Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post-hoc analysis of a randomized controlled trial

BackgroundCytokines are involved in the development of metabolic abnormalities that may result in metabolic syndrome (MetS). Since curcumin has shown anti-inflammatory properties, the aim of this study was to evaluate the effect of curcumin supplementation on serum cytokines concentrations in subjects with MetS.MethodsThis study was a post-hoc analysis of a randomized controlled trial in which males and females with diagnosis of MetS, according to the criteria defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, were studied. Subjects who met the inclusion criteria were randomly assigned to either curcumin (daily dose of 1 g/day) or a matched placebo for a period of 8 weeks.ResultsOne hundred and seventeen subjects were assigned to either curcumin (n = 59) or placebo (n = 58) groups. Within-group analysis revealed significant reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 following curcumin supplementation (p < 0.001). In the placebo group, serum levels of TGF-β were decreased (p = 0.003) but those of IL-6 (p = 0.735), TNF-α (p = 0.138) and MCP-1 (p = 0.832) remained unaltered by the end of study. Between-group comparison suggested significantly greater reductions in serum concentrations of TNF-α, IL-6, TGF-β and MCP-1 in the curcumin versus placebo group (p < 0.001). Apart from IL-6, changes in other parameters remained statistically significant after adjustment for potential confounders including changes in serum lipids and glucose levels, and baseline serum concentration of the cytokines.ConclusionResults of the present study suggest that curcumin supplementation significantly decreases serum concentrations of pro-inflammatory cytokines in subjects with MetS.     

Changes of serum adhesion molecules and cytokines in post-ERCP pancreatitis: Adhesion molecules and cytokines in acute pancreatitis

ObjectivesTo assess the early changes of soluble IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, TNF-α, TNF-β, IL-17A, IL-22, soluble (s) P-Selectin, sE-Selectin and sICAM-1 in post-ERCP pancreatitis (PEP).MethodsSingle center, prospective study of 318 ERCP procedures. Serum samples were acquired from all patients prior to ERCP, 6 hours and 24 hours after the procedure. For every PEP case, another patient was chosen as a control, matched for gender, age and time period in which ERCP took place.ResultsTotally, 28 cases and 28 controls were studied. Except for significantly higher IL-1b levels in cases at baseline, no significant differences were observed between cases and controls after Bonferroni corrections. An increase in IL-6 was noted between baseline and 6 h in cases alone (p = 0.016). There was a significant fall in sP-selectin levels at 6 and 24 hours compared to baseline in all patients (corrected p = 0.008 and 0.016 for cases and 0.016 and 0.048 for controls respectively). An increase of sE-selectin in cases was observed between 6 and 24 hours post-ERCP (corrected p = 0.03).ConclusionsSoluble forms of cytokines and adhesion molecules studied seem not to play a major role in PEP.     

Pro-inflammatory cytokine profile of critically ill septic patients following therapeutic plasma exchange

Severe sepsis involves a generalized inflammatory response, mediated by a number of various cytokines and factors. Plasma exchange (PE) has been proposed as a therapeutic approach to improve survival of patients with severe sepsis and septic shock. The theory is that removing harmful excessive endogenous inflammatory mediators is beneficial. Upon establishment of a diagnosis of severe sepsis, twelve patients received PE plus conventional sepsis treatment. Interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α were assayed before and after each session of PE.ResultsThere were no significant changes in cytokine plasma levels after each PE session compared to pre-procedure levels. Among measured pro-inflammatory cytokines, only the plasma levels of IL-6 before the 2nd and 3rd PE sessions were lower than baseline levels (p = 0.011 and p = 0.012, respectively). All patients tolerated PE therapy well without any adverse effects or homodynamic instability. The results of this study showed that PE does not have a direct and rapid effect on plasma level of TNF-α, IL-1β and IL-6.     

