Effect of folic acid supplementation on the change of plasma S-adenosylhomocysteine level in Chinese hypertensive patients: a randomized, double-blind, controlled clinical trial.

The relationship between folic acid and S-adenosylhomocysteine (SAH) is controversial. This study aims to explore the effect of different doses of folic acid supplementation on SAH levels in hypertensive patients and the modification of methylene-tetrahydrofolate reductase (MTHFR) C677T gene polymorphism. A randomized, double-blind, controlled clinical trial was conducted. Hypertensive patients aged 45-75 years without a history of stroke and cardiovascular disease were selected, who were randomly assigned to one of 8 dose groups. This trial has been registered with Trial Number: ChiCTR1800016135. In the total population, folic acid supplementation of 0.4-2.0 mg/day had no effect on SAH level (ß = 0.47, 95% CI: -0.86-1.79, p = 0.491), while folic acid supplementation of 2.4 mg/day significantly increased SAH level (ß = 1.93, 95% CI: 0.22-3.64, p = 0.027). Stratified analysis found that MTHFR C677T genotype CC supplemented with 2.4 mg/day folic acid had no effect on SAH level (ß = 0.30, 95% CI: -2.74-3.34, p = 0.847), while CT and TT genotype supplemented with 2.4 mg/day folic acid showed a significant increase in SAH level (CT: ß = 2.98, 95% CI: 0.34-5.62, p = 0.027; TT: ß = 3.00, 95% CI: -0.51-6.51, p = 0.095; CT combined with TT: ß = 2.99, 95% CI: 0.90-5.09, p = 0.005). In conclusion, supplementation of 2.4 mg/day folic acid can lead to increased SAH levels, especially in MTHFR C677T genotype CT and TT.

Laterality of Attentional Networks in Patients With Cerebral Small Vessel Disease.

Introduction: Problems with attention are common in patients with cerebral small vessel disease (CSVD). The normal human brain exhibits functional and structural asymmetry. However, it is unknown whether there is lateralization of attention in patients with CSVD. Objective: This study aims to investigate attention separately in both cerebral hemispheres in patients with CSVD using the computer-based Lateralized Attention Network Test-Revised (LANT-R). Methods: The total number of subjects included was 58, which includes the CSVD (N = 35) and healthy control (HC, N = 23) groups. All subjects completed the LANT-R paradigm and neuropsychological background tests. Results: The results indicate that there is an left hemisphere (LH) lateralization in orienting network efficiency in the HC group. However, this lateralization was not apparent in the CSVD group. Furthermore, the difference between groups was significant (interaction P = 0.02). In addition, the scores of subjects in the CSVD group are lower in several cognitive domains, including attention function, memory function, information processing speed, and executive function, compared with the controls. Conclusion: Patients with CSVD change in the lateralization of attention compared with the normal elderly. The decrease in attention in patients with CSVD might be caused by the reduced ability of selecting useful information in the LH.

Impact of red blood cell transfusion on acute coronary syndrome: a meta-analysis.

The impact of red blood cell transfusion on outcomes in patients with acute coronary syndrome is controversial. Pubmed, EMBASE, and Cochrane Library were searched for studies of red blood cell transfusion and acute coronary syndrome that were published in any language, from January 1, 1966, to April 1, 2016. We analyzed 17 observational studies, of 2,525,550 subjects. We conducted a systematic review with meta-analysis of studies assessing the association between blood transfusion and the risk for all-cause mortality and reinfarction. The search yielded 17 observational studies, of 2,525,550 subjects, during a study follow-up period, ranging from 30 days to 5 years. Red blood cell transfusion compared with no blood transfusion is associated with higher short- and long-term all-cause mortality as well as reinfarction rates (adjusted RR 2.23; 95% CI 1.47-3.39; HR 1.93; 95% CI 1.12-3.34; RR 2.61; 95% CI 2.17-3.14, respectively). In hemoglobin-stratified analyses, a graded association between red blood cell transfusion and mortality was observed, transfusion and risk of all-cause mortality was borderline significant at hemoglobin levels below 8.0 g/dL (RR 0.52; 95% CI 0.25-1.06), and was associated with an increased risk of mortality at a hemoglobin above 10 g/dL (RR 3.34; 95% CI 2.25-4.97). Red blood cell transfusion was associated with an increased risk of short- and long-term mortality as well as myocardial reinfarction. However, transfusion appeared to have beneficial or neutral effects on mortality at hemoglobin levels below 8.0 g/dL, and harmful effects above 10 g/dL. A large definitive randomized controlled trial addressing this issue is urgently required.

