A neurotoxin called acrolein found in tobacco smoke that is thought to increase pain in people with spinal cord injury has now been shown to accumulate in mice exposed to the equivalent of 12 cigarettes daily over a short time period.
One implication is that if acrolein is exacerbating pain its concentration in the body could be reduced using the drug hydralazine, which has been approved by the U.S. Food and Drug Administration for hypertension, said Riyi Shi (pronounced Ree Shee), a professor in Purdue University's Department of Basic Medical Sciences, College of Veterinary Medicine, and Weldon School of Biomedical Engineering.
The drug has been shown to be effective in reducing acrolein levels in research animals, and Shi is working to develop a low-dose version for that purpose in humans.
Mice were exposed to a level of acrolein equivalent to 12 cigarettes per day over three weeks. Previous research has focused on acrolein accumulation in the respiratory system but not in the bloodstream and spinal cord. It is known that acrolein is accumulated in urine in human smokers after years of smoking.
"This is the first animal study demonstrating that an acute short term of weeks of smoking could also cause acrolein to accumulate in urine and more importantly in spinal cord tissue, a part of central nervous system known to be vulnerable to acrolein, he said.
The researchers documented the concentration of biochemical markers for acrolein in the urine and spinal cord. Findings, appearing this week in the journal Neuroscience Bulletin, indicate the accumulation of the toxin was about 50 percent higher than normal, a level known to have pathological implications.
"The data indicated that acrolein is absorbed into the circulatory system and some enters the nervous system," Shi said. "It is expected that these findings may facilitate further studies to probe the pathological role of acrolein in the nervous system resulting from smoke and other external sources through long and short term, both active and passive exposure."
The research paper was authored by Melissa Tully, a graduate student at Purdue and the Indiana University School of Medicine; Purdue graduate students Lingxing Zheng, Glen Acosta, and Ran Tian; and Shi.
Acrolein is produced within the body after nerve cells are damaged. In spinal cord injury and in multiple sclerosis, the myelin insulation surrounding nerve cells is destroyed and the nerve fibers themselves are damaged by acrolein. The toxin acrolein also is found in air pollutants including tobacco smoke and auto exhaust.
"It is already known that smoking can increase pain for people with spinal cord injury and worsen the condition of multiple sclerosis, but we don't know exactly why," Shi said. "I am saying that acrolein might be the key culprit here and that inhaled acrolein could intensify multiple sclerosis and increase pain sensation."
The research is ongoing and was funded by the Indiana State Department of Health, the National Institutes of Health, and an Indiana CTSI CBR/CTR Pilot Program Grant.
Source: Purdue University © 2014 Purdue University (05/12/14)
A study by Dr. Anna Karin Hedström and a team of researchers from Sweden's Karolinska Intstitute have discovered a possible link between alcohol consumption and a reduction in the risk of having multiple sclerosis, the degenerative disease of the central nervous system.
According to the abstract of the study published in the Journal of the American Medical Association, the researchers' goal was to “investigate the possible association of alcohol consumption with the risk of developing MS and to relate the influence of alcohol to the effect of smoking.”
The team conducted two case-control studies in which researchers followed more than 6,500 participants from Sweden aged between 16 and 70 years old. The studies took place from April 2005 to November 2011.
In an interview with medical website Medscape, Hedström said the researchers conducted the large-scale study because previous research showed alcohol can have an anti-inflammatory effect.
“The current case-control studies are the largest to look at this association. We wanted to study this as experimental studies and clinical observations have suggested that alcohol has an effect on the immune system and may have anti-inflammatory actions,” she said in the interview. “As MS is an inflammatory condition, we thought alcohol may have a protective effect.”
The results of the test showed a 50 percent reduction in the risk of MS for frequent alcohol drinkers.
The study defined frequent drinkers as men who drank 14 drinks a week and women who drank 9 drinks a week. According to a press release by the National Multiple Sclerosis Society, the results of Hedström's research conflict with earlier studies done by the Harvard School of Public Health (HSPH).
“In a previous study, researchers at (HSPH) examined the association between alcohol and caffeine intake and risk of developing MS in two large groups of women and found no connection between either and the development of MS,” the release stated.
The results of the Karolinska study, however, are encouraging, the society said in the release.
“Unlike a previous study in MS, this study shows some evidence that alcohol consumption is associated with a decrease risk of developing MS,” the release said.
The study did not observe the effect of alcohol on patients who already have MS, Hedström said in her Medscape interview.
“We didn't look at patients who already had MS, so we cannot make firm recommendations on this, but previous research has shown an anti-inflammatory effect of moderate intake,” she said. “I would say that if an MS patient wants to drink alcohol that is absolutely fine.”
Her recommendation comes with the implicit rule that patients should consult their doctors before making a lifestyle change of this sort.
As for MS patients who are concerned about their children's risk for having MS, Hedström say her team's findings aren't a license to begin heavy drinking.
