Modulating effects of humic acids on genotoxicity induced by water disinfectants in Cyprinus carpio

The use of chlorinated disinfectants during drinking-water production has been shown to generate halogenated compounds as a result of interactions of humic acids with chlorine. Such chlorinated by-products have been shown to induce genotoxic effects and consumption of chlorinated drinking-water has been correlated with increased risk for cancer induction in human populations. The aim of this work was to test the potential genotoxic effects on circulating erythrocytes of the fish Cyprinus carpio exposed in vivo to well-waters disinfected with sodium hypochlorite (NaClO), chlorine dioxide (ClO2) or peracetic acid (CH3COO2H, PAA), in the absence or presence of standard humic acids (HA). The effects were measured by use of the micronucleus (MN) and the single-cell gel electrophoresis (Comet) assays at different sampling times after a 3-day exposure period. The exposure to chlorine disinfectants without the addition of HA produced a clear toxic effect. Significant cytogenetic damage (i.e. MN induction) was detected in fish populations exposed to both NaClO and ClO2 with humic acids. In the Comet assay, a significant decrease of DNA migration was observed in erythrocytes of specimens after exposure to NaClO-disinfected water without HA. No effects were observed in any other experimental condition. (c) 2005 Elsevier B.V. All rights reserved

Comet assay and micronucleus test in circulating erythrocytes of Cyprinus carpio specimens exposed in situ to lake waters treated with disinfectants for potabilization

The detection of a possible genotoxic effect of surface water treated with disinfectants for potabilization is the aim of the present work. The Comet assay and the micronucleus test were applied in circulating erythrocytes of Cyprinus carpio. Young specimens (20-30g) were exposed in experimental basins, built within the potabilization plant of Castiglione del Lago (Perugia, Italy). In this plant the water of the Trasimeno Lake is treated and disinfected for potabilization before it is distributed to the people in the net of drinkable water. A continuous flow of water at a constant rate was supplied to basins; the water was continuously treated at a constant concentration with one of the three tested disinfectants (sodium hypochlorite, peracetic acid and chloride dioxide), one control basin being supplied with untreated water. Three sampling campaigns were performed: October 2000, February 2001 and June 2001. Repeated blood samplings through intracardiac punctures allowed to follow the same fish populations after different exposure times: before introduction of the disinfectant, and 10 or 20 days afterwards. An additional blood sampling was performed 3h after addition of the disinfectant in other, simultaneously exposed, fish populations. Genotoxic damage was shown in fish exposed to water disinfected with sodium hypochlorite and chloride dioxide. The Comet assay showed an immediate response, i.e. DNA damage that was induced directly in circulating erythrocytes, whereas micronuclei reached their highest frequencies at later sampling times, when a genotoxic damage in stem cells of the cephalic kidney is expressed in circulating erythrocytes. The quality of the untreated surface water seems to be the most important parameter for the long-term DNA damage in circulating erythrocytes. © 2003 Elsevier B.V. All rights reserved

Farmacocinética de la cefalexina administrada por vía oral conjuntamente con enalapril en caninos adultos

El objetivo de este estudio fue caracterizar la farmacocinética de la cefalexina administrada por vía oral a caninos y determinar si la administración conjunta con enalapril produce modificaciones en la misma. Se trabajó con 6 caninos mestizos sanos. Cada uno recibió una dosis única de 25 mg/kg de una suspensión de cefalexina (grupo 1) o cefalexina 20 minutos después de administrada una dosis oral única de 0,5 mg/kg de enalapril (grupo 2), con un diseño cross over (3x3). Las concentraciones plasmáticas de cefalexina se determinaron mediante el método microbiológico. El T>CIM fue siempre superior al 60% del intervalo posológico de 12 horas para ambos grupos. Los parámetros farmacocinéticos se compararon mediante el test de Wilcoxon (p≤0,05). Los resultados obtenidos se expresaron como media ± desvío estándar y para los grupos 1 y 2 fueron respectivamente: Cmax 27,66±4,20 y 26,51±6,04 μg/ml, Tmax 1,41±0,58 y 1,58±0,58 h, T1/2 1,55±0,12 y 1,62±0,22 h, ABC0-∞ 110,8±10,98 y 110,6±17,64 μg·h/ml, TMR 3,19±0,39 y 3,46±0,55 h. No se encontraron diferencias estadísticamente significativas entre los parámetros farmacocinéticos de efalexina obtenidos en cada grupo, por lo cual nuestros resultados sugieren que el tratamiento simultáneo con ambas drogas no modifica la farmacocinética del antibiótico

