After its discovery DihydrotestosteroneDHT nmr in the mid 1970s, antifungal and cytotoxic effects were the first of its properties to be explored, but the most significant advancement was found in its use as an immunosuppressive agent to reduce transplant rejection. This was viewed as an important step forward for immunosuppression, as early studies suggested that rapamycin was less nephrotoxic than calcineurin inhibitors (CNIs). Later, detrimental effects of rapamycin on kidney function were found in some patients. Nonetheless, a fascination with the mTOR pathway and its central role in multiple

cellular processes has ensued. Among the potential positive clinically relevant effects is rapamycin’s capacity to interfere with fibrotic processes that often accompany transplant rejection, and to influence the preferential development of immunological tolerance. A feature of increasing importance is that the mTOR pathway is central for vital aspects of tumor development, including angiogenesis and cell growth; rapamycin, therefore, has anticancer activities, which may prove critical in the fight against high cancer rates in transplant recipients. The final chapters defining the value of rapamycin have not been written yet, and indeed remain a work in progress. Only further research will reveal the full potential of rapamycin in organ transplantation.

Kidney International (2010) 78, 1075-1079; doi: 10.1038/ki.2010.324; published online 22 September 2010″
“Dopaminergic nigro-striatal E7080 in vitro depletion interferes with the detection of novel stimuli. This suggests that Parkinson’s disease (PD) may generate from the initial stages a failure in involuntary attention (IA), which can be studied through the distraction potential, composed by the mismatch negativity (MMN), the P3a and the

reorientation negativity (RON). check details This study analyzed IA using event-related potentials (ERPs) in patients with early PD with and without dopaminergic replacement therapy. Twenty-five medicated, and 17 non-medicated patients with early PD were studied, as well as 20 healthy control subjects. All subjects performed an auditory distraction task while a digital EEG was being recorded. The distraction potential was obtained by averaging methodology. Each wave was analyzed with a Repeated Measures ANOVA test. The MMN was obtained in all subjects and no significant differences in mean amplitude were found among the groups. There was a main effect of group for the amplitude of P3a (F(2,59) = 4.8, p = 0.01, epsilon = 0.411), with a significant lower amplitude in the medicated group compared to the control group (MD = -1.03, p = 0.003). RON also showed a main effect of group (F(2,59)=4.8, p = 0.01, epsilon = 0.467), with significantly lower amplitudes in non-medicated patients with respect to both the control and medicated groups (MD = 1.19, p = 0.01, MD = 1.27,p = 0.005, respectively).