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Biomedical subjects

M Dumont

Publications and source records attributed to M Dumont.

At least 91 records · Page 5Linked to original sources

Evidence for defective primary bile acid secretion in children with progressive familial intrahepatic cholestasis (Byler disease).

To clarify the relationship of progressive familial intrahepatic cholestasis (Byler disease) to bile acid metabolism, we analysed, by high performance liquid chromatography, the bile acid composition of serum and bile in seven children with Byler disease and in eight control children with other cholestatic diseases. In serum, total bile acid concentration was increased in patients with Byler disease (0.30 +/- 0.05 mmol/l) and in control patients (0.21 +/- 0.08 mmol/l). Cholate (C) and chenodeoxycholate (CDC) comprised the major proportion of total bile acids in patients with Byler disease as in control patients. Hyocholate (HC) was only detected in patients with Byler disease and lithocholate was only present in control children. In bile, total bile acid concentration was very low in patients with Byler disease (1.1 +/- 1.4 mmol/l) compared to control patients (88.9 +/- 83.2 mmol/l). C and CDC were the major bile acids in control patients, whereas C and HC comprised the major proportion of bile acids in patients with Byler disease. These results suggest the existence of a defect of primary bile acid secretion in Byler disease characterized by the presence of high concentration of bile acids in serum and absence or very low concentration of bile acids in bile.

Bile↗

Effects of octreotide on biliary lipid composition and occurrence of cholesterol crystals in patients with acromegaly. A prospective study.

Treatment with the somatostatin analog octreotide is associated with increased gallstone formation. The mechanism of formation of these stones is unclear. The purpose of this study was to examine the effect of a three-month treatment with octreotide on biliary lipid composition and the occurrence of cholesterol crystals in patients with acromegaly. Thirteen patients with active acromegaly, aged 24-76 years, received octreotide (100 micrograms three times daily) for three months. Fasting gallbladder bile was obtained during upper gastrointestinal endoscopy after ceruletide stimulation. Bile was studied before and at the end of the treatment period (N = 7), only before (N = 4), or only at the end of treatment (N = 2). Before treatment, all bile samples but one were supersaturated with cholesterol. However, none contained cholesterol crystals on microscopic examination. At the end of the treatment period, all but two samples were supersaturated with cholesterol. Three of nine samples contained cholesterol crystals, a proportion significantly higher than before treatment. The relative proportions of bile acids, cholesterol, and phospholipids, and the mean cholesterol saturation index were not different before and during treatment. Follow-up ultrasonography showed the occurrence of gallstones in four patients, including the three patients who had cholesterol crystals. We conclude that: (1) fasting gallbladder bile of patients with acromegaly is frequently supersaturated with cholesterol; (2) treatment with octreotide does not increase cholesterol saturation index, but may induce the occurrence of cholesterol crystals. The data are consistent with the view that gallstones induced by octreotide are cholesterol stones and suggest that the drug may impair gallbladder motility and/or decrease cholesterol nucleation time.

Acromegaly↗

Perceptual defense and vulnerability to postpartum depression.

The objective was to assess the relationship between vulnerability to postpartum depression and perceptual defense evoked by tachistoscopic stimuli alluding to perinatal themes in pregnant women. Tachistoscopic stimuli have been shown to produce different thresholds of conscious identification according to their emotional content: a phenomenon termed perceptual defense. A total of 412 women in their 3rd of 4th month of pregnancy were asked to identify 14 pictures and 18 verbal stimuli shown for initially very brief but increasing durations. Presentation times required for a correct identification were measured. Depression was assessed, at 2 and 6 months postdelivery, by the Hamilton Depression Rating Scale: 53 women were defined as depressed by a score > or = 15. Discriminant analysis showed that the women who would become depressed 7 to 11 months later were slower than the nondepressed to identify 5 stimuli alluding to pregnancy, sexuality or a father image. Particular attitudes towards the themes of being pregnant, of sexuality and of the father could be components of a psychological predisposition to the development of depressed mood in the postpartum.

Adult↗

Effects of phalloidin and colchicine on diethylmaleate-induced choleresis and ultrastructural appearance of rat hepatocytes.

