Treatment of Bovine Leptospirosis with Enrofloxacin HCl 2H2O (Enro-C): A Clinical Trial.

Pharmacokinetics/pharmacodynamics ratios of enrofloxacin HCl-2H2O (enro-C) in cows to treat bovine leptospirosis prompted this clinical trial in the highlands (HL) and the tropics (TL) in Mexico. In the HL, 111 Holstein-Friesian cows were included and 38 F1 Zebu-Holstein/Friesians in the TL. Affected cows were randomly divided into two treatment groups, both in the HL and TL. PCR and MAT tests were performed before and after treatment. Treatments in both groups were administered for 5 d with either IM injections of enro-C or streptomycin/penicillin-G. Reproductive performance data were gathered for 90 d. The cows treated with enro-C became PCR negative: 87.5% and 78.94% on day 5, 92.85% and 94.73% on day 28 (in the HL and TL, respectively). For streptomycin/penicillin-G, the same values were 65.45% and 70.90% on day 5, and 73.68% twice on day 28 in the HL and TL, respectively. In both groups and geographical settings, the MAT titers dropped on day 28 but remained above reference values usually considered negative. The gestation rates were: 86.53% and 79.06% and 88.88% and 87.5% for the HL and TL, either with enro-C or streptomycin/penicillin-G, respectively. This is the first report of successful treatment with a fluoroquinolone derivative in treating bovine leptospirosis with a high bacteriological cure rate.

Tilmicosin modulates the innate immune response and preserves casein production in bovine mammary alveolar cells during Staphylococcus aureus infection.

Tilmicosin is an antimicrobial agent used to treat intramammary infections against Staphylococcus aureus and has clinical anti-inflammatory effects. However, the mechanism by which it modulates the inflammatory process in the mammary gland is unknown. We evaluated the effect of tilmicosin treatment on the modulation of the mammary innate immune response after S. aureus infection and its effect on casein production in mammary epithelial cells. To achieve this goal, we used immortalized mammary epithelial cells (MAC-T), pretreated for 12 h or treated with tilmicosin after infection with S. aureus (ATCC 27543). Our data showed that tilmicosin decreases intracellular infection (P < 0.01) and had a protective effect on MAC-T reducing apoptosis after infection by 80% (P < 0.01). Furthermore, tilmicosin reduced reactive oxygen species (ROS) (P < 0.01), IL-1ß (P < 0.01), IL-6 (P < 0.01), and TNF-α (P < 0.05) production. In an attempt to investigate the signaling pathways involved in the immunomodulatory effect of tilmicosin, mitogen-activated protein kinase (MAPK) phosphorylation was measured by fluorescent-activated cell sorting. Pretreatment with tilmicosin increased ERK1/2 (P < 0.05) but decreased P38 phosphorylation (P < 0.01). In addition, the anti-inflammatory effect of tilmicosin helped to preserve casein synthesis in mammary epithelial cells (P < 0.01). This result indicates that tilmicosin could be an effective modulator inflammation in the mammary gland. Through regulation of MAPK phosphorylation, ROS production and pro-inflammatory cytokine secretion tilmicosin can provide protection from cellular damage due to S. aureus infection and help to maintain normal physiological functions of the bovine mammary epithelial cell.

Mycobacterium tuberculosis Catalase Inhibits the Formation of Mast Cell Extracellular Traps.

Tuberculosis is one of the leading causes of human morbidity and mortality. Mycobacterium tuberculosis (Mtb) employs different strategies to evade and counterattack immune responses persisting for years. Mast cells are crucial during innate immune responses and help clear infections via inflammation or by direct antibacterial activity through extracellular traps (MCETs). Whether Mtb induce MCETs production is unknown. In this study, we report that viable Mtb did not induce DNA release by mast cells, but heat-killed Mtb (HK-Mtb) did. DNA released by mast cells after stimulation with HK-Mtb was complexed with histone and tryptase. MCETs induced with PMA and HK-Mtb were unable to kill live Mtb bacilli. Mast cells stimulated with HK-Mtb induced hydrogen peroxide production, whereas cells stimulated with viable Mtb did not. Moreover, MCETs induction by HK-Mtb was dependent of NADPH oxidase activity, because its blockade resulted in a diminished DNA release by mast cells. Interestingly, catalase-deficient Mtb induced a significant production of hydrogen peroxide and DNA release by mast cells, indicating that catalase produced by Mtb prevents MCETs release by degrading hydrogen peroxide. Our findings show a new strategy employed by Mtb to overcome the immune response through inhibiting MCETs formation, which could be relevant during early stages of infection.

