Combination chemotherapy is more effective in postspillage prophylaxis for hydatid disease than either albendazole or praziquantel alone.
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Albendazole↗
Biomedical subjects
D H Taylor
Publications and source records attributed to D H Taylor.
Physiologically based pharmacokinetic modeling of the pregnant rat: a multiroute exposure model for trichloroethylene and its metabolite, trichloroacetic acid.
A physiologically based pharmacokinetic (PB-PK) model was developed to describe trichloroethylene (TCE) kinetics in the pregnant rat exposed to TCE by inhalation, by bolus gavage, or by oral ingestion in drinking water. The kinetics of trichloroacetic acid (TCA), an oxidative metabolite of TCE, were described by a classical one-compartment pharmacokinetic model. Among the required model parameters for TCE, partition coefficients (PCs) and kinetic constants for oxidation were determined by vial equilibration and gas uptake methods, respectively. The fat:blood PC was 33.9; the blood:air PC was 13.2; and the fetal tissue:fetal blood PC was 0.51. TCE was readily metabolized with high substrate affinity. In naive and pregnant female rats the maximum velocities of oxidative metabolism were 10.98 +/- 0.155 and 9.18 +/- 0.078 mg/kg/hr, while the estimated Michaelis constant for the two groups of rats was very low, 0.25 mg/liter. The first-order rate constant for oral absorption of TCE from water was 5.4 +/- 0.42/hr-1 in naive rats. With TCA, the volume of distribution (0.618 liter/kg) and the plasma elimination rate constant (0.045 +/- 0.0024/hour) were estimated both from intravenous dosing studies with TCA and from an inhalation study with TCE. By comparison of the two routes of administration, the stoichiometric yield of TCA from TCE was estimated to be 0.12 in pregnant rats. To develop a data base for testing the fidelity of the PB-PK model, inhalation and bolus gavage exposures were conducted from Day 3 to Day 21 of pregnancy and a drinking water exposure from Day 3 to Day 22 of pregnancy. Inhalation exposures with TCE vapor were 4 hr/day at 618 ppm. The TCE concentration in drinking water was 350 micrograms/ml and the gavaged rats received single daily doses of 2.3 mg TCE/kg. Time varying physiological parameters for compartment volumes and blood flows during pregnancy were obtained from the published literature. Using the kinetic parameters determined by experimentation, TCE concentrations in maternal and fetal blood and TCA concentrations in maternal and fetal plasma were predicted from the PB-PK model by computer simulation and compared favorably with limited data obtained at restricted time points during pregnancy for all three routes of exposure. On the basis of the PB-PK model, fetal exposure to TCE, as area-under-the-curve, ranged from 67 to 76% of maternal exposure. For TCA the fetal exposure was 63 to 64% of the maternal exposure. The fetus is clearly at risk both to parent TCE and its TCA metabolite.(ABSTRACT TRUNCATED AT 400 WORDS)
Administration, Inhalation↗
Rapid recovery of Echinococcus granulosus following 'successful' albendazole therapy in a gerbil model.
Peritoneal Echinococcus granulosus in gerbils was treated with albendazole. Both early and late infections were studied; response to albendazole therapy and the ability of the parasite to recover after treatment was found to depend on dose and length of therapy. Even after treatment at 50 mg/kg for 2 months late infections retained the ability to recover over 3 months.
Albendazole↗
Echinococcus multilocularis: ultrastructural effect of in vivo albendazole and praziquantel therapy, singly and in combination.
Cotton rats with Echinococcus multilocularis infections of one month's standing were treated for six months with albendazole (50 mg kg-1 day-1), or praziquantel (500 mg kg-1 day-1), or both drugs simultaneously. The germinal layer of albendazole-treated cysts differed little from control tissue apart from marginal increase in cyton vesiculation and the presence of small lamellated residual bodies. Protoscolex tissue appeared unaffected. The germinal layer of praziquantel-treated cysts differed markedly from control tissue, with increased vesiculation and mitochondrial number in those with intact germinal layers, and disintegration and detachment of the layer in other cysts. Protoscoleces were necrotic. After combined therapy, the germinal layer was either intact but with increased vesiculation and residual bodies present, or was disintegrating and detaching from the laminated layer.
Albendazole↗
Albendazole is effective against established Echinococcus granulosus in gerbils: comparison of serum concentrations achieved by gavage and feed administration.
Serum levels of albendazole sulphoxide in gerbils infected with Echinococcus granulosus and treated with albendazole (20 or 50 mg kg-1 day-1) by gavage were dose dependent, whereas albendazole administered in feed at a rate equivalent to 80 mg kg-1 day-1 achieved serum levels calculated to be equivalent to those produced by administration of 40 mg kg-1 day-1 by gavage. This regimen, over a three-month period, was effective and reduced parasite weight to 4.6% of that in control gerbils, and the treated parasite tissue showed ultrastructural changes ranging from severe accumulation of residual bodies to total disintegration of the germinal layer.
