Acute glycemic variability on admission predicts the prognosis in hospitalized patients with coronary artery disease: a meta-analysis.

PURPOSE: Increased glycemic variability has been related with poor prognosis in patients with coronary artery disease (CAD). However, whether diabetic status or subtype of CAD could affect the association remains unknown. We performed a meta-analysis to systematically evaluate the association between the mean amplitude of glycemic excursions (MAGE) on continuous glucose monitoring and the incidence of major adverse cardiovascular events (MACEs) in CAD patients. METHODS: Relevant prospective cohort studies were identified through search of PubMed, Embase, WanFang, and CNKI databases. A random-effect model was used to pool the results. Subgroup analyses were performed to evaluate the influences of the predefined study characteristics on the outcome. RESULTS: Eleven cohort studies with 2666 hospitalized patients with acute coronary syndrome (ACS) or stable CAD for percutaneous coronary intervention were included. Pooled results showed that higher MAGE at admission was associated with higher incidence of MACEs during follow-up (adjusted relative risk [RR]: 1.84, p < 0.001; I2 = 12%). Stratified analyses showed that the association between higher MAGE and higher risk of MACEs in CAD patients were consistent in patients with or without diabetes, and in those with ACS or stable CAD (p for subgroup difference both >0.05). Significant publication bias was detected (p = 0.041). Trim-and-fill analysis retrieved three studies to generate symmetrical funnel plots. Meta-analysis that incorporated these studies showed similar results (RR: 1.80, p < 0.001). CONCLUSIONS: Increased glycemic variability may be associated with poor prognosis in CAD patients regardless of the diabetic status and the subtype of CAD.

Effects of ANRIL polymorphisms on the likelihood of coronary artery disease: A meta-analysis.

BACKGROUND: Whether antisense noncoding RNA in the INK4 locus (ANRIL) polymorphisms are associated with the likelihood of coronary artery disease (CAD) remains controversial. Therefore, we performed this study to explore correlation between ANRIL polymorphisms and CAD. METHODS: Literature retrieve was conducted in PubMed, Medline and Embase. Odds ratios and 95% confidence intervals were calculated. RESULTS: Nineteen studies were enrolled for analyses. Pooled overall analyses showed that rs1333040 (dominant model: P < 0.0001; recessive model: P < 0.0001; allele model: P < 0.0001), rs1333049 (dominant model: P = 0.02; allele model: P = 0.02) and rs2383207 (additive model: P = 0.004; allele model: P = 0.03) polymorphisms were significantly associated with the likelihood of CAD. Further subgroup analyses revealed that rs1333040, rs1333049, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms were all significantly correlated with the likelihood of CAD in East Asians. Additionally, rs2383206, rs10757274, and rs10757278 polymorphisms were also significantly correlated with the likelihood of CAD in Caucasians and West Asians. CONCLUSIONS: Our findings indicated that rs1333040, rs1333049, rs2383206, rs2383207, rs10757274, and rs10757278 polymorphisms may serve as genetic biomarkers of CAD in East Asians. Moreover, rs2383206, rs10757274, and rs10757278 polymorphisms may also serve as genetic biomarkers of CAD in Caucasians and West Asians.

Macrophage-targeting Fasudil treatment protects liver from the ischemia/reperfusion injury by promoting M2 macrophage polarization.

Macrophages play essential roles in the generation and resolution of inflammation. Ischemia-reperfusion injury (IRI) triggers a systemic inflammatory response and leads to cellular injury and organ failure. During surgical procedures of the liver, such as hepatic resection and liver transplantation, IRI leads to the dysfunction of the liver. Rho-associated protein kinase (ROCK) inhibitors were reported protecting the liver from IRI. However, the systematic administration of ROCK inhibitors causes severe hypotension. Here, using Fasudil carried liposomes, we specifically inhibited the ROCK-II expression in Kupffer cells and blood monocytes. Through this macrophage/monocyte specific treatment of Fasudil, we successfully protected the liver from IRI by shifting Kupffer cells/monocytes from M1/classical to M2/patrolling phenotype in the liver and peripheral blood. Our finding provides novel insights into the macrophage/monocyte-specific drug delivery and the treatment of liver IRI.