Diethylmaleate is used as a model compound whose glutathione conjugates are secreted into bile, and which induce choleresis and the formation of Golgi-derived vesicles in hepatocytes. This study was performed to test the assumption that these vesicles are involved in the bile canalicular secretion of diethylmaleate. We reasoned that phalloidin and colchicine, two drugs acting on microfilaments and microtubules, respectively, can modify the movements of diethylmaleate-induced vesicles towards the bile canaliculus. Phalloidin induced the formation of a thick microfilamentous network around the bile canalicular plasma membrane domain. A significant decrease in diethylmaleate-stimulated choleresis was observed, associated with a striking accumulation of pericanalicular vesicles, which were confirmed by morphometric analysis. In contrast, in rats pretreated with colchicine, after diethylmaleate administration, only a few vesicles were observed around the bile canaliculus, while diethylmaleate-induced choleresis also decreased. These results suggest that: a) the thick microfilament network induced by phalloidin prevents diethylmaleate-associated vesicles reaching the bile canalicular plasma membrane; and b) colchicine produces a dispersion of these vesicles in the cytoplasm of hepatocytes by inhibiting the polymerization of microtubules. These observations support a role of vesicles in the transport of diethylmaleate by hepatocyte into bile, and are consistent with the existence of a vesicular pathway for the biliary secretion of diethylmaleate and possibly other organic anions.

Animals↗

[Toxicity of cholestatic bile acids on intrahepatic biliary cells of the rat].

The aim of this study is: 1. to isolate intrahepatic biliary epithelial cells and, 2. to study the toxicity of cholestatic biliary acids on these cells. Cells were isolated from rats with proliferated bile duct-cells, that were induced by a 21 days bile duct ligation. They were characterized by glutamyltranspeptidase and cytokeratins 7 and 19 using histochemical or immuno cytochemical methods. Isolated cells were incubated with different concentrations (250, 500, 1000 and 2000 microM) of cholestatic biliary acids, lithocholate sulfate (LCS) and taurolithocholate sulfate (TLCS. Cells viability is estimated by three methods: Trypan blue, LDH release and MTT test. We obtained purified fractions of non parenchymal liver cells enriched in biliary epithelial cells (> 95%). On these cells, we showed toxicity of LCS and TLCS and determined CI 10 and CI 50 of these acids which were respectively 800 microM and 2 mM for LCS; 1.4 and 2 mM for TLCS. These results indicate that cholestatic biliary acids (LCS and TLCS) are toxic for biliary cells. This cytotoxicity can be probably a possible mechanism of cholestasis.

Animals↗

[Effects of cholestatic bile acids on cytosolic calcium in isolated intrahepatic biliary cells].

In this study we measured biliary cytosolic calcium and examined the effect of cholestatic bile acids LCS and TLCS on intrahepatic isolated biliary cells cytosolic calcium. Cells have been isolated from bile duct ligated rats. Cytosolic calcium has been measured by using the Ca++ sensitive indicator Fura 2 and a cytofluorimetric method. LCS and TLCS (200 microM and 300 microM) increased the cytosolic Ca++ concentration of the cells. In contrast, the bile acids cholate and urso-desoxycholate which are choleretic had no effect. The number of cells which have increased their cytosolic calcium was directly correlated with the biliary acid toxicity. The increase induced by LCS and TLCS was abolished by removing external calcium. It is suggested that the calcium increase results from external calcium influx. This cytosolic calcium increase is known to be toxic for cells so it is concluded that this calcium increase is probably involved in the toxicity of LCS and TLCS.

Animals↗

Isolation and characterization of histogranin, a natural peptide with NMDA receptor antagonist activity.

