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Biomedical subjects

C Monteil

Publications and source records attributed to C Monteil.

17 recordsLinked to original sources

[Evaluation of an information document about patients and transfusion].

OBJECTIVE: To evaluate the understanding of written information contained in the information sheet for patients intended to receive an homologous transfusion and to know their opinion about this document. TYPE OF THE STUDY: A prospective cohort survey carried out by people unrelated to clinical units and transfusion services. METHODS: A document divided in two parts, the first one summarized, the second detailed, was distributed to transfused adult patients. The patients were hospitalized in the general surgery and orthopedic wards of two hospitals and in the hematology and oncology wards of two different hospitals. A questionnaire was filled out in the presence of the inquirer. RESULTS: Sixty one subjects have been enrolled, among them 53 considered the information as adequate; 53 as comforting and neutral. 53 patients considered a written information as essential and 52 estimated that both part of the information sheet (summarized and detailed) were mandatory. Conversely, a more in depth investigation revealed there was a gap between patients statements and their true understanding. CONCLUSION: The value of a written information for the patients is confirmed by the study. In addition, patients were not generally worried by this information. The partition of the document has been appreciated. It is noteworthy that a gap exist between the patient's perception of the information and their actual level of understanding.

Adult↗

Acrolein toxicity: comparative in vitro study with lung slices and pneumocytes type II cell line from rats.

Toxicological effects of acrolein have been studied in precision-cut rat lung slices and in L2 cells, a rat pneumocyte II cell line. These two models were cultured for 24 h with or without acrolein (0-100 microM in L2 cells; 0-200 microM in lung slices). Treatment with this pneumotoxicant produced a concentration dependent decrease in intracellular ATP levels. Acrolein concentrations higher than 50 microM induced ATP decrease in slices, while this decrease occurred from 10 microM acrolein in L2 cells. Detoxification marker evaluations showed that mostly the glutathione pathway was altered after acrolein treatment in both models. Intracellular glutathione (GSH) levels were drastically increased with an acrolein concentration of 10 microM. This increase was concomitant with glutathione-S-transferase (GST) and glutathione reductase (GRED) activities in L2 cells. After this strong increase, these enzymatic activities as well as GSH levels were quickly decreased. In precision-cut rat lung slices, the induction of the glutathione pathway was less clear-cut. A bell-shaped dose response curve was observed with a maximum for 5 microM acrolein for GST and GRED activities. These differences between acrolein toxic ranges could be explained by the presence of an active detoxification pathway in slices compared to its relative lack in L2 cells.

Acrolein↗

Development of a new in vitro system for continuous in vitro exposure of lung tissue to complex atmospheres: application to diesel exhaust toxicology.

The purpose of this study was the development of a new incubation system that can allow continuous exposure of lung tissue to complex atmospheres as a tool for the assessment of aerial environmental lung toxicology. To assess the pertinence of this new exposure system, we studied the impact of diesel engine exhausts as a complex atmosphere containing both gaseous and particulate fractions and have been able to discriminate between the toxicological impacts of the gaseous phase and particulate matter from diesel exhausts. Continuous flow-through rotating chambers with controlled PO2, pCO2, and hygrometry have been designed in which lung slices are positioned in rolling inserts that allow free access of atmosphere to the exposed lung tissue. Under control conditions, cell viability was preserved for at least 48 h as assessed by intracellular ATP, GSH, and K+ levels and slice O2 consumption levels. Short-term exposure (1 h) to diesel whole exhausts did not affect intracellular potassium or slice O2 consumption, while intracellular ATP and GSH levels were markedly decreased. Exposure to filtered exhausts showed less marked effects on both ATP and GSH levels. Superoxide dismutase activity was decreased in a similar way by both total and filtered exhausts while Se(+)-dependent glutathione peroxidase activity was induced by filtered exhausts to a larger extent than after total exhaust exposure, showing different response patterns of lung tissue after exposure to whole or filtered exhausts. In conclusion, this newly designed model opens a promising area in in vitro environmental lung toxicology testing.

