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1.
Res Vet Sci ; 136: 609-615, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33901785

RESUMO

In this study, we conducted study to explore the association between serum cross-linked N-telopeptide of type I collagen (NTx), a marker of bone resorption, and age, body weight, and blood biochemical parameters as well as the neutered and intact status in male and female dogs. We targeted 145 healthy dogs (aged 0.33-18.33 years); 70 were males (38 intact, 32 castrated), and 75 were females (31 intact, 44 ovariohysterectomized). We found that the NTx levels were significantly higher in dogs aged ≤2 years than in older dogs. NTx concentration tended to decrease with age in dogs aged ≤2 years, but not significantly, and remained constant in dogs aged >2 years. Accordingly, we investigated sex/sterilization status in two age cohorts (juvenile-to-young-adult, ≤2 years of age; adult-to-geriatric, >2 years of age). In the adult-to-geriatric cohort, NTx concentration was highest in intact males, followed by neutered males, neutered females, and intact females. The intact vs. neutered difference was significant in males, but not in females. Our results suggested that estradiol deficiency may not affect bone metabolism in female dogs, but androgen deficiency may affect bone metabolism in male dogs. Furthermore, age did not affect bone metabolism after 2 years. NTx concentrations were significantly higher in the juvenile-to-young-adult cohort than in the adult-to-geriatric cohort and tended to decrease with age, similar to young humans. This study unveils novel sex differences in canine serum NTx concentrations and suggests the effect of neutering on bone metabolism, showing that serum NTx concentrations change with age.


Assuntos
Envelhecimento/sangue , Colágeno Tipo I/sangue , Cães/sangue , Peptídeos/sangue , Animais , Biomarcadores/sangue , Peso Corporal , Reabsorção Óssea/sangue , Reabsorção Óssea/veterinária , Castração , Feminino , Masculino , Caracteres Sexuais
2.
Medicine (Baltimore) ; 100(3): e24259, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33546047

RESUMO

BACKGROUND: Osteoporosis (OP) results in an increased risk of fragility fractures, representing a major public health problem. In preventing OP, complementary and alternative medicine, such as acupuncture, was recommended because of the low efficiency and side effects of medications. Recently, there is insufficient evidence on electroacupuncture as an effective therapy for OP management. Hence, we evaluated the effectiveness of electroacupuncture for OP treatment. METHODS: We conducted a systematic review and meta-analysis of clinical studies on patients with OP. Five databases (PubMed, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang) were searched from the earliest publication date to March 12, 2020. Randomized controlled trials (RCTs) were included if electroacupuncture was applied as the sole treatment or as an adjunct to other treatments compared with medications in patients with OP. The measurement outcomes included serum aminoterminal propeptide of type I procollagen (PINP) and C-telopeptide of type I collagen (CTX) levels, bone mineral density (BMD) of lumbar, and visual analog scale scores for OP-related pain. Acupoints were extracted when available. RESULTS: In total, 11 RCTs involving 731 participants were included for further meta-analysis. The meta-analysis showed that the use of electroacupuncture as a sole treatment or as an adjunct to other treatments could relieve OP-related pain compared with medications [mean difference (MD) =  -0.58, 95% confidence interval (CI); MD =  -0.97 to -0.19, P = .003, I2 = 88%; MD =  -1.47, 95% CI = -2.14 to -0.79, P < .001, I2 = 96%). Meanwhile, the results showed a favorable effect of electroacupuncture on decreasing serum beta-CTX levels. However, there were no significant differences in serum PINP levels and BMD of lumbar. Shenshu (BL23) was the most frequent acupoint stimulation among these studies. CONCLUSIONS: The application of electroacupuncture as an independent therapy or as an adjunct to other treatments might attenuate OP-related pain and serum beta-CTX levels. However, to overcome the methodological shortcomings of the existing evidence, due to a small size of samples and high risk of bias in these included RCTs, further rigorous studies are required.


Assuntos
Eletroacupuntura , Osteoporose/terapia , Dor nas Costas/terapia , Densidade Óssea , Colágeno Tipo I/sangue , Humanos , Osteoporose/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue
3.
J Bone Miner Metab ; 39(3): 484-493, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33389132

