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Biomedical subjects

J Garric

Publications and source records attributed to J Garric.

At least 19 recordsLinked to original sources

Do differences between metal body residues reflect the differences between effects for Chironomus riparius exposed to different sediments?

Sediment characteristics are well known to interfere with toxicity, mainly through differences in terms of bioaccumulation. Here, with chironomids exposed to zinc in an artificial and a field sediment, we investigated the differences of zinc accumulation and of effects on the life cycle, at individual and population level. We used biology and energy-based modeling to analyze the data at all the levels of biological organization. This permits a reliable estimation of thresholds values for tissue residues. Differences in zinc tissue residues accounted for most of the differences between the results for both sediments (a factor of 11 for differences from 20 to 100 depending on the parameter which is considered). Taking into account accumulation and background variability, the differences relative to thresholds could be accounted for. However, it appeared that, once the threshold was passed, effects were much more pronounced for organisms exposed to artificial sediment compared to field sediment. We concluded that some sediment characteristics can enhance toxicity, in addition to their influence on the compound accumulation, even if the latter was the major source of differences in our study.

Animals↗

Non destructive in vivo measurement of ethoxyresorufin biotransformation by zebrafish prolarva: development and application.

Biotransformation enzymatic activities, such as the cytochrome P450 one, have been used as biomarkers for pollution assessment for a long time. Nevertheless, such biochemical tools are destructive processes, because they are performed on fish liver or total larvae homogenates. Moreover, the adaptation of this bioassay to some fish larvae, like Danio rerio ones, is ineffective because it needs a lot of organisms. We thus developed an original, nondestructive method to detect the induction of a biotransformation activity in the prolarva of the fish, Danio rerio, exposed to chemicals. This methodology is based on the assessment of EROD activity, by measurement in the culture medium of the fluorescence increase due to the excretion of resorufin by fish during an ethoxyresorufin exposure. After exposure of fish embryos to known inducers (BaP and beta-naphtoflavone), the prolarvae were exposed to the substrate (ethoxyresorufin), and the kinetic of the fluorescence increase was measured. A dose-effect relationship was observed, with a three to five fold increase of EROD basal activity. This methodology also allowed us to compare between EROD activity induction by different environmental samples. The proposed methodology thus allows to perform a simple, sensitive, and reproducible microbiotest for the detection of sublethal concentrations of AhR chemical inducers in environmental samples.

Animals↗

Impacts of 17beta-estradiol, including environmentally relevant concentrations, on reproduction after exposure during embryo-larval-, juvenile- and adult-life stages in zebrafish (Danio rerio).

Zebrafish (Danio rerio) were exposed for 3 weeks to low concentrations of estradiol including environmentally relevant concentrations (5, 25 and 100 ng/l), encompassing either their embryo-larvae (from fertilization to 21 day post-fertilization (dpf)), juvenile (from 21 to 42 dpf) or adult life stages (>200 dpf) with a view to investigating the most sensitive life stage of the zebrafish to 17beta-estradiol (E2). At all sampling points, whole-body vitellogenin concentrations and gonadal development were analyzed in order to investigate the effects of estrogen exposure on these endpoint in the zebrafish. In the adult stage, additional endpoints were measured including secondary sexual characteristics (manifestation of the uro-genital papillae (UGP) in males), gonadal growth (the gonado-somatic index (GSI)) and sex ratio. For all the different life stage exposures, reproductive performance of the F0 generation was assessed (egg production) and survival and development of the F1 embryo-larvae. Exposure to low concentrations of E2 resulted in vitellogenin induction whatever the life stage exposed but these effects were reversible after depuration. The effective concentration for vitellogenin induction in zebrafish early life stages was 100 ng E2/l, and in adult male zebrafish the effective concentration for vitellogenin induction (between 5 and 25 ng/l) was lower than for the early life stage fish. Exposure to E2 prior to (from fertilization to 21 dpf) and during the time of sex differentiation (from 21 to 42 dpf) also caused disruptions in the process of sexual differentiation (resulting in formation of a retrogonadal cavity in presumptive male, germ cell development and leading to a significant change of the sex ratio towards the female sex at the dose of 100 ng E2/l for the fish exposure as embryo-larvae) and altered patterns of egg production in the subsequent adults. Exposure of adult fish to E2 resulted in a modification of the secondary sexual characteristic in males at 25 and 100 ng E2/l as well as a dose-dependent inhibition of egg production. The findings from this study show that the nature and intensity of the reproductive effects of E2 are dependent of the time and concentration of exposures of zebrafish to E2, some of these effects being permanent (effect on the sexual differentiation) while others being reversible (effect on the Vtg induction). This study demonstrated that early life stages of zebrafish are sensitive to low concentrations of E2 and provides relevant data that could be used for the adaptation of existing fish early life stage test for the in vivo testing of estrogenic compounds. The data presented raise further concerns about the effects of steroid estrogens in the environment on fish reproductive health.