Perturbation of cytochrome P450, generation of oxidative stress and induction of DNA damage in Cyprinus carpio exposed in situ to potable surface water

Epidemiological evidence suggests a link between consumption of chlorinated drinking water and various cancers. Chlorination of water rich in organic chemicals produces carcinogenic organochlorine by-products (OBPs) such as trihalomethanes and haloacetic acids. Since the discovery of the first OBP in the 1970s, there have been several investigations designed to determine the biological effects of single chemicals or small artificial OBP combinations. However, there is still insufficient information regarding the general biological response to these compounds, and further studies are still needed to evaluate their potential genotoxic effects. In the current study, we evaluated the effect of three drinking water disinfectants on the activity of cytochrome P450 (CYP)-linked metabolizing enzymes and on the generation of oxidative stress in the livers of male and female Cyprinus carpio fish (carp). The fish were exposed in situ for up 20 days to surface water obtained from the Trasmene lake in Italy. The water was treated with 1-2 mg/L of either sodium hypochlorite (NaClO) or chlorine dioxide (ClO2) as traditional disinfectants or with a relatively new disinfectant product, peracetic acid (PAA). Micronucleus (MN) frequencies in circulating erythrocytes from the fish were also analysed as a biomarker of genotoxic effect. In the CYP-linked enzyme assays, a significant induction (up to a 57-fold increase in the deethylation of ethoxyresorufin with PAA treatment) and a notable inactivation (up to almost a 90% loss in hydroxylation of p-nitrophenol with all disinfectants, and of testosterome 2 beta-hydroxylation with NaClO) was observed in subcellular liver preparations from exposed fish. Using the electron paramagnetic resonance (EPR) spectroscopy radical-probe technique, we also observed that CYP-modulation was associated with the production of reactive oxygen species (ROS). In addition, we found a significant increase in MN frequency in circulating erythrocytes after 10 days of exposure of fish to water treated with ClO2, while a non-significant six-fold increase in MN frequency was observed with NaClO, but not with PAA. Our data suggest that the use of ClO2 and NaClO to disinfect drinking water could generate harmful OBP mixtures that are able to perturb CYP-mediated reactions, generate oxidative stress and induce genetic damage. These data may provide a mechanistic explanation for epidemiological studies linking consumption of chlorinated drinking water to increased risk of urinary, gastrointestinal and bladder cancers. (c) 2006 Elsevier B.V. All rights reserved

Comparative pharmacokinetics of a long-acting amoxicillin formulation following its subcutaneous and intramuscular administration to dogs

The influence of the route of administration on the amoxicillin pharmacokinetics in dogs was\ninvestigated following the subcutaneous or intramuscular administration of 15 mg/kg amoxicillin\nformulated as a long-acting aqueous suspension. Serial blood samples were collected at predetermined\ntimes. Pharmacokinetic parameters were calculated from the disposition curves for both routes for\neach animal. Significant differences were observed for the parameters area under the curve (73.8\n± 13.1 mg.h/ml versus 88.3 ± 17.0 mg.h/ml) and mean residence time (6.9 ± 2.8 h versus 10.3 ±\n6.1 h) following the intramuscular and subcutaneous injections, respectively. The subcutaneous\nadministration exhibited higher depot effect than the intramuscular administration. No significant\ndifferences were observed for the time above the minimun inhibitory concentrations for bacteria\nof low (4 mg/ml) and high (0.250 mg/ml) amoxicillin sensitivity. Our data suggest that the tested\nformulation can be used with a prolonged interval of 48 h for high sensitivity bacteria, and that\nboth routes of administration provide similar kinetic profiles and thus, similar clinical outcomes.Fil: Porta, N. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Farmacología; ArgentinaFil: Prados, A.P. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Farmacología; ArgentinaFil: Kreil, V. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Farmacología; ArgentinaFil: Tarragona, L. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Farmacología; ArgentinaFil: Monfrinotti, A. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Farmacología; ArgentinaFil: Rebuelto, M. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Cátedra de Farmacología; ArgentinaSe investigó la influencia de la vía de administración en la farmacocinética de la amoxicilina en caninos,\nluego de la administración por las vías subcutánea e intramuscular de 15 mg/kg de amoxicilina\nformulada como una suspensión acuosa de larga acción. Se tomaron muestras de sangre en tiempos\npredeterminados, y se calcularon los parámetros farmacocinéticos de las curvas de disposición para\ncada animal y para cada vía de administración. Se observaron diferencias significativas para los\nparámetros área bajo la curva (73.8 ± 13.1 mg.h/ml versus 88.3 ± 17.0 mg.h/ml) y tiempo medio\nde residencia (6.9 ± 2.8 h versus 10.3 ± 6.1 h) luego de las inyecciones intramuscular y subcutánea,\nrespectivamente. La administración subcutánea mostró un mayor efecto depot que la intramuscular.\nNo se observaron diferencias significativas para el tiempo sobre la concentración inhibitoria mínima\npara bacterias de baja (4 mg/ml) y alta (0.250 mg/ml) susceptibilidad a la amoxicilina. Nuestros datos\nsugieren que la formulación probada puede ser utilizada con un intervalo posológico prolongado de\n48 h para bacterias muy susceptibles, y que ambas vías de administración proveen perfiles cinéticos\nsimilares, y por ende, similares resultados clínicos. \

