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Biomedical subjects

J N Clark

Publications and source records attributed to J N Clark.

At least 19 recordsLinked to original sources
PubMed1996

Efficacy of an ivermectin and pyrantel pamoate combination against adult hookworm, Ancylostoma braziliense, in dogs.

A chewable tablet incorporating ivermectin and pyrantel was tested in 12 Beagle dogs for efficacy against the adult hookworm, Ancylostoma braziliense. The dogs were administered infective larvae of A braziliense orally. Twenty-one days after infection the dogs were weighed and allocated randomly to receive either an oral treatment with ivermectin and pyrantel in a beef-based chewable tablet or no treatment. The chewable tablet was a commercially available product, which was made to deliver ivermectin at 6 micrograms/kg and pyrantel at 5.0 mg/kg to each dog. Seven days after treatment the dogs were euthanased, necropsied, and examined for adult hookworms. At necropsy, no adult A braziliense was observed in any of the 6 treated dogs and all 6 dogs that had been left untreated were infected with adult A braziliense (range, 48 to 161). It was concluded that this combination product is 100% efficacious against adult A braziliense.

Administration, Oral↗
PubMed1995

Activity of a novel nonpeptidyl growth hormone secretagogue, L-700,653, in swine.

L-700,653 is a potent nonpeptidyl GH secretagogue consisting of a benzolactam structure: (4'-[[3(R)-[[3-[(2(S),3-dihydroxypropyl) amino]3-methyl-1-oxobutyl]amino]2,3,4,5-tetrahydro-2-oxo-1H-1-benzaze pin- 1-yl]methyl][1,1'-biphenyl]2-carboxamide hydrochloride). When administered sc by a Medi-Jector device at 0, 0.003, 0.01, 0.03, and 0.1 mg/kg BW to male castrated swine (approximately 50 kg BW), L-700,653 stimulated dose-related increases in peak plasma GH concentrations by 20% (P = NS), 150% (P = NS), 250% (P < 0.05), and 340% (P < 0.05), respectively, over the saline vehicle control value (11.3 +/- 6.5 ng/ml) and stimulated increases in GH areas under the curve (AUCs) by 10% (P = NS), 30% (P = NS), 90% (P < 0.05), and 100% (P < 0.01), respectively, over the saline vehicle control value (799 +/- 145 ng/min.ml). After sc administration of L-700, 653, there were no significant changes in plasma LH levels. Subcutaneous dose of 0.03 or 0.1 mg/kg increased plasma cortisol AUCs by 60% (P = NS) and 150% (P < 0.03) over the control value (2461 +/- 935 ng/min.ml) and increased cortisol peaks by 80% (P = NS) and 200% (P < 0.01), respectively, over the control value (38.3 +/- 12.3 ng/ml). Repeated sc administration of L-700,653 (0.03 or 0.1 mg/kg) at 0800, 1400, and 2000 h daily over 3 days consistently increased mean GH peak and GH AUC at each treatment period, with minimal and maximal increases of 40% and 190% in GH peak level at the 0.03 mg/kg dose and 100% and 400% increases in GH peak level at the 0.01 mg/kg dose, respectively. Continuous i.v. infusion of L-700,653, at either 0.01 or 0.1 mg/kg BW.h over a 180-min period, increased GH AUCs by 60% (P = NS) or 470% (P < 0.01) and GH peaks by 190% (P = NS) or 1520% (P < 0.01), respectively, over the control value (589 +/- 313 ng/min.ml; 7.0 +/- 11.1 ng/ml). After a 180- to 300-min saline infusion, an iv bolus dose of 0.1 mg/kg L-700,653 resulted in GH responses inversely proportional to the previous infusion dose, i.e. 0, 0.01, or 0.1 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1992

Efficacy of ivermectin and pyrantel pamoate combined in a chewable formulation against heartworm, hookworm, and ascarid infections in dogs.

