Biomedical subjects
Publications and source records attributed to P Brun.
The 1H and 13C NMR chemical shifts of four 2,5-diaryltetrahydrofuran derivatives and their dihydro precursors were assigned completely with certainty using a concerted application of one- and two-dimensional experiments (DEPT, gs-COSY, gs-HMQC and gs-HMBC)
Identification of the meticillin-resistant Staphylococcus aureus (MRSA) reservoir by active screening followed by the implementation of contact precautions is one of the major components of MRSA control programmes. The objective of this study was to evaluate the results of a programme of selective screening in an emergency department (ED) and the appropriateness of the contact precautions implemented. This was estimated by distinguishing necessary and unnecessary days of contact precautions. This estimation was performed for all days of contact precautions and, more specifically, for days of preventive contact precautions implemented before the availability of screening results. During a three-year period, screening of MRSA carriers was performed on 0.95% (N=605) of patients visiting the emergency ward. Among the 193 (31.9%) MRSA carriers identified, 159 were hospitalized in the short-length-hospitalization area (SLHA) of the ED and/or in other wards. Among the 140 patients admitted to the SLHA, 44 were hospitalized for at least 48 h, with a mean length of hospitalization of 5.9 days. The cumulative duration of hospitalization of carriers identified by screening was 1897 days. In total, 2370 days of contact precautions (including 924 days of preventive precautions) were implemented for patients screened in the ED. Considering the whole hospital, the appropriateness of this entire programme of contact precautions for patients screened in the ED was 80.0% (52.1% for the SLHA), whereas the specific appropriateness of preventive isolation days was 48.6% (43.6% for the SLHA). This study underscores the risk of MRSA cross-transmission in the SLHA, and the usefulness of implementing a control programme of screening carriers in the ED.
The 1H and 13C NMR resonances of five 6,6a-dihydrochromeno(3,4-b)chromene derivatives were assigned completely with certainty using a concerted application of one- and two-dimensional experiments (DEPT, gs-COSY, gs-HMQC and gs-HMBC).
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Several epidemiologic studies show in a concordant way that the prevalence of the overweight and that of obesity increase in France. Obesity is an important risk factor in public health. The main aim of the National Program of Nutrition and Health is to stop the increasing prevalence of childhood obesity. In this framework, we conducted a prevalence study among 1507 schoolchildren (boys: 51,6%; girls: 48,4%) aged from 11 to 17 years old. A self-questionnaire was used to collect information concerning the weight, height and diet. The findings show that 17,6% of collegians are either over weighted or obese, 7,7% of the girls and 10,0% of the boys are in overweight; 5,5% of the girls and 11,7% of the boys are obese, according to the French charts of body mass index (BMI). This study shows a decreasing frequency of the overweight with the age in both males and females: 28,9% at the 11 years old and 13,2% at the 17 years old. Preventive actions are needed at early stages to try to stop and, if possible, to reverse the present increase of overweight. In this context, the itinerant forum of health promotion carried out in the Hauts-de-Seine department with school doctors can play a determining part.
The caprine arthritis-encephalitis lentivirus (CAEV) causes a lifelong persistent infection in goats, and induces infiltrations of leucocytes and tissue reorganization in target organs, with a cyclical pattern of viral expression. The mammary gland is an important site of infection, associated with mother-to-kid transmission by infected cells in colostrum and milk. The monocyte/macrophage is the principal target cell, but other cell types, including epithelial and endothelial cells and fibroblasts, are susceptible to in vitro infection with varying levels of viral replication. Such cells, perhaps at specific differentiation states, might play a role in the regulation and transfer of in vivo infection in target organs. In this paper we describe the in vitro infection of endothelial cell monolayers by the transmigration of monocytes carrying the CAEV provirus. The infected endothelial cells progress to expression of the viral p30 capsid antigen, suggesting viral proliferation. Such a process occurring in vivo during angiogenesis and leucocyte homing to the mammary gland in the final third of mammogenesis, might contribute to viral spread in this crucial target organ.
