W A A V P guideline for evaluating the efficacy of anticoccidials in mammals (pigs, dogs, cattle, sheep).

This guideline is intended as an aid in the design, implementation and interpretation of studies for the assessment of drug efficacy against Eimeria in cattle and sheep, Cystoisospora in pigs and dogs, and Cryptosporidium in cattle. It deals with the most important aspects of how to conduct both experimental and field studies for dose determination, dose confirmation and assessment of field effectiveness. Also, guidance on the selection of animals, diagnostic techniques, statistical evaluation and methods for the preparation, maintenance and use of parasites is provided. The specific management conditions that may influence the course of natural infections and consequently determine treatment schemes are mentioned and suggestions for best practice in sampling and evaluation of data prior to conducting of efficacy studies are given. The guideline is also intended to assist investigators in carrying out specific studies, provide relevant information for registration authorities involved in the decision-making process, assist in the approval of anticoccidial drugs in the target species, and facilitate the world-wide adoption of standard procedures. Although currently not implemented, issues of drug resistance testing and alternative methods for drug testing are also discussed as future issues in drug testing against mammalian coccidia.

The 3Rs Concept: Time to Change How We Evaluate the Efficacy of Anthelmintics in Companion Animals.

Experimental infections are required by current guidelines for investigating the efficacy of anthelmintics in dogs and cats. Recently, alternatives to experimental infections and the sacrificing of research dogs and cats have been evaluated, and novel conceptual investigations and methods of examination have been explored. Several of these approaches could potentially be used in efficacy studies for anthelmintics in dogs and cats. Here, we provide food for thought towards using new tools for evaluating the efficacy of anthelmintics in companion animals, for promoting the value of field trials, and for updating the existing guidelines for the efficacy testing of anthelmintics in dogs and cats.

Efficacy of closantel against ivermectin- and fenbendazole-resistant Haemonchus sp. in sheep in Ontario, Canada.

In Ontario, Canada, widespread resistance to ivermectin and fenbendazole, the only readily available ovine anthelmintics, has been documented, primarily in Haemonchus sp. In other parts of the world, closantel has been used to control such infections; however, the drug was not currently licensed for use in Canada and the USA. A randomized controlled trial was conducted on six client-owned farms in Ontario in 2013 and 2014 to determine the efficacy of closantel (Flukiver® 5% Oral Suspension, Elanco Animal Health, 10mg/kg bodyweight) against ivermectin- and fenbendazole-resistant Haemonchus sp. infections in periparturient ewes and grazing lambs. Three farms were randomly assigned to treat all ewes, and three farms were randomly assigned to selectively treat individual ewes at lambing, using predetermined criteria. Fecal samples were collected from a minimum of 15 randomly selected ewes and 13 lambs per group on each farm at the time of treatment and approximately 14days later. Trichostrongyle-type fecal egg counts (FEC) were performed using a modified McMaster technique with a lower detection limit of 8.3 eggs per gram of feces (epg). Haemonchus-specific FECs were determined by multiplying FECs by the proportion of Haemonchus sp. identified from coproculture for each farm; Haemonchus-specific FEC reductions were calculated for each farm. Twenty grazing lambs had FECs conducted monthly, and when mean monthly FECs surpassed 200 epg, all lambs were randomly allocated to either closantel, positive control (ivermectin, fenbendazole, or levamisole) or negative control groups. Pre-treatment Haemonchus-specific mean FECs ranged from 27 to 3359 epg in ewes and 0-5698 epg in lambs. Efficacy of closantel against Haemonchus sp. ranged from 99% (95% CI: 97%-99%) to 100% in recently lambed ewes on all farms in both years (total n=274 ewes), and from 99% (95% CI: 98%-99%) to 100% in grazing lambs in both years on all but one farm (total n=171 lambs). On the latter farm, a whole flock treated farm, closantel efficacy in grazing lambs was 84% (95%CI: 81%-88%) in the first year, but 100% in the second year. Levamisole was effective against overall GIN in lambs on only two farms. Ivermectin and fenbendazole resistance continued to be present, particularly in Haemonchus sp. Closantel had excellent efficacy against Haemonchus sp. over the two year study period, regardless of treatment group, and therefore should be considered one viable component of sustainable integrated parasite control programs for farms with documented anthelmintic resistance and problems with haemonchosis.

A quantitative evaluation of the extent of fluralaner uptake by ticks (Ixodes ricinus, Ixodes scapularis) in fluralaner (Bravecto) treated vs. untreated dogs using the parameters tick weight and coxal index.