Eight trials were conducted in dogs to document the efficacy of ivermectin (6 micrograms/kg of body weight) and pyrantel pamoate (5 mg of active pyrantel/kg) in a beef-based chewable formulation against Dirofilaria immitis, Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, and Toxascaris leonina. Three studies involved induced infection with D immitis, and 5 studies involved induced or natural infection with hookworms and ascarids. In 3 intestinal parasite trials, the efficacy of the combination chewable tablet was compared with each of its components. Results indicated that 1 component did not interfere with the activity of the other. In 1 heartworm and 2 intestinal parasite trials, the efficacy of pyrantel, ivermectin/pyrantel combination, or ivermectin with pyrantel dosage of 10 mg/kg was evaluated. The ivermectin/pyrantel combination was 100% effective in preventing development of D immitis larvae. Efficacy of the combined product against T canis, Toxascaris leonina, A caninum, and U stenocephala was 90.1, 99.2, 98.5, and 98.7%, respectively. In the intestinal parasite trials, each individual component was found not to interfere with the anthelmintic action of the other. Increasing the dosage of pyrantel to 10 mg/kg (2 x that in the combination) did not interfere with the efficacy of ivermectin against heartworm or increase the activity of pyrantel against intestinal parasites.

Administration, Oral↗
PubMed1992

Safety study of a beef-based chewable tablet formulation of ivermectin and pyrantel pamoate in growing dogs, pups, and breeding adult dogs.

To determine the safety of a new combination of ivermectin and pyrantel (as pamoate salt) in a novel beef-based chewable tablet formulation, 3 tolerance trials were conducted and included growing dogs, pups, and breeding adult dogs. Growing dogs, given the combination orally for 5 consecutive days at recommended dosages (5 mg of pyrantel/kg of body weight, 6 micrograms of ivermectin/kg) or at twice the pyrantel dosage in combination with the recommended dosage of ivermectin, had no adverse effects. The combination also was administered to 6-week-old pups at 1, 3, and 5 times the recommended dose on 3 successive days for 3 times in 1 month. Compared with age-matched controls, treatment had no effect on clinical status, growth rate, or gross or histologic features. Breeding male and female dogs given the combination at 3 times the recommended dose for extended periods had no adverse effects, and prevalence of abnormalities in the offspring was not greater than that in nonmedicated controls.

Abnormalities, Drug-Induced↗
PubMed1991

Evaluation of a beef-based chewable formulation of pyrantel pamoate against induced and natural infections of hookworms and ascarids in dogs.

Pyrantel pamoate, formulated in a beef-based chewable tablet, was evaluated for efficacy in dogs against induced and natural infections of Toxocara canis, Toxascaris leonina, Ancylostoma caninum and Uncinaria stenocephala. Dose titration trials were conducted in Canada, the UK and Germany in dogs treated with pyrantel (as pamoate salt) at 0, 2.5, 5 or 10 mg kg-1 body weight. These studies showed that a dose rate of 2.5 mg kg-1, the efficacy of pyrantel against adult T. canis, T. leonina, U. stenocephala and A. caninum was 76.1, 85.6, 100 and 87.9%, respectively. Efficacy at 5 mg kg-1 against the same parasites was 94.2, 92.0, 93.5 and 93.8%, respectively, and at 10 mg kg-1 efficacy was 91.2, 97.6, 98.7 and 91.3%, respectively. No adverse effects due to treatment were seen in any of these trials.

Administration, Oral↗
PubMed1983

Effect of retinoic acid on the synthesis of glycoproteins of mouse skin tumors during progression from promoted skin through papillomas to carcinomas.

