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1.
BMC Endocr Disord ; 19(1): 83, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362731

RESUMO

BACKGROUND: Thyroid dysfunction is one of the prevalent endocrine disorders. The relationship between lifestyle factors and thyroid dysfunction was not clear and some of the factors seemed paradoxical. METHODS: We conducted this population-based study using data from 5154 She ethnic minority people who had entered into the epidemic survey of diabetes between July 2007 to September 2009. Life style information was collected using a standard questionnaire. Body mass index (BMI), Blood pressure and serum TSH, TPOAb, triglycerides (TG), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL) were collected. RESULTS: The study showed that people who drank, had higher education or suffered from insomnia have lower incidence of hyperthyroidism. On the other hand, smoking, alcohol consumption, exercise, undergoing weight watch and chronic headache were associated with decreased incidence of hypothyroidism. Using multivariable logistic regression analysis, we found that alcohol consumption was associated with decreased probability of hyperthyroidism, hypothyroidism, as well as positive TPOAb. The amounts of cigarettes smoked daily displayed a positive correlation with hyperthyroidism among smokers. Accordingly, smoking seemed to be associated with decreased risk for hypothyroidism and positive TPOAb. Exercise and maintaining a healthy weight might have a beneficial effect on thyroid health. Interestingly, daily staple amount showed an inverse correlation with incidence of positive TPOAb. CONCLUSIONS: Within the Chinese She ethnic minority, we found associations between different lifestyle factors and the incidence of different thyroid diseases. Understanding the nature of these associations requires further investigations.

2.
J Pak Med Assoc ; 69(6): 828-833, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31189290

RESUMO

OBJECTIVE: To examine receptors for advanced glycation end-products Gly82Ser polymorphism in patients of type 2 diabetes with comorbid depression. METHODS: The case-control study was conducted at Fujian Provincial Hospital, Fuzhou, China, between December 2011 and December 2012, and comprised unrelated Chinese Han patients of type 2 diabetes, and diabetics with diagnosed clinical depression. Gly82Ser polymorphism polymorphism was determined using polymerase chain reaction amplification-high resolution melting curve protocol. Serum levels of endogenous secretory receptor for advanced glycation end products were measured using enzyme-linked immunosorbent assay. SPSS 16 was used for data analysis. RESULTS: Of the 114 subjects, 72(63.15%) were clinically depressed. Lower levels of endogenous secretory receptor were found in the depression group compared with the other group (p=0.049). No difference in genotypes or allele frequencies existed between the two groups (p>0.05). Gly82Ser carriers had significantly higher Hamilton Rating Scale scores (p<0.001) and lower serum endogenous secretory receptor (p=0.012) among the depressed diabetics. There were also significant differences in body mass index (p=0.005), abdominal circumference (p=0.038), carotid intima-media thickness (p=0.037) and high-sensitivity C-reactive protein (p=0.005) concentration between the different genotypes.. CONCLUSIONS: Receptors for advanced glycation end-products-ligands system may be involved in type 2 diabetes with comorbid depression at the genetic level.

3.
Endocr Pract ; 25(4): 299-305, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30995429

RESUMO

Objective: To assess the association between famine exposure in early life and osteoporosis in adulthood. Methods: A total of 2,292 participants born between 1955 and 1965 in Fujian Province were selected; after 3 years, 1,378 participants attended a follow-up research visit. Calcaneus bone mineral density and bone quality were measured by quantitative ultrasound. The T-score was used to assess bone mineral density, and the parameters quantitative ultrasound index (QUI), speed of sound (SOS), and broadband ultrasonic attenuation (BUA) were used to assess bone quality. A T-score threshold of -1.8 was defined as osteoporosis, and a possible vertebral fracture was considered as a prospective height loss of 0.8 inches or more. Results: Compared with the nonexposed cohort, risks of osteoporosis for fetal-, early childhood, and mid-childhood famine-exposed cohorts in postmenopausal women were adjusted odds ratio (OR), 3.741 (95% confidence interval [CI], 1.233, 11.44) versus OR 2.894 (95% CI, 0.997, 8.571) versus OR 4.699 (95% CI, 1.622, 13.612) by logistic regression but not significant in men. Moreover, the fetal-exposed cohort had a weak negative relation with QUI (ß, -5.07 [-10.226, 0.127]) and BUA (ß, -4.321 [-0.88, 0.238]). The early- and mid-childhood-exposed cohorts had significantly lower QUI (ß, -7.085 [-11.799, -2.372] versus ß, -10.845 [-15.68, -6.01]) and BUA (ß, -6.381 [-10.515, -2.246] versus ß, -8.573 [-12.815, -4.331]) than the nonexposed cohort by linear regression. None of the famine-exposed cohorts had a significant relationship with SOS. Conclusion: Famine exposure during early life is associated with higher risk of osteoporosis in adulthood, which is most obvious in postmenopausal women. Furthermore, famine exposure in early life has adverse effects on bone quality. Abbreviations: BMD = bone mineral density; BUA = broadband ultrasonic attenuation; CI = confidence interval; OR = odds ratio; QUI = quantitative ultrasound index; QUS = quantitative ultrasound; SOS = speed of sound.


