Search PubMed⌕ Search

Biomedical subjects

J M Sanders

Publications and source records attributed to J M Sanders.

66 records · Page 4Linked to original sources
PubMed1980

Health needs of adolescents in the military services.

The decade of the 1970's has seen the integration of educational concepts concerning adolescent medicine into pediatric residency training programs within the military medical centers. A nucleus of professionals with this specialized training has been developed, and is currently providing health care to eligible adolescents residing in close proximity to these medical centers. The goal of the next decade is to expand these services and make them available to all dependents of active duty and retired military personnel around the world. Perhaps then, with continued growth and development, attention could be directed toward further expansion of these services to include the young active duty military personnel.

Adolescent↗
PubMed1976

Antimalarials. 11. 2-Vinylogs of substituted 2-aryl-4-quinoline amino alcohols.

3-(P-Chlorobenzylidene)-5, 7-dimethyl-2, 3-dihydro-1H-cyclopenta[b]quinoline-9-(di-n-butylaminomethyl)methanol and 2-[beta-(p-chlorostyryl)]-6, 8-dimethylquinoline-4-(di-n-butylaminomethyl)methanol were synthesized from 6, -8-dimethyl-4-hydroxycarbostyril by 3, 3-dichlorination, dimethoxylation th the 3-ketal, basic hydrolysis to the glyoxal acetal, Pfitzinger condensation with cylopentanone or acetone to the 2, 3-trimethylene or 2-methylquinoline, condensation with p-ClPhCHO at the 2-methylene or 2-methyl group, hydrolysis to the 4-quinaldehyde, methylenation to the epoxide, and condensation with Bu2NH. Both were curative against P. berghei in mice. The first was the more effective: active at 10 mg/kg, completely curative at 40 mg/kg, and only mildly phototoxic in animals.

Animals↗
PubMedDate not supplied

Arterial injury increases expression of inflammatory adhesion molecules in the carotid arteries of apolipoprotein-E-deficient mice.

Recent studies demonstrate increased cellular adhesion molecule expression by neointimal endothelium overlying primary and restenotic atherosclerotic plaque. In this study, we developed an atherosclerotic mouse model of arterial injury and characterized adhesion molecule expression after injury. Sixteen apolipoprotein-E-(ApoE)-deficient mice fed a Western-type diet for 4 weeks underwent carotid artery wire denudation at week 2. For each segment, the extent of neointima formation and medial thickening, or adhesion molecule expression, were scored separately on a scale from 0 (no plaque/thickening or expression) to 3 (extensive plaque/thickening or expression) using Movat staining (n = 3) or immunohistochemical analysis (n = 13). Histology revealed significant medial thickening (1.8 +/- 0.9 vs. 0.3 +/- 0.5, p < 0. 001) versus controls and pronounced staining for monocytes/macrophages in the wall of injured vessels. Immunohistochemical analysis showed more robust expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the luminal surface of injured arteries versus controls (2.2 +/- 0.6 vs. 1.4 +/- 0.7, p < 0.01, and 2.5 +/- 0.5 vs. 1.2 +/- 0.6, p < 0.001, respectively). Injury increased adventitial ICAM-1 expression (2.6 +/- 0.5 vs. 1.6 +/- 0.5, p < 0.002) and medial VCAM-1 expression (2.2 +/- 0.6 vs. 1.2 +/- 0. 7, p < 0.004). Thus, carotid injury results in significant medial thickening and increases adhesion molecule expression beyond that induced in ApoE-deficient mice fed a Western diet alone. The observation of macrophage infiltration into the media at sites of increased ICAM-1 and VCAM-1 expression suggests that these molecules may mediate monocyte/macrophage trafficking into the wall of injured arteries.

Animals↗
PubMedDate not supplied

Brain distribution and fate of tris(2-chloroethyl) phosphate in Fischer 344 rats.

