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Biomedical subjects

P Bonnet

Publications and source records attributed to P Bonnet.

At least 37 records · Page 2Linked to original sources

Halothane differentially decreases 5-hydroxytryptamine-induced contractions in normal and chronic hypoxic rat pulmonary arteries.

The mechanism of action of halothane is not fully understood in pulmonary circulation and especially in chronic hypertension models. As the 5-hydroxytryptamine (5-HT) pulmonary vasoconstrictor response increases in chronic hypoxic rat, halothane could differentially attenuate this vasoconstriction response on normoxic and chronic hypoxic rats. The effect of halothane on 5-HT-induced contractions on pulmonary arteries isolated from normoxic and chronic hypoxic rats was compared. Rings dissected from proximal pulmonary artery without endothelium were attached to a force transducer to record tone and placed in an organ chamber gassed either by air or air + halothane (1-5%). Contractions induced by (10(-4) M) 5-HT were used to test the effect of halothane on rings isolated from normoxic and chronic hypoxic rats. 5-Hydroxytryptamine-mediated contractions were more sensitive to external calcium in normoxic than chronic hypoxic rings. In calcium-free solution, with verapamil or cadmium the amplitude of remaining 5-HT-induced contractions were greater in chronic hypoxic rings. Halothane (1-5%) decreased 5-HT-mediated contractions in normoxic and chronic hypoxic rings. The effect occurred with no change of pD2 for 5-HT and was more pronounced in normoxic rings. The effect of halothane on both rings was abolished in the absence of external calcium or in the presence of verapamil. In the presence of cadmium, 5% halothane had no effect on normoxic rings but still decreased the remaining 5-HT contraction on chronic hypoxic rings. The findings suggested that halothane decreased sarcolemmal calcium entry in pulmonary artery rings by a cadmium-sensitive pathway in normoxic rats and by a cadmium-insensitive pathway in chronic hypoxic rats.

Anesthetics, Inhalation↗

Possible role of nitric oxide and arachidonic acid pathways in hypoxia-induced contraction of rabbit coronary artery rings.

In isolated coronary arteries, hypoxia induces an increase in tone by releasing an unidentified endothelium-derived contracting factor (EDCF). Isometric force was measured in an isolated rabbit coronary artery ring at 37 degrees C in control and high K+ (40 mM) pre-contracted conditions. Hypoxia (15 mmHg pO2) induced by equilibrating the perfusate with nitrogen. Hypoxia did not affect the resting tone but induced an endothelium-dependent contraction on pre-contracted rings. Inhibitors of nitric oxide (NO) were tested, L-NAME (10(-4) M) totally and L-NMMA (10(-4) M) partially convert the hypoxic contraction to an hypoxic relaxation. The addition of L-arginine (10(-4) or 10(-3) M) did not restore the response. Methylene blue (10( -5) M) and ODQ (1 H-[1,2,4] oxadiazolo-[4,3-a] quinoxalin-1-one, 10(-5) M), both inhibitors of guanylate cyclase, also changed the hypoxic contraction into a hypoxic relaxation. Catalase (1200 U/ml), which decomposes hydrogen peroxide (H2O2), and superoxide dismutase (150 U/ml, SOD), a free radical scavenger, did not change the hypoxic response but quinacrine (50 microM), an inhibitor of phospholipase A2, significantly decreased it. Inhibitors of arachidonic acid metabolism (indomethacin, diethylcarbamazine, miconazole) however did not affect the hypoxic response. We conclude that in K+ pre-contracted rabbit coronary artery rings, hypoxia induces a contraction which is nitric oxide and arachidonic acid dependent.

Animals↗

Chronic hypoxia-induced spontaneous and rhythmic contractions in the rat main pulmonary artery.

