Left ventricular function is related with amphiregulin and fibrosis markers in cirrhotic cardiomyopathy.

The relationship between left ventricle (LV), extracellular matrix remodeling and fibrosis-linked amphiregulin (ARG) in cirrhotic cardiomyopathy (CCM) is unknown. The aim of the study was to investigate the associations between markers of extracellular matrix remodeling and ARG in cirrhosis and their association with indicators of ventricular remodeling and LV functional parameters. In hepatitis C virus (HCV) patients with cirrhosis, who underwent echocardiography, the presence of left ventricular diastolic dysfunction (LVDD) was determined by having gradable diastolic dysfunction in accordance with modified 2020 Cirrhotic Cardiomyopathy Consortium criteria. A total of 87 cirrhotic patients were consecutively analyzed. Based on detailed echocardiographic assessment - 35 HCV patients with cirrhosis had normal left ventricular diastolic function (non-CCM group), whereas 52 patients had LVDD (CCM group). ARG was measured by enzyme-linked immunosorbent assay. The ARG levels were significantly increased in the CCM group compared to the non-CCM group (P<0.001). ARG levels in all HCV patients were independently associated to the presence of CCM, and showed significant correlations with LVDD. The close relationship between ARG levels and the direct serum marker of fibrosis, and selected markers of extracellular matrix (i.e. transforming growth factor-beta1 (TGF-ß1), and carboxyterminal propeptide of type I collagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), tissue inhibitor of matrix proteinase-1 (TIMP-1), respectively), ventricular remodeling (i.e. N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-T (hs-TnT)), and LV functional parameters suggest an active role in the myocardial injury. Using ROC analysis, the best marker for the diagnosis of CCM was NT-proBNP with AUROC = 0.796. The area under the curve of ARG (AUROC = 0.709) for predicting CCM was greater than this for PICP (AUROC = 0.662) and similar to this hs-TnT (AUROC = 0.753). The simultaneous monitoring of serum ARG and markers of extracellular matrix and ventricular remodeling can be helpful for the alterations in myocardial function control in HCV patients with cirrhosis.

Serum betatrophin and irisin levels in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) development is a complex process with well-known risk factors, however the role of betatrophin/angiopoietin-like protein 8 and irisin has been poorly investigated thus far. The aim of this study is to measure betatrophin and irisin serum levels in HCC, cirrhotic patients and controls, assess their relationship with cancer etiology and grade, metabolic abnormalities and liver dysfunction severity. Serum betatrophin and irisin concentrations were measured with commercially available ELISA kits in 69 cirrhotic patients with HCC, 24 patients with non-viral cirrhosis and 20 healthy volunteers. The severity of liver disfunction was assessed according to Child-Pugh (C-P) score, while HCC grade according to the Barcelona clinic liver cancer (BCLC) staging system. Serum betatrophin concentration was significantly higher (33.7 ± 13.4 versus 12.3 ± 2.0 ng/ml; P < 0.001), while serum irisin level significantly lower in HCC patients compared to controls (2.52 ± 1.14 versus 4.46 ± 1.34 µg/ml; P = 0.02). Betatrophin level was also significantly elevated among cirrhotic patients compared to healthy volunteers. More evident serum betatrophin increase was found in patients with viral disease (34.8 ± 12.9 versus 26.1 ± 13.8 ng/ml; P < 0.001). Serum irisin concentration was significantly decreased in more advanced HCC cases (stage A versus C according to BCLC: 3.4 ± 1.3 versus 1.89 ± 1.1 µg/ml; P = 0.02). Decline of serum irisin (A: 3.4 ± 1.2; B: 2.42 ± 0.8; C: 1.91 ± 1.19 µg/ml; P = 0.03) and up-regulation of serum betatrophin levels (A: 24.1 ± 13.8; B: 39.3 ± 11.4; C: 46.2 ± 9.4 ng/ml; P = 0.03) were observed in patients with more advanced cirrhosis according to C-P score. We concluded that betatrophin serum level increased in cirrhotic patients, compared to controls. Since there was no difference between cirrhotic patients with and without intercurrent HCC, we suppose it may have an influence on fibrosis development, however not hepatocarcinogensis. Irisin serum level decreased in HCC patients, especially with more advanced disease grade, and was inversely related to the severity of liver disfunction.

Serum endocan level in diabetes mellitus of patients with cirrhosis and risk of subsequent development of spontaneous bacterial peritonitis.

