O Granuloma \"lepróide canino\", quadro sindrômico, também denominada lepra canina, foi descrito pela primeira vez em 1973, no Zimbábue, em cães da raça Boxer e Bull mastiff e consiste em um dos tipos de micobacterioses tegumentares encontradas nos animais de companhia. No presente estudo, objetivou-se caracterizar os aspectos clínicos e epidemiológicos da enfermidade, nos animais atendidos no período de 1990 a 2010, no Serviço de Dermatologia do Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, bem como determinar a ocorrência de similaridade gênica da micobactéria envolvida, entre os animais brasileiros e os descritos em trabalhos estrangeiros. A amostragem foi composta de 37 animais com diagnóstico estabelecido por exame histopatológico ou citobacterioscópico cutâneo, onde se verificou evidente predisposição racial (83,7%), principalmente da raça Boxer (61,2%), ampla distribuição etária e ausência de predisposição sexual. Os cães apresentavam bom estado geral, sem comprometimento sistêmico, apenas tegumentar, com predomínio das lesões de morfologia nodular (75,6%) e situadas em pavilhões auriculares (86,5%). O diagnóstico foi estabelecido a partir dos seguintes exames subsidiários: histopatologia cutânea (56,8%), citobacterioscopia (21,6%) e por ambas as metodologias (21,6%). Trata-se ainda de enfermidade ocorrente em várias unidades federativas brasileiras, no entanto parece ser pouco diagnosticada e assim submetida a tratamentos equivocados, o que foi verificado em 54% dos cães tratados preteritamente. Os fármacos empregados no tratamento sistêmico, rifampicina ou enrofloxacina, mostraram-se igualmente eficazes, com estabelecimento da alta clínica em tempo médio de 84,1 dias. Já técnica de reação em cadeia de polimerase (PCR) foi executada a partir de cortes histológicos cutâneos, emblocados em parafina, oriundos de 13 animais, sendo que em 09 (69,2%) deles se detectou a presença de Mycobacterium cepa CLGS, pelo método da PCR em tempo real e a confirmação do agente em comum entre os casos do Brasil e de outros países. / Canine leproid granuloma, syndromic, also called \"canine leprosy, was first described in 1973 in Zimbabwe in Boxer dogs and Bull mastiff and consists of a type of soft tissue mycobacterial infections found in pets. In the present study aimed to characterize the clinical and epidemiological aspects of the disease in animals treated between 1990-2010 at the Department of Dermatology, Veterinary Hospital, Faculty of Veterinary Medicine, University of São Paulo, and to determine the occurrence of genetic similarity of mycobacteria involved, of dogs from Brazil and other countries. The sample consisted of 37 animals with diagnosis established by histopathology or cytology skin, where there was clear racial predisposition (83.7%), mainly Boxer (61.2%), broad age distribution and no sexual predisposition. The dogs were in good general condition, without systemic involvement, only cutaneous, with a predominance of nodular lesions morphology (75.6%) located in the ears (86.5%). The diagnosis was established from the following exams: cutaneous histopathology (56.8%), citology (21.6%) and by both methods (21.6%). It is still disease occurring in several Brazilian states, however appears to be underdiagnosed and thus subjected to inappropriate treatment, which was observed in 54% of dogs treated. The drugs used in systemic treatment, rifampin and enrofloxacin, were equally effective, with the establishment of recovery a mean of 84.1 days. Already technique of polymerase chain reaction (PCR) was performed from histological sections of skin, paraffin embedded, from 13 animals, while in 09 (69.2%) of them detected the presence of Mycobacterium strain CLGS by method of real-time PCR and confirmation of the agent in common between the cases of Brazil and other countries.

