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1.
J Orthop Res ; 38(1): 82-91, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31441073

RESUMO

To evaluate the effect of local parathyroid hormone (PTH) administration on rotator cuff tendon-to-bone healing in a rat model compared with systemic PTH injection and untreated controls. PTH-alginate scaffold was prepared and sustained release of PTH was confirmed. Bilateral supraspinatus tendon repairs were performed in 39 rats (group 1, supraspinatus repair only; group 2, supraspinatus repair with systemic PTH injection; group 3, supraspinatus repair with local PTH administration via an absorbable scaffold; n = 13 each). Biomechanical (cross-sectional area, mode of failure, load to failure, and ultimate stress: right side) and histological analyses (hematoxylin and eosin stain, Masson's Trichrome stain Picrosirius red stain, Immunohistochemistry for BMP2, PTH1R, ColI, and ColIII: Left side) were performed to evaluate tendon-to-bone healing quality at 8 weeks after repair, and blood test (osteocalcin and procollagen type I N-terminal pro-peptide [PINP] levels) was performed in all rats. There was no intergroup difference in the healing failure rate (p = 0.910) or failure mode (p = 0.585). Biomechanically, subjects in groups 2 and 3 exhibited significantly larger cross-sectional areas and higher ultimate failure loads and ultimate stress than those in group 1 (all p < 0.05); however, no differences were noted between groups 2 and 3 (all p > 0.05). Histologically, groups 2 and 3 exhibited more organized tendon-to-bone interface structures with higher density, parallel orientation, and collagen fiber continuity than group 1 (all p < 0.05 except collagen fiber continuity in group 1 vs. 2); however, no differences in histological parameters between groups 2 and 3 (all p > 0.05). The protein levels of bone morphogenic protein 2, PTH 1 receptor, and collagen I and III and the serum level of PINP were increased in groups 2 and 3 versus group 1 (all p < 0.05) without showing differences between groups 2 and 3 (all p > 0.05). Local PTH administration using an absorbable scaffold improved the biomechanical and histological outcomes of rotator cuff tendon-to-bone healing comparable with systemic PTH injection at 8 weeks after repair in a rat model. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:82-91, 2020.


Assuntos
Osso e Ossos/fisiopatologia , Hormônio Paratireóideo/administração & dosagem , Lesões do Manguito Rotador/cirurgia , Manguito Rotador/fisiopatologia , Tendões/fisiopatologia , Cicatrização/efeitos dos fármacos , Animais , Fenômenos Biomecânicos , Osso e Ossos/patologia , Imuno-Histoquímica , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Ratos , Ratos Sprague-Dawley , Lesões do Manguito Rotador/tratamento farmacológico , Lesões do Manguito Rotador/patologia , Lesões do Manguito Rotador/fisiopatologia , Tendões/patologia
2.
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
3.
Artigo em Inglês | MEDLINE | ID: mdl-31877849

RESUMO

Introduction: The purpose of this study was to analyze the relationship between the parameters of bone turnover and the levels of hormonal parameters, such as total testosterone (TT), bioavailable and free testosterone (FT), and estradiol (E2) in men. Material and methods: The study group included 63 men with testosterone deficiency syndrome (TDS). The control group consisted of 112 patients without TDS. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of osteocalcin (OC), parathyroid hormone (PTH), E2, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate (DHEAS), insulin (I), Serum CrossLaps (CtX-I), human procollagen I N-terminal peptide (PINP), and TT. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. Results: The groups with TSD and without TDS differed in terms of the following parameters: body weight (p = 0.001), BMI (p = 0.003), TT (p = 0.001), FT (p = 0.004), bioavailable testosterone (p = 0.001), E2 (p = 0.003), SHBG (p = 0.003), and PINP (p = 0.004). In the group without TDS, higher PINP levels were accompanied by higher levels of E2 (beta = 0.360, p = 0.002) and TT (beta = 0.389, p = 0.001). In the group without TDS, PINP was positively correlated with E2 (beta = 0.726, p <0.001). Patients with TDS had significantly lower PINP levels (p < 0.004). Conclusions: Analysis of sex hormones and biochemical bone markers in reflecting the quality of the bone tissue in men may suggest a relationship between these parameters. Nevertheless, further research based on a larger sample size is necessary to better describe this relationship.


Assuntos
Androgênios/sangue , Remodelação Óssea , Osso e Ossos/metabolismo , Absorciometria de Fóton , Idoso , Envelhecimento/metabolismo , Biomarcadores/sangue , Densidade Óssea , Colágeno Tipo I , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Peptídeos , Pró-Colágeno/sangue , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/sangue
4.
Yonsei Med J ; 60(12): 1174-1180, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31769248

RESUMO

PURPOSE: Bone markers can be useful for the diagnosis and treatment of skeletal diseases in children and adolescents. Owing to high skeletal growth velocity and rapid bone turnover, children and adolescents have higher bone marker levels than adults. Thus, a valid age- and sex-specific reference should be established for pediatric populations living in similar environments. We aimed to assess the associations of procollagen type I N-terminal propeptide (P1NP) and osteocalcin with age and sex in a group of healthy Korean children and adolescents. MATERIALS AND METHODS: The participants (290 boys and 290 girls, age range 0-18 years) were Korean outpatients. Serum P1NP and osteocalcin levels were measured in control materials and patient samples by electrochemiluminescence immunoassay using an automated Cobas e411 analyzer. RESULTS: Significant age-dependent variations in bone marker levels were observed in both sexes (p<0.001). The highest P1NP levels were observed during the first year of life; thereafter, levels decreased until puberty. There was no postnatal peak for osteocalcin; however, its levels remained higher than the adult reference range throughout childhood. Significant differences were observed between boys and girls (p<0.05), especially between the ages of 12 and 17 years. Cobas e411 results for P1NP showed satisfactory precision and linearity. CONCLUSION: We established reference data for P1NP and osteocalcin levels in healthy Korean children and adolescents, as the first and only study of these parameters in pre-adulthood in Korea. Cobas e411-quantified bone markers may be useful for determining bone metabolism indices.


