Resumo
Toxocariasis is a zoonotic disease of worldwide distribution. The connection between parasitic diseases and conditions that depress the immune system, such as the use of immunosuppressive drugs, has been studied. The purpose of this study was to evaluate the effect of Cyclosporine A (CsA) on the intensity of infection, humoral response and gene transcription of interleukins IL-4, IL-10 and IL-12 in mice experimentally infected with Toxocara canis. To this end, mice were divided into two groups treated with CsA (G1: 10 mg/Kg and G2: 50 mg/kg), the G3 and G4 group received PBS. After the last administration of the drug or PBS (orally every 48 hours for 15 days), groups G1, G2 and G3 were inoculated with 1200 eggs of T. canis. Was collected blood samples on days zero, 15 and 30 days post-inoculation (PI), for ELISA test and the mice were euthanized 30 days PI. The organs and striated muscle tissue were collected for the recovery of larvae. The splenocytes were analyzed by RT-PCR. The intensity of infection in the mice treated with 50 mg/kg of CsA was 65.5% higher than in the control group (p=0.001). An analysis of the kinetics of anti-Toxocara antibody revealed that the groups treated with CsA showed significantly higher mean levels of antibodies on day 15 PI. The transcription of the three tested interleukins showed no statistical difference between G2 and G3 (control). It was concluded that the immunosuppression triggered by CsA (50 mg/Kg) favored the establishment of a larger number of T. canis larvae without, however, altering immunoglobulin production and IL-4, IL-10 and IL-12 transcription on day 30 PI.
A toxocaríase é uma zoonose de distribuição mundial. A conexão entre doenças parasitárias e condições que deprimem o sistema imunológico, como o uso de drogas imunossupressoras, tem sido estudada. O objetivo deste estudo foi avaliar o efeito da Ciclosporina A (CsA) na intensidade da infecção, resposta humoral e transcrição gênica das interleucinas IL-4, IL-10 e IL-12 em camundongos experimentalmente infectados com Toxocara canis. Para tanto, os camundongos foram divididos em dois grupos tratados com CsA (G1: 10 mg/Kg e G2: 50 mg/kg), os grupos G3 e G4 receberam PBS. Após a última administração da droga ou PBS (via oral a cada 48 horas por 15 dias), os grupos G1, G2 e G3 foram inoculados com 1200 ovos de T. canis. Foram coletadas amostras de sangue nos dias zero, 15 e 30 dias pós-inoculação (PI), para teste de ELISA e os camundongos foram eutanasiados 30 dias PI. Os órgãos e tecido muscular estriado foram coletados para a recuperação das larvas. Os esplenócitos foram analisados por RT-PCR. A intensidade da infecção nos camundongos tratados com 50 mg/kg de CsA foi 65,5% maior do que no grupo controle (p=0,001). Uma análise da cinética do anticorpo anti-Toxocara revelou que os grupos tratados com CsA apresentaram níveis médios de anticorpos significativamente maiores no dia 15 PI. A transcrição das três interleucinas testadas não apresentou diferença estatística entre G2 e G3 (controle). Concluiu-se que a imunossupressão desencadeada pela CsA (50 mg/Kg) favoreceu o estabelecimento de um maior número de larvas de T. canis sem, no entanto, alterar a produção de imunoglobulinas e a transcrição de IL-4, IL-10 e IL-12 no dia 30 PI.
Assuntos
Zoonoses , Ciclosporina , Toxocara canis , CamundongosResumo
Os cães atualmente são um dos mais importantes animais de estimação no mundo, tendo relevância como animais de companhia, guarda, pesquisa e reprodução, dentre outras. Com isso, aumenta a demanda por novos estudos sobre a espécie, principalmente no que diz respeito às doenças uterinas, comuns nos animais e importantes por causarem infertilidade, aborto, trabalho de parto prematuro e doença clínica. As doenças uterinas mais frequentemente encontradas em fêmeas não gestantes são a piometra e a hiperplasia endometrial cística, portanto objetivou-se no primeiro artigo, determinar a casuística das enfermidades reprodutivas de cadelas atendidas no Hospital Veterinário da Universidade Federal de Uberlândia, durante seis anos de avaliação (2012-2017), a fim de identificar quais enfermidades são mais frequentes. Para tanto, foram consultadas informações sobre espécie, idade, raça e sexo de 32.944 animais. Destes, 16.480 eram fêmeas caninas e 1.185 foram diagnosticadas com alterações no sistema reprodutivo. Os animais foram divididos de acordo com a idade em quatro grupos (filhotes, adultos jovens, adultos e idosos); e com as enfermidades do sistema reprodutivo (Grupo 1 alterações de vagina e vulva; Grupo 2 alterações de ciclo estral, ovário e útero; Grupo 3 alterações do período gestacional e parto). A taxa de alterações reprodutivas na população estudada foi de 7,2%, onde as médias de idades que apresentaram maior ocorrência de diagnósticos foram em cadelas adultas jovens (1 a 5 anos) com 47%. As patologias mais frequentes em fêmeas caninas foram a piometra (48,8%), distocias (13,6%) e Tumor Venéreo Transmissível (TVT) (12,6%). Os animais mestiços (SRD) foram os mais acometidos por distúrbios do sistema reprodutor, representando 60% do total de fêmeas diagnosticadas. Diante desses dados, o segundo artigo objetivou avaliar o efeito da inflamação sobre a produção das interleucinas 6 (IL6) e 12 (IL12) em culturas de endométrios caninos ex vivo desafiadas com LPS. Para o estudo, foram coletados úteros de 42 fêmeas caninas saudáveis submetidas a ovariosalpingohisterectomia (OSH) eletiva, de onde retirou-se explantes que foram submetidos a tratamento com controle, LPS, dexametasona, LPS + dexa, sendo então mensurados os valores de IL-6 e IL-12 pelo método de ELISA. Os explantes foram classificados histopatologicamente quanto ao tipo de inflamação em, sem inflamação, inflamação aguda, inflamação sub-aguda e inflamação crônica. Os resultados revelaram que o desafio com LPS não desencadeou síntese significativa de IL12 e principalmente de IL6 nas culturas de amostras de endométrios inflamados, indicando que cadelas com infiltrado inflamatório no endométrio podem apresentar comprometimento da resposta imune inata uterina.
