The Efficacy Comparison of Endoscopic Bariatric Therapies: 6-Month Versus 12-Month Intragastric Balloon Versus Endoscopic Sleeve Gastroplasty.

INTRODUCTION: Intragastric balloon (IGB) insertion and endoscopic sleeve gastroplasty (ESG) are known to be effective and safe in achieving weight loss. The aim of this study was to compare the effects of a 6-month IGB therapy, a 12-month IGB therapy, and ESG. METHODS: We retrospectively analyzed the weight loss at IGB (Orbera) removal after 6 months (124 patients), at IGB (Orbera365) removal after 12 months (61 patients) and at 6 and 12 months after ESG (42 and 34 patients, respectively). Postprocedural care, including medication and diet, was the same for all procedures. RESULTS: Mean TBWL in patients undergoing IGB placement for 6 and 12 months and ESG after 6 and 12 months were 15.2, 15.8, 26.5, and 28.7 kg, respectively. There was no significant difference in the mean %TBWL in patients undergoing IGB placement for 6 or for 12 months (15.3% vs. 14.7%, P = 0.7). ESG patients showed a significantly higher mean %TBWL than IGB patients after 6 months (15.3 vs. 19.8, P = 0.005) and 12 months (14.7 vs. 22.5, P < 0.001). CONCLUSION: All three studied methods were effective for achieving weight loss. However, there was no significant difference between 6-month and 12-month IGB therapies outcomes. ESG appeared to be a more effective obesity treatment modality than IGB.

Covid-19: exploring the "new normal" in gastroenterology training.

The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented disruptions in fellowship training programs worldwide. In gastroenterology, the strain in healthcare service provision and the emphasis on preventing viral transmission has adversely impacted hands-on training opportunities, with trainees facing the constant pressure to meet training requirements under the continuous threat of viral transmission. Emerging evidence highlight the scale of the problem, specifically with regard to endoscopy competence due to cancellation of elective endoscopic procedures, provision of inpatient and outpatient consultative care as well as academic education and the mental well-being of trainees. As such, it has been necessary for trainees, trainers and training programs collectively to adapt to these challenges and incorporate novel and adaptive solutions to circumvent these training barriers. This review aims to summarise data on the global impact of COVID-19 on gastroenterology training and the practical interventions that could be implemented.

Effect of a 1800 MHz electromagnetic field emitted during embryogenesis on chick development and hatchability.

The level of artificial electromagnetic field (EMF) has steadily increased with the development of human civilization. The developing chicken embryo has been considered a good model to study the effects of EMF on living organisms. The aim of the study was to determine the effect of a 1800 MHz electromagnetic field during embryogenesis on the frequency of chick embryo malformations, morphometric parameters of the heart and liver and concentration of corticosterone in blood plasma, lipid and glycogen content in the liver of newly hatched chicks. A 1800 MHz EMF was found to shorten the duration of embryogenesis (earlier pipping and hatching of chicks) while having no effect on the quantity and quality of chicks and on increasing the incidence of embryo malformations. Exposure of chick embryos to EMF caused decreases in relative heart weight and right ventricle wall thickness. The pipping and hatching of chicks can be accelerated by stressful impact of EMF, which is confirmed by a significant increase in plasma corticosterone concentrations and decrease in fat and glycogen in the liver of chicks exposed during embryogenesis on the electromagnetic field with a frequency of 1800 MHz.

Erythropoietin accelerates tumor growth through increase of erythropoietin receptor (EpoR) as well as by the stimulation of angiogenesis in DLD-1 and Ht-29 xenografts.

