In order to evaluate the in vitro neurotoxicity of MM fractions obtained by chromatographic analytical methods from plasma of uremic polyneuropathic patients and urine of healthy subjects, we performed an in vitro test on isolated frog sural nerve. The nerve is incubated in various media and stimulated by a rectangular shock (0.05ms, 1Hz, intensity supramaximal). Action potential are recorded. Results were expressed by the inhibition index Ii = 1 divided by t 1/2 x 100 where t 1/2 is the time (in min) necessary to reduce the 1/2 the spike amplitude. When the nerve is immerged in Ringer solution or plasma of healthy subjects Ii congruent to 0. Among MM fractions obtained by gel chromatography Sephadex G-15 from uremic polyneuropathic subjects' plasma and healthy subjects' urine, only fraction b gives a positive response (Ii congruent to 0.86 +/- 0.02, n = 4). From the 6 sub-fractions obtained by anion exchange chromatography DEAE Sephadex A-25 of fraction b, only sub-fraction b4-2 exhibits a reduction of the spike amplitude, Ii = 0.54 when concentration b4-2 is 6 mg/L, Ii = 1.30 when b4-2 plasma concentration is 14 mg/L. These values increase with the severity of neurologic symptoms. A positive correlation was found between Ii and various b4-2 concentrations of standard solutions and plasma ultrafiltrate (y = 0.089x + 0.046, r = 0.890, n = 13). In vitro sural nerve test demonstrated its sensitivity as a tool for monitoring analytical and preparative procedures developed for isolation of neurotoxic solutes.
1. In a double‐blind, crossover, placebo controlled trial, zolpidem 10 mg, a new imidazopyridine hypnotic drug, was administered in a single dose to 10 healthy non‐obese heavy snorers. 2. Nocturnal polysomnography showed that zolpidem increased total sleep time, sleep efficiency and the percentage of stage 2. 3. Respiratory monitoring showed that zolpidem did not modify the percentage of total sleep time spent snoring. The percentages of total sleep time with a SaO2 < 4% of the baseline value and with a SaO2 < 90% and the mean SaO2 were also unchanged with zolpidem. The respiratory disturbance index was modestly increased by zolpidem although in all but one subject it remained < 5 with both treatments. 4. Zolpidem intake did not impair daytime vigilance and performance evaluated the day after.
The present study was performed to document factors playing a role in the age-related increase of serum total cholesterol, triglycerides, and phospholipids in male WISTAR rats. In 59 and 122 week old rats, serum concentrations of all three parameters were significantly higher than those determined in younger rats (15-17 weeks of age). Serum triglycerides and cholesterol concentrations were higher in post absorptive than in fasting state. In mature rats of same age (59 weeks), mean concentrations of cholesterol, triglycerides, and phospholipids were significantly higher in the heavier animals than in the others. A strong correlation could be established between body weight and serum cholesterol or triglycerides of these animals. The composition of diet appears to play a role in serum cholesterol concentration but not in serum triglycerides concentration in old rats (59-65 weeks of age). This effect is demonstrated even if daily caloric intake and daily body weight gain of old rats (40-50 weeks of age) were not significantly different with both diets tested (2900 and 3250 cal/kg). In conclusion old Wistar rats develop increased concentrations of serum lipids parameters.
Purification of b4-2 sub-peak obtained on DEAE Sephadex A25 chromatography gave us the possibility of quantifying the plasma concentration of the neurotoxin present in uraemic patients with active polyneuropathy. From the purified neurotoxin isolated by kieselguhr and cellulose chromatography we calibrated analytic columns for b4-2 analysis. Plasma concentration, measured in 6 uraemic neuropathic patients, is between 13 and 19 mg/litre. In 52 uraemic patients without neuropathy, the plasma concentration is between 3 and 9 mg/litre. In 20 healthy subjects the plasma concentration is less than 1 mg/litre. The weekly neurotoxin removal in uraemic patients without neuropathy, treated by a five hours RP6 session 3 times a week, is of the same order of magnitude as the weekly urinary excretion in healthy subjects. Preliminary results of a tentative identification of this purified product indicate that it is not a polypeptide but an acid-polyol with carbohydrate structure.
Summary— A double‐blind study comparing the effect of zolpidem 10 mg, and placebo, on sleep architecture, nocturnal ventilation, cardiovascular parameters (heart rate, systolic, diastolic and mean blood pressures) was carried out. Ten healthy middle‐aged males took part in the study. No significant differences were found between zolpidem and placebo in relation to sleep architecture. Mean respiratory disturbance index (RDI) and SaO 2 values (mean SaO 2 , time spent with SaO 2 < 90%) were similar under both conditions. The diastolic and mean blood pressure readings taken from REM periods which occurred during the first third of the night were significantly higher with zolpidem. No changes in systolic blood pressure or heart rate were found with zolpidem in comparison to placebo.
