Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study

Abstract Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccouds arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position 1237 with psychosis and anemia (p 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

Resumo O receptor Toll-like 9 (TLR9) é um componente importante do sistema imunológico inato e tem sido associado a várias doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). O objetivo deste estudo foi investigar polimorfismos no gene TLR9 em um grupo de pacientes brasileiros com LES e sua associação com a manifestação clínica, particularmente a artropatia de Jaccoud (JA). Foram analisadas amostras de DNA de 204 pacientes com LES, e um subgrupo com JA (n=24). Um grupo de controle (n=133) da mesma cidade também foi incluído. Os polimorfismos de nucleotídeos únicos TLR9 (SNPs) (1237 C>T e +2848 G>A) foram identificados pela análise de sequenciamento. A frequência do genótipo genético TLR9 foi semelhante tanto em pacientes com LES quanto no grupo controle. Em toda a população de LES, foi encontrada associação entre a homozigose do alelo C na posição 1237 com psicose e anemia (p 0,01). Da mesma forma, a homozigose do alelo G na posição +2848 foi associada a uma erupção cutânea discoide (p 0,05). Não houve associação entre polimorfismos JA e TLR9. Esses dados mostram que os polimorfismos TLR9 não parecem ser um fator predisponível para o LES na população brasileira, e que os SNPs não estão associados ao JA.

Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study / Polimorfismos do receptor toll-like 9 em pacientes brasileiros com lúpus eritematoso sistêmico: um estudo piloto

Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud’s arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

O receptor Toll-like 9 (TLR9) é um componente importante do sistema imunológico inato e tem sido associado a várias doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). O objetivo deste estudo foi investigar polimorfismos no gene TLR9 em um grupo de pacientes brasileiros com LES e sua associação com a manifestação clínica, particularmente a artropatia de Jaccoud (JA). Foram analisadas amostras de DNA de 204 pacientes com LES, e um subgrupo com JA (n=24). Um grupo de controle (n=133) da mesma cidade também foi incluído. Os polimorfismos de nucleotídeos únicos TLR9 (SNPs) (−1237 C>T e +2848 G>A) foram identificados pela análise de sequenciamento. A frequência do genótipo genético TLR9 foi semelhante tanto em pacientes com LES quanto no grupo controle. Em toda a população de LES, foi encontrada associação entre a homozigose do alelo C na posição −1237 com psicose e anemia (p < 0,01). Da mesma forma, a homozigose do alelo G na posição +2848 foi associada a uma erupção cutânea discoide (p < 0,05). Não houve associação entre polimorfismos JA e TLR9. Esses dados mostram que os polimorfismos TLR9 não parecem ser um fator predisponível para o LES na população brasileira, e que os SNPs não estão associados ao JA.

Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study / Polimorfismos do receptor toll-like 9 em pacientes brasileiros com lúpus eritematoso sistêmico: um estudo piloto

Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccouds arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.(AU)

O receptor Toll-like 9 (TLR9) é um componente importante do sistema imunológico inato e tem sido associado a várias doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). O objetivo deste estudo foi investigar polimorfismos no gene TLR9 em um grupo de pacientes brasileiros com LES e sua associação com a manifestação clínica, particularmente a artropatia de Jaccoud (JA). Foram analisadas amostras de DNA de 204 pacientes com LES, e um subgrupo com JA (n=24). Um grupo de controle (n=133) da mesma cidade também foi incluído. Os polimorfismos de nucleotídeos únicos TLR9 (SNPs) (−1237 C>T e +2848 G>A) foram identificados pela análise de sequenciamento. A frequência do genótipo genético TLR9 foi semelhante tanto em pacientes com LES quanto no grupo controle. Em toda a população de LES, foi encontrada associação entre a homozigose do alelo C na posição −1237 com psicose e anemia (p < 0,01). Da mesma forma, a homozigose do alelo G na posição +2848 foi associada a uma erupção cutânea discoide (p < 0,05). Não houve associação entre polimorfismos JA e TLR9. Esses dados mostram que os polimorfismos TLR9 não parecem ser um fator predisponível para o LES na população brasileira, e que os SNPs não estão associados ao JA.(AU)

Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study / Polimorfismos do receptor toll-like 9 em pacientes brasileiros com lúpus eritematoso sistêmico: um estudo piloto

Abstract Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud's arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

Resumo O receptor Toll-like 9 (TLR9) é um componente importante do sistema imunológico inato e tem sido associado a várias doenças autoimunes, como o Lúpus Eritematoso Sistêmico (LES). O objetivo deste estudo foi investigar polimorfismos no gene TLR9 em um grupo de pacientes brasileiros com LES e sua associação com a manifestação clínica, particularmente a artropatia de Jaccoud (JA). Foram analisadas amostras de DNA de 204 pacientes com LES, e um subgrupo com JA (n=24). Um grupo de controle (n=133) da mesma cidade também foi incluído. Os polimorfismos de nucleotídeos únicos TLR9 (SNPs) (−1237 C>T e +2848 G>A) foram identificados pela análise de sequenciamento. A frequência do genótipo genético TLR9 foi semelhante tanto em pacientes com LES quanto no grupo controle. Em toda a população de LES, foi encontrada associação entre a homozigose do alelo C na posição −1237 com psicose e anemia (p < 0,01). Da mesma forma, a homozigose do alelo G na posição +2848 foi associada a uma erupção cutânea discoide (p < 0,05). Não houve associação entre polimorfismos JA e TLR9. Esses dados mostram que os polimorfismos TLR9 não parecem ser um fator predisponível para o LES na população brasileira, e que os SNPs não estão associados ao JA.

