An Investigation of a Mathematical Model for the Internal Velocity Profile of Conical Diffusers Applied to DAWTs.

The Diffuser Augmented Wind Turbines (DAWTs) have been widely studied, since the diffusers improve the power coefficient of the wind turbine, particularly of small systems. The diffuser is a device which has the function of causing an increase on the flow velocity through the wind rotor plane due to pressure drop downstream, therefore resulting in an increase of the rotor power coefficient. This technology aids the turbine to exceed the Betz limit, which states that the maximum kinetic energy extracted from the flow is 59.26%. Thus, the present study proposes a mathematical model describing the behavior of the internal velocity for three conical diffusers, taking into account the characteristics of flow around them. The proposed model is based on the Biot-Savart's Law, in which the vortex filament induces a velocity field at an arbitrary point on the axis of symmetry of the diffusers. The results are compared with experimental data obtained for the three diffusers, and present good agreement.

Comparative genotoxicity of halogenated acetic acids found in drinking water.

Three short-term assays (SOS chromotest, Ames fluctuation test and newt micronucleus test) were performed to detect the genotoxic activity of organohalides, compounds likely to be found in chlorinated and/or ozonated drinking water: monochloro-, dichloro- and trichloroacetic acids and monobromo-, dibromo- and tribromoacetic acids. With the SOS chromotest, only three of the chemicals studied (dichloroacetic acid, dibromo- and tribromoacetic acids) were found to induce primary DNA damage in Escherichia coli PQ 37. In the Ames fluctuation test, all the compounds except monochloroacetic acid showed mutagenic activity in Salmonella typhimurium strain TA100. In these two in vitro tests, a good correlation between increasing number of substituents and decreasing mutagenicity was observed. Namely, the toxicity of brominated and chlorinated acetic acids decreased when the number of substituents increased. The newt micronucleus test detected a weak clastogenic effect on the peripheral blood erythrocytes of Pleurodeles waltl larvae for trichloroacetic acid only.

1H NMR investigation of toxic effects of lindane and paraquat on Hep 3B and Hep G2 human hepatoma cell lines.

Lindane and paraquat induce biochemical changes in the liver. In order to specify their molecular impact at the cellular level, a 300 MHz 1H NMR investigation of hepatoma cell lines Hep 3B and Hep G2 responses was performed. Cells were exposed over 24 h to 50 mg/L lindane (0.178 mM) or to 100 mg/L (0.389 mM) paraquat concentrations. The main observation following exposure to lindane was a decrease in betaine methyl groups (3.26 ppm) which could be related to the steatosis reported by some authors. Specifically, in Hep G2 cells with this pesticide, the glycine peak (3.56 ppm) was lowered, thus confirming that the glycine synthesis pathway involving methionine, choline, and betaine was disturbed by lindane. Moreover, in this hepatoma cell line, the p-chlorobenzoate ion could be detected as a doublet at 7.55 ppm. In Hep 3B cells, paraquat increased betaine and methionine levels, suggesting disturbance in glycine biosynthesis. Possibilities of cellular uptake were considered, and the presence of this herbicide in cells was revealed by spectrophotometric and NMR measurements after chlorhydric hydrolysis, suggesting interaction with cellular components. The impact of paraquat on Hep G2 cells appeared to be located on mitochondrial function, as indicated by the observed decrease in succinate and pyruvate levels.

Assay of free-radical toxicity and antioxidant effect on the Hep 3B cell line: a test survey using lindane.

The content of reduced glutathione and of glutathione disulfide as well as the activities of glutathione reductase, glutathione peroxidase, glutathione S-transferases, catalase and superoxide dismutases were determined in human hepatoma Hep 3B cells in relation to free-radical toxicity in order to appreciate the defense capacities of these cells compared to data on normal hepatocytes. When Hep 3B cells were exposed to lindane, a known inducer of free-radical production, superoxide dismutase activity appeared as the best-adapted cellular parameter for early detection of the resulting free-radical toxicity.

Genotoxicity assay of chloral hydrate and chloropicrine.

The chlorination by-products chloral hydrate and chloropicrine were assayed for genotoxicity in three short-term tests. Chloropicrine was 100-fold more potent than chloral in inducing mutations in strain TA100 of S. typhimurium (fluctuation test) and, at variance with chloral, was positive in the SOS chromotest using strain PQ37 of E. coli. On the other hand, only chloral caused a significant increase in the frequency of micronucleated erythrocytes following in vivo exposure of the amphibian Pleurodeles waltl newt larvae.