Assuntos
Osteocalcina/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Adolescente , Adulto , Biomarcadores/sangue , Remodelação Óssea , Osso e Ossos/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Valores de Referência , República da Coreia , Adulto Jovem
5.
Cardiovasc Pathol ; 43: 107150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31639652

RESUMO

BACKGROUND: Whether current proposed biomarkers of myocardial fibrosis (BMFs) actually reflect the changes in fibrous characteristics of myocardial tissue remains unclear. The relation between peripheral BMFs and histological myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM) has been unknown. METHODS AND RESULTS: We studied 52 HCM patients who underwent a transaortic extended septal myectomy. Complete medical history was collected, and related examinations were performed. Echocardiography and cardiovascular magnetic resonance were employed to characterize cardiac morphology and function. Procollagen type I carboxy-terminal propeptide (PICP), C-terminal telopeptide of type I collagen (CITP), matrix metalloproteinases (total MMP-2 and total MMP-9), and tissue inhibitor of metalloproteinase 1 (TIMP-1) levels in both plasma and myocardial tissues were determined and compared. Myocardial fibrosis was detected with Masson's trichrome staining, and collagen volume fraction (CVF) was calculated. There was a significant correlation between plasma PICP levels and myocardial PICP contents (r=0.382, P=.007). Besides, plasma PICP (r=0.332, P=.020) levels correlated positively with CVF. In addition, plasma TIMP-1 levels were significantly correlated with myocardial TIMP-1 contents (r=0.282, P=.043). Plasma MMP-2 levels correlated positively with CVF (r=0.379, P=.006). Patients who took calcium channel blockers (CCBs; diltiazem or verapamil) had significantly lower plasma PICP levels, myocardial PICP content, and CVF in comparison with those who did not take CCBs. CONCLUSIONS: In patients with HCM, plasma PICP and MMP-2 levels quantitatively reflect myocardial fibrosis, suggesting that PICP and MMP-2 may be used as reliable BMFs. CCBs may attenuate cardiac fibrosis in patients with HCM.


Assuntos
Cardiomiopatia Hipertrófica/metabolismo , Metaloproteinase 2 da Matriz/análise , Miocárdio/química , Fragmentos de Peptídeos/análise , Pró-Colágeno/análise , Adolescente , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/sangue , Cardiomiopatia Hipertrófica/sangue , Cardiomiopatia Hipertrófica/patologia , Cardiomiopatia Hipertrófica/cirurgia , Criança , Ensaio de Imunoadsorção Enzimática , Feminino , Fibrose , Humanos , Masculino , Metaloproteinase 2 da Matriz/sangue , Pessoa de Meia-Idade , Miocárdio/patologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Adulto Jovem
6.
Maturitas ; 129: 12-22, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31547908

RESUMO

OBJECTIVE: To systematically evaluate the effects of bone anabolic therapies (BATs) - specifically, drug therapy with teriparatide, abaloparatide or romosozumab - on fractures, bone mineral density (BMD), and bone metabolites in postmenopausal osteoporosis. METHODS: Six computerized engines were searched through to November 2018. We selected randomized controlled trials (RCTs) evaluating the effect of BATs on postmenopausal osteoporosis and with at least 6 months of follow-up. Controls were placebo, no treatment, or bisphosphonates. Primary outcomes were vertebral and non-vertebral fractures. Secondary outcomes were: BMD determined by dual energy X-ray absorptiometry at total hip, lumbar spine, and femoral neck; N-terminal propeptide of type I procollagen (PINP); C-terminal telopeptide of type I collagen (CTX); and severe adverse events (SAE). We followed the PRISMA guidelines for reporting, and used version 2 of the Cochrane risk-of-bias tool. Frequentist network meta-analyses were performed per outcome. Effects for dichotomous and continuous outcomes were expressed as relative risks and mean differences and their 95% confidence intervals. We used p-scores to rank best treatments per outcome. RESULTS: Sixteen RCTs (n = 18,940) were evaluated. Mean ages ranged between 61 and 74 years, and follow-up times between 6 and 30 months. Four RCTs (n = 971) excluded patients with previous fractures. In contrast to placebo/no treatment, all BATs significantly reduced the risk of vertebral fractures, but no intervention significantly reduced the risk of non-vertebral fractures; abaloparatide ranked better than other interventions for both fracture types (p-scores: 0.95, and 0.89, respectively). All BATs significantly increased BMD at all locations in comparison with placebo/no treatment; romosozumab consistently ranked better than other interventions at all BMD locations (p-scores >0.86). Teriparatide ranked better than other interventions for increasing PINP. No differences in SAE were observed among treatments. CONCLUSIONS: Abaloparatide, romosozumab, and teriparatide are the best treatments, respectively, to reduce vertebral/non-vertebral fractures, increase BMD, and increase bone formation.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/prevenção & controle , Proteína Relacionada ao Hormônio Paratireóideo/uso terapêutico , Teriparatida/uso terapêutico , Anticorpos Monoclonais/farmacologia , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/farmacologia , Colágeno Tipo I/sangue , Feminino , Humanos , Metanálise em Rede , Osteoporose Pós-Menopausa/sangue , Proteína Relacionada ao Hormônio Paratireóideo/farmacologia , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Teriparatida/farmacologia
7.
Arch Endocrinol Metab ; 63(4): 394-401, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365627

