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P Duprat

Publications and source records attributed to P Duprat.

At least 19 recordsLinked to original sources
PubMed1997

Effect of early body weight and moderate dietary restriction on the survival of the Sprague-Dawley rat.

The effects of ad libitum (AL) feeding, moderate dietary restriction (DR), and initial (6-week) and one-year body weights on the two-year survival of the Sprague-Dawley (SD) rat were evaluated. DR-fed rats were given approximately 75 percent of the adult AL food intake. At two years, body weights of DR-fed males and females were approximately 69 and 58 percent of the AL-fed male and female body weights, respectively. The 2-year survival rate was 80 and 74 percent in DR-fed males and females, respectively, and 28 and 38 percent in AL-fed males and females, respectively. This increase in longevity indicates that DR-fed males and females in carcinogenicity studies would have 14.8 and 9.1 additional weeks of exposure in a 2-year period to test compounds, respectively, compared to AL-fed animals. There was no correlation between initial body weight and 2-year survival in DR or AL-fed rats. There was no association between 1-year body weight and 2-year survival among DR-fed rats. However, AL-fed rats with the greatest 1-year body weight had a lower 2-year average survival compared with the lightest AL-fed rats; this trend was statistically significant only in males. Body weights between the first and second years were statistically significantly correlated for both genders and feeding regimens but no correlation was observed between pretest and 2-year body weights. These findings demonstrate that initial body weight is not the determining factor of 2-year survival, but that the total adult food (caloric) intake is important. In conclusion, moderate dietary restriction prevented excessive body weight gain and greatly increased the 2-year survival of the SD rat. Initial body weights did not correlate to 2-year body weight gain and were not a predictive biomarker of 2-year SD rat survival.

Animals↗
PubMed1995

Quantitative evaluation of glandular and stromal compartments in hyperplastic dog prostates: effect of 5-alpha reductase inhibitors.

The objective of this study was to determine the effects of 2 different 5-alpha reductase inhibitors (finasteride and MK-0434) on the glandular and stromal compartments of hyperplastic canine prostates. In this study, dogs received 1 of the 2 compounds orally, at a dose of 1 mg/kg/day for 16 weeks; control dogs received a placebo. The morphological changes in the glandular and stromal compartments in the prostate were quantitated by a point-counting method on Masson's trichrome-stained sections. Treatment with 5-alpha reductase inhibitors resulted in significant (P < or = 0.05) decreases in mean prostatic volumes, microscopic evidence of prostatic atrophy, and significant (P < or = 0.05) decreases in the absolute volumes of the prostatic glandular and stromal compartments compared to controls. In finasteride-treated dogs, the mean percent change from baseline was: epithelium, -52; lumens, -58; fibrovascular stroma, -41; and smooth muscle, -29. In MK-0434-treated dogs, the mean percent change from baseline was: epithelium, -77; lumens, -58; fibrovascular stroma, -38; and smooth muscle, -42. The effect on the glandular compartment in dogs treated with MK-0434 was slightly greater than in dogs treated with finasteride; however, the effect on the stroma was similar. These results clearly demonstrate that inhibition of 5-alpha reductase enzyme activity affects growth and maintenance of both glandular and stromal compartments of dog hyperplastic prostates. It is likely that the decrease in size of the prostate in finasteride-treated (Proscar) men is due to shrinkage of both glandular and stromal compartments.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

Effects of chronic oral administration of a selective 5 alpha-reductase inhibitor, finasteride, on the dog prostate.

Young mature dogs received finasteride, a selective 5 alpha-reductase inhibitor, orally at 0, 5, 15, and 45 mg/kg/day for 27 or 53 weeks. The effect of finasteride administration on prostatic size and morphology was evaluated macroscopically and microscopically. Changes in glandular and fibromuscular compartments were quantitated by a point counting method on trichrome-stained sections. Finasteride administration induced a decrease of mean prostatic weights and epithelial atrophy in all treated groups. No changes in testicular weights and morphology were observed. The greatest prostatic shrinkage was obtained in the group receiving 45 mg/kg/day for 53 weeks; compared to placebo controls, the percent decreases in absolute volumes occupied by epithelium, lumens, fibrovascular stroma, and smooth muscle were 88, 97, 51 and 72, respectively. These results clearly demonstrate that prostatic shrinkage following finasteride administration results from a decrease in both glandular and fibromuscular compartments.