[Erythrocyte ketone reductase activity, total plasma haloperidol and acute psychoses]. / Activité cétone réductase érythrocytaire, taux plasmatiques d'halopéridol et psychoses aiguës.

Haloperidol (HAL) is a widely used and clinically effective neuroleptic. Its metabolism differs in various animal species. In humans, reduced haloperidol (RHAL), a hydroxy metabolite of HAL, is produced by a cytosolic ketone reductase. Interconversion is known to occur whereby HAL is found in the plasma after administration of RHAL in vivo. Interconversion of HAL and RHAL has been observed in man. However, the capacity for reductive HAL is greater than its oxidation back from RHAL. RHAL, the resulting metabolite of HAL, is reported to be about 10-25% as active as HAL in an animal model. Large intersubject variation has been observed in the pharmacokinetics of HAL and RHAL. A wide variation in reductive drug-metabolizing has been observed in schizophrenic patients treated with HAL. Both high and low RHAL/HAL ratios or RHAL levels were reported to be linked to poor response in HAL-treated patients and might be correlated with the therapeutic window effect of HAL treatment. It is conceivable, therefore, that subjects with high reductive capacity relative to oxidative capacity may have less therapeutic response from the same dose of HAL than those with a low reductive capacity relative to oxidative capacity. This aim of this study was to investigate the HAL reduction among a sample of HAL-treated schizophrenic patients. Because ketone reductases are generally not tissue specific, we investigate the reductase activity in Red blood cells (as described by Inaba), before and during the treatment. Steady-state plasma drug levels during 2 weeks of treatment were quantified. We examined the relationships between fixed doses of HAL treatment, Red blood cells ketone reductase activity, plasma HAL and RHAL levels and the percentage of change of the Positive and Negative Syndrome Scale for Schizophrenia. The participants in this study were 15 inpatients consecutively being treated in the adult psychiatric wards of the University of Lille. All subjects met DSM III-R criteria for schizophrenia (paranoid form). Upon induction subjects were evaluated clinically by trained raters using the Positive and Negative Syndrome Scale for Schizophrenia (PANSS). Subjects were required to score 40 or higher on the general psychopathology subscale of the PANSS to continue participation. All subjects were drug free. Haloperidol was administered orally at three times daily dose. Patients were randomized to treatment at three orally fixed doses: 6 mg per day, 10 mg per day and 15 mg per day. Patients were treated for 2 periods of one week. At the end of each period, dosages could be modified according to the clinic evolution of the patient. PANSS was repeated by the same raters blinded to the haloperidol dosage, plasma concentration and Rbc haloperidol ketone reductase activity, at the beginning and at the end of each period. Blood samples were collected on the same day that clinical assessment were made. Multiple regression analysis (forward stepwise) revealed that Red blood cells reductase activity at D0 is an important variable predicting haloperidol plasma levels at week 2. Similarly Red blood cells reductase activity at D0 and D7 predicted Reduced haloperidol plasma concentrations at week 2. In this sample, no parameter was found to be consistency predicted the percentage change in the PANSS positive subscale from baseline, at week 2. Nevertheless, Red blood cells reductase activity at D0, Reduced haloperidol/haloperidol ratio at week 2, haloperidol plasma levels at week 2 and the dose of haloperidol at week 1 were important variables predicting the percentage change in the PANSS general subscale from baseline at week 2. These results suggest that the knowledge of reductase activity could predict the treatment response in acute schizophrenic patients.

Use of the SOS chromotest, the Ames-fluctuation test and the newt micronucleus test to study the genotoxicity of four trihalomethanes.

Three short-term assays (the SOS chromotest, the Ames-fluctuation test and the newt micronucleus test) were carried out to evaluate the genotoxicity of four trihalomethanes (chloroform, bromodichloromethane, chlorodibromomethane and bromoform). With the SOS chromotest, all the chemicals studied except chloroform were found to induce primary DNA damage in Escherichia coli PQ37. In the Ames-fluctuation test, only bromoform showed mutagenic activity on Salmonella typhimurium strain TA100. The newt micronucleus assay detected a clastogenic effect on the peripheral blood erythrocytes of Pleurodeles waltl larvae for bromodichloromethane and bromoform. It appeared that the presence of bromine substituent(s) generally led to significant genotoxic activity. Moreover, the use of the metabolic system significantly increased the genotoxicity of the brominated trihalomethanes in the SOS chromotest. Unlike previous investigations in which the SOS chromotest was always the least interesting assay, this study exhibited the good efficiency of this in vitro test on E.coli for the detection of trihalomethanes with bromine substituents.

Study of the genotoxic activity of six halogenated acetonitriles, using the SOS chromotest, the Ames-fluctuation test and the newt micronucleus test.

