Concurrent parasitic infections in onchocerciasis and the occurrence of adverse reactions after ivermectin treatment.

Ivermectin is a safe, effective, and relatively well-tolerated drug for the treatment of human onchocerciasis. However, due to side effects of the drug, large-scale ivermectin distribution without medical supervision is not recommended. The mechanisms involved in the pathogenesis of ivermectin-induced adverse reactions are not yet known. Since onchocerciasis patients are likely to have concurrent parasitic infections, we investigated whether side effects that occur after ivermectin treatment could be related to the presence of parasite eggs and cysts in stool samples prior to treatment. One hundred twenty-nine onchocerciasis patients were treated with a single dose of ivermectin (150 micrograms/kg) and side effects were graded according to the classification of Greene and others. Stool samples were collected before and three days after treatment. A high percentage (80.5%) of the patients reported adverse effects (57% mild, 14.1% moderate, and 9.4% severe reactions). Most (95.1%) of the patients had one or more concurrent parasitic infections. No relationship could be found between the occurrence and extent of side effects and the severity of concurrent intestinal parasitic infections. However, side effects were significantly correlated with pretreatment microfilarial counts. Ivermectin treatment did not induce significant short-term changes in Trichuris trichiura or Schistosoma mansoni egg counts. However, a significant reduction in Ascaris lumbricoides egg counts and Entamoeba coli cyst loads was observed; a cure rate of 46% for cysts was reached. In contrast, hookworm egg production increased after ivermectin treatment. Further studies are required to verify ivermectin-induced changes in cyst and hookworm loads as well as the significance of these findings.

Changes induced by diazepam in the synaptic vesicle size of rat phrenic nerve terminals.

The effect of diazepam (Valium), administered by i.p. injection on the cross-sectional area of synaptic vesicle profiles of the endplate-rich area of the rate diaphragm was studied by electron microscopy at 15-180 min after treatment. In the dose range of 0.25-10 mg/kg, diazepam induced a significant increase of the size of the synaptic vesicles. This increase was dose-related within a certain margin, dependent on the treatment time, while the effect of each dose increased significantly with the period after treatment. At 2.5-10 mg/kg a maximum seemed to be reached at 90 min.

Glucocorticoid-induced changes in synaptic vesicles of rat phrenic nerve terminals.

The mean cross sectional area of synaptic vesicle profiles of the myoneural junction of rat diaphragm is increased significantly when rats are injected i.p. with single doses of 200 micrograms/kg dexamethasone 1/2 hr to 8 hr previously to a control injection of 0.9% NaCl. A maximum effect is observed at 8 hr after pretreatment with dexamethasone. The treatment of rats with hemicholinium-3 (300 micrograms/kg) induces a significant reduction of the vesicle size. Complete prevention of this decrease in vesicle size is already observed when the animals are pretreated with a single dose of 200 micrograms/kg dexamethasone 1/2 hr before treatment with 300 micrograms/kg hemicholinium-3. Dexamethasone in the same dose causes an optimum increase of the mean cross sectional area when it is given 1 hr before treatment of the animals with hemicholinium-3. It is concluded that glucocorticoids have direct actions in both "normal" motor nerve terminals and in motor nerve terminals with a deficient choline transport system, which may contribute to their proposed beneficial effects in certain cases of muscle weakness.

Effects of corticosteroids on the myoneural junction. A morphometric and electrophysiological study.

The mean size of the synaptic vesicles in the nerve endings of the isolated rat diaphragm was significantly increased after incubation with the glucocorticoids prednisolone (10(-5) mol/l) and dexamethasone (2 X 10(-7) mol/l). The shape of the vesicles was also changed, i.e. they became rounder. Similar increases in the mean size of the diaphragm synaptic vesicles were seen when the rats were injected with prednisolone (i.p., 2 mg/kg) and dexamethasone (i.p., 50 micrograms/kg) 2-4 h previously. The amplitude of the miniature endplate potentials was also significantly increased in diaphragms isolated from rats which had been injected with prednisolone or with dexamethasone. Changes in frequency of the MEPPs were less marked after injection of prednisolone, but a significant increase was seen after injection of dexamethasone. It is concluded that relatively low concentrations of glucocorticoids have direct effects on the motor endplate in rat diaphragm both in vitro and in vivo. We tentatively suggest that presynaptic effects may contribute to the beneficial effect of corticosteroids in deficient neuromuscular transmission, e.g. in myasthenia gravis.