RESUMO

INTRODUCTION: There have been no reports of the effects of baseline lumbar spine bone mineral density (LS-BMD) and bone turnover marker levels on the therapeutic effect of a 28.2-µg teriparatide formulation for twice-weekly use (2/W-TPTD). MATERIALS AND METHODS: An analysis was performed using data from a double-blind, randomized, non-inferiority trial (TWICE study) conducted with patients who received 2/W-TPTD or a 56.5-µg teriparatide formulation for once-weekly use (1/W-TPTD) for 48 weeks. The patients were divided into tertile groups based on baseline LS-BMD, urinary type I collagen cross-linked N-telopeptide (u-NTX), and serum type I procollagen-N-propeptide (P1NP) levels, respectively. Time profiles of these measurements were analyzed. Furthermore, whether a change in P1NP is a predictor for percentage change in BMD was assessed. RESULTS: Across all tertile groups divided based on baseline LS-BMD and levels of bone turnover markers, the LS-BMD increased significantly. The u-NTX level decreased throughout the study period in the high- and middle-u-NTX-level groups. The P1NP level increased after 4 weeks, but subsequently decreased after 12 weeks and thereafter in the high-P1NP-level group; it increased after 4 weeks and subsequently fluctuated near the baseline level in the middle-P1NP-level group. A cut-off value of 12.0 µg/L for change in P1NP after 4 weeks of 2/W-TPTD as a predictor for percentage change in LS-BMD of 3% or more after 48 weeks gave a positive predictive value of 89.6%. CONCLUSION: 2/W-TPTD, just like 1/W-TPTD, improved LS-BMD significantly, regardless of baseline LS-BMD and bone turnover marker levels.


Assuntos
Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Vértebras Lombares/fisiologia , Teriparatida/farmacologia , Idoso , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Colágeno Tipo I/sangue , Método Duplo-Cego , Esquema de Medicação , Análise Fatorial , Feminino , Humanos , Vértebras Lombares/efeitos dos fármacos , Masculino , Peptídeos/sangue , Curva ROC , Fatores de Tempo
4.
Clin Interv Aging ; 15: 501-518, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308378

RESUMO

Serum biomarkers of osteoarticular diseases have been in the limelight of current clinical research trends. Laboratory validation of defined and candidate biomarkers for both osteoarthritis and osteoporosis is of key importance for future decisional algorithms in the diagnosis, monitoring, and prognosis of these diseases. The current guidelines recommend the use of collagen degradation remnants, eg, CTX-I and CTX-II, in the complementary diagnosis of both osteoporosis and osteoarthritis. Besides the collagen degradation markers, enzymes that regulate bone and articular metabolism are useful in the clinical evaluation of osteoarticular pathologies. Along these, several other recommended and new nominee molecules have been recently studied. Wnts and Wnt-related molecules have a cardinal role in the bone-joint homeostasis, making them a promising target not only for pharmaceutical modulation, but also to be considered as soluble biomarkers. Sclerostin and dickkopf, two inhibitor molecules of the Wnt/ß-catenin signaling, might have a dual role in the assessment of the clinical manifestations of the osteoarticular unit. In osteoarthritis, besides fragments of collagen type II many pathway-related molecules have been studied and proposed for biomarker validation. The most serious limitation is that a significant proportion of studies lack statistical power due to the reduced number of cases enrolled. Serum biomarkers of bone and joint turnover markers represent an encouraging possibility for the diagnosis and prognosis of osteoarticular diseases, although further studies and laboratory validations should be carried out as to solely rely on them.


Assuntos
Osteoartrite/sangue , Osteoporose/sangue , Biomarcadores , Osso e Ossos/metabolismo , Colágeno Tipo I/sangue , Colágeno Tipo II/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/sangue , Via de Sinalização Wnt/fisiologia
5.
Res Vet Sci ; 130: 133-138, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32172002

RESUMO

Ovariohysterectomized (OHE) female dogs do not develop the osteopenia and osteoporosis associated with decreasing estrogen in post-menopausal women, possibly due to post-OHE bone mineral density retention through a mechanism that remains unclear. In this study, we aimed to elucidate this mechanism by investigating estradiol (E2) and bone markers. Samples were collected from 56 OHE and 43 intact bitches (0.33 to 17.58 years old) and analyzed for serum E2, osteoclast-secreted cysteine protease cathepsin K (CTK), and N-telopeptide of type I collagen (NTx) by ELISA. OHE and intact bitches showed no significant difference in serum E2 or NTx, and there was no correlation between serum E2 and NTx and age and time since OHE. Intact bitches showed a very low correlation between E2 and NTx, but OHE bitches showed no correlation, and serum CTK was generally undetectable in both groups. Our findings suggest the influence of gonadal hormones on bone metabolism does not work effectively in dogs; this is consistent with a shorter duration of exposure to E2 in bitches (through the 4-to-8-month anestrus phase) than women.


Assuntos
Catepsina K/sangue , Colágeno Tipo I/sangue , Cães/metabolismo , Estradiol/sangue , Peptídeos/sangue , Animais , Biomarcadores/sangue , Feminino , Histerectomia/veterinária , Ovariectomia/veterinária , Estudos Retrospectivos
6.
J Cardiovasc Magn Reson ; 22(1): 13, 2020 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-32036784

RESUMO

BACKGROUND: Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation. METHODS: LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis. RESULTS: On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P < 0.001), which remained significant on multivariable regression. CONCLUSION: LV fibrosis in patients with AF is associated with left atrial pressure and invasively measured levels of ICTP turnover biomarker.