Administration, Oral↗
Comparison of albendazole, mebendazole and praziquantel chemotherapy of Echinococcus multilocularis in a gerbil model.
The efficacy of albendazole (50 mg/kg/d), mebendazole (50 mg/kg/d) and praziquantel (500 mg/kg/d) against established intraperitoneal infections of Echinococcus multilocularis in gerbils was compared by monitoring parasite weight and making ultrastructural observations on treated and untreated material. Praziquantel was the most active protoscolicidal agent, reducing protoscolex viability to less than 2%, although it did not inhibit cyst growth. Albendazole was the most effective agent in reducing cyst growth and was, when compared with other regimes significantly more effective than mebendazole (p less than 0.05), praziquantel (p less than 0.01) or untreated controls (p less than 0.01).
Albendazole↗
Combination chemotherapy of Echinococcus granulosus--in vitro studies.
Both benzimidazole carbamates and isoquinoline compounds have activity against protoscoleces of Echinococcus granulosus in culture in vitro; combinations of albendazole sulphoxide and praziquantel are more effective than either agent alone.
Albendazole↗
In vitro culture of Echinococcus multilocularis: protoscolicidal action of praziquantel and albendazole sulphoxide.
The metacestode stage of Echinococcus multilocularis was cultured in vitro. Sensitivity of protoscoleces to the presence of albendazole sulphoxide, praziquantel and methanol was assessed. 10 micrograms/litre of praziquantel or 500 micrograms/litre of albendazole sulphoxide significantly reduced protoscolex viability. The presence of methanol (at 0.25%) had no significant effect. In vitro culture of E. multilocularis can be used to assess possible chemotherapeutic agents.
Albendazole↗
Echinococcus multilocularis: in vivo results of therapy with albendazole and praziquantel.
The effects of albendazole and praziquantel on the growth of Echinococcus multilocularis were studied in cotton rats. Albendazole (20 and 50 mg/kg) reduced parasite weight and increased the length of survival of infected animals but viable infection was present after treatment. In an in vitro system albendazole sulphoxide entered cysts of E. multilocularis passively. Praziquantel 100 mg/kg was ineffective but 500 mg/kg significantly inhibited growth. A combination of albendazole and praziquantel was no more effective than either agent alone.
Albendazole↗
Determination of the minimum time of praziquantel therapy required for the in vitro treatment of protoscoleces of Echinococcus granulosus.
Ovine and equine protoscoleces of Echinococcus granulosus were cultured for 26 days with our without praziquantel and viability assessed, by eosin exclusion, for cultures in various drug concentrations (50, 250 and 500 micrograms/l) and periods of exposure (1, 3 or 7 days (d] before removing/'rescuing' to drug-free medium. Drug efficacy was proportional to drug concentration and to length of exposure. At higher drug concentrations shorter exposures were required to produce the effect of continuous drug treatment, 1d therapy at 500 micrograms/l killing 96% ovine protoscoleces by day 14 whereas 7d therapy at 50 micrograms/l was required to produce a similar effect. Equine protoscoleces appeared marginally less susceptible than those of ovine origin. The relevance of the results in the need for peri-operative prophylaxis against spilled protoscoleces in man is discussed.
Animals↗
Optimal timing of post-operative albendazole prophylaxis in E. granulosus.
Recurrence is an important problem following operations for hydatid disease in man. Significant protection against an intraperitoneal injection of 5000 protoscoleces was achieved in gerbils by a one-month course of albendazole (10 mg kg-1 day-1). However, when prophylaxis was delayed for 15 days after peritoneal inoculation albendazole had no protective effect. Whilst higher serum concentrations probably allow treatment of older infections, these data suggest that protoscoleces are most easily killed by therapy immediately following spillage.
Albendazole↗
The current management of hydatid disease.
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Echinococcosis↗
Studies on the effect of short term, high dose praziquantel treatment against protoscoleces of ovine and equine Echinococcus granulosus within the cyst, and in vitro.
Protoscoleces of Echinococcus granulosus were subjected to high concentrations of praziquantel (10-1000 micrograms/ml medium or cyst fluid) for a short, 10 min duration in vitro or in situ within cysts. Drug efficacy was then monitored either by in vitro culture in drug-free medium and/or by passage into rodents. The in vitro test of effectiveness suggested that ovine-derived protoscoleces were more sensitive than those of equine origin, and that the in vitro method of treatment was more successful than that performed in situ. However, the subsequent passage of treated protoscoleces, whether immediately after in situ or in vitro exposure or after culture in drug-free medium, indicated that the in situ administration was as effective as the in vitro treatment. Both methods reduced cyst burdens in rodents to 9-15% of control infections.
