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324 records · Page 18Linked to original sources
PubMed1987

Validation and application of a liquid-chromatographic/enzymatic assay for individual bile acids in the serum of rats.

A liquid-chromatographic technique with a post-column enzymatic reaction and fluorescence detection was validated for analysis of individual bile acids in the serum of rats. Extraction recoveries averaged 91.1% (SD 6.9%) for all bile acids. The assay was sensitive (minimum detection of 16.8 pmol per 100-microL injection), linear (r greater than 0.999 for concentrations ranging between 45 and 112,500 pmol per 100-microL injection), and reproducible (mean CVs for three different concentrations of standards and a serum pool ranged from 4.4% to 12.2%). In rats treated for three days with either neomycin, carbon tetrachloride, alpha-naphthylisothiocyanate, or total bile-duct ligation (five animals per group), total concentrations of bile acids were significantly increased (P less than 0.004). Concentrations of 16 of 17 individual bile acids differed significantly between groups (P less than 0.04). Examination of the relative concentrations (percent of total) of individual bile acids by canonical discriminant analysis placed each animal into the appropriate treatment or control group. Use of this technique in toxicological studies can help detect and identify specific types of disruptions in the enterohepatic circulation of bile acids.

1-Naphthylisothiocyanate↗
PubMed1984

Serum gamma glutamyl transferase as a specific indicator of bile duct lesions in the rat liver.

Serum gamma-glutamyl transferase (GGT), a marker of hepatic injury used extensively in humans, has been used rarely in rats because its specificity has not been previously defined. Studies were designed for investigation of the specificity of serum GGT activity with the use of cell type specific hepatotoxicants in Fischer 344 rats. Single necrogenic doses of CCl4, allyl alcohol (AA), and alpha-naphthylisothiocyanate (ANIT) were used to produce cell specific injury in centrilobular hepatocytes, periportal hepatocytes, and bile duct cells, respectively. Administration of CCl4 markedly increased serum activities of alanine aminotransferase (ALT), alkaline phosphatase (AP), and serum bile acid concentrations within 24 hours but had no effect on serum GGT activity. ANIT treatment increased serum GGT and AP activities and bile acid concentration 24 hours following administration. Allyl alcohol administration increased serum ALT activity but had no effect on GGT activity. Administration of ANIT in the diet at 0.01%, 0.022%, 0.047%, and 0.1% for 2, 4, and 6 weeks produced dose- and time-dependent increases in serum GGT activity which strongly correlated with quantitative increases in hepatic bile duct volume, which was determined morphometrically. These observations support the use of serum GGT activity in the rat as diagnostic of bile duct cell necrosis when increases are detected shortly after the insult and as an indicator of possible bile duct hyperplasia.

1-Naphthylisothiocyanate↗
PubMed1978

Tracheobronchial mucoepidermoid carcinoma. Clinicopathological features and results of treatment.

Mucoepidermoid carcinomas of the tracheobronchial tree are extremely uncommon and, as a result, opinions regarding their natural history are conflicting. In an effort to determine whether the tumors are aggressive or relatively benign, we have collected seven well-documented, previously unreported cases from among 4,250 primary pulmonary carcinomas and 116 bronchial adenomas. The two tracheal and five endobronchial lesions presented here include one high-grade and six low-grade tumors. Curative resections were performed, including segmental tracheal resections in two patients, lobectomy in three patients, and pneumonectomy in two patients, and the follow-up is complete to the time of this report. Long-term survivals ranging from 5 to 23 years, averaging 12.8 years, have been achieved in the six patients with a low-grade carcinoma. The one high-grade variant proved fatal within 28 months of diagnosis despite two surgical attempts at control and radiotherapy. It is concluded that these tumors exhibit a spectrum of virulence with low-grade lesions amenable to long-term surgical cure. The optimum treatment of high-grade lesions remains problematical.

Adolescent↗
PubMed1995

Repeated exposure toxicity of 2-ethyl-1,3-hexanediol by cutaneous applications to the rat for 9 and 90 days.