RESUMO

OBJECTIVE: To measure type 1 serum amino-terminal propeptide procollagen (P1NP) and type 1 cross-linked C-terminal telopeptide collagen (CTX) before parathyroidectomy (PTX) in PHPT patients, correlating these measurements with bone mineral density (BMD) changes. SUBJECTS AND METHODS: 31 primary hyperparathyroidism (HPTP) were followed from diagnosis up to 12-18 months after surgery. Serum levels of calcium, parathyroid hormone (PTH) vitamin D, CTX, P1NP, and BMD were measured before and 1 year after surgery. RESULTS: One year after PTX, the mean BMD increased by 8.6%, 5.5%, 5.5%, and 2.2% in the lumbar spine, femoral neck (FN), total hip (TH), and distal third of the nondominant radius (R33%), respectively. There was a significant correlation between BMD change 1 year after the PTX and CTX (L1-L4: r = 0.614, p < 0.0003; FN: r = 0.497, p < 0.0051; TH: r = 0.595, p < 0.0005; R33%: r = 0.364, p < 0.043) and P1NP (L1-L4: r = 0,687, p < 0,0001; FN: r = 0,533, p < 0,0024; TH: r = 0,642, p < 0,0001; R33%: r = 0,467, p < 0,0079) preoperative levels. The increase in 25(OH)D levels has no correlation with BMD increase (r = -0.135; p = 0.4816). On linear regression, a minimum preoperative CTX value of 0.331 ng/mL or P1NP of 37.9 ng/mL was associated with a minimum 4% increase in L1-L4 BMD. In TH, minimum preoperative values of 0.684 ng/mL for CTX and 76.0 ng/mL for P1NP were associated with a ≥ 4% increase in BMD. CONCLUSION: PHPT patients presented a significant correlation between preoperative levels of turnover markers and BMD improvement 1 year after PTX.


Assuntos
Densidade Óssea , Colágeno Tipo I/metabolismo , Hiperparatireoidismo Primário/metabolismo , Paratireoidectomia/reabilitação , Fragmentos de Peptídeos/metabolismo , Peptídeos/metabolismo , Pró-Colágeno/metabolismo , Idoso , Biomarcadores/sangue , Cálcio/sangue , Feminino , Humanos , Hiperparatireoidismo Primário/cirurgia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Pró-Colágeno/sangue , Estudos Retrospectivos , Vitamina D/sangue
8.
Nutrients ; 11(7)2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31261978

RESUMO

Type 2 diabetes increases bone fracture risk in postmenopausal women. Usual treatment with anti-resorptive bisphosphonate drugs has some undesirable side effects, which justified our interest in the osteogenic potential of nutrition and exercise. Since meal eating reduces bone resorption, downhill locomotion increases mechanical stress, and brief osteogenic responsiveness to mechanical stress is followed by several hours of refractoriness, we designed a study where 40-min of mechanical stress was manipulated by treadmill walking uphill or downhill. Exercise preceded or followed two daily meals by one hour, and the meals and exercise bouts were 7 hours apart. Fifteen subjects each performed two of five trials: No exercise (SED), uphill exercise before (UBM) or after meals (UAM), and downhill exercise before (DBM) or after meals (DAM). Relative to SED trial, osteogenic response, defined as the ratio of osteogenic C-terminal propeptide of type I collagen (CICP) over bone-resorptive C-terminal telopeptide of type-I collagen (CTX) markers, increased in exercise-after-meal trials, but not in exercise-before-meal trials. CICP/CTX response rose significantly after the first exercise-after-meal bout in DAM, and after the second one in UAM, due to a greater CICP rise, and not a decline in CTX. Post-meal exercise, but not the pre-meal exercise, also significantly lowered serum insulin response and homeostatic model (HOMA-IR) assessment of insulin resistance.


Assuntos
Remodelação Óssea , Diabetes Mellitus Tipo 2/terapia , Terapia por Exercício , Fraturas Ósseas/prevenção & controle , Refeições , Osteogênese , Idoso , Biomarcadores/sangue , Colágeno Tipo I/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Fraturas Ósseas/sangue , Fraturas Ósseas/etiologia , Fraturas Ósseas/fisiopatologia , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Resistência à Insulina , Pessoa de Meia-Idade , Valor Nutritivo , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pós-Menopausa/sangue , Período Pós-Prandial , Pró-Colágeno/sangue , Fatores de Tempo , Resultado do Tratamento
9.
Eur J Pharmacol ; 859: 172519, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31271743