Assuntos
Fibrilação Atrial/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Função Ventricular Esquerda , Remodelação Ventricular , Adulto , Idoso , Fibrilação Atrial/sangue , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Função do Átrio Esquerdo , Pressão Atrial , Biomarcadores/sangue , Ablação por Cateter , Colágeno Tipo I/sangue , Técnicas Eletrofisiológicas Cardíacas , Feminino , Fibrose , Galectina 3/sangue , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Valor Preditivo dos Testes , Pró-Colágeno/sangue
7.
Niger J Clin Pract ; 23(2): 154-158, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32031088

RESUMO

Background: There are a lot study confirmed the relationship of bone serum markers changes and skeletal irregularities. But there is no sufficient case control studies about the role of these markers on bisphosphonate induced osteonecrosis of jaws (BRONJ). Aims: The aim of this study is to find out if there is any derangement of bone markers in bisphosphonate-treated patients with ONJ. Methods: We obtained serum bone markers and other relevant endocrine assays on 20 patients with osteonecrosis of the jaw (ONJ) and 20 randomized healthy volunteers. All of the ONJ group treated with zoledronic acid and had been withdrawn from bisphosphonate for at least 6 months. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Serum levels of several indices of bone remodeling were evaluated using commercial enzyme-linked immunosorbent assays. The biochemical assays were performed on N-Telopeptides of type I collagen (NTX), bone-specific alkaline phosphatase (ALP), calcitonin, osteocalcin, intact parathyroid hormone (PTH), T3, T4, TSH, and Vitamin D 25 hydroxy (Vit-D). Results: In ONJ group, PTH level is statistically higher and TSH, Vit-D, osteocalcin and NTX levels statistically lower compared to control group. Conclusion: We conclude that these changes in PTH, Vit-D, TSH, osteocalcin and NTX levels maybe have a role in the pathophysiology of BRONJ. But the data need to be confirmed by future studies.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/sangue , Conservadores da Densidade Óssea/efeitos adversos , Remodelação Óssea/efeitos dos fármacos , Colágeno Tipo I/sangue , Difosfonatos/efeitos adversos , Hormônio Paratireóideo/sangue , Vitamina D/sangue , Fosfatase Alcalina/sangue , Biomarcadores/sangue , Conservadores da Densidade Óssea/administração & dosagem , Estudos de Casos e Controles , Difosfonatos/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteocalcina , Peptídeos , Ácido Zoledrônico/uso terapêutico
8.
BMC Med ; 18(1): 2, 2020 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-31902369

RESUMO

BACKGROUND: Heart failure (HF) has been recognized as a global pandemic with a high rate of hospitalization, morbidity, and mortality. Although numerous advances have been made, its representative molecular signatures remain largely unknown, especially the role of genes in HF progression. The aim of the present prospective follow-up study was to reveal potential biomarkers associated with the progression of heart failure. METHODS: We generated multi-level transcriptomic data from a cohort of left ventricular heart tissue collected from 21 HF patients and 9 healthy donors. By using Masson staining to calculate the fibrosis percentage for each sample, we applied lasso regression model to identify the genes associated with fibrosis as well as progression. The genes were further validated by immunohistochemistry (IHC) staining in the same cohort and qRT-PCR using another independent cohort (20 HF and 9 healthy donors). Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma level in a validation cohort (139 HF patients) for predicting HF progression. RESULTS: Based on the multi-level transcriptomic data, we examined differentially expressed genes [mRNAs, microRNAs, and long non-coding RNAs (lncRNAs)] in the study cohort. The follow-up functional annotation and regulatory network analyses revealed their potential roles in regulating extracellular matrix. We further identified several genes that were associated with fibrosis. By using the survival time before transplantation, COL1A1 was identified as a potential biomarker for HF progression and its upregulation was confirmed by both IHC and qRT-PCR. Furthermore, COL1A1 content ≥ 256.5 ng/ml in plasma was found to be associated with poor survival within 1 year of heart transplantation from heart failure [hazard ratio (HR) 7.4, 95% confidence interval (CI) 3.5 to 15.8, Log-rank p value < 1.0 × 10- 4]. CONCLUSIONS: Our results suggested that COL1A1 might be a plasma biomarker of HF and associated with HF progression, especially to predict the 1-year survival from HF onset to transplantation.


