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1.
Mil Med ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32239167

RESUMO

INTRODUCTION: Psychological stress is associated with sedentary behavior, which may impair exercise performance. The aim of our study was to examine the association between psychological stress and physical fitness in military personnel. METHOD: A military cohort of 4080 subjects in Taiwan was used for the analysis. The Brief Symptoms Rating Scale (BSRS-5) includes items of anxiety, depression, hostility, interpersonal sensitivity, and insomnia measured by a five-point Likert-type scale of 0-4. Psychological stress was defined as normal (n = 3657), slight (n = 314), and great (n = 109) by BSRS-5 score ≤5, 6-9, and ≥10, respectively. Aerobic fitness and anaerobic fitness were evaluated by the time of 3000-meter running and the numbers of 2-min sit-ups and 2-min push-ups, respectively. Multiple linear and logistic regression analyses were used to determine the relationship. RESULTS: As compared with normal stress, slight and great stress were positive dose-dependently correlated with 3000-meter running time (ß = 9.09 and 14.44; P = 0.0032 and 0.048, respectively) after adjusting for age, sex, service specialty, body mass index, systolic blood pressure, cigarette smoking, alcohol intake, hemoglobin levels, and exercise frequency. Similarly, those with slight stress were more likely to be the worst 10% performers in the 3000-meter run test relative to the normal individuals (odds ratio and 95% confidence intervals: 1.50, 1.00-2.24). By contrast, there was no relationship of psychological stress with the numbers of 2-min sit-ups and 2-min push-ups. CONCLUSIONS: Our findings suggest that the presence of higher psychological stress on military personnel may reduce their cardiorespiratory fitness but not affect the anaerobic fitness.

2.
Nature ; 567(7748): 341-346, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30842654

RESUMO

Cancer-specific inhibitors that reflect the unique metabolic needs of cancer cells are rare. Here we describe Gboxin, a small molecule that specifically inhibits the growth of primary mouse and human glioblastoma cells but not that of mouse embryonic fibroblasts or neonatal astrocytes. Gboxin rapidly and irreversibly compromises oxygen consumption in glioblastoma cells. Gboxin relies on its positive charge to associate with mitochondrial oxidative phosphorylation complexes in a manner that is dependent on the proton gradient of the inner mitochondrial membrane, and it inhibits the activity of F0F1 ATP synthase. Gboxin-resistant cells require a functional mitochondrial permeability transition pore that regulates pH and thus impedes the accumulation of Gboxin in the mitochondrial matrix. Administration of a metabolically stable Gboxin analogue inhibits glioblastoma allografts and patient-derived xenografts. Gboxin toxicity extends to established human cancer cell lines of diverse organ origin, and shows that the increased proton gradient and pH in cancer cell mitochondria is a mode of action that can be targeted in the development of antitumour reagents.


Assuntos
Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Aloenxertos , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Linhagem Celular Tumoral , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/enzimologia , Membranas Mitocondriais/metabolismo , Transplante de Neoplasias , Especificidade de Órgãos , Força Próton-Motriz/efeitos dos fármacos , ATPases Translocadoras de Prótons/antagonistas & inibidores , ATPases Translocadoras de Prótons/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Environ Technol ; : 1-11, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30758245

RESUMO

As concern has increased regarding the interaction between efficiency and safety of disinfection, plasma becomes a viable alternative for disinfection in comparison with traditional methods. Dielectric barrier discharge (DBD) is applied to deactivate Bacillus subtilis and Escherichia coli , respectively, and disinfection efficiency is experimentally evaluated in this study. Tests are conducted with different working gases to investigate their effects on disinfection. Results show that Ar plasma diluted with 25% O2 enhances the germicidal effects to5.9 and 6.9 (log reduction) for B. subtilis and E. coli, respectively, and OES results show that active Ar and O species play important roles to weaken cell wall of microbes and further disinfect E. coli and B. subtilis. Analysis of protein and total sugar release indicates that active species such as ozone, NO and Ar* produced by plasma result in hydrolysis of the cell. In the meantime, charged particles produced by plasma would affect the amount of sugar released, resulting in different germicidal effects. Overall, plasma can disinfect microorganisms mainly via the generation of oxidising agents including ozone, NO and UV with a comparatively short treatment period, which is typically less than 5 min.