Time of sampling is crucial for measurement of cell-free plasma DNA following acute aseptic inflammation induced by exercise

ObjectivesTo determine the time-course changes of cell-free plasma DNA (cfDNA) following heavy exercise.MethodscfDNA concentration, C-reactive protein levels (hs-CRP), uric acid concentration (UA), creatine kinase activity (CK) were measured before and post-exercise (immediately post, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 24 h).ResultscfDNA increased (15-fold) 30-min post-exercise and normalized thereafter. hs-CRP increased (56%, p < 0.001) 1 h post-exercise, remained elevated throughout recovery (52–142%, p < 0.0001), and peaked (200% rise, p < 0.0001) at 24 h post-exercise. UA and CK increased (p < 0.05), immediately post-exercise, remained elevated throughout recovery (p < 0.0001), and peaked (p < 0.0001) at 24 h of post-exercise recovery.ConclusionscfDNA sampling timing is crucial and a potential source of error following aseptic inflammation.     

The prognostic value of serum pregnancy-associated plasma protein A,S100 and high sensitivity C-reactive protein in acute ischemic stroke patients without heparin administration

ObjectivesThe concerns regarding the pre-analytical bias caused by medicine treatments have been raised in the diagnosis and prognosis of ischemic stroke recently. The aim of this study was to examine the prognostic value of serum pregnancy-associated plasma protein A (PAPP-A), S100 and high sensitivity C-reactive protein (hs-CRP) in heparin-naïve patients of acute ischemic stroke.Design and methodsSerum levels of PAPP-A, S100 and hs-CRP were determined in 205 heparin-naïve patients of acute ischemic stroke and 50 healthy controls. Clinical information and radiological information were collected. Unfavorable outcomes (stroke recurrence, myocardial infarction or death) were also recorded after six months. The associations between serum biomarker levels and stroke severity/outcome were assessed.ResultsSerum PAPP-A, S100 and hs-CRP levels increased in patients compared with controls (P < 0.05). S100 and hs-CRP levels were significantly higher in patients with larger cerebral infarction sizes (P < 0.05) and more severe neurological impairment (P < 0.05). Serum PAPP-A level showed a progressive increase with the increase of stroke severity (P < 0.05). Serum hs-CRP and National Institutes of Health Stroke Scale (NIHSS) scores were identified as independent predictors for unfavorable outcomes with odds ratios of 2.884 (1.154 to 7.210, P = 0.023) and 2.887 (1.146 to 7.273, P = 0.024), respectively.ConclusionSerum PAPP-A, S100 and hs-CRP were associated with stroke severity or outcome after ischemic stroke and may offer complementary information, essential for clinical decision making. Serum PAPP-A showed a potential value for the evaluation of stroke clinically.     

Interleukin-1β genotype and circulating levels in cancer patients: Metastatic status and pain perception

ObjectivesProinflammatory cytokines released during inflammation can cause hyperexcitability in pain transmission neurons, leading to hyperalgesia and allodynia. Polymorphisms in interleukin 1 (IL-1) family of genes (IL1A, IL1B) and in IL-1 receptor antagonist (IL-1Ra, coded by IL1RN) may therefore induce alterations in cytokine levels/effects and pain related response. Our purpose was to investigate the influence of polymorphisms in IL1A/B/RN on cytokine serum levels and its correlation with pain intensity, performance status, adverse effects, metastases and breakthrough pain in Caucasian cancer patients.Design and methodsSerum IL-1α/β levels of 74 cancer patients were measured by competitive enzyme immunosorbent assay. All patients were also genotyped for the polymorphisms in IL1A (rs17561), IL1B (rs1143634) and IL1RN (rs419598) with Real-Time PCR. Results were then correlated to the appearance of bone or CNS metastases and several pain-related parameters.ResultsIL-1β rs1143634 homozygous for T allele were associated with lower levels of IL1-β (p = 0.032, Mann–Whitney test) and presented a trend for lower levels of pain (p = 0.06, Fisher's Exact Test). Also, IL1-β levels were related with cancer onset status, since a four-fold increase probability of metastatic disease was observed in high IL-1β individuals (OR = 4.074, p = 0.010, Pearson χ² test). Among the female patients presenting metastatic disease and carriers of the TT genotype we observed a trend to lower levels of IL1-β (p = 0.053, Pearson χ² test).ConclusionsOur results indicate that genetic variation at IL1-β gene may influence serum levels of IL1-β, with proportional consequences in cancer-related pain.     