Anemia is a relatively common symptom coexisting with colorectal carcinoma. Besides having a positive impact on hematological parameters, erythropoietin (Epo) has the serious adverse effect of promoting the neoplastic process. The role of Epo in colon cancer has not been clearly shown. The aim of this study was to assess the effects of Epo therapy on colorectal carcinoma cells both in in vitro and in animal models. Human colon adenocarcinoma cells DLD-1 and Ht-29 were cultured in medium with Epo beta in normoxia. Cell proliferation was measured with an automated cell counter. Expression of erythropoietin receptor (EpoR) mRNA, Akt mRNA, and their proteins were assessed by RT-PCR and confocal microscopy, respectively. Nude mice were inoculated with adenocarcinoma cells and treated with a therapeutic dose of Epo. Expression of EpoR, VEGF, Flt-1 and CD31 was evaluated in xenograft tumors. We identified that Epo through EpoR activates Akt, which promotes colon cancer cell growth and proliferation. Epo, and high levels of phosphorylated EpoR, directly accelerates tumor growth through its proliferative and proangiogenic effects. This study demonstrated that Epo had enhanced carcinogenesis through increase of EpoR and Flt-1 expression, and thereby contributed to tumor development. These results suggest that both EpoR-positive and EpoR-negative cancer cells could be regulated by exogenous Epo. However, an increased response to erythropoietin was observed in the EpoR-positive cells. Thus, erythropoietin increases the risk of tumor progression in colon cancer and should not be used to treat anemia in this type of cancer.

Mapping microscopic order in plant and mammalian cells and tissues: novel differential polarization attachment for new generation confocal microscopes (DP-LSM).

Elucidation of the molecular architecture of complex, highly organized molecular macro-assemblies is an important, basic task for biology. Differential polarization (DP) measurements, such as linear (LD) and circular dichroism (CD) or the anisotropy of the fluorescence emission (r), which can be carried out in a dichrograph or spectrofluorimeter, respectively, carry unique, spatially averaged information about the molecular organization of the sample. For inhomogeneous samples-e.g. cells and tissues-measurements on macroscopic scale are not satisfactory, and in some cases not feasible, thus microscopic techniques must be applied. The microscopic DP-imaging technique, when based on confocal laser scanning microscope (LSM), allows the pixel by pixel mapping of anisotropy of a sample in 2D and 3D. The first DP-LSM configuration, which, in fluorescence mode, allowed confocal imaging of different DP quantities in real-time, without interfering with the 'conventional' imaging, was built on a Zeiss LSM410. It was demonstrated to be capable of determining non-confocally the linear birefringence (LB) or LD of a sample and, confocally, its FDLD (fluorescence detected LD), the degree of polarization (P) and the anisotropy of the fluorescence emission (r), following polarized and non-polarized excitation, respectively (Steinbach et al 2009 Acta Histochem.111 316-25). This DP-LSM configuration, however, cannot simply be adopted to new generation microscopes with considerably more compact structures. As shown here, for an Olympus FV500, we designed an easy-to-install DP attachment to determine LB, LD, FDLD and r, in new-generation confocal microscopes, which, in principle, can be complemented with a P-imaging unit, but specifically to the brand and type of LSM.

Need for a comprehensive epidemiologic study of spinal cord injury in Poland: findings from a systematic review.

STUDY DESIGN: Systematic literature review OBJECTIVE: To review and assess the quality of available epidemiologic data of spinal cord injury (SCI) in Poland in the context of general International Classification of Functioning (ICF) domains and to answer the question whether there is a need for a comprehensive epidemiologic study of SCI in Poland. METHODS: Databases Medline, Embase and Polish Medical Bibliography were searched using keywords 'spinal cord injury', 'paraplegia', 'tetraplegia' and 'Poland'. INCLUSION CRITERIA: studies on humans, original papers, publication in 1979 or later. Case reports and studies with unclear inclusion criteria or performed on a population other than Polish were excluded. Full texts were reviewed for data on incidence, prevalence, etiology, mortality, natural history and outcome of comprehensive treatment. Quality of studies was assessed according to the modified Downs and Black criteria. The ICF model was applied to group the studies according to the ICF components. RESULTS: Out of 536 identified papers, 224 articles were extracted and reviewed. Mean quality score was 11.04 points based on a 28-grade scale. Body functions and structures were assessed in 81.6%, activities in 22.4%, participation in 14.8%, environmental factors in 15.2% and personal factors in 47% of the studies reviewed. CONCLUSION: Current epidemiologic data on SCI in Poland are insufficient and biased toward biomedical aspects. There is a need to develop a long-term research strategy for SCI in Poland in the form of a comprehensive cohort study.

