Echocardiographic assessment of pulmonary capillary wedge pressure in patients with frequent premature ventricular complexes.

BACKGROUND: Premature ventricular complex (PVC) is seen in most individuals. It has been shown that the kinetics-tracking index or Kawasaki-Tanaka index (KT index) strongly predicts pulmonary capillary wedge pressure (PCWP) by noninvasively. KT index was defined as log10 (active LAEF/minimum LAV index). We goaled to assess PCWP non-invasively in patients with frequent PVCs with normal left ventricular systolic functions and to evaluate whether there is an increase in PCWP before systolic and diastolic functions are impaired. METHODS: About 55 patients with frequent PVCs as a patient group and 54 healthy volunteers as a control group were involved to the study. After the conventional echocardiographic examination, the vendor-independent software system (EchoPAC version 202) was used to obtain the time-left atrial volume (LAV) curve. total left atrial emptying function (LAEF), passive LAEF, and active LAEF were calculated to evaluate phasic left atrial (LA) function. In this study, ePCWP was calculated using the KT index, and KT index results and other echocardiographic parameters were compared between study groups. RESULTS: LA anterior-posterior dimension, LA maximum volume index, and LA minimum volume index were significantly larger in the patient group (all p values < .001). Total LAEF were significantly reduced in patients with frequent PVC (p < .001). Estimated pulmonary capillary wedge pressure (ePCWP) by KT index was significantly higher in patients with frequent PVCs (p < .001). CONCLUSIONS: Patients with frequent PVC had increased ePCWP as assessed by KT index.

Nickel chloride induces anticancer biological responses in hepatocellular carcinoma cell lines.

Nickel has long been known to have a toxic effect in humans and has been defined as a human carcinogen. However, recent studies have suggested that nickel chloride (NiCl2) may also possess anticancer properties. The liver is one of the target organs for nickel, and thus, the present study aims to evaluate the effect of NiCl2 on anticancer biological responses in hepatocellular carcinoma (HCC) cell lines. Both HuH-7, a well-differentiated HCC cell line, and Mahlavu cell line, a poorly differentiated HCC cell line, were exposed to NiCl2. It was determined that NiCl2 decreased cell viability in both cell lines in a dose- and time-dependent manner. Nickel chloride exposure at IC50 doses were observed to suppress the ability of HCC cells to produce colonies and also induce apoptosis of HCC cells by increasing Cleaved Caspase-3 protein levels. It was found that NiCl2 exposure affected cellular morphology, increased the LC3-II protein levels, and induced autophagy in parallel to increased apoptosis in HCC cells. It was also observed that NiCl2 suppressed cell migration, decreased the size and viability of HCC tumor spheroids generated in 3D cell cultures, and disrupted the spheroid structure of the tumor cells depending on E-cadherin expression levels. Furthermore, it was observed that all anticancer biological responses induced by NiCl2 occurred independently of the AKT signaling pathway. In conclusion, our results suggested that NiCl2 induced anticancer biological responses in HCC cell lines. Moreover, this study provided important new molecular and cellular biological basic data about the action mechanisms of NiCl2 in HCC.

High AST/ALT Ratio Is Associated with Cardiac Involvement in Acute COVID-19 Patients.

