Correlation of Baseline Plasma and Inguinal Connective Tissue Metalloproteinases and Their Inhibitors With Late High-Pressure Endoleak After Endovascular Aneurysm Repair: Long-term Results.

Purpose: To investigate whether plasma and connective tissue matrix metalloproteinases (MMP) and their inhibitors (TIMP) may predict late high-pressure endoleak after endovascular aneurysm repair (EVAR). Materials and Methods: Samples of inguinal fascia and blood were collected in 72 consecutive patients (mean age 73.1 years; 68 men) undergoing primary EVAR with the Endurant stent-graft. Baseline plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 and baseline MMP-2 and MMP-9 activity estimated using gelatin zymography (GZ) were compared between patients who developed late endoleak in follow-up and those who did not. Subgroup analyses were performed between patients with (n=18) and without inguinal hernias and between patients with moderate-diameter (50-59 mm; n=45) or large-diameter (≥60 mm; n=27) abdominal aortic aneurysms (AAA) at primary EVAR. Results: The mean follow-up period was 63.1 months (range 7.5-91.5), during which time 13 (18.1%) patients developed type I (6 Ia and 5 Ib) or 2 type III endoleaks. Only GZ-analyzed proMMP-9 concentrations were higher in the endoleak group than in patients without endoleak (mean difference 8.44, 95% CI -19.653 to -1.087, p=0.03). The patients with primary inguinal hernia at presentation had significantly higher tissue TIMP-2 values (0.8±0.7 vs 0.5±0.4, p=0.018) but lower plasma total (pro- + active) MMP-9 values (11.9±7.8 vs 16.2±7.4, p=0.042) than patients without hernias at the time of EVAR. Patients with AAAs ≥60 mm had significantly higher mean tissue homogenate levels of total (pro- + active) MMP-9 (p=0.025) and total (pro- + active) MMP-2 (p=0.049) as well as higher proMMP-9 (p=0.018) and total (pro- + active) MMP-9 (p=0.021) levels based on GZ compared to patients with moderate-diameter AAAs. Regression analysis revealed a significant association between total (pro- + active) MMP-9 plasma samples and the presence of hernia (OR 0.899, 95% CI 0.817 to 0.989, p=0.029) and between GZ-analyzed proMMP-9 and late endoleak (OR 1.055, 95% CI 1.007 to 1.106, p=0.025). GZ-analyzed proMMP-9 and active MMP-9 were strong predictors of late endoleak in patients with hernia (p=0.012 and p=0.044, respectively) and in patients with AAAs ≥60 mm (p=0.018 and p=0.041 respectively). Conclusion: Inguinal fascial tissue proMMP-9 significantly predicted late endoleak. ProMMP-9 and active MMP-9 biomarkers are significantly associated with late endoleak in hernia patients and in patients with AAAs ≥60 mm. Considering the clinical association between hernia and AAA and the fact that the AAA wall connective tissue environment remains exposed to systemic circulation after EVAR, inguinal fascia extracellular matrix dysregulation and altered MMP activity may reflect similar changes in AAA biology, leading to complications such as endoleak.

Room air versus carbon dioxide pneumoperitoneum: effects on oxidative state, apoptosis and histology of splanchnic organs.

BACKGROUND: Although CO2 is the insufflation gas of choice in laparoscopic procedures, room air is usually used in natural orifice transluminal endoscopic surgery. The aim of the present study was to compare the safety of room air versus CO2 pneumoperitoneum in terms of their effect on the oxidative state, apoptosis and tissue injury of splanchnic organs. METHODS: Eighteen Wistar rats were assigned to three groups (n = 6 per group) and were subjected to 8 mm Hg room air (group Pne-Air) or CO2 pneumoperitoneum (group Pne-CO2) or sham operation for 60 min. Forty-five minutes postdeflation, tissue samples were excised from the liver, stomach, ileum and kidneys for reduced glutathione-to-glutathione disulfide (GSH/GSSG) ratio, caspase-8 and caspase-3 and hypoxia-inducible factor-1α (HIF-1α) immunohistochemical assessment and histopathologic examination. RESULTS: GSH/GSSG ratio substantially declined in both pneumoperitoneum groups. No change was noted in HIF-1α expression. Mild upregulation of caspase-8 and caspase-3 was noted in both pneumoperitoneum groups being less pronounced in group Pne-Air. Histopathologic score was increased in all organs studied, but the stomach, in both pneumoperitoneum groups. CONCLUSION: Pneumoperitoneum established by either room air or CO2 induced substantial oxidative stress, mild apoptosis and mild tissue injury in splanchnic organs. While air pneumoperitoneum conferred a less pronounced apoptotic effect, the oxidative state and histopathologic profile of splanchnic organs did not differ between insufflation gases.

