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Biomedical subjects

D Pessayre

Publications and source records attributed to D Pessayre.

197 records · Page 11Linked to original sources
PubMed1977

Isoniazid-rifampin fulminant hepatitis. A possible consequence of the enhancement of isoniazid hepatotoxicity by enzyme induction.

The authors report 6 cases of fulminant hepatitis in patients treated with isoniazid and rifampin. In 4 of these patients, the treatment had been started within 3 days after a general anesthesia. The course of the disease was remarkably similar in all 6 patients: (1) the time interval from the beginning of the isoniazid-rifampin administration to the onset of jaundice was 6 to 10 days; (2) disorders of consciousness appeared less than 3 days after the onset of jaundice; (3) serum transaminases were 26 to 80 times the upper limit of normal; (4) the main liver lesion was centrilobular necrosis; (5) hypersensitivity manifestations were absent; (6) all 6 patients recovered. Fulminant hepatitis might be attributable to a hepatotoxic metabolite of isoniazid, the production of which would be attributable to a hepatotoxic metabolite of isoniazid, the production of which would be increased as a consequence of the enzyme-inducing effect of rifampin and, possibly, other drugs administered for general anesthesia.

Adolescent↗
PubMed1975

Pancreatic cholera (W.D.H.A. syndrome). Histochemical and ultrastructural studies.

Results of light and electron-microscopic studies of primary pancreatic tumor and of metastasis in a new case of Pancreatic Cholera (P.C.) are reported. The primary tumor but not the metastases, contained unusual, large cystic glandular formations, lined both by pancreatic-duct- and small-intestine-like epithelia and closely connected with the endocrine proliferation. A part from a few D-cells, the endocrine tumoral cells could not be identified by histochemical stainings. Their ultrastructural pattern, with small secretory granules (diameter less than 300 nm) and numerous cytoplasmic bunches of filaments, was very similar to that of gastric and duodenal D1-cells. Normal duodenal D1-cells have been said to produce gastric inhibitory peptide, a substance structurally and biologically similar to the vasoactive intestinal peptide actually secreted by the tumor. The normal histological appearance of gastric, gallbladder, jejunal, ileal, right and left colonic mucosae is consistent with the responsibility of the tumoral secretion in the impairment of gut functions in P.C.

Acute Kidney Injury↗
PubMed1975

Pancreatic cholera. Sudies on tumoral secretions and pathophysiology of diarrhea.

Tumoral secretions and pathophysiology of diarrhea were studied in 1 patient with pancreatic cholera. High concentrations of vasoactive intestinal peptide were found in both systemic blood and tumoral extracts, together with increased plasma levels of calcitonin and protaglandins E and Falpha. Gastric inhibitory peptide and gastrointestinal and pancreatic hormones were absent from the tumor, except for small amounts of glucagon, and their blood levels were normal. Decreased basal but normal pentagastrin-stimulated gastric acid secretion, normal basal and secretin-stimulated pancreatic secretion, increased volume of gallbladder bile with high bicarbonate, and low bile salt concentrations were observed, but the electrolyte content and flow rate of fluid passing the duodenojejunal junction were within normal limits. Small intestine was found to be the origin of the water and electrolyte fasting losses. Jejunum was the site of bicarbonate secretion. Jejunal glucose and leucine-stimulated water and sodium transports were also strikingly decreased, whereas the absorption rates of the sugar and amino acid were normal. Colon reabsorbed high amounts of water and sodium but increased potassium losses. Biological effects of vasoactive intestinal peptide may explain most of the patient's upper digestive secretion abnormalities and small intestinal function impairments, whereas secondary aldosteronism might explain the modified colonic function.

Adult↗
PubMedDate not supplied

Inhibition of the mitochondrial oxidation of fatty acids by tetracycline in mice and in man: possible role in microvesicular steatosis induced by this antibiotic.

Intravenous administration of high doses of tetracycline may produce severe microvesicular steatosis of the liver in man. A similar disease is observed after ingestion of drugs which inhibit hepatic mitochondrial fatty acid beta-oxidation and in subjects with various inborn defects in this metabolic pathway. We therefore determined the effects of tetracycline on the mitochondrial oxidation of fatty acids in mice and in man. In vitro, addition of tetracycline 0.25, 0.5, 1 or 2 mM inhibited by 15, 38, 56 and 65%, respectively, the formation of beta-oxidation products during incubation of palmitic acid with mouse liver mitochondria and the various cofactors necessary for beta-oxidation. Inhibition was reversible. Inhibition appeared even greater with human liver mitochondria. Tricarboxylic acid cycle activity, assessed by the in vitro formation of [14C]CO2 from [1-14C]acetylcoenzyme A by mouse liver mitochondria, was inhibited by 25, 32 and 43%, respectively, in the presence of 0.5, 1 or 2 mM of tetracycline. In vivo, administration of tetracycline, 0.25 or 1 mmole per kg, inhibited by 53 and 84%, respectively, the exhalation of [14C]CO2 during the first 3 hours following the administration of a tracer dose of [U-14C]palmitic acid. Administration of tetracycline, 0.0625, 0.25 or 1 mmole per kg, 6 hr before the measurement, increased hepatic triglycerides by 100, 170 and 250%, respectively. After 1 mmole per kg, accumulation of hepatic triglycerides was maximum at 24 hr, reaching 9-fold the control value; liver histology showed microvesicular steatosis at 6 and 24 hr. We conclude that tetracycline inhibits the mitochondrial oxidation of fatty acids in mice and in man.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Drug-induced immunotoxicity.