Age Factors↗

Energy-based modeling to study population growth rate and production for the midge Chironomus riparius in ecotoxicological risk assessment.

Effects of toxicants are commonly assessed at individual level, whereas the aim of ecotoxicology is to protect ecosystems. We recently built energy-based models to describe and predict growth, emergence and reproduction of the midge Chironomus riparius [Péry (2002) Environ. Toxicol. Chem. 21, 2507-13]. Here we use these models to derive effects at the population level from effects at individual levels. The first endpoint we consider is population growth rate, which is a commonly studied endpoint at the population level. This parameter is informative relative to the risk of disappearance of the population. We also examined the production of organisms per generation or per time unity at population equilibrium, the study of which is allowed by our models and accounts for energy transfers. Such a study is crucial to predict effects on ecosystems, for species of the Chironomidae are keystone species, being the main food source of many other species, including birds and fish. We show in our study that the disappearance of the population can only occur in cases of very severe toxicity (99% decrease of reproduction, more than 97% mortality during a 10 days survival test or a difference of mean emergence times between males and females of more than 10 days). Concerning production of organisms, we show that reproduction decrease has little effect on it, that mortality of young larvae has an impact that cannot be neglected and that mortality of old larvae and delay of emergence has a strong effect. Our study suggests that bioassays should focus on an EC50 for reproduction, a LC30 for young instars, and a No Effect Concentration for old instars (growth and mortality) to prevent effects at the population level.

Animals↗

Effects of advanced oxidation processes (AOPs) on the toxicity of a mixture of pharmaceuticals.

The possibility of applying main AOP techniques, namely ozonation, H2O2/UV photolysis and TiO2 photocatalysis to provide a significant reduction of toxicity of pharmaceutical mixtures has been evaluated. For the preparation of the mixture six pharmaceuticals were chosen among those found at highest concentrations in Sewage Treatment Plant effluents, namely carbamazepine, clofibric acid, diclofenac, sulfamethoxazole, ofloxacin and propranolol. The blue-green alga Synechococcus leopoliensis and the rotifer Brachyonus calyciflorus were utilised to assess the toxicity of the mixtures after AOP treatments. All the toxicity tests were performed using chronic standardized bioassays. The best results were obtained with ozonation. With this type of treatment a complete removal of mixture toxicity on S. leopolensis was obtained even after the shortest time of application (1 min). The ozonation treatment leads also to removal of all the pharmaceutical mixture toxicity on B. calyciflorus, by applying the oxidizing agent for at least for 2 minutes.

Animals↗

Survival tests with Chironomus riparius exposed to spiked sediments can profit from DEBtox model.