Treatment of discoid lupus erythematosus in a dog with human intravenous immunoglobulin

Background: Discoid lupus erythematosus (DLE) is a common canine autoimmune skin disease, in which systemic manifestations are absent. Skin Lesions are usually present on the nasal planum, and characterised by erythema, depigmentation, erosion, ulceration, and crusting. The diagnosis is based on histopathological results, which should demonstrate lymphoplasmacytic lichenoid-interface dermatitis. Human intravenous immunoglobulin (hIVIg) has been used in veterinary medicine to treat cutaneous diseases including erythema multiforme, PF, and severe adverse cutaneous drug reactions. In human medicine, it has been effective to treat DLE. This report firstly describes the clinical response to hIVIg in a dog with DLE resistant to common immunosuppressive drugs. Case: A 5-year-old, intact female Shih Tzu presented with a 1-month history of slowly progressive black crusting on the nasal planum, chin, and claw. Based on the results of a dermatologic examination, superficial pyoderma was diagnosed. The skin lesions did not improve during and after anti-infective treatment. After removing the crusts, a skin biopsy was obtained from the muzzle. Histopathology of lesional skin biopsy specimens revealed lymphoplasmacytic interface dermatitis at the dermoepidermal junction. Microscopic examination also revealed vacuolar changes and pigmentary incontinence of the basal layer as a lichenoid tissue reaction. No mites or fungi were detected on the skin section. The absence of acantholytic cells excluded pemphigus foliaceus, which is also characterised by the lesions of the nasal planum. Based on the distribution of the lesions, histopathology and exclusion of other dermatoses, the dog was diagnosed with DLE. The skin lesions temporarily improved after treatment with prednisolone (2 mg/kg PO q12h). However, after tapering the dose of prednisolone, new black crusts developed on the nasal planum and claw. Although the dog was successively treated with other immunosuppressive drugs, including azathioprine, cyclosporin with dexamethasone, and mycophenolate mofetil, black crusts still remained. Due to the low efficacy of these immunosuppressive drugs, hIVIg was administered at 0.5 g/kg once daily for 4 days, for a total dose of 2 g/kg. During hIVIg administration, the crusted lesions gradually improved. After the hIVIg administration, the dog was treated with prednisolone (1 mg/kg PO q12h). The lesions were almost in complete remission at 21 days after an additional application of prednisolone. The skin lesions did not recur, and the treatment was eventually discontinued after 6 weeks of additional prednisolone application. Discussion: The standard treatment of canine DLE includes glucocorticoids, and second-line immunosuppressive drugs, such as azathioprine and cyclosporine, are usually added in cases resistant to steroids. This case suggests that hIVIg may be beneficial as an adjunctive treatment option for canine DLE, especially when the application of standard immunosuppressive drugs is limited due to adverse effects or low efficacy. There is evidence from several studies that the steroid-sparing effect of hIVIg is significant in human patients. In the current case, the effective dose of prednisolone was reduced to 2 mg/kg/day after hIVIg administration, and prednisolone therapy was finally discontinued completely. The hIVIg appears to lower the daily steroid dose requirement in this dog.

Pemphigus foliaceous in a dog - clinical and laboratorial assessment

Background: The pemphigus complex is defined as a group of blistering autoimmune diseases that affects skin and mucous membrane. Pemphigus foliaceous is the most common disease in this group, being characterized by the productionof autoantibodies against keratinocyte adhesion molecules. The treatment is based on the use of immunosuppressive drugsand requires constant monitoring to assess inflammatory control as well as side effects of therapy. Based on that, the aimof this study was to report the clinical and laboratorial follow-up of a canine with pemphigus foliaceous.Case: An 11-year-old male neutered mongrel dog, weighing 9.8 kg, was presented with a main complaint related to disseminated pruritus and lesions in face, trunk and limbs. Dermatological examination revealed meliceric crusts, epidermalcollars and diffuse pustules in inguinal, abdominal, face, limbs, ears and thoraco-lumbar regions. Cytological examinationwas performed, revealing inflammatory and acantholytic cells and absence of bacterial cells. Biopsy procedure revealedsubcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatible with canine pemphigusfoliaceous. Hemato-biochemical analysis revealed a leukocytosis due to increased neutrophil count. Systemic treatmentwith high dose of prednisolone (2.0 mg/kg) and azathioprine (2.5 mg/kg) was proposed, while topical therapy with a 3%chlorhexidine shampoo was used to prevent secondary bacterial infections. The patient improved the dermatological clinicalsigns, being possible to observe a reduction of systemic and tissue inflammatory process. After 90 days of therapy, therewas a partial loss of hair body coverage, associated with follicular lesions, and after 180 days of therapy it was possibleto notice a new hair mantle, without visible areas of inflammation...

Pemphigus foliaceous in a dog - clinical and laboratorial assessment

Background: The pemphigus complex is defined as a group of blistering autoimmune diseases that affects skin and mucous membrane. Pemphigus foliaceous is the most common disease in this group, being characterized by the productionof autoantibodies against keratinocyte adhesion molecules. The treatment is based on the use of immunosuppressive drugsand requires constant monitoring to assess inflammatory control as well as side effects of therapy. Based on that, the aimof this study was to report the clinical and laboratorial follow-up of a canine with pemphigus foliaceous.Case: An 11-year-old male neutered mongrel dog, weighing 9.8 kg, was presented with a main complaint related to disseminated pruritus and lesions in face, trunk and limbs. Dermatological examination revealed meliceric crusts, epidermalcollars and diffuse pustules in inguinal, abdominal, face, limbs, ears and thoraco-lumbar regions. Cytological examinationwas performed, revealing inflammatory and acantholytic cells and absence of bacterial cells. Biopsy procedure revealedsubcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatible with canine pemphigusfoliaceous. Hemato-biochemical analysis revealed a leukocytosis due to increased neutrophil count. Systemic treatmentwith high dose of prednisolone (2.0 mg/kg) and azathioprine (2.5 mg/kg) was proposed, while topical therapy with a 3%chlorhexidine shampoo was used to prevent secondary bacterial infections. The patient improved the dermatological clinicalsigns, being possible to observe a reduction of systemic and tissue inflammatory process. After 90 days of therapy, therewas a partial loss of hair body coverage, associated with follicular lesions, and after 180 days of therapy it was possibleto notice a new hair mantle, without visible areas of inflammation...(AU)

Frequência das doenças de pele não tumorais em cães no município de João Pessoa, Paraíba, Brasil (2014-2016) / [Frequency of non tumor skin diseases in dogs in the city of João Pessoa, Paraíba, Brazil (2014-2016)]

