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Biomedical subjects

J A Reynoldson

Publications and source records attributed to J A Reynoldson.

At least 37 records · Page 2Linked to original sources
PubMed1996

Cyclosporine a immunosuppression in sheep with response enhancement by concomitant ketoconazole.

1. The pharmacokinetics of a single dose of Cyclosporine A (CsA) administered to sheep by intravenous (i.v.) route were examined. 2. Concomitant administration of ketoconazole was found to increase the area under the blood CsA concentration-time curve (AUC) and was effective when administered by the oral or intraperitoneal route. 3. The effects of CsA and ketoconazole on the immune system of sheep were also assessed. 4. A single dose of CsA 5 mg/kg resulted in abrogation of in vitro lymphocyte function manifest at 24 h after injection of CsA. Normal responsiveness recovered in 48-72 h. Numbers of T lymphocytes in peripheral blood were elevated transiently at 48 h although no other significant alteration in lymphocyte subsets was observed with this treatment. 5. Concomitant ketoconazole administration enhanced the CsA-induced suppression of in vitro lymphocyte responses. Blood levels of CsA (AUC values to 24 h) were significantly elevated with concomitant ketoconazole administration and depression of lymphocyte responses to mitogens were also significantly enhanced. An increase in the proportion of T4 positive cells in the blood was observed at 48 h and at 7 days after administration of CsA with ketoconazole. 6. These findings indicate that CsA effectively abrogates immunocompetence in the sheep and this immunosuppressive effect is enhanced by concomitant administration of ketoconazole.

Animals↗
PubMed1996

A comparison of two methods for assessing drug sensitivity in Giardia duodenalis.

This study compared two published methods for assessing the in-vitro drug sensitivity of Giardia duodenalis: the 3H-thymidine incorporation assay (BOREHAM et al. 1984) which radiometrically measures nucleic acid synthesis; and inhibition of adherence (MELONI et al. 1990). Giardia trophozoites were exposed to a range of concentrations of metronidazole or albendazole for 24 hours and their viability measured by both assays in order to determine the degree of correlation between the two methods of measuring viability. Due to the different modes of action of metronidazole and albendazole on Giardia, measuring the inhibition of adherence appears to be a more accurate indicator of trophozoite viability than measuring 3H-thymidine incorporation.

Albendazole↗
PubMed1996

Giardia duodenalis: exposure to metronidazole inhibits competitive interactions between isolates of the parasite in vitro.

The competitive interactions of genetically distinct isolates of Giardia duodenalis with different growth rates were studied in vitro. Electrophoretic analysis of mixed cultures showed that competition between 2 cloned isolates occurs under normal in vitro culture conditions, with faster-growing isolates outcompeting those with slower growth rates. The addition of sublethal concentrations of metronidazole to clonal mixtures in vitro prevented the competitive exclusion, which was seen in normal culture. This apparently occurred because the drug reduced the growth rate of the faster-growing but not the slower-growing clone.

Animals↗
PubMed1995

In vitro drug susceptibility of 29 isolates of Giardia duodenalis from humans as assessed by an adhesion assay.

Twelve isolates of Giardia duodenalis from Caucasian hosts in the Perth metropolitan area, along with 16 isolates from Aborigines in the north of Western Australia and the reference isolate P1C10 were examined for their in vitro drug sensitivity. Dose-response curves were constructed for each isolate for metronidazole, the most common clinically used antigiardial agent, as well as for the benzimidazole compound albendazole. Less than a 9-fold variation was found in the susceptibility of the isolates to albendazole, while for metronidazole there was well over a 16,000-fold variation between the same group of isolates. In addition, it was found that isolates of Giardia obtained from Aboriginal hosts were significantly less sensitive to albendazole than those obtained from Caucasians. The results of this study have important implications for the continued use of metronidazole and the potential use of albendazole for the treatment of giardiasis.

Albendazole↗
PubMed1994

Evaluation of the effects of albendazole and metronidazole on the ultrastructure of Giardia duodenalis, Trichomonas vaginalis and Spironucleus muris using transmission electron microscopy.

