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Biomedical subjects

T Gauthier

Publications and source records attributed to T Gauthier.

At least 19 recordsLinked to original sources
PubMed2000

Moral reasoning, interpersonal skills, and cognition of rapists, child molesters, and incest offenders.

54 inmates were subdivided into four groups and classified according to their index offense. The groups included Rapists (n = 14), Incest Offenders (n = 9), Child Molesters (n = 11), General Offenders (n = 20). Nonoffenders (n = 20) were included as a control group. Psychometric tests including the Test of Nonverbal Intelligence, the Defining Issues Test, Survey of Interpersonal Values, Porteus Maze, and Minnesota Multiphasic Personality Inventory were administered to all inmate and control groups. Analysis showed the rapists and child molesters scored higher on moral reasoning on the Defining Issues Test; also rapists' scores were more elevated on the Psychopathic Deviate and Paranoia scales of the Minnesota Multiphasic Personality Inventory than those of other offender and control groups. These results imply that rapists and child molesters have the ability to understand moral issues; however, given their personality orientation, they ignore these interpersonal social values.

Adolescent↗
PubMed1998

The beneficial effects of ciprofloxacin on survival and hepatic regenerative activity in a rat model of fulminant hepatic failure.

Recently, we reported that ciprofloxacin, an antimicrobial agent with gamma-aminobutyric acid (GABA(A)) receptor antagonist properties, significantly increases hepatic regenerative activity in animal models of alcohol-induced liver disease and cirrhosis. In the present study, we documented the effects of ciprofloxacin on survival and hepatic regeneration in a D-galactosamine (D-gal)-induced model of acute hepatic injury in rats. One hundred nineteen adult, male Sprague-Dawley rats (n = 19-20/group) were treated with intraperitoneal D-gal (total dose: 2.5 g/kg), followed by gastric gavage with either saline, ciprofloxacin (10, 50, or 100 mg/kg), norfloxacin (250 mg/kg), or intraperitoneal putrescine (300 micromol/kg), a potent hepatic growth promoter. Mortality rates were then documented over a 4-day period. An additional 45 rats (n = 15/group) received a sublethal dose of D-gal (1.0 g/kg), followed by gastric gavage with either saline or ciprofloxacin (100 mg/kg), or intraperitoneal putrescine (300 micromol/kg). In these rats, hepatic regenerative activity was documented at 12, 24, and 60 hours post-D-gal by 3H-thymidine incorporation into hepatic DNA and proliferating cell nuclear antigen (PCNA) staining. In the survival study, a dose-response effect of ciprofloxacin on survival was observed (ciprofloxacin: 10 mg/kg, 10%; 50 mg/kg, 26%; and 100 mg/kg, 35%) with the results in the 100-mg/kg-treated group being significant when compared with the 5% survival rate in saline-treated controls (P < .05). Survival figures in the norfloxacin- and putrescine-treated groups were not significantly improved (15% and 25%, respectively). In the regeneration study, compared with the D-gal + saline-treated control group, DNA synthesis rates at 60 hours were increased in the D-gal + ciprofloxacin and D-gal + putrescine groups (10.2 +/- 3.3 vs. 18.2 +/- 5.1 and 18.8 +/- 6.8 x 10(3) dpm/mg DNA respectively; P < .05). The results of PCNA staining also supported enhanced hepatic regeneration in the ciprofloxacin-treated group at 60 hours (saline, 13.4 +/- 3.7; ciprofloxacin, 47.4 +/- 7.3; and putrescine, 8.4% +/- 2.8% hepatocytes staining positive). Ciprofloxacin at a dose of 100 mg/kg significantly improves survival and hepatic regenerative activity in this animal model of acute hepatic injury.

Alanine Transaminase↗
PubMed1997

Effect of quinolone antibiotics on hepatic growth and protein synthesis following partial hepatectomy in rats.

