Salvianolic Acid B Ameliorates Hyperglycemia and Dyslipidemia in db/db Mice through the AMPK Pathway.

BACKGROUND/AIMS: Salvianolic acid B (Sal B), a major polyphenolic compound of Salvia miltiorrhiza Bunge, has been shown to possess potential antidiabetic activities. However, the action mechanism of SalB in type 2 diabetes has not been investigated extensively. The present study was designed to investigate the effects of Sal B on diabetes-related metabolic changes in a spontaneous model of type 2 diabetes, as well as its potential molecular mechanism. METHODS: Male C57BL/KsJ-db/db mice were orally treated with Sal B (50 and 100 mg/kg) or metformin (positive drug, 300 mg/kg) for 6 weeks. RESULTS: Both doses of Sal B significantly decreased fasting blood glucose, serum insulin, triglyceride and free fatty acid levels, reduced hepatic gluconeogenic gene expression and improved insulin intolerance in db/db mice. High dose Sal B also significantly improved glucose intolerance, increased hepatic glycolytic gene expression and muscle glycogen content, and ameliorated histopathological alterations of pancreas, similar to metformin. Sal B treatment resulted in increased phosphorylated AMP-activated protein kinase (p-AMPK) protein expression in skeletal muscle and liver, increased glucose transporter 4 (GLUT4) and glycogen synthase protein expressions in skeletal muscle, and increased peroxisome proliferator-activated receptor alpha (PPARα) and phosphorylated acetyl CoA carboxylase (p-ACC) protein expressions in liver. CONCLUSION: Our data suggest that Sal B displays beneficial effects in the prevention and treatment of type 2 diabetes at least in part via modulation of the AMPK pathway.

Telmisartan attenuates monocrotaline-induced pulmonary artery endothelial dysfunction through a PPAR gamma-dependent PI3K/Akt/eNOS pathway.

BACKGROUND: Pulmonary artery endothelial dysfunction has been demonstrated in pulmonary arterial hypertension (PAH). Telmisartan has beneficial effects in endothelial function in PAH patients; however, the underlying mechanisms for these effects remain unknown. AIMS: In this study, we observed the effects of telmisartan on monocrotaline (MCT)-induced Sprague Dawley (SD) rat model of PAH. METHODS: After a single-dose injection of MCT (60 mg/kg), oral administration of telmisartan (10 mg/kg/d) was started from day 1 to day 28 or with saline as MCT control. The vasorelaxation and remodelling of pulmonary arteries; the expression of peroxisome proliferator-activated receptor γ (PPARγ), Akt, eNOS; levels of phosphorylation of Akt (p-Akt) and phosphorylation of eNOS (p-eNOS) were analysed in isolated rat pulmonary arteries and cultured human pulmonary artery endothelial cells (HPAECs). RESULTS: Compared to MCT control group, telmisartan treatment ameliorated pulmonary artery endothelial dysfunction and remodelling, prevented the elevation of right ventricular systolic pressure (RVSP) induced by MCT. Immunoblotting results indicated lower levels of PPARγ, p-Akt and p-eNOS in pulmonary arteries treated with MCT alone and levels were significantly restored by co-treatment with telmisartan. In isolated pulmonary arteries, the impaired endothelium-dependent vasorelaxation of pulmonary arteries was improved following incubation with telmisartan for 12 h, whereas this effect was blocked by the inhibition of either PPARγ or phosphoinositide 3-kinase (PI3K) signals transduction. In cultured HPAECs, treatment with telmisartan increased PPARγ expression and promoted the phosphorylation of Akt and eNOS, thereby increasing the production of NO. These effects were abolished by the inhibition of PPARγ or PI3K. CONCLUSION: Telmisartan protected against endothelial dysfunction in MCT-induced PAH through a PPARγ-dependent PI3K/Akt/eNOS pathway. Thus, telmisartan may be a promising therapeutic strategy for patients with a high risk of PAH.

Association between vacA genotypes and the risk of duodenal ulcer: a meta-analysis.

