Anti-Allergic Effects of Vernonia amygdalina Leaf Extracts in Hapten-Induced Atopic Dermatitis-Like Disease in Mice

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritic and ec- zematous skin lesions. In this study, AD-like disease was induced in NC/Nga mice so as to evaluate the antiallergic effects of Vernonia amygdalina leaf extracts (VAM).Methods: Forty NC/Nga mice were purchased for each of the two protocols (prophylactic and curative) of the study. Mice were randomly divided in groups of five or six after sensitization with 5% trinitrochlorobenzene (TNCB): aqueous extracts (VAM1), methanolic extracts (VAM2), hydrocortisone (HCT), buffer for the control (TNCB) and the normal mice (NORM) groups.Results: As for HCT, VAM1 and VAM2-pretreated mice showed significantly lower number of scratching behavior episodes (p < 0.01; vs. TNCB) following TNCB challenge. In addition, VAM1, VAM2 exerted a significant inhibitory effect on the development of AD skin symptoms (vs. TNCB group; p < 0.001), the production of IgE, TNF-alpha (p < 0.05), IL-5 and IFN-gamma (p < 0.01) (vs. TNCB group) and on the increase in ear thickness (p < 0.05) in prophylactic protocol.In the AD curative protocol, topical VAM1, VAM2 markedly improved skin lesions such as erythema/hemorrhage (p < 0.05), scaling/dryness, erosion/excoriation (p < 0.01) (vs. TNCB mice). Furthermore, a significant decrease in ear thickness was noted in VAM1, VAM2, HCT groups (vs. TNCB group; p < 0.05) as well as the serum total IgE, MCP-1 (p < 0.01) and eotaxin (p < 0.05). VAM2 also improved chronic eczema dermatitis skin symptoms in a patient.Conclusions: Results from this report suggest that VAM extracts, known as ERK pathway inhibitor, prevent and improve atopic/eczema dermatitis syndrome.     

CALU polymorphism A29809G affects calumenin availability involving vascular calcification

Calumenin inhibits gamma-carboxylation of matrix-Gla-protein preventing BMP2-dependent calcification. Our aim was to explore the clinical relevance and functionality of the CALU polymorphism rs1043550, and the relationship of calumenin time-dependent expression profile with the active calcification of human vascular smooth muscle cells (hVSMC). Coronary artery calcium score and lesion severity were assessed by cardiac computed tomography in 139 consecutive low-risk patients genotyped for rs1043550. Polymorphic (G) allele carriage was associated with lower calcium (OR: 6.19, p = 0.042). Calcified arteries from CALU ‘A’ allele carriers undergoing cardiovascular surgery exhibited higher residual calcification, higher calumenin immunostaining and lower matrix-Gla-protein, contrary to ‘G’ allele carriers. In a luciferase reporter system in vascular cells, polymorphic ‘G’ allele reduced the mRNA stability by 30% (p < 0.05). Osteogenic high-phosphate media induced active differentiation of hVSMC onto functional osteoblast-like cells as demonstrated by extracellular matrix mineralization and osteoblast markers expression. Calumenin was early over-expressed at day 3 (p < 0.05), but decreased thereafter (mRNA and protein) with implications on gamma-carboxylation system. Calumenin was found released and co-localizing with extracellular matrix calcifications. The CALU polymorphism rs1043550 affects mRNA stability and tissue availability of calumenin thus supporting the protective clinical significance. Calumenin shows a time-dependent profile during induced calcification. These data demonstrate a novel association of vascular calcification with the VSMC phenotypic transition into osteoblast-like cells. Moreover, hyperphosphatemic stimuli render calumenin accumulation in the mineralized extracellular matrix.     

BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells

Vascular calcification is associated with increased risk of cardiovascular events that are the most common cause of death in patients with end-stage renal disease. Clinical and experimental studies indicate that hyperphosphatemia is a risk factor for vascular calcification and cardiovascular mortality in these patients. Our previous studies demonstrated that phosphate transport through the type III sodium-dependent phosphate cotransporter, Pit-1, was necessary for phosphate-induced calcification and osteochondrogenic phenotypic change in cultured human smooth muscle cells (SMC). BMP-2 is a potent osteogenic protein required for osteoblast differentiation and bone formation that has been implicated in vascular calcification. In the present study, we have examined the effects of BMP-2 on human SMC calcification in vitro. We found that treatment of SMC with BMP-2 enhanced elevated phosphate-induced calcification, but did not induce calcification under normal phosphate conditions. mRNAs for BMP receptors, including ALK2, ALK3, ALK6, BMPR-II, ActR-IIA and ActR-IIB were all detected in human SMCs. Mechanistically, BMP-2 dose-dependently stimulated phosphate uptake in SMC (200 ng/ml BMP-2 vs. vehicle: 13.94 vs. 7.09 nmol/30 min/mg protein, respectively). Real-time PCR and Western blot revealed the upregulation of Pit-1 mRNA and protein levels, respectively, by BMP-2. More importantly, inhibition of phosphate uptake by a competitive inhibitor of sodium-dependent phosphate cotransport, phosphonoformic acid, abrogated BMP-2-induced calcification. These results indicate that phosphate transport via Pit-1 is crucial in BMP-2-regulated SMC calcification. In addition, BMP-2-induced Runx2 and inhibited SM22 expression, indicating that it promotes osteogenic phenotype transition in these cells. Thus, BMP-2 may promote vascular calcification via increased phosphate uptake and induction of osteogenic phenotype modulation in SMC.     

皮质抑素调控钙化相关基因减轻大鼠动脉钙化

目的 探讨皮质抑素（cortistatin，CST）对大鼠主动脉钙化的影响及其可能的分子机制。方法 利用维生素D3联合尼古丁（VDN）所致的大鼠动脉钙化模型，分别采用孔雀绿直接显色法、邻甲酚酞络合酮比色法和von Kossa染色法测定大鼠血浆磷、钙水平和主动脉组织的钙含量和钙沉积，应用RT-PCR方法检测主动脉组织钙化相关基因mRNA表达。结果 与对照组相比较，VDN使大鼠主动脉的钙含量增加70.2%（P<0.05），引起弹力纤维紊乱、中断，von Kossa染色阳性的棕黑色颗粒明显增多。VDN+CST组与单独VDN组相比较，持续皮下泵入CST使主动脉的钙含量减少45.6%（P<0.05），弹力纤维紊乱中断减轻和棕黑色颗粒明显减少。而血钙、磷及钙磷乘积在各组间无显著性差异。RT-PCR结果证实VDN组主动脉组织的BMP-2 mRNA和Pit-1 mRNA表达分别增加53.2%（P<0.05）和34.0%（P<0.01），而MGP mRNA表达减少27.0%（P<0.05）。持续皮下泵入CST使主动脉组织BMP-2 mRNA和Pit-1 mRNA表达较单独VDN组分别下降38.3%（P<0.01）和17.4%（P<0.05），而MGP mRNA表达增加34.9%（P<0.01）。主动脉组织OPG mRNA表达在各组间均无显著性差异。结论 CST能够减轻VDN所致的大鼠动脉钙化，可能与其纠正促\抑钙化相关基因表达失衡有关，从而为CST防治动脉钙化提供实验依据。     

Evaluation of left ventricular mechanical dyssynchrony in chronic heart failure patients by two-dimensional speckle tracking imaging

The purpose of this study was to evaluate left ventricular mechanical dyssynchrony (LVMD) in chronic heart failure (CHF) patients using two-dimensional speckle tracking imaging (2D-STI), and also to compare the usefulness of three patterns of myocardial deformation in mechanical dyssynchrony assessment. Furthermore, the relationships between left ventricular ejection fraction (LVEF), QRS duration (QRSd), and LVMD were explored. In total, 78 patients and 60 healthy individuals (group 3) were enrolled. The patients were classified into two subgroups: LVEF ≤ 35% (group 1), 35% < LVEF < 50% (group 2). All participants underwent two-dimensional echocardiography, and dyssynchrony indices derived from 2D-STI were calculated. According to statistical principles, the cut-off value of LVMD was defined as mean ± 1.645 SD of the normal population. Dyssynchrony rates were calculated in CHF subgroups and compared within each subgroup, respectively. Compared with group 3, all indices in group 1 were remarkably higher (p < 0.05), and some of the indices in group 2 were significantly higher (p < 0.05). A significant difference of dyssynchrony rate was noted within both group 1 and group 2 (χ² = 25.55, p < 0.05 vs. χ² = 23.88, p < 0.05), and the highest value was derived from the longitudinal index in both subgroups. LVEF was related to all three forms of strain/strain rate (p < 0.05), whereas no relationship existed between QRSd and dyssynchrony indices (p > 0.05). CHF patients have different extents of LVMD. Longitudinal deformation shows the best detectability of dyssynchrony motion. Left ventricular systolic function was closely related to mechanical dyssynchrony, whereas QRSd showed no significant correlation.     