Dogs are currently one of the most important pets in the world, having relevance as pet animals, guard, research and breeding, among others. This increases the demand for new studies on the species, especially regarding uterine diseases, common in animals and important for causing infertility, abortion, preterm labor and clinical disease. The uterine diseases most frequently found in non-pregnant females are pyometra and cystic endometrial hyperplasia, so it was objectified in the first article to determine the casuistry of the reproductive diseases of bitches attended at the Veterinary Hospital of the Federal University of Uberlândia, during six years of evaluation (2012-2017) in order to identify which diseases are most frequent. For this purpose, information on species, age, race and sex of 32.944 animals was consulted. Of these, 16.480 were female canines and 1.185 was diagnosed with alterations in the reproductive system. The animals were divided according to age in four groups (puppies, young adults, adults and elderly); (Group 1 - alterations of the vagina and vulva, Group 2 - alterations of estral cycle, ovary and uterus, Group 3 - alterations of the gestational period and childbirth). The rate of reproductive alterations in the study population was 7.2%, where the mean ages that presented the highest occurrence of diagnoses were in young adult bitches (1 to 5 years old) with 47%. The most frequent pathologies in canine females were pyometra (48.8%), dystocia (13.6%) and Transmissible Venereal Tumor (TVT) (12.6%). Crossbred animals were the most affected by disturbances of the reproductive system, representing 60% of the total females diagnosed. According to these data, the second article aimed to evaluate the effect of inflammation on the production of interleukins 6 (IL6) and 12 (IL12) in cultures of canine endometrial ex vivo challenged with LPS. For the study, 42 healthy canine females submitted to elective ovariosalpingohisterectomy (OSH) were collected from which explants that were submitted to treatment with control, LPS, dexamethasone, LPS + dexa were collected, and the values of IL- 6 and IL-12 by the ELISA method. Explants were classified histopathologically as to the type of inflammation in, without inflammation, acute inflammation, sub-acute inflammation and chronic inflammation. The results revealed that the challenge with LPS did not trigger significant synthesis of IL12 and mainly IL6 in cultures of inflamed endometrial samples, indicating that bitches with inflammatory infiltrate in the endometrium may present impaired innate immune response.
Resumo
There is an interest in the use of IL-12 as a possible anti-cancer drug to induce immune responses and anti-IL-13 formulations to treat the undesirable effects of IL-13. Thus, the present study aimed at analyzing IL-12 and IL-13 profiles, viral hepatitis serology and blood cultures in acute myeloid leukemia (AML) patients. Forty individuals (20 without septicemia - Group A, and 20 with septicemia - Group B) and 20 healthy controls were evaluated. Hepatitis B virus antigens (HBsAg) and hepatitis C virus antibodies (HCV Ab) were quantified using commercial ELISA kits. IL-12 and IL-13 levels were estimated in culture supernatant of mitogen-stimulated peripheral blood mononuclear cells by ELISA. Significantly low IL-12 values were observed among AML patients compared to controls whereas the opposite was observed regarding IL-13. IL-12 levels were found to be elevated in the follow-up cases. M4 and M5 subtypes of AML presented higher IL-12 levels than M1 and M2 subtypes. The isolated organisms from AML with septicemia were Staphylococcus aureus (35 percent), Esherichia coli (25 percent), coagulase-negative staphylococci (25 percent), and Candida (15 percent). Fungemia cases showed higher IL-12 values than bacteremia cases. In conclusion, IL-12 and IL-13 should be further tested in large-scale studies to provide future immunotherapy against AML.(AU)
Assuntos
Leucemia/metabolismo , Hepatite B , Hepatite C , Sorologia/classificação , Ensaio de Imunoadsorção Enzimática/métodos , HepacivirusResumo
There is an interest in the use of IL-12 as a possible anti-cancer drug to induce immune responses and anti-IL-13 formulations to treat the undesirable effects of IL-13. Thus, the present study aimed at analyzing IL-12 and IL-13 profiles, viral hepatitis serology and blood cultures in acute myeloid leukemia (AML) patients. Forty individuals (20 without septicemia - Group A, and 20 with septicemia - Group B) and 20 healthy controls were evaluated. Hepatitis B virus antigens (HBsAg) and hepatitis C virus antibodies (HCV Ab) were quantified using commercial ELISA kits. IL-12 and IL-13 levels were estimated in culture supernatant of mitogen-stimulated peripheral blood mononuclear cells by ELISA. Significantly low IL-12 values were observed among AML patients compared to controls whereas the opposite was observed regarding IL-13. IL-12 levels were found to be elevated in the follow-up cases. M4 and M5 subtypes of AML presented higher IL-12 levels than M1 and M2 subtypes. The isolated organisms from AML with septicemia were Staphylococcus aureus (35 percent), Esherichia coli (25 percent), coagulase-negative staphylococci (25 percent), and Candida (15 percent). Fungemia cases showed higher IL-12 values than bacteremia cases. In conclusion, IL-12 and IL-13 should be further tested in large-scale studies to provide future immunotherapy against AML.(AU)