Asunto(s)

RESUMEN

Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) belongs to systemic autoinflammatory diseases (AIDs). Many of these syndromes are genetically conditioned and can be inherited. Diagnosis relies on clinical symptoms and should be confirmed by genetic testing. One of the most serious complications is AA amyloidosis. We present the diagnostic route of a 33-year-old male with AA amyloidosis and his children, leading to diagnosis of monogenic autoinflammatory syndrome, confirmed by genetic analysis. A novel variant of the in-frame insertion type in one allele of TNFRSF1A gene was found by whole exome sequencing and confirmed by Sanger sequencing, which allowed a diagnosis of TRAPS. Three-dimensional modeling was used to assess the structural changes introduced into TNFR1 molecule by the insertion. The analysis of the 3D model revealed that accommodation of the 4AA insert induces misalignment of three cysteine bridges (especially the C70-C96 bridge) in the extracellular domain, leading to putatively misfolded and improperly functioning TNFR1. Three of the patient's daughters inherited the same variant of the TNFRSF1A gene and presented TRAPS symptoms. TRAPS is a very rare disease, but in the presence of suggestive symptoms the genetic diagnostic workout should be undertaken. Early diagnosis followed by appropriate clinical management can prevent irreversible complications.

RESUMEN

BACKGROUND: Infection remains a serious clinical problem in liver transplant (LTX) recipients. A higher risk of infection is connected with immunosuppression therapy. The aim of the study was to assess the relationships between infections' incidence and concentrations of cyclosporine (CsA) metabolites after LTX. METHODS: Forty-three liver transplant recipients receiving CsA were included in the study. With the use of liquid chromatography combined with tandem mass spectrometry, concentrations of CsA and its metabolites were measured: dihydroxylated cyclosporine metabolites (DiHCsA), trihydroxylated cyclosporine metabolites (TriHCsA), demethylcarboxylated cyclosporine metabolites (DemCarbCsA), AM1, AM9, and AM4N. The study protocol conformed with the Declaration of Helsinki. RESULTS: Patients with a history of Epstein-Barr virus (EBV) infection had higher DiHCsA, TriHCsA, DemCarbCsA, AM1/CsA, DiHCsA/CsA, TriHCsA/CsA i DemCarbCsA/CsA in comparison with group without such infection (P = .049, P = .037, P = .006, P = .018, P = .005, P = .027, and P = .026, respectively). LTX recipients with a history of all viral infections had higher DiHCsA, TriHCsA, DiHCsA/CsA, TriHCsA/CsA than patients without viral infections (P = .013, P = .021, P = .013, and P = .048, respectively). Multivariable analysis showed that AM1, DiHCsA, TriHCsA, DemCarbCsA, AM4N/CsA had positively influence on the incidence of all viral infections (ß = 0.0302, P = .0328; ß = 0.0699, P = .0453; ß = 0.6781, P = .0382; ß = 0.6767, P = .0414; and ß = 0.8307, P = .0267, respectively). In multivariable analysis, patients with a history of all bacterial infections had higher AM1 and higher AM1/CsA in comparison with LTX recipients without such infections (ß = 0.0118, P = .0279; and ß = 0.0099, P = .036, respectively). CONCLUSION: In liver transplant recipients with a history of viral or bacterial infections higher concentrations of CsA metabolites were found. Possibly CsA metabolites could be used to assess the risk of infection in patients after liver transplantation. It should be confirmed in further investigations.

Asunto(s)

RESUMEN

BACKGROUND: The prolonged survival time after liver transplantation (LTX) creates the possibility of the occurrence and development of complications in the late post-transplantation period. Deterioration of renal function is 1 of these complications. The nephrotoxicity of calcineurin inhibitors (CNIs) and their metabolites produced during pharmacokinetic processes in the body is also postulated. The study was aimed at assessment of the relationship between selected single gene polymorphisms (SNPs) for enzymes and transport proteins and change of estimated glomerular filtration rate (ΔeGFR) during 2-year follow-up in LTX patients. METHODS: The study involved 244 patients after LTX (105 women [43.0%] and 139 men [57.0%]) receiving tacrolimus (191; 78.3%) or cyclosporine A (53; 21.7%). The study protocol conforms with the Declaration of Helsinki. RESULTS: We have not observed significant differences of ΔeGFR between groups distinguished based on analyzed genotypes in patients treated with cyclosporine or tacrolimus. CONCLUSION: Genetic variations of CYP3A4, CYP3A5, MDR1, MRP2, UGT1A9, UGT2B7, and UGT2B7 tested in LTX recipients are not associated with kidney function during the 24-month follow-up.

