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Biomedical subjects

B Fouqueray

Publications and source records attributed to B Fouqueray.

At least 19 recordsLinked to original sources
PubMed2001

Haemodynamic changes and vasopressin release are not consistently associated with carbon dioxide pneumoperitoneum in humans.

BACKGROUND: Conflicting haemodynamic changes, suggested to be caused by vasopressin release, have been reported during carbon dioxide (CO2) pneumoperitoneum. However, peritoneal stimulations including open surgery cause both a systemic vasopressor response and a vasopressin release, which are suppressed by opiate administration. Also, a decreased venous return of blood to the heart causes vasopressin release. Furthermore, previous haemodynamic assessments of laparoscopic surgery have been conducted using various anaesthetic regimens, which are likely to have caused various haemodynamic effects. We hypothesised that intraoperative haemodynamic and/or humoral changes would not be observed in association with laparoscopic surgery provided that, (a) normovolaemia is continuously maintained using transoesophageal echocardiographic (TEE) assessment, and (b) adequate depth of general anaesthesia is continuously maintained by bispectral index (BIS) monitoring and high plasma Ievel opiate administration. METHODS: Twenty ASA 1 women undergoing laparoscopic surgery received 10 ml. kg-1 lactated Ringer's solution and thereafter were randomly allocated to receive intraoperatively either 8 ng. ml-1 or 4 ng. ml-1 plasma remifentanil concentrations while BIS was maintained at 50+/-5 by isoflurane alteration. The group receiving 4 ng. ml-1 remifentanil was used as control. Expired CO2 was maintained within a 32-38 kPa range throughout the investigation. Complete TEE haemodynamic investigation was performed before pneumoperitoneum (PP) (T1), and during PP horizontal (T2), with a head-up tilt (T3), with a head-down tilt (T4), horizontal (T5), and PP released (T6). Plasma vasopressin, epinephrine and norepinephrine levels were measured at T1, T3, and T6. ANOVA, Student's t-test and Mann-Whitney U-test were used for statistical analysis. RESULTS: Haemodynamic indices and humoral values did not change significantly within and between remifentanil groups throughout the investigation (all P<0.05). CONCLUSION: Continuous adequate depth of anaesthesia and normovolaemia may have prevented both a humoral and a haemodynamic response, initiated in the peritoneum by the contact with CO2 in previous investigations.

Adult↗
PubMed2001

Cytokines and hormones with anti-inflammatory effects: new tools for therapeutic intervention.

The inflammation that is involved in the development of glomerulonephritis is tightly regulated by the expression of anti-inflammatory factors. These include circulating hormones, such as glucocorticoids, and mediators that are produced by intrinsic cells and infiltrating leucocytes. The present review focuses on these anti-inflammatory factors, summarizing in particular their activities in existing models of glomerulonephritis. In addition, experimental evidence is presented that anti-inflammatory mediators are able to increase glucocorticoid binding or signalling in target cells. These data help to explain the in-vivo efficacy of anti-inflammatory mediators, and offer a promising new avenue for therapeutic intervention.

Animals↗
PubMed2001

Induction of urokinase receptor expression in nephrotoxic nephritis.

The urokinase receptor (uPAR) is a multifunctional molecule involved in pericellular, fibrinolytic, and proteolytic activities, as well as in cell adhesion and chemotaxis and may play a role in the pathogenesis of tissue remodeling occurring during glomerulonephritis. We analyzed sequentially the expression of uPAR by immunohistochemistry and in situ hybridization in an accelerated model of nephrotoxic nephritis in rats. A strong induction of uPAR mRNA expression was observed in glomeruli as soon as 1 h after nephrotoxic serum injection. The intensity of glomerular uPAR mRNA and antigen expression increased and peaked at 24 h. At that time, numerous glomerular fibrin deposits, monocyte/marcrophage infiltration, and heavy proteinuria were observed. Fibrin deposition was detected at 6 h, peaked at 24 h, and progressively declined over the next 3 weeks, while uPAR antigen expression remained elevated until the end of the study (3 weeks). By double labeling, we showed that the expression of uPAR was mediated by both intrinsic glomerular cells and infiltrating macrophages. Severe podocytic lesions developed within 3 days after antiserum injection, and glomerulosclerosis rapidly progressed within 2-3 weeks. These results show that glomerular uPAR expression is induced in nephrotoxic nephritis and suggest that uPAR may promote local proteolysis and also tissue remodeling, leading to the late development of glomerulosclerosis.

