Cyclosporine A increases the intensity of Toxocara canis infection in swiss mice / Ciclosporina A aumenta a intensidade da infecção por Toxocara canis em camundongos suíços

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.

Protective effect of hydroxysafflor yellow A on cyclosporin A-induced renal oxidative stress in vitro and in vivo

Purpose: To explore the mechanism and investigate the protective effect of hydroxysafflor yellow A (HSYA) on renal oxidative stress, which cyclosporine A (CsA) induces. Methods: HK-2 cells were treated with CsA to get CsA-induced oxidative stress. The effects on oxidative stress and apoptosis of HK-2 cells were detected. The contents of SOD, MDA, GSH-Px, ROS, and CAT in serum were measured, and the expression of apoptosis-related proteins was detected by western blot. Then, established the renal oxidative stress injury rats to verify the efficacy of HSYA. Results: HSYA could reduce the ROS and MDA contents induced by CsA. Compared with the CsA group, the activities of SOD, CAT, and GSH-Px increased significantly when treated with HSYA. HSYA could inhibit CsA-induced apoptosis in HK-2 cells, and promote the protein of Bcl-2 and inhibit the expression of Bax. Animal experiments showed that HSYA could reduce CsA-induced renal cell injury by reducing glomerular cell vacuoles and inflammatory factors in tissues. It also decreased serum creatinine (Crea) and blood urea nitrogen, increased Crea clearance significantly. Conclusions: HSYA could significantly improve the antioxidant capacity of the kidney cells and inhibit cell apoptosis, thereby effectively ameliorating CsA-induced oxidative stress in vitro and in vivo.

Oral mucosa transplantation may improve tear film osmolarity in dogs with keratoconjunctivitis sicca - a preliminary study / [Transplante da mucosa oral na melhoria da osmolaridade do filme lacrimal em cães com ceratoconjuntivite seca - estudo preliminar]

The objective of this study was to evaluate the use of cyclosporine 1% alone or associated with oral mucosa transplantation (OMT) in dogs with dry keratoconjunctivitis (KCS). Schirmer Tear Test (STT-1) and Tear Film Osmolarity (TFO) were measured in both eyes of 30 adult dogs (before and 45 days after treatment. The animals were divided into three groups (10 dogs for group): control (normal dogs), group I (GI, treated with 1% cyclosporine alone), and group II (GII, treated with 1% cyclosporine and OMT). All STT-1 and TFO values were subjected to the Shapiro-Wilk normality test, and all were normally distributed. STT-1 and TFO values before and after treatment were subjected to the T-Student Test. The STT­1 and TFO values of the right eye were subjected to Repeated Measures ANOVA followed by a Tukey Test for comparison between groups I and II. Means with a value of p≤0.05 were considered significant. There was a decreased osmolarity in both groups after treatment. Mean osmolarity in GII (322.60±16.56 mOsm/L) was significantly lower than GI (336.40±5.66 mOsm/L). The OMT associated with cyclosporine 1% improved the osmolarity of the tear film in dogs with KCS with a seeming synergism between the clinical and surgical treatments.(AU)

Avaliou-se o uso de ciclosporina 1% isolada ou associada ao transplante de mucosa oral (TMO) em cães com ceratoconjuntivite seca (CCS). O teste lacrimal de Schirmer (TLS-1) e a osmolaridade do filme lacrimal (OFL) foram medidos em ambos os olhos, em 30 cães adultos, antes e 45 dias após o tratamento. Os animais foram divididos em três grupos (10 cães por grupo): controle (cães saudáveis), grupo I (GI, tratados apenas com ciclosporina 1%) e grupo II (GII, tratados com 1% de ciclosporina associada ao TMO). Todos os valores do TLS-1 e da OFL foram submetidos ao teste de normalidade Shapiro-Wilk, e todos foram distribuídos normalmente. Os valores de TLS-1 e OFT antes e depois do tratamento foram submetidos ao teste T-Student. Os valores TLS-1 e OFT do olho direito foram submetidos à ANOVA de medidas repetidas, seguida por um teste de Tukey para comparação entre os grupos I e II. Valor de P≤0,05 foi considerado significativo. Houve uma diminuição da osmolaridade em ambos os grupos após o tratamento. A osmolaridade média no GII (322,60±16,56 mOsm/L) foi significativamente inferior à no GI (336,40±5,66 mOsm/L). O TMO associado à ciclosporina 1% melhorou a osmolaridade do filme lacrimal em cães com CCS, com uma sinergia aparente entre os tratamentos clínicos e cirúrgicos.(AU)

Eosinophilic cystitis, a rare cause of persistent haematuria in a diabetic dog / Cistite eosinofílica, uma causa rara de hematúria persistente em um cão diabético

Eosinophilic cystitis is a rare inflammatory disorder characterized by eosinophilic infiltration of entire layers of the bladder wall. The condition has been described in adults, children, and dogs. However, there are no consensus guidelines for the treatment of eosinophilic cystitis. Although human and veterinary literature reviews show some effectiveness in management with corticosteroids, antihistamines, and antibiotics, a variety of serious and frequent side effects are associated with steroid therapy. As a result, steroids are relatively contraindicated for patients with diabetes mellitus and Cushing's syndrome. A five-year-old neutered male chow-chow with controlled diabetes was referred with an 18-month history of malodorous urine, gross haematuria, and dysuria that were nonresponsive to antibiotics. The findings on general examination were unremarkable except for abdominal suprapubic discomfort. The complete blood count and biochemical profile (such as urea and creatinine) were normal except for mild peripheral eosinophilia. Although ultrasonography, bladder contrast radiography, and urine cytology findings indicated malignancy, with the presence of atypical urothelial cells, histopathology confirmed eosinophilic cystitis. Management with cyclosporine was adequate with complete remission of haematuria. This case report presents the first reported successful use of cyclosporine for the treatment of eosinophilic cystitis in a dog with diabetes.(AU)