BACKGROUND: Fluralaner is a new antiparasitic drug that was recently introduced as Bravecto chewable tablets for the treatment of tick and flea infestations in dogs. Most marketed tick products exert their effect via topical application and contact exposure to the parasite. In contrast, Bravecto delivers its acaricidal activity through systemic exposure. Tick exposure to fluralaner occurs after attachment to orally treated dogs, which induces a tick-killing effect within 12 h. The fast onset of killing lasts over the entire treatment interval (12 weeks) and suggests that only marginal uptake by ticks is required to induce efficacy. Three laboratory studies were conducted to quantify the extent of uptake by comparison of ticks' weight and coxal index obtained from Bravecto-treated and negative-control dogs. METHODS: Three studies were conducted using experimental tick infestation with either Ixodes ricinus or Ixodes scapularis after oral administration of fluralaner to dogs. All studies included a treated (Bravecto chewable tablets, MSD Animal Health) and a negative control group. Each study had a similar design for assessing vitality and weighing of ticks collected from dogs of both groups. Additionally, in one study the coxal index (I. ricinus) was calculated as a ratio of tick's ventral coxal gap and dorsal width of scutum. Tick weight data and coxal indices from Bravecto-treated and negative-control groups were compared via statistical analysis. RESULTS: Ticks collected from Bravecto-treated dogs weighed significantly less (p ≤ 0.0108) than ticks collected from negative-control dogs, and their coxal index was also significantly lower (p < 0.0001). The difference in tick weights was demonstrated irrespective of the tick species investigated (I. ricinus, I. scapularis). At some assessments the mean tick weights of Bravecto-treated dogs were significantly lower than those of unfed pre-infestation (baseline) ticks. The demonstrated tick-killing efficacy was in the range of 94.6 - 100%. CONCLUSIONS: Tick weights and coxal indices confirm that a minimal uptake results in a sufficient exposure of ticks to fluralaner (Bravecto) and consequently in a potent acaricidal effect.

Sustained speed of kill and repellency of a novel combination of fipronil and permethrin against Ctenocephalides canis flea infestations in dogs.

BACKGROUND: Ctenocephalides canis is a major flea species in dogs in several European countries. The new topical combination of fipronil and permethrin (Frontline Tri-Act/Frontect, Merial) has been developed to control fleas, ticks, mosquitoes, sandflies and biting flies on dogs. Considering the repellent and insecticidal effects of permethrin and the insecticidal effect of fipronil, the efficacy of the combination against fleas including C. canis was expected to be rapid. The study was conducted to measure the 1-hour, 6-hour and 24-hour efficacy, as well as the repellent activity, of the fipronil-permethrin combination on treated versus untreated dogs. METHODS: 12 Beagle dogs were randomly allocated to one of two groups based on pre-treatment live flea counts. Dogs in Group 1 remained untreated whereas dogs in Group 2 were treated once on Day 0. Each dog was infested with 100 unfed adult C. canis on Days 2, 7, 14, 21 and 28. Dogs were combed for fleas 1 and 6 h after each infestation. Following this examination, fleas remaining on the liner at the bottom of each cage were collected and counted. All live fleas were placed back on each dog after the 1- and 6-hour counts. A comb-count was performed at 24 h post infestation on all dogs. RESULTS: Treated dogs had significantly (p ≤ 0.01) lower flea counts than untreated dogs at every time point. The percent efficacy was ≥99.1% at 6 and 24 h after each weekly challenge up to the month. The 1-hour counts also showed good efficacy of 96.5%, 98.9%, 92.0%, 70.2% and 55.7% on Days 2, 7, 14, 21 and 28, respectively. The repellent efficacy, assessed on the liners at 1 h, was 86.5%, 94.9%, 79.5%, 58.4% and 43.9% on Days 2, 7, 14, 21 and 28, respectively. CONCLUSIONS: This study demonstrates the beneficial effect of the fipronil and permethrin combination against C. canis, providing both a repellent and insecticidal effect as early as 1 h post infestation, and >99.1% efficacy calculated at 6 h during a month.

Acaricidal efficacy of a new combination of fipronil and permethrin against Ixodes ricinus and Rhipicephalus sanguineus ticks.

