Influence of muscle mass and bone mass on the mobility of elderly women: an observational study.

BACKGROUND: The purpose of this study was to investigate the influence of muscle mass and bone mineral density on markers of mobility in dwelling elderly women. METHODS: This cross-sectional study included 99 elderly women, who were 65 years old or above, in Campinas-SP, Brazil. To collect data, we used sociodemographic data, the body mass index (BMI), health status, comorbidities, use of medications, mobility tests (TUG and gait speed) and examinations of the body composition (densitometry with dual-emission X-ray absorptiometry "DXA"). In order to examine the relationship between muscle and bone mass with mobility (gait speed and TUG), we applied the Spearman correlation coefficient.Also was applied the analysis of covariance (ANCOVA) adjusted for age and comorbidities. To identify the factors associated with mobility, we used the univariate and multivariate logistic regression analysis. The level of significance for statistical tests was P < 0.05. RESULTS: The correlation between sarcopenia and bone mineral density with mobility tests showed a significant relationship only between sarcopenia and TUG (r = 0.277, P = 0.006) in Spearman correlation coefficient. The result of the correlation analysis (ANCOVA) showed that sarcopenia was associated with gait speed (r2 = 0.0636, P = 0.0018) and TUG (r2 = 0.0898, P = 0.0027). The results of the multivariate analysis showed that age (P = 0.034, OR = 1.081) was associated with worse performance on gait speed. By highlighting the TUG test, the results of the multivariate analysis showed that the age (P = 0.004, OR = 1.111) and BMI in overweight (P = 0.011, OR = 7.83) and obese (P < 0.001, OR = 7.84) women were associated with lower performance of the functionality of the lower limbs. CONCLUSION: The findings with regard to mobility tests which were analyzed in this study indicate the association of variables related to the aging process that contribute to the decline in physical performance, for example, age, BMI and sarcopenia.

Systemic lupus erythematosus associated with vasculitic syndrome (Takayasu's arteritis).

A 43-year-old woman reported pain in the right hypochondrium, which had started 3 years before and had been worsening for the past few days. Claudication in the superior and inferior limbs, diffuse myalgia, dyspnea, precordialgia followed by dizziness and visual turbidity were added to the clinical picture. In the physical examination bilateral carotid bruit was observed, abdominal aorta murmur and the decrease of the right radial and left pedis pulses and arterial hypertension with difference in the diastolic pressure between limbs >10 mmHg was also observed. On cardiac catheterisation with aortography, right coronary with proximal parietal irregularities, slight pressure increase in right chambers and pulmonary artery, preserved left ventricle contractility, competent valves, carotid and subclavian partial obstruction, severe narrowing of the abdominal aorta below the diaphragm (80%) and right renal artery significant stenosis were observed. Takayasu's arteritis (TA) diagnosis was established according to the ACR criteria based on the clinical symptomatology, on physical and image test findings. Two years later she presented malar rash, photosensitivity, nephropathy, leukopenia, lymphopenia and hemolytic anemia confirming the systemic lupus erythematosus (SLE) diagnosis. TA coexisting with SLE has rarely been reported.

Differentiation of dental pulp stem cells into chondrocytes upon culture on porous chitosan-xanthan scaffolds in the presence of kartogenin.

Adhesion, proliferation and differentiation of dental pulp stem cells (DPSCs) into chondrocytes were investigated in this work with the purpose of broadening the array of cell alternatives to the therapy of cartilage lesions related to tissue engineering approaches. A porous chitosan-xanthan (C-X) matrix was used as scaffold and kartogenin was used as a selective chondrogenic differentiation promoter. The scaffold was characterized regarding aspect and surface morphology, absorption and stability in culture medium, thickness, porosity, thermogravimetric behavior, X-ray diffraction, mechanical properties and indirect cytocompatibility. The behavior of DPSCs cultured on the scaffold was evaluated by scanning electron microscopy and cell differentiation, by histological analysis. A sufficiently stable amorphous scaffold with mean thickness of 0.89±0.01mm and high culture medium absorption capacity (13.20±1.88g/g) was obtained, and kartogenin concentrations as low as 100nmol/L were sufficient to efficiently induce DPSCs differentiation into chondrocytes, showing that the strategy proposed may be a straightforward and effective approach for tissue engineering aiming at the therapy of cartilage lesions.