Assuntos
Biomarcadores/sangue , Colágeno Tipo I/sangue , Insuficiência Cardíaca/diagnóstico , Adulto , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estudos Prospectivos , Transcriptoma
9.
Cell Tissue Res ; 379(3): 537-548, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31776823

RESUMO

Abnormal activation of Wnt signaling has been demonstrated in the wound healing process and the pathogenesis of fibrotic disorders, with Wnt4 specifically identified as having a key role in the pathogenesis of renal, pulmonary and liver fibrosis. Wnt4 also was found to be upregulated by transforming growth factor-ß1 (TGF-ß1) in fetal and postnatal murine fibroblasts and bone marrow mesenchymal cells, suggesting an underlying cooperation between Wnt4 and TGF-ß1 in fibrosis. However, the specific roles of Wnt4 in TGF-ß1-induced skin myofibroblast transition and hypertrophic scar formation remain unclear. In the present study, we first observed reduced Wnt4 expression in hypertrophic scar tissue compared with that in normal skin tissue. Following upregulation by TGF-ß1, Wnt4 inhibited the TGF-ß1-induced transdifferentiation of fibroblasts into myofibroblasts. Using fibroblast-populated collagen lattice contraction assays, we showed that the increased contractility induced by TGF-ß1 was significantly blocked by exogenous Wnt4 and the α-smooth muscle actin (α-SMA) expression was decreased in fibroblasts in the collagen lattices. In addition, knockdown of Wnt4 resulted in further increases in α-SMA and collagen I expressions. Further investigation showed that Wnt4 could inhibit the autocrine effect of TGF-ß1 as well as block the phosphorylation of Smad3 and ERK but not of AKT or JNK. Lastly, using hypertrophic scar-derived fibroblasts, we showed that the elevated α-SMA and collagen I levels were markedly reduced after treatment with Wnt4. Taken together, our results suggest that Wnt4 negatively regulates TGF-ß1-induced fibroblast activation, which may represent a novel therapeutic strategy for the treatment and prevention of hypertrophic scars.


Assuntos
Cicatriz Hipertrófica/metabolismo , Fibroblastos/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Miofibroblastos/metabolismo , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proteína Wnt4/metabolismo , Actinas/biossíntese , Animais , Cicatriz Hipertrófica/patologia , Colágeno Tipo I/sangue , Colágeno Tipo I/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Humanos , Miofibroblastos/citologia , Miofibroblastos/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Proteínas Recombinantes/farmacologia , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/biossíntese , Fator de Crescimento Transformador beta1/farmacologia , Regulação para Cima , Proteína Wnt4/biossíntese , Proteína Wnt4/genética
10.
Nutr Metab Cardiovasc Dis ; 30(1): 49-55, 2020 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-31757570

RESUMO

AIM: The aim of this study is to evaluate the relationship between OPG and the degree of glycaemic control in a population of elderly subjects. METHODS AND RESULTS: Data presented included 172 elderly subjects, of whom 107 were hospitalized for a hip fracture and 65 were non fractured outpatients. All participants received a multidimensional geriatric evaluation and underwent blood sampling. HbA1c, OPG, CTX and OC were measured and DXA scans were performed. Carotid intima-media thickness (IMT) was measured in all outpatients. Diabetic patients had more comorbidities, higher mean values of lumbar spine and femoral neck BMD and T-score, lower circulating levels of OC and CTX, and higher circulating levels of OPG compared to non-diabetic subjects. OPG was directly correlated with HbA1c. This association was most evident in non-fractured elderly subjects. Moreover, diabetic patients with IMT>1.5 mm had greater mean values of OPG than non-diabetic subjects with high IMT and than elderly subjects with IMT < 1.5 mm, with and without T2DM. CONCLUSIONS: Diabetic patients have reduced circulating levels of OC and CTX, and elevated serum levels of OPG, suggesting a state of low bone turnover. Reduced bone turnover causes an increase of BMD and could lead to a poor bone quality. OPG and HbA1c were directly correlated and OPG mean values were higher in diabetic patients with poor glucose control. Diabetic osteopathy could be considered a late complication of T2DM, directly related with the degree of glucose control and the duration of the disease.