Assuntos
Osteoporose , Absorciometria de Fóton , Densidade Óssea , Feminino , Humanos , Masculino , Estudos Prospectivos , Inanição
4.
Artigo em Inglês | MEDLINE | ID: mdl-30522793

RESUMO

Gestational diabetes mellitus (GDM), which has an increasing global prevalence, contributes to the susceptibility to metabolic dysregulation and obesity in the offspring via epigenetic modifications. However, the underlying mechanism remains largely obscure. The current study established a GDM mice model to investigate the alternations in the metabolic phenotypes and genomic DNA methylation in the pancreas of the offspring. We found that in the GDM offspring, intrauterine hyperglycemia induced dyslipidemia, insulin resistance, and glucose intolerance. Meanwhile, altered DNA methylation patterns were exhibited in the pancreas and many differentially methylated regions (DMRs)-related genes were involved in glycolipids metabolism and related signaling pathways, including Agap2, Plcbr, Hnf1b, Gnas, Fbp2, Cdh13, Wnt2, Kcnq1, Lhcgr, Irx3, etc. Additionally, the overall hypermethylation of Agap2, verified by bisulfite sequencing PCR (BSP), was negatively correlated with its mRNA expression level. In conclusion, these findings suggest that the DNA methylation changes in the pancreatic genome of the GDM offspring may be associated with the glycolipid metabolism abnormalities, T2DM susceptibility, and obesity in the adult GDM offspring.

5.
Menopause ; 2018 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-30516712

RESUMO

OBJECTIVE: To assess the effect of early life exposure to famine, as endured during 1959 to 1961 in China, on reproductive aging in adult women. METHODS: Between 2011 and 2012, 2,868 women born around the Chinese famine period (1956-1964) were enrolled in this study from three communities in China. Age at natural menopause was obtained retrospectively from a structured questionnaire. The associations of early life famine exposure with reproductive aging during adulthood were estimated, with adjustment of socioeconomic status, lifestyle factors, and body mass index. RESULTS: Women exposed to prenatal famine had a higher risk of early menopause (ie, natural menopause <45 years, odds ratio: 1.59, 95% confidence interval [CI]: 1.07, 2.36), and a nonsignificant trend of higher risk of premature ovarian failure (ie, natural menopause <40 y, odds ratio: 1.94, 95% CI: 0.93, 4.00), compared to unexposed women. Exposure to famine during childhood was not significantly associated with reproductive aging. In a secondary analysis focusing on the fetal exposure, prenatal famine exposure was associated with a higher risk of premature ovarian failure (odds ratio: 2.07, 95% CI: 1.08, 3.87), and a nonsignificant trend of higher risk of early menopause (odds ratio: 1.37, 95% CI: 0.98, 1.91), compared to those unexposed to prenatal famine. CONCLUSIONS: Our study showed that fetal exposure to famine was associated with an increased risk of early menopause. Such findings provided evidence in favor of the thrifty phenotype theory in reproductive aging and helped better understand the etiology of early menopause.