Adenosine Triphosphate↗

Cell lines with extended in vitro growth potential from human renal proximal tubule: characterization, response to inducers, and comparison with established cell lines.

Few model systems exist for the study of injury to human renal proximal tubule epithelium. Optimized differentiated human renal epithelial cell lines with extended in vitro growth potential would provide an alternative model system to primary culture or other available non-human mammalian kidney cell lines. For this purpose, human renal tubule epithelial cells were isolated from normal kidney cortex and exposed in culture to a hybrid immortalizing virus, adenovirus 12-SV40. Cell lines were developed by limiting dilution, and three selected cell lines were screened for growth pattern, production of immortalizing virus, tumorigenicity, and ploidy. Cell lines were also monitored for response to inducer agents and matrix factors and were screened for expression of biochemical properties and differentiation markers of renal epithelium. All three are nonproducers of the immortalizing virus and are nontumorigenic. They grow in monolayer, have intermediate growth kinetics, and express markers of renal proximal tubular epithelium by immunohistochemistry. They also express biochemical properties comparable to other widely used proximal tubular cell lines including LLC-RK1, OK, and HK-2 and comparable to human tubular cells in stable culture. Growth medium containing low levels of fetal calf serum, or epidermal growth factor combined with parathyroid hormone, produced optimal growth characteristics, brush border enzyme expression, biochemical properties, and glucose transport in a selected cell line. The addition of dimethyl sulfoxide allows maintenance in morphologically intact monolayers for prolonged periods. These cell lines should be useful model systems for the study of human renal proximal tubular injury or disease.

Adenosine Triphosphate↗

Comparative impact of cephaloridine on glutathione and related enzymes in LLC-PK1, LLC-RK1, and primary cultures of rat and rabbit proximal tubule cells.

Among kidney tubular epithelial cell types, proximal tubule cells are one of the major renal targets for xenobiotics. Several in vitro culture models have been proposed for use of proximal tubule cells for in vitro pharmacotoxicology studies. This paper reports a comparative study of the response to cephaloridine exposure of two established cell lines from pig (LLC-PK1) and rabbit (LLC-RK1) kidneys and primary cultures of rat and rabbit proximal tubule cells. These cultured cells were first compared for their levels of activity of alpha-methylglucopyranoside transport, alkaline phosphatase, succinate dehydrogenase, and NADPH cytochrome c reductase, their glutathione-dependent activity levels, and their adenylate cyclase response pattern to stimulation by PTH and AVP. The results presented show major phenotypic differences between these four cellular models. The differences observed in glutathione-dependent mechanism activities and regulation may in part be responsible for the variability of the responses of these four cellular models when exposed to cephaloridine.

Animals↗

Short term respiratory health effects of ambient air pollution: results of the APHEA project in Paris.

STUDY OBJECTIVE: To quantify the short term respiratory health effects of ambient air pollution in the Paris area. DESIGN: Time series analysis of daily pollution levels using Poisson regression. SETTING: Paris, 1987-92. MEASUREMENTS AND MAIN RESULTS: Air pollution was monitored by measurement of black smoke (BS) (15 monitoring stations), sulphur dioxide (SO2), nitrogen dioxide (NO2), particulate matter less than 13 microns in diameter (PM13), and ozone (O3) (4 stations). Daily mortality and general admissions to public hospitals due to respiratory causes were considered. The statistical analysis was based on a time series procedure using linear regression modelling followed by a Poisson regression. Meterological variables, epidemics of influenza A and B, and strikes of medical staff were included in the models. The mean daily concentration of PM13 and daily 1 hour maximum of SO2 significantly affected daily mortality from respiratory causes. An increase in the concentration of PM13 of 100 micrograms/m3 above its 5th centile value increased the risk of respiratory death by 17%. PM13 and BS were also associated with hospital admissions due to all respiratory diseases (4.1% increased risk when the BS level exceeded its 5th centile value by 100 micrograms/m3). SO2 levels consistently influenced hospital admissions for all respiratory diseases, chronic obstructive pulmonary disease, and asthma. Asthma was also correlated with NO2 levels. CONCLUSIONS: These results indicate that even though the relative risk is weak in areas with low levels of pollution, ambient air pollution, and especially particulate matter and SO2, nonetheless require attention because of the number of people exposed and the existence of high risk groups.