Plasma concentrations of Gas6 and soluble Axl correlate with disease and predict mortality in patients with critical limb ischemia

IntroductionCritical limb ischemia (CLI) is a severe peripheral arterial disease, characterized by rest pain, ulcers and gangrene in the legs. Gas6 is a vitamin K-dependent protein, which binds and activates the tyrosine kinase receptor Axl. Gas6-mediated Axl-signaling influences endothelial activation, neointima formation and immune regulation. Axl can be cleaved and soluble Axl (sAxl) is detectable in circulation.Design and methodsWe quantified plasma concentrations of Gas6 and sAxl in 189 CLI patients and 204 controls.ResultsGas6 and sAxl concentrations were increased in the CLI patients (p < 0.0001) and correlated to C-reactive protein, interleukin-6, tumor necrosis factor α and neopterin. Patients who died within 3 years of sampling (n = 84) had increased concentrations of Gas6 and sAxl as compared to survivors (p = 0.0009 and p = 0.0011).ConclusionsPlasma concentrations of Gas6 and sAxl correlate to inflammation and predict survival. This indicates that Gas6 and sAxl have a role in CLI, presumably connected to the inflammatory process.     

Association of serum carotenoids with high molecular weight adiponectin and inflammation markers among Japanese subjects

BackgroundSeveral studies have reported that serum concentrations of carotenoids and adiponectin are inversely associated with the risk for cardiovascular disease (CVD). However, no studies have investigated the association between serum concentrations of adiponectin and carotenoids in the general population.MethodsWe investigated cross-sectionally whether serum carotenoids are associated with serum high molecular weight (HMW) adiponectin and some inflammatory markers in 437 Japanese subjects (116 men and 321 women) who attended a health examination.ResultsIn multiple linear regression analysis adjusted for confounding factors, serum β-carotene concentrations were significantly associated with serum HMW adiponectin concentrations in both sexes (standardized β coefficient = 0.197, p = 0.036 for men; standardized β coefficient = 0.146, p = 0.012 for women). Serum α-carotene and β-carotene concentrations were significantly associated with serum C-reactive protein (CRP) concentrations in men. In women, there were significant negative associations between serum carotenoids concentrations and serum interleukin-6 (IL-6) concentrations. Additional adjustment for serum concentrations of IL-6 or CRP did not significantly affect the association between carotenoids and HMW adiponectin in non-smoking men as well as in women.ConclusionSerum β-carotene concentrations were positively associated with serum HMW adiponectin concentrations even after adjustment for possible confounding factors including inflammatory markers.     

Serum interleukin measurement may help identify thyroid cancer patients with active disease

BackgroundInvestigate the clinical utility of serum interleukin dosages of IL-2, IL-2R, IL-4, IL-6, IL-6R, IL-8, IL-10 and IL-12 in the diagnosis and characterization of patients with DTC. In particular, verify ILs utility in the identification of individuals who are evolving disease-free or with the active disease.MethodsWe evaluated 200 patients with malignant nodules (100 patients disease-free and 100 patients with recurrence/active disease); 60 benign nodules and 100 healthy controls, serum levels were assessed by ELISA.ResultsAll ILs, but not IL-4, differentiated these three groups. We observed that IL-2, 2R and 10 serum concentrations were associated with thyroglobulin levels. Serum IL-2 was able to differentiate patients with active disease from the disease-free with a sensitivity of 98%, specificity of 58%, positive predictive value (PPV) of 70% and negative predictive value (NPV) of 97% (p = 0.0007). IL-6R levels differentiated patients with active disease from the disease-free patients with 56% sensitivity, 63% specificity, PPV of 60% and NPV of 59% (p < 0.0001). IL-8 values also distinguished patients with active disease from the disease-free ones with sensitivity of 50%, specificity of 76%, PPV of 68% and NPV of 60% (p = 0.0025); using IL-12, we obtained a sensitivity value of 73%, specificity of 66%, PPV of 68% and NPV of 71% (p < 0.0001). Furthermore, interleukin levels showed association with some tumor characteristics of aggressiveness.ConclusionWe suggest that the serum concentration of ILs may assist in the diagnosis and characterization of tumor malignancy helping identify patients with active disease who deserve closer medical attention.     