Epidemiological studies have reported the relationship between vacuolating cytotoxin A (vacA) s-/m- region genotypes and duodenal ulcer (DU), but the results remained inconclusive. We performed the present meta-analysis to investigate a more authentic association between vacA s-/m- region genotypes and DU. Literature search was performed by searching Embase, PubMed and ISI Web of Science databases as well as checking references from identified articles, reviews and the abstracts presented at related scientific societies meetings. The association was assessed by combined odds ratio (OR) with 95% confidence interval (CI). A total of 42 studies were included in our final meta-analysis. The combined ORs (95% CIs) showed that vacA s1 (OR = 2.96, 95% CI = 2.34-3.75), m1 (OR = 1.46, 95% CI = 1.05-2.04) and s1m1 (OR = 1.89, 95% CI = 1.47-2.42) were associated with increased DU risk significantly in the overall studied population. Subgroup analyses by ethnicity showed that vacA s1 increased the risk of DU in Asian countries (OR = 1.92, 95% CI = 1.30-2.83), European countries (OR = 3.58, 95% CI = 2.13-6.03) and Latin American countries (OR = 4.20, 95% CI = 2.21-7.98); vacA m1 increased the risk of DU in Latin American countries (OR = 2.98, 95% CI = 1.59-5.56); vacA s1m1 increased the risk of DU in Asian countries (OR = 2.04, 95% CI = 1.12-3.73) and Latin American countries (OR = 2.05, 95% CI = 1.20-3.48); vacA s2m1 increased the risk of DU in Latin American countries (OR = 2.30, 95% CI = 1.17-4.50). The data suggest that genotype testing of vacA s- and m- region will be useful in screening susceptible individuals for DU development.

Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) has been reported as a novel predictor for atherosclerosis and cardiovascular outcomes. This study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion (CTO) patients. METHODS: A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up period. Patients were divided into tertiles according to their baseline NLR levels at admission: low (n = 223), intermediate (n = 223), and high (n = 224). The incidence of major adverse cardiac events (MACEs) during the follow-up period, including all-cause death, nonfatal myocardial infarction (MI), or ischemia-driven revascularization, were compared among the three groups. RESULTS: Major adverse cardiac events were observed in 27 patients (12.1%) in the low tertile, 40 (17.9%) in the intermediate tertile, and 61 (27.2%) in the high NLR tertile (P < 0.001). Kaplan-Meier analysis demonstrated a significantly higher incidence of MACE, ischemia-driven coronary revascularization, non-fatal MI, and mortality in patients within the high tertile than those in the low and intermediate groups (all P < 0.001). Multivariable COX regression analysis showed that the high tertile of baseline NLR level showed a strong association with the risk of MACE (hazard ratio [HR] = 2.21; 95% confidence interval [CI]: 1.21-4.03; P = 0.009), ischemia-driven coronary revascularization (HR = 3.19; 95% CI: 1.56-6.52; P = 0.001), MI (HR = 2.61; 95% CI: 1.35-5.03; P = 0.043) and mortality (HR = 3.78; 95% CI: 1.65-8.77; P = 0.001). CONCLUSION: Our findings suggest that NLR is an inexpensive and readily available biomarker that can independently predict cardiovascular risk in patients with CTO.

Unilateral contrast-induced encephalopathy with contrast medium exudation: A case report.

BACKGROUND: Contrast-induced encephalopathy (CIE) is a rare transient, reversible abnormality in the structure or function of the nervous system caused by the intravascular use of contrast agents. CIE can present with a range of neurological manifestations, including focal neurological deficits (hemiplegia, hemianopia, cortical blindness, aphasia, and parkinsonism) and systemic symptoms (confusion, seizures, and coma). However, if not accurately diagnosed and treated in a timely manner, CIE can cause irreversible damage to patients, especially critically ill patients. CASE SUMMARY: A male in his 50 s, 2 h after digital subtraction angiography, had a progressive disorder of consciousness, mixed aphasia, bilateral pupillary sluggish light reflex, and right limb weakness. Seven hours after the procedure, he developed unconsciousness, high fever (39.5 °C), seizures, hemiplegia, neck stiffness (+), and right Babinski signs (+). computed tomography (CT) findings 2 h postprocedure were very confusing and led us to misdiagnose the patient with subarachnoid hemorrhage. Brain CT was performed again 7 h after the procedure. Compared with the CT 2 h after the procedure, the CT 7 h after the procedure showed that the manifestations of subarachnoid hemorrhage in the left cerebral hemisphere had disappeared and were replaced by brain tissue swelling, and the cerebral sulci had disappeared. Combined with the clinical manifestations of the patient and after the exclusion of subarachnoid hemorrhage and cerebrovascular embolism, we diagnosed the patient with CIE, and intravenous fluids were given for adequate hydration, as well as mannitol, albumin dehydration, furosemide and the glucocorticoid methylprednisolone. After 17 d of active treatment, the patient was discharged with no sequelae. CONCLUSION: CIE should be taken seriously, but it is easily misdiagnosed, and once CIE is diagnosed, rapid, accurate diagnosis and treatment are critical steps. Whether a follow-up examination using a contrast agent can be performed should be closely evaluated, and the patient should be fully informed of the associated risks.