Predictive value of cystatin C in people with suspected or established coronary artery disease: A meta-analysis.

BACKGROUND AND AIMS: Circulating cystatin C has been recognized as an independent predictor of cardiovascular and all-cause mortality in the general population. We aimed to evaluate the prognostic value of baseline circulating cystatin C levels in people with suspected or established coronary artery disease (CAD) by conducting a meta-analysis. METHODS: We searched Pubmed and Embase databases up to October 2016 for prospective observational studies investigating the predictive value of elevated circulating cystatin C levels in people with suspected or established CAD. Adverse vascular outcomes included all-cause mortality, cardiovascular mortality, or total adverse vascular events consisting of death, myocardial infarction, revascularization, stroke, and heart failure. RESULTS: Ten studies involving participants with known or suspected CAD were included in this meta-analysis. When comparing the highest with the lowest cystatin C levels, the pooled hazard ratio (HR) was 2.27 (95% confidence interval [CI] 1.86-2.78) for all-cause mortality, 2.24 (95% CI 1.69-2.97) for cardiovascular mortality, and 1.87 (95% CI 1.57-2.24) for total adverse vascular events, respectively. Subgroup analysis results showed that this association was not influenced by follow-up duration, region, or CAD type. CONCLUSIONS: Elevated circulating cystatin C is independently associated with adverse vascular outcomes in people with suspected or established CAD in terms of all-cause mortality, cardiovascular mortality, and total adverse vascular events. This increased risk is probably independent of creatinine/estimated glomerular filtration rate.

Impact of Physician-Coordinated Intensive Follow-Up on Long-Term Medical Costs in Patients with Unstable Angina Undergoing Percutaneous Coronary Intervention.

BACKGROUND: To investigate the impact of professional physician-coordinated intensive follow-up on long-term expenditures after percutaneous coronary intervention (PCI) in unstable angina (UA) patients. METHODS: In this study, there were 669 UA patients who underwent successful PCI and followed up for 3 years, then divided into the intensive follow-up group (N = 337), and the usual follow-up group (N = 332). Patients were provided with detailed discharge information and individualized follow-up schedules. The intensive group received the extra follow-up times and medical consultations, and all patients were followed up for approximately 3 years. RESULTS: At the 3-year mark after PCI, the cumulative major adverse cardiac events (MACE), recurrence of myocardial ischemia, cardiac death, all-cause death and revascularization in the intensive group were lower than in the usual group. Additionally, the proportion of good medication adherence was significantly higher than in the usual group (56.4% vs. 46.1%, p < 0.001). The hospitalization daytime, total hospitalization cost and total medical cost in the intensive group were lower. Multiple linear regression showed that diabetes, hypertension, intensive follow-up and good medication adherence were associated with emergency and regular clinical cost (p < 0.05), the re-hospitalization cost (p < 0.05) and the total medical cost (p < 0.05) of patient care. Intensive follow-up and good adherence were negatively correlated with the cost of re-hospitalization (standardized coefficients = -0.132, -0.128, p < 0.05) and total medical costs (standardized coefficients = -0.072, -0.086, p < 0.05). CONCLUSIONS: Intensive follow-up can reduce MACE, improve medication adherence and save long-term total medical costs, just by increasing the emergency and regular clinical visits cost in UA patients after PCI.

Impacts of intensive follow-up on the long-term prognosis of percutaneous coronary intervention in acute coronary syndrome patients - a single center prospective randomized controlled study in a Chinese population.