Sperm head defects and disturbances in spermatozoal chromatin and DNA integrities in idiopathic infertile subjects: Association with cigarette smoking

ObjectivesTo evaluate sperm chromatin and DNA integrities in idiopathic infertile men and determine the possible association(s) of cigarette smoking on oxidative stress markers, antioxidant capacity and semen quality.Subjects and methodsSemen samples from men referring to the andrology laboratory were categorized into 3 groups: fertile non-smokers (n = 16), infertile non-smokers (n = 36), and infertile smokers (n = 34). Semen analysis was performed according to WHO criteria. The percentage of sperm DNA fragmentation index (%DFI) and the percentage of sperm with abnormally high DNA stainability (HDS%; immature spermatozoa) were determined by SCSA using the metachromatic properties of acridine orange. Lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) levels in seminal plasma and spermatozoa were measured by spectrophotometric assays.ResultsThe classical semen parameters were negatively correlated with lipid peroxidation in spermatozoa; motility and morphology were negatively correlated with %DFI (p < 0.05). HDS% was also negatively correlated with above markers except for morphology (r = ? 0.352, p = 0.081). DFI% and HDS% were significantly higher in the infertile smokers group than in infertile non-smokers (p = 0.032; p = 0.001 respectively). Cigarette smoking was significantly associated with DFI%, HDS%, TBARS and the fraction of “round-headed” sperm (r = 0.796, p = 0.0001; r = 0.371, p = 0.033; r = 0.606, r = 0.591, p = 0.001 respectively), and decreased SOD levels (r = ? 0.545).ConclusionDFI%, HDS% and round-head sperms are increased in idiopathic infertile men; this increase is associated with cigarette smoking. These defects may be attributed to increased oxidative stress and insufficient scavenging antioxidant enzymes in the seminal fluid of infertile patients.     

Serum amyloid A is independently related to apolipoprotein A-I but not to HDL-cholesterol in patients with angina pectoris

BackgroundInflammation processes are considered important links between classical lipid risk factors and the progression of atherosclerosis. The interrelationship of high density lipoproteins (HDL) and apolipoprotein apoA-1 with acute phase proteins and cytokines was examined in a clinical setting of patients with angina pectoris.MethodsOn exclusion criteria (myocardial infarction, heart failure, CHD > 2 years, anticoagulant therapy), 198 patients were recruited and were subdivided according to angiographically documented stenosis, no stenosis vs. = 50% stenosis, in accordance with CASS guidelines. Lipids, apoA-1 and apoB, C-reactive protein (hs-CRP), fibrinogen, serum amyloid A (SAA) and cytokines (IL-6, IL-8, IL-10, IL2R, TNFα) were measured.ResultsLow HDL-C (and apoA-I) is associated with advanced coronary stenosis (= 50%) and with the number of diseased vessels, independent of age, gender, diabetes, smoking and lipid-lowering therapy. In contrast to hs-CRP and fibrinogen, SAA as well as cytokine levels were not significantly associated with stenosis. SAA (P = 0.0003) and diabetes (P = 0.0002) were strong predictors of apoA-I concentration independent of age, gender, BMI, smoking, CRP, as well as IL-6 in a multiple regression model. High SAA (P = 0.0067) and TG (P = 0.0123) were significant predictors of apoA-I/HDL-C ratio. However, SAA was not independently related to HDL-C.ConclusionsSAA is independently and inversely related to apoA-I but not to HDL-C in patients with angina pectoris, reflecting the effect of SAA on the quality of HDL particles. However, HDL-c but not SAA is inversely related to the degree of coronary artery stenosis.     