A cistite eosinofílica é uma doença inflamatória rara caracterizada por infiltração eosinofílica de todas as camadas da parede da bexiga. Essa enfermidade já foi descrita em adultos, crianças e cães. No entanto, não há um consenso de diretrizes sobre o seu tratamento. Mesmo que as literaturas humana e veterinária mostrem alguma eficácia no manejo com corticosteroides, anti-histamínicos e antibióticos, uma variedade de efeitos colaterais graves e frequentes está associada à terapia com esteroides. Dessa forma, o uso de esteroides é relativamente contraindicado para pacientes com diabetes mellitus e síndrome de Cushing, por exemplo. Um chow-chow, macho, castrado, de cinco anos e diabético estável foi encaminhado para atendimento com histórico de urina fétida, hematúria macroscópica e disúria não responsiva a antibióticos há 18 meses. A avaliação dos parâmetros físicos estava dentro dos padrões, exceto por desconforto abdominal suprapúbico à palpação. O hemograma e o perfil bioquímico (como a ureia e a creatinina) estavam dentro da normalidade para a espécie, exceto por eosinofilia periférica leve. Embora a ultrassonografia, a radiografia contrastada da bexiga e os achados da urinálise indicassem malignidade, com a presença de células uroteliais atípicas, a histopatologia confirmou o diagnóstico definitivo de cistite eosinofílica. O manejo com ciclosporina foi satisfatório, com ausência completa da hematúria. Este relato de caso apresenta o primeiro uso documentado de ciclosporina para o tratamento de cistite eosinofílica com sucesso em um cão com diabetes.(AU)

Eosinophilic cystitis, a rare cause of persistent haematuria in a diabetic dog / Cistite eosinofílica, uma causa rara de hematúria persistente em um cão diabético

Eosinophilic cystitis is a rare inflammatory disorder characterized by eosinophilic infiltration of entire layers of the bladder wall. The condition has been described in adults, children, and dogs. However, there are no consensus guidelines for the treatment of eosinophilic cystitis. Although human and veterinary literature reviews show some effectiveness in management with corticosteroids, antihistamines, and antibiotics, a variety of serious and frequent side effects are associated with steroid therapy. As a result, steroids are relatively contraindicated for patients with diabetes mellitus and Cushing's syndrome. A five-year-old neutered male chow-chow with controlled diabetes was referred with an 18-month history of malodorous urine, gross haematuria, and dysuria that were nonresponsive to antibiotics. The findings on general examination were unremarkable except for abdominal suprapubic discomfort. The complete blood count and biochemical profile (such as urea and creatinine) were normal except for mild peripheral eosinophilia. Although ultrasonography, bladder contrast radiography, and urine cytology findings indicated malignancy, with the presence of atypical urothelial cells, histopathology confirmed eosinophilic cystitis. Management with cyclosporine was adequate with complete remission of haematuria. This case report presents the first reported successful use of cyclosporine for the treatment of eosinophilic cystitis in a dog with diabetes.(AU)

A cistite eosinofílica é uma doença inflamatória rara caracterizada por infiltração eosinofílica de todas as camadas da parede da bexiga. Essa enfermidade já foi descrita em adultos, crianças e cães. No entanto, não há um consenso de diretrizes sobre o seu tratamento. Mesmo que as literaturas humana e veterinária mostrem alguma eficácia no manejo com corticosteroides, anti-histamínicos e antibióticos, uma variedade de efeitos colaterais graves e frequentes está associada à terapia com esteroides. Dessa forma, o uso de esteroides é relativamente contraindicado para pacientes com diabetes mellitus e síndrome de Cushing, por exemplo. Um chow-chow, macho, castrado, de cinco anos e diabético estável foi encaminhado para atendimento com histórico de urina fétida, hematúria macroscópica e disúria não responsiva a antibióticos há 18 meses. A avaliação dos parâmetros físicos estava dentro dos padrões, exceto por desconforto abdominal suprapúbico à palpação. O hemograma e o perfil bioquímico (como a ureia e a creatinina) estavam dentro da normalidade para a espécie, exceto por eosinofilia periférica leve. Embora a ultrassonografia, a radiografia contrastada da bexiga e os achados da urinálise indicassem malignidade, com a presença de células uroteliais atípicas, a histopatologia confirmou o diagnóstico definitivo de cistite eosinofílica. O manejo com ciclosporina foi satisfatório, com ausência completa da hematúria. Este relato de caso apresenta o primeiro uso documentado de ciclosporina para o tratamento de cistite eosinofílica com sucesso em um cão com diabetes.(AU)

Doença inflamatória intestinal em cães: relato de casos / Inflammatory bowel disease in dogs: case reports

A doença inflamatória intestinal (DII) é uma enteropatia crônica idiopática que provoca distúrbios gastrointestinais em cães e gatos. Ocorre em animais com meia idade e as manifestações clínicas mais comuns incluem êmese e diarreia intermitente. A análise histológica permite classificar a DII de acordo com o infiltrado celular e pode ser obtida principalmente por laparotomia ou endoscopia. A terapia é baseada na dieta, oferta de fibras e medicações imunossupressoras. O objetivo do estudo é relatar três casos de DII, confirmada após biopsia. Neste relato os animais foram submetidos em procedimento de laparotomia e endoscopia digestiva alta para coleta de amostra histopatológica. Todos os animais foram diagnosticados com DII, contudo houve complicações pós-operatórias. O manejo dietético com proteínas de alta digestibilidade, suplementação de fibras e prednisona, azatioprina ou ciclosporina se demonstraram eficazes nestes pacientes.