Background and Objectives: We aimed to assess the effect of AST/ALT ratio on echocardiographic and cardiac magnetic resonance imaging (CMRI) parameters after COVID-19 patients recover. Materials and Methods: 87 patients with COVID-19 were included in the study. The patients were hospitalized with COVID-19 pneumonia, but the patients did not need intensive care unit follow-up or non-invasive mechanical ventilation support. After a discharge and two weeks following the positive swab test result, patients were considered eligible if they had any symptoms. Transthoracic echocardiography (TTE) was performed within 24 h prior to CMRI. The median value of AST/ALT ratio was found, and the study population was divided into two subgroups based on the median AST/ALT ratio value. The clinical features, blood test, TTE and CMRI results were compared between subgroups. Results: C-reactive protein, D-dimer and fibrinogen were found to be significantly higher in patients with high AST/ALT ratio. LVEF, TAPSE, S', and FAC were significantly lower in patients with high AST/ALT ratio. LV-GLS were significantly lower in patients with high AST/ALT ratio. In CMRI, native T1 mapping signal, native T2 mapping signal and extracellular volume raised significantly in patients with high AST/ALT ratio. Right ventricle stroke volume and right ventricle ejection fraction were significantly lower in patients with high AST/ALT ratio, but right ventricle end systolic volume was significantly higher in patients with high AST/ALT ratio. Conclusion: High AST/ALT ratio is related to impaired right ventricular function parameters with CMRI and echocardiography after recovery from acute COVID-19. Assessment of AST/ALT ratio at hospital admission may be used to assess the risk of cardiac involvement in COVID-19 disease, and these patients may require closer follow-up during and after the course of COVID-19.

Anticancer effects of imidazole nucleus in hepatocellular carcinoma cell lines via the inhibition of AKT and ERK1/2 signaling pathways.

BACKGROUND: Imidazole nucleus has been used efficiently in the development of many drug molecules due to its therapeutic effects. Many derivatives of it have been produced particularly for use in cancer treatment. However, the anti-cancer effects of imidazole nucleus in liver cancer cells are as yet unclear. In this study, we aimed to investigate the anti-cancer effects of imidazole nucleus in hepatocellular carcinoma (HCC) cell lines. METHODS AND RESULTS: Anti-cancer effect of imidazole nucleus was investigated using cell viability assay, apoptosis analysis, cell migration analysis, cell morphology analysis, colony formation assay and 3D cell culture techniques in HuH-7 and Mahlavu cell lines. Also, effect of imidazole on AKT and ERK1/2 pathways were determined using by western blot analysis. Imidazole decreased cell viability in both HCC cell lines in a dose and time-dependent manner and also suppressed the colony forming ability of the cells (p < 0.05). Imidazole increased the cleaved caspase 3 protein levels and thus induced apoptosis (p < 0.05). Imidazole induced morphological alterations and autophagy by increasing intracellular vacuolization. Also, imidazole decreased the viability and dimensions of HCC cell tumor spheroids produced in 3D cell cultures (p < 0.05). Moreover, it was observed that all of these effects, are defined above, appeared in parallel with suppression of AKT and ERK1/2 signaling pathways by imidazole nucleus. CONCLUSIONS: The findings of this present study established the anti-cancer effects of imidazole nucleus in HCC cell lines and showed that it could be a potential molecule in the treatment of HCC via inhibition of AKT and ERK1/2 signaling pathways.

Could premature ventricular contractions lead to atrial remodeling?

