Didėjant vyresnių žmonių populiacijai amžinė geltonosios dėmės degeneracija (AGDD) yra vis dažnesnė vyresnio nei 50 metų amžiaus žmonių negrįžtamo regos netekimo priežastis. AGDD prevencinės priemonės bei gydymo galimybės ribotos, nes ligos etiopatogenezė iki šiol nėra visiškai aiški. Disertacinio darbo metu įvertintos AGDD ir išeminės širdies ligos (IŠL) sąsajos, atsižvelgiant į vainikinių arterijų aterosklerozinius pažeidimus. Pirmą kartą analizuota SCARB1 rs5888 C/T genotipų įtaka AGDD ir IŠL pasireiškimui. Tyrimo rezultatai parodė, kad AGDD ir IŠL, kai vainikinėse arterijose yra aterosklerozinių pažeidimų (IŠLath+), sieja bendri, šių ligų pasireiškimo galimybę didinantys, klinikiniai veiksniai ir oksidacinis stresas. Nustatytas „apsauginis“ SCARB1 rs5888 T/T genotipas, mažinantis AGDD ir IŠLath+, bei „rizikingas“ SCARB1 rs5888 C/T genotipas, didinantis AGDD+IŠLath+ galimybę. Pritaikius matematinės morfologijos metodus, nustatyta, jog sergantiems vėlyvąja AGDD SCARB1 rs5888 „rizikingas“ genetinis variantas susijęs su didesniu centrinės tinklainės dalies pažeidimo plotu. Bendrų AGDD ir IŠL patogenezinių grandžių tyrimas suteikia naujos informacijos apie AGDD etiologiją, patogenezę ir galbūt pasitarnaus efektyvaus gydymo bei prevencijos krypčių kūrimui. Tyrimo metu taikyti morfometriniai geltonosios dėmės pažaidos ploto matavimai gali būti naudojami gydytojų-oftalmologų klinikinėje praktikoje, siekiant tiksliau įvertinti centrinės tinklainės dalies pokyčius dinamikoje... [toliau žr. visą tekstą] / Age-related macular degeneration (ARMD) is the commonest cause of blindness among persons over the age of 50 and its prevalence is likely to increase as a consequence of population ageing. ARMD is a disorder of unknown cause and pathogenesis, therefore current options for ARMD prevention and treatment are limited. In the recent study the associations between ARMD and CAD, according the angiographic findings of atherosclerosis in the coronary arteries, were analyzed. The oxidative stress impact and clinical factors determining susceptibility to ARMD and CADath+, separately and common susceptibility factors for both diseases prediction were ascertained. Analysis of novel genetic biomarker, the rs5888 variant of SCARB1 gene, identified the „protective“ SCARB1 rs5888 TT genotype, associated with the lower risk of ARMD and CADath+, and a „risk-determining“ CT genotype, determining higher ARMD+CADath+ risk. The evaluation of macular lesion area by using the methods of mathematical morphology revealed that in late stage ARMD subjects carriers of SCARB1 rs5888 CT genotype the area of macular lesion was larger than in TT genotype carriers. New information about ARMD and CAD discovered additional knowledge about ARMD etiopathogenesis and might be helpfull in search of new treatments or strategies for ARMD prevention. Evaluation of macular lesion area by mathematical morphology methods used in this study may be useful in ophthalmological practice to monitor the dynamics of ARMD.