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5–11 December, to 17.5% (25/143 samples) in the week 12–18, to 65.9% (89/135 samples) in the week 19–25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool

The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5–11 December, to 17.5% (25/143 samples) in the week 12–18, to 65.9% (89/135 samples) in the week 19–25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased fromone in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons

Eficaci del ricobendazole-Vía cubcutánea- contra los nematodes gastro intestinales del bovino

A controlled efficacy trial to determine the anthelmintic efficacy of Ricobendazole -RBZ- (Albendazole sulfoxide) administered at different dose rates to cattle harbouring natural trichostrongyle infections was carried out. Thirty Aberdeen Angus castrated male calves ageaging 12-15 months old belonging to a cattle farm located nearby Tandil and previously exposed to parasitic infections, were identified and transferred to concrete floor pens (day 0). Dry grass free of trichostrongyle infective larvae and fresh water was supplied. On day + 7, the animals were divided into 5 comparable experimental groups of 6 calves each. The animals of groups 1 to 4 were treated with RBZ (15% formulation) by subcutaneous via at the dose rates of 3.5, 3.75, 5.0 and 7.5 mg/k body weight, respectively. The group 5 was the untreated control group. Faeces were collected from animals at different time intervals after treatment to determine the levels of nematode egg excretion (e.p.g.) and the ovicidal effects throughout cultivation of samples. On days + 15 and + 16 the experimental animals were necropsied to determine the anthelmintic efficacy. The e.p.g. counts were reduced drastically (100%) at day 3 after treatments while faecal cultivation showed that a complete ovicidal effect was observed at 12 hs after treatments. Faecal cultures from group 5 showed that Cooperia spp., Trichostrongylus spp., Ostertagia spp., Haemonchus spp and Oesophagostomum spp. were the predominant parasites in the infection. The anthelmintic efficacy of RBZ was 96.5 to 100 % (P< 0.01) for any of the dose rate levels applied to animals against the adult and immature worms of the abomasum, small and large intestine: Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Cooperia oncophora and Oesophagostomum radiatum. The efficacy against inhibited larvae (L4I) of Ostertagia ostertagi was 95.7 % (P< 0.01) at the dose rate of 7.5 mg/k.b.w. It may be concluded that RBZ - subcutaneous via - was highly effective against the most economically important worms usually established in grazing cattle of the Humid Pampa in Argentina. Moreover, the ovicidal effect showed by RBZ may facilitate the developing of control programmes in set-stocked cattle.Se llevó a cabo una prueba controlada de eficacia para determinar la actividad terapéutica del Ricobendazole -RBZ- (sulfóxido de Albendazole) aplicado por vía parenteral a diferentes dosis, en bovinos infectados naturalmente con parásitos gastrointestinales. En un establecimiento ganadero de la zona de Tandil, se seleccionaron e identificaron 30 novillitos de 12-15 meses de edad. Los animales fueron trasladados a corrales con piso de cemento (día 0) donde se alimentaron con heno de alfalfa libre de larvas de nematodes trichostrongylideos y agua corriente ad-libitum. En el día + 7, se formaron 5 grupos comparables de 6 animales cada uno; los novillitos de los grupos 1 al 4, fueron tratados por vía subcutánea con RBZ (formulación al 15%) a las dosis de 3.5, 3.75, 5.0 y 7.5 mg/kg de peso vivo, respectivamente. El grupo 5 fue el control no tratado. Se extrajeron muestras de materia fecal de todos los animales a diferentes intervalos post-tratamiento, para determinar el número de huevos de nematodes por gramo (h.p.g.) y el efecto ovicida, a través de los coprocultivos. En los días + 15 y + 16, los animales fueron necropsiados para determinar la eficacia antihelmíntica de las diferentes dosis de RBZ aplicadas. Los niveles de h.p.g. fueron reducidos completamente (100%) hacia el día 3 de los tratamientos y el efecto ovicida se observó a las 12 h para todos los tratamientos. Los cultivos de materia fecal del grupo 5 demostraron que Cooperia spp., Trichostrongylus spp., Ostertagia spp., Haemonchus spp. y Oesophagostomum spp. fueron los nematodes predominantes en la infección parasitaria. La eficacia antihelmíntica del RBZ varió entre 96.5 y 100 % (P< 0.01) contra los estadíos adultos e inmaduros de los parásitos localizados en el abomaso, intestino delgado e intestino grueso: Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Cooperia oncophora y Oesophagostomum radiatum, para cualquiera de las dosis aplicadas a los animales. La eficacia contra larvas inhibidas (L4I) de Ostertagia ostertagi fue de 95.7 % (P< 0.01) a la dosis de 7.5 mg/k.p.v. Se concluye que el RBZ aplicado por vía subcutánea fue altamente efectivo contra los nematodes internos que afectan a los bovinos en pastoreo de la Pampa Húmeda en Argentina. El efecto ovicida observado a las pocas horas del tratamiento puede colaborar en el control de la enfermedad

