Correlations of pseudouridine in 8-hour and 24-hour urinary samples determined by high-performance liquid chromatography

Summary The correlations of Pseudouridine () values in 8 h and 24 h urinary samples from 23 healthy persons were determined. Pseudouridine in the 8 h urinary samples was measured by high-performance liquid chromatography and the 24 h excretion was calculated from the results of three 8 h determinations. Simultaneous determinations of urinary creatinine were performed by Jaffe's reaction. Based on the 8 h values of urinary Pseudouridine the results demonstrated a constant excretion of Pseudouridine in the 24 h periods, if the values were related to the urinary creatinine. The precision in using this ratio as an indicator for normal 24 h excretion of Pseudouridine was 90.5% for males and 92.5% for females.     

Post-operative pain and inflammatory reaction reduced by injection of a corticosteroid

Summary In a controlled crossover study, identical surgical procedures, the prophylactic removal of bilateral non-erupted 3rd molar teeth, were performed on two separate occasions in 24 healthy patients. Prior to each procedure, either betamethasone 9 mg (Celeston Chronodose^®) or placebo was administered intramuscularly, in a randomized fashion. Objective and subjective assessments were recorded for paired comparison of the post-operative course, including swelling, pain, trismus, local temperature, bleeding, wound-healing and preference for treatment. In 23 patients, less swelling occurred when betamethasone was given pre-operatively. The mean reduction on the 3rd and 6th post-operative days was 55% (p<0.001) and 69% (p<0.001), respectively. Pain assessments (visual analogue scale) were significantly lower after the corticosteroid injection; mean response: 1st evening 17 vs 56 mm, 2nd evening 5 vs 37 mm, and 3rd evening 2 vs 13 mm. No significant correlation between the steroid-induced reduction in swelling and pain could be made. This may indicate that dissociation may exist between pain and other inflammatory events like swelling. No clinically apparent infection or other disturbance of wound-healing was noted after corticosteroid administration. This treatment course was preferred by 23 of the 24 patients.     

Tryptophan tolerance and metabolism in endogenous depression

The concentration of free and total tryptophan and kynurenine in plasma from 49 female depressives and 26 female controls was measured following oral loading with l-tryptophan, 100 mg/kg body weight. There was no significant difference between five depressives and six controls in the area under curve for free or total tryptophan or kynurenine in plasma. The peak concentration of kynurenine occured 4 h after loading and it correlated significantly with the area under curve for kynurenine. There was no significant correlation between the l-tryptophan dose (g) and the plasma concentration of kynurenine at 4 h in the 49 depressives or 26 controls. The mean plasma levels of tryptophan and kynurenine at 4 h in the depressives were not significantly different from control levels. There was no clear relationship between the plasma levels of tryptophan or kynurenine at 4 h and the therapeutic response in 13 depressives treated with l-tryptophan for 14 days.It is concluded that the absorption, the plasma clearance, and the degradation to kynurenine of loading doses of l-tryptophan are normal in depressed patients. Results further-more suggest that the plasma levels of tryptophan and kynurenine at 4 h are poor predictors of the response to l-tryptophan treatment in depressives.     

Permeability of single muscle capillaries to potassium ions

A frog muscle preparation suitable for capillary micropuncture is described. The K⁺ permeability of single muscle capillaries was measured using the methods developed for frog mesenteric capillaries (C. Crone, J. Frøkjaer-Jensen, J. J. Friedman, and O. Christensen (1978), J. Gen. Physiol.71, 195–220). The K⁺ permeability of arterial capillaries was 8.6 × 10^?5 cm/sec (SD = 1.8; n = 7). The initial K⁺ permeability of venous capillaries was 13.1 × 10^?5 cm/sec (SD = 4.3; n = 6). In venous capillaries—unlike in arterial capillaries—a gradual increase in permeability associated with endothelial gap formation was observed in repeated measurements on the same capillary segment. This inflammatory response to exposure, micromanipulation, or perfusion could be partially blocked by pretreatment with promethazine. The study shows that frog muscle capillaries differ markedly from frog mesenteric capillaries, being 5–10 times less permeable to potassium ions although both belong to the category of continuous capillaries. The results demonstrate that whole-organ and single-capillary techniques for studying muscle capillary permeability yield values which comply within a factor of about 2.     

Motor nerve conduction velocity in asymptomatic lead workers

Summary No difference was found between the nerve conduction velocities of the ulnar nerve of 32 lead exposed workers in the mill of a lead-zinc mine, compared to that of a control group of 14 persons. The lead exposure period was 2–37 months (mean: 12.9 months).The blood lead of the exposed group was as an average (± SD): 53 ± 16 g per 100 ml compared to 11 ± 4 g per 100 ml for the control group.Further studies are needed to establish a possible dose-time-response relationship for the possible, subclinical neuropathy found by some investigators.     

