Programmed cell death in Giardia.

Programmed cell death (PCD) has been observed in many unicellular eukaryotes; however, in very few cases have the pathways been described. Recently the early divergent amitochondrial eukaryote Giardia has been included in this group. In this paper we investigate the processes of PCD in Giardia. We performed a bioinformatics survey of Giardia genomes to identify genes associated with PCD alongside traditional methods for studying apoptosis and autophagy. Analysis of Giardia genomes failed to highlight any genes involved in apoptotic-like PCD; however, we were able to induce apoptotic-like morphological changes in response to oxidative stress (H2O2) and drugs (metronidazole). In addition we did not detect caspase activity in induced cells. Interestingly, we did observe changes resembling autophagy when cells were starved (staining with MDC) and genome analysis revealed some key genes associated with autophagy such as TOR, ATG1 and ATG 16. In organisms such as Trichomonas vaginalis, Entamoeba histolytica and Blastocystis similar observations have been made but no genes have been identified. We propose that Giardia possess a pathway of autophagy and a form of apoptosis very different from the classical known mechanism; this may represent an early form of programmed cell death.

Successful tacrolimus treatment following renal transplant in a HIV-infected patient with raltegravir previously treated with a protease inhibitor based regimen.

A HIV positive patient who received a cadaveric renal transplantation developed tacrolimus toxicity as manifest by renal failure and decreased consciousness. This was due to atazanavir and ritonavir therapy for her HIV inhibiting the CYP3A4 hepatic enzyme resulting in accumulation of tacrolimus. Her HIV treatment was switched to raltegravir which is metabolized by UGT1A1 which does not affect tacrolimus. Tacrolimus was then reintroduced, and follow-up at 1 year demonstrated successful immunosuppression and undetectable HIV viral loads.