Inflammatory Bowel Disease (IBD) is an idiopathic chronic enteropathy characterized by gastrointestinal diseases in dogs and cats. The middle-aged animals are more affected and the clinical signs include vomiting and intermittent diarrhea. The histopathological analysis shows IBD classification according to the form of cellular infiltration in the lamina propria, mainly obtained by laparotomy or endoscopy. The treatment is based on diet, fiber supply, and immunosuppressive drugs. The objective of this trial is to report three IBD cases confirmed through histopathologic evaluation. In the trial the animals were submitted to laparotomy and upper gastrointestinal endoscopy to take histopathological samples. All animals were diagnosed with IBD, although there were some postoperative complications. The diet management with high digestibility fiber, fiber supplementation, prednisone and azathioprine or cyclosporine demonstrated effective in these patients.

Doença inflamatória intestinal em cães: relato de casos / Inflammatory bowel disease in dogs: case reports

A doença inflamatória intestinal (DII) é uma enteropatia crônica idiopática que provoca distúrbios gastrointestinais em cães e gatos. Ocorre em animais com meia idade e as manifestações clínicas mais comuns incluem êmese e diarreia intermitente. A análise histológica permite classificar a DII de acordo com o infiltrado celular e pode ser obtida principalmente por laparotomia ou endoscopia. A terapia é baseada na dieta, oferta de fibras e medicações imunossupressoras. O objetivo do estudo é relatar três casos de DII, confirmada após biopsia. Neste relato os animais foram submetidos em procedimento de laparotomia e endoscopia digestiva alta para coleta de amostra histopatológica. Todos os animais foram diagnosticados com DII, contudo houve complicações pós-operatórias. O manejo dietético com proteínas de alta digestibilidade, suplementação de fibras e prednisona, azatioprina ou ciclosporina se demonstraram eficazes nestes pacientes.(AU)

Inflammatory Bowel Disease (IBD) is an idiopathic chronic enteropathy characterized by gastrointestinal diseases in dogs and cats. The middle-aged animals are more affected and the clinical signs include vomiting and intermittent diarrhea. The histopathological analysis shows IBD classification according to the form of cellular infiltration in the lamina propria, mainly obtained by laparotomy or endoscopy. The treatment is based on diet, fiber supply, and immunosuppressive drugs. The objective of this trial is to report three IBD cases confirmed through histopathologic evaluation. In the trial the animals were submitted to laparotomy and upper gastrointestinal endoscopy to take histopathological samples. All animals were diagnosed with IBD, although there were some postoperative complications. The diet management with high digestibility fiber, fiber supplementation, prednisone and azathioprine or cyclosporine demonstrated effective in these patients.(AU)

Effects of cyclosporine on ischemia-reperfusion injuries in rat kidneys. An experimental model

Abstract Purpose To assess Cyclosporine A (CsA) therapy at an intraperitoneal dose of 15 mg.kg -1 in a rodent model of non-septic renal ischemia. Methods Twenty male Wistar rats were randomized to receive CsA therapy or none therapy before undergoing 30 minutes of renal ischemia followed by reperfusion. Additionally, 10 rats were randomized to undergo the same surgical procedure of the aforementioned animals with neither ischemia nor CsA therapy. Twelve hours after kidney ischemia, the left kidneys were evaluated for histological injury according to Park's criteria. Serum creatinine (Cr), urea nitrogen (Ur) and sodium levels were obtained at different times of the experimental protocol. Results Rodents in the CsA group showed negative results (p<0.05) in serum variables (Cr: 0.41±0.05mg/dL vs . 4.17±1.25mg/dL; Ur: 40.90±3.98mg/dL vs . 187.70±22.93mg/dL) even the non CsA or control group (Cr: 0.35±0.07mg/dL vs . 3.80±1.20mg/dL; Ur: 40.10±4.70mg/dL vs . 184.50±49.80mg/dL). The negative results were also verified in histological evaluation, CsA group had 50% in the very severe grade of lesion, 10% in the severe and 40% in the moderate to severe whereas the control group had 90% in the very severe grade. Conclusion CsA was incapable of preventing the deleterious effects of ischemia-reperfusion injury in rat kidneys.(AU)

Avaliação clínica e laboratorial da dermatite atópica canina / Clinical and laboratory evaluation of canine atopic dermatitis

A dermatite atópica canina (DAC) é uma dermatopatia inflamatória, crônica e pruriginosa que afeta indivíduos geneticamente predispostos, sendo comumente associada à produção de anticorpos do tipo IgE. O presente relato objetivou descrever um caso de DAC, evidenciando seus sinais clínicos, diagnóstico e tratamento. Foram realizados teste com lâmpada de Wood, raspado profundo de pele, imprint cutâneo, cultura fúngica e bacteriana, citologia de ouvido, exame sorológico para leishmaniose visceral canina (LVC) e teste de sensibilidade a alérgenos. O paciente apresentava uma série de lesões dermatológicos disseminadas acompanhadas de prurido intenso, onde pode-se observar presenças de infecções secundárias por bactérias e leveduras fúngicas. Dessa forma, optou-se por tratamento tópico com shampoo a base de clorexidina 2% associado a miconazol 2,5% e uso de creme hidratante. Para otite bilateral, prescreveu-se solução otológica de ciclopirox olamina 1% e ácido glicirrízico 0,5%. Após resposta negativa ao tratamento inicial, introduziu-se o uso oral de prednisolona associado à hidroxizina e logo depois a ciclosporina, ocorrendo um controle do quadro. Embora várias alternativas terapêuticas estejam disponíveis, a cura ainda não é possível, sendo o controle do quadro lesional a melhor abordagem de tratamento.