Eficacia del ricobendazole-via subcutanéa- contra los nematodes gastrointestinales del bovino

Se llevó a cabo una prueba controlada de eficacia para determinar la actividad terapéutica del Ricobendazole -RBZ- (sulfóxido de Albendazole) aplicado por vía parenteral a diferentes dosis, en bovinos infectados naturalmente con parásitos gastrointestinales. En un establecimiento ganadero de la zona de Tandil, se seleccionaron e identificaron 30 novillitos de 12-15 meses de edad. Los animales fueron trasladados a corrales con piso de cemento (día 0) donde se alimentaron con heno de alfalfa libre de larvas de nematodes trichostrongylideos y agua corriente ad-libitum. En el día + 7, se formaron 5 grupos comparables de 6 animales cada uno; los novillitos de los grupos 1 al 4, fueron tratados por vía subcutánea con RBZ (formulación al 15%) a las dosis de 3.5, 3.75, 5.0 y 7.5 mg/kg de peso vivo, respectivamente. El grupo 5 fue el control no tratado. Se extrajeron muestras de materia fecal de todos los animales a diferentes intervalos post-tratamiento, para determinar el número de huevos de nematodes por gramo (h.p.g.) y el efecto ovicida, a través de los coprocultivos. En los días + 15 y + 16, los animales fueron necropsiados para determinar la eficacia antihelmíntica de las diferentes dosis de RBZ aplicadas. Los niveles de h.p.g. fueron reducidos completamente (100%) hacia el día 3 de los tratamientos y el efecto ovicida se observó a las 12 h para todos los tratamientos. Los cultivos de materia fecal del grupo 5 demostraron que Cooperia spp., Trichostrongylus spp., Ostertagia spp., Haemonchus spp. y Oesophagostomum spp. fueron los nematodes predominantes en la infección parasitaria. La eficacia antihelmíntica del RBZ varió entre 96.5 y 100 % (P< 0.01) contra los estadíos adultos e inmaduros de los parásitos localizados en el abomaso, intestino delgado e intestino grueso: Haemonchus placei, Ostertagia ostertagi, Trichostrongylus axei, Cooperia oncophora y Oesophagostomum radiatum, para cualquiera de las dosis aplicadas a los animales. La eficacia contra larvas inhibidas (L4I) de Ostertagia ostertagi fue de 95.7 % (P< 0.01) a la dosis de 7.5 mg/k.p.v. Se concluye que el RBZ aplicado por vía subcutánea fue altamente efectivo contra los nematodes internos que afectan a los bovinos en pastoreo de la Pampa Húmeda en Argentina. El efecto ovicida observado a las pocas horas del tratamiento puede colaborar en el control de la enfermedad

Effet de différentes méthodes d'échantillonnage sur les valeurs d'indices biotiques de la qualité de l'eau du cours inférieur d'un fleuve méditerranéen : le Tibre

Cette note se propose de confronter l'aptitude de deux indices biotiques à la détermination de la qualité de l'environnement du cours inférieur du Tibre et d'évaluer si et comment la méthode d'échantillonnage peut influencer la valeur finale de ces indices. Une des méthodes met en œuvre un filet troubleau utilisé pendant 3', tandis que les autres sont basées sur l'utilisation de substrats artificiels immergés à chaque station pendant toute la durée de l'étude. Nos résultats semblent démontrer une sensibilité différente pour les deux indices biotiques dans la description des changements de la qualité de l'environnement et une influence significative de la technique d'échantillonnage sur la détermination de la qualité des eaux obtenue avec les indices biotiques