Rosuvastatin can regress the atherosclerosis

March 14, 2006 — Rosuvastatin, 40 mg, can regress the atherosclerosis burden, according to the results of a prospective, open-label Study published in the March 13 JAMA Express issue of JAMA. However, the editorialists temper the enthusiasm for these findings.

"Although statins rank among the most extensively studied therapies in contemporary medicine, the optimal target levels for low-density lipoprotein cholesterol (LDL-C) remain controversial," write Steven E. Nissen, MD, From Cleveland Clinic Foundation in Ohio, and colleagues From the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID) Investigators. "Prior intravascular ultrasound (IVUS) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume (PAV), the most rigorous IVUS measure of disease progression and regression."

To determine whether very intensive statin therapy could regress coronary atherosclerosis measured by IVUS imaging, the ASTEROID Study was performed at 53 community and tertiary Care centers in the United States, Canada, Europe, and Australia. A motorized IVUS pullback was used to evaluate, in a blinded fashion, coronary atheroma burden at baseline and after 24 months of treatment. Of 507 patients who had a baseline IVUS examination and received at least 1 dose of Study Drug between November 2002 and October 2003, 349 patients had evaluable serial IVUS examinations after 24 months. All patients received intensive statin therapy with rosuvastatin, 40 mg/day. Two prespecified, primary outcome measures for efficacy were change in PAV and change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline. A secondary prespecified efficacy outcome was change in normalized total atheroma volume for the entire artery.

Mean baseline LDL-C level decreased From 130.4 ± 34.3 mg/dL at baseline to 60.8 ± 20.0 mg/dL (mean reduction, 53.2%; P <.001). Mean high-density lipoprotein cholesterol (HDL-C) level increased From 43.1 ± 11.1 to 49.0 ± 12.6 mg/dL (mean increase, 14.7%; P < .001).

For the entire vessel, the mean change in PAV was -0.98% ± 3.15% (median, -0.79%; 97.5% confidence interval [CI], -1.21% to -0.53%; P < .001 vs baseline). Mean change in atheroma volume in the most diseased 10-mm subsegment was -6.1 ± 10.1 mm3 (median, -5.6 mm3; 97.5% CI, -6.8 to -4.0 mm3; P < .001 vs baseline). Median reduction in total atheroma volume was 6.8% (mean reduction, -14.7 ± 25.7 mm3; median, -12.5 mm3; 95% CI, -15.1 to -10.5 mm3; P < .001 vs baseline). Adverse events were infrequent and similar to those reported in other statin trials.

"Very high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7%, resulting in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden," the authors write. "Treatment to LDL-C levels below currently accepted guidelines, when accompanied by significant HDL-C increases, can regress atherosclerosis in coronary disease patients. Further studies are needed to determine the effect of the observed changes on Clinical outcome."

Study limitations include lack of a control group receiving either placebo or a less active statin; withdrawal of 22 patients for ischemic events creating a potential Source of bias; and inability to determine the degree to which regression documented by IVUS will translate into a reduction in morbidity and mortality.

AstraZeneca, the maker of rosuvastatin, funded this Study. Several authors have disclosed relevant financial relationships with AstraZeneca, Eli Lilly, Pfizer, Takeda, Sankyo, Sanofi-Aventis, diaDexus, GeneLogic, GlaxoSmithKline, Integrated Therapeutics, Kos, Merck, Novartis, Roche, Sanofi-Synthelabo, Schering-Plough, Bayer, and/or Reliant.

In an accompanying editorial, Roger S. Blumenthal, MD, and Navin K. Kapur, MD, From The Johns Hopkins Ciccarone Preventive Cardiology Center in Baltimore, Md, note various Study limitations.

"Unfortunately, the ASTEROID Study does not provide definitive Information regarding the relationship of LDL-C lowering and extent of coronary atherosclerosis regression to determine if high-intensity treatment is required to achieve regression," Drs. Blumenthal and Kapur write. "While IVUS-documented atherosclerotic regression is an intriguing finding, clinicians must remember that this may not be the best measure of the treatment's effect on hard cardiovascular end points.... The results of several ongoing trials will help determine what agent or combination of pharmacologic agents is most efficacious in the long-term management of at-risk patients."

Dr. Blumenthal has disclosed receiving Clinical Research support and honoraria From speakers' bureau activities From Pfizer, Merck, Schering Plough, AstraZeneca, KOS, and Sanofi during the past 12 months. Dr. Kapur has disclosed no relevant financial relationships.

JAMA. 2006 Posted online March 13, 2006.

Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
List benefits of intensive vs moderate lipid-lowering therapy among patients with coronary atherosclerosis.
Identify the effect of very high-intensity statin therapy on coronary atheroma volume.
Clinical Context
The REVERSAL (Reversal of Atherosclerosis With Aggressive Lipid-Lowering) trial demonstrated that intensive therapy with statins could improve outcomes compared with moderate statin therapy among patients at high risk for coronary heart disease. This research, published in the March 3, 2004, issue of JAMA, compared 40 mg of pravastatin (moderate therapy) with 80 mg of atorvastatin (intensive therapy) and followed up patients for lipid levels as well as C-reactive protein levels and coronary atheroma volume.