Regional disparities in cancer mortality across the rural-urban axis: a case study from north-eastern Greece.

INTRODUCTION: The aim of this study was to identify differences in cancer mortality in north-eastern Greece, to describe potential drivers operating at the population level and to propose practical interventions and mitigation strategies. METHODS: Cancer mortality data were collected from local registries using the WHO 10th edition of International Classification of Disease (ICD-10). The direct standardization method was used to address demographic differences in the two regions, with the Standard European Population as reference. Rate ratios (RR) were employed for comparisons and 95% confidence intervals (95%CI) were calculated according to the Poisson approximation method. RESULTS: An increased risk of digestive system cancers (excluding liver neoplasms) was observed in rural versus urban areas (RR=1.25, 95%CI=1.02-1.54). Stomach cancer, in particular, was more prevalent in the older cohorts (>65 years), suggesting a historical epidemiological perspective. A more pronounced discrepancy was observed for prostate cancer mortality (RR=1.86, 95%CI=1.10-3.14), indicating a strong positive correlation with rurality. CONCLUSIONS: Cancer mortality disparities have been observed between rural and urban regions of north-eastern Greece. Health promotion and education, including improved access to medical facilities and early cancer screening, can help mitigate the burden and extend survival rates. Decreasing cancer staging at the time of diagnosis and reversing social and economic inequalities is key for combating these types of malignancy.

Lipopolysaccharide-binding protein: a potential marker of febrile urinary tract infection in childhood.

BACKGROUND: Urinary tract infections (UTIs) are encountered frequently in children, and their early diagnosis and treatment are important. This study evaluates the diagnostic value of serum concentrations of lipopolysaccharide-binding protein (LBP), an acute-phase protein, in children with febrile UTI and compares it to those of the total white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). METHODS: The study population comprised 77 consecutive patients with a first-episode febrile UTI (33 boys) with a median age of 11 months [interquartile range (IQR), 5.5-33 months], 21 healthy controls (11 boys) with a median age of 10 months (IQR, 5-20.5 months) and 58 febrile controls with a fever due to other causes (28 boys) with a median age of 12.5 months (IQR, 7-30 months). LBP, IL-6, PCT, and CRP were measured for both patients and control groups. RESULTS: The serum levels of LBP (p < 0.001), CRP (p < 0.001), PCT (p = 0.001), IL-6 (p = 0.002), ESR (p = 0.020), and WBC (p < 0.001) were higher in patients with febrile UTI than in the healthy and febrile control groups. The LPB cut-off value for best sensitivity and specificity in patients with febrile UTI was >43.23 mg/l. Furthermore, the area under the receiver operating characteristic curve was significantly greater for LBP than for CRP (p = 0.014), PCT (p < 0.001), ESR (p < 0.001), WBC (p = 0.002) and IL-6 (p = 0.006). CONCLUSIONS: The results of this study suggest that the serum LBP concentration constitutes a reliable biologic marker for the diagnosis of a febrile UTI in children.

Tissue inhibitor of metalloproteinase 4 in aqueous humor of patients with primary open angle glaucoma, pseudoexfoliation syndrome and pseudoexfoliative glaucoma and its role in proteolysis imbalance.

