The kinases aurora B and mTOR regulate the G1-S cell cycle progression of T lymphocytes

CD28-deficient T cells arrest at the G1-S transition of the cell cycle. Here we show that this is controlled by the kinase aurora B, which exists in a complex with survivin and mammalian target of rapamycin (mTOR). Expression of aurora B in Cd28-/- T cells augmented phosphorylation of mTOR substrates, expression of cyclin A, hyperphosphorylation of retinoblastoma protein and activation of cyclin-dependent kinases 1 and 2 and promoted cell cycle progression. Interleukin 2 enhanced aurora B activity, and inactive aurora B prevented interleukin 2-induced proliferation. Moreover, expression of aurora B restored Cd28-/- T cell proliferation and promoted inflammation in vivo. These data identify aurora B, along with survivin and mTOR, as a regulator of the G1-S checkpoint in T cells.     

Topical Metronidazole can Reduce Pain after Surgery and Pain on Defecation in Postoperative Hemorrhoidectomy

Background Topical metronidazole (10 percent) has been previously demonstrated to decrease postoperative pain after hemorrhoidectomy. The aim of this study was to evaluate the effect of topical metronidazole (10 percent) in reducing postoperative and after-defecation pain of hemorrhoidectomy. Materials and Methods A double-blind, randomized trial was conducted to compare posthemorrhoidectomy pain with use of topical metronidazole (10 percent) vs. placebo carrier, applied to surgical site. Forty-seven patients were randomly allocated to receive metronidazole (n = 25) or placebo (n = 22). Pain was assessed using a visual analog scale preoperatively and on postoperative hours 6 and 12 and at days 1, 2, 7, and 14. The use of narcotic, additional analgesics, and complications were recorded. (Pain scores were calculated and compared with baseline values and control group (t test, SPSS ver.10). Results Patients in the topical metronidazole group had significantly less postoperative pain than those in the placebo group up to day 14 (P ≤ 0.04). There was no significant difference in narcotic analgesic requirements between groups, except on hour 12 (P < 0.05). In the metronidazole group, after-defecation pain was ranked significantly lower at day 2 (P = 0.016) and patients required fewer additional analgesics postoperatively on days 2 and 7 (P ≤ 0.04). Conclusion These finding indicate that topical 10 percent metronidazole significantly reduce posthemorrhoidectomy discomfort, and postoperative defecation pain is reduced compared with that of the placebo control group. Support: A grant of vice-chancellor for research of Mazandaran University of Medical Sciences     

Interleukin-4 Modulation of Platelet-Derived Growth Factor–Induced Smooth Muscle Cell Urokinase Plasminogen Activator

Platelet-derived growth factor (PDGF) stimulates smooth muscle cell (SMC) migration owing to stimulation of SMC tissue plasminogen activator (t-PA) production. In this study we examined the effects of the T-cell lymphokine interleukin-4 (IL-4) on PDGF induction of human aortic SMC antigen levels of urokinase-type plasminogen activator (u-PA) and those of plasminogen activator inhibitor-1 (PAI-1), the endogenous inhibitor of t-PA and u-PA, measured by enzyme-linked immunosorbent assays (ELISAs). u-PA antigen levels from human aortic SMC incubated with PDGF 100 ng/mL and IL-4 500 U/mL were significantly greater than those incubated with PDGF 100 ng/mL alone. Coincubation of PDGF with IL-4 did not significantly increase SMC u-PA antigen levels in cellular lysates. Coincubation with PDGF 100 ng/mL and IL-4 500 U/mL did not significantly affect SMC PAI-1 antigen levels in conditioned media or cellular lysates. Therefore, interleukin-4 modulates vascular SMC u-PA production induced by PDGF.     

Intestinal fungal and parasitic infections in kidney transplant recipients: a multi-center study

Kidney transplant recipients are susceptible to various infections due to the use of immunosuppressive drugs. The present study was performed as studies on the prevalence of intestinal fungal and parasitic infections in kidney transplant recipients are limited. A total of 150 kidney transplant recipients and 225 matched immunocompetent outpatients, who were referred to the laboratory of Noor Hospital, Isfahan, were studied. After recording demographic characteristics, direct test and specific laboratory cultures were carried out on the stool specimens. Patients were instructed on sanitary rules and, during each medical visit, they were reminded of the same. The overall prevalence of intestinal parasitic and fungal infections was 33.3% and 58.7%, respectively, in transplant recipients and 20% and 51%, respectively, in the control group; the difference was not statistically significant. The most prevalent intestinal parasite was Entameba coli, which was seen in 9.3% of the study patients and 6.7% of the controls. The most prevalent fungus was Candida sp., which was seen in 22% of the study patients and 24.4% of the control group. Co-existing infection with two or more fungi was seen in 14.8% and 3.4% in the case and control groups, respectively; P <0.001. Interestingly, there was no significant difference in the prevalence of infection by a single organism between the two groups. However, co-existing infection with two or more species was more prevalent in transplant recipients. We conclude that further investigations are needed to evaluate the pathogenesis of infection with these microorganisms.