Asunto(s)

RESUMEN

BACKGROUND: Calcineurin inhibitors (CNIs), tacrolimus and cyclosporine, undergo pharmacokinetic processes. Enzymes and transport proteins found in various organs are involved. It is possible that genetic polymorphisms of these proteins influence CNIs pharmacokinetics and the generation of CNIs metabolites. CNIs may be nephrotoxic, and it is thought that some CNIs' metabolites may have a similar effect. The study was aimed at the assessment of the relationship between selected gene polymorphisms for enzymes and transport proteins and change of estimated glomerular filtration rate (eGFR) during a 2-year follow-up in kidney transplant (KTX) patients. METHODS: The study involved 366 patients after KTX (160 women; 43.7%) receiving tacrolimus (62.57%) and cyclosporine (37.43%). The mean age was 50.1 years, and the median time after KTX was 60.5 months. The study protocol conformed with the Declaration of Helsinki. The percent of difference between eGFR at baseline and at 24 months (ΔeGFR) was calculated. We evaluated selected genetic polymorphisms of CYP3A4, CYP3A5, MDR1, UGT1A9, UGT2B7, UGT1A8, and MRP2. RESULTS: In the tacrolimus group, there were no significant differences of ΔeGFR between groups distinguished based on analyzed genotypes. In the cyclosporine group, differences were found for CYP3A4∗22 C/C -12.3 (-26.8 to -1.8) versus C/T 13.2 (12.4 to 13.9), P = .034; MDR1 3435C>T C/T -18.2 (-31.5 to -5.7) versus C/C -1.8 (-17.1 to 6.9) vs T/T -8.1 (-18.4 to 12.4), P = .031; and UGT1A9 2152C>T C/C -9.0 (-25.5 to 2.8) versus C/T -26.8 (-31.9 to -24.1), P = .017. CONCLUSION: The study results suggest that in KTX metabolic transformations and transport, especially of cyclosporine, dependence on the genetic variability of CYP3A4, UGT1A9, and MDR1 may contribute to kidney damage.

Asunto(s)

RESUMEN

BACKGROUND AND PURPOSE: Therapeutic drug monitoring is a valuable tool supporting immunosuppressive therapy. Significant variation of immunosuppressive drug (ISD) concentrations during their use at similar doses is the basis of dose-normalization strategy. The strategy of dose-adjustment is proposed to identify variability in the rate of ISD metabolism. While the parent drug-to-metabolite ratio (metabolic ratio, MR) represents the rate of formation of individual metabolites. The present study was aimed at evaluation of associations between ISDs' metabolism rate expressed as dose-adjusted concentrations (C/D) and dose/kg-adjusted concentrations (C/D/kg) and MRs of individual metabolites of tacrolimus, cyclosporine A and MPA precursors. EXPERIMENTAL APPROACH: 506 patients have participated: 284 males (56.13%) and 222 females (43.87%); 318 after kidney (62.85%) and 188 after liver transplantation; median age was 51.34 (39.32-59.95) years and median time after transplantation 78.92 (33.87-138.4) months. KEY RESULTS: Generally, we have not observed significant relationships between dose-adjusted and dose/kg-adjusted concentrations and MRs of cyclosporine and tacrolimus. Significant correlations were found for: AM9/CsA and dMC-CsA/CsA in kidney transplant recipients and MIII/Tac, AM1/CsA and AM4N/CsA in liver transplant recipients. In contrast, MRs of mycophenolic acid (MPA) metabolites correlated significantly with MPA C/D and C/D/kg both in kidney and liver transplant recipients. CONCLUSION AND IMPLICATIONS: In conclusion, easily available and easy to use in clinical practice C/D and C/D/kg ratios cannot be considered as parameters directly reflecting the rate of generation of major metabolites of cyclosporine and tacrolimus both in liver and kidney transplant recipients.

