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Biomedical subjects

P Benard

Publications and source records attributed to P Benard.

At least 19 recordsLinked to original sources

Cortisol disposition and production rate in horses during rest and exercise.

The influence of a 56-km endurance exercise on cortisol kinetics and production rate was evaluated in six horses administered [3H]cortisol. Exercise resulted in an immediate two- to threefold increase in plasma cortisol, with values returning very rapidly to preexercise levels. During exercise, clearance and steady-state volume of distribution of total cortisol were greatly increased (338 +/- 95 vs. 137 +/- 34 ml.kg-1.h-1 for clearance and 359 +/- 82 vs. 229 +/- 18 ml/kg for volume of distribution), whereas the terminal half-life decreased significantly (0.97 +/- 0.16 vs. 1.55 +/- 0.33 h). The estimated cortisol production rate was 4.41 +/- 1.06 micrograms.kg-1.h-1 at rest and 26.75 +/- 5.11 micrograms.kg-1.h-1 during exercise. We conclude that exercise triggers a large increase (x 6) in the adrenal secretion rate, which is not accurately reflected by the more limited increase (x 2-3) in plasma cortisol concentration, the actual measurement of plasma cortisol clearance being a prerequisite to assessment of adrenal gland function during exercise.

Animals↗

Pharmacokinetics of 14C-N-N'-dicyclopropyl-methyl-piperazine-dichlorhydrate. 3rd communication: whole-body autoradiographic study in Cynomolgus monkeys after oral administration.

A distribution study was carried out on Cynomolgus monkeys (Macaca fascicularis) dosed orally with 14C-labelled N-N'-dicyclopropyl-methyl-piperazine-dichlor-hydrate 14C-Ino 2628-CZ and sacrificed 2, 8 and 24 h after dosage, using whole-body autoradiography. It is demonstrated that radioactivity is found in all the body; high intakes occur in melanin containing tissues, in blood-forming organs, and in accessory genital glands. Moreover, radioactivity crosses the blood-brain barrier and is mainly localized in hippocampus, caudate, putamen and frontal cortex.

Administration, Oral↗

Pharmacokinetics of 14C-N-N'-dicyclopropyl-methyl-piperazine-dichlorhydrate. 1st Communication: balance of elimination, plasma and blood kinetics, metabolism in rats.

N-N'-Dicyclopropyl-methyl-piperazine-dichlorhydrate (Ino 2628-CZ) is a novel inotropic compound. The absorption, distribution, excretion and metabolism of radiochemically labelled 14C-Ino 2628-CZ has been studied in male and female rats after intravenous and oral administration. The compound was mainly excreted during the first 24 h after both administrations, although traces of radioactivity were still measured at 7 days post-dose. About 20% of the drug is excreted in the urine unchanged. Nine metabolites were separated, four of them being characterized.

Administration, Oral↗

Pharmacokinetics of 14C-N-N'-dicyclopropyl-methyl-piperazine-dichlorhydrate. 2nd communication: tissue distribution in rats.

The distribution of radioactivity in rats after intravenous or oral administration of 14C-labelled N-N'-dicyclopropyl-methyl-piperazine-dichlorhydrate (14C-Ino 2628-CZ) demonstrated that the labelled compound was widely distributed in the body. An important diffusion of the isotope was found in the central nervous system, the gastric mucosa and several glands. Only small amounts of radioactivity were found in these organs 24 h after dosage.

Animals↗

Hematological and plasma biochemical disturbances in experimental molybdenum toxicosis in sheep.

Two groups of 4 sheep received a daily iv injection of sodium heptamolybdate (100mg/day) or of saline for 2 weeks to study the hematological and plasma biochemical effects of molybdenum toxicosis. In molybdenum-dosed sheep, there was hypercupremia, mild anemia due to the decrease of copper concentration in the liver and moderate hepatocellular damage probably due to a direct toxic effect of molybdenum against the liver.

Anemia, Hypochromic↗

Autoradiographic distribution of [14C]-labelled pimonidazole in rhabdomyosarcoma-bearing rats and pigmented mice.

The hypoxic cell radiosensitizer [2-14C] pimonidazole (2-nitro-alpha-(piperidinomethyl)-l-imidazole ethanol) was injected i.p. into pigmented mice and rats bearing transplanted rhabdomyosarcoma. The injected dose level was 200 mg/kg, and the delivered activity was 96 microCi/kg. Whole-body autoradiography was carried out on all animals. We noted an extensive whole-body distribution of radioactivity. At short intervals, the autoradiograms were characterized by an accumulation of radioactivity in the metabolic and excretory organs (liver, kidney, urinary tract, and intestinal content) as well as in lymphomyeloid tissues (thyroid gland, suprarenal gland, and hypophysis) and salivary glands. In pigmented mice, the uveal and biliary tracts were the highest labelled. The liver and particularly the renal medulla were identified as sites of retention of radioactivity. In the tumor the radioactivity was detected only in peripheral regions, with higher uptake in viable zones than in necrotic islets.

Animals↗

Distribution and tumor penetration properties of a radiosensitizer 2-[14C] misonidazole (Ro 07-0582), in mice and rats as studied by whole-body autoradiography.

