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Researchers at the University of Pennsylvania School of Medicine have modified a honeybee venom toxin so that it can be used as a tool to study the inner workings of ion channels that control heart rate and the recycling of salt in kidneys. In general, ion channels selectively allow the passage of small ions such as sodium, potassium, or calcium into and out of the cell.
Buy viagra pills The study, published in the Proceedings of the National Academy of Sciences, is from the laboratory of Zhe Lu, M.D, Ph.D., Professor of Physiology and a Howard Hughes Medical Institute Investigator, who looked at the action of a natural bee toxin on inward-rectifier potassium channels, Kir channels for short, to identify new approaches to treat cardiovascular disease.
The honeybee venom toxin, called tertiapin, or TPN, stops the flow of potassium ions across cell membranes by plugging up the opening of Kir channels on the outside of cells. Kir channels in kidneys are potential new targets for treating hypertension. "The clue comes from patients with genetic defects in these channels who lose a lot of sodium because it cannot be effectively reabsorbed and thus have low blood pressure," notes Lu. "An inhibitor specifically against these kidney channels will allow this idea to be tested."
Developing a specific inhibitor for one type of Kir channel has been challenging because the target site is very similar among different types of Kir channels. For example, while TPN inhibits Kir type 1 channels in kidney cells, it also inhibits other types of Kir channels in heart cells. After more than a decade, Lu and his colleagues succeeded in bioengineering a TPN that selectively inhibits Kir channels important for salt recycling in kidneys.
By introducing two mutations into TPN, they engineered a variant, called TPNLQ, which stems the flow of potassium ions in renal Kir type 1 channels at low concentrations, and with a 250-fold sensitivity over six other types of Kir channels.
The development of TPNLQ demonstrates that a highly specific inhibitor of potassium channels can be engineered. TPNLQ can now be used as a tool to prove the concept, in animal studies, that reducing salt reabsorption by plugging up renal Kir type 1 potassium channels is a potential new way to treat hypertension.
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Article adapted by Medical News Today from original press release.
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Yajamana Ramu and Yanping Xu of Penn conducted this study with Dr. Lu. The research was supported by the National Institutes of General Medical Sciences and the University of Pennsylvania Research Foundation.
PENN Medicine is a $3.5 billion enterprise dedicated to the related missions of medical education, biomedical research, and excellence in patient care. PENN Medicine consists of the University of Pennsylvania School of Medicine (founded in 1765 as the nation’s first medical school) and the University of Pennsylvania Health System.
Penn’s School of Medicine is currently ranked #4 in the nation in U.S.News & World Report’s survey of top research-oriented medical schools; and, according to most recent data from the National Institutes of Health, received over $379 million in NIH research funds in the 2006 fiscal year. Supporting 1,400 fulltime faculty and 700 students, the School of Medicine is recognized worldwide for its superior education and training of the next generation of physician-scientists and leaders of academic medicine.
The University of Pennsylvania Health System includes three hospitals - its flagship hospital, the Hospital of the University of Pennsylvania, rated one of the nation’s top 10 "Honor Roll" hospitals by U.S.News & World Report; Pennsylvania Hospital, the nation’s first hospital; and Penn Presbyterian Medical Center - a faculty practice plan; a primary-care provider network; two multispecialty satellite facilities; and home care and hospice.
Source: Karen Kreeger
University of Pennsylvania School of Medicine
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Patients who experience a range of ear, nose, and throat-related health problems exhibited a greater prevalence of depression than is observed in the general population, says new research presented at the 2008 American Academy of Otolaryngology - Head and Neck Surgery Foundation (AAO-HNSF) Annual Meeting & OTO EXPO in Chicago, IL.
In any given one-year period, approximately 9.5 percent of the population, or about 18.8 million American adults suffer from a depressive illness. The new study, which analyzed the health of 12,516 distinct otolaryngology patients, found that 30 percent of these patients either had been diagnosed with depressive illness or took antidepressants.
The study further broke down different otolaryngologic diagnoses to determine which conditions had the highest co-morbidity with depression. Researchers found that patients diagnosed with sleep apnea had the highest levels of depression and use of antidepressant medications (21 percent and 46 percent).
Findings from this study could help clinicians diagnose and treat co-morbid depressive and otolaryngolic symptoms in patients.
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Article adapted by Medical News Today from original press release.
