Collagens - structure, function and biosynthesis.

The extracellular matrix represents a complex alloy of variable members of diverse protein families defining structural integrity and various physiological functions. The most abundant family is the collagens with more than 20 different collagen types identified so far. Collagens are centrally involved in the formation of fibrillar and microfibrillar networks of the extracellular matrix, basement membranes as well as other structures of the extracellular matrix. This review focuses on the distribution and function of various collagen types in different tissues. It introduces their basic structural subunits and points out major steps in the biosynthesis and supramolecular processing of fibrillar collagens as prototypical members of this protein family. A final outlook indicates the importance of different collagen types not only for the understanding of collagen-related diseases, but also as a basis for the therapeutical use of members of this protein family discussed in other chapters of this issue

Optical aids fo low vision : the use of the internet by teachers of people with visual impairment

Orientador: Edmea Rita Temporini NastariTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: A presente pesquisa teve os objetivos de verificar a viabilidade do uso de internet para transmissão de informações e orientações a professores, a respeito do uso de auxílios ópticos no ambiente escolar; descrever e discutir percepções e condutas de professores em relação ao uso de internet; verificar opiniões sobre apresentação e conteúdo do site "Auxílios Ópticos"; e identificar fatores que influem na receptividade a orientações, divulgadas por internet, sobre o uso de auxílios ópticos para baixa visão. O método consistiu em pesquisa com enfoques quantitativo e qualitativo. A pesquisa quantitativa caracterizou-se como estudo transversal analítico, com aplicação de questionário estruturado disponibilizado on-line. A abordagem qualitativa referiu-se a estudo descritivo-exploratório, com aplicação de técnica de grupo focal. A população foi constituída por 58 professores do sistema estadual de ensino de Campinas. Para análise dos resultados foram avaliados aspectos estatísticos e aplicada a técnica de análise do discurso do sujeito coletivo, respectivamente. A pesquisa foi realizada a partir de informações fornecidas por site na internet, sob o domínio www.auxiliosopticos.fcm.unicamp.br, construído especificamente para orientação sobre o uso de auxílios ópticos utilizados por pessoas com baixa visão, e dirigido especialmente a professores, alunos e funcionários de escolas. Os dados estatísticos mostraram que os sujeitos consideraram fácil acessar a internet (96,4%) e encontrar informações no site (64,9%); opinaram que o site despertou muito interesse sobre o assunto (77,6%). O fato de o professor lecionar para alunos com deficiência visual não influiu no recebimento de explicações sobre o uso de auxílios ópticos (p=0,829) e na periodicidade do uso de internet na prática educativa (p=0,574) ou na facilidade de acesso à internet (p=0,122). Os resultados qualitativos permitiram perceber que os sujeitos acessam a internet usualmente na busca de informações, embora tenham declarado encontrar restrições de acesso nas escolas; foi reconhecida a necessidade de informações sobre deficiência visual. Observadas as limitações tecnológicas existentes nas escolas incluídas neste estudo, pode-se concluir ter sido considerado viável o uso de internet em programa de disseminação de informações a respeito do uso de auxílios ópticos para baixa visãoAbstract: The aim of this study was to verify the viability of using the Internet to inform and guide teachers regarding the use of optical aids into the school environment; to describe and discuss teachers' perceptions and behaviors related to the use of the Internet; to verify opinions about presentation and content of the site "Optical Aids"; and to identify factors that affect receptivity to orientations spread across the Internet concerning the use of optical aids for low vision. The method consisted of a research with quantitative and qualitative approaches. The quantitative research characterized as an analytical transversal study in which a structured online questionnaire was applied. The qualitative approach referred to a descriptive-exploratory study in which the focus group technique was applied. The population comprised 58 teachers of the state teaching system in the city of Campinas. The analysis included statistical aspects and the collective subject discourse technique. The research was performed from information provided by the Internet site, under the domain name www.auxiliosopticos.fcm.unicamp.br, specifically built for orientation about the use of optical aids by low vision people and especially directed to teachers, students and school employees. The statistical data showed that the subjects considered easy the access to the Internet (96.4%) and to find information on the site (64.9%); others said that the site aroused interest on the subject (77.6%). The fact that the teacher teaches students with visual impairments did not affect the acceptance of explanations about the use of optical aids (p=0.829) and the period of Internet usage in the educative practice (p=0.574) or the easy access to the Internet (p=0.122). The qualitative results allowed to observe that the subjects usually access the Internet in search of information, although they declared having found restrictions in the access to the Internet in schools; it was recognized the need for information regarding visual impairments. After observing the technological limitations of the schools included in this study, we could conclude that the use of the Internet was considered viable in the program for the dissemination of the information concerning the use of optical aids for low visionDoutoradoCiencias BiomedicasDoutor em Ciências Médica

Molecular differentiation between osteophytic and articular cartilage – clues for a transient and permanent chondrocyte phenotype