OBJECTIVES: To investigate the impact of cardiologist-coordinated intensive follow-up on the long-term prognosis of percutaneous coronary intervention in Chinese patients. METHODS: We recruited 964 patients who had acute coronary syndrome and underwent successful percutaneous coronary intervention in the First Hospital Affiliated to Henan University of Science and Technology, China. Participants were randomly assigned into the intensive follow-up (n = 479) and usual follow-up group (control group, n = 485). They received secondary prevention education during hospitalization and telephone follow-ups after discharge. The control group received telephone calls from nurses, while the intensive follow-up group received telephone calls and medical consultations from cardiologists. Both groups were followed up for 36 months. RESULTS: (1) At 36 months, the proportions of all-cause death, cardiac death and cumulative major adverse cardiovascular events (MACEs) were 5.3%, 4.4% and 18.6% in the intensive follow-up group. These events were significantly lower than in the control group (10.1%, 9.3 % and 28.8% (p = 0.004, p = 0.003 and p < 0.001). (2) Multivariable Cox regression analysis identified intensive follow-up as an independent predictor of survival, cardiac death-free survival and MACE-free survival. (hazard ratio (HR) = 0.487, 95% confidence interval (CI) 0.298-0.797, p = 0.004; HR = 0.466, 95% CI 0.274-0.793, p = 0.005; HR = 0.614, 95% CI 0.464-0.811, p = 0.001). Kaplan-Meier analysis revealed that patients in the intensive follow-up groups had longer survival (log rank = 8.565, p = 0.003), cardiac death-free survival (log rank = 8.769, p = 0.003) and MACE-free survival (log rank = 15.928, p < 0.001). (3) The average medical cost was significantly less in the intensive follow-up group, especially the cost for re-hospitalization (US$582.74 ± 1753.20 vs. US$999.32 ± 2434.57, p = 0.003). The bleeding events were similar. (4) Patients in the intensive follow-up group had significantly better controls of cardiovascular risk factors and medication adherence. CONCLUSIONS: A cardiologist-coordinated intensive follow-up program markedly decreased cardiovascular risk factors, reduced medical costs, promoted medication adherence and improved the long-term prognosis of patients after percutaneous coronary intervention in the Chinese population.

Synthesis and Antimicrobial Activity of the Hybrid Molecules between Sulfonamides and Active Antimicrobial Pleuromutilin Derivative.

A series of novel hybrid molecules between sulfonamides and active antimicrobial 14-o-(3-carboxy-phenylsulfide)-mutilin were synthesized, and their in vitro antibacterial activities were evaluated by the broth microdilution. Results indicated that these compounds displayed potent antimicrobial activities in vitro against various drug-susceptible and drug-resistant Gram-positive bacteria such as Staphylococci and streptococci, including methicillin-resistant Staphylococcus aureus, and mycoplasma. In particular, sulfapyridine analog (6c) exhibited more potent inhibitory activity against Gram-positive bacteria and mycoplasma, including Staphylococcus aureus (MIC = 0.016-0.063 µg/mL), methicillin-resistant Staphylococcus aureus (MIC = 0.016 µg/mL), Streptococcus pneumoniae (MIC = 0.032-0.063 µg/mL), Mycoplasma gallisepticum (MIC = 0.004 µg/mL), with respect to other synthesized compounds and reference drugs sulfonamide (MIC = 8-128 µg/mL) and valnemulin (MIC = 0.004-0.5 µg/mL). Furthermore, comparison between MIC values of pleuromutilin-sulfonamide hybrids 6a-f with pleuromutilin parent compound 3 revealed that these modifications at 14 position side chain of the pleuromutilin with benzene sulfonamide could greatly improve the antibacterial activity especially against Gram-positives.

[Effects of docosahexaenoic acid on ion channels of rat coronary artery smooth muscle cells].