Assuntos
Doenças Ósseas/sangue , Diabetes Mellitus Tipo 2/sangue , Osteoprotegerina/sangue , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Glicemia/análise , Densidade Óssea , Doenças Ósseas/diagnóstico por imagem , Doenças Ósseas/epidemiologia , Colágeno Tipo I/sangue , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Idoso Fragilizado , Hemoglobina A Glicada/análise , Nível de Saúde , Humanos , Masculino , Osteocalcina/sangue , Peptídeos/sangue , Prevalência , Fatores de Risco , Cidade de Roma/epidemiologia
11.
Maturitas ; 132: 24-29, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31883659

RESUMO

OBJECTIVE: To evaluate trabecular bone score (TBS) in Spanish postmenopausal women from our area. To analyze its relationship with bone mineral density (BMD), bone quantitative ultrasound (QUS) and serum concentrations of 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH) and bone turnover markers. STUDY DESIGN: A total of 1450 postmenopausal women aged 44-94 (62 ± 10) participated in this cross-sectional study nested in a population-based cohort. BMD and TBS were assessed by DXA. QUS measurements were performed using a Sahara Clinical Sonometer. Serum 25(OH)D, PTH, P1NP, ß-CTX were determined by electrochemiluminescence. RESULTS: Mean TBS of postmenopausal women in our region was 1.341 ± 0.111. Nearly 50 % of them had normal values. Only 11 % had scores compatible with a clearly degraded microarchitecture. TBS decreased with age, correlated negatively with BMI and was lower in current smokers than in non-smokers. An association was observed between TBS and QUS, although the association was weak and lower than that found between TBS and BMD or QUS and BMD. No association was found between TBS and 25(OH)D, PTH or bone turnover markers. CONCLUSIONS: Half of postmenopausal women in our region have TBS values that indicate a preserved microarchitecture. Only about 10 % have scores compatible with a clearly degraded microarchitecture. A weak association was observed between TBS and QUS, suggesting that the two techniques capture different aspects of bone microarchitecture. The absence of association with 25(OH)D, PTH, and bone turnover markers may be due to the fact that TBS assesses a specific (mostly trabecular) part of the skeleton, whilst the three serum factors are related to the whole skeleton.


Assuntos
Densidade Óssea , Osso Esponjoso/diagnóstico por imagem , Pós-Menopausa , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Colágeno Tipo I/sangue , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pós-Menopausa/sangue , Pró-Colágeno/sangue , Espanha , Ultrassonografia , Vitamina D/análogos & derivados , Vitamina D/sangue
12.
Am J Cardiol ; 125(4): 542-548, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31812227

RESUMO

Identification of biomarkers can help monitor and prevent cardiovascular disease (CVD) risk. We performed an exploratory analysis to identify potential biomarkers for coronary heart disease (CHD) in participants from the Life Conditions, Stress, and Health study. A total of 1,007 participants (50% women), randomly selected from the general population, were followed for incident CHD at 8 and 13 years of follow-up. Plasma levels of 184 CVD-related biomarkers were measured in samples collected at baseline in 86 cases with CHD and 184 age- and sex-matched controls by proximity extension assay. Biomarker levels were presented as normalized protein expression values (log 2 scale). After adjusting for confounding factors, 6 biomarkers showed significant association with incident CHD at 13 years. In a sensitivity analysis, this association remained significant at 8 years for 3 biomarkers; collagen α-1(I) chain (COL1A1), bone morphogenetic protein-6 (BMP-6), and interleukin-6 receptor α chain (IL-6Rα). When entering these biomarkers in the full adjustment model simultaneously, their association with incident CHD at 13 years remained significant, hazards ratio being 0.671, 0.335, and 2.854, respectively per unit increase in normalized protein expression values. Subjects with low COL1A1, low BMP-6, and high IL-6Rα levels had a hazards ratio of 5.097 for incident CHD risk (p = 0.019), compared with those without. In conclusion, we identified COL1A1, BMP-6 and IL-6Rα as biomarkers for incident CHD over a long-term follow-up in this exploratory analysis. For COL1A1 and BMP-6 this has not been previously reported. Further studies are needed to confirm our findings and establish their clinical relevance.


Assuntos
Biomarcadores/sangue , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Idoso , Proteína Morfogenética Óssea 6/sangue , Colágeno Tipo I/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptores de Interleucina-6/sangue , Sensibilidade e Especificidade , Suécia/epidemiologia
14.
J Bone Miner Metab ; 38(2): 240-247, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31667583

RESUMO

INTRODUCTION: In terms of the balance between benefits and risks of long-term treatment with bisphosphonate, uncertainties remain regarding the optimal treatment duration. We investigated effects of continuous long-term treatment for 10 years with bisphosphonate in postmenopausal osteoporosis patients. MATERIALS AND METHODS: Fifty five patients in the outpatient clinic of our hospital have been continuously treated with alendronate or risedronate for 10 years. All data were retrospectively collected. The age, height, weight, total muscle volume, total fat volume, and BMD at the lumbar spine, total hip and distal 1/3 radius, alkaline phosphatase (ALP), urinary type I collagen cross-linked N-telopeptide (uNTX) and tartrate-resistant acid phosphatase-5b (TRAP5b), calcium (Ca) and phosphate (P) levels were measured pre- and after the start of 10-year continuous treatment. RESULTS: BMD at the lumbar spine increased continuously over the 10-year period, while BMD at the total hip slightly but significantly decreased, and that at the 1/3 radius did not show any significant change over the 10 years. Serum Ca value was significantly decreased after the start of treatment, and became stable within the reference range from the second year. Bone resorption markers such as uNTX and TRAP5b significantly decreased from the second year after the start of treatment and no significant changes were observed thereafter. There were no serious medical adverse events including atypical femoral fractures and osteonecrosis of the jaw. CONCLUSION: We believe that the continuous use of alendronate and risedronate for 10 years could be an option for the treatment of postmenopausal osteoporosis patients.


