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1.
Doundoulakis Ioannis Gavriilaki Maria Tsiachris Dimitris Arsenos Petros Antoniou Christos-Konstantinos Dimou Smaro Soulaidopoulos Stergios Farmakis Ioannis Akrivos Evangelos Stoiloudis Panagiotis Notas Konstantinos Kimiskidis Vasilios K. Giannakoulas George Paraskevaidis Stylianos Gatzoulis Konstantinos A. Tsioufis Konstantinos 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2022,36(5):951-958
Cardiovascular Drugs and Therapy - Atrial high-rate episodes (AHREs) recorded with cardiac implantable electronic devices (CIEDs) have been associated with the development of clinical atrial... 相似文献
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Mechanisms of Action and Resistance of Somatostatin Analogues for the Treatment of Hepatocellular Carcinoma: A Message Not Well Taken 总被引:1,自引:0,他引:1
Samonakis DN Notas G Christodoulakis N Kouroumalis EA 《Digestive diseases and sciences》2008,53(9):2359-2365
Somatostatin (SST) acts as an inhibitory peptide of various secretory and proliferative processes. Apart from neuroendocrine tumors, where SST analogues have an established role, they have been tested in other tumors such as hepatocellular carcinoma (HCC) in the view of the fact that chemotherapy is not working. Several positive reports have been published. Approximately 40% of patients respond with improved survival and an impressive quality of life. A usual misunderstanding in trial designs is that, although SST is not a rescue drug, selection of patients is inappropriate, with mostly moribund patients being recruited. SST analogues do not seem to work in 60% of HCCs and this has been linked to the presence of SST receptors (SSTR) in the tumor, while several resistance mechanisms might be involved. Future management should engage more specific SST analogues targeted to a tumor with a known SSTR map. The use of somatostatin analogues as an adjunct therapy in combination with other treatment modalities should also be investigated. 相似文献
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Constantinos?Chatzicostas Maria?RoussomoustakakiEmail author Georgios?Notas Ioannis?G?Vlachonikolis Demetrios?Samonakis John?Romanos Emmanouel?Vardas Elias?A?Kouroumalis 《BMC gastroenterology》2003,3(1):7
Background
The aim of this study was to assess the prognostic accuracy of Child-Pugh and APACHE II and III scoring systems in predicting short-term, hospital mortality of patients with liver cirrhosis. 相似文献4.
Octreotide regulates CC but not CXC LPS-induced chemokine secretion in rat Kupffer cells 总被引:4,自引:0,他引:4
Valatas V Kolios G Manousou P Notas G Xidakis C Diamantis I Kouroumalis E 《British journal of pharmacology》2004,141(3):477-487
Kupffer cells (KC) and lipopolysaccharide (LPS) interaction is the initial event leading to hepatic inflammation and fibrosis in many types of liver injury. We studied chemokine secretion by KC activated with LPS and the possible effect of the somatostatin analogue octreotide, in the regulation of this process. KC isolated from Sprague-Dawley rats were cultured in the presence of LPS added alone or with different concentrations of octreotide for 24 and 48 h, and chemokine production was assessed in culture supernatants by ELISA. CC chemokine mRNA expression was assessed by semiquantitative RT-PCR. Vehicle-stimulated KC produced a basal amount of CC and CXC chemokines. LPS-stimulated KC secreted significantly increased amounts of IL-8 (GRO/CINC-1) (P<0.001), MIP-2 (P<0.001), MCP-1 (P<0.001), and RANTES (P<0.01). Octreotide inhibited LPS-induced secretion of the CC chemokines MCP-1 (P<0.05) and RANTES (P<0.05), but not the CXC chemokines IL-8 (GRO/CINC-1) and MIP-2, in a concentration-dependent manner. Downregulation of basal and LPS-induced mRNA expression of the CC chemokines was also observed in the presence of octreotide. Pretreatment with phosphatidylinositol 3 (PI3)-kinase inhibitors reduced chemokine production by LPS-treated KC in both the mRNA and protein level. Furthermore, it prevented the octreotide inhibitory effect on LPS-induced chemokine secretion, indicating a possible involvement of the PI3-kinase pathway. In conclusion, these data demonstrate that chemokine secretion by KC can be differentially regulated by octreotide, and suggest that this somatostatin analogue may have immunoregulatory effects on resident liver macrophages.British Journal of Pharmacology (2004) 141, 477-487. doi:10.1038/sj.bjp.0705633 相似文献
5.