BACKGROUND: To quantify the levels of tissue inhibitor of metalloproteinase 4 (TIMP4) and its ratios with free metalloproteinases (MMP) in the aqueous humor of patients with primary open angle glaucoma (POAG), pseudoexfoliation syndrome (PXS) and pseudoexfoliative glaucoma (PXG) and to evaluate a possible imbalance between MMPs and TIMPs in these samples. METHODS: Free MMP2, MMP3, MMP9, TIMP1, TIMP2, TIMP4 concentrations and active levels of MMP2 and MMP3 were determined with immunoassay ELISA and activity assay kits in 168 aqueous samples. RESULTS: TIMP4 was elevated in glaucoma patients(POAG: 0.95 ± 0.49 PXG: 1.28 ± 1.38 pg/ml. p < 0.001). POAG, PXS and PXG samples demonstrated higher MMP2, TIMP1 and TIMP2 concentrations (p < 0.001). Samples from the PXS and PXG groups had a lower total/active MMP2 ratio (p < 0.004 and p < 0.008 respectively). Stoichiometric analysis showed an overbalance of TIMPsover MMPs in both POAG & PXG groups,especially of TIMP4. CONCLUSION: TIMP4 elevation is a novel finding in glaucomatous eyes. A disregulation of extracellular matrix homeostasis is suggested in POAG, PXS and PXG.

Phenotype and genotype frequency of ß-thalassemia and sickle cell disease carriers in Halkidiki, Northern Greece.

A decade of screening (years 2000 to 2010) for hemoglobinopathies in 3,931 patients was performed at the General Hospital of Poligiros, Halkidiki, Northern Greece. Among the patients examined, 10.8% heterozygotes for ß-thalassemia (ß-thal) were found, as well as 4.1% with sickle cell disease and 1.2% with double ß-thal/Hb S [ß6(A3)Glu→Val] heterozygosity. Iron deficiency was observed in 23.4%. The geographical distribution in the region revealed a substantial incidence of hemoglobinopathies even in mountainous areas. This pattern did not follow the typical distribution according to the malaria hypothesis, as incidence did not dovetail with swamp locations recorded in the past. The HBB gene mutations for 85 patients were also analyzed. Most prevalent in Halkidiki, Northern Greece, was the codon 39 (C>T) mutation (27.1%) followed by the IVS-I-110 (G>A) mutation (22.4%); this was in direct contrast to the current distribution of the same mutations seen in the rest of Greece (Greek National Genetic Database, GNGD). This frequency inversion was statistically significant, with the difference from the GNGD being 20.6% for the IVS-I-110 mutation (p <0.0005) and 7.6% for the codon 39 mutation (p = 0.0238). The history of Halkidiki, denoting a clear example of geographical isolation from the rest of the country, may possibly account for a potentially diverse genetical identity of the disease in this region.

Lysophospholipid Metabolism and Signalling in Non-Alcoholic Fatty Liver Disease.

Non-alcoholic liver disease (NAFLD) constitutes a global health pandemic. It is estimated that about 25% of the world's population suffers from NAFLD. In the long-term, a subgroup of the patients can develop inflammation and fibrosis. The end result in some cases is cirrhosis and even liver-related death. The epidemiology and natural history of NAFLD lead to extreme financial costs.

Red Blood Cell Malfunction in COVID-19: Molecular Mechanisms and Therapeutic Targets.

The world has been facing a pandemic for the past 2 years. COVID-19 still leads to millions of deaths worldwide, while deteriorating the global economy. The need for therapeutic targets, thus, remains. Interestingly, red blood cells, apart from gas exchange, also serve as modulators of innate and adaptive immunity. This function is accommodated mainly by surface molecules (proteins, lipids, and carbohydrates) and increased antioxidant capacity. However, under the circumstances of a disease state, red blood cells can become proinflammatory cells. Recent evidence has shown that, in the context of COVID-19, erythrocytes present protein oxidation, decreased antioxidant capacity, increased glycolysis, altered membrane lipidome, increased binding of Cytosine-Guanine (CpG) DNA and complement proteins, and low CD47 levels. These changes lead to an erythrocyte-dependent inflammation, which possibly participates in the hyperinflammation status of COVID-19. The current knowledge for the dysfunction of red blood cells during COVID-19 implies that the BAND3 protein and toll-like receptor 9 are potential therapeutic targets for COVID-19.

Red Blood Cell-Conditioned Media from Non-Alcoholic Fatty Liver Disease Patients Contain Increased MCP1 and Induce TNF-α Release.