Efectividad clínica de mallas de alginato de sodio para el control de la diseminación de infección con Escherichia coli y Staphylococcus epidermidis en heridas cavitadas con cierre primario en ratas / Clinical efficacy of sodium alginate meshes for the control of infectious dissemination by Escherichia coli and Staphylococcus epidermidis in cavitated wounds with primary healing

The potential wound healing ability of sodium alginate (SA) meshes was determined in cavitated rat wounds infected either with Escherichia coli or Staphylococcus epidermidis. Wound progress was evaluated macroscopically and histopathologically to assess dissemination of the induced infection through evaluation of granuloma formation and adjacent tissue irritation. Five groups of 24 female Wistar rats weighing 280 ± 34 g were formed as follows: control group with SA mesh without inoculum, control group with Escherichia coli inoculum without SA mesh, control group with Staphylococcus epidermidis inoculum without mesh, group with SA mesh + Escherichia coli inoculum and group with SA mesh + Staphylococcus epidermidis inoculum. Abdominal flank incisions were performed under anaesthesia and groups were formed. Both macroscopic and histopathological follow up were carried out and results indicated that the presence of SA meshes avoids or greatly diminishes bacteria dissemination and adjacent tissue irritation. This reaction occurs even in the presence of Escherichia coli or Staphylococcus epidermidis. In the control groups with SA mesh without inoculum and in the groups with Escherichia coli inoculum without SA mesh, and control group with Staphylococcus epidermis inoculum without mesh and group with SA mesh + Escherichia coli inoculum re-epithelialization and wound healing aspect were better than in groups inoculated with Staphylococcus epidermidis, the general odd ratios showed that the dissemination risk was 58 times greater in treatment with SA mesh and E. coli as infectious agent (IC 95% 6.2-210). These results indicate that SA mesh is capable of providing adequate conditions to allow granulation of cavitated wounds, without irritation to adjacent tissues and avoiding dissemination of the infection by E. coli and Staphylococcus epidermidis in rats. However, presence of granuloma can be a healing or esthetic disadvantage, as observed in control group with SA mesh without inoculum.

Se determinó el efecto potencial de cicatrización de mallas de alginato de sodio (AS) en heridas cavitadas infectadas con Escherichia coli y Staphylococcus epidermidis, y se evaluó histopatológica y macroscópicamente la diseminación del proceso infeccioso, formación de granuloma e irritación de los tejidos adyacentes. Se formaron 5 grupos de 24 ratas Wistar hembras de 280 ± 34 g de la siguiente manera: grupo testigo con malla de AS sin inóculo; testigo con inóculo de Escherichia coli sin malla; otro grupo testigo con inóculo de Staphylococcus epidermidis, sin malla; grupo con malla de AS + inóculo de Escherichia coli; grupo con malla de AS + inóculo de Staphylococcus epidermidis. Bajo anestesia se realizaron las incisiones en los flancos absominales y se formaron los grupos. Se realizó un seguimiento macroscópico e histopatológico de la zona afectada y se encontró que la presencia de mallas de AS evita o disminuye drásticamente, tanto la diseminación de la infección a tejidos adyacentes como su irritación. Ello ocurre aun en presencia de Escherichia coli o de Staphylococcus epidermidis. En los grupos testigo con malla de AS sin inóculo, testigo con inóculo de Escherichia coli sin malla, otro grupo testigo con inóculo de Staphylococcus epidermidis sin malla y el grupo con malla de AS + inóculo de Escherichia coli, la reepitelización y la reducción en la herida fueron superiores a los grupos que fueron inoculados con Staphylococcus epidermidis. Los odd ratios generales mostraron que el riesgo de diseminación fue 58 veces menor con el uso de malla de AS y E. coli como organismo infectante (IC 95% 6.2-210). Los resultados encontrados indican que la malla de AS es capaz de proporcionar condiciones adecuadas para la formación de tejido de granulación, sin irritación en los tejidos adyacentes y evitando la diseminación de la infección en heridas cavitadas y contaminadas por E. coli y por Staphylococcus epidermidis en ratas. Sin embargo, la presencia de granuloma puede significar una desventaja cicatrizal o estética, como se observó en el grupo testigo con malla de AS sin inóculo.

[Experimental bacterial contamination of bile and liver in mongrel dogs: an alternative treatment with cephalone, a hybrid of cephalosporine fluoroquinolone]. / Contaminación bacteriana experimental de bilis e hígado en perros criollos. Tratamiento alternativo con (cefalona), un híbrido de cefalosporina y fluoroquinolona.