BACKGROUND: Two blinded, controlled laboratory studies were conducted to assess the acaricidal efficacy of a new combination of fipronil and permethrin (Frontline Tri-Act/Frontect) against two tick species. Study A evaluated the efficacy of the product against both Ixodes ricinus and Rhipicephalus sanguineus and Study B evaluated the efficacy against R. sanguineus only. METHODS: 16 (Study A) and 12 (Study B) healthy adult dogs were allocated to two groups in each study. Dogs in Group 1 served as untreated controls. Dogs in Group 2 were treated with a new topical spot-on formulation containing 6.76% (w/v) fipronil + 50.48% (w/v) permethrin once on Day 0. Each dog of study A was infested with 50 unfed adult ticks of each species and each dog of study B was infested with 50 unfed adult Rhipicephalus sanguineus prior to treatment (Day -2 in Study A, Day -1 in Study B) and post treatment on Days 7, 14, 21 and 28. The ticks were removed and counted 48 h after treatment (Day 2) or subsequent infestations (Days 9, 16, 23 and 30). Acaricidal efficacy was defined as the percent reduction in the number of live ticks in the treated group compared to the untreated control group. RESULTS: The percent efficacy in the treated group for R. sanguineus was 100%, 100%, 100%, 100% and 96.7% in Study A, and 94.4%, 100%, 100%, 98.7% and 98.0% in Study B, for counts performed on Days 2, 9, 16, 23 and 30, respectively. For I. ricinus, in Study A, the percent efficacy of the treatment was 100%, 100%, 100%, 100% and 99.2% for counts performed on Days 2, 9, 16, 23 and 30, respectively. There was a significant difference of the geometric mean numbers of live ticks between the treated and control groups at each time point in each study (p = 0.005 for every day in Study A, and p < 0.005 for every day in Study B). CONCLUSIONS: A single topical administration of a combination of fipronil and permethrin provides excellent acaricidal efficacy against both I. ricinus and R. sanguineus for at least 4 weeks.

Intoxicação de ovinos que receberam duas aplicações de closantel, na dosagem terapêutica (7,5mg/kg), com intervalo de 28 dias / Poisoning of sheep that received two treatments of closantel in a therapeutic dose (7.5mg/kg), with an interval of 28 days

This study reports poisoning in sheep wich have received two applications of closantel in therapeutic dosage (7.5mg/kg) within a preestablished 28-day period for effectiveness formulation. A high percentage of efficiency was observed after the first and second treatment, but around 72 hours after the second administration of closantel (D30), three sheep have showed mild apathy, anorexia, diarrhea, bilateral blindness, and dilated pupils without reaction. These three animals, were observed in the following 250 days, and the bilateral blindness remained. Numerous reports of animals poisoned by closantel emphasize that overdose and/or nutritional status of the animals are key factors to occur poisoning due closantel administration. However, in this experiment the signs of poisoning (mild apathy, anorexia, diarrhea and ophthalmic disturbance), observed in the three clinically healthy sheep, occurred when they received two applications of closantel (7.5mg/kg), in a interval of 28 days, highlighting the fact of obtaining a cumulative residual effect of closantel in the animal organism, caused by two consecutive applications, may also be a predisposing factor for sheep to demonstrate irreversible signs of intoxication.

O presente estudo notifica a intoxicação de ovinos que receberam duas aplicações de closantel, na dosagem terapêutica (7,5mg/kg), com intervalo de 28 dias pré-estabelecido pela eficácia da formulação. Referente aos resultados de eficácia foi possível observar elevado percentual após o primeiro e o segundo tratamento. Cerca de 72 horas após a administração do segundo tratamento (D+30), três animais que receberam closantel demonstraram leve apatia, anorexia, diarréia e cegueira bilateral com ausência de reflexo e midríase bilateral. Estes três ovinos foram observados por cerca de 250 dias após o segundo tratamento, e a cegueira bilateral não regrediu. Os inúmeros casos de animais intoxicados por closantel descritos na literatura enfatizam que a sobredosagem e/ou qualidade nutricional dos animais, são fatores determinantes para que ocorra intoxicação destes animais pelo closantel. Entretanto, no presente trabalho, os sinais de intoxicação (leve apatia, anorexia, diarréia e a alteração oftálmica) observada nos três ovinos clinicamente sadios, ocorreram quando estes receberam duas aplicações de closantel (7,5mg/kg) com o intervalo de 28 dias, evidenciando que o possível efeito residual cumulativo de closantel no organismo animal, desencadeado por duas aplicações consecutivas, também pode ser um fator predisponente para que ovinos demonstrem sinais irreversíveis de intoxicação pelo princípio ativo em questão.

Power of treatment success definitions when the Canine Brief Pain Inventory is used to evaluate carprofen treatment for the control of pain and inflammation in dogs with osteoarthritis.

