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1.
Bioorg Med Chem ; 68: 116877, 2022 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-35714534

RESUMO

The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) plays a central role in metabolic processes. PPARγ full agonists have side effects, arguing for the discovery of PPARγ partial agonists with novel chemotypes. We report the unique binding mode of the known allosteric retinoic acid receptor-related orphan receptor gamma t (RORγt) ligand MRL-871 to PPARγ. MRL-871 binds between PPARγ helices 3, 5, 7 and 11, where it stabilizes the beta-sheet region with a hydrogen bond between its carboxylic acid moiety and PPARγ Ser370. Its unique binding mode differs from that of the benzoyl 2-methyl indoles which are well-studied, structurally similar, PPARγ ligands. MRL-871's high affinity for PPARγ induces only limited coactivator stabilization, highlighting its attractive partial agonistic characteristics. Affinity comparison of MRL-871 and related compounds towards both RORγt and PPARγ indicates the possibility for tuning of selectivity, bringing MRL-871 forward as an interesting starting point for novel PPARγ ligands.


Assuntos
Indazóis , PPAR gama , Indazóis/farmacologia , Ligantes , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , PPAR gama/agonistas , Estrutura Secundária de Proteína
2.
Nutr Metab Cardiovasc Dis ; 28(11): 1106-1113, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30287123

RESUMO

BACKGROUNDS AND AIMS: We aimed to reveal the association between subclinical inflammation and metabolic risk factors and to determine the difference in the association between normal-weight and obese Korean individuals. METHODS AND RESULTS: Data collected from the Korean National Health and Nutrition Examination Survey (KNHANES) 2015, conducted from January to December 2015, were analyzed. Overall, 4620 subjects were examined and divided into two subgroups: 2987 and 1633 subjects in the normal-weight and obese groups, respectively. The prevalence of obesity in the study population was 34.5% (n = 1633). After multivariate adjustment, impaired fasting glucose (IFG) (odds ratio [OR] 1.22, 95% confidence interval [CI] 1.05-1.42, P = 0.010), high triglyceride (TG) levels (OR 1.29, 95% CI 1.13-1.47, P < 0.001), and low high-density lipoprotein-cholesterol (HDL-C) levels (OR 1.47, 95% CI 1.31-1.64, P < 0.001) were significantly associated with increased high-sensitivity C-reactive protein (hs-CRP) levels in the normal-weight group but not in the obesity group. CONCLUSION: Subclinical inflammation was associated with IFG, high TG levels, and low HDL-C levels in normal-weight Korean individuals. Prospective and biochemical research is necessary to clarify the role of subclinical systemic inflammation in individuals with normal body weight and its impact on insulin resistance and abnormal lipid metabolism, which promote the incidence of metabolic syndrome and cardiovascular disease.


Assuntos
Dislipidemias/epidemiologia , Transtornos do Metabolismo de Glucose/epidemiologia , Inflamação/epidemiologia , Doenças Assintomáticas , Biomarcadores/sangue , Glicemia/metabolismo , Proteína C-Reativa/análise , HDL-Colesterol/sangue , Estudos Transversais , Dislipidemias/sangue , Dislipidemias/diagnóstico , Feminino , Transtornos do Metabolismo de Glucose/sangue , Transtornos do Metabolismo de Glucose/diagnóstico , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Mediadores da Inflamação/sangue , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/diagnóstico , Obesidade/epidemiologia , Prevalência , República da Coreia/epidemiologia , Fatores de Risco , Triglicerídeos/sangue
3.
Int J Cosmet Sci ; 39(2): 149-155, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27503111

RESUMO

OBJECTIVE: Coacervates are inevitably formed on scalp on using hair washing products. Our goal was to analyse the coacervates in detail to identify the part responsible for scalp stimulation. METHODS: Shampoo that increases coacervate formation was applied to in vitro skin and was washed. The residue was then analysed using Fourier transform infrared spectroscopy-focal plane array (FTIR-FPA) and X-ray photoelectron microscopy (XPS). And HaCaT cells were used for irritant test of coacervate. RESULTS: Through this research, it was confirmed that the coacervate was a macromolecule structurally similar to a cationic polymer and contains an anionic surfactant. Its anionic surfactant was structurally semi-stable so that it released onto scalp when it absorbs moisture. CONCLUSION: Coacervate releases sulphate bonding into the matrix when it is exposed to water. Thus, the scalp stimulation would be expected.