The effect of chronic hypoxia (CH; 1-4 wk) on the electromechanical properties of the rat main pulmonary artery (MPA) was investigated. MPA rings obtained from rats exposed for 14 days to hypobaric (50.5 kPa) CH exhibited spontaneous and rhythmic contractions (SRCs) that were never observed in control (normoxic) rats. SRCs were unaffected by tetrodotoxin, phentolamine, BQ-123 and BQ-788, N-nitro-L-arginine methyl ester, or endothelium removal. CH depolarized smooth muscle cells from -58.8 +/- 9 to -38.6 +/- 5.4 mV and increased the resting cytosolic Ca2+ concentration from 67.3 +/- 11.9 to 112.5 +/- 16.4 nM. CH also induced spontaneous spikelike depolarizations. All of these effects were inhibited by external Ca2+ removal or nifedipine (1 microM). Moreover, depletion of intracellular Ca2+ stores with ryanodine (1-5 microM) or cyclopiazonic acid (3 microM) progressively attenuated SRCs. This study demonstrates that CH switches the MPA from a quiescent to a spontaneously active mechanical state. Finally, the fact that SRCs precede the development of right ventricle hypertrophy and disappear when this hypertrophy reaches a maximal value (after 3-4 wk of CH) suggests that SRCs may play a role in the adaptive process of the pulmonary circulation to CH.

Animals↗

[Update on pancreatic transplantation].

Pancreas transplantation significantly improves the quality of life as well as the survival of the diabetic patient. It is also associated with stabilization and reversal of secondary diabetic complications. Improvements in organ preservation, surgical techniques and immunosuppression have achieved one-year graft survival of more than 90% for combined kidney-pancreas transplant and 80% for isolated pancreas transplantation. Recipient evaluation must weigh the benefits of the procedure with the risk associated with surgery and chronic immunosuppression. Combined kidney-pancreas transplantation appears today as the best treatment for the diabetic patient with end stage renal disease. Isolated pancreas transplantation is reserved to non-uremic patients with severe diabetic complications or with brittle glycaemic control and severe impairment of quality of life.

Humans↗

[Recommendations for writing patient information statements].

With Evidence-Based Medicine, shared decision making is attracting considerable interest as a means by which patient preferences can be incorporated into clinical decisions. Patients cannot express informed preferences unless they are given sufficient and appropriate information, including a detailed explanation concerning their condition, the different therapeutic options and the likely outcomes with and without treatment. A patient education leaflet is a potentially powerful tool for communicating information to patients, who will be able to participate in the process of decision making. The present article is a review of available guides for the writing of patient information materials. It also includes criteria for evaluating their quality.

Decision Making↗

Fibrinogen Alès: a homozygous case of dysfibrinogenemia (gamma-Asp(330)-->Val) characterized by a defective fibrin polymerization site "a".

Congenital homozygous dysfibrinogenemia was diagnosed in a man with a history of 2 thrombotic strokes before age 30. His hemostatic profile was characterized by a dramatically prolonged plasma thrombin clotting time, and no clotting was observed with reptilase. Complete clotting of the abnormal fibrinogen occurred after a prolonged incubation of plasma with thrombin. The release of fibrinopeptides A and B by thrombin and of fibrinopeptide A by reptilase were both normal. Thrombin-induced fibrin polymerization was impaired, and no polymerization occurred with reptilase. The polymerization defect was characterized by a defective site "a," resulting in an absence of interaction between sites A and a, indicated by the lack of fragment D(1) (or fibrinogen) binding to normal fibrin monomers depleted in fibrinopeptide A only (Des-AA fm). By SDS-PAGE, the defect was detected on the gamma-chain and in its fragment D(1). The molecular defect determined by analysis of genomic DNA showed a single base change (A-->T) in exon VIII of the gamma-chain. The resulting change in the amino acid structure is gamma 330 aspartic acid (GAT) --> valine (GTT). It is concluded that the residue gamma-Asp(330) is essential for the normal functioning of the polymerization site a on the fibrinogen gamma-chain.

Adult↗

Inhalation of toluene diisocyanate affects cytochrome P450 2B1 expression in rat lung.