OBJECTIVE: To determine the optimal method for use of the Canine Brief Pain Inventory (CBPI) to quantitate responses of dogs with osteoarthritis to treatment with carprofen or placebo. ANIMALS: 150 dogs with osteoarthritis. PROCEDURES: Data were analyzed from 2 studies with identical protocols in which owner-completed CBPIs were used. Treatment for each dog was classified as a success or failure by comparing the pain severity score (PSS) and pain interference score (PIS) on day 0 (baseline) with those on day 14. Treatment success or failure was defined on the basis of various combinations of reduction in the 2 scores when inclusion criteria were set as a PSS and PIS ≥ 1, 2, or 3 at baseline. Statistical analyses were performed to select the definition of treatment success that had the greatest statistical power to detect differences between carprofen and placebo treatments. RESULTS: Defining treatment success as a reduction of ≥ 1 in PSS and ≥ 2 in PIS in each dog had consistently robust power. Power was 62.8% in the population that included only dogs with baseline scores ≥ 2 and 64.7% in the population that included only dogs with baseline scores ≥ 3. CONCLUSIONS AND CLINICAL RELEVANCE: The CBPI had robust statistical power to evaluate the treatment effect of carprofen in dogs with osteoarthritis when protocol success criteria were predefined as a reduction ≥ 1 in PIS and ≥ 2 in PSS. Results indicated the CBPI can be used as an outcome measure in clinical trials to evaluate new pain treatments when it is desirable to evaluate success in individual dogs rather than overall mean or median scores in a test population.

Efeitos de detomidina e xilazina intravenosa sobre as variáveis basais e respostas comportamentais em bovinos / Effects of intravenous detomidine and xilazine on basal parameters and behavioral responses in bovine

Avaliaram-se, durante 60 minutos, 10 bovinos após administração intravenosa de 0,1mg.kg-1 de xilazina ou 10μg.kg-1 de detomidina, quanto às frequências cardíaca e respiratória, movimentos ruminais, pressão arterial média, temperatura retal e respostas comportamentais como ataxia ou decúbito, ptose palpebral, estado de alerta ou sedação e redução da altura da cabeça em relação ao solo, além da presença de salivação, micção e concentração sanguínea de glicose. Observou-se que a xilazina, via intravenosa, em bovinos, ao mesmo tempo que promove sedação mais intensa e prolongada que a detomidina, induz a uma maior quantidade de efeitos indesejáveis, como salivação e decúbito, e redução das frequências cardíaca e respiratória, da pressão arterial média, da motilidade ruminal e da temperatura, sendo estas alterações mais prolongadas. Conclui-se que a detomidina pode ser utilizada com segurança em bovinos na dose de 10μg.kg-1, promovendo sedação e permanência do animal em posição quadrupedal.

Ten bovine were evaluated after intravenous injection of 0,1mg.kg-1 of xylazine or 10μg.kg-1 of detomidine during 60 minutes for heart and respiratory rate, ruminal motility, mean arterial pressure, rectal temperature and behavioral responses like ataxia or recumbency, palpebral ptoses, state of sedation or alert and head drop, besides the measurement of salivation, urination and blood glucose concentration. It was observed that intravenous xylazine in bovine promotes more intense and prolonged sedation than detomidine, and at the same time induces a larger and more prolonged quantity of unwanted side effects such as salivation, recumbency, decrease of cardiac and respiratory rate, mean arterial pressure, ruminal motility and temperature. We concluded that detomidine can be used safely in bovines at 10μg.kg-1 dose, promoting sedation with standing position.

Therapeutic effect of an anaplasmicid and anti-protozoa product againstthe blood parasites of cattle / Efecto terapéutico de un fármaco frente a los hemoparásitos del bovinoBabesia bovis, Babesia bigemina y Anaplasma marginale / Efeito terapêutico de um fármaco protoarizida e anaplasmicida frente aoshemoparasitos do bovino

In Colombia all cattle raising areas located in tropical areas of low and medium altitude are considered endemic for haemoparasites of cattle, but sometimes losses are minimized by the development of immunity and the achievementof a state of equilibrium in populations. Generally, in the field the use of effective drugs is required as a help in the control of clinical manifestations associated with the occurrence of these diseases. This study was aimed to validate the benefit of the use of an anaplasmicid and anti-protozoa product (Ganaplus ®) for the control of clinical events associated with blood parasites in cattle. The study consisted of a experimental phase based on artificialinoculation of cattle with Anaplasma marginale, Babesia bigemina and Babesia bovis; and a field phase that evaluated clinical events in animals raised in endemic areas. In both phases, blood sample collection and measurement of body temperature were conducted. Complete hemogram, hematocrit, and blood smears for parasite analysis wereperformed. Cattle of the experimental phase showed very low parasitemia, with slight changes in hematologicparameters, but the animals that demonstrated clinical acute states successfully responded to the application of the compound, restoring their hematologic parameters. The cattle of the field phase showed higher parasitemias, with clear reductions in the hematocrit and the presence of an acute clinical syndrome, which responded appropriately tothe product application. It was confirmed that the compound tested is a good medicine for the treatment of clinical disease associated with blood parasites.