4.
Psychiatry Investig ; 15(10): 1000-1006, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30301302

RESUMO

OBJECTIVE: Post weanling isolation-reared (IR) rats are featured with depressive phenotype, yet its mechanism is not clearly defined particularly in terms of the involvement of central 5-HT1A receptors. The present study aims to examine the effects of 5HT1A activation on forced swim test (FST) in IR rats following 5-HT depletion. METHODS: Social control (SOC) and IR rats received an intracerebraoventricular (ICV) injection of 5-HT depletion agent, 5,7-DHT. 14 days after the surgery, rats were assessed their performance in FST with or without the challenge with a 5-HT1A agonist, 8-OH-DPAT. Rats were then sacrificed for analyzing their 5-HT tissue levels and the expressions of their 5-HA1A receptors in prefrontal cortex (PFC), hippocampus (HPX), and amygdala (AMY). RESULTS: 5,7-DHT decreased the tissue concentration of 5-HT in both IR and SOC rats. IR rats were more immobile and less sensitive to the lesion-induced immobility, however this effect was reversed by acute challenge of 8-OH-DPAT. 5,7-DHT lesion increased the expression of PFC 5-HT1A receptors. CONCLUSION: The integrity of central 5-HT system is developmentally crucial for the 5-HT1A-relevant depression profile in rats of social isolation.

5.
BMC Neurol ; 18(1): 25, 2018 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-29523097

RESUMO

BACKGROUND: Spiral drawing on papers is a common tremor evaluation tool for diagnosing patients with essential tremor (ET) or Parkinson's disease (PD). No standard drawing methods and parameters that use graphic tablets are yet available for objective evaluation. METHODS: This study established a tremor assessment system for tremor severity by using graphic tablets. Twelve patients with ET and twelve patients with PD were tested to establish system algorithms, and six additional patients were tested with the developed system to evaluate its performance. The patients also performed spiral drawing with three guiding paradigms on a graphic tablet: traced along a given spiral (S1), performed freehand drawing (S2), and traced along a guiding point (S3). Three parameters were calculated to quantify tremor severity: the means of radial difference per radian (|dr/dθ|), the means of radial difference per second (|dr/dt|), and the area under curve (AUC) of the frequency spectrum of the velocity. Each patient's drawing was also evaluated using a visual rating scale (VRS) by experienced physicians. The interrater reliability was examined to identify the most consistent test paradigm. RESULTS: The parameter |dr/dθ| and AUC correlated well with the VRS (R > 0.8) in S1, S2 and S3 tests. The S1 test presented the best interrater reliability (Weighted Kappa coefficient, k = 0.80) among three tests. The Weighted Kappa coefficients are 0.67 and 0.71 in S2 and S3 tests, respectively. CONCLUSIONS: We developed three different guiding paradigms for spiral drawing on a digital graphic tablet for clinical tests. Three parameters were calculated to represent the tremor severity in spiral drawing and used to quantify temporal and spatial characteristics of tremor, and provided good correlation with current clinical assessments. The test "traced along a given spiral" is recommended due to its good interrater reliability.