6.
Sleep Breath ; 22(1): 223-232, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28238100

RESUMO

STUDY OBJECTIVES: Renal hyperfiltration (RHF) has emerged as a novel marker of early renal damage in various conditions such as diabetes and metabolic syndrome. Aberrant sleep duration and excessive daytime napping may affect the development of chronic kidney disease (CKD). In this study, the association between sleep duration, daytime napping, and renal hyperfiltration was assessed. SETTING: This study was conducted in three communities in China. PARTICIPANTS: A total of 16,119 community volunteers (5735 males and 10,384 females) aged 40-65 years without CKD were included for the study. METHODS AND RESULTS: Participants with short sleep duration (<6 h/day) or long sleep duration (≥10 h/day) were at a significantly increased risk of renal hyperfiltration. The fully adjusted ORs (95% CI) were 2.112 (1.107, 4.031) and 2.071 (1.504, 2.853), respectively (P < 0.05). In addition, those who took naps longer than 1.5 h per day had a higher risk of renal hyperfiltration compared with those without napping (OR 1.400, 95% CI 1.018-1.924). Further joint analysis indicated that participants with long sleep duration (≥10 h/day) had a more than twofold increased risk of RHF regardless of nap status compared with those who slept 8-9 h per day without daytime napping. The association between sleep duration or daytime napping and RHF could not be explained by the influence of sleep quality. Additional subgroup analysis showed long sleep duration (≥9 h/day) and long daytime napping (≥1.5 h) were associated with an increased risk of RHF among individuals with good sleep quality. CONCLUSION: Sleep duration less than 6 h/day or more than 10 h/day and long daytime napping tend to be associated with an increased risk of renal hyperfiltration in middle-aged general population, and this relationship was independent of diabetes, hypertension, obesity, or poor sleep quality.

7.
J Endocr Soc ; 1(8): 1085-1094, 2017 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-29264561

RESUMO

Purpose: To explore the association between bone mineral density (BMD) and ß-cell function. Methods: A cross-sectional study was performed in Fujian, China, from 2011 to 2012. The study included 572 elderly men older than age 60 years and 1558 postmenopausal women aged 45 to 86 years, excluding those with diabetes and insulin resistance. Fasting glucose and insulin concentrations were measured. Pancreatic ß-cell function was estimated by using the homeostasis model assessment (HOMA-ß). Calcaneus BMD was measured by using quantitative ultrasonography. Multiple regression analyses were applied to explore the association. Results: Participants with decreased BMD had lower fasting glucose (P < 0.001 in postmenopausal women; P = 0.007 in elderly men) and greater HOMA-ß (P = 0.001 in postmenopausal women; P = 0.008 in elderly men) than those with normal BMD, whereas no statistical differences in insulin were seen among categories of BMD. After adjustment for all confounders, HOMA-ß was still significantly negatively related to BMD in both groups (all P < 0.001), and remarkable positive relationships were found between BMD and fasting glucose. Furthermore, binary logistic regression presented fully adjusted odds ratios for diabetes in those with osteoporosis vs those with normal BMD: 0.60 [95% confidence interval (CI), 0.38 to 0.94] and 0.66 (95% CI, 0.49 to 0.91) in the original selected population of elderly men (n = 1070) and postmenopausal women (n = 2825), respectively. Conclusions: BMD was independently inversely associated with HOMA-ß and positively associated with fasting glucose in both elderly men and postmenopausal women, suggesting that bone mass may be a predictor of glucose metabolism. Further research is needed to verify the associations and determine the exact mechanism underlying them.

8.
Cell Death Dis ; 8(8): e3008, 2017 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-28837146

RESUMO

The limited efficacy of current treatment methods and increased type 2 diabetes mellitus (T2DM) incidence constitute an incentive for investigating how metabolic homeostasis is maintained, to improve treatment efficacy and identify novel treatment methods. We analyzed a three-generation family of Chinese origin with the common feature of T2DM attacks and fatty pancreas (FP), alongside 19 unrelated patients with FP and 58 cases with T2DM for genetic variations in Enho, serum adropin, and relative Treg amounts. Functional studies with adropin knockout (AdrKO) in C57BL/6J mice were also performed. It showed serum adropin levels were significantly lower in FP and T2DM patients than in healthy subjects; relative Treg amounts were also significantly decreased in FP and T2DM patients, and positively associated with adropin (r=0.7220, P=0.0001). Sequencing revealed that the patients shared a Cys56Trp mutation in Enho. In vivo, adropin-deficiency was associated with increased severity of glucose homeostasis impairment and fat metabolism disorder. AdrKO mice exhibited reduced endothelial nitric oxide synthase (eNOS) phosphorylation (Ser1177), impaired glycosphingolipid biosynthesis, adipocytes infiltrating, and loss of Treg, and developed FP and T2DM. Adropin-deficiency contributed to loss of Treg and the development of FP disease and T2DM.