En Colombia todas las zonas ganaderas localizadas en áreas de trópico bajo y trópico medio se consideran regionesenzoóticas para los hemoparásitos del ganado, pero en ocasiones las pérdidas se minimizan por el desarrollo deinmunidad y el alcance de un estado de equilibrio en las poblaciones. Generalmente, en el campo se requiere de fármacos eficaces que ayuden a controlar las manifestaciones clínicas que se asocian con la ocurrencia de estos hemoparasitismos. Esta investigación buscó validar la bondad del uso de un producto protozoaricida y anaplasmicida (Ganaplus®) para el control de episodios clínicos asociados con los hemoparásitos del ganado. El estudio constó de una fase experimental basada en inoculación artificial de bovinos, con Anaplasma marginale, Babesia bovis y Babesia bigemina; y una fase de campo que evaluó episodios clínicos en animales ubicados en zonas endémicas. En ambas fases se realizó recolección de muestras de sangre y medición de temperatura corporal. Se evaluaron cuadros hemáticos completos, hematocrito y los extendidos sanguíneos para análisis parasitológico. Los bovinos de la fase experimental presentaron parasitemias muy bajas, con leves cambios en los parámetros hematológicos, pero los animales que presentaron cuadros clínicos agudos respondieron de forma satisfactoria a la aplicación del compuesto restableciendo sus parámetros hematológicos. Los bovinos de la fase de campo presentaron parasitemias mayores, con reducciones evidentes en el hematocrito y la presencia de cuadros clínicos agudos, que respondieronadecuadamente a la aplicación del producto. Se confirmó que el compuesto evaluado es un buen medicamento parael tratamiento de cuadros clínicos asociados con enfermedad por hemoparásitos.

Na Colômbia todas as zonas da pecuária bovina em áreas do trópico baixo e trópico médio consideram-se regiõesendêmicas para os hemoparasitos do gado bovino, mas em ocasiões as perdas se minimizem pelo desenvolvimentode imunidade e o alcance de um estado de equilíbrio nas populações. Geralmente, no campo requerem-se de fármacoseficazes que controlem as manifestações clínicas que se associam com a ocorrência destes hemoparasitos. Esta pesquisa teve como objetivo validar a efetividade do uso de um produto protozoaricida e anaplasmicida (Ganaplus®)para o controle de episódios clínicos associados com os hemoparasitos bovinos. O estudo teve uma fase experimentalbaseada em inoculação artificial de bovinos com Anaplasma marginale, Babesia bigemina e Babesia bovis; euma fase de campo que avaliou episódios clínicos em animais localizados em zonas endêmicas. Nas duas fases realizou-se a colheita de amostras de sangue e a mensuração da temperatura corpórea. Avaliou-se a hematologia, hematocrito e esfregaços de sangue para análise parasitológica. Os bovinos da fase experimental apresentaramparasitemias baixas, com leves mudanças nos parâmetros hematológicos, mas os animais que apresentaramquadros clínicos agudos responderam satisfatoriamente à aplicação do produto, restabelecendo os seus parâmetroshematológicos. Os bovinos da fase de campo apresentaram parasitemias maiores, com reduções evidentes nohematocrito e a presença de quadros clínicos agudos, que responderam adequadamente à aplicação do produto.Confirmou-se que o composto avaliado é um bom medicamento para o tratamento de quadros clínicos associados com a doença por hemoparasitos.

Efficacy of imidacloprid + moxidectin and selamectin topical solutions against the KS1 Ctenocephalides felis flea strain infesting cats.

BACKGROUND: Two studies were conducted to evaluate and compare the efficacy of imidacloprid + moxidectin and selamectin topical solutions against the KS1 flea strain infesting cats. In both studies the treatment groups were comprised of non-treated controls, 6% w/v selamectin (Revolution®; Pfizer Animal Health) topical solution and 10% w/v imidacloprid + 1% w/v moxidectin (Advantage Multi® for Cats, Bayer Animal Health) topical solution. All cats were infested with 100 fleas on Days -2, 7, 14, 21, and 28. The difference in the studies was that in study #1 efficacy evaluations were conducted at 24 and 48 hours post-treatment or post-infestation, and in study #2 evaluations were conducted at 12 and 24 hours. RESULTS: In study #1 imidacloprid + moxidectin and the selamectin formulation provided 99.8% and 99.0% efficacy at 24 hours post-treatment. On day 28, the 24 hour efficacy of the selamectin formulation dropped to 87.1%, whereas the imidacloprid + moxidectin formulation provided 98.9% efficacy. At the 48 hour assessments following the 28 day infestations, efficacy of the imidacloprid + moxidectin and selamectin formulations was 96.8% and 98.3% respectively. In study # 2 the efficacy of the imidacloprid + moxidectin and selamectin formulations 12 hours after treatment was 100% and 69.4%, respectively. On day 28, efficacy of the imidacloprid + moxidectin and selamectin formulations 12 hours after infestation was 90.2% and 57.3%, respectively. In study #2 both formulations provided high levels of efficacy at the 24 hour post-infestation assessments, with selamectin and imidacloprid + moxidectin providing 95.3% and 97.5% efficacy, following infestations on day 28. CONCLUSIONS: At the 24 and 48 hour residual efficacy assessments, the imidacloprid + moxidectin and selamectin formulations were similarly highly efficacious. However, the imidacloprid + moxidectin formulation provided a significantly higher rate of flea kill against the KS1 flea strain infesting cats at every 12 hour post-infestation residual efficacy assessment. Both formulations should provide excellent flea control for an entire month on cats.