OBJECTIVES: A longitudinal, randomized, single blind study was done to evaluate the efficacy of an antibacterial hybrid molecule (beta-lactamic-fluoroquinolone) named cephalone after biliary-enteric-bypass (BEB). MATERIAL AND METHODS: Four groups of mongrel dogs were operated on three consecutive periods. Cultures of bile and liver were obtained and assessed, followed by obliteration of common bile duct and BEB to groups A, B and C. Group D served as a control. Ten days later the group A received conventional treatment based on ampicillin/gentamicin and groups B and C, cephalone in two different concentration schemes during 10 consecutive days. Further samples were processed for bacteria and additional liver biopsies were obtained for histopathological analysis. RESULTS: All three treatments reverted bacterial contamination in the liver and most of the bile samples were negative or showed a significant decrease in the number of colony forming units (p = 0.002). Histopathological analysis proved no lesions. CONCLUSIONS: Comparison of efficacy among antibacterial treatments revealed undistinguishable efficacy in this short-term assessment of bacterial contamination after BEB in dogs. The use of cephalone could be considered as a viable treatment or prophylaxis in bacterial infections occurring after BEB. Further studies are needed to assess long-term impact of the cephalone in this setting.

Genotoxicidad de la furazolidona y la forma libre de su metabolito 3-amino-2-oxazolidona, mediante la prueba de micronúcleos en linfocitos humanos / Genotoxicity of furazolidone and the free form of the metabolite: 3-amino-2-oxazolidone, based on human lymphocytes micronucleus test

The aim of this trial was to assess the genotoxic effects of the main metabolite of furazolidone (3-amino-2-oxazolidone-AOZ), which is usually protein-bound (PB-AOZ). Because PB-AOZ is not available as a tool for biomedical research, the synthetic free form of AOZ (F-AOZ) was used to challenge human lymphocytes in the genotoxic quantification test of induced micronuclei on human lymphocytes. The level of exposure of lymphocytes to F-AOZ was calculated by determining the residual quantity of the Bg-AOZ (from liver and muscle) by HPLC, derived from broilers fed furazolidone included at 0.11% and 0.22% in feed, and allowing a seven day withdrawal time. Then F-AOZ and furazolidone as positive genotoxic group were added at various concentrations higher than the residual level indication to the in vitro preparations diluted both in dimethyl sulfoxide (DMSO) as follows: for furazolidone (FZD) groups of 10 μM (225 mg/g), 1.0 μM (225 mg/g), 0.1 μM (22.5 mg/g), and 0.001 μM (0.225 mg/g), as well as a negative control group and positive control with DMSO 10-3 M (0.130 mg/g) and arsenic 10-3 M (0.747 mg/g), respectively; for F-AOZ 0.01 μM (1.020 mg/g); 0.102 μM; 0.0005 μM (0.051 mg/g); and 0.0001 μM (0.001 mg/g) were tested, having the same controls groups as for FZD. Results show that furazolidone from 10.0 μM through 0.1 μM possesses a well defined genotoxic effect. Association frequency, relative risk and ANOVA test showed a statistically significant effect vs the negative control group (P = 0.001; P = 0.03 and P = 0.04, respectively). For F-AOZ the same statistical tests showed that only 0.01 μM was capable of inducing a genotoxic effect. These results suggest that furazolidone as parent compound is potentially capable of inducing genotoxicity in consumers. In contrast, only the highest concentration of F-AOZ was shown to induce a similar effect. Yet this concentration is well above the expected residual concentration after a 7-day withdrawal period. These results do not support the use of furazolidone in humans as it is now accepted and reveals that F-AOZ is a considerably lower hazard to public health than the parent compound. Yet, lack of evidence of the effect of bound-AOZ in a similar setting precludes further comparisons, but these results suggest that it seems unlikely that PB-AOZ is a real risk to public health. Further studies are warranted.