Assuntos
Grupo com Ancestrais do Continente Asiático , Difosfonatos/uso terapêutico , Osteoporose/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Alendronato/farmacologia , Alendronato/uso terapêutico , Fosfatase Alcalina/sangue , Densidade Óssea/efeitos dos fármacos , Cálcio/sangue , Colágeno Tipo I/sangue , Difosfonatos/farmacologia , Feminino , Humanos , Japão , Osteoporose/sangue , Osteoporose/induzido quimicamente , Osteoporose/fisiopatologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Peptídeos/sangue , Fósforo/sangue , Estudos Retrospectivos , Ácido Risedrônico/uso terapêutico , Fosfatase Ácida Resistente a Tartarato/sangue , Fatores de Tempo , Resultado do Tratamento
15.
Int Urogynecol J ; 31(1): 133-137, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-30483853

RESUMO

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse has a multifactorial etiology. There is increasing evidence that genetic factors greatly impact its development. This study aimed to evaluate the possible relation of the collagenous polymorphism -1997 G/T with genital prolapse in Brazilian women. METHODS: A cohort study of 180 women with stage 0 or I (group A) pelvic organ prolapse disorder and 112 women with stage III or IV (group B) was conducted. Blood DNA was isolated, and the -1997 G/T polymorphism was identified by amplifying a region of the COLIA1 gene starting prior to the protein's coding sequence. RESULTS: No significant difference in the prevalence of genotypes TG and TT was found between groups (p = 0.67); differences were not found even when patients were grouped by the presence of 0 or ≥ 1 polymorphic alleles (p = 0.46). Age and home birth were found to be independent risk factors for prolapse. CONCLUSIONS: Our study could not find any association between the -1997G/T polymorphism and genital prolapse in Brazilian women.


Assuntos
Colágeno Tipo I/sangue , Predisposição Genética para Doença/genética , Doenças dos Genitais Femininos/genética , Prolapso de Órgão Pélvico/genética , Polimorfismo Genético/genética , Alelos , Brasil , Estudos de Coortes , Feminino , Genótipo , Humanos , Pessoa de Meia-Idade , Fatores de Risco
16.
AIDS Care ; 32(8): 984-993, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31137948

RESUMO

There are limited studies regarding bone health among people living with HIV (PLHIV) in Asia. We compared bone mineral density (BMD), serum 25-hydroxyvitamin D (25(OH)D) status and bone turnover markers (serum procollagen type1 N-terminal propeptide (P1NP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type1 collagen) among 302 antiretroviral therapy (ART) naive PLHIV compared to 269 HIV-uninfected controls from Thailand. People aged ≥30 years, with and without HIV infection (free of diabetes, hypertension, and active opportunistic infection) were enrolled. BMD at the lumbar spine, total hip, and femoral neck were measured using Hologic DXA at baseline and at 5 years. We analyzed BMD, serum 25(OH)D levels, and bone turnover markers at the patients' baseline visit. PLHIV were 1.5 years younger and had lower BMI. PLHIV had higher mean serum 25(OH)D level and similar BMD to the controls. Interestingly, PLHIV had significantly lower bone formation (serum P1NP and OC), particularly those with low CD4 count. Only a few participants had low bone mass. ARV naïve middle-aged PLHIV did not have lower BMD or lower vitamin D levels compared to the controls. However, PLHIV had lower bone formation markers, particularly those with low CD4 count. This finding supports the benefit of early ART.


Assuntos
Biomarcadores/sangue , Densidade Óssea/efeitos dos fármacos , Remodelação Óssea/efeitos dos fármacos , Infecções por HIV/diagnóstico , Osteogênese/efeitos dos fármacos , Vitamina D/análogos & derivados , Absorciometria de Fóton , Adulto , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais , Estudos de Casos e Controles , Colágeno Tipo I/sangue , Feminino , Colo do Fêmur/diagnóstico por imagem , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Articulação do Quadril/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Osteocalcina/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Estudos Prospectivos , Tailândia/epidemiologia , Vitamina D/sangue
17.
Blood Purif ; 49(1-2): 129-131, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31461701