Asunto(s)

RESUMEN

Cardiovascular disease (CVD) remains one of the primary causes of death after kidney transplantation (KTX). Cyclosporine (CsA) metabolites may play a role in CVD. Metabolic ratio (MR) may be considered a measure of intra-individual differences of CsA metabolism. The study was aimed at analysis of associations of CVD with indices of CsA metabolism: MRs and dose-adjusted CsA concentrations (C/D and C/D/kg). The study was performed in the Department of Immunology, Transplant Medicine, and Internal Diseases of the Medical University of Warsaw and involved 102 KTX recipients. Whole blood concentrations of cyclosporine A, AM1, AM9, AM4N, demethylcarboxylated (dMC-CsA), dihydroxylated (DiH-CsA), trihydroxylated (TriH-CsA) cyclosporine metabolites were determined by liquid chromatography coupled with tandem mass spectrometry. Lower AM9/CsA were observed in diabetics. Patients with coronary disease and/or myocardial infarction had lower dMC-CsA/CsA and higher AM4N/CsA. Supraventricular arrhythmia (SVA) was associated with higher AM1/CsA and AM4N/CsA. Hypertriglyceridemia (hTG) was associated with lower AM9/CsA, higher C/D and C/D/kg. Decrease of AM9/CsA and AM4N and higher D/C were associated with overweight/obesity. Systolic blood pressure (BP) positively correlated with dMC-CsA/CsA and negatively with C/D/kg. Diastolic BP correlated positively with AM1/CsA, dMC-CsA/CsA, DiH-CsA/CsA and TriH-CsA/CsA. We have demonstrated the association of coronary disease/myocardial infarction, SVA, hTG, overweight/obesity and elevated arterial BP with higher MRs of AM1, AM4N, dMC-CsA, DiH-CsA and TriH-CsA, and lower MRs of AM9, which may indicate deleterious and favourable effects of individual CsA metabolites on cardiovascular system and suggest engagement of specific enzymatic pathways.

Asunto(s)

RESUMEN

BACKGROUND Mycophenolic acid (MPA) prodrugs are anti-proliferative immunosuppressive agents commonly used after organ transplantation. Although they are generally well tolerated by patients, adverse effects may occur. It is postulated that MPA metabolites could also contribute to these adverse effects. MATERIAL AND METHODS The objective of this study was the assessment of concentrations of total MPA and its metabolites, phenyl glucuronide (MPAG), acyl glucuronide (AcMPAG) and glucoside (GluMPA), using liquid chromatography combined with mass spectrometry (LC/MS/MS) in two groups: kidney transplant recipients and liver transplant patients. Associations of MPA and its metabolites with adverse effects were analyzed. RESULTS The study group consisted of 211 recipients of liver or kidney transplants who received immunosuppressive therapy, including MPA prodrugs. Multivariant analysis showed a positive influence of MPA on gastroenterotoxicity in kidney transplant recipients. In liver patients, gastroenterotoxicity was associated with lower MPAG concentrations. A positive influence of AcMPAG on bacterial infections in liver transplant patients was observed. In liver transplant recipients, a positive influence of MPA and a negative influence of GluMPA levels on the PLT count were revealed. MPA and its metabolites did not influence the hemoglobin levels in both groups. There were no significant relationships among MPA, its metabolites and WBC counts. CONCLUSIONS In kidney transplant recipients, total MPA trough concentration is associated with gastroenterotoxicity and its monitoring could have important role in management of gastrointestinal complications. The quantification of AcMPAG in liver recipients receiving MPA may be helpful in avoiding bacterial infections. GluMPA seems to have a toxic effect on thrombopoiesis.

