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Biomedical subjects

C Chauvin

Publications and source records attributed to C Chauvin.

At least 19 recordsLinked to original sources

Effects of permeability transition inhibition and decrease in cytochrome c content on doxorubicin toxicity in K562 cells.

As mitochondria play a key role in the commitment to cell death, we have investigated the mitochondrial consequences of resistance to doxorubicin (DOX) in K562 cells. We found that the permeability transition pore (PTP) inhibitor cyclosporine A (CsA) failed to inhibit PTP opening in the resistant clone. Moreover, the Ca2+ loading capacity in the resistant clone was identical to that observed in the parent cells in the presence of CsA, suggesting that the PTP was already inhibited in a CsA-like manner in the resistant cells. In agreement with this proposal, the mitochondrial target of CsA cyclophilin D (CyD) decreased by half in the resistant cells. The levels of adenine nucleotide translocator, voltage anion-dependent channel, Bax, Bcl-2, Bcl-xL, AIF and Smac/Diablo, were similar in both cell lines, whereas cytochrome c content was divided by three in the resistant cells. Since P-glycoprotein inhibition did not restore DOX toxicity in the resistant cells, while DOX-induced cell death in the parent cells was prevented by either PTP inhibition or siRNA-induced decrease in cytochrome c content, we conclude that the inhibition of PTP opening and the decrease in cytochrome c content participate in the mechanism that makes K562 cells resistant to DOX.

Antibiotics, Antineoplastic↗

Accepting loss: the temporal limits of reciprocity in brown capuchin monkeys.

Delayed reciprocity is a potentially important mechanism for cooperation to occur. It is however rarely reported among animals, possibly because it requires special skills like the ability to plan a loss. We tested six brown capuchin monkeys (Cebus apella) in such skills. Subjects were studied in exchange tasks in which they had to retain a food item for a given time lag before returning it to an experimenter and obtaining a more desirable reward. Experiments showed that the subjects could wait for several minutes when allowed to return only part of the initial item. When required to return the full item intact, however, most subjects could not sustain a time lag longer than 10 s. Although the duration of waiting increased with the amount of return expected by subjects, in most cases it did not extend beyond 20 s even when the eperimenter offered a food amount 40 fold the initial item. The failure of capuchin monkeys to sustain long-lasting waiting periods may be explained by limited self-control abilities. This would prevent them achieving reciprocal altruism.

Altruism↗

Use of avilamycin for growth promotion and avilamycin-resistance among Enterococcus faecium from broilers in a matched case-control study in France.

We assessed the putative link between avilamycin-resistant Enterococcus faecium carriage and avilamycin consumption in broilers. As part of the French programme of monitoring for antimicrobial resistance, broilers sampled at slaughterhouse in 1999 and 2000 and carrying avilamycin-resistant E. faecium were matched by slaughterhouse, slaughter month and production type (free-range, standard, light) with control broilers carrying avilamycin-susceptible strains. History of antibiotics consumption (either for growth promotion or therapeutic purpose) in the broiler flocks sampled was collected from the monitoring programme and consumption of each antibiotic class was screened as a potential risk factor. Avilamycin was a risk factor for avilamycin-resistant E. faecium carriage: OR=2.3.

Abattoirs↗

Invoices and farmer interviews for vaccine-exposure measurement in turkey-broiler production.