Higher Adiposity Is Associated With Slower Cognitive Decline in Hypertensive Patients: Secondary Analysis of the China Stroke Primary Prevention Trial.

BACKGROUND: Obesity is a risk factor for many diseases. However, the potential association between adiposity and cognitive decline in hypertensive patients is inconclusive. We performed a secondary data analysis of the CSPPT (China Stroke Primary Prevention Trial) to examine whether adiposity is correlated with longitudinal cognitive performance in hypertensive adults. METHODS AND RESULTS: The analysis included 16 791 patients in the CSPPT who received at least 2 cognitive assessments by the Mini-Mental State Examination (MMSE) during the follow-up (median, 4.5 years; interquartile range, 4.2-4.8 years). Outcomes included changes in MMSE scores and cognitive impairment (defined as MMSE score less than education-specific cutoff point). A marked reduction in MMSE scores at the final (compared with at the 1-year) follow-up was apparent in both men (n=4838; mean [SD] score, 0.41 [3.62]) and women (n=7190; mean [SD] score, 1.07 [4.61]; both P<0.001). Analysis using a mixed-effects model revealed an association between higher body mass index with less MMSE decline, even after controlling for demographics and comorbidities (men, ß=0.0134 [SE, 0.0036]; women, ß=0.0133 [SE, 0.0034]; both P<0.001). A total of 1037 men (15.3%) and 3317 women (33.1%) developed cognitive impairment. In multivariable Cox regression analyses, being obese in men (11.3% versus 18.0%; hazard ratio, 0.75; 95% confidence interval, 0.60-0.94) and women (30.1% versus 36.5%; hazard ratio, 0.82; 95% confidence interval, 0.74-0.91) was a protective factor against cognitive impairment compared with normal body mass index. CONCLUSIONS: Higher adiposity is independently associated with slower cognitive decline in Chinese hypertensive adults. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885 CSPPT.

[Prevalence of Anxiety and Depression in Hospitalized Patients with Heart Failure].

OBJECTIVES: To determine the prevalence of anxiety and depression in hospitalized patients with heart failure. METHODS: From September 2015 to March 2016, 301 patients who were admitted to the cardiac ward of a tertiary hospital for heart failure were consecutively enrolled in this study. They were assessed with the Hospital Anxiety Depression Scale (HADs). Multivariate logistic regression analysis was performed to identify risk factors associated with anxiety and depression. RESULTS: Of the 301 participants, 124 (41.2%) were identified with anxiety and 177 (58.8%) with depression; 98 (32.6%) had both anxiety and depression. Higher prevalence of anxiety was found in female patients and those who resided in rural areas, had poor family support, had a class IV New York heart association (NYHA), and were admitted repeatedly (3 or more) for heart failure over the past year. Higher prevalence of depression was found in the patients with poor family support and those who had primary or lower education, had a class IV NYHA, and were in normal or under-weight range. The severity of the two conditions was positively correlated ( r=0.617, P<0.05). The multivariate logistic regression models identified female (OR=2.045), class IV NYHA (OR=1.955), 3 or more repeated admissions for heart failure (OR=2.288) as predictors for anxiety and/or depression. CONCLUSIONS: Anxiety and depression is prevalent in hospitalized patients with heart failure. Increased attention needs to be paid to the psychological health of those patients in high risk.

Prospective study of serum uric acid levels and stroke in a Chinese hypertensive cohort.

