Effective purification of human chorionic gonadotropin and production of highly specific polyclonal anti-ßHCG as a component of radioimmunoassay kit.

This study aimed to purify human chorionic gonadotropin (HCG) from the urine of pregnant women with high biological activity (10811 IU/mg) and purity (98.2%), by simple capturing of HCG using DEAE Sepharose FF and polishing using Sephacryl S200 HR. The HCG obtained was characterized by SDS-PAGE and dissociated into alpha and beta subunits using the urea treatment method. The ßHCG subunits were injected into rabbits for the production of highly specific polyclonal anti-ßHCG antisera. The polyclonal anti-ßHCG was locally produced in rabbits and assessed for binding titer (1/10000), displacement (84.8%), and specificity (98.8%). Purified HCG along with locally prepared polyclonal anti-ßHCG antisera were used as basic components of the in-house Radioimmunoassay system for quantitative estimation of HCG in human serum.

Vulvar intraepithelial neoplasia (VIN)--diagnostic and therapeutic challenges.

PURPOSE: Vulvar intraepithelial neoplasia (VIN) represents a current diagnostic and therapeutic challenge. The present retrospective study is an institutional experience on the diagnosis and management of VIN. METHODS: One hundred and thirteen women with VIN were reviewed and analyzed. Diagnosis was established by colposcopically directed biopsies whereas treatment was performed by either a surgical or a laser CO2 approach. RESULTS: The mean age of all VIN patients was 47.4 years. The most common symptom was pruritus (60.1%). The majority of the lesions were multifocal (N = 64, 56.6%) and located in the non-hairy part of the vulva (87.6%). VIN management consisted of laser CO2 treatment in 51 patients (45.1%), surgical treatment in 37 (32.7%) whereas 25 VIN, cases were managed by conventional medical treatment. The risk of disease relapse was not associated with VIN grade (p = 0.35) nor with the treatment modality used (p = 0.42). The risk of disease relapse was significantly higher for multifocal lesions (p < 0.001). Long-term follow-up of our patients showed that four patients (3.5%) developed an invasive vulvar carcinoma. CONCLUSION: Our study confirms other reports concerning the diagnostic and treatment difficulties of the management of VIN. Although the benefits of treatment are obvious there seems to be no guarantee that invasion will not occur.

Effect of griseofulvin on the toxicity of signal grass (Brachiaria decumbens) in sheep.

The effect of griseofulvin treatment on signal grass (Brachlaria decumbens) toxicity was studied in 27 male Wiltshire Indigenous Malaysian crossbred sheep. Grazing on signal grass generally decreased the activity of the drug metabolizing enzymes in livers and kidneys. Griseofulvin oral administration of 5 mg/kg body weight for 5 consecutive days every other week for 10 w increased the hepatic concentration of cytochrome P-450 and the activity of phase II drug metabolizing enzymes (UDP-glucuronyltransferase and glutathione-S-transferase) while it decreased the hepatic and increased the renal activity of phase I enzymes aminopyrine-N-demethylase and aniline-4-hydroxylase. Griseofulvin did not protect sheep against B decumbens toxicity as 5/7 animals treated with griseofulvin and grazed on B decumbens showed signs of the plant toxicity.

Disposition kinetics of enrofloxacin (Baytril 5%) in sheep and goats following intravenous and intramuscular injection using a microbiological assay.

The pharmacokinetics of enrofloxacin were determined in Desert sheep and Nubian goats after intravenous and intramuscular administration of Baytril at the dose of 5mgkg(-1) bodyweight. A two compartment open model best represented the intravenous plasma concentration versus time data in both species. Comparisons between the means of the pharmacokinetic parameters obtained after intravenous administration of enrofloxacin (Baytril) revealed a significantly smaller distribution rate constant (lambda(1)) and consequently a shorter half-life time of distribution in sheep (P<0.05). A larger volume of the central compartment (Vc) was observed in goats (P<0.05). Similar values were obtained for sheep and goats for the remaining parameters. Plasma concentrations versus time data of enrofloxacin after 5mgkg(-1) intramuscular administration of Baytril in sheep and goats were adequately described by one-compartment open model with first order absorption and elimination. There were no significant differences between sheep and goats in any of the estimated pharmacokinetic parameters. The results indicate that the pharmacokinetics of enrofloxacin did not differ significantly between sheep and goats; similar intravenous and intramuscular dose rates of enrofloxacin should therefore be applicable to both species. Owing to the high variations in MIC (minimal inhibitory concentration) of sensitive veterinary pathogens, it is recommended that enrofloxacin dosage regimens be calculated according to the sensitivity of the individual pathogen, site of infection and clinical response, than by following a preset dosage regimen.

