Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

Perdas devido à natimortalidade, mumificação fetal, abortamentos e morte embrionária são responsáveis por uma considerável queda no desempenho da indústria suinícola no Brasil e no mundo. Dentre os agentes mais freqüentemente descritos como causadores de falhas reprodutivas em suínos pode-se citar o Parvovírus suíno, Leptospira spp. O diagnóstico das causas infecciosas de mortalidade embrionária e fetal torna-se muitas vezes inviável pelo estado de autólise do material ou dificuldades inerentes às características de crescimento do vírus ou bactéria envolvido. O presente estudo teve por objetivo avaliar os resultados obtidos no período de oito anos de detecção de Parvovirus suíno e Leptospira spp. em falhas reprodutivas e discutir alguns aspectos relativos ao diagnóstico destas infecções. Foram avaliados 1901 fetos, sendo coletadas de cada animal, uma amostra de pool de órgãos e uma de conteúdo gástrico, perfazendo um total de 3642 análises. Observou-se uma freqüência de 27,6% dos fetos positivos para Parvovirus suíno, 19,8% positivos para Leptospira spp e 1,1% positivos para os dois agentes em associação. Dentre as 339 granjas avaliadas em oito Estados Brasileiros, 48,5% foram positivas para um ou ambos agentes pesquisados. Avaliou-se a freqüência de fetos positivos em casos de abortamento, natimortalidade e mumificação fetal e comparou-se a eficiência da pesquisa dos agentes em amostras de órgãos, conteúdo gástrico e em ambos. Os resultados obtidos indicam a grande importância destes agentes infecciosos nos quadros de falha reprodutiva em granjas de suínos no Brasil, apesar da ampla utilização de vacinas contra os mesmos. . / Losses due to stillbirths, mummification, embryonic death and abortions account for a considerable drop in performance of the pig industry in Brazil and the world. Among the agents most frequently described as causes of reproductive failure in pigs may be mentioned the swine parvovirus, Leptospira spp. The diagnosis of infectious causes of fetal and embryonic mortality it is often impossible for the state of autolysis of the material or the difficulties inherent growth characteristics of the virus or bacteria involved. Present study has the goal evaluate the results obtained in eight year period of Parvovirus and Leptospira spp. detection in reproductive failure and discuss some aspects related to diagnosis of these infections. A total of 1901 fetuses were examined, and from each animal a sample of different tissues and a sample of gastric contents were collected, representing 3642 analysis. A frequency of 27.6% of Parvovirus positive fetuses were observed, followed by 19.8% of Leptospira spp. positive fetuses, and 1.1% positive to both agents. Among 339 swine herds evaluated from eight Brazilian States, 48,5% were positive to one or both infectious agents. The frequency of positive fetuses in abortion, stillbirths and mummification, and the efficiency of virus and bacterial detection from organs and gastric contents were compared. The results obtained indicate the high importance of these infectious agents in reproductive failure in Brazilian swine herds, beside the large utilization of commercial vaccines against then.

Perdas devido à natimortalidade, mumificação fetal, abortamentos e morte embrionária são responsáveis por uma considerável queda no desempenho da indústria suinícola no Brasil e no mundo. Dentre os agentes mais freqüentemente descritos como causadores de falhas reprodutivas em suínos pode-se citar o Parvovírus suíno, Leptospira spp. O diagnóstico das causas infecciosas de mortalidade embrionária e fetal torna-se muitas vezes inviável pelo estado de autólise do material ou dificuldades inerentes às características de crescimento do vírus ou bactéria envolvido. O presente estudo teve por objetivo avaliar os resultados obtidos no período de oito anos de detecção de Parvovirus suíno e Leptospira spp. em falhas reprodutivas e discutir alguns aspectos relativos ao diagnóstico destas infecções. Foram avaliados 1901 fetos, sendo coletadas de cada animal, uma amostra de pool de órgãos e uma de conteúdo gástrico, perfazendo um total de 3642 análises. Observou-se uma freqüência de 27,6% dos fetos positivos para Parvovirus suíno, 19,8% positivos para Leptospira spp e 1,1% positivos para os dois agentes em associação. Dentre as 339 granjas avaliadas em oito Estados Brasileiros, 48,5% foram positivas para um ou ambos agentes pesquisados. Avaliou-se a freqüência de fetos positivos em casos de abortamento, natimortalidade e mumificação fetal e comparou-se a eficiência da pesquisa dos