Typescript (photocopy). / Digitized by Kansas Correctional Industries

Introdução: a vasculopatia livedoide é uma doença cutânea rara que acomete principalmente mulheres adultas, cursando inicialmente com lesões purpúricas e necróticas intensamente dolorosas, acometendo extremidades inferiores, que podem evoluir com úlceras de tamanhos variados. Estas lesões costumam evoluir com cicatrizes atróficas, estreladas e com telangiectasias, denominadas cicatrizes de atrofia branca. Apesar da etiologia não estar totalmente esclarecida, os distúrbios da coagulação parecem ser o mecanismo fisiopatológico primário da vasculopatia livedoide. Inúmeras trombofilias já foram associadas à vasculopatia livedoide, porém cerca de metade dos casos permanece sem etiologia definida. Recentemente foi documentado aumento de lipoproteína(a) na vasculopatia livedoide. Níveis plasmáticos elevados de lipoproteína(a) são considerados um fator de risco causal independente para o desenvolvimento de doenças cardiovasculares e trombóticas, devido à sua similaridade estrutural com o plasminogênio. A deposição tecidual da lipoproteína(a) em vasos ateroscleróticos é bem descrita, porém na vasculopatia livedoide a participação da lipoproteína(a) não é conhecida. Objetivos: analisar os níveis séricos da lipoproteína(a) e a sua expressão tecidual na pele dos pacientes com vasculopatia livedoide e comparar os resultados com um grupo controle. Métodos: amostras de pele obtidas através de biópsia de pele de 38 pacientes com vasculopatia livedoide (27 do sexo feminino e 11 do sexo masculino) e 9 indivíduos do grupo controle (5 do sexo feminino e 4 do sexo masculino) foram avaliados para a presença de lipoproteína(a) através de imuno-histoquímica utilizando anticorpo policlonal anti- lipoprotéina(a). Os níveis plasmáticos da lipoprotéeíina(a) foram analisados por imunoturbidimetria e comparados com setenta pacientes portadores de outras doenças dermatológicas. Resultados: utilizando anticorpo policlonal contra lipoproteína(a), observou-se que a pele perilesional em pacientes com vasculopatia livedoide apresentava dez vezes mais lipoprotéina (a) do que a pele controle. O coeficiente de correlação de Pearson (r = 0,02) mostrou que os níveis teciduais de lipoproteína(a) não se correlacionaram com os níveis plasmáticos nos pacientes com vasculopatia livedoide. Níveis plasmáticos elevados de lipoproteína(a) foram observados nos portadores de vasculopatia livedoide, no entanto não pode ser demonstrada diferença estatística em relação ao grupo controle. Conclusões: achados de aumento da expressão tecidual de lipoproteína(a) na pele lesionada e níveis plasmáticos elevados desta proteína em pacientes com vasculopatia livedoide podem corroborar com a hipótese de que a lipoproteína(a) possa contribuir para a patogênese da vasculopatia livedoide através dos seus efeitos antifibrinolíticos, pró- trombóticos e ação direta no endotélio vascular, induzindo a formação do trombo / Background: livedoid vasculopathy is a chronic disorder that usually presents as recurrent reticulated purpura on the lower limbs, with recurrent painful, purpuric and/or necrotic macules that may lead to ulcerative lesions. These lesions usually heal into atrophic white scars, with depigmentation and telangiectasias, known as \"atrophie blanche\". Although the etiology of the livedoid vasculopathy is not fully understood, coagulation disorders appear to be the primary pathophysiological mechanism. Hereditary thrombophilia has been associated with livedoid vasculopathy, but about half of the cases remain without defined etiology. Recently, high serum levels of lipoprotein(a) in livedoid vasculopathy patients have been documented. Elevated plasma levels of lipoprotein(a) are an independent risk factor for the development of cardiovascular and thrombotic diseases due to their structural similarity with plasminogen. Lipoprotein(a) deposition in atherosclerotic vessels is well described, but its role in livedoid vasculopathy is unknown. Objectives: To analyze the serum levels of lipoprotein(a) and tissue expression in the skin of patients with livedoid vasculopathy and to compare the results with a control group. Methods: Skin biopsy samples from 38 patients (27 women-11 men) with active lesions diagnosed with livedoid vasculopathy and 9 samples of normal skin (5 women-4 men) from control individuals without livedoid vasculopathy were evaluated for skin expression of lipoprotein(a) by immunohistochemistry using polyclonal anti-lipoprotein(a) antibody. Plasma levels of lipoprotein(a) were analyzed by immunoturbidimetry and compared with seventy patients with other dermatological diseases. Results: We found lesional skin in patients with livedoid vasculopathy expressed tenfold higher lipoprotein(a) immunostaining than controls. High plasma levels of lipoprotein(a) were observed in livedoid vasculopathy patients, but we cannot observed a positive correlation (p = 0.02) between skin expression of Lipoprotein(a) and plasma levels of Lipoprotein(a) in patients with livedoid vasculopathy. Conclusions: Increased of lipoprotein(a) tissue expression on lesioned skin and elevated plasma levels of this protein in patients with livedoid vasculopathy may corroborate the hypothesis that lipoprotein(a) may contribute to the pathogenesis of livedoid vasculopathy through its antifibrinolytic effects, prothrombotic and direct action on the vascular endothelium, inducing thrombosis