Our aim was to investigate the association between serum uric acid (SUA) levels and the risk of first stroke in a Chinese population of hypertensive patients. This prospective study enrolled 20,577 hypertensive participants who without a history of stroke, and was conducted from May 2008 to August 2013 in Anqing and Lianyungang (China). A total of 632 (3.1%) first stroke events (510 ischemic events, 120 hemorrhagic events and 2 unspecified stroke events) were identified during a mean 4.5-year follow-up period. The risk of first stroke was not significantly associated with the increased SUA levels; this conclusion was also found after adjustment for gender and age. However, a statistically significant decreased risk of hemorrhagic stroke for the second SUA quartile (Q2) compared to the first quartile (Q1) (HR 0.56, 95%CI: 0.32-0.97, P = 0.037) was found. In addition, when grouped by tertiles of diastolic blood pressure (DBP), the results showed that high SUA lowered the risk of total stroke in participants in the third SUA quartile (Q3) (HR 0.69, 95%CI: 0.49-0.96, P = 0.028) and fourth SUA quartile (Q4) (HR 0.70, 95%CI: 0.50-0.99, P = 0.043) as compared with that in the first quartile (Q1). To sum up, no significant evidence in present study indicates that increased SUA levels are predictive of first stroke in a Chinese population of hypertensive patients.

Homocysteine and all-cause mortality in hypertensive adults without pre-existing cardiovascular conditions: Effect modification by MTHFR C677T polymorphism.

BACKGROUND: Previous studies support an association between elevated total homocysteine (tHcy) levels and increased all-cause mortality. However, few prospective studies have examined this association in hypertensive patients, and/or tested any effect modification by the methylene tetrahydrofolate reductase (MTHFR) C677T genotype. METHODS: This was a post hoc analysis of the China Stroke Primary Prevention Trial. Serum tHcy and folate were measured at baseline. Individual MTHFR C677T genotype (CC, CT, and TT) was determined. Evidence for death included death certificates or home visits. Cumulative hazards of all-cause mortality by tHcy quartiles were estimated using the Kaplan-Meier method, and group differences were compared by log-rank tests. Hazard ratios (HRs) and 95% confidence intervals were estimated by Cox proportional-hazard regression models, adjusting for age, sex, baseline folate, vitamin B12, blood pressure, body mass index, smoking and alcohol drinking status, study center, total cholesterol, triglycerides, high-density lipoprotein cholesterol, fasting glucose, creatinine, and treatment group. Potential effect modification by the MTHFR genotype on the relationship between tHcy and all-cause mortality was tested. RESULTS: The analyses included 20,424 hypertensive patients (41% males) without a history of myocardial infarction or stroke. Baseline mean age (SD) was 60 ±â€Š7.5 years and mean (SD) serum tHcy was 14.5 ±â€Š8.4 µmol/L. After a mean follow-up period of 4.5 years, there were 612 (3%) all-cause deaths. Kaplan-Meier survival curves revealed a graded relationship between tHcy quartiles and all-cause mortality. The HRs, using the lowest quartile as the reference, were 1.2, 1.2, and 1.5 in Q2, Q3, and Q4, respectively. A linear trend test, using natural log-transformed tHcy, resulted in an HR of 1.5 (95% confidence interval 1.2-1.9, P < .001) after adjustment for lifestyle and health-related variables. Whereas the MTHFR genotype alone had little effect on mortality, it significantly modified the tHcy-mortality association, which was much stronger in the CC/CT genotype than in the TT genotype (P for interaction < 0.05). CONCLUSIONS: Among Chinese hypertensive patients without cardiovascular comorbidities, elevated tHcy was a significant risk marker for death from all causes, and the association was subject to effect modification by MTHFR genotypes. If confirmed that tHcy and MTHFR genotypes may serve as useful biomarkers for mortality risk assessment and targeted intervention.

Off-pump versus on-pump coronary artery bypass grafting in patients with diabetes: a meta-analysis.

AIMS: The effects of off-pump CABG (OFF-CABG) versus on-pump CABG (ON-CABG) in diabetic patients remain controversial. The aim of our study was to compare mortality and postoperative morbidity between OFF-CABG and ON-CABG for diabetic patients. METHODS: Electronic databases including PubMed, EMBASE and Cochrane Library for studies investigating clinical outcomes of OFF-CABG versus ON-CABG in diabetic patients were searched, collecting data from inception until June 2016. We pooled the odds ratios from individual studies and performed heterogeneity, quality assessment and publication bias analysis. RESULTS: A total of 543,220 diabetic patients in 10 studies were included. The overall mortality (OR, 0.87; 95% CI, 0.58-1.31; p = 0.50) was comparable between the OFF-CABG and ON-CABG. OFF-CABG was associated with significantly fewer cerebrovascular accidents (OR, 0.45; 95% CI, 0.31-0.65; p < 0.0001), bleeding complications (OR, 0.59; 95% CI, 0.43-0.80; p < 0.001) and pulmonary complications. However, no differences in myocardial infarction (OR, 0.76; 95% CI, 0.52-1.12; p = 0.16), renal failure (OR, 0.74; 95% CI, 0.50-1.11; p = 0.14) and other postoperative morbidity outcomes were found. CONCLUSIONS: OFF-CABG significantly reduces the incidence of postoperative cerebrovascular accidents and bleeding complications compared with ON-CABG in diabetic patients. No differences were found regarding mortality, myocardial infarction and renal failure between these two techniques. Our study suggests that OFF-CABG may be an optimal strategy for diabetic patients although adequately powered randomized trials are needed to further verify the finding.

Restrictive versus liberal blood transfusion in patients with coronary artery disease: a meta-analysis.

OBJECTIVES: To compare clinical outcomes between restrictive versus liberal blood transfusion strategies in patients with coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: A literature search from January 1966 to May 2016 was performed in PubMed, EMBASE and Cochrane Library to find trials evaluating a restrictive hemoglobin transfusion trigger of ≤8 g/dL, compared with a more liberal trigger. Two study authors independently extracted data from the trials. The primary outcome was mortality and the secondary outcome was subsequent myocardial infarction. Relative risks (RRs) with their 95% confidence intervals (CIs) were assessed. RESULTS: Six trials involving 133,058 participants were included in this study. Pooled results revealed no difference in mortality between the liberal transfusion and restrictive transfusions (RR = 1.17, 95% CI = 0.91-1.52, P = .22). Subgroup analysis revealed that a restrictive transfusion strategy was associated with a higher risk of in-hospital mortality (RR = 1.38, 95% CI = 1.15-1.67, P < .001) and 30 day mortality (RR = 1.21, 95% CI = 1.01-1.45, P = .03), compared with the liberal strategy. No significant difference was found between the liberal transfusion strategy and restrictive transfusion strategy in risk for subsequent myocardial infarction (RR = 1.09, 95% CI = 0.57-2.06, P = .80). LIMITATIONS: Limitations include (1) limited number of trials, especially those evaluating myocardial infarction, (2) observed heterogeneity, (3) confounding by indication and other inherent bias may exist. CONCLUSION: The findings suggest that restrictive blood transfusion was associated with higher in-hospital and 30 day mortality than liberal blood transfusion in CAD patients. The conclusions are mainly based on retrospective studies and should not be considered as recommendation before they are supported by randomized controlled trials.

Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients.

BACKGROUND AND PURPOSE: We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial. METHODS: A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke. RESULTS: The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (<200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84; P<0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024). CONCLUSIONS: Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Repair or replace ischemic mitral regurgitation during coronary artery bypass grafting? A meta-analysis.

BACKGROUND: No agreement has been reached for the best surgical treatment for patients with chronic ischemic mitral regurgitation (IMR) undergoing coronary artery bypass grafting (CABG). Our objective was to meta-analyze the clinical outcomes of repair and replacement. METHODS: A computerized search was performed using Pubmed, Embase, Ovid medline and Cochrane Library. The search terms "ischemic or ischaemic" and "mitral valve" and "repair or replacement or annuloplasty" and "coronary artery bypass grafting" were entered as MeSH terms and keywords. The primary outcomes were operative mortality and late mortality. Secondary outcomes were 2+ or greater recurrence of mitral regurgitation and reoperation rate. RESULTS: Eleven studies were eligible for the final meta-analysis. These studies included a total of 1750 patients, 60.4 % of whom received mitral valve repair. All patients underwent concomitant coronary artery bypass graft. No differences were found in operative mortality (summary odds ratio [OR] 0.65; 95 % confidence interval [CI] 0.43-1.00; p = 0.05), late mortality (summary hazard ratio [HR] 0.87; 95 % confidence interval [CI] 0.67-1.14; p = 0.31) and reoperation (summary odds ratio [OR] 1.47; 95 % confidence interval [CI] 0.90-2.38; p = 0.12). Regurgitation recurrence was lower in the replacement group (summary odds ratio [OR] 5.41; 95 % confidence interval [CI] 3.12-9.38; p < 0.001). CONCLUSION: In patients with chronic ischemic mitral regurgitation during CABG, mitral valve replacement is associated with lower recurrence of regurgitation. No differences were found regarding survival and reoperation rates.

Distinct Patterns of Cognitive Aging Modified by Education Level and Gender among Adults with Limited or No Formal Education: A Normative Study of the Mini-Mental State Examination.

BACKGROUND: Dementia is increasingly prevalent due to rapid aging of the population, but under-recognized among people with low education levels. This is partly due to a lack of appropriate and precise normative data, which underestimates cognitive aging in the use of screening tools for dementia. OBJECTIVE: We aimed to improve the precision of screening for cognitive impairment, by characterizing the patterns of cognitive aging and derived normative data of the Mini-Mental State Examination (MMSE) for illiterate and low-educated populations. METHODS: This community-based study included data from 2,280 individuals aged 40 years or older from two rural areas. Multiple linear modeling examined the effect of aging on cognition reflected by the MMSE, stratified by education level and gender. Threshold effect of age on cognition was performed using a smoothing function. RESULTS: The majority of participants (60.4%) were illiterate or had attended only primary school (24.6%). The effect of aging on cognition varied by gender and education. Primary-school educated females and males remained cognitively stable up to 62 and 71 years of age, respectively, with MMSE score declining 0.4 and 0.8 points/year in females and males thereafter. Illiterates females scored 2.3 points lower than illiterate males, and scores for both declined 0.2 points/year. According to these results, normative data stratified by age, education and gender was generated. CONCLUSION: This study suggests gender and educational differences exist in cognitive aging among adults with limited or no formal education. To improve screening precision for cognitive impairment with the use of MMSE in low-educated population, age, gender, and education level should be considered.

Effect of folic acid supplementation on risk of new-onset diabetes in adults with hypertension in China: Findings from the China Stroke Primary Prevention Trial (CSPPT).

BACKGROUND: The aim of the present post hoc analysis of the China Stroke Primary Prevention Trial (CSPPT) was to evaluate the effect of folic acid supplementation on the risk of new-onset diabetes in hypertensive adults in China. METHODS: In all, 20 702 hypertensive adults with no history of stroke and/or myocardial infarction (MI) were randomly assigned to receive double-blind daily treatment with tablets containing either: (i) 10 mg enalapril and 0.8 mg folic acid (n = 10 348); or (ii) 10 mg enalapril alone (n = 10 354). New-onset diabetes was defined as either self-reported physician-diagnosed diabetes or the use of glucose-lowering drugs during the follow-up period of the CSPPT. RESULTS: Over a median treatment duration of 4.5 years, new-onset diabetes occurred in 198 (2.0%) and 214 (2.1%) subjects in the enalapril-folic acid and enalapril groups, respectively (hazard ratio [HR] 0.92; 95% confidence interval [CI] 0.76-1.12). Similar results were observed when analyses were limited to subjects with baseline fasting glucose (FG) <7.0 mmol/L (HR 0.85; 95% CI 0.62-1.14). Furthermore, there was no significant group difference in: (i) the risk of new-onset FG ≥7.0 mmol/L (defined as FG <7.0 at baseline and ≥7.0 mmol/L at the last visit; relative risk [RR] 1.07; 95% CI 0.96-1.20); or (ii) the composite of new-onset diabetes or new-onset FG ≥7.0 mmol/L (RR = 1.06; 95% CI 0.95-1.19). CONCLUSIONS: Among adults with hypertension with no history of stroke and/or MI in China, folic acid supplementation had no significant effect on the risk of new-onset diabetes.

Glutamine starvation enhances PCV2 replication via the phosphorylation of p38 MAPK, as promoted by reducing glutathione levels.

Glutamine has a positive effect on ameliorating reproductive failure caused by porcine circovirus type 2 (PCV2). However, the mechanism by which glutamine affects PCV2 replication remains unclear. This study was conducted to investigate the effects of glutamine on PCV2 replication and its underlying mechanisms in vitro. The results show that glutamine promoted PK-15 cell viability. Surprisingly, glutamine starvation significantly increased PCV2 replication. The promotion of PCV2 replication by glutamine starvation disappeared after fresh media with 4 mM glutamine was added. Likewise, promotion of PCV2 was observed after adding buthionine sulfoximine (BSO). Glutamine starvation or BSO treatment increased the level of p38 MAPK phosphorylation and PCV2 replication in PK-15 cells. Meanwhile, p38 MAPK phosphorylation and PCV2 replication significantly decreased in p38-knockdown PK-15 cells. Promotion of PCV2 replication caused by glutamine starvation could be blocked in p38-knockdown PK-15 cells. Therefore, glutamine starvation increased PCV2 replication by promoting p38 MAPK activation, which was associated with the down regulation of intracellular glutathione levels. Our findings may contribute toward interpreting the possible pathogenic mechanism of PCV2 and provide a theoretical reference for application of glutamine in controlling porcine circovirus-associated diseases.

Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial.

IMPORTANCE: Uncertainty remains about the efficacy of folic acid therapy for the primary prevention of stroke because of limited and inconsistent data. OBJECTIVE: To test the primary hypothesis that therapy with enalapril and folic acid is more effective in reducing first stroke than enalapril alone among Chinese adults with hypertension. DESIGN, SETTING, AND PARTICIPANTS: The China Stroke Primary Prevention Trial, a randomized, double-blind clinical trial conducted from May 19, 2008, to August 24, 2013, in 32 communities in Jiangsu and Anhui provinces in China. A total of 20,702 adults with hypertension without history of stroke or myocardial infarction (MI) participated in the study. INTERVENTIONS: Eligible participants, stratified by MTHFR C677T genotypes (CC, CT, and TT), were randomly assigned to receive double-blind daily treatment with a single-pill combination containing enalapril, 10 mg, and folic acid, 0.8 mg (n = 10,348) or a tablet containing enalapril, 10 mg, alone (n = 10,354). MAIN OUTCOMES AND MEASURES: The primary outcome was first stroke. Secondary outcomes included first ischemic stroke; first hemorrhagic stroke; MI; a composite of cardiovascular events consisting of cardiovascular death, MI, and stroke; and all-cause death. RESULTS: During a median treatment duration of 4.5 years, compared with the enalapril alone group, the enalapril-folic acid group had a significant risk reduction in first stroke (2.7% of participants in the enalapril-folic acid group vs 3.4% in the enalapril alone group; hazard ratio [HR], 0.79; 95% CI, 0.68-0.93), first ischemic stroke (2.2% with enalapril-folic acid vs 2.8% with enalapril alone; HR, 0.76; 95% CI, 0.64-0.91), and composite cardiovascular events consisting of cardiovascular death, MI, and stroke (3.1% with enalapril-folic acid vs 3.9% with enalapril alone; HR, 0.80; 95% CI, 0.69-0.92). The risks of hemorrhagic stroke (HR, 0.93; 95% CI, 0.65-1.34), MI (HR, 1.04; 95% CI, 0.60-1.82), and all-cause deaths (HR, 0.94; 95% CI, 0.81-1.10) did not differ significantly between the 2 treatment groups. There were no significant differences between the 2 treatment groups in the frequencies of adverse events. CONCLUSIONS AND RELEVANCE: Among adults with hypertension in China without a history of stroke or MI, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. These findings are consistent with benefits from folate use among adults with hypertension and low baseline folate levels. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00794885.

Selenium-enriched probiotics improve antioxidant status, immune function, and selenoprotein gene expression of piglets raised under high ambient temperature.

This research was conducted to evaluate the effects of selenium-enriched probiotics (SP) on growth performance, antioxidant status, immune function, and selenoprotein gene expression of piglets under natural high ambient temperature in summer. Forty-eight crossbred weanling piglets randomly allocated to four groups were fed for 42 days ad libitum a basal diet without (Con, 0.16 mg Se/kg) and with supplementation of probiotics (P, 0.16 mg Se/kg), sodium selenite (SS, 0.46 mg Se/kg), and SP (0.46 mg Se/kg). From each group, three piglets were randomly selected for blood collection on days 0, 14, 28, and 42 and tissue collection on day 42. The SP improved growth performance of piglets. Both SS and SP increased blood glutathione peroxidase activity and tissue thioredoxin reductase 1 mRNA expression, with SP being higher than SS. All P, SS, and SP supplementation increased the superoxide dismutase activity (40.1, 53.0, and 64.5%), glutathione content (84.6, 104, and 165%), TCR-induced T lymphocyte proliferation (20.8, 26.4, and 50.0%), and IL-2 concentration (24.9, 27.2, and 46.2%) and decreased malondialdehyde content (25.1, 26.3, and 49.3%), respectively. The greatest effects of SP supplementation suggest that SP may serve as a better feed additive than P or SS for piglets under high-temperature environments.

Protective effect of selenomethionine on aflatoxin B1-induced oxidative stress in MDCK cells.

AFB1 is a mycotoxin which exerts their cytotoxicity through increasing oxidative damage in target organ. Kidney is one of target organs vulnerable to damage caused by AFB1. In this study, Madin-Darby canine kidney (MDCK) cells were used to evaluate the AFB1-induced cell damage by the MTT assay. The results revealed that the toxic effect of AFB1 on MDCK cells is both dose and time dependent. Half maximal toxic concentration (IC50) was noted at 0.25 µg/ml of AFB1. Further, protective effect of six different concentrations (0.2, 0.8, 1, 2, 4, and 8 µM) of selenomethionine (SeMet) was observed against 0.25 µg/ml of AFB1-induced damage. The results showed that 0.25 µg/ml of AFB1 caused significant increase in oxidative stress, which was demonstrated by significant increase of malondialdehyde (MDA) level, reduction of intracellular GSH level, as well as GPX1 activity and mRNA level in MDCK cells when compared with control. SeMet protected the cells from AFB1-induced oxidative damage in a dose-dependant manner. Good protection could be achieved between 1 and 4 µM of concentration. Amid this range, MDA level significantly decreased while intracellular GSH level and GPX1 activity in addition to mRNA level significantly increased. Moreover, cell viability was significantly improved. It could be concluded that SeMet is a potential antioxidative agent to alleviate AFB1-induced oxidative stress.

Interaction of porcine circovirus type 2 replication with intracellular redox status in vitro.

OBJECTIVES: Redox status influences replication of some viruses but its effect on porcine circovirus type 2 (PCV2), the primary causative agent of the emerging swine disease post-weaning multisystemic wasting syndrome is not known. The interaction of PCV2 replication with intracellular redox status in PK15 cells was examined in this study. METHODS: Intracellular glutathione (GSH) was measured spectrophotometrically by reaction with 5, 5'-dithiobis (2-nitrobenzoic acid). Total superoxide dismutase activity (SOD) was assayed by inhibition of oxyamine oxidation by the xanthine oxidase system. Malondialdehyde (MDA) was assayed spectrophotometrically using the thiobarbituric acid reaction. Both quantification of PCV2 DNA by real-time polymerase chain reaction and indirect immunofluorescence of PCV2-infected cells were used to evaluate the replication of PCV2. RESULTS: Both GSH and SOD decreased significantly at 48 hours after PCV2 infection, whereas MDA concentration increased significantly after 48 hour post-infection. Furthermore, PCV2 replication in PK15 cells was significantly impaired after the elevation of intracellular GSH through treatment with the antioxidant N-acetyl-l-cysteine (NAC), a precursor in GSH synthesis. In contrast, PCV2 replication in PK15 cells was enhanced after reduction of GSH levels through H2O2-mediated oxidation. In addition, NAC treatment blocked the increase of virus replication induced by H2O2. CONCLUSIONS: This study suggests that PCV2 infection induces oxidative stress and that intracellular redox status influences PCV2 replication in PK15 cells.

Effects of selenium-enriched probiotics on heat shock protein mRNA levels in piglet under heat stress conditions.

The effects of selenium-enriched probiotics (SP) on tissue selenium (Se) deposition, glutathione peroxidase-1 (GPx1) activity and mRNA level, and heat shock protein (Hsp) mRNA levels of piglets under heat stress conditions were investigated. A total of 48 crossbred ([Landrace × Yorkshire] × Duroc) piglets were randomly divided into 4 groups and fed a basal diet (Con, 0.16 mg Se/kg) or basal diets with added probiotics (P, 0.16 mg Se/kg), sodium selenite (SS, 0.46 mg Se/kg), or SP (0.46 mg Se/kg), respectively, for 42 days. Three piglets were randomly selected from each group for blood sample collection at days 0, 14, 28, and 42 and for liver, kidney, and spleen sample collection at day 42. The results showed that P, SS, and SP could significantly down-regulate the average mRNA levels of Hsp70 (17.3, 23.7, and 40.1%) and Hsp27 (22.4, 24.4, and 44.7%) of the tissues, respectively (P < 0.05), whereas SS and SP could significantly elevate Se concentration, GPx1 activity and mRNA level (P < 0.05). The maximal effects of these parameters were observed in SP. It was concluded that SP is a feasible dietary supplementation of piglets under heat stress conditions during the summer season.

Selenium blocks porcine circovirus type 2 replication promotion induced by oxidative stress by improving GPx1 expression.

Porcine circovirus type 2 (PCV2) is recognized as a key infectious agent in postweaning multisystemic wasting syndrome (PMWS), but not all pigs infected with PCV2 will develop PMWS. The aim of this work was to explore the relationships among PCV2 infection, oxidative stress, and selenium in a PK-15 cell culture model of PCV2 infection. The results showed that oxidative stress induced by H(2)O(2) treatment increased PCV2 replication as measured by PCV2 DNA copies and the number of infected cells. Furthermore, PCV2 replication was inhibited by selenomethionine (SeMet) at a high concentration (6µM) and the increase in PCV2 replication by oxidative stress was blocked by SeMet at physiological concentrations (2 or 4µM). PCV2 infection caused a decrease in glutathione peroxidase 1 (GPx1) activity but an increase in GPx1 mRNA levels, suggesting that GPx1 may represent an important defense mechanism during PCV2 infection. SeMet did not significantly block the promotion of PCV2 replication in GPx1-knockdown cells. This observation correlates with the observed influence of SeMet on GPx1 mRNA and activity in GPx1-knockdown cells, indicating that GPx1 plays a key role in blocking the promotion of PCV2 replication. We conclude that differences in morbidity and severity of PMWS observed on different pig farms may be related to variations in oxidative stress and that selenium has a potential role in the control of PCV2 infection.