Alpha-synuclein protein levels are increased in alcoholic patients and are linked to craving

BACKGROUND: Alpha synuclein has been found to be increased in dopamine neurones of cocaine abusers and in rats whose alcohol preference is inbred. Furthermore, increased alpha-synuclein messenger RNA expression has been linked to craving in patients with alcoholism. The aim of the current study was to investigate whether protein levels of alpha synuclein in alcoholics are changed and possibly influence alcohol craving. METHODS: The alpha-synuclein protein expression level was measured by enzyme-linked immunosorbent assay in the serum of 49 male alcoholics and 50 nondrinking healthy controls. Alcohol craving was assessed by the Obsessive-Compulsive Drinking Scale total score, including subscales for obsessive and compulsive craving. RESULTS: Alpha-synuclein protein expression in patients with alcoholism (14.33 ng/ml; SD, 13.01 ng/ml) was significantly higher (t test, T = 3.66, p < 0.0001) when compared with that of healthy controls (5.92 ng/ml; SD, 9.72 ng/ml). Using a multivariate analysis, all craving scores (Obsessive-Compulsive Drinking Scale total score and obsessive and compulsive subscale scores) in alcoholics were significantly associated with their alpha-synuclein protein levels (multiple linear regression, p < 0.014). CONCLUSIONS: To our knowledge, this is the first study evaluating alpha-synuclein protein expression in alcoholics. The current study provides further evidence of altered alpha-synuclein levels in patients with alcoholism and their linkage to alcohol craving. Because alpha synuclein is involved in the modulation of dopaminergic neurotransmission, these results deliver further pathophysiological explanations of craving mechanisms.     

Peripheral dendritic cell chimerism in allogeneic hematopoietic stem cell recipients

BACKGROUND: Relapse and graft-versus-host disease (GVHD) represent major causes of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Although leukocyte and T-cell chimerism analyses are performed routinely suggesting a predictive value on the patients outcome, little is known about chimerism of dendritic cells (DC) representing strong initiators of immune responses. METHODS: In this prospective study, peripheral DC1 (CD11c+) and DC2 (CD123+) chimerism was determined in hematopoetic stem cell recipients. DCs were isolated from peripheral blood by fluorescence activated cell sorting. Chimerism analyses were performed by fluorescent in situ hybridization or by polymerase chain reaction-based typing of short tandem repeats. RESULTS: At time of engraftment, DC chimerism analyses showed complete chimerism in 76.3% (DC1)/79.5% (DC2), mixed chimerism (MC) in 21.0% (DC1)/17.9% (DC2) and no chimerism in 2.7% (DC1)/2.6% (DC2) of the patients. Peripheral DC chimerism had no significant effect on relapse-free or overall survival. Although acute GVHD was observed more often in patients with MC for DC1/DC2 and chronic GVHD occurred more often in patients with MC for DC2, there was no statistically significant correlation. CONCLUSIONS: Although DCs as antigen presenting cells are supposed to have an impact on the induction of GVHD, there was no significant correlation between incidence of GVHD and DC chimerism after HSCT.     

Severe hypoglycaemia,metabolic control and diabetes management in children with type 1 diabetes in the decade after the Diabetes Control and Complications Trial – a large-scale multicentre study

Hypoglycaemia is frequently the limiting factor in achieving optimal glycaemic control. Therefore, insulin therapy, the incidence of hypoglycaemia, and glycaemic control were investigated in 6309 unselected children with type 1 diabetes in a large-scale multicentre study. Using standardised computer-based documentation, the incidence of severe hypoglycaemia, HbA1 _c levels, insulin regimen, diabetes duration, and the number of patients attending a treatment centre were investigated for the age groups 0-<5 years ( n =782), 5-<7 years ( n =1053), and 7-<9 years ( n =4474). The average HbA1 _c level was 7.6% (no significant difference between age groups). Young children had more severe hypoglycaemic events (31.2/100 patient years) as compared to older children (19.7; 21.7/100 patient years, P <0.05) independent of the treatment regimen. Our data suggest that diabetes centres treating less than 50 patients per year have a higher incidence of hypoglycaemia in 0-<5-year-old children (43.0/100 patient years) as compared to larger centres (24.1/100 patient years; P <0.0001). Significant predictors of hypoglycaemia were younger age ( P <0.0001), longer diabetes duration ( P <0.0001), higher insulin dose/kg per day ( P <0.0001), injection regimen ( P <0.0005), and centre experience ( P <0.05). Conclusion:Despite modern treatment, young children have an elevated risk for developing severe hypoglycaemia compared to older children, especially when treated at smaller diabetes centres. The therapeutic goal of carefully regulating metabolic control without developing hypoglycaemia has still not been achieved. Further advances in diabetic treatment may result from giving more attention to hypoglycaemia in young children.On behalf of the German Initiative on Quality Control in Paediatric Diabetology.     