Diante da carência de estudos sobre a frequência de dermatopatias que acometem cães por região geográfica no Brasil, o presente estudo objetivou conhecer a frequência das principais doenças cutâneas que afetam cães na região metropolitana de João Pessoa, Paraíba, Brasil. Os dados foram coletados de cães que passaram por atendimento dermatológico no período de setembro de 2014 a dezembro de 2016. Além dos exames clínicos e dermatológicos os cães foram submetidos a exames complementares (citológico, raspado de pele, parasitológico, tricograma, bacteriológico, micológico, histopatológico e molecular). No período do estudo, foram atendidos 1.083 cães, em que 18,65% (202/1.083) apresentavam algum tipo de dermatopatia não tumoral. Dos 202 cães acometidos, 51,49% (104/202) eram machos e 48,51% (98/202), fêmeas. Desses 202 cães, 13 tinham dois diagnósticos, totalizando 215 dermatopatias. Dos cães afetados, 62,87% (127/202) eram de raça definida e 37,13% (75/202), sem raça definida (SRD). As lesões observadas com mais frequência caracterizaram-se por áreas alopécicas, hipotricoicas, maculosas, erosivas e ulcerativas, placoides, eritematosas, assim como comedões, colaretes, seborreia. As dermatopatias parasitárias foram as mais frequentes (35,35%; 76/215), seguidas pelas dermatopatias bacterianas (24,19%; 52/215), dermatopatias alérgicas (20,00%; 43/215), dermatopatias fúngicas (17,21%; 37/215), dermatopatias por outras causas (2,32%; 5/215) e pelas dermatopatias autoimunes (0,93%; 2/215). Os exames físicos e dermatológicos, incluindo anamnese detalhada, histórico clínico apurado, associado a exames complementares, são ferramentas importantes para o diagnóstico das dermatopatias em cães. Presume-se que a frequência de dermatopatias em cães na região de estudo possa ser maior do que a observada.(AU)

Faced with the lack of studies on the frequency of dermatopathies that affect dogs by geographical region in Brazil, the present study aimed to evaluate the frequency of dermatopathies that affect the canine species in the metropolitan region of João Pessoa, Paraíba, Brazil. Data was collected from dogs that underwent dermatological care from September 2014 to December 2016. In addition to the clinical and dermatological examinations, dogs underwent complementary exams, such as cytological, skin scraping, parasitological skin examination, trichogram, bacteriological, mycological, histopathological and/or polymerase chain reaction. During the study period, 1,083 dogs were examined, in which 18.65% (202 /1,083) had some form of non-tumoral dermatopathy. Of the 202 dogs affected, 51.49% (104/202) were males and 48.51% (98/202) females. Of these 202 dogs, thirteen had two diagnoses, totaling 215 dermatopathies. 62.87% (127/202) of the affected dogs were purebred and 37.13% (75/202) were without a defined breed (WDB). The most frequently observed lesions were alopecia, hypotric, macular, erosive and ulcerative, placoid, erythematous areas, as well as comedones, collaretes and seborrhoea. The parasitic dermatopathies were the most frequent (35.35%; 76/215), followed by bacterial dermatopathies (24,19%; 52/215), allergic dermatopathies (20,00%; 43/215), dermatomycosis (17,21%; 37/215), dermatopathies for other causes (2,32%; 5/215) and autoimmune dermatopathies (0.93%; 2/215). Clinical and dermatological examination, including a detailed anamnesis, accurate clinical history and associated complementary exams are important tools for the diagnosis of dermatopathies in dogs. Available literature present some studies with canine dermatopathies frequencies superior to that obtained in the present study; however, the number of animals examined was smaller. In this survey, it was possible to establish the primary and secondary diagnoses in 100.0% of the non-tumoral dermatopathies in dogs, results higher than in previous studies. Probably, the frequency of canine dermatopathies in this region is higher than that observed, thus requiring additional studies with greater sampling.(AU)

Frequência das doenças de pele não tumorais em cães no município de João Pessoa, Paraíba, Brasil (2014-2016) / [Frequency of non tumor skin diseases in dogs in the city of João Pessoa, Paraíba, Brazil (2014-2016)]

Diante da carência de estudos sobre a frequência de dermatopatias que acometem cães por região geográfica no Brasil, o presente estudo objetivou conhecer a frequência das principais doenças cutâneas que afetam cães na região metropolitana de João Pessoa, Paraíba, Brasil. Os dados foram coletados de cães que passaram por atendimento dermatológico no período de setembro de 2014 a dezembro de 2016. Além dos exames clínicos e dermatológicos os cães foram submetidos a exames complementares (citológico, raspado de pele, parasitológico, tricograma, bacteriológico, micológico, histopatológico e molecular). No período do estudo, foram atendidos 1.083 cães, em que 18,65% (202/1.083) apresentavam algum tipo de dermatopatia não tumoral. Dos 202 cães acometidos, 51,49% (104/202) eram machos e 48,51% (98/202), fêmeas. Desses 202 cães, 13 tinham dois diagnósticos, totalizando 215 dermatopatias. Dos cães afetados, 62,87% (127/202) eram de raça definida e 37,13% (75/202), sem raça definida (SRD). As lesões observadas com mais frequência caracterizaram-se por áreas alopécicas, hipotricoicas, maculosas, erosivas e ulcerativas, placoides, eritematosas, assim como comedões, colaretes, seborreia. As dermatopatias parasitárias foram as mais frequentes (35,35%; 76/215), seguidas pelas dermatopatias bacterianas (24,19%; 52/215), dermatopatias alérgicas (20,00%; 43/215), dermatopatias fúngicas (17,21%; 37/215), dermatopatias por outras causas (2,32%; 5/215) e pelas dermatopatias autoimunes (0,93%; 2/215). Os exames físicos e dermatológicos, incluindo anamnese detalhada, histórico clínico apurado, associado a exames complementares, são ferramentas importantes para o diagnóstico das dermatopatias em cães. Presume-se que a frequência de dermatopatias em cães na região de estudo possa ser maior do que a observada.(AU)

