RESUMO
OBJECTIVE: This study investigated the association between serum uric acid (sUA) and stroke risk in men with hypertriglyceridemia. METHODS: Between 2002 and 2012, male patients with pure hypertriglyceridemia and a triglyceride (TG) level ≥ 150 mg/dL were enrolled. Eligible patients were categorized into two groups according to their sUA levels (≥ and < 8 mg/dL). Clinical characteristics and comorbidities that are risk factors for stroke were recorded and compared between the groups. RESULTS: A total of 265 male patients (95 with sUA ≥ 8 mg/dL and 170 with sUA < 8 mg/dL) were enrolled. The incidence of ischemic type of stroke was significantly higher in patients with sUA ≥ 8 mg/dL (p = 0.038), particularly in the age range of 45-65 years. Multivariate Cox proportional analyses confirmed that age (p = 0.003) and UA (p = 0.019) were major predictive factors for stroke free (ischemic type of stroke) survival. CONCLUSION: Among men with hypertriglyceridemia, the incidence rate of ischemic type of stroke significantly increased with sUA levels ≥ 8 mg/dL, particularly in men aged 45 to 65 years. Hyperuricemia is considered a potential predictive factor for ischemic type of stroke and may indicate the need for preventive management in patients with hypertriglyceridemia (Tab. 3, Fig. 1, Ref. 28).
Assuntos
Biomarcadores , Hipertrigliceridemia , Hiperuricemia , Acidente Vascular Cerebral , Ácido Úrico , Idoso , Biomarcadores/sangue , Humanos , Hipertrigliceridemia/complicações , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etiologia , Ácido Úrico/sangueRESUMO
BACKGROUND: Obesity affects immune function by increasing the number of T helper lymphocytes, which may reduce the risk of tuberculosis (TB) infection. However, the effect of obesity on TB development has not been extensively studied. This nationwide population-based cohort study investigated the effect of obesity on TB development in Taiwanese adults. METHODS: We included 46 028 adult participants (age ⩾18 years) from three rounds (2001, 2005 and 2009) of the Taiwan National Health Interview Survey. Obesity and overweight were defined as a body mass index (BMI) ⩾27 and 24-26.9 (kg/m2), respectively. Data on BMI and other covariates at baseline were collected by in-person interviews. Incident cases of active TB were identified from the National Health Insurance database. Multivariable logistic regression was used to estimate the associations of obesity and overweight with active TB, with adjustment for age, sex, smoking, alcohol consumption, socioeconomic status and other covariates. RESULTS: In total, 241 new cases of active TB occurred during the study period. Obesity (adjusted odds ratio [AOR], 0.43; 95% confident interval [CI], 0.28-0.67) and overweight (AOR, 0.67; 95% CI, 0.49-0.91) were associated with lower risk of incident TB, after adjusting for demographic characteristics and comorbidities. There was a linear dose-response relation of BMI with active TB incidence (AOR per unit change in BMI, 0.92; 95% CI, 0.88-0.95; P <0.001). CONCLUSION: Obesity and overweight are associated with lower risk of active TB. Future studies should investigate the underlying mechanisms and clinical and epidemiological consequences of these findings.