OBJECTIVE: To investigate the effects of docosahexaenoic acid (DHA) on large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels and voltage-dependent K(+) (K(V)) channels in rat coronary artery smooth muscle cells (CASMCs), and evaluate the vasorelaxation mechanisms of DHA. METHODS: BK(Ca) and K(V) currents in individual CASMC were recorded by patch-clamp technique in whole-cell configuration. Effects of DHA at various concentrations (0, 10, 20, 40, 60 and 80 µmol/L) on BK(Ca) and K(V) channels were observed. RESULTS: (1) DHA enhanced IBK(Ca) and BK(Ca) tail currents in a concentration-dependent manner while did not affect the stably activated curves of IBK(Ca). IBK(Ca) current densities were (68.2 ± 22.8), (72.4 ± 24.5), (120.4 ± 37.9), (237.5 ± 53.2), (323.6 ± 74.8) and (370.6 ± 88.2)pA/pF respectively (P < 0.05, n = 30) with the addition of 0, 10, 20, 40, 60 and 80 µmol/L DHA concentration, and half-effect concentration (EC(50)) of DHA was (36.22 ± 2.17)µmol/L. (2) IK(V) and K(V) tail currents were gradually reduced, stably activated curves of IK(V) were shift to the right, and stably inactivated curves were shifted to the left in the presence of DHA. IK(V) current densities were (43.9 ± 2.3), (43.8 ± 2.3), (42.9 ± 2.0), (32.3 ± 1.9), (11.7 ± 1.5) and (9.6 ± 1.2)pA/pF respectively(P < 0.05, n = 30)post treatment with 0, 10, 20, 40, 60 and 80 µmol/L DHA under manding potential equal to +50 mV, and EC(50) of DHA was (44.19 ± 0.63)µmol/L. CONCLUSION: DHA can activate BK(Ca) channels and block K(V) channels in rat CASMCs, the combined effects on BK(Ca) and K(V) channels lead to the vasodilation effects of DHA on vascular smooth muscle cells.

[Effects of docosahexaenoic acid on sodium channel current and transient outward potassium channel current in rat ventricular myocytes].

OBJECTIVE: To investigate the effects of docosahexaenoic acid (DHA) on sodium channel current (I(Na)) and transient outward potassium channel current (I(to)) in rat ventricular myocytes and to evaluate potential anti-arrhythmic mechanisms of DHA. METHODS: I(Na) and I(to) of individual ventricular myocytes were recorded by patch-clamp technique in whole-cell configuration at room temperature. Effects of DHA at various concentrations (0, 20, 40, 60, 80, 100 and 120 micromol/L) on I(Na) and I(to) were observed. RESULTS: (1) I(Na) was blocked in a concentration-dependent manner by DHA, stably inactivated curves were shifted to the left, and recover time from inactivation was prolonged while stably activated curves were not affected by DHA. At -30 mV, I(Na) was blocked to (1.51 ± 1.32)%, (21.13 ± 4.62)%, (51.61 ± 5.73)%, (67.62 ± 6.52)%, (73.49 ± 7.59)% and (79.95 ± 7.62)% in the presence of above DHA concentrations (all P < 0.05, n = 20), and half-effect concentration (EC(50)) of DHA on I(Na) was (47.91 ± 1.57)micromol/L. (2) I(to) were also blocked in a concentration-dependent manner by DHA, stably inactivated curves were shifted to the left, and recover time from inactivation was prolonged with increasing concentrations of DHA, and stably activated curves were not affected by DHA. At +70 mV, I(to) was blocked to (2.61 ± 0.26)%, (21.79 ± 4.85)%, (63.11 ± 6.57)%, (75.52 ± 7.26)%, (81.82 ± 7.63)% and (84.33 ± 8.25)%, respectively, in the presence of above DHA concentrations (all P < 0.05, n = 20), and the EC(50) of DHA on I(to) was (49.11 ± 2.68)micromol/L. CONCLUSION: The blocking effects of DHA on APD and I(to) may serve as one of the anti-arrhythmia mechanisms of DHA.

[Effects of docosahexaenoic acid on action potential and transient outward potassium current on ventricular myocytes of Sprague-Dawley rat].