Kynurenine and its metabolites in Alzheimer's disease patients.

PURPOSE: The kynurenine pathway (KP) is a major route of tryptophan metabolism. Several metabolites of this pathway are proposed to be involved in the pathogenesis of Alzheimer's disease. The aim of this study was to evaluate peripheral KP in patients with Alzheimer type dementia and a detailed analysis of correlation between kynurenine (KYN), kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), anthranilic acid (AA), quinolinic acid (QUIN) and degree of neuropsychological changes in AD. MATERIAL/METHODS: The plasma concentration of tryptophan and its products degradation by kynurenine pathway were analyzed in 34 patients suffering from Alzheimer type dementia and 18 controls in similar age using high-performance liquid chromatography technique. RESULTS: In demented patients we found lower tryptophan and KYNA concentrations. There was a non-significant increase of KYN, 3-HK and AA levels, and a Marked increase of QUIN in Alzheimer's disease group. We observed positive correlations between cognitive function tests and plasma KYNA levels, and inversely correlations between these tests and QUIN levels in Alzheimer type dementia. CONCLUSIONS: Increased TRP degradation and simultaneous altered kynurenines levels were found in plasma of AD patients. It proves activation of peripheral kynurenine pathway in this type of dementia. The alterations of two main KYN metabolites: KYNA and QUIN seem to be associated with the impairment of the cognitive function in AD patients. This appears to offer Novel therapeutic opportunities, with the development of new compounds as a promising perspective for brain neuroprotection.

Kynurenine pathway - a new link between endothelial dysfunction and carotid atherosclerosis in chronic kidney disease patients.

PURPOSE: The endothelium dysfunction is an important component of atherosclertic cardiovascular disease. It has been also suggested that kynurenine pathway activation may be involved in the pathogenesis of this disease. MATERIAL/METHODS: This is a cross-sectional study in chronic kidney disease (CKD) patients (n=106; 60 Males). The plasma markers of endothelial dysfunction and kynurenine (KYN), 3-hydroxykynurenine (3-HKYN), kynurenic acid (KYNA), anthranilic acid (AA) and quinolinic acid (QA) were measured in relation to an early indicator of the systemic atherosclerosis - intima-media thickness (IMT). RESULTS: Kynurenines, von Willebrand factor (vWF), thrombomodulin (TM), soluble adhesion molecules (sICAM-1, sVCAM-1) and IMT in each uraemic group were significantly higher than in healthy people. In contrast, no significant differences in sE-selectin and sP-selectin concentrations were observed between CKD patients and controls. Kynurenines were positively associated with vWF, TM, sICAM-1 and sVCAM-1, whereas sP-selectin was inversely associated with the most of kynurenines. IMT was positively correlated both with kynurenines: KYN, 3-HKYN, QA as well as with endothelial markers: TM, vWF, sICAM-1 and sVCAM-1 (all p<0.01). Finally, multiple regression analysis identified age, vWF, sVCAM-1 and QA levels as the independent variables significantly associated with increased IMT in this population (adjusted r² = 0.51). CONCLUSIONS: This study suggests a relationship between kynurenine pathway activation, endothelial dysfunction and the progression of atherosclerosis in CKD patients. It opens a new idea that the inhibition of kynurenine pathway may provide an effective strategy to slow down endothelial dysfunction and thereby the prevalence of atherosclerosis in this population.

Tissue factor pathway inhibitor release and depletion by sulodexide in humans.