El objetivo de este estudio fue evaluar los efectos genotóxicos del metabolito principal de la furazolidona 3-amino-2-oxazolidona (AOZ) que usualmente se encuentra unido a la proteína (AOZ-UP). Debido a que no se dispone para investigación biomédica de AOZ-UP, se utilizó la forma libre de AOZ (AOZ-L) como desafío genotóxico por medio de la técnica de cuantificación de micronúcleos inducidos en linfocitos humanos. El nivel de exposición de linfocitos a AOZ-libre fue establecido con base en la determinación por cromatografía líquida de alta resolución (CLAR) de los residuos de AOZ-UP encontrados en músculo e hígado de pollos, producidos en forma comercial, expuestos a furazolidona (FZD) por medio del alimento a dosis de 0.11% y 0.22%, permitiendo un tiempo de retiro de 7 días. Se conformaron dos grupos furazolidona (FZD) con las siguientes concentraciones de 10 μM (225 mg/g), 1 μM (225 mg/g), 0.1 μM (22.5 mg/g), y 0.001 μM (0.225 mg/g), así como el grupo testigo negativo sulfoxido de dimetilo (DMSO) 10-3 μM (0.130 mg/g) y el testigo positivo arsénico 10-3 μM (0.747 mg/g). Para AOZ-libre las concentraciones fueron 0.01 μM (1.020 mg/g); 0.001 μM (0.102 mg/g); 0.0005 μM (0.051 mg/g); y 0.0001 μM (0.001 mg/g) con los mismos grupos testigo. Los resultados muestran que la furazolidona a concentraciones de 1.0 μM y 0.1 μM posee un efecto genotóxico bien definido. El grado de asociación se calculó por medio del riesgo relativo y prueba de ANDEVA, que mostró el efecto estadísticamente significativo al compararlo con el grupo testigo negativo (P = 0.001; P = 0.03 y P = 0.04, respectivamente). Para AOZ-L las mismas pruebas estadísticas mostraron que sólo la concentración 0.01 μM era capaz de inducir un efecto genotóxico. Estos resultados sugieren que la furazolidona como sal pura es potencialmente capaz de inducir efectos genotóxicos en humanos, en los que no se apoya su uso. En contraste, sólo la concentración más alta de AOZ-L mostró un efecto similar, pero dicha concentración es mayor que la encontrada como residual a los siete días de retiro y puede considerársele como un peligro mucho menor para la salud pública que el compuesto progenitor. Dada la falta de evidencia científica del efecto genotóxico del AOZ-UP no se pueden realizar comparaciones adicionales con lo obtenido aquí para AOZ-L, pero parecería poco probable calificar a los residuos de AOZ-UP como peligros reales para la salud pública, por lo que se requieren pruebas adicionales.

Vigilancia sanitaria en el uso ilícito del clenbuterol y su coordinación intersectorial en dos entidades de México / Sanitary surveillance on illegal use of clenbuterol and its intersectoral coordination in two states of Mexico

The illegal use of clenbuterol in feeding of cattle has caused outbreaks of food poisoning in humans that consume beef and internal organs. Since 2007, with the modification of the Ley Federal de Sanidad Animal, the use of clenbuterol as growth promoter is penalized and coordinated actions are announced between the Secretaria de Salud (SSA) and the Secretaria de Agricultura, Ganaderia, Desarrollo Rural, Pesca y Alimentacion (Sagarpa) on concurrent issues. This study analyzed the implementation of the procedures in the public health sector, as well as the coordinated activities between SSA and Sagarpa in Queretaro and Jalisco states in Mexico. Results indicate that a higher degree of collaboration between these two institutions is required in the exchange of information from Sagarpa to SSA derived from penal procedures, as well as in the identification of improvement action procedures, thus optimizing the results achieved by both institutions in concurring actions related to sanitary surveillance of clenbuterol use.

El uso ilegal del clenbuterol en la alimentación de los bovinos ha ocasionado la presentación de brotes de intoxicación a partir del consumo de carne y vísceras. A partir de la modificación en 2007 de la Ley Federal de Sanidad Animal, el uso de esta sustancia como promotora del crecimiento está tipificado como delito y a su vez, se anuncian acciones coordinadas entre la Secretaría de Salud (SSA) y la Secretaría de Agricultura, Ganadería, Desarrollo Rural, Pesca y Alimentación (Sagarpa) en asuntos concurrentes. En el presente estudio se analizaron las actividades de la SSA en concurrencia con la Sagarpa de tipo intersectorial, para la vigilancia sanitaria, tomando como estudio de caso las entidades de Querétaro y Jalisco. Los resultados indicaron que se requiere mayor colaboración por parte de la Sagarpa hacia la SSA para notificar sus resultados derivados de los procedimientos penales, así como en la colaboración para la identificación de procesos de acciones de mejora, lo cual ayudará a optimizar las iniciativas de ambas autoridades en las acciones concurrentes de la vigilancia sanitaria en el uso del clenbuterol.

Eficacia clínica del florfenicol oftálmico vs florfenicol parenteral en el tratamiento de queratoconjuntivitis infecciosa bovina / Clinical efficacy of parenteral vs ophthalmic florfenicol for the treatment of infectious bovine keratoconjunctivitis

The clinical and bacteriological efficacy, the quantity of mg and florfenicol treatment length for infectious bovine keratitis (Moraxella bovis) was assessed using either the parenteral administration of florfenicol (PF), or the ophthalmic administration of the drug in spray (OF). Sixty four cows and heifers were randomly divided into the two referred treatments. All animals were cured, however, the OF group required a mean of 378 mg/bovine and 12 days of treatment, while the PF group needed 22 800 mg/bovine (3.8 treatments per bovine) and 7.6 days. Although 100% efficacy was obtained in both groups cost-benefit ratio in the OF group is pondered.

