Effect of Beer Consumption on Methylation and Redox Metabolism.

To investigate the influence of beer consumption on levels of homocysteine (HCY), vitamin B6, B12, folic acid (FA), dimethylglycine (DMG), betaine (BET) and other selected markers. One hundred and sixteen male volunteers were enrolled in the study. A one-month period of alcohol abstinence was followed by a one month when participants drank 830 mL of alcoholic beer every day. After that phase, one month of alcohol abstinence followed. At the beginning and after every phase blood samples were taken and analysed. Ninety-three participants completed the study. After the phase of alcohol consumption, uric acid (UA) (p<0.0001), antioxidative capacity (AOC) (p=0.02), superoxide dismutase (SOD) (0.025), glutathione reductase (GRH) (0.0001), total cholesterol (p<0.0001), HDL-cholesterol (p<0.0001), Apolipoprotein-AI (ApoAI) (p<0.0001), LDL-cholesterol (p<0.039) and Apolipoprotein B (ApoB) (p<0.009) increased, while vitamin B12 (p=0.0001) and fibrinogen (p<0.0001) decreased. Other tested parameters (DMG, BET, vitamin B6 and FA) did not show any significant changes. UA changes and changes in AOC were statistically significantly correlated (r=0.52, p<0.0001). HCY, DMG and BET levels did not show any statistically significant changes after beer consumption, whereas some markers of redox metabolism increased (UA, AOC, SOD and GRH). A statistically significant correlation denotes the dependence of UA and AOC changes in connection with beer consumption.

NGAL, albumin and cystatin C during cisplatin therapy.

Cisplatin is a commonly used chemotherapeutic drugs. It is known for its nephrotoxic side effects with an increased risk of acute kidney injury. Finding of clinically feasible cisplatin nephrotoxicity markers is of importance. In our study, we compared neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine, the estimated glomerular filtration rate (based on serum cystatin C) and urine albumin as markers of nephrotoxicity. The study involved 11 men and 9 women (mean ± SD age 58.2±9.5 years) with different malignancies treated with cisplatin in four cycles of chemotherapy (I - IV). Samples 0-4 were taken before, immediately after, in 3, 6 and 24 hours after administering chemotherapy. We detected significant increase of ACR in Sample 2 (p=0.03) and decrease of eGFR in Sample 4 (p=0.03) up to 24 hours after cisplatin administration in the first chemotherapy cycle only. When cumulative effect of cisplatin was assessed, significantly increased values of urine albumin (vs cycle I) were found in Sample 0 (p=0.00058), 1 (p=0.00256), 2 (p=0.00456), 3 (p=0.00006) and 4 (p=0.00319) in cycles II to IV. We found a correlation between values of urine NGAL and urine albumin (r=0.68, p<0.0001). In conclusion, urine albumin was the only measured marker that consistently and statistically significantly increased after cisplatin containing chemotherapy cycles.

Creatine Kinase and Myoglobin Levels as Indicators of Perioperative Muscle Damage during Open- and Mini-Invasive Stabilization of Thoracic and Lumbar Spine Fracture - a Prospective Randomized Study.

PURPOSE OF THE STUDY In this randomized prospective study, we monitored and compared perioperative changes in skeletal muscle enzymes blood levels in open and mini-invasive stabilization of thoracolumbar spine fractures. The established hypothesis was to confirm higher blood levels of muscle enzymes in open stabilization. MATERIAL AND METHODS This study included 38 patients with the mean age of 46.4 years. 19 injuries were managed in an open procedure and 19 procedures were mini-invasive. Venous blood was taken intermittently at short intervals to determine the levels of skeletal muscle enzymes. The catalytic concentration of creatine kinase was determined via an enzymatic UV-test, and the concentration of myoglobin via electro-chemiluminescent immunoassay. Enzyme levels were processed statistically. The Wilcoxon test was used. RESULTS The median increase in the values of both enzymes is higher in the mini-invasive method than in the open method in both the surgery phase for the injury and in the extraction phase. The median increase in the values of both enzymes is higher in both methods for the primary procedure phase compared to the extraction phase. All results are statistically significant at p of <0.05. All tests were calculated using the MATLAB Statistics Toolbox. DISCUSSION A very surprising finding, when testing the hypothesis of the levels increasing mainly in open stabilization, was confirming the opposite. Both enzymes were higher in the mini-invasive approach to stabilising the spine after the injury, but also after the extraction. This contradicts the available literature. However, this can be explained by the methodology of enzyme levels determination in the previously published studies. We believe that this phenomenon can be partially caused by an iatrogenic mini-compartment of muscles in the postoperative period, absence of wound drainage, but also by higher muscle contusion when inserting bolts through the tubes via small incisions, when the tubes penetrate to the entry points relatively violently and the muscles in this area are affected more than in the classical skeletization. CONCLUSIONS Analysis of biochemical changes in open and mini-invasive surgery did not confirm the hypothesis that levels of creatine kinase and myoglobin enzymes increase especially in open stabilization. On the contrary, they were statistically significantly higher in mini-invasive procedures. Key words: creatine kinase, myoglobin, muscle enzymes, spine fracture, spine surgery, miniinvasive surgery.

