The association of the Klotho polymorphism rs9536314 with parameters of calcium-phosphate metabolism in patients on long-term hemodialysis.

BACKGROUND: Patients on long-term hemodialysis frequently suffer from complications, such as secondary hyperparathyroidism, bone fractures, and arteriosclerosis. The process of regulating Ca/P metabolism depends on factors, such as FGF23 and Klotho. This study aimed to answer the question of whether the Klotho polymorphism rs9536314 is associated with FGF23 plasma concentration. METHODS: In 118 patients undergoing hemodialysis, blood was collected before and after hemodialysis. The following parameters were measured in plasma: FGF23, serum: Ca, P, PTH, HGB, and iron concentrations. The KL gene polymorphism rs9536314 was identified by PCR-RFLP. RESULTS: The KL polymorphism rs9536314 was not associated with Ca, P, PTH, or FGF23. There was a negative correlation between FGF23 and blood HGB levels and positive correlation between FGF23 and ESA dose. CONCLUSIONS: The results obtained may indicate that there is no association between the KL polymorphism and FGF23 concentration in patients undergoing long-term.

Soluble receptors for advanced glycation end products and receptor activator of NF-κB ligand serum levels as markers of premature labor.

BACKGROUND: This study aimed to determine the relationships between secretory and endogenous secretory receptors for advanced glycation end products (sRAGE, esRAGE), sRANKL, osteoprotegerin and the interval from diagnosis of threatened premature labor or premature rupture of the fetal membranes to delivery, and to evaluate the prognostic values of the assessed parameters for preterm birth. METHODS: Ninety women between 22 and 36 weeks' gestation were included and divided into two groups: group A comprised 41 women at 22 to 36 weeks' gestation who were suffering from threatened premature labor; and group B comprised 49 women at 22 to 36 weeks' gestation with preterm premature rupture of the membranes. Levels of sRAGE, esRAGE, sRANKL, and osteoprotegerin were measured. The Mann-Whitney test was used to assess differences in parameters between the groups. For statistical analysis of relationships, correlation coefficients were estimated using Spearman's test. Receiver operating characteristics were used to determine the cut-off point and predictive values. RESULTS: In group A, sRAGE and sRANKL levels were correlated with the latent time from symptoms until delivery (r = 0.422; r = -0.341, respectively). The sensitivities of sRANKL and sRAGE levels for predicting preterm delivery were 0.895 and 0.929 with a negative predictive value (NPV) of 0.857 and 0.929, respectively. In group B, sRAGE and sRANKL levels were correlated with the latent time from pPROM until delivery (r = 0.381; r = -0.439). The sensitivity of sRANKL and sRAGE for predicting delivery within 24 h after pPROM was 0.682 and 0.318, with NPVs of 0.741 and 0.625, respectively. Levels of esRAGE and sRANKL were lower in group A than in group B (median = 490.2 vs 541.1 pg/mL; median = 6425.0 vs 11362.5 pg/mL, respectively). CONCLUSIONS: Correlations between sRAGE, sRANKL, and pregnancy duration after the onset of symptoms suggest their role in preterm delivery. The high prognostic values of these biomarkers indicate their usefulness in diagnosis of pregnancies with threatened premature labor.

Prooxidative-antioxidative balance of cells in different types of renal replacement therapy.

BACKGROUND: Patients suffering from chronic kidney disease (CKD) are exposed to increased oxidative stress and disturbances manifesting in the enzymatic and non-enzymatic antioxidative defence system. The object of the research was to assess the differences between conservative treatment, peritoneal dialysis and haemodialysis in moderating cellular antioxidative agents. METHODS: The group examined comprised 145 patients. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase were obtained using kinetic methods. The spectrophotometric method established the concentrations of reduced glutathione, albumin, uric acid, glucose, total protein and lipids. RESULTS: The type of treatment determined significant changes in antioxidative enzyme activities and concentrations of non-enzymatic antioxidative compounds. CONCLUSIONS: Peritoneal dialysis provides better antioxidant protection than other types of therapy in CKD and should be considered as first-choice treatment despite more metabolic disorders.