LDL-C levels decreased to a greater degree with intensive therapy compared with moderate therapy, and the mean reduction in C-reactive protein levels was 5.2% with pravastatin therapy and 36.4% among subjects receiving atorvastatin. While coronary atheroma volume increased by an average of 2.7% among subjects receiving pravastatin, atheroma volume was stable for the 18-month treatment period among participants in the atorvastatin group.

Rosuvastatin is the most powerful statin in terms of LDL-C reduction. The authors of the current study examine the effects of rosuvastatin on lipid values and coronary atheroma volume.

Study Highlights
Patients eligible for study participation were adults undergoing coronary angiography for a clinical indication, such as chest pain or follow-up of an abnormal cardiac stress test. All subjects had at least 1 coronary obstruction between 20% and 50% in luminal diameter and had not received statins for at least 4 weeks prior to study enrollment. Patients with previous angioplasty in the target vessel, triglyceride levels higher than 500 mg/dL, or poorly controlled diabetes were excluded from study participation.
All study participants received 40 mg of rosuvastatin daily. The authors deemed it ethically unacceptable to include a control group receiving no therapy or low-intensity statin therapy.
The treatment period was 24 months. The main study outcome was coronary atheroma volume as measured by IVUS. The imaging sequence (baseline vs 24 months) was concealed from clinicians who read the study in an attempt to reduce possible observer bias. The authors also followed lipid levels.
1183 patients were screened for study participation, and 507 subjects were included at 53 centers. 349 participants had follow-up IVUS data available at 24 months. 22 subjects withdrew due to ischemic events. Baseline characteristics between study completers and noncompleters were similar.
The mean LDL-C level on treatment was 60.8 mg/dL, a 53.2% reduction from the mean baseline value. The mean high-density lipoprotein level on treatment was 49 mg/dL, a 14.7% increase from baseline.
The mean decrease in PAV was -0.98%, a significant decrease from baseline.
In the 10-mm subsegment of artery with the greatest degree of severity, rosuvastatin therapy was associated with a 9.1% decrease in atheroma volume.
The total reduction in atheroma volume was 6.8% after the treatment period. 63.6% of subjects demonstrated regression of PAV following rosuvastatin therapy.
There was no significant difference in the study's main findings after examining subgroups based on baseline demographic or lipid factors.
The authors performed analyses in which the 158 study noncompleters experienced no regression of atheroma volume, and rosuvastatin's positive results remained statistically significant. This outcome was also again found true in an analysis in which the 22 subjects with ischemic events were evaluated as having atheroma progression.
Adverse events were fairly rare, with 1.8% of the study population experiencing liver enzyme levels more than 3 times above normal. Creatine kinase levels rose more than 5 times above normal in 1.2% of subjects. 3.7% of participants discontinued rosuvastatin because of musculoskeletal complaints.
Pearls for Practice
The REVERSAL trial demonstrated that high-dose atorvastatin was superior to moderate-dose pravastatin in reducing LDL-C and C-reactive protein levels. While subjects receiving pravastatin had some progression of coronary atheroma volume, atorvastatin was associated with stable coronary atheroma volumes.
In the current study, 40 mg of rosuvastatin daily was associated with a reduction in PAV, atheroma volume in the portion of artery with the most severe disease, and total atheroma volume. Most subjects experienced regression of atheroma volume with rosuvastatin.


Saludos Cordiales

Dr. José Manuel Ferrer Guerra

Two New Cancer Drugs Discovered

Main Category: Cancer/Oncology News
Article Date: 28 Mar 2006 - 13:00pm (UK)

Delegates at the European Breast Cancer Conference (EBCC-5) were given two examples of promising new drugs to watch in the future - raloxifene and lapatinib.

New anticancer drugs are usually developed specially for the job, but occasionally they are borrowed from another field of medicine, and applied speculatively in cancer. Tamoxifen was designed as an anti-oestrogen, based on the observation that at least a third of breast cancers depend on female sex hormones such as oestrogen for survival. Tamoxifen has shown to be an exceptionally effective molecule in cancer treatment; It was never planned to be a preventive agent, but so it has proved to be! It is now licensed to be used to prevent breast cancer in certain women at high risk of the disease.

Contrast this with raloxifene, a drug first developed to treat osteoporosis in women. A selective benzothiophene oestrogen receptor modulator (SERM), raloxifene binds to oestrogen receptors as a mixed oestrogen and anti-oestrogen effect. It functions as an oestrogen sometimes (in bones and on lipid metabolism) and as an anti-oestrogen in other target tissues (endometrium and breast). So, it has the potential for producing some of oestrogen's beneficial effects without producing its adverse effects. In a trial of its use in osteoporosis, it appeared to have another completely different effect, namely prevention of new hormone dependant breast cancers.