Vaccine strategies of meningococcal disease: results of a 10-year population-based study

Invasive meningococcal disease (IMD) is an important cause of morbidity and mortality in children and adults. This study was conducted to determine a possible increase in IMD in recent years with special interest focused on serogroup C disease. From January 1st 1993 to December 31st 2002, IMD was studied in one million residents of Austria. We used active, population-based surveillance data from the Office of Public Health. A total of 126 patients with positive blood and/or cerebrospinal fluid culture or positive swabs for Neisseria meningitidis were studied. The median age of all patients was 9.5 years (range 1 month to 63 years). The average incidence of all IMD subgroups was 1.05 cases per 100,000 person years and was highest in children 0–4 years old (7.08 cases per 100,000 person years) followed by young adults aged 15 to 19 years (4.35 cases per 100,000 person years). Serogroup C IMD occurred in 1.30 cases/100,000 person years in patients aged 0 to 4 years and in 1.92 cases/100,000 person years in patients aged 15 to 19 years. Overall mortality was 11.1%. There was a significant increase ( P =0.001) in IMD due to serogroup B disease within the last 10 years. In contrast, serogroup C disease did not increase during the last decade. Conclusion:Currently, we do not recommend mass vaccination against serogroup C disease in Austria, but young adults aged 15 to 19 years display a high incidence of meningococcal C disease. In this age group, vaccination against serogroup C disease should be considered.     

Implementation of standard operating procedures for the initial empirical antimicrobial therapy for adults--a new computer program at the University Hospital Charité

Nowadays 40-50 % of the patients receive inappropriate antibiotic treatment. Evidence based recommendations are not considered and there is an increasing burden of resistant pathogens. Therefore, standard operating procedures (SOPs) should be implemented considering guidelines and resistant species in the specific ICU. The authors developed algorithms and generated a user friendly computer program available for all ICU physicians all the time.     

The tobacco industry's response to the COMMIT Trial: an analysis of legacy tobacco documents

We analyzed internal tobacco industry documents that describe the industry's response to the Community Intervention Trial for Smoking Cessation (COMMIT), a multi-center community-based tobacco intervention project funded by the National Cancer Institute from 1988 to 1992. Our analysis of documents from the Legacy Tobacco Documents Library (www.legacy.library.ucsf.edu) suggests that the tobacco industry reacted to COMMIT by (1) closely monitoring trial activities, (2) confronting COMMIT in communities where it was most active, (3) distorting COMMIT findings on underage smoking data reported in the media, and (4) using COMMIT activities as practice to strengthen their attack against the subsequent ASSIST trial, falsely accusing both studies of illegal political lobbying with taxpayers' money. The tobacco industry closely monitored COMMIT activities and organized local responses to findings and activities perceived as threatening to the industry's public image or interests. Although we could not document a concerted attack by the tobacco industry that impacted the results of the COMMIT trial, data suggest that the industry used COMMIT as a learning opportunity to mount a well orchestrated and potentially damaging response to the larger American Stop Smoking Intervention Study for Cancer Prevention Trial.     

In vivo evaluation of a nasal insulin delivery system based on thiolated chitosan

The aim of this study was the preparation and in vivo evaluation of a nasal insulin delivery system based on thiolated chitosan. 2-Iminothiolane was covalently attached to chitosan. The resulting conjugate (chitosan-TBA) exhibited 304.9 +/- 63.5 micromol thiol groups per gram polymer. Microparticles were prepared via a new precipitation-micronization technique. The microparticulate delivery system comprised insulin, reduced glutathione and chitosan-TBA (Chito-TBA/Ins) or unmodified chitosan (Chito/Ins) and control microparticles were composed of insulin and mannitol (Mannitol/Ins). Due to a hydration process the size of Chito-TBA/Ins and Chito/Ins microparticles increased in phosphate buffer pH 6.8 2.6- and 2.2-fold, respectively. Fluorescent-labeled insulin-loaded chitosan-TBA microparticles showed a controlled release over 4 h. Chito-TBA/Ins administered nasally to rats led to an absolute bioavailability of 6.9 +/- 1.5%. The blood glucose level decreased for more than 2 h and the calculated absolute pharmacological efficacy was 4.9 +/- 1.4%. Chito/Ins, in comparison, displayed a bioavailability of 4.2 +/- 1.8% and a pharmacological efficacy of 0.7 +/- 0.6%. Mannitol/Ins showed a bioavailability of 1.6 +/- 0.4% and no reduction of the blood glucose level at all. According to these findings microparticles comprising chitosan-TBA seem to have substantial higher potential for nasal insulin administration than unmodified chitosan.