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1.
J Endocrinol Invest ; 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38493245

RESUMO

BACKGROUND: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health. PURPOSE: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women. METHODS AND RESULTS: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk. CONCLUSIONS: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women.

2.
Osteoporos Int ; 30(11): 2363, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31506788

RESUMO

Two sentences in the Discussion section were incorrect.

3.
Osteoporos Int ; 30(5): 1059-1069, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30719548

RESUMO

Analyses using the largest Korean cohort of adrenal incidentaloma (AI) revealed that subtle cortisol excess in premenopausal women and reduced dehydroepiandrosterone-sulfate (DHEA-S) in postmenopausal women and men are associated with bone mineral density (BMD) reduction in Asian patients with subclinical hypercortisolism (SH). INTRODUCTION: Few studies evaluated bone metabolism in Asians with SH. We investigated associations of cortisol and DHEA-S, an adrenal androgen, with BMD in Asians with AI, with or without SH. METHODS: We used cross-sectional data of a prospective multicenter study from Korea. We measured BMD, bone turnover markers, cortisol levels after 1-mg dexamethasone suppression test (1-mg DST), DHEA-S, and baseline cortisol to DHEA-S ratio (cort/DHEA-S) in 109 AI patients with SH (18 premenopausal, 38 postmenopausal women, and 53 men) and 686 with non-functional AI (NFAI; 59 premenopausal, 199 postmenopausal women, and 428 men). RESULTS: Pre- and postmenopausal women, but not men, with SH had lower BMDs at lumbar spine (LS) than those with NFAI (P = 0.008~0.016). Premenopausal women with SH also had lower BMDs at the hip than those with NFAI (P = 0.009~0.012). After adjusting for confounders, cortisol levels after 1-mg DST demonstrated inverse associations with BMDs at all skeletal sites only in premenopausal women (ß = - 0.042~- 0.033, P = 0.019~0.040). DHEA-S had positive associations with LS BMD in postmenopausal women (ß = 0.096, P = 0.001) and men (ß = 0.029, P = 0.038). The cort/DHEA-S had inverse associations with LS BMD in postmenopausal women (ß = - 0.081, P = 0.004) and men (ß = - 0.029, P = 0.011). These inverse associations of cort/DHEA-S remained significant after adjusting for cortisol levels after 1-mg DST (ß = - 0.079~- 0.026, P = 0.006~0.029). In postmenopausal women, the odds ratios of lower BMD by DHEA-S and cort/DHEA-S was 0.26 (95% CI, 0.08-0.82) and 3.40 (95% CI, 1.12-10.33), respectively. CONCLUSION: Subtle cortisol excess in premenopausal women and reduced DHEA-S in postmenopausal women and men may contribute to BMD reduction in Asians with SH.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Densidade Óssea/fisiologia , Síndrome de Cushing/sangue , Sulfato de Desidroepiandrosterona/sangue , Hidrocortisona/sangue , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Adulto , Idoso , Biomarcadores/sangue , Remodelação Óssea/fisiologia , Estudos Transversais , Síndrome de Cushing/fisiopatologia , Feminino , Colo do Fêmur/fisiopatologia , Humanos , Hidrocortisona/fisiologia , Achados Incidentais , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoporose/sangue , Osteoporose/fisiopatologia , Pós-Menopausa/sangue , Pós-Menopausa/fisiologia , Pré-Menopausa/sangue , Pré-Menopausa/fisiologia
4.
Osteoporos Int ; 30(5): 1071-1078, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30719549