The canine atopic dermatitis (CAD) is an inflammatory skin disease, chronic itchy that affects genetically predisposed individuals, being commonly associated with production of IgE antibodies. The aim of this study was to describe a case of CAD, evidencing its clinical signs, diagnosis and treatment. A Wood lamp, skin deep scraping, skin imprint, fungal and bacterial culture, ear cytology, serological examination for canine visceral leishmaniasis (LVC) and allergen sensitivity test were performed. The animal presented a series of disseminated dermatological lesions accompanied by intense pruritus, where it is possible to observe presences of secondary infections by bacteria and yeasts fungi. Thus, it was decided to topical treatment with shampoo chlorhexidine base 2% associated with miconazole 2.5% and use moisturizer. For bilateral otitis, otologic solution of cyclopirox olamine 1% and glycyrrhizic acid 0.5% was prescribed. After negative response to the initial treatment, the oral use of prednisolone associated with hydroxyzine and soon after cyclosporine was introduced, and clinical control was performed. Although several therapeutic alternatives are available, cure is still not possible, and lesion control is the best treatment approach.

Avaliação clínica e laboratorial da dermatite atópica canina / Clinical and laboratory evaluation of canine atopic dermatitis

A dermatite atópica canina (DAC) é uma dermatopatia inflamatória, crônica e pruriginosa que afeta indivíduos geneticamente predispostos, sendo comumente associada à produção de anticorpos do tipo IgE. O presente relato objetivou descrever um caso de DAC, evidenciando seus sinais clínicos, diagnóstico e tratamento. Foram realizados teste com lâmpada de Wood, raspado profundo de pele, imprint cutâneo, cultura fúngica e bacteriana, citologia de ouvido, exame sorológico para leishmaniose visceral canina (LVC) e teste de sensibilidade a alérgenos. O paciente apresentava uma série de lesões dermatológicos disseminadas acompanhadas de prurido intenso, onde pode-se observar presenças de infecções secundárias por bactérias e leveduras fúngicas. Dessa forma, optou-se por tratamento tópico com shampoo a base de clorexidina 2% associado a miconazol 2,5% e uso de creme hidratante. Para otite bilateral, prescreveu-se solução otológica de ciclopirox olamina 1% e ácido glicirrízico 0,5%. Após resposta negativa ao tratamento inicial, introduziu-se o uso oral de prednisolona associado à hidroxizina e logo depois a ciclosporina, ocorrendo um controle do quadro. Embora várias alternativas terapêuticas estejam disponíveis, a cura ainda não é possível, sendo o controle do quadro lesional a melhor abordagem de tratamento.(AU)

The canine atopic dermatitis (CAD) is an inflammatory skin disease, chronic itchy that affects genetically predisposed individuals, being commonly associated with production of IgE antibodies. The aim of this study was to describe a case of CAD, evidencing its clinical signs, diagnosis and treatment. A Wood lamp, skin deep scraping, skin imprint, fungal and bacterial culture, ear cytology, serological examination for canine visceral leishmaniasis (LVC) and allergen sensitivity test were performed. The animal presented a series of disseminated dermatological lesions accompanied by intense pruritus, where it is possible to observe presences of secondary infections by bacteria and yeasts fungi. Thus, it was decided to topical treatment with shampoo chlorhexidine base 2% associated with miconazole 2.5% and use moisturizer. For bilateral otitis, otologic solution of cyclopirox olamine 1% and glycyrrhizic acid 0.5% was prescribed. After negative response to the initial treatment, the oral use of prednisolone associated with hydroxyzine and soon after cyclosporine was introduced, and clinical control was performed. Although several therapeutic alternatives are available, cure is still not possible, and lesion control is the best treatment approach.(AU)

Eficácia dos colírios ciclosporina e tacrolimo no tratamento de ceratoconjuntivite seca em cães / Efficacy of cyclosporine and tacrolimus drops in the treatment of keratoconjunctivitis sicca in dogs

O objetivo deste estudo foi avaliar os efeitos do tacrolimo e da ciclosporina na produção lacrimal de cães com ceratoconjuntivite seca (CCS) durante 90 dias. Para tanto, foram utilizados colírios de tacrolimo 0,02% (TcL) e ciclosporina 0,1% (CsA) em 14 cães com CCS. Os animais foram distribuídos em dois grupos e avaliados antes do início do tratamento (T0) e aos 15 (T1), 30 (T2), 45 (T3), 60 (T4), 75 (T5) e 90 (T6) dias após o início do tratamento. Na avaliação clínica, observou-se maior redução da secreção ocular, da opacidade e do edema corneano e da vascularização conjuntival. no grupo tacrolimo. No teste de Schirmer, verificou-se produção basal de 6(4,07 e 5,86(2,85mm/min no TcL e CsA, respectivamente, com aumento significativo da produção lacrimal em ambos os grupos, contudo houve aumento significativo da produção lacrimal a partir dos 15 dias de tratamento no grupo TcL (17,88(5,51mm/min), mas apenas a partir dos 45 dias no grupo CsA (11,86(4,74mm/min). Conclui-se que o uso do colírio tacrolimo aumentou em 68,83% a produção lacrimal em 90 dias de tratamento, comparado com a ciclosporina (56,82%), além de diminuir as manifestações clínicas inerentes à CCS, quando comparado à terapia com ciclosporina.(AU)

The objective of this study was to evaluate the effects of tacrolimus and cyclosporine on the lacrimal production of dogs with ketaroconjunctivitis sicca (KCS) for 90 days. Tacrolimus 0.02% (TcL) and 0.1% cyclosporine (CsA) eye drops were used in 14 dogs with KCS. The animals were randomly assigned to two groups and evaluated before treatment (T0) and at 15 (T1), 30 (T2), 45 (T3), 60 (T4), 75 (T5) and 90 (T6) days after initiation of treatment. Clinical evaluation showed significant reduction of ocular secretion, corneal opacity and edema and conjunctival vascularization in the tacrolimus group. Schirmer test showed basal lacrimal production of 6(4.07 and 5.86(2.85mm/min for TcL and CsA, respectively, with significant increase in lacrimal production in both groups. There was a significant increase in lacrimal production after 15 days of treatment in the TcL group (17.88(5.51mm/min), but only after 45 days in the CsA group (11.86(4.74mm/min). Tacrolimus drops increased lacrimal production in 68.83% after 90 days of treatment, compared to cyclosporine (56.82%), and also reduced clinical manifestations related to KCS when compared to cyclosporine.(AU)

