Combined perioperative plasma endoglin and VEGF-A assessment in colorectal cancer patients

Colorectal cancer growth and spread is absolutely dependent on angiogenesis with vascular endothelial growth factor (VEGF) being the most important cytokine involved in the process. Endoglin, a membrane co-receptor for TGF-beta, has recently emerged as a sensitive index of cancer stage. There is now sufficient evidence indicating that microvessel density assessed by endoglin-immunostaining correlates with stage of colorectal cancer and patient survival. An association of a soluble form of endoglin with lymph node and distant metastases has recently been reported in two studies. Both of them used local elaborated immunoassays for endoglin assessment. The aim of our study was to determine the efficacy of plasma endoglin, assessed using a commercial kit, as a marker of tumor spread and distant metastases in colorectal cancer patients. We studied 48 colorectal cancer patients, compared with 22 healthy subjects, using ELISA. We observed that colorectal cancer patients had increased plasma VEGF-A, but not endoglin levels. However, we found an association of plasma endoglin with the stage of malignancy. Endoglin levels were increased in metastasis-positive patients when compared to both metastasis-negative patients and healthy volunteers. Plasma endoglin correlated with VEGF-A, CEA and CA19.9. Endoglin assessment in plasma does not seem useful as a maker of colorectal cancer. Our observations indicate however that it might be helpful in selecting patients with metastatic disease

Persistent organic pollutants (POPs) as an indicator of surface water quality in the vicinity of the Polish Polar Station, Horsund

Surface waters were collected in the vicinity of the Polish Polar Station in Hornsund (Svalbard) to determine their concentration of various persistent organic pollutants (POPs), such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs). In addition, parameters such as pH, SEC and TOC were measured. In total, 15 samples of lake water from and 15 samples of stream water were analysed. The sampling took place between August and September 2010. Total PAHs and PCBs concentrations in surface water ranged from < LOD to 6212 ng/dm3 and < LOD to 273 ng/dm3. Moreover, the main compounds detected in the samples from these two groups were naphthalene and PCB 153. Based on the cluster analysis, it was found that there are no significant differences between the water taken from the lakes and the water taken from the streams

Soluble angiogenesis markers in gastric tumor patients.

Gastric cancer is the second commonest cause of cancer-associated death in the world. Its molecular markers can be useful not only for diagnostic, but also prognostic purposes. The aim of the study was to assess the usefulness of soluble angiogenesis markers such as endoglin and VEGFR2 in gastric cancer patients and to compare these results with those of VEGF levels. As a secondary objective, we compared the concentrations of all three soluble markers in plasma and serum. The study was performed on 26 patients with gastric cancer (17 intestinal-type and 9 diffuse-type), and additionally in 2 patients with B cell lymphoma and 2 with gastro-intestinal stromal tumor. In summary, we showed increases in circulating VEGF-A in patients with both types of gastric cancer. The levels of VEGFR2 did not change significantly in patients with gastric cancer as compared to healthy subjects. Interestingly, after the operation greater levels of VEGFR2 were observed in patients without metastases. Both VEGF and VEGFR2 circulating levels were greater in patients with lymphoma, when compared to both gastric cancer patients and the control group. However, because of small number of patients, this requires further studies. Presented data suggests that endoglin does not seem to be a valuable tool in the assessment of gastric cancer invasion and spread

Tryptophan metabolism in experimental necrotizing acute pancreatitis

Pancreatic encephalopathy is a serious, often lethal complication of acute pancreatitis (AP). Its pathomechanism remains obscure. We have previously described increased blood levels of quinolinic acid (QUIN) – an endogeneous neurotoxine – during edematous experimental acute pancreatitis. Several other metabolites of tryptophan (TRP) are also known to be neuroactive. The aim of the present study was to assess tryptophan and its main metabolites: kynurenine (KYN), 3-hydroxykynurenine, quinolinic acid (QUIN), kynurenic acid (KYNA), serotonin (5HT) during experimental acute necrotizing acute pancreatitis. Experimental necrotizing acute pancreatitis was induced in rats by intraductal injection of 5% sodium taurocholate. Control groups consisted of sham-operated and not operated rats. The animals were sacrificed 5 and 24 hours after the operation. We evaluated -amylase, pancreas weight and histology as parameters of pancreatitis. A simplified neurological scoring system was applied. To assess TRP and its metabolites in plasma, we used high performance liquid chromatography. Five hours after the onset of AP we found significant increase in TRP metabolites: QUIN, KYNA, KYN, and 3HKYN in the plasma of animals with AP, as compared to the control group. When assessed 24 hours after induction of AP, those changes were no longer observed in blood. Instead, a decrease in TRP level appeared. Increase in plasma QUIN was associated with neurologic disturbances. In the present study we demonstrated transient activation of kynurenine pathway during early stages of experimental necrotizing AP, with increased blood levels of QUIN, KYNA, KYN, and 3HKYN and subsequent depletion of TRP. As some kynurenine derivatives, e.g. quinolinic acid, are endogenous toxins, they might contribute to neurologic and other organs disturbances during AP