RESUMO

The plasma n-3 fatty acid level was 26.2% lower in patients with osteoporotic hip fracture than in those with osteoarthritis. In all patients, n-3 fatty acid was positively associated with bone mineral density and inversely associated with tartrate-resistant acid phosphatase-5b level in bone marrow aspirates, reflecting the bone microenvironment. INTRODUCTION: Despite the potential beneficial role of n-3 fatty acid (FA) on bone metabolism, the specific mechanisms underlying these effects in humans remain unclear. Here, we assessed whether the plasma n-3 level, as an objective indicator of its status, is associated with osteoporosis-related phenotypes and bone-related markers in human bone marrow (BM) samples. METHODS: This was a case-control and cross-sectional study conducted in a clinical unit. n-3 FA in the blood and bone biochemical markers in the BM aspirates were measured by gas chromatography/mass spectrometry and immunoassay, respectively. BM fluids were collected from 72 patients who underwent hip surgery because of either osteoporotic hip fracture (HF; n = 28) or osteoarthritis (n = 44). RESULTS: After adjusting for confounders, patients with HF had 26.2% lower plasma n-3 levels than those with osteoarthritis (P = 0.006), and each standard deviation increment in plasma n-3 was associated with a multivariate-adjusted odds ratio of 0.40 for osteoporotic HF (P = 0.010). In multivariate analyses including all patients, a higher plasma n-3 level was associated with higher bone mass at the lumbar spine (ß = 0.615, P = 0.002) and total femur (ß = 0.244, P = 0.045). Interestingly, the plasma n-3 level was inversely associated with the tartrate-resistant acid phosphatase-5b level (ß = - 0.633, P = 0.023), but not with the bone-specific alkaline phosphatase level, in BM aspirates. CONCLUSIONS: These findings provide clinical evidence that n-3 FA is a potential inhibitor of osteoclastogenesis that favors human bone health.


Assuntos
Densidade Óssea/fisiologia , Ácidos Graxos Ômega-3/sangue , Fraturas do Quadril/fisiopatologia , Fraturas por Osteoporose/fisiopatologia , Fosfatase Ácida Resistente a Tartarato/metabolismo , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/metabolismo , Reabsorção Óssea/fisiopatologia , Estudos de Casos e Controles , Estudos Transversais , Ácidos Graxos Ômega-3/fisiologia , Ácidos Graxos Ômega-6/sangue , Feminino , Fêmur/fisiopatologia , Fraturas do Quadril/sangue , Humanos , Vértebras Lombares/fisiopatologia , Masculino , Fraturas por Osteoporose/sangue
5.
Osteoporos Int ; 29(10): 2299-2307, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29971455

RESUMO

Despite ethnic differences in cortisol sensitivity, only one study in Caucasians has assessed trabecular bone score (TBS) in patients with subclinical hypercortisolism (SH). We showed that both subtle cortisol excess and reduced adrenal androgen may contribute to impaired bone quality in Asian women with SH. INTRODUCTION: One study in Caucasians has assessed trabecular bone score (TBS), an index of bone microstructure, in adrenal incidentaloma (AI) patients with subclinical hypercortisolism (SH). There are ethnic differences in cortisol sensitivities between Caucasian and Asian populations. We investigated the associations of cortisol and the adrenal androgen dehydroepiandrosterone-sulfate (DHEA-S) with TBS in AI patients with SH, adrenal Cushing's syndrome (CS), and nonfunctional AI (NFAI). METHODS: We measured TBS, cortisol levels after the overnight 1 mg dexamethasone suppression test (1 mg DST), and cortisol/DHEA-S in 61 patients with SH (30 men; 31 women), 19 with adrenal CS (4 men; 15 women), and 355 with NFAI (213 men; 142 women). RESULTS: After adjusting for confounders, the serum cortisol level after 1 mg DST was inversely correlated with TBS in men (ß = -0.133, P = 0.045) and women (ß = - 0.140, P = 0.048). Higher cortisol/DHEA-S ratio was associated with lower TBS in women (ß = - 0.252, P < 0.001), but not men. This inverse association of cortisol/DHEA-S ratio in women remained statistically significant after adjusting for the serum cortisol level after 1 mg DST (ß = - 0.221, P = 0.008). Compared with women with NFAI, women with SH had 2.2% lower TBS (P = 0.040). Deteriorated bone microstructure (TBS < 1.230) was associated with the serum cortisol level after 1 mg DST (odds ratio [OR], 2.18; 95% confidence interval [CI], 1.04-4.53) and cortisol/DHEA-S ratio (OR, 2.05; 95% CI, 1.03-4.08). CONCLUSIONS: Subtle cortisol excess in both genders and reduced DHEA-S, especially in women, may contribute to impaired bone quality in Asian patients with SH.