Eficácia dos colírios ciclosporina e tacrolimo no tratamento de ceratoconjuntivite seca em cães / Efficacy of cyclosporine and tacrolimus drops in the treatment of keratoconjunctivitis sicca in dogs

O objetivo deste estudo foi avaliar os efeitos do tacrolimo e da ciclosporina na produção lacrimal de cães com ceratoconjuntivite seca (CCS) durante 90 dias. Para tanto, foram utilizados colírios de tacrolimo 0,02% (TcL) e ciclosporina 0,1% (CsA) em 14 cães com CCS. Os animais foram distribuídos em dois grupos e avaliados antes do início do tratamento (T0) e aos 15 (T1), 30 (T2), 45 (T3), 60 (T4), 75 (T5) e 90 (T6) dias após o início do tratamento. Na avaliação clínica, observou-se maior redução da secreção ocular, da opacidade e do edema corneano e da vascularização conjuntival. no grupo tacrolimo. No teste de Schirmer, verificou-se produção basal de 6(4,07 e 5,86(2,85mm/min no TcL e CsA, respectivamente, com aumento significativo da produção lacrimal em ambos os grupos, contudo houve aumento significativo da produção lacrimal a partir dos 15 dias de tratamento no grupo TcL (17,88(5,51mm/min), mas apenas a partir dos 45 dias no grupo CsA (11,86(4,74mm/min). Conclui-se que o uso do colírio tacrolimo aumentou em 68,83% a produção lacrimal em 90 dias de tratamento, comparado com a ciclosporina (56,82%), além de diminuir as manifestações clínicas inerentes à CCS, quando comparado à terapia com ciclosporina.(AU)

The objective of this study was to evaluate the effects of tacrolimus and cyclosporine on the lacrimal production of dogs with ketaroconjunctivitis sicca (KCS) for 90 days. Tacrolimus 0.02% (TcL) and 0.1% cyclosporine (CsA) eye drops were used in 14 dogs with KCS. The animals were randomly assigned to two groups and evaluated before treatment (T0) and at 15 (T1), 30 (T2), 45 (T3), 60 (T4), 75 (T5) and 90 (T6) days after initiation of treatment. Clinical evaluation showed significant reduction of ocular secretion, corneal opacity and edema and conjunctival vascularization in the tacrolimus group. Schirmer test showed basal lacrimal production of 6(4.07 and 5.86(2.85mm/min for TcL and CsA, respectively, with significant increase in lacrimal production in both groups. There was a significant increase in lacrimal production after 15 days of treatment in the TcL group (17.88(5.51mm/min), but only after 45 days in the CsA group (11.86(4.74mm/min). Tacrolimus drops increased lacrimal production in 68.83% after 90 days of treatment, compared to cyclosporine (56.82%), and also reduced clinical manifestations related to KCS when compared to cyclosporine.(AU)

Análises macroscópica e histopatológica do alotransplante parcial de vesícula urinária com células-tronco mesenquimais alogênicas derivadas do tecido adiposo em coelhos / Macroscopic and histopathological analysis of partial urinary bladder allograft using allogenic adipose tissue derived mesenchymal stem cells in rabbits

O número de transplantes de órgãos e tecidos em humanos e animais tem crescido significativamente nos últimos anos, principalmente após o advento de técnicas modernas e mais seguras indutoras de imunossupressão. Objetiva-se com o presente estudo avaliar macro e microscopicamente o alotransplante parcial de bexiga a fresco em coelhos, utilizando como agente imunomodulador células-tronco mesenquimais derivadas do tecido adiposo (ADSC) alogênicas. Foram utilizados 25 coelhos, sendo um deles macho e doador das ADSCs, e os outros 24 eram fêmeas, submetidas a alotransplante parcial de bexiga, tratadas com ciclosporina (GCi) ou células-tronco mesenquimais (GCe). Conclui-se que o GCe teve melhor aceitação histológica do implante em relação ao GCi aos 30 dias de avaliação.(AU)

The number of organ and tissue transplantation in humans and animals has grown significantly recently, especially after the advent of modern and safer techniques of immunosuppression. The objective of this study was to evaluate macro and microscopically partial urinary bladder fresh allograft in rabbits, using as immunomodulatory agent cyclosporine or allogenic adipose tissue derived mesenchymal stem cells (ADSCs). For this purpose, 25 rabbits were used. One male was the donor of ADSCs; 24 females received a partial urinary bladder allograft and were treated with cyclosporine (GCi) or mesenchymal stem cells (GCe). We conclude that the GCe group had better histological acceptance of the implant than GCi group at 30 days evaluation.(AU)

Análises macroscópica e histopatológica do alotransplante parcial de vesícula urinária com células-tronco mesenquimais alogênicas derivadas do tecido adiposo em coelhos / Macroscopic and histopathological analysis of partial urinary bladder allograft using allogenic adipose tissue derived mesenchymal stem cells in rabbits

O número de transplantes de órgãos e tecidos em humanos e animais tem crescido significativamente nos últimos anos, principalmente após o advento de técnicas modernas e mais seguras indutoras de imunossupressão. Objetiva-se com o presente estudo avaliar macro e microscopicamente o alotransplante parcial de bexiga a fresco em coelhos, utilizando como agente imunomodulador células-tronco mesenquimais derivadas do tecido adiposo (ADSC) alogênicas. Foram utilizados 25 coelhos, sendo um deles macho e doador das ADSCs, e os outros 24 eram fêmeas, submetidas a alotransplante parcial de bexiga, tratadas com ciclosporina (GCi) ou células-tronco mesenquimais (GCe). Conclui-se que o GCe teve melhor aceitação histológica do implante em relação ao GCi aos 30 dias de avaliação.(AU)

