Low distribution of synaptic vesicle protein 2A and synaptotagimin-1 in the cerebral cortex and hippocampus of spontaneously epileptic rats exhibiting both tonic convulsion and absence seizure.

The spontaneously epileptic rat (SER) is a double mutant (zi/zi, tm/tm) which begins to exhibit tonic convulsions and absence seizures after 6 weeks of age, and repetitive tonic seizures over time induce sclerosis-like changes in SER hippocampus with high brain-derived neurotrophic factor (BDNF) expression. Levetiracetam, which binds to synaptic vesicle protein 2A (SV2A), inhibited both tonic convulsions and absence seizures in SERs. We studied SER brains histologically and immunohistochemically after verification by electroencephalography (EEG), as SERs exhibit seizure-related alterations in the cerebral cortex and hippocampus. SERs did not show interictal abnormal spikes and slow waves typical of focal epilepsy or symptomatic generalized epilepsy. The difference in neuronal density of the cerebral cortex was insignificant between SER and Wistar rats, and apoptotic neurons did not appear in SERs. BDNF distributions portrayed higher values in the entorhinal and piriform cortices which would relate with hippocampal sclerosis-like changes. Similar synaptophysin expression in the cerebral cortex and hippocampus was found in both animals. Low and diffuse SV2A distribution portrayed in the cerebral cortex and hippocampus of SERs was significantly less than that of all cerebral lobes and inner molecular layer (IML) of the dentate gyrus (DG) of Wistar rats. The extent of low SV2A expression/distribution in SERs was particularly remarkable in the frontal (51% of control) and entorhinal cortices (47%). Lower synaptotagmin-1 expression (vs Wistar rats) was located in the frontal (31%), piriform (13%) and entorhinal (39%) cortices, and IML of the DG (38%) in SER. Focal low distribution of synaptotagmin-1 accompanying low SV2A expression may contribute to epileptogenesis and seizure propagation in SER.

Changes of ROS during a two-day ultra-marathon race.

To assess oxidative stress (OS) induced by endurance exercise, concentrations of serum reactive oxygen species (ROS) were determined in 70 Japanese male amateur runners completing a two-day ultra-marathon race. Serum ROS levels were analyzed at three time points: before the race (baseline), after the 1st day race (mid-race), and after the 2nd day race (goal) (post-race). The means (SE) of ROS were 151.4(3.7) (U. CARR.), 168.7(4.4), and 156.8(4.4), respectively. Significant positive trends were noted between age and serum ROS concentrations at the three race points (p<0.05 for all). After adjusting for age, BMI and average monthly running distance, the baseline serum ROS concentrations were positively associated with completion times of the first-day race, in particular (p<0.05), suggesting that the concentrations may predict physical performance. The ROS production increased at mid-race (p<0.05), but the levels returned to baseline levels at post-race, indicating that an antioxidant defense system may develop post-race to reduce OS.

Changes of mental stress biomarkers in ultramarathon.

We investigated the possible influence of an exhaustive physical exercise on mental stress biomarkers (serotonin, tryptophan, and beta-endorphin) along with dopamine, noradrenaline and free fatty acids in an ultramarathon race in which 45 km was run on the first day and 90 km on the second. We obtained serum samples at 6 different time points during and after the race from 18 Japanese male runners who completed the marathon. Overall changes of serum serotonin and tryptophan concentrations were statistically significant according to ANOVA for repeated measurements (p < 0.05). Serum serotonin levels elevated rapidly on the first day with the post hoc Tukey's test. Tryptophan concentrations inversely decreased during the race, possibly because of utilization for synthesis of serotonin. Levels of beta-endorphin appeared to increase on the first and second days, but were not statistically significant. In conclusion, serum serotonin, tryptophan and beta-endorphin appeared to be used for mental stress markers in physical exercise.

Changes of urinary 8-hydroxydeoxyguanosine levels during a two-day ultramarathon race period in Japanese non-professional runners.