Efeito de medicamentos indicados para a prevenção da mastite bovina no período seco sobre a função fagocítica in vitro de leucócitos do leite de caprinos / Effect of dry cow therapy products on the in vitro phagocytic function of goat milk leukocytes

O uso de medicamentos antimamíticos específicos para vacas no período seco é indicado para prevenção de infecções na lactação seguinte. Não obstante, a ação das células envolvidas no período de secagem tem fundamental importância para a involução da glândula mamária e seu restabelecimento para a lactação subseqüente. A indisponibilidade de tais medicamentos para uso em cabras tem resultado na extrapolação do uso de produtos recomendados para vacas sem que se considerem as particularidades e diferenças anátomo-fisiológicas entre as espécies bovina e caprina. O presente estudo teve por objetivo avaliar a influência de cinco antimamíticos específicos para vacas secas sobre a função dos fagócitos provenientes de leite caprino. Para tal, fez-se o isolamento de células somáticas de 20 amostras de leite provenientes de 10 cabras lactantes, sem antecedentes de tratamento de mamite nos últimos 30 dias, sob condições higiênico-sanitárias de colheita e com resultados negativos ao cultivo microbiológico do leite. As células aderidas a lamínulas de vidro foram confrontadas com formulações contendo princípios ativos disponíveis no mercado como Gentamicina (M1), Cefalônio Anidro (M2), Ampicilina (M3), Cloxacilina Benzatínica (M4) e Cefapirina Benzatínica (M5). Avaliou-se, por microscopia, a fagocitose de partículas de Zymosan. As médias dos índices de fagocitose das células submetidas ao tratamento com M2 (15,12 por cento ± 16,22), M3 (6,02 por cento ± 7,96), M4 (4,54 por cento ± 5,45) e M5 (2,47 por cento ± 4,64) foram menores (p<0,001) que a média dos índices de fagocitose do grupo controle (40,67 por cento ± 19,68). A média dos índices de fagocitose das células submetidas ao tratamento com M2 foi maior (p<0,05) que as médias dos tratamentos com M3, M4 e M5 enquanto estas foram estatisticamente iguais entre si. As amostras celulares submetidas ao medicamento M1 exibiram adesão insuficiente ou ausente às lamínulas, inviabilizando a avaliação da fagocitose...

The use of specific anti-mastitis drugs is indicated in dry cow therapy to prevent infections in the following lactation. Nonetheless, cells active in the dry period are of fundamental importance for the involution of the mammary gland and its recovery for the following lactation. Since there are no specific drugs for dry goat therapy, the dry cow therapy drugs tend to be misused in goats despite of the anatomical and physiological differences apart from the particularities of the two species. The objective of the present study was to evaluate the influence of five drugs specific for dry cow therapy on the function of goat milk phagocytes. Somatic cells were isolated from 20 milk samples of 10 lactating goats that had not been treated for mastitis during the previous 30 days. Milk samples were collected properly and microbiological culture yielded negative results. Cells adherent to glass coverslips were treated with commercially available dry cow therapy drugs containing active principles such as Gentamicin (M1), Cephalonium anhydrous (M2), Ampicillin (M3), Cloxacillin benzathine (M4) and Cephapirin benzathine (M5). Phagocytosis of Zymosan particles was evaluated. Mean phagocytosis indexes of cells treated with M2 (15.12 percent ± 16.22), M3 (6.02 percent ± 7.96), M4 (4.54 percent ± 5.45) and M5 (2.47 percent ± 4.64) were lower (p<0.001) than mean phagocytosis index of the control group (40.67 percent ± 19.68). Mean phagocytosis index of cells treated with M2 was greater (p<0.05) than those treated with M3, M4 and M5, whereas means of the latter three treatments were statistically similar. M1-treated cells did not adhere adequately to the cover slips, making it impossible to evaluate phagocytosis in this group. The results obtained enable the conclusion that drugs used affected milk phagocytes negatively. However, interference on somatic cell function is not the sole factor determining an unsuccessful dry period therapy, since the efficacy...