Assuntos
Computadores de Mão , Tremor Essencial/diagnóstico , Destreza Motora , Exame Neurológico/métodos , Doença de Parkinson/complicações , Tremor/diagnóstico , Idoso , Tremor Essencial/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/diagnóstico , Reprodutibilidade dos Testes , Tremor/etiologia
6.
Neurol Sci ; 39(6): 1057-1063, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29572654

RESUMO

In a spiral task, the accuracy of the spiral trajectory, which is affected by tracing or tracking ability, differs between patients with Parkinson's disease (PD) and essential tremor (ET). However, not many studies have analyzed velocity differences between the groups during this task. This study aimed to examine differences between the groups related to this characteristic using a tablet. Fourteen PD, 12 ET, and 12 control group participants performed two tasks: tracing a given spiral (T1) and following a guiding point (T2). A digitized tablet was used to record movements and trajectory. Effects of direct visual feedback on intergroup and intragroup velocity were measured. Although PD patients had a significantly lower T1 velocity than the control group (p < 0.05), they could match the velocity of the guiding point (3.0 cm/s) in T2. There was no significant difference in the average T1 velocity between ET and the control groups (p = 0.26); however, the T2 velocity of ET patients was significantly higher than the control group (p < 0.05). They were also unable to adjust the velocity to match the guiding point, indicating that ET patients have a poorer ability to follow dynamic guidance. When both groups of patients have similar action tremor severity, their ability to follow dynamic guidance was still significantly different. Our study combined visual feedback with spiral drawing and demonstrated differences in the following-velocity distribution in PD and ET. This method may be used to distinguish the tremor presentation of both diseases, and thus, provide accurate diagnosis.


Assuntos
Tremor Essencial/fisiopatologia , Retroalimentação , Mãos , Destreza Motora , Doença de Parkinson/fisiopatologia , Percepção Visual , Idoso , Idoso de 80 Anos ou mais , Fenômenos Biomecânicos , Computadores de Mão , Tremor Essencial/psicologia , Mãos/fisiopatologia , Humanos , Pessoa de Meia-Idade , Destreza Motora/fisiologia , Doença de Parkinson/psicologia
7.
Am J Pathol ; 188(4): 1031-1042, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29366678

RESUMO

Highly pathogenic avian influenza A H5N1 virus causes pneumonia and acute respiratory distress syndrome in humans. Virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. Galectin-3, a ß-galactoside-binding protein widely distributed in immune and epithelial cells, regulates various immune functions and modulates microbial infections. Here, we describe galectin-3 up-regulation in mouse lung tissue after challenges with the H5N1 influenza virus. We investigated the effects of endogenous galectin-3 on H5N1 infection and found that survival of galectin-3 knockout (Gal-3KO) mice was comparable with wild-type (WT) mice after infections. Compared with infected WT mice, infected Gal-3KO mice exhibited less inflammation in the lungs and reduced IL-1ß levels in bronchoalveolar lavage fluid. In addition, the bone marrow-derived macrophages (BMMs) from Gal-3KO mice exhibited reduced oligomerization of apoptosis-associated speck-like proteins containing caspase-associated recruitment domains and secreted less IL-1ß compared with BMMs from WT mice. However, similar levels of the inflammasome component of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) were observed in two genotypes of BMMs. Co-immunoprecipitation data indicated galectin-3 and NLRP3 interaction in BMMs infected with H5N1. An association was also observed between galectin-3 and NLRP3/apoptosis-associated speck-like proteins containing caspase-associated recruitment domain complex. Combined, our results suggest that endogenous galectin-3 enhances the effects of H5N1 infection by promoting host inflammatory responses and regulating IL-1ß production by macrophages via interaction with NLRP3.


Assuntos
Aves/virologia , Galectina 3/metabolismo , Virus da Influenza A Subtipo H5N1/fisiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Pneumonia/metabolismo , Pneumonia/virologia , Animais , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Cães , Células HEK293 , Humanos , Interleucina-1beta/metabolismo , Pulmão/patologia , Pulmão/virologia , Macrófagos/metabolismo , Células Madin Darby de Rim Canino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infecções por Orthomyxoviridae/metabolismo , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Pneumonia/patologia , Piroptose , Análise de Sobrevida , Regulação para Cima
8.
World J Gastroenterol ; 23(25): 4587-4594, 2017 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-28740347