Asunto(s)

RESUMEN

Hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (GLUT-1), and carbon anhydrase IX (CAIX) are important molecules that allow adaptation to hypoxic environments. The aim of our study was to investigate the correlation between HIF-1α, GLUT-1, and CAIX protein level with the clinicopathological features of endometrial cancer patients. Materials and Methods. 92 endometrial cancer patients, aged 37-84, were enrolled to our study. In all patients clinical stage, histologic grade, myometrial invasion, lymph node, and distant metastases were determined. Moreover, the survival time was assessed. Immunohistochemical analyses were performed on archive formalin fixed paraffin embedded tissue sections. Results. High significant differences (P = 0.0115) were reported between HIF-1α expression and the histologic subtype of cancer. Higher HIF-1α expression was associated with the higher risk of recurrence (P = 0.0434). The results of GLUT-1 and CAIX expression did not reveal any significant differences between the proteins expression in the primary tumor and the clinicopathological features. Conclusion. The important role of HIF-1α in the group of patients with the high risk of recurrence and the negative histologic subtype of the tumor suggest that the expression of this factor might be useful in the panel of accessory pathomorphological tests and could be helpful in establishing more accurate prognosis in endometrial cancer patients.

Asunto(s)

RESUMEN

UNLABELLED: Recurrent miscarriage occurs in 1-5% of women at reproductive age. The most common cause of recurrent miscarriage is chromosomal abnormalities of the embryo (41%), chromosomal aberrations parents (10%), anatomical abnormalities of the uterus (5%), infectious and hormonal factors. In about 25% of women, no cause of recurrent miscarriage is usually found. Therefore it seems important to study all factors possibly inducing pregnancy disorders. OBJECTIVE: The aim of this study was to find a difference in serum protein fractions between women with primary and secondary recurrent miscarriage. METHODS: The study group consisted of 52 women (aged 36.0 +/- 4.9) with recurrent miscarriage. Nine of them (17%) reported one earlier regular pregnancy ending with childbirth without complications. Control group comprised 30 non-pregnant women (aged 36.1 +/- 3.6), who had given vaginal birth to healthy children at least twice. Serum protein fractions were separated by electrophoresis in the SDS PAGE buffer system using a Mini PROTEAN 3 cell device. BioRad SDS PAGE Molecular Weight Standards covering mass range of 6.5-200 kDa were used as a reference. Gels were stained with Coomassie Blue R 250 solution. BioRad QuantityOne software was used for the assessment of molecular weight of each protein fraction. RESULTS: Electrophoretic separation revealed 39 protein fractions of 10,243 kDa. Particularly interesting was a 38 kDa fraction present exclusively in serum of women with recurrent pregnancy who had never given birth. Another fraction (74 kDa), not detected in the control group, was found in all women with recurrent pregnancy loss. Protein fractions of 76 and 151 kDa were present only in the control group. CONCLUSIONS: The presence of the protein fractions of low- or mid-weight in serum from women with recurrent miscarriage may potentially play a role in the pathomechanism of this disorder

Asunto(s)

RESUMEN

Therapeutic drug monitoring of immunosuppressive agents is a critical and essential part of patient therapy after organ transplantation. We have developed high-throughput, robust, and rapid liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) methods with common pretreatment procedures for simultaneous quantification of four immunosuppressive agents (everolimus, sirolimus, tacrolimus, and cyclosporin A) in whole blood and one immunosuppressant (mycophenolic acid) in plasma. The new approach used in this work is based on improved sample preparation procedures allowing the analysis of five immunosuppressive drugs. Whole blood was prepared by transferring 100µL of blood into a 1.5-mL silanized conical test tube. Zinc sulfate solution (150µL), containing deuterated internal standards, was added to perform hemolysis. The samples were vortexing for 10s, followed by the addition of 250µL acetonitrile, containing internal standard for cyclosporin A, to precipitate proteins. The mixture was vortexed for 1min and centrifuged for 2min at 14,000rpm. The whole supernatant was transferred to a vial. To prepare blood plasma, the hemolysis step involving the addition of zinc sulfate was omitted and, instead of acetonitrile, methanol was used as the solvent for the internal standard (mycophenolic acid-d3). The volumes of chemicals used in this procedure were the same as those used in the procedure for immunosuppressants in whole blood. The basic validation parameters for the analytical methods were limits of detection (0.5ng/mL for everolimus, sirolimus and tacrolimus, 25ng/mL for cyclosporin A and 100ng/mL for mycophenolic acid), precision (<15%), recovery (>84%), repeatability and reproducibility. Possible mutual ion suppression was eliminated in the presence of internal standards. The method developed for the quantitation of immunosuppressants in whole blood was used to analyze 276 patient samples containing tacrolimus and 55 samples containing cyclosporin A. The results from LC/MS/MS were compared to those obtained from immunoassays of the same samples. Immunoassays significantly overestimated the concentrations of immunosuppressants.