Phosphorylation of eIF2α mitigates endoplasmic reticulum stress and hepatocyte necroptosis in acute liver injury

Introduction and objectivesNecroptosis and endoplasmic reticulum (ER) stress has been implicated in acute and chronic liver injury. Activated eukaryotic initiation factor 2 alpha (eIF2α) attenuates protein synthesis and relieves the load of protein folding in the ER. In this study, we aimed to analyze the impact of eIF2α phosphorylation on hepatocyte necroptosis in acute liver injury.Materials and methodsMale BALB/c mice were injected with tunicamycin or d-galactosamine, and LO2 cells were incubated with tunicamycin to induce acute liver injury. 4-Phenylbutyric acid (PBA) and salubrinal were used to inhibit ER stress and eIF2α dephosphorylation, respectively. We analyzed the eIF2α phosphorylation, ER stress, and hepatocyte necroptosis in mice and cells model.ResultsTunicamycin or d-galactosamine significantly induced ER stress and necroptosis, as well as eIF2α phosphorylation, in mice and LO2 cells (p < 0.05). ER stress aggravated tunicamycin-induced hepatocyte necroptosis in mice and LO2 cells (p < 0.05). Elevated eIF2α phosphorylation significantly mitigated hepatocyte ER stress (p < 0.05) and hepatocyte necroptosis in mice (34.37 ± 3.39% vs 22.53 ± 2.18%; p < 0.05) and LO2 cells (1 ± 0.11 vs 0.33 ± 0.05; p < 0.05). Interestingly, tumor necrosis factor receptor (TNFR) 1 protein levels were not completely synchronized with necroptosis. TNFR1 expression was reduced in d-galactosamine-treated mice (p < 0.05) and cells incubated with tunicamycin for 12 and 24 h (p < 0.05). ER stress partially restored TNFR1 expression and increased necroptosis in tunicamycin-incubated cells (p < 0.05).ConclusionsThese results imply that ER stress can mediate hepatocyte necroptosis independent of TNFR1 signaling and elevated eIF2α phosphorylation can mitigate ER stress during acute liver injury.     

Tumor burden score predicts tumor recurrence of non-functional pancreatic neuroendocrine tumors after curative resection

BackgroundTo investigate the feasibility of Tumor Burden Score (TBS) to predict tumor recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs).MethodThe TBS cut-off values were determined by a statistical tool, X-tile. The influence of TBS on recurrence-free survival (RFS) was examined.ResultsAmong 842 NF-pNETs patients, there was an incremental worsening of RFS as the TBS increased (5-year RFS, low, medium, and high TBS: 92.0%, 73.3%, and 59.3%, respectively; P < 0.001). TBS (AUC 0.74) out-performed both maximum tumor size (AUC 0.65) and number of tumors (AUC 0.5) to predict RFS (TBS vs. maximum tumor size, p = 0.05; TBS vs. number of tumors, p < 0.01). The impact of margin (low TBS: R0 80.4% vs. R1 71.9%, p = 0.01 vs. medium TBS: R0 55.8% vs. R1 37.5%, p = 0.67 vs. high TBS: R0 31.9% vs. R1 12.0%, p = 0.11) and nodal (5-year RFS, low TBS: N0 94.9% vs. N1 68.4%, p < 0.01 vs. medium TBS: N0 81.8% vs. N1 55.4%, p < 0.01 vs. high TBS: N0 58.0% vs. N1 54.2%, p = 0.15) status on 5-year RFS outcomes disappeared among patients who had higher TBS.ConclusionsTBS was strongly associated with risk of recurrence and outperformed both tumor size and number alone.     

Effects of cardiac rehabilitation on physical function and exercise capacity in elderly cardiovascular patients with frailty