BACKGROUND: Premature ventricular contraction (PVC) is a frequent kind of arrhythmia that affects around 1% of the general population. While PVC most frequently impairs ventricular function in structurally normal heart, retrograde ventriculo-atrial conduction can occur in people with PVC. These retrograde atrial activations may mimic pulmonary vein-derived atrial ectopies. As a result, PVC may raise the risk of atrial fibrillation (AF) by retrograde ventriculo-atrial conduction. The Four-Dimensional Automated Left Atrial Quantification (4D Auto LAQ) tool is a left atrial analytical approach that utilizes three-dimensional volume data to quantify the volume, as well as LA longitudinal and circumferential strains. The purpose of this study was to determine if clinical diagnosis of PVC is connected with abnormal LA function as determined by LA strain evaluation utilizing a 4D Auto LAQ compared to the healthy population. METHODS: The 58 patients with frequent PVCs and 53 healthy volunteers as a control group were enrolled in the study. Imaging was performed using the GE Vivid E95 echocardiography equipment (GE Healthcare; Vingmed Ultrasound, Horten, Norway) equipped with an M5S probe (frequency range: 1.5-4.6 MHz) and a 4V probe (frequency range: 1.5-4.0 MHz). Images were imported into and were selected for analysis using the EchoPAC203 software (GE Healthcare). The analysis mode was selected, followed by the volume and 4D Auto LAQ submodes. Following that, the sample point was positioned in the center of the mitral orifice in each of the three planes. The review function was used to acquire the LA parameters measured by 4D Auto LAQ, including volume and strain parameters. RESULTS: The maximum left atrial volume (LAVmax) and minimal left atrial volume (LAVmin) were significantly higher in the patient group (38.91 ± 9.72 vs. 46.31 ± 10.22, 17.75 ± 4.52 vs. 23.10 ± 7.13, respectively, all p values <.001). On the other hand left atrial reservoir longitudinal strain (LASr), conduit longitudinal strain (LAScd), contraction longitudinal strain (LASct), reservoir circumferential strain (LASr-c), conduit circumferential strain (LAScd-c), and contraction circumferential strain (LASct-c) were significantly lower in patient group (26.64 ± 5.64 vs.19.16 ± 4.58, -19.53 ± 3.72 vs. -11.28 ± 3.47, -10.34 ± 1.56 vs. -4.59 ± 1.49, 30.72 ± 4.04 vs. 19.31 ± 2.60, -19.91 ± 1.78 vs. -13.38 ± 2.85, -15.89 ± 6.37 vs. -9.24 ± 1.63, respectively, all p values <.001). CONCLUSIONS: The present study found that premature ventricular complexes can lead to atrial remodeling as well as ventricular remodeling in patients with PVC and 4D LAQ technology can quantitatively examine left atrial function and determine these alterations early.

Assessment of right ventricular sequelae by speckle tracking echocardiography in recovered COVID-19 patients.

BACKGROUND: TTE is the main modality used to assess RV function, but conventional TTE parameters have limited diagnostic value because they may fail to detect early abnormalities in RV systolic function. Due to its ability to detect subclinical impairment of cardiac function, 2D STE has been widely used to investigate RV function. In this study, we aimed to investigate whether there are sequelae of RV function in recovered COVID-19 patients with pulmonary involvement. METHODS: This is a prospective observational cohort study of 57 healthy volunteers and 54 patients. Participants had no history of chronic illness and no evidence of respiratory or cardiac symptoms. The patients had been hospitalised with COVID-19 with pulmonary involvement but did not require intensive care unit follow-up or non-invasive mechanical ventilation support. TTE was performed. Demographic and clinical characteristics and laboratory test results were collected. RESULTS: LVEF, TAPSE, St and FAC were significantly lower in the patient group. LV-LS 3-chamber, LV-GLS, RV-FWS, RV-GLS were significantly lower in the patient group. CONCLUSIONS: RV-LS and LV-GLS were shown to decrease in the patient group. Although no obvious pathological values were observed in RV parameters on conventional echocardiography, TAPSE, St and FAC values were lower in the patient group.

Synthesis, characterization, thermokinetic analysis and biological application of novel allyl glucosamine based glycopolymers.

The synthesis of glycopolymers by copolymerising an allyl glucosamine (AG) monomer with co-monomers methyl methacrylate (MMA), acrylonitrile (AN) and 2-hydroxyethyl methacrylate (HEMA) was investigated via free-radical polymerisation of 2,2-azobisisobutyronitrile (AIBN) in dimethylformamide (DMF). Three new copolymers, poly(AG-co-MMA), poly(AG-co-AN) and poly(AG-co-HEMA), were obtained. The chemical structures of the glycopolymers were analysed using 1H-NMR, 13C-NMR and FTIR. The thermal properties and degradation kinetics of the three glycopolymers were examined by thermogravimetric (TG) analysis at different heating rates. The effects of different co-monomers on the copolymerisation yield, thermal properties and biological activities of the resulting glycopolymers were investigated. The activation energies of the decomposition stages were calculated using the Flynn-Wall-Ozawa (FWO) and Kissinger methods. Furthermore, the biological activity of AG monomers and glycopolymers was studied and compared to chitosan. Poly(AG-co-HEMA) had the most significant effect on MCF-7 cell viability, and all glycopolymers have a low toxic effect profile on MCF-7 cell lines.