Assuntos
Sobrepeso/imunologia , Magreza/imunologia , Tuberculose/imunologia , Adulto , Índice de Massa Corporal , Relação CD4-CD8 , Comorbidade , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Leptina/metabolismo , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Sobrepeso/epidemiologia , Sobrepeso/fisiopatologia , Fatores de Risco , Linfócitos T/imunologia , Taiwan/epidemiologia , Magreza/epidemiologia , Magreza/fisiopatologia , Tuberculose/epidemiologia , Tuberculose/fisiopatologiaRESUMO
BACKGROUND AND AIMS: Increased body fat relates to enhanced inflammatory cytokine production, which, in turn, activates the renin-angiotensin-aldosterone system and increases the risk of chronic kidney disease (CKD). Herein, we aimed to examine the association between obesity and the risk of CKD in a population-representative cohort in Taiwan. METHODS AND RESULTS: A multistage systematic sampling process was applied in the National Health Interview Survey (NHIS) 2000, 2005, and 2009. Participants were interviewed by a standardized face-to-face questionnaire to obtain information on their demographics, socioeconomic status, lifestyle factors, and body mass index (BMI). The BMI values were classified as follows: underweight (<18.5 kg/m2), normal (18.5-23.9 kg/m2), overweight (24-26.9 kg/m2), and obesity (≥27 kg/m2). The NHIS dataset was linked to National Health Insurance claims data to identify the incidence of CKD. Univariate and multivariate Cox proportional hazard models with competing risks were used to investigate the association between BMI and CKD incidence. We analyzed 45,012 subjects (mean age, 42.03 years; 50.09% males). During 374,254 person-years of follow-up, a total of 1913 new-onset CKD cases were identified. Kaplan-Meier curves comparing the four BMI groups revealed a significant difference (p < 0.01, log-rank test). After controlling for confounding factors, the relative risk of incident CKD was significantly higher in the obese group compared to the normal-weight group (adjusted hazard ratio = 1.32; 95% confidence interval: 1.17-1.49), with a significant linear trend (p < 0.01). CONCLUSION: Obesity was suggested as an independent risk factor for CKD. Further studies focusing on the effect of losing weight on CKD prevention are warranted.
Assuntos
Obesidade/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Incidência , Estimativa de Kaplan-Meier , Modelos Lineares , Masculino , Análise Multivariada , Obesidade/diagnóstico , Modelos de Riscos Proporcionais , Insuficiência Renal Crônica/diagnóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taiwan/epidemiologia , Fatores de TempoRESUMO
Objective: To investigate the efficacy of the first-day suspension method for improving the success rate of construction of nasopharyngeal carcinoma-patient derived organoids (NPC-PDO). Methods: The tumor samples of 14 nasopharyngeal carcinoma(NPC) patients, i.e.,13 males and 1 female, with a mean age of 43.0±12.0 years old, were collected from the Affiliated Tumor Hospital of Guangxi Medical University and the First Affiliated Hospital of Guangxi Medical University from January 2022 to July 2022. The tumor samples of 3 patients were digested into single cell suspension and divided into 2 groups, for comparing the efficacy of NPC-PDO construction by the direct inoculation method and the first-day suspension method. The remaining 11 patients were randomized to receive either the direct inoculation method or the first-day suspension method for NPC-PDO construction. The diameter and the number of spheres of NPC-PDO constructed by the two methods were compared by optical microscope; the 3D cell viability detection kit was used to compare the cell viability; the survival rates were compared by trypan blue staining; the success rates of the two construction methods were compared; the number of cases which could be successfully passaged for more than 5 generations and were consistent with the original tissue by pathological examination was counted; and the dynamic changes of cells in suspension overnight were observed by live cell workstation. The independent sample t-test was applied to compare the measurement data of the two groups, and the chi-square test was used to compare the classification data. Results: Compared with the direct inoculation, the diameter and the number of spheres of NPC-PDO constructed by the first-day suspension method were increased, with a higher cell activity, and the success rate of construction was obviously improved (80.0% vs 16.7%, χ2=4.41, P<0.05). In the suspension state, some of the cells aggregated and increased their ability to proliferate. Conclusion: The first-day suspension method can improve the success rate of NPC-PDO construction, especially for those whose original tumor sample size is small.
Assuntos
Microscopia , Neoplasias Nasofaríngeas , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , China , OrganoidesRESUMO
This study explored the role of TCOF1 insertion mutations in Taiwanese patients with craniofacial anomalies. Twelve patients with single or multiple, asymmetrical congenital craniofacial anomalies were enrolled. Genomic DNA was prepared from leukocytes; the coding regions of TCOF1 were analyzed by polymerase chain reaction and direct sequencing. Clinical manifestations were correlated to the TCOF1 mutation. Six of 12 patients diagnosed with hemifacial microsomia exhibited a novel insertion mutation 4127 ins G (frameshift) in exon 24 in the TCOF1 gene. All six patients were diagnosed with anomalies on the left side. In addition, four of these six patients had hearing impairment; three had other major anomalies; and two had developmental delay. The insertion caused a frameshift, an early truncation, the loss of two putative nuclear localization signals (residues 1404-1420 and 1424-1440), and the loss of coiled coil domain (1406-1426) in treacle protein. These findings support the existence of two regulators of growth of the mandibular condyles.