Spatial Differences in the Chemical Composition of Surface Water in the Hornsund Fjord Area: A Statistical Analysis with A Focus on Local Pollution Sources

Surface catchments in Svalbard are sensitive to external pollution, and yet what is frequently considered external contamination may originate from local sources and natural processes. In this work, we analyze the chemical composition of surface waters in the catchments surrounding the Polish Polar Station in Svalbard, Hornsund fjord area. We have pooled unpublished and already published data describing surface water composition in 2010, related to its pH, electrical conductivity (EC), metals and metalloids, total organic carbon (TOC) and selected organic compound concentrations, including persistent organic pollutants (POPs) and surfactants. These data were statistically analyzed for spatial differences, using Kruskal–Wallis ANOVA and principal component analysis (PCA), with distance from the station in the PCA approximating local human activity impact. The geological composition of the substratum was found to be a strong determinant of metal and metalloid concentrations, sufficient to explain significant differences between the studied water bodies, except for the concentration of Cr. The past and present human activity in the area may have contributed also to some of the polycyclic aromatic hydrocarbons (PAHs), although only in the case of naphthalene can such an effect be confirmed by an inverse correlation with distance from the station. Other likely factors contributing to the chemical concentrations in the local waters are marine influence, long‐range pollution transport and release from past deposition in the environment

Immune-cell BDNF expression in treatment-naïve relapsing-remitting multiple sclerosis patients and following one year of immunomodulation therapy

Although neurons are the main source of neurotrophins in the healthy brain, neurotrophins can also be expressed in the immune system. We have previously shown that in relapsing-remitting multiple sclerosis (RRMS) lower immune-cell neurotrophin levels are associated with brain atrophy and cognitive impairment. The aim of the present study was to assess if immune-cell neurotrophin expression is impaired in MS as compared with the healthy controls, and to describe if these levels change in treatment-naïve RRMS patients, following one year of immunomodulation. Fifty treatment-naïve RRMS patients were assessed at baseline and after one year of immunomodulation (beta-interferons/glatiramer acetate). The control group included 39 healthy subjects matched according to age and gender. Peripheral blood mononuclear cells (PBMCs) were isolated from heparinized blood using Ficoll-Histopaque gradient. The levels of brain-derived-neurotrophic-factor (BDNF), beta-nerve-growth-factor (beta-NGF), neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) were measured in PBMC lysates with ELISA. BDNF levels were significantly lower in MS than in the healthy controls (median 613 vs. 1657pg/mg protein, p&lt;0.001). After one year of immunomodulation, BDNF expression did not change significantly (p=0.06) on the group level. In 70% of patients there was no increase in BDNF level, and in 30% it increased. We observed no differences between treatment groups. Other neurotrophins were detected in a minority of MS samples (as opposed to the controls). To conclude, we have shown that immune-cell production of neurotrophins is impaired in MS patients. In our MS cohort standard immunomodulation failed to restore normal BDNF levels in PBMCs within one year of therapy

Seasonal and Spatial Differences in Metal and Metalloid Concentrations in the Snow Cover of Hansbreen, Svalbard