Assuntos
Preparações para Cabelo/química , Irritantes/farmacologia , Microscopia/métodos , Couro Cabeludo/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Linhagem Celular , Humanos
4.
Int J Dent Hyg ; 14(2): 151-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26074207

RESUMO

OBJECTIVES: The aim of this study was to determine the associations between the number of present teeth (NT) and socio-economic, demographic and oral health behavioural factors among Korean adults aged 55-84 years. METHODS: The total subjects comprised 3767 individuals who were examined and who answered the questions on socio-economic status and oral health behaviour from the fourth Korean National Health and Nutrition Examination Survey conducted from 2007 to 2009. The dependent variable was NT, with binary status divided by the median. Socio-economic and demographic factors included gender, educational level, parent's educational levels, region of residence, household income, type of health insurance and mother's economic activity. Oral health behaviours were as follows: daily toothbrushing frequency, smoking status, recent dental visit and illegal dental treatment. Multivariate logistic regression models were applied to explain the associations between NT and other variables. RESULTS: In a model adjusted by socio-economic, demographic and oral health behavioural variables, subjects who lived in urban areas were more likely to have larger NT compared to those in suburban areas (OR: 1.22, P = 0.025). Males were more likely to have larger NT (OR: 1.90, P < 0.001), and daily toothbrushing frequency was associated with NT (OR = 1.25, P = 0.023). Non-smokers (OR: 2.44, P < 0.001) and past smokers (OR: 1.70, P < 0.001) were more likely to have lager NT compared to current smokers. Subjects without illegal dental treatments were more likely to have lager NT compared to those with illegal dental treatments (OR = 2.21, P < 0.001). CONCLUSIONS: Interventions aiming to preserve present teeth in elderly adults should consider socio-economic, demographic and oral health behavioural factors.


Assuntos
Assistência Odontológica , Saúde Bucal , Perda de Dente , Idoso , Idoso de 80 Anos ou mais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores Socioeconômicos , Escovação Dentária
5.
Dis Esophagus ; 27(8): 798-801, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24152165

RESUMO

Two recent genome-wide association studies have identified that the rs2274223 single-nucleotide polymorphism inphospholipase C epsilon 1 and the single-nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high-resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.08-3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR=0.71, 95% CI=0.52-0.97) and no significant association in the older group (OR=1.19, 95% CI=0.87-1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Proteínas de Membrana Transportadoras/genética , Fosfoinositídeo Fosfolipase C/genética , Adulto , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Carcinoma de Células Escamosas do Esôfago , Feminino , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo de Nucleotídeo Único , Reprodutibilidade dos Testes , República da Coreia , Risco
6.
J Nutr Health Aging ; 26(5): 515-520, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35587765