This research was designed to address important issues for the effective prescription of, and training in the use of, magnifiers for reading patients with visual impairment. The emphasis was on the development of simple methods of assessment and training that could be easily implemented, at no great cost, by low vision practitioners in clinical practice. To ensure that the results would be widely applicable, the research focused on subjects with age-related macular degeneration (AMD) using stand magnifiers (being the most common cause of low vision and the most commonly prescribed magnifiers respectively). From this research, modifications to the current methods of reading rehabilitation are suggested to more effectively improve low vision reading for the millions of people with low vision around the world. The magnification and reading performance achieved with the magnifier determined by the fixed acuity reserve method was as valid as that achieved with the magnifier determined by the individual acuity reserve method. The fixed acuity reserve is a simpler method to calculate the required magnification, as it requires only near visual acuity and the patient's goal reading task. This method was primarily used to select the appropriate illuminated stand magnifiers for the subjects participating in the subsequent studies and is recommended for use as the starting point in clinical low vision practice. The main study of this thesis was a longitudinal investigation of the benefit of large print reading practice on reading performance with stand magnifiers. Instead of the intensive training programs on magnifier use which have been suggested by previous studies, this study aimed to investigate the effect of simple large print reading practice, under either full or restricted field of view (the latter simulated by a practice stand), on reading rate with stand magnifiers for subjects with AMD. The experimental hypothesis was that reading practice prior to the prescription of stand magnifiers would improve reading performance with the stand magnifiers for subjects with AMD. As previous studies have shown, reading rate reduced when a stand magnifier was first introduced. One week of reading practice on large print, with or without a reduced field of view, gave an improvement in reading rate with the stand magnifier for passages of text (such that the reading rates with and without magnifiers were not significantly different). There was a suggestion that this practice may give a more rapid improvement in reading rate than that achieved by the control subjects who did not do any large print reading practice, but this did not reach statistical significance. Even very brief reading with the stand magnifiers by the control subjects gave some improvement in reading rate. Therefore, home or in-office reading practice on large print or with magnifiers is recommended for patients with AMD before magnifiers are prescribed. Subjects who had neither reading practice nor exposure to the magnifier prior to its prescription required two weeks practice using their stand magnifiers to achieve their maximum reading rate. This suggests that home practice in using stand magnifiers is beneficial and a follow up visit is recommended two weeks after the provision of a magnifier to assess any change in reading rate. If no improvement in the magnifier reading rate is found or the rate is less than the reading rate on large print without a magnifier, further investigations of the patients' vision and/or their magnifier manipulation strategy are necessary. In the last study, a simple method aimed at alleviating difficulties with magnifier manipulation and navigation, the attachment of a line guide to the base of the stand magnifier, was investigated using both objective methods (recording magnifier movements and reading rate measures) and subjective methods (simple questionnaire). Although there was no improvement in the objective measures of reading or navigation performance with the line guide, more than half of the subjects with low vision preferred to have the line guide on their stand magnifiers. This suggests that the objective measures might not be sensitive enough to predict the subjective response, or that other factors that were not measured in this study influenced subjects' preferences in selecting the line guide (e.g., psychological support provided by the line guide in reading orientation). Clinically, the subjective response of patients to the use of low vision aids as well as their motivation are important criteria for success in low vision rehabilitation. There was a tendency for less experienced users to prefer the line guide to assist their use of the stand magnifier for reading. Therefore, a line guide could be offered as a preliminary training aid when stand magnifiers are first prescribed for AMD patients. Possible improvements to the design of the line guide were identified. Further research is required to assess the benefits of this or similar devices for new magnifier users and to understand the difficulties that people with visual impairment have with page navigation in order to determine improved methods of training navigation strategies. The unique contribution of this study to the field of low vision rehabilitation is that the benefit of short-term reading practice, on large print or with magnifiers, as simple, cheap methods of enhancing reading performance with stand magnifiers was demonstrated. The results of this study have led to the development of recommendations for assessing and training AMD patients who are prescribed stand magnifiers.