OBJECTIVE: To investigate the effects of docosahexaenoic acid (DHA) on action potential (AP) and transient outward potassium current (I(to)) on ventricular myocytes of Sprague-Dawley rat. METHODS: Calcium-tolerant ventricular myocytes were isolated by enzyme digestion. The changes of AP and I(to) with increasing DHA at concentrations of 0, 10, 20, 40, 60, 80, 100, 120 and 200 micromol/L were recorded by whole-cell patch clamp configuration. RESULTS: (1) Action potential durations (APDs) were not affected by DHA at concentrations from 0 micromol/L to 30 micromol/L, while APDs were gradually prolonged in proportion with increasing DHA concentrations from 30 micromol/L to 200 micromol/L within 5 minutes and remained stable thereafter. APD(25), APD(50) and APD(75) were (7.7 +/- 2.0) ms, (21.2 +/- 3.5) ms, and (100.1 +/- 9.8) ms respectively at 100 micromol/L DHA. APD(25), APD(50), and APD(75) were (15.2 +/- 4.0) ms, (45.7 +/- 6.8) ms, and (215.6 +/- 15.7) ms respectively at 200 micromol/L DHA. (2) I(to) was gradually reduced with the increasing DHA concentrations from 10 micromol/L to 200 micromol/L. I(to) was blocked by DHA in a dose-dependent manner. I(to) current density was (30.1 +/- 7.2) pA/pF at DHA concentration of 60 micromol/L and its half-inhibition concentration was 58.3 micromol/L. CONCLUSION: APDs are gradually prolonged while I(to) reduced with increasing concentrations of DHA which might contribute to the anti-arrhythmia mechanisms of DHA.

Effects of docosahexaenoic acid on large-conductance Ca2+-activated K+ channels and voltage-dependent K+ channels in rat coronary artery smooth muscle cells.

AIM: To investigate the effects of docosahexaenoic acid (DHA) on large-conductance Ca(2+)-activated K(+)(BK(Ca)) channels and voltage-dependent K(+) (K(V)) channels in rat coronary artery smooth muscle cells (CASMCs). METHODS: Rat CASMCs were isolated by an enzyme digestion method. BK(Ca) and K(V) currents in individual CASMCs were recorded by the patch-clamp technique in a whole-cell configuration at room temperature. Effects of DHA on BK(Ca) and K(V) channels were observed when it was applied at 10, 20, 30, 40, 50, 60, 70, and 80 micromol/L. RESULTS: When DHA concentrations were greater than 10 micromol/L, BK(Ca) currents increased in a dose-dependent manner. At a testing potential of +80 mV, 6.1%+/-0.3%, 76.5%+/-3.8%, 120.6%+/-5.5%, 248.0%+/-12.3%, 348.7%+/-17.3%, 374.2%+/-18.7%, 432.2%+/-21.6%, and 443.1%+/-22.1% of BK(Ca) currents were increased at the above concentrations, respectively. The half-effective concentration (EC(50)) of DHA on BK(Ca) currents was 37.53+/-1.65 micromol/L. When DHA concentrations were greater than 20 micromol/L, K(V) currents were gradually blocked by increasing concentrations of DHA. At a testing potential of +50 mV, 0.40%+/-0.02%, 1.37%+/-0.06%, 11.80%+/-0.59%, 26.50%+/-1.75%, 56.50%+/-2.89%, 73.30%+/-3.66%, 79.70%+/-3.94%, and 78.1%+/-3.91% of K(V) currents were blocked at the different concentrations listed above, respectively. The EC(50) of DHA on K(V) currents was 44.20+/-0.63 micromol/L. CONCLUSION: DHA can activate BK(Ca) channels and block K(V) channels in rat CASMCs, and the EC(50) of DHA for BK(Ca) channels is lower than that for K(V) channels; these findings indicate that the vasorelaxation effects of DHA on vascular smooth muscle cells are mainly due to its activation of BK(Ca) channels.

Effects of (S)-amlodipine and (R)-amlodipine on L-type calcium channel current of rat ventricular myocytes and cytosolic calcium of aortic smooth muscle cells.