[Activation of transient receptor potential vanilloid 1 inhibits RhoA/Rho kinase and improves vasorelaxation dysfunction mediated by high-fat diet in mice].

OBJECTIVE: To investigate the role of dietary capsaicin in activating transient receptor potential vanilloid 1 (TRPV1) and thus influencing the vascular dysfunction mediated by high-fat diet and the potential mechanisms. METHODS: A total of 80 male C57BL/6J mice aged 10 weeks were equally divided into four groups, in which the mice were fed with normal diet (ND), normal diet plus capsaicin (NC), high-fat diet (HD), or high-fat diet plus capsaicin (HC) for 20 weeks. Tail-cuff blood pressure (BP), vascular function of mice aortic rings, expressions of voltage-gated potassium-channel Kv1.4, RhoA and Rho kinase in aorta were examined. RESULTS: Compared with ND group, both nitroglycerin [(18.9 +/- 13)% vs. 100%, P < 0.01] and acetylcholine [(26 +/- 12)% vs. 100%, P < 0.01] induced vasorelaxation of aortic rings were significantly reduced in HD group. Both endothelium dependent and independent aortic rings vasorelaxation in HC group were significantly improved compared with that in HD group [acetylcholine: (69 +/- 15)%; nitroglycerin: (46.5 +/- 6)%, P < 0.05], but still reduced compared with that in ND group (P < 0.05, P < 0.01). High fat diet induced the expression of RhoA and Rho kinase. Dietary capsaicin down-regulated the expression of RhoA and Rho kinase but up-regulated the expression of Kv1.4 in aorta in mice fed with normal or high fat diet (all P < 0.05). CONCLUSION: Dietary capsaicin can ameliorate vasorelaxation dysfunction mediated by high-fat diet. The potential mechanisms may be related with TRPV1 activation, which in turn stimulates potassium channel and inhibits RhoA and Rho kinase in the vasculature.

Dual versus Single Antiplatelet Therapy in Carotid Artery Endarterectomy: Direct Comparison of Complications Related to Antiplatelet Therapy.

BACKGROUND: Dual and single antiplatelet therapies are routinely used in carotid artery endarterectomy (CEA). However, the efficacy and safety of these therapies are controversial. The present study aimed to comprehensively compare the clinical outcomes between dual and single antiplatelet therapies in CEA. METHODS: This study retrieved available academic studies evaluating the complications related to antiplatelet therapy between dual and single antiplatelet therapies in CEA from the databases of ScienceDirect, the Cochrane Library, EMBASE, and PubMed. References to previous reviews and related clinical trials were manually checked to retrieve potential literature that was not included in our electronic search results. RESULTS: A total of 10 articles (1 randomized controlled trial, 9 non-randomized controlled trials) were included in the study. The overall number of patients in the dual antiplatelet group was 14,280, and the number of patients in the single antiplatelet group was 125,850. The results revealed that the single antiplatelet group had a lower incidence of 30-day death (rate difference [RD] 0.002; 95% confidence interval [CI] 0.000-0.003; P = 0.014), neck hematoma (odds ratio [OR] 2.120; 95% CI 1.431-3.142; P < 0.001), myocardial infarction (RD 0.004; 95% CI 0.001-0.007; P = 0.003), and major bleeding (RD 0.005; 95% CI 0.002-0.008; P < 0.001). Meanwhile, the single antiplatelet group was associated with a shorter operation time (weighted mean difference 4.000; 95% CI= 2.564-5.436; P < 0.001). However, there was no significant difference in the rate of postoperative transient ischemic attack (P = 0.215), stroke (P = 0.130), or length of stay (P = 0.563). CONCLUSIONS: Based on current evidence, using single antiplatelet therapy in CEA may reduce operation time and the incidences of 30-day death, neck hematoma, major bleeding, and myocardial infarction without increasing the risks of transient ischemic attack, stroke, or a longer operation time.