Results from the MORE (The Multiple Outcomes of Raloxifene Evaluation) study of 7,705 women that were randomised to raloxifene or placebo demonstrated that among postmenopausal women with osteoporosis, the risk of invasive breast cancer was decreased by 76% during three years of treatment with raloxifene.

Stronger evidence on the safety and efficacy of raloxifene is awaited from the STAR Trial. This trial includes almost 20,000 postmenopausal women in the US who are at increased risk of breast cancer to determine whether raloxifene is as effective in reducing the chance of developing breast cancer as tamoxifen. Women taking raloxifene demonstrated some side effects and in clinical trials have about three times the chance of developing a deep vein thrombosis or pulmonary embolism as women on a placebo, however there is less risk of cancer of the uterus (a serious side effect of tamoxifen).

An example of a molecule causing much interest in breast cancer treatment is lapatinib, which administered orally. It was designed to hit a subset of the popular Epidermal Growth Factor Receptors (EGFR), which are targeted by other successful agents such as trastuzamab (Herceptin), cetuximab (Erbitux) and gefitinib (Iressa). The first two are monoclonal antibodies, against ErbB2 and ErbB1 respectively, the third is a 'designer' drug. Trials of the combination of antibodies have been promising, so the development of lapatinib to block both receptors via their tyrosine kinase portions is giving rise to optimism. It is a small molecule, like gefitinib, and may have pharmacological advantages over the antibody formulations, such as penetrating the blood-brain barrier.

Early clinical trials with lapatinib suggest that it may hit cancer cells, resistant to other commonly used breast cancer drugs, and to the other EGFR targeting agents, including trastuzamab. Its activity as a single agent is modest, but combination trials already underway are looking promising enough to start randomised comparative large scale investigation. Side effects reported so far suggest a good safety profile, though skin rash, lung and heart effects seen with other members of the drug class will be monitored carefully in the next generation of trials. And, following the example of tamoxifen, it is being tested as a chemo-preventive too.

Dr F. Cardoso from the Jules Bordet Institute, Brussels, who is involved in the drug research comments, "Raloxifene and lapatinib are exciting new drugs which will be of interest in prevention and treatment of breast cancer patients in the future."

###

Notes: For more information on the MORE trail see JAMA. 1999;281:2189-2197 The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women.

For further information please contact:
Stephanie Makin, Tonic Life Communications, stephanie.makin@toniclc.com

EBCC5 press office: Tuesday 21st March – Friday 24th March 2006 Tel: +33 4 93 92 84 02 Fax: +33 4 93 92 84 04

Catalognr: 10
SS3 Prevention strategies
The NSABP's second breast cancer prevention study, the STAR trial
L. Wickerham, V. Fourchotte
NSABP, East Commons Professional Building 5th F1, Pittsburgh, USA

The Study of Tamoxifen and Raloxifene (STAR), the NSABP's second breast cancer prevention study, is designed to determine if raloxifene is as good as or better than tamoxifen in the prevention of primary breast cancer.

Between July 1999 and November 2004, 19,747 postmenopausal women at increased risk for breast cancer were randomly assigned to receive either tamoxifen (20 mg) or raloxifene (60 mg) daily for 5 years. Breast cancer risk was estimated using a modified Gail model. Factors incorporated into the model include, age, race, reproductive history, previous benign breast biopsies, and number of first-degree female relatives who have had breast cancer. Ten percent of the women in the STAR trial were between 35 and 49 years of age, 50% were 50-59, and 40% were 60 +. Their estimated risk of developing breast cancer over the next 5 years varied from 1.67% to over 5%. Seventy-one percent of the women had one or more first-degree female relatives with breast cancer; 9.1% of the women entered had a history of LCIS, and 19.8% had a previous breast biopsy documenting atypical hyperplasia. 51.7% of the participants had undergone a hysterectomy prior to entry. Final analysis of the trial will begin when a previously determined number of invasive breast cancers has occurred, which is expected in late spring 2006.

Human brain continues to evolve, history of two genes shows

12 Sep 2005

Scientists from the University of Chicago say that the human brain is probably still evolving and has been doing so for, at least, the last five thousand years.

Two genes determine and regulate brain size, say the scientists. The genes are called microcephalin and ASPM. These genes seem to be creating new and improved versions of themselves and causing the brain to mutate (evolve) in a way that enhances our brain function.

Lead researcher, Bruce Lahn and his team carried out two studies. One on 90 humans and an ape (chimpanzee). The second was carried out on 1,200 volunteers. They studied, particularly, the microcephalin and ASPM genes - identifying how they mutated. As they found more recent mutations they focussed their work on this area (younger variations).

The scientists say that around 37,000 years ago a microcephalin gene variant emerged. It may be no coincidence that this period coincided with the appearance of art, music and man made tools and instruments. The ASPM gene mutation appeared more recently, nearly 6,000 years ago. Again, it was during this period that man started writing, farming and creating urban areas. 30% of his volunteers had the ASPM variant gene while 70% had the mocrecephalin variant gene.

According to the studies, the two gene variations are most common among Europeans, people of European descent and people from South Asia.

