Day: 03/17/2011

Amygdala circuitry mediating reversible and bidirectional control of anxiety

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Anxiety—a sustained state of heightened apprehension in the absence of immediate threat—becomes severely debilitating in disease states1. Anxiety disorders represent the most common of psychiatric diseases (28% lifetime prevalence)2 and contribute to the aetiology of major depression and substance abuse3, 4. Although it has been proposed that the amygdala, a brain region important for emotional processing5, 6, 7, 8, has a role in anxiety9, 10, 11, 12, 13, the neural mechanisms that control anxiety remain unclear. Here we explore the neural circuits underlying anxiety-related behaviours by using optogenetics with two-photon microscopy, anxiety assays in freely moving mice, and electrophysiology. With the capability of optogenetics14, 15, 16 to control not only cell types but also specific connections between cells, we observed that temporally precise optogenetic stimulation of basolateral amygdala (BLA) terminals in the central nucleus of the amygdala (CeA)—achieved by viral transduction of the BLA with a codon-optimized channelrhodopsin followed by restricted illumination in the downstream CeA—exerted an acute, reversible anxiolytic effect. Conversely, selective optogenetic inhibition of the same projection with a third-generation halorhodopsin15 (eNpHR3.0) increased anxiety-related behaviours. Importantly, these effects were not observed with direct optogenetic control of BLA somata, possibly owing to recruitment of antagonistic downstream structures. Together, these results implicate specific BLA–CeA projections as critical circuit elements for acute anxiety control in the mammalian brain, and demonstrate the importance of optogenetically targeting defined projections, beyond simply targeting cell types, in the study of circuit function relevant to neuropsychiatric disease.

source: nature

Is Drinking Wine a Key to Antiaging?

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Richard Baxter, MD, talks about the benefits of wine

The latest antiaging weapon is not an injection or a wonder cream, and it doesn’t involve any nipping or tucking either.

It’s a glass of red wine a day for women and two for men, according to Richard A. Baxter, MD, a plastic surgeon in Seattle and the author of Age Gets Better with Wine. Baxter gave a talk on wine and beauty at the annual meeting of the American Society for Aesthetic Plastic Surgery in Washington, D.C.

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WebMD sat down with him to discuss exactly how age gets better with wine.

Here’s what he had to say:

Wine and beauty, really?

There is quite a lot of data on the wine and beauty connection. I was surprised at how extensive the data is on wine as an antiaging intervention.

What is it about wine that can help us age and look better?

The mechanism is the antioxidants in red wine. Antioxidants sop up damaging free radicals that play a role in aging and age-related diseases. There is a much higher concentration of antioxidants called polyphenols, including resveratrol, in wine compared to grape juice. In wine, the skin and seeds are part of the fermenting process, but both are removed when making grape juice.

I think stress has something to do with it, too. It is difficult to sort out how much of the benefits are from the chemical properties of wine vs. the types of behaviors that wine drinkers tend to have such as less stress in their lives. Wine is part of the Mediterranean diet, which is also rich in fresh fruits and vegetables, whole grains, nuts and seeds, legumes, seafood, yogurt, and olive oil. This diet is more of a lifestyle that includes drinking wine with dinner. Studies show that the Mediterranean diet is associated with longer, healthier lives.

Any caveats?

Drinking a glass of red wine a day is the single most important thing that you can do other than nonsmoking, from an antiaging point of view, but you can have too much of a good thing. Drinking more than recommended can have the opposite effect on your appearance and health.

What is your wine prescription for WebMD readers?

A glass a day and your skin will glow. As antiaging advice, this is as good as it gets.

Specifically, what benefits can a person expect if they follow your advice?

You will look better, your skin will glow, and you will live five years longer than a teetotaler. There are also good studies that show people who drink red wine on a regular basis have fewer actinic keratoses [precancerous skin lesions]. You will have a significantly lower risk of Alzheimer’s disease, cancer, diabetes, and all of the things that go along with aging. People assume that drinking would decrease brainpower as you get old, but the most amazing thing is that regular wine drinkers have an 80% lower risk of developing Alzheimer’s disease.

What about people who can’t consume alcohol?