The hypoxic cell radiosensitizer 2-[14C] misonidazole: 1-(2-nitro-1-imidazolyl)-3-methoxy-2-propanol (Ro 07-0582) MISO was administered to mice, control rats, and rats bearing chemically induced rhadbdomyosarcoma. The dose injected was 250 mg/kg and the delivered activity was 100 microCi/kg. Whole-body autoradiography was performed in all animals. We noted the highest uptake of radioactivity in the liver and the kidney. In the liver there was an accumulation of [14C] from 5 min to the 2 hour after treatment, followed by a decrease; this observation is probably related to the metabolic pathway of the drug. The radioactivity was also concentrated in the renal medulla (30 min after injection); this organ is the excretion route for most of the misonidazole or its metabolites. Fecal excretion is also important following biliary elimination. Radioactivity is present in the central nervous system in the first hours after dosage. [14C] Tumor activity was lowest 5 min after IP treatment. By contrast, 12 h after administration of labeled compound the highest activity was detected in this tissue.

Animals↗

Effect of flunixin meglumine on the breakdown of the blood-aqueous barrier following paracentesis in the canine eye.

The protein and PGE2 metabolite content of the aqueous humor from untreated and flunixin meglumine pretreated dogs was determined prior to and after anterior chamber paracentesis. In the untreated dogs the concentrations of protein and PGE2 metabolite in aqueous humor were greatly elevated secondary to paracentesis. Intravenously administered flunixin meglumine (1.1 mg/kg or 2.2 mg/kg) significantly reduced these inflammatory parameters, confirming that prostaglandins are involved in the stability of the blood-aqueous barrier by paracentesis in the canine eye. The clinical implication of these results is that intravenous administration of flunixin meglumine before intraocular surgery should be considered as an adjunct therapy to reduce intraoperative and postoperative uveitis.

Animals↗

Enzyme patterns of the organs of the goose. Effects of fattening on liver enzymes.

The distribution of some enzymes in the organs of the goose was investigated: Creatine-kinase was specific for muscles, Glutamate Dehydrogenase for liver and Gamma-Glutamyl Transferase for pancreas and liver. The production of fatty liver induced an important dilution of liver enzymes except for Lactate Dehydrogenase which was only moderately lowered. This latter enzyme is probably one of the most interesting markers of liver disturbances while fattening is occurring.

Animals↗

Gamma Glutamyl Transferase in domestic animals.

In domestic animals, Gamma Glutamyl Transferase is mainly in the kidneys, the pancreas and the intestine; its liver activity is relatively high in cows, horses, sheep and goats and very low in dogs, cats and birds. The use of plasma reference values can help to interpret the variations of serum GGT mainly in hepatobiliary diseases of cattle, sheep, goats and cholestatic disorders of dogs. Urinary GGT is a good test of kidney toxic damage.

Age Factors↗

Protection against mercuric chloride nephrotoxicity by cold exposure in rats.

The influence of cold exposure (+ 1 degree C for 24 h) was studied in rats dosed i.p. with 0, 2.5 or 5.0 mumol HgCl2/kg. Cold exposure of controls caused an increased diuresis and solute elimination, except sodium, with almost no variations in urine alkaline phosphatase (ALP) and gammaglutamyl transferase (GGT). Proximal tubule brush border damage was demonstrated by a marked increase in ALP and GGT in HgCl2-dose animals at room temperature. Cold exposure protected against this kidney damage.

Animals↗

Value of so called cholestasis markers in the dog: an experimental study.

In experimental bile obstruction in dogs, the most sensitive change in blood plasma composition is the increase in alkaline phosphatase activity which occurs after eight hours. Maximum alkaline phosphatase activities (approximately 100 times normal values) occur between the fifth and the 14th day. The increase in activity is accompanied by smaller increases in gamma-glutamyl transferase activity, and total bilirubin concentration also increases to a smaller extent and less regularly. Cholestasis also induces an intense cytolysis which is demonstrated mainly by increases in glutamate dehydrogenase and alanine amino transferase activities which are more intense and lasting than those induced by 0.5 ml/kg carbon tetrachloride.

Alanine Transaminase↗

[Gamma glutamyl transferase and cancer (author's transl)].

Attention has been drawn in recent years to the diagnostic interest offered by increases in serum gamma GT in the detection of liver metastases and various cancers in man. Although this analysis is not specific and presents a few false positive and negative results, it seems however profitable to include it either in detection or in supervision tests. Furthermore, in the rat and mouse, this enzyme practically absent from the adult liver, reappears during liver cancer Whatever the cause: this onco-foetal character may be useful to exploit in studies of experimental carcinogenesis, but does not seem to be a valid model for the increases observed in man.

Animals↗

Methoxyethylmercury nephrotoxicity: effects on enzymuria and kidney function.

The fungicide, methoxyethylmercury chloride, was given in a saline solution to four groups of Sprague-Dawley C D rats (5 male, 5 female) as a single injection (IP) of 0, 0.5, 1.0, and 2.0 mg Hg/kg. In a three-day period, no changes were observed in urine collected every 24 h from rats given 0 or 0.5 mg Hg/kg; 1 mg Hg/kg induced only a transient increase of urine gamma glutamyl transferase (x 4) and alkaline phsophatase (x 2.5) on the day 2; 2.0 mg Hg/kg caused an early increase of enzymuria (day 1 and day 2) and a decrease of Na+, Cl-, K+, urea, and creatinin excretion. Urine enzymes and total mercury excretion were higher in males. These time-related variations of enzymuria, compared to previous results with Hg Cl2, could reflect the existence of metabolites more toxic than the native compound.

Alkaline Phosphatase↗