[Truncated abstract] Sporadic inclusion body myositis (sIBM) is a chronic inflammatory disease that is the most common myopathy in individuals above the age of 50 in the Caucasian population. sIBM is characterised by cytotoxic immune infiltration of skeletal muscle, consisting primarily of CD8+ T-cells and macrophages, as well as a degenerative process, with muscle fibre vacuolation and intracellular filamentous inclusions. The pathogenesis of sIBM is likely to involve a complex interaction between genetic and environmental factors. Whilst the physiological and pathological characteristics of sIBM have been clearly identified, the exact origin and genetic basis of the disease remains unknown. A number of studies show that sIBM is associated with alleles of the major histocompatibility complex (MHC) on chromosome 6p21.3 and specifically with two ancestral haplotypes (AH) in Caucasians – the 8.1AH, defined by HLA-B*0801, HLA-DRB1*0301 and the 35.2AH, defined by HLA-B*3501, HLA-DRB1*0101. Mapping studies subsequently showed that sIBM susceptibility likely originates from a 389kb region of the MHC, spanning from centromeric of PBX2 to telomeric of HLA-DRB1. The central hypothesis of this thesis was that susceptibility to sIBM is conferred by a single allele found within a region defined using the 8.1AH, which is also carried by other haplotypes associated with sIBM. Three patient cohorts from Australia, the U.S.A and Japan were studied. ... Of the 32 alleles genotyped, none were found in all susceptibility haplotypes and one was common, but not unique, to the 8.1AH, 7.2AH and 52.1AH. Five SNPs were also found in two of the three haplotypes, although none were specific to the sIBM susceptibility haplotypes. These data suggest that the 8.1AH is likely to carry an sIBM susceptibility allele independent of the 35.2AH, 7.2AH and 52.1AH. Based on the possible mechanism of action in cellular differentiation and its location within the 8.1AH-defined sIBM susceptibility region reported in 2004, NOTCH4 was a strong candidate for conferring sIBM susceptibility. NOTCH4 coding region polymorphisms were thus investigated in a Caucasian patient cohort to assess any possible role in sIBM susceptibility. While the frequency of some alleles were increased in sIBM patients, the strong linkage disequilibrium throughout the MHC prevented confirmation of any alleles as playing a direct role in sIBM. The 8.1AH-derived sIBM susceptibility region was further refined using recombination mapping. This approach used markers characterised against multiple haplotypes to genotype patients carrying part of the 8.1AH to locate a common, overlapping susceptibility region. Recombination mapping of patients revealed a common overlapping region of the 8.1AH, extending from BTNL2 to HLA-DRB3. The results of the study indicate that 8.1AH-derived susceptibility for sIBM is likely to originate from a 172kb region encompassing HLA-DRA, HLA-DRB3 and part of BTNL2. These genes warrant further investigation in future studies.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Tennessee, Memphis, 2006. / The electronic version of this thesis is available at http://d.utmem.edu/CAMPUS-ACCESS-ONLY/2006-001-chona.pdf Includes bibliographical references (leaves 128-136).

Made available in DSpace on 2016-08-15T20:31:23Z (GMT). No. of bitstreams: 1 CarlaMFR_DISSERT.pdf: 8952326 bytes, checksum: aa0d56e13b65d722f12ebb158cf3f48d (MD5) Previous issue date: 2014-07-15 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / This study aimed to determine the rate of ovarian follicles degeneration and search for the presence of parasite DNA by PCR in ovarian tissue from goats experimentally infected with Trypanosoma vivax. Six goats, females, adults were infected with 1.25 x105 trypomastigotes of T. vivax and four others formed the control group. After 60 days of infection, was collected from the ovaries and performed the pathological examination. Samples of ovaries were taken to perform the polymerase chain reaction (PCR). The parasitemia was observed from the third day post-infection (dpi) with peaks in the 7-14th dpi. Histological analysis showed that the group of infected goats, the average value of follicles was significantly lower (P <0.05) compared to the control group. As the stage of development in the control group, the number of primordial and primary follicles was significantly higher (p <0.05) than the secondary and tertiary. As for integrity, no significant difference in the