RESUMO

Juvenile Paget disease (JPD1), an autosomal-recessive disorder, is characterized by extremely rapid bone turnover due to osteoprotegerin deficiency. Its extra-skeletal manifestations, such as hypertension and heart failure, suggest a pathogenesis with shared skeletal and cardiovascular system components. In spite of this, the effects of anti-hypertensive drugs on bone morphometry remain unknown. We administered an angiotensin II type 1 receptor blocker, olmesartan (5 mg/kg/day) to 8-week-old male mice lacking the osteoprotegerin gene, with and without 1 µg/kg/min of angiotensin II infusion for 14 days. Olmesartan treatment decreased systolic blood pressure, and echocardiography showed increased left ventricular systolic contractility. Three-dimensional micro-computed tomography scans demonstrated that olmesartan treatment increased trabecular bone volume (sham, +176%; angiotensin II infusion, +335%), mineral density (sham, +150%; angiotensin II infusion, +313%), and trabecular number (sham, +407%; angiotensin II infusion, +622%) in the tibia. Olmesartan increased cortical mineral density (sham, +19%; angiotensin II infusion, +24%), decreased the cortical bone section area (sham, -16%; angiotensin II infusion, -18%), decreased thickness (sham, -18%; angiotensin II infusion, -31%), and decreased the lacunar area (sham, -41%; angiotensin II infusion, -27%) in the tibia. Similar trend was observed in the femur. Moreover, olmesartan decreased angiotensin II-induced increases in tartrate-resistant acid phosphatase concentrations in plasma, but it affected neither type I procollagen N-terminal propeptides, nor the receptor activator of nuclear factor kappa-B ligand. Our data suggest that blockade of the angiotensin II type 1 receptor improves bone vulnerability, and helps to maintain the heart's structural integrity in osteoprotegerin-deficient mice.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Densidade Óssea/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , Osteíte Deformante/tratamento farmacológico , Osteíte Deformante/fisiopatologia , Disfunção Ventricular Esquerda/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Pressão Sanguínea/efeitos dos fármacos , Modelos Animais de Doenças , Fêmur/efeitos dos fármacos , Fêmur/patologia , Fêmur/fisiopatologia , Hipertrofia/tratamento farmacológico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Osteíte Deformante/metabolismo , Osteíte Deformante/patologia , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Ligante RANK/sangue , Sístole/efeitos dos fármacos , Sístole/fisiologia , Fosfatase Ácida Resistente a Tartarato/sangue
10.
BMC Musculoskelet Disord ; 20(1): 293, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31215422

RESUMO

BACKGROUND: The objective of this pilot study was to identify biological, clinical or structural biomarkers of an intra-articular hyaluronic acid injection efficacy (HYMOVIS®) for the design of a larger placebo-controlled clinical trial studying the disease-modifying activity of this treatment. METHODS: Forty six patients with symptomatic knee Osteoarthritis (OA) were enrolled in this open-label, prospective, multicenter, pilot study. Patients received two treatment cycles of intra-articular injections (3 mL) of HYMOVIS® (8 mg/mL of hyaluronic acid hexadecylamide) at 6 months interval. Each treatment cycle involved two intra-articular injections 1 week apart. All patients had Magnetic Resonance Imaging (MRI) of the target knee at baseline and 1 year, and blood samples to assess joint biomarkers. The primary outcome was the change in type II collagen-specific biomarkers (Coll2-1, Coll2-1NO2 and CTX-II) after HYMOVIS® treatment versus baseline. Secondary endpoints included levels changes in aggrecan chondroitin sulfate 846 epitope (CS-846), Cartilage Oligomeric Matrix Protein (COMP), procollagen type II N-terminal propeptide (PIIANP), Matrix Metalloprotease (MMP)-3, Myeloperoxidase (MPO) and Interleukin (IL)-6 serum biomarkers, the ratio Coll2-1/PIIANP, CTX-II/PIIANP, variation of MRI cartilage volume, and Knee injury and Osteoarthritis Outcome Score (KOOS) index. RESULTS: Coll2-1 serum levels significantly increased overtime while Coll2-1NO2 levels were only increased at D360. Serum PIIANP levels also progressively and significantly enhanced with time. In contrast, other serum biomarker levels including CTX-II, CS-846, COMP, MMP-3, MPO or IL-6 did not change significantly overtime. Interestingly, the ratios Coll2-1/PIIANP and CTX-II/PIIANP decreased, indicating a decrease of cartilage catabolism. Compared to baseline value, MRI cartilage volume and thickness increased in lateral femoral and lateral trochlea compartments and not in medial compartment. These results, in addition to an improvement of T2 mapping score suggest a positive structural effect of the product. Interestingly, WORMS effusion score, an indicator of synovitis, significantly decreased. Finally, global KOOS score and subscales significantly increased overtime while pain at rest, walking pain and patients or investigators global assessment of disease activity decreased. The safety profile was favorable with a low incidence of injection-site pain. CONCLUSION: HYMOVIS®, a well-tolerated intra-articular treatment, significantly enhanced type II collagen turnover as suggested by the increase in Coll2-1 and PIIANP levels and cartilage volume observed by MRI in lateral knee compartment. Importantly, this study provides critical information for the design of a larger phase III clinical trial investigating Disease Modifying effect of HYMOVIS®. TRIAL REGISTRATION: http://www.isrctn.com/ISRCTN12227846 11/02/2015.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Colágeno Tipo II/metabolismo , Ácido Hialurônico/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Fragmentos de Peptídeos/metabolismo , Viscossuplementos/administração & dosagem , Idoso , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/metabolismo , Colágeno Tipo II/sangue , Feminino , Humanos , Ácido Hialurônico/análogos & derivados , Hidrogéis/administração & dosagem , Injeções Intra-Articulares , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/diagnóstico por imagem , Fragmentos de Peptídeos/sangue , Projetos Piloto , Pró-Colágeno/sangue , Pró-Colágeno/metabolismo , Estudos Prospectivos , Resultado do Tratamento
11.
Fertil Steril ; 112(2): 362-370, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31227287