Assuntos
Assimetria Facial/genética , Mutagênese Insercional , Proteínas Nucleares/genética , Fosfoproteínas/genética , Adulto , Criança , Pré-Escolar , Anormalidades Craniofaciais/genética , Anormalidades Craniofaciais/patologia , Éxons , Feminino , Mutação da Fase de Leitura , Genoma Humano/genética , Humanos , Lactente , Recém-Nascido , Masculino , Sinais de Localização Nuclear/genética , Proteínas Nucleares/metabolismo , Fenótipo , Fosfoproteínas/metabolismo , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA , TaiwanRESUMO
Leukocyte adhesion to endothelium plays a critical initiating role in inflammation. Berberine, an anti-inflammatory natural compound, is known to attenuate lipopolysaccharide (LPS)-induced lung injury and improve survival of endotoxemic animals with mechanism not fully clarified. This study investigated the effects of berberine on the LPS-induced leukocyte-endothelial cell adhesion both in vivo and in vitro. We first established an animal model to observe the in vivo LPS-induced adhesion of leukocytes to the endothelium of venules in the lung tissue dose-dependently. Pretreatment of LPS-stimulated rats with berberine for 1 h reduced the leukocyte-endothelium adhesion and vascular cell adhesion molecule-1 (VCAM-1) expression in lung. Pretreatment of LPS-stimulated vascular endothelial cells with berberine also dose-dependently decreased the number of adhered THP-1 cells and VCAM-1 expression at both RNA and protein levels. Berberine was further confirmed to inhibit the nuclear translocation and DNA binding activity of LPS-activated nuclear factor-kappa B (NF-kappa B). These data demonstrated an additional molecular mechanism for the profound anti-inflammatory effect of berberine.
Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Adesão Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Leucócitos/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Pulmão/irrigação sanguínea , Molécula 1 de Adesão de Célula Vascular/metabolismo , Vênulas/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Sítios de Ligação , Células Cultivadas , Técnicas de Cocultura , DNA/metabolismo , Relação Dose-Resposta a Droga , Regulação para Baixo , Células Endoteliais/imunologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/imunologia , Leucócitos/imunologia , Masculino , NF-kappa B/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Molécula 1 de Adesão de Célula Vascular/genética , Vênulas/imunologiaRESUMO
An accumulating body of evidence incriminates Rho kinase (ROCK) in the pathogenesis of pulmonary hypertension (PH). The therapeutic efficacy of azaindole-1, a novel highly selective and orally active ROCK inhibitor, has not yet been investigated in PH. This study aimed to investigate the effects of azaindole-1 on 1) acute hypoxic pulmonary vasoconstriction (HPV), 2) proliferation of pulmonary arterial smooth muscle cells (PASMCs) and 3) animal models of PH. Azaindole-1 significantly inhibited HPV in isolated, ventilated and buffer-perfused murine lungs and proliferation of primary rat PASMCs in vitro. Azaindole-1 was administered orally from 21 to 35 days after monocrotaline (MCT) injection in rats and hypoxic exposure in mice. Azaindole-1 (10 and 30 mg per kg body weight per day in rats and mice, respectively) significantly improved haemodynamics and right ventricular hypertrophy. Moreover, the medial wall thickness and muscularisation of peripheral pulmonary arteries were ameliorated. Azaindole-1 treatment resulted in a decreased immunoreactivity for phospho-myosin phosphatase target subunit 1 and proliferating cell nuclear antigen in pulmonary vessels of MCT-injected rats, suggesting an impaired ROCK activity and reduced proliferating cells. Azaindole-1 provided therapeutic benefit in experimental PH, and this may be attributable to its potent vasorelaxant and antiproliferative effects. Azaindole-1 may offer a useful approach for treatment of PH.