2-Ethyl-1,3-hexanediol (EHD; CASRN 94-96-2), an industrial chemical and insect repellent, has a high potential for recurrent skin contact. Short-term (9 d) and subchronic (13 w) repeated epicutaneous contact studies were conducted to determine the potential for cumulative local skin irritation and systemic toxicity in Fischer 344 rats. Doses were 0.5, 2.0 or 4.0 ml/kg/d of undiluted EHD. There were no clinical signs and no treatment-related effects on hematology, clinical chemistry or histology of a large number of organs and tissues including the treated skin. The only effects where slight decreases in body weight gain for the high-dose males in the 9-d study and males and females of the high-dose group in the subchronic study; slight decreases in food consumption for females of all treatment groups in the subchronic study; and slight increases in relative liver weight for high-dose females in the 9-d study and high-dose males in the subchronic study, which is probably a compensatory hypertrophy for the metabolism of EHD. Thus, recurrent epicutaneous applications of undiluted EHD to the rat did not cause any local skin irritation or cumulative or organ-specific toxicity.

Administration, Cutaneous↗
PubMed1994

The efficacy of indium-111-polyclonal IgG for the detection of infection and inflammation.

UNLABELLED: The purpose of this study was to determine the efficacy of 111In-polyclonal immunoglobulin (IgG) for the diagnosis of infection or inflammation. METHODS: Fifty-three patients with suspected infection were prospectively studied. Each underwent an 111In-polyclonal IgG study; biopsy, surgery, additional nuclear medicine scans and radiographic studies were used to confirm the IgG scan results. RESULTS: The polyclonal IgG scan had a sensitivity of 97.9% and a specificity of 94% for infection or inflammation. When only infection or severe inflammation such as bowel infarction was considered, the sensitivity remained the same but the specificity fell to 83%. Chronic infections were detected equally as well as acute infections. Antibiotics, steroids, anti-inflammatory agents, diabetes and diminished renal function did not affect scan sensitivity. There were no adverse reactions to the radiopharmaceutical. Three patients underwent extended imaging. Their scans stayed positive for an average of 8 days. Three patients treated for infection had their scans turn negative on repeat study, confirming the efficacy of their antibiotic therapy. CONCLUSION: Indium-111-polyclonal IgG is an effective imaging agent of infection and/or inflammation that is useful in a variety of infections and in severe inflammatory diseases. The ease of preparation and safety make it an attractive alternative to labeled leukocytes.

Adult↗
PubMed1996

Harmonization of animal clinical pathology testing in toxicity and safety studies. The Joint Scientific Committee for International Harmonization of Clinical Pathology Testing.

Ten scientific organizations formed a joint international committee to provide expert recommendations for clinical pathology testing of laboratory animal species used in regulated toxicity and safety studies. For repeated-dose studies in rodent species, clinical pathology testing is necessary at study termination. Interim study testing may not be necessary in long-duration studies provided that it has been done in short-duration studies using dose levels not substantially lower than those used in the long-duration studies. For repeated-dose studies in nonrodent species, clinical pathology testing is recommended at study termination and at least once at an earlier interval. For studies of 2 to 6 weeks in duration in nonrodent species, testing is also recommended within 7 days of initiation of dosing, unless it compromises the health of the animals. If a study contains recovery groups, clinical pathology testing at study termination is recommended. The core hematology tests recommended are total leukocyte (white blood cell) count, absolute differential leukocyte count, erythrocyte (red blood cell) count, evaluation of red blood cell morphology, platelet (thrombocyte) count, hemoglobin concentration, hematocrit (or packed cell volume), mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. In the absence of automated reticulocyte counting capabilities, blood smears from each animal should be prepared for reticulocyte counts. Bone marrow cytology slides should be prepared from each animal at termination. Prothrombin time and activated partial thromboplastin time (or appropriate alternatives) and platelet count are the minimum recommended laboratory tests of hemostasis. The core clinical chemistry tests recommended are glucose, urea nitrogen, creatinine, total protein, albumin, calculated globulin, calcium, sodium, potassium, total cholesterol, and appropriate hepatocellular and hepatobiliary tests. For hepatocellular evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alanine aminotransferase, aspartate aminotransferase, sorbitol dehydrogenase, glutamate dehydrogenase, or total bile acids. For hepatobiliary evaluation, measurement of a minimum of two scientifically appropriate blood tests is recommended, e.g., alkaline phosphatase, gamma glutamyltransferase, 5' -nucleotidase, total bilirubin, or total bile acids. Urinalysis should be conducted at least once during a study. For routine urinalysis, an overnight collection (approximately 16 hr) is recommended. It is recommended that the core tests should include an assessment of urine appearance (color and turbidity), volume, specific gravity or osmolality, pH, and either the quantitative or semiquantitative determination of total protein and glucose. For carcinogenicity studies, only blood smears should be made from unscheduled sacrifices (decedents) and at study termination to aid in the identification and differentiation of hematopoietic neoplasia.

Animal Welfare↗