Assuntos
Neoplasias das Glândulas Suprarrenais/sangue , Densidade Óssea/fisiologia , Sulfato de Desidroepiandrosterona/sangue , Hidrocortisona/sangue , Absorciometria de Fóton/métodos , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/epidemiologia , Neoplasias das Glândulas Suprarrenais/fisiopatologia , Idoso , Osso Esponjoso/fisiopatologia , Síndrome de Cushing/sangue , Síndrome de Cushing/epidemiologia , Síndrome de Cushing/etiologia , Síndrome de Cushing/fisiopatologia , Feminino , Humanos , Achados Incidentais , Vértebras Lombares/fisiopatologia , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores Sexuais
6.
Osteoporos Int ; 29(8): 1713-1720, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29777277

RESUMO

Bone fractures in older adults are often preceded by a loss of muscle mass and strength. Likewise, bone loss with prolonged bed rest, spinal cord injury, or with exposure to microgravity is also preceded by a rapid loss of muscle mass. Recent studies using animal models in the setting of hindlimb unloading or botulinum toxin (Botox) injection also reveal that muscle loss can induce bone loss. Moreover, muscle-derived factors such as irisin and leptin can inhibit bone loss with unloading, and knockout of catabolic factors in muscle such as the ubiquitin ligase Murf1 or the myokine myostatin can reduce osteoclastogenesis. These findings suggest that therapies targeting muscle in the setting of disuse atrophy may potentially attenuate bone loss, primarily by reducing bone resorption. These potential therapies not only include pharmacological approaches but also interventions such as whole-body vibration coupled with resistance exercise and functional electric stimulation of muscle.


Assuntos
Envelhecimento/fisiologia , Atrofia Muscular/complicações , Osteoporose/etiologia , Animais , Repouso em Cama/efeitos adversos , Toxinas Botulínicas , Modelos Animais de Doenças , Humanos , Proteínas Musculares/uso terapêutico , Músculo Esquelético/fisiopatologia , Atrofia Muscular/fisiopatologia , Osteoporose/fisiopatologia , Osteoporose/prevenção & controle , Voo Espacial , Traumatismos da Medula Espinal/complicações , Ausência de Peso/efeitos adversos
7.
Osteoporos Int ; 29(6): 1397-1405, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29511792

RESUMO

Data gathered from a nationally representative cohort demonstrate that higher dietary protein intake was positively associated with the composite indices of femoral neck strength in both men and women, suggesting that higher protein intake may contribute to lower risk of hip fracture through the improvement of bone strength. INTRODUCTION: Despite the general belief that higher protein intake may be helpful for bone homeostasis, its impact on human bone health is still debated. Furthermore, the association of dietary protein intake with femoral neck (FN) strength, which can predict fracture risk independently of bone mineral density (BMD), has not been thoroughly studied. METHODS: This is a population-based, cross-sectional study from Korea National Health and Nutrition Examination Surveys, including 592 men aged 50 years or older and 590 postmenopausal women. The composite indices of FN strength, such as the compression strength index (CSI), bending strength index (BSI), and impact strength index (ISI), were generated by combining BMD, body weight, and height with the femoral axis length and width, which were measured by dual-energy X-ray absorptiometry. RESULTS: After adjustment for confounders, total protein intake (g/kg/day) positively correlated with all three FN composite indices in both genders (P = 0.006 to 0.035), except for BSI showing marginal significance in postmenopausal women (P = 0.093). Consistently, compared with subjects in lowest total protein intake quartile, those in the highest quartile showed markedly higher CSI, BSI, and ISI values (P = 0.043 to < 0.001), with a dose-response manner across increasing total protein intake quartile categories in both men and women (P for trend = 0.028 to < 0.001). CONCLUSIONS: These findings provide the clinical evidence that higher dietary protein intake can play a beneficial role on bone health through the increase of FN strength relative to load in adults.


