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Biomedical subjects

R Kirkpatrick

Publications and source records attributed to R Kirkpatrick.

27 records · Page 2Linked to original sources

Availability of infective larvae of parasitic nematodes of sheep grazing on Kikuyu (Pennisetum clandestinum) pastures in the winter rainfall area.

Thirteen groups of 4 South African mutton Merinos grazed for 4 weeks with the flock on Kikuyu pastures and were slaughtered for total and differential worm counts at necropsy. Subsequently 12 groups of 8 week tracers grazed on the pastures and were killed for worm counts post mortem. The following were present in most sheep: Teladorsagia (syn. Ostertagia) circumcincta, Trichostrongylus axei, Trichostrongylus colubriformis, Dictyocaulus filaria and Oesophagostomum venulosum. Haemonchus contortus, Nematodirus spathiger and Trichuris skrjabini were less frequently recovered. Optimal conditions for infestation of grazing sheep occurred from June (late autumn)--October (spring) when mean temperatures in any 4 week period were less than 20 degrees C and a total of greater than 40 mm of rain fell on 8 or more separate days. When the mean temperatures exceeded 20 degrees C pastures were safe, sheep acquiring less than 1,000 worms in 4 weeks.

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Parasites in sheep grazing on Kikuyu (Pennisetum clandestinum) pastures in the winter rainfall region.

Regular worm counts were done post-mortem on sheep that had grazed on Kikuyu pastures at the Elsenburg Research Station near Stellenbosch, a winter rainfall region. Major species were Trichostrongylus colubriformis, Trichostrongylus axei, while Ostertagia circumcincta was usually present in large numbers. Minor species were Haemonchus contortus, Nematodirus spathiger, Dictyocaulus filaria, Oesophagostomum venulosum, Trichuris spp., Chabertia ovina and larvae of the arthropod Oestrus ovis. Muellerius capillaris caused the formation of nodules in the lungs but were not counted. The trial started in April 1982 and was concluded in March 1984. One hundred and four sheep died or were slaughtered and 99 were examined post-mortem during this period. Total worm burdens rose to a peak of 88,763 (range 67,281-124,735) worms in March 1983, i.e. sheep mortality was such that the flock had to be treated with an anthelmintic in April 1983 to prevent further losses. Kikuyu pastures provide shade, form an excellent mat, the humus layer under the grass retains moisture and is an excellent incubator for preinfective larvae and a protector for infective larvae. If these qualities are combined with more than 100 mm of rain in spring and summer, Kikuyu pastures are a paradise for the free-living stages.

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Evaluation of poly(styrene-4-sulfonate) as a preventive agent for conception and sexually transmitted diseases.

A commercial preparation of a sodium polystyrene sulfonate (designated as N-PSS; its molecular weight is 500000 daltons) was tested as an inhibitor of sperm function and as a preventive agent for conception and the transmission of sexually transmitted diseases. The polymer is an irreversible inhibitor of hyaluronidase and acrosin; its IC50 values are 5.7 microg/mL and 0.5 microg/mL, for hyaluronidase and acrosin, respectively. N-PSS is also a stimulus of human sperm acrosomal loss. It produces maximal acrosomal loss at 2.5 microg/mL. Contraception in rabbits is nearly complete when rabbit spermatozoa are pretreated with 0.5 mg/mL of N-PSS before artificial insemination; however, N-PSS does not immobilize spermatozoa at concentrations as high as 50 mg/mL. N-PSS has broad spectrum antiviral and antibacterial activities. Infection by human immunodeficiency virus and herpes simplex virus are inhibited by N-PSS; 3-log reductions are produced by 7 microg/mL and 3 microg/mL, respectively. N-PSS is active against Chlamydia trachomatis and Neisseria gonorrhoeae. At 1 mg/mL, N-PSS inhibits chlamydial infectivity by more than 90%. N-PSS produces a 3-log reduction in gonococcal growth at 15 microg/mL. In contrast, N-PSS (5 mg/mL) does not affect the growth of Lactobacillus (normal component of the vaginal flora). N-PSS can be classified as a noncytotoxic contraceptive antimicrobial agent. These properties justify bringing a polystyrene sulfonate into clinical trials for its evaluation as a preventive agent for conception and several sexually transmitted diseases.

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Basis for the anti-tumor and chemopreventive activities of glucarate and the glucarate:retinoid combination.

The biochemical basis for the cancer chemopreventive and anti-cancer activities of glucarate, retinoids (13-cis-retinoic acid, hydroxyphenyl retinamide) and their synergistic combination, has been evaluated. Neither alone nor in combination did these agents affect the level in the rat, of enzymes which are (a) known to correlate with reduced risk of carcinogenesis (detoxification enzyme, catalase, glutathione reductase) nor (b) enzymes which correlate with increased risk of carcinogenesis (beta-glucuronidase, xanthine oxidase, glucose-6-phosphate dehydrogenase). Retinoids, but neither glucarate nor its lactone inhibited free radical-induced lipid peroxidation. Both agents alone and synergistically in combination, raise cellular cAMP levels, repress protein kinase C and more generally inhibited DNA synthesis.

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Characterization of cysteamine as a potential contraceptive anti-HIV agent.

Cysteamine (beta-mercaptoethylamine, or MEA) is a thiol-reducing agent and has anti-HIV activity. Because of these properties, cysteamine was evaluated as a vaginal contraceptive and tested for its effects on sperm function and on other sexually transmitted microbes. Cysteamine was contraceptive in the rabbit. Conception was inhibited completely when sperm were pretreated with 500 microg/ml cysteamine and was inhibited by more than 60% when 7.5 mg cysteamine was applied vaginally as a suspension in 50% K-Y Jelly. Cysteamine had multiple effects on spermatozoa. Both acrosin (EC 3.4.21.10) and hyaluronidase (EC 3.2.1.35) were reversibly inhibited by cysteamine. Calculated IC50 values were 370 microg/ml and 150 microg/ml for acrosin and hyaluronidase, respectively. Cysteamine behaved as a poor spermicide when activity was measured by the 30-second Sander-Cramer test. However, sperm motility was inhibited completely when cysteamine was preincubated for 10 minutes prior to motility evaluation, at concentrations as low as 50 microg/ml. The calcium ionophore A23187-induced human acrosome reaction was inhibited by cysteamine (IC50 = 0.5 microg/ml). Neither herpes simplex virus nor Neisseria gonorrhoeae was affected by cysteamine at concentrations as high as 500 microg/ml and 100 microg/ml, respectively. Cysteamine appears to have no effect on normal vaginal flora (i.e., lactobacillus). These results, together with published data, strongly support the further development of cysteamine as a topical contraceptive anti-HIV agent.

Acrosin↗