Adolescent↗

The cellular toxicity of two antitumoural agents derived from platinum, cisplatinum versus oxaliplatinum, on cultures of tubular proximal cells.

There is a large scope for the use for cisplatin and its derivatives in the treatment of human malignancies. Nephrotoxicity is their most important use-limiting factor. The aim of this study has been to compare cisplatin (CDDP) and oxaliplatin (1-OHP), a new derivative, on cultures of tubular proximal cells. Three cells models were used: primary culture of rabbit kidney, proximal tubular cells (RPTC) and established opossum kidney (OK) and pig kidney (LLC-PK1) epithelial cell lines. Results indicate that in these three culture systems, the cytotoxicity-ranking of the two molecules were in agreement with their in vivo nephrotoxicity (CDDP > 1-OHP), but were less cytotoxic for OK and LLC-PK1 cells than for RPTC. Functional and biochemical evaluations in RPTC indicate that toxic effects of platinum derivates are exerted on DNA, protein synthesis and glucose uptake. 1-OHP effect on DNA synthesis seems to be more effective, but induced a more progressive cytotoxicity. Alteration of glutathione-dependent detoxication activities may reflect the occurrence of a lipid peroxidation process. The present study showed that 1) RPTC are more suitable that LLC-PK1 or OK cells for investigating the nephrotoxicity of platinum derivatives; 2) 1-OHP seems to have a more powerful pharmacological effect than CDDP. The toxic effect ratio seems to promise greater safety with 1-OHP than with CDDP.

Animals↗

Expression and subcellular distribution of phosphoenolpyruvate carboxykinase in primary cultures of rabbit kidney proximal tubule cells: comparative study with renal and hepatic PEPCK in vivo.

The behaviour of the phosphoenolpyruvate carboxykinase (PEPCK) in rabbit proximal tubule cells in primary culture was investigated and compared with renal and hepatic PEPCK in vivo. The enzyme activity decreased rapidly in rabbit proximal tubule cells developed in hormonally defined medium supplemented with glucose and insulin. In this condition, the cytosolic form disappears with time. Without glucose and insulin, the subcellular location of PEPCK is similar to the location observed in proximal tubule freshly isolated and in renal cortex, with approx. 50% of mitochondrial form and approx. 50% of cytosolic form. However, the levels of mRNA that encode the cytosolic PEPCK are not detectable in cell cultures, whatever the medium composition. Treatment with dibutyryl cAMP caused a 14-fold induction of PEPCK mRNA in 6 h. This result indicates that the transcription of cytosolic PEPCK can be induced in cell cultures. Lactate or pyruvate additions did not modify the levels of PEPCK mRNA whereas specific activity increased rapidly, suggesting an activation of an inactive form in cell cultures. Moreover, lactate induced increased specific activity of the sole mitochondrial form while pyruvate induced increased specific activities of both mitochondrial and cytosolic form. Thus, subcellular location of PEPCK in rabbit proximal tubule cells appears to be modulated by the available substrate in culture medium. This observation parallels the changes observed in vivo since a modification of subcellular location of this enzyme was seen between fed and fasted rabbit, when subcellular distribution remains similar between fed and starved rats. Moreover, in the fasted liver of rabbit, a decrease of the mitochondrial PEPCK specific activity is seen concomitant with an increase in cytosolic PEPCK activity. These results point out the relative contributions of the cytosolic and mitochondrial PEPCK to rabbit gluconeogenesis.

Animals↗

Impact of cephaloridine on glutathione and related enzymes: comparison of in vivo and in vitro rat models.