In the lung the expression of xenobiotic-metabolizing enzymes such as cytochromes P450 (CYP) and glutathione S-transferases (GST) may be affected by inhaled pollutants. Toluene diisocyanate (TDI) is a highly volatile chemical compound known to induce a wide array of diseases in workers exposed to vapors or sprays, including respiratory allergy and asthma. We investigated the effect of inhaled TDI on expression of CYP 1A1, 2B1, 2E1, and 3A1 and of alpha-, mu-, and pi-GST in rat lung. Animals were exposed to targeted concentrations of 0.01, 0.1, or 1 ppm TDI vapors or to cleaned filtered air for 8 h. Expression of CYP and GST was analyzed 18 24 h after the end of exposure using western blotting, northern blotting, and immunohistochemistry. Constitutive levels of CYP 2B1 and 3A1 proteins were found in lung tissue from control rats, whereas CYP 1A1 and 2E1 proteins were not detectable. Animal exposure to TDI vapors neither modified CYP 3A1 protein expression, nor led to any detectable expression of CYP 1A1 or 2E1. In contrast, exposure to 1 ppm TDI induced a 40% reduction in CYP 2B1 protein levels. This decrease was associated with a 33% decrease in CYP 2B1 mRNA levels. Additionally, CYP 2B1 immunolabeling localized to ciliated epithelial cells, Clara cells, and type II alveolar cells in the lung tissue of control rats was markedly decreased in animals exposed to 1 ppm TDI. Constitutive levels of alpha-, mu-, and pi-GST proteins were found in lung tissue from control rats. Exposure to TDI had no effect on lung expression of either of the GST. In conclusion, this study clearly shows a selective decrease in CYP 2B1 expression by TDI vapors in rat lung. The contribution of CYP 2B1 to metabolize further xenobiotics is therefore altered.

Administration, Inhalation↗

Combined effects of exposure to styrene and ethanol on the auditory function in the rat.

In order to study the auditory effects of a metabolic interaction between ethanol and styrene, a first group of rats was gavaged once a day with ethanol (4 g/kg), a second group was exposed to 750 ppm styrene by inhalation, and a third group was exposed to both ethanol and styrene (5 days/week, 4 weeks). Auditory function was tested by recording brainstem (inferior colliculus) auditory evoked potentials, and cochlear hair cell loss was estimated by light microscopy. Cytochrome P450 2E1 and the main urinary styrene metabolites, namely mandelic, phenylglyoxylic and hippuric acids, were measured by high-performance liquid chromatography to check the effects of ethanol on styrene metabolism. In our experimental conditions, ethanol alone did not have any effect on auditory sensitivity, whereas styrene alone caused permanent threshold shifts and outer hair cell damage. Hearing and outer hair cell losses were larger after the exposure to both ethanol and styrene than those induced by styrene alone, indicating a clear potentiation of styrene ototoxicity by ethanol. As expected, metabolic data showed that ethanol alters styrene metabolism and can therefore be considered a modifying factor of styrene toxicokinetics.

Administration, Inhalation↗

Direction of human motor responses by men and women to aversive stimulation.

The frequency of extensions and flexions of the arms of 12 men and 12 women (ages 20-30 years) responding to a neutral tone or to an electric shock was recorded. Subjects had to choose between pushing or pulling a lever upon receipt of an acoustic signal which was paired or unpaired with an electric shock. They were instructed to perform either long duration movements, allowing for on-line control of the execution, or short duration movements with prior specification of amplitude. Regardless of duration of movements, the aversive signal increased the frequency of extensions and intraindividual variability of choices of the men but decreased the frequency of extensions and intraindividual variability of choices of the women. These findings show that stimuli such as pain or fear automatically elicit patterns of terminal motor states corresponding to fight or flight, initiating processes of preparation of spatially oriented movements which are automatic and sex-typed and impair the use of the terminal cues for simultaneous preprogrammed voluntary movements.

Acoustic Stimulation↗

Human motor responses to simultaneous aversive stimulation and failure on a valued task.

The effects of presentation of an aversive stimulus and simultaneous failure on a bogus intelligence test upon a subject's aggressive reactions were studied. The subject's fist clenching was used as an indicator of aggression. Four conditions, generated by the combinations of two kinds of stimulus delivered to the subjects (aversive or nonaversive) and two outcomes of the task (failure or success), were investigated. 20 female and 20 male students (ages: 17-34 years) were instructed, upon the reception of an aversive or nonaversive acoustic signal, to press with the right hand a device that displayed a slide. Each slide presented an item from an intelligence test, to which the subjects were either allowed to answer successfully (success) or not (failure). Failure increased the subject's autonomic arousal, as measured by photoplethysmographic sensors, in all stimulation conditions, but only the condition with aversive stimulation increased the speed of clenching. This was interpreted as indicating subject's tendencies to aggression. These results are discussed in relation to the effects of frustration.

