Contribution of TRPV1 Receptor–Expressing Fibers to Spinal Ventral Root After-Discharges and Mechanical Hyperalgesia in a Spared Nerve Injury (SNI) Rat Model

Neuropathic pain induces allodynia and hyperalgesia. In the spared nerve injury (SNI) model, marked mechanical hyperalgesia is manifested as prolongation of the duration of paw withdrawal after pin stimulation. We have previously reported that spinal ventral root discharges (after-discharges) after cessation of noxious mechanical stimulation applied to the corresponding hindpaw were prolonged in anesthetized spinalized rats. Since these after-discharges occurred through transient receptor potential (TRP) V1–positive fibers, these fibers could contribute to mechanical hyperalgesia. Therefore, we examined whether selective deletion of TRPV1-positive fibers by resiniferatoxin, an ultrapotent TRPV1 agonist, would affect the behavioral changes and ventral root discharges in SNI rats. Mechanical allodynia in the von Frey test, mechanical hyperalgesia after pin stimulation, and enhancement of ventral root discharges, but not thermal hyperalgesia in the plantar test, appeared in Wistar rats with SNI. Mechanical hyperalgesia was abolished by treatment with resiniferatoxin, whereas mechanical allodynia was not affected. Moreover, resiniferatoxin eliminated after-discharges completely. These results show that TRPV1-positive fibers do not participate in the mechanical allodynia caused by sensitization of Aβ-fibers, but contribute to the enhancement of after-discharges and mechanical hyperalgesia following SNI. It is suggested that the mechanisms responsible for generating mechanical allodynia differ from those for prolongation of mechanical hyperalgesia.     

Perioperative infliximab application has marginal effects on ischemia–reperfusion injury in experimental small bowel transplantation in rats

Purpose  

Ischemia-reperfusion injury leads to impaired smooth muscle function and inflammatory reactions after intestinal transplantation. In previous studies, infliximab has been shown to effectively protect allogenic intestinal grafts in the early phase after transplantation with resulting improved contractility. This study was designed to reveal protective effects of infliximab on ischemia–reperfusion injury in isogenic transplantation.     

Preheparin serum lipoprotein lipase mass is negatively related to coronary atherosclerosis

In preheparin serum, there exists lipoprotein lipase (LPL) mass with little activity. The clinical significance of this preheparin serum LPL mass (preheparin LPL mass) is unclear. We studied the levels of preheparin LPL mass in patients with coronary atherosclerosis, comparing the results with those in healthy men. We also evaluated the correlation between preheparin LPL mass and the severity of coronary atherosclerosis by comparing with other risk factors such as age, smoking, family history, hypertension, hyperuricemia, diabetes mellitus, total cholesterol, triglyceride, high density lipoprotein-cholesterol and body mass index. The subjects, 70 men presenting with symptoms of coronary artery disease, underwent coronary angiographic examination. Significant narrowness was defined as > or = 75%. Control group comprised 77 men who had annual health checks and showed no abnormal findings. Preheparin LPL mass in the stenosis group was lower than normal coronary group and also than the control group. Multivariate analysis showed that preheparin LPL mass had the highest t-value (-2.53) for the number of lesions among the risk factors listed above. These results suggest that low preheparin LPL mass may be deeply involved in the progression of coronary atherosclerosis.     

Dual mechanism involved in the hydrolysis of polyphosphoinositides in rat pancreatic islets

We investigated insulin secretion and inositol phosphate formation in intact and permeabilized rat pancreatic islets, the objective being to elucidate mechanisms of activation of phospholipase-C in pancreatic islets. The intact islets prelabeled with myo-[3H]inositol were incubated in Krebs-Ringer bicarbonate buffer containing 10 mM LiCl and 1 mM myoinositol. Glucose, alpha-ketoisocaproate (KIC), and sulfated cholecystokinin (CCK8S) increased insulin secretion and formation of [3H]inositol phosphate, [3H]inositol bisphosphate, and [3H] inositol trisphosphate. Mannoheptulose, a glucokinase inhibitor, inhibited glucose-induced insulin secretion and [3H]inositol phosphate formation; however, it did not inhibit KIC- and CCK8S-induced secretion and formation. Both glucose- and KIC-induced insulin secretion and [3H]inositol phosphate formation were blocked by 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation in the mitochondria. The islets prelabeled with myo-[3H]inositol were permeabilized by digitonin and then incubated in intracellular mimicking medium containing 1 microM Ca2+ and 2.5 mM ATP. Glucose had no effect on [3H]inositol phosphate formation in the permeabilized islets, and CCK8S increased the formation of [3H]inositol phosphates. Thus, phospholipase-C in pancreatic islets is activated not only via ligand-receptor interaction in the plasma membrane in the case of hormone stimulation, but also by metabolic product(s) in the case of fuel stimulation.     

Mortality risk attributable to atrial fibrillation in middle-aged and elderly people in the Japanese general population: nineteen-year follow-up in NIPPON DATA80.

BACKGROUND: The extent to which atrial fibrillation (AF) contributes to mortality in the Japanese general population has not been clarified. METHODS AND RESULTS: A randomly sampled general population from all over Japan (4,154 men, 5,329 women; age > or =30 years) was enrolled. Single electrocardiogram recordings were taken in the baseline survey. Stroke death, cardiovascular deaths and all-cause deaths during the subsequent 19 years were analyzed by the presence of AF at baseline. Cox's regression analysis was carried out to estimate the hazard ratios (HRs) of each cause of death attributable to AF after adjusting for other risk factors. Prevalence of AF was 0.64% in the study. The observed person-years were 162,980 among persons without AF and 699 among persons with AF. There were 1,919 deaths. Multivariate adjusted HRs for stroke death, cardiovascular death and all-cause death were 2.69, 2.76 and 1.88, respectively (p<0.05). These HRs were 14.7, 9.63 and 4.00 among persons aged 64 years or younger (p<0.05). CONCLUSION: AF affects stroke mortality, cardiovascular mortality and all-cause mortality in the Japanese general population. Careful attention should be paid to persons with AF in order to prevent future cardiovascular events.