[Bioactive lipids in kidney physiology and pathophysiology]. / Bioaktywne lipidy w fizjologii i patofizjologii nerek.

Lipids not only have structural functions, but also play an important role as signaling and regulatory molecules and participate in many cellular processes such as proliferation, differentiation, migration, and apoptosis. Bioactive lipids act both as extracellular mediators, which are associated with receptors on the surface of cells, and intracellular mediators triggering different signal pathways. They are present and active in physiological conditions, and are also involved in the pathogenesis of inflammation, asthma, cancer, diabetes, and hypertension. Bioactive lipids such as derivatives of arachidonic acid and sphingolipids have an important role in renal development, physiology and in many renal diseases. Some of them are potential indicators of kidney damage degree and/or function of the transplanted kidneys.

An intensified systemic trafficking of bone marrow-derived stem/progenitor cells in patients with pancreatic cancer.

Various experimental studies indicate potential involvement of bone marrow (BM)-derived stem cells (SCs) in malignancy development and progression. In this study, we comprehensively analysed systemic trafficking of various populations of BM-derived SCs (BMSCs), i.e., mesenchymal, haematopoietic, endothelial stem/progenitor cells (MSCs, HSCs, EPCs respectively), and of recently discovered population of very small embryonic/epiblast-like SCs (VSELs) in pancreatic cancer patients. Circulating CD133(+)/Lin(-)/CD45(-)/CD34(+) cells enriched for HSCs, CD105(+)/STRO-1(+)/CD45(-) cells enriched for MSCs, CD34(+)/KDR(+)/CD31(+)/CD45(-) cells enriched for EPCs and small CXCR4(+) CD34(+) CD133(+) subsets of Lin(-) CD45(-) cells that correspond to VSELs were enumerated and sorted from blood samples derived from 29 patients with pancreatic cancer, and 19 healthy controls. In addition, plasma levels of stromal-derived factor-1 (SDF-1), growth/inhibitory factors and sphingosine-1-phosphate (S1P; chemoattractants for SCs), as well as, of complement cascade (CC) molecules (C3a, C5a and C5b-9/membrane attack complex--MAC) were measured. Higher numbers of circulating VSELs and MSCs were detected in pancreatic cancer patients (P < 0.05 and 0.01 respectively). This trafficking of BMSCs was associated with significantly elevated C5a (P < 0.05) and C5b-9/MAC (P < 0.005) levels together with S1P concentrations detected in plasma of cancer patients, and seemed to be executed in a SDF-1 independent manner. In conclusion, we demonstrated that in patients with pancreatic cancer, intensified peripheral trafficking of selected populations of BMSCs occurs. This phenomenon seems to correlate with systemic activation of the CC, hepatocyte growth factor and S1P levels. In contrast to previous studies, we demonstrate herein that systemic SDF-1 levels do not seem to be linked with increased mobilization of stem cells in patients with pancreatic cancer.

Clinical analysis of selected complement-derived molecules in human adipose tissue.

BACKGROUND: It has been suggested that action of complement cascade [CC]-derived anaphylatoxins/molecules may represent a missing link between obesity and metabolic disorders. However, to date, the direct biochemical/immunomodulatory composition of the human AT environment remains poorly understood. In this study, we examined plasma and AT (subcutaneous and visceral/omental) levels of selected CC-derived anaphylatoxins/molecules, and adipsin as well as verified their associations with immune and stem cells chemoattractant - stromal-derived factor-1 (SDF-1). METHODS: A total of 70 (35 subcutaneous and 35 omental) AT samples were obtained from patients undergoing elective surgery. Plasma and AT-derived interstitial fluid levels of C3a, C5a, C5b-9/membrane attack complex (MAC), complement factor D (adipsin) were measured using ELISA. RESULTS: AT levels of all examined substances were significantly lower than the corresponding levels in the plasma (in all cases P < 0.0000001). Moreover, in subcutaneous AT, robust C3a and adipsin concentrations were observed, whereas high levels of C5b-9/MAC were detected in the visceral depots. In addition, we established the correlations between analyzed molecular substances and body composition, BMI and/or the adiposity index of the examined patients. CONCLUSIONS: Our study demonstrated for the first time that significantly reduced levels of complement-derived molecules were present in human AT than in the peripheral blood, and that these factors are associated with the metabolic status of examined individuals. Moreover, in human AT, various associations between complement-derived molecules and SDF-1 levels exist.