Histogranin, was co-purified with bombesin-like immunoreactive peptides from bovine adrenal medulla. Its structure, H-Met-Asn-Tyr-Ala-Leu-Lys-Gly-Gln-Gly-Arg-Thr-Leu-Tyr-Gly-Phe-COOH, was determined by gas-phase Edman degradation. It was in accordance with its amino acid composition and corresponded to a 15 amino acid fragment (fragment 86-100) of histone H4 with substitutions in positions 1 (Val), 2 (Val) and 7 (Arg). The peptide was synthesized by the solid-phase procedure and the synthetic product was identical to the natural peptide as determined by its retention time on three analytical high-performance liquid chromatography systems. An antibody was raised against synthetic [Ser1]histogranin and used to monitor the presence of histogranin in various rat tissues and subcellular fractions of bovine adrenal medulla. In rats, immunoreactive histogranin was mainly concentrated in the pituitary (5065 pmol/g) and the adrenal glands (268 pmol/g), but it was also present in other tissues including the brain (1.6 pmol/g) and blood plasma (24 fmol/ml). A neuropeptide function for the adrenal peptide was suggested by its relative high concentration in chromaffin granules (42 fmol/mg protein as compared with 1 fmol/mg protein in cytosol) and its release from perfused bovine adrenal glands. In rat brain membrane preparations, synthetic histogranin displaced the binding of [3H]CGP 39653, a specific ligand of N-methyl-D-aspartate (NMDA) receptor. The displacement curve was biphasic with IC50 of 0.6 and 3955 nM, representing 33% and 67% of the binding sites, respectively. Intracerebroventricular (i.c.v.) injection of the peptide (5-100 nmol) in mice produced a dose-dependent protection against NMDA (0.5-1.0 nmol) -induced convulsions but not against (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.25-2.0 nmol), kainate (0.25-0.75 nmol) and bicuculline (1-10 nmol)-induced convulsions. These results suggest that histogranin may be an endogenous modulator of NMDA receptor functions.

2-Amino-5-phosphonovalerate↗

Increase of hemoglobin A2 in human immunodeficiency virus-1-infected patients treated with zidovudine.

We observed increased hemoglobin A2 (HbA2) levels in an asymptomatic human immunodeficiency virus-1 (HIV1) patient with no previous history of beta-thalassemia. He was treated only with zidovudine (AZT). In an attempt to understand this observation, a retrospective study was initiated to determine whether mean HbA2 levels are higher in AZT-treated patients than in subjects not receiving this drug and to assess if other hematologic alterations are associated with elevated HbA2. One hundred fifty-one HIV-positive cases were investigated; AZT was administered to 81 of them. The mean value of HbA2 was 0.032 (SD +/- 0.005) for the treated group vs. 0.027 (SD +/- 0.004) for the controls. This difference was highly significant (P < 0.001). Twenty-four patients (31%) in the treated group had elevated HbA2 levels vs. none in the controls. Bone marrow toxicity seemed to be more significant in patients with heightened HbA2 values, and HbA2 levels did not increase with CDC clinical stage. We conclude that AZT may be linked to high HbA2 levels in some patients.

Acquired Immunodeficiency Syndrome↗

Characterization of non-opioid [3H]dynorphin A-(1-13) binding sites in the rat heart.

The binding characteristics of [3H]Dynorphin A-(1-13) ([3H]Dyn A-(1-13) were examined in membrane preparations of rat heart. Saturation binding studies with increasing concentrations between 2.5 and 500 nM indicated that [3H]Dyn A-(1-13) binds to a single population of sites with a Kd of 285 nM and a Bmax of 215 pmol/mg protein. [3H]Dyn A-(1-13) binding is sensitive to trypsin treatment and it is inhibited by Zn2+ and Mg2+ with IC50 values of 159 and 310 microM, respectively. Dyn A and related peptides competes with the binding of [3H]Dyn A-(1-13) with the following order of potency: Dyn A-(1-13) > Dyn A > Dyn B > alpha-neo-endorphin > Dyn A-(1-8). The non-opioid peptides Dyn A-(2-13), Dyn A-(3-13) and Dyn A-(5-13) are as potent (Ki of 0.35, 0.44 and 0.59 microM, respectively) as Dyn A-(1-13) (Ki of 0.36 microM) in inhibiting [3H]Dyn A-(1-13) binding while Leu-enkephalin (Leu-Enk) exhibits no inhibitory effect at 100 microM. Selective ligands for kappa (kappa: U-50,488H, U-69,593), mu (mu: [D-Ala2, MePhe4, Glyol5]Enk) and delta (delta: [D-Ser2, Thr6]Leu-Enk) opioid receptors as well as for phencyclidine (PCP: MK-801, TCP) and sigma (sigma: (+)-SKF-10047, DTG, 3(+)-PPP) receptors show little or no inhibition of [3H]Dyn A-(1-13) binding at 100 microM. These results indicate that the heart contains a low affinity high capacity binding site for Dyn A and related peptides, distinct from opioid, PCP and sigma receptors.