RESUMO

OBJECTIVES: Muscle health plays an important role in maintaining function and independence in the elderly, and some nutrients provide protection against the age-related decline of muscle strength and function. Minerals are important nutrients that may contribute to the prevention and treatment of sarcopenia, but they have not been well-studied. This study investigated whether hair mineral concentrations differ between subjects with low muscle mass (LMM) and subjects with normal muscle mass. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A total of 232 adults ≥ 20 years of age who visited the Health Promotion Center of the University Hospital in Gyeonggi-do, Republic of Korea. MEASUREMENTS: The data from 232 subjects were analyzed and divided into LMM and normal groups based on the appendicular skeletal muscle mass index (ASMI) (LMM was defined as ASMI < 7.0 kg/m2 in men and < 5.7 kg/m2 in women). Skeletal muscle mass was estimated using a multi-frequency bioelectrical impedance analysis (BIA) device with a body composition analyzer. RESULTS: Overall mean age of participants was 50.4±11.6 years (29.7% women). Subjects with LMM showed significantly lower triglyceride levels, greater high-density lipoprotein cholesterol levels, and lower body mass index (BMI), compared with subjects who had normal muscle mass. No significant differences in hair mineral concentrations were observed between subjects with LMM and subjects with normal muscle mass, with the exception of copper. Hair copper concentrations were significantly greater in subjects with LMM than in subjects with normal muscle mass after adjustment for covariates and factors (65.7±14.2 vs 33.1±4.3 µg/g, P = 0.035). CONCLUSION: These results suggest that hair mineral status may play a role in the development of LMM. Therefore, further studies with larger numbers of subjects are required to identify the effects of mineral imbalances, their relationships with sarcopenia, and the differences between subjects with LMM and subjects with normal muscle mass.


Assuntos
Sarcopenia , Idoso , Cobre , Estudos Transversais , Feminino , Cabelo , Humanos , Masculino , Minerais , Músculo Esquelético/fisiologia , República da Coreia
7.
J Viral Hepat ; 18(10): e447-52, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21914062

RESUMO

Widespread use of lamivudine in antiretroviral therapy may lead to hepatitis B virus resistance in HIV-HBV coinfected patients from endemic settings where tenofovir is not readily available. We evaluated 389 Kenyan HIV-infected adults before and for 18 months after starting highly active antiretroviral therapy with stavudine, lamivudine and nevirapine. Twenty-seven (6.9%) were HBsAg positive and anti-HBs negative, 24 were HBeAg negative, and 18 had HBV DNA levels ≤ 10,000 IU/mL. Sustained HBV suppression to <100 IU/mL occurred in 89% of 19 evaluable patients. Resistance occurred in only two subjects, both with high baseline HBV DNA levels. Lamivudine resistance can emerge in the setting of incomplete HBV suppression but was infrequently observed among HIV-HBV coinfected patients with low baseline HBV DNA levels.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Farmacorresistência Viral , Infecções por HIV/tratamento farmacológico , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/tratamento farmacológico , Lamivudina/administração & dosagem , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , DNA Viral/sangue , Feminino , Infecções por HIV/complicações , Hepatite B/complicações , Hepatite B/virologia , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/isolamento & purificação , Humanos , Quênia , Masculino , Nevirapina/administração & dosagem , Estavudina/administração & dosagem , Resultado do Tratamento , Carga Viral
8.
Osteoporos Int ; 22(7): 2165-74, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20976592

RESUMO

SUMMARY: We studied femoral geometry in relation to age and ethnicity in a cross-sectional study. Age-associated cortical thinning showed the most pronounced effect, and Koreans studied here had thicker cortices and lower buckling ratios than those reported for other races. Cortical thickness may thus be a major determinant of hip fracture risk. INTRODUCTION: The rate of hip fracture varies by age and ethnicity. The geometric properties of the femur influence femoral strength and fragility, but differences in femoral geometry according to age and ethnicity are poorly understood. To explain the high prevalence of hip fractures in the elderly and the relatively low hip fracture rate in Asian populations, we studied age-related changes and ethnic differences in femoral geometry. METHODS: We recruited 214 peri- or postmenopausal women aged 46 to 85 years (mean age, 60.6 years). Their proximal femoral bone mineral densities (BMD) were measured by quantitative computed tomography and further analyzed geometric properties. RESULTS: We observed large declines in trabecular volumetric bone mineral density associated with aging (33.03% less than the reference value in the oldest group, respectively). Cortical thickness decreased remarkably with age as well, and only 53.94% of the baseline value remained in the oldest group. As a result, the cortical buckling ratio increased geometrically and reached 239.14% of the reference value in the oldest group. In comparisons with other ethnic groups, Korean subjects had thicker cortices than their American, European, and African counterparts. CONCLUSIONS: In this cross-sectional study, cortical thickness showed a pronounced age-associated decrease, and the cortical buckling ratio showed a strong age-associated increase. This may in part explain the higher rates of hip fractures in the elderly. When compared with other races, Asians had thicker cortical bone and lower buckling ratios, which may partially explain the lower prevalence of hip fractures in Asians.