Tissue engineering is a promising approach to developing hepatic tissue suitable for the functional replacement of a failing liver. The aim of the present study was to investigate whether an extracellular cell matrix obtained from fibroblasts-cultured within scaffolds of hyaluronic acid (HYAFF) could influence the proliferation rate and survival of rat hepatocytes both during long-term culture and after in vivo transplantation. Cultures were evaluated by histological and morphological analysis, a proliferation assay and metabolic activity (albumin secretion). Hepatocytes cultured in extracellular matrix-enriched scaffolds exhibited a round cellular morphology and re-established cell-cell contacts, growing into aggregates of several cells along and/or among fibers in the fabric. Hepatocytes were able to secrete albumin up to 14 days in culture. In vivo results demonstrated the biocompatibility of HYAFF-11 implanted in nude mice, in which hepatocytes maintained small well-organised aggregates until the 35th day. In conclusion, the presence of a fibroblast-secreted extracellular matrix improved the biological properties of the hyaluronan scaffold, favoring the survival and morphological integrity of hepatocytes in vitro and in vivo.
Taking advantage of the proximity of bowel mucosa to luminal bacteria, we have attempted to deliver a therapeutic gene to the colonic mucosa by oral administration of an invasive and non-pathogenic Escherichia coli. E. coli diamenopimelate (dap) auxotroph, harboring plasmid pGB2Omegainv-hly, express the inv gene from Yersinia pseudotubercolosis that confers the ability to invade nonprofessional phagocytic cells and the hly gene from Listeria monocytogenes that allows expression of lystreriolysin O, a perforin cytolysin able to perfore phagosomal membranes. This bacterial vector invades and transfers functional DNA to epithelial cells in vitro. We have shown that this strain carrying a therapeutic gene (pC1OmegaTGF-beta1) can significantly reduce the severity of experimental colitis in mice. However, as a consequence of mucosal barrier disruption during colitis, vector-specific mRNA transcripts could be recovered from the colon and also from extra-colonic tissues. We therefore replaced the constitutive CMV promoter in pC1OmegaTGF-beta1 by the inflammation-inducible interleukin-8 promoter generating plasmid pC1OmegaTGF-beta1IND. Plasmid-specific TGF-beta1 mRNA transcripts were detectable in mouse CMT-93 epithelial cells incubated with E. coli BM2710/pGB2Omegainv-hly carrying pC1OmegaTGF-beta1IND following exposure to inflammatory cytokines. Furthermore, the transcripts were detectable only within inflamed tissues and the therapeutic effects were comparable to those in animals treated with E. coli BM2710/pGB2Omegainv-hly+pC1OmegaTGF-beta1. In summary, engineered enteric bacteria can efficiently deliver in vivo therapeutic genes to the intact intestinal mucosa and regulation expression of the therapeutic gene by an inflammation-inducible promoter prevents its dissemination during colitis.
A 31-year old Egyptian was referred to evaluate the etiology of elevated liver enzymes. The patient had been suffering from diabetes type 1 for three years and complained about episodes of light diarrhea. Laboratory investigation revealed a moderate elevation of cholestatic enzymes. Ultrasound examination and computed tomography did not show mechanical biliary obstruction. Drug-induced cholestasis, viral hepatitis and primary biliary cirrhosis could be excluded as well. Finally, schistosomiasis mansoni was diagnosed by microscopic stool examination as well as histological evaluation of biopsy specimens obtained during colonoscopy. This parasitic disease may cause slowly progressive liver injury by the release of schistosome eggs into the portal vein system. Histological evaluation of liver specimens of this patient showed portal inflammation and the presence of pigmented macrophages. This pattern, though unspecific, was consistent with the diagnosis of schistosomiasis mansoni. Treatment with praziquantel resulted in regression of diarrhea episodes and normalization of cholestatic enzymes within three months.