RESUMO

AIM: To investigate the association of chronic hepatitis B and nonalcoholic steatohepatitis with physical fitness in a Taiwanese military male cohort. METHODS: We made a cross-sectional examination of this association using 3669 young adult military males according to cardiorespiratory fitness and hospitalization events recorded in the Taiwan Armed Forces study. Cases of chronic hepatitis B (n = 121) were defined by personal history and positive detection of hepatitis B surface antigen. Cases of nonalcoholic steatohepatitis (n = 129) were defined by alanine transaminase level > 60 U/L, liver ultrasound finding of steatosis, and absence of viral hepatitis A, B or C infection. All other study participants were defined as unaffected (n = 3419). Physical fitness was evaluated by performance in 3000-m run, 2-min sit-ups, and 2-min push-ups exercises, with all the procedures standardized by a computerized scoring system. Multiple linear regression analysis was used to determine the relationship. RESULTS: Chronic hepatitis B negatively correlated with 2-min push-up numbers (ß = -2.49, P = 0.019) after adjusting for age, service specialty, body mass index, systolic and diastolic blood pressures, current cigarette smoking, alcohol intake status, serum hemoglobin, and average weekly exercise times. Nonalcoholic steatohepatitis was borderline positively correlated with 3000-m running time (ß = 11.96, P = 0.084) and negatively correlated with 2-min sit-up numbers (ß = -1.47, P = 0.040). CONCLUSION: Chronic hepatitis B viral infection and nonalcoholic steatohepatitis affects different physical performances in young adult military males, and future study should determine the underlying mechanism.


Assuntos
Vírus da Hepatite B/imunologia , Hepatite B Crônica/fisiopatologia , Militares/estatística & dados numéricos , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Aptidão Física/fisiologia , Adulto , Alanina Transaminase/sangue , Índice de Massa Corporal , Estudos Transversais , Exercício Físico , Hepacivirus/isolamento & purificação , Vírus da Hepatite A Humana/isolamento & purificação , Antígenos de Superfície da Hepatite B/isolamento & purificação , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/virologia , Humanos , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prevalência , Estudos Retrospectivos , Taiwan/epidemiologia , Ultrassonografia , Adulto Jovem
9.
Sci Rep ; 7(1): 2984, 2017 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-28592793

RESUMO

Hypervalent molecules are one of the exceptions to the octet rule. Bonding in most hypervalent molecules is well rationalized by the Rundle-Pimentel model (three-center four-electron bond), and high ionic bonding between the ligands and the central atom is essential for stabilizing hypervalent molecules. Here, we produced one of the simplest hypervalent anions, HF-, which is known to deviate from the Rundle-Pimentel model, and identified its ro-vibrational features. High-level ab inito calculations reveal that its bond dissociation energy is comparable to that of dihalides, as supported by secondary photolysis experiments with irradiation at various wavelengths. The charge distribution analysis suggested that the F atom of HF- is negative and hypervalent and the bonding is more covalent than ionic.

10.
World J Cardiol ; 8(8): 464-71, 2016 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-27621774

RESUMO

AIM: To investigate the association between cardiorespiratory fitness and hospitalization events in a cohort of large voluntary arm forces in Taiwan. METHODS: The cardiorespiratory fitness and hospitalization events in armed forces (CHIEF) is a retrospective cohort consisting of more than 4000 professional military members aged 18-50 years in Eastern Taiwan. All participants received history taking, physical examination, chest radiography, 12-lead electrocardiography, blood tests for cell counts and fasting glucose, lipid profiles, uric acid, renal function and liver function in the Hualien Armed Forces General Hospital during 2014. In addition, participants were required to undergo two indoor resistant exercise tests including 2-min push-up and 2-min sit-up, both scored by infrared sensing, and one outdoor endurance 3000-m none weight-bearing running test, the main indicator of cardiorespiratory fitness in the Military Physical Training and Testing Center in Eastern Taiwan in 2014. RESULTS: Hospitalization events for cardiovascular disease, acute kidney injury, rhabdomyolysis, severe infectious disease, acute psychiatric illness, diabetes, orthopedic surgery and mortality will be identified in the National Insurance Research Database for 10 years. CONCLUSION: CHIEF will be among the largest Eastern Asian armed forces cohort, in which physical status was strictly evaluated to follow up the hospitalization events for severe illness.