DEBtox model is a biologically based model used to analyse aquatic toxicity data (The analysis of aquatic toxicity data, VU University Press, Amsterdam, The Netherlands, 1996, 149pp.). To date, it has not been used to analyse sediment survival tests, mainly because this would require daily counting of survivors, which is difficult for benthic organisms. In the present study, we adapted survival toxicity tests with the midge Chironomus riparius to permit survival data analysis with DEBtox. To validate the adaptation proposed, we exposed organisms to two chemicals, copper and methiocarb. We exposed larvae of second, third and fourth instar to different concentrations of the tested compounds and two different diets to assess the influence of diet and instar on DEBtox parameter estimates. Daily counting of organisms did not affect survival and did not lead to much more effort when compared to usual tests. Moreover, the analysis profited much from use of the DEBtox model. It was possible, with only survival data to estimate and validate the kinetics of the compounds, to predict survival during the recovery of exposed organisms and to assess the influence of food availability on toxicity. Food availability did not influence methiocarb toxicity, but copper was more toxic to food-limited organisms when a threshold concentration was exceeded. Comparison of parameters estimate also helped in understanding the differences in toxicity responses between instars. For the two compounds we studied, the difference was entirely explained by differences in threshold values.

Animals↗

Multibiomarker responses in fish from the Moselle River (France).

The response of wild fish to pollutants was studied using two biomarkers in chub (Leuciscus cephalus) at five stations in the Moselle River (France) in 1998 and in 1999. The induction of cytochrome P450 1A was quantified by the ethoxyresorufin O-deethylase (EROD) activity in the liver and the level of DNA single-strand breaks was determined in erythrocytes using the comet assay. EROD activity was observed to be up to 10-fold induced in both males and females from the downstream stations in comparison to the fish from the upstream station. Levels of DNA damage did not parallel EROD induction. Chemical analyses did not clearly explain the responses of the studied biomarkers, confirming the great difficulty in relating chemical and biological information in the field. This study confirms the difficulty in assessing the biological effects of mixtures of pollutants and points out the usefulness of a large array of biomarkers.

Animals↗

The measurement of cholinesterase activities as a biomarker in chub (Leuciscus cephalus): the fish length should not be ignored.

Biomarkers are early warning systems of the exposure of aquatic organisms to pollutants. Among them, the measurement of the cholinesterase (ChE) activities in fish muscle is a biomarker of the exposure to organophosphosphates and carbamates pesticides. As such it has been used in numerous field studies both in marine and continental waters. Cyprinids (chub, Leuciscus cephalus) were sampled in river sites (France) in relatively clean and polluted areas. We performed the statistical analysis of the ChE activities and we generally observed a statistical relationship between ChE activities and fish length, the larger fish having the lower ChE activities. We concluded that the great majority of the significant differences in ChE activities between sites could be due in fact to differences in fish length between field samples. We stress the importance of taking into account the fish length whenever differences in ChE levels between field sites must be interpreted.

Animals↗

Impact assessment of a wastewater treatment plant effluent using the fish biomarker ethoxyresorufin-O-deethylase: field and on-site experiments.

The impact of a wastewater treatment plant (WWTP) effluent was assessed with the fish biomarker ethoxyresorufin-O-deethylase (EROD) using field and on-site laboratory experiments. EROD activity was measured in chub (Leuciscus cephalus) and stone loach (Noemacheilus barbatulus) caught at three sites of the Chalaronne River (southeast France). Liver somatic index (LSI) and organochloride bioaccumulation in muscle were estimated for chub only. In September, EROD activity and LSI of chub increased significantly between the sites above and below the WWTP effluent discharge. EROD induction detected in chub was confirmed by on-site tank experiments. EROD levels were determined in juvenile rainbow trout (Oncorhynchus mykiss) and mirror carp (Cyprinus carpio) exposed to different concentrations of the WWTP effluent and river water for 16 days. After a 4-day exposure, EROD activities of the carp exposed to the effluent increased significantly compared with the control. The response was linked to the effluent concentration and was stable with exposure time. WWTP effluent induced EROD activity, whereas organic and metal analyses, performed on fish muscle and sediment, did not indicate any difference between upstream and downstream of the discharge.