Administration, Oral↗
PubMed1992

Rat urinary bladder hyperplasia induced by oral administration of carbonic anhydrase inhibitors.

The carbonic anhydrase inhibitors, acetazolamide and MK-0927, were given by oral route to male Sprague-Dawley rats at 200 mg/kg/day and 25 mg/kg/day, respectively, for up to 4 weeks. Sequential necropsies were performed and urinary bladders were examined by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Similar urinary bladder changes were seen with both compounds. SEM evidenced slight multifocal urothelial changes consisting of cell swelling, dissociation, degeneration, and exfoliation after 3 and 5 days of treatment. After 2 and 4 weeks of treatment, elevated or leafy microridges on the luminal cell surfaces were seen together with foci of swollen cells. After a 2-month-recovery-period, the urothelial surfaces were normal. LM and TEM showed multifocal vacuolation of the urothelium associated with inflammation of the underlying lamina propria after 3 and 5 days of treatment. Cellular hypertrophy and hyperplasia of the transitional epithelium was seen after a 5-day treatment, persisted without increasing severity after 2 and 4 weeks of treatment, and totally regressed after the recovery period. It was concluded that, in the rat urinary bladder, oral administration of acetazolamide and MK-0927 induced early degeneration and inflammation followed by epithelial regeneration, resulting in a reversible hyperplasia of the transitional epithelium.

Acetazolamide↗
PubMed1989

Corneal endothelial changes with azone, a penetration enhancer.

Azone has been used to enhance percutaneous absorption. Its ability to improve penetration makes it an attractive candidate for incorporation into ophthalmic formulations to increase therapeutic action of a drug or achieve an equivalent effect with a lower concentration of the active ingredients. Ophthalmic vehicles containing 0, 1, or 2% Azone were studied to determine their ocular irritation potential in the rabbit. The vehicle ingredients were poloxamer 188, hydroxy-ethylcellulose, benzalkonium chloride and phosphate buffer. Rabbits received 30mcl topically of each of the test products three times daily for 29 days. Clinical and histopathological evidence of ocular toxicity occurred in eyes treated with the vehicle containing 1 or 2% Azone, but not in the vehicle without Azone. Clinical signs of ocular irritation were transient and included redness of conjunctivae and iris, discharge and corneal edema. Scanning electron microscopy and semi-thin sections revealed corneal changes characterized by ballooning and vacuolation of endothelial cells resulting in distortion of the typical polygonal appearance. These results indicate that instillation of ophthalmic vehicles containing 1 or 2% Azone damages corneal endothelial cells of the rabbit. It is not clear, however, if this irritation is due to the direct action of Azone on the endothelium or the enhanced penetration of potential irritants in the formulation such as benzalkonium chloride.

Absorption↗
PubMed1989

[Paris V and vertical dimension].

For pedagogic reasons, the department of dento-facial orthopedics of the university of Paris V thinks that: the diagnosis would be based on the evaluation of some characteristics; the prognosis would appreciate possible dento-alveolar compensations; the orthopedic, orthodontic and surgical treatment would coincide perfectly with these diagnosis and prognosis data. The authors' opinion is based on records of dysmorphic and normal persons.

Adolescent↗
PubMed1989

Drug-induced changes in dogs after long term application of a beta-blocker.