average value of the follicles degenerate type I between control and infected. The number of follicles degenerate type II was significantly higher (p <0.05) in the infected group than in the control group, and most degenerate type II follicles were primordial and primary. The analysis of T. vivax in ovarian tissues by PCR specific for T. vivax (TviCatL-PCR) showed amplification of a DNA fragment of approximately 177 bp was observed in right and left ovaries of all the goats of the infected group. The result of PCR, however, was negative for all samples in the control group. The follicular degeneration associated with the presence of the parasite in the ovaries, as detected by PCR, suggesting the involvement of the parasite in the etiopathogenic mechanism of reproductive harm / Este estudo teve como objetivo a determinação da taxa de degeneração de folículos ovarianos e pesquisar por PCR a presença do DNA do parasita em tecido ovariano de cabras infectadas experimentalmente com Trypanosoma vivax. Seis cabras, fêmeas, adultas, foram infectadas com 1,25x105 tripomastigotas de T. vivax e outras quatro formaram o grupo controle. Após 60 dias de infecção, foi feita a coleta dos ovários e realizado o exame anatomopatológico. Amostras de ovários foram tomadas para a realização da reação em cadeia da polimerase (PCR). A parasitemia foi observada a partir do 3o dia pós-infecção (dpi) com picos nos 7-14os dpi. A análise histológica mostrou que no grupo de cabras infectadas, o valor médio de folículos, foi significativamente menor (P <0,05) quando comparado ao grupo controle. Quanto ao estágio de desenvolvimento, no grupo controle, o número de folículos primordiais e primários foi significativamente maior (p <0,05) do que o secundário e terciário. Quanto à integridade, não houve diferença significativa no valor médio dos folículos degenerados tipo I entre o controle e infectados. O número de folículos degenerados do tipo II foi significativamente maior (p <0,05) no grupo infectado que no grupo controle, e a maioria dos folículos degenerados tipo II eram primordiais e primários. A análise de T. vivax nos tecidos ovariano pelo PCR específico para T. vivax (TviCatL-PCR) mostrou a amplificação de um fragmento de DNA de aproximadamente 177 pb que foi observado nos ovários direito e esquerdo de todos as cabras do grupo infectado. O resultado do PCR, entretanto, foi negativo para todas as amostras do grupo controle. A degeneração folicular associada à presença do parasita nos ovários, detectada por PCR, sugerem a participação do parasita no mecanismo etiopatogênico de danos reprodutivos

Semiochemicals are chemicals used to communicate. Animals tend to use these e.g. to locate food sources or to find a suitable mate. In this study, the sex pheromone of the Indian meal moth, Plodia interpunctella, was analysed. Since this is an economically important species, it is mass-reared in labs and science centers worldwide for experimental purposes. A culture of these moths was brought into the lab at Lund University for studies and has after that served as a model species demonstrating up-wind pheromone-mediated male flight in different courses held by the university. As years went by, the culture got less successful in up-wind flights, most probably because of inbreeding and bottleneck effects, and therefore, a new culture was taken in. This study focuses on using various experiments to see if there was a behavioral and/or physiological difference between the two cultures. Results show a significant difference in behavioral traits (frequency of calling behavior in females and in male up-wind flights) but not in physiological traits (female pheromone production or male antennal response). This study discusses some effects of mass-reared lab cultures.

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Intervertebral disc disease (IVD) is a common pathology in clinical neurology of dogs, representing 45.8% of neurological cases treated at Veterinary Hospital of the Universidade Federal de Santa Maria. The most affected segments are the thoracolumbar (T3-L3) and cranial cervical (C1-C5) of the spinal cord. The clinical sign occurs due a combination of the compressive effect of the disc material and the injury of impact on spinal cord, probably due to an extrusion. A clinical sign varies according to the affected segment of the spinal cord and the severity of the injury. It could be presented only by spinal hyperesthesia, whereas more severe injuries can lead to tetra / paraplegia with no nociception (deep pain) caudal to the lesion. Clinical management for IVD is generally indicated for dogs with hyperesthesia with or without minimal neurological deficits and consists of absolute rest in cage between four to six weeks. Surgery is the treatment of choice for dogs with severe neurological deficits (not ambulatory tetraparesis, tetraplegia, paraplegia with or without nociception in less than 48 hours) in dogs with unsuccessful of clinical management, or dog that have recurrence of disease. In contrast to the numerous