“Whilst we wouldn't recommend them drinking large quantities of alcohol because of other negative consequences, we can probably say that alcohol in moderation will not increase risk and may reduce it somewhat,” she told Medscape. “So I wouldn't advise people to start drinking alcohol specifically to reduce their risk of developing MS, but I would say that you don't need to avoid alcohol or stop drinking alcohol.”
Source: Snooth Copyright © 2014 Snooth, Inc (21/11/14)
Environmental exposures and the risk of multiple sclerosis Several environmental exposures, including infection with Epstein-Barr virus, low levels of vitamin D and smoking are established risk factors for multiple sclerosis (MS). Also, high hygienic standard and infection with parasites have been proposed to influence MS risk.
The aim of this study was to investigate the influence of various environmental exposures on MS risk in a Norwegian cohort, focusing on factors during childhood related to the hygiene hypothesis.
Methods: A questionnaire concerning environmental exposures, lifestyle, demographics and comorbidity was administrated to 756 Norwegian MS patients and 1090 healthy controls. Logistic regression was used to calculate odds ratio (OR) with 95% confidence interval (CI) for the risk of MS associated with the variables infectious mononucleosis, severe infection during childhood, vaccination and animals in the household during childhood.
Age, gender, HLA-DRB1*15:01, smoking and infectious mononucleosis were included as covariates. General environmental exposures, including tobacco use, were also evaluated.
Results: Infectious mononucleosis was confirmed to be significantly associated with increased MS risk, also after adjusting for the covariates (OR?=?1.79, 95% CI: 1.12-2.87, p?=?0.016).
The controls more often reported growing up with a cat and/or a dog in the household, and this was significant for ownership of cat also after adjusting for the covariates (OR?=?0.56, 95% CI: 0.40-0.78, p?=?0.001). More patients than controls reported smoking and fewer patients reported snuff use.
Conclusions: In this Norwegian MS case control study of environmental exposures, we replicate that infectious mononucleosis and smoking are associated with increased MS risk.
Our data also indicate a protective effect on MS of exposure to cats during childhood, in accordance with the hypothesis that risk of autoimmune diseases like MS may increase with high hygienic standard.
Author: Marte GustavsenChristian PageStine MoenAnja BjÃ¸lgerudPÃ¥l Berg-HansenGro NygaardLeiv SandvikBenedicte LieElisabeth CeliusHanne F Harbo
Credits/Source: BMC Neurology 2014, 14:196
Source: 7thSpace Interactive © 2014 7thSpace Interactive (03/10/14)
The diagnosis and treatment of Multiple Sclerosis (MS) have dramatically improved over recent decades due to scientific advancements, yet MS persists as one of the most disabling neurological disorders, having a significant impact on young adults - the age group most affected by the disease.
Continuing medical education provider, EXCEMED - Excellence in Medical Education, will draw leading international experts in MS to explore the roles of genetics and environment in MS pathology. The conference, "Multiple sclerosis: Improving patient outcomes through scientific and clinical advances" takes place in Dubai, United Arab Emirates, from 9 to 10 May 2014.
"This meeting will present the latest epidemiological and genetic knowledge about MS and link it to pathology and the practical management of therapy for people with MS" says Professor David Bates, Department of Neurology, Royal Victoria Infirmary, Newcastle upon Tyne, UK, and - scientific organizer of the event.
"We are proud to gather, year after year, an outstanding international panel of experts in neurology and MS research in order to contribute to the debate from the perspective of clinical practices. The goal is to identify the most appropriate treatments for this disease," says Professor Giancarlo Comi, President of the EXCEMED Scientific Committee and Professor in Neurology at University Vita-Salute San Raffaele, Milan, Italy.
The scientific programme of the event offers three sessions and six workshops: Session one will address basic research in MS pathogenesis including epidemiology, risk factors, genetics of MS and mechanism and prevention of neurodegeneration. Session two will address clinical approaches to MS and session three will deal with therapeutic management. The six workshops will be attended in rotation by each participant to allow for optimal exchange of opinions and a deeper understanding of the different MS related topics.
Source: Digital Journal copyright © 2014 digitaljournal.com (09/05/14)
Multiple sclerosis shows a "striking" association with obesity at age 20 years that strongly interacts with genetic susceptibility, according to an analysis of data from two case-control studies that examined environmental and genetic risk factors for MS.
This relationship between adolescent obesity and MS is of the same magnitude as the separate associations between MS and carriage of the high-risk HLA-DRB1*15 allele, absence of the protective HLA-A*02 allele, and smoking, said Dr. Anna Karin Hedström of the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, and her associates.
"The biological explanations for these interactions are far from clear, but the data open [the way] for mechanistically oriented studies," they said.
Three previous studies have suggested that obesity in early life may be linked to increased risk of developing MS later. Dr. Hedström and her colleagues examined this association using data from a Swedish population-based, case-control study and from a separate American case-control study.
In the Swedish study, 1,510 adults with incident MS who were treated at 40 clinics across the country during a 7-year period and 2,017 control subjects completed detailed questionnaires concerning environmental exposures and other factors. The controls were matched for age, sex, and area of residence, and all the participants gave blood samples for HLA typing.
