Andreo Larsen

Experimental alcoholic neuropathy in the rat: histological and electrophysiological study on the myoneural junctions and the peripheral nerves.

SummaryPeripheral nerves and myoneural junctions of the tibialis anterior muscle of the rat were studied histologically and electrophysiologically after various periods of peroral ethanol treatment. Histochemical distributions of non-specific cholinesterase (ns. ChE; E.C. 3.1.1.8) and acetylcholinesterase (AChE; E.C. 3.1.1.7) activity of the muscle were normal during the first 3 months of daily ethanol drinking. After 5 months of exposure to 10–25% (v/v) ethanol as the sole drinking fluid, pathological ns. ChE activity was seen sporadically along the intramuscular nerves with slight ultrastructural changes in the Schwann cells. After 7 months of ethanol treatment there was further increased pathological ns. ChE activity in the intramuscular nerves while the AChE activity remained normal in the muscle. More prominent ultrastructural changes were seen in the Schwann cells namely swelling and vacuolization of the cytoplasm and dilatation of the rough endoplasmic reticulum. Increased numbers of small axons were also seen. After 9.5 months on alcohol marked increase in the ns. ChE activity was observed along most of the intramuscular nerves. AChE activity of the myoneural junctions was only sporadically weakened.A slight slow-down in the conduction velocity of the large myelinated size A fibers was observed in the animals on alcohol from 7–9.5 months, whereas the conduction velocity of the smaller myelinated B fibers was not appreciably changed. The present experiment indicates that progressive neuropathy can be induced in rats by oral alcohol feeding along with the normal laboratory diet. The first pathological changes were seen in the Schwann cells and could well be followed by the methods employed. The present experimental model can possibly be used in future studies concerning the development of toxic polyneuropathy.

Clofibrate-induced myopathy in the rat.

SummaryRats were given daily injections of 0.2 or 0.5 g/kg chlorophenoxyisobutyrate (clofibrate) for 9 to 46 days. Lower leg muscles were studied with light and electron microscopy.Daily treatment with 0.5 g/kg of the drug for 26–46 days caused myopathic changes.

Comparison between the effects of pindolol and propranolol on essential tremor

The effects of 120 mg propranolol and 15 mg pindolol daily on positional tremor of 24 patients with benign essential tremor were analyzed with a double-blind crossover trial and electrical tremor recording. Compared with the placebo effect, tremor amplitude was smaller under propranolol and larger under pindolol, whereas the frequency did not change.

Effect of propranolol on essential tremor

The investigators tested the effect of 120 mg propranolol daily on 21 patients with essential tremor using a double-blind cross-over method and electrical recording of tremor amplitude and frequency. The patients varied in age between 15 and 60 years and had a mean tremor frequency of 10 cps. Propranolol had no effect on the tremor frequency but reduced the amplitude in 15 of the patients. Propranolol was most effective in older patients and in those with slow tremor frequencies.

Peripheral neuropathy and myopathy

The effects of variable dietary thiamine concentrations (deficient, normal, surplus) on the development of alcoholic neuromyopathy in rats exposed for 36 weeks to 10–25% (v/v) ethanol or water (control group) as the sole drinking fluid were studied by histological and electrophysiological methods. Abnormalities in the structure of the sciatic nerve (phagocytosis, myelin abnormalities, increase in nonspecific cholinesterase activity) and tibial muscles (angular atrophic fibers, group atrophy, fibre necrosis) developed more frequently in animals on diets deficient in thiamine than in animals on diets with normal or surplus thiamine, and more frequently in animals drinking alcohol and water than in those drinking water alone. No differences were observed between the different groups in the number of perivascular sympathetic nerves, in the motor nerve conduction velocities and in the muscle fibrillation potentials. Thus, thiamine deficiency, established as a significant reduction of red blood cell transketolase activity, seems to have a deleterious effect on the peripheral nerves and muscles. The effect is enhanced by the simultaneous consumption of ethyl alcohol.

Sleep alterations in juvenile neuronal ceroid-lipofuscinosis

In juvenile neuronal ceroid-lipofuscinosis (JNCL), sleep disorders are common. The purpose of this study was to investigate the sleep structure of 28 patients with JNCL compared with healthy controls subjects and to clarify the pathophysiology underlying the sleep disturbances in these patients. Each of 28 patients with JNCL (age range = 6-27 years), with or without sleep complaints, underwent one night of polysomnography. Electroencephalographic, electro-oculographic, electromyographic, and electrocardiographic findings were recorded. Sleep was scored and analyzed visually. The sleep parameters of the patients were compared with those of healthy control subjects. In most of the patients, the total sleep time, sleep efficiency, and percentages of rapid eye movement (REM) and non-REM (NREM) stage 2 sleep were significantly decreased, and the percentages of NREM stage 1 and slow-wave sleep and the number of nocturnal awakenings significantly increased. The percentage of NREM stage 1 and the number of awakenings increased with age and clinical stage. Paroxysmal epileptiform activity during light sleep (NREM stages 1-2) and high-amplitude delta-wave activity with intermingled sharp waves during slow-wave sleep were characteristic of the recordings. The present study revealed that in patients with JNCL, sleep is consistently altered.

Effect of guanidine on quantal release of acetylcholine in the mammalian myoneural junction

The effect of guanidine on acetylcholine release was studied by investigating end-plate potentials and miniature end-plate potentials in the rat diaphragm in vitro. Guanidine hydrochloride (2 × 10−5 g/ml) significantly increased the amount of acetylcholine released from nerve endings by increasing the number of quanta of acetylcholine released by nerve impulse.

Effects of the optical isomers of propranolol on neuromuscular transmission in the rat

Abstract The effects of d- and l-propranolol on neuromuscular transmission were tested using rat phrenic nerve-hemidiaphragm preparations, intracellular microelectrode recording of resting membrane potentials, miniature end plate potentials and end plate potentials, and recording of muscle contractions after nerve stimulation. Both isomers of propranolol had a postsynaptic, curare-like effect, reducing the amplitudes of both miniature end plate potentials and end plate potentials in a dose-dependent manner, without influencing their time courses. Both d- and l-propranolol also had presynaptic effects. They reduced the number of acetylcholine quanta released from the motor nerve endings per nerve impulse and decreased the excitability of motor nerve to electrical stimulation. Neither of the isomers of propranolol had significant effects on the resting membrane potential of the muscle fibers or on the frequency of the spontaneously released miniature end plate potentials.

Myopathy Associated with Chronic Alcohol Drinking

Muscles of the lower legs of rats given 25% ethanol in water ad libitum for up to 9.5 months were studied using histological, histochemical and electrophysiological techniques. Ethyl alcohol was substituted for about 20% of the total calorific input of the animals. The observations were compared with the structure of the gastrocnemius muscle of five alcoholics with clinical neuropathy. Fibrillation potentials and angulated atrophic fibers were observed in the muscles of animals on alcohol for 9.5 months. No fiber type grouping was present. There was also phagocytosis of the muscle fibers and changes in their internal structure, as reflected by the distribution of NADH-diaphorase. The observed muscle changes in the alcoholics and those in the experimental animals on alcohol differed mainly quantitatively, the only exception being the presence of fiber type grouping in the biopsies from the alcoholics.