RESUMO

Immobilization and prolonged bed rest are harmful to the skeleton, which suffers increased resorption, and contribute to reducing survival rates among patients in critical care units. We report a patient who presented hypercalcemia 10 days after continuous venovenous hemofiltration has ended. Investigative tests showed an increase of serum C-terminal telopeptide of type I collagen (CTx), with suppressed parathormone and calcitriol. Denosumab was administered with a significant response, decreasing ionized calcium and CTx levels. The calcium infusion rate during dialysis procedures, used for citrate anticoagulation compensation, has progressively decreased, suggesting that endogenous calcium was taking part in the citrate chelation. In this report, we highlight the challenges in early diagnosis of immobilization-induced hypercalcemia among patients who are on continuous renal replacement therapy undergoing citrate anticoagulation.


Assuntos
Anticoagulantes/administração & dosagem , Ácido Cítrico/administração & dosagem , Terapia de Substituição Renal Contínua , Denosumab/administração & dosagem , Hipercalcemia/terapia , Restrição Física/efeitos adversos , Calcitriol/sangue , Colágeno Tipo I/sangue , Estado Terminal , Humanos , Hipercalcemia/sangue , Hipercalcemia/etiologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Peptídeos/sangue
18.
Nutr J ; 18(1): 82, 2019 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791333

RESUMO

BACKGROUND: Deficient and insufficient vitamin D status (defined as serum 25(OH)D < 30 nmol/L and > 50 nmol/L) is prevalent worldwide and associated with decreased muscle strength and poor bone health. We aimed to investigate the effect of vitamin D fortification on bone markers and muscle strength among younger adult women at risk of vitamin D deficiency. METHODS: A 12-week randomised double-blinded placebo-controlled winter intervention trial, providing 30 µg vitamin D3/day through fortified yoghurt, cheese, eggs and crisp-bread or similar placebo products. Participants were 143 women of Danish and Pakistani origin 18-50 years of age, living in Denmark, randomised into four groups stratified by ethnicity. Serum 25-hydroxyvitamin D (25(OH)D) by LC-MS/MS and the secondary endpoints: four specific bone markers (osteocalcin (OC), Bone specific Alkaline Phosphatase (BALP), Procollagen type 1 amino-terminal propeptide (P1NP), C-terminal crosslinked telopeptide of type 1 collagen (CTX)) and three muscle strength measures (handgrip, knee extension strength, chair-standing), were assessed using one-way ANOVA, Tukey HSD and subsequent linear ANCOVA models, adjusted for relevant covariates. RESULTS: Significantly increased serum 25(OH)D concentration from 53.3 (17) to 77.8 (14) nmol/L and from 44.5 (21) to 54.7 (18) nmol/L among Danish and Pakistani women in the fortified groups, respectively (P <  0.05). The bone turnover markers OC, BALP, P1NP and CTX did not change significantly. Muscle strength by handgrip, knee extension and chair-standing test did not change significantly following the intervention. CONCLUSIONS: Consumption of vitamin D fortified foods for 12 weeks did not result in significant changes of the bone turnover markers OC, BALP, P1NP and CTX. Muscle strength measured as hand grip strength, knee extension strength and chair-standing did not change significantly following the intervention.


Assuntos
Fosfatase Alcalina/sangue , Colágeno Tipo I/sangue , Alimentos Fortificados , Força Muscular , Osteocalcina/sangue , Vitamina D/administração & dosagem , Vitamina D/sangue , Adolescente , Adulto , Biomarcadores/sangue , Remodelação Óssea , Dinamarca , Método Duplo-Cego , Feminino , Humanos , Pessoa de Meia-Idade , Paquistão , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Vitaminas/administração & dosagem , Vitaminas/sangue , Adulto Jovem
19.
Orthop Surg ; 11(6): 1135-1141, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31823500