Assuntos
Compostos Azabicíclicos/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Indóis/uso terapêutico , Animais , Proliferação de Células , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Hemodinâmica , Pulmão/patologia , Masculino , Camundongos , Ratos , Ratos Sprague-Dawley , Telemetria/métodos , Sais de Tetrazólio/farmacologia , Tiazóis/farmacologia , Timidina/química , Resultado do Tratamento , Quinases Associadas a rho/antagonistas & inibidoresRESUMO
AIM: To assess the ability of coronary angiography performed using dual-source computed tomography (DSCT) to evaluate coronary artery disease (CAD) in a population with unselected heart rates and extensive coronary calcification. MATERIALS AND METHODS: Forty-four patients at intermediate to high risk for CAD underwent both DSCT coronary angiography and invasive coronary angiography (ICA) within 30 days. No beta blockers were administered prior to imaging. Image quality and quantitatively stenosis of all coronary segments with a diameter > or = 1.5mm were accessed. Patients were stratified according to mean heart rate (< 70 versus > or = 70 bpm) and heart rate variability (< 10 versus > or = 10 bpm). DSCT detection of coronary stenosis by segment, vessel, and patient characteristics were compared to the reference standard of ICA. RESULTS: Diagnostic accuracy for all patients was high regarding sensitivity (97%), positive predictive value (PPV, 84.2%), and negative predictive value (NPV, 83.3%) but low regarding specificity (45.5%) with a moderate interobserver agreement (Kappa = 0.50). The accuracy for vessel-based diagnosis was high regarding sensitivity (96.6%), specificity (80.8%), PPV (80.3%), and NPV (96.7%). The segment-based diagnostic results revealed a moderate interobserver agreement for image quality and sensitivity, specificity, PPV and NPV for all segments of 66.9, 97.8, 90.8, and 89.9%, respectively. CONCLUSION: DSCT coronary angiography has high diagnostic accuracy in assessing CAD among patients at intermediate to high risk without using heart rate-modulating premedication. DSCT is not superior to ICA for diagnosis of calcified segments.
Assuntos
Calcinose/diagnóstico por imagem , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Eletrocardiografia , Métodos Epidemiológicos , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Interpretação de Imagem Radiográfica Assistida por Computador/métodosRESUMO
OBJECTIVE: Methyltransferase-like 3 (Mettl3), one of "writers" for N6-methyladenosine RNA methylation is determined to participate in a variety of cell biological functions. However, the functions of Mettl3 on tumor growth of glioma remain unknown. Here, we conducted a research to explore the contribution of Mettl3 in the progression of glioma. PATIENTS AND METHODS: To detect the expression level of RNAs, quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed. To access the relative level of proteins, Western blot was conducted. The proliferative ability of glioma cells was detected by CCK-8 assay and colony formation assay. The migration and invasion of glioma cells were determined by wound healing assay and transwell invasion assay. RESULTS: The expression of Mettl3 was significantly downregulated in tumor tissues compared to the adjacent normal tissues. The downregulation of Mettl3 led to the enhancement of glioma cell proliferation, migration, and invasion in vitro, and promoted the tumor growth of glioma cells in vivo. In addition, further investigation confirmed that Mettl3 plays critical roles in the development of glioma by targeting PI3K/Akt pathway. CONCLUSIONS: Our study proves that Mettl3 plays a critical role in the proliferation, migration, and invasion of glioma cells by inactivating PI3K/Akt signaling pathway, providing a novel mechanism of glioma tumorigenesis and raising a new target for the treatment of glioma.
Assuntos
Movimento Celular , Glioma/metabolismo , Metiltransferases/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proliferação de Células , Glioma/patologia , Humanos , Metiltransferases/genética , Transdução de Sinais , Células Tumorais CultivadasRESUMO
OBJECTIVE: We investigated the effects of long non-coding RNA (lncRNA) H19 on glioma cell proliferation, invasion, migration, and apoptosis and the underlying mechanisms. PATIENTS AND METHODS: H19 expression in glioma tissues, para-carcinoma tissues, and glioma cell lines was analyzed by Real-time polymerase chain reaction (RT-PCR). After transfecting U251 and U87MG cells with siRNA-H19, cell proliferation was detected by the cell counting kit-8 (CCK8) assay. Invasion and migration were detected by a transwell assay; cell cycle distribution and apoptosis were measured by flow cytometry analysis; Dvl2, GSK-3ß, cyclin D1, and ß-catenin expressions were detected by RT-PCR and Western blotting. RESULTS: H19 expression in glioma tissues was higher than that in para-carcinoma tissues and associated with poor prognosis in glioma patients. Cell proliferation, invasion, and migration significantly decreased, the percentage of glioma cells in G0/G1 significantly increased, the percentage of glioma cells in the S phase significantly decreased, and apoptosis significantly increased in U251 and U87MG cells transfected with siRNA-H19 compared to those in the siRNA-NC group. Downregulation of H19 decreased DVL2, cyclin D1, and ß-catenin expression and increased GSK-3ß expression. The inhibitory effects of downregulation of H19 on glioma cell proliferation, invasion, and migration were reversed by SKL2001 via the activation of the Wnt/ß-catenin signal pathway, which was further enhanced by inhibition of the Wnt/ß-catenin signal pathway by XAV939. CONCLUSIONS: H19 was overexpressed in glioma tissues and glioma cell lines. Downregulation of H19 inhibited cell proliferation, invasion, and migration, arrested cell cycle progression in the G0/G1 phase, and induced cell apoptosis by restraining activation of the Wnt/ß-catenin signaling pathway in glioma cells. Therefore, H19 is a potential therapeutic target for glioma therapy.
Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/genética , Glioma/patologia , RNA Longo não Codificante/efeitos dos fármacos , RNA Longo não Codificante/genética , Via de Sinalização Wnt/genética , beta Catenina/genética , Adulto , Idoso , Antineoplásicos/farmacologia , Apoptose/genética , Contagem de Células , Linhagem Celular Tumoral , Proliferação de Células , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitose/genética , Invasividade Neoplásica/genética , Prognóstico , Transfecção , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Phosphodiesterase (PDE) inhibitors are currently under investigation for the therapy of pulmonary hypertension. The present study was designed to investigate chronic effects of oral pumafentrine, a mixed selective PDE-3/4 inhibitor, in monocrotaline (MCT)-induced pulmonary hypertension in rats. Treatment with pumafentrine (10 mg.kg(-1) daily) from week 4 to 6 after a single injection of MCT (60 mg.kg(-1)) partially reversed pulmonary hypertension and right heart hypertrophy in rats. In addition, small pulmonary arterial muscularisation, media hypertrophy and decrease in lumen area were largely reversed. Inhibition of smooth muscle proliferation under pumafentrine was demonstrated in vivo as was a pro-apoptotic effect of pumafentrine on vascular cells. Moreover, pumafentrine dose-dependently increased cyclic adenosine monophosphate levels and inhibited proliferation of cultured pulmonary arterial smooth muscle cells. In conclusion, oral pumafentrine partially reverses monocrotaline-induced pulmonary hypertension, lung vascular remodelling and right heart hypertrophy in rats.
Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Hipertrofia Ventricular Direita/tratamento farmacológico , Pulmão/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Miócitos de Músculo Liso/efeitos dos fármacos , Naftiridinas/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Animais , Nucleotídeo Cíclico Fosfodiesterase do Tipo 3/efeitos dos fármacos , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/efeitos dos fármacos , Modelos Animais de Doenças , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/patologia , Hipertrofia Ventricular Direita/induzido quimicamente , Pulmão/patologia , Masculino , Monocrotalina/administração & dosagem , Inibidores da Fosfodiesterase 3 , Inibidores da Fosfodiesterase 4 , RatosRESUMO
BACKGROUND: The myocardial sleeve of the superior vena cava (SVC) has been identified as a potential initiating focus in atrial fibrillation, but information on cell-to-cell linkage at this site is lacking. METHODS AND RESULTS: We examined the SVC in 8 dogs by immunoconfocal and electron microscopy. Cardiomyocytes outlined with vinculin and bearing striations positive for alpha-actinin are found in the proximal segment of the SVC. These cells, grouped in bundles of various orientations according to location, extend cephalically as far as 3 cm from the right atrium (RA)-SVC junction. Comparison between the junctional level and the level 2 cm distal shows that the myocardial layer in the latter is thinner and not as compact and is composed of longer cells (87.3+/-15.7 versus 71.6+/-14.4 micrometer, P<0.01). Gap junctions made of connexin43 (Cx43), Cx40, and Cx45 are aggregated mainly at the intercalated disks, and colocalization of connexins is a common feature throughout the myocardial sleeve. Areas of atypical expression exist, however, characterized by a center of abundant Cx43 labels surrounded by a periphery of scattered tiny Cx40-labeled spots. Although in the ventral subluminal compact myocardial layer, individual cells at both levels are surrounded by similar numbers of cells, the number of aggregation of labeled gap junctions at the distal level is less (2.3+/-0.6 versus 3.7+/-0.9, P<0.01). In addition, electron-microscopic examination demonstrates that the gap junctions at the distal level are smaller in size (0.37+/-0.30 versus 0.55+/-0.34 micrometer, P<0.01). CONCLUSIONS: The myocardial sleeve in the canine SVC is a heterogeneous structure, which could potentially form a substrate for heterogeneity of electrical coupling.