The presence of type 2 diabetes mellitus (DM) in patients with cirrhosis is associated with an increased risk of spontaneous bacterial peritonitis (SBP) which may represent an increased susceptibility to infections. Endocan is a key player in the regulation of inflammatory disorders, and a biomarker in bacteremia and sepsis. To investigate the association between both endocan and DM, and developing SBP, we conducted a retrospective cohort study. Three hundred and thirty patients (179 men, 151 women; mean age 61.0 ± 8.5 years) who were treated for liver cirrhosis were studied between January 2007 and December 2016. Univariate and multivariate analyses using age, type 2 diabetes mellitus, severity of cirrhosis (Child-Pugh or MELD score), platelet count, serum proinflammatory cytokines, procalcitonin, C-reactive protein, and endocan level were conducted to identify factors related to the development of SBP. Among 330 patients with the median follow-up of 6.0 years, the cumulative incidence of SBP at 5 years was 28.6%. On multivariate analysis, a high serum endocan level and DM were independent and significant risk factors for SBP development (hazard ratio (HR) 1.634 (95% CI: 1.012 - 2.638; P = 0.047) and 2.482 (95% CI: 1.134 - 5.412; P = 0.023), respectively). Furthermore, the cumulative incidence rate of SBP in cirrhotic patients with high endocan levels was significantly greater than that in patients with low endocan levels (P = 0.035; log-rank test). Endocan is an independent predictor of SBP development in patients with cirrhosis. Cirrhotic patients with type 2 diabetes mellitus who have a higher endocan levels should be monitored carefully for the development of spontaneous bacterial peritonitis.

Clinical, functional and radiological outcomes of extracorporeal irradiation in limb salvage surgery for bone tumours.

AIMS: We present a retrospective review of patients treated with extracorporeally irradiated allografts for primary and secondary bone tumours with the mid- and long-term survivorship and the functional and radiographic outcomes. PATIENTS AND METHODS: A total of 113 of 116 (97.4%) patients who were treated with extracorporeally irradiated allografts between 1996 and 2014 were followed up. Forms of treatment included reconstructions, prostheses and composite reconstructions, both with and without vascularised grafts. Survivorship was determined by the Kaplan-Meier method. Clinical outcomes were assessed using the Musculoskeletal Tumor Society (MSTS) scoring system, the Toronto Extremity Salvage Score (TESS) and Quality of Life-C30 (QLQ-30) measures. Radiographic outcomes were assessed using the International Society of Limb Salvage (ISOLS) radiographic scoring system. RESULTS: There were 61 (54%) men with a mean age of 22 years (6 to 70) and 52 (46%) women with a mean age of 26 years (3 to 85). There were 23 deaths. The five-year patient survivorship was 82.3% and the ten-year patient survivorship was 79.6%. The mean follow-up of the 90 surviving patients was 80.3 months (2 to 207). At the last follow-up, 105 allografts (92.9%) were still in place or had been at the time of death; eight (7%) had failed due to infection, local recurrence or fracture. Outcome scores were comparable with or superior to those in previous studies. The mean outcome scores were: MSTS 79% (sd 8); TESS 83% (sd 19); QLQ 82% (sd 16); ISOLS 80.5% (sd 19). Pearson correlation analysis showed a strong relationship between the MSTS and ISOLS scores (r = 0.71, p < 0.001). CONCLUSION: This study shows that extracorporeal irradiation is a versatile reconstructive technique for dealing with large defects after the resection of bone tumours with good functional and radiographic outcomes. Functional outcomes as measured by MSTS, TESS and QLQ-30 were strongly correlated to radiographic outcomes. Cite this article: Bone Joint J 2017;99-B:1681-8.

Increased circulating endocan in patients with cirrhosis: relation to bacterial infection and severity of disease.

Life expectancy of patients with liver cirrhosis is closely linked to the degree of liver dysfunction and the occurrence of bacterial infection. An early diagnosis of infection helps to initiate adequate and timely measures and improves outcome of cirrhotic patients. Endocan is a newly recognized biomarker of sepsis. However, there have been no studies of the trends in endocan levels in cirrhotic patients with bacterial infection and their associations with markers of infection and inflammation. This study sought to assess the diagnostic value of serum levels of endocan, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in 126 patients with cirrhosis: 51 with decompensated infected cirrhosis, 56 with decompensated uninfected and 19 with compensated uninfected cirrhosis at inclusion. We analyzed the association of endocan with clinical factors in cirrhosis by comparison with indicators of infection and inflammation. Endocan, PCT, CRP, IL-6 and TNF-α were assayed in serum samples by ELISA analyses. Serum levels of endocan, PCT, CRP and TNF-α were significantly higher in cirrhotic patients with clinically overt infections. Endocan levels were correlated to neither PCT levels nor IL-6 levels in each group of patients with cirrhosis. CRP and TNF-α levels and Child-Pugh score correlated only in the infected group of patients with endocan levels, while in the uninfected groups of cirrhotic patients no significant correlation could be detected. The diagnostic accuracy of endocan increased in advanced stage of the disease. Serum endocan levels ≥ 2.05 ng/ml had a sensitivity of 76.1% and specificity of 85% for the diagnosis bacterial infection in decompensated cirrhotic patients. The endocan measured at admission is a good clinical parameter predicting the occurrence of infection in these patients. Elevated endocan may reflect the degree of endothelial cell injury induced by a systemic inflammatory response, a pathologic process that could modify the course of advanced cirrhosis.

