Capsaicin, the active ingredient in chilli peppers, generally is viewed as an irritant that produces a burning sensation when applied to a sensitive area of the body, such as the cornea.
Paradoxically, the same compound also may reduce pain. Capsaicin creams are natural pain-relieving folk medicines, commonly found over the counter, and are effective for a variety of pain syndromes, from minor muscle or joint aches to those that are very difficult to treat, such as arthritis and neuropathic pain.

Scientists at University at Buffalo now link the analgesic effects of capsaicin to a lipid called PIP2 in the cell membranes.

Results of the research, headed by Feng Qin, PhD, associate professor in the Department of Physiology and Biophysics in the University at Buffalo’s School of Medicine and Biomedical Sciences, appear in the journal PLoS Biology.

Capsaicin works by stimulating a receptor on nerve endings in the skin, which sends a message to the brain and generates the sensation of pain. The receptor also senses heat, making chilli peppers taste hot.

“The receptor acts like a gate to the neurons,” said Qin. “When stimulated it opens, letting outside calcium enter the cells until the receptor shuts down, a process called desensitisation. The analgesic action of capsaicin is believed to involve this desensitisation process. However, how the entry of calcium leads to the loss of sensitivity of the neurons was not clear.”

Previous research from the UB group and others implicated the significance of the PIP2 lipid. Calcium influx induces strong depletion of the lipid in the plasma membrane. By combining electrical and optical measurements, the authors now have been able to directly link the depletion of PIP2 to the desensitisation of the receptor.

The authors also found that the receptor is still fully functional after desensitisation. “What changed was the responsiveness threshold,” said Qin. “In other words, the receptor had not desensitised per se, but its responsiveness range was shifted. This property, called adaptation, would allow the receptor to continuously respond to varying stimuli over a large capsaicin concentration range.”

“Adaptation” is a property that is found in other sensory receptors, such as those in hearing and vision, and is identified in pain receptors as well.

The findings have implications for pain-sensation mechanisms as well as clinical applications, the authors note. With an adaptive response, the receptors are essentially auto regulated without a fixed threshold. The intensity that causes pain is dependent on the history of activity.

Plasticity of pain is known at the central level. The study now shows that it may also be present at the peripheral site, although the sensation of pain is complex and involves many types of receptors and messengers. The lipid dependence of the receptor also will provide novel strategies for development of safe analgesics like capsaicin, a natural pain reliever, but with less irritation.

Jing Yao, PhD, a post-doctoral research student in the UB Department of Physiology and Biophysics, is second author on the paper.

A new, recently licensed medical device developed by University at Buffalo researchers would introduce into intensive care settings the powerful and effective method of anaesthetising patients that works so well in the operating room.
The new UB ventilator has the potential to shorten the length of patient stays in the intensive care unit (ICU) because it will greatly reduce complications and habituation to sedatives used in the ICU. It also is expected to be more cost-effective than current methods of ventilating ICU patients.

The device also may have promising applications in treating large numbers of patients during pandemics or other events with mass casualties because it can safely enable multiple patients to share a single ventilator without the risk of cross-contamination.

The device is designed to cost effectively deliver to patients small amounts of powerful inhalation anaesthetic agents as they breathe or are mechanically ventilated.

The portable patient ventilator was invented by Bradley Fuhrman, MD, professor of paediatrics and anaesthesiology and chief of critical care at Women & Children’s Hospital of Buffalo, and Mark Dowhy, director of the Pediatric Critical Care Laboratory in the UB Department of Pediatrics; both are on staff in the UB School of Medicine and Biomedical Sciences.

The invention, which has been presented at numerous technology exhibitions, including the 2008 World’s Best Technologies Showcase, was licensed from UB to Medical Conservation Devices (MCD) of Buffalo, located in UB’s New York State Center of Excellence in Bioinformatics and Life Sciences.

Fuhrman and Dowhy are founding partners in MCD, and will receive the UB Entrepreneurial Spirit Award at the UB Inventors and Entrepreneurs Reception.

MCD is raising funds to further develop the prototype for FDA medical-device evaluation. Initial prototype devices have been validated in laboratory experiments. First Wave Technologies Inc. is a partial owner and manager of MCD. It is a technology-development company that partners with UB’s Office of Science, Technology and Economic Outreach to expand the commercialisation of early-stage university technologies utilising private-sector resources.