Prevalence and factors associated with rheumatic diseases and chronic joint symptoms in the elderly.

AIM: In the elderly population, rheumatic conditions are major causes of pain that restrict participation in activities and mobility, and cause difficulties in the execution of self-care tasks. The present study aimed to analyze the prevalence and factors associated with the self-reported rheumatic diseases and chronic joint symptoms of the elderly. METHODS: This transversal epidemiological survey involved 2209 older adults (aged ≥ 60 years). The investigation included sociodemographic factors, anthropometrics, activities of daily living, chronic conditions, medication and quality of life. Univariate and multivariate regression analysis were used for statistical procedures, P ≤ 0.05. RESULTS: The prevalence of rheumatism was 22.7%. Multivariate analysis showed that rheumatism was correlated with the following: female sex (OR = 1.91), high income (OR = 2.34), cardiovascular disease (OR = 1.42), cataracts (OR = 1.39), glucocorticoids (OR = 5.24), other anti-inflammatory medications (OR = 2.24) and pain (OR = 0.983). After adjusting for age and glucocorticoids, an association between cataracts and rheumatism was detected (OR = 1.32). The prevalence of symptoms was 45.6%. Multivariate regression results for symptoms included the following: female sex (OR = 1.40), body mass index ≥ 30.0 kg/m(2) (OR = 3.31), functional capacity (OR = 0.990), general health (OR = 0.993) and pain (OR = 0.981). After adjustment for age and glucocorticoids, an association between cataracts and symptoms was detected (OR = 1.26). CONCLUSION: There was a significant association of rheumatism and symptoms with women and high incomes. Obesity was associated with joint symptoms, which in turn were associated with an impaired quality of life. Cataracts and cardiovascular disease were associated with rheumatism. The identification of these characteristics in the elderly will contribute to a better understanding of this systemic disease and should be used to plan effective preventive measures.

Regulation of chondrogenesis by transforming growth factor-beta 3 and insulin-like growth factor-1 from human mesenchymal umbilical cord blood cells.

OBJECTIVE: Mature articular cartilage is vulnerable to injuries and disease processes that cause irreversible tissue damage because of its limited capacity for self-repair. Umbilical cord blood is a source of mesenchymal stem cells, which can give rise to cells of different lineages, including cartilage, bone, and fat. Cellular condensation is a required step in the initiation of mesenchymal chondrogenesis. We attempted to differentiate cells from umbilical cord blood into chondrocytes with insulin-like growth factor 1 (IGF-1) and transforming growth factor-ss3 (TGF-ss3). METHODS: Cells were grown in high density micromass and monolayer culture systems and then evaluated for expression of type II collagen, aggrecan, and Sox9. Umbilical cord blood from 130 patients was harvested. RESULTS: Expression of type II collagen, aggrecan, and Sox9 was detected after 14 days in TGF-ss3- and IGF-1-stimulated cells in both types of culture (monolayer and micromass). On Day 21 in the micromass culture, expression levels were greater than they were at 14 days for all genes. TGF-ss3 was found to be more efficient at promoting chondrogenesis than IGF-1. By western blot, we also found that after 3 weeks, the expression of type II collagen was greater in micromass culture with TGF-ss3. CONCLUSION: TGF-ss3 used in micromass culture is the best growth factor for promoting the proliferation and differentiation of mesenchymal cells from umbilical cord blood during chondrogenesis. This approach may provide an alternative to autologous grafting.

Hypoxia inducible factor-1 alpha expression in human normal and osteoarthritic chondrocytes.

