The role of proteinuria, paricalcitol and vitamin D in the development of post-transplant diabetes mellitus.

INTRODUCTION: Post-transplant diabetes mellitus (PTDM) occurs most frequently during the first year after transplantation. We focused on parameters of calcium-phosphate metabolism and proteinuria as possible new risk factors for PTDM after kidney transplantation. MATERIALS AND METHODS: We have prospectively identified risk factors for post-transplant diabetes mellitus with follow-up of 12 months in a set of 167 patients after kidney transplantation. Patients with diabetes mellitus type 1 and type 2 as well as patients using ciclosporin A or mTOR inhibitor have been excluded from the monitoring. From the perspective of immunosuppression it was a homogeneous set of patients. RESULTS: We identified the following independent risk factors for PTDM in our set: average proteinuria > 0.300 g/24 h (HR 3.0785, (95 % CI 1.6946-5.5927), p=0.0002), level of vitamin D<20 ng/ml (HR 5.4517, (95 % CI 2.3167-11.8209), p1.45 mmol/l (HR0.0821, (95 % CI0.0042-1.5920), p=0.0439). The lowest occurrence of PTDM and proteinuria was recorded in patients whose treatment included paricalcitol (p<0.0001) and these patients had at the same time the highest level of vitamin D (p<0.0001). CONCLUSION: Deficit of vitamin D, proteinuria and hyperphosphatemia have been independent risk factors for the development of PTDM in our set. We identified the usage of paricalcitol as protective factor with regard to the PTDM development (Tab. 6, Fig. 4, Ref. 29).

Flow Cytometry Panel-Reactive Antibody Screening of Anti-HLA Antibodies in the Waiting List Significantly Reduces the Occurrence of Acute Rejection After Kidney Transplantation.

INTRODUCTION: The presence of preformed HLA-reactive antibodies in recipient serum before transplantation has long been recognized as a prominent risk factor for a generally worse graft outcome. Screening and identification of HLA antibodies can be used to stratify patients into high- and low-risk categories. MATERIALS AND METHODS: We determined patients' anti-HLA antibodies using flow cytometry panel-reactive antibody (flowPRA) screening, specifying more than 5% after positive screening. According to the results of the screening test, patients were allocated to the induction immunosuppressive protocol according to the actual immunologic risk. RESULTS: In the group of 78 patients, screening with flowPRA of anti-HLA antibodies was done twice a year. Patients were divided into 2 groups of immunologic risk (low or medium), and we chose the induction immunosuppressive protocol according to the risk. Stratification of the risk was correct, because the only predictor for development of acute rejection in the monitored period of 12 months was delayed graft function (odds ratio 33.2501; 95% confidence interval 10.0095-110.4508; P < .0001). The occurrence of acute rejection upon implementing the screening was reduced in our transplant center from 44% to 19% (P < .0001). No difference was recorded in the 12-month survival of grafts and patients according to the applied induction immunosuppressive protocol. CONCLUSION: We confirmed significantly reduced occurrence of acute rejection in the follow-up period of 12 months by using individualized induction according to flowPRA screening of anti-HLA antibodies. FlowPRA screening represents a suitable alternative for screening and specification of anti-HLA antibodies in case the Luminex methodology is unavailable.

Metabolic syndrome and new onset diabetes after kidney transplantation.

AIMS: The metabolic syndrome developed after kidney transplantation is the result of several factors which are identical with the risk factors in normal population, however, also some factors typical for the transplanted patients-especially the effects of immunosuppressive therapy. MATERIAL AND METHODS: In the groupof 268 patients after kidney transplantation, which had no type 1 or type 2 diabetes mellitus before transplantation, we identified patients with metabolic syndrome(based on IDF criteria), 12 months from the kidney transplantation. In all patients, we recorded the following parameters: age at the time of transplantation, type of immunosuppression, waist measure, the value of triacylglycerols, the value of HDL cholesterol, presence of arterial hypertension, andthe value of glycaemia in fasting state (or presence of diabetes mellitus). The groupof patients was divided into the control group and the group of patients with metabolic syndrome. RESULTS: The average age of patients was 46.1±11.6years. The control group included 149 patients (55.6%),and we identified the metabolicsyndromein 119patients (44.4%). The patients with metabolicsyndrome were significantly older (P<0.0001), had significantly larger waist (both the entiregroup and the males andfemales) P<0.0001.The femaleswith metabolic syndrome had significantly lower value of HDL-cholesterol (P=0.0013), and significantly higher number of patients with metabolic syndrome had hyperglycaemia in fasting state or diabetes mellitus (P=0.0006). CONCLUSION: By controlling the weight and waist, we may identify the risk patients for development of metabolic syndrome after kidney transplantation.

