Massive post-transplantation ascites is a rare but serious condition following liver transplantation. Although, many etiologies are suggested as the cause of this complication, in some cases the definitive etiology remains unknown. Drug-induced post-transplantation ascites is one of the possible etiologies. In this study we present a case of ascites caused by TACROLIMUS in the post-liver transplantation period. A 49-year-old man with hepatitis B virus cirrhosis underwent liver transplantation and received TACROLIMUS, mycophenolate and prednisolone, as the immunosuppressive regimen. Progressive ascites developed after 10 days, in spite of a normal liver function. Various studies, including liver biopsy, were performed but we could not find any etiology for this complication. The TACROLIMUS was switched to rapamune. Ascites was completely disappeared and up to the last follow-up visit, the patient remained asymptomatic for more than two years. We concluded that after ruling out other etiologies, TACROLIMUS as a rare cause of post-transplantation ascites should be taken into account. The treatment is discontinuation of the drug.

Background: Recently there are a number of reports on the cardiotoxicity of TACROLIMUS in post-transplant patients. There is no protocol for cardiovascular evaluation in these patients. This study was performed to evaluate the cardiotoxicity of TACROLIMUS in liver transplant recipients.Patients and Methods: We evaluated 63 post-liver transplant patients who received TACROLIMUS. They were evaluated for cardiovascular complications by physical examination, electrocardiographic and echocardiographic examinations within three and six months following liver transplantation. Serum TACROLIMUS levels were checked by ELISA. For comparison, we selected 50 post-liver transplant patients who received no TACROLIMUS and evaluated them for cardiovascular function identically.Results: Among 63 patients, 42 were male (66.7%) and 21 were female (33.3%); 70% of the patients were adults, and 19 (30%) were within the pediatric age group. The cardiovascular examinations, electrocardiogram and echocardiography of all patients three months post transplantation were normal except for two children who developed TACROLIMUS related cardiac complications. Both had high serum TACROLIMUS levels. No adults developed cardiovascular complications. In the control group, the results of the cardiovascular evaluations were normal in all cases. Conclusion: The cardiovascular toxicity of TACROLIMUS, such as hypertrophic cardiomyopathy, may be observed in pediatric patients. Therefore, we recommend routine regular cardiovascular evaluation of children after liver transplantation.

Background and Objectives: to compare the efficacy of combined TACROLIMUS and 308-nm excimer laser therapy vs 308-nm excimer laser monotherapy in treating vitiligo.Materials and Methods: This study was a comparative, prospective, randomized, and intraindividual trial. For each patient (n=14), 4 to 10 target lesions were chosen. The treatment applied to each target lesion was randomized by drawing lots. Each lesion was treated twice a week by the 308-nm excimer laser, for a total of 24 sessions. Initial fluences were 12 mcal/cm2 (50 mJ/cm2) less than the minimal erythemal dose in vitiliginous skin.Then, fluences were increased by 12 mcal/cm2 every second session. Moreover, topical 0.1% TACROLIMUS ointment was applied twice daily on target lesions receiving the combined TACROLIMUS and excimer laser treatment (group A). Group B target lesions received only excimer laser monotherapy. For each treated lesion, the untreated lesion on the opposite side served as the control. Tolerance was evaluated by a visual analog scale, and secondary events were recorded at each session. Results: Forty-three lesions were treated (23 in group A and 20 in group B). Repigmentation was observed in all group A lesions (100%) and in 17 (85%) of the 20 group B lesions. Repigmentation was not observed in the untreated lesions (control group). A repigmentation rate of 75% or more was obtained in 16 (70%) of the 23 group A lesions and in 4 (20%) of the 20 group B lesions. In UV-sensitive areas (the face, neck, trunk, and limbs, with the exception of bony prominences and extremities), 10 (77%) of 13 group A lesions had a repigmentation rate of 75% or more vs 4 (57%) of 7 group B lesions. In classically UV resistant areas, 6 (60%) of 10 group A lesions had a repigmentation rate of 75% or more vs 0 of the 13 group B lesions.Conclusions: The combination treatment is superior to 308-nm excimer laser monotherapy for the treatment of UV-resistant vitiliginous lesions. The efficacy and the good tolerance of the 308-nm excimer laser in monotherapy for treating localized vitiligo were also confirmed, but this treatment regimen should be proposed only for UV-sensitive areas.