Asunto(s)

RESUMEN

AIM: Growth factors play a major role in the pathogenesis of uterine myomas. The aim of this study was to evaluate vascular endothelial growth factor (VEGF) mRNA expression during leiomyoma growth at different phases of the menstrual cycle with RT-PCR. METHOD: We studied 56 patients: 43 with myomas, 13 with healthy myometriums. In patients with myomas (secretory phase), VEGF expression was 2.82 times higher than in control patients (p < 0.05). In patients with myomas (phase I), VEGF expression was 2.53 times higher (p < 0.05) than in control patients. For all patients with myomas, those who were in menopause had 1.52 times higher VEGF expression than those who menstruated. For patients with healthy myometriums, those who were in menopause had 1.97 times higher VEGF expression than those who menstruated. A comparison of all the patients in menopause revealed that VEGF expression was 2.03-fold higher in those with myomas than in those with healthy myometriums. CONCLUSION: We observed the highest VEGF mRNA expression in women with myomas who were in menopause. Among menstruating patients, VEGF expression was significantly higher in those with myomas compared to those with a healthy myometrium. This suggested that VEGF may play a significant role in the pathogenesis of uterine myomas.

Asunto(s)

RESUMEN

Resent years have brought fast development of one of the molecular biology methodology, real time polymerase chain reaction. It has been introduced in common use. Real time PCR allows to detect and qualify very small amounts of specific nucleic acid sequences. As a research tool, a major application of this method is the rapid and accurate detection of genes expression changes as a result of physiological and pathophysiological mechanisms. In clinical diagnostics, this method is used to measure viral or bacterial load or to assess cancer status.

Asunto(s)

RESUMEN

AIMS: To determine how sirolimus (SRL), in comparison to calcineurin inhibitors (CNI), influences gene expression of cytokines: interleukin 1beta, tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin 10 (IL-10) in peripheral blood mononuclear cells (PBMC) of transplant recipients. MATERIAL AND METHODS: Twenty-two patients (13 kidney and 9 liver transplant recipients), in which: CNI was replaced by SRL (n=11); SRL was added to CNI (n=7); or SRL was replaced by CNI (n=4), were recruited. PBMC were obtained before and after modification of immunosuppression. Real-time polymerase chain reaction was used for quantitative assessment of expression of investigated genes. RESULTS: During therapy with SRL either with, or without CNI (SRL+/-CNI), the pro-inflammatory genes expression was increased, and IL-10 gene expression was decreased, in comparison to treatment with CNI. In subgroup of patients with malignancy as the reason of liver transplantation, gene expression of TNF-alpha and IFN-gamma was higher when SRL+/-CNI was used in comparison to treatment with CNI. Patients with viral infection receiving SRL+/-CNI had higher expression of pro-inflammatory genes than during therapy with CNI. CONCLUSIONS: Transplant recipients during therapy with SRL+/-CNI have increased gene expression of Th1 cytokines, and decreased gene expression of Th2 cytokine, IL-10, in PBMC, compared to treatment with CNI. Our data may influence management of transplant recipients.