SummaryObjectiveTo identify the molecular differences between the transient and permanent chondrocyte phenotype in osteophytic and articular cartilage.MethodsTotal RNA was isolated from the cartilaginous layer of osteophytes and from intact articular cartilage from knee joints of 15 adult human donors and subjected to cDNA microarray analysis. The differential expression of relevant genes between these two cartilaginous tissues was additionally validated by quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and by immunohistochemistry.ResultsAmong 47,000 screened transcripts, 600 transcripts were differentially expressed between osteophytic and articular chondrocytes. Osteophytic chondrocytes were characterized by increased expression of genes involved in the endochondral ossification process [bone gamma-carboxyglutamate protein/osteocalcin (BGLAP), bone morphogenetic protein-8B (BMP8B), collagen type I, alpha 2 (COL1A2), sclerostin (SOST), growth arrest and DNA damage-induced gene 45ß (GADD45ß), runt-related transcription factor 2 (RUNX2)], and genes encoding tissue remodeling enzymes [matrix metallopeptidase (MMP)9, 13, hyaluronan synthase 1 (HAS1)]. Articular chondrocytes expressed increased transcript levels of antagonists and inhibitors of the BMP- and Wnt-signaling pathways [Gremlin-1 (GREM1), frizzled-related protein (FRZB), WNT1 inducible signaling pathway protein-3 (WISP3)], as well as factors that inhibit terminal chondrocyte differentiation and endochondral bone formation [parathyroid hormone-like hormone (PTHLH), sex-determining region Y-box 9 (SOX9), stanniocalcin-2 (STC2), S100 calcium binding protein A1 (S100A1), S100 calcium binding protein B (S100B)].Immunohistochemistry of tissue sections for GREM1 and BGLAP, the two most prominent differentially expressed genes, confirmed selective detection of GREM1 in articular chondrocytes and that of BGLAP in osteophytic chondrocytes and bone.ConclusionsOsteophytic and articular chondrocytes significantly differ in their gene expression pattern. In articular cartilage, a prominent expression of antagonists inhibiting the BMP- and Wnt-pathway may serve to lock and stabilize the permanent chondrocyte phenotype and thus prevent their terminal differentiation. In contrast, osteophytic chondrocytes express genes with roles in the endochondral ossification process, which may account for their transient phenotype

Chondrogenic differentiation of growth factor-stimulated precursor cells in cartilage repair tissue is associated with increased HIF-1α activity

SummaryObjectiveTo investigate the chondrogenic potential of growth factor-stimulated periosteal cells with respect to the activity of Hypoxia-inducible Factor 1α (HIF-1α).MethodsScaffold-bound autologous periosteal cells, which had been activated by Insulin-like Growth Factor 1 (IGF-1) or Bone Morphogenetic Protein 2 (BMP-2) gene transfer using both adeno-associated virus (AAV) and adenoviral (Ad) vectors, were applied to chondral lesions in the knee joints of miniature pigs. Six weeks after transplantation, the repair tissues were investigated for collagen type I and type II content as well as for HIF-1α expression. The functional role of phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling on BMP-2/IGF-1-induced HIF-1α expression was assessed in vitro by employing specific inhibitors.ResultsUnstimulated periosteal cells formed a fibrous extracellular matrix in the superficial zone and a fibrocartilaginous matrix in deep zones of the repair tissue. This zonal difference was reflected by the absence of HIF-1α staining in superficial areas, but moderate HIF-1α expression in deep zones. In contrast, Ad/AAVBMP-2-stimulated periosteal cells, and to a lesser degree Ad/AAVIGF-1-infected cells, adopted a chondrocyte-like phenotype with strong intracellular HIF-1α staining throughout all zones of the repair tissue and formed a hyaline-like matrix. In vitro, BMP-2 and IGF-1 supplementation increased HIF-1α protein levels in periosteal cells, which was based on posttranscriptional mechanisms rather than de novo mRNA synthesis, involving predominantly the MEK/ERK pathway.ConclusionThis pilot experimental study on a relatively small number of animals indicated that chondrogenesis by precursor cells is facilitated in deeper hypoxic zones of cartilage repair tissue and is stimulated by growth factors which enhance HIF-1α activity

Causes Of Low Vision And Use Of Optical Aids In The Elderly.