Serum glycated albumin levels,but not glycated hemoglobin,is low in relation to glycemia in non-diabetic men with nonalcoholic fatty liver disease with high alanine aminotransferase levels

ObjectivesWe have reported that serum glycated albumin (GA) levels are low in obese subjects, smokers and hyperuricemic subjects in whom high sensitive CRP (hs-CRP) is elevated. Because patients with nonalcoholic fatty liver disease with high alanine aminotransferase (ALT) levels are reported to show high levels of hs-CRP, the relationship between serum ALT and serum GA levels was investigated.Design and methodsThis study comprised 196 non-diabetic men without drinking habit.ResultsCompared with the normal ALT group (serum ALT ≤ 30 U/L; n = 158), the high ALT group (serum ALT > 30 U/L; n = 38) had significantly higher fasting plasma glucose (PG), OGTT 2-h PG and HbA_1C levels. Meanwhile, serum GA was significantly lower, and hs-CRP was significantly higher in the high ALT group.ConclusionsThe results obtained indicate that serum GA is under a negative control of hs-CRP in subjects with high ALT without drinking habit.     

Relationship of proprotein convertase subtilisin-kexin type 9 levels with resistin in lean and obese subjects

ObjectivesProprotein convertase subtilisin-kexin type 9 (PCSK9), a key regulator of low density lipoprotein receptor expression, has recently been reported to be upregulated by resistin in HepG2 cells and human primary hepatocytes. Whether this translates into a positive relationship of plasma PCSK9 with resistin levels in humans with varying degrees of obesity is unknown.Design and methodsWe assessed the extent to which plasma PCSK9 levels are determined by resistin in individuals with varying degrees of obesity.ResultsIn 80 subjects (35 women; no diabetes mellitus) with body mass index ranging from 19.4 to 40.4 kg/m², plasma PCSK9 levels were not positively related to resistin (r = ? 0.161, p = 0.154). Despite positive correlations of non-high density lipoprotein cholesterol (r = 0.378, p < 0.001), low density lipoprotein (r = 0.292, p < 0.01) and apolipoprotein B (apoB) (r = 0.266, p < 0.05) with PCSK9, none of these apolipoprotein (apo) B-containing lipoprotein measures was positively related to resistin (p > 0.10 for all). In subjects with BMI < 25.0 kg/m² (n = 38), PCSK9 was even inversely related to resistin (r = ? 0.322, p = 0.049), and this relationship remained present after controlling for either leptin (p = 0.027) or insulin resistance (P = 0.031). In subjects with BMI ≥ 25.0 kg/m² (n = 42), PCSK9 was unrelated to resistin (r = ? 0.064, p = 0.69).ConclusionsThis study demonstrates that there is no positive association of plasma PCSK9 with resistin in lean and moderately obese individuals. Our data question whether circulating resistin is a physiologically important determinant of higher PCSK9 levels.     

VEGF-A gene promoter polymorphisms and microvascular complications in patients with essential hypertension

ObjectivesWe investigated the possible involvement of vascular endothelial growth factor (VEGF-A) gene promoter polymorphisms in essential hypertension (EH).Design and methods1225 bp of the VEGF-A gene promoter were screened for polymorphisms using PCR amplification and direct DNA sequence analysis in 62 EH and 62 normotensive (HS) individuals. Circulating VEGF-A levels were determined by immunoassay.Results?152G/A (p = 0.009) and ?116G/A (p = 0.016) polymorphisms were correlated to hypertension (p < 0.05). Median platelet VEGF-A load in EH was 2.10 fg/plt. Patients with microvascular complications (MC) had higher platelet VEGF-A load than those without (p = 0.005). Multivariate analyses showed that ?116 A allele was an independent predictor of microalbuminuria (p = 0.014) and increased platelet VEGF-A load (p = 0.009) in EH. Platelet VEGF-A load independently predicted MC (p = 0.049) in addition to ?116G/A polymorphism (p = 0.035).ConclusionsAbnormal regulation of VEGF-A due to polymorphism at position ?116 might represent a genetic factor for increased VEGF-A production and MC in EH.     

Plasma osteopontin concentration correlates with the severity of hepatic fibrosis and inflammation in HCV-infected subjects

BackgroundThe association between OPN level and the histological severity of hepatic fibrosis and inflammation in hepatitis C virus (HCV) induced liver fibrosis remains unknown.Methods120 chronic HCV-infected subjects and 75 controls were enrolled in this study. Assessment of liver histology was performed based on liver biopsy. Plasma OPN levels were determined.ResultsSignificant differences were noted in the mean plasma OPN levels between subjects with extensive fibrosis and those with mild fibrosis (4.29 ± 1.01 ng/ml vs. 2.15 ± 0.63 ng/ml, respectively; p < 0.001). Similarly, the subjects with higher histological activity index (HAI) score had elevated OPN levels than those with mild HAI score (4.41 ± 1.11 ng/ml vs. 2.25 ± 0.94 ng/ml, respectively; p < 0.001). The correlation between the plasma OPN levels and the severity of liver fibrosis degree and HAI score were noted (r = 0.945, and r = 0.788, respectively both p < 0.001). Logistic regression analysis showed that serum OPN was an independent risk factor contributing to extensive liver fibrosis and inflammation (p = 0.0018 and p < 0.001, respectively) in patients with HCV subjects.ConclusionThe plasma OPN level is correlated with the severity of liver fibrosis and inflammation, suggesting OPN could be used as a biomarker to evaluate the severity of liver damages in HCV subjects.     

Impact of radiotherapy and chemotherapy on biomarkers of oxidative DNA damage in lung cancer patients

ObjectivesTo assess oxidative damage to DNA during lung cancer (LC) treatments.Design and methodsUrinary levels of 8-oxoguanine (8-oxoGua) and levels of 8-oxo-2′-deoxyguanosine (8-oxodG) from urine and whole blood were determined in 36 non-cancer controls and 65 LC patients before any treatments. Samples were also obtained of LC patients during and after radiotherapy (RT, n = 33) and chemotherapy (CT, n = 16).ResultsStage IV LC patients had higher urinary 8-oxoGua and 8-oxodG levels than patients with stage I–III disease (p = 0.044 and p = 0.034, respectively). Urinary 8-oxodG levels increased during the first week of RT (p < 0.001). Nuclear 8-oxodG increased during RT and 3 months after start of RT. Nuclear 8-oxodG levels also rose between the first two CT cycles (p = 0.043), and urinary 8-oxodG levels during the sixth CT cycle (p = 0.009).ConclusionsUrinary DNA damage biomarker levels may be associated with LC stage. Both RT and CT increase the parameters of DNA oxidation.     

Prevalence of gastric parietal cell antibodies and intrinsic factor antibodies in primary biliary cirrhosis

BackgroundWe investigated the prevalence of antibodies against gastric parietal cells (GPA), intrinsic factor antibodies (IFA) and the presence of pernicious anemia in a large cohort of primary biliary cirrhosis (PBC) patients as similar data is missing.Methods157 PBC patients and 357 controls (73 with autoimmune hepatitis (AIH), 35 primary sclerosing cholangitis (PSC), 45 HBV, 37 HCV, 36 alcoholic liver disease (ALD), 35 non-alcoholic fatty liver disease (NAFLD) and 96 healthy) were investigated for IgG-isotype-specific GPA and IFA by ELISAs and vitamin-B₁₂ levels by a microparticle enzyme immunoassay.ResultsThe detection of IgG-GPA was significantly higher in PBC (31.8%) compared to AIH (10.9%; p = 0.001), PSC (0%; p = 0.000), HCV (13.5%; p = 0.01), HBV (13.3%; p = 0.006), ALD (8.3%; p = 0.004), NAFLD (11.4%; p = 0.003) and healthy (10.4%; p = 0.001). IgG-IFA were detected in 12% of GPA-positive PBC patients and in none of the other liver diseases or in healthy (p = 0.001). This reactivity was significantly associated with lower vitamin-B₁₂ levels compared to those with an IFA-negative test (p = 0.025).ConclusionsA significant proportion of PBC patients had IgG-GPA and IFA compared to controls. IgG-IFA were detected only in GPA-positive PBC patients and associated with lower vitamin-B₁₂ levels compared to those with an IFA-negative test.     