Para el tratamiento de la queratitis infecciosa bovina (Moraxella bovis) se evaluaron la eficacia clínica y bacteriológica, la cantidad en mg utilizada y el tiempo en que se lograba la curación, utilizando florfenicol parenteral (FP) o florfenicol en aerosol oftálmico (FO). En ambos tratamientos se utilizaron 64 bovinos divididos aleatoriamente. Todos los animales curaron, pero se requirieron valores medios de 378 mg/bovino y 12 días de tratamiento para FO y 22 800 mg/bovino (3.8 tratamientos por bovino) y 7.6 días para FP. Se pondera tanto la eficacia del florfenicol en ambos grupos, como la posibilidad de una drástica reducción en los costos de tratamiento en el grupo tratado con FO.

Epilepsia en perros / Canine epilepsy

Idiopathic epilepsy (IE) and other convulsive disorders represent at least 14% of neurological consultations in veterinary medicine. In spite of this, there is a gap in the information usually handled by the small animal clinician, because the pathophysiological aspects of this disease are still not completely understood. Since there is no specific method for diagnosing IE, exclusion criteria are used to reach diagnosis. Although the electroencephalogram (EEG) can provide diagnostic elements, abnormalities in the EEG record are not always found. Pharmacologic treatment options are reduced and not void of ad verse effects. The possibility of encountering IE refractory to antiseizure pharmacological treatment is high and it has been concluded that non pharmacological treatment options should be explored through systematic clinical studies. Up to date, early diagnosis, appropriate pharmacological treatment, owners' education and a combination with non pharmacological options represent the only way to improve prognosis for dogs with IE.

La epilepsia idiopática (EI), así como otras enfermedades convulsivas representan al menos 14% de las consultas neurológicas en la medicina veterinaria. A pesar de esto último, se reconoce que existe un vacío en la información que maneja el clínico especialista en pequeñas especies porque aún no se han elucidado todos los aspectos patofisiológicos de ese padecimiento. Debido a que no existe un método diagnóstico específico, se llega a él por exclusión. Aunque el electroencefalograma (EEG) brinda algunos elementos diagnósticos no siempre se tiene la fortuna de ubicar anormalidades en el registro. Las alternativas terapéuticas farmacológicas son reducidas y no carentes de efectos adversos. Es mucha la posibilidad de encontrar EI refractaria al tratamiento farmacológico y se ha concluido que deben evaluarse las alternativas de tratamiento no farmacológico mediante estudios clínicos sistemáticos. El diagnóstico temprano, la instauración de un tratamiento farmacológico, la educación de los propietarios de animales y la combinación con terapias no farmacológicas representan a la fecha la única forma de mejorar el pronóstico de perros afectados con EI.

Administration of ciprofloxacin and capsaicin in rats to achieve higher maximal serum concentrations.

To test if capsaicin could improve the bioavailability of ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, CAS 85721-33-1, Bay q 3939) in rats, 0.01, 0.1, 0.5 and 1% capsaicin ((E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methyl-6-nonenamide, trans-8-methyl-N-vanillyl-6-nonenamide, CAS 404-86-4) dissolved in ethanol and mixed with 20 mg/kg of ciprofloxacin were orally administered to groups of 10 rats each. Control groups were dosed with capsaicin-free, ethanol-containing or ethanol-free ciprofloxacin. Reference intravenous pharmacokinetics of ciprofloxacin was also established. The results revealed that capsaicin increased ciprofloxacin bioavailability by approximately 70% in groups receiving preparations containing capsaicin at a rate of 0.01, 0.1 and 0.5%. Higher concentrations failed to further increase bioavailability. However, capsaicin appears to have little or no impact on the rate of absorption or clearance of ciprofloxacin. Considering that 0.01% or 0.1% capsaicin are unlikely to upset the gastrointestinal tract, it may be worth attempting to study if a similar effect occurs in man, and to evaluate if the addition of capsaicin can be used as a method to increase the area under the curve/minimum inhibitory concentration rate, a key variable to improve clinical efficacy of ciprofloxacin.

Effect of a cysteine protease inhibitor on Fasciola hepatica (liver fluke) fecundity, egg viability, parasite burden, and size in experimentally infected sheep.