PURPOSE: Anticoagulant tissue factor pathway inhibitor (TFPI) is released from its endothelial stores by heparin, which may lead to its untoward depletion. We investigated the effects of sulodexide--a commercially available mixture of heparan and dermatan sulfate, on plasma TFPI release and depletion. MATERIAL AND METHODS: An open-label pilot trial of intravenous and/or oral sulodexide effects on plasma immunoreactive total TFPI antigen level was performed in 11 healthy men. The drug was initially administered i.v. at a single dose of 120 mg, thenorally for 12 days (50 mg b.i.d), and again by i.v route after 2 weeks. RESULTS: Sulodexide injections induced marked increases in plasma TFPI; they were more pronounced on day 14 than on study initiation (3-fold vs. 2-fold after 10 min) and still evident after 120 min. TFPI levels did not change when measured at 120 min after oral sulodexide administration. The percentage increment in plasma TFPI after 10 min from initial sulodexide injection inversely correlated with baseline TFPI levels (r = - 0.664, P = 0.026). On day 14, the association became strong (r = - 0.970, P < 0.0001) and evident also after 120 min (r = - 0.810, P < 0.002). Baseline TFPI levels decreased over the trial; on day 14 they were lower by 34% than on study initiation (P = 0.001). CONCLUSIONS: TFPI release by i.v. sulodexide and its depletion during oral administration of this heparinoid compound constitute novel and likely important hemostatic effects of the drug.

Apelin, a novel adipocytokine, in relation to endothelial function and inflammation in kidney allograft recipients.

Apelin, a newly discovered adipocytokine produced by white adipose tissue, is also expressed in kidney and heart. It has been reported that apelin is related to echocardiographic features in hemodialyzed patients. Cardiovascular disease is a major contributor to the mortality and morbidity among patients with chronic renal failure as well as kidney allograft recipients. The aim of this study was to assess the association between apelin and coronary artery disease (CAD) among kidney allograft recipients. We investigated plasma apelin levels in 100 clinically stable, kidney allograft recipients with versus without CAD. We also assessed markers of endothelial cell injury-von Villebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), and CD146; markers of inflammation-high-sensitivity-reactive protein (hsCRP); other hemostatic parameters-tissue plasminogen activator (tPA) and its inhibitor (PAI-1); as well as other adipocytokines-adiponectin and resistin-using commercially available kits. Markers of endothelial dysfunction and inflammation were significantly elevated among patients with CAD levels, as well as with CAD or diabetes, compared with those without CAD. Apelin was significantly lower among patients with CAD, but higher in diabetic patients. Apelin content was similar in hypertensive versus normotensive kidney allograft recipients. We observed significant correlations between apelin and ICAM, resistin, adiponectin, calcium, phosphate, alanine and aspartate aminotransferase levels, with CAD or diabetes. Upon multiple regression analysis as well as CAD, adiponectin, and ICAM were predictors of apelin. Apelin was significantly reduced in kidney allograft recipients with CAD; its level was predicted by the presence of CAD, endothelial damage, or inflammation. Apelin and other adipocytokines may be associated with inflammation and its clinical consequences.

Endothelial function and novel adhesion molecule CD44 in kidney allograft recipients.

BACKGROUND: Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these 2 processes and inflammation is closely related to endothelial dysfunction. PATIENTS AND METHODS: This cross-sectional study on serum concentrations of markers of endothelial damage and inflammation in relation to adhesion molecules was performed in 90 kidney allograft recipients and 30 healthy volunteers. We measured markers of endothelial damage-von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), vascular adhesion molecule (VCAM), CD146, CD44, and CD40L; markers of inflammation-high-sensitivity C-reactive protein (hsCRP), tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6); and other hemostatic parameters-thrombin-antithrombin complexes (TAT), plasmin-antiplasmin complexes, and thrombin activatable fibrinolysis inhibitor (TAFI) using commercially available kits. RESULTS: Markers of endothelial dysfunction and inflammation were significantly elevated in kidney allograft recipients compared with control subjects. CD44 was independently related to hsCRP (r = .37; P < .01), ICAM (r = .23; P < .05), eGFR (r = -.37; P < .01), thrombomodulin (r = .43; P < .001), VCAM (r = -.44; P < .001), hemoglobin (r = -.26; P < .01), red blood cell count (r = -.25; P < .05), creatinine (r = .37; P < .01), CD146 (r = .34; P < .01), and CD40L (r = .23; P < .05). Upon multiple regression analysis the predictors of elevated CD44 were hsCRP concentration (beta = .25; P < .05), CD146 (beta = .39; P < .05), creatinine (beta = .55; P < .01), and thrombomodulin (beta = .39; P < .05) with an adjusted R(2) = .40 (F = 4.12; P < .00028; SE of estimate = 151.19). CONCLUSIONS: As demonstrated in multiple regression analysis, kidney function was strictly linked to the degree of inflammation and endothelial injury. Endothelial cell injury and the presence of an inflammatory state, as reflected by elevated marker concentrations, and endothelial activation/injury may play roles in the pathogenesis of atherosclerosis and cardiovascular complications among kidney allograft recipients.