Assuntos
Proteínas Sanguíneas/deficiência , Diabetes Mellitus Tipo 2/terapia , Dieta Hiperlipídica/efeitos adversos , Obesidade/complicações , Pâncreas/patologia , Peptídeos/deficiência , Animais , Diabetes Mellitus Tipo 2/patologia , Feminino , Homeostase , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Obesidade/patologia
9.
J Diabetes ; 9(7): 707-716, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27613695

RESUMO

BACKGROUND: ß-Cells at different stages have different functions and capacity for proliferation, regenerative and apoptosis. The aim of the present study was to investigate whether there are changes in ß-cell phonotype in the development of diabetes to identify potential ß-cell targets to prevent the progression of diabetes. METHODS: A cross-sectional study was performed on pancreatic tissues obtained from 80 patients classified into three groups: 25 with type 2 diabetes (T2D), 25 with impaired fasting glucose (IFG), and 30 non-diabetics (ND). The ratio of the insulin-positive area to pancreatic area was used as an indirect marker of ß-cell mass. Insulin-positive duct cells and scattered ß-cells were defined as newly generated ß-cells, whereas insulin/neurogenin 3 (Ngn3), insulin/v-maf musculoaponeurotic fibrosarcoma oncogene family, protein A (MafA) and insulin/P16 double-positive cells were defined as immature, mature, and senescent ß-cells, respectively; Ki67 was used as a marker of cell proliferation, and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) was used as a marker of cell apoptosis. Data were analyzed using the Kruskal-Wallis test. RESULTS: There were no significant differences in ß-cell mass, the prevalence of insulin-positive duct cells, scattered ß-cells, or insulin/Ngn3, insulin/MafA, and Insulin/Ki67 double-positive cells among groups. The incidence of insulin/P16 double-positive cells was significantly higher in T2D than ND. ß-Cell apoptosis was significantly higher in T2D and IFG than ND. CONCLUSION: The senescence and apoptosis of ß-cells may be involved in the course of diabetes.


Assuntos
Senescência Celular , Diabetes Mellitus Tipo 2/metabolismo , Intolerância à Glucose/metabolismo , Células Secretoras de Insulina/metabolismo , Adulto , Idoso , Apoptose , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Biomarcadores/metabolismo , Glicemia/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Intolerância à Glucose/sangue , Intolerância à Glucose/diagnóstico , Humanos , Insulina/metabolismo , Antígeno Ki-67/metabolismo , Fatores de Transcrição Maf Maior/metabolismo , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Estudos Retrospectivos
10.
JBMR Plus ; 1(2): 107-115, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30283884

RESUMO

Low bone mineral density (BMD) and microvascular diseases (MVD) share various common risk factors; however, whether MVD is an independent risk factor of vertebral fractures is incompletely understood. The aim of this study is to clarify whether MVD is an independent risk factor of vertebral fractures. In this prospective study, calcaneal BMD and retinal microvascular abnormalities were assessed at baseline from June 2011 to January 2012. A total of 2176 premenopausal women, 2633 postmenopausal women, 2998 men aged <65 years, and 737 men aged ≥65 were included. Then with/without retinal microvascular abnormalities cohorts were followed for an average of 2.93 years to find out the relationship between MVD and vertebral fractures. At the baseline, after full adjustment, retinal microvascular abnormalities were related to risk of low BMD only in men aged ≥65 years (odds ratio [OR] = 2.506; 95% confidence interval [CI] 1.454-4.321; p = 0.001). After follow-up of 2.93 years, retinal microvascular abnormalities were related to risk of vertebral fractures in men aged ≥65 years (OR = 2.475; 95% CI 1.085-5.646; p = 0.031) when adjustment for confounding factors. However, no associations were found between MVD and vertebral fractures in men aged <65 years, premenopausal women, and postmenopausal women. When stratified by diabetes, in the without-diabetes group, the men with retinal microvascular abnormalities had higher risk for vertebral fractures than without retinopathy (OR = 2.194; 95% CI 1.097-4.389; p = 0.026); however, the difference was not found in women. In the diabetes group, there were no significant differences of risk for vertebral fractures between those with retinal microvascular abnormalities and those without both in men and women. Stratified by hypertension, the men with retinopathy had higher risk for vertebral fractures than those without among the hypertension group (OR = 2.034; 95% CI 1.163-3.559; p = 0.013), but a difference was not found among women. In the without-hypertension group, no relation was found between MVD and fracture both in men and women. In conclusion, MVD is an independent risk factor of vertebral fractures in old men. © 2017 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