The American study involved 937 white adults with prevalent MS who were members of a single large health maintenance organization covering northern California and 609 white control subjects matched for age, sex, and area of residence. All the participants completed computer-assisted telephone interviews regarding environmental exposures and lifestyle factors.
All the subjects in both studies reported what their heights and weights had been at age 20 years, from which the investigators calculated body mass index (BMI).
In both studies, participants whose BMI at age 20 years was 27 kg/m2 or greater showed an increased risk of developing MS later in life, compared with those whose BMI was 18.5-21 kg/m2. The odds ratios (ORs) were 2.2 for subjects in the Swedish study and 1.8 for those in the American study, Dr. Hedström and her associates said (Neurology 2014 [doi:10.1212/WNL.0000000000000203]).
Similarly, participants with a slightly lower but still above-normal BMI of 25-27 kg/m2 showed a modestly increased risk of developing MS later in life: The ORs were 1.4 in the Swedish study and 1.3 in the American study.
These ORs were unchanged when a sensitivity analysis was performed, including only the study subjects who had been genotyped.
Participants who carried the high-risk HLA-DRB1*15 gene, did not carry the protective HLA-A*02 gene, and had a BMI of 27 kg/ m2 or greater at age 20 years had an OR of 16.2 for developing later MS, compared with those who had none of those risk factors. In contrast, subjects who had the same HLA profile but had not been obese at age 20 years had an OR of only 5.1.
The investigators proposed that the low-grade chronic inflammation associated with obesity, together with obesity’s adverse effects on autoimmunity, may raise the risk of HLA-related activation of T cells that attack the CNS.
Both the Swedish and the American study were limited in that they were retrospective and relied on participants’ self-reports. In addition, Dr. Hedström and her associates modified the usual definition of obesity for the purposes of their study. The typical standard for obesity is a BMI of greater than 30 kg/m2, not greater than 27 kg/m2. However, the number of subjects at this level of BMI was too small in the Swedish cohort to allow accurate analysis, so the researchers combined the top two categories of BMI into one designation of "obese."
This study was supported by several private nonprofit foundations, the Swedish Research Council for Health, Working Life and Welfare, and the U.S. National Institute of Neurological Disorders and Stroke. Dr. Hedström and five of the other seven authors reported no financial conflicts of interest. One coauthor reported ties to numerous industry sources and one reported receiving research support from Swedish government agencies.
Causality not yet established
This study and other research linking obesity early in life with the later development of MS are observational and cannot establish causality, so we don’t yet know whether decreasing obesity with diet and exercise will lead to a decrease in the incidence of MS.
Nevertheless, these findings are concerning. “It is time to begin developing a targeted approach to prevent MS by improving common health behaviors, including body weight and smoking,” Dr. Marrie and Dr. Beck said.
People who are at high genetic risk can be readily identified by focusing HLA genotyping on the first-degree relatives of known MS patients, they added.
Dr. Marrie is in the departments of internal medicine and community health sciences at the University of Manitoba, Winnipeg. She has received funding from Sanofi-Aventis and Canadian governmental agencies and nonprofit organizations, including the MS Society of Canada and the MS Scientific Foundation. Dr. Beck is in the department of biostatistics and computational biology at the University of Rochester (N.Y.) Medical Center. Dr. Beck has received support from a variety of healthcare companies as well the U.S. Food and Drug Administration and the U.S. National Institutes of Health.
These remarks were taken from their editorial accompanying Dr. Hedström’s report (Neurology 2014 [doi:10.1212/WNL.0000000000000195]).
Source: Clinical Endocrinology New Copyright © 2014 Frontline Medical Communications LLC (12/02/14)
Drinking alcohol appears to have a dose-dependent inverse (opposite) association with the risk of developing multiple sclerosis (MS) and researchers suggest their findings give no support to advising patients with MS to completely refrain from alcohol, according to a study by Anna Karin Hedstrom, M.D., of the Karolinska Institutet, Sweden, and colleagues.
The results of previous studies have been inconsistent about the impact of alcohol and the risk of developing MS.
Researchers investigated the association using two population studies in Sweden with participants between the ages of 16 and 70 years: 745 cases of MS plus 1,761 controls in the Epidemiological Investigation of Multiple Sclerosis (EIMS) study and 5,874 cases of MS with 5,246 controls in the Genes and Environment in Multiple Sclerosis (GEMS) study.
In EIMS, women who reported high alcohol consumption had an odds ratio (OR) of 0.6 of developing MS compared with nondrinking women, and men with high alcohol consumption had an OR of 0.5 compared with nondrinking men, according to the results. The corresponding OR comparison in GEMS was 0.7 for both women and men. Alcohol consumption also appeared to be associated with the attenuation (lessening) of the effect of smoking, the results also indicate.
"Although the effect of alcohol on already established MS has not been studied herein, the data may have relevance for clinical practice since they give no support for advising persons with MS to completely refrain from alcohol," the authors conclude.
Source: MedicalXpress © Medical Xpress 2011-2014 (07/01/14)