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E B Wheeldon

Publications and source records attributed to E B Wheeldon.

45 records · Page 3Linked to original sources
PubMedDate not supplied

Reduced disease in aged rats treated chronically with ibopamine, a catecholaminergic drug.

As part of preclinical safety testing for carcinogenicity, postpubertal (50 days old) rats were dosed (0, 30, 90 or 180 mg/kg/day) with ibopamine (N-methyldopamine, 0,0'-diisobutyroyl ester.HCl; SK&F 100168) for 730 consecutive days. Neoplastic and nonneoplastic lesions were identified histologically in all rats that died during the period of dosing, as well as in those that were killed after it was completed. Six neoplastic lesions (adrenal cortical, mammary, and pituitary adenoma, skin papilloma, pheochromocytoma and mammary adenocarcinoma) and five nonneoplastic lesions (chronic glomerulonephropathy, renal pelvic mineralization, hepatocellular proliferative nodule, galactoceles and chronic cardiomyopathy) were significantly reduced in a dose-related fashion in at least one sex of ibopamine-treated rats. In addition, age-related alopecia and atrophy of the adrenal zona glomerulosa were retarded by ibopamine treatment. Squamous cell skin carcinoma was the only lesion that was significantly (p less than 0.05) increased in the treated groups. Mortality during the study was not significantly different in treated and control groups, indicating that the lower incidence of disease in ibopamine-treated rats was a drug effect and not an artifact of differential survival. Although life span was not measured, ibopamine-treated rats had significantly less malignant lesions than controls at the end of dosing, suggesting a potentially positive effect of treatment on population survival. As the result of these beneficial effects, ibopamine may be useful for future study of factors affecting the occurrence of disease during aging.

Aging↗
PubMedDate not supplied

Quantitation of apoptotic bodies in rat liver by in situ end labelling (ISEL): correlation with morphology.

Nongenotoxic hepatocarcinogens have been proposed to inhibit hepatocyte apoptosis, preventing the removal of DNA-damaged cells. Conclusive proof of this hypothesis has been hindered by the lack of a marker or stain for apoptosis suitable for high throughput counting. A method is described for the detection of apoptotic bodies (AB) in paraffin sections of rat liver using an in situ end labeling (ISEL) technique that detects DNA damage. Results of this AB quantitation were compared with routine hematoxylin-eosin (H&E)-stained sections. The number of apoptotic bodies was enhanced by the withdrawal of the rodent nongenotoxic hepatocarcinogens and hepatomitogens nafenopin (naf) or cyproterone acetate (CPA) after 7 days of daily dosing. In rat livers 24-96 hr after cessation of dosing with naf, and in control livers, an AB index of approximately 0.1% of hepatocyte nuclei was seen when stained by H&E or ISEL. However, livers examined 48 hr after cessation of 7 days of daily dosing with CPA had an AB index of approximately 1% hepatocyte nuclei when stained with H&E, but only approximately 0.4% hepatocyte nuclei using the ISEL technique. Thus, CPA withdrawal from the hyperplastic liver generated a wave of apoptosis in contrast to naf withdrawal where little was seen up to 96 hr after withdrawal. The differing kinetics of CPA and naf clearance may explain this discrepancy. Less apoptosis was detected by the ISEL method following CPA withdrawal; this could arise if the stage of apoptosis labeled by ISEL is shorter than the morphologically recognizable stages (using H&E). The ISEL method for the evaluation of AB indices is useful in parallel with H&E, although more validation is required before it can be used routinely for the quantitation of AB in tissue sections.

Animals↗
PubMedDate not supplied

Leukotriene D4 (LTD4) induces mucus secretion from goblet cells in the guinea pig respiratory epithelium.

To study the potential role of leukotriene (LTD4) as a mucus secretagogue, anesthetized and spontaneously breathing guinea pigs were intubated and challenged with various concentrations of an LTD4 aerosol. The resulting changes in airway resistance and compliance were then observed for 20 min, after which the animals were euthanized and the lower respiratory tract airways fixed for morphometric evaluation. Sections for these airways were stained with alcian blue-periodic acid Schiff (AB-PAS), photographed, and the content of AB-PAS positive granules in the epithelium of the extrapulmonary bronchi quantified. The fractional volume of mucus granules in the respiratory epithelial volume. Aerosol LTD4 produced a dose-dependent decrease in the granule fractional volume (GFV) over the range of 0.1 to 1 microgram/ml when compared with epithelia challenged with saline aerosols. Increasing the concentration of administered LTD4 from 1 microgram to 3 micrograms/ml produced further bronchoconstriction but had no further effect on the GFV. Decreases in GFV did not appear to be secondary to smooth muscle contraction since aerosols of other agonists (0.05% histamine and 1% acetylcholine), which yielded resistance changes similar to those of LTD4, did not effect the GFV. Pretreatment with an aerosol of the specific LTD4 receptor antagonist SK&F 104353-Z2 produced a dose-dependent inhibition of the changes in both the airway resistance and GFV. The data suggest that LTD4 mediates epithelial mucus secretion as well as bronchoconstriction in the guinea pig airway and may provide an additional therapeutic use for specific LTD4 receptor antagonists in the treatment of obstructive pulmonary disease.

Animals↗
PubMedDate not supplied

A histochemical study of mucosubstances in the bovine respiratory tract with special reference to cuffing pneumonia.

The mucosubstances of the bronchial epithelial goblet cells in non-pneumonic calves were almost exclusively sulphomucin; neutral mucin, sialomucin and sulphomucin were produced by the submucosal glands. Calves with lesions of cuffing pneumonia from which M. dispar was frequently cultured had increased numbers of epithelial goblet cells extending into the peripheral airways as far as the bronchioles. These pneumonic animals had epithelial goblet cells, some of which contained sialomucin, while in the gland a switch from neutral to acid mucosubstance in the form of increased sulphomucins and sialomucins was detected.

Animals↗
PubMedDate not supplied

A histochemical study of the tracheobronchial epithelial mucosubstances in normal dogs and dogs with chronic bronchitis.

The tracheobronchial mucosubstances in a group of normal dogs and a group of dogs with chronic bronchitis have been characterized histochemically. Sulphomucin was the predominant mucosubstance in the epithelial goblet cells of normal dogs and a mixture of sulphomucin and sialomucin was found in the bronchial glands. In the dogs with chronic bronchitis there was a shift towards the production of sialomucin in both sites.

Animals↗