11.
Neuroendocrinology ; 103(3-4): 230-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26088945

RESUMO

INTRODUCTION: Many missense variants in G protein-coupled receptors (GPCRs) involved in the neuroendocrine regulation of reproduction have been identified by phenotype-driven or large-scale exome sequencing. Computational functional prediction analysis is commonly performed to evaluate their impact on receptor function. METHODS: To assess the performance and outcome of functional prediction analyses for these GPCRs, we performed a statistical analysis of the prediction performance of SIFT and PolyPhen-2 for variants with documented biological function as well as variants retrieved from Ensembl. We obtained missense variants with documented biological function testing from patients with reproductive disorders from a comprehensive literature search. Missense variants from individuals with known reproductive disorders were retrieved from the Human Gene Mutation Database. Missense variants from the general population were retrieved from the Ensembl genome database. RESULTS: The accuracies of SIFT and PolyPhen-2 were 83 and 85%, respectively. The performance of both prediction tools was greater in predicting loss-of-function variants (SIFT: 92%; PolyPhen-2: 95%) than in predicting variants that did not affect function (SIFT: 54%; PolyPhen-2: 57%). Concordance between SIFT and PolyPhen-2 did not improve accuracy. Surprisingly, approximately half of the variants retrieved from Ensembl were predicted as loss-of-function variants by SIFT (47%) and PolyPhen-2 (54%). CONCLUSION: Our findings provide new guidance for interpreting the results and limitations of computational functional prediction analyses for GPCRs and will help to determine which variants require biological function testing. In addition, our findings raise important questions regarding the link between genotype and phenotype in the general population.


Assuntos
Biologia Computacional , Mutação de Sentido Incorreto/genética , Sistemas Neurossecretores/fisiopatologia , Receptores Acoplados a Proteínas-G/genética , Reprodução/genética , Feminino , Humanos , Infertilidade Masculina/genética , Masculino , Técnicas de Diagnóstico Molecular , Fenótipo , Polimorfismo de Nucleotídeo Único , Valor Preditivo dos Testes , PubMed/estatística & dados numéricos , Receptores de Kisspeptina-1 , Receptores LHRH/genética , Receptores da Neurocinina-3/genética , Receptores de Peptídeos/genética , Software
13.
J Clin Endocrinol Metab ; 100(6): 2420-4, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25668199

RESUMO

CONTEXT: Primary hyperparathyroidism (PHPT) is reported to be associated with an increased frequency of hypertension, however, information in this regard is sparse in relation to normocalcemic primary hyperparathyroidism (NPHPT). OBJECTIVE: The aim of this study was to determine the association between NPHPT and blood pressure. DESIGN, SETTING, AND PATIENTS: We retrospectively enrolled 940 patients who visited the Fujian Provincial Hospital between September 2010 and December 2013 with a measured serum parathyroid hormone (PTH) and calcium level. Among them, 11 patients were diagnosed with NPHPT, while 296 cases with normal PTH and albumin-adjusted serum calcium. MAIN OUTCOMES MEASURES: Systolic blood pressure (SBP), diastolic blood pressure (DBP), intact serum PTH, and serum calcium were recorded. RESULTS: There were no significant differences between subjects identified with NPHPT and those with normal PTH in terms of age, sex, body mass index, serum calcium, 25-Hydroxyvitamin D, serum creatinine, fasting plasma glucose, triglycerides, total cholesterol, high density lipoprotein, and low density lipoprotein. The subjects with a diagnosis of NPHPT had higher levels of SBP (141.9 ± 20.2 vs 131.2 ± 16.5, P = .041) and DBP (85.2 ± 12.4 vs 76.8 ± 10.3, P = .026) than the subjects in the cohort with normal PTH. After adjustment for all potential confounders, risks (odds ratios and 95% confidence interval) of SBP and DBP in NPHPT patients were 1.035 (1.000, 1.071) and 1.063 (1.004, 1.125), respectively (P < .05). CONCLUSIONS: The NPHPT had higher risk of high blood pressure than subjects with normal PTH. It is worth considering the necessity of more aggressive therapeutic intervention aimed to normalize PTH even if patients with NPHPT continue to be normocalcemic.