Background: Non-alcoholic fatty liver disease (NAFLD) constitutes a global pandemic. An intricate network among cytokines and lipids possesses a central role in NAFLD pathogenesis. Red blood cells comprise an important source of both cytokines and signaling lipids and have an important role in molecular crosstalk during immunometabolic deregulation. However, their role in NAFLD has not been thoroughly investigated. Methods: Conditioned media from erythrocytes derived from 10 NAFLD patients (4 men, 6 women, aged 57.875±15.16) and 10 healthy controls (4 men, 6 women, aged 39.3±15.55) was analyzed for the cytokines IFN-γ, TNF-α, CCL2, CCL5, IL-8, IL-1ß, IL-12p40, IL-17, MIP-1ß, the signaling lipids sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA), and cholesterol. Their effect on the cytokine profile released by RAW 264.7 macrophages was also studied. Results: MCP1 levels were greater in conditioned growth medium from NAFLD patient erythrocytes than in that from healthy controls (37±40 vs 6.51±5.63 pg/ml). No statistically significant differences were found between patients and healthy controls with regard to S1P, LPA, cholesterol, or eight other cytokines. TNF-a release by RAW 264.7 cells was greater after incubation with patient-derived erythrocyte-conditioned medium than in medium without RAW 264.7 cells from either healthy or NAFLD subjects. Conclusion: Erythrocytes may contribute to liver infiltration by monocytes, and macrophage activation, partially due to CCL2 release, in the context of NAFLD..

Serum VEGF levels and tissue activation of VEGFR2/KDR receptors in patients with breast and gynecologic cancer.

OBJECTIVES: Vascular endothelial cell growth factor (VEGF) plays an important role in the biology of gynecological cancer, usually linked with aggressive tumour behaviour and a poor postoperative outcome. Yet, its role in benign breast/gynecological conditions is less clear. METHODS: Serum VEGF was analysed in a series of 49 patients with gynecological cancer and 61 patients with benign disease and compared to those of 12 normal female subjects. In addition, the activation status of VEGFR2/KDR receptors was investigated in formalin-fixed paraffin embedded tissues and related to VEGF. RESULTS: Mean serum levels of VEGF were significantly higher in patients with breast, endometrial and ovarian cancer compared to healthy controls and those with benign breast/gynecologic disease in the respective organs. A similar trend was noted in some cases of simple endometrial hyperplasia, fibroadenoma and fibrocystic disease of the breast. The expression of phosphorylated VEGFR2/KDR receptors was higher in breast, endometrial, ovarian cancer in patients with high VEGF serum levels and this reached a level of statistical significance when all malignancies were combined. CONCLUSIONS: Serum VEGF levels are increased in patients with breast and gynecological malignancies, but this can not be considered pathognomonic for cancer as it is also increased in certain benign conditions, including cases of fibroadenoma, fibrocystic disease of breast and simple endometrial hyperplasia. Furthermore, high serum VEGF levels are closely related to the activation status of the VEGFR2/KDR receptor in cancer cells, indicating a stimulatory effect of serum VEGF on the VEGF pathway contributing to tumor progression.

Mesna preserves hepatocyte regenerating capacity following liver radiofrequency ablation under Pringle maneuver.

BACKGROUND: The objectives of the present study were to test the hypothesis that hepatocyte regenerating activity induced by radiofrequency ablation (RFA) of the liver is attenuated when performed under Pringle maneuver, and to investigate the potentially protective effect of mesna prophylactic administration. MATERIALS AND METHODS: Wistar rats were subjected to liver RFA (group RFA), RFA plus Pringle maneuver for 30 min (group RFA+P), RFA plus Pringle plus mesna (400mg/kg, per os, 3h prior to operation) (group RFA+P+M), Pringle only (group P), or sham operation (group S) after midline laparotomy. At 1h, liver oxidative state (glutathione to glutathione disulfide ratio-GSH/GSSG) and nuclear factor κB (NF-κB) activity were assessed in liver specimens. At 1, 3, and 6h, the levels of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were measured in blood serum. At 24h, 48 h, 1 wk, and 3 wk, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured in blood serum and the histopathologic profile and hepatocyte mitotic activity were assessed in liver specimens. RESULTS: Mitotic activity was low but sustained in groups RFA and RFA+P+M, more intense in group P, while suppressed in group RFA+P. Histopathologic profile was deteriorated with lesions being more intense in group RFA+P but significantly less severe in group RFA+P+M. Oxidative stress was equally induced in all experimental groups. NF-κB was activated in groups RFA, RFA+P, and P, but not in group RFA+P+M. IL-6 and TNF-α serum levels were increased; the levels were significantly higher in group RFA+P, while lower in group RFA+P+M. Serum transaminases levels were increased during the first 48 h. CONCLUSIONS: Hepatocyte regenerating activity is suppressed following liver RFA under Pringle maneuver. Prophylactic administration of mesna preserves hepatocyte regenerating capacity by attenuating acute inflammatory response and minimizing hepatic tissue injury in the non-ablated liver parenchyma.

