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Biomedical subjects

P Petit

Publications and source records attributed to P Petit.

At least 19 recordsLinked to original sources

Effects of a peripheral-type benzodiazepine on glucose-induced insulin secretion.

Benzodiazepines, besides interacting with central-type receptors which mediate their well-known pharmacological actions, bind to peripheral-type receptors that are distributed in a variety of peripheral tissues including numerous endocrine organs. The present work was designed to investigate the effects of a selective peripheral-type benzodiazepine, 4'-chlordiazepam (Ro 5-4864), on glucose-induced insulin secretion in vitro. In the rat isolated pancreas perfused with a Krebs-bicarbonate buffer containing 8.3 mM glucose, the drug (10(-6) and 10(-5) M) induced a progressive and significant decrease in insulin release. Concomitantly, it induced a vasodilator response of the pancreatic vascular bed. In rat isolated islets incubated for 1 h in the presence of 15 mM glucose, 4'-chlordiazepam (10(-5) and 10(-4) M) induced a significant and dose-dependent inhibition of insulin release. In contrast, the selective central-type benzodiazepine, clonazepam (10(-6) - 10(-4) M), did not significantly modify glucose-induced insulin secretion. In addition, experiments were performed to test the effect of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamid e (PK 11195), a peripheral non-benzodiazepine ligand proposed as a putative antagonist. This substance did not counteract the inhibitory effect of 4'-chlordiazepam but itself (10(-6) and 10(-5) M) elicited a potent inhibitory effect on insulin secretion. These results show that drugs such as 4'-chlordiazepam and PK 11195 which have a high affinity for peripheral-type benzodiazepine receptors, in contrast to a central-type benzodiazepine agonist, inhibit glucose-induced insulin secretion in vitro.

Animals

Evidence for a direct stimulatory effect of cibenzoline on insulin secretion in rats.

The effect of cibenzoline succinate, a new antiarrhythmic agent, was studied on insulin secretion in rats. Experiments were performed both in vivo and in vitro using two preparations: the isolated perfused pancreas and isolated islets. In anaesthetized rats, cibenzoline was able to increase plasma insulin levels and to reduce glycaemia. These effects were observed at 1 mg/kg i.v. in fed rats and at 3 mg/kg i.v. in fasted rats. In the isolated pancreas perfused in the presence of a slightly stimulating glucose concentration (8.3 mM), cibenzoline (2 and 6 microM) elicited a progressive and sustained insulin response in a concentration-dependent manner. In the presence of a non-stimulating glucose concentration (4.2 mM), cibenzoline was ineffective at 2 microM and slightly increased basal insulin release at 6 microM. In isolated islets incubated with 8.3 mM glucose, cibenzoline (6 and 20 microM) caused a concentration-dependent stimulation of insulin release. It is concluded that cibenzoline stimulates insulin secretion by a direct action on pancreatic B cells in rats.

Animals

Acrofacial dysostosis syndrome type Rodriguez: a new lethal MCA syndrome.

We present a female fetus with the lethal acrofacial dysostosis syndrome recently delineated by Rodriguez et al. [1990]. The present findings confirm that this syndrome constitutes a true MCA syndrome in which mandibulofacial dysostosis and severe limb reduction defects are associated with complex malformations of different organs and systems especially the CNS, the urogenital tract, heart, and lungs.

Abnormalities, Multiple

[Hemodynamic parameters in the severely burnt patient during the 1st 72 hours].

The haemodynamic time course of 16 patients with severe burn injury was investigated using a flow-directed balloon-tipped pulmonary artery catheter. The patients, aged 33.8 +/- 5.5 years, were burnt over 60 +/- 10% of body surface area, with a UBS score of 228 +/- 43. The measurements were obtained every six hours after insertion of the catheter. Fluid load was determined with Evans' formula, and modified according to the haemodynamic data. Catecholamines were introduced when this and a trial of fluid loading with 5 ml.kg-1 of macromolecules during a 20 min period had failed, starting with dobutamine or dopamine, followed by adrenaline as required. During the first hours after the injury, circulatory shock was partly linked to hypovolaemia: mean arterial pressure was 60.1 +/- 7.8 mmHg, right auricular pressure 4.5 +/- 2 mmHg, pulmonary wedge pressure 4.7 +/- 2 mmHg, cardiac index 3.5 +/- 0.8 l.min-1 x m-2. However, during the second and third days, cardiac output increased, with a cardiac index at 4.7 +/- 0.6 l.min-1 x m-2 and 5.2 +/- 0.2 l.min-1 x m-2 respectively, and arterial vascular resistances were decreased (536 +/- 125 dyn.s.cm-5). These data suggest a specific haemodynamic profile in severe burn patients which justifies invasive monitoring, and the use of catecholamines, in those patients that do not respond to fluid loading. The link between these data and the concomitant metabolic disturbances due to the burn injury has not yet been established. The increase in cardiac index could be related to the inflammatory response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Total knee arthroplasty infection due to Gemella haemolysans.

Gemella haemolysans, a relatively unknown commensal of the upper respiratory tract, rarely causes clinically important infections. This report deals with an infection of a total knee arthroplasty due to Gemella haemolysans in a patient with rheumatoid arthritis. The microbiology of this bacterium is discussed and the clinical features of previously reported cases of Gemella infections are briefly reviewed.

Aged

Risks associated with intestinal perforation during experimental percutaneous drainage.