Papillomas and carcinomas were induced on the skin of mice by initiation with dimethylbenzanthracene, followed by promotion with 12-O-tetradecanoylphorbol-13-acetate. Retinoic acid was applied topically, either chronically, throughout the promotion period, or acutely, to the papillomas or carcinomas. All tumor types were verified histologically. Tumor tissue was incubated with labeled glucosamine and labeled glycoproteins released into media were fractionated on DEAE-Sephadex. For papillomas, one peak (eluted with 0.17 M NaCl) appeared and another (0.40 M) all but disappeared as a result of retinoic acid treatment. Carcinomas also showed the 0.40 M peak released by papillomas, which was also suppressed by retinoic acid. Carcinomas released a 0.26 M peak instead of the 0.17 M peak in response to the retinoid. All three peaks yielded single, symmetrical peaks on gel filtration columns. They were all resistant to mild alkaline hydrolysis. Labeling experiments revealed the presence also of mannose, galactose, and traces of fucose in all three glycoproteins. The 0.17 and 0.26 M peaks were bound by concanavalin A-Sepharose columns, the 0.40 M peak was not. Molecular weights, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, were approximately 80,000 and 105,000 (0.17 M peak), 67,000 (0.26 M peak), 70,000 and 80,000 (0.4 M peak).

Animals↗
PubMed1981

Modulation of growth, differentiation, and mucous glycoprotein synthesis by retinyl acetate in cloned carcinoma cell lines.

The ability of retinyl acetate to alter growth, differentiation, and synthesis of mucous glycoproteins in cell lines cloned from an adenocarcinoma (T-8) and a squamous cell carcinoma (1000 WT) was investigated with the use of F344 rats. Growth rate was inhibited approximately 25 and 50% in 6.6 x 10(-6) and 3.3 x 10(-5) M retinyl acetate, respectively. In both cell lines. Cell line T-8 grew mainly as a monolayer, whereas cell line 1000 WT grew as a stratified epithelium. In the presence of both concentrations of retinyl acetate, this stratification was decreased and cells became enlarged and more cuboidal. Retinyl acetate induced the formation of numerous vacuoles and periodic acid-silver methenamine-positive granules in both T-8 and 1000 WT cells. The granules appeared with and without dense cores in electron micrographs. Golgi hypertrophy and increased numbers of microvilli were also evident. After T-8 cells were cultured for 7 days in 6.6 x 10(-6) or 3.3 x 10(-5) M retinyl acetate, [3H]glucosamine incorporation increased 133- to 147-fold and [14C]serine incorporation increased twelvefold to twentyfold in the high-molecular-weight mucous glycoprotein fraction (peak A) from the cell cytosol. In 1000 WT cells, [3H]glucosamine incorporation creased only 4.2- to 7.5-fold, and [14C]serine incorporation increased only 2.6- to 4.6-fold under the same culture conditions. A similar difference in the amount of stimulation was seen for peak A isolated from the secretions. Thus T-8 cells showed a marked increase in the synthesis and secretion of mucins, whereas 1000 WT cells showed a comparatively small but significant increase.

Animals↗
PubMed1980

Reestablishment of a mucociliary epithelium in tracheal organ cultures exposed to retinyl acetate: a biochemical and morphometric study.

Tracheal explants derived from vitamin A-deficient rats underwent keratinizine squamous metaplasia in organ culture when grown in serum-free medium. Within 1 d after the addition of 0.1, 2, or 10 microgram retinyl acetate per ml of medium, there was a concentration-dependent increase in the uptake of [3H]glucosamine and [14C]serine into both the total mucous glycoprotein and the principal purified mucin fraction eluted from a DEAE-Sephacel column with 0.2 M NaCl. The stimulation of mucin synthesis continued throughout the 21-d exposure period in a concentration-dependent fashion. It was also found that vitamin A had a greater effect on the incorporation of [3H]glucosamine than on [14C]serine into the secreted mucins, particularly at the higher retinyl acetate concentrations. This result indicated a greater effect of the vitamin on the synthesis of the carbohydrate moiety of the mucins. Morphological analysis by light and electron microscopy demonstrated that the keratinizing squamous epithelium began to revert to a mucus-secreting tissue as early as 24 h after addition of 10 microgram retinyl acetate to the medium. The response was slower with the lower vitamin concentrations. Stereological analysis revealed that the increase in the volume fraction of the Golgi apparatus reached a stable level which could not be altered with continued exposure to retinyl acetate, but that the volume fraction of mucin droplets continually increased and apparently did not reach a maximum in the 21-d exposure period. Conversely, the volume fraction of filament bundles and the number of desmosomes decreased during the vitamin A treatment.