Tris(2-chloroethyl) phosphate (TRCP) is a flame retardant that has a wide variety of industrial applications. In subchronic studies, oral administration of TRCP to rats and mice has been reported to produce dose-, sex-, and species-dependent lesions in the hippocampal brain region. The present investigation has examined the metabolism, elimination, and regional brain distribution of [14C]TRCP in male and female rats. [14C]TRCP was administered by gavage (0, 175, 350, or 700 mg/kg) and urine, feces, exhaled volatiles, CO2, and selected tissues were collected. Regional brain distribution of 14C was determined 2 hr following single doses of TRCP to male and female rats, and 24 hr after a single dose and the last of 14 daily doses of TRCP to female rats. Results of these studies indicate that TRCP is readily absorbed from the gastrointestinal tract, distributed to all brain regions, and that metabolism and excretion are nearly complete in 72 hr. Most of the TRCP-derived radioactivity was excreted in urine (up to 85%), with feces, volatiles, and CO2 combined accounting for less than 10% of the dose. Predominant signs of toxicity associated with TRCP administration (350 and 700 mg/kg) were seizures within 2 hr of treatment, when most of the TRCP-derived radioactivity present in brain tissue was in the form of the parent compound. Traces of inextractable 14C were detected at later times, but this material was not concentrated in brain relative to other tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Metabolism of tris(2-chloroethyl) phosphate in rats and mice.

Tris(2-chloroethyl) phosphate (TRCP), a flame retardant, produces a dose-, sex-, and species-dependent lesion in the hippocampal region of the brain following subchronic oral administration. This lesion is more common and more severe in female F344 rats than in male F344 rats, and is not observed in B6C3F1 mice. The present investigation of the metabolism of TRCP was designed to detect sex and species variations that might account for differences in toxicity. Elimination of TRCP-derived radioactivity was more rapid in mice, which excreted greater than 70% of an oral dose of 175 mg/kg in urine in 8 hr vs. approximately 40% for male or female rats. However, the metabolic profile of TRCP-derived radioactivity in urine was similar for both species. The major metabolite in female rat urine was identified as bis(2-chloroethyl) carboxymethyl phosphate. This metabolite co-chromatographed with the major metabolite found in both male rat and mouse urine. Two additional metabolites identified in female rat urine were bis(2-chloroethyl) hydrogen phosphate and the glucuronide of bis(2-chloroethyl) 2-hydroxyethyl phosphate. These metabolites also cochromatographed with metabolites found in male rat and mouse urine. TRCP metabolism in rats was not induced or inhibited by nine daily 175 mg/kg doses. Toxicity, as evidenced by seizures, was potentiated in male rats pretreated with inhibitors of aldehyde dehydrogenase.

Animals↗
PubMedDate not supplied

Absorption, distribution, metabolism, and excretion of 1,2-dihydro-2,2,4-trimethylquinoline in the male F344 rat.

1,2-Dihydro-2,2,4-trimethylquinoline (TMQ), an antioxidant used in the rubber industry, was readily absorbed from the gastrointestinal tract of the male Fischer 344/N rat and rapidly distributed throughout the body tissues. Absorption, distribution, metabolism, and excretion were not significantly affected by dose in the range 11.5-1150 mumol/kg. Following iv administration, the greatest amounts of TMQ-derived radioactivity were present in the high volume tissues including muscle, adipose, skin, liver, and blood. TMQ had no particular affinity for any tissue. TMQ-derived radioactivity was excreted primarily in urine (60-70%) and feces (20-30%) within 3 days after administration. Greater than 99% of the TMQ dose excreted in urine and feces was in the form of metabolites. Urine contained two major and ten minor metabolites while feces contained two major and four minor metabolites. The two major TMQ metabolites in urine were identified by NMR and mass spectroscopy as the O-sulfate conjugate of 1,2-dihydro-6-hydroxy-2,2,4-trimethylquinoline and the monosulfate conjugate of 1,2-dihydro-1,6-dihydroxy-2,2,4-trimethylquinoline. In vitro studies with liver subcellular fractions suggest that most of the metabolites present in urine, feces, and bile are the products of mixed function oxidase activity and conjugates of these metabolites. Multiple exposure of rats to high TMQ doses (1150 mumol/kg) resulted in some bioaccumulation of TMQ-derived radioactivity in all tissues examined, but these residues did not persist when dosing was discontinued.

Animals↗
PubMedDate not supplied

Metabolism and disposition of ethylene glycol monobutyl ether (2-butoxyethanol) in rats.