Exposure measurement in pharmaco-epidemiological studies can be based on various sources that do not always concur. However, reliability is an important criterion when selecting the method used to assess exposure and interpreting the results obtained. An analysis based on invoices might be more informative and more accurate to assess vaccines exposure (yes/no) in turkey broiler production than a questionnaire administered to farmers, which is nevertheless more feasible and less time-consuming. We compared the two methods to assess vaccination exposure in 239 turkey broiler flocks reared in 129 farms in 2000-2001. The agreement (crude agreement and kappa) was calculated, and association between discrepancy and farm and flock characteristics was investigated. Marek's-disease vaccine, Newcastle-disease vaccine, turkey haemorrhagic-enteritis vaccine and turkey-rhinotracheitis vaccine exposures were reported on the questionnaire for 2.1, 27.6, 93.0, and 98.3% of flocks, respectively, and for 2.1, 29.3, 89.4, and 86.6%, of invoices for the flocks studied, respectively. A discrepancy was observed in 24.9% of flocks. A discrepancy was observed more frequently in specialised farms without any other animal production (OR = 3.6; CI = 1.5, 8.9) and when the farmer did not know whether vaccination had been performed in the hatchery (OR = 7.1; CI = 2.6, 19.7).

Animals↗

An original system for the continuous monitoring of antimicrobial use in poultry production in France.

Data collection at the flock level on a continuous basis, for antimicrobial use surveillance purposes, provides a complex challenge. Using existing on-farm records, produced as part of the regulations for meat inspection, a sampling scheme was implemented to collect on a simple, representative and continuous basis, the forms providing history of antimicrobial consumption of poultry flocks slaughtered in Brittany. Relational database-stored information provided by the forms includes treatment purpose, antimicrobial drug administered, age at treatment and treatment duration. The aim of this study was to collect information describing antimicrobial drug use quantitatively and qualitatively, by computing the frequency of antimicrobial use according to species, therapeutic class, treatment purpose, duration, and animal age at treatment. A study was carried out to check the validity of farmers' declarations. Examples of data and results are presented such as the relative importance of the different antimicrobial classes in relation to the live weight treated, which shows that beta-lactams and tetracyclines are the main classes used in broilers and turkeys respectively. Average bird weight at treatment was 0.5 kg for a broiler and 3 kg for a turkey. Nevertheless, several 'at-risk' periods could be identified. Initial results after 1 year of data collection showed that this surveillance system provides valid, detailed and useful data about antimicrobial drug use in poultry production at a low cost and with only a moderate time involvement.

Animals↗

Risk factors for Salmonella enterica subsp. enterica shedding by market-age pigs in French farrow-to-finish herds.

Fattening-pigs carriers of Salmonella enterica are believed to be a main source of carcass and pork contamination at the later steps of the meat process. We did a prospective study in 2000-2001 in 105 French farrow-to-finish pig farms. In each farm, a batch of contemporary fattening pigs housed in the same room was followed throughout the fattening period. Salmonella shedding was assessed on environmental samples of faecal material (taken by means of pairs of gauze socks) analysed by classical bacteriological methods. 36.2% of the batches studied had at least one contaminated environmental sample and therefore were classified as Salmonella-shedding batches. Logistic regression was used to assess the association between managerial and hygiene practices and health status and the shedding risk at the end of the finishing period. Emptying the pit below the slatted floor after the previous batch of sows was removed and frequent removal of sow dung during the lactation period were protective. Presence of residual Salmonella contamination of the floor and pen partitions in the fattening rooms before loading the growing pigs also was a risk factor. The risk for Salmonella shedding at the end of the fattening period was increased when dry feed (versus wet feed) was provided during the fattening period. Lastly, Lawsonia intracellularis seroconversion and PRRSV seropositivity during the fattening period also was a risk factor for Salmonella shedding.

Animal Feed↗

Transfer of hexazinone and glyphosate through undisturbed soil columns in soils under Christmas tree cultivation.