Assuntos
Proteínas Alimentares/farmacologia , Colo do Fêmur/efeitos dos fármacos , Absorciometria de Fóton/métodos , Idoso , Idoso de 80 Anos ou mais , Antropometria/métodos , Estatura/fisiologia , Peso Corporal/fisiologia , Densidade Óssea/efeitos dos fármacos , Estudos Transversais , Dieta/estatística & dados numéricos , Proteínas Alimentares/administração & dosagem , Feminino , Colo do Fêmur/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Caracteres Sexuais
8.
RSC Adv ; 8(10): 5158-5165, 2018 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35542437

RESUMO

Among the techniques to create VO2 nanostructures, the sol-gel method is the most facile and benefits from simple, manipulable synthetic parameters. Here, by utilizing various TEM techniques, we report the sequential morphological evolution of VO2 nanostructures in a sol-gel film spin-coated on a customized TEM grid, which underwent oxygen reduction as the annealing temperature increased. In situ TEM dark-field imaging and Raman spectroscopy allowed us to confirm the sharp phase transition behavior of an individual nanowire by illustrating the effect of electrode-clamping-induced tensile stress on the nucleation of the R phase from the M1 phase. The electrical transport properties of a single-nanowire device fabricated on a customized TEM grid showed excellent control of the stoichiometry and crystallinity of the wire. These results offer critical information for preparing tailored VO2 nanostructures with advanced transition properties by the sol-gel method to enable the fabrication of scalable flexible devices.

9.
RSC Adv ; 8(56): 31984, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-35547529

RESUMO

[This corrects the article DOI: 10.1039/C7RA10865F.].

10.
RSC Adv ; 8(58): 33228, 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-35548119

RESUMO

[This corrects the article DOI: 10.1039/C7RA10865F.].

11.
Int J Obes (Lond) ; 41(4): 660-663, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28100915

RESUMO

Recently, the prevalence of childhood obesity has significantly increased in industrialized countries, including Korea, and now controlling obesity is becoming an economic burden. However, knowledge of the risk factors associated with obesity is still limited. In this study, we aimed to discover additional obesity-associated loci in children. To achieve this, we conducted an exome-wide association analysis of copy number variation (CNV) using whole-exome sequencing (WES) data from a total of 102 cases and 86 controls. We newly identified a CNV locus that overlapped two protocadherin genes, PCDHB7 and PCDHB8, which are brain function-related genes (P-value=6.40 × 10-4, odds ratio=2.2189). A subsequent replication analysis using WES data from 203 obese and 291 normal weight children showed that this CNV region satisfied the genome-wide significance standard (Fisher's combined P-value=3.76 × 10-5). Moreover, correlation test using 199 additional samples supported significant association between CNV and increased body mass index. This region also showed a meaningful association with 273 cases and 2596 controls in adult samples. Our findings suggest that differences in the common CNV region at 5q31.3 may have an impact on the pathophysiology of obesity.


Assuntos
Povo Asiático/genética , Caderinas/genética , Variações do Número de Cópias de DNA/genética , Sequenciamento do Exoma , Exoma/genética , Obesidade Infantil/genética , Adolescente , Criança , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Reprodutibilidade dos Testes , República da Coreia
12.
Osteoporos Int ; 28(3): 1099-1108, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27866216

RESUMO

Postmenopausal women with osteoporotic fracture (OF) had higher plasma dipeptidyl-peptidase 4 (DPP4) levels than those without. Furthermore, higher plasma DPP4 levels were significantly associated with higher bone turnover and a higher prevalence of OF. These results indicated that DPP4 may be associated with OF by mediating bone turnover rate. INTRODUCTION: Evidence indicates that dipeptidyl-peptidase 4 (DPP4) plays a distinct role in bone metabolism. However, there has been no report on the association, if any, between circulating DPP4 levels and osteoporosis-related phenotypes, including osteoporotic fracture (OF). Therefore, we performed a case-control study to investigate these associations in postmenopausal women. METHODS: This study was conducted in multiple centers in Korea. We enrolled 178 cases with OF and 178 age- and body mass index-matched controls. OF was assessed by an interviewer-assisted questionnaire and lateral thoracolumbar radiographs. Bone turnover markers (BTMs), bone mineral density (BMD), and plasma DPP4 levels were obtained in all subjects. RESULTS: After adjustment for potential confounders, subjects with OF had significantly higher DPP4 levels than those without (P = 0.021). Higher DPP4 levels were significantly positively associated with higher levels of all BTMs, but not with BMD at all measured sites. The differences in DPP4 levels according to OF status disappeared after an additional adjustment for each BTM, but not after adjustment for any BMD values. BTMs explained approximately half of the relationship between DPP4 and OF. The risk of OF was 3.80-fold (95% confidence interval = 1.53-9.42) higher in subjects in the highest DPP4 quartile than in those in the lowest quartile after adjustment for potential confounders, including femoral neck BMD. CONCLUSIONS: DPP4 may be associated with OF by at least partly mediating the bone turnover rate. Circulating DPP4 levels may be a potential biomarker that could increase the predictive power of current fracture risk assessment models.


