Curcumin (diferuloylmethane), found in the spice turmeric, exhibits anti-inflammatory, antioxidant, and chemopreventive activities. However, the effect of curcumin on the immunological responses largely remains unknown. In this study we have investigated the effect of curcumin on mitogen (phytohaemagglutinin; PHA) stimulated T-cell proliferation, natural killer (NK) cell cytotoxicity, production of cytokines by human peripheral blood mononuclear cells (PBMCs), nitric oxide (NO) production in mouse macrophage cells, RAW-264.7. Furthermore, we have carried out an electromobility shift assay to elucidate the mechanism of action of curcumin at DNA protein interaction level. We observed that curcumin inhibits PHA-induced T-cell proliferation, interleukin-2 production, NO generation, and lipopolysachharide-induced nuclear factor-kappaB (NF-kappaB) and augments NK cell cytotoxicity. Our results suggest that curcumin most likely inhibits cell proliferation and cytokine production by inhibiting NF-kappaB target genes involved in the induction of these immune parameters.

No abstract

Introduction: Vitamin D deficiency can impact post-transplant outcomes due to its effect on graft function and rejection. The effect of pre-and post-transplant serum vitamin D levels was evaluated on graft function. Objectives: This study aims to determine the incidence of vitamin D deficiency and its effect on post kidney transplant allograft function in a North Indian cohort. Patients and Methods: We evaluated 57 patients on dialysis, going for transplantation. Estimated glomerular filtration rate (eGFR) was measured using modification of diet in renal disease (MDRD) formula at 2 weeks and 3, 6, 12 months interval after kidney transplantation. Results: Pre-and post-transplant (3 months) vitamin D levels were evaluated for vitamin D deficiency and graft function. Before transplant vitamin D levels were 25.77 ± 13.68 ng/mL, 40.4% of these recipients had vitamin D deficiency (levels <20 ng/mL). After transplant, vitamin D levels at 3 months were 22.08 ± 11.15 ng/mL and 54.4% of recipients had vitamin D deficiency. No patient was on vitamin D supplementation after transplantation. At 3 months post-transplant, recipients with vitamin D levels <20 ng/mL, had significantly lower eGFR and higher serum creatinine value as compared to the group with vitamin D levels >20ng/mL. Recipients were divided into 3 groups based on pre-and post-transplant vitamin D levels (<20, 20-30 and >30ng/mL). Pre-transplant vitamin D levels correlated with graft function at 14 days. On multiple regression analysis, 3-month post-transplant vitamin D levels correlated with 12 months eGFR. There was increased incidence of acute rejection episodes in vitamin D deficiency group. Conclusion: There is a high incidence of vitamin D deficiency and insufficiency in kidney transplant recipients. Low levels of post-transplant vitamin D levels at 3 months were associated with inferior allograft function (eGFR) at 1 year.

BackgroundThe objectives of this pilot study were to assess the efficacy and safety of an interferon-free sofosbuvir and ribavirin combination regimen to treat chronic hepatitis C virus (HCV) infection in kidney transplant recipients and to study the impact of sofosbuvir on calcineurin inhibitor (CNI) drug levels.MethodsA total of 10 kidney transplant recipients with chronic HCV infection were included in the study. All received sofosbuvir and ribavirin combination therapy. The virological response to therapy and the adverse effects of the drugs were studied. The area under the curve (AUC) and pharmacokinetic data of levels of CNI were compared while the patients were receiving sofosbuvir and ribavirin drugs and when they were no longer on these drugs.ResultsIn all, 9 of 10 patients (90%) achieved rapid virological response (RVR) with undetectable HCV RNA at 4 weeks and the remaining patient achieved undetectable HCV RNA at 8 weeks. A sustained virological response was seen at 3, 6 and 12 months and was maintained in all 10 patients (100%). The important aspect of the study is the effect of treatment with the sofosbuvir–ribavirin combination regimen on the CNI AUC levels, which resulted in a reduction in the CNI AUC. While used as part of triple-drug immunosuppression, no change in the dose of CNI (tacrolimus and cyclosporine) was required based on measurement of C0 levels.ConclusionsThe sofosbuvir and ribavirin combination therapy is effective and safe to treat HCV infection in the post-renal transplant setting. There is a need for close CNI level monitoring while these patients are on sofosbuvir therapy. With therapy and viral clearance, there could be reduction in CNI levels due to increased clearance of CNI drugs, which is shown by the AUC measurements. This could be important for patients at high risk for rejection.

The opioid pentapeptides called enkephalins were originally described as the endogenous ligands for the opioid receptors. Although their precise physiological significance still remains elusive, the enkephalins have been reported to exhibit analgesic, antidepressant, antianxiety and anticonvulsant activities. In addition, enkephalins have also been shown to act as immunomodulator. The first generation of dimeric peptides was derived from enkephalins. Biphalin [(Tyr-D-Ala-Gly-Phe-NH)2] is a bivalent opioid analog containing two tyrosine residues. We have evaluated the immunomodulatory properties of biphalin and its analogs in various in vitro tests. We report that biphalin and one of its analogs [Tyr-D-Ala-Gly-Phe-NH.NH-Phe(p-Cl)-H] stimulate human T cell proliferation, natural killer (NK) cell cytotoxicity in vitro and interleukin-2 (IL-2) production. Biphalin and its analog also released chemokine like factor in the culture supernatant that was responsible for increased chemotaxis of monocytes. Furthermore, these peptides inhibited tumor necrosis factor (TNF-alpha) production in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) and nitric oxide (NO) production in mouse macrophage cells, RAW 264.7. Our observations suggest immunomodulatory property of biphalin and its analog.

Objectives: There are no reports of de novo donorspecific antibody monitoring by a low-cost solid-phase crossmatch assay using donor lysate after renal transplant. Conclusions: Solid-phase crossmatch testing using donor lysate on a Luminex platform is less expensive and can be used for posttransplant donor-specific monitoring and for diagnosis of antibody-mediated rejection. Materials and Methods

No abstract

No abstract