studies evaluating the efficacy of surgical treatment in dogs with thoracolumbar and cervical IVD, studies demonstrating the effectiveness of conservative treatment are rare. The aim of this study was to identify dogs with presumptive diagnosis of thoracolumbar and cervical IVD who underwent clinical management and evaluate the response to therapy; and to analyze the effect of age, gender, duration of clinical signs, neurological degree and therapy, as prognostic factors in clinical outcome of the patient. Five hundred six neurological records were used to identify affected dogs (n = 379 thoracolumbar; n = 127 cervical), and was selected those patients with presumptive diagnosis of IVD submitted to clinical management as a first option. The outcome was satisfactory in 73.3% of cases of thoracolumbar IVD, and 92.7% of cases of cervical IVD, demonstrating that clinical management (cage rest, anti-inflammatory and analgesic opioid administration) is effective, especially in milder disease. Conservative treatment has a substantial rate of recurrence and neurological signs may be more severe than the first clinical presentation. The gender, age and duration of clinical signs has no prognostic effect on clinical outcomes of patients IVD of thoracolumbar and cervical, in the sample of the study. / A doença do disco intervertebral (DDIV) é uma afecção frequente na clínica neurológica de cães, representando 45,8% dos casos neurológicos atendidos pelo Serviço de Neurologia do Hospital Veterinário Universitário da Universidade Federal de Santa Maria. Os locais mais acometidos pela doença são os segmentos toracolombar (T3-L3) e cervical cranial (C1-C5) da medula espinhal. A manifestação clínica ocorre devido a uma combinação do efeito compressivo do material de disco e da lesão de impacto na medula espinhal, decorrente principalmente da extrusão do disco e varia de acordo com o segmento da medula espinhal afetado e da severidade da lesão. Pode ser evidenciada apenas por hiperestesia espinhal, enquanto as lesões mais graves podem levar a tetra/paraplegia com ausência da nocicepção (dor profunda) caudal a lesão. O tratamento clínico para DDIV geralmente é indicado para cães com hiperpatia associada ou não a mínimas deficiências neurológicas e consiste em repouso absoluto em gaiola entre quatro a seis semanas. Já a cirurgia é o tratamento de eleição para cães com deficiências neurológicas graves (tetraparesia não ambulatória, tetraplegia, paraplegia com ou sem nocicepção em menos de 48 horas), em cães refratários ao tratamento clínico, ou que apresentem recidiva da doença. Em contraste com os inúmeros estudos avaliando a eficácia do tratamento cirúrgico em cães com DDIV toracolombar e cervical, estudos demonstrando a eficácia do tratamento conservativo são escassos na literatura. Diante desses fatores, o objetivo desse estudo foi identificar cães com diagnóstico presuntivo de DDIV toracolombar e cervical que foram submetidos ao tratamento clínico e avaliar a resposta à terapia instituída; além de avaliar a relação da idade, do gênero, da duração dos sinais clínicos e do tratamento de acordo com o grau neurológico como fatores prognósticos na evolução clínica desses pacientes. Foram analisados 506 registros neurológicos (n=379 toracolombar; n=127 cervical), e selecionados aqueles pacientes com diagnóstico presuntivo de DDIV submetidos ao tratamento clínico como primeira opção. A evolução clínica foi satisfatória em 73,3% dos casos de DDIV toracolombar, e 92,7% dos casos de DDIV cervical, demonstrando que o tratamento clínico com repouso absoluto, administração de anti-inflamatórios e analgésicos opióides é efetivo, principalmente em graus mais leves da doença. O tratamento conservativo apresenta um índice considerável de recidiva, cujos sinais neurológicos poderão ser mais graves do que a primeira apresentação clínica. O gênero, a idade e a duração dos sinais clínicos não apresentam efeito prognóstico na evolução clínica dos pacientes de DDIV toracolombar e cervical, na amostra estudada.

Made available in DSpace on 2014-06-11T19:29:46Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-04-08Bitstream added on 2014-06-13T19:39:12Z : No. of bitstreams: 1 ribeiro_ps_me_arafcl.pdf: 3302773 bytes, checksum: c44d37171b9fe9ebf6a7f082af8a517a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / O presente trabalho é um estudo sobre as relações e contribuições do pensamento médico (do último quartel do século XIX) para com o processo de institucionalização das Ciências Sociais no Brasil. Mais especificamente, o objeto de estudo se define não apenas pela tentativa de reiterar o papel de um grupo específico de intelectuais na construção de um pensamento social brasileiro, mas vai além, pois, mantendo-se nessa mesma temática, busca-se aqui trazer à tona uma reflexão sobre o trabalho intelectual – que em grande parte, revela-se também político – de um dos nomes mais importantes da história da psiquiatria e do alienismo brasileiro, Dr. Francisco Franco da Rocha. O que se levanta como hipótese é a existência