Winter-swimming as a building-up body resistance factor inducing adaptive changes in the oxidant/antioxidant status.

The aim of our research was to examine whether winter-swimming for five consecutive months results in adaptational changes improving tolerance to stress induced by exposure to cryogenic temperatures during whole-body cryostimulation (WBC). The research involved 15 healthy men, with normal bodyweight, who had never been subjected to either WBC or cold water immersion. During the experiment, the participants were twice subjected to WBC (3 min/- 130°C), namely before the winter-swimming season and after the season. Blood was taken seven times: In the morning before each cryostimulation, 30 min after each cryostimulation and the next morning. Additionally, control blood was collected in the middle of the winter season, in February. Our analysis concerned changes in hematological parameters as well as in reduced glutathione and oxidized glutathione, total oxidant status, total antioxidant status and in components of the antioxidant system: Superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase and 8-Isoprostanes as a sensitive indicator of oxidative stress. We found significant changes in hemoglobin concentration, the number of red blood cells, the hematocrit index and mean corpuscular volume of red blood cell and the percentage of monocytes and granulocytes after the winter swimming season. The response to cryogenic temperatures was milder after five months of winter-swimming. The obtained results may indicate positive adaptive changes in the antioxidant system of healthy winter-swimmers. These changes seem to increase the readiness of the human body to stress factors.

[Sphingosine-1-phosphate--molecular maestro]. / Sfingozyno-1-fosforan--dyrygent wsród czasteczek.

Sphingosine-1-phosphate (S1P), which is a bioactive lipid from the family of sphingolipids is synthesized i.e. by platelates and stored in erythrocytes. The effects of this compound on the cells are connected with the presence of specific receptors on their surface (S1P1-S1P5). S1P acts upon, i.e, hematopoetic and nervous cells, having influencing their migration, adhesion, differentation and survival. This molecule plays mediator role in inflammatory responses, angiogenesis and wound healing. In contrast to spingosine and ceramid, S1P counteracts apoptosis. Recent studies have shown that S1P is a factor, which participates in the process of release stem cells from bone marrow to peripherial blood. Cell and tissue damaged, stress, physical exercise and some drugs have influence on the numbers of stem cells. The research on S1P as the main chemotactic factor for stem cells may have substantial impact on the development of regenerative medicine.

Evaluation of the Health-related Behaviour of Pregnant Women from Warsaw, Poland.

BACKGROUND: Pregnancy is a period of time when women tend to suffer from the weakening of their psychophysical fitness. This research evaluated several selected elements of the lifestyle of pregnant women compared to those of non-pregnant women. METHODS: Overall, 482 women attended to the Childbirth School in Gynecological-Obstetric Hospital "Inflancka" in Warsaw, Poland, in the years 2011-2013; Group 1 contained 214 pregnant, and Group 2 contained 268 non-pregnant completed a survey inquiry. The research tool applied was Juczynski's "Inventory of Health Behaviour" (Inwentarz Zachowan Zdrowotnych). In this tool, the author evaluates health behaviors through four separate categories: dietary habits, prophylactic behaviors, mental attitude, and health behaviors. The differences between the data were defined through the Student's t-test for independent groups, with a minimal level of significance set at P ≤ 0.05. RESULTS: Pregnant women take care of following a healthy lifestyle. The general health behaviour index figure was significantly higher in Group 1 as compared with the Group 2 (P<0.001). A higher level (P<0.001) of healthy behaviour was typical of physically-active individuals, regardless of their Group (1 & 2). CONCLUSION: Pregnancy might cause women to increase their interest in matters of their own health and adopt a healthier lifestyle. Physical activity can influence other health-related practices.