Quinolone antibiotics inhibit eukaryotic as well as prokaryotic cell growth and protein synthesis. To determine whether these properties adversely affect hepatic growth and recovery following surgical resection, five groups of healthy, adult male rats (n = 7-8/group) were treated for 10 days with equal volumes of either ofloxacin (50 mg/kg), fleroxacin (25 mg/kg), ciprofloxacin (25 mg/kg), norfloxacin (15 mg/kg) or sterile saline (controls) prior to 70% partial hepatectomy (PH) and daily thereafter until death. Restituted liver mass, DNA and protein synthesis rates were determined at 24, 48 and 72 h PH. The results of the study revealed that all parameters of hepatic regeneration were similar in the five study groups at each time interval. To ensure that an effect on hepatic regeneration was not dose-dependent, additional experiments were performed where 1, 10 and 100 mg/kg ciprofloxacin was administered and DNA synthesis was measured 24 h post-PH. Once again, the results were similar to sterile saline-treated controls. These findings suggest that the quinolone antibiotics are unlikely to have an adverse effect on hepatic recovery following surgical resection of the liver and are safe to use in that setting.

Animals↗
PubMed1996

Changes in liver membrane potentials after partial hepatectomy in rats.

Changes in potential differences (PD) across hepatocyte membranes after partial hepatectomy may play an important role in hepatic homeostatic mechanisms and regenerative activity. To date, few studies have attempted to describe the extent and duration of such changes. In the present study, we documented PD values immediately before and for a 24-hour period after a partial hepatectomy (PHx) of 70% in healthy adult rats. We also documented PD changes after 30% and 90% PHx and PD values in different lobes of the same liver before and after PHx. Our findings showed that the liver depolarizes promptly (within 5 minutes of PHx) and that changes in PD are sustained for approximately 18 hours before returning to baseline values. We also observed that the magnitude of hepatic depolarization correlates with the extent of PHx. Finally, we did not observe regional differences in PD recordings from various lobes before and after PHx. These findings enhance our understanding of the physiological changes that occur in regenerating livers after PHx in rats.

Animals↗
PubMed1996

Digestive leishmaniasis in acquired immunodeficiency syndrome: a light and electron microscopic study of two cases.

An increased incidence of visceral leishmaniasis in patients infected with the human immunodeficiency virus (HIV) is observed in areas in which both infectious diseases are endemic. Intensive worldwide traveling has also resulted recently in an increasing number of leishmanial and HIV coinfections in nonendemic areas. We describe the clinical, light microscopic, and ultrastructural features of two cases of imported, HIV-related, visceral leishmaniasis involving the alimentary tract, including the esophagus, the stomach, the duodenum, the ileum, the colon, and the rectum. We also discuss the differentiation of leishmanial infections from other HIV-related gastrointestinal opportunistic infections.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Experimental use of a semipulsatile rotary blood pump for cardiopulmonary bypass.

We tested our valveless pulsatile rotary blood pump (CORA) extensively in animals, but only as a temporary implantable left ventricular assist device. To expand the scope of future clinical applications, we recently undertook experiments to assess the feasibility of our pump for use in a standard cardiopulmonary bypass circuit. We conducted 4 experiments in adult sheep (body weight, 40 kg): 2 with CORA and 2 with the BioMedicus pump (BP) for comparison. In all experiments, a currently used extracorporeal circuit with reservoir, filter, and membrane oxygenator (Sorin monolith) was installed, and open chest extracorporeal circulation (ECC) was performed for 6 h. Hemodynamic performance and hemolysis were evaluated. CORA provided semipulsatile systemic flow at a level comparable to that of the BP. Free plasma hemoglobin levels were slightly higher with CORA, but the decrease in platelet count was the same for both devices. There was no significant difference in the extent of blood trauma. We conclude that CORA could be successfully used for ECC with an oxygenator. Negative pressure can be prevented by our specially designed control system.

Animals↗
PubMed1995

Effect of exogenous gamma-aminobutyric acid (GABA) on hepatic insulin-like growth factor I (IGF-I) and IGF-I binding protein (IGFBP-I) mRNA abundance following partial hepatectomy in rats.

Insulin-like growth factor I (IGF-I) and IGF-I binding protein (IGFBP-I) are highly expressed in the liver and may play an important role in enhancing hepatic regeneration following partial hepatectomy in rats. Since hepatic levels of these growth factors are influenced by pituitary growth hormone release, which in turn is regulated by systemic serum gamma-aminobutyric acid (GABA) concentrations, we chose to examine the effects of elevated serum GABA concentrations on hepatic IGF-I and IGFBP-I mRNA abundance following partial hepatectomy in the rat. The results of our experiments revealed that at serum GABA concentrations similar to those associated with liver failure, peak hepatic IGF-I and IGFBP-I mRNA levels were significantly lower in GABA-treated rats compared with saline-treated controls (p < 0.05 and 0.01, respectively). To exclude a direct effect of GABA on hepatocyte IGF-I and IGFBP-I mRNA expression, suspensions of isolated hepatocytes were incubated in the presence and absence of exogenous GABA. In these experiments GABA treatment did not lower either IGF-I or IGFBP-I mRNA or protein levels. These findings suggest that increased concentrations of GABA in the systemic circulation could contribute to the impairment in hepatic regenerative activity that occurs in animals and humans with advanced liver failure.

