupuncture on points throughout the body. After four weeks of treatment, both groups reported improvement in urge incontinence and urinary leakage, and the women who received bladder-specific acupuncture reported making fewer trips to the bathroom and less urgency to urinate.

Acupuncture May Ease Overactive Bladder (news release, San Diego: Padfi’c College of Oriental Medicine, Aug 3, 2005).