Introdução: a vasculopatia livedoide é uma doença cutânea rara que acomete principalmente mulheres adultas, cursando inicialmente com lesões purpúricas e necróticas intensamente dolorosas, acometendo extremidades inferiores, que podem evoluir com úlceras de tamanhos variados. Estas lesões costumam evoluir com cicatrizes atróficas, estreladas e com telangiectasias, denominadas cicatrizes de atrofia branca. Apesar da etiologia não estar totalmente esclarecida, os distúrbios da coagulação parecem ser o mecanismo fisiopatológico primário da vasculopatia livedoide. Inúmeras trombofilias já foram associadas à vasculopatia livedoide, porém cerca de metade dos casos permanece sem etiologia definida. Recentemente foi documentado aumento de lipoproteína(a) na vasculopatia livedoide. Níveis plasmáticos elevados de lipoproteína(a) são considerados um fator de risco causal independente para o desenvolvimento de doenças cardiovasculares e trombóticas, devido à sua similaridade estrutural com o plasminogênio. A deposição tecidual da lipoproteína(a) em vasos ateroscleróticos é bem descrita, porém na vasculopatia livedoide a participação da lipoproteína(a) não é conhecida. Objetivos: analisar os níveis séricos da lipoproteína(a) e a sua expressão tecidual na pele dos pacientes com vasculopatia livedoide e comparar os resultados com um grupo controle. Métodos: amostras de pele obtidas através de biópsia de pele de 38 pacientes com vasculopatia livedoide (27 do sexo feminino e 11 do sexo masculino) e 9 indivíduos do grupo controle (5 do sexo feminino e 4 do sexo masculino) foram avaliados para a presença de lipoproteína(a) através de imuno-histoquímica utilizando anticorpo policlonal anti- lipoprotéina(a). Os níveis plasmáticos da lipoprotéeíina(a) foram analisados por imunoturbidimetria e comparados com setenta pacientes portadores de outras doenças dermatológicas. Resultados: utilizando anticorpo policlonal contra lipoproteína(a), observou-se que a pele perilesional em pacientes com vasculopatia livedoide apresentava dez vezes mais lipoprotéina (a) do que a pele controle. O coeficiente de correlação de Pearson (r = 0,02) mostrou que os níveis teciduais de lipoproteína(a) não se correlacionaram com os níveis plasmáticos nos pacientes com vasculopatia livedoide. Níveis plasmáticos elevados de lipoproteína(a) foram observados nos portadores de vasculopatia livedoide, no entanto não pode ser demonstrada diferença estatística em relação ao grupo controle. Conclusões: achados de aumento da expressão tecidual de lipoproteína(a) na pele lesionada e níveis plasmáticos elevados desta proteína em pacientes com vasculopatia livedoide podem corroborar com a hipótese de que a lipoproteína(a) possa contribuir para a patogênese da vasculopatia livedoide através dos seus efeitos antifibrinolíticos, pró- trombóticos e ação direta no endotélio vascular, induzindo a formação do trombo / Background: livedoid vasculopathy is a chronic disorder that usually presents as recurrent reticulated purpura on the lower limbs, with recurrent painful, purpuric and/or necrotic macules that may lead to ulcerative lesions. These lesions usually heal into atrophic white scars, with depigmentation and telangiectasias, known as \"atrophie blanche\". Although the etiology of the livedoid vasculopathy is not fully understood, coagulation disorders appear to be the primary pathophysiological mechanism. Hereditary thrombophilia has been associated with livedoid vasculopathy, but about half of the cases remain without defined etiology. Recently, high serum levels of lipoprotein(a) in livedoid vasculopathy patients have been documented. Elevated plasma levels of lipoprotein(a) are an independent risk factor for the development of cardiovascular and thrombotic diseases due to their structural similarity with plasminogen. Lipoprotein(a) deposition in atherosclerotic vessels is well described, but its role in livedoid vasculopathy is unknown. Objectives: To analyze the serum levels of lipoprotein(a) and tissue expression in the skin of patients with livedoid vasculopathy and to compare the results with a control group. Methods: Skin biopsy samples from 38 patients (27 women-11 men) with active lesions diagnosed with livedoid vasculopathy and 9 samples of normal skin (5 women-4 men) from control individuals without livedoid vasculopathy were evaluated for skin expression of lipoprotein(a) by immunohistochemistry using