Metals and metalloids in snow on glaciers, depending on the season of deposition, may come from various sources: local rock dust (erosion of the geological substratum), marine aerosol, local human activity (e.g., impurities in combusted fuel and waste incineration), and long-range atmospheric transport. Hansbreen, a glacier located close to the Polish Polar Station in southern Svalbard, is a perfect site to study metals and metalloids: it has a complex geological substratum, has a year-round presence of a small group of people, and is near the coast. We analyzed a snapshot of metal and metalloid concentrations in snow samples fromshallow cores corresponding to autumn, winter, and spring deposition on Hansbreen. Eighteen cores of snow were collected across the glacier, revealing the influence of potential local sources of metals and metalloids. In these samples, we predominantly found Na, Mg, and K, followed by Zn, Ca, Al, and Fe. Heavy metals, such as Bi or Hg, were also detected. Cluster analysis of the determined elemental concentrations divided them into three distinct groups: Group 1: Ag, As, Bi, Cd, Hg, Mo, Sb, Se, and Zn-the most diverse cluster, representing mostly long-range transported volatile elements, with possible extra local geological sources; Group 2: Al, Fe, Cu, and Mn-elements with crustal sources; and Group 3: Na, Ca, Mg, K, and Sr-with the main source in sea spray aerosol. The latter interpretation was confirmed by the calculation of sea salt contribution based on the composition of mean seawater and the positive significant correlation between their concentrations and the electrical conductivity of snow samples. In the study site, snow was up to six times more efficient in bringing metal pollution into terrestrial environment, when compared to rain

Prohepcidin and its possible role in anaemia of pregnancy

A b s t r a c t I In nt tr ro od du uc ct ti io on n: : Hepcidin is the predominant negative regulator of iron absorption in the small intestine, iron transport across the placenta, and iron release from macrophages. The aim of the study was to assess prohepcidin levels in pregnant women in relation to anaemia, inflammatory cytokines and iron status. M Ma at te er ri ia al l a an nd d m me et th ho od ds s: : The studies were performed on 37 healthy pregnant women (third trimester), 34 anaemic pregnant women (third trimester), 20 healthy pregnant women (first trimester) and 30 healthy female volunteers. Prohepcidin, hsCRP, soluble receptor of transferrin (sTfR) and interleukin-6 were studied using commercially available kits. R Re es su ul lt ts s: : Prohepcidin was higher in pregnancy, namely in anaemic patients, than in healthy females. In anaemic pregnant females prohepcidin showed a correlation with haemoglobin, haematocrit and total protein. In pregnant females in the first trimester prohepcidin was related to hsCRP. In all non-anaemic pregnant women (first and third trimester) prohepcidin correlated with sTfR and ferritin. In healthy volunteers prohepcidin was related to ferritin. C Co on nc cl lu us si io on ns s: : Elevated prohepcidin in pregnancy related to ferritin and sTfR may reflect an acute phase reaction, and either the cellular need for iron or the rate of erythropoiesis. In anaemia in pregnancy a cause-effect relationship between haematocrit and hepcidin might exist. A rise in prohepcidin in pregnancy may also be due to the fact that some proinflammatory cytokines play a fundamental role in inducing hepcidin gene expression, namely IL-6. K Ke ey y w wo or rd ds s:

Indoxyl Sulfate Promotes Arterial Thrombosis in Rat Model via Increased Levels of Complex TF/VII, PAI-1, Platelet Activation as Well as Decreased Contents of SIRT1 and SIRT3

Patients suffering from chronic kidney disease (CKD) are at a 20-fold higher risk of dying due to cardiovascular diseases (CVDs), primarily thrombosis following vascular injury. CKD is connected with retention of uremic toxins, especially indoxyl sulfate (IS), which are currently considered as a non-classical CKD-specific risk factor for CVDs. The present study aimed to examine the effect of chronic exposure to IS on the hemostatic system and arterial thrombosis in a model without greater interferences from the uremic milieu consisting of additional uremic toxins. Forty-eight male Wistar Crl:WI (cmdb) rats were divided into three groups: one control group and two experimental groups, which were exposed to 100 or 200 mg/kg of b.w./day of IS in drinking water for a period of 28 days. The control group received water without IS. At the end of the experiment, the induction of arterial thrombosis was performed. We investigated the impact of IS on thrombosis incidence, kinetics and strength of clot formation, platelet activity, aortic contents of sirtuin (SIRT) 1 and sirtuin 3 (SIRT3), hemostatic system, cardiorespiratory parameters, biochemistry of plasma and urine as well as histology of the thrombus, kidney, and liver. Obtained data revealed that chronic exposure to IS promotes arterial thrombosis via increased levels of complex tissue factor/factor VII, plasminogen activator inhibitor-1 (PAI-1), platelet activation, as well as decreased aortic levels of SIRT1 and SIRT3. Therefore, we hypothesize that IS enhances primary hemostasis leading to augmented formation of platelet plug with increased amounts of fibrin and affects secondary hemostasis through the influence on plasma coagulation and fibrinolysis factors, which results in the increased kinetics and strength of clot formation. The findings described may contribute to a better understanding of the mechanisms leading to increased thrombotic events in patients with CKD with elevated levels of IS