BackgroundThe effects of cardiac rehabilitation (CR) on long-term prognosis of cardiovascular disease (CVD) are well known. However, the effect of CR on frail CVD patients has not been fully addressed.MethodsThis study consisted of 89 CVD patients with their age ≥65 years old (68 males, 75 ± 6 years), who participated in the outpatient CR program for 3 months. All the patients underwent cardiopulmonary exercise testing and the physical frailty was assessed using the Japanese Version of the Cardiovascular Health Study Standard before and after CR. Based on the assessment of frailty before CR, the patients were divided into the following two groups: frailty group (n = 23) and non-frailty group (n = 66: robust in 10 and pre-frail in 56 patients).ResultsIn the frailty group, 20 patients (87%) improved from frail status after CR, and usual walking speed, maximal grip strength, and lower extremity strength were significantly improved (1.06±0.20 vs. 1.20±0.18 m/sec, p<0.001; 21.7 ± 5.5 vs. 23.6 ± 6.3 kg, p<0.01; 0.37±0.09 vs. 0.43±0.11 kgf/kg, p = 0.001, respectively), but peak VO₂ did not change after CR (15.9 ± 3.1 vs. 16.2 ± 3.8 ml/min/kg, NS). In the non-frailty group, all these parameters were significantly improved after CR (1.24±0.19 vs. 1.29±0.23 m/sec, p<0.05, 28.7 ± 7.0 vs. 30.2 ± 7.3 kg, p<0.001, 0.50±0.18 vs. 0.54±0.13 kgf/kg, p<0.05, 17.7 ± 4.7 vs 18.5 ± 4.2 ml/min/kg, p<0.01, respectively).ConclusionShort-term CR could obtain the improvement of the physical function, providing the prerequisite step for possibly following improvement of exercise capacity in elderly CVD patients with frailty. It may be inferred that longer duration of CR would be needed to obtain the improvement of exercise capacity in these patients, being the future consideration to be determined.     

Orexin A associates with inflammation by interacting with OX1R/OX2R receptor and activating prepro-Orexin in cancer tissues of gastric cancer patients

ObjectiveGastric cancer (GC) has been become the second leading cause for cancer-associated death. This study aimed to investigate Orexin A levels and associated receptors in tumor tissues of GC patients.Patients and methodsForty-six consecutive gastric cancer patients (GC, n = 46) and 13 chronic atrophic gastritis patients (CAG, n = 13) were recruited. Meanwhile, 18 health individuals visiting Medical Examination Department were involved as control (N group, n = 18). ELISA was used to examine Orexin A concentration. Immunohistochemistry assay was used to examine OX1R and OX2R. HE staining was applied to evaluate inflammation. qRT-PCR was employed to detect OX1R, OX2R, prepro-Orexin mRNAs. Serum Helicobacter pylori (H. pylori) infection was measured.ResultsOrexin A expression in GC patients was significantly up-regulated compared to N group and CAG group (p < 0.05). Orexin A expression was increased in CAG group compared to N group (p < 0.05). Gastric cancer tissues exhibited significantly obvious inflammation compared to N group and CAG group (p < 0.05). OX1R and OX2R expressions were significantly down-regulated in GC group compared to N group and CAG group (p < 0.05). OX1R and OX2R were lower significantly in GC group compared to CAG group (p < 0.05). Prepro-Orexin was significantly depleted in tumor tissues of GC group compared to N group and CAG group (p < 0.05). Orexin A expression was un-associated with gender, age and differential grades (p > 0.05). CAG and GC patients demonstrated higher H. pylori infection rates.ConclusionOrexin A was associated with inflammation by interacting with OX1R/OX2R receptor and activating prepro-Orexin in tumor tissues of gastric cancer patients.     

Effects of six months of vitamin D supplementation in patients with heart failure: A randomized double-blind controlled trial

Background and aimLow plasma vitamin D levels have been associated with heart failure (HF). This research attempts to explain the role of vitamin D supplementation on myocardial function in elderly patients with HF.Methods and resultsTwenty-three chronic HF patients were randomized in a small parallel group, double-blind, placebo-controlled trial. All patients, with a mean age of 74 years and vitamin D levels <30 ng/mL, received 800,000 IU (4000 IU/daily) of cholecalciferol or placebo for 6 months. The outcomes measured at baseline and after 6 months were ejection fraction (EF) and other echocardiography parameters, carboxyterminal propeptide of procollagen type I (PIP), natriuretic peptides, lipid profile, renin, parathyroid hormone, blood pressure, and body mass index (BMI).In 13 patients under active treatment for 6 months, mean plasma 25-hydroxy vitamin D concentrations (15.51 vs. −1.40 ng/mL, p < 0.001) and plasma calcium (from 9.3 to 9.6 mmol/L, p < 0.05) increased significantly. However, other biomarkers of bone metabolism did not differ between the treatment and placebo groups. EF increased significantly in the intervention group (6.71 vs. −4.3%; p < 0.001), and the serum concentration of PIP increased only in the placebo group after 6 months (1140.98 vs. −145 mcg/L; p < 0.05). Systolic blood pressure was lower after 6 months of cholecalciferol treatment (from 129.6 to 122.7 mm Hg, p < 0.05).No significant variations were observed for other parameters.ConclusionsSix months of vitamin D supplementation significantly improves EF in elderly patients with HF and vitamin D deficiency.     

