RESUMEN
OBJECTIVE: To explore the impact of patient compliance on the long-term outcomes in hypertensive patients receiving hydrochlorothiazide (HCTZ) based combination therapy with spironolactone or captopril. METHODS: A total of 853 patients with mild to moderate hypertension were recruited and randomly divided into HCTZ group (HCTZ 12.5 mg q.d), spironolactone group (HCTZ 12.5 mg q.d and spironolactone 20 mg q.d), and captopril group (HCTZ 12.5 mg q.d and captopril 25 mg bid) after 2-week placebo washout period and 6-week loading period for HCTZ. Since the efficacy of combination therapy was proven to be better than monotherapy 1 year after therapy beginning, patients in HCTZ group were randomly assigned to spironolactone group or captopril group. The patients were followed up for 4 years. Patients were divided to compliance (n = 424) or non-compliance group (n = 429) according test drug taking questionnaire. During the follow-up time, the blood pressure and the outcomes were recorded monthly, and blood biochemical parameters were determined once a year. RESULTS: At the end of follow up, incidence of cardio-cerebral vascular events was significantly lower in compliance group (2 fatal, 8 non-fatal) than that in noncompliance group (7 fatal, 21 non-fatal, P < 0.05). Systolic blood pressure [-(19.4 +/- 20.6) mm Hg, 1 mm Hg = 0.133 kPa] and diastolic blood pressure [-(10.7 +/- 13.5) mm Hg] were significantly reduced compared values at baseline and noncompliance group (all P < 0.001) while the reduction did not reach statistically significance in noncompliance group [-(7.3 +/- 18.2) mm Hg and -(3.5 +/- 10.2) mm Hg, all P > 0.05 vs. baseline]. The serum BUN, Cr and UA levels in the compliance group were significantly higher and the serum K(+), CHO, LDL-C level were significantly lower than baseline values. The serum BUN, UA levels in the compliance group were significantly higher while the serum K(+), cholesterol levels were significantly lower than those in the noncompliance group (all P < 0.05). CONCLUSIONS: This study indicates that patient compliance could affect the long-term outcome and antihypertensive efficacy in hypertensive patients receiving HCTZ based combination therapy with spironolactone or captopril.
Asunto(s)
Hipertensión/tratamiento farmacológico , Cooperación del Paciente , Anciano , Antihipertensivos/uso terapéutico , Captopril/uso terapéutico , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Hidroclorotiazida/uso terapéutico , Masculino , Persona de Mediana Edad , Espironolactona/uso terapéutico , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the chronic efficacy of low-dose hydrochlorothiazide (HCTZ) in patients with mild-to-moderate hypertension. METHODS: After a 2-weeks placebo run-in period, 232 patients with mild or moderate hypertension were recruited and received HCTZ (12.5 mg once daily) therapy for one year. Patient compliance and blood pressure were monitored and serum BUN, Cr, glucose, electrolytes, and lipids were measured before, 6 weeks and 1 year after treatment. RESULTS: (1) Reduction of SBP, DBP and MAP were more significantly at 1 year [(10.45 +/- 17.28) mm Hg, (8.45 +/- 11.06) mm Hg, (9.12 +/- 10.88) mm Hg] than that at 6 weeks post therapy [(6.01 +/- 16.05) mm Hg, (2.90 +/- 10.33) mm Hg, (3.94 +/- 10.68) mm Hg, all P < 0.05]. Blood pressure were reduced to normal in 35.1% patients at 1 year and in 20.3% patients at 6 weeks (P < 0.05). (2) No patient developed diabetes mellitus or hypokalemia during therapy while the serum uric acid at 1 year post therapy was significantly higher than that at before therapy (P < 0.05). CONCLUSION: The study indicates that low dose HCTZ is an effective and safe antihypertensive agent for patients with mild-to-moderate hypertension and uric acid changes during therapy need to be monitored.