Assuntos
Densidade Óssea/fisiologia , Colo do Fêmur/diagnóstico por imagem , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Estudos Transversais , Feminino , Colo do Fêmur/anatomia & histologia , Humanos , Coreia (Geográfico)/etnologia , Pessoa de Meia-Idade , Pós-Menopausa , Fraturas da Coluna Vertebral/diagnóstico por imagem , Tomografia Computadorizada por Raios X
9.
Dis Esophagus ; 24(8): 596-600, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21595775

RESUMO

The aim of this study was to assess whether p53 codon 72 polymorphism is associated with an increased risk of esophageal cancer (EC) in South Korea. We conducted a case-control study including 340 patients with EC, and 1700 controls. P53 codon 72 polymorphism was determined by real-time polymerase chain reaction. The frequencies of p53 codon 72 polymorphisms (Arg/Arg, Arg/Pro, and Pro/Pro) in EC were 39.4%, 45.6%, and 15.0%, respectively; frequencies in the controls were 43.2%, 45.6%, and 11.2%, respectively. Compared with the Arg/Arg genotype, the OR of the Arg/Pro genotype was 1.09 (95% CI = 0.85-1.41) and that of the Pro/Pro genotype was 1.47 (95% CI = 1.02-2.11) for EC overall. When adjusted by age, gender, and smoking status, the OR of the Arg/Pro genotype was 1.24 (95% CI = 0.92-1.67) and that of the Pro/Pro genotype was 1.77 (95% CI = 1.15-2.74) for EC overall. In never-smokers and ever-smokers, the OR of the Arg/Pro genotype was 0.59 (95% CI = 0.37-0.95) and 1.39 (95% CI = 1.00-1.91), respectively, and there was a significant difference in the homogeneity test (P= 0.011). We observed that the p53 codon 72 polymorphism was associated with an increased risk of EC in this Korean case-control study, and smoking status modified the association between the p53 codon 72 polymorphism and the risk of EC.


Assuntos
Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Genes p53 , Polimorfismo Genético , Fumar , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase em Tempo Real , República da Coreia/epidemiologia , Fatores de Risco
10.
medRxiv ; 2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34909782

RESUMO

OBJECTIVES: To define the incidence of clinically-detected COVID-19 in people with HIV (PWH) in the US and evaluate how racial and ethnic disparities, comorbidities, and HIV-related factors contribute to risk of COVID-19. DESIGN: Observational study within the CFAR Network of Integrated Clinical Systems cohort in 7 cities during 2020. METHODS: We calculated cumulative incidence rates of COVID-19 diagnosis among PWH in routine care by key characteristics including race/ethnicity, current and lowest CD4 count, and geographic area. We evaluated risk factors for COVID-19 among PWH using relative risk regression models adjusted with disease risk scores. RESULTS: Among 16,056 PWH in care, of whom 44.5% were Black, 12.5% were Hispanic, with a median age of 52 years (IQR 40-59), 18% had a current CD4 count < 350, including 7% < 200; 95.5% were on antiretroviral therapy, and 85.6% were virologically suppressed. Overall in 2020, 649 PWH were diagnosed with COVID-19 for a rate of 4.94 cases per 100 person-years. The cumulative incidence of COVID-19 was 2.4-fold and 1.7-fold higher in Hispanic and Black PWH respectively, than non-Hispanic White PWH. In adjusted analyses, factors associated with COVID-19 included female sex, Hispanic or Black identity, lowest historical CD4 count <350 (proxy for CD4 nadir), current low CD4/CD8 ratio, diabetes, and obesity. CONCLUSIONS: Our results suggest that the presence of structural racial inequities above and beyond medical comorbidities increased the risk of COVID-19 among PWHPWH with immune exhaustion as evidenced by lowest historical CD4 or current low CD4:CD8 ratio had greater risk of COVID-19.