Prognostic role of serum C-reactive protein in patients with advanced-stage NSCLC treated with pemetrexed.

Pemetrexed is an intravenously administered antifolate cytostatic agent targeting several folate-dependent enzymatic pathways, widely used in the treatment of patients with advanced non-small cell lung cancer (NSCLC). It has been previously demonstrated that the superiority of pemetrexed is limited to patients with non-squamous histology. Aside from the non-squamous histology, there is still no available molecular biomarker predicting treatment efficacy of pemetrexed-based chemotherapy. The aim of our retrospective study was to evaluate the association of baseline serum levels of C-reactive protein (CRP) with outcomes in a large cohort of patients with non-squamous NSCLC treated with pemetrexed. Clinical data of 325 patients were analysed. Serum samples were collected within one week before the initiation of treatment. The median progression-free (PFS) and overall survival (OS) for patients with high CRP was 2.1 and 9.5 compared to 4.2 and 20.5 months for those with normal CRP (p=0.002 and p<0.001, respectively). The multivariable Cox proportional hazards model revealed that serum CRP (HR=1.46, p=0.002) was significantly associated with PFS and also with OS (HR=1.95, p<0.001). In conclusion, the study results suggest that pretreatment serum CRP is associated with poor outcome of non-squamous NSCLC patients treated with pemetrexed.

Serum albumin is a strong predictor of survival in patients with advanced-stage non-small cell lung cancer treated with erlotinib.

Molecular targeted therapy based on tyrosine kinase inhibitors (TKI), directed at epidermal growth factor receptor (EGFR) is one of the novel effective agents in management of advanced-stage of Non Small Cell Lung cancer (NSCLC). However several candidate predictors have been extensively studied, apart from activating EGFR gene mutations, no reliable biochemical or molecular predictors of response to erlotinib have been validated. The aim of our retrospective study was to evaluate the association of baseline serum albumin with outcomes in a large cohort of patients with advanced-stage NSCLC treated with erlotinib. Clinical data of 457 patients with locally-advanced (III B) or metastatic stage (IV) NSCLC treated with erlotinib were analysed. Serum samples were collected and the measurement was performed one day before the initiation of erlotinib treatment. Before the treatment initiation, low albumin was (<35 g/l) measured in 37 (8.1%) patients and normal albumin (≥ 35 g/l) was measured in 420 (91.9%). The median PFS and OS for patients with low serum albumin was 0.9 and 1.9 months compared to 1.9 and 11.4 months for patients with normal serum albumin (p=0.001 and p<0.001). The multivariate Cox proportional hazards model revealed that EGFR mutation status (HR=2.50; CI: 1.59-3.92; p<0.001) and pretreatment serum albumin (HR=1.73; CI: 1.21-2.47; p=0.003) were significant independent predictive factors for PFS, whereas EGFR mutation status (HR=3.14; CI: 1.70-5.81; p<0.001), stage (HR=1.48; CI: 1.09-2.02; p=0.013), ECOG PS (HR=1.77; CI: 1.37-2.29; p<0.001) and pretreatment serum albumin (HR=4.60; CI: 2.98-7.10; p<0.001) were significant independent predictive factors for OS. In conclusion, the results of present retrospective study indicate that pretreatment hypoalbuminemia is associated with poor outcome of NSCLC patients treated with erlotinib. Based on these results, measuement of serum albumin is an objective laboratory method feasible for estimation of prognosis of patients with advanced-stage NSCLC.