Prognostic implication of out-of-hospital cardiac arrest in patients with cardiogenic shock and acute myocardial infarction

ObjectivesTo compare outcome in patients with acute myocardial infarction (MI) and cardiogenic shock (CS) presenting with and without out-of-hospital cardiac arrest (OHCA).BackgroundDespite general improvement in outcome after acute MI, CS remains a leading cause of death in acute MI patients with a high 30-day mortality rate. OHCA on top of cardiogenic shock may further increase mortality in these patients resulting in premature withdrawal of supportive therapy, but this is not known.Methods and resultsIn a retrospective study from 2008 to 2013, 248 consecutive patients admitted alive to a tertiary centre with the diagnosis of CS and acute MI were enrolled, 118 (48%) presented with OHCA and 130 (52%) without (non-OHCA patients). Mean lactate level at admission was significantly higher in OHCA patients compared with non-OCHA patients (9 mmol/l (SD 6) vs. 6 mmol/l (SD 4) p < 0.0001). Co-morbidities were more prevalent in the non-OHCA group. By univariate analysis age (Hazard ratio (HR) = 1.02 [CI 1.00–1.03], p = 0.01) and lactate at admission (HR = 1.06 [CI 1.03–1.09], p < 0.001), but not OHCA (HR = 1.1 [CI 0.8–1.4], p = NS) was associated with mortality. In multivariate analysis, only age (HR = 1.02 [CI 1.01–1.04], p = 0.003) and lactate level at admission (HR = 1.06 [1.03–1.09], p < 0.001) were independent predictors of mortality. One-week mortality was 63% in the OHCA group and 56% in the non-OHCA group, p = NS.ConclusionOHCA is not an independent predictor of mortality in patients with acute MI complicated by cardiogenic shock. This should encourage active intensive treatment of CS patients regardless of OHCA.     

Association of genetic variations in aromatase gene with serum estrogen and estrogen/testosterone ratio in Chinese elderly men

BackgroundSingle nucleotide polymorphism (SNP) rs2470152 of the gene CYP19A1 is associated with serum estradiol (E2) levels in Caucasian men. However, it remains to be verified if rs2470152 is the sole determinant accounting for the association. We determined whether 2 CYP19A1 SNPs tagging different haploblocks (rs2470152 and rs2899470) are associated with sex steroid levels in Chinese men.MethodSerum sex steroid level including E2, estrone (E1) and testosterone (T), of 1402 Chinese men aged ≥ 65 years were analyzed. Genotyping of the two CYP19A1 SNPs was performed using T_m-shift allele-specific PCR.ResultsSNP rs2899470 was significantly associated with serum E2, E1 levels and E2/T ratio (p < 0.001). However, SNP rs2470152 was only modestly associated with E2/T ratio (p = 0.023). Analysis of haplotype showed a significant association between C-G, T-T haplotype with serum E2/T ratio (p = 0.019 and p = 1 × 10^? 5, respectively). Similarly, E2 levels was also associated the T-T and T-G haplotypes (p = 1 × 10^? 5).ConclusionThe genetic variation of CYP19A1 was associated with circulating estrogen levels in Chinese elderly men. In addition, it revealed that haplotype of rs2899470 and rs2470152, rather than rs2899470 alone, was a better indicator for the serum E2/T ratio and E2 levels.