Field studies monitoring pesticide pollution in the Morvan region (France) have revealed surface water contamination by some herbicides. The purpose of this study was to investigate in greater detail the transport of two herbicides, used in Christmas tree production in the Morvan, under controlled laboratory conditions. Thus, the leaching of hexazinone (3-cyclohexyl-6-dimethyl-amino-1-methyl-1,3,5-triazine-2,4 (1H,3H) dione) and glyphosate (N-(phosphono-methyl-glycine)) through structured soil columns was studied using one loamy sand and two sandy loams from sites currently under Christmas tree cultivation in the Morvan. The three soils were cultivated sandy brunisol [Sound reference base for soils, D. Baize, M.C. Girard (Coord.), INRA, Versailles, 1998, 322 p] or, according to the FAO [FAO, World reference base for soil resources, ISSS-ISRIC-FAO, FAO, Rome, Italy, 1998], the La Garenne was an arenosol and the two other soils were cambisols. The clay contents of the soils ranged from 86 to 156 g kg(-1) and the organic carbon ranged from 98 to 347 g kg(-1). After 160 mm of simulated rainfall applied over 12 days, 2-11% of the applied hexazinone was recovered in the leachate. The recovery was much higher than that of glyphosate, which was less than 0.01%. The greater mobility of hexazinone might be related to its much lower adsorption coefficient, K(oc), 19-300 l kg(-1), compared with 8.5-10231 l kg(-1) for glyphosate (literature values). Another factor that may explain the higher amounts of hexazinone recovered in the leachates of the three soil columns is its greater persistence (19.7-91 days) relative to that of glyphosate (7.9-14.4 days). The mobility of both herbicides was greater in the soils with higher gravel contents, coarser textures, and lower organic carbon contents. Moreover, glyphosate migration seems negatively correlated not only to soil organic carbon, but also to aluminium and iron contents of soils. This soil column study suggests that at the watershed scale, surface water contamination by hexazinone could occur via the horizontal subsurface flow in upper centimeters of soil. In contrast, the surface water contamination with glyphosate by this mechanism appears unlikely.

Carbon↗

Longitudinal serological responses to Salmonella enterica of growing pigs in a subclinically infected herd.

A longitudinal survey was conducted in France in a subclinically Salmonella-infected farrow-to-finish pig farm to describe the time-course of the serological response to Salmonella enterica in growing pigs. We used three batches of sows and their corresponding litters (n = 31 litters). Among these, 256 pigs randomly selected and individually identified were followed from the first week of age until slaughter. Serial individual blood samples were submitted to indirect Salmonella-ELISA testing. Salmonella shedding was investigated by bacteriological testing of faecal material regularly collected from the sows and pigs and by environment swabs taken from the pens. Caecal contamination was checked at the slaughterhouse. Information about litter composition (filiation), location of the pigs in post-weaning and fattening pens, sanitary events, sex and body weights was recorded. 11.6% of the pigs shed S. enterica; 52% of pigs seroconverted before slaughter. The age-related variation of the natural logarithm of calibrated optical densities (COD) of pigs was described with two linear mixed models. From 8 to 61 days of age, the decrease in COD with age was fitted with a model including random effects of the animal and the dam on the intercept and slope, a batch random effect on the intercept and an individual birth-weight fixed effect on the intercept. The dam random effect was explained by the parity of the sow, Salmonella shedding by the sow during the farrowing phase and the value of the optical density of colostrum collected at parturition. A second model fitting the increase in COD from 61 days of age until slaughter included the random effect on intercept of the batch and the random effects on slope and intercept of the animal, the dam and the pen in which the followed animals were located during the fattening phase and the environmental contamination as fixed effect. In this second model, no relation was found between individual slaughter-bacteriological results and increasing COD values. Considering seroconversion time between 61 days of age and slaughter, survival function were constructed using the Cox proportional-hazards model. Both methods suggested that seroconversions generally occurred during the last third of the fattening phase (from 140 days of age to slaughter), while shedding was observed during the first half of the fattening period. The fitted models suggest the existence of clusters (such as pen and litter of origin).

Animal Husbandry↗

Mitochondrial metabolism and type-2 diabetes: a specific target of metformin.