Background: TACROLIMUS is commonly used in the medical area to avoid the rejection of grafted organs. Some studies have suggested that TACROLIMUS is an immune suppressor that increases bone turnover and the development of severe osteopenia. In dentistry this effect may interfere with oral treatments.Objectives: A systematic literature review to test the hypothesis that treatment with immunosuppressor TACROLIMUS may interfere with alveolar bone metabolism. Search Strategy: Research in the health science databases was performed and includes articles published up to August 2011. Selection Criteria: Studies in animals and humans using TACROLIMUS as an immune suppressor and capable of interfering with alveolar bone metabolism were included. Data Collection and Analysis: The key words used were: TACROLIMUS and alveolar bone or TACROLIMUS and alveolar bone loss or FK506 and alveolar bone or FK506 and alveolar bone loss. The articles were initially selected by title and abstract and then potentially eligible articles were read and those that fulfilled the inclusion criteria were carefully analyzed and classified (A, B and C).Results: From a total of 745 references, only 6 articles fulfilled the eligibility criteria. Three articles were classified as A and 3 as C. In spite of the methodological differences in the 6 articles (3 animal and 3 human) TACROLIMUS was not found to cause damage to alveolar bone tissue.Conclusions: In humans the results are still not conclusive. In animals: TACROLIMUS does not produce alveolar bone loss, whereas in humans there is no evidence that this immune suppressor produces alveolar bone loss.

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 (t1/2b) 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 t1/2b 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 t1/2b 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.

Posterior reversible leukoencephalopathy syndrome (PRES) is an acute neurologic dysfunction accompanied by imaging abnormalities of brain which can follow the treatment with calcineurin inhibitors. 1 While clinical PRES is mainly reversible when expeditiously recognized, it could be associated with significant morbidity and mortality if diagnosed late. 2 A 14-years old boy with end-stage renal disease received a kidney transplant from a deceased donor. He was given polyclonal antibody, for induction, and mycophenolate mofetil, prednisolone, and TACROLIMUS, as maintenance therapy. Five days after transplantation, he developed headache and seizures. Neurologic examination, vital signs, and other general physical examination were normal. TACROLIMUS trough level was within therapeutic range. Lumbar puncture, blood and urine cultures, and other laboratory findings were normal. Echocardiography showed no vegetation. A brain magnetic resonance imaging showed hyperintensity in the subcortical and cortical regions of the bilateral parieto-occipital lobes in T2-weighted, matching PRES. TACROLIMUS was replaced by cyclosporine. Seizures were controlled with low-dose antiepileptics. One year after transplantation, the patient had no more episodes of seizure, while the antiepileptic dose was tapered; however, the follow-up imaging showed lesions remained almost unchanged.

Introduction: Umbilical cord blood is a rich source of hematopoietic cells and can be used in the clinical setting for hematopoietic cell transplantation in graft versus host disease (GVHD). A number of different drugs have been used as prophylaxis against GVHD including corticosteroids, Cyclosporine A (Cy A) and FK506. In this study, the in vitro effects of FK506 on cord blood mononuclear cells were assessed. Material and Methods: After cord blood collection and separation of mononuclear cells, the viability of them was assessed. Then, following 7-day liquid culture in the DMEM medium and in the presence of early acting growth factors such as SCF, FL, TPO and IL-6 and different doses of FK506, cells were counted and myeloid/erythroid ratios were determined. Furthermore, the percentage of CD34+ cells was assessed by flow cytometry. In this study, clonogenic assay was carried out in two stages (before and after 7- day liquid culture).Results: Under the mentioned culture conditions, cell counts and M/E ratios did not change in comparison with control (P=0.126 and P=0.819, respectively). The percentage of CD34+ cells rose considerably (P=0.018). Compared with control, colony numbers decreased in the first stage (P=0.000), whereas the number of colonies did not change in the second (P=0.109).Conclusion: Our results demonstrate that FK506 is not only an immunosuppressive agent but also has stimulating effects on expansion and clonogenesity of cord blood mononuclear cells. But in has no effect on differentiation of these cells.