Faced with the lack of studies on the frequency of dermatopathies that affect dogs by geographical region in Brazil, the present study aimed to evaluate the frequency of dermatopathies that affect the canine species in the metropolitan region of João Pessoa, Paraíba, Brazil. Data was collected from dogs that underwent dermatological care from September 2014 to December 2016. In addition to the clinical and dermatological examinations, dogs underwent complementary exams, such as cytological, skin scraping, parasitological skin examination, trichogram, bacteriological, mycological, histopathological and/or polymerase chain reaction. During the study period, 1,083 dogs were examined, in which 18.65% (202 /1,083) had some form of non-tumoral dermatopathy. Of the 202 dogs affected, 51.49% (104/202) were males and 48.51% (98/202) females. Of these 202 dogs, thirteen had two diagnoses, totaling 215 dermatopathies. 62.87% (127/202) of the affected dogs were purebred and 37.13% (75/202) were without a defined breed (WDB). The most frequently observed lesions were alopecia, hypotric, macular, erosive and ulcerative, placoid, erythematous areas, as well as comedones, collaretes and seborrhoea. The parasitic dermatopathies were the most frequent (35.35%; 76/215), followed by bacterial dermatopathies (24,19%; 52/215), allergic dermatopathies (20,00%; 43/215), dermatomycosis (17,21%; 37/215), dermatopathies for other causes (2,32%; 5/215) and autoimmune dermatopathies (0.93%; 2/215). Clinical and dermatological examination, including a detailed anamnesis, accurate clinical history and associated complementary exams are important tools for the diagnosis of dermatopathies in dogs. Available literature present some studies with canine dermatopathies frequencies superior to that obtained in the present study; however, the number of animals examined was smaller. In this survey, it was possible to establish the primary and secondary diagnoses in 100.0% of the non-tumoral dermatopathies in dogs, results higher than in previous studies. Probably, the frequency of canine dermatopathies in this region is higher than that observed, thus requiring additional studies with greater sampling.(AU)

Pemphigus foliaceus in a sheep / Pênfigo foliáceo em uma ovelha

Pemphigus foliaceus (PF) is an autoimmune disease of the skin and is the most common form of pemphigus in domestic animals. This work reports a case of pemphigus foliaceus in a Santa Inês hair sheep. The ewe presented with multifocal bilateral crusted alopecic dermatitis affecting the chest, abdomen, and pelvic and thoracic limbs. Parakeratotic hyperkeratosis and acanthosis, in addition to subcorneal pustules, were observed histologically, and acantholytic cells and neutrophils were observed within the pustules. In the superficial and deep dermal tissues, there was intense eosinophilic infiltration and the presence of rare macrophages. These microscopic findings were characteristic of PF, and treatment with dexamethasone was ineffective. This disease is rare in sheep, and this is the first case report to be published in Brazil.(AU)

Pênfigo foliáceo (PF) é uma doença autoimune da pele e é a forma mais comum de pênfigo em animaisdomésticos. Este trabalho relata um caso de pênfigo foliáceo em uma ovelha Santa Inês. A ovelhaapresentava dermatite alopécica crostosa bilateral e assimétrica no tórax, abdômen, e membros pélvicose torácicos. Hiperceratose paraqueratótica e acantose, além de pústulas subcorneais, foram observadoshistologicamente, e células acantolíticas e neutrófilos foram observadas dentro das pústulas. Naderme superficial e profunda, havia intenso infiltrado de eosinófilos e raros macrófagos. Os achadosmicroscópicos são característicos de PF, e o tratamento com dexametasona foi ineficiente. Esta doençaé rara em ovinos e este é o primeiro relato de caso a ser publicado no Brasil.(AU)

Mupirocin pemphigus-like drug reaction in a dog

Background: Pharmacodermia is defined as adverse reaction in skin, mucosa and appendages, which generates morphofunctional alterations in cutaneous barrier, inducing autoimmune diseases, such as pemphigus foliaceous, which is known asthe most common autoimmune skin disease in dogs. This disease involves autoantibodies against desmoglein and desmocolinmolecules, being induced by the use of certain drugs. Mupirocin (pseudomonic acid A) is a broad-spectrum antibiotic withbacteriostatic activity, being effective against Gram-positive pathogens and used to control superficial bacterial folliculitis.Based on that, the aim of this study was to report a pemphigus-like lesions after topical use of mupirocin in dog.Case: An 1-year-old, uncastrated male, Poodle dog, weighing 13.8 kg was treated in a private clinic in Fortaleza. The maincomplaint was related to pruritus in abdominal and inguinal region, in addition of legs licking. Dermatological examination revealed melanic crusts, epidermal collars and diffuse pustules in inguinal, abdominal, perianal and thoraco-lumbarregions. The therapy was based on topical use of Mupirocin in form of 0.2% aquous spray. After drug administration, theanimal presented urticaria, diffuse epidermal collars, papulo-crusted and pustular lesions, which were more evident inabdominal and inguinal region. Nasal erythema, binocular blepharitis, apathy and fever were also observed. Cytologicalexamination and bacterial culture were performed, revealing inflammatory and acantholytic cells and no bacterial growth.Biopsy procedure revealed subcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatiblewith canine pemphigus foliaceous. The topical treatment of ocular lesions with 0.1% Tacrolimus associated with systemictreatment with high dose of prednisolone (1.2 mg kg-1)...

Mupirocin pemphigus-like drug reaction in a dog

Background: Pharmacodermia is defined as adverse reaction in skin, mucosa and appendages, which generates morphofunctional alterations in cutaneous barrier, inducing autoimmune diseases, such as pemphigus foliaceous, which is known asthe most common autoimmune skin disease in dogs. This disease involves autoantibodies against desmoglein and desmocolinmolecules, being induced by the use of certain drugs. Mupirocin (pseudomonic acid A) is a broad-spectrum antibiotic withbacteriostatic activity, being effective against Gram-positive pathogens and used to control superficial bacterial folliculitis.Based on that, the aim of this study was to report a pemphigus-like lesions after topical use of mupirocin in dog.Case: An 1-year-old, uncastrated male, Poodle dog, weighing 13.8 kg was treated in a private clinic in Fortaleza. The maincomplaint was related to pruritus in abdominal and inguinal region, in addition of legs licking. Dermatological examination revealed melanic crusts, epidermal collars and diffuse pustules in inguinal, abdominal, perianal and thoraco-lumbarregions. The therapy was based on topical use of Mupirocin in form of 0.2% aquous spray. After drug administration, theanimal presented urticaria, diffuse epidermal collars, papulo-crusted and pustular lesions, which were more evident inabdominal and inguinal region. Nasal erythema, binocular blepharitis, apathy and fever were also observed. Cytologicalexamination and bacterial culture were performed, revealing inflammatory and acantholytic cells and no bacterial growth.Biopsy procedure revealed subcorneal pustule with presence of epithelial acantholytic cells and neutrophils, compatiblewith canine pemphigus foliaceous. The topical treatment of ocular lesions with 0.1% Tacrolimus associated with systemictreatment with high dose of prednisolone (1.2 mg kg-1)...(AU)

Canine sporotrichosis: report of 15 advanced cases / Esporotricose canina: descrição de 15 casos avançados