Structural analysis of IPC zeolites and related materials using positron annihilation spectroscopy and high-resolution argon adsorption.

The advanced investigation of pore networks in isoreticular zeolites and mesoporous materials related to the IPC family was performed using high-resolution argon adsorption experiments coupled with the development of a state-of-the-art non-local density functional theory approach. The optimization of a kernel for model sorption isotherms for materials possessing the same layer structure, differing only in the interlayer connectivity (e.g. oxygen bridges, single- or double-four-ring building units, mesoscale pillars etc.) revealed remarkable differences in their porous systems. Using high-resolution adsorption data, the bimodal pore size distribution consistent with crystallographic data for IPC-6, IPC-7 and UTL samples is shown for the first time. A dynamic assessment by positron annihilation lifetime spectroscopy (PALS) provided complementary insights, simply distinguishing the enhanced accessibility of the pore network in samples incorporating mesoscale pillars and revealing the presence of a certain fraction of micropores undetected by gas sorption. Nonetheless, subtle differences in the pore size could not be discriminated based on the widely-applied Tao-Eldrup model. The combination of both methods can be useful for the advanced characterization of microporous, mesoporous and hierarchical materials.

Crossfit training changes brain-derived neurotrophic factor and irisin levels at rest, after wingate and progressive tests, and improves aerobic capacity and body composition of young physically active men and women.

Brain-derived neurotrophic factor (BDNF) is a protein that stimulates processes of neurogenesis, the survival of neurons and microglia, stimulates neuroplasticity, and takes part in the differentiation of cells developed in the hippocampus. BDNF is also released from skeletal muscles during exercise and can facilitate cross-talk between the nervous and muscular system. Irisin, the exercise hormone, is also released from skeletal muscles and is involved in oxidation processes in the organism. It is a vital issue from the point of view of prophylaxis and treatment through exercise of age-related diseases (e.g. senile dementia), obesity, type-2 diabetes. The aim of the study was to assess the changes in BDNF and irisin levels in young people after a 3-month CrossFit training program. At baseline and after the training, levels of BDNF and irisin were assayed before and after Wingate and progressive tests. Physical performance, body mass and composition, and muscle circumferences were also measured. There were noted: an improvement in aerobic capacity, an increase in VO2max, a reduction in adipose tissue percentage in women and an increase in LBM in all subjects. After CrossFit training the resting BDNF level increased significantly in all subjects while the resting level of irisin decreased in women, without changes in men. The resting level of BDNF at baseline was higher in men than in women. At baseline we observed an increased level of BDNF in women after Wingate and progressive tests, but in men only after the progressive test. After 3 months of CrossFit training the level of BDNF increased in all subjects, and also was higher in men than in women. In women we did not observe significant differences after both tests in comparison to rest. After the training BDNF was lower in men after Wingate and progressive tests than at rest. At baseline irisin level decreased in women after the Wingate and progressive tests. Changes in men were not observed after both tests. There were no differences in irisin levels between the baseline and 3 months after the training after Wingate and progressive tests. A beneficial influence of CrossFit training on the subjects' body composition, anaerobic capacity and cardiovascular fitness as well as an increase in BDNF makes it possible to assume that this type of training could have a very high application value, especially in a therapeutic process leading to improving a patient's wellbeing.

Use of an 'internal proximal femoral replacement' with distal fixation in revision arthroplasty of the hip.

We have managed 27 patients (16 women and 11 men) with a mean age of 68.4 years (50 to 84), with failed total hip replacement and severe proximal femoral bone loss by revision using a distal fix/proximal wrap prosthesis. The mean follow-up was for 55.3 months (25 to 126). The mean number of previous operations was 2.2 (1 to 4). The mean Oxford hip score decreased from 46.2 (38 to 60) to 28.5 (17 to 42) (paired t-test, p < 0.001) and the mean Harris Hip score increased from 30.4 (3 to 57.7) to 71.7 (44 to 99.7) (paired t-test, p < 0.001). There were two dislocations, and in three patients we failed to eradicate previous infection. None required revision of the femoral stem. This technique allows instant distal fixation while promoting biological integration and restoration of bone stock. In the short term, the functional outcome is encouraging and the complication rates acceptable in this difficult group of patients.

Melatonin decreases homocysteine level in blood of rats.