Bruce Lahn works at:

University of Chicago
Department of Human Genetics
Cummings Life Sciences Center
920 E. 58th St., 3rd Floor
Chicago, Illinois 60637

The Lahn Lab is a group of researchers making discoveries in:

-- Mammalian developmental genetics
-- Mammalian stem cell biology
-- Evolutionary genetics and comparative genomics

Written by Christian Nordqvist
Editor
Medical News Today

Remission of Maternal Depression May Also Benefit Children

March 21, 2006 — Children have less psychopathology if depression in their mothers is successfully treated, according to an assessment of Children whose mothers were enrolled in a multicenter trial, as reported in the March 22/29 issue of JAMA.

"Children of depressed parents have high rates of anxiety, disruptive, and depressive Disorders that begin early, often continue into adulthood, and are impairing," write Myrna M. Weissman, PhD, From Columbia University and the New York State Psychiatric Institute, and colleagues From the Sequenced Treatment Alternatives to Relieve Depression (STAR*D)–Child Team. "Only a few studies of Children of depressed parents have suggested some benefit for Children of reducing parental symptoms, but none of those published have directly treated parental depression in a definitive large sample."

Between December 16, 2001, and April 24, 2004, 151 Children whose depressed mothers were being treated with medication in the multicenter STAR*D trial were assessed by a team of evaluators not involved in maternal treatment and unaware of maternal outcomes. The Study, which is being conducted in 8 primary Care and 11 psychiatric outpatient clinics across 7 regional centers in the United States, is ongoing, and cases are being followed up at 3-month intervals. Children were aged 7 to 17 years.

Primary outcomes include Child diagnoses based on the Kiddie Schedule for Affective Disorders and Schizophrenia; Child symptoms based on the Child Behavior Checklist; and Child functioning based on the Child Global Assessment Scale. Remission of depression in the mothers was defined as a score of 7 or lower on the Hamilton Rating Scale for Depression (HRSD).

Remission of maternal depression after 3 months of treatment was significantly associated with reductions in the Children's diagnoses and symptoms. Children of mothers whose depression remitted had an overall 11% decrease in rates of diagnoses compared with an approximate 8% increase in rates of diagnoses in Children of mothers whose depression did not remit. After controlling for the Child's age, sex, and possible confounding factors, this rate difference remained significant (P = .01).

Of the Children with a diagnosis at baseline, remission occurred in 33% of those whose mothers' depression remitted, and in 12% of those whose mothers' depression did not remit. All Children of mothers whose depression remitted after treatment and who themselves had no baseline diagnosis of depression remained free of psychiatric diagnoses at 3 months. However, 17% of the Children whose mothers remained depressed acquired a psychiatric diagnosis.

Findings were similar when Child symptoms were used as an outcome. A greater level of maternal response was associated with fewer current diagnoses and symptoms in the Children. To detect an improvement in the Child, a maternal response of at least 50% was required.

"Remission of maternal depression has a positive effect on both mothers and their Children, whereas mothers who remain depressed may increase the rates of their Children's Disorders," the authors write. "These findings support the importance of vigorous treatment for depressed mothers in primary Care or psychiatric clinics and suggest the utility of evaluating the Children, especially Children whose mothers continue to be depressed."

Study limitations include lack of experimental design; inability to demonstrate causality or to rule out reverse causation in which Children's improvement had a positive impact on mothers; low rate of women with Children in the overall STAR*D Study; use of a single antidepressant in an open trial design without a placebo control; lack of blinding of Child assessors; inability to account for the impact of the fathers' psychiatric State; and maternal bias in reporting Children's symptoms.

"From a Clinical vantage point, our findings suggest that vigorous treatment of depressed mothers to achieve remission is associated with positive outcomes in their Children as well, whereas failure to treat depressed mothers may increase the burden of illness in their Children," the authors conclude. "At a time when there are many questions about the appropriate and safe treatment of psychiatric Disorders in Children, these findings suggest that it is important to provide vigorous treatment to mothers if they are depressed."

The National Institute of Mental Health supported this Study. Some of the authors have disclosed various relevant financial relationships with Eli Lilly, GlaxoSmithKline, Abbott Laboratories, Lichtwer Pharma GmbH, Lorex Pharmaceuticals, Bayer AG, Compellis, Janssen Pharmaceutica, Knoll Pharmaceutical Co, Lundbeck, Dov Pharmaceuticals, Biovail Pharmaceuticals Inc, BrainCells, Grunenthal GmBH, Sepracor, Somerset Pharmaceuticals, Aspect Medical Systems, AstraZeneca, Bristol-Myers Squibb, Cephalon, J&J Pharmaceuticals, Novartis, Organon Inc, Pharmavite, Pfizer Inc, Roche, Sanofi/Synthelabo, Solvay Pharmaceuticals, Wyeth-Ayerst, Healthcare Technology Systems Inc, Forest Pharmaceuticals, Johnson&Johnson, Cyberonics, National Institutes of Health, National Institute of Mental Health, Predix, Pfizer/Parexel, and Corcept Therapeutics Inc. Forest Laboratories provided citalopram at no cost.