11.
Complement Ther Med ; 26: 21-7, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27261977

RESUMO

AIMS: The aim of this study was to assess the effects of oral Chinese herbal medicine (CHM) combined with phototherapy for vitiligo. METHODS: We undertook a meta-analysis of relevant randomized controlled trials (RCTs) and searched eight bibliographic databases from inception to December 2015. RESULTS: A total of 5 RCTs with 513 participants which assessed the efficacy of oral CHM in combination with narrow-band ultraviolet B (NB-UVB) in treating vitiligo were included. The meta-analysis revealed a superior effectiveness in those receiving oral CHM plus NB-UVB when compared to phototherapy alone (risk difference 0.22, 95% confidence interval 0.14 to 0.29, P<0.00001). Only mild adverse events were reported without significant renal or liver function impairment. CONCLUSIONS: The current evidence demonstrates that oral CHM in combination with NB-UVB has a superior effectiveness in terms of repigmentation rate of vitiligo when compared to NB-UVB alone. Although the overall quality of included trials was low, oral CHM in combination with NB-UVB may be an alternative option of treatment for vitiligo. As to safety, there were only mild adverse events reported without significant renal or liver function impairment. However, there is limited available evidence of long-term follow-up and poor methodological quality of the available trials. Well-designed RCTs of adequate length and sample size that include life quality as an outcome are warranted.


Assuntos
Medicamentos de Ervas Chinesas , Fototerapia , Vitiligo/terapia , Administração Oral , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto Jovem
12.
J Neurosci Methods ; 266: 78-83, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27058772

RESUMO

BACKGROUND: Clinical assessment scales are the most common means used by physicians to assess tremor severity. Some scientific tools that may be able to replace these scales to objectively assess the severity, such as accelerometers, digital tablets, electromyography (EMG) measurement devices, and motion capture cameras, are currently available. However, most of the operational modes of these tools are relatively complex or are only able to capture part of the clinical information; furthermore, using these tools is sometimes time consuming. Currently, there is no tool available for automatically quantifying tremor severity in clinical environments. NEW METHOD: We aimed to develop a rapid, objective, and quantitative system for measuring the severity of finger tremor using a small portable optical device (Leap Motion). RESULTS: A single test took 15s to conduct, and three algorithms were proposed to quantify the severity of finger tremor. The system was tested with four patients diagnosed with essential tremor. COMPARISON WITH EXISTING METHOD: The proposed algorithms were able to quantify different characteristics of tremor in clinical environments, and could be used as references for future clinical assessments. CONCLUSIONS: A portable, easy-to-use, small-sized, and noncontact device (Leap Motion) was used to clinically detect and record finger movement, and three algorithms were proposed to describe tremor amplitudes.


Assuntos
Acelerometria/instrumentação , Acelerometria/métodos , Algoritmos , Tremor Essencial/diagnóstico , Dispositivos Ópticos , Índice de Gravidade de Doença , Idoso , Tremor Essencial/fisiopatologia , Estudos de Viabilidade , Feminino , Dedos/fisiopatologia , Humanos , Masculino , Processamento de Sinais Assistido por Computador , Tremor/diagnóstico , Tremor/fisiopatologia
13.
Anesthesiology ; 121(6): 1270-80, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24937074