RATIONALE AND OBJECTIVES: The authors evaluated the complication rate of transgressing small or large bowel during intraperitoneal percutaneous catheter placement in an animal model. METHODS: Twenty-four 8-F catheters were percutaneously placed through the small and large bowel of 12 pigs. In six animals, the catheters were left in place until autopsy, whereas in the remaining six animals, the catheters were withdrawn 5 days after insertion. Computed tomographic (CT) scans were performed on days 1 and 8 after catheter placement in pigs in which catheters were in place at time of autopsy, and on days 1, 5, and 8 in pigs in which catheters were removed. RESULTS: CT results showed no abscess or peritoneal effusion, but a pneumoperitoneum was present in four animals whose signs resolved on subsequent studies. Autopsy was performed in all animals 9 days after catheter placement. No clinical complication occurred, and no significant biochemical changes were observed. At autopsy, no bowel leakage, peritonitis, or abscess was visible. Bowel and peritoneal adhesions were found around the catheter tract. There was no difference between the animals with catheters in place at the time of autopsy and the animals without catheters. There also was no difference between the group of animals with small or large bowel transgression. CONCLUSION: This study suggests that traversing the intestine during percutaneous placement of an intra-abdominal catheter should not be considered an absolute contraindication when no other approach is available.

Abdomen

Potassium channels of the insulin-secreting B cell.

Ionic and electrical events play a central role in the stimulus-secretion coupling of the pancreatic B cell. Potassium permeability is critically involved in the regulation of B cell membrane potential and insulin secretion. In the absence of glucose, membrane potential remains stable, around -65 mV. This resting potential is mainly determined by the high potassium conductance of the membrane. The ATP generated by glucose metabolism in B cells blocks the K+(ATP) channels controlling resting membrane potential. Thus, glucose metabolism leads to closure of the ATP-dependent potassium channels; the resulting decrease in K+ permeability induces depolarization and opening of voltage-activated Ca-channels. The subsequent increase in Ca2+ influx raises the cytoplasmic concentration of free Ca2+, which in turn triggers exocytosis of secretory granules. Other types of K+ channels have also been identified in the B cell, such as voltage- and Ca(2+)-dependent K+ channels, which are not a target for the action of glucose, but may play a role in the repolarization of spikes. The modulation of insulin release by some hormones and neurotransmitters involves, among other mechanisms, an interference with the plasma membrane K+ conductance. Thus, galanine, somatostatin and adrenaline, which inhibit insulin release, increase K+ conductance by a G protein-dependent mechanism; both peptides were reported to open ATP-sensitive K+ channels in insulin-secreting cell line RINm5F. It was also observed that extracellular purine nucleotides could interfere with K+ channels. Among the various drugs interfering with insulin secretion, sulfonylureas, such as tolbutamide and glibenclamide, directly inhibit ATP-dependent K+ channels in the B cell membrane and thereby initiate insulin release. In contrast, potassium channel openers such as diazoxide, antagonize the effects of glucose by increasing K+ permeability of the B cell membrane. Furthermore, other classes of drugs have recently been shown to interact with K+ (ATP) channels. Thus, K+ channels of the pancreatic B cell, particularly ATP-dependent ones, play a crucial role in the electrophysiology of insulin secretion; they are an important target for pharmacological agents designed to modulate this secretion.

Animals

Differential effects of cromakalim on pancreatic vascular resistance and insulin secretion in vitro.

The effects of the potassium channel opener cromakalim on vascular resistance and insulin output were investigated in vitro within the same experimental preparation, the isolated rat pancreas perfused at a constant pressure with a physiological solution containing 8.3 mM glucose. Cromakalim induced a clear and concentration-dependent dilatory response of pancreatic vessels; the concentration-response curve obtained in the range of 10(-8) - 10(-5) M had a sigmoidal shape with a linear part between 10(-7) and 10(-6) M. Cromakalim did not inhibit insulin release at these concentrations. These results differ from those obtained with diazoxide, which has been previously shown both to inhibit insulin secretion and induce vasodilatation of the pancreatic vascular bed in a similar range of concentrations (10(-6) - 10(-5) M). The data presented provide evidence for a selective effect of cromakalim on pancreatic vascular resistance. Our present and previous results support the view that cromakalim is effective on K+ channels of vascular smooth muscle that differ from the ATP-sensitive K+ channel opened by diazoxide in insulin-secreting B-cells.

Animals

Laryngeal atresia sequence as part of the DiGeorge developmental field defect.

The subject of the present report is a male newborn with laryngeal atresia (LA) type I, giving rise to a malformation sequence consisting of overdistended polyalveolar lungs and nonimmune fetal hydrops with massive ascites. The infant was chromosomally normal and the first child of consanguineous parents. Retention of liquid secreted by the fetal lungs in utero was the pathogenetic mechanism, responsible for the LA sequence. The LA was part of a complex constellation of anomalies, compatible with the DiGeorge developmental field defect.

Asphyxia Neonatorum

Computed tomographic detection of skeletal muscle calcifications in rhabdomyolysis.

The authors report a case of rhabdomyolysis with extensive calcification of the paravertebral muscles secondary to ingestion of desipramine hydrochloride, a tricyclic antidepressant. Computed tomography (CT) and isotope scanning were performed, and pathological confirmation of the condition was obtained. The extent of the calcification was probably due to the administration of supplementary calcium to correct hypocalcemia. The authors discuss the correlation between the CT and isotope scan findings.

Adult

[Value of fibrin glue in surgery of patients with severe burns].

From January 1985 to May 1986, fibrin glue was used for graft sealing in 158 cases of our 200 skin grafts performed for the treatment of burns. When the graft area was less than 200 cm2, primary and complete healing was routinely observed. In the remainder, we noticed a higher quality of healing when fibrin glue was used compared to the other grafts. In 2 patients, infection of the wound was responsible for a total graft lysis which occurred immediately in the non-sealed grafts and was delayed in the sealed ones. Fibrin glue shortens skin graft healing time while it procures a better quality of life in patients with burns during in hospital stay. However the use of this healing-facilitating compound has to be limited to well-defined indications.

Adult