Endoscopic findings in the upper gastrointestinal tract in patients with Crohn's disease are common, highly specific, and associated with chronic gastritis.

Crohn's disease (CD) may affect the entire gastrointestinal tract including its upper part. However, this aspect is poorly addressed in scientific literature and considered a rare finding. Here we aimed to prospectively investigate the prevalence, characteristics and clinical significance of upper gastrointestinal tract involvement in patients with CD, with particular focus on stomach bamboo joint-like appearance (BJA), Helicobacter pylori status and presence of microscopic changes. 375 prospectively recruited patients were included. In CD patients the prevalence of gastric and duodenal, but not esophageal, mucosal lesions, such as gastric mucosal inflammation, duodenal edema, ulcerations, and duodenal bulb deformation was significantly higher (at least p < 0.01 for all). Similar results were found when only H. pylori negative individuals were analyzed. Moreover, BJA of the stomach and in case of H. pylori negative patients also duodenal bulb deformation were detected exclusively in CD patients. Presence of BJA lesion was not significantly associated with neither duration of the disease nor use/history of biologic treatment. Despite absence of H. pylori infection microscopic features of chronic gastritis were found in almost all (93.5%) patients, and in 31% of controls (p < 0.00001). Our analysis outlines that upper gastrointestinal tract involvement in CD is a very common event and frequently manifests with a highly specific BJA lesion. Furthermore, our study reveals that in almost all CD patients features of H. pylori negative gastritis are present.

Lipoxins and Resolvins in Patients With Pancreatic Cancer: A Preliminary Report.

Eicosanoids are bioactive lipids derived from arachidonic acid, which have emerged as key regulators of a wide variety of pathophysiological processes in recent times and are implicated as mediators of gastrointestinal cancer. In this study, we investigated the systemic levels of lipoxygenase (LOX)-derived lipoxin A4 and B4, together with resolvin D1 and D2 in patients with pancreatic adenocarcinoma (n = 68), as well as in healthy individuals (n = 32). Systemic concentrations of the aforementioned immunoresolvents were measured using an enzyme-linked immunosorbent assay (ELISA). In this study, we observed that compared with concentrations in healthy individuals, the peripheral concentrations of the aforementioned eicosanoids were significantly elevated (2- to 10-fold) in patients with pancreatic cancer (in all cases p<0.00001). No significant association was observed between eicosanoid levels and the TNM clinical staging. Furthermore, we observed no significant differences in concentrations of the analyzed bioactive lipids between patients diagnosed with early-stage (TNM stage I-II) and more advanced disease (TNM stage III-IV). Receiver operating characteristic (ROC) curve analysis of each aforementioned immunoresolvent showed area under the curve values ranging between 0.79 and 1.00. Sensitivity, specificity, as well as positive and negative predictive values of the eicosanoids involved in the detection/differentiation of pancreatic adenocarcinoma ranged between 56.8% and 100%. In summary, our research is the first study that provides clinical evidence to support a systemic imbalance in LOX-derived lipoxins and resolvins as the mechanism underlying the pathogenesis of pancreatic adenocarcinoma. This phenomenon occurs regardless of the clinical TNM stage of the disease. Furthermore, our study is the first to preliminarily highlight the role of peripheral levels of immunoresolvents, particularly resolvin D1, as potential novel biomarkers of pancreatic cancer in humans.

Clinical significance of various growth factors in patients with different gastric neoplasms.

Growth factors represent a family of important biological molecules that can also be critical in the pathogenesis of various gastrointestinal cancers. In this study, we conducted a comprehensive analysis of the systemic levels of selected growth factors - hepatocyte, vascular-endothelial, fibroblast, and insulin-like 1 growth factors (HGF, VEGF, FGF, and IGF-1, respectively), as well as granulocyte-colony stimulating factor (G-CSF) in 75 patients with different gastric neoplasms (carcinomas, gastrointestinal stromal tumors - GISTs, neuroendocrine neoplasms - NENs, and lymphomas) and 40 healthy volunteers. Patients with gastric carcinoma or other types of gastric neoplasms had higher HGF and IGF-1 levels than healthy individuals (P < 0.05 in all cases). In comparison to healthy control subjects, systemic VEGF concentrations were elevated in patients with gastric carcinoma (P < 0.05), but not in individuals with other types of gastric malignancies. No statistically significant differences were observed between the analyzed groups in terms of FGF and G-CSF levels. When patients with gastric carcinoma were subdivided according to the Japanese classification system, significantly elevated levels of HGF, VEGF, and IGF-1 concentrations were observed in patients with advanced gastric carcinoma (extending beyond the submucosal layer of the stomach). Only the systemic levels of HGF were associated with tumor node metastasis - TNM staging, the absolute numbers of bone marrow-derived mesenchymal cells, and very small embryonic/epiblast-like stem cells circulating in patients with gastric carcinoma. ROC curves analyses demonstrated that AUC values of systemic levels of examined growth factors ranged from 0.40-0.65 (P > 0.06 in all cases). In conclusion, patients with gastric malignancies showed a systemic biochemical imbalance in multiple growth factors, which appears to be associated with clinical presentation of these neoplasms in humans. However, none of the growth factors examined here seem to be suitable diagnostic biomarkers for detecting or differentiating different types of gastric malignancies in humans.