Visfatin and apelin, new adipocytokines, and their relation to endothelial function in patients with chronic renal failure.

PURPOSE: Visfatin and apelin are novel adipocytokines that have recently generated much interest. The aim of the study was to assess visfatin and apelin in correlation with markers of endothelial cell injury and inflammation in 22 patients with chronic kidney disease-CKD and 22 age- and sex-matched healthy volunteers. METHODS: We assessed visfatin, apelin, markers of coagulation: TAT (thrombin-antithrombin complexes), prothrombin fragments 1+2; fibrinolysis: tPA (tissue plasminogen activator), PAI-1 (plasminogen activator inhibitor), PAP (plasmin-antiplasmin complexes); endothelial function/injury: vWF (von Willebrand factor), thrombomodulin, ICAM (intracellular adhesion molecule), VCAM (vascular cell adhesion molecule), CD146, CD40L, CD44, E-selectin, inflammation: hsCRP. RESULTS: Triglycerides, hsCRP, creatinine, vWF, prothrombin fragments 1+2, TAT, thrombomodulin, ICAM, VCAM, CD146, CD44, CD40L, PAI-1, PAP, visfatin and E-selectin were elevated in chronic kidney disease patients when compared with the control group. Visfatin correlated significantly in patients with chronic kidney disease, in univariate analysis, with CD40L (r=-0.27, p<0.05), apelin (r=0.27, p<0.05), ICAM (r=0.26, p<0.05), VCAM (r=0.31, p<0.05) and tended to correlate with CD146 (r=0.21, p=0.10). Apelin correlated significantly with E-selectin (r=0.31, p<0.05) and VCAM (r=0.31, p<0.05). In the healthy volunteers visfatin correlated significantly with ICAM (r=-0.37, p<0.05) and serum creatinine (0.38, p<0.05). CONCLUSIONS: Elevated visfatin in CKD patients may be due to renal failure and/or inflammation. Adipocytokines related to adhesion molecules might support the importance of inflammation/endothelial cell injury in the pathogenesis of atherosclerosis and its consequences in CKD.

Adipokines, linking adipocytes and vascular function in hemodialyzed patients, may also be possibly related to CD146, a novel adhesion molecule.

Possible correlations between adiponectin, leptin, CD146, a novel adhesion molecule localized at the endothelial junction, and other markers of endothelial cell injury, von Willebrand factor, thrombomodulin, vascular cell adhesion molecule, and intracellular adhesion molecule, and markers of inflammation, tumor necrosis factor-alpha, interleukin-6, and high-sensitivity C-reactive protein in nondiabetic hemodialyzed patients with and without coronary artery disease were studied. Markers of endothelial dysfunction were elevated in hemodialyzed patients, predominantly with coronary artery disease. In multivariate analysis, kinetic urea modeling and plasminogen activator inhibitor-1 remained the only positive predictors of adiponectin. In multivariate analysis, predictors of leptin were triglycerides, tissue plasminogen activator, CD146, and coronary artery disease. In multivariate analysis, predictors of CD146 were age, hemoglobin, and adiponectin. Elevated adiponectin correlated to CD146 may be the expression of a counterregulatory response aimed at mitigating the consequences in endothelial damage and increased cardiovascular risk in renal failure. The data provide further support for a link between adipocytokines, endothelial dysfunction, cardiovascular risk, and renal failure.

