Intrahepatic CD4+ cell depletion in hepatitis C virus/HIV-coinfected patients

Coinfection with HIV and hepatitis C virus (HCV)-specific immune responses, increases hepatic inflammation, accelerates hepatic fibrosis, and is associated with deceased treatment responses. We quantified intrahepatic lymphocyte and hepatocyte phenotypes in HCV-infected patients with (n = 38) and without (n = 41) HIV infection. A single pathologist counted positive cells in 5 portal and 5 lobular areas. Coinfected patients had 6.81 +/- 1.9 fewer CD4 cells per portal field (10.58 +/- 1.12 vs. 4.97 +/- 1.09 cells/high-power field [HPF]; P < 0.001) and 0.48 +/- 0.15 more apoptotic lymphocytes per lobular field (0.16 +/- 0.06 vs. 0.64 +/- 0.15 cell/HPF; P = 0.002) than monoinfected patients. The number of portal CD4 cells was not associated with the peripheral CD4 cell number. Portal and lobular CD8 cells did not differ between the 2 groups. Portal proliferative hepatocytes were increased in coinfected patients with HIV RNA levels of >400 copies/mL (1.13 +/- 0.32 cells/HPF; P = 0.01) compared with those with undetectable HIV RNA (0.46 +/- 0.09 cell/HPF) and monoinfected patients (0.45 +/- 0.08 cell/HPF). In conclusion, HIV coinfection is associated with fewer portal CD4 cells and increased lobular lymphocyte apoptosis that may impact on the natural history of HCV infection.     

Mycobacterium bovis BCG urease attenuates major histocompatibility complex class II trafficking to the macrophage cell surface

We have previously shown that Mycobacterium tuberculosis attenuates cell surface expression of major histocompatibility complex class II molecules in response to gamma interferon (IFN-gamma) by a mechanism dependent on intracellular sequestration of alpha,beta dimers. In this study we examined whether intracellular alkalinization due to mycobacterial urease could account for the defect in intracellular trafficking of class II molecules. Phagocytosis of wild-type Mycobacterium bovis BCG was associated with secretion of ammonia intracellularly, which increased substantially upon addition of exogenous urea to the culture medium. Increased intracellular ammonia, due to urea degradation by the bacterium, correlated with inhibition of class II surface expression. Conversely, no ammonia was detected in cells infected with a urease-negative mutant strain of M. bovis BCG, which also displayed a reduced effect on surface expression of class II molecules. A direct cause-effect relationship between urease and class II molecule trafficking was established with experiments where cells ingesting beads coated with purified urease showed an increased ammonia level and decreased surface expression of class II in response to IFN-gamma. In contrast to BCG, infection of macrophages with Mycobacterium smegmatis, which expresses relatively greater urease activity in cell-free culture, had a marginal effect on both the intracellular level of ammonia and class II expression. The limited effect of M. smegmatis was consistent with a failure to resist intracellular killing, suggesting that urease alone is not sufficient to resist macrophage microbicidal mechanisms and that this is required for a more distal effect on cell regulation. Our results demonstrate that alkalinization of critical intracellular organelles by pathogenic mycobacteria expressing urease contributes significantly to the intracellular retention of class II dimers.     

Fetal fibronectin as a predictor of spontaneous preterm labour in asymptomatic women with a cervical cerclage

Objective  To assess the accuracy of fetal fibronectin (fFN) testing for prediction of preterm labour in asymptomatic high-risk women with a cervical cerclage.
Design  Retrospective observational study.
Setting  United Kingdom.
Population  Nine hundred and ten asymptomatic women at high-risk of Preterm birth referred to specialist antenatal clinics and undergoing fFN testing between November 1997 and December 2007.
Methods  Women had fFN tests taken between 23⁺⁰ and 27⁺⁶ weeks' gestation, on one or more occasions.
Main outcome measures  Sensitivity, specificity, positive predictive values and negative predictive values of fFN testing for predicting delivery <30 and <37 weeks were compared in those with and without cerclage.
Results  For delivery <30 weeks' gestation, the specificity of fFN testing was significantly lower in women with cervical cerclage (77% vs 90%; P  ≤ 0.00001). The sensitivity of the test was similar between the groups (78.6 (no-cerclage) vs 60% (cerclage); P  > 0.4). The negative predictive value of the fFN test for delivery <30 weeks was high in both groups (>98%).
Conclusions  Asymptomatic high-risk women with cerclage in situ are more likely to have a false positive fFN test. The negative predictive value is similar.     

Evaluation of anti-resistant activity of Auklandia (Saussurea lappa) root against some human pathogens

Objective

The antimicrobial activity of the ethanol extract of the Auklandia (Saussurea lappa)root plant was investigated to verify its medicinal use in the treatment of microbial infections.

Methods

The antimicrobial activity of the ethanol extract was tested against clinical isolates of some multidrug-resistant bacteria using the agar well diffusion method. Commercial antibiotics were used as positive reference standards to determine the sensitivity of the clinical isolates.

Results

The extracts showed significant inhibitory activity against clinical isolates of methicillin resistant Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia, Extended Spectrum Beta-Lactemase, Acinetobacter baumannii. The minimum inhibitory concentration values obtained using the agar dilution test ranged from 2.0 µg/µL-12.0 µg/µL. In the contrary the water extract showed no activity at all against the tested isolates. Furthermore, the results obtained by examining anti-resistant activity of the plant ethanolic extract showed that at higher concentration of the plant extract (12 µg) all tested bacteria isolates were inhibited with variable inhibition zones similar to those obtained when we applied lower extract concentration using the well diffusion assay.

Conclusion

The results demonstrated that the crude ethanolic extract of the Auklandia (Saussurea lappa) root plant has a wide spectrum of activity suggesting that it may be useful in the treatment of infections caused by the above clinical isolates (human pathogens).     

Proliferative cell activity in correlation to human chorionic gonadotrophin release of trophoblast tissue of tubal pregnancy

The degree to which the relative rise of serum human chorionic gonadotrophin (HCG) concentration was related to proliferative cell activity and the biological vitality of tubal pregnancy was investigated. Salpingectomy was performed in 15 patients diagnosed as having non-ruptured tubal pregnancy. Serum HCG was evaluated twice preoperatively, with a 48-h time interval. Proliferative cell activity was measured through the use of the cell proliferation marker 'Ki-67'. A significant correlation between the relative increase in HCG over a 48-h period, independent of the initial serum HCG value, and the biological cell activity of the trophoblast was shown. Furthermore, it became evident that cell activity was also correlated to the intracellular HCG of the trophoblast. The relative increase in serum HCG over a period of 48 h can serve as a parameter for the biological activity of the trophoblast in tubal pregnancies.      

Effect of castration and sex hormone treatment on survival, anti- nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice

NZB/NZW F1 mice of both sexes were castrated at 2 wk of age and implanted subcutaneously with silastic tubes containing either 5-alpha-dihydrotestosterone or estradiol-17-beta. Mice receiving androgen showed improved survival, reduced anti-nucleic acid antibodies, or less evidence of glomerulonephritis as determined by light, immunofluorescent, and electron microscopy. By contrast, opposite effects were observed in castrated mice receiving estrogen. Intact male NZB/NZW F1 mice received androgen implants at 8 mo, an age when they develop an accelerated autoimmune disease associated with a decline in serum testosterone concentration. Such treated mice had improved survival and reduced concentrations of antibodies to DNA and to polyadenylic acid (Poly A). Prepubertal castration of male NZB/NZW F1 mice results in an earlier appearance of IgG antibodies to Poly A. This effect of castration was prevented if neonatal thymectomy was also performed.