Transitioning Youth into Adult Mental Health and Addiction Services: An Outcomes Evaluation of the Youth Transition Project.

The Youth Transition Project was designed to provide youth with mental health and addiction issues with individualized transitional care plans as they transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS). Over an 18-month period, a total of 127 (59.1%) youth were transitioned and seen by an AMHS provider, 41 (19.1%) remained on a waitlist for services and 47 (21.8%) canceled services. The average time to transition was 110 days (SD = 100). Youth exhibited a wide range of diagnoses; 100% of the population was identified as having serious psychiatric problems. Findings demonstrate that the Youth Transition Project has been successful in promoting continuity of care by transitioning youth seamlessly from youth to adult services. Inconsistencies in wait times and service delivery suggest that further model development is needed to enhance the long-term sustainability of the Youth Transition Project.

Betaine increases the butyrylcholinesterase activity in rat plasma.

The physiological function of butyrylcholinesterase (EC 3.1.1.8, BChE) is not clearly understood, but a role was suggested in the fat utilization process, resulting in positive correlation between plasma triglyceride (TG) levels and BChE activity. Consequently we tested the hypothesis that regular intake of betaine, a natural compound intervening in the liver TG metabolism could influence the BChE activity. The BChE activity was estimated spectrophotometrically in plasma of rats fed with betaine enriched standard (B) or high-fat diet (HFB). The results confirmed decreased TG plasma levels after betaine treatment independently on the type of diet (0.15+/-0.03 (B) vs. 0.27+/-0.08 (control) mmol/l; p=0.003 and 0.13+/-0.03 (HFB) vs. 0.27+/-0.08 (control) mmol/l; p=0.005). The BChE activity increased significantly with betaine administration, however the change was more distinct in the HFB group (0.84+/-0.34 (HFB) vs. 0.22+/-0.04 (control) O.D./min/mg; p<0.001 and 0.41+/-0.11 (B) vs. 0.22+/-0.04 (control) O.D./min/mg; p=0.001). In conclusion, betaine intake led to elevated BChE activity in plasma and this effect was potentiated by the HF diet. Since betaine is in general used as a supplement in the treatment of liver diseases accompanied by TG overload, its impact on the BChE activity in the role of the liver function marker should be taken into account.

Effect of exercise on markers of vascular health in renal transplant recipients.

The cornerstone of cardiovascular risk management is lifestyle intervention including exercise which could exert favorable impact also in renal transplant recipients. Nevertheless, reliable assessment of the effect of lifestyle interventions is complicated and the available data in this population are not consistent. The aim of the study was to evaluate the effect of physical activity on selected laboratory markers of vascular health including circulating stem cells, endothelial progenitor cells, microparticles, and plasma asymmetric dimethyl arginine in renal transplant recipients. Nineteen men and 7 women were recruited in 6-month program of standardized and supervised exercise. Control group consisted of 23 men and 13 women of similar age and body mass index not included into the program. One year after the transplantation, the main difference between intervention and control group was found in the change of endothelial progenitor cells (p=0.006). Surprisingly, more favorable change was seen in the control group in which endothelial progenitor cells significantly increased compared to the intervention group. The explanation of this finding might be a chronic activation of reparative mechanisms of vascular system in the population exposed to multiple risk factors which is expressed as relatively increased number of endothelial progenitor cells. Therefore, their decrease induced by exercise might reflect stabilization of these processes.

[Tumour-stroma interactions in urothelial cancer]. / Tumor-Stroma-Interaktionen im Harnblasenkarzinom.