Animals↗

Is endotoxin and cytokine release related to a decrease in gastric intramucosal pH after hemorrhagic shock?

OBJECTIVES: (a) To investigate the relationship between gut ischemia parameters (gastric intramucosal pH [pHi], mucosal-arterial carbon dioxide difference [PCO2-gap]), and endotoxin or cytokine release during hemorrhagic shock; (b) to compare the predictive value of pHi, PCO2-gap and arterial lactate concentrations. DESIGN: Prospective study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: 20 multiple trauma patients with severe hemorrhagic shock. INTERVENTIONS: Intramucosal measurements and blood samples were obtained on admission to the emergency room and repeatedly over 48 h. MEASUREMENTS AND RESULTS: Endotoxin was measured using a chromogenic limulus amoebocyte assay. Cytokine [tumor necrosis factor-alpha (TNF alpha) and interleukin-6 (IL-6)] values were evaluated by immunoradiometric assays. Only 3 patients had positive blood cultures but endotoxins were detected at least once in all patients. Endotoxin levels were similar in survivors and non-survivors over the study period and were not related to pHi or PCO2-gap. Initially, high levels of IL-6 were observed in both nonsurvivors and survivors [median 1778 pg/ml (range 435-44,540) vs 2068 pg/ml (range 996-92,300)]. IL-6 levels progressively decreased in the survivors but not significantly. On admission, TNF alpha concentrations were similar in nonsurvivors and survivors (42 +/- 35 vs 46 +/- 27 pg/ml). From the 24th h, TNF alpha values were higher in the nonsurvivors than in the survivors (24 h: 72 +/- 38 vs 34 +/- 17 pg/ml, p < 0.05). The greatest IL-6 levels were found for a pHi < 7.20 (28.5 +/- 36.5 vs 1.8 +/- 1.3 ng/ml, p < 0.05) or a PCO2-gap > 7.5 mmHg (1 kPa) (32.5 +/- 37.5 vs 1.7 +/- 1.3 ng/ml, p < 0.01). With the same pHi threshold, no difference was found in endotoxin levels. The lactate concentrations were predictive for outcome from the 12th h (9.5 +/- 5.9 vs 3.6 +/- 2.3 mmol/l, p < 0.05). CONCLUSIONS: During severe hemorrhagic shock, endotoxin translocation from the gut was a common phenomenon that seemed independent of both pHi values and outcome. It could not explain IL-6 and TNF alpha release. In severe hemorrhagic shock, neither pHi nor PCO2-gap provides additional information to the lactate measurements.

Adult↗

Differential quantitative blood cultures in the diagnosis of catheter-related sepsis in intensive care units.

The aim of this prospective study was to compare differential blood cultures and quantitative catheter tip cultures for the diagnosis of catheter-related sepsis. Over a period of 2 years, 283 central venous catheters were inserted in 190 adult patients. Catheters were removed when they were no longer needed or when infection was suspected. Immediately before removal of the central venous catheters, blood cultures were performed, with blood drawn simultaneously from the catheter and the peripheral vein. After removal, quantitative catheter culture was performed according to the Brun-Buisson modified Cleri technique. Fifty-five quantitative catheter cultures were positive. They were classified as contaminated (n = 18), colonized (n = 23), or infected (n = 14). Differential blood cultures correctly identified 13 infections. With a catheter/peripheral cfu ratio of 8, differential blood cultures had a sensitivity of 92.8% and a specificity of 98.8%. When the catheters were removed because of suspected infection, differential blood cultures had a sensitivity of 92.8% and a specificity of 100%. Differential blood culture, a technique that does not necessitate catheter removal, seems effective in the diagnosis of catheter-related sepsis in patients in the intensive care unit.

Adult↗

Influence of the sample preservation mode to assess the chronic toxicity of an industrial effluent.