Elevated plasma homocysteine level promotes atherosclerosis in blood vessels due to, among others, generation of reactive oxygen species and reduction of nitric oxide bioavailability. The aim of this study was to investigate whether melatonin administration reduces plasma homocysteine level in rats consuming increased doses of methionine in the diet. The trial lasted for two months. The rats were divided into a few groups - 2 groups consisted of animals fed a standard diet, 2 groups consisted of animals fed a diet rich in methionine for one and two months, a group which had methionine removed from the diet in the second month, a group which had methionine removed from the diet and melatonin administered in the second month, a group still fed a diet rich in methonine in the second month and also given melatonin, and a group of animals on a diet rich in methionine for two months and given melatonin at the same time. Hcy, lipid peroxidation markers (MDA+4HNE) and nitric oxide metabolite (NO(2)(-)/NO(3)(-)) concentrations were determined in the plasma of all the rats. As a result of the tests it was found that plasma Hcy concentration increases in the first month of a methionine-rich diet but then decreases in the second month. MDA+4HNE changes are similar. Melatonin significantly intensifies the effects. The changes of NO(2)(-)/NO(3)(-) concentrations were noticed especially in the groups receiving melatonin. Elimination of methionine from the feed does not change the value of NO(2)(-)/NO(3)(-). NO production increases only after administration of melatonin. On the basis of received results it might be stated that melatonin administration together with a methionine-rich diet significantly decreases Hcy concentration, the level of oxidative stress and increases NO production. It might have some practical implications, especially when the level of endogenous melatonin decreases e.g. in elderly people or people with hyperhomocysteinemia.

[Tricyclic antidepressants as inhibitors of brain glutathione-S-transferase]. / Trójpierscieniowe leki przeciwdepresyjne jako inhibitory mózgowej transferazy glutationowej.

Tricyclic antidepressants, amitriptyline, doxepin--derivatives of cycloheptadiene as well as imipramine and clomipramine, derivatives of dibenzazepine inhibit the activity of glutathione-S-transferase pi isolated from different regions of human brain (parietal cortex, frontal cortex, brain stem). The inhibitory effect of studied drugs depends more on their chemical structure than on brain localization of the enzyme. All tricyclics bind nonspecifically to the effector site of glutathione-S-transferase (GST). The obtained results indicate that the inhibitory effect of tricyclic antidepressants on brain GST may decrease the efficiency of the enzymatic barrier, which protects brain against toxic electrophiles, and contribute in their adverse effects. On the other hand, brain GST may decrease the therapeutic effects of tricyclic antidepressants by binding them as ligands.

Internalization study using EDTA-prepared hepatocytes for receptor-mediated endocytosis of haemoglobin-haptoglobin complex.

We have demonstrated the internalization of haemoglobin-haptoglobin (Hb-Hp) complex using rat hepatocytes prepared by EDTA perfusion, followed by Percoll. The isolated hepatocytes exhibited a saturation curve of the binding of fluorescein isothiocyanate-labelled haemoglobin-haptoglobin complex (FITC-Hb-Hp. Furthermore, competition between the binding of FITC-Hb-Hp and unlabelled Hb to the hepatocytes, was observed. The cells exhibited approximately 9 x 10(4) 'high affinity sites' (Kd approximately 1.2 microM) for the Hb-Hp complex. The data in toto suggest the presence of only one type of receptor i.e. the high affinity receptor (in both affinity and number of sites per cell). The results were similar to those obtained from rat hepatocytes prepared by collagenase digestion [1]. In order to verify whether EDTA-prepared hepatocytes could be used for the study of receptor-mediated endocytosis, the internalization of pre-bound Hb-Hp in the isolated hepatocytes was assessed by two methods. First, acid-insensitive FITC-Hb-Hp time-dependently increased following incubation at 37 degrees C. Secondly, Hb-Hp became inaccessible to the exogenous FITC-anti-haemoglobin antibody. These processes were dependent on ATP, but independent of Ca2+ and stimulated by GTP. The results demonstrate that the receptor-mediated endocytosis of Hb-Hp occurred in the EDTA-prepared hepatocytes.

Acute phase reactants and circulating immune complexes in patients with ovarian carcinoma.

Serum levels of haptoglobin (HP), sialic acid total (NAN) and lipid-bound (NAL), seromucoid (SER), its content in total protein (%SER), as well as circulating immune complexes (CIC), were measured in sera of women with ovarian carcinoma, prior to their treatment and through the course of chemotherapy, remission and recurrence of malignancy, respectively. Control groups consisted of healthy women and patients with benign tumors (ovarian cysts and uterine myomas). Pretreatment measurements of acute phase reactants discriminated cancers (FIGO stages I+II, III, IV) from healthy group, however differences between benign tumors and stages of ovarian cancer were not so distinct. Changes in the examined parameters (acute phase reactants) indicated satisfactorily a response to the administered chemotherapy and early signs of the progression of the disease. Because of great variations in serum CIC concentrations, they were found to be of no value either in diagnosis or in the surveillance of the disease status.