Animals↗

Clindamycin/primaquine versus trimethoprim-sulfamethoxazole as primary therapy for Pneumocystis carinii pneumonia in AIDS: a randomized, double-blind pilot trial.

The aim of this double-blind pilot trial was to compare clindamycin/primaquine with trimethoprim-sulfamethoxazole (TMP-SMZ) as primary treatment for AIDS-related Pneumocystis carinii pneumonia (PCP). The focus was on toxicity and tolerability since comparisons of efficacy were limited by the small sample size. Sixty-five individuals with a first episode of possible PCP were randomly assigned to receive clindamycin/primaquine (34 patients) or TMP-SMZ (31 patients). PCP was subsequently proven microbiologically in 27 and 22 of the patients in these respective groups. Half of the participants had an arterial partial oxygen pressure at enrollment of < or = torr. The incidence and severity of adverse reactions were lower--but not significantly lower (P = .07 and .08, respectively)--with clindamycin/primaquine. The markers of severity improved in a similar manner regardless of which regimen was administered. No significant differences were documented in outcome, duration of survival, length of the PCP-free interval, or rate of relapse. The results of this pilot study show a trend toward less toxicity with clindamycin/primaquine than with TMP-SMZ. This result must be confirmed by larger-scale clinical trials, which are also needed to better compare the efficacy of the two regimens.

AIDS-Related Opportunistic Infections↗

Ursodeoxycholic acid improves ethinyl estradiol-induced cholestasis in the rat.

The effect of oral chronic administration of ursodeoxycholic acid has been examined in rats with cholestasis induced by ethinyl estradiol. Ursodeoxycholic acid at the dose of 25 mg kg-1 per day during 4 days, did not improve the decrease in basal bile flow and bile acid secretion induced by ethinyl estradiol alone. In contrast, when ursodeoxycholic acid was given at the same dose during 10 days, basal bile flow was significantly improved and basal bile acid secretion was restored to control values. When ursodeoxycholic acid was given at the dose of 500 mg kg-1 per day, basal bile flow and bile acid output were not further improved. However, bile flow and bile acid output under taurocholate infusion were restored to control values. Bile of rats treated with ursodeoxycholic acid was enriched with this bile acid. These results show a significant improvement of ethinyl estradiol-induced cholestasis in rats after chronic administration of ursodeoxycholic acid and support the use of this bile acid in intrahepatic cholestasis in man.

Alanine Transaminase↗

Thoracic splenosis after blunt trauma: frequency and imaging findings.

OBJECTIVE: Thoracic splenosis is an uncommon sequela of simultaneous splenic and diaphragmatic injury. The aim of this prospective study was to evaluate the prevalence of thoracic splenosis in 17 subjects who had sustained splenic and diaphragmatic injury and to describe the CT and MR features of thoracic splenosis. SUBJECTS AND METHODS: All patients had 99mTc-RBC scintigraphy. Subjects with radionuclide uptake in the thorax were further examined with radiography, CT, and MR imaging of the chest. RESULTS: Three subjects (18%) had evidence of ectopic splenic activity in the left side of the thorax. The CT features consisted of one pleural nodule and two pleural masses. The MR appearance of the ectopic splenic tissue was similar to that of normal spleen. CONCLUSION: Thoracic splenosis occurs with moderate frequency after combined splenic and diaphragmatic injury. The CT appearance is that of pleural masses or nodules. The MR appearance is relatively similar to that of normal spleen.

Adult↗

[Cocultures: diagnostic and therapeutic value].

Results of french multiple collaborative studies are reported to evaluate the possible benefits of coculture in human IVF program. Prospective randomized study of IVF with transfer on day two versus IVF with transfer on day 6 shows that coculture does not improve overall results but leads to a reduction of triple or quadruple pregnancies. When applied to patients with more than 4 failures of embryo transfers on day 2, delayed transfer of blastocyst results in a high rate of clinical pregnancy (39%). Transfers of frozen-thawed blastocysts result in 17.8% ongoing pregnancies. Coculture is also a powerful tool for understanding early embryo development: when fertilization arises from sperm with poor characteristics or from frozen sperm of donor, embryo development appears to be altered: in these situations, rate of normally developing embryo is reduced and early embryo development becomes independent of fertilization rate.

Adult↗