Comparative pharmacokinetics of theophylline in camels (Camelus dromedarius) and goats (Caprus hircus).

A comparative randomized crossover study was conducted to determine the pharmacokinetics of theophylline in male and female camels (Camelus dromedarius) and goats (Caprus hircus). Theophylline is an established 'probe drug' to evaluate the drug metabolizing enzyme activity of animals. It was administered by the intravenous (i.v.) route and then intramuscularly (i.m.) at a dose of 2 mg/kg. The concentration of the drug in plasma was measured using a high-performance liquid chromatography (HPLC) technique on samples collected at frequent intervals after administration. Following i.v. injection, the overall elimination rate constant (lambda z,) in goats was 0.006 +/- 0.00076/min and in camels was 0.0046 +/- 0.0008/min (P < 0.01). The elimination half-life (t 1/2 lambda z) in goats (112 .7 min) was lower than in camels (154.7 min) (P < 0.01). The apparent volume of distribution (Vz) and the total body clearance (Cl) in goats were 1440.1 +/- 166.6 ml/kg and 8.9 +/- 1.4 ml/min/kg, respectively. The corresponding values in camels were 1720.3 +/- 345.3 ml/kg and 6.1 +/- 1.0 ml/min/kg, respectively. After i.m. administration, theophylline reached a peak plasma concentration (Cmax) of 1.8 +/- 0.1 and 1.7 +/- 0.2 microg/ml at a post-injection time (Tmax) of 67.5 +/- 8.6 and 122.3 +/- 6.7 min in goats and camels, respectively. The mean bioavailability (T) in both goats and camels was 0.9 +/- 0.2. The above data suggest that camels eliminate theophylline at a slower rate than goats.

Effect of phenobarbitone treatment against signal grass (Brachiaria decumbens) toxicity in sheep.

The effect of phenobarbitone against signal grass (Brachiaria decumbens) toxicity was studied in 26 male crossbred sheep. Grazing on signal grass significantly decreased the concentration of cytochrome P-450 and the activity of drug metabolizing enzymes, viz. aminopyrine-N-demethylase, aniline-4-hydroxylase, UDP- glucuronyltransferase and glutathione-S-transferase in liver and kidneys of affected sheep.Oral administration of phenobarbitone (30 mg/kg body weight) for five consecutive days before grazing on B. decumbens pasture, and thereafter, for three consecutive days every two weeks, resulted in significant increases in hepatic and renal activities of drug-metabolizing enzymes. The induction of drug metabolizing activity in sheep grazing on signal grass group was found to be lower than in animals given phenobarbitone alone. Induction by phenobarbitone provided a degree of protection against the toxic effects of B. decumbens as indicated by the delay in the appearance of signs of toxicity. Furthermore, these were much milder compared to those in the sheep not treated with phenobarbitone. The present study suggests that phenobarbitone-type cytochrome P-450 isoenzyme-induction may increase resistance against signal grass (B. decumbens) toxicity in sheep.

The effect of signal grass (Brachiaria decumbens) on drug-metabolizing enzymes in sheep and comparison with normal cells.

The effect of Brachiaria decumbens (signal grass) on drug-metabolizing enzymes was studied in sheep. After 14 d of grazing a pure signal grass pasture, significant declines were observed in hepatic aminopyrine N-demethylase and aniline 4-hydroxylase (phase I biotransformation) and in conjugative enzymes UDP-glucuronyltransferase and glutathione S-transferase. Kidney enzymes were significantly decreased except for UDP-glucuronyltransferase. Enzyme activities were also compared for normal sheep and cattle livers and kidneys. Lower activities were found in cattle, indicating that factors other than biotransformation are responsible for the clincial tolerance of cattle to B. decumbens toxicity.

Disposition kinetics of tylosin administered intravenously and intramuscularly in desert sheep and Nubian goats.

The pharmacokinetic behaviour of tylosin was compared in five Desert sheep and five Nubian goats. The animals were given a single dose of 20% tylosin (15 mg/kg), either intravenously (i.v.) or intramuscularly (i.m.). Following i.v. administration, the volumes of distribution and the elimination half-life times were similar in both species, whereas in goats a greater volume of the central compartment and faster clearance were observed. For the i.m. route, similar pharmacokinetics were observed in both species. The bioavailability (f) of the drug in goats (0.84 +/- 0.11) was not significantly higher than that in sheep (0.73 +/- 0.08). The present study has shown that, despite the significant differences in some of the drug pharmacokinetic parameters between sheep and goats for the i.v. route, identical intravenous and intramuscular dosage regimens of tylosin may be recommended for the two species.