BACKGROUND: The histopathological structure of malignant tumours involves two essential compartments - the tumour parenchyma with the actual transformed cells, and the supportive tumour stroma. The latter consists of specialized mesenchymal cells, such as fibroblasts, macrophages, lymphocytes and vascular cells, as well as of their secreted products, including components of the extracellular matrix, matrix modifying enzymes and numerous regulatory growth factors and cytokines. In consequence, the tumour stroma has the ability to influence virtually all aspects of tumour development and progression, including therapeutic response. AIM: In this article we review the current knowledge of tumor stroma interactions in urothelial carcinoma and present various experimental systems that are currently in use to unravel the biological basis of these heterotypic cell interactions. RESULTS: For urothelial carcinoma, an extensive tumour stroma is quite typical and markers of activated fibroblasts correlate significantly with clinical parameters of advanced disease. Another clinically important variable is provided by the stromal expression of syndecan-1. CONCLUSION: Integration of markers of activated stroma into clinical risk evaluation could aid to better stratification of urothelial bladder carcinoma patients. Elucidation of biological mechanisms underlying tumour-stroma interactions could provide new therapeutical targets.

Reduction of renal function during mechanical ventilation of healthy lungs in an animal biomodel.

OBJECTIVES: To identify factors involved in reno-pulmonary interactions during mechanical ventilation. MATERIALS AND METHODS: The study included a total of 25 domestic piglets. The animals were divided into three groups based on different strategies of ventilation. Group A; spontaneously breathing piglets; group B animals ventilated with tidal volume of 6 ml.kg-1 and group C with animals ventilated with tidal volume 10 ml.kg-1. Clinical monitoring and laboratory tests were performed for all groups at baseline and then at 1 hour and 12 hours for groups B and C. Ventilation indices, hemodynamics, urine output, creatinine clearance, glomerular filtration index, fractional excretion of sodium, free water clearance and tissue samples were recorded. The data obtained were statistically analysed. RESULTS: Lower creatinine clearance and renal indices were seen in group B (p < 0.05) and in group C (p < 0.001) at 1 hour, and a difference in urine output for group C (p < 0.01) compared to group A was observed. At 12 hours, there was a further reduction in creatinine clearance and renal indices for group B (p < 0.05) and group C (p < 0.01). The lung mechanics and hemodynamics were not significantly influenced. CONCLUSIONS: The study showed a causal relationship between renal dysfunction and positive pressure mechanical ventilation with respect to tidal volume and time (Tab. 4, Fig. 2, Ref. 17).

Two cases of spuriously elevated cerebrospinal glucose concentration.

We present two cases of spuriously high cerebrospinal fluid glucose concentration with approximately normal blood glucose concentrations. The cause of these abnormal findings was the use of inappropriate collection tubes during the pre-analytical phase. Whilst no patient harm was identified following this error, significant time and effort were expended by both laboratory and clinical staff to explain the cause of these findings.

Asymmetric dimethylarginine and endothelial progenitor cells after renal transplantation: the effect of exercise training.

Level of asymmetric dimethylarginine (ADMA) is elevated and endothelial progenitor cells (EPC) and stem cells (SC) are decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. We tested the hypothesis that ADMA, EPC and SC can be influenced with regular physical exercise early after Tx. Blood samples of ADMA, EPC, SC, adipocytokines and metabolic parameters were randomly obtained from 50 transplant patients before and 6 months after exercise program (Group I). Fifty age, sex, HLA typing, duration of dialysis and immunosupression regimen-matched non exercising transplant were examined as controls (Group II). After 6 months, in Group I ADMA decreased (3.50+/-0.45 vs 2.11+/-0.35 micromol/l, P<0.01) and was lower comparing to Group II (P<0.01), SC and EPC also decreased (2816+/-600 vs 2071+/-480 cells/ml resp. 194+/-87 to 125+/-67 cells/ml, P<0.02). Next changes in Group I: adiponectin (P<0.01), leptin (P<0.01), resistin (P<0.02). Visfatin, blood lipids, HbA1c, insulin and blood pressure were also influenced by training program (P<0.05).

[Regular exercise training decreases asymmetric dimethylarginine after kidney transplantation]. / Casný pohybový rezim snizuje asymetrický dimetylarginin po transplantaci ledviny.

