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Effects of Nitroglycerin and Ethylene Glycol Dinitrate Mixture (Blasting Oil) on Rat Brain, Liver and Kidney
228
MISCELLANEOUS
Acute Toxicity of Prostaglandin Bx in Male, Albino, ICR Mice BURKMAN, Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio
A. M.
point to interaction of hydrolytically released nitrite with hemoproteins. The results are tenable with the proposed denitrification of nitroglycerin and ethylene glycol dinitrate by the glutathione-dependent pathway. W. W. H. 3 tables, 27 references
Res. Comm. Chem. Path. Pharm., 37: 97-104 (July) 1982 Prostaglandin Bx (PGBx) is a complex mixture of oligomers derived from the base catalyzed polymerization of 15 ketoPGBl methyl ester. It has been reported to exert effects on a variety of biological systems, including the 1) phosphorylating ability of age-degraded rat liver mitochondria, 2) short-term survival of monkeys with induced myocardial infarctions, 3) inotropic response of anoxic canine papillary muscle, 4) autonomic cardiopulmonary activity during cerebral anoxia, 5) peripheral vascular response to sympathetic stimulation and 6) body weight and blood glucose levels of diabetic and genetically obese, nondiabetic mice. The concentrations of PGBx that were observed to provide measurable responses in in vivo systems vary over a considerable range, and differences in the routes of administration, dosing regimens and animal subjects make it virtually impossible to determine the true breadth of the dose range over which this material might be pharmacologically active and, more importantly, the concentrations that approach levels that threaten the life of the animal. In an attempt to establish upper dosing limits for PGBx in ICR mice, the acute median lethal doses were established by the intraperitoneal and intravenous routes of administration. The results indicated that the incident of lethality was timedependent for 96 hours. The animals were active and responsive, and they took nourishment during the 4 days after injection so that they apparently died of the direct effects of PG Bx (or its metabolites) and not as a consequence of depressioninduced dehydration or starvation. W W. H. 1 figure, 3 tables, 14 references
Effects of Nitroglycerin and Ethylene Glycol Dinitrate Mixture (Blasting Oil) on Rat Brain, Liver and Kidney A.
ZITTING AND H. SAVOLAINEN, Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland
Res. Comm. Chem. Path. Pharm., 37: 113-121 (July) 1982 Nitroglycerin and ethylene glycol dinitrate are used as a mixture to make dynamite. The compound may be absorbed through the skin and lungs in occupational setting, and cause vasodilatory effects in workers. However, to date there apparently have not been any reports on the biochemical effects of these compounds in the liver, kidney or brain. To study and to document these changes the authors injected rats intraperitoneally with a mixture of nitroglycerin and ethylene glycol dinitrate (1: 3) at a dosage of 150 mg./kg. The results indicate that there was a transient small increase in methemoglobin content in the blood and diminished content of reduced glutathione in the liver and brain. Hepatic cytochrome P-450 concentration and ethoxycoumarin deethylase activity decreased shortly after exposure but later the effect disappeared. Succinate dehydrogenase activity decreased in the liver, kidney and brain. In the brain activity of creatine kinase increased significantly and slight increase in hepatic UDP glucuronosyltransferase and epoxide hydrolase activity was observed. Renal ethoxycoumarin activity increased transiently. The results
Cimetidine and Plasma Levels of Gonadotropins, Prolactin and Gonadal Steroids in Women
F. M. PATRY AND L. TETREAULT, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Sherbrooke and Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Province of Quebec, Canada
S. B:ELISLE,
Canad. Med. Ass. J., 127: 29-32 (July 1) 1982 Cimetidine, a histamine Hrreceptor antagonist, is used widely in the treatment of peptic ulcer disease and related acid peptic disorders. A prospective investigation of endocrine effects of cimetidine throughout the menstrual cycle was done on 7 healthy female volunteers. The women were observed for 6 menstrual cycles divided into pre-treatment phase, a phase with 1.2 gm. cimetidine administered orally daily for 2 cycles and a post-treatment phase. Cimetidine therapy induced a significant increase in plasma follicle-stimulating hormone during the periovulatory period and mild hyperprolactinemia during the luteal phase. There were no significant changes in plasma luteinizing hormone and progesterone. There was a significant decrease in plasma estradiol in the mid proliferative and mid luteal phases of the cycle. After a bolus injection ofthyrotropinreleasing hormone mean plasma prolactin levels in the mid luteal phase during cimetidine administration did not differ from responses in the control phases, suggesting that cimetidine modulates release of prolactin at a suprapituitary locus. The clinical significance of the endocrine changes noted remains to be established. M. G. F. 3 figures, 1 table, 14 references
MISCELLANEOUS Virilizing Tumor of Adrenal Cortex in an Infant A. BAUMAN AND C. G. BAUMAN, Endocrine Section, Depart-
ment of Medicine, Montefiore Hospital and Medical Center, Bronx, Department of Endocrinology and Pediatrics, White Plains Hospital Medical Center, White Plains, and Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York N. Y. State J. Med., 82: 1070-1072 (June) 1982 The authors describe a virilizing tumor in an 11-month-old girl who presented with a rapid onset of virilizing features during a 3-week period. The child had acne, pubic hair, coarse rugated labia and a low pitched voice. She was known to have a high serum testosterone, which did not suppress with high doses of dexamethasone. Ultrasonography showed a 2 cm. mass overlying the left kidney. Removal of the tumor resulted in prompt return of the clinical course to normal. Such tumors remain extremely rare in children and adults. The key point to be made in this case was that the patient had no signs of masculinization at birth and did not develop them until she was 11 months old, unlike what one would see in congenital adrenal hyperplasia. C.L.P. 1 figure, 16 references
MISCELLANEOUS
Acute Toxicity of Prostaglandin Bx in Male, Albino, ICR Mice BURKMAN, Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus, Ohio
