Aza-CGP37157-lipoic hybrids designed as novel Nrf2-inducers and antioxidants exert neuroprotection against oxidative stress and show neuroinflammation inhibitory properties.

Two multitarget hybrids, derived from an aza-analogue of CGP37157, a mitochondrial Na /Ca exchanger antagonist, and lipoic acid were designed in order to combine in a single molecule the antioxidant and Nrf2 induction properties of lipoic acid and the neuroprotective activity of CGP37157. The hybrid derivatives showed Nrf2 induction and radical scavenging properties, leading to a good neuroprotective profile against oxidative stress, together with an interesting antineuroinflammatory activity. The results obtained show differences in activity depending on the configuration of the chiral center of LA.

ITH14001, a CGP37157-Nimodipine Hybrid Designed to Regulate Calcium Homeostasis and Oxidative Stress, Exerts Neuroprotection in Cerebral Ischemia.

During brain ischemia, oxygen and glucose deprivation induces calcium overload, extensive oxidative stress, neuroinflammation, and, finally, massive neuronal loss. In the search of a neuroprotective compound to mitigate this neuronal loss, we have designed and synthesized a new multitarget hybrid (ITH14001) directed at the reduction of calcium overload by acting on two regulators of calcium homeostasis; the mitochondrial Na/Ca exchanger (mNCX) and L-type voltage dependent calcium channels (VDCCs). This compound is a hybrid of CGP37157 (mNCX inhibitor) and nimodipine (L-type VDCCs blocker), and its pharmacological evaluation revealed a moderate ability to selectively inhibit both targets.

Clinical impact of residual renal function on patients starting dialysis treatment.

We describe our clinical experience of monitoring residual renal function of patients on regular dialysis treatment as residual renal function can play an important role in the management of patients undergoing regular dialysis. With active residual renal function it is possible to delay the start of haemodialytic programmes. In managing dialysis treatments, it is important to maintain residual renal function by preventing hypotensive events.

Clinical impact of residual function in haemodialysis.

The term residual renal function (RRF) refers to the small renal function activity persisting in patients affected by chronic renal failure in the uraemic phase. It is associated with better clinical features as well as better laboratory values (1). Nevertheless, RRF usually decreases with variable rates over time; in particular peritoneal dialysis is associated with a better preservation of RRF than haemodialysis.