Efeito de medicamentos indicados para a prevenção da mastite bovina no período seco sobre a função fagocítica in vitro de leucócitos do leite de caprinos / Effect of dry cow therapy products on the in vitro phagocytic function of goat milk leukocytes

O uso de medicamentos antimamíticos específicos para vacas no período seco é indicado para prevenção de infecções na lactação seguinte. Não obstante, a ação das células envolvidas no período de secagem tem fundamental importância para a involução da glândula mamária e seu restabelecimento para a lactação subseqüente. A indisponibilidade de tais medicamentos para uso em cabras tem resultado na extrapolação do uso de produtos recomendados para vacas sem que se considerem as particularidades e diferenças anátomo-fisiológicas entre as espécies bovina e caprina. O presente estudo teve por objetivo avaliar a influência de cinco antimamíticos específicos para vacas secas sobre a função dos fagócitos provenientes de leite caprino. Para tal, fez-se o isolamento de células somáticas de 20 amostras de leite provenientes de 10 cabras lactantes, sem antecedentes de tratamento de mamite nos últimos 30 dias, sob condições higiênico-sanitárias de colheita e com resultados negativos ao cultivo microbiológico do leite. As células aderidas a lamínulas de vidro foram confrontadas com formulações contendo princípios ativos disponíveis no mercado como Gentamicina (M1), Cefalônio Anidro (M2), Ampicilina (M3), Cloxacilina Benzatínica (M4) e Cefapirina Benzatínica (M5). Avaliou-se, por microscopia, a fagocitose de partículas de Zymosan. As médias dos índices de fagocitose das células submetidas ao tratamento com M2 (15,12 por cento ± 16,22), M3 (6,02 por cento ± 7,96), M4 (4,54 por cento ± 5,45) e M5 (2,47 por cento ± 4,64) foram menores (p<0,001) que a média dos índices de fagocitose do grupo controle (40,67 por cento ± 19,68). A média dos índices de fagocitose das células submetidas ao tratamento com M2 foi maior (p<0,05) que as médias dos tratamentos com M3, M4 e M5 enquanto estas foram estatisticamente iguais entre si. As amostras celulares submetidas ao medicamento M1 exibiram adesão insuficiente ou ausente às lamínulas, inviabilizando a avaliação da fagocitose ...

The use of specific anti-mastitis drugs is indicated in dry cow therapy to prevent infections in the following lactation. Nonetheless, cells active in the dry period are of fundamental importance for the involution of the mammary gland and its recovery for the following lactation. Since there are no specific drugs for dry goat therapy, the dry cow therapy drugs tend to be misused in goats despite of the anatomical and physiological differences apart from the particularities of the two species. The objective of the present study was to evaluate the influence of five drugs specific for dry cow therapy on the function of goat milk phagocytes. Somatic cells were isolated from 20 milk samples of 10 lactating goats that had not been treated for mastitis during the previous 30 days. Milk samples were collected properly and microbiological culture yielded negative results. Cells adherent to glass coverslips were treated with commercially available dry cow therapy drugs containing active principles such as Gentamicin (M1), Cephalonium anhydrous (M2), Ampicillin (M3), Cloxacillin benzathine (M4) and Cephapirin benzathine (M5). Phagocytosis of Zymosan particles was evaluated. Mean phagocytosis indexes of cells treated with M2 (15.12 percent ± 16.22), M3 (6.02 percent ± 7.96), M4 (4.54 percent ± 5.45) and M5 (2.47 percent ± 4.64) were lower (p<0.001) than mean phagocytosis index of the control group (40.67 percent ± 19.68). Mean phagocytosis index of cells treated with M2 was greater (p<0.05) than those treated with M3, M4 and M5, whereas means of the latter three treatments were statistically similar. M1-treated cells did not adhere adequately to the cover slips, making it impossible to evaluate phagocytosis in this group. The results obtained enable the conclusion that drugs used affected milk phagocytes negatively. However, interference on somatic cell function is not the sole factor determining an unsuccessful dry period therapy, since the efficacy ...

Evaluation of a xenogeneic VEGF vaccine in dogs with soft tissue sarcoma.

