Serum leptin, resistin and TNF-α levels in patients with systemic sclerosis: the role of adipokines in scleroderma.

AIM: Systemic sclerosis (SSc) is a chronic fibrotic collagen tissue disease. Leptin's role in regulating immune and inflammatory response has become increasingly evident. Resistin has pro-inflammatory properties and also is associated with inflammatory markers in some rheumatologic diseases. The purpose of this study was to determine serum leptin, resistin and tumor necrosis factor alpha (TNF-α) in SSc patients and evaluate their association with other frequently used laboratory and clinic findings. METHOD: Sixteen patients were compared with 30 healthy women of similar age and body mass index. Serum leptin, resistin and TNF-α levels were measured by enzyme-linked immunosorbent assay and results were assessed by Mann-Whitney U -test and Spearman's correlation test. RESULTS: Leptin levels were significantly increased in the SSc group compared to controls (7789.43 ± 1180.72 pg/mL, 1790.55 ± 333.68 pg/mL, P < 0.0001). TNF-α was significantly elevated in patients and it was also positively correlated with leptin (25.30 ± 2.16 pg/mL, 20.95 ± 0.30 pg/mL, P = 0.001), (P = 0.002, r = 0.523). There was no association between leptin, resistin, TNF-α levels and skin score, activity score and disease duration in the SSc patients (P > 0.05). CONCLUSION: Leptin, resistin and TNF-α levels were found to be higher in SSc in contrast to the control group. These adipokines may have differentiating roles in the pathogenesis of SSc. In order to verify these findings, further clinical studies are needed with larger patient groups.

The role of resistin in Behçet's disease: a Turkish experiment.

The objective of this study was to assess the role of resistin, a proinflammatory cytokine potentially involved in Behçet's disease (BD), and to determine its relationship with tumor necrosis factor α (TNF-α), another important inflammatory cytokine known to be involved in BD. Forty-five persons diagnosed with BD were enrolled into this study, 25 of whom were being followed or had recently been diagnosed with clinically active BD, whereas the remaining 20 were previously diagnosed and had clinically inactive BD for the previous 3 months. Thirty persons were recruited as a healthy control group. Patients' C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), resistin, and TNF-α levels were determined with enzyme-linked immunosorbent assay (ELISA). Resistin and TNF-α levels were significantly higher in patients with BD (p < 0.05 and p < 0.05) than in the control group. The major interest of this study was to investigate the role of resistin in patients with BD. An elevated resistin level was associated with activation of BD. Elevated TNF-α and resistin levels could be determined simultaneously, and the presence of these two cytokines together suggests that resistin plays an important role in the pathogenesis and activation of BD.

Increased urotensin-II activity in patients with Raynaud's phenomenon and systemic lupus erythematosus.

AIM: Raynaud's phenomenon (RP) commonly co-exists with systemic lupus erythematosus (SLE). The obvious pathophysiological mechanism in RP is vasoconstriction. Although the roles of certain vasoconstrictor substances, like endothelin-1, have been identified in RP, underlying mechanisms remain unclear. METHODS: In this pilot study, we researched a relatively recently identified, very potent vasoconstrictor peptide, urotensin-II (U-II), in SLE patients versus those without RP. In addition to its vasoconstrictor effect, U-II has been implicated in cardiovascular events and atherosclerosis. Increased frequencies of atherosclerosis and cardiovascular events comprise another issue in SLE patients. To address these effects, we included 15 Raynaud's (+) and 15 Raynaud's (-) SLE patients and compared both cohorts against age and sex-matched controls. RESULTS: We found significantly elevated U-II activity in both RP (+) and RP (-) SLE patients, relative to controls (P < 0.0001); however, the difference among RP (+) SLE patients was more prominent. U-II was significantly elevated in RP (+) SLE patients when compared to RP (-) SLE patients (P < 0.001). CONCLUSIONS: The results of our study suggest that, either as a cause or by-product, U-II may have some role in Raynaud's-related vasoconstriction. It also might contribute to atherosclerosis and cardiovascular diseases in SLE patients. Further studies clearly are warranted.

Protective effects of dexpanthenol and y-27632 on stricture formation in a rat model of caustic esophageal injury.

BACKGROUND: This experimental study was conducted to investigate the effect of dexpanthenol (converted in the body to pantothenic acid) and Y-27632 (a selective Rho-kinase inhibitor) on stricture formation after caustic (alkaline) esophageal injury in rats. MATERIALS AND METHODS: Sixty male Wistar albino rats were randomly allocated into six groups. In group 1 (sham) the distal esophagus was isolated and cannulated but no caustic injury was induced. In all remaining groups, a caustic esophageal burn was induced with 50% sodium hydroxide solution for 90 s and drug treatment was given by daily intraperitoneal injection, beginning 24 h after injury and continuing for 21 d. In group 2 (controls), animals were treated with 0.9% saline; in groups 3 and 4, with 50 and 500 mg/kg/d of dexpanthenol, respectively; and in groups 5 and 6, with 0.3 and 3 mg/kg/d of Y-27632, respectively. Rats were sacrificed 22 d after caustic injury and the distal esophagus was isolated for histopathology and biochemical investigation. RESULTS: Stenosis index and collagen deposition scores were significantly lower in both the dexpanthenol and Y-27632 treated groups (P<0.05). Dexpanthenol and Y-27632 treatment markedly depressed esophageal tissue malondialdehyde and hydroxyproline levels. CONCLUSION: In this experimental model of caustic esophageal stricture, dexpanthenol and Y-27632 significantly attenuated esophageal stricture formation. These findings indicate that inhibition of Rho-kinase or dexpanthenol administration may offer novel therapeutic approaches in the treatment of caustic esophageal injury.