Asunto(s)

RESUMEN

BACKGROUND: The storage of organs for liver transplantation has resulted in expanding the donor pool for the "living-related" organ donors. Hence, understanding the factors that moderate liver regeneration, both in donor and recipient, is of great importance. Liver regeneration is accompanied by an appearance of cytokines, growth factors and hormones which enable hepatocytes acquiring the ability to reenter the cell cycle. Within few hours after partial hepatectomy (PH) increase concentration of a large number of mitogens for hepatocytes. Among them essential function in recovering after PH plays interleukin 6 (IL-6). However the gene expression of this factor after the reconstruction of the liver is completed is still uncertain. We have assessed the gene expression of IL-6 during liver regeneration in tissue of regenerating liver in tenth day after PH. MATERIAL/METHODS: Materials for the research were obtained from 12 rats. PH surgeries were performed on 7 rats (study group), on the 5 left laparotomy was performed (control group). In the tenth day after surgery on whole 12 animals hepatectomy was performed. RNA was isolated from tissues and then copied to cDNA. Using real-time polymerase chain reaction (real-time PCR) the gene expression of IL-6 was defined. The Mann-Whitney-Wilcoxon Test was performed for the statistic analysis. The p<0,05 was considered as statistically significant. RESULTS: mRNA transcripts for IL-6 in study group compared to control group were 6-fold elevated 10 days following PH (p=0,03). CONCLUSIONS: These results indicate that IL-6 plays a pivotal role in liver regeneration. Elevated level of mRNA transcripts for IL-6 is sustained even after the operation and rebuild of the organ size.

Asunto(s)

RESUMEN

Some clinical factors have been useful in predicting prognosis in high-grade gliomas, however, unexpected differences in survival time have generated attempts to search for more precise parameters. It is clear that tumour behaviour depends mostly on gene alterations. Known single gene alterations failed to accurately define survival time, however, recently, the gene profiling based on microarray technology has raised hopes. Our aim was to assess whether the genetic predictor exceeds clinical parameters in the prognosis of malignant gliomas. We performed gene expression analysis of 28 gliomas (3 grade II, 10 grade III and 15 grade IV, according to WHO classification), and 5 control, normal brain samples, using Clontech oligonucleotide arrays with 3,757 known genes. The signal-to-noise statistics was used to separate classes, and the leave-one-out method was used to assess the smallest number of genes make it clear with a minimal cross-validation error. All gliomas, or only high-grade tumours, were clearly separated from the normal brain samples using 7 or 9 most differentially expressed genes. Hierarchical clustering failed, but the fuzzy c-means method was useful in high-grade gliomas to find a gene prediction model, which, with clinical factors, was assessed in survival analysis. Univariate analysis demonstrated that age, WHO grade (IV vs. III), radiation dose (> or = 50 Gy vs. 42 Gy), postoperative KPS score (100 points vs. others), neurological deficit as the first sign of the disease vs. others, and gene expression profile were significant predictors of survival. In multivariate analysis, the gene expression profile remained the only independent predictor (p = 0.007). Thus, our conclusion is that gene expression pattern predicts outcome in high-grade gliomas independently of other factors.

Asunto(s)

RESUMEN

Human herpesvirus 6 (HHV-6) is a lymphotropic herpesvirus of emerging clinical significance in immunocompromised patients. Little is known about clinical impact and relevance of HHV-6 variant A infection in renal transplant recipients. We describe the case of a 44-year-old woman who underwent second allogenic kidney transplantation (Tx). On day 6 after Tx she presented with high fever. She developed thrombocytopenia, anemia, diarrhea, liver dysfunction and graft failure. Renal graft biopsies that followed revealed acute rejection. Apart from the introduction of anti-rejection therapy, empiric gancyclovir, as well as antibacterial treatment was initiated. To determine the serostatus of HHV-6 and load of HHV-6A and -6B DNA in paired sera samples an enzyme-linked immunosorbent assay, indirect immunofluorescence assay and real time quantitative polymerase chain reaction (PCR) assay based on the exonuclease format (TaqMan) was devised. HHV-6A was the sole pathogen, the DNA of which was retrospectively detected in patient's serum. HHV-6 IgM seroconversion was demonstrated. No other viral (e.g. cytomegalovirus (CMV)) or other pathogens were detected in the blood, urine, and stool. Following therapy with gancyclovir, viral load declined to undetectable levels. Gradual improvement in clinical status of the patient was observed. HHV-6 infection may be associated with specific clinical manifestations and should be considered in a transplant recipient who presents with a clinical syndrome resembling CMV infection, where CMV assays are negative. This case confirm symptomatic HHV-6 infection and suggests that HHV-6 variant A reactivation may potentially trigger graft rejection.