11.
Gene Ther ; 17(8): 1052-61, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20485381

RESUMO

Cell-permeable peptides (CPPs) promote the transduction of nonpermissive cells by recombinant adenovirus (rAd) to improve the therapeutic efficacy of rAd. In this study, branched oligomerization of CPPs significantly enhanced the transduction of human mesenchymal stem cells (MSCs) by rAd in a CPP type-independent manner. In particular, tetrameric CPPs increased transduction efficiency at 3000-5000-fold lower concentrations than did monomeric CPPs. Although branched oligomerization of CPPs also increases cytotoxicity, optimal concentrations of tetrameric CPPs required for maximum transduction are at least 300-1000-fold lower than those causing 50% cytotoxicity. Furthermore, although only approximately 60% of MSCs were maximally transduced at 500 muM of monomeric CPPs, >95% of MSCs were transduced with 0.1 muM of tetrameric CPPs. Tetrameric CPPs also significantly increased the formation and net surface charge of CPP/rAd complexes, as well as the binding of rAd to cell membranes at a greater degree than did monomeric CPPs, followed by rapid internalization into MSCs. In a critical-size calvarial defect model, the inclusion of tetrameric CPPs in ex vivo transduction of rAd expressing bone morphogenetic protein 2 into MSCs promoted highly mineralized bone formation. In addition, MSCs that were transduced with rAd expressing brain-derived neurotrophic factor in the presence of tetrameric CPPs improved functional recovery in a spinal cord injury model. These results demonstrated the potential for tetrameric CPPs to provide an innovative tool for MSC-based gene therapy and for in vitro gene delivery to MSCs.


Assuntos
Adenoviridae/genética , Peptídeos Penetradores de Células/química , Terapia Genética/métodos , Células-Tronco Mesenquimais/metabolismo , Transdução Genética/métodos , Animais , Doenças Ósseas/genética , Doenças Ósseas/terapia , Proteína Morfogenética Óssea 2/genética , Técnicas de Transferência de Genes , Vetores Genéticos , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Osteogênese/genética , Ratos , Ratos Sprague-Dawley , Crânio/crescimento & desenvolvimento
12.
Int J STD AIDS ; 20(9): 595-600, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19710329

RESUMO

Immunization with hepatitis B (HBV) vaccine is recommended for all HIV-infected individuals without immunity to HBV. This patient population, however, has relatively poor HBV vaccine responses. Factors associated with this impaired HBV vaccine response in HIV-infected individuals may include older age, uncontrolled HIV replication, and low nadir CD4 cell count. Postvaccination testing for HBV surface antibody is recommended and vaccine non-responders should undergo repeat immunization with a full series. The benefit of double dosage, the appropriate strategy for HIV-infected patients with isolated HBV core antibody and the timing and number of vaccinations in persons with advanced immunosuppression on highly active antiretroviral therapy remain controversial areas.


Assuntos
Infecções por HIV/imunologia , Vacinas contra Hepatite B/imunologia , Vacinação , Adulto , Contagem de Linfócito CD4 , Humanos , Esquemas de Imunização , Guias de Prática Clínica como Assunto , Fatores de Risco , Fatores de Tempo
14.
Neuroscience ; 133(2): 507-18, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-15878646