Assuntos
Junções Comunicantes/metabolismo , Miocárdio/metabolismo , Veia Cava Superior/metabolismo , Actinina/análise , Animais , Conexina 43/análise , Conexinas/análise , Cães , Junções Comunicantes/ultraestrutura , Coração/anatomia & histologia , Imuno-Histoquímica , Microscopia Confocal , Microscopia Eletrônica , Miocárdio/ultraestrutura , Veia Cava Superior/ultraestrutura , Fator de von Willebrand/análise , Proteína alfa-5 de Junções ComunicantesRESUMO
A series of 2-[(substituted phenylpiperazin-1-yl)methyl]- and 2-[(substituted phenylpiperidin-1-yl)methyl]-2,3-dihydroimidazo[1,2- c]quinazolin-5(6H)-ones or -5(6H)-thiones, and 3-[(substituted phenylpiperazin-1-yl)methyl]-2,3-dihydroimidazo[1,2-c]quinaz oline derivatives were synthesized, as conformationally restricted analogues of SGB-1534 and ketanserin, for evaluation as alpha-antagonists and antihypertensive agents. Most compounds containing a (substituted phenylipiperazinyl)methyl side chain displayed high binding affinity for alpha 1-adrenoceptor with no significant activity at alpha 2-sites. Compounds having a (substituted phenylpiperazinyl)methyl at the 3-position of 2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one ring system had a better activity than those with the same substituent at the 2-position. Structure-activity relationships for alpha 1-adrenoceptor affinity are presented and indicate that compounds with substitution at the ortho position on the benzene ring of the phenylpiperazine side chain moiety are more potent than those without substitution and/or substitutions at the 3- and 4-positions. Computer-assisted superimposition of SGB-1534 and 20b showed little structural correspondence between the quinazolinone and 2,3-dihydroimidazo[1,2-c]quinazoline nucleus, and specific interactions of these molecular fragments with the receptor protein appear unlikely. Antihypertensive activity was evaluated via intravenous administration of each compound to spontaneously hypertensive rats, and compounds (16a, 16b, 20b, and 28b) illustrated similar efficacy to SGB-1534 when assessed after 6 h. The pA2 value for 16a against phenylephedrine in rat aorta was much higher than that of prazosin. On the basis of alpha 1-adrenoceptor affinity/selectivity in vitro and duration of antihypertensive action in vivo, compounds 20b and 28b warrant further evaluation.
Assuntos
Antagonistas Adrenérgicos alfa/síntese química , Anti-Hipertensivos/síntese química , Quinazolinas/síntese química , Antagonistas Adrenérgicos alfa/metabolismo , Antagonistas Adrenérgicos alfa/farmacologia , Animais , Ligação Competitiva , Pressão Sanguínea/efeitos dos fármacos , Quinazolinas/metabolismo , Quinazolinas/farmacologia , Ratos , Ratos Endogâmicos SHR , Relação Estrutura-AtividadeRESUMO
BACKGROUND: An epidemic of enterovirus 71 (EV71) occurred in Taiwan from April to December of 1998, with two peaks, one in June and the other in October. Many enteroviruses were isolated in our laboratory from 258 cases during this outbreak. Approximately half of the enteroviruses isolated were EV71 and one fifth were coxsackievirus A16. OBJECTIVES: To analyze laboratory findings in the EV71 epidemic of 1998 in Taiwan, various EV71 specimens in different cell lines were examined. In addition, genetic analysis of 5' non-coding region (NCR) was performed to analyze the strain variation in this outbreak. RESULTS: The cytopathic effect induced by EV71 was observed 2-13 (mean of 4.5) days post-inoculation in Vero cells and 4-15 (mean of 6.6) days in green monkey kidney (GMK) cells inoculated with throat swabs. Of the total positive EV71 cases, virus was most frequently obtained from throat swabs (91.7%), less from stools (64.8%), and none from cerebral spinal fluid (CSF). Molecular analyses of EV71 by sequencing the 5' NCR of 34 strains obtained from different clinical categories and various geographic areas showed that their sequences differed (0-13 bp in 681 bp sequenced) by approximately 0-2%. The sequences of these isolates differed from EV71 prototype BrCr or MS strain by 17.5-19%, with the exception of two samples which exhibited nucleotide variation by only 8.9 and 8.2%, when compared to the MS strain. CONCLUSION: EV71 was most frequently isolated from throat swab specimens in Vero cells. The molecular analyses of the 5' NCR of EV71 revealed that most isolates from this epidemic belonged to a group of closely related clones and only two were in a different group which was clustered with the EV71 MS strain.