Several links relate mitochondrial metabolism and type 2 diabetes or chronic hyperglycaemia. Among them, ATP synthesis by oxidative phosphorylation and cellular energy metabolism (ATP/ADP ratio), redox status and reactive oxygen species (ROS) production, membrane potential and substrate transport across the mitochondrial membrane are involved at various steps of the very complex network of glucose metabolism. Recently, the following findings (1) mitochondrial ROS production is central in the signalling pathway of harmful effects of hyperglycaemia, (2) AMPK activation is a major regulator of both glucose and lipid metabolism connected with cellular energy status, (3) hyperglycaemia by inhibiting glucose-6-phosphate dehydrogenase (G6PDH) by a cAMP mechanism plays a crucial role in NADPH/NADP ratio and thus in the pro-oxidant/anti-oxidant cellular status, have deeply changed our view of diabetes and related complications. It has been reported that metformin has many different cellular effects according to the experimental models and/or conditions. However, recent important findings may explain its unique efficacy in the treatment of hyperglycaemia- or insulin-resistance related complications. Metformin is a mild inhibitor of respiratory chain complex 1; it activates AMPK in several models, apparently independently of changes in the AMP-to-ATP ratio; it activates G6PDH in a model of high-fat related insulin resistance; and it has antioxidant properties by a mechanism (s), which is (are) not completely elucidated as yet. Although it is clear that metformin has non-mitochondrial effects, since it affects erythrocyte metabolism, the mitochondrial effects of metformin are probably crucial in explaining the various properties of this drug.

Adenosine Triphosphate↗

Listeria spp. contamination in piggeries: comparison of three sites of environmental swabbing for detection and risk factor hypothesis.

Listeria monocytogenes is a foodborne pathogen of major concern for public health in industrialized countries. Listeria carriage by pigs at the herd level could be a primary source for carcass contamination. Forty-seven finishing pig facilities were involved in the present study designed to compare three environmental swabbing sites in order to detect Listeria spp. in piggeries. Swabs were taken from the pen walls, the perianal regions of the pigs and the trough/feeder of the piggery premises. Listeria contamination of wet or dry feed given to the pigs was also investigated. The capacity of the various sampling sites for Listeria spp. detection were compared with a maximum likelihood estimation method. Listeria spp. were recovered in 74% of the pens studied and L. monocytogenes was detected in 15% of pens. With a specificity of 99%, sensitivity estimates (and 95% CI) of the Listeria spp. detection method were 93.4% (72.7-98.7) for pen walls, 73.1% (54.9-85.9) for pigs and 66.6% (48.6-80.7) for the trough/feeder. Listeria spp. were isolated from 84% of wet feed samples and 5% of dry feed samples. Listeria monocytogenes was found in 13% of wet feed samples. The type of feeding (wet versus dry) was associated (P < 0.001) with Listeria spp. contamination of both the pen and the feed. The results of this study confirm that Listeria spp., including L. monocytogenes, are present in pig facilities. Pen wall swabbing appears to be an effective way to assess Listeria spp. status of finishing pigs. The type of feeding (wet versus dry) could play a role in pig contamination.

Animal Feed↗

Tonkean macaques ( Macaca tonkeana) find food sources from cues conveyed by group-mates.

It is possible that non-specialised cues transmitted by conspecifics guide animals' food search provided they have the cognitive abilities needed to read these cues. Macaques often check the mouth of their group-mates by olfactory and/or visual inspection. We investigated whether Tonkean macaques ( Macaca tonkeana) can find the location of distant food on the basis of cues conveyed by group-mates. The subjects of the study were two 6-year-old males, who belonged to a social group of Tonkean macaques raised in semi-free-ranging conditions. In a first experiment, we tested whether the subject can choose between two sites after having sniffed a partner who has just eaten food corresponding to one of the sites. We found that both subjects were able to choose the matching site significantly above the chance level. This demonstrated that Tonkean macaques are capable of delayed olfactory matching. They could associate a food location with an odour conveyed by a partner. In a second experiment, the same subjects were allowed to see their partner through a Plexiglas window. Both subjects were still able to choose the matching site, demonstrating they could rely on visual cues alone. Passive recruitment of partners appears possible in macaques. They can improve their foraging performances by finding the location of environmental resources from olfactory or visual cues conveyed by group-mates.