OBJECTIVE: Amlodipine (Aml) has R- and S-isomers with different pharmacological effects. However, no data are available on the influence of (S)-Aml and (R)-Aml on L-type calcium channel current (I(Ca-L)) or cytosolic calcium (Ca2+). This study is to investigate effects on I(Ca-L) and cytosolic Ca2+. METHODS: I(Ca-L), peak currents, I-V curves, steady state activation curves, steady state inactivation curves and recovery curves from inactivation with (S)-Aml and (R)-Aml were recorded by whole-cell patch clamp configuration. Cytosolic Ca2+ of smooth muscle cells was assayed by Fura-2/AM. RESULTS: At the concentrations of 0.1, 0.5, 1, 5, and 10 micromol/L, 1.5 +/- 0.2%, 25.4 +/- 5.3%, 65.2 +/- 7.3%, 78.4 +/- 8.1%, and 94.2 +/- 5.0% of I(Ca-L) were blocked by (S)-Aml. I-V curves were shifted upward. Half-activation voltages were -16.01 +/- 1.65 mV, -17.61 +/- 1.60 mV, -20.17 +/- 1.46 mV, -21.87 +/- 1.69 mV and -24.09 +/- 1.87 mV (P < 0.05). Half-inactivation voltages were -27.16 +/- 4.48 mV, -28.69 +/- 4.52 mV, -31.19 +/- 4.17 mV, -32.63 +/- 4.34 mV and -35.16 +/- 4.46 mV (P < 0.05). Recovery time were prolonged gradually (P < 0.05). 10.3 +/- 1.2%, 35.2 +/- 3.5%, 60.1 +/- 5.0%, 78.9 +/- 6.1%, and 91.2 +/- 7.6% of cytosolic Ca2+ were reduced at different concentrations (P < 0.05). However, (R)-Aml at different concentrations had no effect on I(Ca-L) and cytosolic Ca2+ (P > 0.05). CONCLUSION: Only (S)-Aml has calcium channel blockade activity, while (R)-Aml has none of the pharmacologic actions associated with CCBs.

[Anti-Trichinella antibody level in muscle juice of experimentally infected mice].

OBJECTIVE: To detect the anti-Trichinella antibody level in muscle juice of experimentally infected mice and their correlation with serum antibodies. METHODS: Two hundred and eighty-eight Kunming mice were randomly divided into 3 groups (96 mice each), each mouse was inoculated with 100, 300 or 500 muscle larvae of T spiralis, respectively. Anti-Trichinella antibodies in serum and muscle juice taken weekly up to 18 weeks post-infection (wpi) were detected by ELISA using T. spiralis muscle larval excretory-secretory (ES) antigens. Thirty mice were inoculated with T. spiralis muscle larvae(500 larvae each). The muscle samples taken in 6 wpi were kept in plastic containers and conserved at 4 degrees C for 7 days or at -20 degrees C for 20 weeks for detecting anti-Trichinella antibodies later. RESULTS: Anti-Trichinella antibodies in muscle juice of the mice infected with 100, 300 or 500 larvae were detected in 4, 3 and 3 wpi, with antibody positive rate of 87.5%, 50% and 87.5% respectively. In the three groups of mice, the antibody positive rate of muscle juice increased gradually after infection and up to 100% in 6, 4 and 4 wpi, and the antibody level reached its peak in 8 wpi with an absorbance value of 0.43, 0.49 and 0.52 respectively. Thereafter, the antibody level decreased slightly, but the positive rate was still 100% and lasted to 18 wpi when the experiment was ended. The antibody level in muscle juice showed significant positive correlation with serum antibodies at different time intervals after infection in three groups (r100=0.940, r300=0.970, r500=0.983, P<0.05). The absorbance value of muscle samples conserved at 4 degrees C for 7 d and 1 d was the same (0.53) (F=0.250, P>0.05), and those conserved at -20 degrees C for 8 wk and 1 wk was 0.46 and 0.50 respectively, showing that the antibody level in muscle juice did not decreased considerably after the muscle samples were frozen at -20 degrees C for 8 weeks (F=2.273, P>0.05). The absorbance value of Trichinella-infected muscle conserved at -20 degrees C for 10 wk decreased to 0.43, with significant difference from that conserved at -20 degrees C for 1 wk, but the positive rate was also 100%, and antibodies were detected in all muscle samples conserved at -20 degrees C for 20 weeks when the experiment was ended. CONCLUSION: When animals died or were slaughtered and serum samples could not be collected, muscle juice can be collected from fresh, cool and frozen meat and used as a substitute sample for detecting anti-Trichinella antibodies.