Fasciola hepatica secretes proteolytic enzymes during liver invasion. The present study examined the effects of the cysteine protease inhibitor Ep-475 on sheep considering the following variables: serum levels of aspartate aminotransferase, L-lactate dehydrogenase, and gamma-glutamyltransferase, liver fluke fecundity, egg viability, parasite burden, and size. Twenty-four male sheep were randomly allocated in four groups of six animals each as follows: group A was infected with F. hepatica metacercariae and treated with 50 mg/kg of Ep-475, group B was infected and untreated, group C was uninfected and treated, and group D was uninfected and untreated. All animals were euthanized 10 weeks after the experimental infection. Serum activities of enzymes in infected animals were significantly lower in Ep-475-treated sheep than in untreated controls, although liver damage was produced. No significant reduction in total worm burden was observed between treated and untreated sheep. However, there was a significant difference on the average size, structure development, ova counts, and egg viability of liver flukes from these two groups. Results showed that Ep-475 reduces liver damage due to fasciolosis and induces an impairment of liver fluke growth and fecundity. These effects pinpoint liver fluke proteases as potential targets for pharmacological intervention.

The influence of butorphanol dose on characteristics of xylazine-butorphanol-propofol anesthesia in horses at altitude.

OBJECTIVE: To characterize behavioral and physiological responses to short-term, unsupplemented intravenous (IV) anesthesia in healthy horses at high altitude (2240 m), and to test the hypothesis that the dose of butorphanol modifies the response of the horse to propofol anesthesia following xylazine pre-medication. STUDY DESIGN: Randomized prospective butorphanol dose cross-over experimental design. Animals Eight healthy horses, 13 +/- 6 (mean +/- SD) years of age, and weighing 523 +/- 26 kg. METHODS: Each horse was anesthetized three times with at least 3 weeks between each anesthesia. After collecting pre-drug data, xylazine (0.5 mg kg(-1)) was given IV. Five minutes later butorphanol was given IV according to a randomized order of three doses: 0.025, 0.05 and 0.075 mg kg(-1). Five minutes later, anesthesia was induced with propofol, 2 mg kg(-1) IV. Data on heart rate (HR) and respiratory rate (f(r)), mean arterial blood pressure, P(a)O(2), P(a)CO(2) and pH(a) were collected before, during and for 60 minutes following anesthesia, and quality of induction and recovery was scored. RESULTS: The pre-drug values for the three butorphanol groups did not differ. The combined pre-drug values from the 24 studies were HR, 33 +/- 7 beats minute(-1); f(r), 11 +/- 3 breaths minute(-1); P(a)O(2), 67 +/- 7 mmHg; P(a)CO(2), 36 +/- 4 mmHg; and pH(a), 7.42 +/- 0.04. Five minutes after anesthetic induction P(a)O(2) decreased and P(a)CO(2) increased 14.5 +/- 7.7 and 5.1 +/- 4.9 mmHg, respectively, but returned to pre-drug levels within 15 minutes of anesthetic recovery. There were no significant butorphanol dose-related differences in physiological results, anesthetic induction and recovery quality scores or recovery time. CONCLUSIONS AND CLINICAL RELEVANCE: Dose of butorphanol did not markedly influence study results. Notably, low P(a)O(2) values related to geographic location of study and general anesthesia indicates a narrow margin of error for hypoxemia-related complications in anesthetized horses breathing unsupplemented air at high altitude.

Dose-response inhibition of proteolytic activity by a cysteine protease inhibitor in a murine model of fasciolosis.

Using the film in situ zymography (FIZ) technique, it has been demonstrated that N-[N-(L: -3-trans-carboxyoxirane-2-carbonyl)-L: -leucyl]-agmatine (E-64) inhibits Fasciola hepatica proteolytic activity in vivo. The aim of this study was to establish the dose-response relationship of the inhibition of proteolysis as assessed by FIZ with E-64 at different dosages in a murine model of fasciolosis. Maximum effective inhibition of proteolysis was achieved at 50 mg/kg/day (87%). Mice treated with this dose survived for a mean of 10.92 days more than untreated controls, and their ova counts and egg viability were significantly (P<0.05) lower than this latter group. These results indicate that intraperitoneal administration of E-64 not only inhibited liver proteolytic activity in a dose-dependent manner but also produced anti-fecundity and anti-embryonation effects, delaying the progression of fasciolosis. Yet, residual proteolysis may suggest that other E-64-non-sensitive enzymes are involved, or that E-64-enzyme chemical interactions are only capable of a partial agonistic-like effect.

Fasciola hepatica proteolytic activity in liver revealed by in situ zymography.

Fasciola hepatica secretes cysteine proteases that play a role in facilitating parasite migration. The aim of this study was to detect the inhibition of the proteolytic activity of F. hepatica cysteine proteases in the liver of C57BL/6 cathepsin B knockout mice (cat B-/-) and wild-type controls (cat B+/+) by intraperitoneal administration of N-[N-(L-3-trans-carboxyoxirane-2-carbonyl)-L-leucyl]-agmatine, (E-64) using the film in situ zymography (FIZ) technique and image analysis. The FIZ technique revealed that intraperitoneal administration of E-64 dramatically reduced (85%) F. hepatica proteolytic activity in the liver of experimentally infected mice with no discernable side effects. These results suggest the usefulness of the FIZ for determining in vivo activity of F. hepatica proteases, as well as their inhibition by intraperitoneal administration of E-64 in hepatic tissue of infected mice.