Experiences coming from many cell-culture studies has brought about the concept that tissue and organ reconstruction should be performed in a three-dimensional environment as it normally occurs in vivo. As far as endothelial cell culture is concerned, it has been shown that angiogenesis can be successfully achieved only when cells are cultured in the presence of collagen-based matrices or basal membrane substrates. The aim of the present investigation is to demonstrate that human umbilical vein endothelial cells (HUVEC) can be grown and differentiated on an artificial dermis obtained by fibroblasts cultured on hyaluronic acid-based scaffolds. For this purpose, we have cultured HUVEC, retrieved by collagenase digestion of perfused human umbilical vein either alone and with fibroblast at 1/1 ratio into HYAFF-11 non-woven mesh. Cultures were maintained for up to 3 weeks. Samples were taken at different time points within this period for the MTT proliferation test and for immunohistochemical analysis. Our results demonstrate that hyaluronan-based biomaterials (HYAFF-11 NW mesh) represent a suitable substrate for HUVEC adhesion, proliferation and reorganization in microcapillary network.
OBJECTIVE: To identify the CD44-receptor-mediated effects of 5-7 x 10(5)MW hyaluronan (HA, Hyalgan) on cell viability in normal and damaged human chondrocyte primary cultures isolated from articular cartilage. DESIGN: Primary cultures of human chondrocytes were established from normal articular biopsies and expanded to the second culture passage. The dose-response effects of HA on the viability of normal cultures were identified. Chondrocytes were then treated with either hypoxanthine (2 mM) and xanthine oxidase (20-60 mU), or with activated polymorphonuclear leukocytes (PMNs) to induce injury. Damaged and control cells were then treated with 5-7 x 10(5)HA in the previously identified optimal dose of 0.05 mg/ml. Viability was assessed at specific time periods for the chemically and PMN-damaged cells. To identify if HA effects were mediated by the CD44 receptor, chondrocytes were incubated with anti-CD44 antibody at saturating concentrations (5 microg/ml for 100,000 cells) to produce a maximum inhibition of HA binding. Cells were evaluated using the MTT viability assay, histology, electron microscopy and immunohistochemistry. RESULTS: Direct addition of HA (optimal dose, 0.5 mg/ml) significantly increased cell survival in normal chondrocyte primary cultures (P<0.05). Similarly, addition of this same dose of HA to cultures of free radical-damaged chondrocytes, restored the viability to baseline conditions. Cell viability rates dropped significantly (P<0.05) when CD44 receptor binding was inhibited, indicating that cell growth was mediated by the CD44 receptor. CONCLUSIONS: HA (0.5 mg/ml of 5-7 x 10(5)) significantly increased the viability of normal human chondrocytes in primary culture and restored cell viability to near normal levels after oxidative cell injury.
BACKGROUND: Studies on the inflammatory process in the large airways of patients with mild/moderate COPD have shown a prevalent T lymphocyte and macrophage infiltration of the bronchial mucosa. However, bronchial inflammation in more severe disease has not been extensively studied. OBJECTIVE: The aim of the present study was to characterize the lymphocyte infiltration in the bronchial mucosa of subjects with severe, compared to mild, COPD, and to examine the relationship between airflow limitation and T lymphocyte numbers in the bronchial mucosa. METHODS: We examined bronchial biopsies obtained from nine smokers with severe airflow limitation, nine smokers with mild/moderate airflow limitation and 14 smokers with normal lung function. Immunohistochemical methods on cryostat sections were used to assess the number of CD3+, CD4+, CD8+ cells and the number of CD3+ cells coexpressing the chemokine receptor CCR5 (CCR5+CD3+) in the subepithelium. RESULTS: Subjects with severe COPD had lower numbers of CD3+, CD8+ and CCR5+CD3+ cells than mild/moderate COPD (P < 0.012, P < 0.02 and P < 0.02, respectively) and control smokers (P < 0.015, P < 0.005 and P < 0.015, respectively). In subjects with airflow limitation the number of CD3+ and CD8+ cells was inversely correlated with the degree of airway obstruction (r = 0.59, P < 0.015 and r = 0.52, P < 0.032, respectively). CONCLUSIONS: Bronchial inflammation in severe COPD is characterized by lower numbers of CD3+ and CD8+ cells and decreased numbers of CD3+ cells coexpressing the chemokine receptor CCR5. T lymphocyte infiltration is inversely correlated with the degree of airflow limitation.