To determine the causes of low vision in an elderly population attended by a university visual rehabilitation service and to check for the use of prescribed optical aids. A cross-sectional study was carried out on patients aged 60 years or over attending for the first time a university low vision service in 2001. Ophthalmic reevaluation and interview were performed by means of a structured questionnaire in 2002. The sample comprised 50 subjects aged between 60 and 90 years. Severe low vision (< or =20/200) was present in 68.0% of patients. The main cause of low vision was age-related macular degeneration (44.0%). Regarding literacy, 16.0% were illiterate and 72.0% had completed fundamental schooling. Thirty-one patients (62.0%) had been prescribed optical aids; 54.8% of these patients stated that they use them. A majority (70.6%) held a favorable opinion of these aids. The main cause of low vision was age-related macular degeneration. Approximately half of those receiving prescriptions reported actually using the aids in their daily activities. Making best use of residual vision in the elderly population with visual impairment is a priority, given the social context, if the independence necessary for enhanced quality of life is to be achieved.59157-6

Causas de baixa visão e uso de auxílio óptico por idosos

PURPOSE: To determine the causes of low vision in an elderly population attended by a university visual rehabilitation service and to check for the use of prescribed optical aids. METHOD: A cross-sectional study was carried out on patients aged 60 years or over attending for the first time a university low vision service in 2001. Ophthalmic reevaluation and interview were performed by means of a structured questionnaire in 2002. RESULTS: The sample comprised 50 subjects aged between 60 and 90 years. Severe low vision (;OBJETIVO: Determinar causas de baixa visão de população idosa atendida por serviço universitário de reabilitação visual e verificar a utilização dos auxílios ópticos prescritos. MÉTODO: Foi realizado estudo transversal entre pacientes de idade igual ou superior a 60 anos, atendidos pela primeira vez por serviço de visão subnormal em 2001. Foram submetidos à reavaliação oftalmológica e entrevistados mediante a aplicação de questionário estruturado em 2002. RESULTADOS: A amostra foi formada por 50 sujeitos de idades entre 60 e 90 anos. Apresentaram baixa visão acentuada (acuidade visual < 20/200) 68,0% dos pacientes. A principal causa de baixa visão foi a doença macular relacionada à idade (44,0%). No que se refere à situação de leitura, 16,0% não sabem ler e 72,0% cursaram até a 4ª série. Em relação aos auxílios ópticos, 31 (62,0%) receberam prescrição e 54,8% desses afirmaram utilizá-los, sendo causas de não prescrição a idade elevada e fatores sócio-culturais como pouco interesse na leitura. Quanto à opinião sobre a validade do auxílio 70,6% responderam positivamente. CONCLUSÃO: A principal causa de baixa visão foi a degeneração macular relacionada à idade. Aproximadamente metade da população que recebeu prescrição relatou o uso efetivo dos auxílios ópticos nas atividades diárias. O aproveitamento do resíduo visual de população idosa com baixa visão reveste-se de prioridade quando se considera o contexto social e a independência necessária à melhor qualidade de vida

Pulmonary and cardiovascular syndrome due to hantavirus: clinical aspects of an emerging disease in southeastern Brazil

A síndrome pulmonar e cardiovascular por hantavírus é doença causada pela aspiração de aerossóis dos dejetos de roedores silvestres contaminados por vírus da família Bunyaviridae. Estudamos manifestações clínicas e laboratoriais de 70 casos ocorridos de 1998 a 2007 na região de Ribeirão Preto, SP. A freqüência de sintomas foi dispnéia (87%), febre (81%), tosse (44%), cefaléia (34%), taquicardia (81%), hipotensão arterial (56%), hipóxia (49%), acidose metabólica (57%), linfocitopenia (51%), hematócrito >45% (70%), leucocitose com desvio à esquerda (67%), creatinina (51%) e uréia (42%) séricas elevadas. A letalidade (54,3%) ocorreu principalmente no 4o dia. Insuficiência respiratória, hipotensão arterial e choque ocorreu 24-48 horas; o hematócrito elevado e a plaquetopenia são sinais fortemente sugestivos da doença. A hipótese diagnóstica de pneumonia atípica associada a bom prognóstico (p:0,0136); a infusão hídrica >2.000ml e hipotensão arterial associadas a mau prognóstico (p:0,0286 e p:0,0453).Pulmonary and cardiovascular syndrome due to hantavirus is a disease caused by inhalation of aerosols from the excreta of wild rodents contaminated by viruses of the Bunyaviridae family. We studied the clinical and laboratory manifestations of 70 cases that occurred in the region of Ribeirão Preto, SP, Brazil, between 1998 and 2007. The frequency of symptoms was as follows: dyspnea (87%), fever (81%), coughing (44%), headache (34%), tachycardia (81%), low arterial blood pressure (56%), metabolic acidosis (57%), lymphocytopenia (51%), hematocrit > 45% (70%), leukocytosis with left deviation (67%), creatinine (51%) and urea (42%). Mortality (54.3%) occurred mainly on the fourth day. Respiratory insufficiency, low arterial blood pressure and shock occurred after 24 to 48 hours. High hematocrit and decreased platelet levels were signs strongly suggestive of the disease. The diagnostic hypothesis of atypical pneumonia was associated with a good prognosis (p = 0.0136). Fluid infusion greater than 2,000 ml and arterial hypotension were associated with a poor prognosis (p = 0.0286 and p = 0.0453)

PU.1 controls fibroblast polarization and tissue fibrosis

Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs