Cisplatin, Cis-diamminedichloroplatinum (CDDP), is a platinum-based chemotherapy drug, and its chemotherapeutic use is restricted by nephrotoxicity. Inflammatory and apoptotic mechanisms play a central role in the pathogenesis of CDDP-induced acute kidney injury (AKI). The aim of this study was to compare the therapeutic potential of candesartan, angiotensin II receptor blocker, versus bone marrow-derived mesenchymal stem cells (BM-MSCs) in a rat model of CDDP-induced nephrotoxicity. Adult male Wistar rats (n ¼ 40) were divided into four groups; Normal control: received saline injection, CDPP group: received CDDP injection (6 mg/kg single dose), Candesartan group: received candesartan (10 mg/kg/day) for 10 days þ CDDP at day 3, and Stem cells group: received CDDP þ BM-MSCs intravenously one day after CDDP injection. The rats were sacrificed seven days after CDDP injection. Significant elevation in serum creatinine and urea, renal levels of tumor necrosis factor (TNF)-a and monocyte chemoattractant protein (MCP)-1, renal expressions of nuclear factor kappa B (NF-kB), p38-mitogen-activated protein kinase (MAPK), caspase-3 and Bcl-2-associated x protein (Bax) were found in CDDP-injected rats when compared to normal rats. Both candesartan and BM-MSCs ameliorated renal function and reduced significantly the inflammatory markers (TNF-a , NF-jB, p38-MAPK and MCP-1) and apoptotic markers (caspase-3 and Bax) in renal tissue after CDDP injection. Candesartan as well as BM-MSCs have anti-inflammatory and anti-apoptotic actions and they can be used as nephroprotective agents against CDDP-induced nephrotoxicity. BM-MSCs is more effective than candesartan in amelioration of AKI induced by CDDP.

Objective : To assess the impact of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on risk of stroke in patients with or at high-risk of cardiovascular diseases (CVD) Design and method: A meta-analysis of randomized-controlled trials was performed. Bibliographic databases were searched until 31 July 2019 for ACEIs & ARBs trials versus placebo or active therapy & supported with head-to-head trials in participants with or at high-risk of CVD. Only trials with at least 100 participants & at least one year's follow-up were included. Trials were excluded if they were redacted or combined ACEIs with ARBs. Outcome was fatal & non-fatal stroke: including ischaemic and haemorrhagic stroke excluded transient ischaemic attack (TIA). Dichotomous outcome data was analysed using risk ratio (RR) measure and its 95% confidence interval (CI) with random-effects model. A random-effects meta-regression analysis was performed to explore role systolic blood pressure (SBP) reduction achieved. Results: This study included 72 trials with 297,451 patient-years of follow-up. Compared with placebo, both ACEIs and ARBs reduced the risk of stroke by 14% & 9%; respectively (ACEIs: RR, 0.86; 95% CI, 0.76–0.98; p = 0.02 & ARBs: RR, 0.91; 95% CI, 0.86–0.97; p = 0.003). No difference was observed when ACEIs & ARBs were compared with active (ACEIs: RR, 1.14; 95% CI, 1.04–1.26; p = 0.006 & ARBs: RR, 0.94; 95% CI 0.79–1.12; p = 0.50). Pooled data from trials comparing ARBs to ACEIs showed no difference in stroke event rates (RR, 0.96; 95% 0.87–1.06; p = 0.42). A meta-regression analysis revealed that the relative risk reduction of stroke by ACEIs (p = 0.03) and ARBs (p = 0.01) therapy was proportional to the magnitude of SBP reduction achieved. Conclusions: In patients with or at high-risk of CVD, evidence from placebo-controlled trials & head-to-head trials demonstrated that ARBs to be as effective as ACEIs on preventing of stroke. Cerebro-protective effect of ARBs & ACEIs therapies are strongly associated with BP reduction.