Animals↗
PubMed2001

Transforming growth factor-beta inhibits interleukin-10 synthesis by human monocytic cells.

Transforming growth factor-beta (TGF-beta1) enhances interleukin-10 (IL-10) synthesis by mouse monocytes/macrophages, suggesting a potential role of IL-10 in mediating some of the anti-inflammatory properties of TGF-beta1. Since differences exist between the transcriptional regulation of human and mouse IL-10, the studies reported here examined whether TGF-beta1 up-regulated IL-10 production by human monocytes/macrophages as well. Exposure of PMA-differentiated U-937 promonocytic cells to TGF-beta1 resulted in an unexpected, dose-dependent decrease in IL-10 production as assessed by specific ELISA. TGF-beta1 was effective when added at the time of the PMA stimulus or 6 hours after. In addition, TGF-beta1 suppressed induction of IL-10 by three different stimuli other than PMA. TGF-beta1 inhibition of IL-10 protein release was associated with proportional changes in IL-10 mRNA accumulation as assessed by quantitative kinetic ELISA PCR. This would result from a decrease in IL-10 gene transcription as TGF-beta1 did not affect IL-10 mRNA stability, and TGF-beta1 limited the luciferase activity in cells transfected with reporter gene constructs containing 1,308 bp of the 5' non-coding sequence of human IL-10 gene. Blocking tumour necrosis factor-alpha (TNF-alpha) with neutralizing anti-TNF-alpha antibody did not modify the response to TGF-beta1, indicating the involvement of TNF-alpha-independent mechanisms in the overall process. Thus, the present study provides the first evidence that TGF-beta1 prevents IL-10 production by human monocytic cells at a transcriptional level.

Cell Differentiation↗
PubMed2000

Glomerulosclerosis in mice transgenic for human insulin-like growth factor-binding protein-1.

BACKGROUND: The growth hormone (GH)/insulin-like growth factor (IGF) system is thought to participate in the glomerulosclerosis process. Because IGF-binding proteins (IGFBPs) modulate IGF actions and hence GH secretion, this study assessed whether mice transgenic for human IGFBP-1 have altered susceptibility to glomerulosclerosis. METHODS: A line of transgenic mice that express human IGFBP-1 mRNA in the liver under the control of the alpha1-antitrypsin promoter has been obtained, and morphological changes in the kidney tissue were assessed. Glomerulosclerosis was identified using light microscopy, light microscopic morphometry, and electron microscopy. Extracellular matrix components were analyzed by immunohistochemistry. RESULTS: There was a marked increase in mesangial extracellular matrix area in homozygous transgenic mice at three months of age as compared with heterozygous transgenic mice and nontransgenic littermates. These changes were not associated with alterations in glomerular volume or cellularity. The expansion of extracellular matrix area was related to a marked increase in laminin and type IV collagen and to the appearance of type I collagen. CONCLUSIONS: These observations indicate that the enhanced expression of IGFBP-1 may result in the development of glomerulosclerosis without glomerular hypertrophy. The changes are potentially related to a decrease in IGF-I availability and/or to an IGF-I-independent role of IGFBP-1.

Animals↗
PubMed2000

Nephrotoxic nephritis and obstructive nephropathy: evaluation with MR imaging enhanced with ultrasmall superparamagnetic iron oxide-preliminary findings in a rat model.

PURPOSE: To evaluate the role of magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation and differentiation of different types of nephropathies. MATERIALS AND METHODS: Two experimental rat models of nephropathies were studied: a model of nephrotoxic nephritis induced by means of intravenous injection of sheep anti-rat glomerular basement membrane serum (n = 43) and a model of obstructive nephropathy (n = 6). Imaging sessions were performed with a spectrometer operating at 4.7 T with fast low-angle shot, or FLASH, sequences. Signal intensity was measured in each kidney compartment before and 24 hours after intravenous injection of USPIO (90 micromol of iron per kilogram of body weight). MR findings were compared with histologic data and urine protein levels. RESULTS: In the nephrotoxic nephritis model 24 hours after injection of USPIO, a significant signal intensity decrease (P: <.05) was present only in the cortex where the glomerular lesions were located. In the obstructive nephropathy model, the signal intensity decrease (P: <.05) was located in all kidney compartments in response to diffuse interstitial lesions. The decrease in signal intensity was due to iron uptake by either macrophages or mesangial cells gaining endocytic activity and was correlated, in the nephrotoxic nephritis model, to the degree of proteinuria. CONCLUSION: Twenty-four-hour delayed USPIO-enhanced MR imaging may help identify and differentiate various types of nephropathies.