People who can’t drink wine should such look to other whole foods with polyphenols and antioxidants, like pomegranates and blueberries. Or go for dark chocolate. It does a lot of the same things as wine. Both dark chocolate and red wine have been shown to protect the skin from sun damage.

Will winemakers put plastic surgeons out of business?

No. It’s an adjunctive thing.

There are some supplements out there that say they have the ingredients — namely resveratrol — that make red wine so healthy. Do they work?

The data is really minimal in terms of the effectiveness of resveratrol supplements. The jury is out about whether you get same benefits in a pill that you get with a glass of red wine.

What about skin creams with resveratrol?

This will be the next big thing in skin care. Stay tuned.

Are any wines better than others?

White wines do not have as many antioxidants as red wines. In terms of reds, it has more to do with the way the grapes are grown than the varieties of wine. Oregon pinot noirs tend to have higher levels of polyphenols and European wines tend to have more polyphenols than American wines, in general.

What type of wine do you drink?

I like all red wines, but I am really partial to Australian shiraz.

source: webMD exclusive interview

 

Zalutumumab Plus Best Supportive Care Versus Best Supportive Care Alone in Patients With Recurrent or Metastatic Squamous-Cell Carcinoma of the Head and Neck After Failure of Platinum-Based Chemotherapy

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No treatments are presently available to increase survival in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck after failure of platinum-based chemotherapy. We aimed to assess efficacy and safety of zalutumumab, a human IgG1 monoclonal antibody targeting the epidermal growth factor receptor, for overall survival in such patients.

Methods: In our open-label, parallel-group, phase 3, randomised trial, we randomly allocated patients with squamous-cell carcinoma of the head and neck who were regarded as incurable with standard therapy, a WHO performance status of 0—2, and progressive disease within 6 months of platinum-based therapy in a 2:1 ratio to receive zalutumumab plus best supportive care (zalutumumab group) or best supportive care with optional methotrexate (control group) at medical centres in Europe, Brazil, and Canada. Randomisation was done via a centralised interactive voice-response system, stratified by performance status. Data were analysed when the randomisation code was broken, after the completion of the accrual and cleaning of the relevant data. An independent review committee, masked to treatment assignment, assessed tumour response and disease progression according to response evaluation criteria in solid tumours. Zalutumumab was given weekly by individual dose titration on the basis of skin rash. After a prespecified 231 deaths, we included all randomised patients in the survival analyses and all patients receiving at least one session of therapy in the safety analysis. The primary endpoint was overall survival, although progression-free survival was also assessed. This trial is registered with ClinicalTrials.gov, NCT00382031.

Findings: We randomly allocated 191 (67%) of 286 eligible patients to the zalutumumab group and 95 (33%) to the control group. Median overall survival was 6•7 months (95% CI 5•8—7•0) in the zalutumumab group and 5•2 months (4•1—6•4) in the control group (hazard ratio [HR] for death, stratified by WHO performance status, was 0•77, 97•06% CI 0•57—1•05; unadjusted p=0•0648). Progression-free survival was longer in the zalutumumab group than in the control group (HR for progression or death, stratified by WHO performance status, was 0•63, 95% CI 0•47—0•84; p=0•0012). 189 patients given zalutumumab and 94 controls were included in the safety analysis. The most common grade 3—4 adverse events were rash (39 [21%] patients in the zalutumumab group vs none in the control group), anaemia (11 [6%] vs five [5%]), and pneumonia (nine [5%] vs two [2%]). 28 (15%) patients in the zalutumumab group had grade 3/4 infections compared with eight (9%) in the control group. The most common serious adverse events were tumour haemorrhage (28 [15%] patients given zalutumumab vs 13 [14%] controls), pneumonia (13 [7%] vs three [3%]), and dysphagia (11 [6%] vs two [2%]).

Interpretation: Although zalutumumab did not increase overall survival, progression-free survival was extended in patients with recurrent squamous-cell carcinoma of the head and neck who had failed platinum-based chemotherapy. Zalutumumab dose titration on the basis of rash is safe.

source: Oncostat

Reducing Central Line–Associated Bloodstream Infections

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The number of such infections in intensive care units in the U.S. has fallen markedly because of improved central line insertion and maintenance techniques.

Central line–associated bloodstream infections (CLABSIs) are common and often fatal (mortality rate, 12%–25%). In 2002, the CDC issued guidelines for the prevention of such infections. Have these guidelines had the desired effect?