Animal Communication↗

Pharmaco-epidemiology and -economics should be developed more extensively in veterinary medicine.

Pharmaco-epidemiology, which has emerged within the last 20 years as a new discipline in human medicine, deals with the quantities of drugs consumed and their effects on populations in terms of epidemiological concepts and tools. To a lesser extent, it is also practised in veterinary medicine. The applications presented in this review are illustrative of pharmaco-epidemiological and -economical concepts. Assessment of drug consumption, the study of adverse drug effects, and the economic implications of drug use are the three main fields considered. Developments can be expected in veterinary medicine within the next few years relative to novel areas of interest such as antimicrobial resistance and new therapeutic class uses. These applications will require methodological progress and the elimination of current gaps. Pharmaco-epidemiological methods need to be developed, which implies close co-operation between statisticians, pharmacologists, veterinary practitioners and epidemiologists. A greater use of the term 'pharmaco-epidemiology' as a keyword in literature would facilitate recognition of this domain which associates closely epidemiology and pharmacology.

Animals↗

Rotenone inhibits the mitochondrial permeability transition-induced cell death in U937 and KB cells.

The permeability transition pore (PTP) is a mitochondrial inner membrane Ca(2+)-sensitive channel that plays a key role in different models of cell death. Because functional links between the PTP and the respiratory chain complex I have been reported, we have investigated the effects of rotenone on PTP regulation in U937 and KB cells. We show that rotenone was more potent than cyclosporin A at inhibiting Ca(2+)-induced PTP opening in digitonin-permeabilized cells energized with succinate. Consistent with PTP regulation by electron flux through complex I, the effect of rotenone persisted after oxidation of pyridine nucleotides by duroquinone. tert-butyl hydroperoxide induced PTP opening in intact cells (as shown by mitochondrial permeabilization to calcein and cobalt), as well as cytochrome c release and cell death. All these events were prevented by rotenone or cyclosporin A. These data demonstrate that respiratory chain complex I plays a key role in PTP regulation in vivo and confirm the importance of PTP opening in the commitment to cell death.

Cell Death↗

Glucose 6-phosphate hydrolysis is activated by glucagon in a low temperature-sensitive manner.

Glucagon affects liver glucose metabolism mainly by activating glycogen breakdown and by inhibiting pyruvate kinase, whereas a possible effect on glucose-6-phosphatase has also been suggested. Although such a target is of physiological importance for liver glucose production it was never proven. By using a model of liver cells, perifused with dihydroxyacetone, we show here that the acute stimulation of gluconeogenesis by glucagon (10(-7) m) was not related to the significant inhibition of pyruvate kinase but to a dramatic activation of the hydrolysis of glucose 6-phosphate. We failed to find an acute change in glucose-6-phosphatase activity by glucagon, but the increase in glucose 6-phosphate hydrolysis was abolished at 21 degrees C; conversely the effect on pyruvate kinase was not affected by temperature. The activation of glucose 6-phosphate hydrolysis by glucagon was confirmed in vivo, in postabsorptive rats receiving a constant infusion of glucagon, by the combination of a 2-fold increase in hepatic glucose production and a 60% decrease in liver glucose 6-phosphate concentration. Besides the description of a novel effect of glucagon on glucose 6-phosphate hydrolysis by a temperature-sensitive mechanism, this finding could represent an important breakthrough in the understanding of type II diabetes, because glucose 6-phosphate is proposed to be a key molecule in the transcriptional effect of glucose.

Allosteric Site↗

Exogenous Mg-ATP induces a large inhibition of pyruvate kinase in intact rat hepatocytes.