RESUMO

BACKGROUND: Toll-like receptor 4 (TLR4), the receptor for endotoxin, mediates hyperinflammatory response and contributes to high mortality during both endotoxin shock and severe sepsis. However, little is known about the role of TLR4 in the pathogenesis of low-grade polymicrobial sepsis, which is often associated with immunosuppression. METHODS: Low-grade polymicrobial sepsis was generated by cecum ligation and puncture. Mortality was monitored in wild- type (C57BL/10ScSn) and TLR4def (C57BL/10ScCr) mice. Ex vivo heart and individual cardiomyocyte function were assessed in Langendorff (Hugo Sachs Elektronik; Harvard Apparatus, Holliston, MA) and IonOptix systems (IonOptix, Milton, MA), respectively. Serum chemistry was tested for liver and kidney injury. Cytokines were examined using a multiplex immunoassay. Neutrophil migratory and phagocytic functions were assessed using flow cytometry. Reactive oxygen species were measured using redox-sensitive dichlorodihydrofluorescein dye. RESULTS: Following cecum ligation and puncture, wild-type mice developed bacterial peritonitis with mild cardiac dysfunction (n=3 in sham and n=8 in cecum ligation and puncture) and a mortality of 23% within 14 days (n=22). In comparison, septic TLR4def mice had deleterious cardiac dysfunction (n=6 in sham and n=10 in cecum ligation and puncture), kidney and liver injury (n=7), and much higher mortality at 81% (n=21). The deleterious effects observed in septic TLR4def mice were associated with increased local and systemic cytokine response, reduced neutrophil migratory and phagocytic function, increased reactive oxygen species generation in leukocytes, and impaired bacterial clearance. CONCLUSION: TLR4 plays an essential role in host defense against low-grade polymicrobial sepsis by mediating neutrophil migratory/phagocytic functions, attenuating inflammation, reducing reactive oxygen species generation, and enhanced bacterial clearance.


Assuntos
Coração/fisiopatologia , Sepse/fisiopatologia , Receptor 4 Toll-Like/fisiologia , Animais , Carga Bacteriana/genética , Cálcio/metabolismo , Feminino , Técnicas In Vitro , Nefropatias/fisiopatologia , Hepatopatias/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Sarcômeros/genética , Sepse/diagnóstico por imagem , Sepse/mortalidade , Choque Séptico/diagnóstico por imagem , Choque Séptico/mortalidade , Choque Séptico/fisiopatologia , Receptor 4 Toll-Like/genética , Ultrassonografia
14.
Astrobiology ; 14(2): 119-31, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24512484

RESUMO

The detection of nucleobases, the informational subunits of DNA and RNA, in several meteorites suggests that these compounds of biological interest were formed via astrophysical, abiotic processes. This hypothesis is in agreement with recent laboratory studies of irradiation of pyrimidine in H2O-rich ices with vacuum UV photons emitted by an H2-discharge lamp in the 6.9-11.3 eV (110-180 nm) range at low temperature, shown to lead to the abiotic formation of several compounds including the nucleobases uracil, cytosine, and thymine. In this work, we irradiated H2O:pyrimidine ice mixtures under astrophysically relevant conditions (14 K, ≤10(-9) torr) with high-energy UV photons provided by a synchrotron source in three different ranges: the 0(th) order light (4.1-49.6 eV, 25-300 nm), the He i line (21.2 eV, 58.4 nm), and the He ii line (40.8 eV, 30.4 nm). The photodestruction of pyrimidine was monitored with IR spectroscopy, and the samples recovered at room temperature were analyzed with liquid and gas chromatographies. Uracil and its precursor 4(3H)-pyrimidone were found in all samples, with absolute and relative abundances varying significantly from one sample to another. These results support a scenario in which compounds of biological interest can be formed and survive in environments subjected to high-energy UV radiation fields.


