Effect of diltiazem on exercise tolerance in patients with stable coronary artery disease and hypertension.

The present study aimed to investigate the effect of diltiazem on cardiovascular risk and exercise tolerance in patients with stable coronary artery disease and hypertension. From 2016 to 2018, 80 patients with stable coronary artery disease (5 < Gensini score < 20) and hypertension were enrolled into the present study. These patients were randomly divided into two groups: diltiazem group (Dil, 90 mg, bid), and control group (angiotensin-converting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB) for reducing blood pressure and ß-receptor blockers for controlling heart rate). Liver and kidney function, heart rate variability (HRV), blood pressure variability (BPV) and bicycle exercise were measured at baseline and after six months. The incidence of cardiovascular events (re-hospitalization due to angina pectoris, acute myocardial infarction, and cardiogenic death) was also assessed. The differences in all indexes at baseline between these two groups were not statistically significant (P > 0.05, respectively). After six months of treatment, both groups of patients had significant improvements in HRV, BPV and exercise tolerance compared that before treatment (p < 0.05). The difference in the decrease in systolic blood pressure, improvement of HRV and BPV, and cardiovascular events between these two groups was not statistically significant (P = 0.588, 0.431, 0.152, 1.000, respectively). But the Dil group was significantly better than the control group in degree of heart rate decline, diastolic blood pressure decline, and improvement of ST segment depression (P < 0.001), and the improvement in exercise tolerance was also better than that of the control group. We found that diltiazem compared with ACEI/ARB and ß-receptor blockers can further improve the exercise tolerance of patients with stable coronary artery disease and hypertension.

Comparison of valsartan and benazepril when combined with atorvastatin in protecting patients with early cardio-renal syndrome (CRS).

OBJECTIVE: The aims to investigate the different protective effects of valsartan and benazepril when combined with atorvastatin in the cardio-renal functions of cardio-renal syndrome (CRS) patients. PATIENTS AND METHODS: A total of 200 early CRS patients were enrolled in the present study, including 104 males and 96 females, with an average age of 62.2 ± 7.7 years. The same group of patients were set as the control group prior to treatment, and then randomly divided into two groups; the A group was treated with valsartan (80 mg/d) and atorvastatin (20 mg/d); the B group was treated with benazepril (10 mg/d) and atorvastatin (20 mg/d). The treatment period was 24 months. RESULTS: The clinical efficacy and clinical events were observed and the following parameters of each patient were measured before and after treatment: 24h urine protein; creatinine clearance; serum brain natriuretic peptide (BNP); high sensitivity C-reactive protein (hsCRP); blood lipid level; liver function and ejection fraction (EF) value. Compared with the control group, the clinical symptoms of the treatment groups were improved with decreased blood lipid levels, significantly decreased serum BNP and hsCRP levels and significantly increased EF values and creatinine clearance rates (p < 0.01). The differences between the two treatment groups were not statistically significant. The number of patients that stopped treatment due to the development of a cough was significantly higher in the B group than the A group (p < 0.01). CONCLUSIONS: When combined with atorvastatin, both valsartan and benazepril effectively improved the cardio-renal functions of early CRS patients. There was no significant difference between the two treatments however, valsartan appeared to be better tolerated by patients.

Protective effects of valsartan and benazepril combined with atorvastatin on cardiorenal syndrome in rats.

OBJECTIVE: To study the protective effects of valsartan (Val) and benazepril, (Ben) combined with atorvastatin (Ato), on cardiorenal syndrome (CRS) in rats. MATERIALS AND METHODS: After establishing cardiorenal syndrome model, the rats were randomly divided into control, Ato, Ben+Ato and Val+Ato groups, which were treated with corresponding drugs. Before and 4 weeks after treatment, the serum creatinine (Scr), blood urea nitrogen (BUN), type-B natriuretic peptide (BNP), aldosterone (ALD), angiotensin (Ang) II, C-reactive protein (CRP), blood lipid and urine protein were determined. The left ventricular systolic pressure (LVSP), left ventricular diastolic pressure (LVDP), left ventricular end-diastolic pressure (LVEDP) as well as maximum rising and falling rates of left ventricular pressure (±dp/dtmax) were detected. The heart weight index was also determined. RESULTS: 6, 3, 1 and 2 rats control, Ato, Ben+Ato and Val+Ato groups died, respectively. Compared with control group, the serum Cr, BUN, BNP, ALD, CRP and urinary protein levels in treatment groups significantly decreased, and the blood lipid level, LVDP, LVEDP and heart weight index significantly decreased, with increased LVSP. No statistically significant difference was observed among treatment groups. CONCLUSIONS: Valsartan and benazepril, combined with atorvastatin, can have significant protective effects on cardiorenal functions of rats with CRS, with no significant difference between these two drugs.