Sporotrichosis is a chronic, granulomatous and usually lymphocutaneous infection of animals and humans, caused by a dimorphic fungus, Sporothrix schenckii complex. The disease in dogs is considered rare, however, in the last years a crescent registration of cases was observed in Brazil, especially in the city of Rio de Janeiro. Fifteen dogs with ulcerated cutaneous lesions were seen at the Dermatology Service in the Small Animal's Hospital at Universidade Federal Rural do Rio de Janeiro, between January 2014 and October 2015. Most lesions were located on the head, mainly the nose. Lesions were even seen on the chest, disseminated on the body and on the limbs. Three dogs (20%) exhibited the cutaneous-lymphatic form, with lesions initially on the distal aspect of one leg and ascending via lymphatics up the leg to the trunk and head. It was not ruled out the disseminated form in at least 3 dogs (20%). They had consistent signs of generalized or disseminated disease exhibiting respiratory symptoms (nasal discharge, sneezing, stertorous breathing), anorexia and weight loss. Draining tracts and cellulitis were very common. Some had large areas of skin necrosis with exposure of muscle and bone. Definitive diagnosis was obtained by cytological examination of exudates, histological examination, and/or isolation of S. schenckii complex by fungal culture. Because of the severity of the lesions that mimic other disorders like neoplasms or autoimmune skin diseases, and due to the difficulties of getting an accurate diagnosis, this study describes 15 advanced cases of canine sporotrichosis.(AU)

A esporitricose é uma doença infecciosa crônica, granulomatosa e frequentemente linfocutânea, causada por um fungo dimórfico do Complexo Sporothrix schenckii. A doença em cães é considerada rara, no entanto, nos últimos anos, um número crescente de casos foi registrado no Brasil, especialmente no Rio de Janeiro. Quinze cães com lesões cutâneas ulceradas foram atendidos no Setor de Dermatologia do Hospital Veterinário de Pequenos Animais da Universidade Federal Rural do Rio de Janeiro, entre Janeiro de 2014 e Outubro de 2015. Todos os animais foram submetidos ao exame clínico e dermatológico. A maioria das lesões estava localizada na cabeça, principalmente no plano nasal. Havia também lesões no tórax, disseminada pelo corpo e nos membros. Três cães (20%) apresentaram a forma cutâneo-linfática, com lesões inicialmente nos membros e se propagavam via vasos linfáticos para o tronco e a cabeça. Não foi descartada a forma disseminada em pelo menos 3 cães (20%). Estes cães apresentaram sinais consistentes de doença generalizada ou disseminada, exibindo sinais respiratórios (descarga nasal, espirros, estertoração), anorexia e perda de peso. Fístulas e celulite eram muito comuns. Alguns tinham grandes áreas de necrose que desencadearam a exposição de músculo e osso. O diagnóstico definitivo da infecção foi obtido por exame citológico de exsudato e por exame histológico, e/ou apenas isolamento do complexo S. schenckii pela cultura de fungos. Por causa da severidade das lesões que imitam outras enfermidades, principalmente neoplasias e doenças autoimunes, e pela dificuldade de se obter o diagnóstico correto, este estudo descreve 15 casos avançados de esporotricose canina.(AU)

Canine sporotrichosis: report of 15 advanced cases / Esporotricose canina: descrição de 15 casos avançados

Sporotrichosis is a chronic, granulomatous and usually lymphocutaneous infection of animals and humans, caused by a dimorphic fungus, Sporothrix schenckii complex. The disease in dogs is considered rare, however, in the last years a crescent registration of cases was observed in Brazil, especially in the city of Rio de Janeiro. Fifteen dogs with ulcerated cutaneous lesions were seen at the Dermatology Service in the Small Animal's Hospital at Universidade Federal Rural do Rio de Janeiro, between January 2014 and October 2015. Most lesions were located on the head, mainly the nose. Lesions were even seen on the chest, disseminated on the body and on the limbs. Three dogs (20%) exhibited the cutaneous-lymphatic form, with lesions initially on the distal aspect of one leg and ascending via lymphatics up the leg to the trunk and head. It was not ruled out the disseminated form in at least 3 dogs (20%). They had consistent signs of generalized or disseminated disease exhibiting respiratory symptoms (nasal discharge, sneezing, stertorous breathing), anorexia and weight loss. Draining tracts and cellulitis were very common. Some had large areas of skin necrosis with exposure of muscle and bone. Definitive diagnosis was obtained by cytological examination of exudates, histological examination, and/or isolation of S. schenckii complex by fungal culture. Because of the severity of the lesions that mimic other disorders like neoplasms or autoimmune skin diseases, and due to the difficulties of getting an accurate diagnosis, this study describes 15 advanced cases of canine sporotrichosis.(AU)

A esporitricose é uma doença infecciosa crônica, granulomatosa e frequentemente linfocutânea, causada por um fungo dimórfico do Complexo Sporothrix schenckii. A doença em cães é considerada rara, no entanto, nos últimos anos, um número crescente de casos foi registrado no Brasil, especialmente no Rio de Janeiro. Quinze cães com lesões cutâneas ulceradas foram atendidos no Setor de Dermatologia do Hospital Veterinário de Pequenos Animais da Universidade Federal Rural do Rio de Janeiro, entre Janeiro de 2014 e Outubro de 2015. Todos os animais foram submetidos ao exame clínico e dermatológico. A maioria das lesões estava localizada na cabeça, principalmente no plano nasal. Havia também lesões no tórax, disseminada pelo corpo e nos membros. Três cães (20%) apresentaram a forma cutâneo-linfática, com lesões inicialmente nos membros e se propagavam via vasos linfáticos para o tronco e a cabeça. Não foi descartada a forma disseminada em pelo menos 3 cães (20%). Estes cães apresentaram sinais consistentes de doença generalizada ou disseminada, exibindo sinais respiratórios (descarga nasal, espirros, estertoração), anorexia e perda de peso. Fístulas e celulite eram muito comuns. Alguns tinham grandes áreas de necrose que desencadearam a exposição de músculo e osso. O diagnóstico definitivo da infecção foi obtido por exame citológico de exsudato e por exame histológico, e/ou apenas isolamento do complexo S. schenckii pela cultura de fungos. Por causa da severidade das lesões que imitam outras enfermidades, principalmente neoplasias e doenças autoimunes, e pela dificuldade de se obter o diagnóstico correto, este estudo descreve 15 casos avançados de esporotricose canina.(AU)