RESUMO

In a previous study, we reported that the distribution of inhibitory input, in contrast to excitatory input, decreased somatofugally along dendrites of cat jaw-closing alpha-motoneurons [J Comp Neurol 414 (1999) 454]. The present study examined the distribution of GABA, glycine, and glutamate immunopositive boutons covering horseradish peroxidase-labeled cat jaw-opening motoneurons. The motoneurons were divided into four compartments: the soma, and primary, intermediate, and distal dendrites. Ninety-seven percent of the total number of studied boutons had immunoreactivity for at least one of the three amino acids. The proportion of boutons immunoreactive for GABA and/or glycine was lower than the proportion of boutons immunoreactive for glutamate. Boutons immunoreactive to glycine alone were more numerous than boutons double-labeled for GABA and glycine, which, in turn, occurred more frequently than boutons immunoreactive to GABA alone. The percentage synaptic covering (proportion of membrane covered by synaptic boutons) of the putatively excitatory (glutamate containing) and putatively inhibitory (GABA and/or glycine containing) boutons decreased somatofugally along the dendrites. Such systematic variations were not seen in the packing density (number of boutons per 100 microm(2)); the packing density showed a distinct drop between the soma and primary dendrites but did not differ significantly among the three dendritic compartments. Overall, the packing density was slightly higher for the putatively excitatory boutons than for the inhibitory ones. When taken together with previous analyses of jaw-closing alpha-motoneurons the present data on jaw-opening alpha-motoneurons indicate that the two types of neuron differ in regard to the nature of synaptic integration in the dendritic tree.


Assuntos
Arcada Osseodentária/fisiologia , Neurônios Motores/fisiologia , Inibição Neural/fisiologia , Sinapses/classificação , Sinapses/fisiologia , Sistema X-AG de Transporte de Aminoácidos/metabolismo , Animais , Gatos , Dendritos/ultraestrutura , Glicina/metabolismo , Imuno-Histoquímica/métodos , Arcada Osseodentária/inervação , Microscopia Imunoeletrônica/métodos , Neurônios Motores/ultraestrutura , Terminações Pré-Sinápticas/ultraestrutura , Sinapses/ultraestrutura , Ácido gama-Aminobutírico/metabolismo
15.
Aliment Pharmacol Ther ; 21(9): 1127-33, 2005 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-15854175

RESUMO

BACKGROUND: Studies suggest obstructive sleep apnea syndrome (OSAS) frequently manifests in patients with gastroesophageal reflux disease (GERD) and that there may be a causal relationship. AIM: To determine the relationship between OSAS and symptoms of GERD. METHODS: Consecutive patients referred to the Sleep Disorders Center (SDC) 18 years and older with polysomnographically defined OSAS were evaluated prospectively for GERD using a validated symptoms questionnaire. The GERD and OSAS relationship was assessed by 1) determining frequency of GERD in patients with and without OSAS; 2) ascertaining the relationship between OSAS severity categories and presence of GERD; 3) examining GERD score in relation to those factors that might affect both GERD and OSAS, e.g. obesity. RESULTS: One thousand and twenty-three SDC patients met entry criteria. Amongst participants, GERD was common (29% of women and 17% of males) and OSAS extremely common (58% of women and 80% of males). GERD score did not correlate with OSAS variables. The severity of OSAS did not influence the prevalence of GERD. CONCLUSION: In a large group of patients referred to a sleep disorders center, there was no relationship between OSAS and GERD symptoms. Also, there was no relationship between the severity of OSAS and the likelihood of GERD symptoms.


Assuntos
Refluxo Gastroesofágico/complicações , Apneia Obstrutiva do Sono/complicações , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Encaminhamento e Consulta
16.
J Med Genet ; 40(4): 242-8, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12676893

RESUMO

Recessive mutations of SLC26A4 (PDS) are a common cause of Pendred syndrome and non-syndromic deafness in western populations. Although south and east Asia contain nearly one half of the global population, the origins and frequencies of SLC26A4 mutations in these regions are unknown. We PCR amplified and sequenced seven exons of SLC26A4 to detect selected mutations in 274 deaf probands from Korea, China, and Mongolia. A total of nine different mutations of SLC26A4 were detected among 15 (5.5%) of the 274 probands. Five mutations were novel and the other four had seldom, if ever, been identified outside east Asia. To identify mutations in south Asians, 212 Pakistani and 106 Indian families with three or more affected offspring of consanguineous matings were analysed for cosegregation of recessive deafness with short tandem repeat markers linked to SLC26A4. All 21 SLC26A4 exons were PCR amplified and sequenced in families segregating SLC26A4 linked deafness. Eleven mutant alleles of SLC26A4 were identified among 17 (5.4%) of the 318 families, and all 11 alleles were novel. SLC26A4 linked haplotypes on chromosomes with recurrent mutations were consistent with founder effects. Our observation of a diverse allelic series unique to each ethnic group indicates that mutational events at SLC26A4 are common and account for approximately 5% of recessive deafness in south Asians and other populations.