de uma peculiar análise social elaborada na esteira do desenvolvimento da medicina psiquiátrica no Brasil, mais especificamente empreendida por este médico paulista. Para tanto, a metodologia adotada pautou-se pelo cotejamento da obra de Franco da Rocha com a de outros médicos numa esfera de discussão na qual se incluem nomes que vão de Nina Rodrigues, passando por Arthur Ramos e Afrânio Peixoto, até Manoel Bonfim, tendo-se como pano de fundo um contexto histórico e intelectual permeado por prescrições médicas acerca da construção de uma identidade nacional. Ao final, conclui-se haver uma originalidade na fala de Franco da Rocha o qual, ao esboçar sua explicação da etiologia social da loucura, faz uso de um senso crítico quanto aos contornos da estrutura social que vê, fato que se comprova na multilateralidade de seus temas. Se por um lado não descartava a teoria da degenerescência nem da eugenia, por outro não reproduziu as mais pessimistas opiniões sobre a miscigenação racial e a presença do negro na constituição do caráter nacional, servindo como uma ponte entre as alternativas de explicação do Brasil empreendidas por outros médicos / The present work is a study on the relationships and contributions of medical thought, in the last quarter of the nineteenth century, regarding the institutionalization process of Social Sciences in Brazil. The object of this study may be established not only by its attempt of reasserting the role of a particular group of intellectuals who contributed to build a Brazilian social thought, but also and moreover as an undertaking of reflecting on the intellectual (and greatly political) work of Dr. Francisco Franco da Rocha, regarded as one of the most important names in the history of Brazilian psychiatry and alienism. Our inference concerns the existence of a peculiar social analysis, elaborated as psychiatric medicine evolved in Brazil, particularly the one drawn by such ‗paulista‘ physician. In order to do so, we performed an investigation on Franco da Rocha‘s and other doctor‘s work and discussions - which includes names from Nina Rodrigues, Arthur Ramos, Afrânio Peixoto to Manoel Bonfim. The referred work and discussions took place in a time of a historical and intellectual context full of medical prescriptions towards the establishment of a national identity. Ultimately, we concluded that there is a certain originality in the speech of Franco da Rocha who, by outlining his account on the social etiology of madness, makes use of a critical sense, shaping the social structure he sees - made evident by the multiplicity of his work. If on one side he did not rule out the theory of degeneration or eugenics, on the other, he did not resonate the most pessimist views on racial mixing and the presence of color people in the formation of national character, bridging between the alternative explanations of Brazil, already undertaken by other physicians

Orientador: Maria Alice da Cruz Hofling, Albetiza Lôbo de Araújo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-17T23:01:57Z (GMT). No. of bitstreams: 1 Barbosa-Souza_Valeria_M.pdf: 7722866 bytes, checksum: 7544e873dc1e9f79280e8045930c4c37 (MD5) Previous issue date: 2011 / Resumo: Os acidentes por serpentes venenosas podem causar alterações locais graves e de rápido desenvolvimento. O veneno de Bothrops lanceolatus (VBL) contém, dentre outras toxinas, metaloproteinases hemorrágicas e pouco hemorrágicas (SVMPI e SVMPIII) e atividade pró-trombina que causam inflamação (vias das ciclooxigenases-COX e lipoxigenases), alterações hemostáticas e degenerativas. O veneno de Bothrops lanceolatus (100 ?g/100 ?l) foi injetado no gastrocnêmio de ratos para investigar a patogênese da mionecrose (1,3,6,18 horas 1, 2 dias) e regeneração muscular (3,7,14 e 21 dias) ocasionada pelo envenenamento através de análise histológica quantitativa (medida do menor diâmetro 1 hora e 21 dias pós- VBL) e imunohistoquímica para a osteopontina (OPN), citocina inflamatória, quimiotática, com sítios de ligação para integrinas de matriz e células. A medida da expressão dos macrófagos residentes (CD68+) e dos macrófagos migrantes (CD163+), de myoD e miogenina, membros da família de fatores transcricionais miogênicos foi feita com o objetivo de correlacionar com a expressão da OPN nos diferentes estágios patológicos (n=6/período) ao longo do período experimental. Os grupos controles foram injetados com PBS (100 ?l). O envenenamento produziu hemorragia local, edema, infiltrado neutrofílico e macrofágico e desorganização das bainhas perimisiais de tecido conjuntivo, após 48 horas. As fibras mionecróticas apresentavam-se em número moderado. Aos 3 dias, havia focos de deposição de colágeno (tipo I) no meio dos quais se viam mioblastos. O número de macrófagos CD68+ atingiu o máximo às 24 horas, e manteve-se significativamente maior que nos grupos controles até aos sete dias. A expressão de OPN foi significativamente maior das 6 horas aos 3 dias e dos 7 aos 14 dias, sendo expressa em fibras musculares, macrófagos, mioblastos, miotubos e