Mg-ATP infusion in vivo has been reported to be beneficial both to organ function and survival rate in various models of shock. Moreover, a large variety of metabolic effects has been shown to occur in several tissues due to purinergic receptor activation. In the present work we studied the effects of exogenous Mg-ATP in rat liver cells perifused with dihydroxyacetone to investigate simultaneously gluconeogenetic and glycolytic pathways. We found a significant effect on oxidative phosphorylation as characterized by a decrease in oxygen consumption rate and in the cellular ATP-to-ADP ratio associated with an increase in lactate-to-pyruvate ratio. In addition, exogenous Mg-ATP induced rapid and reversible inhibition of both gluconeogenesis and glycolysis. The main effect on gluconeogenesis was located at the level of the fructose cycle, whereas the decrease in glycolysis was due to a strong inhibition of pyruvate kinase. Although pyruvate kinase inhibition induced by exogenous Mg-ATP was allosteric when assessed in vitro after enzyme extraction, we found a large decrease in the apparent maximal velocity when kinetics were assessed in vivo in intact perifused hepatocytes. This newly described short-term regulation of pyruvate kinase occurs only in the intact cell and may open new potentials for the pharmacological regulation of pyruvate kinase in vivo.

Adenosine Diphosphate↗

A microplate assay for DNA damage determination (fast micromethod).

A rapid and convenient procedure for DNA damage determination in cell suspensions and solid tissues on single microplates was developed. The procedure is based on the ability of commercially available fluorochromes to interact preferentially with dsDNA in the presence of ssDNA, RNA, and proteins at high pH (>12.0), thus allowing direct measurements of DNA denaturation without sample handling or stepwise DNA separations. The method includes a simple and rapid 40-min sample lysis in the presence of EDTA, SDS, and high urea concentration at pH 10, followed by time-dependent DNA denaturation at pH 12.4 after NaOH addition. The time course and the extent of DNA denaturation is followed in a microplate fluorescence reader at room temperature for less than 1 h. The method requires only 30 ng DNA per single well and could conveniently be used whenever fast analysis of DNA integrity in small samples has to be done, e.g., in patients' lymphocytes after irradiation or chemotherapy (about 3000 cells per sample), in solid tissues or biopsies after homogenization (about 25 microg tissue per well), or in environmental samples for genotoxicity assessment.

Animals↗

Assessment of DNA damage and repair in human peripheral blood mononuclear cells using a novel DNA unwinding technique.

A newly developed, fast and sensitive microplate assay (Fast Micromethod) was used for the assessment of gamma-radiation-induced DNA damage in peripheral blood mononuclear cells (PBMC) from healthy donors of various ages and from cancer patients undergoing radiotherapy. This assay detects the presence of DNA single-strand breaks and alkali-labile sites by monitoring the rate of DNA unwinding under alkaline conditions using the fluorescent dye PicoGreen, which preferentially binds to double-stranded DNA at high pH (>12.0); it requires only minimal amounts of material (approximately 3 x 10(3) cells/well) and can be performed within 3 hrs. or less. EDTA blood samples were collected from patients not undergoing chemotherapy prior and immediately after irradiation, or were collected from healthy donors and irradiated ex vivo. The results revealed that the amount of DNA strand breaks in PBMC, induced by application of a single dose to patients in the course of radiotherapy treatment, markedly varied between different individuals. To examine the effect of age on DNA damage, the basal levels of DNA damage in PBMC from a total of 30 healthy donors were determined: 10 were 20 to 30 years of age, 10 were 40 to 60 years of age and 10 were >70 years of age. It was found that the mean basal level of DNA damage from donors in the >70-year age group was significantly higher (by 97%) than that of the 20- to 30-year age group and 27% higher than that of the 40- to 60-year age group. Measurements of the level of induced DNA damage in PBMC isolated from blood after 2 Gy irradiation with 60Co gamma-rays revealed no significant differences between donors aged 20-30 and 40-60. However, there was a strong increase (by 2.3- to 2.9-fold) in radiosensitivity in the age group >70. The microplate assay described may be used as a pretherapeutic sensitivity test for the assessment of the individual radiosensitivity of patients prior to radiation therapy.

Adult↗