Assuntos
Pressão Sanguínea , Cálcio/sangue , Hiperparatireoidismo Primário/sangue , Hiperparatireoidismo Primário/diagnóstico , Adulto , Idoso , Pressão Sanguínea/fisiologia , China/epidemiologia , Feminino , Humanos , Hiperparatireoidismo Primário/epidemiologia , Hiperparatireoidismo Primário/fisiopatologia , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Prognóstico , Valores de Referência , Estudos Retrospectivos
14.
Endocrine ; 48(1): 187-94, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24853883

RESUMO

Early postoperative hyperglycemia in non-diabetic patients is an important risk factor affecting postoperative complications and mortality. This study aimed at investigating the effects of early postoperative hyperglycemia on postoperative complications, hospital costs, and length of hospital stay in non-diabetic patients with gastrointestinal malignancies; data of 1,015 non-diabetic patients with gastrointestinal malignancies, who underwent surgical intervention between January 2010 and January 2012, were retrospectively evaluated. Records on fasting plasma glucose (FPG), liver function, and kidney function were collected before and one day after surgery. Correlation of early postoperative FPG levels with postoperative complications, hospital costs, and length of hospital stay was further assessed in non-diabetic patients with gastrointestinal malignancies. One day after surgery, FPG results were significantly increased compared to preoperative values. FPG levels greater than or equal to 9.13 mmol/L (or 164.34 mg/dL) were associated with significant increases in the incidence of postoperative complications, length of hospital stay, and hospital costs. An association is shown between FPG and postoperative hyperglycemia in non-diabetic patients undergoing surgery for gastrointestinal malignancies. Significant increases in postoperative complications among these patients suggest that measurement of early postoperative FPG levels is critical to identify patients with postoperative hyperglycemia.


Assuntos
Glicemia/metabolismo , Neoplasias Gastrointestinais/economia , Neoplasias Gastrointestinais/cirurgia , Custos Hospitalares/estatística & dados numéricos , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Fatores Etários , Idoso , Feminino , Neoplasias Gastrointestinais/sangue , Humanos , Hiperglicemia/sangue , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/economia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
15.
Cell Immunol ; 292(1-2): 53-6, 2014 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25277607

RESUMO

Osteoclasts are bone-resorbing multinuclear cells derived from hematopoietic stem cells which are specialised to carry out lacunar bone resorption. The immunophenotype of giant cell-containing bone lesions in a wide range of osteoclast-like giant cells was similarly assessed. Both multinucleated macrophages and osteoclasts were found to express CD68. Multinucleated macrophages, but not osteoclasts, expressed GrB and Ki67. CD13+/CD14+/CD68+/GrB-/Ki67-/CD56- all giant-cell lesions noted in giant cells of bone. Giant cells have an osteoclast phenotype in most giant cell-rich lesions of bone, which do not express the macrophage-associated antigens GrB and Ki67. Our results indicate that they are formed from osteoclast precursors of mononuclear phagocyte.


Assuntos
Macrófagos/imunologia , Osteoclastos/imunologia , Antígenos/imunologia , Osso e Ossos/imunologia , Células Gigantes/imunologia , Humanos , Imuno-Histoquímica , Imunofenotipagem , Fagocitose
16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 30(4): 306-10, 313, 2014 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-25330663

RESUMO

OBJECTIVE: To investigate the effects of advanced glycosylation end products (AGEs) modified bovine serum albumin (AGE-BSA) on the expression of reactive oxygen species (ROS) and monocyte chemoattractant protein-1 (MCP-1) in human renal mesangial cells (HRMCs). METHODS: HRMCs were cultured in vitro with medium containing different doses of AGE-BSA or BSA (50,100, 200, 400 mg/L) for 48 hours, or with AGE-BSA (200 mg/L) for different times (12, 24, 48, 72 h). Immunocytochemistry assay was used to estimate the protein level of RAGE. The ROS in cells were measured by flow cytometry and the mRNA expression of MCP-1 were analyzed by semi-quantiative reverse transcription-polymerase chain reaction (RT-PCR) after treatment with AGE-BSA or BSA. RESULTS: The protein level of RAGE was upregulated in the HRMCs with AGE-BSA. The expression of ROS and MCP-1 significantly enhanced by incubation of AGE-BSA in a time- and dose-dependent manner. The effects of AGE-BSA-induced up-regulation of ROS and MCP-1 level was significantly blocked by neutralizing antibodies to RAGE, while the expression of ROS and MCP-1 stood nearly unchanged after cultured with huamn IgG. CONCLUSION: The expression of ROS and MCP-1 in HRMCs is induced by AGE-BSA through RAGE, which may have potential effects in the pathgenic mechanism of diabetic nephropathy.