Asunto(s)

RESUMEN

Long-term risk of mortality in patients with myocardial infarction is thought to be linked with plasma concentrations of proinflammatory cytokines and CRP (markers of inflammation). The aim of our study was to analyze plasma levels of interleukin (IL) 1, interleukin 6, interleukin 8 and C-reactive protein (CRP) in patients with myocardial infarction. One hundred and seven (107) patients with myocardial infarction hospitalized at the Cardiac Care Unit of St. Elizabeth's Sisters' Hospital in Warsaw and a control group of 10 subjects were enrolled in our study. The samples of peripheral venous blood were withdrawn from the patients on 2nd and 7th of infarction and plasma levels of IL-1, IL-6, IL-8 and CRP were determined. The patients were followed-up for a year. The analysis of survivals and deaths caused by acute coronary syndrome allowed to determine the predictive value of IL-1, IL-6, IL-8 and CRP in myocardial infarction. Twenty-two (22) of the total 107 patients died of acute coronary syndrome during one-year follow-up. Plasma IL-6 and CRP levels were higher in non-survivors as compared to the levels of IL-6 and CRP in living subjects, whereas plasma levels of IL-1 and IL-8 were comparable in both groups. IL-6 and CRP proved to be of predictive value in patients with myocardial infarction during one-year follow-up. It has also been found that plasma IL-6 level correlates with plasma CRP concentration and that there is a positive correlation between the former and CK-MB levels. IL-6 and CRP levels were higher in patients with Q wave infarction in comparison with non-Q wave infarction. Plasma levels of IL-1 and IL-8 have not been found to be good predictors of death during 12-month follow-up.

Asunto(s)

RESUMEN

Diabetes mellitus (DM) is the most common metabolic disease, an independent risk factor of coronary disease, and shortens lifetime in all populations of patients, including kidney transplant recipients. Patients after kidney transplantation are exceptionally predisposed to develop or to exacerbate the preexisting DM. Age, DM in family, CMV infections, genetic factor (HLA A26 and B27), immunosuppressive treatment with steroids or calcineurin inhibitors belong to the major risk factors of diabetes. We analyzed 1300 renal transplant recipients in our center. Out of them 153 suffered from DM. DM de novo revealed 80 pts. Mean age in type I pts was 44.88 years and in type II pts was 57.27 years. De novo diabetics were 56.41 years old in average. CMV infection, potentially pathogenic in development of DM de novo, coexisted in 7.5% of these cases as frequently as in whole TPN population. Most frequently detected HLA antigens were: A2, B8 and DR5. Use of cyclosporine and tacrolimus promoted incidence of DM. We conclude, that low percentage of de novo DM in patients after renal transplantation may result from flexibility in administration of immunosuppressive regimens. Cyclosporine and tacrolimus treatment was switched to sirolimus or mycophenolate mofetil when the glucose intolerance was detected to prevent development of DM.

Asunto(s)

RESUMEN

Progression to end-stage renal failure is the final common pathway of many forms of glomerular diseases, independent of the type of initial insult. Tubulointerstitial fibrosis is tis near invariable finding and significant prognostic feature. We have reviewed immunological (cytokines, inflammatory cells) and nonimmunological factors (extracellular matrix proteins and proteolytic enzymes), being involved in mechanisms leading from glomerular disease to tubulointerstitial scarring, from the point of view of potential clinical usefulness of measuring its urine activities and levels to noninvasive diagnostic of kidney diseases.

Asunto(s)