SR-142948A belongs to the second generation of potent, selective, non-peptide antagonists of neurotensin receptors. It was used to investigate the role of endogenous neurotensin in the regulation of dopamine efflux in the nucleus accumbens and striatum of anaesthetized and pargyline-treated rats. All the data were obtained using in vivo electrochemistry. Electrically evoked (20 Hz, 10 s) dopamine efflux was monitored by differential pulse amperometry, whereas variations in basal (tonic) dopamine efflux were monitored by differential normal pulse voltammetry. Like the first-generation compound SR-48692, SR-142948A did not affect the tonic and evoked dopamine efflux, but dose-dependently enhanced haloperidol (50 microg/kg, i.p.) induced facilitation of the electrically evoked dopamine release in the nucleus accumbens. In contrast to SR-48692, SR-142948A dose-dependently potentiated haloperidol (50 microg/kg, i.p.) induced increase in the basal dopamine level in the nucleus accumbens. This potentiating effect did not appear in the striatum. When dopaminergic and/or neurotensinergic transmissions were modified by a higher dose of haloperidol (0.5 mg/kg, i.p.), apomorphine, amphetamine or nomifensine, SR-142948A pre-treatment affected only the effect of apomorphine on the basal dopamine level in the nucleus accumbens. These results strengthen the hypothesis that endogenous neurotensin could exert a negative control on mesolimbic dopamine efflux.
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Management and treatment of disease do not always conform with official recommendations. African-quin is a pragmatic multicentric study carried out in 13 African countries to evaluate non-conformities in the management and treatment of uncomplicated malarial attacks using quinine. This study involved a total of 3,981 patients with documented uncomplicated malarial attacks diagnosed by 500 clinical physicians. Physicians were supplied with quinine tablets (125 mg et 500 mg Quinimax containing 125 mg and 500 mg of quinine base respectively) to allow treatment according to the dose recommendations of the WHO (24 mg/kg/day of quinine base). In 38% of the 3,981 patients, diagnosis was based on clinical findings without measurement of parasitemia. The median dose of Quinimax was 15.4 mg/kg/day in 3 intakes in 67% and 2 intakes in 33%. The dose was 23.2 mg/kg/day for patients under 12 years and 14.7 mg/kg/day for patients over 18 years (p < 0.001). Treatment lasted for at least 5 days in 62% of patients. Fever control was achieved within a mean delay of 3.9 +/- 1.5 days and was followed by a rapid decrease in clinical symptoms. Clinical control (normal temperature) was obtained in 96% of patients. The dose of Quinimax was the same regardless of whether treatment was a success or failure. The results of this study demonstrate the gap between official recommendations and everyday clinical practice and raise several important questions concerning the basis for decision-making, treatment goals, drug dosage, and treatment duration.
The title compound, [Cr(C(15)H(14)O)(CO)(3)], is a chromene complexed with tricarbonylchromium and it exhibits photochromic properties. The molecular geometry is compared to that of two similar complexes. The analysis results indicate that complexation has minor effects on the chromene structure.
The tolerability and safety of hyaluronan-based three-dimensional scaffolds as a culture vehicle for mesenchymal progenitor cells was investigated in this pilot study. The proliferation patterns and extracellular matrix production of rabbit and human mesenchymal, bone-marrow-derived progenitors first were characterized in vitro. Subsequently rabbit autologous cells were cultured in this hyaluronan-based scaffold and implanted in a full-thickness osteochondral lesion. In vitro histologic findings showed that mesenchymal progenitor cells adhered and proliferated onto the hyaluronan-derived scaffold. Human stem cells were shown to produce the main extracellular matrix molecules, accompanied by an occasional synthesis of mature type II collagen. In vivo data demonstrated that the biomaterial, with or without mesenchymal progenitors, did not elicit any inflammatory response and was completely degraded within 4 months after implantation. With regard to the efficacy of this cell therapy, even among the small number of animals tested there was histologic evidence that lesions filled with the biomaterial, either seeded or unseeded with cells, achieved a faster and better healing compared to empty controls. The present data suggest that the hyaluronan-based scaffolds are well tolerated and safe and may be a valuable delivery vehicle for tissue engineering in the repair of articular cartilage defects.