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Title: Prevalence of Depression in Otolaryngology Patients
Presenters: Victoria A. Epstein MD; Andrew J. Fishman, MD; Rakesh K. Chandra, MD
Date: September 21, 2008
About the AAO-HNS
Buy diflucan pills The American Academy of Otolaryngology - Head and Neck Surgery (), one of the oldest medical associations in the nation, represents more than 12,000 physicians and allied health professionals who specialize in the diagnosis and treatment of disorders of the ears, nose, throat, and related structures of the head and neck. The Academy serves its members by facilitating the advancement of the science and art of medicine related to otolaryngology and by representing the specialty in governmental and socioeconomic issues. The organization’s vision: "Empowering otolaryngologist-head and neck surgeons to deliver the best patient care."
Source: Jessica Mikulski
American Academy of Otolaryngology — Head and Neck Surgery
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A new study published in the August 15th issue of Biological
Psychiatry finds that hippocampal neurogenesis (neuron birth
in the hippocampus part of the brain) might be used by the
monoaminergic antidepressants (related to the secretion of monoamine
neurotransmitters such as dopamine and serotonin) to counteract the
effects of stress, whereas similar effects could be achieved by
directly targeting the hypothalamo-pituitary-adrenal (HPA)
axis and related neuropeptides (amino acid chains).
Results from studies of antidepressant medications over the past
several years have been mixed, and Alexandre Surget (Universit?©
Fran?§ois Rabelais de Tours, Tours, France) and colleagues wonder if it
is time to abandon corticotrophin releasing factor-1 (CRF1)
antagonists as antidepressants - ones that recently failed in a large
clinical trial - or time to analyze the agents from a different
perspective. It has been known that depression and anxiety disorders
are linked to dysfunction of the
hypothalamo-pituitary-adrenal (HPA) axis as well as structural changes
within
the hippocampus itself. Animal studies in mice have shown that
unpredictable chronic mild stress (UCMS) can reignite these effects,
and UCMS-induced changes -
including downregulation of hippocampal neurogenesis - can be reversed
by antidepressant (AD) treatment. Knowing that stress-related
disruption of hippocampal neurogenesis can be reversed is important to
the actions of available AD medications. Surget and colleagues
investigated causality between
changes in hippocampal neurogenesis and the effects of both chronic
stress and chronic ADs.
One result of the study revealed that eliminating hippocampal
neurogenesis has no effect on animals’ sensitivity to UCMS in several
behavioral assays; that is, reduced neurogenesis does not cause
stress-related behavioral deficits. The researchers also show
the existence of both neurogenesis-dependent and -independent
mechanisms for the reversal of stress-induced behaviors by AD drugs.
Using two experimental approaches for treating
depression, blockade of the CRF1 receptor or the
vasopressin-1B (V1B) receptor, the researchers show their efficacy in
reversing the impact of stress on behavior even when neurogenesis is
disrupted. Corresponding author Catherine Belzung, Ph.D., clarifies
that, "We now report evidence that restoration of the functioning of
the stress axis may be the key to how these new antidepressant
approaches might work."
Surget and colleagues’ findings indicate that neurogenesis disruption
may be causing CRF1 receptor antagonists to be effective in treating
stress-related behavioral disturbances even in a context where other
antidepressants do not work.
John H. Krystal, M.D. (Editor of Biological Psychiatry and affiliated
with both Yale University School of Medicine and the VA Connecticut
Healthcare System) writes in a comment that, "These findings
lend weight to the hope that CRF1 antagonists might play a role in the
treatment of antidepressant-resistant symptoms of depression or
posttraumatic stress disorder. If so, CRF1 antagonists could fulfill an
important unmet need…We do not need another Prozac, but we urgently
need to find ways to help the large number of patients who fail to
respond adequately to our available treatments."
Drug-Dependent Requirement of Hippocampal Neurogenesis in a
Model of Depression and of Antidepressant Reversal
Alexandre Surget, Michael Saxe, Samuel Leman, Yadira Ibarguen-Vargas,
Sylvie Chalon, Guy Griebel, Ren?© Hen, Catherine Belzung
Generic cialis pills no prescription Biological Psychiatry (2008). 64[4]:
pp 293 - 301.
doi:10.1016/j.biopsych.2008.02.022
Click
Here to View Journal Website
Written by: Peter M Crosta
View drug information on Prozac Weekly.