Assuntos
Dipeptidil Peptidase 4/sangue , Osteoporose Pós-Menopausa/enzimologia , Fraturas por Osteoporose/enzimologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Densidade Óssea/fisiologia , Remodelação Óssea/fisiologia , Estudos de Casos e Controles , Ensaios Enzimáticos Clínicos/métodos , Feminino , Colo do Fêmur/fisiopatologia , Humanos , Vértebras Lombares/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/fisiopatologia , Fraturas por Osteoporose/etiologia , Fraturas por Osteoporose/fisiopatologia , Medição de Risco/métodos
13.
Genet Mol Res ; 15(3)2016 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-27706627

RESUMO

Odontobutis obscura is a bottom-dwelling freshwater fish native to East Asia. Its range encompasses southwest China, western Japan, and Geoje Island in South Korea. Despite its widespread range in China and Japan, only a small and spatially isolated population is found in South Korea. We developed a total of 23 novel and polymorphic microsatellite loci of O. obscura using Illumina paired-end shotgun sequencing and characterized them using 80 Japanese and Korean samples. An extensive genetic polymorphism was detected at these 23 loci, with the observed number of alleles at a locus ranging from 2 to 15 and expected and observed heterozygosities ranging from 0 to 0.656 and 0 to 0.547, respectively. Korean O. obscura exhibited a much lower level of genetic variability than the Japanese population did, probably as a result of long-term isolation combined with historical bottlenecks. The Japanese and Korean populations showed a high level of genetic differentiation with FST = 0.700 and RST = 0.913. Many of our primer sets were successfully transferable to congeneric O. interrupta and O. platycephala, which exhibited even greater polymorphism than Korean O. obscura. In conclusion, our study showed that these 23 microsatellite markers are useful for understanding the conservation biology and population genetic structure of O. obscura and other congeneric species.


Assuntos
Loci Gênicos , Genética Populacional , Genoma , Repetições de Microssatélites , Perciformes/genética , Alelos , Animais , Mapeamento Cromossômico , Água Doce , Heterozigoto , Polimorfismo Genético , Análise de Sequência de DNA
14.
Nanotechnology ; 27(43): 435704, 2016 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-27658734

RESUMO

Nano-scale VO2 wires with controlled parameters such as electron-doping have attracted intense interest due to their capability of suppressing the temperature of the metal-insulator transition (MIT). However, because their diameters are smaller than the spatial resolutions of the conventional measuring equipment, the ability to perform a thorough examination of the wires has been hindered. Here, we report the fabrication of a transmission electron microscopy (TEM) grid with an optimum design of Si3N4 windows on which the photolithography for individual electron-doped VO2 nanowire devices can be safely accomplished, allowing the cross-examination of the structural and electrical properties. TEM dark-field imaging was used to quantitatively investigate the fractions of rutile and M1 phases, and their lattice alignments were observed using high-resolution TEM (HRTEM) with small area diffraction. Moreover, electron energy loss spectroscopy (EELS) revealed that the rutile domain would be created by the strain induced by oxygen vacancies. Importantly, we successfully tuned the transition temperature by changing the rutile fraction while maintaining a high level of resistivity change. The resistivity at room temperature linearly decreased with the rutile fraction, following a simple model. Furthermore, the T dependence of the threshold voltage can be attributed to the Joule heating, exhibiting an identical thermal dependence, irrespective of the rutile fraction.