A key advantage of inhaled anaesthetics over intravenous sedation, which is the current approach in the ICU, is that inhaled anaesthesia delivers and clears sedatives by way of the lungs, bypassing the metabolic and excretory systems. That’s a critical factor, Fuhrman said, for patients who have sustained damage to their kidneys or livers, as a result of their illness.

When anaesthesia is delivered through the lung, there is a much more rapid onset of effect and much quicker reversal once it is removed, an important consideration especially in patients who need to be frequently or abruptly awakened, such as children who have suffered trauma to the skull.

The invention addresses a problem common in ICU settings in which sedation must be deep enough that the patient is not aware of pain, but not so deep that it will cause withdrawal issues once the patient is no longer sedated.

“We administer significant amounts of narcotics and other agents to keep patients comfortable,” explained Fuhrman. “But if we sedate them too well, we often face problems with withdrawal.”

In those cases, patients can exhibit shakiness, combativeness and anxiety, symptoms that are then treated with methadone, usually requiring the patient to remain in the ICU for several more days.

By contrast, Fuhrman explained, patients in operating rooms are sedated using intravenous sedatives combined with precisely controlled concentrations of inhalation agents delivered by an expensive, specially designed anaesthesia ventilator. An anaesthesiologist or nurse anaesthetist then monitors and controls a patient’s vital signs and depth of anaesthesia on a moment-by-moment basis.

“It’s that kind of control that we are seeking to duplicate at each ICU bedside,” said Fuhrman.

“With our ventilator, the patient is continually re-breathing the same anaesthetic and oxygen mixture, so the amount of anaesthetic that is used can be reduced by about 80 percent,” he said.

The ventilator was developed with initial assistance from the UB Product Development Fund and the UB Center for Biomedical and Bioengineering Technology (CAT).

(Source: University at Buffalo: March 2009)

Mild to moderate eczema sufferers who are looking for a cost-effective way to control and heal this skin condition without a prescription now have a new option to consider. A new study in the March 2009 issue of the Journal of Cosmetic Dermatology finds that an over-the-counter moisturiser is just as efficacious as a leading prescription moisturiser – for a fraction of the price and easier availability right on the drug store shelf – in the reduction of dryness, scaling and itching related to mild to moderate eczema.
“It was very interesting to see that an over-the-counter moisturising formulation that has been around for more than 100 years, was equally as efficacious as a more modern prescription moisturising cream for the treatment of mild and moderate eczema,” says Zoe Diana Draelos, MD, dermatologist and lead researcher/author of the study. This opens up opportunities to larger populations of sufferers of certain skin issues who have limited access to dermatologists or, even, prescription medications, she adds.

Eczema is one of the most common conditions that results in dermatologic visits. Most of the skin damage associated with eczema is not from the condition itself, but comes as a result of the scratching due to the itchiness and irritation. Additionally, eczema is also a condition that returns if the skin is not cared for properly on a regular basis.

Many common, over-the-counter skin moisturisers are now water-based to make them lighter to apply and easy to absorb by the skin, but this water content within the product doesn’t actually penetrate the skin’s deeper layers and cannot moisturise the skin.

“Water-based moisturisers cannot add water to the skin, and, ironically, can actually serve to dry out the skin further in some people because the continual wetting/evaporation of moisture from the surface of the skin produces skin damage,” explains Dr Draelos. “Moisturisers that reduce transepidermal water loss (TEWL) are those that occlude, or trap, moisture in the skin due to their more oily ingredients, such as mineral oil, petrolatum and paraffin.” These types of moisturisers are great for the tens of millions of people with dry skin issues, like eczema, she adds.

The objective of this investigator-blinded study was to determine if there would be similarities in the improvement of eczema using either an over-the-counter moisturiser found at stores across the US, and a prescription moisturiser for the treatment of mild and moderate eczema (both topical products were combined with use of a 0.1% triamcinolone cream for moderate eczema and used alone for mild eczema). Fifty-nine/sixty (59/60) subjects who completed the four-week study were randomly assigned based on whether their eczema was mild or moderate, and used each of the test products on either one arm or one leg.