Ocular irritation studies are important in the safety evaluation of ocular formulations. There are many reports on acute ocular irritation studies, but almost nothing about prolonged ocular instillation of ophthalmic formulations. This report discusses the predominantly lymphocytic infiltrates seen in the limbus corneae and eyelids of dogs treated with 1 and 2% solutions of L-653,328, an ocular hypotensive beta-adrenoceptor antagonist, for up to 53 weeks. The number of animals affected and severity of the lesions increased with time and concentration. A minimal effect was seen microscopically with the 2% solution as early as 14 weeks. Rabbits treated similarly for 14 weeks had no such changes. The first and only clinical sign in dogs was diffuse pinkness of the bulbar conjunctiva seen from Drug Week 22 onwards. Although not seen with similar molecular structures, given the equivocal results in sensitization studies and the long time required for the development of change, delayed contact hypersensitivity was suspected as the cause of the ocular infiltrates. Simple chronic irritation was not ruled out, however. These findings suggest that delayed contact hypersensitivity in dogs may be a phenomenon not limited to skin, but may also involve the eye after repeated ocular instillation.

Adrenergic beta-Antagonists↗
PubMed1989

Corneal toxicity studies in rabbits and dogs with hydroxyethyl cellulose and benzalkonium chloride.

Hydroxyethyl cellulose (HEC) is used as a viscosity-enhancing agent in ophthalmic formulations to prolong corneal contact time and increase intraocular drug levels. Benzalkonium chloride (BAK) is the preservative most frequently used in ophthalmic formulations. Corneal epithelial changes were seen by slit lamp and light microscopic examination in rabbits but not dogs after multiple instillations of an ophthalmic vehicle containing 0.01% BAK and 0.5% HEC. Microscopically, there was sloughing of superficial epithelial cells and a slight loss of polarity of the basal cells. Formulations with 0.01% BAK and HEC, at concentrations between 0.3 and 0.8%; caused these changes but not with BAK or HEC alone. It was concluded that hydroxyethyl cellulose increased the viscosity and prolonged the contact time of BAK with cornea resulting in corneal epithelial damage in the rabbit. Physiological and anatomical features of the rabbit combined with the increased contact time were concluded to favor these changes in this species. The results confirm that the rabbit is a sensitive and unique species in studies of ocular toxicity of drugs.

Animals↗
PubMed1985

[Different models for the study of a new anti-asthmatic substance].

The various physiopathological components of asthmatic disease are interwoven. Experimental models used to study the sites of impact of an anti-asthmatic substance seek to separate the different mechanisms. The in vitro bronchial tissue model is rarely available in man. Progress is being made towards the development of a multicellular and membrane experimental model. However, it is still difficult to establish links between clinical findings, the results of respiratory function tests and biological results at cell or membrane level. There would seem to be a number of essential basic factors in this area: determination of the categories of asthma studied, regular surveillance of respiratory function tests combining spirometric and plethysmographic studies with pharmacodynamic tests, precise therapeutic protocols and the simultaneous use of several cellular biological models.

Anaphylaxis↗
PubMed1984

Pizotifen increases 5-HIAA urinary excretion in male healthy volunteers.

A single dose of 0.5 mg pizotifen or a placebo was administered to 10 healthy male volunteers in a double blind cross-over trial. 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in hourly urine samples were determined by liquid chromatography with amperometric detection. The 5-HIAA levels were strongly correlated with the HVA levels in control samples (r = 0.95, p less than 0.001). Pizotifen produced a significant increase in the urinary 5-HIAA/HVA ratio over the 3 hours following absorption of the drug (+0.21, +0.18, +0.19, p less than 0.05). The increase demonstrates an interaction between pizotifen and 5-HT metabolism, which may be involved in its antimigraine effect.

Adult↗
PubMed1981

[Interaction between benzene and toluene in long term inhalation exposure in rats (author's transl)].

Industrial chemicals are seldom used as pure substances; hazards resulting from exposure to mixtures have, however not been solved. Our study deals with chronic inhalation toxicity of a mixture of benzene and toluene; few studies have been completed on this subject. Our results show: - leucopenia with benzene alone, at a concentration of 50 p.p.m., that is not detectable in the presence of toluene; - metabolic variations consisting in: a decrease in the phenol urinary rate versus time with benzene alone; a sharp decrease of this rate from the third month of exposure on, in presence of toluene.

Animals↗