agentes em amostras de órgãos, conteúdo gástrico e em ambos. Os resultados obtidos indicam a grande importância destes agentes infecciosos nos quadros de falha reprodutiva em granjas de suínos no Brasil, apesar da ampla utilização de vacinas contra os mesmos. . / Losses due to stillbirths, mummification, embryonic death and abortions account for a considerable drop in performance of the pig industry in Brazil and the world. Among the agents most frequently described as causes of reproductive failure in pigs may be mentioned the swine parvovirus, Leptospira spp. The diagnosis of infectious causes of fetal and embryonic mortality it is often impossible for the state of autolysis of the material or the difficulties inherent growth characteristics of the virus or bacteria involved. Present study has the goal evaluate the results obtained in eight year period of Parvovirus and Leptospira spp. detection in reproductive failure and discuss some aspects related to diagnosis of these infections. A total of 1901 fetuses were examined, and from each animal a sample of different tissues and a sample of gastric contents were collected, representing 3642 analysis. A frequency of 27.6% of Parvovirus positive fetuses were observed, followed by 19.8% of Leptospira spp. positive fetuses, and 1.1% positive to both agents. Among 339 swine herds evaluated from eight Brazilian States, 48,5% were positive to one or both infectious agents. The frequency of positive fetuses in abortion, stillbirths and mummification, and the efficiency of virus and bacterial detection from organs and gastric contents were compared. The results obtained indicate the high importance of these infectious agents in reproductive failure in Brazilian swine herds, beside the large utilization of commercial vaccines against then.

Cancer is a worldwide health problem and despite advances in traditional treatments i.e. surgery, chemotherapy and radiotherapy, the cure rate remains disappointing for some cancers. Different novel therapeutic strategies are being developed. In this thesis two nontraditional cancer therapy approaches are studied: gene therapy using viral vectors and antitumour vaccination with dendritic cell - tumour cell (DC/TC) hybrids. We have developed a novel ELISPOT titration method for viral vectors that is based on the actual expression of the transgene in target cells. This method was developed with recombinant parvovirus MVM-IL2, but it should be adaptable for other vectors carrying expression cassettes for secreted transgene products for which antibodies are available. The ELISPOT titration method allows for faster and better quantification of transducing units present in vector stocks as opposed to titration by in situ hybridisation (annexe I). The MVMIL2 vector has shown an anti-tumour effect against melanoma in an immunocompetent mouse model (annexe IV). Previous work concerns photodynamic inactivation of adenoviral vectors for biosafety and an in vivo study in which a synergistic effect of antiangiogenesis gene therapy combined with radiotherapy could be shown (annexes V and VI). DC/TC hybrids have been proposed as cancer vaccines for their simultaneous expression of antigen presentation machinery and tumour associated antigens. Hybrids are classically generated by polyethylene glycol (PEG) or electrofusion. These methods however require special skills and equipment and cause rather high cell lethality. Fusion via the expression of viral fusogenic membrane glycoproteins (FMG), such as the vesicular stomatitis virus-G (VSV-G) (annexe III) or the Gibbon ape Leukemia Virus (GaLV) FMG, have recently been described. We have mainly focussed on the latter. Transduction of cells with GaLV-FMG proved to be a limiting step for an efficient generation of hybrids. On the other hand, constitutive expression of GaLV-FMG leads to lethal syncytia formation in human cells. Therefore we developed a novel fusion strategy for the generation of DC/TC cell hybrids that involves the use of a non-human fusogenic cell line that constitutively expresses the GaLV-FMG. With this method we were able to generate reproducible yields of DC/TC triparental hybrids. The formation of tri-parental hybrids via the fusogenic cell line is an interesting alternative to existing DC/TC fusion methods because of its simplicity and its flexibility in the choice of fusion partners, i.e. autologous or allogeneic DCs and tumour cells. Moreover, the tri-parent hybrid system offers the possibility to further enhance the immune response by the addition of transgenes that code for immuno-modulating factors to the fusogenic cell line (annexe II).

Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Raymond R. R. Rowland / Emerging viral diseases threaten the health of the US swineherd and have the potential to impact the industry. Parvoviruses are capable of infecting birds, livestock and humans, however, in swine, parvoviruses cause reproductive failure and contribute to a devastating set of diseases termed porcine circovirus associated disease (PCVAD). Here, a divergent porcine parvovirus, porcine parvovirus 7 (PPV7), distantly related to known parvovirus sequences, was identified in market pigs in the US. The PPV7 non-structural protein displayed 42.4% similarity to Eidolon helvum parvovirus 2 and 37.9% similarity to turkey parvovirus. Conserved parvovirus replicase motifs including three rolling circle replication (RCR), two NTP-binding motifs and a helicase- binding domain, were present in PPV7. Analysis by qPCR of 182 porcine samples found 16 (8.6%) positive, suggesting moderate nucleic acid prevalence in US swine. Paramyxoviruses are capable of infecting various species including cattle, pigs and humans, causing respiratory disease and importantly, can overcome species barriers causing disease. In 2013, a novel paramyxovirus sequence was described in Hong Kong, China in slaughterhouse pigs, and subsequently named porcine parainfluenza virus 1 (PPIV1). The second study identifies two complete PPIV1 genomes in US pigs originating in Oklahoma and Nebraska that display 90.0-95.3% identity to the Chinese strains. Molecular analysis by qPCR resulted in 6.1% prevalence in 279 porcine respiratory samples. Further serological analysis revealed 66.1% of 59 porcine sera samples were positive by PPIV1 F ELISA. Eleven 3-week old nursery pigs from a PPIV1 naturally infected herd were monitored for signs of infection. No clinical signs were seen in the animals, however, six pigs and the lungs of one animal tested qPCR positive by the conclusion of the study. Taken together, PPIV1 is moderately prevalent in US swine-herds. Previously known to infect avian species, canines and swine, recent reports have identified circoviruses in bats, mink, and human feces. In pigs, porcine circovirus 2 (PCV2) is essential to PCVAD, a group of diseases including reproductive failure, respiratory disease complex (PRDC), porcine dermatitis and nephropathy syndrome (PDNS) and postweaning multisystemic wasting syndrome (PMWS). Additionally, PCV2 nucleic acid has been detected in mammalian species other than swine such as cattle and mink. The final study focuses on the identification and characterization of a divergent circovirus, porcine circovirus 3, identified in aborted mummies taken from sows displaying clinical and histological signs of PDNS. Putative capsid and replicase open reading frames display 37% and 55% identity to PCV2, respectively. A retrospective study of 48 PDNS cases, PCV2 negative by immunohistochemistry (IHC), identified 45 positive and 60% of a subset, positive for PCV3 by IHC. Molecular and serological prevalence studies revealed 12.5% nucleic acid and 55% antibody prevalence in US swine samples. Collectively, these studies identify emerging porcine viruses with the potential to cause disease using metagenomic sequencing. The results of these studies will help to mitigate the risk attributed to emerging swine viruses causing disease outbreaks.

Memoria para optar al Título Profesional de Médico Veterinario / Fundamentos: Parvovirus B19 (PV-B19) pertenece a la familia Parvoviridae, género Eritrovirus. Es un virus ADN de hebra simple que presenta secuencias palindrómicas en sus extremos. Es muy prevalente en la población general, llegando a detectarse anticuerpos anti PV-B19 en más del 85% de la población geriátrica. Este virus es el agente causal de una amplia gama de manifestaciones clínicas, cuya severidad depende del estado inmunológico y hematológico del hospedero, e incluye el eritema infeccioso, problemas hematológicos y reumatológicos e hidrops fetal, entre otras. Objetivo: Se determinó la presencia de Parvovirus B19 en pacientes con manifestaciones clínicas asociadas a este virus. Materiales y Métodos: Se analizaron 262 muestras de sangre de pacientes provenientes de distintos centros hospitalarios de la Región Metropolitana y del Servicio de Diagnóstico del Programa de Virología, Facultad de Medicina, Universidad de Chile. De estas muestras, 211 fueron analizadas mediante la técnica de ELISA para la pesquisa de IgM anti PV-B19, 244 con PCR anidado (PCR-Nested), para detectar genoma viral y 185 muestras con ambas técnicas. Resultados: De las muestras analizadas mediante la técnica de PCR anidado, se detectó genoma viral en un 25% de éstas y de las muestras analizadas mediante la técnica de ELISA, se localizó IgM anti PV-B19 en un 19%. Considerando sólo las 185 muestras que fueron analizadas con ambas técnicas, se detectó un 31.9% de positividad. En los casos positivos para el virus, las manifestaciones clínicas prevalentes fueron síndrome febril y eritema infeccioso