RESUMO

OBJECTIVE: To study the effects of metformin treatment on bone turnover in women with polycystic ovary syndrome (PCOS), as measured by serum concentrations of bone turnover markers. DESIGN: Post hoc study of a previously conducted prospective multicenter, placebo-controlled, randomized study. SETTING: University clinic. PATIENT(S): The study cohort consisted of 74 non-obese women (body mass index < 27 kg/m2) and 44 obese women (body mass index ≥ 27 kg/m2) diagnosed with PCOS, with a mean age of 27.6 ± 4.0 (SD) years. INTERVENTION(S): Randomization to receive metformin or placebo for 3 months. MAIN OUTCOME MEASURE(S): Serum levels of bone formation marker procollagen type I amino-terminal propeptide (PINP) and bone resorption marker carboxy-terminal cross-linking telopeptide of type I collagen (CTX) at baseline and after metformin/placebo treatment. RESULT(S): Serum levels of PINP and CTX were similar between the metformin and placebo groups at baseline in the whole study population. Obese women, when compared with non-obese, had lower baseline levels of PINP and CTX. Levels of PINP and CTX were significantly reduced in the whole study population, as well as in both non-obese and obese women after 3 months of metformin treatment, whereas no significant changes were observed in the placebo group. CONCLUSION(S): Metformin treatment, when compared with placebo, was associated with reduced bone turnover, as suggested by reductions in markers of bone formation and resorption, leading to slower bone remodeling in premenopausal women with PCOS. CLINICAL TRIAL REGISTRATION NUMBER: NCT00994812.


Assuntos
Biomarcadores/sangue , Remodelação Óssea/efeitos dos fármacos , Metformina/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Adulto , Densidade Óssea/efeitos dos fármacos , Colágeno Tipo I/sangue , Feminino , Humanos , Metformina/farmacologia , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Placebos , Síndrome do Ovário Policístico/sangue , Pró-Colágeno/sangue , Estudos Retrospectivos , Adulto Jovem
12.
Nutrients ; 11(6)2019 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-31234587

RESUMO

The diurnal rhythm of bone remodeling suggests nocturnal dietary intervention to be most effective. This study investigated the effect of bedtime ingestion of a calcium-fortified, milk-derived protein matrix (MBPM) or maltodextrin (CON) on acute (0-4 h) blood and 24-h urinary change in biomarkers of bone remodeling in postmenopausal women with osteopenia. In CON, participants received 804 ± 52 mg calcium, 8.2 ± 3.2 µg vitamin D and 1.3 ± 0.2 g/kg BM protein per day. MBPM increased calcium intake to 1679 ± 196 mg, vitamin D to 9.2 ± 3.1 µg and protein to 1.6 ± 0.2 g/kg BM. Serum C-terminal cross-linked telopeptide of type I collagen (CTX) and procollagen type 1 amino-terminal propeptide (P1NP), and urinary N-telopeptide cross-links of type I collagen (NTX), pyridinoline (PYD) and deoxypyridinoline (DPD) was measured. Analyzed by AUC and compared to CON, a -32% lower CTX (p = 0.011, d = 0.83) and 24% (p = 0.52, d = 0.2) increase in P1NP was observed for MBPM. Mean total 24 h NTX excreted in MBPM was -10% (p = 0.035) lower than CON. Urinary PYD and DPD were unaffected by treatment. This study demonstrates the acute effects of bedtime ingestion of a calcium-fortified, milk-based protein matrix on bone remodeling.


Assuntos
Doenças Ósseas Metabólicas/dietoterapia , Remodelação Óssea , Cálcio na Dieta/administração & dosagem , Ritmo Circadiano , Suplementos Nutricionais , Alimentos Fortificados , Proteínas do Leite/administração & dosagem , Pós-Menopausa/sangue , Idoso , Biomarcadores/sangue , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/diagnóstico , Doenças Ósseas Metabólicas/fisiopatologia , Cálcio na Dieta/efeitos adversos , Colágeno Tipo I/sangue , Suplementos Nutricionais/efeitos adversos , Feminino , Alimentos Fortificados/efeitos adversos , Humanos , Irlanda , Pessoa de Meia-Idade , Proteínas do Leite/efeitos adversos , Hormônio Paratireóideo/sangue , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Pró-Colágeno/sangue , Fatores de Tempo , Resultado do Tratamento , Vitamina D/administração & dosagem
13.
Nutrients ; 11(5)2019 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-31130694

RESUMO

The purpose of this work was to describe changes in metabolic activity in the bones of young male competitive cyclists (CYC) as compared with age-matched controls (CON) over a one-year period of study. Eight adolescent male cyclists aged between fourteen and twenty, and eight age-matched controls participated in this longitudinal study. Serum osteocalcin (OC), amino-terminal propeptide of type I procollagen (PINP), beta-isomerized C-telopeptides (ß-CTx) and plasma 25 hydroxyvitamin D [25(OH)D], were investigated by an electrogenerated chemiluminescence immunoassay. Analysis of variance revealed no significant differences in formation and resorption markers between cyclists and controls. Within the groups, both CYC and CON showed decreased OC at -30% and -24%, respectively, and PINP where the figures were -28% and -30% respectively (all p < 0.05). However, only the CYC group showed a decrease in [25(OH)D], lower by 11% (p < 0.05). The similarity in the concentrations of markers in cyclists and controls seems to indicate that cycling does not modify the process of bone remodeling. The decrease in vitamin D in cyclists might be detrimental to their future bone health.