To answer this question, CDC researchers — using several national data sources — estimated the number of CLABSIs among patients aged 1 year in intensive care units (ICUs) in the U.S. before and after publication of the guidelines. For 2001, the number of CLABSIs (after adjustment to account for a change in CLABSI definition in 2008) was estimated to be 43,000. For 2009, the number was estimated to be 18,000 — a 58% reduction.

The researchers also estimated that 37,000 CLABSIs occurred in outpatient hemodialysis facilities in 2008, and that 23,000 occurred on non-ICU inpatient wards in 2009. These categories have no corresponding data for 2001 but provide benchmarks for future comparison.

Comment: Although the definition of CLABSI has changed over the years, and some infections may have gone undiagnosed because blood cultures were not performed, the number of CLABSIs in ICUs has dropped significantly. The use of meticulous placement and care techniques in this setting is no doubt responsible.

In non-ICU settings, where central lines are less frequently inserted, rate reductions may be harder to achieve. Additional preventive strategies (particularly measures designed to improve central line maintenance, to ensure prompt removal of unneeded lines, and to reduce central line use for hemodialysis) will be necessary in these venues to produce CLABSI decreases similar to those realized in ICUs.

— Stephen G. Baum, MD

Published in Journal Watch Infectious Diseases

 

Guidelines: Extracranial Carotid and Vertebral Artery Disease

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Experts address the appropriate use of contemporary imaging and revascularization techniques and identify important gaps in the evidence base to guide future research.

Sponsoring Organizations: American College of Cardiology, American Heart Association, American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, Society for Vascular Surgery, American Academy of Neurology, Society of Cardiovascular Computed Tomography

Background and Purpose: These new guidelines on caring for patients with extracranial carotid and vertebral artery disease (ECVD) provide recommendations for diagnostic testing, modification of risk factors, and medical and surgical therapies, focusing on the use of stenting and surgery for carotid revascularization.

Key Points:
1. Population screening for asymptomatic carotid artery stenosis is not recommended (Class III, level C).

2. Duplex ultrasonography is the recommended initial diagnostic test in asymptomatic patients with known or suspected carotid artery stenosis (Class I, level C).

3. Duplex ultrasonography is also the recommended initial diagnostic test in patients with focal neurological symptoms corresponding to the territory supplied by the left or right internal carotid artery (Class I, level C).

4. Magnetic resonance angiography or computed tomography angiography is recommended in symptomatic patients when sonography either is unavailable or yields uncertain results (Class I, level C).

5. Recommendations for the medical management of ECVD include:

  • Blood pressure control to <140/90 mm Hg (Class I, level A)
  • Smoking cessation (Class I, level B)
  • Statin therapy to reduce LDL level to <100 mg/dL (Class I, level B) or to ≤70 mg/dL in patients with diabetes (Class IIa, level B)
  • In patients with diabetes, diet, exercise, and glucose-lowering treatment; however, stroke prevention benefit has not been demonstrated at glycosylated hemoglobin A1c levels <7% (Class IIa, level A).

6. Regarding antithrombotic therapy for ECVD:

  • Aspirin, 75 to 325 mg daily, is recommended for prevention of myocardial infarction and other cardiovascular events; however, no benefit has been demonstrated for primary prevention of stroke (Class I, level A).
  • After stroke or transient ischemic attack (TIA), aspirin (75 to 325 mg daily), clopidogrel (75 mg daily), or the combination of aspirin and extended-release dipyridamole (25 mg and 200 mg twice daily, respectively) is recommended and preferable to the combination of aspirin and clopidogrel, which increases hemorrhagic risk (Class I, level B).

7. In patients with symptomatic carotid stenosis, the choice between stenting and surgery has been controversial. Upon reviewing the evidence, the authors conclude that choosing surgery over stenting is reasonable in older patients, particularly when arterial anatomy is unfavorable for stenting; similarly, choosing stenting over surgery is reasonable when neck anatomy is unsuitable for surgery (Class IIa, level B).

8. Carotid duplex ultrasound screening before coronary artery bypass grafting is reasonable in patients aged >65 and in those with left main coronary stenosis, a history of stroke or TIA, or carotid bruit (Class IIa, level C); however, the safety and efficacy of carotid revascularization before or during myocardial revascularization remain unproven in asymptomatic patients (Class IIb, level C).