The number of organ and tissue transplantation in humans and animals has grown significantly recently, especially after the advent of modern and safer techniques of immunosuppression. The objective of this study was to evaluate macro and microscopically partial urinary bladder fresh allograft in rabbits, using as immunomodulatory agent cyclosporine or allogenic adipose tissue derived mesenchymal stem cells (ADSCs). For this purpose, 25 rabbits were used. One male was the donor of ADSCs; 24 females received a partial urinary bladder allograft and were treated with cyclosporine (GCi) or mesenchymal stem cells (GCe). We conclude that the GCe group had better histological acceptance of the implant than GCi group at 30 days evaluation.(AU)

Cyclosporine A attenuates apoptosis and necrosis after ischemia-reperfusion-induced renal injury in transiently hyperglycemic rats

Purpose: To investigate the effects of cyclosporine A on renal ischemia-reperfusion injury during transient hyperglycemia in rats. Methods: In a model of ischemia-reperfusion-induced renal injury and transiently induced hyperglycemia by intraperitoneal injection of glucose, 2.5 g.kg-1, Wistar rats were anesthetized with either isoflurane or propofol and received intravenous cyclosporine A, 5 mg.kg-1, five minutes before reperfusion. Comparison groups were isoflurane and propofol sham groups and isoflurane and propofol ischemia-reperfusion-induced renal injury. Renal tubular cell viability was quantitatively assessed by flow cytometry after cell culture and classified as early apoptosis, necrotic cells, and intact cells. Results: Early apoptosis was significantly higher in isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury when compared to both cyclosporine A treated and sham groups. Necrosis percentage was significantly higher in propofol-anesthetized animals subjected to renal ischemia-reperfusion injury. The percentage of intact cells was lower in both, isoflurane and propofol anesthetized animals subjected to renal ischemia-reperfusion injury. Conclusion: In a model of ischemia-reperfusion-induced renal injury, cyclosporine A, 5 m.kg-1, administered five minutes before renal reperfusion in rats with acute-induced hyperglycemia under either isoflurano or propofol anesthesia, attenuated early apoptosis and preserved viability in renal tubular cells, regardless of the anesthetic used.(AU)

Eficácia da ciclosporina no controle da dermatite atópica em cães

ABSTRACT: Atopic dermatitis is an itchy, chronic inflammatory skin disease of genetic origin, resulting from loss of the physical barrier function of the skin and hyper-reactivity to environmental allergens, trofoallergens, microbial allergens and to primary irritants. The efficacy of cyclosporine in the control of pruritus and lesions associated with atopic dermatitis in dogs was evaluated. Twenty-four dogs with atopic dermatitis were selected, based on Favrot et al.s criteria (2010). They were divided into two groups of 12 dogs, where Group 1 received cyclosporine (5mg/kg/vo/24h), and Group 2 was treated with prednisone (0.5mg/kg/vo/24h) in decreasing doses, both for 60 days. The animals were continuously evaluated, and theirits lesional symptomatology scores were based on a Cadesi-03 scale, set on days 0, 30 and 60. Pruritus scores of each dog, based on Rybnicek´s criteria, were weekly evaluated, from day 0 to day 63. All collected data were analyzed by the nonparametric Kruskal-Wallis´ test, followed by Dunns test, and for the analysis between the groups, considered the minimum significance level of 5%, t-test was used. Cyclosporin had similar efficacy in lesional control in the group which received prednisone on day (+30) (p 0.05) and on the day (+60) (p 0.001) of treatment, compared with day zero. A significant difference of the itching score was observed on days +28, +35, +42, +49, +56 and +63 (p 0.001), and on day +21 (p 0.01) when compared to initial treatment. However, its efficacy was lower than Group 2, from 42 days of evaluation on, keeping such difference on days +49, +56 and +63 (p>0.05). Although cyclosporin have been less effective in controlling itching, it remained at acceptable levels, and its continued use was not associated with significant side effects.

RESUMO: A dermatite atópica é uma dermatopatia inflamatória, pruriginosa, crônica, de origem genética, resultante da perda da função de barreira física da pele e da hiperreatividade à alérgenos ambientais, trofoalérgenos, alérgenos microbianos e a irritantes primários. Este estudo avaliou a eficácia da ciclosporina no controle do prurido e das lesões associadas à dermatite atópica em cães. Selecionaram-se 24 cães com diagnóstico de dermatite atópica baseados nos critérios de Favrot et al. (2010), os quais foram divididos em dois grupos de 12 cães, onde o Grupo 1, recebeu ciclosporina (5mg/kg/vo/24h), e o Grupo 2, foi tratado com prednisona (0,5mg/kg/vo/24h) em doses decrescentes, ambos por 60 dias. Os animais foram continuamente avaliados, e seus escores sintomato-lesionais, baseados na escala de CADESI-03, estabelecidos nos dias 0, 30 e 60. Em adição, os escores de prurido de cada animal, baseado nos critérios de Rybnicek, foram semanalmente avaliados, do dia 0 ao 63. Todos os dados coletados foram analisados pelo teste não paramétrico de Kruskal-Wallis, seguido do teste de Dunn´s e para as análises entre os grupos foi utilizado o teste t, considerado o nível de significância mínimo de 5%. A ciclosporina teve uma eficácia similar, no controle lesional, ao grupo que recebeu prednisona no dia (+30) (p 0,05) e no dia (+60) (p 0,001) do tratamento, em relação ao dia zero. Uma diferença significativa do escore do prurido foi observada nos dias +28, +35, +42, +49, +56 e +63 (p 0,001), e no dia +21 (p 0,01) em relação ao momento inicial do tratamento, porém sua eficácia foi inferior ao Grupo 2, a partir do 42º dia de avaliação, mantendo-se esta diferença nos dias +49, +56 e +63 (p>0,05). Apesar da ciclosporina ter sido menos eficaz no controle do prurido, este se manteve em níveis aceitáveis, e seu uso contínuo não foi associado a efeitos colaterais relevantes.