Assuntos
Ciclismo/fisiologia , Remodelação Óssea , Reabsorção Óssea , Osso e Ossos/efeitos dos fármacos , Osteogênese , Adolescente , Atletas , Biomarcadores/sangue , Densidade Óssea , Osso e Ossos/metabolismo , Estudos de Casos e Controles , Colágeno Tipo I/sangue , Humanos , Estudos Longitudinais , Masculino , Osteocalcina/sangue , Osteoporose/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue
14.
Tumour Biol ; 41(5): 1010428319847081, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31122159

RESUMO

Type 1 collagen is an important part of the extracellular matrix and changes in its metabolism and distribution are essential in breast cancer induction and progression. Serum concentrations of type 1 collagen synthesis (aminoterminal propeptide (PINP)) and degradation markers (carboxyterminal telopeptide (ICTP)) have previously been studied in early and metastatic breast cancer, but no data are available on specific breast cancer subtypes. We assayed 662 preoperative serum samples for PINP and ICTP and 109 postoperative serum samples for ICTP. The results were linked to prospectively collected clinical data and the cases were divided into breast cancer subtypes for survival analyses. The concentrations of both pre- and postoperative ICTP serum levels increased linearly from ductal in situ carcinoma to stage I-II tumors, stage III tumors, and finally to those with concomitant primary metastases (preoperative ICTP, p = 0.009; postoperative ICTP, p = 0.016). High-preoperative ICTP levels were associated with better breast cancer-specific survival in connection with luminal-B-like (HER2-negative) tumors (p = 0.017), which was confirmed in Cox regression analysis (relative risk = 3.127; 95% confidence interval = 1.081-9.049, p = 0.035), when T-class (relative risk = 4.049; 95% confidence interval = 1.263-12.981; p = 0.019) and nodal status (relative risk = 3.896; 95% confidence interval = 1.088-13.959; p = 0.037) were included in the analysis. In patients with triple-negative breast cancer, a high-preoperative ICTP level was a significant predictor of local relapse-free survival in univariate (p = 0.0020) and multivariate analyses (relative risk = 13.04; 95% confidence interval = 1.354-125.5; p = 0.026; for T-class, relative risk = 2.128 and 95% confidence interval = 0.297-15.23; p = 0.452; for N-class, relative risk = 0.332 and 95% confidence interval = 0.033-3.307; p = 0.347). A preoperatively elevated serum ICTP level appears to be an important marker of better prognosis in triple-negative breast cancer and luminal-B-like (HER2-negative) subtypes.


Assuntos
Biomarcadores Tumorais/sangue , Colágeno Tipo I/sangue , Neoplasias de Mama Triplo Negativas/sangue , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Intervalo Livre de Doença , Matriz Extracelular/genética , Feminino , Humanos , Masculino , Estadiamento de Neoplasias , Fragmentos de Peptídeos/sangue , Peptídeos/sangue , Período Pré-Operatório , Pró-Colágeno/sangue , Prognóstico , Modelos de Riscos Proporcionais , Receptor ErbB-2/genética , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
15.
Int J Mol Sci ; 20(11)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141909

RESUMO

BACKGROUND: Cardiac collagen remodeling is important in the progression of heart failure. Estimation of cardiac collagen turnover by serum levels of serological markers is used for monitoring cardiac tissue repair and fibrosis. Peritoneal dialysis (PD) is used for the long-term management of refractory congestive heart failure (CHF). In this study, we investigated the effect of PD treatment on circulating fibrosis markers levels in patients with refractory CHF and fluid overload. METHODS: Twenty-five patients with refractory CHF treated with PD were prospectively enrolled in the study. Circulating fibrosis markers procollagen type III C-peptide (PIIINP), matrix metalloproteinase 2 (MMP-2), and tissue inhibitor of metalloproteinases I (TIMP-1) levels were checked at baseline and after three and six months of treatment. RESULTS: The clinical benefit of PD manifested by improved NYHA functional class and reduced hospitalization rate. Serum brain natriuretic peptide (BNP) levels decreased significantly during the treatment. Serum MMP-2 and TIMP-1 decreased significantly on PD. Circulating PIIINP showed two patterns of change, either decreased or increased following PD treatment. Patients in whom circulating PIIINP decreased had significantly lower baseline serum albumin, lower baseline mean arterial blood pressure, higher serum CRP, and a less significant improvement in hospitalization rate compared to the patients in whom circulating PIIINP increased. Patients in whom all three markers decreased demonstrated a trend to longer survival compared to patients whose markers increased or did not change. CONCLUSION: In refractory CHF patients PD treatment was associated with a reduction in circulating fibrosis markers.