Drug therapy and adverse drug reactions to terbutaline in obstetric patients: a prospective cohort study in hospitalized women.

BACKGROUND: Adverse drug reactions (ADR's) could be expected more frequently in pregnant women. This study was performed in order to identify ADR's to tocolytic drugs in hospitalised pregnant women. METHODS: A prospective cohort study was performed in two General Hospitals of the Instituto Mexicano del Seguro Social (IMSS) in Mexico City. Two hundred and seven women undergoing labor, premature labor, threatened abortion or suffering any obstetric related disease were included. Drug prescription and signs and symptoms of any potential ADR were registered daily during the hospital stay. Any potential ADR to tocolytic drugs was evaluated and classified by three of the authors using the Kramer's algorithm. RESULTS: Of the 207 patients, an ADR was positively classified in 25 cases (12.1%, CI95% 8.1 to 17.5%). All ADR's were classified as minor reactions. Grouping patients with diagnosis of threatened abortion, premature labor or under labor (n= 114), 24 ADR's were related to terbutaline, accounting for a rate of 21.1 ADR's per 100 obstetric patients. Obstetric patients suffering an ADR were older than obstetric patients without any ADR. However, the former received less drugs/day x patient-1 and had a shorter hospital stay (p < 0.05) whereas the dose of terbutaline was similar between the two groups. Terbutaline inhibited uterine motility in women with and without any ADR at a similar rate, 70 and 76% respectively (x2 = 0.07; p = 0.8). CONCLUSION: Terbutaline, used as a tocolytic drug, was related to a high frequency of minor ADRs and to a high rate of effcicacy.

Inducción experimental de anestesia general en potros con la administración intravenosa de isoflurano / Experimental induction of general anesthesia in foals with an intravenous administration of isoflurane

Se realizaron dos fases para evaluar la factibilidad de la inducción a la anestesia general con la administración intravenosa de isofluorano. Para la fase I, in vitro, se utilizó sangre de equinos heparinizada, y para la fase II, in vivo, se utilizaron cinco potros. Los resultados de la fase in vitro mostraron cambios en los valores de hematócrito (HCT), glóbulos rojos (GR), glóbulos blancos (HB) y concentración de hemoglobina corpuscular media (CHCM). Sin embargo, no hubo daño importante en la integridad de las células sanguíneas, por lo que se continuó con el desarrollo de la fase in vivo, cuyos valores hemáticos antes y después de la administración de isoflurano fueron diferentes únicamente para la dosis de 0.01 mL de isoflurano/kg de peso corporal. No se vieron afectadas las respuestas de las variables fisiológicas por las diferentes dosis de isoflurano. Las variables clínicas (tiempo antes de que el animal se levante y tiempo total acostado) fueron diferentes con las dosis de 0.04 o 0.06 mL de isoflurano/kg en comparación con las dosis más bajas. Estas dosis (0.04 o 0.06 mL) mostraron un efecto de inducción de anestesia aceptable. Con base en los resultados de esta investigación piloto, la vía intravenosa para la administración de isoflurano puede convertirse en una opción para inducir anestesia, aunque se reconoce que es indispensable realizar estudios adicionales para determinar todas las recomendaciones clínicas necesarias para su uso.

Farmacocinética de la cefalona (CQMPCA)* en vacas, una nueva serie de antimicrobianos / Pharmacokinetics of a cefalone (CQMEPCA), a new group of antibacterial in cows in Mexico

Se establecieron las variables farmacocinéticas en bovinos, de una cefalona perteneciente a un nuevo grupo de antimicrobianos de diseño nacional y con patente internacional. Con este propósito se utilizaron 24 vacas Holstein divididas en cuatro grupos de seis vacas cada uno. El grupo 1 recibió una dosis de cefalona de 10 mg/kg de peso vía IV, el grupo 2 similar dosis, pero vía IM; el grupo 3 recibió dosis de 5 mg/kg vía IV; el grupo 4, dosis similar, vía IM. A todos los animales se les tomaron muestras de sangre por punción de la vena yugular a diferentes tiempos hasta las 8 h. Para el análisis de muestras se utilizó espectrometría (UV-visible) y cromatografía líquida de alta resolución (HPLC). Las relaciones de concentración plasmáticas/tiempo en los cuatro grupos se ajustaron mejor a un modelo abierto de dos compartimentos. Se detectó que la cefalona se comporta con una cinética de primer orden a las dosis utilizadas. Los datos cinéticos revelan que posee una biodisponibilidad del 84 por ciento por la vía IM (grupos 2 y 4), una concentración plasmática pico (Cpmax) de 1.6 µg/ml a las 2.6 h, con un volumen aparente de distribución (Vd área) de 2.86 L/kg a 10 mg/kg y una vida media b de 3.58 h. Con base en estos resultados, se concluye que las cefalonas tienen características muy similares a las cefalosporinas de tercera generación; esto es, elevada penetración tisular, aunque una eliminación lenta, lo que sugiere, junto con su amplio espectro y potencia antibacteriana in vitro, una excelente eficacia clínica.

