Paradoxical enhancement of spinal-cord-evoked potentials rostral and caudal to the site of progressive cord compression in the cat

STUDY DESIGN: Analysis of the sequential waveform changes of the spinal-cord-evoked potentials (SCEPs) associated with progressive cord compression in the cat. OBJECTIVES: To document the phenomenon of paradoxical enhancement of SCEPs despite conduction abnormalities and to evaluate its possible significance. SETTING: Kochi Medical School, Kochi, Japan. METHODS: SCEPs were recorded simultaneously at four serial intervertebral levels, from T6-7 to T9-10 caudal to, and at three serial levels from T2-3 to T4-5 rostral to the compression site at T5-6 following epidural stimulation at L6 in 14 cats. RESULTS: Caudal to the compression site, the area of negative peak significantly increased toward maximal values of 277+/-36 (mean+/-SE), 151+/-9 and 110+/-4% as compared to the baseline precompression values (100%) at T6-7, T7-8, and T8-9, respectively. Rostral to the compression site, the area of negative peak significantly increased before subsequent deterioration and reached 105+/-2, 106+/-2, and 104+/-2% at T4-5, T3-4, and T2-3, respectively. The onset of negative peak enhancement, recorded either caudal or rostral to the compression site, showed a close temporal correlation (r>0.8, P&<0.001) with that of the prolongation in latency of SCEPs at T2-3. CONCLUSIONS: A progressive focal conduction block induced by compression of the spinal cord can paradoxically enhance the ascending SCEPs both caudally and, though less consistently, rostrally, representing a warning of the impending risk of paraplegia.     

Activation of natural killer cell function in recreational athletes with paraplegia during a wheelchair half-marathon race

OBJECTIVE: To investigate a part of the immune homeostasis in recreational athletes with spinal cord injury (SCI) during and after a wheelchair half-marathon race. DESIGN: Case-control study in an actual race. SETTING: The half-marathon division of an international wheelchair marathon race in Japan. PARTICIPANTS: Seven male wheelchair racers with SCI between T7 and L1. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Changes in the number and function of natural killer (NK) cells and the endocrine effects, including plasma catecholamines and cortisol in blood samples obtained the day before the race, immediately after it, and 1 day after the race. RESULTS: Both the percentage and absolute number of peripheral NK cells did not change significantly throughout the experiment. Mean NK cell cytotoxic activity +/- standard deviation increased significantly, from 45.5%+/-7.5% to 56.1%+/-5.1% (P<.01) immediately after the race and remained increased until the next day. Plasma adrenaline levels were increased (P<.05) immediately after the race and recovered 1 day later; the plasma concentration of cortisol did not change throughout the experiment. CONCLUSIONS: The wheelchair half-marathon race induced activation of NK cell function in recreational athletes with SCI between T7 and L1.     

Improved diabetic syndrome in C57BL/KsJ-db/db mice by oral administration of the Na(+)-glucose cotransporter inhibitor T-1095

1. The therapeutic effects of an orally active inhibitor of Na(+)-glucose cotransporter (SGLT), T-1095 (a derivative of phlorizin; 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl-beta-D-glycopyranoside)) were examined in C57BL/KsJ-db/db (db/db) mice, a genetic animal model of obese type 2 diabetes. 2. The higher renal SGLT activity in db/db mice than normoglycaemic C57BL/KsJ-db/+m (db/+m) mice may support the rationale for using an SGLT inhibitor in the treatment regimen for type 2 diabetes. Both T-1095 and its metabolite, T-1095A, which had approximately 10 times more potency, effectively inhibited renal SGLT activity of these mice in vitro. 3. Single oral administration of T-1095 (10, 30, 100 mg kg(-1), p.o.) to db/db mice caused a dose-dependent reduction in blood glucose levels and a concomitant increase in glucose excretion into urine. In contrast, T-1095 only slightly affected blood glucose levels in db/+m mice. 4. Chronic administration of T-1095 (0.1% w w(-1) pellet chow, for 12 weeks) decreased blood glucose and haemoglobin A(1C) levels, and improved glucose intolerance in db/db mice. The age-related decrease in plasma insulin levels was markedly inhibited and there was a 2.5 fold increase of insulin content in the pancreas of T-1095-treated db/db mice. Food consumption was not changed, while impaired body weight gain was ameliorated by T-1095 treatment. 5. Both the development of albuminuria and the expansion of glomerular mesangial area in db/db mice were significantly suppressed by chronic T-1095 treatment, indicating the prevention of the progression of diabetic nephropathy. 6. These results demonstrate that the SGLT inhibitor T-1095 is able to improve the metabolic abnormalities and inhibit the development of diabetic complications in db/db mice. Thus, T-1095 can be used for therapy of type 2 diabetic patients.     

Rewarming eliminates the protective effect of cooling against delayed neuronal death

Mild intra-ischemic hypothermia provides neuroprotection against delayed neuronal death in the hippocampal CA1. It has recently been reported that reduction in the metabolic rate of arachidonic acid (AA) liberated during ischemia might contribute to this neuroprotection. To examine whether rewarming during the early period of recirculation accelerates AA consumption and eliminates the neuroprotection, we measured the levels of AA in the hippocampus after various recirculation times under normothermia and hypothermia with or without rewarming. The tendency for AA to disappear was significantly different between each pair of groups. Histological examination 7 days after ischemia revealed no protection in the rewarmed group. These results suggest that neuronal injury during rewarming after hypothermia may be attributed to the rate of AA metabolism.     