The aim of this study was to investigate the early effects of cephaloridine (CPH) on glutathione-dependent phase II detoxification in the rat proximal tubular cell and to find an in vitro alternative to the in vivo model. The in vivo study was conducted in three groups of rats which received CPH at doses of 250, 500 or 750 mg/kg per day for 3 days, while another group received 500 mg/kg as a single dose. For the in vitro study, rat renal proximal tubular cultured cells were exposed to CPH at concentrations of 0.3, 0.6, 1, 1.7 mM for 24, 48 and 72 h. Glutathione-dependent detoxification was evaluated in vivo and in vitro on the basis of total intracellular glutathione (GSH), glutathione S-transferase (GST) and glutathione peroxidase (GPX). Glutathione reductase (GRED) and GST mRNA levels were also determined. Results of in vivo and in vitro models were comparable in terms of the early increase of GSH, GST and GRED. This increase had a bell-shaped dose-response with a maximum at 500 mg/kg in vivo and 1 mM in vitro. Beyond these doses, GSH and its dependent enzyme levels decreased, associated with cytotoxicity in vitro and renal insufficiency in vivo. The increased GST activity was associated with an increased level of GST7 in vivo and a markedly increased level of GST1-2 in vitro. We concluded that the in vitro model can be used as an alternative to animal experimentation to study glutathione-dependent detoxication. Low cytotoxic doses of CPH induced an early increase of glutathione phase II-dependent detoxification enzymes.

Animals↗

Effects of the medium HCO3-/CO2 buffer system on differentiation and intermediary metabolism properties of rabbit proximal tubule cells in primary culture.

In vivo, bicarbonate can affect proximal tubule intermediary metabolism, including gluconeogenesis, ammoniagenesis and maintenance of the mitochondrial substrate supply. In vitro, rabbit proximal tubule cells (RPTC) in primary culture revert from gluconeogenesis to glycolysis and their mitochondrial metabolism remains lower than in vivo. To determine whether the bicarbonate buffer system could have an effect on these deregulations, RPTC in primary culture grown in the absence of insulin and glucose in the culture medium were developed either with the standard sodium bicarbonate buffer with 5% CO2 or with a Hepes hydrogen ion buffer in the presence of 0.5% CO2. Duration of the bicarbonate-free cultures was increased until at least day 17 after seeding, compared with day 11 in bicarbonate-buffered cultures. As could be expected, succinate dehydrogenase activity remained stable as a function of time in bicarbonate-free cultures while an early marked decrease of this activity occurred from seeding in cultures developed in the presence of bicarbonate buffer. Compared to bicarbonate-buffered cells, higher phosphoenolpyruvate carboxykinase activity concomitant with lower intracellular lactate dehydrogenase activity was observed in cultures developed in the absence of bicarbonate, which is indicative of closer carbohydrate metabolism orientation to the in vivo situation for RPTC. Immunofluorescence staining of RPTC with monoclonal antibodies directed to neutral endopeptidase (NEP), and dipeptidyl-peptidase IV (DPP II) showed similar extensive labelling with DPP and NEP in both culture conditions. Confocal microscopy analysis of NEP subcellular distribution, showed exclusive targetting of NEP to the apical plasma membranes. In both models, cAMP production was stimulated by parathyroid hormone and unaffected by arginine vasopressin. In conclusion, bicarbonate withdrawal from the culture medium (without changing the pH of the medium) allows a marked improvement of mitochondrial capacity and carbohydrate metabolism pattern without any loss of differentiated properties.

Adenosine Triphosphate↗

Modulation of glycolysis induction in primary cultures of rabbit kidney proximal tubule cells: the role of shaking, glucose and insulin.

We have assessed the impact of increasing oxygen availability on cellular phenotype expression of rabbit proximal tubule cells in primary culture developed with variable glucose and/or insulin contents. To mitigate hypoxia at the cell/medium interface, cells were shaken for the whole culture duration and their expressed phenotype was compared with those expressed by static cultures. O2 and CO2 tensions were kept constant in the incubator atmosphere. Glycolysis and gluconeogenesis pathways, detoxication system, and mitochondrial, apical and basolateral membrane marker enzyme activities were assessed. This study showed that the induction of glycolysis which appear in primary cultures of proximal tubule cells may be partially prevented by continuously shaking the cultures. This effect was more marked in the presence of glucose, suggesting better substrate oxidation in shaken cultures.