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today
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Though effective treatments are available for individuals suffering from chronic depression and anxiety, very little is known about how often these treatments are used or how prevalent these conditions are among the nation’s general population.
But in a first-of-its-kind study, UCLA researchers have developed estimates for both the prevalence of chronic psychiatric illness in the general population and how often individuals suffering from such illnesses receive appropriate treatment.
In the study, published in the December issue of the peer-reviewed journal Psychiatric Services and currently available online, researchers found that approximately 4.7 percent of the nation’s population suffers from persistent depression or anxiety disorders, with a minority of those afflicted receiving adequate medication or counseling.
"From a policy perspective, this study indicates that we have to do much better in terms of helping people in the population and clinicians in primary care," said lead author Dr. Buy lasix pills Alexander S. Young, a UCLA professor of psychiatry and director of health services for the Department of Veterans Affairs Desert Pacific Mental Illness Research, Education and Clinical Center (MIRECC). "We need to understand that psychiatric disorders are treatable with psychotherapy and/or medication. Patients would benefit if we improved linkages between primary care and specialty mental health care so that patients are referred and accept referrals to mental health specialists, especially when they are chronically ill.
"Also, we have to improve insurance arrangements so that they encourage more intensive treatment in people who remain ill," he said.
The study was based on data from Healthcare for Communities, a nationally representative household survey of adults in the United States. The researchers analyzed responses from 1,642 adults with major depression or anxiety disorders. These surveys, conducted in 1997 and 1998, with follow-ups approximately two-and-a-half years later, assessed diagnosis, quality of life, treatment satisfaction, medical conditions, suicidal thoughts, insurance, and the use of medications and counseling.
At follow-up, the researchers found that 59 percent of the individuals no longer met the criteria for having a psychiatric disorder. But to their surprise, they found that among those who remained ill, there were only modest increases in medication use and no statistically significant increase in the use of counseling for their disorders - measures that are known to significantly improve outcomes, especially when used in combination. Among this subgroup:
87 percent had a chronic, co-morbid medical disorder.
In the prior year, 88 percent had seen a primary care practitioner, but only 22 percent had consulted a mental health specialist.
In the two-and-a-half years between baseline and follow-up, use of medication rose from 21 percent to 29 percent, and use of counseling fell from 23 percent to 19 percent.
Only 12 percent with persistent illness were getting both medication and counseling (the appropriate treatment in this situation).
51 percent had suicidal thoughts at follow-up.
Men and those with less education received less treatment.
"Persistent depressive and anxiety disorders are remarkably common in the U.S. population and are associated with substantial morbidity. There are significant problems with the quality of care received by this population, and these problems persist over time," the researchers concluded. "In the population with persistent depressive and anxiety disorders, increasing the rate of appropriate care from its current low level could result in substantial improvement in individuals’ lives."
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Article adapted by Medical News Today from original press release.
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In addition to Young, study authors included Ruth Klap, Ph.D., of the Health Services Research Center at UCLA; Rebecca Shoai, M.P.H., M.S.W., affiliated with MIRECC; and Kenneth B. Wells, M.D., M.P.H., of the UCLA Department of Psychiatry and the RAND Corp.
The Robert Wood Johnson Foundation funded the study, with additional support from the National Institute of Mental Health and the U.S. Department of Veterans Affairs.
The UCLA Department of Psychiatry and Biobehavioral Sciences within the David Geffen School of Medicine is home to faculty who are experts in the origins of and treatments for disorders of complex human behavior. The department is part of the Semel Institute for Neuroscience and Human Behavior at UCLA, a world-leading interdisciplinary research and education institute devoted to the understanding of complex human behavior and the causes and consequences of neuropsychiatric disorders.
Source: Enrique Rivero
University of California - Los Angeles
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This is according to an American study. Its authors recommend screening
for diabetes, arterial hypertension and cardiovascular disease in
patients with COPD.
The study, to be published in the forthcoming issue of the
European Respiratory Journal (ERJ), the scientific publication
of the European Respiratory Society, finds that chronic
obstructive pulmonary disease (COPD) is often associated
with other serious illnesses.
Conversely, a patient with diabetes or arterial hypertension
should also be screened for COPD and other respiratory conditions,
according to the study’s authors.