Assuntos
Gelo , Fótons , Pirimidinas/efeitos da radiação , Raios Ultravioleta , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Meia-Vida , Espectrofotometria Infravermelho , Síncrotrons
15.
J Cardiol ; 62(6): 354-60, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23838556

RESUMO

BACKGROUND: Hyperuricemia is associated with a higher risk of death in patients with coronary artery disease (CAD). In contrast, overweight or obesity was associated with survival benefits in this population. However, the relation of body mass index (BMI) and serum uric acid (SUA) to mortality has not been clarified in this population. METHODS: We studied a cohort of 1202 patients with angiographic CAD from the ET-CHD registry during 1997-2003 in Taiwan. To evaluate the relation of BMI and SUA on mortality, the subjects were categorized into 4 groups by BMI >/= 25 kg/m(2) (overweight or obesity) or BMI<25 kg/m(2) (normal- or under-weight), and SUA levels higher or lower than the median of 6.6 mg/dl. At a median follow-up of 5.4 years, cardiac and all-cause deaths were the primary end points. RESULTS: Multivariate analyses demonstrated that high SUA group had a significantly higher cardiac mortality [hazard ratio (HR): 1.79, 95% confidence interval (CI): 1.14-2.82, p=0.023] and overall mortality (HR: 1.68, 95% CI: 1.19-2.36, p=0.003) than low SUA group only in overweight or obese patients. Additionally, high BMI was associated with a significantly lower cardiac mortality (HR: 0.58, 95% CI: 0.38-0.99, p=0.023) and overall mortality (HR: 0.62, 95% CI: 0.41-0.82, p=0.003) than low BMI in patients with low SUA levels. Furthermore, normal-low weight and underweight patients (BMI<21 kg/m(2)) were found to have a higher risk of mortality regardless of SUA levels. CONCLUSIONS: Among patients with established CAD, SUA may be a potent predictor to mortality in overweight or obese patients. Moreover, the obesity-mortality paradox phenomenon was mainly driven by higher mortality risk in underweight patients and lower mortality risk in overweight and obese patients with low SUA.


Assuntos
Índice de Massa Corporal , Doença da Artéria Coronariana/mortalidade , Sistema de Registros , Ácido Úrico/sangue , Idoso , Estudos de Coortes , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/fisiopatologia , Feminino , Previsões , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Risco , Taiwan/epidemiologia
17.
Schizophr Bull ; 39(2): 407-16, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22045828

RESUMO

BACKGROUND: Both genetic and environmental factors have been reasoned for cancer development in schizophrenia patients. However, the influence of age of onset and duration of schizophrenia on cancer incidence has rarely been emphasized. Besides, bipolar disorder tends to resemble schizophrenia from the perspective of multiple rare mutations. Comparing pattern and risk of cancers between schizophrenia and bipolar patients is illuminating. METHODS: This study used the Taiwan National Health Insurance Database. A total of 71,317 schizophrenia and 20,567 bipolar disorder patients from 1997 to 2009 were enrolled. Both cohorts were followed up for cancer during the same period by record linkage with the cancer certification in Taiwan. Age and gender standardized incidence ratios (SIRs) of overall and site-specific cancers were calculated. RESULTS: The SIR for all cancers was 1.17 for the schizophrenia cohort. Increased cancer risk (SIR: 1.31, 95% CI: 1.17-1.48) was observed in females but not males. For the bipolar disorder cohort, the SIR for all cancers was 1.29, but the excess risk was found in males (SIR: 1.42, 95% CI: 1.14-1.77) and not females. Cancer risk decreases as the duration and age of onset of schizophrenia increases. If schizophrenia is diagnosed before 50, the SIRs for colorectal, breast, cervical, and uterine cancers increase but if diagnosed after 50, the SIRs for all cancers decrease except for breast cancer. In bipolar disorder, the SIRs for all site-specific cancers were insignificant. CONCLUSIONS: Among schizophrenia patients, overall cancer risk varies inversely with age at diagnosis and disease duration. Besides, gender-specific cancer risks differ between schizophrenia and bipolar disorder.


