Effect of shigella enterotoxin 1 (ShET1) on rabbit intestine in vitro and in vivo

The purpose of this study was to identify the optimal knot construction for interrupted dermal sutures. A synthetic braided absorbable suture, sizes 3-0 and 5-0, was selected for this evaluation. With reproducible mechanical performance tests, we determined that the construction of secure knots without ears required one additional throw as compared with secure knots with 3-mm ears. The direction of applied tension did not alter knot security, with the exception of granny knots, which required an extra throw when tension was applied parallel to the suture loop. Because interrupted dermal knot construction is accomplished without knot ears and with an applied tension parallel to the wound, one additional throw must be added to the knot to ensure knot security.     

The effects of betamethasone derivatives on endotoxin-induced uveitis in guinea pigs

OBJECTIVE AND DESIGN: We reported previously that the betamethasone derivative betamethasone dipropionate behaves as an anti-glucocorticoid in rat endotoxin-induced uveitis (EIU). In the present study, we produced EIU in guinea pigs and investigated the effects of betamethasone dipropionate on the EIU. MATERIAL: Male Hartley guinea pigs were used. TREATMENT: Glucocorticoids were instilled into the eye. METHOD: To elicit EIU, lipopolysaccharide (LPS) was injected into the anterior chamber of the eye. Cell numbers in the aqueous humor after LPS injection were determined by flow cytometry. Prostaglandin E2 (PGE2) production after LPS injection into the anterior chamber was also examined. RESULTS: Intracameral injection of LPS (1 microgram/eye) induced cell infiltration into the anterior chamber and PGE2 production. Betamethasone dipropionate inhibited cell infiltration and PGE2 production more strongly than betamethasone. These results suggest that betamethasone dipropionate is a potent glucocorticoid in guinea pigs. CONCLUSIONS: Structure-activity relationships of glucocorticoids in the guinea pig EIL model may differ from those in the rat EIU model.     

Autoimmunity caused by disruption of central T cell tolerance. A murine model of drug-induced lupus

A side effect of therapy with procainamide and numerous other medications is a lupus-like syndrome characterized by autoantibodies directed against denatured DNA and the (H2A-H2B)-DNA subunit of chromatin. We tested the possibility that an effect of lupus-inducing drugs on central T cell tolerance underlies these phenomena. Two intrathymic injections of procainamide-hydroxylamine (PAHA), a reactive metabolite of procainamide, resulted in prompt production of IgM antidenatured DNA antibodies in C57BL/6xDBA/2 F1 mice. Subsequently, IgG antichromatin antibodies began to appear in the serum 3 wk after the second injection and were sustained for several months. Specificity, inhibition and blocking studies demonstrated that the PAHA-induced antibodies showed remarkable specificity to the (H2A-H2B)-DNA complex. No evidence for polyclonal B cell activation could be detected based on enumeration of Ig-secreting B cells and serum Ig levels, suggesting that a clonally restricted autoimmune response was induced by intrathymic PAHA. The IgG isotype of the antichromatin antibodies indicated involvement of T cell help, and proliferative responses of splenocytes to oligonucleosomes increased up to 100-fold. As little as 5 microM PAHA led to a 10-fold T cell proliferative response to chromatin in short term organ culture of neonatal thymi. We suggest that PAHA interferes with self-tolerance mechanisms accompanying T cell maturation in the thymus, resulting in the emergence of chromatin-reactive T cells followed by humoral autoimmunity.     

Scarring trachoma is associated with polymorphism in the tumor necrosis factor alpha (TNF-alpha) gene promoter and with elevated TNF-alpha levels in tear fluid

Tumor necrosis factor alpha (TNF-alpha) may play a central role in the disease pathogenesis which occurs as a consequence of chlamydial infection. To investigate the importance of TNF-alpha gene promoter polymorphisms and TNF-alpha levels in tear fluid in scarring trachoma, a large matched-pair case-control study was performed in The Gambia. The -308A allele was present in a higher proportion of patients (28.4%) than controls (18.4%), with an increasing association for homozygotes (chi2 for trend, P = 0.032; allele frequency, 0.163 in patients and 0.099 in controls; chi2, P = 0.025). For the -238A allele, the association was similar but not significant. The disease association was highly significant when the number of either -308A or -238A sites in an individual was considered (P = 0.003). TNF-alpha promoter alleles are tightly linked to some HLA class I and II alleles, but multivariate analysis confirmed that the disease associations were independent of HLA, although a class I allele, A*6802, is also associated with disease. TNF-alpha was more frequently detected in tear samples from patients (27.6%) than from controls (15.9%), increasingly so for higher levels of detectable TNF-alpha (P = 0.015). Among patients, detectable TNF-alpha in tears was highly associated with the presence of ocular chlamydial infection (P < 0.001). The results indicate that TNF-alpha plays a major role in the tissue damage and scarring which occurs as a consequence of Chlamydia trachomatis infection.     

Behavioural effects induced by nitrous oxide in rats performing a vigilance task

Nitrous oxide (N2O) effects were evaluated, as a behavioural model of inert gas narcosis, in rats performing a vigilance task in which they were required to respond to a slight luminous increment of the house-light. A dose-related decrease of correct responses was produced by the tested range of concentrations of N2O (from 30 to 70% N2O), with a parallel increase of anticipatory responses up to 60% N2O and a dramatic increase of omissions at 70% N2O. The influence of preparatory period duration on hits delays suggested a 'conditional probability effect' conserved under N2O. Pretreatment of animals with flumazenil (a central benzodiazepine receptor antagonist) did not improve performance under 40% N2O. Naltrexone, an opiate receptor antagonist, however, increased the N2O-induced deficits. These results suggest that benzodiazepine receptors are not involved in N2O-induced impairments in this attentional task, but opiate mechanisms may be implicated.     

The usefulness of the timeliness of endoscopic sphincterotomy in severe acute pancreatitis of biliary origin

There are evidence indicating that endoscopic retrograde cholangiopancreatography with sphincterotomy (ERCP+S) reduces the rate of complications in patients with severe acute biliary pancreatitis (ABP). The aim of this study was to analyze our experience in the treatment of severe ABP with ERCP+S and compare the evolution of the patients treated early (3 days or less following admission) with those treated late (after the 3rd day). A retrospective review of the clinical histories of the 16 patients with severe ABP treated with ERCP+S over the last two years is presented, analyzing their clinical features on admission and evolution. Biliary stones or biliary sludge was observed in 11 cases (69%). Nine patients had undergone early, and 7 late, ERCP+S. The patients of the latter group presented a greater number of complications during evolution than the former group (43% vs 0%; p = 0.025). The mortality of the patients of the late ERCP+S was also greater although without statistical significance (28.6% vs 0%; p = 0.15). No complication secondary to ERCP+S was detected. These findings confirm the fact that ERCP+S performed early in severe ABP significantly reduces the number of complications and is associated with a lower mortality.