Dogs exposed for 4 hours to a simulated altitude of 32,000 feet showed hyperglycemia and a sharp rise in serum glutamic oxalacetic transaminase (SGO-T), serum glutamic pyruvic transaminase (SGP-T), serum lactic dehydrogenase (SLD), and serum alkaline phosphatase (SAk-P). Hyperglycemia reached a peak in about 6 hours and subsided within 24 hours. Other elevations reached a peak in 6–24 hours and subsided in 3–7 days. The increases in SGO-T, SGP-T and SLD were diminished by the adrenergic blocking agent phenoxybenzamine (Dibenzyline) and the hyperglycemia by the ganglionic blocking agent chlorisondamine dimethochloride (Ecolid). These findings support the view that high altitude hypoxia causes hyperglycemia by releasing catecholamines from the adrenal medulla and increases certain serum enzyme values by increasing selectively cellular permeability to such enzymes. Pretreatment with epinephrine-in-oil before an exposure greatly increased the serum enzyme rise at 24 hours but diminished the 6-hour rise of SGO-T; this suggests partial inactivation of some serum enzymes by an excess of metabolites associated with hypoxia and/or epinephrine.
Groups of rats, given 2.5 ml/kg CCl4 subcutaneously or 1.5 ml/kg of 50% CCl4 in olive oil perorally developed in 24 hours hepatic centrolobular necrosis and increased serum levels of glutamic oxalacetic and pyruvic transaminases, lactic dehydrogenase and aldolase. These changes were greater after a peroral dose. A whole-body exposure to 550 R 24 hours before CCl4 administration decreased food consumption and augmented the changes in nonfasted rats. A 24-hour fast, begun 16 hours before CCl4 administration, further aggravated changes in both irradiated and nonirradiated groups, and group differences were minor. The effect of irradiation on CCl4 toxicity seems due largely to reduced food consumption on the second day. However, augmentation of tissue and serum enzyme changes occurs even when the irradiation is given 11 days before CCl4 and food consumption has returned to normal. This suggests that occult damage to the liver or residual damage to the intestine or other organs directly or indirectly may contr...
The establishment of the National Center for Toxicological Research (NCTR), Jefferson, AR, to study long term effects of low doses of potentially toxic substances, including carcinogens, resulted in the initiation of chronic experiments requiring histophatologic studies of large numbers of animals. Processing the tissues and recording and analyzing the massive amount of pathologic data from these studies required innovative automated technics. The result was a unique computerized pathology data system of NCTR. The system encompasses the development of training programs for necropsy techincians, histology technicians, and pathology tissue screeners; the use of automated equipment for processing, embedding, sectioning, and staining tissue; the use of prelabeled cassettes, slides, and pathology forms; the use of mark-sensitive forms for the collection of gross and microscopic findings; the use of data collection terminals for animal identification, animal weights, and organ weights; the collection of gross and microscopic data on a Mod Comp III minicomputer; and the storage, analysis, and generation of pathology reports and tables over a data link from an IBM 370-158 computer. Some of the features of this system may be applicable in other toxicology laboratories and medical pathology departments.
Methylal, CH kOCH3 l nown also as formal, C2Y,'OCH3 dimethoxymethane, formaldehyde dimethyl acetal and methylene dimethyl ether, the simplest of the group of acetals, can be prepared very simply by the interaction of formaldehyde and methanol catalyzed by dry hydrogen chloride or even by calcium chloride.It is a clear, thin, mobile liquid, lighter than water, and soluble in water to the extent of one part in three of water.Methylal boils at 42.30 C., melts at -1050 C., has a density of d 2 of 0-8608 and a refractive index of N 1-3589.
C3H/HeN female mice with low murine mammary tumor virus titer (MTV-) were fed diets containing a targeted concentration of 640 ppb diethylstilbestrol [(DES) CAS: 56-53-1; 4,4'-(1,2-diethyl-1,2-ethenediyl)bis-phenol]. Mice were started on DES at 3, 5, 7, or 9 weeks of age. Some continued on the diet throughout the rest of their life-spans, whereas others were killed as soon as they had been fed DES for 2, 4, 6, 8, 10, or 12 weeks. Controls were also examined throughout the study. Among mice killed early, the only observation significantly influenced by age at the start of DES treatment was the presence or absence of corpora lutea (CL). DES did not prevent CL from appearing in mice started on DES at 7 or 9 weeks of age, but it did prevent their appearance in about 25% of the mice started at 5 weeks and in up to 75% of the mice started at 3 weeks of age. In the life-span-exposure groups, CL either disappeared or were never formed in 88% or more of the mice, regardless of age at the start of treatment. Neoplastic or presumptive preneoplastic lesions apparently influenced by DES in the life-span-treatment groups included ovarian tubular adenomas; granulosa cell tumors and luteomas; pituitary cystoid degeneration, hyperplasia, and adenomas; uterine adenocarcinomas and cervical adenosis; mesotheliomas; and mammary hyperplastic alveolar nodules (HANs) and adenocarcinomas. Luteoma and granulosa cell tumor incidences were reduced by DES, regardless of age at the start of treatment. Influence of age at the start of treatment was minimal or not apparent for mesotheliomas, uterine adenocarcinomas, or pituitary adenomas; however, pituitary cystoid degeneration and hyperplasia and cervical adenosis occurred in higher frequency and/or with shorter duration of DES exposure the earlier that treatment was started. A delay in the start of DES treatment was associated with a remarkable delay in HAN and mammary adenocarcinoma development. This was especially apparent in young mice (3-7 wk old) in which a 2-week delay in treatment resulted in a 20-week delay in HAN or tumor onset. Age at the start of treatment was a major factor in susceptibility of C3H/HeN-MTV- female mice to DES-induced mammary tumorigenesis.