Assuntos
Quimiocina CCL2/metabolismo , Produtos Finais de Glicação Avançada/farmacologia , Células Mesangiais/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Soroalbumina Bovina/farmacologia , Células Cultivadas , Humanos , Células Mesangiais/efeitos dos fármacos , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismo
17.
Endocrinology ; 155(11): 4433-46, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25147978

RESUMO

Hypothalamic GnRH is the master regulator of the neuroendocrine reproductive axis, and its secretion is regulated by many factors. Among these is kisspeptin (Kp), a potent trigger of GnRH secretion. Kp signals via the Kp receptor (KISS1R), a Gαq/11-coupled 7-transmembrane-spanning receptor. Until this study, it was understood that KISS1R mediates GnRH secretion via the Gαq/11-coupled pathway in an ERK1/2-dependent manner. We recently demonstrated that KISS1R also signals independently of Gαq/11 via ß-arrestin and that this pathway also mediates ERK1/2 activation. Because GnRH secretion is ERK1/2-dependent, we hypothesized that KISS1R regulates GnRH secretion via both the Gαq/11- and ß-arrestin-coupled pathways. To test this hypothesis, we measured LH secretion, a surrogate marker of GnRH secretion, in mice lacking either ß-arrestin-1 or ß-arrestin-2. Results revealed that Kp-dependent LH secretion was significantly diminished relative to wild-type mice (P < .001), thus supporting that ß-arrestin mediates Kp-induced GnRH secretion. Based on this, we hypothesized that Gαq/11-uncoupled KISS1R mutants, like L148S, will display Gαq/11-independent signaling. To test this hypothesis, L148S was expressed in HEK 293 cells. and results confirmed that, although strongly uncoupled from Gαq/11, L148S retained the ability to trigger significant Kp-dependent ERK1/2 phosphorylation (P < .05). Furthermore, using mouse embryonic fibroblasts lacking ß-arrestin-1 and -2, we demonstrated that L148S-mediated ERK1/2 phosphorylation is ß-arrestin-dependent. Overall, we conclude that KISS1R signals via Gαq/11 and ß-arrestin to regulate GnRH secretion. This novel and important finding could explain why patients bearing some types of Gαq/11-uncoupled KISS1R mutants display partial gonadotropic deficiency and even a reversal of the condition, idiopathic hypogonadotropic hypogonadism.


Assuntos
Arrestinas/fisiologia , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/fisiologia , Hormônio Luteinizante/metabolismo , Receptores Acoplados a Proteínas-G/fisiologia , Animais , Arrestinas/genética , Busserrelina/farmacologia , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de Kisspeptina-1 , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , beta-Arrestina 1 , beta-Arrestina 2 , beta-Arrestinas
18.
Fertil Steril ; 102(3): 838-846.e2, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25016926

RESUMO

OBJECTIVE: To analyze the GNRHR in patients with normosmic isolated hypogonadotropic hypogonadism (IHH) and constitutional delay of growth and puberty (CDGP). DESIGN: Molecular analysis and in vitro experiments correlated with phenotype. SETTING: Academic medical center. PATIENT(S): A total of 110 individuals with normosmic IHH (74 male patients) and 50 with CDGP. INTERVENTION(S): GNRHR coding region was amplified and sequenced. MAIN OUTCOME MEASURE(S): Novel variants were submitted to in vitro analysis. Frequency of mutations and genotype-phenotype correlation were analyzed. Microsatellite markers flanking GNRHR were examined in patients carrying the same mutation to investigate a possible founder effect. RESULT(S): Eleven IHH patients (10%) carried biallelic GNRHR mutations. In vitro analysis of novel variants (p.Y283H and p.V134G) demonstrated complete inactivation. The founder effect study revealed that Brazilian patients carrying the p.R139H mutation shared the same haplotype. Phenotypic spectrum in patients with GNRHR mutations varied from complete GnRH deficiency to partial and reversible IHH, with a relatively good genotype-phenotype correlation. One boy with CDGP was heterozygous for the p.Q106R variant, which was not considered to be pathogenic. CONCLUSION(S): GNRHR mutations are a frequent cause of congenital normosmic IHH and should be the first candidate gene for genetic screening in this condition, especially in autosomal recessive familial cases. The founder effect study suggested that the p.R139H mutation arises from a common ancestor in the Brazilian population. Finally, mutations in GNRHR do not appear to be involved in the pathogenesis of CDGP.