DNA hypermethylation regulates the expression of members of the Mu-class glutathione S-transferases and glutathione peroxidases in Barrett's adenocarcinoma.

BACKGROUND: The accumulation of reactive oxygen species and subsequent oxidative DNA damage underlie the development of Barrett's oesophagus (BO) and its progression to Barrett's dysplasia (BD) and adenocarcinoma (BAC). METHODS: The promoter regions of 23 genes of the glutathione S-transferase (GST) and glutathione peroxidase (GPX) families were systematically analysed. Quantitative bisulfite pyrosequencing, real-time RT-PCR, western blot and immunohistochemical (IHC) analysis methods were utilised in this study. RESULTS: 14 genes were identified that have CpG islands around their transcription start sites: GSTs (GSTM2-M5, GSTA4, GSTP1, GSTZ1, GSTT2, GSTO1 and GSTO2) and GPXs (GPX1, GPX3, GPX4 and GPX7). Analysis of an initial set of 20 primary samples demonstrated promoter DNA hypermethylation and mRNA downregulation of GPX3, GPX7, GSTM2, GSTM3 and GSTM5 in more than half of the BAC samples. Further analysis of 159 primary human samples (37 normal, 11 BO, 11 BD and 100 BACs) indicated frequent hypermethylation (>or=10% methylation) of GPX3 (62%), GPX7 (67%), GSTM2 (69.1%) and GSTM3 (15%) in BACs. A significant inverse correlation between DNA methylation and mRNA expression level was shown for GPX3 (p<0.001), GPX7 (p = 0.002), GSTM2 (p<0.001) and GSTM5 (p = 0.01). Treatment of oesophageal cancer cell lines with 5-aza-2'-deoxycytidine and trichostatin-A led to reversal of the methylation pattern and re-expression of these genes at the mRNA and protein levels. The IHC analysis of GPX3, GPX7 and GSTM2 on a tissue microarray that contained 75 BACs with normal squamous oesophageal samples demonstrated an absent to weak staining in tumours (52% for GPX3, 57% for GPX7 and 45% for GSTM2) and a moderate to strong immunostaining in normal samples. CONCLUSION: Epigenetic inactivation of members of the glutathione pathway can be an important mechanism in Barrett's tumourigenesis.

Bromodeoxyuridine induces p53-dependent and -independent cell cycle arrests in human gastric carcinoma cell lines.

OBJECTIVES: This study was designed to clarify the effects of bromodeoxyuridine (BrdU) on cell cycle progression and induction of apoptosis, and to demonstrate the role of P53 in these processes. METHODS: We continuously exposed four human gastric carcinoma cell lines with different P53 status (P53 wild-type AGS and MKN-45, P53-mutated MKN-28 and P53-deleted KATO-III) to BrdU in asynchronous and synchronous culture conditions, and analyzed DNA histograms of apoptotic and nonapoptotic cells determined by static DNA cytofluorometry. RESULTS: Continuous exposure to 20 microM BrdU after synchronization with hydroxyurea resulted in S phase delay and G1 arrest in MKN-45 and an increase of apoptosis in the first S/G(2) phase in AGS and MKN-45. In the second S phase, a delay of 3-6 h was observed in all the four cell lines. In asynchronous cultures, continuous exposures to 20 and 200 microM BrdU for 72 h or more caused growth suppression with G(1) and G(2) arrests, respectively, in all the cell lines. CONCLUSIONS: These data suggested that the BrdU-induced growth suppression of the cell lines examined was mainly caused by cell cycle arrest rather than cell death, and that the cell cycle arrests in the first S and G(1) phases (elicited by BrdU in the single DNA strand) and those in the second S, G(2) and G(1) phases (elicited by BrdU in the double DNA strands) were mediated by p53-dependent and -independent pathways, respectively.