Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice

Antibodies to tumor necrosis factor (TNF)-α have been recently proposed as effective treatment for patients with Crohn's disease. Here, we analyze the functional role of TNF-α in a mouse model of chronic intestinal inflammation induced by the hapten reagent 2,4,6,-trinitrobenzene sulfonic acid (TNBS) that mimics some characteristics of Crohn's disease in humans. Macrophage-enriched lamina propria (LP) mononuclear cells from mice with TNBS-induced colitis produced 10–30-fold higher levels of TNF-α mRNA and protein than cells from control mice. When mice with chronic colitis were treated by intraperitoneal injection of antibodies to TNF-α, an improvement of both the clinical and histopathologic signs of disease was found. Isolated macrophage-enriched LP cells from anti-TNF-α-treated mice produced strikingly less pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 in cell culture. The predominant role of TNF-α in the mouse TNBS-induced colitis model was further underlined by the finding that striking colonic inflammation and lethal pancolitis was induced in TNF-α-transgenic mice upon TNBS treatment. Conversely, no significant TNBS-induced colitis could be induced in mice in which the TNF-α gene had been inactivated by homologous recombination. Complementation of TNF-α function in TNF^?/? mice by the expression of a mouse TNF-α transgene was sufficient to reverse this effect. Taken together, the data provide direct evidence for a predominant role of TNF-α in a mouse model of chronic intestinal inflammation and encourage further clinical trials with antibodies to TNF-α for the treatment of patients with Crohn's disease.     

TNBS-colitis

Disease states, such as the occurrence of gastrointestinal inflammation (Crohn's disease and ulcerative colitis), can be secondary to a host of determinants that act in conjunction to bring about pathologic change. The underlying factors that mediate the development of such mucosal inflammation has recently been brought to the forefront with the advent of animal models. The examination of these animal models have given researchers a better understanding of the mechanisms involved in the pathogenesis of inflammatory bowel disease. This review discusses one such model, TNBS-colitis, and the insights that it provides into the occurrence of IBD and its future treatment.     

葛根素的心血管系统药理作用及机理研究

纵观近年来对葛根素在心血管系统药理作用及机理研究方面的进展发现，葛根素对心血管系统具有抗心律失常、降血压、扩张冠状动脉、抗心肌缺血、抗过氧化、抗缺血-再灌注损伤、影响血液动力学和血小板聚集、保护血管等作用。其临床应用前景良好，其药效机制研究及临床应用有待更深一步的探究。     

Uterine-umbilical velocimetry in open heart surgery

The effect of the nonpulsating cardiac pump in uterine and umbilical circulation has not been studied extensively by measuring the resistance of the uterine and umbilical circulation with velocimetry. During open heart surgery, we were able to demonstrate the effects of the nonpulsatile cardiac pump.     

Über spontane und traumatische Meniscusschäden

Ohne ZusammenfassungHerrn Prof.E. v. Redwitz zum 65. Geburtstag.     

Splenic lymphoma with villous lymphocytes involves B cells with extensively mutated Ig heavy chain variable region genes

Splenic lymphoma with villous lymphocytes (SLVL) is a recently defined subgroup of chronic B-cell lymphoproliferative diseases. The characteristic morphology of the tumor cells, together with phenotypic and cytogenetic findings, indicate that it is a distinct entity, but the nature of the cell or origin and its relationship to other low- grade lymphomas is unclear. For B-cell tumors, analysis of the variable region heavy chain (VH) genes used to encode the clonal Ig has shown marked differences between histologic categories, both in gene usage and extent of somatic mutation. An investigation of VH genes used in five typical cases of SLVL has shown somatic hypermutation from germline sequences in all cases, indicating that the cell of origin has been exposed to the hypermutation mechanism. However, no clonal heterogeneity was detectable, demonstrating that the tumor cell does not accumulate further mutations. These characteristics are similar to those found in mature postfollicular B cells, such as plasma cells. The distribution of mutations leading to replacement amino acids differed among the cases, with three of five cases showing clear evidence for antigen selection.     