Three short-term assays (the SOS chromotest, the Ames-fluctuation test and the newt micronucleus test) were carried out to evaluate the genotoxicity of six halogenated acetonitriles identified in chlorinated waters (monochloro-, dichloro-, trichloro-, monobromo-, dibromo- and bromochloroacetonitrile). With the SOS chromotest, three of the chemicals studied (dichloro-, dibromo- and bromochloroacetonitrile) were found to induce primary DNA damage in Escherichia coli PQ37. In the Ames-fluctuation test, all the compounds except dibromoacetonitrile showed mutagenic activity on Salmonella typhimurium strain TA100. The newt micronucleus assay detected a clastogenic effect on the peripheral blood erythrocytes of Pleurodeles waltl larvae for all the six haloacetonitriles studied. Moreover, two structure-activity relationships were noted: (1) the genotoxic activity of haloacetonitriles containing bromine substituents appeared higher than the corresponding chlorinated acetonitriles and (2) the clastogenic activity of the chlorinated acetonitriles increased with the number of chlorine substituents.

Study of the genotoxic activity of five chlorinated propanones using the SOS chromotest, the Ames-fluctuation test and the newt micronucleus test.

Three short-term assays (the SOS chromotest, the Ames-fluctuation test and the newt micronucleus test) were carried out to evaluate the genotoxicity of five chlorinated propanones identified in several chlorinated waters (monochloropropanone, 1,1-dichloropropanone, 1,3-dichloropropanone, 1,1,1-trichloropropanone and 1,1,3-trichloropropanone). In the SOS chromotest, all the compounds except monochloropropanone were found to induce primary DNA damage in Escherichia coli. With the fluctuation test, all five chloropropanones showed mutagenic activity on Salmonella typhimurium strain TA100. The newt micronucleus assay detected a clastogenic effect on the peripheral blood erythrocytes of Pleurodeles waltl larvae only for 1,3-dichloropropanone and 1,1,3-trichloropropanone. Moreover, two structure-activity relationships are noticeable: (1) chloropropanones with chlorine substituents on both carbon positions (1,3-DCP and 1,1,3-TCP) are by far more genotoxic than chloropropanones substituted only on one carbon position (1,1-DCP and 1,1,1-TCP); (2) the increase of the number of chlorine substituents decreases the mutagenic activity (fluctuation test) of the chlorinated propanones studied.

Application of the kinetic of RNA synthesis on Hep 3B cells. Study of the medium-term cytotoxicity of atrazine.

The test based on measuring the RNA synthesis rate, already described on Hela S3 in culture (Fauris et al., Les colloques de l'INSERM 106 (1981) 455-463), has been adapted to a human hepatoma cell line Hep 3B which retains a certain capacity towards metabolising. These modifications make it easier to point to the presence of possible water micropollutions and to envisage the study of the medium-term toxicity of such pollutants to be found in traces in water, with adequate sensitivity if we take into account their low concentration level. This trial has been carried out to compare the cytotoxicity of atrazine, over short- and medium-term periods: prolonged exposure to atrazine (1 or 10 micrograms/l) leads to an increase in the RNA synthesis rate (not to be detected after 24 h of exposure). Pre-exposure to 1 or 10 micrograms/l pesticide (over 6 days) would cause results to increase considerably during any future intoxication (250 micrograms/l).

[Erythrocyte superoxide dismutase (eSOD) determination in positive moments of psychosis]. / Dosages de la superoxyde dismutase érythrocytaire (SODe) dans les moments productifs de psychose.

Dysregulation of free radical metabolism has been supposed to be involved in schizophrenia etiopathogeny. Recently, Wang et al. showed a red blood cell super oxide dismutase increase in positive schizophrenia (Crow's type I), but neither in negative schizophrenia (Crow's type II) nor in controls. The study included 28 in-patients suffering from acute positive psychosis who were compared with 15 controls. We confirmed the results of Wang. We found a significantly red blood cell Super oxide dismutase increase in positive psychosis, in comparison to negative psychosis and controls (p = 0.0001). This SOD increase was in relationship with the degree of clinical psychomotor excitement. After 21 days of neuroleptic treatment, SOD activity decreased and reached standard values. These results support the hypothesis of striking relationships between catecholaminergic hyper-metabolism and SOD increase, in positive psychosis. These could account for psychotic positive symptoms improvement with neuroleptic treatment, which blocks dopamine pathways.

Correlation of clinical response (PANSS) and plasma levels of haloperidol and reduced haloperidol in schizophrenia.