Pharmacokinetics of amoxicillin trihydrate in Desert sheep and Nubian goats.

The pharmacokinetics of amoxicillin were studied in five Desert sheep and five Nubian goats after intravenous (i.v.) or intramuscular (i.m.) administration of a single dose of 10 mg/kg body weight. Following i.v. injection, the plasma concentration-versus-time data were best described by a two-compartment open model. The kinetic variables were similar in both species except for the volume of the central compartment (Vc), which was larger in sheep (p<0.05). Following i.m. injection, except for the longer half-life time of absorption in goats (p<0.05), there were no significant differences in other pharmacokinetic parameters between sheep and goats. The route of amoxicillin administration had no significant effect on the terminal elimination half-life in either species. The bioavailability of the drug (F) after i.m. administration was high (> 0.90) in both species. These results indicate that the pharmacokinetics of amoxicillin did not differ between sheep and goats; furthermore, because of the high availability and short half-life of absorption, the i.m. route gives similar results to the i.v. route. Therefore, identical intramuscular and intravenous dose regimens should be applicable to both species.

Pharmacokinetics of ampicillin trihydrate following intravenous administration to water deprived Nubian goats.

The present study reports the effect of water deprivation in the Nubian goat on the pharmacokinetics of ampicillin trihydrate following intravenous administration at a dose rate of 10 mg kg(-1). Water deprivation for two days, which resulted in about 7.5 per cent loss in bodyweight, produced no significant effects on the pharmacokinetic parameters of the drug. In dehydrated goats that had lost an average of 9.8 per cent of their initial bodyweights, within three days of water deprivation, ampicillin showed significantly slower clearance values (P<0.001), without affecting significantly the pharmacokinetic parameters describing the distribution of the drug. After four days of water deprivation a dehydration level at which goats lost an average of 12.6 per cent bodyweight was reached, which resulted in significant alterations in the distribution and elimination pharmacokinetic parameters of ampicillin. The volume of the central compartment (Vc) and the volume of distribution at steady state (Vdss) were significantly decreased (P<0.01) leading to significant elevation in plasma concentrations of the drug (P<0.01) compared with the normally hydrated animals. In water deprived goats, significantly slower clearance of the drug (P<0.001) and reduced elimination rate constant (P<0.01) with the subsequent increases in the half-life time were also observed. Dosage intervals between the usual doses of ampicillin can be increased in dehydrated goats and concentrations which were high enough to kill susceptible microorganisms could still be achieved.

Effect of dehydration on the pharmacokinetics of oxytetracycline hydrochloride administered intravenously in goats (Capra hircus).

1. The effects of various levels of dehydration induced by water deprivation were studied in six Nubian goats on the pharmacokinetics of oxytetracycline after intravenous administration (5 mg/kg). 2. In goats that had lost an average of 7.6% body weight after 2 days of water deprivation, the elimination rate constant of the drug was significantly decreased (P<0.01) and the total body clearance was significantly slower (P<0.001). No statistically significant changes were observed in the pharmacokinetic parameters describing the distribution of the drug at this dehydration level. 3. Water deprivation for 3 or 4 days resulted in a level of dehydration at which the goats lost an average of 10.3% or 12.7% of their body weight, respectively; significant changes were observed in the pharmacokinetic distribution and elimination parameters of oxytetracycline. The volume of distribution at steady state was significantly decreased (P<0.01). Significantly slower total body clearance (P<0.001) and subsequent prolongation of the elimination half-life were found at these dehydration levels. 4. The alterations caused by dehydration on the disposition kinetics of the drug should be considered for better definition of dosage regimens for sick, dehydrated animals.

Comparative pharmacokinetics of ampicillin trihydrate, gentamicin sulphate and oxytetracycline hydrochloride in Nubian goats and desert sheep.