Eficácia da ciclosporina no controle da dermatite atópica em cães / Efficacy of cyclosporine in the control of atopic dermatitis in dogs

A dermatite atópica é uma dermatopatia inflamatória, pruriginosa, crônica, de origem genética, resultante da perda da função de barreira física da pele e da hiperreatividade à alérgenos ambientais, trofoalérgenos, alérgenos microbianos e a irritantes primários. Este estudo avaliou a eficácia da ciclosporina no controle do prurido e das lesões associadas à dermatite atópica em cães. Selecionaram-se 24 cães com diagnóstico de dermatite atópica baseados nos critérios de Favrot et al. (2010), os quais foram divididos em dois grupos de 12 cães, onde o Grupo 1, recebeu ciclosporina (5mg/kg/vo/24h), e o Grupo 2, foi tratado com prednisona (0,5mg/kg/vo/24h) em doses decrescentes, ambos por 60 dias. Os animais foram continuamente avaliados, e seus escores sintomato-lesionais, baseados na escala de CADESI-03, estabelecidos nos dias 0, 30 e 60. Em adição, os escores de prurido de cada animal, baseado nos critérios de Rybnicek, foram semanalmente avaliados, do dia 0 ao 63. Todos os dados coletados foram analisados pelo teste não paramétrico de Kruskal-Wallis, seguido do teste de Dunn´s e para as análises entre os grupos foi utilizado o teste t, considerado o nível de significância mínimo de 5%. A ciclosporina teve uma eficácia similar, no controle lesional, ao grupo que recebeu prednisona no dia (+30) (p<0,05) e no dia (+60) (p<0,001) do tratamento, em relação ao dia zero. Uma diferença significativa do escore do prurido foi observada nos dias +28, +35, +42, +49, +56 e +63 (p<0,001), e no dia +21 (p<0,01) em relação ao momento inicial do tratamento, porém sua eficácia foi inferior ao Grupo 2, a partir do 42º dia de avaliação, mantendo-se esta diferença nos dias +49, +56 e +63 (p>0,05). Apesar da ciclosporina ter sido menos eficaz no controle do prurido, este se manteve em níveis aceitáveis, e seu uso contínuo não foi associado a efeitos colaterais relevantes.(AU)

Atopic dermatitis is an itchy, chronic inflammatory skin disease of genetic origin, resulting from loss of the physical barrier function of the skin and hyper-reactivity to environmental allergens, trofoallergens, microbial allergens and to primary irritants. The efficacy of cyclosporine in the control of pruritus and lesions associated with atopic dermatitis in dogs was evaluated. Twenty-four dogs with atopic dermatitis were selected, based on Favrot et al.'s criteria (2010). They were divided into two groups of 12 dogs, where Group 1 received cyclosporine (5mg/kg/vo/24h), and Group 2 was treated with prednisone (0.5mg/kg/vo/24h) in decreasing doses, both for 60 days. The animals were continuously evaluated, and theirits lesional symptomatology scores were based on a Cadesi-03 scale, set on days 0, 30 and 60. Pruritus scores of each dog, based on Rybnicek´s criteria, were weekly evaluated, from day 0 to day 63. All collected data were analyzed by the nonparametric Kruskal-Wallis´ test, followed by Dunn's test, and for the analysis between the groups, considered the minimum significance level of 5%, t-test was used. Cyclosporin had similar efficacy in lesional control in the group which received prednisone on day (+30) (p<0.05) and on the day (+60) (p<0.001) of treatment, compared with day zero. A significant difference of the itching score was observed on days +28, +35, +42, +49, +56 and +63 (p<0.001), and on day +21 (p<0.01) when compared to initial treatment. However, its efficacy was lower than Group 2, from 42 days of evaluation on, keeping such difference on days +49, +56 and +63 (p>0.05). Although cyclosporin have been less effective in controlling itching, it remained at acceptable levels, and its continued use was not associated with significant side effects.(AU)

Eficácia da ciclosporina no controle da dermatite atópica em cães / Efficacy of cyclosporine in the control of atopic dermatitis in dogs

A dermatite atópica é uma dermatopatia inflamatória, pruriginosa, crônica, de origem genética, resultante da perda da função de barreira física da pele e da hiperreatividade à alérgenos ambientais, trofoalérgenos, alérgenos microbianos e a irritantes primários. Este estudo avaliou a eficácia da ciclosporina no controle do prurido e das lesões associadas à dermatite atópica em cães. Selecionaram-se 24 cães com diagnóstico de dermatite atópica baseados nos critérios de Favrot et al. (2010), os quais foram divididos em dois grupos de 12 cães, onde o Grupo 1, recebeu ciclosporina (5mg/kg/vo/24h), e o Grupo 2, foi tratado com prednisona (0,5mg/kg/vo/24h) em doses decrescentes, ambos por 60 dias. Os animais foram continuamente avaliados, e seus escores sintomato-lesionais, baseados na escala de CADESI-03, estabelecidos nos dias 0, 30 e 60. Em adição, os escores de prurido de cada animal, baseado nos critérios de Rybnicek, foram semanalmente avaliados, do dia 0 ao 63. Todos os dados coletados foram analisados pelo teste não paramétrico de Kruskal-Wallis, seguido do teste de Dunn´s e para as análises entre os grupos foi utilizado o teste t, considerado o nível de significância mínimo de 5%. A ciclosporina teve uma eficácia similar, no controle lesional, ao grupo que recebeu prednisona no dia (+30) (p<0,05) e no dia (+60) (p<0,001) do tratamento, em relação ao dia zero. Uma diferença significativa do escore do prurido foi observada nos dias +28, +35, +42, +49, +56 e +63 (p<0,001), e no dia +21 (p<0,01) em relação ao momento inicial do tratamento, porém sua eficácia foi inferior ao Grupo 2, a partir do 42º dia de avaliação, mantendo-se esta diferença nos dias +49, +56 e +63 (p>0,05). Apesar da ciclosporina ter sido menos eficaz no controle do prurido, este se manteve em níveis aceitáveis, e seu uso contínuo não foi associado a efeitos colaterais relevantes.(AU)