15.
Osteoporos Int ; 27(8): 2533-41, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-26984570

RESUMO

UNLABELLED: A high level of circulating sphingosine-1-phosphate (S1P) is associated with a high incidence of osteoporotic fracture and a high rate of an insufficient response to bisphosphonate therapy. INTRODUCTION: Sphingosine-1-phosphate (S1P) is a significant regulator of bone metabolism. Recently, we found that a high plasma S1P level is associated with low bone mineral density (BMD), high levels of bone resorption markers (BRMs), and a high risk of prevalent vertebral fracture in postmenopausal women. We investigated the possibility that S1P is a predictor of incident fracture. METHODS: A total of 248 postmenopausal women participated in this longitudinal study and were followed up for a mean duration of 3.5 years (untreated [n = 76] or treated with bisphosphonate or hormone replacement therapy [n = 172]). The baseline plasma S1P level and prevalent and incident fracture occurrence were assessed. RESULTS: A high S1P level was significantly associated with a higher rate of prevalent fracture after adjusting for femoral neck (FN) BMD, BRM, and potential confounders (odds ratio = 2.05; 95 % confidence interval [CI] = 1.03-4.00). Incident fractures occurred more frequently in the highest S1P tertile (T3) than in the lower two tertiles (T1-2) after adjusting for confounders, including baseline FN BMD, prevalent fracture, antiosteoporotic medication, annualized changes in FN BMD, BRM, and potential confounders (hazard ratio = 5.52; 95 % CI = 1.04-56.54). Insufficient response to bisphosphonate therapy occurred more frequently in T3 than T1-2 (odds ratio = 4.43; 95 % CI = 1.02-21.25). CONCLUSIONS: The plasma S1P level may be a potential predictor of fracture occurrence and an insufficient response to bisphosphonate therapy in postmenopausal women.


Assuntos
Densidade Óssea , Fraturas Ósseas/sangue , Lisofosfolipídeos/sangue , Osteoporose Pós-Menopausa/sangue , Pós-Menopausa , Esfingosina/análogos & derivados , Idoso , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Fatores de Risco , Esfingosina/sangue
16.
J Endocrinol Invest ; 39(3): 297-303, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26219613

RESUMO

BACKGROUND: Although recent studies provide clinical evidence that sphingosine-1-phosphate (S1P) may primarily affect bone resorption in humans, rather than bone formation or the osteoclast-osteoblast coupling phenomenon, those studies could not determine which bone resorption mechanism is more important, i.e., chemorepulsion of osteoclast precursors via the blood to bone marrow S1P gradient or receptor activator of NF-κB ligand (RANKL) elevation in osteoblasts via local S1P. AIM: To investigate how S1P mainly contributes to increased bone resorption in humans, we performed this case-control study at a clinical unit in Korea. METHODS: Blood and bone marrow samples were contemporaneously collected from 70 patients who underwent hip surgery due to either osteoporotic hip fracture (HF) (n = 10) or other causes such as osteoarthritis (n = 60). RESULTS: After adjusting for sex, age, BMI, smoking, alcohol, previous fracture, diabetes, and stroke, subjects with osteoporotic HF demonstrated a 3.2-fold higher plasma/bone marrow S1P ratio than those without HF, whereas plasma and bone marrow S1P levels were not significantly different between these groups. Consistently, the risk of osteoporotic HF increased 1.38-fold per increment in the plasma/bone marrow S1P ratio in a multivariate adjustment model. However, the odds ratios for prevalent HF according to the increment in the plasma and bone marrow S1P level were not statistically significant. CONCLUSION: Our current results using simultaneously collected blood and bone marrow samples suggest that the detrimental effects of S1P on bone metabolism in humans may depend on the S1P gradient between the peripheral blood and bone marrow cavity.