Immune-related drug responses are one of the most common sources of idiosyncratic toxicity. A number of organs may be the target of such reactions; however, this review concentrates mostly on the liver. Drug-induced hepatitis is generally divided into two categories: acute hepatitis in which the drug or a metabolite destroys a vital target in the cell; immunoallergic hepatitis in which the drug triggers an adverse immune response directed against the liver. Their clinical features are: a) low frequency; b) dose independence; c) typical immune system manifestations such as fever, eosinophilia; d) delay between the initiation of treatment and onset of the disease; e) a shortened delay upon rechallenge; and f) occasional presence of autoantibodies in the serum of patients. Such signs have been found in cases of hepatitis triggered by drugs such as halothane, tienilic acid, dihydralazine and anticonvulsants. They will be taken as examples to demonstrate the recent progress made in determining the mechanisms responsible for the disease. The following mechanisms have been postulated: 1) the drug is first metabolized into a reactive metabolite which binds to the enzyme that generated it; 2) this produces a neoantigen which, once presented to the immune system, might trigger an immune response characterized by 3) the production of antibodies recognizing both the native and/or the modified protein; 4) rechallenge leads to increased neoantigen production, a situation in which the presence of antibodies may induce cytolysis. Toxicity is related to the nature and amount of neoantigen and also to other factors such as the individual immune system. An effort should be made to better understand the precise mechanisms underlying this kind of disease and thereby identify the drugs at risk; and also the neoantigen processes necessary for their introduction into the immune system. An animal model would be useful in this regard.

Antibody Formation↗
PubMedDate not supplied

[Hepatitis caused by cyproheptadine (Periactine). A case and review of the literature].

We report the case of a patient who developed jaundice after receiving cyproheptadine for 29 days. Complete recovery occurred within 3 months after cyproheptadine withdrawal. Analysis of 3 previously reported cases and this observation shows that cyproheptadine-induced hepatitis is uncommon. Hepatitis occurs within the first month of treatment and is of the cytolytic or mixed-pattern type. Jaundice is constant. Most often, recovery occurs quickly after the discontinuation of cyproheptadine. However, acute hepatitis can be followed by prolonged anicteric cholestasis.

Adult↗
PubMedDate not supplied

[Cytochromes P450 and formation of reactive metabolites. Role in hepatotoxicity of drugs].

During the millennia of evolution, animals have been subjected to a relentless biological warfare mounted by the plants that they ingested. By duplication of an ancestral gene, divergent evolution of these 2 genes, and so forth, surviving animals have been endowed with multiple cytochromes P450s which can metabolize (and thus eliminate) a multitude of environmental liposoluble xenobiotics. A disadvantage of this system (fortunately limited by the concomitant installation of several protective systems) is that cytochrome P450 transforms some of these xenobiotics into chemically reactive metabolites. These free radicals or electrophilic metabolites attack tissue constituents, and may lead to mutation, cancer or tissue necrosis. Tissue necrosis affect mainly the liver, whose content in cytochrome P450 is particularly high. Indeed, reactive metabolites are usually extremely unstable, and react mainly in situ, in the same organ that forms them. When the formation of reactive metabolites is extensive, protective mechanisms are overwhelmed, extensive alterations of diverse hepatic constituents occur, and toxic hepatitis ensues. When the formation of reactive metabolites is moderate, severe toxic lesions do not occur. However, the covalent binding of reactive metabolites to hepatic proteins modifies the self of the subject. In some subjects, the presence of this modified self triggers immunization, and leads to immunoallergic hepatitis. The immune response may be directed either against protein (or peptide) epitopes modified by the presence of a reactive metabolite (reaction against modified self) and/or against normal, unmodified, epitopes of proteins (autoimmune reaction against the self, triggered by the modified self). Both metabolic factors, and the HLA phenotype, appear to modulate the likelihood of immunization.

Autoimmune Diseases↗