COPD, which includes chronic bronchitis and emphysema, is
increasingly prevalent throughout the world. This serious respiratory
disease, caused largely by smoking, could become the third most
common cause of death in Western countries by 2020, according to
calculations by the World Health Organization (WHO).
In view of this danger, considerable efforts are under way to improve
management and prevention of COPD. In particular, researchers are
attempting to identify which illnesses are frequently linked with
COPD and assess their impact on the way the disease progresses.
Among them are David Mannino (Department of Preventive Medicine and
Environmental Health, University of Kentucky, Lexington, USA) and his
team, who set out to determine what links COPD to cardiovascular
disease, hypertension and diabetes, and to assess to what degree the
simultaneous presence of several diseases (comorbidity) could affect
hospitalisation and mortality rates.
Over 20,000 patients monitored for five years
For their project, two existing databases were combined, one from the
ARIC (Atherosclerosis Risk In Communities) cohort and the other from
the Cardiovascular Health Study (CHS). Launched in the late 1980s by
the US National Institutes of Health, both studies included thousands
of subjects, aged over 65 for the CHS and from 45 to 64 for ARIC.
Mannino’s team only studied patients for whom adequate pulmonary
function data were available, selecting 15,341 volunteers from the
ARIC cohort and 4,955 from the CHS.
The total of 20,296 subjects were classified according to the
severity of their COPD, using a scale based on the GOLD (Global
Initiative for Chronic Obstructive Lung Disease) classification. This
involves five stages, from 0 (respiratory symptoms such as chronic
cough and expectoration, but without reduction of respiratory
function) to 4 (very severe disease with major anomalies revealed by
spirometric testing).
In each group of patients, the authors analysed the presence or
absence of diabetes, arterial hypertension, or a cardiovascular
disease, including angina pectoris, antecedents of myocardial
infarction, heart failure, stroke and transient ischaemic attack (TIA).
They also noted the levels of hospitalisation and mortality over the
five-year monitoring period of the studies.
Over half of patients have a comorbidity
The results published by the ERJ provide food for thought.
A total of 530 patients were in one of the more severe COPD
categories (GOLD 3 or 4), with another 2,076 suffering from moderate
COPD (GOLD 2) and 2,892 for whom the disease was just beginning (GOLD 1).
A further 4,511 subjects could be considered as potentially at risk
(GOLD 0) and 2,868 others were found by functional respiratory
testing to be suffering from restrictive syndrome (excessively small
lung volume).
Finally, the remaining 7,419 subjects, or approximately one-third of
the participants, could be classed as "normal" in terms of
respiratory function.
Mannino and his team report in the ERJ article that, having analysed
each of the groups for comorbidities, they found over half of the
COPD patients to be suffering from an associated condition.
This was particularly striking among patients with one of the severe
forms of COPD (GOLD stage 3 or 4), for whom the risk of diabetes was
increased by 50%, hypertension by 60% and cardiovascular disease by
140%.
Results are similar for the group of non-COPD patients with
restrictive syndrome.
In total, less than half of COPD patients (48.9%) did not have a
comorbidity. Over one-third (7,359, or 36.3%) had a single
comorbidity, while 2,597 (12.8%) had two. There were even 415
patients (2%) with all three.
What is more, the authors emphasise, the risk of hospitalisation
during the five-year study period was significantly higher for those
with one or more comorbidities.
The association between COPD and cardiovascular disease has not been
completely elucidated.
It could arise from a number of factors, including chronic infection,
inflammation or a shared risk factor, such as smoking.
Strangely, though, the association with cardiovascular disease
appears to be independent of the severity of the respiratory
condition: "the risk of cardiovascular disease is the same in
patients with severe COPD and those with only early signs of the
condition", Mannino comments.
He believes, therefore, that there would be benefits from systematic
screening for cardiovascular disease, hypertension and diabetes in
COPD patients, and vice versa.
Title Of The Original Article
"Prevalence and outcomes of diabetes, hypertension, and cardiovascular disease in COPD."
D.M. Mannino, D. Thorn, A. Buy generic viagra Swensen, F. Holguin
Eur Respir J 2008, doi:10.1183/09031936.00012408
Click here to view abstract online.
The European Respiratory Journal is the peer-reviewed scientific publication of the European Respiratory Society (more than 8,000 specialists in lung diseases and respiratory medicine in Europe, the United States and Australia).
European Respiratory Journal
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