NGAL (neutrophil gelatinase-associated lipocalin) and cystatin C: are they good predictors of contrast nephropathy after percutaneous coronary interventions in patients with stable angina and normal serum creatinine?

The aim of the study was to assess whether NGAL and cystatin C could predict contrast-induced nephropathy in non-diabetic patients (n=60, mean age 60+/-11 years) with normal serum creatinine undergoing elective PCI. We found a significant rise in serum NGAL after 2, 4 and 8 h, and in urinary NGAL after 4, 8 and 24 h after PCI. Cystatin C rose significantly 8 and 24 h after the procedure. Prevalence of CIN was 10%. We found 90% sensitivity and 74% specificity of serum and 76% sensitivity and 80% specificity of urinary NGAL increase. NGAL may represent a sensitive early biomarkers of renal impairment after PCI.

Could neutrophil-gelatinase-associated lipocalin and cystatin C predict the development of contrast-induced nephropathy after percutaneous coronary interventions in patients with stable angina and normal serum creatinine values?

The value of neutrophil-gelatinase-associated lipocalin (NGAL) was highlighted as a novel biomarker for the detection of acute renal failure. We tested the hypothesis whether NGAL could represent an early biomarker of contrast-induced nephropathy (CIN) in 100 patients with normal serum creatinine values undergoing percutaneous coronary interventions (PCI). In addition, we assessed serum and urinary NGAL in relation to cystatin C, estimated glomerular filtration rate, and serum and urinary creatinine in these patients. We measured urinary and serum NGAL values before and 2, 4, 8, 24, and 48 h after the PCI. We found a significant rise in serum NGAL levels 2, 4, and 8 h after the PCI and in urinary NGAL values 4, 8, and 24 h after a PCI procedure. Cystatin C rose significantly 24 h after the procedure. The prevalence of CIN was 11%. The NGAL levels were significantly higher 2 h after the PCI (serum NGAL) or 4 h after the PCI (urinary NGAL), whereas the cystatin C values were higher only 8 and 24 h after a PCI procedure in patients with CIN. In multivariate analysis, only serum creatinine was a predictor of serum NGAL before a PCI. NGAL may represent a sensitive early biomarker of renal impairment after PCI. Serum creatinine level, the presence of diabetes, and the duration of the PCI may affect serum NGAL values and kidney function following a PCI procedure.

Regulation of estrogen receptor (ER) levels in MCF-7 cells by progesterone metabolites.

Estradiol-17beta (E2) may participate in carcinoma of mammary cells containing estradiol receptors (ER) at sufficient levels. Hence, the regulation of ER levels may be important for the progression of estrogen-dependent mammary carcinomas. Our previous findings that the progesterone metabolite, 5alpha-pregnane-3,20-dione (5alphaP), exhibits marked mitogenic and metastatic properties, whereas the progesterone metabolites, 4-pregnen-3alpha-ol-20-one (3alphaHP) and 4-pregnen-20alpha-ol-3-one (20alphaHP), oppose these actions, prompted examination of the possible effects of these progesterone metabolites on ER concentration in MCF-7 breast cancer cells. Cells were exposed for 24h to 0 (control) or 10(-10) to 10(-6)M E2, 5alphaP, 3alphaHP, 20alphaHP or combinations of these steroids, and ER concentrations were determined for intracellular estrogen receptors by specific binding of [(3)H]E2. The total ER number (nuclear plus cytosolic) in control samples was 2551+/-164 per cell. E2 and 5alphaP resulted in significant dose-dependent increases in total ER numbers ( approximately 1.6-fold and approximately 2.2-fold at 10(-6)M, respectively). In combination, E2+5alphaP resulted in additive increases in ER numbers. Individually, 3alphaHP and 20alphaHP each resulted in dose-dependent decreases (43% and 54% at 10(-6)M, respectively) in total ER numbers and inhibited the E2- or 5alphaP-induced increases in ER levels. In combination, 3alphaHP+20alphaHP resulted in dose-dependent additive suppression of ER levels. Treatment with cycloheximide or actinomycin D indicated that both transcription and translation are involved in 5alphaP and 3alphaHP action on ER numbers. Real time RT-PCR showed increases in expression of ERalpha transcripts due to 5alphaP and increases in expression of ERbeta due to 3alphaHP; expression levels of either ERalpha or ERbeta were not significantly altered when cells were treated with 5alphaP+3alphaHP. The results are the first to show that the pro- and anti-cancer progesterone metabolites also have marked selective (up or down) regulatory effects on ER levels in MCF-7 breast cancer cells.