JAMA. 2006;295:1389-1395

Learning Objectives for This Educational Activity

Upon completion of this activity, participants will be able to:

• Describe the prevalence and consequences of psychiatric illness during childhood.
  
• Identify the psychiatric outcomes among Children of mothers with controlled depression.

Clinical Context

The risk for psychiatric illness is increased by a factor of 2 to 3 among Children whose parents have a diagnosis of depression, and psychiatric symptoms are usually present in such children prior to the advent of puberty. While psychiatric illness places children at increased risk for social and occupational dysfunction as well as some medical problems, the best treatment of children with psychiatric illness is often controversial and based on relatively few clinical trials.

No large trials have examined whether treatment of parental depression can reduce the risk for psychiatric illness in children. The authors of the current study examine a mother-child cohort from a depression research project, STAR*D, which was described in an article by Rush and colleagues in the February 2003 issue of the American Journal of Psychiatry. The authors sought to determine if remission of maternal depression had a significant psychiatric impact on their children.

Study Highlights

• Women were drawn into the current study from the STAR*D study, which examined the most effective treatment of major depression. All participants were between the ages of 25 and 60 years and had children between 7 and 17 years of age. Women had a diagnosis of major depression with a HRSD score of 14 or more.
  
• All women were treated with citalopram, which was followed by other therapy for nonresponders. Maternal remission was defined by an HRSD score of 7 or less, while response was defined as a reduction in the baseline HRSD score by 50% or more.
  
• Children were examined at baseline and 3 months using validated surveys for psychiatric illness, psychiatric symptoms, and global functioning.
  
• The main study outcome was the relationship between maternal remission from depression and the change in psychiatric diagnoses and symptoms among children.
  
• 151 mother-child pairs were recruited into the study, and 75% completed the 3-month assessment. 33% of women met remission criteria within 3 months, and the overall response rate to treatment was 47%. Women whose depression was not significantly improved were more likely to be economically disadvantaged vs responders, and they also had more severe baseline depression and higher rates of comorbid anxiety disorders.
  
• No difference in child baseline demographic or clinical characteristics based on mothers' response or nonresponse to treatment existed. The prevalence of anxiety, depression, or disruptive behavior disorders in children was 16%, 10%, and 22%, respectively. Approximately half of the children had a previous diagnosis of psychiatric illness.
  
• During the 3-month study period, an 11% decrease in the rates of diagnosis of psychiatric illness among children with a mother exhibiting remission of depression occurred. Conversely, an 8% increase in the rates of psychiatric illness among children of mothers with continuing depression occurred. This difference remained significant after multivariate analysis.
  
• Baseline psychiatric illness resolved in 33% vs 12% of children of mothers with and without remission, respectively. No child of a mother with depression in remission developed new or relapsing psychiatric illness, although 17% of children of mothers with continuing depression experienced new or relapsing psychiatric illness.
  
• Symptoms of depression and disruptive behavior decreased from baseline among children of mothers with depression in remission, while these symptoms increased along with anxiety symptoms among children whose mothers' depression did not improve.
  
• Children's level of functioning was not affected by maternal remission status.
  
• A linear relationship was found between maternal response level to treatment and the change in rates of children's psychiatric diagnoses. A maternal response of at least 50% was associated with significantly improved outcomes in children.
  
• The study's main results were unchanged when controlling for children receiving psychiatric treatment.

Pearls for Practice

• Parental depression increases the risk for psychiatric illness in children, but a dearth of research exists regarding the treatment of psychiatric illness in children or the effects of treatment of parental depression on children.
  
• The current study demonstrates that maternal remission of depression can improve the rates of psychiatric diagnoses in children, the incidence of new cases of psychiatric illness in children, and symptoms of depression and disruptive behaviors in children. However, maternal remission did not affect children's global functioning.
  
  
  Saludos afectuosos
  
  Dr. José Manuel Ferrer Guerra
  

New Tools Developed For Studying Neurodegenerative Brain Disorders

Penn State researchers have created an elegantly simple model of an axon - the extension of a neuron that communicates with other neurons - and have used this model to reproduce a change in the axon's shape that is characteristic of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. This achievement is the first of its kind in a highly simplified biophysical model system. The model provides a novel avenue for investigating the specific mechanisms that contribute to complex brain diseases. It also provides a means of discovering new kinds of drugs for the treatment of these disorders. The research will be described in a paper to be published in the 4 April 2006 issue of the Proceedings of the National Academy of Science.

This model, produced in the laboratory of Paul S. Weiss, Distinguished Professor of Chemistry and Physics at Penn State, has the essential features of an axon, including a lipid membrane that encloses a "cytoskeleton" scaffolding, which produces the axon's shape. The outer membrane was prepared to contain a very small amount of dye molecules that are sensitive to ultraviolet light. Shining light on the artificial axons initiated a photochemical reaction that produced highly reactive "free radicals" and triggered a catastrophic oxidative-stress reaction. The result was that the previously protruding microtubule cytoskeleton collapsed into a constricted and deformed structure resembling a string of beads--the same morphology observed during the degeneration of actual neurons.

