Inhibition of glycosidases by Astragalus lusitanicus and correlation with toxicity.

This study determined whether Astragalus lusitanicus inhibits glycosidase enzymes other than alpha-mannosidase. Plasma collected from lambs given fresh A lusitanicus inhibited beta-glucosidase and beta-galactosidase, indicating the presence of inhibitors in their blood. The residual activity of these enzymes was also modified in tissues of dead animals. beta-glucosidase activity was reduced in liver and kidney specimens with pronounced effects in tissues of animal that presented with prominent clinical signs of poisoning; beta-galactosidase activity was decreased by 88.5 to 95% in kidney, while that of liver remained unchanged. Fractions of the plant butanol extract inhibited the gycosidase enzymes. Chemical analysis revealed the presence of hypaphorin in the extract of A lusitanicus. As a tryptophan derivative, this alkaloid may play a role in the toxicity of this legume.

Toxicology of Astragalus lusitanicus Lam.

Astragalus lusitanicus is a toxic legume grown in Morocco and in some other Mediterranean countries. In small ruminants, poisoning by this plant is dominated by nervous signs characterized by many cycles of excitement-depression. Macroscopic examination of poisoned animals showed congestive lesions and oedema in the brain and lungs. Microscopic lesions consisted mainly of vacuolar degeneration in neurons, hepatocytes and in spleen and kidney cells. Serum activity of AST and CK as well as blood glucose and urea were increased as a result of poisoning. However, serum activity of alpha-mannosidase was not modified as is the case in locoism. Chemical investigations showed that A. lusitanicus does not contain swainsonine or miserotoxin and its selenium concentration is very low. However, this legume contains indolizidin alkaloids and a first compound was purified and identified.

Clinical and analytical studies of sheep dosed with various preparations of Astragalus lusitanicus.

Dosing different preparations and extracts of Astragalus lusitanicus to lambs showed the fresh plant or its dry powder were highly toxic while the ethyl acetate or methanol extract did not cause toxicosis, suggesting the toxic principle is an extremely water soluble compound. The animals alternated excitement and depression, with cardiac and respiratory disorders terminally. Alpha-mannosidase inhibition was not detected in blood of dosed lambs, but an inhibitory activity was in tissues from lambs given the fresh plant or its powder. There was increased aspartate aminotransferase and creatine kinase activity, suggesting skeletal muscle and neurological effects. Thin-layer chromatography and the alpha-mannosidase inhibition assay did not detect swainsonine in ethyl acetate, methanol or water: methanol plant extracts.

Human fluorosis in Morocco: analytical and clinical investigations.

A clinical investigation of human chronic fluorosis, known as "Darmous" in Morocco, was carried out in Youssoufia city and its region. Fluoride concentrations were also measured in soil and water from this area and in urine collected from the surveyed persons; soil and to a lesser extent water were rich in fluoride (948.6 +/- 356.2 micrograms/g and 1.03 +/- 0.19 micrograms/ml, respectively). Fluoride concentrations in urine were heterogenous and varied from 0.17 to 47.5 micrograms/ml. There was a good correlation between these values and the age of the sampled persons. This study revealed that 14% of the urine samples were at or above the maximum fluoride concentration in urine from non-intoxicated individuals (ie 10 micrograms/ml). Dental caries, teeth loss and teeth pigmentation and deviation were the most frequent dental effects in this area. Skeletal effects were mostly joint pain and exostosis. With the exception of dental caries, teeth and bone abnormalities were more frequent and pronounced in people living in the rural area.

Thiamphenicol pharmacokinetics in beef and dairy cattle.

The pharmacokinetics of thiamphenicol were investigated in 10 calves and six lactating cows. It was found that this drug is rapidly absorbed (15 min) following intramuscular injection with an absorption rate constant and a bioavailability of 8.7 h-1 and 84%, respectively. The drug appears to be widely distributed into various body fluids, yielding a volume of distribution (Vd(area) of approximately 0.9 l/kg. The micro-rate constants indicated that the antibiotic rapidly diffuses into the peripheral compartment (k12 > k21). Elimination from plasma is relatively rapid, with a biological half-life of about 1.75 h. Thiamphenicol appears shortly in milk (15 min) after its intravenous administration, and gives milk to plasma concentration ratios greater than one between 4 and 12 h.