Comment: These recommendations concur with recently released guidelines on primary and secondary stroke prevention. The main message about revascularization for symptomatic carotid stenosis is that stenting should be avoided in older patients (e.g., aged ≥70) but might be as safe as endarterectomy in younger patients. However, a more important question is how either revascularization technique compares with intensive contemporary medical therapy, particularly in asymptomatic patients. As evidenced by the number of recommendations that are based on consensus in the absence of definitive evidence, opportunities for further research abound (e.g., the “imperfect correlation” between severity of carotid stenosis and ischemic events, methods to improve diagnostic accuracy, the effectiveness of carotid surgery in women). Large gaps in knowledge about vertebral arterial disease will be difficult to fill because of its relative infrequency compared with carotid artery disease.

— Beat J. Meyer, MD

Published in Journal Watch Cardiology March 16, 2011

Revisiting the concept of cancer stem cells in prostate cancer

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The cancer stem cell (CSC) model proposes that cells within a tumor are organized in a hierarchical lineage relationship and display different tumorigenic potential, suggesting that effective therapeutics should target rare CSCs that sustain tumor malignancy. Here we review the current status of studies to identify CSCs in human prostate cancer as well as mouse models, with an emphasis on discussing different functional assays and their advantages and limitations. We also describe current controversies regarding the identification of prostate epithelial stem cells and cell types of origin for prostate cancer, and present potential resolutions of these issues. Although definitive evidence for the existence of CSCs in prostate cancer is still lacking, future directions pursuing the identification of tumor-initiating stem cells in the mouse may provide important advances in evaluating the CSC model for prostate cancer.

source: oncogene

 

Tequila plant holds promise as arid biofuel source

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A plant more commonly known for its role in the production of the alcoholic drink tequila  has been overlooked as a source of biofuel that would not compete with food crops, say experts.

Agave plants can sustain high yields while enduring extreme temperatures, droughts and CO2 increases, with little need for irrigation, according to a series of papers in a special issue of Global Change Biology Bioenergy published last month (February).

With around 20 per cent of the world semi-arid, and some 200 agave species growing worldwide, the plant could help usher in an energy revolution, experts say.

Field trials of the biofuel potential of some common Mexican varieties have begun in Australia and “there are vast areas of abandoned agave plantations in Africa [once used for sisal fibre production, but abandoned after synthetic fibre production came along] that might be re-established [for biofuel use] without incurring economic and environmental costs of indirect land use change”, according to one of the papers.

Two varieties — Agave mapisaga and Agave salmiana — produce, under intensive management, yields that far exceed corn, soybean, sorghum, and wheat productivities; and even without irrigation they still maintain high yields, argues another paper.

Arturo Velez, a former coordinator at the National Confederation of Forestry Producers and head of the Agave Project, an initiative to scale up agave biofuel production in Mexico, told SciDev.Net that some varieties produce twicethe dry biomass per hectare of hybrid poplar, three times the sugar of sugarcane, and four times more cellulose than eucalyptus, and capture five times more CO2 than the most productive ecosystem.

“Mexico has 80 million hectares of arid and semiarid areas with no productive potential in which 5,600 million tons of dry biomass could be obtained from agave,” he said. This would be enough to meet the United States’ transport fuel needs.

Different agave species are already widely used in Mexico for production of tequila and bacanora drinks and henequen fibre, but in some cases up to 80 per cent of the plant’s biomass is being thrown away.

“We would be putting to good use the wastes of industries that are already running,” Felipe Barahona, researcher at the Yucatan Center for Scientific Research, Mexico, and co-author of one of the articles, told SciDev.Net. “Agave can be used because it is already being produced, whereas to obtain oil from jatropha or ethanol from sugarcane these would have to be farmed.”

Martín Esqueda, a researcher at the Feeding and Development Research Centre in Mexico, working with the country’s University of Sonora on a project seeking bioenergy in arid lands, warned that agave should be sustainably managed to avoid over-exploitation of the wild populations. This has happened with angustifolia species, which is now endangered because of unsustainable use to produce bacanora, he said.

author: Lucina Melesio Friedman

source: sciDev Net