La etiología de la arteritis de células gigantes (ACG) es desconocida y sus aspectos etiopatogénicos están poco estudiados.Objetivos. 1. Estudiar la presencia de parvovirus B19 y los virus herpes en las arterias temporales positivas y negativas para la ACG. 2. Estudiar la asociación entre la expresión de metaloproteinasa-2 (MMP-2) y 9 (MMP-9) y el resultado de la biopsia de la arteria temporal (BAT), qué células las expresan y su localización. 3. Analizar si la presencia de estas MMP o los virus se relaciona con las alteraciones histológicas y con las variables clínico-epidemiológicas de los pacientes. 4. Conocer cuáles son los factores predictores del resultado de la BAT. Material y métodos. Se incluyeron todas las BAT valorables realizadas de forma consecutiva en el Hospital Universitari Vall d'Hebron por sospecha clínica de ACG entre Enero de 1997 y Marzo del 2002. Como criterios anatomopatológicos se utilizaron los del ACR. La presencia de ADN vírico se determinó mediante reacción en cadena de la polimerasa. Se realizaron nuevas tinciones de hematoxilina-eosina, de fibras elásticas y tricrómicro de Masson. Los macrófagos CD68, la MMP-2 y la MMP-9 se detectaron mediante inmunohistoquímica. De las historias clínicas se obtuvieron datos clínicos y epidemiológicos. Para el ajuste multivariable se utilizó la regresión logística múltiple.Resultados. En el período en estudio se encontraron 147 BAT válidas, 50 (35%) positivas para ACG y 97 (66%) negativas. Se recuperó la historia clínica de 125 pacientes, 46 (36,8%) con BAT (+) y 79 (63,2%) BAT (-). No se encontró presencia de ADN de los virus estudiados en ninguna de las BAT. La MMP-9 se expresaba con más frecuencia en BAT positivas que negativas para ACG (OR=2,93 p=0,005). Para la MMP-2 la diferencia no fue estadísticamente significativa (p=0,08). Ambas MMP se expresaban en macrófagos de la íntima y de la media cercanos a la lámina elástica interna, en células gigantes y en células con apariencia de músculo liso de la media y de la íntima. Le expresión de MMP-2 se relacionó de forma inversa con la afectación exclusiva de la adventicia (p=0,047) y de forma positiva con la fiebre (p=0,025). La MMP-9 se relacionó de forma positiva con: hiperplasia intimal (0,037), degeneración lámina elástica (0,0001), disminución de la luz (0,008), hipercolesterolemia (0,032), hiperestesia craneal (0,009). Ajustando por variables que podrían influir en el resultado de la biopsia, (edad, género, tiempo de evolución de los síntomas hasta la BAT, tratamiento previo con glucocorticoides y año de realización de la biopsia), se mantuvieron los resultados entre la expresión de MMP-2 y MMP-9. El engrosamiento de la arteria temporal, la disminución de su pulso y la pérdida de peso se asociaron de forma independiente con el resultado de la biopsia, ajustando por edad, género, días de evolución, tratamiento previo, año de realización, cefalea, hiperestesia craneal, claudicación mandibular, alteraciones visuales y VSG.Conclusiones. Ninguno de los virus estudiados parece estar implicado en la etiopatogenia de la ACG. La MMP-9, al contrario de la MMP-2, parece tener un papel en dicha etiopatogenia. La MMP-9 se asocia con hipercolesterolemia y la MMP-2 con la fiebre. El engrosamiento, la disminución de la luz de la arteria temporal y la pérdida de peso se han encontrado asociadas a una elevada probabilidad de resultado positivo de la biopsia en los enfermos estudiados. / The etiology of giant cell arteritis (GCA) is unknown and their etiopathogenic aspects have been little studied.Aims. 1. To study the presence of parvovirus B19 and herpes viruses in positive and negative temporal artery biopsies (TAB) for GCA. 2. To study the association between metalloproteinase-2 (MMP-2) and 9 (MMP-9) expression and TAB result, the type of cells expressing them and their location. 