Assessment of atrial conduction times in patients with frequent premature ventricular complex.

Background: Premature ventricular complex (PVC) is a frequent finding in the general population. The atrial conduction time (ACT) is the period between the electrocardiographic P wave and the atrial mechanical contraction, and its prolongation indicates an atrial electromechanical delay (EMD). In our study, we compared atrial conduction parameters by echocardiographic methods between patients with frequent PVC and healthy control subjects. Methods: The study included 54 patients with PVC and 54 healthy volunteers. Atrial conduction parameters were measured with echocardiographic examination. The time difference between the p wave and the Am wave was measured in the septal, lateral, and tricuspid annulus regions. The interatrial EMD, left atrial intra-atrial delay, and the right atrial intra-atrial delay were calculated from these measurements. The groups were compared for demographic and electrocardiographic features and echocardiographic parameters. Results: Left intra-atrial EMD, right intra-atrial EMD, and interatrial EMD were significantly longer in the patient group (p = .001, p < .001, p < .001, respectively). PA lateral, PA septal, and PA tricuspid durations were significantly prolonged in the patient group (all p < .001). All ACT parameters were significantly prolonged in patients with PVC QRS duration of 150 ms and above (all p < .001). All ACT parameters were prolonged in PVCs of right ventricular origin than those of left ventricular origin (all p < .001). ACT parameters were prolonged in patients with a coupling interval time below 485 ms (all p < .001). Conclusions: Atrial conduction times are prolonged in patients with frequent PVC.

May myocardial work predict the risk of cardiomyopathy in patients with premature ventricular complex?

BACKGROUND: An increased premature ventricular complex (PVC) frequency is related to an increased risk of cardiomyopathy. Changes in myocardial work (MW) parameters in patients with PVC may be a predictor of the development of cardiomyopathy. METHODS: The study included 56 patients with PVC and 50 healthy volunteers as a control group. A comprehensive echocardiographic examination was done. A speckle tracking echocardiography was used to obtain the left ventricle (LV) global longitudinal strain (GLS). A bull's eye plot of the global MW index and the global work efficiency of 17 left ventricle segments with MW component values were generated. RESULTS: Global work index (GWI), global constructive work (GCW), and global work efficiency (GWE) were significantly lower in the patient group (2377.84 ± 216.52 vs.1818.30 ± 283.73, 2734.00 ± 208.90 vs. 2283.73 ± 321.65, 92.48 ± 2.85 vs. 87.75 ± 3.87, respectively, all p values <0.001). Global wasted work (GWW) was significantly higher in the patient group (216.80 ± 26.86 vs. 302.13 ± 41.81, p < 0.001) Patients were compared according to the origin of PVCs. GWI, GCW, GWE were significantly lower and GWW was significantly higher in patients with PVC originating from the right ventricle or the epicardial region (p < 0.001). CONCLUSIONS: Compared to healthy individuals, patients with PVC had lower GCW, GWI, GWE values and a higher GWW value than healthy individuals, similar to cardiomyopathy patients. Therefore, the detoriation in MW parameter in patients with PVC may be a predictor of cardiomyopathy development.

Does Premature Ventricular Complex Impair Left Ventricular Diastolic Functions?