Atopic dermatitis is an itchy, chronic inflammatory skin disease of genetic origin, resulting from loss of the physical barrier function of the skin and hyper-reactivity to environmental allergens, trofoallergens, microbial allergens and to primary irritants. The efficacy of cyclosporine in the control of pruritus and lesions associated with atopic dermatitis in dogs was evaluated. Twenty-four dogs with atopic dermatitis were selected, based on Favrot et al.'s criteria (2010). They were divided into two groups of 12 dogs, where Group 1 received cyclosporine (5mg/kg/vo/24h), and Group 2 was treated with prednisone (0.5mg/kg/vo/24h) in decreasing doses, both for 60 days. The animals were continuously evaluated, and theirits lesional symptomatology scores were based on a Cadesi-03 scale, set on days 0, 30 and 60. Pruritus scores of each dog, based on Rybnicek´s criteria, were weekly evaluated, from day 0 to day 63. All collected data were analyzed by the nonparametric Kruskal-Wallis´ test, followed by Dunn's test, and for the analysis between the groups, considered the minimum significance level of 5%, t-test was used. Cyclosporin had similar efficacy in lesional control in the group which received prednisone on day (+30) (p<0.05) and on the day (+60) (p<0.001) of treatment, compared with day zero. A significant difference of the itching score was observed on days +28, +35, +42, +49, +56 and +63 (p<0.001), and on day +21 (p<0.01) when compared to initial treatment. However, its efficacy was lower than Group 2, from 42 days of evaluation on, keeping such difference on days +49, +56 and +63 (p>0.05). Although cyclosporin have been less effective in controlling itching, it remained at acceptable levels, and its continued use was not associated with significant side effects.(AU)

The effects of propolis on sperm quality, reproductive organs and testicular antioxidant status of male rats treated with cyclosporine-A

This study was designed to determine the effects of propolis on the quality of sperm and reproductive organs in male rats treated with cyclosporine-A. In this study, 24 male Sprague-Dawley rats (280-300 g BW) at 8-10 weeks of age were used. The rats were randomly divided into control and 3 treatment groups. Each rat was placed into a cage. During 21 days (experimental period), Group 1 served as control group; Group 2 (CsA) was given 15 mg/kg BW/day of CsA by subcutaneously; Group 3 (P) was given 100 mg/kg BW/day of propolis by gavage; Group 4 (CsA+P) was given 15 mg/kg BW/day of CsA subcutaneously and 100 mg/kg BW/day of propolis by gavage. Administration of CsA to rats decreased sperm motility (P < 0.01) and sperm concentration (P < 0.01), and it increased total abnormal sperm rates (P < 0.05) as compared with the control group. Significant improvements were observed in the sperm motility (P < 0.01) and total abnormal sperm rates (P < 0.05) in CsA+P group. No significant differences were observed in the weights of right and left testes among all groups. The weight values of right and left epididymis were found similar to each other in CsA administrated groups. Seminal vesicle (P < 0.01) and prostat glands weights (P < 0.01) were significantly higher in CsA+P group than CsA group. As a result, it was determined that oral supplementation of 100 mg/kg of propolis had amendatory effect on the quality of sperm and reproductive organs treated with CsA administered rats. CsA treatment caused a significant increase in MDA level (P < 0.01) and significant decreases (P < 0.01) in GSH level and CAT activity when compared with the control group. Ingestion of propolis by CsA-treated rats significantly decreased the MDA level and significantly increased the GSH level when compared with the CsA alone group (P < 0.01).

The effects of propolis on sperm quality, reproductive organs and testicular antioxidant status of male rats treated with cyclosporine-A

This study was designed to determine the effects of propolis on the quality of sperm and reproductive organs in male rats treated with cyclosporine-A. In this study, 24 male Sprague-Dawley rats (280-300 g BW) at 8-10 weeks of age were used. The rats were randomly divided into control and 3 treatment groups. Each rat was placed into a cage. During 21 days (experimental period), Group 1 served as control group; Group 2 (CsA) was given 15 mg/kg BW/day of CsA by subcutaneously; Group 3 (P) was given 100 mg/kg BW/day of propolis by gavage; Group 4 (CsA+P) was given 15 mg/kg BW/day of CsA subcutaneously and 100 mg/kg BW/day of propolis by gavage. Administration of CsA to rats decreased sperm motility (P < 0.01) and sperm concentration (P < 0.01), and it increased total abnormal sperm rates (P < 0.05) as compared with the control group. Significant improvements were observed in the sperm motility (P < 0.01) and total abnormal sperm rates (P < 0.05) in CsA+P group. No significant differences were observed in the weights of right and left testes among all groups. The weight values of right and left epididymis were found similar to each other in CsA administrated groups. Seminal vesicle (P < 0.01) and prostat glands weights (P < 0.01) were significantly higher in CsA+P group than CsA group. As a result, it was determined that oral supplementation of 100 mg/kg of propolis had amendatory effect on the quality of sperm and reproductive organs treated with CsA administered rats. CsA treatment caused a significant increase in MDA level (P < 0.01) and significant decreases (P < 0.01) in GSH level and CAT activity when compared with the control group. Ingestion of propolis by CsA-treated rats significantly decreased the MDA level and significantly increased the GSH level when compared with the CsA alone group (P < 0.01).(AU)