Animals↗
PubMed1999

Somatostatin increases glucocorticoid binding and signaling in macrophages by blocking the calpain-specific cleavage of Hsp 90.

Somatostatin has direct anti-inflammatory actions and participates in the anti-inflammatory actions of glucocorticoids, but the mechanisms underlying this regulation remain poorly understood. The objective of this study was to evaluate whether somatostatin increases glucocorticoid responsiveness by up-regulating glucocorticoid receptor (GR) expression and signaling. Somatostatin promoted a time- and dose-dependent increase in [(3)H]dexamethasone binding to RAW 264.7 macrophages. Cell exposure to 10 nM somatostatin for 18 h promoted a 2-fold increase in the number of GR sites per cell without significant modification of the affinity. Analysis of GR heterocomplex components demonstrated that somatostatin increased the level of heat shock protein (Hsp) 90, whereas the level of GR remained almost unchanged. The increase in Hsp 90 was associated with a decrease in the cleavage of its carboxyl-terminal domain. Evidence for the involvement of calpain inhibition in this process was obtained by the demonstration that 1) somatostatin induced a dose-dependent decrease in calpain activity and 2) calpain inhibitors, calpain inhibitor I and calpeptin, both abolished the cleavage of Hsp 90 and induced a dose-dependent increase in [(3)H]dexamethasone binding. Increases in glucocorticoid binding after somatostatin treatment were associated with similar increases in the ability of GR to transactivate a minimal promoter containing two glucocorticoid response elements (GRE) and to interfere with the activation of nuclear factor-kappaB (NF-kappaB). Thus, the present findings indicate that somatostatin increases glucocorticoid binding and signaling by limiting the calpain-specific cleavage of GR-associated Hsp 90. This mechanism may represent a novel target for intervention to increase glucocorticoid responsiveness.

Animals↗
PubMed1999

Reduction of tumour necrosis factor alpha expression and signalling in peripheral blood mononuclear cells from patients with thalassaemia or sickle cell anaemia upon treatment with desferrioxamine.

Recent evidence indicates that the rate of progression of the HIV-1 disease is significantly reduced in thalassaemia major patients upon treatment with high doses of desferrioxamine (DFX). The authors have previously demonstrated that in vitro exposure of mononuclear cells to DFX decreases the bioavailability of tumour necrosis factor alpha (TNF-alpha) which has a stimulatory effect on HIV-1 replication. In this study, therefore, TNF-alpha bioavailability from mononuclear cells isolated from 10 patients with thalassaemia or sickle cell anaemia given DFX as compared to 10 untreated subjects has been evaluated. Evidence is presented showing that DFX treatment reduces TNF-alpha bioavailability (P<0.05) by inhibiting its steady state (P<0.05) and by enhancing its inactivation through binding to soluble TNF-alpha receptor type II (P<0.05). We also show that DFX treatment limits the in vivo activation of NF-kappaB, a transcription factor involved in both TNF-alpha gene transcription and TNF-alpha signalling (P<0.005). We conclude that TNF-alpha bioavailability and signalling are impaired in patients upon DFX treatment. This mechanism may contribute to delayed progression of the HIV-1 infection in vivo.

Adolescent↗
PubMed1999

Hepatitis C virus genotypes in France: relationship with epidemiology, pathogenicity and response to interferon therapy. The GEMHEP.

The aim of this study was to investigate the following in a large population of French patients with chronic hepatitis C: the geographical distribution of hepatitis C virus (HCV) genotypes; the relationship between HCV genotypes and epidemiological characteristics; severity of the disease; and response to interferon (IFN) therapy. Data from 14 tertiary referral centres, corresponding to 1872 patients with chronic hepatitis C, were prospectively collected from 1989 to 1997. HCV genotyping was performed using the line probe assay (LiPA). HCV genotypes 1b, 3, 1a, 2, 4 and a mixed infection were found in 41%, 22%, 16%, 11%, 4% and 4% of our population, respectively. HCV genotype distribution was homogeneous, except for genotype 2 that was found more frequently in the southwest than in the other regions (21% vs 9.2%) (P=0.001). HCV distribution was associated with gender, age, and source and duration of infection. In multivariate analysis, these correlations were related to the source of infection, which was the only independent factor significantly associated with genotype (P=0.001). Genotype 1b was significantly more common in patients with cirrhosis, but in multivariate analysis cirrhosis was independently related to older age at exposure and longer duration of infection (P=0.001). A sustained response to IFN therapy was observed in 11% of patients infected with genotypes 1a or 1b vs 32% of those infected with genotypes 2 or 3 (P=0.001). This study shows that HCV genotype is mainly related to the source infection, but not to the intrinsic pathogenicity of HCV, and is a strong predictor of sustained response to therapy.

