Reduction of ischemia/reperfusion injury by antithrombin III after experimental pancreas transplantation

BACKGROUND: Graft pancreatitis is a major complication after pancreas transplantation. Antithrombin III (AT III) is an anticoagulatory and anti-inflammatory substance. The aim of our study was to evaluate a prophylactic application of AT III in experimental pancreas transplantation. METHODS: Pancreas transplantation was performed in rats. Cold ischemia time (University of Wisconsin solution at 4 degrees C) was 12 hours. After 4 hours of reperfusion, pancreatic enzymes were assessed and the pancreas was evaluated by intravital microscopy and histologic and immunohistochemical examination. Recipients were allocated randomly to 2 groups: 1 control group (n = 6) and 1 group in which recipients received 125 IU AT III/kg 30 minutes before reperfusion (n = 6). Six animals that did not undergo transplantation served as healthy controls. RESULTS: Enzyme levels showed no differences between the 2 transplantation groups but were significantly (P <.05) higher than in the control group. Histologic damage was significantly less evident in animals that received AT III compared with transplantation animals that did not receive AT III. During intravital microscopy, animals receiving AT III showed significantly higher capillary and venular erythrocyte velocities compared with untreated transplantation animals. The leukocyte-endothelium interaction in postcapillary venules was decreased significantly in animals with AT III treatment. CONCLUSIONS: AT III pretreatment decreases tissue damage by attenuating microcirculatory disturbances and leukocyte adherence in experimental graft pancreatitis by its anti-inflammatory and anticoagulatory properties.     

Association of NOD1 polymorphisms with atopic eczema and related phenotypes

BACKGROUND: Interactions with microbial pathogens are crucial for the maturation of the immune system. The nucleotide-binding oligomerization domain protein 1 (NOD1) is a cytosolic receptor sensing a muropeptide found mostly in gram-negative bacterial peptidoglycans. NOD1 is located on chromosome 7p14-p15, a region that has been linked with atopy. Recently, polymorphisms of the closely related NOD2 have been associated with atopy-related traits. OBJECTIVES: Within a large population-based cohort of German adults (n = 1417), a case-control population for atopic eczema (n = 454), and a large cohort of parent-offspring trios for atopic eczema (189 trios), we evaluated 11 NOD1 polymorphisms for associations with atopic phenotypes. Methods Subjects were phenotyped by standardized questionnaires and interviews, skin examination, and serum IgE measurements. Genotyping was performed by using matrix-assisted laser desorption ionization-time of flight mass spectrometry. RESULTS: Analyses revealed significant association of one NOD1 haplotype with atopic eczema in the population-based cohort ( P = .004) and the case-control population ( P = .003). Another NOD1 haplotype was associated with decreased total IgE ( P = .008). In addition, significant associations with total serum IgE levels were observed for polymorphisms rs2907748 ( P = .006), rs2907749 ( P = .012), and rs2075822 ( P = .018). These polymorphisms were significantly associated with atopic eczema and asthma in the family-based association analyses ( P = .001-.043). Seven polymorphisms showed significant transmission distortion for total IgE levels ( P values < .0001-.029). CONCLUSION: These data indicate that genetic variants within NOD1 are important determinants of atopy susceptibility.     

Visuospatial abilities, memory, and executive functioning in trichotillomania and obsessive-compulsive disorder

Few studies have compared neuropsychological functioning in trichotillomania (TTM) and obsessive-compulsive disorder (OCD). In OCD, most studies suggest abnormal visuospatial abilities, memory, and executive functioning. We compared 23 TTM, 21 OCD and 26 healthy control individuals on neuropsychological tasks assessing these abilities. Neither the TTM nor the OCD groups suffered from generalized neuropsychological deficits compared to the healthy control group. TTM participants showed increased perseveration on the Object Alternation Task suggesting difficulties with response flexibility. OCD participants showed impaired ability to learn from feedback on the Wisconsin Card Sorting Test. Other executive functions, as well as memory and visuospatial abilities were unimpaired in TTM and OCD. Our data suggest that TTM and OCD are characterized by different patterns of neuropsychological dysfunction.     

Expression of gp130 in tumors and inflammatory disorders of the skin: formal proof of its identity as CD146 (MUC18, Mel-CAM)

Two antibodies, BT14 and L101, detect a tumor-associated cell surface glycoprotein (gp130) whose properties in normal and diseased skin were assessed, and whose molecular identity was determined in this study. In normal skin, gp130 was constitutively expressed on dermal blood vessels and epidermal appendages, but not in interfollicular epidermis. Marked induction was detected within benign and malignant tumors of various origins including viral warts, basal cell carcinomas, squamous cell carcinomas, metastatic melanomas, and cutaneous T cell lymphomas. In vitro studies confirmed the general upregulation of gp130 expression in malignantly transformed cells. Surprisingly, gp130 was also induced in inflammatory skin diseases including psoriasis and allergic contact dermatitis. Halting proliferation of transformed keratinocytes through cytostatic drugs or increasing the Ca2+ concentration in the medium resulted in increased gp130 expression. In addition, overexpression of Bcl-2 led to upregulation of gp130. When the protein was purified and analyzed by peptide mass fingerprinting, we could demonstrate that it is MUC18 (Mel-CAM, CD146). Sequential immunoprecipitations and western blot analyses confirmed the identity of the antigen. Thus, both expression pattern and regulation characteristics of the now-known glycoprotein gp130 extended beyond previously published data regarding MUC18, thus shedding some new light on a supposedly well-known antigen.     

Independent effects of tobacco abstinence and bupropion on cognitive function in schizophrenia

OBJECTIVE: The objective of this study was to examine the effects of tobacco abstinence and bupropion treatment on cognitive functioning in adult smokers with schizophrenia in the setting of a randomized, double-blind, placebo-controlled clinical trial of bupropion for smoking cessation. METHOD: Fifty-three adults with schizophrenia (DSM-IV) took part in a trial of bupropion for smoking cessation. Subjects were enrolled in the study from August 1999 to March 2003. Forty-five subjects remained in the trial at week 4; 41 subjects, 19 taking bupropion and 22 taking placebo, completed the baseline and week 4 cognitive assessments and were included in the analysis of adjusted effects of abstinence and bupropion treatment on cognitive function. RESULTS: Controlling for bupropion treatment and baseline performance, 7 days of tobacco abstinence was associated with slowed motor speed (finger tapping) but was not associated with worsening of performance on tests of attention (AX Continuous Performance Test [AX-CPT]), verbal learning and memory (California Verbal Learning Test [CVLT]), working memory (digit span), or executive function/inhibition (Stroop) and was not associated with worsening of any clinical measures. Controlling for abstinence status, bupropion was associated with reduction (improvement) in reaction time variability on the AX-CPT and with reduction in perseverative errors on the CVLT. CONCLUSION: We conclude that 1 week of tobacco abstinence is associated with slowed motor speed but is not associated with detectable worsening in performance on a range of neuropsychological tests or clinical symptoms in the subset of patients who were able to quit smoking. We also conclude that bupropion treatment may be associated with improvement in variability of attention.     

Use of primary prevention services among male adults with cerebral palsy, multiple sclerosis, or spinal cord injury in managed care and fee-for-service

Future research needs to clarify the biases in clinical practice and potential barriers that may exist at both the provider and health plan levels that exclude men with physical disabilities from routine preventive services. As the population of people with disabilities ages and lives longer, it is necessary that routine preventive services are accessible and made available to them, regardless of gender, disability, or health insurance type.