Resting Cardiac Efficiency Affects Survival Following Transcatheter Aortic Valve Replacement

ObjectiveCardiac power to left ventricular mass (LVM) ratio, also termed cardiac efficiency (CE), reflects the rate of cardiac work delivered to the potential energy stored in LVM. We sought to assess the association between baseline resting CE and survival post transcatheter aortic valve replacement (TAVR).MethodsWe retrospectively extracted data of patients who received TAVR in the Mayo Clinic Foundation with follow up data available at 1 year. Cardiac output was measured using Doppler echocardiography at baseline. CE was calculated using the formula, (cardiac output × mean arterial blood pressure)/(451 × LVM × 100) W/100 g. Survival score analysis was performed to identify cut off value for CE to identify the maximum difference in mortality in the study cohort. Patients were subsequently divided into 2 groups CE < 0.38 W/100 g and CE ≥ 0.38 W/100 g. Survival was determined using Kaplan-Meier method.ResultsWe included 954 patients in the final analysis. CE in group1 vs group 2 was 0.31 ± 0.05 W/100 g vs 0.59 ± 0.18 W/100 g. Patients in group1 were more likely to be male, had a higher prevalence of atrial fibrillation, prior myocardial infarction, mitral and tricuspid regurgitation. They also had a higher STS risk score, NYHA functional class, and lower aortic valve area. The remainder of the baseline characteristics was similar in both groups. A lower CE was associated with higher 1-year mortality following TAVR based on multivariate analysis. (Group1: 22.18% vs Group 2: 9.89%, p < .0001).ConclusionIn our cohort, a low baseline CE (<0.38 W/100 g) conferred higher mortality risk following TAVR.     

Expression of chemokine receptor-4 in bone marrow mesenchymal stem cells on experimental rat abdominal aortic aneurysms and the migration of bone marrow mesenchymal stem cells with stromal-derived factor-1

This study investigated the expression and role of chemokine receptor-4 (CXCR4) in bone marrow mesenchymal stem cells (BMSCs) from experimental rats with abdominal aortic aneurysms (AAA) for migration of BMSCs. Sprague–Dawley rats were divided into an experimental group and control group (n = 18 each). AAA was induced with 0.75 M solution infiltrate for 30 minutes, after which the abdomen was rinsed and closed. Saline was used in place of CaCl₂ in the control group. CD34 and CD29 were detected by flow cytometry, the gene and protein expression of CXCR4 were detected by real-time polymerase chain reaction and western blot, respectively. The migration of BMSCs with stromal-derived factor-1 was detected by Transwell chamber. CD34 expression was negative and CD29 expression was positive. The gene and protein expression of CXCR4 were significantly higher in experimental group than them in control group (p < 0.05), the migration ability of BMSCs from the experimental group was significantly higher than that from the control group (p < 0.05). Stromal-derived factor -1/CXCR4 can enhance the migration of BMSCs in vitro in a rat AAA model.     

Clinical features and comorbidity pattern of HCV infected migrants compared to native patients in care in Italy: A real-life evaluation of the PITER cohort

BackgroundDirect-acting antivirals are highly effective for the treatment of hepatitis C virus (HCV) infection, regardless race/ethnicity. We aimed to evaluate demographic, virological and clinical data of HCV-infected migrants vs. natives consecutively enrolled in the PITER cohort.MethodsMigrants were defined by country of birth and nationality that was different from Italy. Mann-Whitney U test, Chi-squared test and multiple logistic regression were used.ResultsOf 10,669 enrolled patients, 301 (2.8%) were migrants: median age 47 vs. 62 years, (p < 0.001), females 56.5% vs. 45.3%, (p < 0.001), HBsAg positivity 3.8% vs. 1.4%, (p < 0.05). Genotype 1b was prevalent in both groups, whereas genotype 4 was more prevalent in migrants (p < 0.05). Liver disease severity and sustained virologic response (SVR) were similar. A higher prevalence of comorbidities was reported for natives compared to migrants (p < 0.05). Liver disease progression cofactors (HBsAg, HIV coinfection, alcohol abuse, potential metabolic syndrome) were present in 39.1% and 47.1% (p > 0.05) of migrants and natives who eradicated HCV, respectively.ConclusionCompared to natives, HCV-infected migrants in care have different demographics, HCV genotypes, viral coinfections and comorbidities and similar disease severity, SVR and cofactors for disease progression after HCV eradication. A periodic clinical assessment after HCV eradication in Italians and migrants with cofactors for disease progression is warranted.     