“After assessing the subjects at weeks one, two and four, there was improvement in both groups; however, there were no statistically significant differences between the subjects using the OTC formulation or the prescription moisturiser,” adds Dr Draelos. The individual subjects also felt that they performed comparably in terms of the healing of the eczema, when evaluating the redness, peeling, dryness, stinging, itching and overall assessment.

Acid reflux, often dismissed by many as a minor inconvenience when pondering the enticing prospect of a spicy salsa or curry dish, can come back to bite you – literally.
Even the arsenal of little pastel “anti-burp” tablets readily available at convenience stores is no match for the acid’s assault on the oesophagus that can lead to pain, erosion of tissue and future complications. Left untreated, repeated bouts of acid reflux can result in chronic gastro-oesophageal reflux disease (GORD), characterised by heartburn – a gnawing, burning sensation often experienced at night or after eating.

In a more serious form, a daily history of GORD can lead to Barrett’s oesophagus, a pre-cancerous condition of the lining of the oesophagus. Traditionally, patients with Barrett’s oesophagus were managed with aggressive surveillance.

Now a treatment for Barrett’s oesophagus in patients with dysplasia (abnormal cells within tissue that are a signal for progression to possible cancer) is showing promise. According to the Mayo Clinic gastroenterologists who studied and treated 63 patients with both low-grade and high-grade dysplasia, ablation – a procedure where a localised heat treatment is used to destroy abnormal cells – appears to be a safe and effective intervention.

Low-grade dysplasia is evidenced by smaller, pre-cancerous changes in cells. High-grade dysplasia is diagnosed when the most advanced pre-cancerous changes are observed.

The study, led by Virender K. Sharma, MD, Gastroenterology, Mayo Clinic in Arizona, enrolled the 63 patients with dysplasia and treated them with radio frequency ablation, using the HALO system, developed by BARRX Medical. The two-pronged system, one called “circumferential ablation” and the second, “focal ablation”, directly targets the abnormal oesophageal tissue.

The circumferential ablation (HALO 360) procedure uses a sizing balloon, ablation catheter and an energy generator. The focal ablation (HALO 90) uses an endoscope that brings an electrode into contact with the targeted tissue. Bursts of energy destroy the diseased tissue.

When the final results were tallied on the 62 patients who were eligible at a median 24 months of follow-up, there was a complete response for dysplasia in 95 percent and 79 percent of patients with low-grade dysplasia and high-grade dysplasia, respectively. It was determined that the circumferential and focal ablation methods employed to treat Barrett’s oesophagus with dysplasia appeared to be an effective and safe intervention, according to Dr Sharma.

The procedures are minimally invasive and are done on an outpatient basis, allowing patients to go home the same day.

“This study is an important advance for gastrointestinal medicine because it was able to demonstrate a real-life experience for the management of Barrett’s oesophagus for patients with low and high-grade dysplasia,” notes Dr Sharma. He calls for further evaluation of these ablative procedures and adds, “Because of the ease of use, the relative low cost and lack of significant side effects, we have compelling reasons to study and use this treatment.”

The incidence of Barrett’s oesophagus is rising rapidly in the US and is estimated to affect some 3.3 million adults. Men are at greater risk and the prevalence of Barrett’s increases with advancing age until a plateau is reached in the 60s. Patients with Barrett’s oesophagus are 30 to 125 times more likely to develop oesophageal cancer than the general population.

The Mayo Clinic oesophageal physicians from the Division of Gastroenterology perform cutting-edge therapeutic procedures in Barrett’s patients. “We not only have the largest experience of using the HALO in Barrett’s, but also we are spearheading the investigation of a new ablative technique, cryotherapy, in these patients,” said the director of oesophageal clinic, H. Jae Kim, MD. “These techniques may have a significant impact on reducing the incidence of oesophageal cancer by ablating the pre-cancerous lesion, Barrett’s oesophagus. The initial results for cryotherapy appear promising, and we are currently involved in the large multicentre study,” adds Dr Kim.

