An antinociceptive profile of kojic amine: an analogue of gamma-aminobutyric acid (GABA)

Kojic amine [2-(aminomethyl)-5-hydroxy-4H-pyran-4-one], an analogue of gamma-aminobutyric acid (GABA), produced dose-related, but short-lived, antinociceptive activity in the 48 degrees C [ED50 = 9.2 (8.2-10.3) mg/kg i.p.] and 55 degrees C [ED50 = 13.8 (12.2-15.7) mg/kg i.p.] hot-plate tests in the mouse. The antinociceptive activity of kojic amine at 48 degrees C was found to be insensitive to bicuculline (1.0 mg/kg i.p.) and picrotoxin (0.5 mg/kg i.p.). At this temperature, antinociception was distinctly separate from the impairment of motor function (measured by a rotorod assay) and was not significantly affected by prior treatment with the cholinergic antagonist, atropine sulfate (10.0 mg/kg i.p.). However, at 55 degrees C, the antinociceptive effect of a large dose (20 mg/kg i.p.) of kojic amine was significantly attenuated by similar pretreatment with atropine sulfate, but not by the peripheral cholinergic antagonist, atropine methylnitrate (10.0 mg/kg i.p.). Kojic amine exhibited no significant interaction with haloperidol (0.5 mg/kg i.p.) at this temperature. In animals made tolerant to morphine, THIP or baclofen, there was analgesic cross-tolerance between kojic amine, morphine and baclofen but not between kojic amine and THIP. It is suggested that kojic amine-induced antinociception is similar to that produced by both THIP and baclofen. Thus, kojic amine represents a unique tool with which to study GABA-ergic antinociceptive processes.     

Computed tomography of the brain in the Smith-Lemli-Opitz syndrome

Computed tomographic (CT) scans of the brain in a child with Smith-Lemli-Opitz syndrome revealed enlargement of the ventricular system, hypoplasia of the cerebellum, and abnormal thickening of the gray matter, consistent with pachygyria. These findings have been previously noted in autopsies performed on patients with this disorder. We conclude that CT scanning is a valuable tool in the evaluation of children suspected of having the Smith-Lemli-Opitz syndrome.     

Cerebral venous thrombosis as a cause of neonatal seizures

Intracranial venous thrombosis has been described in newborns, but there have been no reports of intractable neonatal seizures due to this condition. We report cortical venous sinus thrombosis in two term neonates who presented with seizures in the first 24 hours of life. The diagnosis was made by cranial computed tomography and was confirmed by cerebral angiography. Both patients improved clinically after the intracranial venous thrombosis resolved. These patients demonstrate that intracranial venous thrombosis should be considered in the differential diagnosis of neonatal seizures.     

Biomechanical comparison of stimulated and nonstimulated skeletal muscle pulled to failure

We compared the biomechanical properties of passive and stimulated muscle rapidly lengthened to failure in an experimental animal model. The mechanical parameters compared were force to tear, change in length to tear, site of failure, and energy absorbed by the muscle-tendon unit before failure. Paired comparisons were made between 1) muscles stimulated at 64 Hz (tetanic stimulation) and passive (no stimulation) muscles, 2) muscles stimulated at 16 Hz (wave-summated stimulation) and passive muscles, and 3) muscles stimulated at 64 Hz and at 16 Hz. Both tetanically stimulated and wave-summation contracted muscles required a greater force to tear (at 64 Hz, 12.86 N more, P less than 0.0004; and at 16 Hz, 17.79 N more, P less than 0.003) than their nonstimulated controls, while there was no statistical difference in failure force between muscles stimulated at 16 Hz and 64 Hz. The energy absorbed was statistically greater for the stimulated muscles than for the passive muscles in Groups 1 and 2 (at 64 Hz, 100% more, P less than 0.0003; and 16 Hz, 88% more, P less than 0.0002). In Group 3, the tetanically contracted muscle-tendon units absorbed 18% more energy than the wave-summated stimulated muscles (P less than 0.01). All muscles tore at the distal musculotendinous junction, and there was no difference in the length increase at tear between muscles in each group. These findings may lead to enhanced understanding of the mechanism and physiology of muscle strain injuries.     

Obesity and beta-blockers: influence of body fat on their kinetics and cardiovascular effects

Beta-blockers are among the most widely used antihypertensive drugs. They differ from each other in regard to several factors such as: beta-agonist activity, beta 1-selectivity and solubility. Aim of this work was to evaluate the influence of obesity on the kinetics and the antihypertensive effect of two Beta-blockers with different solubility such as: the water-soluble, atenolol and the liposoluble, metoprolol. The study was carried out according to an open randomized cross-over design. Eight obese hypertensive patients, after a two week washout period, were randomly allocated to a four week treatment. After a two week intermediate washout period, each patient switched to the other treatment for an additional four week period. On the first and the last day of each treatment the subjects were hospitalized to collect blood samples for the assay of the two drugs and to measure cardiovascular parameters. Obesity does not exert any effect on the kinetics of the water-soluble beta-blocker, atenolol, while markedly interferes with that of the liposoluble, without any apparent influence on its anti-hypertensive effect. These findings extend to obese hypertensives the concept that the plasma concentrations of beta-blocking agents are not reliable predictors of their therapeutic effect.     

Leading etiologic factors in periventricular bleeding and periventricular leukomalacia

Prenatal, intrapartum and postnatal factors were investigated in less than 32 gestational age preterm infants known to have periventricular haemorrhage or periventricular leukomalacia. The diagnoses were established on cranial ultrasonography and/or autopsy. Factors associated with periventricular haemorrhage were: postnatal severe hypercapnia, acidosis and hypoxia. In the periventricular leukomalacia group the incidence of antepartum and intrapartum hypoxia and/or ischaemia (antepartum haemorrhage) were significantly higher than in the control group.