Thiamphenicol pharmacokinetics in sheep.

The pharmacokinetics of thiamphenicol were investigated after intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administration to sheep. It was found that the drug is almost completely absorbed following intramuscular injection, with a bioavailability of about 87.5%. Thiamphenicol appears to be widely distributed into extravascular compartments, yielding a volume of distribution [V(b)] of approximately 1 l/Kg. Elimination from the blood is relatively rapid, with a biological half-life of about 1.5 h. Oral treatment showed that thiamphenicol is absorbed from the gastrointestinal tract yielding very low plasma concentrations which were maintained for at least 24 h. Although only 30% of the oral dose was systemically available, in contrast to chloramphenicol, thiamphenicol is truly absorbed when given orally to adult sheep. One possible reason for this observation is that rumen flora do not biotransform this drug as they do for chloramphenicol. Metabolism investigations are, however, needed to confirm this finding.

[Pharmacokinetics and plasma protein binding of sulfamethoxypyridazine in camels (Camelus dromedarius)]. / Etude de la pharmacocinétique et de la liaison aux protéines plasmatiques de la sulfaméthoxypyridazine chez le dromadaire (Camelus dromedarius).

The pharmacokinetics of sulfamethoxypyridazine (SMPD) were investigated in the camel after intravenous and oral administration. After intravenous injection, the plasma concentration of the drug followed the kinetics of a two-compartment model. The steady-state volume of distribution (Vss) of 0.47 l/kg suggested that sulfamethoxypyridazine was mostly distributed within the vascular compartment and the strongly vascularized tissues. The elimination from the body was rather slow, with a biological half-life [t1/2(beta)] and a total plasma clearance of about 9.5 h and 0.037 l/kg.h, respectively. Oral treatment showed that the maximum plasma concentration was reached 17 hours post drug administration and that the bioavailability ranged around 57%. Study of the plasma protein binding showed that the percentage of SMPD binding to plasma proteins varied from 47 to 72% and seemed to be concentration-dependent. The total binding capacity and the dissociation constant at equilibrium were 196 micrograms/ml and 335 micrograms/ml, respectively.

Pharmacokinetics and distribution of thiamphenicol in sheep given repeated intramuscular doses.

The pharmacokinetics of thiamphenicol and its distribution in various body fluids were studied after repeated intramuscular injection in clinically healthy adult Moroccan crossed Sardi-D'Man sheep. Thiamphenicol was rapidly absorbed from injection sites yielding peak plasma concentrations within 15-30 min. The elimination from the blood was also rapid, with a biological half-life of 1.51 +/- 0.51 h. The distribution pattern of thiamphenicol revealed that this antibiotic can penetrate many remote sites of the body. With the exception of the cerebrospinal fluid, concentrations of the drug in other body fluids were higher than the corresponding plasma concentrations.

Determination of thiamphenicol in bovine plasma by liquid chromatography.

A liquid chromatographic method is described for the measurement of thiamphenicol in bovine plasma. The plasma (1 mL) is extracted with ethyl acetate. After the solvent is evaporated under a stream of nitrogen, the residue is reconstituted in methanol-water and analyzed by reverse-phase liquid chromatography with UV detection at 224 nm. The intra-day recoveries for bovine plasma spiked with 5 and 50 micrograms/mL of thiamphenicol were 102 and 101%, respectively, with coefficients of variation of 2.40 and 0.28%, respectively. The interday recoveries for the 5 and 50 micrograms/mL samples were 103 and 101%, respectively, with coefficients of variation of 3.40 and 0.94%, respectively. The sensitivity of the method allows quantitation to at least the 100 ng/mL level.

Analysis of detomidine in horse blood, plasma and urine samples utilizing a sensitive gas chromatography-mass spectrometry method.

Chemical ionization- and electron impact ionization-selective ion monitoring provided a simple and sensitive method for measuring detomidine (Domosedan), a potent sedative-analgesic drug for horses and cattle. Chemical ionization was at least 10 times more sensitive than electron impact ionization. By using propranolol as an internal standard, we found that the recovery of detomidine from the extraction procedure used in this study was greater than 75% for plasma, whole blood, or urine samples. Approximately 68% of detomidine was bound to plasma protein and 53% was bound to red blood cells.