BACKGROUND: Articular cartilage is a unique tissue in that it is avascular with its nutrition and oxygen supply being dependent on the diffusion of solutes through the synovial fluid and to and from the subchondral bone. The oxygen levels in articular cartilage, therefore, are assumed to be low. Oxygen is an important modulator of gene expression and this regulation occurs largely through the activation of the transcriptional complex hypoxia-inducible factor-1 (HIF-1). However, little is known about how articular cartilage regulates genes in response to O(2)tension and whether this regulation occurs through HIF-1. AIM: The aim of this study was to investigate the expression profile of HIF-1alpha in normal and osteoarthritic (OA) chondrocytes under normoxic and hypoxic conditions, and in response to treatment with tumor necrosis factor alpha (TNFalpha). METHODS: Articular chondrocytes from human normal and OA knee cartilage were isolated and cultured in suspension under normoxic (21% O(2)) or hypoxic conditions (1% O(2)). Chondrocytes were also treated with TNF-alpha under normoxic conditions. Nuclear extracts and total RNA were prepared and HIF-1alpha protein and mRNA levels were assayed by immunoblotting and Northern hybridization. Localization of HIF-1alpha by immunofluorescence was performed on frozen sections of cartilage tissue by confocal microscopy. RESULTS: HIF-1alpha expression was detectable in human normal and OA chondrocytes and cartilage by Northern analysis, immunoblotting and immunofluorescence under normoxic conditions. Culture of OA or normal chondrocytes under hypoxic conditions for up to 16h resulted in a modest stabilization and/or increase of HIF-1alpha expression. Treatment of articular chondrocytes with TNFalpha resulted in an increase in HIF-1alpha protein steady state levels under normoxic conditions. The increase in HIF-1alpha expression induced by TNFalpha was partially blocked by pretreatment of the chondrocytes with inhibitors of NFkappaB or p38 MAP kinase. We also observed the expression of HIF-2alpha mRNA in human chondrocytes. CONCLUSION: HIF-1alpha is expressed in human normal and OA articular chondrocytes cultured under normoxic conditions. HIF-1alpha can be further induced or stabilized in articular chondrocytes by hypoxia or by treatment with TNFalpha. The relatively high constitutive expression of HIF-1alpha by chondrocytes may be an important adaptation to survival in the avascular-hypoxic environment of cartilage. Modulation of HIF-1alpha levels by TNF-alpha may have important implications for chondrocyte metabolism during degenerative joint disease. In addition, we detected for the first time the expression of HIF-2alpha mRNA in chondrocytes.

Assessment of the gene expression profile of differentiated and dedifferentiated human fetal chondrocytes by microarray analysis.

OBJECTIVE: To study the changes in patterns of gene expression exhibited by human chondrocytes as they dedifferentiate into fibroblastic cells in culture in order to better understand the mechanisms that control this process and its relationship to the phenotypic changes that occur in chondrocytes during the development of osteoarthritis (OA). METHODS: Human fetal epiphyseal chondrocytes (HFCs) were cultured either on poly-(2-hydroxyethyl methacrylate)-coated plates (differentiated HFC cultures) or in plastic tissue culture flasks as monolayers (dedifferentiated HFC cultures). Following 11 days of culture under either condition, poly(A+) RNA was isolated from the two cell populations and subjected to a gene expression analysis using a microarray containing approximately 5,000 known human genes and approximately 3,000 expressed sequence tags (ESTs). RESULTS: A > or =2-fold difference in the expression of 62 known genes and 6 ESTs was observed between the two cell types. The differences in expression of several of the genes detected by the microarray hybridization were confirmed by Northern analyses. Two transcription factor genes, TWIST and HIF-1alpha, and a cellular adhesion protein gene, cadherin 11, were markedly regulated in response to differentiation and dedifferentiation. Expression of these genes was also detected in adult normal and OA cartilage and chondrocytes. Analysis of the gene expression profile of HFCs revealed a complex pattern of gene expression, including many genes not yet reported to be expressed by chondrocytes. CONCLUSION: Chondrocytes in monolayer become dedifferentiated, acquiring a fibroblast-like appearance and changing their pattern of gene expression from one of expression of chondrocyte-specific genes to one that resembles a fibroblastic or chondroprogenitor-like pattern. Changes in gene expression associated with the process of dedifferentiation of HFCs in vitro were observed in a wide variety of genes, including genes encoding extracellular matrix proteins, transcription factors, and growth factors. At least 3 of the genes that were regulated in response to dedifferentiation were also found to be expressed in adult normal and OA articular cartilage and chondrocytes.