Assuntos
Proteínas de Transporte/genética , Surdez/genética , Proteínas de Membrana Transportadoras , Sudeste Asiático/epidemiologia , Cromossomos Humanos Par 7/genética , DNA/química , DNA/genética , Análise Mutacional de DNA , Surdez/epidemiologia , Surdez/patologia , Saúde da Família , Feminino , Frequência do Gene , Genes Recessivos/genética , Haplótipos , Humanos , Coreia (Geográfico)/epidemiologia , Masculino , Mutação , Mutação de Sentido Incorreto , Linhagem , Mapeamento Físico do Cromossomo , Transportadores de Sulfato
17.
Genes Brain Behav ; 14(4): 345-56, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25809424

RESUMO

Although several genome-wide association (GWA) studies of human personality have been recently published, genetic variants that are highly associated with certain personality traits remain unknown, due to difficulty reproducing results. To further investigate these genetic variants, we assessed biological pathways using GWA datasets. Pathway analysis using GWA data was performed on 1089 Korean women whose personality traits were measured with the Revised NEO Personality Inventory for the 5-factor model of personality. A total of 1042 pathways containing 8297 genes were included in our study. Of these, 14 pathways were highly enriched with association signals that were validated in 1490 independent samples. These pathways include association of: Neuroticism with axon guidance [L1 cell adhesion molecule (L1CAM) interactions]; Extraversion with neuronal system and voltage-gated potassium channels; Agreeableness with L1CAM interaction, neurotransmitter receptor binding and downstream transmission in postsynaptic cells; and Conscientiousness with the interferon-gamma and platelet-derived growth factor receptor beta polypeptide pathways. Several genes that contribute to top-ranked pathways in this study were previously identified in GWA studies or by pathway analysis in schizophrenia or other neuropsychiatric disorders. Here we report the first pathway analysis of all five personality traits. Importantly, our analysis identified novel pathways that contribute to understanding the etiology of personality traits.


Assuntos
Transtornos de Ansiedade/genética , Genoma Humano , Personalidade/genética , Adolescente , Adulto , Feminino , Estudo de Associação Genômica Ampla , Humanos , Interferon gama/genética , Molécula L1 de Adesão de Célula Nervosa/genética , Neuroticismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Receptores de Prostaglandina/genética
18.
J Tissue Eng Regen Med ; 9(3): 265-75, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23225767

RESUMO

Gellan gum (GG)-based hydrogels are advantageous in tissue engineering not only due to their ability to retain large quantities of water and provide a similar environment to that of natural extracellular matrix (ECM), but also because they can gelify in situ in seconds. Their mechanical properties can be fine-tuned to mimic natural tissues such as the nucleus pulposus (NP). This study produced different formulations of GG hydrogels by mixing varying amounts of methacrylated (GG-MA) and high-acyl gellan gums (HA-GG) for applications as acellular and cellular NP substitutes. The hydrogels were physicochemically characterized by dynamic mechanical analysis. Degradation and swelling abilities were assessed by soaking in a phosphate buffered saline solution for up to 170 h. Results showed that as HA-GG content increased, the modulus of the hydrogels decreased. Moreover, increases in HA-GG content induced greater weight loss in the GG-MA/HA-GG formulation compared to GG-MA hydrogel. Potential cytotoxicity of the hydrogel was assessed by culturing rabbit NP cells up to 7 days. An MTS assay was performed by seeding rabbit NP cells onto the surface of 3D hydrogel disc formulations. Viability of rabbit NP cells encapsulated within the different hydrogel formulations was also evaluated by Calcein-AM and ATP assays. Results showed that tunable GG-MA/HA-GG hydrogels were non-cytotoxic and supported viability of rabbit NP cells.