Surprisingly, the model reproduced this highly characteristic "beading" or "pearling" even though it does not include proteins that were previously thought to be essential for causing this kind of axon destruction. "One of the beauties of a simplified model is that it allows you to ask very simple questions, which sometimes are difficult to answer in a complex living system, and sometimes to get surprising answers," Weiss said. "What makes this model so exciting is that it generates many more questions than it answers," Weiss said. "It will allow us to test hypotheses of how damage occurs, and importantly, how we might prevent it. There is a real opportunity to come up with novel therapeutic treatments."

"There is tremendous urgency right now to determine which processes cause the destructive mechanisms that we see in neurodegenerative diseases," said coauthor and Assistant Professor of Veterinary and Biomedical Sciences, Anne Milasincic Andrews. "Our study shows that oxidative stress, whatever its origin, is capable of causing the cytoskeleton of this artificial system to collapse in the same way that it does in diseased or aging brains." One of the future experiments planned by the team is to induce oxidative stress in the presence of key proteins thought to be involved in the underlying causes of the brain pathologies associated with Alzheimer's and Parkinson's diseases to see whether these proteins accelerate the damaging effects of oxidative stress.

The study also revealed many specifics about the process of axon collapse. For example, the degradation rate is faster when the lipids comprising the membrane have more multiple bonds (they are more highly unsaturated). The researchers also added free-radical scavengers, such as vitamins C, E, and K, to the model system and found that these vitamins delayed or prevented the degradation of the cytoskeleton. "These antioxidant vitamins neutralized the free radicals before they had a chance to degrade the model axon," Weiss explained.

"Simple models also allow us to build more complicated hypotheses, which later can be tested in complex living systems, such as laboratory animals. We plan to build into our model the different brain chemicals that have been implicated in neurodegenerative processes to see which are the good and bad actors--which are the most effective in promoting the radical attack from the membrane to the interior of the axon and which are the best at disabling free radicals."

One of the types of neurons that degenerate in diseases such as Alzheimer's disease and that also contribute to depression and anxiety disorders are neurons that produce the neurotransmitter serotonin. Andrews and her colleagues have made a specific model of serotonin-axon degeneration using a chemical neurotoxin. Evidence of serotonin axon damage, including beading and pearling, was published recently by Andrews and her colleagues in the journal Neuropharmacology. This study used antibodies to label serotonin axons so that the degenerative process could be visualized. The researchers injected mice with the chemical neurotoxin, 2'-NH2-MPTP, that Andrews discovered and has been studying for nearly two decades. "This latest study shows conclusively that this toxin destroys serotonin-transmitting neurons," Andrews said, "and it currently is one of the best models to destroy this type of neuron. We clearly observed evidence for axonal collapse into the beaded structures in the brains of these animals a short time after we gave them the neurotoxin."

Neurodegenerative disorders typically involve many different types of neurons that produce different neurotransmitter chemicals. "Our chemical model of neurodegeneration gives us a tool to disable just one type of neuron so we can begin to tease apart how each neurotransmitter system participates in these complex disorders," Andrews said. "We then can study the behavioral effects of the degeneration of each system and can test the effectiveness of potential therapeutics to prevent or reverse the damaging effects."

###

Other researchers involved in the paper to be published in the Proceedings of the National Academy of Science include Anne E. Counterman, previously an NIH postdoctoral fellow in the Weiss laboratory and now a researcher at Yale University; and Terrence G. D'Onofrio, a former graduate student in chemistry in the Weiss group, who is currently a scientist at the U.S. Army laboratory at Edgewood. The scientists who worked on the studies published in Neuropharmacology include Beth A. Luellen, a former neuroscience graduate student in the Andrews group who is now a postdoctoral fellow at the Penn State Neuroscience Institute; Matthew E. Szapacs, a former chemistry graduate student in the Andrews group who currently is a postdoctoral fellow at the Vanderbilt University School of Medicine; and Christopher K. Materese, a former chemistry undergraduate student researcher in the Andrews group who is now a graduate student in chemistry at the University of North Carolina at Chapel Hill.

The research project led by Professor Weiss was funded by the National Science Foundation. The project led by Professor Andrews was funded by the National Institute of Mental Health.