To improve the preservation of effluent samples, the contribution of refrigeration, freezing, and freeze-drying techniques to maintain the toxic characteristics of the samples was evaluated. To achieve this evaluation one acute test, three long-term toxicity tests, a biochemical test (P450 induction), and a mutagenicity test (Ames test) were used on the same industrial effluent. Refrigeration and freezing demonstrated a similar capacity of preservation. However, freezing should be recommended when the delay between sampling and the start of the bioassay exceeds 48 hr. Freeze-drying did not prove to be useful in that case but this could be due to methodological problems. Nevertheless, this technique allowed the detection of mutagenic compounds because of its aptitude to concentrate effluent samples. For the toxic evaluation of the samples the advantages of the use of a battery of biotests were confirmed and it was noted that the cladoceran (Ceriodaphnia dubia) reproduction test and the algal (Selenastrum capricornutum) growth test had a higher sensitivity within the three tests used.

Animals↗

[Clonidine premedication and isoflurane anesthesia to reduce bleeding in otologic surgery].

Seventy-seven ASA 1 patients scheduled for ear surgery were premedicated orally, 90 min before anaesthesia. They were randomly assigned to two groups, according to the drug used: hydroxyzine alone (group T, n = 39) or combined with clonidine (4.9 +/- 0.3 micrograms.kg-1) (group C, n = 38). Anaesthesia was induced with midazolam (0.3 mg.kg-1) and alfentanil (30 micrograms.kg-1). Ventilation was controlled with a 50/50 v/v mixture of oxygen and nitrous oxide (FETCO2 = 4 to 4.5%), and anaesthesia was maintained with repeated injections of alfentanil (15 micrograms.kg-1 at the start of surgery, and then every 15 min) and with isoflurane (mean end-expiratory concentration 0.6 +/- 0.3 vol %). Surgical bleeding was assessed every ten minutes on a numerical scale with four values. A bloodless surgical field was obtained by adjusting the isoflurane concentration up to 2 MAC, and by using a trinitrine infusion as required. Cardiovascular monitoring included an electrocardioscope and automatic blood pressure measurements. Before induction of anaesthesia, the blood pressure was lower in group C (84.7 +/- 11.2 vs. 95.9 +/- 106 mmHg) (p less than 0.001); the difference in heart rate was not significant (65 +/- 15 vs. 70.6 +/- 14 b.min-1). Moderate stable intraoperative hypotension was obtained in both groups. However, mean arterial blood pressure (C:65.8 +/- 7.8 mmHg; T: 73 +/- 9.4 mmHg) and heart rate (C: 53.4 +/- 6.8 b.min-1; T: 60.4 +/- 8 b.min-1) were significantly lower in the patients premedicated with clonidine (p less than 0.001). There were more periods of sinus bradycardia (heart rate less than or equal to 50 b.min-1), mostly seen before the beginning of surgery, in group C patients (p less than 0.01); atropine was also required more often (when the heart rate was less than or equal to 40 b.min-1) in this group of patients (NS). The comparative assessment of surgical field quality was in favour of group C (no troublesome bleeding) as opposed to the control group (16% troublesome bleeding); there were also more bloodless surgical fields in the former group (73.7% vs. 48.7% in group T, p less than 0.05). This study therefore demonstrated that clonidine premedication before anaesthesia with isoflurane was helpful in decreasing bleeding during ear surgery.

Adult↗

Freshwater fish cytochrome P450-dependent enzymatic activities: a chemical pollution indicator.

Fish mixed function oxidase activities were measured during four sampling campaigns in the river Durance in the southeast of France. Six hundred fish belonging to four species were caught for this study; the use of factorial analysis emphasizes the strong pollution dependence of the P450-dependent enzymatic activities which vary with the season, the species, and the sex of the fish. Regression analysis of the data allowed prediction of the type of location from which the fish came (polluted or unpolluted) for 80% of the fish. This supports use of such activities as chemical pollution indicators.

Animals↗