Assuntos
Medula Óssea/metabolismo , Reabsorção Óssea/metabolismo , Osso e Ossos/metabolismo , Lisofosfolipídeos/metabolismo , Osteoartrite/metabolismo , Fraturas por Osteoporose/metabolismo , Plasma/metabolismo , Esfingosina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Reabsorção Óssea/etiologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/complicações , Osteoartrite/cirurgia , Fraturas por Osteoporose/complicações , Fraturas por Osteoporose/cirurgia , Prognóstico , Estudos Retrospectivos , Esfingosina/metabolismo
17.
J Endocrinol Invest ; 38(8): 891-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25841894

RESUMO

BACKGROUND: It was recently reported that G protein-coupled receptor 65 (GPR65) suppresses ovariectomy-induced bone loss. AIM: The present study investigated the role of the lysosphingolipid psychosine, a GPR65 ligand, on osteoclastic differentiation and bone resorption. METHODS: Osteoclasts were differentiated from mouse bone marrow macrophages. Tartrate-resistant acid phosphatase-positive multinucleated cells were considered to be osteoclasts, and the resorption area was measured by incubating the cells on dentine discs. The expression levels of osteoclast differentiation markers were assessed by qRT-PCR. GPR65 siRNA and its scrambled siRNA were transfected with lipofectamine. Intracellular cyclic adenosine monophosphate (cAMP) levels were assessed using a direct enzyme immunoassay. RESULTS: Psychosine inhibited osteoclastogenesis and in vitro bone resorption without any significant effect on the viability of pre-osteoclasts, decreased the expression of osteoclast differentiation markers significantly, and increased intracellular cAMP levels. The knockdown of GPR65 by its siRNA restored osteoclastogenesis and decreased cAMP levels in the presence of psychosine. CONCLUSION: Psychosine inhibits osteoclastogenesis by increasing intracellular cAMP levels via GPR65.


Assuntos
Reabsorção Óssea/metabolismo , Reabsorção Óssea/prevenção & controle , Osteoclastos/efeitos dos fármacos , Psicosina/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos C57BL , Osteoclastos/fisiologia , Psicosina/uso terapêutico , Receptores Acoplados a Proteínas G/metabolismo
18.
Osteoporos Int ; 26(2): 737-47, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25391247

RESUMO

SUMMARY: Data gathered from a nationally representative cohort demonstrated that subject with low skeletal muscle mass had consistently low femoral neck composite strength indices for compression, bending, and impact, especially in older women, supporting the highly integrated nature of skeletal muscle and bone. INTRODUCTION: Skeletal muscle and bone interact mechanically and functionally. The present study was performed to investigate the association between muscle mass and femoral neck composite strength indices using a nationally representative cohort. METHODS: This is a population-based, cross-sectional study from Korea National Health and Nutrition Examination Surveys, including 1,275 Koreans (674 women and 601 men) aged 50 years or older. Femoral neck axis length and width were measured by hip DXA scans and were combined with BMD, body weight, and height to create composite indices of femoral neck strength relative to load in three different failure modes: compression, bending, and impact. Presarcopenia was defined as an appendicular skeletal muscle mass (ASM) divided by body weight that was less than 1 SD below the sex-specific mean for young adults. RESULTS: After adjusting for confounders, women with presarcopenia had consistently lower indices for compression strength (CSI), bending strength (BSI), and impact strength (ISI) than women without this condition. Men with presarcopenia had a lower ISI value than men without presarcopenia. Multiple regression analyses revealed that lower relative skeletal muscle mass (ASM/weight) associated significantly with lower values for all three femoral neck composite indices in women and with lower CSI and ISI in men. CONCLUSIONS: These findings provide the first clinical evidence for the notion that age-related low muscle mass may increase the risk of osteoporotic hip fractures by decreasing femoral neck strength relative to load, especially in older women, and support the highly integrated nature of skeletal muscle and bone.


Assuntos
Colo do Fêmur/fisiopatologia , Músculo Esquelético/patologia , Sarcopenia/fisiopatologia , Absorciometria de Fóton/métodos , Idoso , Idoso de 80 Anos ou mais , Antropometria/métodos , Densidade Óssea/fisiologia , Estudos Transversais , Feminino , Colo do Fêmur/patologia , Articulação do Quadril/patologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Tamanho do Órgão/fisiologia , Sarcopenia/patologia , Suporte de Carga/fisiologia
19.
Spinal Cord ; 52 Suppl 3: S16-8, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25376310