Active immunization against pro-angiogenic growth factors or their receptors is an emerging strategy for controlling tumor growth and angiogenesis. Previous studies in rodent tumor models have indicated that immunization against xenogeneic growth factors is more likely to induce effective anti-tumor responses than immunization against the autologous growth factor. However, the effectiveness or safety of the xenogeneic vaccination approach has not been previously assessed in a clinically relevant outbred, spontaneous tumor model. Therefore, we investigated the safety and anti-tumor and anti-angiogenic effects of a xenogeneic vascular endothelial cell growth factor (VEGF) vaccine in pet dogs with spontaneous cancer. Nine dogs with soft tissue sarcoma were immunized with a recombinant human VEGF vaccine over a 16-week period. The effects of immunization on antibodies to human and canine VEGF, circulating VEGF concentrations, tumor microvessel density (MVD), and tumor growth were assessed. The xenogeneic VEGF vaccine was well-tolerated by all dogs and resulted in induction of humoral responses against both human and canine VEGF in animals that remained in the study long enough to receive multiple immunizations. Three of five multiply immunized dogs also experienced sustained decreases in circulating plasma VEGF concentrations and two dogs had a significant decrease in tumor MVD. The overall tumor response rate was 30% for all treated dogs in the study. We conclude therefore that a xenogeneic VEGF vaccine may be a safe and effective alternative means of controlling tumor growth and angiogenesis.

Determinação de tetraciclinas em medicamentos veterinários utilizando análise por injeção em fluxo (FIA) / Determination of tetracyclines in veterinarian medicines by flow injection analysis (FIA)

Foi desenvolvido um método de análise por injeção em fluxo (FIA) com detector de fluorescência para determinação de oxitetraciclina (OTC), doxiciclina (DC) e tetraciclina (TC) em medicamentos veterinários. O sistema FIA foi otimizado com relação ao carregador (NaOH 2,5 10-3 mol L-1) e vazão (0,5 mL min-1). Os comprimentos de onda de excitação e emissão do detector foram 420 e 530 nm, respectivamente. O método foi validado mediante avaliação dos seguintes parâmetros: faixa linear (0,02 a 0,15 mg mL-1), linearidade r(OTC) 0,9975; r(DC) 0,9903; e r(TC) 0,9913; precisão intra- e inter-ensaio (RSD < 1,0 por cento e < 3,0 por cento, respectivamente), detectabilidade (120 ng), exatidão (98 a 104 por cento) e freqüência de amostragem (50 injeções h-1). Na determinação de tetraciclinas em preparações farmacêuticas, disponíveis no comércio, foi verificada variação de 90 a 104 por cento, na quantidade nominal de princípio ativo presente no medicamento

Evaluation of a single injection of a sustained-release formulation of moxidectin for prevention of experimental heartworm infection after 12 months in dogs.

OBJECTIVE: To evaluate the efficacy of a single injection of a sustained-release formulation of moxidectin in preventing heartworm (Dirofilaria immitis) infection for 12 months in dogs. ANIMALS: 14 healthy dogs. PROCEDURE: Group A (nontreated control dogs; n = 6) received sterile vehicle administered SC, and group B (treated dogs; n = 6) received a sustained-release formulation of moxidectin administered SC. All dogs were housed in a heartworm-endemic area for 11.5 months, and heartworm antigen and modified Knott tests were performed monthly. All dogs (including 2 additional control dogs [group C]) were then inoculated with infective-stage larvae (L3) of D. immitis, and 4.5 months later, all dogs were euthanatized and post-mortem examinations were performed. Adult D. immitis were counted and measured, and their age was estimated. RESULTS: All dogs in groups A and C were infected with young (4- to 4.5-month old) adult male and female D. immitis. No dogs in group B were infected with heartworms. CONCLUSIONS AND. CLINICAL RELEVANCE: The age of heartworms recovered suggests that infection was the result of experimental inoculation and not natural exposure to mosquitoes during the 11.5-month period the dogs resided in a heartworm-endemic area. A single SC injection of a sustained-release formulation of moxidectin was effective in providing protection against heartworm infection after 12 months in dogs. This formulation is a convenient method of heartworm prophylaxis that could eliminate the problem of poor owner compliance.

World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines for evaluating the efficacy of anticoccidial drugs in chickens and turkeys.

These guidelines have been written to aid in the design, implementation and interpretation of studies for the assessment of drug efficacy against Eimeria species in chickens and turkeys. The information provided deals with many aspects of how to conduct controlled studies in battery cages (dose determination), floor pens (dose confirmation), and commercial facilities (field effectiveness studies), the selection of birds, housing, feeding, preparation of medicated rations, record keeping, diagnostic techniques, and methods for the preparation, maintenance and use of parasites. These guidelines are also intended to assist investigators in conducting specific studies, provide specific information for registration authorities involved in the decision-making process, assist in the approval and registration of new anticoccidial drugs, and facilitate the world-wide adoption of standard procedures.