Adenosine Triphosphate↗

Characterization of gentamicin-induced dysfunctions in vitro: the use of optimized primary cultures of rabbit proximal tubule cells.

Compared to prior studies which frequently pinpoint the impairment of one parameter or function, this paper reports for the first time an extensive characterization of the toxic effects of gentamicin in a single model of primary cultured rabbit proximal tubule cells developed without insulin and glucose. Biochemical, functional and morphological approaches were used. Cellular response pattern was examined after a 72-h exposure during either the exponential growth phase or the stationary confluency phase of the culture to 0.2, 1, and 2.5 mM gentamicin. The biochemical study after gentamicin exposure showed increased activities for N-acetyl-beta-D-glucosaminidase and alkaline phosphatase, decreased activities for sphingomyelinase, cathepsin B, Na+/K(+)-ATPase, lactate dehydrogenase and NADPH cytochrome C reductase. Functional evaluation revealed decreased protein synthesis and alpha-methylglucose transport after gentamicin exposure. Morphometric study made it possible to show that the density of lysosomes, the cell fractional volume of the lysosomal compartment, and the mean size of the lysosomal profiles are increased in the cells. Intracellular accumulation of gentamicin in proximal tubular cells was dose dependent and reached high levels in cultured cells. In conclusion, this model compared to others in the literature allowed us to demonstrate in vitro a close response pattern to the in vivo situation after gentamicin exposure.

Acetylglucosaminidase↗

[Toxic effect of two antitumoral agents derived from platinum, the cisplatin and the oxaliplatin on primary cultures of proximal tubular cells of the kidney in rabbits].

There is a large field of use for cisplatin and its derivatives in the treatment of human malignancies. The nephrotoxicity is their most important use-limiting factor. The aim of this work has been to study comparatively the cisplatin and a new molecule, the oxaliplatin on primary culture of proximal tubular cells of rabbit kidney. Several markers, functional, enzymatic and biochemical have been evaluated after exposure to platinum's derivatives. The results indicates that their toxic effects are exerted on DNA and proteins synthesis, and for the cisplatin on the glucose uptake. Oxalyplatin's effect on DNA synthesis seems to be more effective, but induced a more progressive cytotoxicity. The lipids peroxidation's role with abnormalities of glutathione dependent detoxication system of the cell is possible. In conclusion, oxaliplatin seems to have a pharmacological effect more powerful than cisplatin. Its low dose effect ratio seems to promise greater safety in its use.

Animals↗

[Hospitalization for HIV infection in public hospitals in Paris. Recent evolution (1988-1990) and short-term projections (1991-2)].

Acute-care hospitalization of subjects infected with HIV in Parisian public hospitals (Assistance Publique-Hôpitaux de Paris) increased by 10% between 1988 and 1990, while outpatient day-care rose by 73%. During this time, the percentage of patients coming from the Paris suburbs rose from 30 to 35%. The average length of stay increased from 14.2 to 14.9 days during the same period, and hospital stays lasting longer than 30 days (9.2%) accounted for 39.2% of all hospitalizations. Forecasts for 1991 and 1992 show acute-care hospitalization rising from 25 to 30% and outpatient care increasing from 45 to 94%, depending upon the hypothesis considered.

Acquired Immunodeficiency Syndrome↗

Insulin and glucose impact on functional and morphological differentiation of rabbit proximal tubule cells in primary culture.

Glucose and insulin impact on cellular phenotype expression was assessed on rabbit proximal tubule cells in primary culture. Glycolysis, gluconeogenesis pathways and lysosomal, mitochondrial, detoxication system, apical and basolateral membrane marker enzyme activities were assessed. Both insulin and glucose deprivation partially prevented the rise in glycolysis and delayed the drop of gluconeogenesis pathways. Scanning electron microscopy analysis of the apical surface of the monolayer revealed a much higher density of microvilli in glucose-free cultures compared to cultures developed with glucose. In conclusion, culture medium deprivation in both glucose and insulin allowed closer functional, biochemical and morphological properties to those which exist in the in vivo situation for proximal tubule cells.

Animals↗