Assuntos
Surtos de Doenças , Infecções por Enterovirus/epidemiologia , Enterovirus/isolamento & purificação , Adolescente , Animais , Linhagem Celular , Criança , Pré-Escolar , Chlorocebus aethiops/virologia , Enterovirus/genética , Infecções por Enterovirus/líquido cefalorraquidiano , Infecções por Enterovirus/mortalidade , Infecções por Enterovirus/virologia , Fezes/virologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Faringe/virologia , Filogenia , Polimorfismo Genético , RNA não Traduzido/genética , RNA Viral/genética , Reto/virologia , Estações do Ano , Análise de Sequência de RNA , Taiwan/epidemiologia , Células VeroRESUMO
There are many evidences suggest that ascorbate in the extracellular space can affect glutamate concentration in the rat's brain. In this report, we studied how ascorbate in microdialysis perfusion medium affected glutamate level at the striatum in freely-moving rats. Three perfusion mediums were used: 0, 250, and 400 microM of ascorbate in perfusion medium. The extracellular basal concentrations of glutamate were determined to be 1.29+/-0.52 microM for the no ascorbate group, 0.86+/-0.35 microM for the low ascorbate group and 4.76+/-1.48 microM for the high ascorbate group. By using 400 microM of ascorbate in a perfusion medium, we found that the extracellular basal concentration of glutamate significantly increased and its in vivo recovery significantly decreased. This indicated that ascorbate concentration in a perfusion medium was important and must be carefully considered while using microdialysis technique to monitor glutamate concentration in vivo.
Assuntos
Ácido Ascórbico/farmacologia , Circulação Cerebrovascular , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Ácido Glutâmico/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Microdiálise , Animais , Ácido Ascórbico/metabolismo , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The zero-net flux microdialysis method was used to determine (1) the basal concentration of dopamine (DA) in the extracellular space, and (2) the in vivo recovery of Da in the striatum and the medial prefrontal cortex by using three different kinds of perfusion medium. They were, (a) commercial Ringer's solution, (b) low Ca2+ Ringer's solution, and (c) artificial cerebrospinal fluid (aCSF). Our results not only support previous findings that the high Ca2+ concentration in the perfusion medium could increase the baseline concentration of DA in the dialysate, which was collected from extracellular space through dialysis probe; but also provides evidence that this baseline increase was primarily due to an increase of basal DA concentration, and not from the increase of the in vivo recovery. Additionally, there was no significant difference in the basal DA concentration by using either commercial Ringer's solution or aCSF. This indicates that both commercial Ringer's solution and aCSF are suitable as good perfusion medium to determine the basal DA in the rat's brain.
Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Meios de Cultura/farmacologia , Dopamina/metabolismo , Espaço Extracelular/metabolismo , Córtex Pré-Frontal/metabolismo , Córtex Visual/metabolismo , Animais , Cálcio/farmacologia , Masculino , Microdiálise , Ratos , Ratos Sprague-DawleyRESUMO
We evaluated the effects of two anesthetics on the cocaine-induced electroencephalographic (EEG) desynchronization in male, Sprague-Dawley rats. One group was anesthetized with chloral hydrate (400 mg/kg, i.p., 80 mg/kg/h i.v. supplement; group A). The other group was anesthetized with pentobarbital sodium (50 mg/kg, i.p., 10 mg/kg/h i.v. supplement; group B). The degree of EEG desynchronization after cocaine administration (1.5 mg/kg, i.v.) was expressed as an increase in the mean power frequency (MPF) and a decrease in the root mean square (RMS). These maximal increases and decreases were observed to be larger in group A (MPF: 43.3 +/- 7.0% increase; RMS: 47.4 +/- 5.0% decrease) than in group B (MPF: 17.8 +/- 3.6% increase; RMS: 19.2 +/- 2.5% decrease). Our laboratory previously proved that dopaminergic neurotransmission at the medial prefrontal cortex (mPFC) participated in the cocaine-induced EEG desynchronization and that both D-1 and D-2 receptors were involved in the process. Therefore, in vivo microdialysis coupled with high performance liquid chromatography was used to quantify the changes of extracellular dopamine (DA) concentrations at the mPFC for 90 minutes at 10 minute intervals after 1.5 mg/kg cocaine i.v. injection. The extracellular DA increases in both groups was rapid and reached the maximal peak within 10 min. There was no significant difference in the maximal increase of DA between groups (group A: 375.2 +/- 35.77% versus group B: 332.2 +/- 16.69% over basal value). These results suggest that different anesthetics may differentially affect cocaine-induced EEG desynchronization and this difference has no bearing on the DA response in the mPFC.
Assuntos
Hidrato de Cloral/farmacologia , Cocaína/farmacologia , Eletroencefalografia/efeitos dos fármacos , Lobo Frontal/efeitos dos fármacos , Pentobarbital/farmacologia , Animais , Dopamina/metabolismo , Lobo Frontal/fisiologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The defect excitation and nonuniform melting of a two-dimensional Coulomb cluster with 300 charged particles (interacting with 1/r type force) in a uniform neutralizing background are studied numerically. Intrinsic defects exist around the outer circular shells surrounding the inner triangular lattice. They are the source regions for anisotropic particle thermal vibrations and then cyclic hoppings with the increasing temperature. It leads to the nonuniform melting associated with the thermal motion of intrinsic defects, and then the thermal excitation of dislocation pairs and disclinations. The intrinsic defect free center core has the highest melting temperature. It shows the sequential losses of translational and then orientational orders.
RESUMO
Measurement of amino acid levels in the cerebrospinal fluid (CSF) of children with various neurological disorders was performed with high performance liquid chromatography (HPLC). Glutamate increased in patients with bacterial meningitis, aseptic meningitis and encephalitis. Aspartate increased in bacterial meningitis and seizure disorders. Glycine increased in both bacterial and aseptic meningitis. Taurine increased in bacterial meningitis and encephalitis. GABA, the main inhibitory amino acid, increased in encephalitis. Excitatory and inhibitory amino acids are richly distributed in brain tissue and are related to neuron activity. Changes in amino acid levels in the CSF may reflect the pathologic state and severity of brain insults, and may be useful in monitoring disease processes. Further study is necessary to determine whether CSF aminos acid levels have a role in practical clinical application.
Assuntos
Aminoácidos/líquido cefalorraquidiano , Encefalite/líquido cefalorraquidiano , Meningite/líquido cefalorraquidiano , Neurotransmissores/líquido cefalorraquidiano , Convulsões/líquido cefalorraquidiano , Biomarcadores , Estudos de Casos e Controles , Criança , Aminoácidos Excitatórios/líquido cefalorraquidiano , HumanosRESUMO
Different MR imaging patterns of cerebral fat embolism have been reported in the literature without a systematic review. Our goal was to describe the patterns, explore the relationship between disease course and the imaging patterns, and discuss the underlying mechanism. We reveal 5 distinctive MR imaging patterns: 1) scattered embolic ischemia occurring dominantly at the acute stage; 2) confluent symmetric cytotoxic edema located at the cerebral white matter, which mainly occurs at the subacute stage; 3) vasogenic edematous lesions also occurring at the subacute stage; 4) petechial hemorrhage, which persists from the acute to the chronic stage; and 5) chronic sequelae, occurring at late stage, including cerebral atrophy, demyelinating change, and sequelae of infarction or necrosis. Underlying mechanisms of these imaging patterns are further discussed. Recognition of the 5 evolving MR imaging patterns of cerebral fat embolism may result in adjustment of the appropriate management and improve the outcome.