3. To analyse if the presence of these MMP or the viruses is related to histologic findings and to clinical-epidemiological variables of the patients. 4. To identify predictive factors of TAB result. Material and methods. All the valid TAB consecutively performed in Hospital Universitari Vall d'Hebron because of clinical suspicion of GCA between January 1997 and March 2002. ACR anatomopathological criteria were used. The presence of viral DNA was determined by means of polymerase chaín reaction. New hematoxilin-eosin, elastic fibers and Masson's trichromic stainings were performed. CD68 macrophages, MMP-2 and MMP-9 were detected by immunohistochemistry. Clinical and epidemiological data were obtained from clinical files. The multiple logistic regression was used for multivariable analysis. Results. During the study period, 147 valid TAB were found, 50 (35%) positive and 97 (66%) negative for GCA. Clinical files of 125 patients were retrieved, 46 (36.8%) with positive TAB and 79 (63.2%) with negative TAB. DNA of the viruses studied was not found in any of the TAB. MMP-9 was more frequently expressed in positive than in negative TAB for GCA (OR=2.93; p=0.005). The difference was not statistically significant for MMP-2 (p=0.08). Both MMP were expressed in macrophages of the intima and the media near internal elastic lamina, in giant cells and in cells of the media and the intima resembling smooth muscle cells. The expression of MMP-2 was inversely related to the isolated involvement of the adventitia (p=0.047) and positively to fever (p=0.025). MMP-9 was positively related to: intimal hyperplasia (0.037), elastic lamina degeneration (0.0001), luminal narrowing (0.008), hypercholesterolemia (0.032), scalp tenderness (0.009). Controlling for variables which could influence the biopsy result (age, gender, evolution of symptoms before TAB, previous glucocorticoids treatment and year of biopsy performance), the results between MMP-2 and MMP-9 expression remained unaltered. Temporal artery thickening, pulse decrease and weight loss were independently associated with biopsy result, controlling for age, gender, days of evolution of symptoms, previous treatment, year of biopsy performance, headache, scalp tenderness, jaw claudication, visual disturbances and erythrocyte sedimentation rate.Conclusions. None of the viruses studied seems to be involved in GCA etiopathogenesis. MMP-9, in contrast to MMP-2, seems to play an etiopathogenic role in GCA. MMP-9 is associated with hypercholesterolemia and MMP-2 with fever. Temporal artery thickening and luminal narrowing and weight loss are associated with a high probability of positive biopsy result in the patients studied.

Tikslas - Ištirti pirmą kartą vakcinuojamų šuniukų motininio imuniteto trukmę ir įvertinti specifines profilaktikos priemones šunų parvovirusinio enterito sukėlėjui. Tyrimai buvo atlikti Lietuvos sveikatos mokslų universiteto Veterinarijos akademijoje, Anatomijos ir fiziologijos katedros Imunologijos laboratorijoje ir privačioje veterinarijos klinikoje 2013 metais. Per šį periodą buvo surinkti duomenys apie atliktas 324 vakcinacijas prieš CPV infekciją. Buvo registruojama informacija apie amžių, lytį, veislę, naudotą vakciną ir laikymo sąlygas. 15 šunų buvo įtraukti į tyrimą paremtą imunofermentine analize. Kraujas buvo imamas iš ≤ 3 mėnesių amžiaus nevakcinuotų, kliniškai sveikų šuniukų. Buvo nustatyti parvovirusui specifiniai antikūnai. Standartinėje smulkių gyvūnų klinikoje šuniukų parvovirusinio enterito vakcinacijos atliekamos 6, 8-9 ir 12 savaičių laikotarpyje, kuomet motininio imuniteto parvovirusui specifinių antikūnų vidutinis titras yra ne mažesnis nei 1:1007. Šešių savaičių amžiaus šuniukų grupėje nustatyti aukšti (iki 1:1040) parvovirusui specifinių antikūnų titrai įrodo, kad pirmą kartą vakcinuojamų šuniukų motininis imunitetas šiame amžiuje gali nuslopinti aktyvų imuninį atsaką. Aštuonių savaičių amžiaus šuniukų motininių antikūnų parvovirusams titras kraujo serumo mėginiuose sumažėjo 3,7 karto iki 1:272 ir todėl leidžia atlikti sėkmingą vakcinaciją jau nuo 8 savaičių amžiaus. Nors didžiausias antikūnų parvovirusams kiekis prieš vakcinaciją buvo nustatytas Kinų... [toliau žr. visą tekstą] / Purpose – to investigate maternal immunity duration among the puppies vaccinated for the first time and to evaluate specific preventive measures against canine parvovirus agent. Studies have been carried out at LSMU Veterinary academy, Anatomy and physiology department, Laboratory of immunology and private veterinary clinic „Dainavos veterinarija“ in 2013. During this period data was collected about 324 cases that preventive vaccination was used in the clinic against CVP infection. Registered data of dogs: age, sex, breed, used vaccine and dogs housing conditions. 