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Antihipertensivos/administración & dosificación , Hidroclorotiazida/administración & dosificación , Hipertensión/tratamiento farmacológico , Adulto , Anciano , Presión Sanguínea , Femenino , Humanos , Hipertensión/fisiopatología , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
MicroRNAs (miRNAs), as a class of naturally occurring small non-coding RNAs, play profound and pervasive roles in cancer initiation and progression. Extensive decrease in miRNA levels are frequently observed in human cancers, indicating that miRNAs may function intrinsically in tumor suppression. However, the underlying mechanisms of miRNA interactions with cellular pathways are still unclear. The expression of miR-34b in non-small cell lung cancer (NSCLC) tissues was detected using quantitative real-time PCR. The relations between miR-34b expression levels and pathological stage or lymph node metastasis were assessed using the Spearman correlation test. For in vitro studies, lung cancer cells were transfected with double stranded synthetic miRNA mimics (syn-hsa-miR-34b miScript miRNA) and scrambled controls. Immunohistochemistry was used to validate the related downstream proteins of miR-34b. The expression of miR-34b was lower in NSCLC tissues compared to that in pericarcinous tissues of lung cancer. Additionally, the Spearman correlation test showed that lower miR-34b expression was correlated with higher lymph node metastasis. In vitro gain-of-function experiments indicated that miR-34b suppressed cell proliferation by inducing cell apoptosis. IHC results showed association between lower miR-34b and overexpression of phospho-Met, p53 (phospho S392) and Mdm2. Consistent with the opposing correlation between the expression of miR-34b and lymph node metastasis in NSCLC, miR-34b may play an important role in NSCLC progression. Furthermore, miR-34b downregulates Met, with subsequent changes of downstream p53 (phospho S392) and Mdm2, and inversely p53 upregulates miR-34b in a feedback loop, which provides new insights into the roles of miR-34 family members in the regulation of signaling pathways of NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Genes Supresores de Tumor , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Apoptosis/genética , Carcinoma de Pulmón de Células no Pequeñas/secundario , Proliferación Celular , Regulación hacia Abajo , Retroalimentación Fisiológica , Femenino , Humanos , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , MicroARNs/genética , Persona de Mediana Edad , Proteínas Proto-Oncogénicas c-mdm2/biosíntesis , Transducción de Señal , Proteína p53 Supresora de Tumor/metabolismoRESUMEN
OBJECTIVE: Arrestins act as mediators of G protein-coupled receptor (GPCR) desensitization and trafficking, also actin as a scaffold for many intracellular signaling network. The role that ß-arrestin 1 plays in gastric cardiac adenocarcinoma (GCA) and its clinicopathologic significance are untouched. METHODS: Fifty patients with gastric cardiac adenocarcinoma were retrospectively enrolled and ß-arrestin 1 was detected using immunohistochemistry in tissue samples. RESULTS: Nuclear expression of ß-arrestin 1 was observed in 78% of GCA samples (39/50) and cytoplasmic expression in 70% (35/50). ß-arrestin 1 could be found in both nucleus and cytoplasm of 54% GCA (27/50) or in either of them in 94% (47/50). ß-arrestin 1 protein positivity in well/ moderately differentiated carcinomas was significantly higher than that in poorly differentiated carcinomas (P=0.005). We found increased expression of ß-arrestin 1 in cytoplasm was correlated with lymph nodal metastasis (P=0.002) and pathological lymph nodal staging (P=0.030). We also found ß-arrestin 1 to be over-expressed in glandular epithelia cells of mucinous adenocarcinoma, a tumour type associated with an adverse outcome of gastric cardiac adenocarcinoma (P=0.022). CONCLUSION: ß-arrestin 1 is over-expressed in the nucleus and/or cytoplasm of gastric cardiac adenocarcinoma. However, ß-arrestin 1 has no relationship with the prognosis of gastric cardiac adenocarcinoma (P>0.05). Our data imply that ß-arrestin 1 in cytoplasm may be involved in differentiation and metastasis of gastric cardiac adenocarcinoma.
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Adenocarcinoma Mucinoso/patología , Adenocarcinoma/patología , Arrestinas/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Gástricas/patología , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/mortalidad , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/mortalidad , Tasa de Supervivencia , beta-Arrestina 1 , beta-ArrestinasRESUMEN
AIM: To observe the effect and mechanism of scopolamine on morphine(Mor)-induced mice dependence. METHODS: The Mor-dependent mice model was established by intraperitoneal (ip) administered Mor for seven days. Pain threshold, times of jump and hippocampus intracellular free calcium ion concentration ([Ca2+]i) were determined by the heat plate test, naloxone (Nal)-precipitated jumping response and flow cytometry, respectively. RESULTS: The pain threshold of Mor-dependent mice decreased significantly while there was a marked increase in times of jump, the rate of jumping animals and hippocampus [Ca2+]i. Co-administered scopolamine, the pain threshold of Mor-dependent mice increased significantly; the number of jump, the rate of jumping animals and hippocampus [Ca2+]i all decreased significantly. CONCLUSION: Scopolamine could antagonize the Mor-induced mice dependence, which could be related to decreasing the levels of brain intracellular free calcium.