BACKGROUND: Levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine are elevated in patients undergoing kidney transplantation and may contribute to vascular complications. In this study we tested the hypothesis that elevated asymmetric dimethylarginine can be reduced in patients after kidney transplantation by early regular physical exercise. Selected cytokines and metabolic parameters were also analysed. METHODS: Plasma samples for analysis of asymmetric dimethylarginine, adiponectin, leptin, soluble leptin receptor, resistin, visfatin, CRP, TNFα and selected metabolic parameters were obtained from randomly selected sixty eight patients after kidney transplantation who agreed to participate in a supervised aerobic exercise program for six months. Samples were collected before the training began (one month after surgery with stabilized graft function) and at six months after initiation. Sixty transplant patients matched for age, sex, HLA typing, duration of previous dialysis, history of cardiovascular disease and immunosupression regimen who did not exercise regularly and did not participate in the training program were examined as controls. RESULTS: There were no differences in elevated asymmetric dimethylarginine levels between both groups before the training program began. After six months of exercise, asymmetric dimethylarginine concentration in the exercising group I significantly decreased (3.5 ± 0.45 vs 2.11 ± 0.35 µmol/L, P < 0.01) and was also significantly lower comparing to non-exercising group II (2.11 ± 0.23 vs 3.25 ± 0.34 µmol/L, P < 0.01). We found significant changes in exercising group I: adiponectin (15.4 ± 6.6 vs 22.3 ± 6.2 mg/mL, P < 0.01), leptin (51.3 ± 11.2 vs 20.3 ± 9.2 ng/L, P < 0.01), soluble leptin receptor (24.6 ± 8.4 vs 46.1 ± 11.4 U/mL, P < 0.01), resistin (20.8 ± 10.1 vs 14.6 ± 6.4 mg/mL, P < 0.025) and visfatin (1.8 ± 0.2 vs 1.2 ± 0.01 ng/mL, P < 0.05). Blood lipids, HbA1c, CRP and TNFα were also affected by the training program. CONCLUSIONS: Elevated asymmetric dimethylarginine level, selected adipocytokines and proinflammatory cytokines in patients after kidney transplantation were significantly influenced by early regular exercise. This regimen may decrease cardiovascular risk in patients after kidney transplantation.

Immediately preoperative use of biological therapy does not influence liver regeneration after large resection--porcine experimental model with monoclonal antibody against epidermal growth factor.

BACKGROUND: The aim of this work was to study the influence of isolated biological therapy administered immediately before extended liver resection on liver function and regenerative capacity of future liver remnant (FLR) in a large-animal experiment. MATERIALS AND METHODS: Nineteen piglets were included in this study (10 in the control group and 9 in the experimental group). A port-a-cath was introduced into the superior caval vein. On days 11 and 4 before liver resection, cetuximab was administered via this port at 400 mg/m2 of piglet body surface. Physiological solution was applied to the control group. Resection of the left lateral, left medial and right medial hepatic lobes was followingly performed (reduction of 50-60% of liver parenchyma). Blood samples were collected at different times before the operation and after liver resection. Serum levels of bilirubin, urea, creatinine, alkaline phosphatase, gamma glutamyltransferase, cholinesterase, aspartate aminotransferase, alanine aminotransferase, albumin, C-reactive protein and transforming growth factor-ß1 were assessed. The ultrasonographic examinations at different time points were performed pre-operatively and after liver resection in order to assess the liver volume. The biopsies from the liver parenchyma were examined for proliferative activity, binocluated hepatocytes, size of hepatocytes, and the length of the lobuli. The comparison of distribution of the studied parameters between the groups was carried out using the Wilcoxon test. The Spearman rank correlation co-efficient was used because of the non-Gaussian distribution of the parameter values. The whole development of the studied parameters over time was compared between the groups using ANOVA. RESULTS: There were no important complications of administration of biologic therapy during the operation or throughout the peri-operative period. There was no statistically significant difference in the regeneration of FLR nor were any differences in biochemical, immunoanalytical and histological parameters detected. CONCLUSION: The achieved results of comparable liver regeneration in both the experimental and control groups confirms the use of biological treatment with cetuximab in the pre-operative period for minimizing the recovery period.