Assuntos
Transtorno Bipolar/epidemiologia , Neoplasias/epidemiologia , Esquizofrenia/epidemiologia , Adulto , Distribuição por Idade , Idade de Início , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Distribuição por Sexo , Taiwan/epidemiologia , Adulto Jovem
19.
PLoS One ; 7(9): e44937, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23028692

RESUMO

Proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR) are characterized by the development of epi-retinal membranes which may exert a tractional force on retina. A lot of inflammatory growth factors may disturb the local ocular cells such as retinal pigment epithelial (RPE) cells, causing them to migrate and proliferate in the vitreous cavity and ultimately forming the PVR membrane. In this study, the signal pathways mediating cell migration of RPE induced by growth factors were investigated. Hepatocyte growth factor (HGF), epidermal growth factor (EGF) or heparin-binding epidermal growth factor (HB-EGF) induced a greater extent of migration of RPE50 and ARPE19 cells, compared with other growth factors. According to inhibitor studies, migration of RPE cells induced by each growth factor was mediated by protein kinase C (PKC) and ERK (MAPK). Moreover, HGF coupled with EGF or HB-EGF had synergistic effects on cell migration and enhanced activation of PKC and ERK, which were attributed to cross activation of growth factor receptors by heterogeneous ligands. Furthermore, using the shRNA technique, PKCδ was found to be the most important PKC isozyme involved. Finally, vitreous fluids from PVR and PDR patients with high concentration of HGF may induce RPE cell migration in PKCδ- and ERK- dependent manner. In conclusion, migration of RPE cells can be synergistically induced by HGF coupled with HB-EGF or EGF, which were mediated by enhanced PKCδ activation and ERK phosphorylation.


Assuntos
Movimento Celular/efeitos dos fármacos , Fator de Crescimento Epidérmico/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fator de Crescimento de Hepatócito/farmacologia , Proteína Quinase C-delta/metabolismo , Epitélio Pigmentado da Retina/citologia , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular , Sinergismo Farmacológico , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Fator de Crescimento Derivado de Plaquetas/farmacologia , Epitélio Pigmentado da Retina/patologia , Fator de Crescimento Transformador beta/farmacologia , Vitreorretinopatia Proliferativa/patologia
20.
Prog Neuropsychopharmacol Biol Psychiatry ; 39(1): 149-55, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22691714

RESUMO

OBJECTIVE: Early growth response genes (EGR1, 2, 3, and 4) encode a family of nuclear proteins that function as transcriptional regulators. They are involved in the regulation of synaptic plasticity, learning, and memory, and are implicated in the pathogenesis of schizophrenia. METHODS: We conducted a genetic association analysis of 14 SNPs selected from the EGR1, 2, 3, and 4 genes of 564 patients with schizophrenia and 564 control subjects. We also conducted Western blot analysis and promoter activity assay to characterize the EGR genes associated with schizophrenia RESULTS: We did not detect a true genetic association of these 14 SNPs with schizophrenia in this sample. However, we observed a nominal over-representation of C/C genotype of rs9990 of EGR2 in female schizophrenia as compared to female control subjects (p=0.012, uncorrected for multiple testing). Further study showed that the average mRNA level of the EGR2 gene in the lymphoblastoid cell lines of female schizophrenia patients was significantly higher than that in female control subjects (p=0.002). We also detected a nominal association of 4 SNPs (rs6747506, rs6718289, rs2229294, and rs3813226) of the EGR4 gene that form strong linkage disequilibrium with schizophrenia in males. Reporter gene assay showed that the haplotype T-A derived from rs6747506 and rs6718289 at the promoter region had significantly reduced promoter activity compared with the haplotype A-G. CONCLUSION: Our data suggest a tendency of gender-specific association of EGR2 and EGR4 in schizophrenia, with an elevated expression of EGR2 in lympoblastoid cell lines of female schizophrenia patients and a reduced EGR4 gene expression in male schizophrenia patients.


Assuntos
Fatores de Transcrição de Resposta de Crescimento Precoce/genética , Predisposição Genética para Doença/genética , Esquizofrenia/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Feminino , Genes Reporter/genética , Estudos de Associação Genética/métodos , Estudos de Associação Genética/estatística & dados numéricos , Genótipo , Haplótipos/genética , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Caracteres Sexuais
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