1. The authors attempted to correlate plasma concentrations in H/rH and clinical efficacy from 8 schizophrenic patients (DSM IIIR) on H. 2. No significant correlations were found between H, rH plasma levels and positive and negative subscale for each patient. 3. The authors observed an opposite evolution concerning the mean results between plasma concentrations and PANSS total score.

[Value of the determination of erythrocyte haloperidol ketone reductase activity in the evaluation of haloperidol therapy]. / Intérêt du dosage de l'activité halopéridol cétone réductase érythrocytaire dans l'optimisation d'un traitement par halopéridol.

Serum levels of haloperidol and reduced haloperidol as well as the reduced haloperidol/haloperidol ratios were determined in nine acute schizophrenics on oral haloperidol medication and correlated over 21 days with psycho pathology and extra-pyramidal symptom scores. We have investigated red blood cells haloperidol reductase activity in the group of patients. Significant correlations were found between haloperidol plasma levels and positive sub scale for each patient (r = 0.86 and p < 0.01; r = 0.70 and p < 0.05). We found a correlation between red blood cells reductase activity and the improvement of the psychotic anxiety scale (r = 0.64/and p < 0.05; r = 0.67 and p < 0.05), but not with reduced haloperidol/haloperidol ratios in plasma. The knowledge of reductase activity could predict the treatment response in acute schizophrenic patients. We suggest that the reported inter individual and inter ethnic differences in haloperidol and reduced haloperidol and in clinical response and adverse effects may be a reflection of genetic control of the two oxidative pathways mediated by cytochrome P450 isozyme and/or the reductase pathway mediated by haloperidol reductase in individual subject.

Comparison of three short-term assays: results on seven chemicals. Potential contribution to the control of water genotoxicity.

Three short-term assays (the SOS chromotest, the Ames fluctuation test and the newt micronucleus test) were used to evaluate the genotoxicity of seven chemicals (4-nitroquinoline 1-oxide, potassium dichromate, formaldehyde, sodium hypochlorite, benzo[a]pyrene, cyclophosphamide and 2-naphthylamine). In the SOS chromotest, all seven compounds except sodium hypochlorite and cyclophosphamide were found to induce primary DNA damage in E. coli. With the Ames fluctuation test, all seven chemicals except sodium hypochlorite showed mutagenic activity on Salmonella typhimurium TA100, TA102 or TA98. The newt micronucleus assay detected a clastogenic effect of all seven compounds except formaldehyde on the peripheral blood erythrocytes of Pleurodeles waltl larvae. For each compound, the sensitivity of the tests was compared; (1) the SOS chromotest is the least sensitive assay in every case, (2) the Ames fluctuation test is the most sensitive assay for studied chemicals with direct genotoxic effect and (3) the newt micronucleus assay is the most sensitive test for tested compounds with indirect genotoxic activity. The potential contribution of these three tests in the monitoring of water genotoxicity is discussed.

Comparison of metabolic activities in two human hepatoma cell lines, HEP 3B and HEP G2. Application to lindane.

In a preliminary investigation, the evolution with time of the levels of ATP and glutathione species [reduced glutathione (GSH) and glutathione disulphide (GSSG)], glutathione reductase activity and RNA synthesis rate were studied in two human hepatoma cell lines, Hep 3B and Hep G2. Both cell lines exhibited higher cellular activities, during the first 48 hr. In a second investigation, the cells were exposed to lindane. Different cytotoxicological parameters such as viability, lactate dehydrogenase release, ATP, GSH and GSSG contents, RNA synthesis rate and glutathione reductase activity, were measured. Results showed that Hep 3B cells were more susceptible to lindane than Hep G2 cells, which perhaps have superior defence capacity and metabolism.

Cellular uptake and biotransformation of arsenic V in transformed human cell lines HeLa S(3) and Hep G(2).

The biotransformation of arsenate was studied in two human transformed cell lines (epithelial HeLa S(3) and hepatoma Hep G(2) cells) by the determination of several arsenic species both in the culture medium and in the cells. Arsenate reduction, which was observed in the two cell lines, was higher in Hep G(2) cells. Methylation appeared to be a minor pathway for HeLa cells, but was more important in the hepatoma cells.

Determination of haloperidol and hydroxy haloperidol in human plasma by high performance liquid chromatography.

A method has been developed for the separation and measurement of haloperidol and hydroxy haloperidol in human plasma through high performance liquid chromatography. The method uses chlorohaloperidol as an internal standard and provides a limit of detection of about 0.7 nmol/l for haloperidol and 0.67 nmol/l for hydroxy haloperidol. HPLC and RIA radioimmunoassay methods are compared.