Not only do teens with type 1 diabetes have the normal adolescent concerns of school, work and social activities, but they are responsible for taking insulin, monitoring blood glucose (blood sugar) levels and keeping doctor visits, too. Now a new study suggests that feelings such as anger or sadness could interfere with teens’ diabetes management.
“Adolescence is a difficult time to manage diabetes, for multiple reasons: some of them are physiological, like puberty; some are psychological, such as increasing autonomy. Also, there’s a rise during adolescence of negative emotions,” said Cynthia Berg, PhD, chairperson of the psychology department at the University of Utah in Salt Lake City.

Berg, a study co-author, and colleagues had 62 adolescents with type 1 diabetes complete daily diaries for two weeks, detailing their mood, average blood glucose levels, overall confidence in their ability to manage their diabetes and ability to manage daily diabetes tasks, such as eating healthy foods and taking insulin.

The findings appear in the Annals of Behavioral Medicine.

During the two-week study period, when teens reported more positive feelings, such as happiness or excitement, they tended to have lower, nearer normal blood glucose levels. In contrast, when teens reported negative feelings, daily diary entries revealed a tendency toward higher blood glucose levels.

Researchers measured positive and negative emotions on a one- to five-point scale. “The important issue is that for every one-point change in emotion, there is a rather sizeable change in blood glucose,” Berg said.

Ann Goebel-Fabbri, PhD, a psychologist at Joslin Diabetes Center in Boston, cautioned that the act of entering the blood glucose number in journals might cloud teens’ moods. As a result, “they may feel negatively or positively charged from that result,” she said.

“The take-home message for health care providers, parents and teens is that both emotions can potentially influence their confidence in blood sugar management,” Goebel-Fabbri said. “At the same time, it can go in the opposite direction the actual outcomes can also influence their emotions. It’s a bidirectional relationship.”

New computer models can now link strangers in a life-saving chain of kidney transplants, promising to increase the number of transplants and overcome obstacles posed by logistics or donors who renege, a team of researchers report in the current edition of the New England Journal of Medicine.
Designed to optimise the “matching market” principles involved in kidney transplantation, donor registry software programs sift through thousands of pairs of recipients and their living donors, analyse participant characteristics, then construct an optimal chain of transplant pairs, report the co-authors, many of whom helped pioneer the creation of donor chains.

For the approximately 70,000 US patients in need of a kidney transplant, the data-driven approach to transplantation pairings should shrink the rolls of patients on waiting lists.

The donor chains start with a single “altruistic” volunteer donor.

“The Good Samaritan who comes forward to donate a kidney serves as the catalyst for a series of donations in a much more efficient system,” says Boston College Assoc. Prof. M. Utku Unver, a theoretical economist. “It is not an easy decision to give up a kidney to help a stranger. These advances may encourage more donors because they now know they can save many lives.”

The approximately 4,000 living donor kidney transplantations that take place in America each year rest upon a fragile balance of donors and recipients engaged in a “matching market” where volunteers provide life-saving organs without monetary compensation, says Unver, who has been examining kidney exchange for five years.

The computer-generated chains provide a viable alternative to the relatively new strategy of paired donation, where organs are exchanged between two donor-recipient pairs during simultaneous surgeries.

Paired donations are prone to breakdowns because a willing donor is not a compatible match, a recipient is too far away or a donor backs out of the extremely personal transaction.

Unver and his fellow researchers highlight a chain of kidney transplantations that started with a 28-year-old Michigan man in July of 2007 and led to 10 transplantations coordinated during 8 months by two large paired-donation registries, the 25-state Alliance for Paired Donation and Incompatible Kidney Transplantation Program at Johns Hopkins Hospital.

The transplantations took place at six medical centres in five states. Three kidneys from living donors were shipped – two using commercial flights – rather than requiring donors to travel to the recipient’s hospital.

The computer models assign values to the characteristics of donors and recipients stored in massive databases. The programs then generate pairings based on with similar scores, imposing an order on these exchanges by overcoming issues that disrupt a market.

“Economists have been looking at solving the ‘mechanism design’ problem of paired donations by using data to increase efficiency,” says Unver, whose early work on these models with fellow BC economist Tayfun Sonmez led to the founding of the New England Program for Kidney Exchange. “As work progressed, people began to see this was a way of overcoming the problems involved with paired donations.”

Paired kidney donation surgeries are performed simultaneously to reduce the possibility of a donor backing out once a friend or relative has received a kidney.