Comparison of the toxicity and distribution of cadmium and lead in plant cells.

The toxicity of heavy metals (Cd, Zn, and Pb) was assessed by in vivo observations of their effect on cytoplasmic streaming in Allium cepa L. bulb scale epidermal cells. On the basis of our results, the order of toxicity of the studied cations is Zn < Pb << Cd. The difference in toxicity between cadmium and lead was found to be very large. When cytoplasmic streaming was assessed, this difference was threefold. When the total content of cadmium and lead (determined by inductively coupled plasma mass spectrometry) was the criterion, the difference in toxicity was 15-fold. Fractionation of the tissue and enzymatic digestion of the cells revealed that the largest proportion of cadmium was located in the cell walls (56%), whereas almost all of the lead (97.6%) was accumulated in an insoluble form. The speciation of water-soluble Pb and Cd fractions is discussed on the basis of analysis by capillary zone electrophoresis interfaced with inductively coupled plasma mass spectrometry of water extracts from epidermal cells. Lead and cadmium appeared to be bound mainly to salts, which explains their toxicity. Cadmium was complexed (detoxified) by organic acids, while thiols were the metal-complexing species for lead. Histidine formed complexes with both cadmium and lead. Ultrastructural analyses showed that lead was encapsulated in small vesicles in the cytoplasm. Fluorescence studies of the endoplasmic reticulum (ER) revealed that it underwent extensive fragmentation under the influence of lead, with numerous ER vesicles appearing in the cells. In other words, the lead deposits in the cytoplasm were contained in vesicles arising from fragmentation of the ER. These observations indicate that epidermal cells have a rapid and effective mechanism for detoxifying lead involving the ER, and this may be one of the mechanisms accounting for the lower toxicity of lead in comparison with cadmium. The suitability of Allium cepa bulb scale epidermal cells for use in ecotoxicological studies is also discussed. Step-by-step directions for this test are given.

Serum erythropoietin and angiogenetic factors in human colorectal cancer.

AIMS AND BACKGROUND: Erythropoietin, VEGF, VE-cadherin are involved in angiogenesis. Besides that erythropoietin stimulates erythropoiesis and increases haemoglobin and hematocrit levels as well. Moreover, erythropoietin could directly stimulate colorectal cancer cell growth due to the presence of both erythropoietin receptor and erythropoietin production in malignant cells of this neoplasm. Therefore we aimed at measurement and comparison of serum erythropoietin with VEGF, VE-cadherin levels, blood haemoglobin and hematocrit in colorectal cancer patients of different clinicopathological profiles. METHODS: We applied ELISA kits to evaluate preoperative serum levels of endogenous erythropoietin, VEGF and VE-cadherin in samples from 92 colorectal cancer patients and control group of 16 healthy volunteers. RESULTS: Endogenous erythropoietin was significantly elevated in preoperative sera in colorectal cancer patients (p = 0.013) compared with healthy volunteers, however, erythropoietin levels were not significantly higher with the advancement of colorectal cancer. There were significantly higher levels of erythropoietin in the group of anaemic men in comparison to men with normal haemoglobin levels (p < 0.0001). VEGF and VE-cadherin did not correlate with erythropoietin. Erythropoietin levels negatively correlated with haemoglobin and hematocrit levels in all cancer patients; particularly in node positive cancers (N+), moderately differentiated tumours (G2) and deeply invading neoplasms (pT3+pT4). CONCLUSIONS: Erythropoietin levels increase in colorectal cancer but circulating erythropoietin does not associate with progression of the disease. Thus, the use of recombinant erythropoietin seems to be safe. Our results suggest that negative feedback regulation persists between haemoglobin and erythropoietin in colorectal cancer. Production of erythropoietin remains therefore anaemia-associated, hypoxia-dependent and doesn't seem to be autonomic despite abundant expression of erythropoietin by colorectal cancers.