The three closely related parasitic protozoa, Giardia duodenalis, Trichomonas vaginalis and Spironucleus muris, all have very different sensitivities to albendazole and metronidazole. Ultrastructural studies reveal that the cytoskeletal elements of the ventral disk in G. duodenalis are affected by albendazole, whereas the other two parasites, neither of which possess this structure, are not affected by albendazole to the same extent. This suggests that albendazole may be having its primary affect on G. duodenalis by binding to cytoskeletal proteins and ultimately causing death of the parasite. Death may be occurring as the parasite loses its ability to adhere to the intestinal villi and obtain nutrients. Metronidazole showed a different pattern of activity against the three parasites. The evidence obtained from these ultrastructural studies supports the current theory that metronidazole adversely affects protozoa by disrupting inner cell membranes.

Albendazole↗
PubMed1993

Xylazine or medetomidine premedication before propofol anaesthesia.

The duration of action and cardiopulmonary effects of propofol (6.55 mg/kg intravenously), xylazine (0.8 mg/kg intramuscularly), medetomidine (30 micrograms/kg intramuscularly), xylazine plus propofol (3 mg/kg intravenously) and medetomidine plus propofol (3 mg/kg intravenously) were compared in dogs. A cannula inserted into a raised carotid artery before the drugs were given allowed the continuous recording of blood pressure and heart rate and the measurement of arterial pH, PCO2, PO2, bicarbonate and base balance. Xylazine and medetomidine premedication prolonged propofol anaesthesia in dogs. Propofol alone reduced blood pressure and transiently raised heart rate. The apnoea and hypoxaemia induced by propofol alone also occurred in the premedicated groups with hypoxaemia being most evident in the medetomidine/propofol group. Bradycardia was a common feature in all the dogs given xylazine or medetomidine, but hypertension was consistently recorded in all the dogs given medetomidine.

Acid-Base Equilibrium↗
PubMed1993

The prevalence of Giardia and other intestinal parasites in children, dogs and cats from aboriginal communities in the Kimberley.

OBJECTIVE: To determine the prevalence of Giardia duodenalis and other intestinal parasites in children, dogs and cats from Aboriginal communities in the west Kimberley region of Western Australia. DESIGN: A four-year parasitological survey of faecal specimens from humans and faecal and intestinal specimens from dogs and cats. SETTING: Local hospital servicing Aboriginal communities surveyed in this study and the Veterinary School, Murdoch University. POPULATION: Children (under 14 years) and adults, as well as dogs and cats, from five Aboriginal communities. RESULTS: G. duodenalis was the most prevalent parasite in children and adults (32.1% in children, n = 361; 12.5% in adults, n = 24). Human infections with Hymenolepis nana (20.5%) and Entamoeba coli (13.0%) were also common. Ancylostoma duodenale (1.3%), Pentatrichomonas hominis (1.0%), Chilomastix mesnili (0.52%), Entamoeba hartmanni (0.52%), Sarcocystis sp. (0.52%), Trichuris trichiura (0.26%), Enterobius vermicularis (0.26%), Strongyloides stercoralis (0.26%) and Isospora belli (0.26%) were present at low rates. Dogs were most commonly infected with Ancylostoma caninum (51.1%) and G. duodenalis (17.0%). Cats were found to have a high prevalence of Ancylostoma tubaeforme (18.2%), Toxoplasma gondii (18.2%), Isospora felis (15.1%) and Spirometra erinacei (15.1%). CONCLUSIONS: This study has shown that children from Aboriginal communities in the west Kimberley region of Western Australia, particularly in the age group one to five years, are commonly infected with intestinal parasites. The dogs and cats in these communities are also infected. The high prevalence rates of Giardia and other enteric parasites in this survey are indicative of poor living conditions and low levels of hygiene. In addition, the high prevalence of hookworm and Giardia infection in dogs and hookworm and Toxoplasma infection in cats is of potential zoonotic significance for humans in these communities.

Adolescent↗
PubMed1993

The efficacy of two electron transport inhibitors (720C80 and 993C76) on murine strongyloidiasis: a comparison with albendazole.

The clinical efficacy of albendazole (ABZ) in the treatment of chronic uncomplicated strongyloidiasis has been reported to be highly variable. In our murine model of strongyloidiasis a single oral dose of 5 and 10 mg kg-1 ABZ reduced (at day 4 post infection) the faecal larval count (FLC) by 54.2 +/- 12.5% and 81.5 +/- 10.2%, respectively. 100 mg kg-1 ABZ reduced the FLC by 100%. Two inhibitors of protozoan and filarial electron transport (720C80 and 993C76) inhibited the endogenous O2 consumption of intact infective (L3) larvae of S. ratti by > 50% at 2 x 10(-5) M in vitro, and reduced the FLC by 72 +/- 9.3% and 62.0 +/- 10.3% respectively in vivo, at a dose of 70 mg kg-1. These results suggest that compounds designed as selective inhibitors of protozoan electron transport have significant efficacy against murine strongyloidiasis and may prove useful in the management of human strongyloidiasis.