Mobilization of Peripheral Blood Stem Cells and Changes in the Concentration of Plasma Factors Influencing their Movement in Patients with Panic Disorder.

In this paper we examined whether stem cells and factors responsible for their movement may serve as new biological markers of anxiety disorders. The study was carried out on a group of 30 patients diagnosed with panic disorder (examined before and after treatment), compared to 30 healthy individuals forming the control group. We examined the number of circulating HSCs (hematopoetic stem cells) (Lin-/CD45 +/CD34 +) and HSCs (Lin-/CD45 +/AC133 +), the number of circulating VSELs (very small embryonic-like stem cells) (Lin-/CD45-/CD34 +) and VSELs (Lin-/CD45-/AC133 +), as well as the concentration of complement components: C3a, C5a and C5b-9, SDF-1 (stromal derived factor) and S1P (sphingosine-1-phosphate). Significantly lower levels of HSCs (Lin-/CD45 +/AC133 +) have been demonstrated in the patient group compared to the control group both before and after treatment. The level of VSELs (Lin-/CD45-/CD133 +) was significantly lower in the patient group before treatment as compared to the patient group after treatment.The levels of factors responsible for stem cell movement were significantly lower in the patient group compared to the control group before and after treatment. It was concluded that the study of stem cells and factors associated with their movement can be useful in the diagnostics of panic disorder, as well as differentiating between psychotic and anxiety disorders.

Peripheral trafficking of bone-marrow-derived stem cells in patients with different types of gastric neoplasms.

Recently, there has been a growing interest in the importance of stem cells (SCs) in the development/progression of gastric neoplasms. In this study, we performed a comprehensive analysis of different populations of bone-marrow-derived stem cells (BMSCs) in patients with various types of gastric malignancies, including gastric cancer, gastrointestinal stromal tumors (GISTs), neuroendocrine neoplasms (NENs), and lymphomas. We found significantly lower numbers of circulating Lin-/CD45 +/ CD133 + hematopoietic stem/progenitor cells (HSPCs), and intensified peripheral trafficking of both Lin-/CD45-/CXCR4+/CD34+/CD133+ very small embryonic/epiblast-like stem cells (VSELs) and CD105 + /STRO-1 +/ CD45- mesenchymal SCs (MSCs) in patients with gastric cancer, but not in those with other types of gastric neoplasms. No significant differences in the absolute numbers of circulating CD34 +/ KDR +/ CD31 +/ CD45- endothelial progenitor cells (EPCs) were observed between the groups. This abnormal balance in the peripheral trafficking of BMSCs in patients with gastric cancer was neither associated with clinical stage of the disease nor with systemic levels of stromal-derived factor-1 (SDF-1), as these were comparable to the values observed in control individuals. Interestingly, the absolute numbers of circulating BMSCs correlated with the concentrations of complement cascade-derived anaphylatoxins/molecules (mainly C5b-9/membrane attack complex-MAC) and sphingosine-1-phosphate (S1P). In summary, our translational study revealed that abnormal peripheral trafficking of BMSCs occurs in patients with gastric cancer, but not in those with other types of gastric neoplasms. Further, our findings indicate that highlighted complement cascade-derived molecules and S1P, but not SDF-1, are significant players associated with this phenomenon.

Diagnostic Potential of Evaluation of SDF-1α and sRAGE Levels in Threatened Premature Labor.