Pringle maneuver deteriorates gut barrier dysfunction induced by extended-liver radiofrequency ablation.

BACKGROUND: Large volume radiofrequency ablation (RFA) of the liver disrupts intestinal mucosa barrier with subsequent bacterial translocation. AIMS: To investigate the effect of the Pringle maneuver applied concurrently with extended liver RFA on gut barrier integrity and bacterial translocation. MATERIALS AND METHODS: Rats were subjected to 30% liver RFA following laparotomy (group RFA), RFA plus 30 min Pringle (group RFA + P), Pringle (group P) or sham operation (group S). Intestinal tissue specimens were excised for histopathological examination and assessment of mucosal morphometry, apoptotic activity, mitotic activity and oxidative state. Tissue specimens were collected from the mesenteric lymph nodes, non-ablated liver parenchyma, kidneys and lungs for bacterial culture. Blood samples were collected from the portal and systemic circulation for endotoxin level measurement. RESULTS: In group RFA + P, intestinal histopathologic lesions, mucosal atrophy and crypt cell apoptosis were more prominent compared to group RFA. Mitotic activity was suppressed. Oxidative stress was equally induced in all experimental groups. The incidence of positive bacterial cultures, bacterial counts and endotoxin levels were higher in group RFA + P compared to the other groups. CONCLUSION: The application of the Pringle maneuver concurrently with extended liver RFA aggravates gut barrier dysfunction with more aggressive translocation of endotoxins and intestinal bacteria.

Immune and Metabolic Interactions of Human Erythrocytes: A Molecular Perspective.

Apart from their main function as oxygen carriers in vertebrates, erythrocytes are also involved in immune regulation. By circulating throughout the body, the erythrocytes are exposed and interact with tissues that are damaged as a result of a disease. In this study, we summarize the literature regarding the contribution of erythrocytes to immune regulation and metabolism. Under the circumstances of a disease state, the erythrocytes may lose their antioxidant capacity and release Damage Associated Molecular Patterns, resulting in the regulation of innate and adaptive immunity. In addition, the erythrocytes scavenge and affect the levels of chemokines, circulating cell-free mtDNA, and C3b attached immune complexes. Furthermore, through surface molecules, erythrocytes control the function of T lymphocytes, macrophages, and dendritic cells. Through an array of enzymes, red blood cells contribute to the pool of blood's bioactive lipids. Finally, the erythrocytes contribute to reverse cholesterol transport through various mechanisms. Our study is highlighting overlooked molecular interactions between erythrocytes and immunity and metabolism, which could lead to the discovery of potent therapeutic targets for immunometabolic diseases.

Lipotoxicity Disrupts Erythrocyte Function: A Perspective.

BACKGROUND: Lipid accumulation in the liver, skeletal and cardiac muscle, kidneys and pancreas causes cell dysfunction, death and inflammation, a biological phenomenon named lipotoxicity. Erythrocytes participate in the transport of lipids in the circulation, and their lipidome is determined by exchange with blood components. OBJECTIVE: The objective of this study is to summarize the current knowledge regarding the effect of toxic lipid accumulation in erythrocytes. RESULTS: Erythrocyte lipidome is altered in lipotoxic diseases, such as fatty liver disease, heart failure and diabetes. In addition, ceramide, lysophosphatidylcholine, lysophosphatidic acid, palmitic acid and free cholesterol induce erythrocyte malfunction. CONCLUSION: Erythrocytes are an additional cell target of lipotoxicity. Further exploration of the implicated molecular mechanisms could lead to novel therapeutic targets for cardiometabolic and hematological diseases.