Comparative study of direct and indirect immunofluorescence for diagnosis of canine pemphigus foliaceus / Estudo comparativo da imunofluorescência direta e indireta para o diagnóstico do pênfigo foliáceo canino

Pemphigus foliaceus (PF) is the most common autoimmune skin disease in dogs. It is characterized by pustules, erosions, and crusts which occur due to the presence of autoantibodies that target intercellular adhesion. Histopathological examination is considered the gold standard pattern in the diagnosis, but may sometimes be inconclusive, especially when the characteristic findings are not identified. New diagnostic tests are continuously being developed and immunofluorescence assays, could be a valuable alternative diagnostic tool. This study aimed to evaluate the applicability of direct and indirect immunofluorescence (DIF and IIF) tests for the diagnosis of canine PF. Twenty eight dogs were divided into two groups: Group I with 14 dogs with PF and Group II (control) with 14 dogs with Superficial pyoderma (differential diagnoses of PF). All animals were submitted to skin biopsy to histopathological and DIF. Blood samples were collected to assess IIF. Comparing the DIF results against the histopathology test, there was an agreement of 75% (9/12) with a Kappa index of 0.77 (P<0.001). Considering IIF, the agreement was 100% (14/14), with a Kappa index of 1.0 (P<0.001). We conclude that DIF and IIF are highly effective and were useful and effective complementary examination tests for an improvement in the diagnosis of canine PF.(AU)

O pênfigo foliáceo (PF) é considerado uma das doenças tegumentares autoimunes mais frequentes em cães. Clinicamente, caracteriza-se pela presença de pústulas, erosões e crostas. O exame histopatológico é considerado o teste diagnóstico de eleição, porém pode se mostrar inconclusivo, sobretudo quando os achados característicos da doença não são observados. Novas ferramentas diagnósticas têm sido desenvolvidas e os testes de imunofluorecência são uma valiosa alternativa. Este estudo teve como objetivo avaliar a aplicabilidade das reações de imunofluorescência direta (IFD) e indireta (IFI) para o diagnóstico do PF canino. Vinte e oito cães foram divididos em dois grupos: grupo I com 14 cães com PF e grupo II (controle) com 14 cães com piodermite superficial (um dos principais diagnósticos diferenciais do PF). Todos os animais foram submetidos à biópsia cutânea, seguida de exame histopatológico e IFD. Amostras de sangue foram coletadas para realização da IFI. Comparando-se os valores de IFD com o histopatológico, obtiveram-se valores de concordância de 75% (9/12), com índice Kappa de 0,77 (P<0,001). Já na IFI, a concordância foi de 100% (14/14), com índice Kappa de 1,0 (P<0,001). Concluiu-se, então, que a IFD e a IFI apresentaram excelentes resultados e podem ser consideradas novas alternativas diagnósticas do PF canino.(AU)

Comparative study of direct and indirect immunofluorescence for diagnosis of canine pemphigus foliaceus / Estudo comparativo da imunofluorescência direta e indireta para o diagnóstico do pênfigo foliáceo canino

Pemphigus foliaceus (PF) is the most common autoimmune skin disease in dogs. It is characterized by pustules, erosions, and crusts which occur due to the presence of autoantibodies that target intercellular adhesion. Histopathological examination is considered the gold standard pattern in the diagnosis, but may sometimes be inconclusive, especially when the characteristic findings are not identified. New diagnostic tests are continuously being developed and immunofluorescence assays, could be a valuable alternative diagnostic tool. This study aimed to evaluate the applicability of direct and indirect immunofluorescence (DIF and IIF) tests for the diagnosis of canine PF. Twenty eight dogs were divided into two groups: Group I with 14 dogs with PF and Group II (control) with 14 dogs with Superficial pyoderma (differential diagnoses of PF). All animals were submitted to skin biopsy to histopathological and DIF. Blood samples were collected to assess IIF. Comparing the DIF results against the histopathology test, there was an agreement of 75% (9/12) with a Kappa index of 0.77 (P<0.001). Considering IIF, the agreement was 100% (14/14), with a Kappa index of 1.0 (P<0.001). We conclude that DIF and IIF are highly effective and were useful and effective complementary examination tests for an improvement in the diagnosis of canine PF.(AU)

O pênfigo foliáceo (PF) é considerado uma das doenças tegumentares autoimunes mais frequentes em cães. Clinicamente, caracteriza-se pela presença de pústulas, erosões e crostas. O exame histopatológico é considerado o teste diagnóstico de eleição, porém pode se mostrar inconclusivo, sobretudo quando os achados característicos da doença não são observados. Novas ferramentas diagnósticas têm sido desenvolvidas e os testes de imunofluorecência são uma valiosa alternativa. Este estudo teve como objetivo avaliar a aplicabilidade das reações de imunofluorescência direta (IFD) e indireta (IFI) para o diagnóstico do PF canino. Vinte e oito cães foram divididos em dois grupos: grupo I com 14 cães com PF e grupo II (controle) com 14 cães com piodermite superficial (um dos principais diagnósticos diferenciais do PF). Todos os animais foram submetidos à biópsia cutânea, seguida de exame histopatológico e IFD. Amostras de sangue foram coletadas para realização da IFI. Comparando-se os valores de IFD com o histopatológico, obtiveram-se valores de concordância de 75% (9/12), com índice Kappa de 0,77 (P<0,001). Já na IFI, a concordância foi de 100% (14/14), com índice Kappa de 1,0 (P<0,001). Concluiu-se, então, que a IFD e a IFI apresentaram excelentes resultados e podem ser consideradas novas alternativas diagnósticas do PF canino.(AU)