Assuntos
Transtornos do Crescimento/genética , Mutação , Puberdade Tardia/genética , Receptores LHRH/genética , Adolescente , Animais , Células COS , Cercopithecus aethiops , Análise Mutacional de DNA , Feminino , Frequência do Gene , Estudos de Associação Genética , Transtornos do Crescimento/complicações , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Puberdade Tardia/complicações
19.
J Clin Endocrinol Metab ; 99(8): 2869-77, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24848706

RESUMO

CONTEXT: Associations between sleep, daytime nap duration, and osteoporosis remain uncertain, and far less is even known about the influence of sex, menopause, and sleep quality on them. OBJECTIVE: The objective of the study was to test the associations between sleep, daytime nap duration, and osteoporosis and whether they vary by sex, menopause, and sleep quality. DESIGN, SETTING, AND PATIENTS: This cross-sectional study was based on two communities in China. A total of 8688 participants (3950 males and 4738 females) aged 40 years or older were enrolled in the study. MAIN OUTCOMES MEASURES: Self-reported sleep duration, daytime nap duration, sleep quality, and calcaneus bone mineral density were recorded. RESULTS: Sleep duration of 8-9 h/d and nap duration of 0 min/d were regarded as reference values. In postmenopausal women, risks (odds ratio and 95% confidence interval) of osteoporosis for sleep durations of 7-8 h/d, 9-10 h/d, and 10 h/d or longer were 1.531 (1.106, 2.121), 1.360 (1.035, 1.787), and 1.569 (1.146, 2.149), respectively (P < .05), and risks of osteoporosis for daytime nap durations of 30-60 min/d and longer than 60 min/d were 1.553 (1.212-1.989) and 1.645 (1.250-2.165), respectively (P < .05). However, a significant difference was not consistently observed in men or premenopausal women, regardless of sleep or daytime nap duration. As for sleep quality, positive results were seen most remarkably in postmenopausal females with good sleep. CONCLUSIONS: Sleep durations of 7-8 h/d, 9-10 h/d, and 10 h/d or longer, as well as longer daytime napping times, tend to present higher risks of having osteoporosis, and this tendency is most obvious in postmenopausal women reporting good-quality sleep.


Assuntos
Menopausa/fisiologia , Osteoporose/epidemiologia , Sono/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , China/epidemiologia , Ritmo Circadiano , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/etiologia , Osteoporose/fisiopatologia , Fatores Sexuais , Fatores de Tempo
20.
Endocr Pract ; 20(8): 775-84, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24518175

RESUMO

OBJECTIVE: To investigate the association between alanine aminotransferase (ALT) levels and risk of osteopenia in middle-aged and elderly Chinese with ALT within the normal range. METHODS: This was a cross-sectional study. A total of 4,890 men and women (pre- and postmenopausal) aged 40 years or older were randomly recruited from Fujian, China. Each participant was required to complete a questionnaire and then undergo anthropometric, biochemical, and bone mineral density measurements. RESULTS: The odds ratio of osteopenia decreased significantly with increasing ALT level at baseline. The three groups (men, pre- and postmenopausal women) were divided by ALT quartiles. In multiple logistic regression models using the first quartile as the reference, after adjusting for corresponding confounding factors, the odds ratios of osteopenia across the other ALT quartiles were 0.576 (95% confidence interval [CI], 0.390 to 0.851), 0.654 (95% CI, 0.460 to 0.930), and 0.629 (95% CI, 0.427 to 0.926) for premenopausal women, and 0.949 (95% CI, 0.699 to 1.289), 0.733 (95% CI, 0.540 to 0.995), and 0.692 (95% CI, 0.508 to 0.943) for postmenopausal women (not significant for quartile 2). However, no significantly different results were found in men. Multiple linear regression models showed that serum ALT concentrations were positively associated with the homeostasis model assessment of insulin resistance. CONCLUSION: Our study of middle-aged and elderly Chinese men and women demonstrates that the prevalence of osteopenia is inversely associated with ALT level when ALT is within the normal range.


Assuntos
Alanina Transaminase/sangue , Doenças Ósseas Metabólicas/etiologia , Idoso , Doenças Ósseas Metabólicas/enzimologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade
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