Bolus somatostatin but not octreotide reduces hepatic sinusoidal pressure by a NO-independent mechanism in chronic liver disease 总被引:3,自引:0,他引:3
Matrella E Valatas V Notas G Roumpaki H Xidakis C Hadzidakis A Mouzas I Kouroumalis E 《Alimentary pharmacology & therapeutics》2001,15(6):857-864
BACKGROUND: Evidence exists that somatostatin and octreotide might have different effects on hepatic haemodynamics. AIM: The investigation of the effects of somatostatin and its octapeptide analogue, octreotide, on sinusoidal pressure measured by the wedged hepatic venous pressure in patients with cirrhosis or chronic hepatitis and the correlation with the levels of hepatic vein NO. METHODS: Patients were randomly assigned to receive an injection of either 250 microg somatostatin (n=14: cirrhosis six, chronic hepatitis eight) or an injection of 125 microg octreotide (n=19: cirrhosis nine, chronic hepatitis 10) during hepatic vein catheterization. Baseline wedged hepatic venous pressure was measured, followed by measurements at 2, 5, 10 and 15 min after the injection of the drug. Nitrites/nitrates of the hepatic vein were measured before the injection and after 15 min. RESULTS: Both agents showed a similar qualitative but a different quantitative haemodynamic profile. No change in the wedged hepatic venous pressure was observed during the first 2 min after the injection of both drugs. This was followed by a decrease: 18% at 5 min (N.S.), 23% at 10 min (P < 0.01) and 24% at 15 min (P < 0.01) for somatostatin. Octreotide induced a relatively smaller decrease in the wedged hepatic venous pressure: 8% at 5 min (N.S.), 20% at 10 min (P < 0.01) and 16% at 15 min (N.S.). Further analysis of the sub-groups of cirrhotic and chronic hepatitis patients revealed a different effect. In the sub-group of cirrhotic patients, somatostatin caused a maximum decrease of 34% at 15 min post-injection (P < 0.01), but octreotide failed to produce a significant change on the wedged hepatic venous pressure. In contrast, no change was observed in chronic hepatitis patients with either drug. No change in the hepatic vein concentration of NO after treatment was observed with either somatostatin or octreotide. Moreover, no correlation of the levels of NO with the wedged hepatic venous pressure values was found. CONCLUSIONS: This study shows that somatostatin is more effective than octreotide in acutely reducing the wedged hepatic venous pressure after bolus injection and the observed change is probably mediated by a NO-independent mechanism. 相似文献
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The innate immune mechanisms of the liver represent an important first line of defense against bacterial products, toxins, and food antigens coming from the intestine. Natural Killer (NK) and Natural Killer T cells (NKT) are components of the innate immune system with increased presence in the liver compared to other organs and have been reported to participate in the inflammatory processes during hepatic diseases. However significant confusion has been noted in this field mainly due to changes in the characterization of these cells as new knowledge accumulates and due to differences in the approaches used for their study. Both cell types can mediate hepatic injury in several models but studies in human liver diseases have not managed to fully explain their functions. However accumulating evidence supports an antifibrotic role of NK cells mainly via an inhibitory effect on hepatic stellate cells by inducing apoptosis and via production of interferon-gamma. Therefore, downregulation of NK cells during most types of liver injury may facilitate liver fibrosis. Data about the role of NKT cells in liver fibrosis are limited. This review will summarize the studies about the role of NK and NKT cells in liver diseases with a special interest in hepatic injury and liver fibrosis. 相似文献
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Voumvouraki A Koulentaki M Notas G Sfakianaki O Kouroumalis E 《European Journal of Internal Medicine》2011,22(1):77-83
Background
Hyaluronan, leptin, laminin and collagen IV have been used extensively for the assessment of liver fibrosis. The aim of this study was to assay these markers in the peripheral and hepatic vein blood of primary biliary cirrhosis (PBC) patients and to study their ability to discriminate early from advanced disease.Methods
Sera from 62 PBC patients were compared to 60 controls, 44 chronic Hepatitis C, 38 hepatocellular carcinoma and 34 viral cirrhosis patients. Serum from the hepatic vein of 15 cirrhotic PBC patients and 17 patients with viral cirrhosis was also assayed.Results
All disease groups had significantly increased levels of hyaluronan and collagen IV, compared to controls, while laminin was significantly increased only in viral cirrhosis. Hyaluronan levels were statistically different between early (54.5 ng/ml; 95%CI 27.3-426.9) and late PBC (154.5 ng/ml; 95%CI 55.3-764.4, p < 0.05). The area under the curve (AUC) for the identification of late PBC was 0.74 for hyaluronan, 0.63 for leptin, 0.59 for laminin and 0.70 for collagen IV. Hyaluronan had high sensitivity and NPV in identifying late stages of PBC (96% and 90%, respectively). Short term UDCA had no effect on these markers.Conclusion
No single measurement can differentiate between advanced and early fibrosis in PBC. However serum hyaluronan is a promising single serum marker for longitudinal studies in PBC. 相似文献10.
Koutroubakis IE Theodoropoulou A Xidakis C Sfiridaki A Notas G Kolios G Kouroumalis EA 《European journal of gastroenterology & hepatology》2004,16(11):1147-1152
BACKGROUND: Inflammatory bowel disease is associated with an increased incidence of thromboembolic complications. The aim of this study was to investigate the role of the soluble CD40 ligand (sCD40L), which displays prothrombotic properties, in patients with ulcerative colitis (UC) and Crohn's disease (CD) in comparison with inflammatory and healthy controls. METHODS: Plasma levels of sCD40L, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex and soluble P-selectin were measured in 104 inflammatory bowel disease patients (54 ulcerative colitis and 50 Crohn's disease), in 18 cases with other causes of intestinal inflammation and in 80 healthy controls using commercially available enzyme-linked immunosorbent assays. Plasma levels of sCD40L were correlated with disease activity, type, localization and treatment as well as with the measured thrombophilic parameters. RESULTS: CD patients had significantly higher sCD40L levels than both groups of controls (CD vs HC P < 0.001; CD vs non-IBD P < 0.05). UC patients had higher but not significantly different sCD40L levels compared with the controls. Both UC and CD patients with active disease had significantly higher sCD40L levels in comparison with patients with inactive disease. Plasma levels of sCD40L were correlated with platelet count (r = 0.27, P = 0.001). They also showed a correlation with prothrombin F1+2 (r = 0.16, r = 0.03) and TAT (r = 0.15, r = 0.04) as well as with P-selectin (r = 0.19, P = 0.01). CONCLUSIONS: The increased sCD40L plasma levels may represent, at least in some degree, a molecular link between inflammatory bowel disease and the procoagualant state. 相似文献