Animals↗
PubMed1995

Ciprofloxacin prevents the inhibitory effects of acute ethanol exposure on hepatic regeneration in the rat.

To determine whether the inhibitory effects of ethanol on hepatic regeneration could be prevented by ciprofloxacin, a fluroquinolone antibiotic with gamma-aminobutyric acid (GABAA), receptor antagonist properties, adult, male Sprague-Dawley rats (n = 6-8/group) received intraperitoneal injections of saline, putrescine (a hepatic growth promoter, 50 mg/kg), or ciprofloxacin (100 mg/kg), followed 1 hour later by gastric gavage with saline or ethanol (5 g/kg). One hour post-gavage, all rats underwent a 70% partial hepatectomy (PHx). Hepatic regenerative activity was documented 24 hours post-PHx by 3H-thymidine incorporation into hepatic DNA (DNA synthesis), proliferating cell nuclear antigen staining, and hepatic tissue putrescine levels. Compared with healthy controls, DNA synthesis rates were significantly lower in ethanol-gavaged/saline-treated rats (22.7 +/- 4.4 x 10(3) vs. 12.3 +/- 6.9 x 10(3) DPM/mg DNA, respectively, P < .001) but unaltered in putrescine-(18.8 +/- 3.4 x 10(3) DPM/mg DNA) and ciprofloxacin-treated (18.3 +/- 2.6 x 10(3) DPM/mg DNA) rats. Hepatic proliferating cell nuclear antigen staining supported these findings. Hepatic putrescine levels also correlated with DNA synthesis data, being decreased in ethanol-gavaged/saline-treated rats (86 +/- 14 pmoles/mg tissue) compared with healthy controls (120 +/- 12 pmoles/mg, P < .01), ethanol-gavaged/putrescine-treated (112 +/- 14 pmoles/mg, P < .05) and ethanol-gavaged/ciprofloxacin-treated (125 +/- 17 pmoles/mg, P < .05) rats. To determine whether these effects resulted from GABAA receptor-mediated changes in liver membrane potentials, intracellular membrane potentials were recorded before and 1 hour after PHx in healthy control, ethanol-gavaged/saline-treated and ethanol-gavaged/ciprofloxacin-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The differential effects of three forms of interferon alfa on hepatic regeneration after partial hepatectomy in the rat.

The purpose of this study was to determine whether all commercially available forms of interferon alfa (INF alpha) have the same inhibitory effect on hepatic regeneration and whether this inhibitory effect can be prevented by putrescine, a hepatic growth promotor. Adult male Sprague-Dawley rats (n = 92) received either IFN alpha-2a, 2b, n1, or saline, 0 and 18 hours after partial hepatectomy (PHx) or 16 hours before PHx. A subgroup of 29 rats being treated with IFn alpha-2a or saline also received putrescine (5, 50, or 500 mg/kg) 16 hours before PHx. Hepatic regeneration was documented by determining [3H]-thymidine incorporation into hepatic DNA (DNA synthesis), hepatic putrescine levels, and, in selected cases, ornithine decarboxylase (ODC) activity at 24 hours after PHx. The results of the study showed that hepatic regeneration was unaffected when IFN alpha was administered 0 and 18 hours after PHx. When administered at -16 hours, only IFN alpha-2a significantly inhibited DNA synthesis and was associated with decreased hepatic putrescine levels. Inhibition was dose-dependent in that a 10-fold increase in IFN alpha-2a caused a further decrease in both DNA synthesis and hepatic putrescine levels. At the higher dose, IFN alpha-2b and n1 also inhibited DNA synthesis and lowered hepatic putrescine levels and ODC activity. Exogenous putrescine (5 and 50 mg/kg) restored hepatic regenerative activity to normal but was toxic at high concentrations (500 mg/kg). These data indicate that not all commercially available forms of IFN alpha inhibit hepatic regeneration in the rat to the same extent.

Animals↗
PubMed1994

Tissue-type plasminogen activator is a potent mitogen for human aortic smooth muscle cells.