BACKGROUND: A higher frequency of premature ventricular complexes is associated with a higher risk of premature ventricular complex-induced cardiomyopathy. Although there are several studies on the systolic functions of the left ventricle in this patient group, it is clearly not known how the diastolic functions of the left ventricle are affected. This study examined the effect of premature ventricular complex on left ventricle diastolic functions using diastolic strain rate. METHODS: The trial included 57 patients with frequent premature ventricular complexes and 54 healthy volunteers. The patient was evaluated using echocardiography in its entirety. The vendor-independent software system determined systolic and diastolic strain parameters via 2-dimensional speckle tracking analysis. Using the auto strain 3P semi-automated endocardial boundary tracking instrument, the global longitudinal strain was measured from the apical 4-chamber, 2-chamber, and long axis. The diastolic strain rate was determined by averaging the strain rates of 17 cardiac segments at 2 distinct periods of diastole. RESULTS: In the patient group, early diastolic strain rate was significantly lower than that in the control group (1.62 ± 0.58 vs. 1.25 ± 0.38, P <.001). There were found to be significant negative connections between PVC's electrocardiographic QRS wave length and early diastolic strain rate and coupling interval and early diastolic strain rate. Significant positive associations between coupling interval and early diastolic strain rate were discovered (P <.001 and P <.001, respectively). CONCLUSIONS: Patients with premature ventricular complex exhibited a lower early diastolic strain rate than healthy individuals. The early diastolic strain rate can be used to predict left ventricle diastolic dysfunction, and persons with premature ventricular complex may have a higher risk of left ventricle diastolic dysfunction than the general population.

Cardiac magnetic resonance T2* mapping in patients with COVID-19 pneumonia is associated with serum ferritin level?

The coronavirus disease of 2019 (COVID-19)-related myocardial injury is an increasingly recognized complication and cardiac magnetic resonance imaging (MRI) has become the most commonly used non-invasive imaging technique for myocardial involvement. This study aims to assess myocardial structure by T2*-mapping which is a non-invasive gold-standard imaging tool for the assessment of cardiac iron deposition in patients with COVID-19 pneumonia without significant cardiac symptoms. Twenty-five patients with COVID-19 pneumonia and 20 healthy subjects were prospectively enrolled.Cardiac volume and function parameters, myocardial native-T1, and T2*-mapping were measured. The association of serum ferritin level and myocardial mapping was analyzed. There was no difference in terms of cardiac volume and function parameters. The T2*-mapping values were lower in patients with COVID-19 compared to controls (35.37 [IQR 31.67-41.20] ms vs. 43.98 [IQR 41.97-46.88] ms; p < 0.0001), while no significant difference was found in terms of native-T1 mapping value(p = 0.701). There was a positive correlation with T2*mapping and native-T1 mapping values (r = 0.522, p = 0.007) and negative correlation with serum ferritin values (r = - 0.653, p = 0.000), while no correlation between cardiac native-T1 mapping and serum ferritin level. Negative correlation between serum ferritin level and T2*-mapping values in COVID-19 patients may provide a non-contrast-enhanced alternative to assess tissue structural changes in patients with COVID-19. T2*-mapping may provide a non-contrast-enhanced alternative to assess tissue alterations in patients with COVID-19. Adding T2*-mapping cardiac MRI in patients with myocardial pathologies would improve the revealing of underlying mechanisms. Further in vivo and ex vivo animal or human studies designed with larger patient cohorts should be planned.

GSTP1 gene methylation profiles in Helicobacter pylori (+) and (-) antral intestinal metaplasia and distal gastric tumour patients in Turkish population.

BACKGROUND/AIMS: Gastric cancer (GC) is the second most common malignancy worldwide, with a high mortality rate. The incidence of GC has declined in the western countries during the last decades. The glutathione S-transferases comprise a group of enzymes that are critical in the detoxification of carcinogens. In this study we aimed at the relationship GSTP-1 methylation in patients with intestinal metaplasia with and without Helicobacter pylori infection, gastric cancer and controls. METHODOLOGY: The methylation status of GSTP1 gene was analyzed by methylation specific PCR after bisulfate modification in H. pylori (+) (n=25) and (-) (n=25) intestinal metaplasia (IM) patients, GC (n=25) and control subjects (n=15) between September 2009 to November 2011. RESULTS: During the study period 90 patients who underwent endoscopic examination were included in the study. When we considered the GSTP1 gene methylation profile in all of the groups; 26 (28%)patients had methylated GSTP1 gene, 31 (34%) patients had unmethylated GSTP1 gene and 33 (36%) patients had heterogeneously methylated GSTPI gene. CONCLUSIONS: GSTP1 gene methylation profile is not appropriate for early diagnosis of cases with gastric cancer.