Does Sericin,as a Novel Pleurodesis Agent,Have Higher Effectiveness Compared to Talcum Powder,Doxycycline, and Silver Nitrate Pleurodesis?

IntroductionThe usefulness of sericin as pleurodesis agent has previously been described. Present study aims to compare sericin pleurodesis regarding success, effectiveness, tolerability, and side-effects.MethodsAdult, 12-week-old Wistar-albino rats (n = 60), divided to five groups as sericin, talcum-powder, doxycycline, silver-nitrate and control. Agents were administrated through left thoracotomy, rats sacrificed twelve-days after.ResultsHighest ratio of collagen fibers was observed in sericin group, and the intensity was higher than talcum-powder group (p < 0.05). Compared to silver nitrate, sericin group displayed better mesothelial reaction, and multi-layer mesothelium was also better (p < 0.05). Foreign body reaction and emphysema were less frequent in sericin group (p < 0.05). The presence of biological tissue in parenchyma was less prominent in sericin group (p < 0.05). Foreign body reaction on thoracic wall was less common in sericin group (p < 0.05). Presence of biological tissue glue in thoracic wall was less prominent in sericin group (p < 0.05).Glomerular degeneration was lower in sericin group compared to the silver nitrate group (p < 0.05), and tubular degeneration was less common in sericin group than talcum group (p < 0.05). Pericarditis was less common in sericin group compared to the other groups (p < 0.05).ConclusionAs an intrinsic, natural glue protein, sericin protects the lung parenchyma and tissues, and its glue-like characteristics enable pleurodesis. The success of sericin in pleurodesis was demonstrated in the present study based on investigations of the pleurae. Being cost-effective and better tolerated agent associated with a low potential of side effects, sericin is more effective, less expensive and provides more lung parenchyma protection.     

Altered mRNA expression of telomere binding proteins (TPP1, POT1, RAP1, TRF1 and TRF2) in ulcerative colitis and Crohn's disease

AimsTo determine mRNA expression of telomeric binding proteins in inflammatory bowel disease (IBD), and to note any effects of pharmacotherapy on telomere binding protein expression.MethodsPeripheral blood mononuclear cells (PBMC) obtained from 31 IBD patients and 13 controls were activated with phytohaemagglutinin and purified to yield activated (CD25+) T lymphocytes. TPP1, POT1, RAP1, TRF1 and TRF2 mRNA expression in PBMC and activated T lymphocytes was measured with RT-PCR.ResultsIn activated (CD25+) T lymphocytes, mean TRF2 mRNA levels were lower in both UC (6.6 vs 10, p = 0.004) and CD subjects (6.9 vs 10; p = 0.004). Similarly. in activated (CD25+) T lymphocytes mean RAP1 mRNA expression was significantly lower in UC subjects (4.5 vs 9.8, p = 0.029) but not in CD subjects. In resting PBMC, mean TRF1 mRNA levels were lower in both UC (2.6 vs 3.5; p = 0.008) and CD subjects (1.0 vs 3.5; p = 0.04). No difference in PBMC and activated (CD25+) T lymphocytes mRNA levels of TPP1 and POT1 were noted in either UC or CD subjects. An association with 5-aminosalicylate therapy (R² = 0.4) was only detected with RAP1 mRNA expression. TRF2 mRNA expression was inversely associated with disease duration only in UC subjects (p = 0.05; R² = −0.6).ConclusionsThe downregulation of TRF2 and RAP1 mRNA expression in CD25+ T-lymphocytes in IBD suggests that these telomere binding proteins play a role in telomere regulation and may contribute to the telomeric fusions and chromosomal abnormalities observed in UC. These findings may also indicate a systemic process of telomere uncapping which could represent a biomarker for IBD associated cancer risk.     