Albendazole↗
PubMed1993

Activities of several benzimidazoles and tubulin inhibitors against Giardia spp. in vitro.

Previous studies in our laboratory have shown that albendazole is effective against Giardia spp. in vitro and in vivo, prompting an investigation of the effects of several related benzimidazoles (BZs) on the viability of this protozoan parasite. A range of BZs was tested, and their effects were compared with those of a number of microtubule inhibitors. The effects produced by the two types of drugs were markedly similar, namely, trophozoite detachment and distortion of morphology and general structure, indicating a potential antimicrotubule mode of action for BZs. Mebendazole, albendazole, and fenbendazole proved to be among the most effective BZs tested, exhibiting apparent irreversibility. Nocodazole, oxfendazole, and albendazole sulfoxide, among others, produced transient inhibitions only. Further studies are required to evaluate all available BZs and other antigiardial agents to ensure the development of the most effective and safest antigiardial agent possible.

Albendazole↗
PubMed1992

Albendazole as a future antigiardial agent.

Albendazole, one of the more recently developed of the benzimidazole carbamate anthelmintics, has the broadest spectrum of activity of the benzimidazoles released to date. In this article, Jim Reynoldson, Andrew Thompson and John Horton discuss the role of this drug in the fight against giardiasis.

Journal Article↗
PubMed1992

The uptake and conversion of L-[U14C-] aspartate and L-[U14C-] alanine to 14CO2 by intact trophozoites of Giardia duodenalis.

1. Intact trophozoites of Giardia duodenalis (clone P1C10) took up and metabolised L-[U14C-] aspartate to 14CO2 at rates of 10.27 +/- 0.76 and 27.6 +/- 2.07 ng hr-1 10(-6) cells in a simple maintenance medium (MM) and in a complex bile supplemented (BIS-33) medium respectively. 2. Intact trophozoite of G. duodenalis (clone P1C10) also took up and metabolised L-[U14C-] alanine to 14CO2 at rates of 20.6 +/- 1.1 and 91.4 +/- 17.5 ng hr-1 10(-6) cells in the simple (MM) and complex (BIS-33) medium respectively. 3. trophozoite sonicates contained significant levels of aspartate-2-oxoglutarate transaminase (AST; EC 2.6.1.1) and alanine-2-oxoglutarate transaminase (ALT; EC 2.6.2.2.). Specific activities (at 23 degrees C) were 95.1 +/- 11.3 and 87.3 +/- 9.8 nmol (min)-1 (mg protein)-1 respectively. 4. These observations suggest that Giardia has the capacity to utilise aspartate and alanine and possibly other amino acids as alternative sources of energy. 5. The extrusion or uptake of alanine by Giardia trophozoites may be dictated by the intracellular redox-status of the protozoan parasite or components in the external mileu.

Alanine↗
PubMed1991

In vivo efficacy of albendazole against Giardia duodenalis in mice.

The antigiardial effects of albendazole were demonstrated in vivo using experimental infections of Giardia duodenalis in mice. These results complement previous in vivo studies in which albendazole was shown to have more potent antigiardial action than the currently applied antigiardial drugs. In mice, 2-4 doses (greater than 100 mg/kg twice daily) were required for complete inhibition of cyst excretion and full elimination of trophozoites from the small intestine. The high doses necessary in mice were not unexpected and are discussed in light of the possible pharmacokinetics of albendazole in the animal model used in this study.

Albendazole↗
PubMed1991

In vitro and in vivo efficacy of epsiprantel against Echinococcus granulosus.

In vitro, epsiprantel at a concentration of 10 micrograms ml-1 caused tegumental damage and death of protoscoleces, juveniles (seven-day-old) and adult (37-day-old) Echinococcus granulosus. Degenerative changes and death occurred more rapidly in the older parasites. Similarly, epsiprantel was more effective against adult (28-day-old) than seven-day-old experimental infections of E granulosus in dogs. Oral doses of 2.5, 5 and 7.5 mg kg-1 were greater than 96 per cent, 99.9 per cent and 99.99 per cent active, respectively, against mature worms, whereas in seven-day-old infections doses of 5, 7.5 and 10 mg kg-1 produced greater than 94 per cent, 90 per cent and 99.8 per cent reduction in worm burdens, respectively. No side effects from treatment were seen.