Cerebral venous sinus thrombosis in a young patient with ulcerative colitis: A case report.

RATIONALE: Cerebral venous sinus thrombosis (CVST) represents one of the most alarming forms of hemostatic abnormalities that may occur in patients with inflammatory bowel diseases (IBDs). PATIENT CONCERNS: Here we report a case of a 25-year-old male with ulcerative colitis, who developed such thromboembolic complication during flare of the disease. CVST in our patient was clinically manifested by headache and nausea. DIAGNOSIS: Angio-magnetic resonance imaging scan of the head revealed segments of contrast filling defects/absence indicating right dural venous sinus thrombosis of the transverse sinus. INTERVENTION: Immediate treatment with low-molecular-weight heparin has been introduced and led to full remission of symptoms and total recanalization of the thrombotic cerebral regions. OUTCOMES: Currently (over 2 years after diagnosis) the patient is in remission of the disease, and no further thromboembolic complications have been observed. LESSONS: Our case study highlights the clinical difficulties and challenges associated with diagnosis and treatment of CVST, as well as presents the current state of knowledge about this complication among patients with IBDs. Physicians taking care of IBD patients should be aware of this alarming hemostatic abnormality.

Hydroxyeicosatetraenoic acids in patients with pancreatic cancer: a preliminary report.

Previous experimental reports have demonstrated that lipoxygenase (LOX) derivatives of arachidonic acid (AA), such as hydroxyeicosatetraenoic acids (HETEs), may be of significance in the pathogenesis of pancreatic cancer. However, these observations have not been confirmed in clinical studies. In the current study, we comprehensively evaluated the systemic levels of selected LOX-derived HETEs such as 5-, 12- and 15-HETE in patients with pancreatic adenocarcinoma (n=36), chronic pancreatitis (n=39), and in healthy individuals (n=35). Compared to healthy individuals, patients with pancreatic adenocarcinoma showed 3-8-fold higher levels of 5-, 12- and 15-HETE (at least P<0.003). Similar results were observed in patients with chronic pancreatitis, who had elevated concentrations of all examined HETE acids compared to healthy volunteers (in all cases at least P<0.03). Interestingly, the levels of the examined HETEs were not significantly associated with the TNM stage of pancreatic cancer in our patients. Finally, analyses of receiver operating characteristic curves demonstrated that all HETEs examined had relatively low area under the curve values for discriminating pancreatic adenocarcinoma from non-cancerous conditions (0.49-0.61; P>0.05 in each case). Our study provides first preliminary clinical evidence for the significance of the examined HETEs in the clinical pathogenesis of pancreatic cancer and other pancreatic diseases in humans. Moreover, our data demonstrate that the HETEs examined here do not show sufficient clinical potential to be used as independent (bio)markers for differentiating pancreatic adenocarcinoma from other non-cancerous conditions in humans.

Interleukins 17 and 23 in patients with gastric neoplasms.