RESUMO

STUDY DESIGN: A case report. OBJECTIVES: This study discusses a case of spinal segmental myoclonus caused by thoracic myelopathy, mimicking hiccup spasms. Spinal myoclonus caused by thoracic myelopathy is extremely rare. It can be misdiagnosed as chronic intractable hiccups due to similar clinical manifestations. SETTING: Korea University Anam Hospital, Seoul, Republic of Korea. METHODS: A 42-year-old man presented with a history of involuntary jerky movement of the upper abdominal wall muscles that had been continuing for over 3 years. A neurological examination, brain computed tomography and electroencephalogram did not reveal a cause of the symptoms. Electromyography was performed on the abdominal muscles and the findings revealed were compatible with spinal myoclonus. The spinal myoclonus had started in the abdominal muscles, with a spinal magnetic resonance imaging revealing a disc protrusion compressing the anterior spinal cord. RESULTS: The cause of the spinal myoclonus was determined to be spinal myelopathy due to mild T7 disc protrusion. The patient refused surgical or invasive interventions and was conservatively treated with clonazepam. The symptoms were reported to be less frequent following the treatment. CONCLUSION: Compressive myelopathy developed from disc protrusion may cause spinal myoclonus mimicking as hiccup spasms.


Assuntos
Soluço/patologia , Soluço/fisiopatologia , Mioclonia/fisiopatologia , Compressão da Medula Espinal/patologia , Compressão da Medula Espinal/fisiopatologia , Doenças da Medula Espinal/complicações , Traumatismos da Medula Espinal/patologia , Adulto , Soluço/etiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Músculo Esquelético/patologia , Mioclonia/etiologia , Exame Neurológico/métodos , Compressão da Medula Espinal/complicações , Doenças da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico
20.
AJNR Am J Neuroradiol ; 35(8): 1539-42, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24651815

RESUMO

BACKGROUND AND PURPOSE: Developmental venous anomalies are the most common intracranial vascular malformation. Increased signal-intensity on T2-FLAIR images in the areas drained by developmental venous anomalies are encountered occasionally on brain imaging studies. We evaluated diffusion and perfusion MR imaging findings of the abnormally high signal intensity associated with developmental venous anomalies to describe their pathophysiologic nature. MATERIALS AND METHODS: We retrospectively reviewed imaging findings of 34 subjects with signal-intensity abnormalities associated with developmental venous anomalies. All subjects underwent brain MR imaging with contrast and diffusion and perfusion MR imaging. Regions of interest were placed covering abnormally high signal intensity around developmental venous anomalies on fluid-attenuated inversion recovery imaging, and the same ROIs were drawn on the corresponding sections of the diffusion and perfusion MR imaging. We measured the apparent diffusion coefficient, relative cerebral blood volume, relative mean transit time, and time-to-peak of the signal-intensity abnormalities around developmental venous anomalies and compared them with the contralateral normal white matter. The Mann-Whitney U test was used for statistical analysis. RESULTS: The means of ADC, relative cerebral blood volume, relative mean transit time, and TTP of signal-intensity abnormalities around developmental venous anomalies were calculated as follows: 0.98 ± 0.13 10(-3)mm(2)/s, 195.67 ± 102.18 mL/100 g, 16.74 ± 7.38 seconds, and 11.65 ± 7.49 seconds, respectively. The values of normal WM were as follows: 0.74 ± 0.08 10(-3)mm(2)/s for ADC, 48.53 ± 22.85 mL/100 g for relative cerebral blood volume, 12.12 ± 4.27 seconds for relative mean transit time, and 8.35 ± 3.89 seconds for TTP. All values of ADC, relative cerebral blood volume, relative mean transit time, and TTP in the signal-intensity abnormalities around developmental venous anomalies were statistically higher than those of normal WM (All P < .001, respectively). CONCLUSIONS: The diffusion and perfusion MR imaging findings of the signal-intensity abnormalities associated with developmental venous anomaly suggest that the nature of the lesion is vasogenic edema with congestion and delayed perfusion.


Assuntos
Encéfalo/fisiopatologia , Malformações Vasculares do Sistema Nervoso Central/fisiopatologia , Imageamento por Ressonância Magnética/métodos , Adulto , Feminino , Humanos , Interpretação de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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