A donation chain allows for greater flexibility, since not all surgeries must take place at the same time in the same hospital.

The researchers conclude further that kidney donor chains could shorten wait times on lists of unmatched patients in line for deceased-donor organs. The scope of the databases can pair these patients with suitable living donors, who account for approximately one-third of the 14,000 kidney transplantations that take place annually in the US.

Life is hard for the children of a parent suffering from depression. Children take on an enormous amount of responsibility for the ill parent and for other family members. It is therefore important for the health services to be aware of this and have support functions in place for the whole family, and not just for the person who is ill. This is the conclusion of a thesis from the Sahlgrenska Academy, University of Gothenburg, Sweden.
Registered Nurse Britt Hedman Ahlström has examined the way in which family life is affected when a parent is suffering from depression. Nine families, including ten children and young adults between the ages of 5 and 26, and eleven parents were included in the study.

The results show how the family’s daily life changes and becomes more complicated when a parent is suffering from depression. Uncertainty about what is happening has an effect on the daily life of the entire family. Depression also means that the parent becomes tired and exhausted, which then affects and weighs heavily on the children’s daily life. Depression changes the relationship between a parent and his/her children, since they no longer communicate with each other as they used to. Family interplay and reciprocity decrease. The depressed parent withdraws from the family, and the children feel that they have been left to themselves.

Daily family life becomes unfamiliar to the children

The family members try their utmost, both as individuals and together, to cope with the situation, so that daily life can be restored to a more manageable level. The children take responsibility for both the depressed parent, siblings and themselves, when they notice that the parent cannot cope.

“The toughest burden of responsibility that children take on is ensuring that the depressed parent doesn’t commit suicide. So children take on an extremely heavy responsibility by monitoring and keeping an eye on the depressed parent,” says Britt Hedman Ahlström.

For children, the parent’s depression means both a sense of responsibility and a feeling of loneliness. The feelings of responsibility and loneliness include a striving and yearning for reciprocity with the parent, and for things to return to a state of normality.

“Even if the depression goes away for a time, the family is never entirely free from anxiety over it coming back. This means that there is a prolonged period of suffering associated with depression,” says Britt Hedman Ahlström.

People who sleep less than six hours a night appear to have a higher risk of developing impaired fasting glucose – a condition that can precede type 2 diabetes – researchers reported at the American Heart Association’s 49th Annual Conference on Cardiovascular Disease Epidemiology and Prevention.
Type 2 diabetes, the most common form of diabetes, appears most often in middle-aged adults. Adolescents and young adults, however, are developing type 2 diabetes at an alarming rate. It develops when the body makes relatively too much insulin and doesn’t efficiently use the insulin it makes (insulin resistance).

Participants who slept on average less than six hours a night during the work week, when followed over six years, were 4.56 times more likely than those getting six to eight hours of sleep to convert from normal blood sugar levels to impaired fasting glucose, researchers said.

“This study supports growing evidence of the association of inadequate sleep with adverse health issues. Sleep should be assessed in the clinical setting as part of well-care visits throughout the life cycle,” said Lisa Rafalson, PhD, lead author of the study and National Research Service Award fellow and research assistant professor at the University at Buffalo in New York.

“While previous studies have suggested that there may be many genes that each have a very small effect on the risk of diabetes, there is no known genetic predisposition to sleep disturbances that could explain our study’s results, especially in this limited sample size,” Rafalson said. “It is more likely that pathways involving hormones and the nervous system are involved in the impaired-sleep/fasting glucose association.”

Researchers conducted a matched, nested case-control study to address whether sleep duration at baseline predicted progression from normal to impaired fasting glucose during six years of follow-up in the Western New York Health Study. From 1,455 participants, the team identified 91 whose fasting blood glucose levels of less than 100 milligrams per decilitre (mg/dL) during baseline exams in 1996–2001 had risen to between 100 mg/dL and 125 mg/dL at follow-up exams in 2003–2004.

The 91 were matched three-to-one with 273 controls whose glucose levels were below 100 mg/dL at baseline and follow-up. Researchers also matched the groups according to gender, race/ethnicity and year of study enrolment.