TRANSPLANTE DE CÉLULAS-TRONCO MESENQUIMAIS ALOGÊNICAS EM CÃES COM MENINGOENCEFALOMIELITE DE ORIGEM DESCONHECIDA

A meningoencefalomielite de origem desconhecida (MUO) canina é uma doença neuroinflamatória de provável origem imunomediada, altamente debilitante, que apresenta prognostico desfavorável e falha terapêutica com o uso de imunossupressores. As células-tronco mesenquimais (MSCs) são promissoras para o tratamento de doenças neuroimunes, porém, diferentes fontes podem apresentar variações no potencial imunomodulador e neuroprotetor. In vitro, avaliamos a expressão gênica de BDNF, GDNF, HGF, IDO, IL-10 e PTGES2 e o perfil secretório de IL-2, IL-6, IL-8, IL-10, GM-CSF e MCP-1 de MSCs caninas derivadas do tecido adiposo (Ad-MSCs) e placenta (PMSCs) após estimulação única com INF- e combinada com INF- com TNF-. In vivo, avaliamos a resposta terapêutica ao transplante de Ad-MSCs alogênicas em cães com MUO que apresentaram falha terapêutica ao tratamento imunossupressor. Grupo PAC: 12 cães com MUO tratados com o protocolo imunossupressor de citarabina (ara-C) e prednisona. Grupo cMSC: Cinco cães que apresentaram falha terapêutica tratados com dois transplantes de 2,5x106 Ad-MSCs pela via intratecal (IT) (totalizando seis transplantes) ou intravenosa (IV) (totalizando três transplantes), com intervalo de 40 dias. Avaliamos a recuperação funcional, redução das lesões inflamatórias por ressonância magnética (RM) e líquido cefalorraquidiano (LCR). In vitro, observamos aumento significativo na expressão de BDNF, GDNF, HGF e IDO pelas Ad-MSCs após as estimulações, e na expressão de IDO pelas PMSCs após a estimulação combinada. Houve tendência a maior expressão de IL-10 nas células estimuladas de ambas fontes. Houve aumento significativo na secreção de IL-6 pelas Ad-MSCs e de IL-8 pelas PMSCs após estimulação. In vivo, houve tendência a melhora funcional e dos parâmetros inflamatórios no LCR em ambos grupos, indicando efeitos positivos. No grupo cMSC, a maioria dos cães teve remissão parcial e eventos adversos leves foram observados em 4/6 animais após transplantes IT, sendo ausentes pela via IV. Todos os cães do grupo PAC desenvolveram efeitos adversos. Não houve diferenças significativas nas variáveis de hemograma e bioquímica dentro e entre os grupos. O transplante de Ad-MSCs alogênicas em cães com MUO demonstrou efeitos benéficos

Canine meningoencephalomyelitis of unknown origin (MUO) is an immune-mediated neuroinflammatory disease, highly debilitating, with poor prognosis and therapeutic failure. Mesenchymal stem cells (MSCs) are promising for the treatment of neuroimmune diseases. Different sources may present differences in the immunomodulatory/neuroprotective potential. In vitro, we evaluated the gene expression of BDNF, GDNF, HGF, IDO, IL-10 and PTGES2 and the secretory profile of IL-2, IL-6, IL-18, IL-10, GM-CSF and MCP- 1 of canine MSCs derived from adipose tissue (Ad-MSCs) and placenta (PMSCs) after priming with the pro-inflammatory cytokines INF- alone and combined INF- and TNF-. In vivo, we evaluated the clinical response to allogeneic Ad-MSCs transplantation in dogs with MUO. PAC group: 12 dogs treated with immunosuppressant cytarabine (ara-C) and prednisone. cMSC group: 5 dogs of PAC group with therapeutic failure were treated with 2.5x106/kg Ad-MSCs by intrathecal (IT) (n = 6) or intravenous (IV) (n = 3) delivery routes (40 days of interval). Functional recovery and the reduction of inflammatory lesions by magnetic resonance imaging (MR) and cerebrospinal fluid (CSF) were evaluated. In vitro, there was significant increase of BDNF, GDNF, HGF and IDO expression by Ad-MSCs after priming and expression of IDO after combined priming by PMSCs. Ad-MSCs had a significant increase in the secretion of IL-6 and PMSCs of IL-8 after priming. In vivo, a trend towards functional improvement was observed in both groups after treatment. In the cMSC group, most dogs had partial remission and mild adverse events were observed in 4/6 animals after IT transplantations, being absent by IV. Clinical and laboratory variables showed no statistical differences. Allogeneic Ad-MSCs transplantation demonstrated beneficial effects in dogs with MUO.

Papel dos linfócitos B-1 na imunopatogênese do Lúpus eritematoso sistêmico

O Lúpus eritematoso sistêmico (LES) é uma doença autoimune crônica que acomete cães, gatos, cavalos, humanos e primatas. A patogênese é multifatorial, estando associado a fatores genéticos, hormonais e ambientais. O LES leva a deposição de complexos imunes em articulações e diversos órgãos resultando em manifestações clínicas. A participação dos linfócitos T e B é crucial para a patogênese da doença. Linfócitos B-1, uma subpopulação de células B, possuem características que podem contribuir com a patogênese de doenças autoimunes pois são capazes de secretar citocinas como IL-10 exercendo uma ação moduladora tanto da resposta inflamatória aguda como crônica, apresentam antígenos as células T, participam da imunidade inata e adaptativa e são as principais produtoras de anticorpos naturais. O entendimento do papel das células B-1 na imunopatogênese do LES pode abrir frentes de estudos sobre estratégias de imunoterapias que possibilitem o controle dessa doença complexa e multifatorial. O presente trabalho avaliou o papel das células B-1 na imunopatogênese do LES utilizando o modelo de indução pelo pristane. LES foi induzido em camundongos fêmeas BALB/c, XID (deficientes em B-1) e XID repopulados com B-1. Os animais foram avaliados por seis meses. Verificamos que, BALB/c pristane e XID repopulados com B-1 apresentaram sinais característicos da doença como, formação de lipogranulomas e esplenomegalia. Em destaque, BALB/c pristane também apresentou ascite, edema articular, artrite, lesão renal com deposição de imunocomplexo. No baço, os animais que apresentam B-1 tiveram maior porcentagem de células B (CD19+, IgM+), BALB/c pristane de TCD8 (CD3+, CD8+), enquanto XID pristane teve aumento TCD4 (CD3+, CD4+). No lavado peritoneal, após indução com pristane houve diminuição de células B (CD19+, IgM+) e aumento de B1a (CD19+ IgM+ CD5+) em BALB/c pristane. XID pristane apresentou aumento em TCD4 (CD3+, CD4+) e BALB/c pristane de TCD8 (CD3+,CD8+). No sangue periférico, BALB/c apresentou maior quantidade de linfócitos, XID apresentou um perfil neutrofilico, e em todos os grupos com LES houve aumento de monócitos. As citocinas IL-10, IL-6 e IFN-gama foram aumentadas nos BALB/c e XID repopulados. Com base nesses resultados, sugerimos que a presença de células B-1 pode contribuir com o desenvolvimento do LES.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that affects dogs, cats, horses, humans and primates. The pathogenesis is multifactorial, being associated with genetic, hormonal and environmental factors. SLE leads to deposition of immune complexes in joints and various organs, resulting in clinical manifestations. The participation of T and B lymphocytes is crucial for the pathogenesis of the disease. B-1 lymphocytes, a subpopulation of B cells, have characteristics that may contribute to the pathogenesis of autoimmune diseases because they are capable of secreting cytokines such as IL-10, exerting a modulating action on both the acute and chronic inflammatory response, they present antigens on T cells, they participate in innate and adaptive immunity and are the main producers of natural antibodies. Understanding the role of B-1 cells in the immunopathogenesis of SLE may open up fronts for studies on immunotherapeutic strategies that enable the control of this complex and multifactorial disease. The present work evaluated the role of B-1 cells in the immunopathogenesis of SLE using the pristane induction model. SLE was induced in BALB/c, XID (B-1 deficient) and XID female mice repopulated with B-1. The animals were evaluated for six months. We found that BALB/c pristane and XID repopulated with B-1 showed characteristic signs of the disease, such as lipogranuloma formation and splenomegaly. Notably, BALB/c pristane also presented ascites, joint edema, arthritis, kidney damage with immune complex deposition. In the spleen, animals with B-1 had a higher percentage of B cells (CD19+, IgM+), BALB/c pristane than CD8 T (CD3+, CD8+), while XID pristane had increased TCD4 (CD3+, CD4+). In the peritoneal lavage, after induction with pristane, there was a decrease in B cells (CD19+, IgM+) and an increase in B1a (CD19+ IgM+ CD5+) in BALB/c pristane. XID pristane showed an increase in TCD4 (CD3+, CD4+) and BALB/c pristane than TCD8 (CD3+, CD8+). In peripheral blood, BALB/c had a higher number of lymphocytes, XID had a neutrophilic profile, and in all SLE groups there was an increase in monocytes. The cytokines IL-10, IL-6 and IFN-gama were increased in repopulated BALB/c and XID. Based on these results, we suggest that the presence of B-1 cells may contribute to the development of SLE.