Metabolic risk factors in first acute coronary syndrome (MERIFACS) Study

ObjectivesIn acute coronary syndrome (ACS) patients the focus is on major conventional risk factors - CRF [diabetes, hypertension, elevated low-density cholesterol (LDL-C) and smoking] whereas others - specific metabolic risk factors - MRF [high-density lipoprotein cholesterol (HDL-C), body-mass index (BMI), waist-hip ratio (WHR), and triglycerides, and HbA1c get less attention.MethodsThis is a prospective case–control observational study from 15 tertiary care hospitals in India. CRF and MRF in patients presenting with first incidence of ACS (n = 2153) were compared with matched controls (n = 1210).ResultsPropensity score matching (PSM) yielded 1193 cases and matched 1210 controls. Risk factor prevalence in cases vs. controls were CRF: hypertension - 39.4% vs 16.4% (p < 0.0001), diabetes - 42.6% vs 12.7% (p < 0.0001), smoking - 28.3% vs 9.3% (p < 0.0001) and elevated LDL-C - 70.2% vs 57.9% (p < 0.0001). MRF: High BMI - 54.7% vs 55.1% (p = 0.84), increased waist: hip ratio 79.5% vs 63.6% (p < 0.0001), high HbA1c - 37.8% vs 14.9% (p < 0.0001), low HDL-C - 56.2% vs 42.8% (p < 0.0001) and elevated triglycerides - 49.7% vs 44.2% (p = 0.007). Adjusted Odds ratios by multivariate analysis were CRF: hypertension - 2.3 (p < 0.001), diabetes - 4.7 (p < 0.001), high LDL-C - 3.3 (p < 0.001) and smoking- 6.3 (p < 0.001). MRF: High waist: hip ratio - 2.4 (p < 0.001) high HbA1c - 3.2 (p < 0.001), low HDL-C 2.2 (p < 0.001) and elevated triglycerides - 0.878 p = 0.17.ConclusionIn India, the risk of ACS conferred by specific metabolic risk factors (High waist: hip ratio, Low HDL-C and High HbA1c) is comparable to that caused by CRF.     

Impact of HDL on adipose tissue metabolism and adiponectin expression

ObjectiveThe objective of the current study was to investigate the hypothesis that high-density lipoprotein (HDL) influences adipocyte metabolism and adiponectin expression. Therefore, HDL was increased in vivo via apolipoprotein (apo) A-I gene transfer and in vitro via supplementation of HDL to partly differentiated adipocytes, in the presence or absence of lipopolysaccharide (LPS), known to decrease HDL cholesterol and adiponectin levels in vivo.Methods and resultsApo A-I transfer resulted in a significant increase of HDL cholesterol in control and LPS-injected C57BL/6 mice, which was paralleled by an increase in plasma adiponectin levels and adiponectin expression in abdominal fat. Triglyceride and free fatty acids levels after LPS administration were 2.2-fold (p < 0.05) and 1.3-fold (p < 0.05) lower, respectively, in Ad.hapoA-I-LPS than in Ad.Null-LPS mice. In parallel, the LPS-induced mRNA expression of hormone sensitive lipase was 3.5-fold (p = 0.05) decreased in the Ad.hapoA-I-LPS group. On the other hand, apo A-I transfer abrogated the LPS-mediated reduction in lipin-1 and CD36 mRNA expression by 8.2-fold (p < 0.05) and 18-fold (p < 0.05), respectively. Concomitantly, the phosphorylation state of Akt was 2.0-fold (p < 0.05) increased in the Ad.hapoA-I-LPS compared to the Ad.Null-LPS group. Pre-incubation of partly differentiated adipocytes with HDL (50 μg protein/ml) increased adiponectin expression by 1.5-fold under basal conditions (p < 0.05) and could abrogate LPS-induced down-regulation of adiponectin, both in a phosphatidylinositol-3-kinase-dependent manner.ConclusionsHDL affects adipocyte metabolism and adiponectin expression.     

Osteoprotegerin (OPG) and Matrix Gla protein (MGP) in rheumatoid arthritis patients: Relation to disease activity

BackgroundImbalanced Matrix Gla protein (MGP) and Osteoprotegerin (OPG) levels occur in inflammatory diseases.Aim of the workThe aim of the present study was to evaluate serum MGP and OPG levels in Rheumatoid Arthritis (RA) patients and study their relation to the disease activity.Patients and methodsForty-five female RA patients and 45 age and sex-matched healthy controls were included in this study. Disease activity score 28-C-reactive protein (DAS28-CRP) was used for the assessment of disease activity. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), MGP and OPG were measured in patients and controls. The associations of MGP and OPG with DAS28-CRP and the other laboratory and clinical variables were analyzed.ResultsRA patients had significantly higher serum OPG levels (408.3 ± 520.9 pg/ml) and hs-CRP (2.8 ± 1.9 mg/l) than the control (92.5 ± 86.3 pg/ml and 0.9 ± 1.5 mg/l respectively) (p < 0.001 each). There was no significant difference in MGP levels between the patients and control (p = 0.3). The correlation of OPG and MGP with DAS28-CRP in the patients was insignificant (p = 0.4 and p = 0.8 respectively). Age positively correlated with OPG (r = 0.32, p = 0.02), but not with MGP concentration (r = 0.05, p = 0.64) in the RA patients.ConclusionsThe significant elevation of the OPG level in RA patients may through light on its possible role in the pathogenesis of this disease and could be considered as a future therapeutic target. The significant correlation with age suggests that OPG may be an important mediator especially in elderly RA cases.     

