Clinical pharmacokinetics of tacrolimus in iranian liver transplant recipients

Tacrolimus, a cornerstone of immunosuppressive therapy in solid organ transplantation, has a narrow therapeutic range with considerable inter-individual and intra-individual pharmacokinetic variability. To date, there is no information on the pharmacokinetics of tacrolimus in Iranian liver transplant recipients. This study was designed to determine pharmacokinetic properties of orally administered tacrolimus in Iranian adult liver transplant recipients. Tacrolimus doses and steady state whole blood trough concentrations as well as patient demographic and clinical data were obtained retrospectively using the 30 included patients' medical records. Pharmacokinetic parameters were estimated by using a nonlinear mixed effect model program [Monolix version 3.1]. Absorption rate constant was fixed at two hours[-1]. Drug apparent clearance [CL/F], apparent volume of distribution [Vd/F], and elimination half life [t1/2 Beta] were calculated. The administered dose of tacrolimus to the patients ranged from 0.02 to 0.14 mg/Kg/day. Tacrolimus blood trough concentrations varied widely within the range of 1.8 to 30 ng/mL. The mean values of CL/F, Vd/F, and t1/2 Beta were found to be 9.3 +/- 0.96 L/h, 101 +/- 29 L, and 7.5 hours, respectively. The pharmacokinetics of tacrolimus was highly variable among our patients. CL/F, Vd/F, and t«? of tacrolimus in this study were comparable to reported values from Italian heart transplant patients but somewhat different from reported ones from other solid organ transplant populations

Harvesting of bone marrow mesenchymal stem cells from live rats and the in vitro differentiation of bone marrow mesenchymal stem cells into neuron-like cells

In the bone marrow, there are certain populations of stem cell sources with the capacity to differentiate into several different types of cells. Ideally, cell transplants would be readily obtainable, easy to expand and bank, and capable of surviving for sufficient periods of time. Bone marrow mesenchymal stem cells [BM-MSCs] possess all of these characteristics. One of the most important benefits in using BM-MSCs is the possibility of autologous therapy. Recently, numerous studies have evaluated strategies that attempt to promote axonal regeneration in central nervous system [CNS] injuries. Among these strategies, cell transplantation is considered to be the most effective way. The differentiation of stem cells into different neural lineages [such as astrocytes and neural like cells] before transplantation has a critical role in achieving the best results in studies of CNS injury. In this study, BM-MSCs were isolated from bone marrow aspirates taken from the femurs of 103 live rats. The detection of BM-MSCs was performed with RT-PCR analysis, and they were then induced to differentiate into neuron-like cells in serum-withdrawal medium over a two week period using a multistep protocol. In addition to the morphological evaluation of differentiated cells, the process of neural differentiation was proven by immunocytochemical techniques using primary antibodies to Neuron Specific Enolase [NSE] to assess cell differentiation. PT-PCR analysis was performed for the evaluation of neural specific genes, which included NSE, MAP2, nestin, and beta-tubulin. Morphological evaluations detect neuron like cells with longitudinal processes. Using RT-PCR and immunocytochemistry assays, neuron specific genes and proteins following treatment of cells in serum-withdrawal induction medium was expressed. This study showed a simple and practical method for differentiating MSCs into neuron like cells, and feasibility of aspirate bone marrow from a live rat for autologous grafting

Can vaginal pH predict menopause?

To review the role of vaginal pH in the diagnosis of menopause. This descriptive cross-sectional study was performed in the Department of Obstetrics and Gynecology, Amir University Hospital, Semnan, Iran from March 2008 to March 2009 on 200 women [100 non-menopausal and 100 post-menopausal] from 45-65 years old. The pH paper was placed directly in contact in the lower third side wall of the vagina, and the pH was measured. Simultaneous sampling and culture of the vaginal discharge and blood samples for follicle stimulating hormone [FSH] was performed in the same day. Cases of bacterial vaginosis, trichomonas or other vaginitis were treated, and again 2 weeks later, the vaginal pH was measured. The gold standard for the diagnosis of menopause was FSH >35IU, hypoestrogenemia symptoms, and amenorrhea for one year. Receiver operating characteristic curve was used to determine the best cut-off point. The sensitivity, specificity, positive and negative predictive values were evaluated. The mean +/- standard deviation age in the post-menopausal women was 58 +/- 3.8, and in non-menopausal women was 47.6 +/- 2. The vaginal pH in the diagnosis of menopause has a sensitivity of 92.7%, specificity - 83.5%, positivity - 84.9%, and negative -92% predictive values [cut-off point >6]. Our study suggests that the pH of the vagina can be a good alternative to test for the diagnosis of menopause