Preterm birth remains the most prevalent cause of neonatal morbidity. This study aimed to evaluate the diagnostic value of SDF-1α, resistin, secretory RAGE (sRAGE), and endogenous secretory RAGE (esRAGE) in preterm labor. A total of 211 pregnant women participated in the study. Group A contained 72 women between 22 and 36 weeks of gestation, with premature labor, who finally had preterm birth. Group B contained 66 women in labor between 37 and 41 weeks of gestation. Women in group A had lower SDF-1α and sRAGE levels than those in group B. Moreover, in group A, SDF-1α and sRAGE levels were correlated with the latency period from the occurrence of premature labor symptoms until delivery. Sensitivity and specificity of studied parameters for prediction of preterm birth were 95% and 40% for SDF-1α and 51.3% and 93.5% for sRAGE, respectively. The prognostic value of plasma SDF-1α and sRAGE levels was comparable with that of cervical length ultrasound measurement and serum C-reactive protein levels. We conclude that SDF-1α and sRAGE appear to play a major role in the diagnosis of preterm birth and its evaluation could be convenient and useful for predicting preterm birth.

Evaluation of selected interleukins in patients with different gastric neoplasms: a preliminary report.

Abnormal interactions between cytokines may be an overlooked mechanism linking the development of different types of gastric neoplasms. In this study a comprehensive analysis of the systemic levels of interleukins (IL-1,IL-6, IL-8,IL-10 and IL-12) was performed in 75 patients with different gastric neoplasms (cancer, gastrointestinal stromal tumors, neuroendocrine neoplasms, lymphomas) and 40 healthy volunteers. Patients with gastric cancer (GC) have significantly higher IL-6 levels, and lower IL-8 and IL-10 concentrations, in comparison to controls and patients with other gastric neoplasms. Analogous results were observed in terms of IL-6/IL-8 and IL-6/IL-10 ratios, whose values were also higher in GC patients. In GC patients no associations were detected between the systemic levels/values of interleukins (ratios) and TNM staging. IL-6, IL-10, IL-6/IL-8 and IL-6/IL-10 ratios appeared to hold diagnostic potential in confirming/excluding the presence of GC. Their sensitivity/specificity in GC detection/exclusion was approximately 54-72%. In conclusion, disturbed systemic biochemical balance in multiple interleukins exists at the earliest stages of and appears to be specific to GC. The interleukin ratios proposed here seem to be more promising indicators of GC in humans than direct systemic levels of interleukins, and probably possess the potential to be applied as a supporting factor for techniques routinely used.

Soluble and Endogenous Secretory Receptors for Advanced Glycation End Products in Threatened Preterm Labor and Preterm Premature Rupture of Fetal Membranes.

The aim of the study was to compare sRAGE and esRAGE plasma levels in pregnant women with (A) threatened premature labor (n = 41), (B) preterm premature rupture of membranes (n = 49), and (C) preterm rupture of membranes at term (n = 48). The relationship between these and classic intrauterine infection markers and the latent time from symptoms up to delivery depending on RAGE's concentration were investigated. In groups A and B, a positive correlation was found between plasma sRAGE and latent time (r = 0,422; p = 0,001; r = 0,413, p = 0,004, resp.). High prognostic values were found in both groups for plasma sRAGE concentration and the latent time from symptoms up to delivery. Groups B and C presented higher levels of esRAGE than group A (526,315 ± 129,453 pg/mL and 576,212 ± 136,237 pg/mL versus 485,918 ± 133,127 pg/mL, p< 0,05). The conclusion is that sRAGE concentration can be a favorable prognostic factor in the presence of symptoms of threatened premature labor. Higher esRAGE plasma level in case of the rupture of membranes in mature and premature pregnancy suggests its participation in fetal membranes destruction.

Insulin resistance and brain-derived neurotrophic factor levels in chronic kidney disease.