Adult↗
PubMed1999

[Interactions between glucocorticoids and anti-inflammatory peptides].

Both pro- and anti-inflammatory mediators regulate the anti-inflammatory actions of glucocorticoids, in part by modifying the binding of glucocorticoids to specific receptors. For instance, somatostatin has been shown to increase glucocorticoid binding and signaling in macrophages. The mechanism of this regulation does not require an increased expression of glucocorticoid receptors but, rather, a stabilization of glucocorticoid receptor-associated heat shock protein 90. This is related to a decrease in calpain activity. Thus calpain inhibition may offer a new and exciting possibility for enhancing the anti-inflammatory efficiency of glucocorticoids.

Animals↗
PubMed1999

Haemodynamic changes associated with portal triad clamping are suppressed by prior hepatic pedicle infiltration with lidocaine in humans.

Portal triad clamping (PTC) reduces venous return of blood to the heart. However, the decrease in cardiac index (CI) is associated with an unexpected increase in mean arterial pressure (MAP) and the 40% increase in systemic vascular resistance is greater than anticipated in compensation for the 10% decrease in CI. We hypothesized that a reflex elicited in the peritoneum accounted for this unanticipated haemodynamic response. Twenty patients undergoing liver resection were allocated randomly to have hepatic pedicle infiltration before PTC with either lidocaine 200 mg or placebo. MAP was recorded, and plasma osmolality and plasma concentrations of vasopressin, epinephrine, norepinephrine, dopamine, renin and endothelin were measured. After PTC, MAP increased significantly in the placebo group but decreased significantly in the lidocaine group. Plasma concentrations of vasopressin, epinephrine and norepinephrine increased significantly in the placebo group. Plasma concentrations of vasopressin decreased significantly in the lidocaine group, while plasma concentrations of epinephrine and norepinephrine were unchanged. A subsequent study in eight patients found that neither haemodynamic nor hormonal changes associated with PTC in the placebo group were altered by administration of lidocaine 200 mg i.m. before PTC.

Adolescent↗
PubMed1999

Reactive oxygen and nitrogen intermediates increase transforming growth factor-beta1 release from human epithelial alveolar cells through two different mechanisms.

Transforming growth factor (TGF)-beta1 is a growth factor involved in the mechanisms of lung repair and fibrosis that follow inflammatory processes. We sought to examine the link between the generation of reactive oxygen intermediates (ROI) or reactive nitrogen intermediates (RNI) by inflammatory cells and the expression of TGF-beta1 by alveolar epithelial cells. Exposure of the A549 lung epithelial cell line to either an ROI generating system (xanthine and xanthine oxidase) or an RNI donor (S-nitroso-N-acetyl-penicillamine [SNAP]) promoted a time- and dose-dependent increase in TGF-beta1 release, as measured by a specific enzyme-linked immunosorbent assay. At the peak, the levels of TGF-beta1 were twice the control values. The induction of TGF-beta1 release by ROI was blunted by catalase and unaffected by superoxide dismutase, indicating the involvement of hydrogen peroxide. The response was also blunted by 5, 6-dichloro-1-beta-D-ribofuranosyl benzimidazole (DRB), a specific RNA polymerase II inhibitor, and accompanied by a corresponding increase in TGF-beta1 messenger RNA, as measured by quantitative/competitive reverse transcription polymerase chain reaction, suggesting the involvement of transcriptional mechanisms and possibly other downstream mechanisms. In contrast, RNI-induced TGF-beta1 release was unaffected by DRB and blunted by the protein synthesis inhibitor cycloheximide, suggesting the involvement of translational and post-translational mechanisms. This response required cyclic guanosine monophosphate (cGMP)- mediated processes because (1) immunoreactive cGMP accumulated in the culture medium of SNAP-treated cells; (2) SNAP-induced TGF-beta1 release was blunted by KT 5823, an inhibitor of cGMP-dependent protein kinase; and (3) similar increase in TGF-beta1 release was obtained by cell exposure to membrane-permeable dibutyryl-cGMP or to atrial natriuretic factor, a known agonist of particulate guanylate cyclase. These data suggest that in vitro exposure of human alveolar epithelial cells to ROI and RNI enhances TGF-beta1 release through different mechanisms. In vivo, this control may constitute a molecular link between inflammatory and fibrotic processes.