Resistin, a new adipokine, is related to inflammation and renal function in kidney allograft recipients.

BACKGROUND: Among patients without chronic kidney disease, resistin, an adipocytokine, has been related to inflammatory markers, coronary artery disease, and cardiovascular disease in the metabolic syndrome. Moreover, resistin up-regulates adhesion molecules. Since inflammation and endothelial cell damage or injury are invariably associated with thrombosis, atherosclerosis, and their major clinical consequences, resistin may play a role to link inflammation and CVD. The aim of this study was to correlate resistin with markers of inflammation and endothelial cell injury in 96 kidney allograft recipients. METHODS: We measured resistin and the following markers of endothelial function/injury: vWF, thrombomodulin, VCAM, hsCRP, tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6). RESULTS: Triglycerides, CRP (assessed by high-sensitivity method), phosphate, creatinine, IL-6, TNFalpha, vWF, prothrombin fragments 1 + 2, and resistin were elevated among kidney transplant recipients compared with the control group. Kidney allograft recipients with coronary artery disease displayed significantly higher resistin levels than those in patients without this complication. Upon univariate analysis resistin levels in kidney allograft recipients were related to hsCRP, IL-6, thrombomodulin, red blood cell count, white blood cell count, platelet count, creatinine, urea, VCAM, CSA, dose and eGFR. Upon multiple regression analysis, resistin was independently related only to creatinine, hsCRP, and white blood cell count in kidney allograft recipients. CONCLUSIONS: The relation of elevated resistin levels to markers of inflammation may represent a novel link between these conditions and adipocytokines. Renal function was a major determinant of elevated resistin in kidney allograft recipients.

Possible relations between thyroid function, endothelium, and kidney and liver function in kidney allograft recipients.

BACKGROUND: Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and endothelial damage are common complications of kidney disease. Endothelial dysfunction may link these two processes. AIM AND METHODS: This cross-sectional study examined thyroid hormones in relation to markers of endothelial damage and inflammation among 80 kidney allograft recipients and 29 healthy volunteers. Thyroid hormones, markers of endothelial damage (vWF, thrombomodulin, intracellular adhesion molecule [ICAM] vascular adhesion molecule [VCAM], CD146), markers of inflammation (hsCRP), other hemostatic parameters (thrombin-antithrombin complexes [TAT], prothrombin fragments 1 + 2 [F1 + 2], plasmin-antiplasmin complexes, tissue plasminogen activator and its inhibitor, platelet glycoprotein [V-GPV]) as well as P-selectin were measured using commercially available kits. RESULTS: Total T3 was significantly lower among kidney allograft recipients, whereas markers of endothelial dysfunction and inflammation were significantly elevated over controls. In kidney allograft recipients total T3 was independently related to PAI-1, ICAM, and eGFR, whereas free T3 was independently related to thrombomodulin, aspartate, and alanine aminotransferases, hemoglobin, urea, eGFR, dose of cyclosporine and treatment with mycophenolate mofetil/azathioprine. Total T4 was related to aspartate and alanine aminotransferases, dose of cyclosporine, PAI-1, and ICAM. In multiple regression analysis the only correlates of T3 were PAI-1 and ICAM, whereas the only correlates of free T3 were thrombomodulin, aspartate aminotransferase, eGFR, and cyclosporine dose. In healthy volunteers GPV was related only to TSH. CONCLUSIONS: We described novel relations between thyroid hormones and markers of endothelial dysfunction in kidney transplant recipients. In kidney transplant recipients thyroid function metrics were associated with endothelial damage, immunosuppressive treatment, liver and kidney function. Therefore, the relations between thyroid axis and endothelium in kidney allograft recipients merit additional studies.