Animals↗
PubMed1980

Effect of sulfur dioxide on the morphology and mucin biosynthesis by the rat trachea.

Specific-pathogen-free rats were exposed to 400 ppm sulfur dioxide daily for up to 7 weeks. At intervals during exposure, tracheas were removed and incubated in vitro in culture medium containing radioactive glycoprotein precursors. The most prominent histological changes due to SO2 were progressive hypertrophy and hyperplasia of the submucosal mucous glands accompanied by a flattening of the epithelium with eventual recovery. Uptake of radioactive precursors into a highly purified mucin fraction correlated with these histological changes in the submucosal mucous glands, increasing progressively up to 4 times that of control. Uptake of precursors into specific mucins purified by DEAE-Sephacel showed that uptake into the 0.2 and 0.3 M NaCl fractions was stimulated several fold by SO2, and uptake into more highly acidic fractions, which was nearly absent in the control, was also greatly increased. Two weeks following the last exposure of the tracheas to SO2, their morphological and mucus-secreting properties showed signs of returning to that of the control.

Animals↗
PubMed1980

Sexual differences in the distribution of epithelial alterations in vitamin A-deficient rats.

Male and female rats maintained on a vitamin A-deficient diet showed sex-related differences in several pathological features. Males developed severe manifestations of hypovitaminosis A earlier than females. They also presented more extensive squamous metaplasia of the trachea and more severe sialoadenitis, especially of the submaxillary gland. Females, on the other hand, presented earlier and more extensive squamous metaplasia of the renal pelvis. The underlying causes of sexual dimorphism in these pathological features are not known, but hormonal influences are suggested.

Aging↗
PubMed1979

Characterization of mucin isolated from rat tracheal transplants.

Subcutaneous rat tracheal grafts yield several milligrams of secretions from which a homogeneous mucin fraction was isolated and purified. Histological evidence demonstrated that a normal mucociliary epithelium and mucous secretion were maintained for the 4-6 weeks of the experiment. The collected secretions were initially characterized by column chromatography on Sepharose CL-6B which separated the excluded high molecular weight mucins (unpurified mucin fraction) from most of the serum-type glycoproteins and proteins, including albumin. A reductive alkylation treatment of the unpurified mucin fraction followed by Sepharose CL-4B chromatography removed contaminating protein and most of the mannose-containing material from the mucin fraction. The void volume material from this column produced a single high molecular weight band upon sodium dodecyl sulfate agarose/acrylamide gel electrophoresis. The purified mucin fraction contained 16.5% protein and primarily galactose, N-acetylglucosamine, N-acetylgalactosamine, and sialic acid. This fraction also underwent beta-elimination in the presence of alkaline borohydride, demonstrating the presence of O-glycosidic linkages.

Amino Acids↗
PubMed1979

The effect of vitamin A on cellular differentiation and mucous glycoprotein synthesis in long-term rat tracheal organ cultures.

Rat tracheal explants maintained as organ cultures exhibited a normal mucocillary epithelium for at least 46 days in the presence of retinyl acetate. In the absence of vitamin A the explant epithelium became quiescent or underwent a metaplastic change to a keratinizing squamous epithelium. This process was accelerated if explants were derived from vitamin A-deficient animals. Autoradiographic examination showed that [3H]glucosamine label accumulated in various cell types in the explant, but especially in the epithelium. It was found that the explants secreted mucous glycoproteins into the medium and that the production and biochemical characteristics of a specific mucin fraction were dependent upon the vitamin A status of the explant.

Animals↗