Sinais dermatológicos clássicos na medicina veterinária / Classic dermatological signs in veterinary medicine

Arrolam-se os sinais dermatológicos evidenciados na rotina da clínica dermatológica, que permitem aventar um diagnóstico presuntivo ou até estabelecê-lo cabalmente. Os dezesseis sinais reunidos envolvem quadros dermatopáticos etiologicamente relacionados às enfermidades autoimunes, infecciosas, parasitárias, alérgicas, endócrinas, psicopáticas, disqueratinizantes, neoplásicas e genodermatóxicas.(AU)

Dermatological signals observed in routine dermatologic clinical practice, which allow producing any presumptive diagnosis or to establish it fully, are listed. The 16 signals gathered are related to autoimmune, infectious, parasitic, allergic, endocrine, psychopathic, neoplasic, genetic and of abnormal cornification diseases.(AU)

EFEITOS MORFOLÓGICOS DA ADMINISTRAÇÃO DE CURTA DURAÇÃO DO METOTREXATO SOBRE O SISTEMA NERVOSO CENTRAL DE RATOS

O metotrexato (MTX), uma droga antifolato, é amplamente utilizado em protocolos quimioterápicos para tumores cerebrais primários e metastáticos e algumas doenças autoimunes. Sua eficácia para tumores, porém, é limitada pela alta incidência de complicações neurológicas no sistema nervoso central (SNC), embora o mecanismo patogênico e o(s) alvo(s) celular(es) da neurotoxicidade do MTX ainda sejam desconhecidos. Este estudo teve como objetivo observar a resposta astrocitária à administração sistêmica de curto prazo de MTX em ratos adultos. Ratos Wistar machos receberam 5 ou 10 mg/kg/dia de MTX por via intraperitoneal por 4 dias consecutivos (respectivamente, grupos MTX5 e MTX10) ou o mesmo volume de solução salina a 0,9% (controle). No 5º dia, amostras de encéfalo foram coletadas e processadas para as colorações de hematoxilina-eosina e de luxol fast blue, bem como para investigação imuno-histoquímica da proteína ácida fibrilar glial (GFAP) e análise morfométrica no córtex frontal, hipocampo, hipotálamo e camadas molecular/granular do cerebelo. Os níveis encefálicos das citocinas pró-inflamatórias TNF- e IL-1 foram determinados por ELISA. Nenhum sinal de perda neuronal ou de desmielinização foi observado nos diferentes grupos. O aumento da expressão de GFAP foi encontrado em todas as áreas dos grupos MTX, sendo ligeiramente maior no grupo MTX10. Os níveis encefálicos de ambas citocinas diminuíram no grupo MTX5 em relação aos controles. No grupo MTX10, o TNF- diminuiu, embora a IL-1 estivesse aumentada em comparação ao controle. A administração do MTX induziu a astrogliose em várias áreas do encéfalo. No grupo MTX5, aparentemente ocorreu na presença de citocinas pró-inflamatórias diminuídas.

Methotrexate (MTX), an antifolate drug, is widely used in chemotherapeutic protocols for metastatic and primary brain tumors and some autoimmune diseases. Its efficacy for brain tumors is limited by the high incidence of central nervous system (CNS) complications, although the mechanism and cellular target(s) of its neurotoxicity are still unclear. This investigation aimed to observe astrocytic response to systemic short-term MTX administration in adult rats. Male Wistar rats received 5 or 10 mg/kg/day of MTX by intraperitoneal route for 4 consecutive days (respectively, MTX5 and MTX10 groups) or the same volume of 0.9% saline solution (control group). On the 5th day, brain samples were collected for hematoxylin-eosin and luxol fast blue staining techniques, as well as for glial fibrillary acidic protein (GFAP) immunohistochemistry and morphometric analysis in the frontal cortex, hippocampus, hypothalamus and molecular/granular layers of the cerebellum. Brain levels of the proinflammatory cytokines TNF- and IL-1 were determined by Elisa. No signs of neuronal loss or demyelination were observed in all groups. Increased GFAP expression was found in all areas from the MTX groups, although it was slightly higher in the MTX10 group compared to the MTX5. Both TNF- and IL-1 levels were decreased in the MTX5 group compared to controls. In the MTX10 group, TNF- decreased, although IL-1 was increased relative to controls. MTX administration induced astrogliosis in several CNS areas. In the MTX5 group, it apparently occurred in the presence of decreased proinflammatory cytokines.