Assuntos
Insuficiência Cardíaca/sangue , Metaloproteinase 2 da Matriz/sangue , Fragmentos de Peptídeos/sangue , Diálise Peritoneal/efeitos adversos , Pró-Colágeno/sangue , Inibidor Tecidual de Metaloproteinase-1/sangue , Idoso , Biomarcadores/sangue , Feminino , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade
16.
Psychiatry Res ; 276: 39-44, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31003023

RESUMO

Several preclinical and clinical studies show that selective serotonin reuptake inhibitors (SSRI's) are associated with bone loss and an increase in fracture risk, not many reports on their effect on bone turnover markers. This cross-sectional study evaluated the effect of SSRIs treatment on bone turnover markers in Indian population for the first time. Inclusion criteria were subjects of either sex and age 18-45 years undergoing treatment with an SSRI for at least 3 months, regardless of the indication. The results were compared with age-matched healthy controls. A total of 141 subjects were screened out of which 85 were enrolled, 44 in treatment and 41 in the control group. Serum Procollagen Type 1 Amino Terminal Propeptide (P1NP) levels were decreased in patients on SSRI treatment whereas no change was observed in the beta-C-terminal telopeptide (ß-CTX) and receptor activator of nuclear factor kappa-Β ligand (RANKL) levels suggesting that these drugs can reduce bone formation but not resorption. Patients on SSRI treatment also showed reduced pCREB levels indicating that reduced bone formation is possibly through the gut mediated pathway. Our study suggests that SSRIs treatment at therapeutic doses may have a deteriorating effect on bone requiring caution in patients with additional risk factors.


Assuntos
Densidade Óssea/efeitos dos fármacos , Osteoporose/sangue , Osteoporose/induzido quimicamente , Inibidores de Captação de Serotonina/efeitos adversos , Adulto , Biomarcadores/sangue , Densidade Óssea/fisiologia , Colágeno Tipo I/sangue , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Inibidores de Captação de Serotonina/farmacologia , Inibidores de Captação de Serotonina/uso terapêutico
17.
J Physiol Pharmacol ; 70(1)2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-31019126

RESUMO

There is a great urgency of detecting and monitoring myocardial fibrosis in clinical practice with the aim to improve and personalize therapy against cardiac remodelling. Hence, the aim of this study was to describe alterations in and show potential correlations between the structural characteristics and the molecular and biochemical markers of cardiac remodelling on a model of isoproterenol-induced heart failure. Two groups of 3-month-old male Wistar rats (n = 8 per group) were sacrificed after four weeks of treatment: control (placebo), ISO (5 mg/kg/day intraperitoneally). Chronic ISO treatment led to heart failure (HF) characterized by significant reduction of systolic blood pressure (SBP) accompanied by an increase in left ventricular weight (LVW) along with increased collagen content in the LV. The collagen content correlated negatively with SBP (R = -0.776, P < 0.001) and positively with LVW (R = 0.796, P < 0.001), with Col1a1 (0.83; P < 0.001) and Acta2 (0.73; P < 0.01). Moreover, the mRNA expression of fibrotic remodelling indicator, i.e. TGF-ß1 tended to increase, while the level of fibrinolysis markers (MCP-1, TIMP-2, MMP) were unchanged. The plasma markers of collagen, procollagen I C-terminal propeptide (PICP) was 37.34 ± 7.10 pg/mL in control and was reduced by 42% (P < 0.05) in the ISO group and procollagen III N-terminal propeptide (PIIINP) was 1216.7 ± 191.0 pg/mL in control and was decreased by 66% (P < 0.05) in the ISO group. Surprisingly, there was no positive correlation between plasma markers of collagen, i.e. PICP and PIIINP and collagen content or molecular markers of collagen. However, both PICP and PIIINP correlated with BW (R = 0.712, resp. 0.803, P < 0.001), which was significantly reduced (by 25%, P < 0.05) in the ISO group. In conclusion, we assume that the collagen content of the left ventricle does not need unavoidably correlate with plasma markers of collagen, which might be affected by confounding factors in heart failure, such as loss of body weight, presumably associated with a catabolic condition.


Assuntos
Colágeno/metabolismo , Insuficiência Cardíaca/metabolismo , Ventrículos do Coração/metabolismo , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Remodelação Ventricular , Animais , Pressão Sanguínea , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/fisiopatologia , Isoproterenol , Masculino , Ratos Wistar
18.
Rev. chil. cardiol ; 38(1): 37-45, abr. 2019. tab, graf
Artigo em Espanhol | LILACS | ID: biblio-1003636

RESUMO

Resumen: Introducción: Atletas altamente entrenados muestran cambios cardíacos estructurales como adaptación a la sobrecarga, producto del ejercicio repetitivo y extenuante. Se han evidenciado elevación de biomarcadores de remodelado y fibrosis miocárdica posterior al ejercicio intenso en atletas. Sin embargo, el comportamiento de estos biomarcadores según el nivel de entrenamiento previo no se ha evaluado. Objetivo: Investigar biomarcadores de fibrosis y función ventricular derecha en maratonistas con distinto nivel de entrenamiento previo. Métodos: Se incluyeron 36 maratonistas hombres, sanos, que completaron 42 km en la maratón de Santiago. Se dividieron según entrenamiento previo en dos grupos, Grupo 1 (G1): ≥100 km/semana y Grupo 2 (G2): <100 km/semana. Se realizó ecocardiografía transtorácica y se evaluaron niveles plasmáticos de galectina-3 y del propéptido amino terminal del procolágeno tipo III (PIIINP) en la semana previa a la carrera e inmediatamente posterior a ésta. Resultados: Posterior a la maratón, la función sistólica del ventrículo derecho disminuyó en el grupo G2 junto con un aumento significativo de los niveles plasmáticos de PIIIPNP (61±16 a 94±24 ng/mL, p=0,01). Estos cambios no se observaron en el grupo G1 (65 ± 11 a 90±29 ng/mL, p=0,10). Los niveles plasmáticos de galectina-3 aumentaron significativamente en ambos grupos posterior al ejercicio (6,8±2,2 a 19,7±4,9 ng/mL, p 0,012 y 6,0±1,1 a 19,4 ± 5,9 ng/mL, p 0,01) en los grupos G1 y G2, respectivamente). Conclusiones: Atletas con menor grado de entrenamiento, presentan posterior a una maratón un significativo aumento de productos de degradación del colágeno (PIIIPNP) asociado a disminución de la función del ventrículo derecho. Los niveles de galectina-3 plasmática aumentan significativamente en ambos grupos post-esfuerzo independiente del entrenamiento previo.


