Effects of insulin detemir on balloon catheter injured carotid artery in Zucker fatty rats

ObjectiveWe compared the effect of the long acting basal insulin analog detemir with neutral protamine Hagedorn (NPH) insulin, and normal saline on recovery from vascular injury (balloon catheter mediated) in an animal model of insulin resistance.MethodsFemale Zucker fatty rats were administered NPH/detemir/saline for 7 days following which, they underwent balloon catheter mediated injury of left carotid artery, and were continued on the respective regimen for an additional 21 days when they were sacrificed. We evaluated the injured carotid artery for intimal hyperplasia (Intima/Media ratio) and also, aortic arch protein for markers of oxidative stress and inflammation, in addition to expression and phosphorylation of eNOS using well established methods.ResultsThere was a significant difference in intimal hyperplasia (Intima/Media ratio) between control and detemir treated rats (1.3 ± 0.09, 0.82 ± 0.08; p < 0.001) whereas the IM ratio in NPH treated rats was not significantly different from saline (1.17 ± 0.1). Expression of p-eNOS (ser-1177) in both NPH and insulin detemir (1.3 ± 0.15, 1.11 ± 0.12) was significantly higher than controls (0.56 ± 0.13; p < 0.05). We did not find significant differences in the expression of MnSOD, eNOS and NFκB-p65.ConclusionWe conclude that in insulin resistant states, treatment with Insulin detemir but not NPH is associated with less intimal hyperplasia, although both insulins increased eNOS phosphorylation.     

Autism: The role of cholesterol in treatment

Cholesterol is essential for neuroactive steroid production, growth of myelin membranes, and normal embryonic and fetal development. It also modulates the oxytocin receptor, ligand activity and G-protein coupling of the serotonin-1A receptor. A deficit of cholesterol may perturb these biological mechanisms and thereby contribute to autism spectrum disorders (ASDs), as observed in Smith-Lemli-Opitz syndrome (SLOS) and some subjects with ASDs in the Autism Genetic Resource Exchange (AGRE). A clinical diagnosis of SLOS can be confirmed by laboratory testing with an elevated plasma 7DHC level relative to the cholesterol level and is treatable by dietary cholesterol supplementation. Individuals with SLOS who have such cholesterol treatment display fewer autistic behaviours, infections, and symptoms of irritability and hyperactivity, with improvements in physical growth, sleep and social interactions. Other behaviours shown to improve with cholesterol supplementation include aggressive behaviours, self-injury, temper outbursts and trichotillomania. Cholesterol ought to be considered as a helpful treatment approach while awaiting an improved understanding of cholesterol metabolism and ASD. There is an increasing recognition that this single-gene disorder of abnormal cholesterol synthesis may be a model for understanding genetic causes of autism and the role of cholesterol in ASD.     

Influence of extremely low frequency magnetic fields on Ca2+ signaling and NMDA receptor functions in rat hippocampus

The nervous tissue of many vertebrates, including humans, can synthesize beta-alanyl-L-histidine (carnosine). The biological functions of carnosine are still open to question, although several theories supported by strong experimental data have been proposed. The objective of this study was to examine the effects of carnosine on neurotoxicity in differentiated rat pheochromocytoma (PC12) cells. Neurotoxicity was induced by N-methyl-D-aspartate (NMDA), which caused time- and concentration-dependent cell death as measured by MTT and LDH assays. Pretreatment with carnosine significantly prevented the neurotoxicity in a concentration-dependent manner. The protective effect of carnosine was antagonized by the H1 receptor antagonist pyrilamine, but not by the H2 receptor antagonist cimetidine. In addition, alpha-fluoromethylhistidine, a histidine decarboxylase inhibitor, slightly reversed the protective action of carnosine. These results indicate that carnosine can effectively protect against NMDA-induced necrosis in PC12 cells, and its protection may in part be due to the activation of the postsynaptic histamine H1 receptor. The study suggests that carnosine may be an endogenous protective factor and calls for its further study as a new anti-excitotoxic agent.     

Spigelian hernia: CT and ultrasonography diagnosis

The diagnostic potential of CT and sonography in detecting clinically unrecognized cases of spigelian hernia is illustrated and discussed. These imaging modalities can promptly and reliably diagnose spigelian hernia based on the following findings: (1) peritoneal and muscular defect along the spigelian line in the lower abdomen; (2) intraparietal location of the hernial sac; and (3) hernial sac containing omentum and/or mesentery and loops of bowel. Two recently diagnosed cases are presented together with a short review of the literature.