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Biomedical subjects

G Reddy

Publications and source records attributed to G Reddy.

72 records · Page 4Linked to original sources
PubMed1981

Metabolism and biliary excretion of 2,4,5,2',4',5'-hexachlorobiphenyl in the rhesus monkey (Macaca mulatta).

The metabolism and biliary excretion of 3H-2, 4, 5, 2', 4', 5'hexachlorobiphenyl (HCB) were studied in two rhesus monkeys (Macaca mulatta), a young, mature female and a juvenile male. This compound is a major constituent of those commercial polychlorinated biphenyl (PCB) mixtures with high chlorine content, and it is also a prevalent PCB analogue in human adipose tissue. Following cannulation of the common bile duct and duodenum, allowing collection of a known fraction of bile with return of the remaining bile into the duodenum, the animals received 3H-HCB (1 gm/kg body weight) by gastric intubation. Bile was collected daily for 3 weeks. During the 3-week period, 1.3% and 4% (from the female and male, respectively) of the administered radioactivity were excreted in the bile. As has been demonstrated for other species, the monkey apparently metabolizes and excretes HCB at a rate slower than for compounds containing two adjacent unsubstituted carbons. Approximately 2% of the bile radioactivity in the adult female and 12% in the juvenile male were extracted with organic solvents. Thin layer chromatography (TLC), using a benzene:ethyl acetate (12:1) solvent system, of the organic extracts of bile separated four major regions of radioactivity designated as I, II, II, and IV with Rf values of 0.86, 0.67, 0.58, and 0.00, respectively. Region I consisted of the parent HCB, which was identified by analysis with gas chromatography-mass spectrometry (GC-MS). Region II consisted of a metabolite identified as 2,4,5,2',4',5'-hexachloro-3-hydroxybiphenyl (OH-HCB) by analysis with GC-MS of the methylated derivative of the metabolite. Region III probably contained a more polar metabolite, which has not yet been identified. Region IV contained an even more polar material, probably including conjugates of HCB metabolites. Release of OH-HCB from the water-soluble fraction of bile in the presence of beta-glucuronidase and lack of release of OH-HCB in presence of beta-glucuronidase with saccharo-1, 4-lactone (a beta-glucuronidase inhibitor) or in the presence of aryl sulfatase with saccharo-1, 4-lactone provided evidence of water-soluble, glucuronic acid conjugates of OH-HCB in the bile. The hexachlorobiphenyl was excreted in the bile as HCB, OH-HCB, and water-soluble conjugates of HCB metabolites, probably including 2,4,5,2',4',5'-hexachloro-3-hydroxybiphenyl glucuronide. The metabolism of HCB may or may not include the formation of an arene oxide.

Animals↗
PubMed1980

Transcutaneous oxygen monitoring during neonatal transport.

The use of transcutaneous PO2 monitoring during neonatal transport was found to be feasible and clinically useful in maintaining the partial pressure of arterial oxygen within a desired range. Adjustment of fractional inspiratory oxygen (FIO2) to maintain transcutaneous PO2 between 50 to 70 torr resulted in a greater number of infants arriving at a tertiary center without either hypoxemia or hyperoxemia.

Humans↗
PubMedDate not supplied

Fourteen-day toxicity study of 1,3,5-trinitrobenzene in Fischer 344 rats.

Toxic effects of 1,3,5-trinitrobenzene (TNB) in male and female rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of TNB (0, 50, 200, 400, 800 and 1200 mg kg-1 diet) for 14 days. Food intake by female rats in 400, 800 and 1200 mg TNB diet groups was reduced and resulted in a significant decrease in absolute body weights (BW). Food and water consumption by male rats in high-dose groups (800 and 1200 mg TNB kg-1 diet) was also reduced and resulted in a significant decrease in body weight. The calculated average TNB intake (from 1200 mg TNB kg-1 diet) was 92 mg kg-1 BW day-1 for male rats and 80 mg kg-1 BW day-1 for females. A decrease in testicular weight in males and an increase in spleen weight of both sexes in high-dose groups was noted. In addition, histopathological examinations revealed that the susceptible organs for TNB toxicity were kidney (hyaline droplets), spleen (extramedullary hematopoiesis), brain (hemorrhage, malacia and gliosis) and testes (seminiferous tubular degeneration). Hematology and clinical chemistry studies indicated a decrease in red blood cell count and hematocrit, a decrease in alkaline phosphatase, an increase in Heinz bodies and increased methemoglobin concentration as compared to controls in both sexes. A lowest observed adverse effect level of 4.41 mg TNB kg-1 BW day-1 was established based on the findings of this study.

Anemia↗
PubMedDate not supplied

Percutaneous absorption of trinitrobenzene: animal models for human skin.