Assuntos
Hidrogéis/química , Disco Intervertebral/citologia , Teste de Materiais , Polissacarídeos Bacterianos/química , Animais , Sobrevivência Celular , Células Cultivadas , Disco Intervertebral/metabolismo , Coelhos
19.
Environ Health Perspect ; 109(8): 795-9, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11564614

RESUMO

We investigated the function of Clara cells in vivo during exposure to inhaled crystalline silica by examining pulmonary matrix metalloproteinase (MMP)-2 and MMP-9 mRNA levels in mice. The Clara cells of male FVB/n mice (8-12 weeks old) were ablated by intraperitoneal administration of naphthalene (300 mg/kg) in a corn oil vehicle. The mice were then exposed to crystalline silica (Min-U-Sil-5 silica, 97.1 +/- 9.5 mg/m(2), 6 hr/day, 5 days/week) for up to 2 weeks. Transcriptional levels of mRNA extracted from the lungs were assessed by reverse transcription-polymerase chain reaction. Gene expression of both MMP-2 and MMP-9 was significantly more marked in the Clara cell-ablated group than in the group with Clara cells, indicating that Clara cells inhibit MMP expression. Our findings suggest that Clara cells inhibit pulmonary inflammation induced by crystalline silica via MMPs in vivo.


Assuntos
Brônquios/ultraestrutura , Células Epiteliais/enzimologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/enzimologia , Dióxido de Silício/toxicidade , Animais , Brônquios/enzimologia , Cristalização , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Fibrose , Expressão Gênica , Imuno-Histoquímica , Inflamação/enzimologia , Inflamação/patologia , Exposição por Inalação , Pulmão/enzimologia , Pulmão/patologia , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos AKR , Naftalenos/toxicidade , Fibrose Pulmonar/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
20.
Urology ; 51(5): 744-8, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9610587

RESUMO

OBJECTIVES: Both benign prostatic hyperplasia (BPH) and male pattern baldness (androgenic alopecia) share the pathogenesis of an androgen-dependent disorder and afflict a large population of elderly men with chronobiologic progress. However, it is unclear whether these diseases are related epidemiologically. We evaluated the association of frequency and severity of male pattern baldness between patients with BPH and a control group. METHODS: A total of 225 patients with BPH (mean age 69.3 +/- 6.5 years) and 1 60 controls (mean age 68.5 +/- 6.4 years), all over 60 years of age, were included in this study. The estimation of baldness severity was based on Norwood's classification (grade I to VII). The International Prostate Symptom Score (IPSS) and genetic tendency for baldness were also evaluated. The difference between IPSS and grade of baldness between the two groups was analyzed by the Mann-Whitney test and the frequency of inherited baldness was compared by the chi-square test. Correlation between severity of baldness and IPSS in each group was estimated by Spearman's rank correlation method. RESULTS: The patients with BPH had an apparently higher grade of male pattern baldness in comparison with that of controls (median value of grade IV versus III, P <0.001). The proportion of men with male pattern baldness of grade IV or higher in the BPH group was significantly larger than that of controls (53.8% versus 36.9%, P <0.01). There was a greater frequency of inherited baldness in the BPH group than in the controls (31.6% versus 12.5%, P <0.001). No significant correlation was noted between baldness severity and IPSS in either group. CONCLUSIONS: This study demonstrates a strong association of BPH with male pattern baldness.


Assuntos
Alopecia/epidemiologia , Hiperplasia Prostática/epidemiologia , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/fisiologia , Idoso , Envelhecimento/fisiologia , Alopecia/classificação , Alopecia/genética , Distribuição de Qui-Quadrado , Di-Hidrotestosterona/farmacologia , Humanos , Incidência , Coreia (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/classificação , Índice de Gravidade de Doença
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