Objective: Background: The association between depression and cardiovascular disease (CVD) is well documented. However, depression has also been proposed to be involved in the pathological pathways linking the main risk factors of CVDs. Several studies including one meta-analysis have suggested that depression may be an independent risk factor for hypertension. Objective:To evaluate the relationship between depression and incident hypertension Design and method: Bibliographic databases Medline, EMBASE, Web of Science and PsycINFO without language restrictions were searched from 2005 up to 2019. We included prospective cohort studies, involving normotensive subjects at baseline with diagnosis of depression measured using clinical evaluation or a standardised psychometric tool and recorded as a dichotomous variable. Outcome was new-onset hypertension. We excluded studies that enrolled participants with a history of antihypertensive medication at the time of study initiation. Methodological quality was assessed using the Newcastle-Ottawa Scale. Pooled hazard ratios (HR) were calculated using inverse variance method in random effects models. Results: We identified five studies with a total of 201,886 participants and an average follow-up of 7.52 years. Out of the five studies, only two reported a positive association between depression and incident hypertension. The pooled effect of three studies included in the meta-analysis showed that depression was associated with 20% increased risk of hypertension (HR = 1.20, 95%CI 1.01–1.43) but with a substantial heterogeneity (I2 = 70%). One study reported a null result for a dose-response relationship between depressive symptoms and incident hypertension. Quality analysis showed increased risk of bias notably in the ascertainment of the outcome as most studies relied on self-report and/or prescription of antihypertensive medication as a proxy for hypertension. Conclusions: Our findings indicate a possible increased risk of hypertension with depressive symptoms, but this result is limited by heterogeneity and ascertainment bias in the studies included.

Background: Recent theory suggests that antihypertensive medications may be useful as repurposed treatments for mood disorders, however, empirical evidence is inconsistent Objective: We aimed to assess the risk of depression incidence as indicated by first-ever prescription of antidepressant in patients newly exposed to antihypertensive monotherapy and whether there is a dose-response relationship. Method: This study enrolled 2406 new users of antihypertensive monotherapy aged between 18 and 80 years with no previous history of antidepressant prescriptions. The exposure period (EP) to antihypertensive medication was fixed at one year starting from the first date of antihypertensive prescription between Jan 2005 and Mar 2012 and extended up to 12 months. Follow-up commence after the EP until March 2013. To test for dose-response relationship the cumulative defined daily dose (cDDD) of antihypertensive during the EP were stratified into tertiles. Cox proportional hazards models were used to estimate hazard ratios (HR) for depression incidence. Results: Among the five major classes of antihypertensive medications, calcium channel blocker (CCB) had the highest risk of developing depression after adjusting for covariates (HR = 1.40 95%CI 1.11,1.78) compared to angiotensin-converting enzyme inhibitor (ACEI). Angiotensin-receptor blocker (ARB) treatment showed higher risk of depression incidence with tertile 2(HR= 1.46, 95%CI 0.88,2.44) and tertile 3 (HR= 1.75, 95%CI 1.03,2.97) compared to tertile 1 of cDDD. Conclusion: Our findings confirmed previous evidence suggesting that CCB is associated with increased risk of depression incidence compared to ACEI. Risk of developing depression is also linked to ARB, though it might be dose dependent.

Objective: To evaluate the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) on all-cause & cardiovascular (CV) mortality in patients with or at high-risk of CV diseases Design and method: We performed a meta-analysis with data from randomized-controlled trials. Bibliographic databases were searched until 31 July 2019 for ACEIs & ARBs trials versus placebo or active therapy & supported with head-to-head trials in people with or at high-risk of CV diseases. Only trials with at least 100 participants and at least one year of follow-up were included. Studies were excluded if they were redacted or combined ACEIs with ARBs. Outcomes were all-cause mortality & CV mortality. Dichotomous outcomes data were analysed using risk ratio (RR) measure and its 95% CI with random-effects model. A random-effects meta-regression analysis was performed to explore role systolic blood pressure (SBP) reduction achieved. Results: 97 trials with 317,984 patient-years of follow-up were included. Patients were randomly assigned to ACEIs in 42 trials, ARBs in 45 trials compared with control (placebo or active) & 10 trials compared ACEIs and ARBs head-to-head. Compared with control, those assigned to ACEIs had a 5% lower all-cause (RR, 0.95; 95% 0.91–0.98; p = 0.003) & 9% lower CV (RR, 0.91; 95% CI 0.86–0.97; p = 0.002) mortality. Whereas, no all-cause (RR, 0.99; 0.96–1.02; p = 0.55) & CV (RR, 0.99; 95% CI 0.94–1.05; p = 0.73) mortality could be demonstrated with ARBs therapy. However, head-to-head trials exhibited no difference between ARBs & ACEIs on either all-cause (RR, 1.03; 95% CI 0.98–1.08; p = 0.20) or CV (RR, 1.04; 95% CI 0.98–1.10; p = 0.16) mortality. The meta-regression analysis suggested that the effect of ACEIs on all-cause mortality and CV death was due to reduction in systolic blood pressure (SBP); p-value is 0.01 & 0.02; respectively. This did not appear to be the case for ARBs. Conclusions: ACEIs appear effective in reducing mortality; the evidence for ARBs appears less secure. The effect of ACEIs are associated with and may be due to a reduction in SBP.