Pathogenic aspects of acute cholangitis

The research is aimed at the study of dynamic pathomorphological changes of choledoch and acute cholangitis development factors determined during the experiment. 36 rats of Wistar line were under trial. The main group consisted of 30 animals undergoing the open laparotomy, choledoch ligation and puncture modeling of acute cholangitis by E. coli culture in 1 х 108 CFU/ml concentration under general anesthesia. 6 healthy rats were included in the control group. Samples of general biliary duct under autopsy for pathomorphological study were taken on the 3rd, 7th, 14th, 21st and 30th day. In panoramic samples colored by hematoxilin and eozin the degree of dystrophic, necrobiotic, hemodynamic, inflammatory and atrophic manifestations’ changes were studied. Average depth of choledoch wall and height of its epithelial lining were morphometrically estimated. Collagen of the IV type as well as expressing receptors to CD34 were defined with the help of monoclonal antibodies in choledoch epithelial cells of basal membranes and choledoch vessels endotheliocytes. In choledoch, enhancement of edema and inflammatory infiltration by lymphoplasmocytic elements with the admixture of neutrofils with granulation tissue was detected from the 3rd up to the 30th day of the experiment. From the 14th day formation of bile clots of blood was detected in choledoch clearance, part of which was locked to its de-epitheliolized internal surface. According to morphometrical study data, choledoch wall depth increased from 261.1 ± 3.13 µm on the 3rd day to 572.5 ± 3.42 µm on the 30th day of the experiment. Mucosa membrane has lost its folding on the 14th day, epitheliocytes flattening was replaced by their destruction with fragments rejection into the duct lumen by the 30th day of the experiment. The epithelium height index decreased from 14.8 ± 0.09 µm on the 3rd day to 11.7 ± 0.15 µm on the 30 day of the experiment. Collagen of the IV type fluorescence intensity of vessel basal membranes from the 3rd day closely matched the control, its enhancement was detected by the 30th day. Choledoch epitheliocytes fluorescence, expressing the receptors to CD34 reliably decreased by the 30th day of the study. In its turn, content of collagen of the IV tyre, as well as vessels endothelium expression in preparations treated by PQA to CD34 reliably increased by the 30th day of the experiment. Thus, in pathogenesis of acute cholangitis apart from well-known factors such as cholestasis and infection the third factor was detected, in the way of biliary ducts mucosa membrane lesion. In morphogenesis of choledoch mucosa membrane lesion the decrease in role of epitheliocytes adhesive properties was stated as well as deficit of collagen of the IV type in the structure of epithelial basal membranes. During observations where epithelial covering consistency was preserved, inflammatory changes in choledoch were insignificant, which is proved by sufficient resistance of biliary ducts epithelium to infection in the presence of cholestasis and bacteriocholia, but in cases when mucosa membrane de-epitheliolization took place the development of severe purulent-destructive cholangitis and pericholangitis was detected.

Evaluation of Response of Parenteral Dexamethasone in Pemphigus Vulgaris

A clinical trial was carried out in the Department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University, Dhaka. The total number of patients was thirty and among them fifteen patients were treated with injection dexamethasone (Group-A) and other fifteen were treated with oral prednisolone (Group-B). The study showed that in Group-A, on admission and after 6 weeks, the mean number (±SD) of skin lesion of pemphigus was 36.87±8.40 and 5.27±1.624 respectively. In Group-B, on admission and after 6 weeks, the mean number (±SD) of skin lesion of pemphigus was 36.27±8.980 and 7.73±1.007 respectively. The study also observed that in group-A, on admission and after 6 weeks, the mean number (±SD) of mucous membrane lesion of pemphigus was 3.40±2.633 and 1.00±0.926 respectively. In Group-B, on admission and after 6 weeks, the mean number (±SD) of mucous membrane lesion of pemphigus was 3.33±2.225 and 1.87±1.246 respectively. Statistically significant improvement was observed in both groups in all clinical parameter after 6 weeks. Dexamethasone group showed statistically higher significant improvement than prednisolone group in all clinical parameter except Nikolsky’s sign. Injection dexamethasone appears to be more effective than oral prednisolone in early management of pemphigus vulgaris. DOI: http://dx.doi.org/10.3329/cbmj.v2i2.16694 Community Based Medical Journal 2013 July: Vol.02 No 02: 25-29

Diagnosing Placental Membrane Hypoxic Lesions Increases the Sensitivity of Placental Examination

Context.—Two relatively unknown and recently described placental membrane hypoxic lesions (laminar necrosis and microscopic chorionic pseudocysts) have never been compared with time-honored, focal (infarction), and diffuse hypoxic lesions of placental parenchyma. Objective.—To compare the effect on placental diagnosis of the above placental membrane hypoxic lesions and chorionic disc hypoxic lesions (infarctions and global hypoxic pattern of placental injury). Design.—Twenty-three clinical (maternal and fetal) and 32 gross and microscopic placental features were retrospectively compared in 4590 placentas from a placental database built during a 13-year period: 168 placentas with at least one hypoxic disc lesion (infarct or global hypoxia) and at least one membrane lesion (microscopic chorionic pseudocysts or laminar necrosis (group 1), 750 placentas with at least one hypoxic villous lesion but no membrane lesion (group 2), 480 placentas with at least one membrane lesion but no villous lesion (group 3), and 3192 placentas with no hypoxic villous or membrane lesions (group 4). Results.—Several clinical and fetal conditions and placental features known to be associated with in utero hypoxia had a statistically significant correlation with the index hypoxic placental lesions, both villous and membranous. Of placentas from patients associated with clinical conditions at risk for hypoxia, 15% featured only hypoxic membrane lesions without a chorionic disc hypoxic lesion. Conclusions.—Recognizing placental membrane hypoxic lesions increases the sensitivity of placental examination in diagnosing placental hypoxia by at least 15%. The risk of in utero hypoxia is increased when microscopic chorionic pseudocysts and laminar necrosis occur in conjunction with villous hypoxic lesions.

Sizing the Holin Lesion with an Endolysin-β-Galactosidase Fusion

ABSTRACT Double-stranded DNA phages require two proteins for efficient host lysis: the endolysin, a muralytic enzyme, and the holin, a small membrane protein. In an event that defines the end of the vegetative cycle, the λ holin S acts suddenly to permeabilize the membrane. This permeabilization enables the R endolysin to attack the cell wall, after which cell lysis occurs within seconds. A C-terminal fusion of the R endolysin with full-length β-galactosidase (β-Gal) was tested for lytic competence in the context of the late-gene expression system of an induced λ lysogen. Under these conditions, the hybrid R-β-Gal product, an active tetrameric β-Gal greater than 480 kDa in mass, was fully functional in lysis mediated by the S holin. Western blot analysis demonstrated that the lytic competence was not due to the proteolytic release of the endolysin domain of the R-β-Gal fusion protein. The ability of this massive complex to be released by the S holin suggests that S causes a generalized membrane disruption rather than a regular oligomeric membrane pore. Similar results were obtained with an early lysis variant of the S holin and also in parallel experiments with the T4 holin, T, in an identical lambda context. However, premature holin lesions triggered by depolarization of the membrane were nonpermissive for the hybrid endolysin, indicating that these premature lesions constituted less-profound damage to the membrane. Finally, a truncated T holin functional in lysis with the endolysin is completely incompetent for lysis with the hybrid endolysin. A model for the formation of the membrane lesion within homo-oligomeric rafts of holin proteins is discussed.