15 dogs were included in this study based on enzime-linked immunosorbent assay. Blood samples were taken from ≤ 3 months age non-vaccinated and clinically healthy puppies. Specific parvovirus antibodies were determined. In standard private small animal veterinary clinic puppies against CPV are vaccinated at 6, 8-9 and 12 weeks of age, when maternal immunity specific antibody for parvovirus average titer is not less than 1:1007. In group puppies of 6 weeks age with high titres (up to 1:1040) of specific antibodies for parvovirus were determined and its demonstrate that maternal immunity of first time vaccinated puppies in this age could inhibit active immune response. In group of puppies at 8 weeks of age the titre of maternal antibodies for parvovirus in blood serum samples decrease by 3.7 times down to 1:272 an therefore allow a successful vaccination since the age of 8 weeks. Data of CPV vaccination demonstrate... [to full text]

Regensburg, Univ., Diss., 2008

Orientador: Stélio Pacca Loureiro Luna / Resumo: A parvovirose canina destaca-se como um dos principais agentes etiológicos nas gastroenterites infecciosas em cães jovens, apresentando alta virulência e mortalidade em decorrência da gravidade do estado clínico geral dos pacientes. Seu tratamento clínico é sintomático, principalmente através da reposição eletrolítica e do controle do vômito e diarreia. Este fato aliado ao aumento crescente do índice de óbitos, estimulou o estudo de novas abordagens terapêuticas para o desenvolvimento de novos protocolos. A Ozonioterapia se destaca neste cenário em decorrência de suas múltiplas propriedades farmacológicas, atuando como antiviral, imunoestimulatório, anti-inflamatório, analgésico, dentre outros. Neste estudo, objetivou-se avaliar a Ozonioterapia como tratamento complementar em cães que apresentaram PCR positivo de fezes para parvovirose. Para isso, 25 animais aleatoriamente divididos em 2 grupos por meio de sorteio foram avaliados, sendo 7 animais do grupo controle (GC=7) e 18 animais do grupo ozônio (GO=18). Os animais tinham até dois anos de idade, vacinados e não vacinados contra parvovirose, machos ou fêmeas, sem distinção de raça ou porte. Durante o período de tratamento, os animais tiveram o hemograma, consistência das fezes, presença ou ausência de sangue nas fezes, presença ou ausência de êmese e o desfecho, com a alta ou óbito, como parâmetros. O desfecho pode ser considerado a variável de maior relevância clínica, demonstrando diferença significativa entre os grupos,... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Canine parvovirosis stands out as one of the main etiological agents in infectious gastroenteritis in young dogs, presenting high virulence and mortality due to the severity of the patient’s general clinical condition. Its clinical treatment is symptomatic, mainly through electrolyte replacement and control of vomiting and diarrhea. This fact, combined with the increasing death rate, has stimulated the study of new therapeutic approaches for the development of new protocols. Ozone therapy stands out in this scenario due to its multiple pharmacological properties, acting as an antiviral, immunostimulatory, anti-inflammatory, analgesic agent, among others. The aim of this study was to evaluate ozone therapy as a complementary treatment in dogs with positive stool PCR for parvovirus. For this, 25 animals randomly divided into 2 groups by lot were evaluated, being 7 animals from the control group (CG = 7) and 18 animals from the ozone group (GO = 18). The animals were up to two years old, vaccinated and unvaccinated against parvovirus, male or female, regardless of breed or size. During the treatment period, the animals had blood count, stool consistency, presence or absence of blood in the stool, presence or absence of emesis and the outcome, with discharge or death, as parameters. The outcome can be considered the most clinically relevant variable, demonstrating a significant difference between the groups, where the animals in the control group were 20 times (95% CI 2.2 - 180.9... (Complete abstract click electronic access below) / Mestre