[Comparison of selective oxidative stress parameters in the follicular fluid of infertile women and healthy fertile oocyte donors]. / Srovnání vybraných parametru oxidacního stresu ve folikulární tekutine u zen s poruchou plodnosti a u zdravých fertilních dárkyn oocytu

OBJECTIVE: Follicular fluid (FF) affects oocyte development and disruption of its homeostasis has a crucial effect on egg developmental potential. The aim of this study was to compare the levels of selected oxidative stress markers in the FF of women with impaired fertility and healthy fertile oocytes donors. DESIGN: A retrospective comparative study. SETTING: Faculty of Medicine in Pilsen, Charles University in Prague; Institute of Reproductive Medicine and Endocrinology, IVF Center Prof. Zech, Pilsen. METHODS: Levels of homocysteine (Hcy), malondialdehyde (MDA), glutathione peroxidase (GPx), total antioxidant capacity (AOK) and total protein (CB) were analyzed in the FF. We have analysed FF of 146 women - 74 infertile patients (mean age 31 years, SD = 4.65) and 72 healthy fertile oocyte donors (mean age 26 years, SD = 4.44). Only blood free samples were studied after pooling of all FF samples each patient. RESULTS: The study showed a statistically significantly higher Hcy levels (p < 0.0001) in the FF of healthy fertile women compared with impaired fertility group both - comparing the two groups regardless the age and in groups of the same age range (for the age group between 20 to 29 years isp = 0.0002, for the age group between 30 to 39 years is p < 0.0001). When divided into above age ranges we found statistically significantly higher levels of MDA in the control group aged 20 to 29 years compared to same age infertile patients (p = 0.0374) and statistically significantly higher AOK in infertile women between 30 to 39 years of age compared to same age control group (p = 0.0458). CONCLUSION: The presence or on the contrary the absence of prooxidant parameters in the FF has an important role in the ability of conception and subsequent embryo development.

Signaling molecules for early detection of adverse interactions during mechanical ventilation in animal models.

AIM: The early identification of adverse interactions during mechanical ventilation, investigated by multiplexed immunoanalysis. MATERIALS AND METHODS: Twenty piglets (average age 7 weeks, weight 23 kg) were intubated and divided into groups: A, spontaneously breathing; B, protectively ventilated; C, ventilated with injurious strategy; D, ventilated with lung disability. At the 1st hour (time-1) and 12th hour (time-2) of the study, brain natriuretic peptide (BNP), intercellular cell adhesion molecules (ICAM-1), vascular cell adhesion molecules (VCAM-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (Il-6) were analyzed in the blood. RESULTS: The injurious ventilated group C exhibited an increase in both cell adhesion molecules (p<0.01), TNF-alpha and BNP (p<0.05) at time-1, and at time-2 further increases (p<0.05). In group D, an increase in ICAM-1 and BNP (p<0.05) at time-1, and increases in Il-6 and ICAM-1 (p<0.05) at time-2, with notable decreases in urine output were observed. Overall, the lung damage correlated with TNF-alpha (r=0.904), Il-6 (r=0.740), and ICAM-1 (r=0.756) levels. CONCLUSION: All five monitored molecules quickly and reliably signaled adverse interactions.

Total body response to mechanical ventilation of healthy lungs: an experimental study in piglets.

The objective of our study was to assess the influence of mechanical ventilation on healthy body organs. Fifteen piglets (aged 6 weeks, 19-27 kg) were anesthetized, instrumented, and divided into three groups: Group A - spontaneously breathing, group B - mechanically ventilated with tidal volume 6 ml/kg, and group C - ventilated with tidal volume 10 ml/kg for 12 hours. The parameters of lung, heart, liver and kidney functions neurohumoral regulation and systemic inflammatory reaction were recorded initially (time-1) and after 12 hours (time-12) of mechanical ventilation. At the onset of experiment (time-1) the levels of soluble adhesive molecules were higher (CAM; P<0.01), glomerular filtration index and free water clearance were lower (P<0.05) in both ventilated groups than in group A. Right ventricle myocardial performance index was higher (RIMP; P<0.05) in group C when compared with group A. Levels of CAM (P<0.05) and creatinine clearance (P<0.01) were higher, free water clearance was lower (P<0.05) in group C when compared to group B. At time-12 the RIMP (P<0.05) and levels of CAM were increased (P<0.01), creatinine clearance was decreased (P<0.05) in both ventilated groups compared to the same parameter at time-1. Ventilation index was higher (P<0.05), and hypoxemic index was lower (P<0.01) in group C when compared to group B. In conclusion, this study showed that mechanical ventilation induced changes compatible with early inflammatory response in healthy animals. Higher tidal volumes had detrimental effect on ventilatory parameters, reduced myocardial performance and potentiated adverse reaction of other organs.