Undifferentiated spondyloarthropathies in Brazilians: importance of HLA-B27 and the B7-CREG alleles in characterization and disease progression.

OBJECTIVE: To analyze the profile of the HLA-B27 and B7 cross-reactive group (CREG) alleles and the role of these markers in disease characterization and progression in patients with undifferentiated spondyloarthropathies (uSpA). METHODS: A total of 80 patients with a diagnosis of uSpA (40 HLA-B27 positive and 40 HLA-B27 negative) were prospectively studied for 2 years. The control group consisted of 66 HLA-B27 positive and 112 HLA-B27 negative individuals without a history of seronegative SpA. HLA-B alleles were typed at low (B7-CREG alleles, i.e., B*7, B*54, B*55, B*56, B*40, B*42) or high resolution (B*27 alleles) using polymerase chain reaction-amplified DNA hybridized with sequence-specific oligonucleotide probes. RESULTS: HLA-B*2705 was the most frequent allele, observed in 92.5% of the patients and in 77% of the controls, followed by the HLA-B*2702, observed in 5% of the patients and in 12% of the controls. HLA-B*2704 was observed in only one patient (2.5%), and was absent in the control population. HLA-B*2703 (6%) and HLA-B*2707 (5%) alleles were observed only in controls. No associations between HLA-B*27 alleles or B7-CREG alleles and any specific manifestation of uSpA were observed. HLA-B27 positive patients more frequently presented juvenile onset SpA (p = 0.002) and progression to ankylosing spondylitis (AS) (p = 0.03) than did HLA-B27 negative patients. The B7-CREG alleles were observed in 5% of the HLA-B27 positive uSpA group, in 25% of the HLA-B27 negative uSpA group, in 7% of the HLA-B27 positive controls, and in 13% of the HLA-B27 negative controls; a significant association was observed between the presence of the B7-CREG and the HLA-B27 negative uSpA group (p = 0.012). CONCLUSION: The frequency of the HLA-B*2705 allele among the B27 positive uSpA patients of this series was closely similar to that reported for patients with ankylosing spondylitis (AS). The presence of HLA-B*27 alleles was associated with the progression to AS, and the presence of B7-CREG was associated with uSpA in the HLA-B27 negative group.

Densidade mineral óssea em pacientes com lúpus eritematoso sistêmico e sua relação com níveis estrogênicos / Bone mineral density in patients with systemic lupus erythematosus and its relation to estrogen levels

Objetivos: Avaliar a densidade mineral óssea (DMO) em pacientes com lúpus eritematoso sistêmico (LES), determinar o papel dos corticosteróides e drogas citostáticas, e analisar os efeitos dos estrogênios sobre a densidade mineral óssea no LES. Pacientes e Métodos: Avaliou-se a DMO vertebral (L2-L4) e do fêmur proximal em 60 pacientes com LES na pós-menopausa e em 64 controles. Também os níveis de estradiol plasmático foram medidos. A idade, idade ao início da doença, índice de massa corpórea (IMC), tempo de doença, atividade de doença (pelo SLEDAI), doses de prednisona no momento da avaliação, cumulativa do último ano e cumulativa total, bem como o uso de drogas citostáticas, também foram analisados. Resultados: A média dos níveis de estradiol entre as pacientes foi de 175,8 pg/ml e, entre as mulheres do grupo controle, 149,9. A DMO foi significativamente menor nas pacientes do que nas mulheres sadias (P<0,0001). As médias de doses atual, cumulativa total e do último ano foram, respectivamente, de 19,17 mg/dl, 28,78g e 5,33g. Não houve associação entre as doses de corticosteróides ou de outras drogas citostáticas utilizadas e a perda de massa óssea. As concentrações séricas de estradiol não influíram na perda de massa óssea. O IMC e a idade da paciente ao início da doença, conjuntamente, influíram sobre a DMO em vértebra L2. Conclusão: A DMO foi significativamente menor entre as pacientes com LES sem associação com as doses de corticosteróides ou outras drogas utilizadas. Os níveis de estradiol não parecem influir sobre a DMO nessas pacientes. Baixo IMC interagindo com baixa idade da paciente ao início da doença parece influir sobre a probabilidade de perda de massa óssea no LES