Arginine↗
PubMed1999

[Inflammatory mechanisms of renal fibrosis: glomerulonephritis].

Studies of glomerulonephritis models have shown that inflammatory reaction is responsible for the development of glomerulosclerosis and tubulo-interstitial sclerosis and, hence, for the progression to end stage renal failure. That macrophage accumulation and fibrosis extension are frequently not closely related events suggests that macrophages are not involved in progression process. Glomerular sclerosis is rather associated with the release of mediators from resident cells-mainly growth factors such as platelet-derived growth factor and transforming growth factor-beta--the synthesis and bioactivity of which are enhanced by inflammatory mediators. Tubulo-interstitial sclerosis is induced by inflammatory lesions of the glomerulus that lead to proteinuria. Indeed, reabsorption of proteins in proximal tubule triggers epithelial cells to release proinflammatory and prosclerotic mediators into the interstitium. New therapeutic approaches including gene transfer strategies are directed at suppressing the efficiency of such mediators.

Fibrosis↗
PubMed1998

[Polyuropolydipsic syndromes].

PROGNOSIS: Intracellular dehydration is the major risk in case of a polyuropolydipsic syndrome. Excepting osmotic polyuria, prognosis depends on a possibly progressive functional anomaly of the hypothalamopituitary axis. PATHOPHYSIOLOGY: Polyuropolydipsia occurs when antidiuretic hormone (ADH) secretion is absent (central diabetes insipidis), the kidney does not respond to ADH (nephrogenic diabetes insipidus) or in case of physiological inhibition of ADH secretion (primary polydipsia). EXPLORATION: Dynamic explorations are associated with radioimmunoassay of ADH. They are particularly useful in case of atypical diabetes insipidus and include the water restriction test and a study of the sensitivity to exogenous ADH (dDAVP). The results orient the etiologic diagnosis and allow an evaluation of the fluid intake required as a function of the maximal concentrating capacity of the kidneys. TREATMENT OF CENTRAL DIABETES INSIPIDUS: Treatment is based on ADH analogs (dDAVP). The aim is to obtain a constant antidiuretic effect without hyponatremia or escape. In case of partial central diabetes insipidus, a non-hormone treatment using compounds which increase vasopressin release or its effect on the kidney can be proposed.

Diagnosis, Differential↗
PubMed1998

Low environmental pH is responsible for the induction of nitric-oxide synthase in macrophages. Evidence for involvement of nuclear factor-kappaB activation.

Stimulation of macrophages with endotoxin and/or cytokines is responsible for the expression of the inducible isoform of nitric oxide synthase (iNOS). Because macrophages are exposed to low pH within the microenvironment of inflammatory lesions, the potential role of acidic pH as an additional regulator of iNOS was investigated. Substitution of the culture medium of rat peritoneal macrophages at pH 7.4 with medium at pH 7.0 up-regulated iNOS activity, as reflected by a 2.5-fold increase in nitrite accumulation. The increase in iNOS activity was associated with a similar increase in iNOS mRNA expression that reflected an increase in iNOS mRNA synthesis rather than stability. Low environmental pH-induced iNOS gene transcription involved the activation of nuclear factor-kappaB (NF-kappaB) transcription factor since exposure of macrophages to low environmental pH both increased NF-kappaB binding activity in the nucleus and enhanced NF-kappaB-driven reporter gene expression. In addition, treatment of macrophages with pyrrolidine dithiocarbamate or n-acetyl-leucinyl-leucinyl-norleucinal, two drugs preventing NF-kappaB translocation to the nucleus, canceled low pH-induced nitrite accumulation. The overall mechanism required the synthesis of tumor necrosis factor alpha (TNFalpha). Indeed, 1) elevated TNFalpha bioactivity was observed in the medium of macrophages exposed to pH 7.0, and 2) incubation of macrophages with a neutralizing anti-TNFalpha antibody impaired both NF-kappaB activation and nitrite accumulation in response to acid challenge. In summary, exposure of macrophages to acidic microenvironment in inflammatory lesions leads to the up-regulation of iNOS activity through the activation of NF-kappaB.

Acids↗