polyclonal anti-lipoprotein(a) antibody. Plasma levels of lipoprotein(a) were analyzed by immunoturbidimetry and compared with seventy patients with other dermatological diseases. Results: We found lesional skin in patients with livedoid vasculopathy expressed tenfold higher lipoprotein(a) immunostaining than controls. High plasma levels of lipoprotein(a) were observed in livedoid vasculopathy patients, but we cannot observed a positive correlation (p = 0.02) between skin expression of Lipoprotein(a) and plasma levels of Lipoprotein(a) in patients with livedoid vasculopathy. Conclusions: Increased of lipoprotein(a) tissue expression on lesioned skin and elevated plasma levels of this protein in patients with livedoid vasculopathy may corroborate the hypothesis that lipoprotein(a) may contribute to the pathogenesis of livedoid vasculopathy through its antifibrinolytic effects, prothrombotic and direct action on the vascular endothelium, inducing thrombosis

Controlled drug delivery systems are becoming increasingly interesting with the contribution of nanotechnology. In the case of transdermal applications the greatest limitation is the highly impermeable outermost layer of the skin, the stratum corneum. One promising method of controlled transdermal drug delivery of the skin therapeutics is the use of nanoparticles as carriers. Encapsulation of the drug, as opposed to classical topical application of creams or emulsions, allows the drug to diffuse into hair follicles where drug release can occur in the deeper layers of the skin. The aim of this study was to develop micro and nano sized carriers as drug delivery systems to achieve treatment for skin conditions like psoriasis, aging or UV damage, caused by radiation or health problems. Two different types of bioactive agents, retinyl palmitate (RP) and Dead Sea Water (DSW), were used by encapsulating in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) carriers. In some tests MgCl2 was used as a substitute for DSW when quantification was needed. Bioactive agent loaded nanospheres and nanocapsules were prepared with o/w and w/o/w methods in low micron (1.9 &micro / m), mid nano (426 nm) and nano (166 nm) sizes. Loading, encapsulation efficiency and release kinetics were studied. The encapsulation efficiency and loading values are low especially for the water soluble agents, DSW and MgCl2. It was observed that the capsules loaded with hydrophilic agents released their content in the first 24 h in aqueous media. The encapsulation efficiency and loading values for RP were higher because of the insolubility of the agent in water. In the in vitro studies carried out with L929 mouse fibroblast cells, the nano sized PHBV capsules were detected in the cytoplasm of the cells. Cell viability assay (MTT) for L929 cells showed a growth trend indicating that the particles were not cytotoxic and the values were close to the controls. Hemolytic activity was examined using human erythrocytes and micro/nanoparticles of PHBV were found to be non hemolytic. In vivo testing with BALB/c mice, nanocapsule penetration revealed that a small amount of nano sized particles penetrated the mice skin, despite the highly impermeable outer skin layer. As a result, PHBV micro/nanoparticles have a significant potential for use as topical drug delivery systems in the treatment of skin diseases.

This thesis is an investigation of two common skin conditions of pigs: exudative epidermitis (EE) and ear necrosis (EN). The cause of exudative epidermitis and risk factors are well understood, however the study was prompted because of reports of treatment failure. A survey of veterinary practitioners (n=15) and pork producers (n=58) was conducted to determine which treatments are commonly used. Amongst farmer respondents topical treatments were often used and in serious cases injectable penicillin G was administered. Thirty farms with a history of EE were visited and skin samples taken from affected pigs. The antimicrobial resistance pattern for isolates of Staphylococcus hyicus and Staphylococcus aureus revealed that almost all isolates were resistant to penicillin G and ampicillin. In addition, certain isolates of S. hyicus as well as S. aureus were shown to possess the mecA gene which is associated with resistance to methicillin. The presence of widespread resistance to penicillin G among staphylococci isolates suggests a reason for poor treatment response. The presence of the mecA gene in staphylococci other than S. aureus recovered from pigs has not been reported before and is of interest from a public health standpoint. A second study investigated EN. The causative agent(s) and the associated risk factors are not well understood. Eleven case farms were visited and skin biopsies and oral swabs taken from pigs in early, mid and late stages of the disease. Bacteriological culturing was performed for staphylococci and spirochetes as well as histological