fibroblastos. Não foi obtida marcação para anti-myoD; a expressão de miogenina, que tipicamente é nuclear, foi observada também no citoplasma de mioblastos e miotubos até o 70 dia (pico), sendo sua expressão somente nuclear aos 14 dias. A retenção de miogenina no citoplasma tem sido interpretada como mecanismo de retardo na diferenciação, já que a presença no núcleo é necessária para o seu papel regulador transcricional. Aos 21 dias as fibras regeneradas, com núcleo central, não haviam atingido o tamanho das fibras maduras intactas (VBL) e dos controles. Considerando que as SVMPs e a enzima com atividade tipo trombina de VBL, podem aumentar a capacidade de ligação de sítios da OPN a integrinas de matriz e de superfícies de células, sugerimos que durante a patogênese da regeneração muscular post- VBL a OPN estaria criticamente envolvida no processo inflamatório agudo, e como tal atuaria primordialmente como citocina ativadora de células satélites quiescentes, seguida por atividade quimiotática e adesiva, favorecendo migração, proliferação de mioblastos e a diferenciação de miotubos. Segundo a literatura a OPN é profibrótica em certas doenças. Sugerimos que a fibrose intersticial observada, mais a presença tardia de macrófagos no local, mais a expressão citoplasmática da miogenina podem ter sido fatores relevantes que levaram ao atraso da regeneração das fibras musculares, como constatado pelo tamanho menor diâmetro das fibras. Sugere-se para a OPN um papel dual, isto é, tanto próregenerativo, como anti-regenerativo na patogênese das alterações causadas pelo veneno de B. lanceolatus / Abstract: Accident caused by venomous snakes can lead to local changes of serious and rapid development. Bothrops lanceolatus venom (BLV) contains, among other toxins, hemorrhagic metalloproteinases and non-hemorrhagic (SVMPI and SVMPIII) and prothrombin activity. As result, the venom causes hemostatic and inflammatory (via lipoxygenase and cyclooxygenase) and degenerative alterations. In this study, Bothrops lanceolatus venom (100 ?g/100?l) was injected into the gastrocnemius of rats to investigate the pathogenesis of myonecrosis (one, three, six, 18 hours and two days) and regeneration (three, seven, 14 and 21 days) by quantitative histological analysis (measurement of the small diameter one hour and 21 days post-BLV injection) and immunohistochemistry for osteopontin (OPN) protein, an inflammatory and chemotactic cytokines, with integrin binding sites to matrix proteins and cells. The number of macrophages CD68+ (resident macrophages), and CD163 (migrants macrophages), the expression of myoD and myogenin, members of the myogenic, both transcription factors family were correlated (n = 6/period). Control groups were injected with PBS (100?l). The envenomation produced local hemorrhage (initially massive), acute interstitial edema and myofibers, neutrophil and macrophage infiltration, and disruption of the perimysium sheath of connective tissue. These changes were observed up to 48 hours. The number of myonecrotic fibers was in moderate number. At 3 days, there were foci of collagen (type I) deposition surrounding groups of myoblasts. The number of macrophages (CD68 +) peaked at 24 hours, and remained significantly higher for seven days: there was no expression of CD163 macrophages. The OPN expression showed two steps, a significant increase in, from six hours to three days and seven to 14 days, and it was expressed in muscle fibers, macrophages, myoblasts, myotubes and fibroblasts. There was no MyoD imunolabeling. The myogenin expression, which is known to be typically nuclear, was also observed in the cytoplasm of myoblasts and myotubes until 7 days (peak). At 14 days, the myogenin expression became nuclear. The cytoplasmic retention of myogenin has been interpreted as a mechanism to delay myotube differentiation, since the presence in the nucleus is required for its transcriptional regulatory role. At 21 days, the regenerated fibers with central nucleus had not reached the size of intact fibers (VBL), nor that of controls. Whereas SVMPs and an enzyme with thrombin-like activity are known to increase the capacity of OPN binding to integrin of matrix and cell surfaces, we suggest that, during the pathogenesis of muscle regeneration post-VBL injection, OPN would be critically involved in an acute inflammatory process. OPN would act primarily as a cytokine activator of quiescent satellite cells and later play chemotactic and adhesive activities, promoting migration, proliferation of myoblasts, and formation and differentiation of myotubes. According to the literature, OPN is profibrotic in certain diseases. We suggest that the foci of interstitial fibrosis and the late presence of macrophages at the site of regeneration, as well as the cytoplasmic expression of myogenin may be relevant factors that lead to regeneration delay. It is suggested a pro-regenerative and anti-regenerative roles for OPN in the pathogenesis of alterations caused by B. lanceolatus venom / Mestrado / Farmacologia / Mestre em Farmacologia