Abstracts: Introduction: Highly trained athletes show structural cardiac changes as adaptation to overload. Rise in remodeling biomarkers and myocardial fibrosis after intense exercise in athletes has been evidenced; however, the behavior of these biomarkers according to pre-competition training level has not been evaluated. Objective: To evaluate fibrosis biomarkers levels and right ventricle function in marathon runners according to their previous training level, in the period prior to a marathon race and immediately after it. Methods: Thirty-six healthy male marathon runners were included. Subjects were grouped according to their previous training level: Group 1 (G1): ≥100 km/week and Group 2 (G2): <100 km/week. Transthoracic echocardiography along with plasmatic levels of galectin-3 and amino terminal propeptide of type III procollagen (PIIINP) were measured one week previous and immediately after the marathon. Results: Post-effort right ventricle systolic function decreased in G2, together with a significant elevation of PIIIPNP (61±16 to 94±24 ng/mL, p=0.01). These changes were not observed in G1 (from 65±11 to 90±29 ng/mL, p=0.10). Plasma galectin-3 increased significantly in both groups immediately post-exercise (6.8±2.2 to 19.7±4.9 ng/mL, p=0.012, and 6.0±1.1 to 19.4±5.9 ng/mL, p=0.01, in G1 and G2. respectively). Conclusion: Less trained athletes evidenced higher post marathon levels of PIIIPNP which is associated with a decreased global right ventricle function. Plasma galectin-3 levels increased significantly after intense exertion regardless of the intensity of previous training.


Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Corrida/fisiologia , Fibrose/sangue , Biomarcadores/sangue , Função Ventricular Direita , Traumatismos Cardíacos/sangue , Fragmentos de Peptídeos/sangue , Fibrose/fisiopatologia , Exercício Físico/fisiologia , Método Simples-Cego , Chile , Estudos Prospectivos , Estudos Longitudinais , Função Ventricular Esquerda , Pró-Colágeno/sangue , Galectina 3/sangue , Atletas
19.
Drug Test Anal ; 11(7): 931-936, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30901507

RESUMO

Serum insulin-like growth factor-1 (IGF-1), procollagen type III N-terminal peptide (PIIINP), and human growth hormone (hGH) isoforms were analyzed in identical serum samples collected into BD Vacutainer® SST and BD Vacutainer® SST-II Advance serum separator tubes. Comparing the serum collected into each tube, measurement correlation was high (R2  > 0.83) and percent bias was minimal (<|3.2%|) for all analytes measured using World Anti-Doping Agency (WADA)-approved tests. As such, it is recommended that both SST and SST-II Advance tubes can be used interchangeably for anti-doping purposes.


Assuntos
Coleta de Amostras Sanguíneas/métodos , Hormônio do Crescimento Humano/sangue , Fator de Crescimento Insulin-Like I/análise , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Coleta de Amostras Sanguíneas/instrumentação , Doping nos Esportes , Humanos , Proteínas Recombinantes/sangue , Espectrometria de Massas em Tandem/métodos
20.
Int J Sport Nutr Exerc Metab ; 29(5): 526-531, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30859848

RESUMO

Nutritional strategies to improve connective tissue collagen synthesis have garnered significant interest, although the scientific validity of these interventions lags behind their hype. This study was designed to determine the effects of three forms of collagen on N-terminal peptide of procollagen and serum amino acid levels. A total of 10 recreationally active males completed a randomized double-blinded crossover design study consuming either placebo or 15 g of vitamin C-enriched gelatin or hydrolyzed collagen (HC), or gummy containing equal parts of gelatin and HC. Supplements were consumed 1 hr before 6 min of jump rope. Blood samples were collected immediately prior to supplement consumption and 4 hr after jump rope. A subset of blood samples (n = 4) was collected for amino acid analysis 1 hr after ingestion. Consumption of an equivalent dose of each supplement increased amino acids in the circulation similarly across all interventions. N-terminal peptide of procollagen levels tended to increase ∼20% from baseline in the gelatin and HC interventions but not the placebo or gummy. These results suggest that vitamin C-enriched gelatin and HC supplementation may improve collagen synthesis when taken 1 hr prior to exercise. However, large variability was observed, which precluded significance for any treatment.


Assuntos
Ácido Ascórbico/administração & dosagem , Colágeno/administração & dosagem , Colágeno/biossíntese , Fenômenos Fisiológicos da Nutrição Esportiva , Adolescente , Adulto , Aminoácidos/sangue , Estudos Cross-Over , Suplementos Nutricionais , Método Duplo-Cego , Exercício Físico , Humanos , Masculino , Pró-Colágeno/sangue , Adulto Jovem
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