Ethylene glycol monobutyl ether (2-butoxyethanol, BE) is a major industrial chemical with multiple and diverse uses that may result in significant risk of human exposure and environmental contamination. The current studies were undertaken to investigate the metabolism and disposition of this chemical in male F344 rats. Data presented in this report showed that BE is rapidly absorbed after gavage administration, metabolized, and eliminated. Tissue distribution of BE revealed that BE is distributed to all tissues with the highest levels (determined 48 hr after dosing) detected in the forestomach followed by the liver, kidney, spleen, and the glandular stomach. However, the increase in the tissue concentration in rats treated with 500 mg/kg (as compared to that in rats treated with 125 mg/kg BE) was not proportional to the increase in BE dose. The major route of BE elimination was in the urine, followed by 14CO2 exhalation. The portion of the BE dose eliminated in urine or as 14CO2 was significantly higher in rats treated with 125 mg/kg than in the rats treated with 500 mg/kg. This may indicate that saturation of BE-metabolizing enzymes occurs at the high dose. A small portion (8%) of the administered dose (500 mg/kg) was excreted in the bile in 8 hr after dosing. Qualitative and quantitative HPLC analysis of the urinary and biliary metabolites of BE revealed that the major urinary metabolite, butoxyacetic acid (BAA), accounted for more than 75% of the radioactivity excreted in the urine. The second major metabolite in urine was the glucuronide conjugate of BE (BEG).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Metabolism and disposition of n-butyl acrylate in male Fischer rats.

Butyl acrylate (BA) is one of the major monomers used in the manufacture of polymers and resins. Because little is known regarding its metabolic fate in animals, it was of interest to study the metabolism and disposition of BA in the rat. After oral administration, butyl [2,3-14C]acrylate was rapidly absorbed and metabolized. The acrylate moiety was metabolized primarily to CO2, accounting for elimination of up to 75% of the administered radiolabel. Elimination in urine and feces accounted for approximately 10 and 2% of the dose, respectively. Initial clearance of radioactivity from the tissues was very rapid and then decreased to a negligible rate 2 hr after iv administration. Total radioactivity in the major tissues was relatively constant from 2 to 24 hr. The majority of the radioactivity in the blood at 24 hr was found to be covalently bound to the protein fraction of the red blood cell membranes. There was some evidence of a first-pass effect when BA was administered by gavage because iv administration resulted in less metabolism to CO2 and quantitative differences in urinary metabolites. The two major metabolites in urine were identified as N-acetyl-S-(2-carboxyethyl)cysteine and N-acetyl-S-(2-carboxyethyl)cysteine-S-oxide. Results of this study indicated that the major portion of a BA dose was hydrolyzed to acrylic acid, which was further metabolized to compounds available for oxidative metabolism. Radiolabeled carbons from the BA molecule were excreted as CO2 or incorporated in trace amounts into lipids, proteins, and other products of de novo synthesis. A smaller portion of the BA dose was conjugated with endogenous glutathione.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylates↗
PubMedDate not supplied

Methyl carbamate. Species-dependent variations in metabolism and clearance in rats and mice.

Studies of the chronic toxicity and carcinogenicity of methyl carbamate (MC) in F344 rats and B6C3F1 mice indicate that this compound is more toxic to rats than mice. MC was also a carcinogen for rats but not a carcinogen for mice even when administered at a higher dose. The present study of the comparative metabolism and disposition of MC in these two species was conducted to determine possible sources of these varying responses. Results of this study indicate that, although the initial distribution of MC in the two species is similar, the mouse metabolizes and clears MC much more rapidly than does the rat. In the mouse, clearance was primarily by metabolism to CO2 and elimination in exhaled air, which accounted for approximately 70% of the dose in 48 hr. On the other hand, the rat eliminated approximately 18% of the dose as CO2 in 48 hr and a similar amount in urine. The parent compound accounted for approximately 90% of the material excreted in urine of both rats and mice. Only the parent compound was detected in tissues of either species. Less than 4% of the dose was excreted in feces of either species. The lesser ability of the rat to metabolize and eliminate MC as CO2 results in bioaccumulation of this compound on repeat exposure. Therefore, bioaccumulation of MC by the rat on chronic exposure probably results in both greater total exposure and higher peak exposure of most rat tissues vs. those of mice and may thus account for the greater toxicity and possibly carcinogenicity of MC to rats.

Animals↗