CONTACTS:
Paul S. Weiss: (+1) 814-865-3693, stm@psu.edu, http://www.nano.psu.edu/
Anne M. Andrews: (+1) 814-865-2970, ama11@psu.edu, http://www.brain.psu.edu/
Barbara K. Kennedy (PIO): (+1) 814-863-4682, science@psu.edu

IMAGES: High-resolution images are on the web at http://www.science.psu.edu/alert/Weiss3-2006.htm

OLDER HISPANICS CAN PREVENT HIGH BLOOD PRESSURE

U.S. Department of Health and Human Services
NATIONAL INSTITUTES OF HEALTH
NIH News
National Institute on Aging (NIA)
http://www.nia.nih.gov/

FOR IMMEDIATE RELEASE: Tuesday, March 21, 2006

CONTACT: Kendra L. Gaskins, kgaskins@themedianetwork.com, 301-565-0770 Ext. 247

OLDER HISPANICS CAN PREVENT HIGH BLOOD PRESSURE

Almost half of Hispanics over age 65 have high blood pressure, but many don't know they have it because they feel just fine. Even though high blood pressure doesn't cause symptoms, it is a major Health risk, and if it isn't treated, it can lead to stroke, Heart disease, kidney failure, and other serious Health problems. The good News is that there are ways to prevent high blood pressure and the trouble it can cause. If you already have high blood pressure, there are ways to prevent or treat its complications.

High blood pressure is not a normal part of aging. You can prevent high blood pressure by maintaining a healthy weight; exercising every day; eating more fruits, vegetables, whole grains, and low-fat dairy foods; cutting down on salt and sodium; and drinking less alcohol. You can lower your blood pressure by making these lifestyle changes and, if needed, by taking medicine.

The National Institute on Aging (NIA) is offering a free fact sheet in Spanish with tips on how to control high blood pressure. To order a copy of "Presión Arterial Alta: Consejos para Mantenerla Bajo Control", call 1-800-222-2225 weekdays between 8:30 a.m. And 5:00 p.m. Eastern time. A Spanish-speaking Information specialist is available to respond to calls.. You also can order this and other Spanish publications on healthy aging on the NIA website at www.nia.nih.gov.

The NIA, part of the National Institutes of Health of the U.S. Department of Health and Human Services, leads the federal effort supporting and conducting Research on aging and the special needs of older people. The Institute is committed to making Health Information available to older Hispanic Americans and their families.

The National Institutes of Health (NIH) -- "The Nation's Medical Research Agency" -- includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, Clinical and translational Medical Research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more Information about NIH and its programs, visit http://www.nih.gov.

##

This NIH News Release is available Online at:
http://www.nih.gov/news/pr/mar2006/nia-21.htm.



Saludos Cordiales

Dr. José Manuel Ferrer Guerra

New Research Suggests Abdominal Aortic Aneurysm Will Afflict Millions Of Baby Boomers

People over 55, a demographic group that will soon include a large percentage of baby boomers, are at highest risk to develop an abdominal aortic aneurysm, a little-known but potentially fatal disease that affects the segment of the aorta that runs through the abdomen. The most deadly complication is rupture, a condition in which the aneurysm breaks open and profuse bleeding results. To date, however, the exact cause of abdominal aortic aneurysms (AAA) remains unknown, and in its early stages, the disease often produces few, if any, symptoms.

To combat this deadly disease before it reaches epidemic proportions, researchers have made tremendous strides in diagnosing, preventing and treating cases of AAA. To highlight the latest advances in understanding this disorder, the New York Academy of Sciences and the Columbia University College of Physicians and Surgeons are cosponsoring a three-day conference, The Abdominal Aortic Aneurysm: Genetics, Pathophysiology, and Molecular Biology on April 3 to 5 at St. Luke's Roosevelt Hospital, New York, Amsterdam and 113th street in Manhattan.

More than forty investigators from the U.S., England, Denmark, Sweden, Japan and other countries are expected to attend. The conference is a sequel to a groundbreaking symposium that was held ten years earlier and will examine the kinds of dramatic improvements in diagnosis, prevention of complications and treatment that did not exist a decade earlier.

New Insights into Complex but Poorly Understood Disease

"The incidence and prevalence of AAA is rising," observed Gilbert Upchurch of the University of Michigan, one of the organizers of the conference. Despite this, he notes that much work remains to be done and that the science behind it "is in its infancy."

By taking an interdisciplinary approach that integrates new insights into the etiology and pathology of this disease, however, researchers hope to unlock the mysteries of AAA. "Abdominal aortic aneurysm is a multifactorial disease, involving genetic susceptibilities, features of autoimmunity, and environmental influences like smoking," added Dr. M. David Tilson III of Columbia University and the St. Luke's Roosevelt Hospital Center, a co organizer of the meeting.

Consisting of five plenary sessions and poster sessions, the symposium will present the latest research to unravel the causes and improve treatments for this relatively common but poorly understood disorder. The conference will cover topics such as epidemiology, enzymology, methods for surgical repair, development of new experimental models, and the genetics of the disorder.

Rosemary Helps Prevent Brain Aging, Says Nagase

Tokyo, (JCN) - Nagase, a Japanese trading company specializing in chemical products, recently announced its discovery, in collaboration with Kyoto University, that rosemary helps prevent brain aging.

Specifically, the two partners elucidated that carnosic acid, which is found in rosemary, substantially stimulates the activity of Nrf2, a kind of transcription factor, promoting the growth of neuritis. A derivative of caffeic acid, one of the rosemary components, also produces similar effects.

Furthermore, in experiments on mice, they confirmed that intake of rosemary extract containing a high concentration of carnosic acid, which helps improve memory.