Using the urinary 8-hydroxydeoxyguanosine (8-OHdG) concentration, effects of participation in a two-day ultramarathon race period on oxidative DNA damage were investigated in Japanese nonprofessional runners. Before the first day (baseline), after the first day (mid-race) of 40-km running, and after the second day (post-race) of 90 km running, biomaterials were successfully sampled from 95 participants (males, 79; females, 16) who completed the full race. We analyzed urine for 8-OHdG and blood for aspartate aminotransferase (AST), creatine phosphokinase (CPK) and myoglobin, and evaluated fluctuation in the values at three sampling time points. Adjusted baseline urinary 8-OHdG levels (microg/g creatinine) (mean +/- standard deviation) showed no significant differences between males and females, at 2.85 +/- 1.17 and 3.04 +/- 1.56, respectively. In males, mid-race urinary 8-OHdG levels rose to 3.29 +/- 1.15 (p < 0.01), but then returned to 2.73 +/- 1.16 at the post-race time point (p < 0.01). In females, a similar increase to 3.32 +/- 1.47 and subsequent decline to 2.80 +/- 1.47 were noted. In contrast, AST, CPK and myoglobin were increased at both mid- and post-time points and particularly the latter, independent of the sex. Extreme prolonged exercise in a two-day ultramarathon race period causes oxidative DNA damage but antioxidant repair systems are apparently induced to protect against oxidative DNA stress with physical exercise.

[Recovery from out-of-hospital cardiac arrest after mild hypothermia: report of two cases].

We report two patients with out-of-hospital cardiac arrest who recovered after hypothermia therapy. A 25-year-old man and a 16-year-old boy were transferred to our hospital after cardiopulmonary arrest due to idiopathic ventricular fibrillation and hypertrophic cardiomyopathy, respectively. We carried out hypothermia therapy using cooling blankets, and the patients were maintained at 32-33 degrees C for 96 and 36 h, respectively. After slow rewarming, they regained consciousness and recovered. During hypothermia, hypokalemia and arrhythmia occurred. Their arrest times (no spontaneous circulation and no CPR) were 10 min and 8 min, and CPR times (no spontaneous circulation while CPR was being performed) were 24 min and 20 min, respectively. In cases where the duration of ischemia is prolonged, the prognosis is expected to be poor. Therefore, we believe that hypothermia therapy is beneficial for such patients.

[Left ventricular blood flow dynamics caused by ventricular premature contraction: pulsed Doppler echocardiographic study].

Cardiac function at the time of ventricular premature contractions (VPC) is influenced by the coupling interval or the site of those origin. Clinical and experimental studies of the effects of VPC on intracardiac pressure dynamics have been performed; however, little is known about left ventricular blood flow dynamics. This study was attempted to determine the characteristics of blood flow dynamics in respect to the site of origin of VPC using pulsed Doppler echocardiography. The subjects consisted of 18 cases with VPC but without apparent organic heart disease. Seven cases had VPCs with a left bundle branch block pattern suggesting possible origin in the right ventricle. The other 11 cases had VPCs with a right bundle branch block pattern indicating the left ventricular origin. With the probe in the apical position, the blood flow patterns of the left ventricular outflow, central and inflow tracts were examined. The results were as follows; 1. Except for one case with shortened coupling interval, all six cases with VPCs originated from the right ventricle showed preservation of left ventricular ejection flow. 2. In two of the three cases with VPC which originated from the left ventricle and with left axis deviation, systolic flow in the left ventricular central area showed "back flow" to the apex. Ejection flow at the outflow tract was markedly diminished or disappeared in all three cases. 3. In all eight cases with VPC which originated from the left ventricle and with right axis deviation, ejection flow was slightly disturbed both in the left ventricular outflow and in the central area. 4. Ejection flow volume assessed by velocity integral indicated similar dynamics as did the ejection flow velocity. 5. In left ventriculography, asynchrony due to dyskinetic motion of the anteroapical wall was observed at the times of VPCs with left axis deviation. In conclusion, the patterns of left ventricular ejection flow dynamics depend on the site of origin of VPCs. This disturbed flow is more apparent in VPCs originating from the left ventricle compared to the right ventricle. This is especially true in cases with left axis deviation, in which VPCs arise from the posterior site of the left ventricle.

A new micromethod for colorimetric determination of zinc in serum.

A simple micromethod with a colorimetric reagent of high sensitivity was developed for the determination of zinc in serum. For the color reagent 2-(2-pyridylazo)-5-dimethylaminophenol (PADAP) was used. Coefficients of variation of the within-day precision were 6.65 and 2.24% for zinc standard at concentrations of 0.1 and 0.5 microgram/ml, respectively. The mean recovery by this method was 101.2% (S.D.: 3.56%). Zinc concentrations measured by the above method showed good agreement with those by atomic absorption spectrophotometry, with a correlation coefficient of 0.934. Serum zinc values of 50 healthy adults (38 females, 12 males) ranged from 63 to 116 microgram/100 ml (mean: 89.68 microgram/100 ml, Sd.: 13.28 microgram/100 ml).