The percutaneous absorption of 1,3,5-trinitrobenzene (TNB) was studied in viable skin from hairless guinea pigs (HGP), Fischer 344 rats and humans. Skin was dermatomed and assembled in flow-through diffusion cells followed by TNB application in either an acetone or a water vehicle. Skin absorption was expressed as the percentage of applied dose absorbed into skin and receptor fluid within 24 h. Rapid absorption of TNB by rodent skin was obtained with both vehicles. For HGP skin, TNB absorption was 72.7+/-5.5% in the acetone vehicle and 82.3+/-4.5% in the water vehicle. For rat skin, TNB absorption was 61.0+/-4.1% (acetone) and 66.5+/-4.1% (water). Absorption of TNB from acetone was significantly reduced (38.0+/-11.0%, P = 0.0118) in human skin, but absorption from water remained high (75.5+/-10.8%). Little TNB remained in skin when a thin (200 microm) dermatome section was used (HGP and human skin). A thicker dermatome section was required (350 microm) with haired rat skin, and 13-21% of the absorbed radioactivity remained in the skin at 24 h. Rodent skin did not simulate satisfactorily the barrier properties of human skin when TNB absorption was reduced by application in a volatile solvent.

Animals↗
PubMedDate not supplied

Mutagenic potential of nitroguanidine and nitrosoguanidine in the Drosophila melanogaster sex-linked recessive lethal assay.

Nitroguanidine (NG) and its degradation product nitrosoguanidine (NSG) were evaluated for their mutagenic potential by using Drosophila melanogaster sex-linked recessive lethal (SLRL) assay. Following 72 h of feeding exposure, NG and NSG at concentrations of 4-8 micrograms ml-1 and 15-20 mg ml-1, respectively, were not mutagenic in the test system. The frequencies of mutations for NG and the negative control were 0.188% and 0.096%, respectively. The frequencies of mutations for NSG and the negative control experiments were 0.049% and 0.05%, respectively. The positive control mutation frequencies were 15% and 17.8% for the two assays. The differences between the mutation frequencies of NG and NSG and their negative controls were not significant.

Animals↗
PubMedDate not supplied

Chronic toxicity of 1,3,5-trinitrobenzene in Fischer 344 rats.

The chronic toxicity of 1,3,5-trinitrobenzene (TNB) in male and female Fischer 344 (F344) rats was evaluated by feeding a diet containing 0, 5, 60, and 300 ppm of TNB for 2 years. The calculated average TNB intake over 2 years for males and females was 0.22, 2.64, 13.44 and 0.23, 2.68, 13.31 mg/kg body weight (BW)/day respectively. Terminal body weights were decreased and water intake was increased in both sexes (300 ppm), whereas food consumption was decreased in males (60 and 300 ppm groups) only. The relative spleen weights were significantly decreased in both sexes (300 ppm), whereas the relative brain weights were increased in females only (300 ppm). Hematological effects were not observed in animals killed at the 2-year time point, except significant decrease in the mean corpuscular hemoglobin (MCH) in males (300 ppm) and in females (60 and 300 ppm). Methemoglobin levels were increased in both sexes in the high dose group. Histopathological examination showed treatment-related changes in the kidney (hyaline droplets; 60 and 300 ppm) and the spleen (erythroid cell hyperplasia and pigment deposition; 300 ppm) of both sexes. Cytoplasmic hyaline droplets in the kidneys were characterized by immunohistochemistry as alpha-2mu-globulin. We propose a chronic, oral no-observable-adverse-effect level (NOAEL) of 2.68 mg/kg BW/day for TNB in the rat, based on the hematological and renal changes.

Administration, Oral↗
PubMedDate not supplied

1,3,5-Trinitrobenzene-induced encephalopathy in male Fischer-344 rats.

Administration of 1,3,5-trinitrobenzene (TNB) to male Fischer-344 rats produced ataxia after 6 or 7 oral doses (71 mg/kg). Light microscopic examination after 10 days revealed petechial hemorrhages in the brain stem and cerebellum and bilaterally symmetric degeneration and necrosis (malacia) with reactive gliosis in the cerebellar peduncles. The malacia was dorsal and lateral to the fourth ventricle involving the cerebellar nuclei, medial and lateral vestibular nuclei, and inferior colliculi. Blood vessels associated with the lesion had widened Virchow-Robin spaces, occasionally with extravasated erythrocytes. Rats administered daily oral doses of 35.5 mg/kg of TNB for 10 days and 35.5 and 71 mg/kg of TNB for 1 or 4 days did not have brain lesions.

Administration, Oral↗
PubMedDate not supplied

1,3,5-Trinitrobenzene-induced alpha-2u-globulin nephropathy.

Male and female Fischer-344 (F-344) and male NCI-Black-Reiter (NBR) rats were dosed with 0, 35.5, or 71 mg 1,3,5-trinitrobenzene (TNB)/kg/day for 10 days. Male F-344 rats were dosed with TNB (0 and 35.5 mg/kg) for 20 and 30 days. Hematoxylin and eosin and Mallory-Heidenhain stains and alpha-2u-globulin and proliferating cell nuclear antigen immunohistochemical stains were performed on kidney sections. All treated male F-344 rats exhibited dose-related accumulation of hyaline droplets containing alpha-2u-globulin in proximal tubules. The kidney weights were significantly increased in male and female rats treated with TNB. Significant increases in cell proliferation in proximal tubules were observed in male F-344 rats. Renal changes observed in TNB-treated rats appeared identical to those from other chemicals that induce alpha-2u-globulin nephropathy in male rats. No hyaline droplet accumulation was found in female F-344 and male NBR rats at any doses. We can conclude that TNB induces dose-related exacerbation of hyaline droplets containing alpha-2u-globulin in male rat kidney and subsequent cell proliferation.

Alpha-Globulins↗