Recently there has been heightened interest in the potential significance of interleukin (IL)-17 and IL-23 in the development/progression of human malignancies. Here, we analyzed the systemic levels of these cytokines in 75 patients with different types of gastric neoplasms (carcinoma, gastrointestinal stromal tumors, neuroendocrine neoplasms, and lymphomas) and 42 healthy volunteers. We found that patients with all types of gastric neoplasms have significantly lower IL-23 levels. However, in comparison to the levels in healthy individuals, IL-17 concentrations were lower only in patients with types of gastric neoplasms other than carcinoma. Interestingly, IL-17 levels significantly differed between patients with early and advanced gastric carcinoma. No significant associations were detected between the systemic levels of examined interleukins and TNM staging. However, peripheral levels of IL-23 were correlated with the absolute numbers of circulating populations of bone marrow-derived mesenchymal and very small embryonic/epiblast-like stem cells in patients with gastric carcinoma. ROC curve analyses demonstrated that systemic levels of IL-17 seem to meet basic criteria for consideration as a helpful diagnostic marker in the detection of gastric carcinoma. In conclusion, our study provides translational evidence confirming the clinical significance of IL-17 and IL-23 in the pathogenesis of different types of gastric neoplasms in humans.

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.

Concise Review: Pancreatic Cancer and Bone Marrow-Derived Stem Cells.

UNLABELLED: Pancreatic adenocarcinoma remains one of the most challenging diseases of modern gastroenterology, and, even though considerable effort has been put into understanding its pathogenesis, the exact molecular mechanisms underlying the development and/or systemic progression of this malignancy still remain unclear. Recently, much attention has been paid to the potential role of bone marrow-derived stem cells (BMSCs) in this malignancy. Hence, herein, we comprehensively review the most recent discoveries and current achievements and concepts in this field. Specifically, we discuss the significance of identifying pancreatic cancer stem cells and novel therapeutic approaches involving molecular interference of their metabolism. We also describe advances in the current understanding of the biochemical and molecular mechanisms responsible for BMSC mobilization during pancreatic cancer development and systemic spread. Finally, we summarize experimental, translational, and/or clinical evidence regarding the contribution of bone marrow-derived mesenchymal stem cells, endothelial progenitor cells, hematopoietic stem/progenitor cells, and pancreatic stellate cells in pancreatic cancer development/progression. We also present their potential therapeutic value for the treatment of this deadly malignancy in humans. SIGNIFICANCE: Different bone marrow-derived stem cell populations contribute to the development and/or progression of pancreatic cancer, and they might also be a promising "weapon" that can be used for anticancer treatments in humans. Even though the exact role of these stem cells in pancreatic cancer development and/or progression in humans still remains unclear, this concept continues to drive a completely novel scientific avenue in pancreatic cancer research and gives rise to innovative ideas regarding novel therapeutic modalities that can be safely offered to patients.

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.

An Attempt to Evaluate Selected Aspects of "Bone-Fat Axis" Function in Healthy Individuals and Patients With Pancreatic Cancer.

Recently, much attention has been paid to a potential biochemical cross-talk between the metabolism of the adipose tissue (AT) and bone (marrow), termed "bone-fat axis." We hypothesized that selected substances, participating in this "dialog," are associated with body mass and peripheral trafficking of bone marrow-derived stem cells (BMSCs) in both healthy individuals and patients with obesity-associated malignancies such as pancreatic adenocarcinoma.We performed an analysis of the systemic levels of selected substances involved in the regulation of bone (marrow) homeostasis (parathormone, calcitonin, osteopontin, osteonectin, stem cell factor [SCF], and fibroblast growth factor-23) in 35 generally healthy volunteers and 35 patients with pancreatic cancer. Results were correlated with the absolute number of circulating BMSCs and body mass values. Additionally, subcutaneous and visceral/omental AT levels of the aforementioned molecules were analyzed in lean and overweight/obese individuals.Intensified steady-state trafficking of only Lin-CD45 + CD133 + hematopoietic stem/progenitor cells was observed in overweight/obese individuals and this was associated with BMI values and elevated levels of both osteonectin and SCF, which also correlated with BMI. In comparison to healthy individuals, patients with cancer had significantly higher osteopontin levels and lower values of both osteonectin and osteonectin/osteopontin ratio. While no significant correlation was observed between BMI and the number of circulating BMSCs in patients with cancer, peripheral trafficking of CD34 + KDR + CD31 + CD45-endothelial progenitor cells and CD105 + STRO-1 + CD45-mesenchymal stem cells was associated with the osteonectin/osteopontin ratio, which also correlated with BMI (r = 0.52; P < 0.05). AT levels of the examined substances were similar to those measured in the plasma, except for osteonectin, which was about 10 times lower.Our study highlights the potential role of osteonectin, osteopontin, and SCF as communication signals between the bone (marrow) and AT in both healthy individuals and patients with pancreatic cancer. We postulate that these molecules may be overlooked biochemical players linking body mass and BMSCs with obesity-associated cancer development and/or progression in humans.