High rates of depressive symptoms among patients with systemic sclerosis are not explained by differential reporting of somatic symptoms

OBJECTIVE: Between 36% and 65% of patients with systemic sclerosis (SSc) report symptoms of depression above cutoff thresholds on self-report questionnaires. The objective of this study was to assess whether these high rates result from differential reporting of somatic symptoms related to the high physical burden of SSc. METHODS: Symptom profiles reported on the Center for Epidemiologic Studies Depression Scale (CES-D) were compared between a multicenter sample of 403 patients with SSc and a sample of respondents to an Internet depression survey, matched on total CES-D score, age, race/ethnicity, and sex. An exact nonparametric generalized Mantel-Haenszel procedure was used to identify differential item functioning between groups. RESULTS: Patients with SSc reported significantly higher frequencies (moderate to large effect size; P < 0.01) on 4 CES-D somatic symptom items: bothered, appetite, effort, and sleep. Internet respondents had higher item scores on 2 items that assessed interpersonal difficulties (unfriendly, large effect size; P < 0.01; disliked, large effect size; P < 0.01) and on 2 items that assessed lack of positive effect (happy, moderate effect size; P = 0.01; enjoy, large effect size; P < 0.01). Adjustment of standard CES-D cutoff criteria for potential bias due to somatic symptom reporting resulted in a reduction of only 3.6% in the number of SSc patients with significant symptoms of depression. CONCLUSION: High rates of depressive symptoms in SSc are not due to bias related to the report of somatic symptoms. The pattern of differential item functioning between the SSc and Internet groups, however, suggests some qualitative differences in depressive symptom presentation.     

Prevalence of zinc deficiency and its clinical relevance among hospitalised elderly

Zinc is an essential trace element, and constituent of many metallo-enzymes required for normal metabolism. Age may be associated with altered metallothionein metabolism related to changes in zinc metabolism. The objectives of this study were: (i) to assess the prevalence of zinc deficiency among hospitalised elderly patients; (ii) to define the social, functional, pathological and nutritional characteristics of zinc deficient elderly hospitalised patients; and (iii) to assess the relationship between the zinc status and humoral immune function among hospitalised elderly patients. Fifty consecutive patients underwent comprehensive geriatric assessments included evaluations of the medical (index of the severity of the disease(s)), psychiatric (Geriatric depression scale (GDS)), therapeutic, social, functional (Katz's scale), and nutritional problems (Mini Nutritional Assessment (MNA) and biochemical markers (zinc, albumin, prealbumin (PAB), cholesterol) before their discharge. Fourteen patients (28%) presented a zinc concentrations lower than 10.7 micromol/l, this value is usually considered as the cut-off level below which a zinc deficient status is possible. Higher proportions of respiratory infections, cardiac failure, and depression were observed among zinc deficient patients as compared with the group of patients with normal zinc status. The other parameters of comprehensive geriatric assessment did not allow to discriminate the zinc deficient patients. The only slight differences (which remained unsignificant) concerned the prealbumin levels which tended to be higher in the group of patients presenting normal zinc status than in the group with poor zinc status (0.208+/-0.062 versus 0.171+/-0.068 g/l respectively, P=0.06), and the IgG2 levels which tended to be lower in the group of patients with normal zinc status than in the group presenting poor zinc status (2.77+/-1.91 versus 4.06+/-2.56, respectively, P=0.057). A negative correlation was observed between the Zn concentrations and the IgG2 levels (Spearman R=-0.311, P=0.028). To the best of our knowledge, this is the first study presenting zinc status according to a comprehensive geriatric assessment among European hospitalised geriatric patients. We decided to perform this study to known whom of our patients needed to be supplemented with zinc administration. Considering the low energy intake of hospitalised patients (confirmed here in regards of the nutritional assessment), and the insufficient trace element density in European foods, the relevance of providing medical supplements or enriched foods to this population has to be evaluated. Although most of the current diseases may be relevant to long-term interactions between nutrition and ageing, certain states observed in the elderly, like impaired immune and cognitive functions, could still benefit from an appropriate nutritional supplementation.