Pharmacokinetics of a single oral dose of muzolimine in cardiac failure

Summary The pharmacokinetics of a new high ceiling diuretic, muzolimine (Bay g 2821), were investigated after a single oral dose of 40 mg in 7 patients with cardiac failure (Stages I–IV, New York Heart Association classification), and in 2 healthy subjects. Plasma concentrations peaked 1–3 h after administration and declined according to a two-compartment model. The -phase (distribution phase) lasted until 12–16 h after administration and the mean t_1/2 was 3.6 h (range 2.3–4.7) in patients, and 2.6 h (range 2.3–2.9) in healthy subjects. The mean t_1/2 was 13.5 h (range 7.4–22.4) in the patients and 14.0 h (range 12.4–14.6) in healthy subjects. T_1/2 was not correlated with the degree of heart failure or with the area beneath the plasma concentration curve, which varied three-fold. The renal clearance of muzolimine was in the range 2.7–15.3 ml · min^–1 in 5 subjects in whom it was investigated. The pharmacokinetics of muzolimine appear not to be significantly altered by cardiac failure. The prolonged half-lives of the drug are probably responsible for the longer duration of diuretic action reported for muzolimine than for furosemide and bumetamide.     

Behavioral effects of low,acute doses of d-amphetamine on the dyadic interaction between mother and infant vervet monkeys (Cercopithecus aethiops) during the first six postnatal months

Doses of d-amphetamine sulfate (0.1, 0.15, and 0.2 mg/kg body weight) were given to adult monkeys in mother—infant pairs. The fundamental parental care behavior pattern was disrupted and the mother became isolated in a socially withdrawn phase. She did not respond to the calling signals of the infant and showed behavior in which stereotyped self-grooming and/or staring into space were predominant. The reactions of the infant to this amphetamine-induced behavior were different in the two experimental pairs. In group 1 the infant increased its approach—avoidance movements. In group 2 the infant sat very quietly and close in front of the mother. The mother from group 1 reacted to the increased approaches from its ininfant with active rejection. In both groups the mothers did not react with the typical ventral—ventral grasping to either the infants sitting close or to the social anxiety signals of the infants. In spite of differences in behavior changes induced by amphetamine, the main conclusion is that the mothers totally lost their normal and highly biologic significant interest in their infants.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

Effect of short-term hyperventilation on cerebral blood flow autoregulation in patients with acute bacterial meningitis

BACKGROUND AND PURPOSE: Cerebral blood flow (CBF) autoregulation is impaired in patients with acute bacterial meningitis: this may be caused by cerebral arteriolar dilatation. We tested the hypothesis that CBF autoregulation is recovered by acute mechanical hyperventilation in 9 adult patients with acute bacterial meningitis. METHODS: Norepinephrine was infused to increase mean arterial pressure (MAP) 30 mm Hg from baseline. Relative changes in CBF were concomitantly recorded by transcranial Doppler ultrasonography of the middle cerebral artery, measuring mean flow velocity (V(mean)), and by measurement of arterial to jugular oxygen content difference (a-v DO(2)). The slope of the regression line between MAP and V(mean) was calculated. Measurements were performed during normoventilation and repeated after 30 minutes of mechanical hyperventilation. RESULTS: At normoventilation (median PaCO(2) 4.4 kPa, range 3.5 to 4.9), MAP was increased from 68 mm Hg (60 to 101) to 109 mm Hg (95 to 126). V(mean) increased with MAP from 48 cm/s (30 to 61) to 65 cm/s(33 to 86) (P<0.01), and a-v DO(2) decreased from 2.2 mmol/L (1.0 to 2.7) to 1.4 mmol/L (0.8 to 1.8) (P<0.05). During hyperventilation (PaCO(2) 3.5 kPa, range 3.3 to 4.1), MAP was increased from 76 mm Hg (58 to 92) to 109 mm Hg (95 to 121). V(mean) increased from 45 cm/s (29 to 55) to 53 cm/s (33 to 78) (P<0.01), and a-v DO(2) decreased from 2.5 mmol/L (1.8 to 3.0) to 1.8 mmol/L (1.2 to 2.4) (P<0.05). Four patients recovered autoregulation completely during hyperventilation. The slope of the autoregulation curve decreased during hyperventilation compared with normoventilation (P<0.05). CONCLUSIONS: CBF autoregulation is partially recovered during short-term mechanical hyperventilation in patients with acute bacterial meningitis, indicating that cerebral arteriolar dilation in part accounts for the regulatory impairment of CBF in these patients.