Tissue-type plasminogen activator (t-PA) is a potent and efficacious mitogen for growth-arrested cultured human aortic smooth muscle cells, stimulating an increase in cell number at 0.3-30 nM concentration. Double-chain t-PA is as efficient as single-chain t-PA in stimulating smooth muscle cell mitogenesis, whereas single-chain urokinase-type plasminogen activator (u-PA) or u-PA and plasmin or plasminogen are ineffective. Plasminogen activator inhibitor-1, Pefabloc-TPA, diisopropyl fluorophosphate or alpha 1-anti-trypsin inhibit the mitogenic effect of t-PA for smooth muscle cells in a dose-dependent manner, showing that it is dependent on the enzymatic activity. t-PA activated phosphoinositide turnover in smooth muscle cells through a pertussis toxin-insensitive pathway and stimulated proto-oncogene c-fos and c-jun mRNA levels. These findings indicate that t-PA stimulates vascular human smooth muscle cell proliferation and suggest for the first time that it may contribute to intimal smooth muscle cell proliferation after vascular injury as a result of angioplasty or vascular compromise during atherogenesis.

Aorta↗
PubMed1994

Abbott PKS system: a new version for applied pharmacokinetics including Bayesian estimation.

Abbott Laboratories has developed a new software package (Abbottbase pharmacokinetic system or PKS package) that employs the principles of pharmacokinetics to assist clinical pharmacologists and clinicians in designing dosage regimens. This software, which runs on IBM PC compatibles, allows Bayesian estimation of individual pharmacokinetic parameters. The aim of the present study was to validate this new system in routine clinical practice for amikacin (40 intensive care unit patients) and theophylline (20 patients). By using the program one or more times during the treatment (50 cases for amikacin and 46 cases for theophylline), dosing recommendations were obtained in real time for all patients. The predictive performance (bias and precision) was assessed by comparing predicted drug concentrations with those measured 24-48 h after dosage recommendation. In the case of amikacin, precision and bias were computed separately for peak and trough levels. In all cases, no statistically significant bias was observed. Finally, our results demonstrate the accuracy of the program in predicting drug levels for amikacin and theophylline. Consequently, the PKS package is reliable for the choice of optimal dosage regimen for amikacin and theophylline.

Administration, Oral↗
PubMed1994

Predictive performance of two software packages (USC*PACK PC and Abbott PKS system) for the individualization of amikacin dosage in intensive care unit patients.

Many dosing methods (nomogram, pharmacokinetic methods, Bayesian methods) can be used for the individualization of amikacin dosing. Among these methods, it is now well known that the Bayesian method provides a rapid and accurate means for individualizing dosage requirements for patients with diverse pharmacokinetic profiles. However, one problem has not been fully resolved. Should we use population-based parameters reflecting the patient population being monitored or should we used general population parameters? The aim of this study was to answer this question using two widely used software programs (USC*PACK PC and Abbott PKS system) and two different population parameters sets. Predictive performance of these methods was assessed with respect to the prediction of amikacin serum concentrations in intensive care unit (ICU) patients. Our results show that the differences between predicted and measured concentrations were unbiased when the population parameters used were adequate. Precision values were comparable with previously reported values. The predictive performance of the two tested software programs are very comparable in ICU patients. In addition, we demonstrated that performance can be enhanced when using population-based parameters which reflect the patient population being monitored. It is therefore advisable for each user to properly characterize each particular patient population.

Adolescent↗
PubMed1994

SR 140333, a novel, selective, and potent nonpeptide antagonist of the NK1 tachykinin receptor: characterization on the U373MG cell line.