examination of the biopsy samples. Farm-level risk factors were assessed on 14 case farms and 9 control farms. Staphylococci were generally recovered in abundance from the majority of samples but spirochetes were not cultured and only identified microscopically in a small number of tissue samples. Histology revealed that the disease appeared to occur first as a lesion on the epidermal surface that caused tissue damage and led to subsequent invasion of the dermis. This pathogenesis was consistent with the hypothesis that staphylococci colonize the skin surface and produce exfoliating toxins. Ear biting was noted to be commonly present and may be an important contributing factor. / Ontario Pork Animal Health Strategic Initiative Fund Ontario Ministry of Agriculture, Food and Rural Affairs(OMAFRA) Ontario Veterinary College, University of Guelph

Epitheliogenesis Imperfecta (EI) is a mechanobullous disease that occurs in newborn American Saddlebred and Belgian Draft foals. Necropsy evaluations of two American Saddlebred foals revealed broad skin lesions, dental abnormalities and oral mucosa lesions. Construction of a partial pedigree showing occurrences of EI in American Saddlebred horses was consistent with a recessive pattern of inheritance. An allelic frequency of 0.04 was estimated for the EI gene. The pathological signs of EI were similar to a disease in humans known as Herlitz Junctional Epidermolysis Bullosa (HJEB). HJEB is caused by a defect in one of the three subunits of the laminin 5 protein (LAM 3, LAM 3 and LAM 2), which leads to a separation of the epidermis from the dermis. Transmission electron microscopy revealed a separation within the lamina lucida at the sites of epidermal/dermal splits in the skin of EI affected foals. This indicated that a defect in the laminin 5 protein was responsible for EI. Linkage disequilibrium (LD) between microsatellite markers and the EI disease locus was tested for in the American Saddlebred and Belgian Draft breeds. Genotyping of microsatellite alleles was used to determine fit to Hardy-Weinberg equilibrium for control and EI populations for both breeds using Chi square analysis. Two microsatellite loci (ASB14 and AHT3) were not in Hardy-Weinberg equilibrium in EI affected American Saddlebred horses. This suggested that the EI disease locus was located on ECA 8, the putative location of LAM 3. No evidence of LD between any of the tested microsatellite loci and the EI locus was observed in the Belgian Draft samples. A cDNA library was built from Thoroughbred horse skin to serve as a resource for sequencing equine skin gene transcripts. 313 ESTs were sequenced, of which 207 were putatively identified (66%) by database search. Examination of the pathology and ultrastructure of EI affected foals and comparison with HJEB indicated that laminin 5 was the responsible defective protein. The LD analysis suggested that LAM 3 was the EI disease locus in American Saddlebred horses.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2008. / Härtill 5 uppsatser.

Diss. (sammanfattning) Umeå : Univ., 2004. / Härtill 4 uppsatser.

Cutaneous lupus erythematosus (CLE) is an autoimmune disease that resolves with or without permanent scars depending on the subtype. Interferons (IFNs), including the skin specific IFNλ mainly activate STAT1, which results in inflammation in CLE and may play a significant role in scar formation in chronic discoid CLE. IL-22 activates STAT3 and it is emerging as a mediator with significant impact on normal wound repair, epidermal hyperproliferation and prevention of fibrosis. This work focussed on understanding the regulation and functional impact of IL-22 and IFNλ on skin cells. The counter-regulatory effect of IL-22 on the activities of IFNλ was assessed through downstream interferon stimulated genes (ISGs) expression in healthy and CLE keratinocytes. Cell proliferation and gap closure were investigated in skin resident cells using cell trace dye and scratch assay. Dermal fibroblasts were assessed for the presence of IFNλR1 and IL-22R1, downstream activities of the receptors. Results showed that IL-22 accelerated “scratch” closure in keratinocytes while IFNλ caused a delay in closure. IL-22 significantly downregulated IFNλ-induced chemokines expression in healthy, but not CLE keratinocytes. Reduced IL-22R1 expression and “STAT3 signature genes” was observed in CLE keratinocytes. A key finding of this project is that dermal fibroblasts respond to both IFNλ and IL-22. This work shows that IL-22 can reduce the damaging effect of IFNs in inflamed skin and also identifies dermal fibroblasts as important cells in skin immune responses. In conclusion, IL-10 family members can have both beneficial and destructive effects on the skin organ depending on the micro milieu and cell-type involved. Manipulating the balance of IL-10 family members in the skin may offer new therapeutic approach for both psoriasis and CLE.