Microtia and congenital aural atresia.

The purpose of this study was to show the clinical characteristics of microtia and congenital aural atresia cases in Turkey and to make the classification. For this purpose, records of 28 patients with microtia who were admitted to the ENT Clinic of Eskisehir Military Hospital, Turkey, between 1995 and 2011 and 3 patients admitted to the ENT outpatient clinic of Kocaeli Derince Education and Research Hospital, Turkey, were analyzed retrospectively. Of the total 31 patients with microtia (35 microtic ears), involvement of the right ear of 20 patients (64.5%), the left ear of 7 patients (22.5%), and bilateral involvement in 4 patients (12.9%) were observed. There was a unilateral involvement in 27 patients (87.1%). According to the Marx grading, 2 patients (5.7%) had grade 1 malformation, 3 (8.6%) had grade 2 malformation, 29 (82.9%) had grade 3 malformation, and 1 (2.9%) had grade 4 malformation (anotia). Although the characteristics of microtia vary in different population, the results in Turkey are consistent with those in the literature.

Boric acid exert anti-cancer effect in poorly differentiated hepatocellular carcinoma cells via inhibition of AKT signaling pathway.

BACKGROUND: The possible anti-cancer properties of boron, a trace element for humans, have been demonstrated in various experimental and epidemiological studies, although the effects of boron on liver cancer are unclear. In the present study we evaluate the effects of boric acid on the cell lines of hepatocellular carcinoma (HCC) of the liver, as the leading form of liver cancer, for which a poorly-differentiated HCC cell line (Mahlavu cell line) was used. METHODS: The anti-cancer effect of boric acid was investigated with a cell viability assay, apoptosis analysis, cell migration analysis, cell morphology analysis, colony formation assay and 3D cell culture techniques. Also, the effect of boric acid on the AKT signaling pathway was determined through a western blot analysis. RESULTS: Boric acid was found to reduce cell viability in a dose- and time-dependent manner, and decreased survival, colony formation ability, migration capability and HCC cell tumor spheroid growth in HCC cell lines, while also inducing apoptosis, autophagy and morphological alteration. Furthermore, boric acid inhibited AKT phosphorylation, and anticancer biological responses in HCC cells were observed only in cells in which AKT phosphorylation was suppressed by boric acid. CONCLUSION: Our results suggest that boric acid might be a promising therapeutic candidate in hepatocellular carcinoma via the inhibition of AKT signaling pathway.

Effects of Oxygen Therapies in Experimental Acute Acoustic Trauma.

BACKGROUND: Acute acoustic trauma is defined as a sudden sensorineural hearing loss that occurs after an exposure to acoustic overstimulation. Increasing the oxygen in perilymph can be a treatment modality. Our study aims to investigate the influence of normobaric oxygen therapy on the recovery of acute acoustic trauma and to compare it with the hyperbaric oxygen therapy. METHODS: Three groups of rats (5 rats each) were exposed to white noise for 1 hour. Sensorineural hearing loss was identified using distortion product otoacoustic emission. Subsequently, the first group was treated with hyperbaric oxygen therapy, the second group was treated with normobaric oxygen therapy, and the third group did not receive any treatment and was used as a control group. RESULTS: There was a statistically significant difference within time for frequencies of 1, 1.5, and 2 kHz, but there was no statistically significant difference between groups. For frequencies of 3, 4, 5, and 6 kHz, there was a statistically significant difference within time and between groups. Between groups, recovery of distortion product otoacoustic emission values in all frequencies was better in the control group by the third, fifth, and seventh days. Comparing the values of hyperbaric oxygen therapy and normobaric oxygen therapy groups, it was observed that by the third day, the hyperbaric oxygen therapy values were better than those of the normobaric oxygen therapy values. However, by the fifth and seventh days, the normobaric oxygen therapy values were better (except at a frequency of 1 kHz). CONCLUSION: Because there is a high rate of spontaneous recovery, physicians should be more selective to treat patients with oxygen therapies.