Prognostic value of pleural effusion, CA-125 and NT-proBNP in patients with acute decompensated heart failure.

BACKGROUND: Acute decompensated heart failure (HF) is a serious complication associated with significant morbidity and mortality. The CA-125 and NT-proBNP levels have been shown in some studies to predict the outcome, however, the prognostic value of other simple clinical parameters such as pleural effusion has not been established yet. AIM: To assess the prognostic value of pleural effusion regarding in-hospital and 6-month follow-up outcome in patients with acute decompensated HF and the relationship between pleural effusion and CA-125 and NT-proBNP levels. METHODS AND RESULTS: The CA-125 and NT-proBNP levels were measured at baseline and the presence of pleural effusion was examined on chest radiograms. One hundred patients were prospectively followed until the occurrence of cardiac death, defined as death from worsening HF or sudden cardiac death, or completion of follow-up period. There were 27 deaths over the course of 6 months of follow-up. An insignificant trend towards higher values of CA-125 was found in patients with pleural effusion. Univariate Cox regression analysis showed that there was no relationship between pleural effusion and in-hospital outcome as well as mortality during 6-month follow-up. The CA-125 and NT-proBNP levels predicted mortality. Multivariate Cox regression analysis showed that only CA-125 was an independent predictor of the 6-month outcome (RR: 1.2; 1.04-1.4; p = 0.001). CONCLUSIONS: In patients with acute decompensated HF, accompanying pleural effusion did not predict mortality or rehospitalisation during the 6-month follow-up. The increased CA-125 level was found to be an independent predictor of poor outcome, irrespective of pleural effusion.

Protective effects of Y-27632 on acute dichlorvos poisoning in rats.

Anticholinesterase poisoning is an important health problem in developing countries, and understanding of its underlying mechanisms is essential for the effective treatment. This study is designed to examine the effects of Y-27632, a selective Rho-kinase inhibitor, on organophosphate-induced cardiac toxicity and mortality in rats. Rats were randomly divided into 4 groups: control (corn oil), dichlorvos (30 mg/kg intraperitoneally), and 1- and 10-mg/kg Y-27632 + dichlorvos groups. After 6 hours of intraperitoneal injection, venous blood and cardiac samples were obtained, biochemical or immunohistochemical analyses were performed, and the intensity of muscle fasciculation was recorded. Serum cholinesterase activities were suppressed with dichlorvos, and these reductions were inhibited with Y-27632 pretreatment. Serum creatine kinase, creatine kinase-MB activities, and myoglobin and N-terminal probrain natriuretic peptide concentrations were not markedly affected with poisoning or Y-27632. Although serum nitric oxide concentrations did not change with dichlorvos, cardiac nitric oxide levels were markedly increased with Y-27632 pretreatment. Cardiac glutathione levels also increased with 1 mg/kg Y-27632. There was no staining for apoptosis, and immunohistochemical analyses of inducible nitric oxide synthase showed no change in cardiac tissue for all of the groups. Both doses of Y-27632 abolished mortality in rats with acute dichlorvos exposure (100% survival). These results show that administration of Rho-kinase inhibitor can produce protective effects against dichlorvos intoxication in rats. These findings may provide new possibilities for the treatment of organophosphate poisoning.

Therapeutic effect of caffeic acid phenethyl ester on cerulein-induced acute pancreatitis.

AIM: To evaluate the therapeutic role of caffeic acid phenethyl ester (CAPE) in a rat model of cerulean-induced acute pancreatitis (AP). METHODS: Seventy male Wistar albino rats were divided into seven groups. Acute edematous pancreatitis was induced by subcutaneous cerulein injection (20 microg/kg) four times at 1-h intervals. CAPE (30 mg/kg) was given by subcutaneous injection at the beginning (CAPE 1 group) and 12 h after the last cerulein injection (CAPE 2 group). Serum amylase, lipase, white blood cell count, and tumor necrosis factor (TNF)-alpha levels were measured, and pancreatic histopathology was assessed. RESULTS: In the AP group, amylase and lipase levels were found to be elevated and the histopathological evaluation showed massive edema and inflammation of the pancreas, with less fatty necrosis when compared with sham and control groups. Amylase and lipase levels and edema formation decreased significantly in the CAPE therapy groups (P < 0001); especially in the CAPE 2 group, edema was improved nearly completely (P = 0001). Inflammation and fatty necrosis were partially recovered by CAPE treatment. The pathological results and amylase level in the placebo groups were similar to those in the AP group. White blood cell count and TNF-alpha concentration was nearly the same in the CAPE and placebo groups. CONCLUSION: CAPE may be useful agent in treatment of AP but more experimental and clinical studies are needed to support our observation of beneficial effects of CAPE before clinical usage of this agent.