[Obesity and gastrointestinal neoplasms]. / Otylosc a nowotwory przewodu pokarmowego.

Being overweight or obese is a significant public health problem in the 21st century due to its scale, common existence and its cause-effect association with multiple diseases. Excessive accumulation of adipose tissue in humans is regarded as a major risk factor for development of cardiovascular and skeletal diseases. However, data from recent years have revealed that obesity is also strongly associated with increased risk of the majority of cancers in humans, including those originating from the gastrointestinal tract. During the last few year this association has been thoroughly proven and supported by several epidemiological analyses. The authors present i) the current state of knowledge regarding key (patho)mechanisms that link metabolism of human adipose tissue to development/progression of neoplasms (especially in the gastrointestinal tract), as well as ii) the results of selected clinical studies in which the influence of obesity on risk of gastrointestinal cancer development has been addressed.

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.

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.

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.

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.

Uterine rupture in the second trimester of pregnancy as an iatrogenic complication of laparoscopic myomectomy.

Uterine rupture is one of the most dangerous obstetric emergencies carrying a high risk for the mother and the fetus. Reports about uterine rupture in pregnancy following previous laparoscopic surgery have not been frequent; however, an increasing rate of the occurrence of this complication has been observed and reviewed in contemporary literature. We report a case of a spontaneous uterine rupture at 22 weeks of gestation in a 25-year old primigravida, who had had a laparoscopic removal of a small, peduncular, asymptomatic myoma located in the right uterine horn 20 months earlier. Ultrasound examination and subsequent urgent laparotomy confirmed a spontaneous uterine rupture with a nonviable fetus in the peritoneal cavity. Women planning to become pregnant should be qualified for laparoscopic myomectomy with special carefulness. Special attention must be paid to the potential solutions that limit the risk of postoperative uterine rupture, if the absolute necessity for the enucleation of myomas during the reproductive age occurs and a decision about laparoscopic intervention is made.

Association between the perioperative antioxidative ability of platelets and early post-transplant function of kidney allografts: a pilot study.

BACKGROUND: Recent studies have demonstrated that the actions of platelets may unfavorably influence post-transplant function of organ allografts. In this study, the association between post-transplant graft function and the perioperative activity of platelet antioxidants was examined among kidney recipients divided into early (EGF), slow (SGF), and delayed graft function (DGF) groups. METHODOLOGY/PRINCIPAL FINDINGS: Activities of superoxide dismutase, catalase, glutathione transferase (GST), glutathione peroxidase, and glucose-6-phosphate dehydrogenase (G6P) were determined and levels of glutathione, oxidized glutathione, and isoprostane were measured in blood samples collected immediately before and during the first and fifth minutes of renal allograft reperfusion. Our results demonstrated a significant increase in isoprostane levels in all groups. Interestingly, in DGF patients, significantly lower levels of perioperative activity of catalase (p<0.02) and GST (p<0.02) were observed. Moreover, in our study, the activity of platelet antioxidants was associated with intensity of perioperative oxidative stress. For discriminating SGF/DGF from EGF, sensitivity, specificity, and positive and negative predictive values of platelet antioxidants were 81-91%, 50-58%, 32-37%, and 90-90.5%, respectively. CONCLUSIONS: During renal transplantation, significant changes occur in the activity of platelet antioxidants. These changes seem to be associated with post-transplant graft function and can be potentially used to differentiate between EGF and SGF/DGF. To the best of our knowledge, this is the first study to reveal the potential protective role of platelets in the human transplantation setting.

Adipose tissue as a potential source of hematopoietic stem/progenitor cells.

It has been more than 30 years since adipose tissue (AT) has been recognized as a central modulator orchestrating sophisticated process termed "immunometabolism". Nonetheless, despite its unique involvement in the regulation of immune and endocrine homeostasis, recent studies demonstrated that AT also contains significant number of hematopoietic stem/progenitor cells (HSPCs) that may be there "settling down" throughout life. In this article we will focus on presenting the current concepts regarding endocrine, immunological, and molecular mechanisms that may contribute to and regulate bone marrow (BM)-derived HSPCs homing into AT environment, as well as, highlight various structural and morphological similarities between BM and AT that might be involved in creating appropriate tissue niches for BM-derived HSPCs in AT. Finally, we will discuss how development of obesity or type 2 diabetes may influence balance of homing signals for HSPCs in AT environment.