INTRODUCTION: Insulin resistance is a frequent abnormality in chronic kidney disease (CKD) appearing in early stages. Factors known to promote insulin resistance in CKD patients include disorders of ion and acid-base equilibrium and circulating uremia toxins. Recent research has focused on the central nervous system as the source of the brain-derived neurotrophic factor (BDNF). The aim of our work was to study plasma BDNF concentrations in stage 3 and 4 CKD patients in relationship with insulin resistance and distribution of adipose tissue. METHOD: Plasma BDNF concentrations were measured in a study group of 31 patients, including a subgroup of 20 non-diabetic subjects. Additionally dual-energy X-ray absorptiometry (DXA) was performed. Homeostatic model assessment of insulin resistance (HOMA-IR) and homeostatic model assessment of B-cell function (HOMA-beta) indices were calculated. RESULTS: Two separate analyses were performed. In the first analysis performed in all 31 CKD patients, there were no correlations between BDNF and: body mass index (BMI), android, gynoid fat distribution, HOMA-IR and HOMA-beta. In the second analysis performed in 20 CKD patients without diabetes, BDNF was negatively related to gynoid fat (Rs = -0.47, P = 0.034) and women revealed significantly lower levels of BDNF than men (P = 0.046). Normotensive patients disclosed significantly higher BDNF levels than hypertensive patients in the whole CKD group (P = 0.039) and in the non-diabetic subgroup (P = 0.028). No correlations between BDNF and eGFR were found. CONCLUSIONS: Female sex and arterial hypertension are associated with lower BDNF plasma concentration in CKD patients.

Perioperative release of pro-regenerative biochemical signals from human renal allografts subjected to ischemia-reperfusion injury.

Complement-derived molecules modulate the intensity of renal ischemia-reperfusion injury and may lead to the generation of biochemical signals [such as stromal-derived factor-1 (SDF-1) or sphingosine-1-phosphate (S1P)], which stimulate tissue/organ regeneration after injury. We tested the association between perioperative C5b-9/membrane attack complex (MAC) levels and intensified erythrocyte lysis, and asked whether significant changes in the levels of pro-regenerative substances occur during the early phase of renal allograft reperfusion. Seventy-five recipients were enrolled and divided into the early, slow, and delayed graft function (DGF) groups. Perioperative blood samples were collected from the renal vein during consecutive minutes of reperfusion. Extracellular hemoglobin (eHb), albumin (plasma S1P transporter), 8-iPF2α-III isoprostane, SDF-1 and S1P concentrations were measured. Throughout the reperfusion period, erythrocyte lysis intensified and was most pronounced in the DGF group. However, perioperative eHb levels did not correlate significantly with C5b-9/MAC values, but rather with the intensity of oxidative stress. No significant changes were observed in S1P, its plasma transporter (albumin) or SDF-1 levels, which were relatively low in all groups throughout the reperfusion period. Our study therefore demonstrates that no known biochemical signal for bone marrow-derived stem cell mobilization is released from human renal allografts to the periphery during the early phase of reperfusion.

Selected hemostatic parameters in patients with pancreatic tumors.

INTRODUCTION: Recent experimental studies have suggested that various coagulation-related molecules may be important players in the development and progression of pancreatic cancer. However, these findings have not yet been verified in a clinical setting. METHODS: In this study, we comprehensively examined the levels of multiple hemostatic substances, including prothrombin, antithrombin, plasminogen, thrombin-anti-thrombin (TAT) and plasmin-anti-plasmin (PAP) complexes, as well as, soluble CD40 (sCD40) in patients diagnosed with pancreatic cancer (n = 37) or other tumors (neuroendocrine neoplasms - NEN [n = 7] or solid pseudopapillary tumors-SPT [n = 3]), and healthy individuals (n = 31). RESULTS: We found significantly higher anti-thrombin, PAP and sCD40 levels in patients with pancreatic cancer compared to healthy controls and patients diagnosed with other types of pancreatic tumors (for all, at least p < 0.05). Cancer patients had lower plasminogen concentrations than individuals from the other analyzed groups (for both, p < 0.05). None of the examined coagulation-related parameters was significantly associated with neither systemic sCD40 concentrations nor clinical staging of malignancy. Levels of analyzed molecules were comparable between pancreatic cancer patients presenting with early and advanced disease. Moreover, our study identified a potential diagnostic value of prothrombin/TAT and anti-thrombin/TAT coefficients in detection of pancreatic cancer in humans. However, both of these were inferior to currently used marker-CA19.9. CONCLUSIONS: Subclinical hemostatic alterations (mainly in plasmin-related molecules) i) appear as soon as during the earliest stages of the pancreatic adenocarcinoma development in humans, ii) do not seem to alter within progression of the disease nor are associated with clinical staging, iii) are not observed in patients with other types of pancreatic tumors, as well as, iv) do not seem to be associated with elevated sCD40 concentrations in pancreatic cancer patients. Moreover, examined thrombin- and plasmin-related substances do not appear to possess a sufficient diagnostic value to serve as makers of pancreatic adenocarcinoma in humans.