Molecular Interactions between Erythrocytes and the Endocrine System.

Hormones are secreted by the endocrine glands and reach their targets after circulating in the blood. Many studies have documented that erythrocytes can bind hormones, and possible interactions have been reported. Erythrocytes are responsive to signaling initiated after binding of epinephrine, norepinephrine, estrogen, progesterone, thyroid hormones, parathyroid hormone, and angiotensin. Signaling results in regulation of cellular metabolism and membrane fluidity. In addition, erythrocytes are circulating pools for dopamine, thyroid hormones, cortisol, and aldosterone. Erythrocyte function and structure are regulated by endocrine signals, while erythrocytes are important constituents for the transport of hormones in the body.

Bacterial translocation in a rat model of large volume hepatic radiofrequency ablation.

BACKGROUND: In this experimental study, we investigated the possibility of bacterial translocation, constituting a potential cause of infectious complications, after performing large volume hepatic radiofrequency ablation (RFA). MATERIALS AND METHODS: Wistar rats were subjected to RFA of the left median liver lobe (approximately 28.5% of the liver volume) after midline laparotomy. At 30 min, 24 h, 48 h, 72 h or 1 wk postoperatively, (1) blood samples were collected from the portal and systemic circulation for assessment of endotoxin concentration, (2) tissue specimens were excised from mesenteric lymph nodes, non-ablated liver, pancreas, spleen, kidneys, and lungs for bacterial culture, and (3) segments of terminal ileum were excised for histopathologic examination, morphometric analysis, and apoptotic and mitotic rate estimation. At 1 and 48 h, ileal mucosa was collected for oxidative state assessment on the basis of glutathione to glutathione disulfate (GSH/GSSG) ratio. RESULTS: Endotoxin levels were increased in both the portal and systemic circulation. Intestinal bacteria were isolated from all the organs at all time points. Ileal mucosa became gradually atrophic, with a decrease in villous height and density. There was an increase of crypt apoptotic rate, a decrease of GSH/GSSG ratio, while there were only mild signs of inflammation. CONCLUSIONS: Large volume liver RFA in the rat resulted to endotoxemia and translocation of intestinal bacteria to proximal and distal to the intestine organs at both the early and late post-RFA periods. The intestinal mucosa barrier was disrupted as suggested by ileal mucosal atrophy, increased crypt apoptosis, and induction of oxidative stress.

Red Blood Cell Dysfunction in Non-Alcoholic Fatty Liver Disease: Marker and Mediator of Molecular Mechanisms.

Despite efforts to unravel the pathogenetic mechanisms of non-alcoholic fatty liver disease (NAFLD), there is still a need for approved treatments and biomarkers. Interestingly, red blood cells present alterations in their characteristics during NAFLD. The phosphatidylcholine to phosphatidylethanolamine ratio, fatty acid profile, red blood cell count and red cell distribution width reflect molecular changes that are taking place in the liver. In addition, glycosylated hemoglobin, chemokine binding and release, and phosphatidylserine exposure actively participate in NAFLD pathogenesis. In this review, we describe the neglected red blood cell dysfunction in NAFLD, with the aim to unveil potent biomarkers and therapeutic targets.

Cholesterol and Phospholipid Distribution Pattern in the Erythrocyte Membrane of Patients with Hepatitis C and Severe Fibrosis, before and after Treatment with Direct Antiviral Agents: A pilot Study.

Objectives: Hepatitis C virus requires and induces changes in liver lipidome for its life cycle. In addition, alterations in plasma and erythrocyte lipidome are observed during a range of chronic liver diseases. Methods: A total of six subjects (three males and three females) were included in our study. All subjects were HCV positive according to virus RNA detection. Erythrocyte ghosts were prepared from blood and collected upon diagnosis and also at the end of the treatment with Direct Antiviral Agents (DAA). Lipids were extracted from the erythrocyte ghosts, and cholesterol and phospholipids were analyzed by thin layer chromatography. A semi-quantitative estimation of cholesterol (CHOL), phosphatidylethanolamine (PE), phosphatidylinositol (PI), phosphatidylserine (PS), phosphatidylcholine (PC) and sphingomyelin (SM) was performed by densitometric analysis of the chromatographs. Results: After the antiviral treatment, PE percentage decreased, whereas the PC/PE and CHOL/PE ratio increased significantly. There were also other weaker differences for CHOL, PI, PS, PC and SM. Before DAA there was a very weak correlation between ALT and PC/PE ratio. In contrast, there was a steep negative correlation between these two parameters after DAA. Conclusion: Red blood cell lipid composition and especially the PC/PE ratio could be a candidate real time biological marker for inflammation resolution during hepatitis C treatment.