Ischemia-reperfusion injury in kidney transplantation from non-heart-beating donor--do antioxidants or antiinflammatory drugs play any role?

BACKGROUND: Ischemia reperfusion injury (IRI) is a serious problem of transplanted kidneys from a non-heart-beating donor (NHBD). IRI is probably the main cause of primary disfunction or delayed graft function. The aim of this study was to demonstrate the reduction of IRI by intravenous application of antioxidants or immunosuppressives to the recipient before the kidney transplantation in an experimental model. METHOD: Piglets weighing between 20-25 kg were used (n=45) for the experiment. Intravenous application of multivitamins (GI) and a combination of immunosuppressives (GII) was tested one hour before the kidney transplantation from the NHBD. In control group (GIII) simple NHBD modelling was used. Plasma levels of malondiadehyde (MDA) and reduced glutathione (GSH) were assessed at intervals of 0, 20, 60 and 120 minutes after the kidney transplantation. Concentrations of both MDA and GSH were also assessed in the transplanted kidney before and 120 minutes after transplantation. RESULTS: A permanent increase in MDA plasma concentrations occurred in GIII. In GI and GII, after a transient increase in MDA plasma levels within the first 20 minutes after reperfusion, it decreased permanently (p<0.05, p<0.01). MDA plasma levels were not significantly different between GI and GII groups, but both groups differed from GIII (p<0.001). GSH plasma levels and tissue concentrations of MDA and GSH were not statistically significant in any group in the course of the experiment. CONCLUSION: Intravenous application of multivitamins or immunosuppressives before kidney transplantation could have a significant influence on the immediate function of transplanted kidneys from a NHBD (Tab. 3, Fig. 1, Ref. 13). Full Text (Free, PDF) www.bmj.sk.

[Ischemia-reperfusion injury in kidney transplantation from non-heart beating donor--do antioxidants or antiinflammatory drugs play any role?]. / Ischemicko-reperfuzní poskození ledvin transplantovaných z nebijícího dárce (NHBD)--mají antioxidanty nebo protizánetlivé léky význam v jeho prevenci?

BACKGROUND: Ischemia reperfusion injury (IRI) represents a serious problem of transplanted kidneys from a non-heart-beating donor (NHBD). It is probably the main cause of primary a function or delayed graft function. The aim of the experimental study was to demonstrate on an experimental model the possibilities of reduction of IRI by intravenous application of antioxidants or immunosuppressives to the recipient before the kidney transplantation. METHOD: Piglets weighing between 20-25 kg were used (N = 45) for the experiment. Intravenous application of multivitamins (GI) and a combination of immunosuppressives (GII) was tested one hour before the kidney transplantation from the NHBD. As a control a group (GIII) with simple NHBD modelling was used. At intervals of 0, 20, 60 and 120 minutes after the kidney transplantation, plasma levels of malondiadehyde (MDA) and reduced glutathione (GSH) were assessed. Before and 120 minutes after transplantation tissue concentrations of both factors were assessed in the transplanted kidney. RESULTS: A permanent increase in MDA plasma concentrations occurred in GIII. In GI and GII, after a temporary increase of MDA plasma levels in the first 20 minutes after reperfusion, there was their permanent decrease then. (p < 0.05, resp. p < 0.01). The differences in the MDA plasma levels of GI and GII groups did not reach statistical significance. The both groups differed from GIII (p < 0.001). GSH plasma levels and also tissue concentrations of MDA and GSH were not statistically significant in any group in the course of the experiment. CONCLUSION: Intravenous application of multivitamins or immunosuppressives before kidney transplantation could have a significant influence on the immediate function of transplanted kidneys from a NHBD.