Achievement↗

Inhalation study on exposure to bitumen fumes. Part 1: Development and validation of the equipment.

Bitumen fumes emitted during road paving or roofing contain polycyclic aromatic hydrocarbons (PAHs). Experimental studies have been previously performed to test the carcinogenic potency of bitumen fumes. Some of them have been criticised either on the grounds that the fume condensates were not representative of fumes to which humans are exposed or because the fumes were never characterised in terms of particle size and poorly in terms of composition and concentration in the chambers. For a nose-only inhalation study, we have evaluated the ability of a new fume generation system to deliver stable and reproducible atmospheres of bitumen fumes to an inhalation chamber and investigated the representativity of the fumes generated at a concentration level of 5 mg/m3. The fume generator comprises: (1) an insulated 20 l heated kettle (200 degrees C for bitumen); (2) an insulated inlet pipe with a needle valve to adjust the flow of the test compound from the kettle; (3) a fume generation chamber equipped with a series of interchangeable channels of different width. The fume concentration in the exposure chamber can be controlled by changing the channel width or by restricting the evaporation surface with aluminium foil, and/or by changing the flow rate. Samples of the atmosphere in the chamber were collected and analysed for quantitative determination of total particulate matter (TPM), soluble matter, benzo[a]pyrene (B[a]P) content of the fumes and other PAHs, and evaluation of the particle size distribution. The representativeness of the fumes has been tested by comparison with fumes generated in the Shell small-scale fume rig, which was previously validated against field fumes collected during paving operations. Evaporative losses from the filters during sampling, transport and storage have been also assessed. At 5 mg/m3 TPM, the agreement between laboratories was quite good for the TPM analyses and was good for the soluble matter and B[a]P. Evaporative losses may lead to underestimation of the true exposure level in the inhalation chambers but the use of an XAD-2 cartridge backup is one approach to partially recover losses which occur on the filter. The particle size distributions are somewhat different from those reported for fumes associated with roofing and indoor mastic laying works, in that we found more than 85% of particles to be smaller than 1 micron, compared with 40% particles in the previous analyses. In conclusion, this equipment allows reproducible generation of fumes at the 5 mg/m3 TPM that are fairly representative of those produced in the field with the same bitumen.

Equipment Design↗

Inhalation study on exposure to bitumen fumes. Part 2: Analytical results at two exposure levels.

During the hot application of bitumen-containing materials, e.g. in road paving or roofing, fumes are emitted that contain traces of polycyclic aromatic compounds (PACs). Although worker's exposure to these fumes is low, it might lead to health problems. For studying DNA adduct formation as a consequence of inhalation of bitumen fumes we developed and validated an inhalation system (a dynamic fume generator plus a nose only inhalation chamber). This paper presents and discusses the analytical results from the different laboratories involved in this study on the fumes sampled in the inhalation chamber during three series of experiments where the animals were exposed to fumes at the 5 mg/m3 and 50 mg/m3 level, coming from bitumen heated at 200 degrees C and, as a positive control, fumes from coal tar, heated to 110 degrees C at the 5 mg/m3 level. The following parameters were controlled: temperatures at different key places in the generator; humidity of the chamber; the bitumen or coal tar flow rate; and Total Particulate Matter (TPM). Analyses were performed for Benzene Soluble Matter (BSM), the EPA polycyclic aromatic hydrocarbon (PAH) mixture and for a number of heteroatom-containing PACs. The data show that the coal tar fumes produced at 110 degrees C were very volatile and that most of the differences in particulate matter found between the laboratories can be attributed to evaporative losses. The bitumen fumes boil 25-50 degrees C higher and contain higher boiling compounds. A comparison is made between the PAC exposure profiles for bitumen experiments aimed at 5 and 50 mg/m3. Although the same molecules are found in both fumes their proportion is dramatically different. This effect is largest with the 2- and 3-ring PACs, the ratio of the concentrations found in the 50 mg/m3 TPM concentration to that in the 5 mg/m3 experiment gradually declines from 5500 for acenaphthene to 500 for pyrene, for the 5-ring PACs this ratio is 20-30. As function of their vapour pressure, the ratios of the concentrations of the hetero PACs follow the same trend as that of the 16 EPA PAHs and are of the same order of magnitude. In conclusion, for the compounds investigated, the equipment delivers a fume atmosphere in a reproducible manner. The 50 mg/m3 bitumen fumes are not representatives of field fumes. The reason for these quantitative differences is unclear and further work would be needed to clarify this. Nevertheless it was felt that these fumes at 50 mg/m3 might be a useful tool for qualitative detection of DNA adducts in an animal exposure study.