Animals↗
Effects of computers on the practice.
Recent reports predicting the future of veterinary practice give reason for concern. They point out the challenges to the profession: improve practice management, increase client visitation, improve income, practice better medicine. The computer is the tool that will give the practitioner the ability to do this. The decision to invest in a computer system is an important one. It will affect nearly every aspect of the practice, so one must carefully consider all the factors. Fortunately, if one makes the decision to computerize and carries it out properly, the computer will have a dramatic, positive effect on your practice.
Animals↗
2-Deoxyglucose uptake in the developing rat brain upon pre- and postnatal exposure to trichloroethylene.
Trichloroethylene (TCE) is a widespread contaminant of drinking water sources. The effects of TCE on 2-deoxyglucose uptake by brain tissue were examined in pups from rat dams exposed to TCE in their drinking water. The pups were exposed throughout gestation and lactation. Deoxyglucose uptake in the cerebellum, hippocampus and whole brain of the pups during the first 21 days of life was measured using a modification of the 2-deoxy-D-glucose (2-DG) technique. We determined that TCE at a nominal concentration of 312 mg/l significantly depressed 2-DG uptake in the whole brains and cerebella of 7- to 21-day old pups. 2-DG uptake was also lower in the hippocampus of exposed pups at 7, 11 and 16 days, but returned to control levels by 21 days. No overt toxicity, such as lower body or brain weight, was observed at this exposure level. This decrease in 2-DG uptake reflects a decrease in glucose uptake and/or metabolism in the brains of animals exposed to TCE.
Age Factors↗
Effect of trichloroethylene on the exploratory and locomotor activity of rats exposed during development.
Trichloroethylene (TCE) is a common contaminant of underground water supplies. To examine the effect of TCE on the developing central nervous system, rats were exposed to TCE throughout gestation until 21 days postpartum via their dams' drinking water. TCE concentrations of 312 mg/l, 625 mg/l and 1250 mg/l were tested. Exploratory behavior was higher in 60- and 90-day old male rats which were exposed to any level of TCE. The effect of TCE-exposure on locomotor activity (running wheel) was also examined in 60-day old males (625 and 1250 ppm exposure groups). Locomotor activity was significantly higher in rats exposed to 1250 ppm TCE. These data suggest that TCE has long-term effects on behaviour.
Aging↗
Effects of chlorine dioxide on thyroid function in neonatal rats.
Chlorine dioxide (ClO2), an alternative to chlorine for drinking water disinfection, has been implicated as a potential antithyroid agent (Bercz et al., 1982). Because antithyroid compounds are known to alter neurobehavioral development, the present study was designed to determine if perinatal exposure to ClO2 affects behavioral activity in rat pups. The activity cage system was designed to monitor the development of locomotor activity of a litter of pups between ages 14-21 d. Pups were exposed to ClO2 either directly, by gavaging 14 mg/kg . from age 5 to 20 d, or indirectly via their dams' drinking water in concentrations of 2, 20, or 100 mg/l from gestation to weaning (21 d postpartum). Although the activity of the indirectly exposed group was not different from controls, the gavaged group showed significantly depressed activity for d 18 and 19 postpartum. The T4 levels of the 21-d-old pups was significantly depressed in the 100-mg/l ClO2 group. The gavaged pups showed an even greater T4 depression, which correlates with their activity levels. These data support the hypothesis that ClO2 affects thyroid function and suggests that a slight depression in T4 can result in developmental delays.
Administration, Oral↗
Seasonal and daily plasma corticosterone rhythms in American toads, Bufo americanus.
Concentrations of corticosterone were measured in the plasma of American toads, Bufo americanus, on a seasonal basis using a radioimmunoassay technique. Two populations of toads, maintained under different light conditions, were monitored to observe the effects of photoperiod on the seasonal rhythm of plasma corticosterone. Under a natural photoperiod toads demonstrated a rhythm consisting of a spring peak and a fall peak in corticosterone concentration. Toads maintained under a 12L:12D photoperiod all year round demonstrated a similar rhythm with peaks in the spring and fall. This suggests that an endogenous (circannual) rhythm of corticosterone may be playing an important role in the seasonal change of overt behavior and physiology of Bufo americanus. A daily rhythm of corticosterone was also detected in toads when blood samples were taken every 4 hr. When compared to a previously published circadian rhythm study of locomotor activity, the surge in corticosterone concentration for the day occurred at 1730 just prior to the peak in locomotor activity.
Animals↗