RESUMO

OBJECTIVE: To investigate the changes of inflammatory factors and bone metabolism markers in postmenopausal women with H-type hypertension and to assess the relationship between them. METHODS: Postmenopausal women who were diagnosed with osteoporosis were selected as observation objects. Participants were divided into three groups: only osteoporosis group (osteoporosis group), hypertension combined with osteoporosis group (hypertension group), and H-type hypertension combined with osteoporosis group (H-type hypertension group). The changes in bone mineral density and bone metabolic markers (osteocalcin [OC], procollagen type I N-terminal propeptide (PINP), and C-terminal cross-linking telopeptide of type I collagen [CTX]) and inflammatory factors (interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]) were compared among three groups. RESULTS: In the hypertension group and the H-type hypertension group, the bone mineral density of the lumbar spine (0.647 ± 0.038 vs 0.638 ± 0.034 vs 0.668 ± 0.047, P < 0.05) and the femoral neck (0.567 ± 0.047 vs 0.552 ± 0.053 vs 0.618 ± 0.059, P < 0.05) was significantly lower than that in the osteoporosis group. The concentrations of CTX (266.61 ± 64.65 vs 293.09 ± 72.34 vs 235.48 ± 62.85, P < 0.05), IL-6 (44.36 ± 6.45 vs 48.05 ± 8.04 vs 39.06 ± 7.95, P < 0.05) and TNF-α (30.53 ± 6.28 vs 34.52 ± 7.15 vs 28.66 ± 6.19, P < 0.01) in the hypertension group and in the H-type hypertension group were significantly higher than those in the osteoporosis group. The concentrations of OC (30.59 ± 6.43 vs 27.10 ± 6.51, P < 0.05) and PINP (36.36 ± 6.16 vs 33.16 ± 6.77, P < 0.05) in the H-type hypertension group were increased dramatically. The concentration of CTX was positively correlated with the concentration of IL-6 (r = 0.587, P < 0.01) and TNF-α (r = 0.474, P < 0.01) and negatively related with the concentration of OC (r = -0.591, P < 0.01) and PINP (r = -0.646, P < 0.01) and the bone mineral density of the lumbar spine (r = -0.470, P < 0.01) and the femoral neck (r = -0.509, P < 0.01). CONCLUSION: Higher concentration of serum CTX is found in postmenopausal women with H-type hypertension, which is positively correlated with inflammatory factors. Besides, H-type hypertension could further enhance the activity of osteoclasts and increase the expressions of inflammatory factors, resulting in the aggravation of osteoporosis.


Assuntos
Colágeno Tipo I/sangue , Hipertensão/sangue , Interleucina-6/sangue , Osteoporose Pós-Menopausa/sangue , Peptídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Idoso , Biomarcadores/sangue , Densidade Óssea , Feminino , Humanos , Inflamação , Pessoa de Meia-Idade
20.
Eur Rev Med Pharmacol Sci ; 23(23): 10204-10210, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31841173

RESUMO

OBJECTIVE: The aim of this study was to investigate the effect of micro ribonucleic acid (miR)-21 on tibial fracture healing in rabbits by regulating the extracellular signal-regulated kinase (ERK) signaling pathway, and to explore its possible underlying mechanism. MATERIALS AND METHODS: A total of 15 healthy male rabbits were randomly divided into three groups, including: model group A (fracture group, n=5), model group B (fracture treatment group, n=5), and model group C (miR-21 siRNA + treatment group, n=5). Fracture healing was observed by imaging. The content of the serum collagen I and collagen II in rabbits was detected via enzyme-linked immunosorbent assay (ELISA). The morphology of bone tissues was observed via staining. Moreover, the expressions of ERK, transforming growth factor-ß1 (TGF-ß1), and Smad in osteoblasts of tibia were observed via Western blotting and Reverse Transcription-Polymerase Chain Reaction (RT-PCR), respectively. RESULTS: There was bony callus formation in group B and C when compared with group A. Compared with group B, bony callus formation was significantly accelerated in group C, while healing cycle was shortened. Hematoxylin-eosin (HE) staining and Masson staining indicated that compared with group A, group C had more fibrous calluses, new capillaries, and fibroblasts in tissues. Meanwhile, group C exerted better maturity of collagen tissues and higher osteoid content at 20 d after modeling. Compared with group C, there were more osteoid tissues with poor maturity in group B. Meanwhile, intramembranous bone formation was deformed, and collagen content was remarkably lower in group B. The content of serum collagen I and collagen II remarkably increased in group B compared with group A (p<0.05). However, it was significantly upregulated in group C compared with group B, showing statistically significant differences (p<0.05). According to the results of Western blotting, the protein expressions of TGF-ß1, Smad, and ERK in osteoblasts were significantly upregulated in group B when compared with those in group A (p<0.05). However, they increased remarkably in group C when compared with group B (p<0.05). Besides, RT-PCR results revealed that the messenger RNA (mRNA) expressions of TGF-ß1, Smad, and ERK in osteoblasts were significantly higher in group B than those in group A (p<0.05). However, they were markedly raised in group C in comparison with group B (p<0.05). CONCLUSIONS: Down-regulation of miR-21 promotes tibial fracture healing in rabbits by activating the ERK signaling pathway.


Assuntos
Consolidação da Fratura/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , MicroRNAs/fisiologia , Animais , Osso e Ossos/metabolismo , Osso e Ossos/patologia , Colágeno Tipo I/sangue , Colágeno Tipo II/sangue , Masculino , Proteína Quinase 3 Ativada por Mitógeno/biossíntese , Coelhos , Proteínas Smad/biossíntese , Fator de Crescimento Transformador beta1/biossíntese
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