A. M.
point to interaction of hydrolytically released nitrite with hemoproteins. The results are tenable with the proposed denitrification of nitroglycerin and ethylene glycol dinitrate by the glutathione-dependent pathway. W. W. H. 3 tables, 27 references
Res. Comm. Chem. Path. Pharm., 37: 97-104 (July) 1982 Prostaglandin Bx (PGBx) is a complex mixture of oligomers derived from the base catalyzed polymerization of 15 ketoPGBl methyl ester. It has been reported to exert effects on a variety of biological systems, including the 1) phosphorylating ability of age-degraded rat liver mitochondria, 2) short-term survival of monkeys with induced myocardial infarctions, 3) inotropic response of anoxic canine papillary muscle, 4) autonomic cardiopulmonary activity during cerebral anoxia, 5) peripheral vascular response to sympathetic stimulation and 6) body weight and blood glucose levels of diabetic and genetically obese, nondiabetic mice. The concentrations of PGBx that were observed to provide measurable responses in in vivo systems vary over a considerable range, and differences in the routes of administration, dosing regimens and animal subjects make it virtually impossible to determine the true breadth of the dose range over which this material might be pharmacologically active and, more importantly, the concentrations that approach levels that threaten the life of the animal. In an attempt to establish upper dosing limits for PGBx in ICR mice, the acute median lethal doses were established by the intraperitoneal and intravenous routes of administration. The results indicated that the incident of lethality was timedependent for 96 hours. The animals were active and responsive, and they took nourishment during the 4 days after injection so that they apparently died of the direct effects of PG Bx (or its metabolites) and not as a consequence of depressioninduced dehydration or starvation. W W. H. 1 figure, 3 tables, 14 references
Effects of Nitroglycerin and Ethylene Glycol Dinitrate Mixture (Blasting Oil) on Rat Brain, Liver and Kidney A.
ZITTING AND H. SAVOLAINEN, Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland
Res. Comm. Chem. Path. Pharm., 37: 113-121 (July) 1982 Nitroglycerin and ethylene glycol dinitrate are used as a mixture to make dynamite. The compound may be absorbed through the skin and lungs in occupational setting, and cause vasodilatory effects in workers. However, to date there apparently have not been any reports on the biochemical effects of these compounds in the liver, kidney or brain. To study and to document these changes the authors injected rats intraperitoneally with a mixture of nitroglycerin and ethylene glycol dinitrate (1: 3) at a dosage of 150 mg./kg. The results indicate that there was a transient small increase in methemoglobin content in the blood and diminished content of reduced glutathione in the liver and brain. Hepatic cytochrome P-450 concentration and ethoxycoumarin deethylase activity decreased shortly after exposure but later the effect disappeared. Succinate dehydrogenase activity decreased in the liver, kidney and brain. In the brain activity of creatine kinase increased significantly and slight increase in hepatic UDP glucuronosyltransferase and epoxide hydrolase activity was observed. Renal ethoxycoumarin activity increased transiently. The results
Cimetidine and Plasma Levels of Gonadotropins, Prolactin and Gonadal Steroids in Women
F. M. PATRY AND L. TETREAULT, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Sherbrooke and Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Province of Quebec, Canada
S. B:ELISLE,
Canad. Med. Ass. J., 127: 29-32 (July 1) 1982 Cimetidine, a histamine Hrreceptor antagonist, is used widely in the treatment of peptic ulcer disease and related acid peptic disorders. A prospective investigation of endocrine effects of cimetidine throughout the menstrual cycle was done on 7 healthy female volunteers. The women were observed for 6 menstrual cycles divided into pre-treatment phase, a phase with 1.2 gm. cimetidine administered orally daily for 2 cycles and a post-treatment phase. Cimetidine therapy induced a significant increase in plasma follicle-stimulating hormone during the periovulatory period and mild hyperprolactinemia during the luteal phase. There were no significant changes in plasma luteinizing hormone and progesterone. There was a significant decrease in plasma estradiol in the mid proliferative and mid luteal phases of the cycle. After a bolus injection ofthyrotropinreleasing hormone mean plasma prolactin levels in the mid luteal phase during cimetidine administration did not differ from responses in the control phases, suggesting that cimetidine modulates release of prolactin at a suprapituitary locus. The clinical significance of the endocrine changes noted remains to be established. M. G. F. 3 figures, 1 table, 14 references
MISCELLANEOUS Virilizing Tumor of Adrenal Cortex in an Infant A. BAUMAN AND C. G. BAUMAN, Endocrine Section, Depart-
ment of Medicine, Montefiore Hospital and Medical Center, Bronx, Department of Endocrinology and Pediatrics, White Plains Hospital Medical Center, White Plains, and Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York N. Y. State J. Med., 82: 1070-1072 (June) 1982 The authors describe a virilizing tumor in an 11-month-old girl who presented with a rapid onset of virilizing features during a 3-week period. The child had acne, pubic hair, coarse rugated labia and a low pitched voice. She was known to have a high serum testosterone, which did not suppress with high doses of dexamethasone. Ultrasonography showed a 2 cm. mass overlying the left kidney. Removal of the tumor resulted in prompt return of the clinical course to normal. Such tumors remain extremely rare in children and adults. The key point to be made in this case was that the patient had no signs of masculinization at birth and did not develop them until she was 11 months old, unlike what one would see in congenital adrenal hyperplasia. C.L.P. 1 figure, 16 references