Selected cytokines in patients with pancreatic cancer: a preliminary report.

BACKGROUND/AIMS: Recent experimental studies have suggested that various cytokines may be important players in the development and progression of pancreatic cancer. However, these findings have not yet been verified in a clinical setting. METHODS: In this study, we examined the levels of a broad panel of cytokines, including interleukin (IL)-1, IL-6, IL-8, IL-10, IL-12, IL-17, and IL-23, as well as tumor necrosis factor alpha (TNFα) and granulocyte-colony stimulating factor (G-CSF) in patients with pancreatic adenocarcinoma (n=43), other pancreatic malignancies (neuroendocrine [n=10] and solid pseudopapillary tumors [n=3]), and healthy individuals (n=41). RESULTS: We found that there were higher levels of IL-6, IL-8, IL-10 and TNFα in patients with pancreatic cancer compared to healthy controls (for all, at least p<0.03). Cancer patients had lower IL-23 concentrations than healthy individuals and patients diagnosed with other types of malignancies (for both, p=0.002). Levels of IL-6, IL-8, IL-10, and IL-23 were significantly associated with the direct number of circulating bone marrow (BM)-derived mesenchymal or very small embryonic/epiblast-like stem cells (SCs) in patients with pancreatic cancer. Moreover, our study identified a potential ability of IL-6, IL-8, IL-10, IL-23, and TNFα levels to enable discrimination of pancreatic cancer from other pancreatic tumors and diseases, including acute and chronic pancreatitis and post-pancreatitis cysts (with sensitivity and specificity ranging between 70%-82%). CONCLUSIONS: Our study i) supports the significance of selected cytokines in the clinical presentation of pancreatic cancer, ii) highlights numerous associations between selected interleukins and intensified BMSCs trafficking in patients with pancreatic cancer, and iii) preliminarily characterizes the diagnostic potential of several cytokines as potential novel clinical markers of pancreatic cancer in humans.

Clinical analysis of perioperative complement activity during ischemia/reperfusion injury following renal transplantation.

BACKGROUND AND OBJECTIVES: The complement cascade seems to be an important mediator modulating renal ischemia/reperfusion injury. This study analyzed whether significant changes occur in the levels of a terminal panel of complement molecules (C3a, C5a, and C5b-9/membrane attack complex) during the early phase of human kidney allograft reperfusion and evaluated the potential association of these changes with clinical post-transplant graft function in kidney transplant recipients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Seventy-five renal transplant recipients undergoing transplantation between 2004 and 2006 were enrolled in the study and divided into early, slow, and delayed graft function groups. Blood samples were collected perioperatively during consecutive minutes of allograft reperfusion from the renal vein. Levels of complement molecules were measured using ELISA. RESULTS: Analysis revealed no significant changes in C3a and C5a levels throughout reperfusion. The main complement molecule that was significantly associated with post-transplant graft function was C5b-9/membrane attack complex; throughout the reperfusion period, perioperative levels of C5b-9/membrane attack complex were around two to three times higher in delayed graft function patients than early and slow graft function individuals (P<0.005). In addition, C5b-9/membrane attack complex levels had a relatively high clinical sensitivity and specificity (70%-87.5%) for the prediction of early and long-term (1 year) post-transplant allograft function. CONCLUSIONS: This clinical study supports a role for the complement cascade in delayed graft function development. However, additional studies are needed to elucidate the exact mechanisms responsible for this phenomenon. In addition, perioperative measurements of C5b-9/membrane attack complex are highlighted as promising potential clinical markers of post-transplant renal allograft function.