Comparison of neurotoxicity induced by some glutathione depletors in mouse cortical cell cultures

We examined the neurotoxic effects of 3 glutathione (GSH) depletors, buthionine sulfoximine (BSO), diethyl maleate (DEM) and phorone, under the presence of trolox, cycloheximide (CHX), pyrrolidine dithiocarbamate (PDTC) or MK-801 in primary mouse cortical cell cultures. All three depletors induced neuronal death in dose and exposure time dependent manner, and decreased total cellular GSH contents. The patterns of the neuronal death and the GSH decrements were dependent on the individual agents. DEM (200 micrometer) induced rapid and irreversible decrement of the GSH. BSO (1 mM) also decreased the GSH irreversibly but the rate of decrement was more progressive than that of DEM. Phorone (1 mM) reduced the GSH content to 40% by 4 hr exposure, that is comparable to the decrement of BSO, but the GSH recovered and reached over the control value by 36 hr exposure. BSO showed a minimal neurotoxicity (0-10%) at the end of 24 hr exposure, but marked neuronal cell death at the end of 48 hr exposure. The BSO (1 mM)-induced neurotoxicity was markedly inhibited by trolox or CHX and partially attenuated by MK-801. DEM induced dose-dependent cytotoxicity at the end of 24 hr exposure. Over the doses of 400 micrometer, glial toxicity also appeared. DEM (200 micrometer)-induced neurotoxicity was markedly inhibited by trolox or PDTC. Phorone (1 mM) induced moderate neurotoxicity (40%) at the end of 48 hr exposure. Only CHX showed significant inhibitory effect on the phorone-induced neurotoxicity. These results suggest that the GSH depletors induce neuronal injury via different mechanisms and that GSH depletors should be carefully employed in the researches of neuronal oxidative injuries.

AV Conduction Disturbances Associated with Acute Myocardial Infarction

To evaluate the incidence and clinical course of AV conduction disturbances associated with acute myocardial infarction(MI) and coronary angiographic characteristics in acute inferior MI with AV blocks. We reviewed the medical records and serial ECG's in 89 patients with acute MI treated in CCU of Chonnam National University Hospital from january, 1987 through August, 1990. The subjects were 44 anterior MI's, 43 inferior MI's, and 2 anterior and inferior MI's. AV conduction disturbances were observed in 25.8% of all the patients with acute MI's, 48.8% of 43 inferior MI's and 4.5% of 44 anterior MI's. High degree AV block was observed in 20.0% of all the subjects, 39.3% of inferior MI patients, and none of anterior MI patients. The most severe AV blocks observed in each patients were 7(30.4%) first-degree, 5(21.7%) second-degree, and 11(47.8%) third-degree AV block. The initial AV conduction disturbances developed within 6 hours after onset of symptoms in 9(47.4%) and after 24-hours in 9(47.4%). Seven(30.4%) of 23 patients with AV block showed a transient progression in the degree of AV block, 5(29.4%) of 17 patients with first-or second-degree AV block progressed to third-degree AV block thereby constituting 45.5% of 11 third-degree AV blocks. Nine patients with early AV block less tended to progress in the degree of AV block than the patients with late AV block (1/9 vs 4.9). In early AV block the duration of high-degree AV block was shorter than late AV block(2.5 days vs 6.1 days). The duration of third-degree AV block was less than 2-hurs in 36.4~24 hours in 27.3%, and more than 24 hours in 36.4%. All third-degree AV blocks(90.9%) but one with the longest duration of 13 days returned to 1 : 1 AV conduction within 7 days. There was no significant difference in coronary angiographic findings including the incidence of stenotic lesion in proximal LAD and first septal perforator, number of involved vessel(s), and severity of RCA lesion between the patients with AV block and the patients without AV block in inferior MI.

A Clinical Study on the Hypotensive Effect of Lisinopril

In order to evaluate the hypotensive effect of the lisinopril, a long acting angiotensin converting enzyme inhibitor, 10 to 30mg of lisinopril were administered in 35 hypertensive Korean adults during six weeks after a week observation for washout with stepwise increments of the dose according to the response of the patients blood pressure in every two weeks. The results were ; 1) The supine blood pressures were decreased from 163.7+/-16.6/99.8+/-9.3mmHg to 140.7+/-15.5/87.4+/-9.9mmHg at the end of six weeks' drug therapy(p<0.001). The standing blood pressures were also decreased conferrably and to the some lower levels. 2) In 14 patients to whom the drug was administered longer period(12 to 28 weeks) the blood pressure lowering effects were maintained at the level of that of 6th week. 3) Hematologic examination and blood chemistry revealed no discernible abnormal findings before and after the treatment. 4) In those patients who showed no adequate blood pressure control with other classes of antihypertensive drugs the lisinopril was effective in lowering their blood pressures by adding small doses. 5) During the period of the study a few probably drug-related symptoms developed but not troublesome except dry cough and dry mouth shich forced to stop administering the drug after completion of six weeks' period in one patients. From above results we concluded that lisnopril is effective and safe for the treatment of hypertension in Korean adults.