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

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

Multiscale approach including microfibril scale to assess elastic constants of cortical bone based on neural network computation and homogenization method

The complexity and heterogeneity of bone tissue require a multiscale modelling to understand its mechanical behaviour and its remodelling mechanisms. In this paper, a novel multiscale hierarchical approach including microfibril scale based on hybrid neural network computation and homogenisation equations was developed to link nanoscopic and macroscopic scales to estimate the elastic properties of human cortical bone. The multiscale model is divided into three main phases: (i) in step 0, the elastic constants of collagen-water and mineral-water composites are calculated by averaging the upper and lower Hill bounds; (ii) in step 1, the elastic properties of the collagen microfibril are computed using a trained neural network simulation. Finite element (FE) calculation is performed at nanoscopic levels to provide a database to train an in-house neural network program; (iii) in steps 2 to 10 from fibril to continuum cortical bone tissue, homogenisation equations are used to perform the computation at the higher scales. The neural network outputs (elastic properties of the microfibril) are used as inputs for the homogenisation computation to determine the properties of mineralised collagen fibril. The mechanical and geometrical properties of bone constituents (mineral, collagen and cross-links) as well as the porosity were taken in consideration. This paper aims to predict analytically the effective elastic constants of cortical bone by modelling its elastic response at these different scales, ranging from the nanostructural to mesostructural levels. Our findings of the lowest scale's output were well integrated with the other higher levels and serve as inputs for the next higher scale modelling. Good agreement was obtained between our predicted results and literature data.Comment: 2

Auricular cartilage repair using cryogel scaffolds loaded with BMP-7-expressing primary chondrocytes

The loss of cartilage tissue due to trauma, tumour surgery or congenital defects, such as microtia and anotia, is one of the major concerns in head and neck surgery. Recently tissue-engineering approaches, including gene delivery, have been proposed for the regeneration of cartilage tissue. In this study, primary chondrocytes were genetically modified with plasmid-encoding bone morphogenetic protein-7 (BMP-7) via the commercially available non-viral Turbofect vector, with the aim of bringing ex vivo transfected chondrocytes to resynthesize BMP-7 in vitro as they would in vivo. Genetically modified cells were implanted into gelatin–oxidized dextran scaffolds and cartilage tissue formation was investigated in 15 × 15 mm auricular cartilage defects in vivo in 48 New Zealand (NZ) white rabbits for 4 months. The results were evaluated via histology and early gene expression. Early gene expression results indicated a strong effect of exogenous BMP-7 on matrix synthesis and chondrocyte growth. In addition, histological analysis results exhibited significantly better cartilage healing with BMP-7-modified (transfected) cells than in the non-modified (non-transfected) group and as well as the control

Engineering tendon and ligament tissues : present developments towards successful clinical products

Musculoskeletal diseases are one of the leading causes of disability worldwide. Among them, tendon and ligament injuries represent an important aspect to consider in both athletes and active working people. Tendon and ligament damage is an important cause of joint instability, and progresses into early onset of osteoarthritis, pain, disability and eventually the need for joint replacement surgery. The social and economical burden associated with these medical conditions presents a compelling argument for greater understanding and expanding research on this issue. The particular physiology of tendons and ligaments (avascular, hypocellular and overall structural mechanical features) makes it difficult for currently available treatments to reach a complete and long-term functional repair of the damaged tissue, especially when complete tear occurs. Despite the effort, the treatmentmodalities for tendon and ligament are suboptimal, which have led to the development of alternative therapies, such as the delivery of growth factors, development of engineered scaffolds or the application of stem cells, which have been approached in this review

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

De-excitation of the strongly coupled band in 177Au and implications for core intruder configurations in the light Hg isotopes

Excited states in the proton-unbound nuclide 177Au were populated in the 92Mo(88Sr, p2n) reaction and identified using the Jurogam-II and GREAT spectrometers in conjunction with the RITU gas-filled separator at the University of Jyväskylä Accelerator Laboratory. A strongly coupled band and its decay path to the 11/2− α-decaying isomer have been identified using recoil-decay tagging. Comparisons with cranked HartreeFock-Bogoliubov (HFB) calculations based on Skyrme energy functionals suggest that the band has a prolate deformation and is based upon coupling the odd 1h11/2 proton hole to the excited 0+ 2 configuration in the 178Hg core. Although these configurations might be expected to follow the parabolic trend of core Hg(0+2 ) states as a function of neutron number, the electromagnetic decay paths from the strongly coupled band in 177Au are markedly different from those observed in the heavier isotopes above the midshell. This indicates that a significant change in the structure of the underlying A+1Hg core occurs below the neutron midshell

Role of PACAP and VIP Signalling in Regulation of Chondrogenesis and Osteogenesis

Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are multifunctional proteins that can regulate diverse physiological processes. These are also regarded as neurotrophic and anti-inflammatory substances in the CNS, and PACAP is reported to prevent harmful effects of oxidative stress. In the last decade more and more data accumulated on the similar function of PACAP in various tissues, but its cartilage- and bone-related presence and functions have not been widely investigated yet. In this summary we plan to verify the presence and function of PACAP and VIP signalling tool kit during cartilage differentiation and bone formation. We give evidence about the protective function of PACAP in cartilage regeneration with oxidative or mechanically stress and also with the modulation of PACAP signalling in vitro in osteogenic cells. Our observations imply the therapeutic perspective that PACAP might be applicable as a natural agent exerting protecting effect during joint inflammation and/or may promote cartilage regeneration during degenerative diseases of articular cartilage