Engineered silica nanoparticles are biologically safe vehicles to deliver drugs or genes to liver cells.

Engineered silica nanoparticles (SiNP) are emerging materials for medical applications. Evaluating biological responses of specific cells treated with engineered silica nanoparticles is however essential. We synthesized and characterized the physicochemical properties of silica nanoparticles with two different sizes of 10 and 100 nm (10SiNP and 100SiNP) dispersed in cell culture medium. HuH-7, an epithelial-like human hepatoblastoma cell line and SK-HEP-1, a liver sinusoidal endothelial cell line (LSEC) are employed to evaluate their biological responses for the SiNP treatment. Primary human lymphocytes are used to assess genotoxicity recommended by OECD guidelines while erythrocytes are used to assess hemolytic activity. The engineered silica nanoparticles are not able to produce radical species, to alter the mitochondrial membrane potential, and induce any adverse effects on cell proliferation. The colony formation ability of HuH-7 hepatoblastoma cells was not affected following the SiNP treatment. Furthermore, SiNPs do not induce hemolysis of red blood cells and are not genotoxic. These findings suggest that SiNPs regardless of the size, amount, and incubation time are biologically safe vehicles to deliver drugs or genes to the liver.

High glucose induced c-Met activation promotes aggressive phenotype and regulates expression of glucose metabolism genes in HCC cells.

Hepatocellular carcinoma (HCC) is strongly associated with metabolic dysregulations/deregulations and hyperglycemia is a common metabolic disturbance in metabolic diseases. Hyperglycemia is defined to promote epithelial to mesenchymal transition (EMT) of cancer cells in various cancers but its molecular contribution to HCC progression and aggressiveness is relatively unclear. In this study, we analyzed the molecular mechanisms behind the hyperglycemia-induced EMT in HCC cell lines. Here, we report that high glucose promotes EMT through activating c-Met receptor tyrosine kinase via promoting its ligand-independent homodimerization. c-Met activation is critical for high glucose induced acquisition of mesenchymal phenotype, survival under high glucose stress and reprogramming of cellular metabolism by modulating glucose metabolism gene expression to promote aggressiveness in HCC cells. The crucial role of c-Met in high glucose induced EMT and aggressiveness may be the potential link between metabolic syndrome-related hepatocarcinogenesis and/or HCC progression. Considering c-Met inhibition in hyperglycemic patients would be an important complementary strategy for therapy that favors sensitization of HCC cells to therapeutics.

[The relationship between insulin resistance and left ventricular systolic and diastolic functions and functional capacity in patients with chronic heart failure and metabolic syndrome]. / Kronik kalp yetersizligi olan metabolik sendromlu hastalarda insülin direncinin sol ventrikül sistolik ve diyastolik fonksiyonu ve fonksiyonel kapasite ile iliskisi.

OBJECTIVES: The relationship between chronic heart failure (CHF) and insulin resistance (IR) has long been recognized. We examined the relationship of IR with left ventricular (LV) systolic and diastolic functions and functional capacity of CHF patients with metabolic syndrome. STUDY DESIGN: The study included 50 nondiabetic CHF patients with metabolic syndrome (NYHA class I-III; 40 men, 10 women; mean age 60+/-10 years). Metabolic syndrome was diagnosed according to the AHA/NHLBI (American Heart Association/National Heart, Lung, Blood Institute) criteria. Insulin resistance was determined by the homeostasis model assessment (HOMA). Pulse-wave Doppler echocardiography and tissue Doppler imaging were performed to assess LV structure and functions. RESULTS: Patients with LV ejection fraction 40% (n=25). Fasting plasma insulin concentrations and HOMA-IR did not differ significantly in this respect. No significant differences were found in LV geometrical patterns, diastolic and systolic functions in patients with (HOMA >or=2.7; n=19) or without (HOMA <2.7; n=31) HOMA-IR. However, patients with HOMA-IR had a lower NYHA functional capacity (p<0.0001). HOMA-IR showed significant increases in parallel with NYHA functional class. CONCLUSION: Our findings suggest that IR in CHF patients with metabolic syndrome is not associated with LV systolic and diastolic functions, but is strongly linked with worsening in NYHA functional capacity.