Administration, Oral↗
PubMed1990

Central and peripheral alpha-adrenoceptor actions of amitraz in the dog.

The aim of this study was to determine the contribution of alpha 2- and alpha 1-adrenoceptor agonist activity of the formamidine, amitraz, on peripheral circulation in the dog. Intra-arterial injections of amitraz (0.25-5.0 micrograms/kg) produced a dose-dependent increase in perfusion pressure in the autoperfused hind limbs of methoxyflurane-anaesthetized dogs. A constant blood flow to the hind limbs was maintained using a peristaltic pump. Intravenous phentolamine (0.5 mg/kg), prazosin (35 micrograms/kg) and yohimbine (10 micrograms/kg) in separate experiments antagonized the vasoconstrictor actions of amitraz and produced a parallel shift to the right of the amitraz dose-response curve. Cumulative doses of amitraz (0.5-15 micrograms/kg) given by intracisterna magna (i.c.m.) injections reduced mean arterial pressure and heart rate in a dose-dependent manner. Similar responses were produced by intravenous amitraz but at much higher doses. In separate experiments amitraz-induced hypotension (doses up to 25 micrograms/kg i.c.m.) was prevented by pre-treatment with yohimbine (30 micrograms/kg i.c.m.) but not prazosin (20 micrograms/kg i.c.m.). Both antagonists partially inhibited the bradycardia produced by amitraz. It is concluded that amitraz stimulates alpha 1- and alpha 2-adrenoceptors to produce vascular constriction. The central hypotensive action of amitraz appears to be mediated by alpha 2-adrenoceptors; however, both receptor subtypes appear to be stimulated to produce bradycardia.

Animals↗
PubMed1990

Effects of amitraz on nerve conduction and neuromuscular transmission in anaesthetised dogs.

Ataxia is an occasional side effect of amitraz when used as a wash to treat dogs with demodectic mange. In the present study, successive doses of 0.5, 2, 5 and 10 mg kg-1 amitraz were given intravenously at intervals of nine minutes to thiopentone/methoxyflurane/oxygen anaesthetised dogs. The amplitude of the evoked muscle action potential to electrical stimulation of the right ulnar nerve and the muscle refractory period were unchanged by increasing doses of amitraz but there was a progressive and significant decrease in nerve conduction velocity. The minimum recorded nerve conduction velocity (50.7 +/- 1.5 m s-1) was still within an adequate range. From these results it appears that the ataxia following amitraz is unlikely to be attributable to peripheral mechanisms. The concurrent amitraz-induced rise in mean arterial pressure and bradycardia was consistent with previous findings in which alpha 2-adrenoceptors were shown to be the major mediators.

Action Potentials↗
PubMed1989

Plasma thromboxane B2 levels in horses experimentally infected with Strongylus vulgaris.

Plasma thromboxane B2 (TXB2) the stable inactive metabolite of thromboxane A2 (TXA2), was measured daily by specific radioimmunoassay in three groups of animals before and after experimental infection with Strongylus vulgaris. Infection of four 'parasite naive' foals produced a typical acute syndrome with intermittent but statistically insignificant rises in TXB2 levels. Interpretation of results was complicated by the presence of a non-septic peritonitis associated with implantation of the foals with electrodes for recording myoelectrical activity. In two foals of similar age, with some natural exposure to S. vulgaris, there was little or no clinical response to infection and increases in TXB2 were absent. Baseline levels were also much lower, indicating that the peritonitis may have affected the results obtained in the first group of foals. Severe mesenteric arteritis was confirmed at necropsy in all six foals. A third group of yearling horses, all with natural exposure to the parasite, were generally resistant to infection. One animal developed arteritis with clinical signs of diarrhoea and mild colic, and also showed intermittent increases in TXB2. The mean plasma TXB2 level after infection was significantly higher than in the control period, although absolute levels were lower than those recorded in the 'parasite naive' foals. Other animals in this group had low TXB2 levels and minimal arteritis was found at necropsy. These results indicate that although infection appears to have an effect on plasma TXB2, the changes are inconsistent and not reliable indicators of the presence of verminous arteritis. The results also confirm the difficulty in establishing infection and the variability of the response in animals with previous exposure.

Animals↗