Amiloride-sensitive pressure-induced myogenic contraction in rat cerebral artery

The inhibitory action of amiloride on the pressure-induced contraction was assessed in isolated rat cerebral artery. The artery was mounted in an arteriograph, and the change in intracellular Ca2+ concentration ([Ca2+]i) and vessel diameter were simultaneously measured. The contractile response elicited by intraluminal pressurization was independent of endothelium, i.e. myogenic in nature, and abolished by nicardipine, a Ca2+ antagonist or by removal of extracellular Ca2+, and was potentiated by 25 mM KCl. Cyclopiazonic acid and thapsigargin, inhibitors of the Ca2+-ATPase pump of the sarcoplasmic reticulum, and a protein kinase C inhibitor calphostin C did not suppress the pressure-induced contraction. Amiloride, a putative stretch-activated cation channel blocker, attenuated with an IC50 (50% inhibitory concentration) of about 3 microM the increase in [Ca2+]i and contractile activity in response to pressure, whereas the drug showed no apparent effect on the contraction produced by high KCl or 9,11-dideoxy-11alpha,9alpha-epoxymethano prostaglandin F2alpha (U46619). Furthermore, amiloride (100 microM) did not significantly affect intracellular pH in the artery. In spite of its multiple pharmacological actions, it seems possible that amiloride is a useful alternative tool at the cellular or tissue level to study the mechanotransduction mechanisms involved in the pressure-induced contraction in rat cerebral artery.     

Manganese superoxide dismutase negatively regulates the induction of apoptosis by 5-fluorouracil, peplomycin and gamma-rays in squamous cell carcinoma cells.

We investigated the relationship between manganese superoxide dismutase (Mn-SOD) activity and apoptosis induced by anticancer drugs and radiation. Although the activity of copper, zinc-SOD did not differ greatly among 9 squamous cell carcinoma (SCC) cell lines (OSC-1 to OSC-9), the Mn-SOD activity did differ among the cell lines. The Mn-SOD activity was increased by treatments with 5-fluorouracil (5-FU), peplomycin and 137Cs, reaching plateau levels at 12 h after treatment and then decreasing gradually. When OSC-1 and OSC-3, and OSC-2 and OSC-4 were examined as representative cell lines with low and high Mn-SOD activity, respectively, the decrease was more prominent in OSC-1 and OSC-3 than in OSC-2 and OSC-4. The intracellular levels of superoxide and hydrogen peroxide (H2O2) were increased after treatment with the anticancer agents, and the increases were larger in OSC-1 and OSC-3 than in OSC-2 and OSC-4. The decrease of mitochondrial membrane potential (deltapsi(m)) by the anticancer agents was marked in OSC-1 and OSC-3. Correspondingly, the release of cytochrome c, the activation of caspase-3 and the cleavage of poly(ADP-ribose)polymerase were stronger in OSC-3 than in OSC-4. In addition, apoptosis induced by the anticancer agents was prominent in OSC-3, exhibiting a close relationship with the deltapsi(m) and the H2O2 level. These results indicate that Mn-SOD in SCC cells modulates apoptosis induction and the inactivation of Mn-SOD might be a promising strategy for SCC treatment.     

Pathophysiological roles of galanin-like peptide in the hypothalamus and posterior pituitary gland

The hypothalamo–neurohypophyseal system is known to be involved in the regulation of body fluid balance, reproduction and stress response. Galanin-like peptide (GALP) is a 60-amino acid peptide, which has been isolated and cloned from porcine hypothalamus. GALP is abundantly expressed in the arcuate nucleus (Arc) neurons of the hypothalamus and the pituicytes of the posterior pituitary gland (PP). Intracerebroventricular administration of GALP causes significant increases of neurohypophyseal hormones (arginine vasopressin and oxytocin) and ACTH in rat plasma. GALP-containing neurons in the Arc are activated by foot shock stress. The expression of the GALP gene in the Arc is up-regulated by acute inflammatory stress but not chronic stress. On the other hand, the expression of the GALP gene in the pituicytes of the PP is up-regulated by both acute and chronic stress such as nociception, inflammation and osmotic challenge. These results suggest that GALP in the hypothalamus and PP has different pathophysiological roles in the regulation of stress responses involving the hypothalamo–neurohypophyseal system.     

Involvement of orexins/hypocretins in multiple physiological functions]

Orexins (orexin-A and orexin-B)/hipocretins (hypocretin-1 and hypocretin-2) are novel neuropetides discovered in 1998. Orexin-producing neurons are exclusively distributed in the lateral hypothalamic area (LHA), the posterior hypothalamic area and the perifornical nucleus in rats. The LHA is known to be a feeding center in the hypothalamus. Central administration of orexins stimulated feeding in rats and mice. Therefore, orexins are recognized as potent orexigenic peptides. In a positional cloning study, genetically narcoleptic dogs had a deletion of the orexin receptor 2 gene, resulting in a truncated, nonfunctional receptor. Orexin knockout mice were found to exhibit narcoleptic behavior. In human narcoleptic patients, hypocretin-1 in cerebrospinal fluid was undetectable in almost all patients with narcolepsy. Although the physiological role of feeding seems to be independent of sleep, it is very interesting that orexins may be common bioactive substances that are involved in regulating feeding and sleep. The discovery of orexins may contribute to clarify the pathogenesis of disorders in feeding and sleep and to develop drugs for those disorders.     

A parallel robot to assist vitreoretinal surgery

Purpose  

This paper describes the development and evaluation of a parallel prototype robot for vitreoretinal surgery where physiological hand tremor limits performance.