Sleep duration was self-reported using the Stanford seven-day physical activity recall questionnaire, with patients categorised by their daily work week (Sunday through Thursday) sleep duration: short-sleepers (less than six hours, 25 participants), long-sleepers (more than eight hours, 24 participants) and mid-sleepers (six-to-eight-hour sleepers, 314 participants). Sleep data was unavailable on one person.

After adjusting for age, body mass index, glucose and insulin concentrations, heart rate, high blood pressure, family history of diabetes and symptoms of depression, the researchers found a significantly increased risk of developing impaired fasting glucose among short-sleepers compared to the mid-sleepers. Compared to the mid-sleepers, long-sleepers showed no association with impaired fasting glucose, the researchers report.

“Our findings will hopefully spur additional research into this very complex area of sleep and illness,” Rafalson said.

(Source: American Heart Association: American Heart Association’s 49th Annual Conference on Cardiovascular Disease Epidemiology and Prevention: March 2009)

University of Queensland research has revealed the older a dad is the more likely his children will have reduced cognitive abilities.
Professor John McGrath, from UQ’s Queensland Brain Institute, said the study could have implications for a society that is having children later in life.

He said while recent research had shown a link between the age of a father and an increased chance of schizophrenia and autism in the children, there has been less focus on the age of father and cognition.

“The results were quite startling as it was thought that the age of the father was less of a concern compared to the age of the mother,” Professor McGrath said.

“Now we are getting more evidence of the age of the father being just as important.

“The older a dad is, the worse his children tend to do in intelligence tests.”

The research, published in medical journal PLoS Medicine re-analysed data from one of the largest studies of children in the United States, the Collaborative Perinatal Project.

More than 33,000 children were tested at eight months, four years and seven years on a variety of intelligence tests, and when Professor McGrath and his colleagues looked at the results against the age of the fathers a pattern soon became clear.

“Frankly, we were surprised to come up with such a clear cut finding,” Professor McGrath said.

“We are concerned that older men accumulate more mutations in the developing sperm cells.

“These mistakes then pile up and increase the risks of problems in the children, and it is possible that these mistakes will carry on into the next generation.”

Professor McGrath said the difference in intelligence was the exact opposite for children of older women, which made the findings even more startling.

“Offspring of older women do better in similar tests, but this is usually put down to socio-economic status of women,” he said.

“But with the older dads, we wonder if the association is related to mutations in the developing sperm.”

Professor McGrath and colleagues at QBI and the Queensland Institute of Medical Research are currently using mouse models in order to find the underlying genetic factors that may explain the association between advance paternal age and child development.

New research shows that having ovarian endometriosis doubles the risk of premature birth in women using assisted reproductive technologies.
Professor David Healy Chairman of the Monash University Department of Obstetrics and Gynaecology and Director of the Jean Hailes Foundation for Women’s Health led a comparative study of more than 6,000 births.

“This research is important for all pregnant women and is the first time that endometriosis has been so clearly associated with premature birth,” Professor Healy said.

“Obstetricians will now be able to more readily identify and monitor mothers-to-be who are at increased risk of premature labour and birth.”

Endometriosis affects up to one in 10 women of childbearing age. It occurs when the tissue that normally lines the uterus (the endometrium) is found outside the uterus. The misplaced tissue commonly grows on the ovaries (ovarian endometriosis), but can also occur on the fallopian tubes or the tissue lining the pelvis (the peritoneum).

Professor Healy said further research was needed to determine the clinical benefit of removing ovarian endometriosis prior to using any assisted reproductive technologies and to address the gaps in the understanding of the chain of events leading from ovarian endometriosis to premature birth.

“The earlier endometriosis can be detected the better. Especially as up to 44 per cent of women show no obvious symptoms of endometriosis,” Professor Healy said.

The causes of endometriosis are not fully understood and there may be many reasons why it occurs and may become a chronic condition.

Diagnosis of endometriosis is by laparoscopy, an operation performed under general anaesthetic, where a small telescope is inserted into the abdomen through a cut in the belly button. Ovarian endometriosis can be diagnosed via ultrasound.

Treatment would depend on the severity, symptoms and whether pregnancy is desired, and can include medication for pain relief, natural and/or hormone therapies or surgery.

(Source: Monash University: March 2009.)