The role of resistin on metabolic syndrome-induced erectile dysfunction and the possible therapeutic effect of Boldine.

BACKGROUND: Resistin is known as a potential mediator of obesity-associated insulin resistance. The high resistin level disrupts nitric oxide (NO)-mediated relaxation which is also important in erectile function. An antioxidant alkaloid, Boldine, is known as anti-diabetic and protects endothelial functions. OBJECTIVES: We aimed to investigate resistin expression in penile tissue in the presence of insulin resistance (IR) and the effect of Boldine treatment on erectile functions in the metabolic syndrome (MetS) rat model. MATERIALS AND METHODS: Wistar rats were randomly divided into three groups: Control, MetS, and boldine treated MetS group. MetS parameters were assessed by serum triglycerides (TG), uric acid (UA), glucose, insulin levels, HOMA index, and waist circumference (WC)/tibia length (TL) ratio. To evaluate erectile functions, intracavernous pressure (ICP)/mean arterial pressure (MAP) ratio was performed during cavernous nerve stimulation. Protein expressions of resistin, endothelial nitric oxide synthase (eNOS), p(S1177) eNOS, and insulin receptor-ß were evaluated by Western blotting. RESULTS: TG, glucose, insulin levels, weight, WC/TL ratio, HOMA index and resistin expression in penile tissue were significantly increased and ICP/MAP values, and p (S1177) eNOS expression in penile tissue were decreased in MetS group. Boldine treatment enhanced ICP/MAP values, insulin receptor-ß and p(S1177) eNOS expressions compared with the MetS group. DISCUSSION AND CONCLUSION: MetS caused a deterioration in erectile function accompanied by an increase in resistin expression and a reduction in eNOS enzyme activation in the rat penile tissues. Boldine treatment resulted in an improvement in erectile function, independent of resistin expression.

Asymmetric dimethylarginine levels in patients with coronary artery ectasia.

BACKGROUND: Endothelial dysfunction might be one of the pathophysiological mechanisms in the development of coronary artery ectasia (CAE) although the exact mechanisms have not yet been demonstrated. Asymmetric dimethylarginine (ADMA), an endogenous competitive inhibitor of nitric oxide synthase, is also related to endothelial and structural dysfunction. AIM: To asses the relationship between CAE and ADMA plasma concentrations. METHODS: Thirty patients with CAE in a mean age of 55.5 +/- 3.6 years and 40 patients with normal coronary arteries in a mean age of 53.3 +/- 11.6 years were studied. The ADMA levels of all patients were analysed by ELISA method. RESULTS: The mean ADMA level in the CAE group was found to be significantly higher than the mean ADMA level in the normal coronary artery group (2.26 +/- 0.47 vs. 1.43 +/- 0.40 micromol/l, p < 0.001). The elevated ADMA level (> 1.80 micromol/l) was present in 83.0% of patients from the CAE group and 25.0% of patients from the normal coronary artery group (p < 0.001). Having an increased ADMA level enhanced the risk of CAE 15-fold. The multiple-adjusted OR of the risk of CAE was 18.71 (95% CI 4.95-70.68) for the higher ADMA level compared to the lower level. CONCLUSION: Asymmetric dimethylarginine level is significantly associated with the presence of coronary artery ectasia. These findings suggest that increased ADMA level may be associated with endothelial dysfunction leading to the development of coronary artery ectasia.