Statin use is associated with a significant reduction in cholesterol content of erythrocyte membranes. A novel pleiotropic effect?

PURPOSE: High cholesterol content of erythrocyte membranes (CEM) levels is present in patients with acute coronary syndromes (ACS). Intraplaque hemorrhage and erythrocyte lysis contribute to the deposition of cholesterol on the atherosclerotic plaque and to plaque rupture. With the present study we assessed the effect of statin therapy on CEM levels, a novel marker of coronary artery disease (CAD) instability during a 1-year follow-up in CAD patients. METHODS: 212 consecutive eligible (158 men, 62 +/- 10 years) patients undergoing diagnostic coronary angiography for the assessment of angina pectoris were assessed. The study population comprised of 84 chronic stable angina (CSA) patients and 128 ACS patients. All study participants were commenced on statin treatment in equipotent doses and were followed for up to 1 year (at - 1, - 3, - 6 and - 12 months). RESULTS: Repeated measurements analysis of variance after appropriate adjustment showed a significant decrease (p < 0.001) in CEM content during follow up. CEM levels were decreasing at each time point (1 month : 100 microg/mg 95%CI 94.3-105.6, 3 months : 78.1 microg/mg 95%CI 73.2-83, 6 months : 67.2 microg/mg 95%CI 63.1-71.2, 1 year : 45.3 microg/mg 95%CI 42.2-48.3) compared to admission (112.1 microg/mg 95% CI 105.9-118.3) and to all previous measurements. CONCLUSIONS: The present study showed, that use of statins is associated with a reduction in CEM, an emerging marker of clinical instability and plaque vulnerability in CAD patients. The pleiotropic effects of statins at the cell membrane level represent a promising novel direction for research in CAD.

Impaired liver regeneration following partial hepatectomy using the Pringle maneuver: Protective effect of mesna.

BACKGROUND AND AIM: We investigated the role of the prophylactic administration of the antioxidant 2-mercaptoethane sulfonate (mesna) on the hepatocyte-regenerating capacity following partial hepatectomy (PH) with concurrent Pringle maneuver. METHODS: Wistar rats were subjected to PH (70% hepatectomy), 30 min Pringle maneuver, PH plus Pringle with or without mesna pretreatment (400 mg/kg, per os, 3 h before Pringle), or sham operation. At 24 h, 48 h, 72 h, and 1 week after operation, relative liver weight, hepatocyte mitotic activity (mitotic index), the histopathological score and serum aspartate aminotransferase, and alanine aminotransferase concentrations were assessed. At 1 h after operation, oxidative stress markers (glutathione to glutathione disulfide ratio, malondialdehyde concentration, and superoxide dismutase activity) and nuclear factor-kappaB (NF-kappaB) activity were assessed. RESULTS: Hepatectomy stimulated the regenerating process and induced mild oxidative stress and the activation of NF-kappaB in hepatocytes, while causing tissue injury in the remnant liver. When PH was performed under Pringle maneuver, hepatocyte mitotic activity was substantially suppressed, although Pringle alone initiated a delayed regenerating response. Furthermore, Pringle maneuver deteriorated oxidative stress markers, markedly increased NF-kappaB activity, and aggravated tissue injury, as compared to hepatectomy alone. Mesna pretreatment prevented the Pringle-induced antimitotic effect and the induction of oxidative stress, inhibited the activation of NF-kappaB, while attenuating liver injury after PH under Pringle. CONCLUSION: The excessive activation of NF-kappaB is related to the suppression of hepatocyte-regenerating activity following PH with concurrent liver ischemia. Mesna pretreatment protects the liver against the Pringle-induced antimitotic effect after PH via the prevention of oxidative stress and the inhibition of NF-kappaB activation.