Details of the findings will be presented at the 126th Annual Meeting of the Pharmaceutical Society of Japan, to be held March 28-30 in Sendai.

By Aki Tsukioka, JCN Staff Writer

http://www.medicalnewstoday.com

Traditional Healers In South Africa Trained To Encourage People To Get Tested For HIV

group of traditional healers in South Africa is being trained to encourage people to get tested for HIV, BBC News reports. Traditional healers act as counselors and supply traditional medicine to four out of five South Africans, according to BBC News. The traditional healers, known as sangomas, attended a six-week training workshop at Cape Town's Tygerberg Hospital. The workshop aims to combat the stigma associated with HIV/AIDS and "break down the barriers of distrust" between traditional healers and Western medical systems, Monica Essa, a pediatrician at Tygerberg Hospital, said. According to Essa, people have been reluctant to get tested for HIV because testing typically has been conducted at Western-based medical facilities, which "makes it even more foreign to the predominantly black population" in the country. People also fear the "enormous" stigma surrounding HIV/AIDS, Essa added (BBC News, 3/8).

Research Shows The Biggest Health Threat To Fat And Obese People Isn't The Fat Itself But The Fact That The Fat Fuels A Killer Inflammation Response

New research by the University of Warwick's Warwick Medical School shows that the biggest health threat to fat and obese people isn't the fat itself but the fact that the fat fuels a killer inflammation response in people.

The research published in the International Journal of Obesity on Tuesday 7th March shows that inflammation is a crucial and dangerous step in the development of obesity.

Warwick Medical School researchers Professor F P Cappuccio and Dr M A Miller have studied a large group of people, belonging to 3 different ethnic groups, and have measured a variety of markers of inflammatory activation and related these to measures of obesity or fatness such as body mass index (BMI) and waist-hip ratio (WHR). The study clearly showed that the levels of sE-selectin, a marker of inflammation produced by artery vessel walls, are strongly associated with measures of obesity, and in particular with the amount of fat around the waist. The research found that every 2% increase in sE-selectin led to the increase of 1 unit in Body Mass Index and 0.01 units in Waist - Hip Ratios.

This inflammation can directly trigger thrombosis, heart disease, strokes and diabetes.

There have been suggestions from earlier studies of small patient groups that inflammation had this importance but this is the first ever study to find these results across an unselected population of healthy subjects which covered both sexes and three ethnic groups (White, South Asian and people of African origin)

Dr Miller and Professor Cappuccio said:

"This study highlights the importance of the activation of the endothelium, the inner layer of the artery vessel wall, in the metabolic processes leading to obesity and cardiovascular disease". "This observation opens opportunities to develop new treatments that deal directly with inflammation either through diet or drugs".

Genetic Perversity: Smoking & Gene Avert Parkinson's

It has long been known that smoking offers some protection against developing Parkinson's disease and now a Queensland University of Technology PhD researcher has found out part of the reason why.

Yifu Deng of QUT's School of Public Health studied the interplay between genetics, smoking and the development of Parkinson's disease with 400 people who had Parkinson's disease and 400 people without it.

Dr Deng looked at the genetic background of individuals in each group for the presence of the CYP2D6 gene, which had previously been suggested to metabolise the chemical compounds found in cigarette smoke, in both groups.

He found that smokers with the gene who metabolised the cigarette smoke compounds quickly were less likely to be protected than those who metabolised the chemical compounds more slowly.

"It seems that if the chemical compounds stay in the body longer they are more likely to have a preventative effect," Dr Deng said.

"It also seems that if you have the gene but you are not a smoker the gene may have no use in preventing Parkinson's."

Dr Deng said it was not known how the cigarette smoke compounds protected against Parkinson's.

He warned that there were still many smokers who suffered from Parkinson's. Additionally, smoking was notorious for causing cancers.

Parkinson's disease is a common degenerative neurological disease in the elderly, affecting up to 4.9 percent Australians aged 55 and over.

"Our study findings aid in further understanding of the causes of Parkinson's disease and may help identify people who are at higher risk of the disease," he said.

The study is the first to look at the genetic epidemiology of Parkinson's disease by addressing individual genetic types in relation to cigarette smoke metabolism.

Cats Don't Catch Bird Flu Easily

Article Date: 01 Mar 2006 - 15:00pm (UK)

In the whole world, just ten cats have been infected with bird flu. Bearing in mind that cats like to catch and eat birds, this is a tiny number. Since 2003 hundreds of millions of birds have died as a result of H5N1 bird flu infection.

Experts think a cat runs the highest risk of infection when it eats (parts of) a dead infected bird. Even then, say veterinarians and virologists, the chances of infection are tiny.

Can a cat pass the virus on to a human?

Millions of cats worldwide have caught and touched birds, many of them infected birds. We have not heard of one case of a cat passing on bird flu to a human. If there is a risk, it is too small to worry about - you are more likely to trip over your cat and hit your head against the wall.

Written by: Christian Nordqvist
Editor: Medical News Today