Animals↗

Relative developmental toxicities of acrylates in rats following inhalation exposure.

The developmental toxicities of seven acrylates were studied in Sprague-Dawley rats after inhalation exposure for 6 h/day, during days 6 to 20 of gestation. The exposure concentrations were: for acrylic acid, 50, 100, 200, or 300 ppm; for methyl acrylate, 25, 50, or 100 ppm; for ethyl acrylate, 25, 50, 100, or 200 ppm; for butyl acrylate, 100, 200, or 300 ppm; for ethylhexyl acrylate, 50, 75, or 100 ppm; for hydroxyethyl acrylate, 1, 5, or 10 ppm; and for hydroxypropyl acrylate, 1, 5, or 10 ppm. No treatment-related increases in embryo/fetal mortality or fetal malformations were observed after exposure to any of these acrylates. Fetal toxicity, indicated by reduced fetal body weight, was observed after exposure to 300 ppm acrylic acid, 100 ppm methyl acrylate, 200 ppm ethyl acrylate, and 200 or 300 ppm butyl acrylate in the presence of overt signs of maternal toxicity. While there was evidence of maternal toxicity, no significant developmental toxic effects were observed after exposure to ethylhexyl acrylate, hydroxyethyl acrylate, or hydroxypropyl acrylate at any concentration. These results indicate that inhaled acrylic acid, methyl acrylate, ethyl acrylate, butyl acrylate, ethylhexyl acrylate, hydroxyethyl acrylate, and hydroxypropyl acrylate are not selectively toxic to the embryo or fetus.

Acrylates↗

Developmental toxicities of methacrylic acid, ethyl methacrylate, n-butyl methacrylate, and allyl methacrylate in rats following inhalation exposure.

The developmental toxicities of 4 methacrylates were studied in Sprague-Dawley rats after inhalation exposure for 6 h/day, during days 6 to 20 of gestation. The exposure concentrations were, for methacrylic acid, 0, 50, 100, 200, or 300 ppm; for ethyl methacrylate, 0, 600, 1200, 1800, or 2400 ppm; for n-butyl methacrylate, 0, 100, 300, 600, or 1200 ppm; and for allyl methacrylate, 0, 12, 25, 50, or 100 ppm. No significant increases in embryo/fetal lethality or fetal malformations were observed after exposure to any of these methacrylates. Fetal toxicity evidenced by statistically significant decreases in fetal body weights was observed at exposure levels > or = 1200 ppm ethyl methacrylate, > or = 600 ppm n-butyl methacrylate, and at 100 ppm allyl methacrylate. Statistically significant increases in the incidence of fetuses with skeletal variations and of fetuses with any variations were noted at 1200 ppm n-butyl methacrylate. These developmental effects were observed in the presence of overt signs of maternal toxicity. While maternal toxicity was observed, methacrylic acid caused no evidence of developmental toxicity up to 300 ppm.

Administration, Inhalation↗

[Urinary incontinence in elderly women].

Physical, psychological and economical consequences of urinary incontinence of the elderly woman are underestimated. It often results in depression, social isolation and early institutionalisation. It is often the key factor that determines the decision of institutionalisation, which represent the most important part of the total cost of urinary incontinence. This problem is too often neglected and deserves considerable attention.

Aged↗

Laparoscopic live donor nephrectomy: initial experience.

Transplanting a kidney graft harvested from a live donor has been proposed and used to shorten the waiting time of kidney transplant candidates and to increase the graft pool. Live donor renal transplants have demonstrated better results in term of graft survival rates, compared to renal transplants harvested from brain dead donor. Recently, laparoscopic live donor nephrectomy has been introduced to reduce the live procurement morbidity. This lower morbidity may result in increased acceptance of the donor operation. We initiated a program of laparoscopic live donor nephrectomy in January 1997 and up until June 1998, three cases were successfully performed in our department. The purpose of this paper was to report the first case of this program and its first year of follow-up.

Adolescent↗