[Influence of compatibility on content of berberine in Maxingganshi decoction].

OBJECTIVE: To set up the quantitative method of herberine in decoctions prepared from various combinations of Maxingganshi decotion by HPLC and to determine the change of general contents in different decoction. METHODS: The study was designed by L8 (2(7)) orthogonal and to determine the change of general contents in different decoction by HPLC. RESULTS: In full formula remove Glycyrrhiza uralensis group, the contents of L-ephedrine, d-pseudephedrine and the amygdaloside cut down significantly. In full formula remove armeniacae semen group, the content of glycyrrhetic acid cut down significantly. Four chemical composition in full formula group had higher contents. CONCLUSION: Armeniacae semen can decrease the content of L-ephedrine, D-pseudephedrine. Glycyrrhiza uralensis can help decoctum amygdaloside and armeniacae semen can help decoctum glycyrrhizic acid.

[The empirical study of Maxingganshi decoction and its compatibility in acute lung injury rats].

OBJECTIVE: To explore the pharmacodyniamic action and the mechanism of action of the Maxingganshi decoction in acute lung injury rats in order to supply the pharmacology evidence to cure the SIRS-ALI of Maxingganshi decoction. METHODS: The study designed by orthogonal design. The SIRS-ALI model were Conseructed by the LPS intravenous injection and the effects of Maxingganshi decoction and it's different compatibilities to the SIRS-ALI model were observed. The experiments results were analvsised in order to reveal the compatibility rules of the Maxingganshi decocotion. RESULTS: Maxingganshi decocotion and its different compatibilities had good effects of prevention and cure the SIRS-ALI. The mechanism maybe concerned with the Maxingganshi decocotion can decrease the TNF-alpha and increase the IL-10. The experiments results also indicated that the action of the full formula was the best. The principal drug was the most important in the formula. CONCLUSION: Maxingganshitang has a good effect in anti the ALI; the results indicat that the principal drug is the predominant therapeutic action in the formula ministerial drug. Adjuvant drug and messenger drug can strengthen pharmacodynamic action.

Genetic polymorphism of apolipoprotein A5 gene and susceptibility to type 2 diabetes mellitus: a meta-analysis of 15,137 subjects.

BACKGROUND: Several studies have investigated whether the polymorphism in the apolipoprotein A5 (APOA5) is associated with type 2 diabetes mellitus (T2DM) risk. However, those studies have produced inconsistent results. The purpose of this study was to investigate whether the APOA5 -1131T/C polymorphism (rs662799) confers significant susceptibility to T2DM using a meta-analysis. METHODS: PubMed, Embase, Web of Science, Cochrane database, CBMdisc, CNKI and Google Scholar were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. RESULTS: A total of 19 studies included 4,767 T2DM cases and 10,370 controls (four studies involving 555 T2DM cases and 2958 controls were performed among Europeans and 15 studies involving 4212 T2DM cases and 7412 controls were performed among Asians) were combined showing significant association between the APOA5 -1131T/C polymorphism and T2DM risk (for C allele vs. T allele: OR = 1.28, 95% CI = 1.17-1.40, p<0.00001; for C/C vs. T/T: OR = 1.57, 95% CI = 1.35-1.83, p<0.00001; for C/C vs. T/C+T/T: OR = 1.36, 95% CI = 1.18-1.57, p<0.0001; for C/C+T/C vs. T/T: OR = 1.32, 95% CI = 1.16-1.51, p<0.0001). In the subgroup analysis by ethnicity, significant association was also found among Asians (for C allele vs. T allele: OR = 1.31, 95% CI = 1.22-1.40, p<0.00001; for C/C vs. T/T: OR = 1.61, 95% CI = 1.38-1.88, p<0.00001; for C/C vs. T/C+T/T: OR = 1.39, 95% CI = 1.20-1.61, p<0.0001; for C/C+T/C vs. T/T: OR = 1.42, 95% CI = 1.25-1.62, p<0.00001). However, no significant association was found between the APOA5 -1131T/C polymorphism and T2DM risk among Europeans. CONCLUSIONS: The present meta-analysis suggests that the APOA5 -1131T/C polymorphism is associated with an increased T2DM risk in Asian population.