Reacciones adversas de los fármacos en los equinos / Adverse drug reactions in horses. A review

El conocimiento de las reacciones adversas a los fármacos (RAF), identificadas recientemente o ya conocidas de antemano, limita necesariamente la ocurrencia de iatrogenias y facilita la pronta recuperación de los pacientes equinos. Las RAF pueden ocurrir en cualquier momento y bajo una gran variedad de situaciones clínicas. Sin embargo, si los clínicos mantienen un programa de actualización en este tema en particular e identifican los mecanismos de acción que propiciaron una RAF, podrán administrar los fármacos con mayor certeza y margen de seguridad. Asimismo, los clínicos predecirán la presentación de algunas RAF y sugerirán el uso de un fármaco alternativo. Los objetivos de este estudio retrospectivo fueron la actualización del conocimiento sobre las RAF, identificación del modus operandi, incidencia, magnitud del daño que se pueda generar y, cuando es posible, el tratamiento adecuado. Se espera que de esta revisión se beneficien tanto los clínicos como sus pacientes equinos, pero adicionalmente se pretende favorecer el informe de hallazgos de RAF, con el fin de hacer cada vez más completo el conocimiento farmacológico de los medicamentos usados en la clínica de caballos.

Farmacocinética y eficacia clínica del tianfenicol en pollo de engorda / Pharmacokinetic and clinical efficacy of thiamphenicol in poultry

Se determinaron las variables farmacocinéticas y la eficacia clínica del tianfenicol (TF) en pollo de engorda, para lo cual se utilizaron 60 pollos Arbor Acress de 500 g de peso corporal, divididos en tres grupos: Grupo 1, al que se le administró una dosis bolo única de 20 mg/kg de TF vía intravenosa, para obtener muestras sanguíneas a diferentes tiempos, y determinar la concentración sérica del TF por el método microbiológico de Bennet. Al segundo grupo se le administró TF en el alimento (20 mg/kg), y el tercer grupo recibió TF en el agua de bebida a razón de 400 ppm (20mg/kg). En la fase clínica, se utilizaron brotes clínicos de la enfermedad crónica respiratoria complicada por Escherichia coli y Mycoplasma en tres casetas de 49 000 pollos cada una, de tres semanas de edad, a los que se trató con TF en el agua de bebida de manera comparativa con otros antibacterianos; se estimó la ganancia de peso, conversión alimentaria y análisis de supervivencia. Los resultados revelaron que el TF posee un excelente volumen de distribución 2.8 1/kg, con una Cpmax de 28.8 m g/mL en el grupo medicado en el agua de bebida, y de 9.7 m g/mL el del alimento. En relación con su eficacia, ésta fue favorable al TF, sin haber diferencias significativas en las variables productivas respecto de los otros antibacterianos; por lo que se postula al TF como una excelente alternativa para la avicultura nacional.

Problemática del uso de enrofloxacina en la avicultura en México / The use of enrofloxacin in poultry medicine in Mexico an overview

Hace más de dos décadas se introdujo a México y a gran parte de Latinoamérica la enrofloxacina, un derivado fluorínico, considerado el antibacteriano más potente descubierto a la fecha en medicina veterinaria. Su uso, inicialmente a dosis de 5 mg/kg/día de una presentación al 5 por ciento y más recientemente a dosis de 10 mg/kg/día de una presentación al 10 por ciento, sugiere el inicio de la aparición de resistencias bacterianas y de reducción de su eficacia clínica. Sin embargo, la proliferación de presentaciones similares de dudosa calidad, así como el uso clínico descuidado, en campo, de este antibacteriano puede contribuir, aún más que las resistencias bacterianas, a la disminución de la eficacia percibida (no demostrada) por el clínico. En este artículo se presenta un punto de vista sobre el uso y abuso de uno de los medicamentos de más valor en la historia de la medicina veterinaria, en particular para la industria avícola, la enrofloxacina. El principal objetivo este trabajo es revisar aspectos farmacológicos básicos de la enrofloxacina y orienta al clínico para que haga buen uso del medicamento, al tiempo que se compara el estado actual del uso de este antibacteriano en otras partes del mundo.