In this investigation the pharmacokinetics of three commonly used antibiotics, ampicillin trihydrate (10 mg/kg), gentamicin sulphate (3 mg/kg) and oxytetracycline hydrochloride (5 mg/kg), given intravenously, were each studied in five Nubian goats and five desert sheep. The pharmacokinetic parameters were described by a two-compartment open model. The results indicated that there were significant differences between the two species in some kinetic parameters of ampicillin and oxytetracycline but not gentamicin. Ampicillin elimination half life (t[1/2beta]) in goats (1.20 h) was shorter than that in sheep (2.48 h), and its clearance (Cl) significantly higher in goats (2921 mL/h x kg) compared to sheep (262 mL/h x kg) (P < 0.01). Ampicillin volume of distribution (Vd[area]) was found to be significantly larger in goats (5673 mL/kg) than in sheep (992 mL/kg) (P < 0.01). For oxytetracycline, the t(1/2beta) in goats (3.89 h) was significantly shorter than that in sheep (6.30 h) and the Cl value in goats (437 mL/h x kg) was significantly higher than in sheep (281 mL/h x kg). The results suggest that when treating sheep and goats, the pharmacokinetic differences between the two species must be considered in order to optimize the therapeutic doses of ampicillin and oxytetracycline.

The effect of experimental fascioliasis on the pharmacokinetics of antipyrine and sulphadimidine in desert sheep.

Healthy adult male desert sheep were experimentally infected with Fasciola gigantica, to investigate the influence of experimental fasciolasis on the pharmacokinetics of antipyrine and sulphadimidine. Each animal received 500 metacercariae orally. The experimental infection was confirmed histologically, by detection of Fasciola eggs in faeces and by measuring the activities of the enzymes sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST) in plasma during the course of the disease. Changes in the pharmacokinetics of antipyrine and sulphadimidine were reported in the experimentally infected animals. Significant prolongation of antipyrine half life was observed 16 weeks after infection. The half-life of sulphadimidine was also significantly prolonged 5, 9 and 16 weeks after infection. Clearance of the sulphonamide was decreased significantly 5 and 9 weeks after infection and it regained its pre-infection value 16 weeks after infection.

The effect of water deprivation on the pharmacokinetics of antipyrine and sulphadimidine following intravenous administration in Nubian goats.

The effect of water deprivation on the pharmacokinetic parameters of antipyrine and sulphadimidine in the Nubian goat was studied. Water deprivation, to a level of dehydration at which the animals lost an average of 7.5% body weight, resulted in a significant reduction in antipyrine clearance (p < 0.05), and a consequently increased AUC value (p < 0.05). No effect was observed on the distribution parameters of the drug. In dehydrated animals which had lost an average of 10% or 12.5% of their body weight owing to water deprivation, significant changes were found in the distribution and elimination pharmacokinetic parameters of antipyrine and sulphadimidine. The volume of distribution was significantly decreased, resulting in elevated plasma levels for the two drugs compared to normally watered animals. Significant decreases in clearance and subsequent prolongation of the elimination half-lives were observed during these periods of water deprivation. These changes in the disposition kinetics of the two drugs may be attributed to the loss of total body water and extracellular fluids and changes in the liver and kidney functions taking place during dehydration.

Accuracy of freely adapted resin record bases.

Forty autopolymerizing resin record bases were made; 10 bases were adapted by finger pressure on tray resin material dough, 10 bases by sprinkling orthodontic resin, and 10 of repair material by either of the two previous techniques. Stone casts and acrylic resin bases were sectioned at canine, premolar, and molar coronal planes. Width of the gap between base and cast and the thickness of the base were measured at the buccal sulcus, ridge crest, lateral palatal slope, and palatal midpoint. Measurements were made through the eyepiece of a microhardness tester. Statistical analysis of 760 pairs of measurements revealed that (1) sprinkled bases fit better than finger-adapted dough bases; (2) specifically formulated materials fit better than repair material with either technique; (3) gap widths differed at different areas of the same base; and (4) gap width was not related to base thickness at any point.

The effect of praziquantel on the activities of some drug-metabolizing hepatic enzymes in rabbits.

The effect of oral administration of praziquantel at different dose levels on the activities of metabolizing hepatic enzymes (aminopyrine N-demethylase, aniline 4-hydroxylase and UDP-glucuronyltransferase) was studied in healthy locally bred rabbits. The pathological changes resulting from drug's toxicity were assessed histologically, by measurement of total plasma protein concentration and of the activities of the plasma enzymes sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST). No significant changes were obtained after praziquantel administration at dose levels of 40 and 800 mg/kg body weight, whereas 1600 mg/kg and 2000 mg/kg of praziquantel resulted in a significant decrease in the activities of the three drug-metabolizing hepatic enzymes under investigation in the livers of treated rabbits. All rabbits which received praziquantel at the dose rate of 2000 mg/kg died 10-20 hours following praziquantel treatment.