Acute kidney injury in patients with cirrhosis: Prospective longitudinal study in 405 patients

BackgroundAcute kidney injury (AKI) is common in patients with cirrhosis. In 2015, the International Club of Ascites (ICA) proposed new definitions of AKI in order to improve the prediction of outcomes. Our aim was to assess the prevalence and prognostic value of ICA 2015 – AKI criteria in hospitalised patients with cirrhosis.MethodsWe prospectively collected data from 405 consecutive cirrhotic patients admitted to the hospital between November 2016 and November 2017. AKI was diagnosed at inclusion according to ICA 2015 criteria, and was assessed to predict 30-day and 90-day in-hospital mortality.ResultsAKI was diagnosed in 78 (19.3%) patients. AKI was independently associated with 90-day death (HR 7.61; 95% CI 4.75–12.19; p < 0.001). In hospital, 30-day and 90-day survival was lower in the group of patients with AKI compared to the group with no AKI (72% vs. 98%, p < 0.001; 64% vs. 96%, p < 0.001; and 49% vs. 81%, p < 0.001, respectively). Patients with stage 1a AKI had a lower 30-day and 90-day survival compared to the group of patients who did not develop AKI (71% vs. 96%, p < 0.001, and 71% vs. 91%, p < 0.01, respectively) and better survival than patients with more severe AKI (71% vs. 40%, p < 0.01).ConclusionsAKI was independently associated with mortality in patients with cirrhosis, even at the very early 1a stage. Response to treatment improved survival, and was inversely proportional to the stage of AKI, which suggests that treatment should be started at the earliest stage of AKI.     

Particularities in coronary revascularization in elderly patients presenting with ST segment elevation acute myocardial infarction (STEMI)

Nowadays, ST elevation acute myocardial infarction (STEMI) is seen with greater incidence in older patients. Current guidelines recommend an immediate invasive evaluation and eventually primary percutaneous coronary intervention (PCI) in all STEMI patients regardless of age. Nevertheless, data in literature show a significant underuse of interventional treatment in older patients with STEMI.Our objective is to assess the in-hospital outcome of the elderly STEMI patients compared to the younger ones in the setting of systematic interventional management. We also discussed some particular aspects which we considered as significant concerning the management of elderly patients with STEMI.We evaluated 975 consecutive STEMI patients admitted to a single centre between January 2012 to July 2013. There were 203 (20.8%) patients ≥75 years old.Compared to the younger group, in the older group there were more women (47. 2% vs 22.7%; p < 0.001), an increased prevalence of hypertension (78.8% vs 65.0%; p < 0.001) but a decreased prevalence of smoking (13.7% vs 48.8%; p < 0.001) and dyslipidemia (54.7% vs 41.3%; p = 0.03). The ≥75 years group had more cardiovascular comorbidities: stroke (11.8% vs 4.1%; p < 0.001), atrial fibrillation (23.6% vs 53.9%; p < 0.001) and severe valvulopathies (6.8% vs 1.2%; p < 0.001). Elderly patients presented more frequently with signs of heart failure (Killip class > 1: 21.1% vs 7.2%; p < 0.001). Both groups had similar ischaemia time with 54.1% vs 55.1% presenting within 6 h.There were fewer PCIs performed in the elderly group (74.3% vs 85.7%; p = 0.02). The extension of coronary lesions was not significantly different between the two groups, except for left main disease in favour of the elderly (12.2% vs 5.1%; p < 0.001). There were no significant differences between the two groups regarding the in-hospital treatment (dual antiplatelet, anticoagulation, beta-blockers, ACEI/ARB and statin). The in-hospital mortality for our entire study group was 4.41%, with a rate of 11.3% in the older group and 2.59% in the <75 years group (p < 0.001).In-hospital outcome in older patients with STEMI is worse, with an increased mortality rate, especially when associated with heart failure on admission. Fewer PCI were performed in the older patients, although there was no difference in the pharmacological treatment. A strategy based on urgent coronary angiography and, if necessary, primary PCI, should be applied in all eligible patients irrespective of age.