The effects of a novel nonpeptide NK1 tachykinin receptor antagonist, SR 140333, on the functional consequences of NK1 receptor activation in a human astrocytoma cell line, U373MG, were investigated. Radioligand binding conducted with 125I-Bolton-Hunter substance P revealed a competitive inhibition by SR 140333 and its R enantiomer SR 140603 with Ki values of 0.74 and 7.40 nM, respectively. The NK1-selective agonist, [Sar9,Met(O2)11]-substance P, stimulated the formation of inositol phosphates with an EC50 of 3.8 x 10(-9) M. SR 140333 blocked the stimulatory effect of this agonist (10(-7) M) with an IC50 of 1.6 x 10(-9) M, whereas the effect of another NK1 agonist, septide (EC50 = 1.5 x 10(-8) M) was antagonized with an IC50 of 2.1 x 10(-10) M. Enhancement of [3H]taurine release by [Sar9,Met(O2)11]-substance P (EC50 = 7.4 x 10(-9) M) was also inhibited by SR 140333 with an IC50 of 1.8 x 10(-9) M. SR 140603 was 10-fold less potent than SR 140333 in inhibiting inositol monophosphate formation and [3H]taurine release. The calcium mobilization induced by [Sar9,Met(O2)11]-substance P (10(-8) M) was totally prevented by 10(-8) M SR 140333. Patch-clamp experiments showed that SR 140333 depressed the outward current evoked by 5 x 10(-8) M [Sar9, Met(O2)11]-substance P with an IC50 of 1.3 x 10(-9) M. The expression of c-fos was stimulated by [Sar9,Met(O2)11]substance P with an EC50 of 2.5 x 10(-10) M, an effect that was also inhibited by SR 140333 with an IC50 of 1.1 x 10(-9) M.(ABSTRACT TRUNCATED AT 250 WORDS)

Astrocytoma↗
PubMed1993

Human liver microsomal cytochrome P450 3A isozymes mediated vindesine biotransformation. Metabolic drug interactions.

Vindesine biotransformation was investigated using a bank of human liver microsomes. The drug was converted into one major metabolite (M) upon incubation with the microsomes. Large interindividual variations were observed: vindesine biotransformation rates ranged from 1.2 to 12.9 pmol/min/mg protein. Vindesine metabolic processes followed Michaelis-Menten kinetics: Km = 24.7 +/- 9.4 microM, Vmax = 1.5 +/- 0.8 nmol/min/mg protein. The involvement of human cytochrome P450 3A isozymes in vindesine metabolism was demonstrated by: (1) competitive inhibition of vindesine biotransformation by compounds known to be specifically metabolized by human cytochrome P450 3A. Apparent Ki values were 3.6, 17.9 and 19.8 microM for quinidine, troleandomycin and erythromycin, respectively; (2) immunoinhibition of vindesine metabolism by polyclonal anti-P450 3A antibody; (3) significant correlation between immunoquantified P450 3A and vindesine biotransformation (r = 0.800, P < 0.001); and (4) significant correlation between erythromycin N-demethylase activity, which was supported by P450 3A in humans, and vindesine biotransformation (r = 0.853, P < 0.001). Other vinca alkaloids also exerted an inhibitory effect on vindesine biotransformation with apparent Ki values of 3.8, 10.6 and 19.2 microM for vinblastine, vincristine and navelbine, respectively, suggesting a possible involvement of the same cytochrome subfamily in their hepatic metabolism. Moreover, a number of anticancer drugs currently associated with the vinca alkaloids, such as teniposide, etoposide, doxorubicin, lomustine, folinic acid and mitoxantrone, significantly inhibited vindesine biotransformation.

Adult↗
PubMed1993

Expression and release of interleukin-1 by human glioblastoma cells in vitro and in vivo.

The present study demonstrates interleukin-1 (IL-1) production by human glioblastoma cells both in vitro and in vivo. The presence of IL-1 alpha and IL-1 beta transcripts was analyzed in 4 cell lines. IL-1 alpha mRNA was expressed constitutively in one cell line whereas constitutive IL-1 beta mRNA could not be detected in any of the cell lines. IL-1 alpha transcripts could be induced with phorbol myristate acetate (PMA) or PMA plus lipopolysaccharide (LPS) in 2 of 4 cell lines and IL-1 beta mRNA in 2 of 4 cell lines. Culture fluid from these cell lines was tested for the presence of IL-1 using a specific radio-immuno-assay for either IL-1 alpha or IL-1 beta. In agreement with the results on RNA, one of 4 cell lines was found to constitutively produce IL-1 alpha but not IL-1 beta. After treatment with PMA and LPS, IL-1 alpha was detected in the culture fluid from two other lines and IL-1 beta in the medium from three lines. That the IL-1 produced by these cell lines was biologically active was confirmed in a two step thymocyte proliferation assay. IL-1 like activity was detected in all samples that were positive in the radio-immuno-assay. Finally, immunohistological analysis on fresh frozen tumour sections provided evidence for IL-1 production by glioblastoma cells in vivo. Fourteen out of 28 glioblastomas were stained with an anti-IL-1 alpha monoclonal antibody while none of them was stained with an anti-IL-1 beta antibody.

Brain Neoplasms↗