Incidence of Diabetes Mellitus After Kidney Transplantation in Slovakia: Multicentric, Prospective Analysis.

BACKGROUND: The incidence rate of post-transplant diabetes mellitus (PTDM) after kidney transplantation (KT) is 5% to 40%. The objective of this analysis was to identify the risk factors of PTDM after KT in the Slovak Republic (SR). METHODS: In the group of 133 patients/non-diabetics, we identified the risk factors of PTDM in the monitored period of 12 months from transplantation. RESULTS: The incidence of PTDM in the SR in 2014 was 38.3%. By logistic regression, we discovered that the age at the time of KT [odds ratio, 1.0885; 95% CI, 1.0222-1.1592; P = .0082], the value of body mass index (BMI) at the time of KT [odds ratio, 1.4606; 95% CI, 1.0099-2.1125; P = .0442], and the value of insulin resistance index (homeostatic model assessment for insulin resistance) at the time of KT [odds ratio, 2.5183; 95% CI, 1.7119-3.4692; P < .0001] represented predictive factors of PTDM. The independent risk factors of PTDM in our group were age at the time of KT of more than 60 years [HR 0.3871; 95% CI 0.1659-1.7767; P = .0281], waist circumference at the time of KT in men more than 94 cm and in women more than 80 cm [HR, 3.4833; 95% CI, 1.2789-9.4878 (P = .0146)], BMI at the time of KT [HR 3.0011; 95% CI 1.0725-8.3977 (P = .0363)], and triacylglycerols at the time of KT more than 1.7 mmol/L [HR, 2.9763; 95% CI, 1.0141-8.7352; P = .0471]. CONCLUSIONS: In the group of Slovak patients after kidney transplantation, the dominating risk factor for PTDM development was insulin resistance prior to KT.

Correlation between CMV Infection and Post-transplantation New-onset Diabetes Mellitus.

BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a well-known complication of transplantation. OBJECTIVE: To determine the correlation between CMV infection and NODAT. METHODS: Retrospectively, we detected CMV replication (PCR) in every month after renal transplantation in the first 12 months of the procedure in a homogenous group of patients from the immunosuppression point of view. RESULTS: In 167 patients (64 with NODAT and 103 in the control group), the average amount of CMV viremia was not significantly different between the NODAT and the control group (p=0.929). In the 10th month of transplantation, we recorded a significantly higher CMV viremia in the NODAT group (p<0.0001), however, in the multivariant analysis, the observed statistical difference vanished. The survival of patients and grafts was 12 months after kidney transplantation without any statistically significant difference between the studied groups (p=0.611 and p=0.538, respectively). CONCLUSION: CMV is not a risk factor for NODAT.

Twelve-Month and Five-Year Analyses of Risk Factors for New-Onset Diabetes After Transplantation in a Group of Patients Homogeneous for Immunosuppression.

OBJECTIVE: In the case of new-onset diabetes after transplantation (NODAT) development, it is suitable to reduce calcineurin inhibitors and corticosteroids. But change of immunosuppression can be counterproductive and can cause development of rejection and leads to further NODAT aggravation. METHODS: We retrospectively evaluated risk factors after kidney transplantation. Comparison groups were homogeneous in terms of administered immunosuppression, and individual monitored parameters were not distorted by the immunosuppression administered. RESULTS: In the 12-month analysis we identified these risk factors for NODAT: age at the time of transplantation, 50-59 years (P = .0034); age at the time of transplantation, ≥ 60 years (P < .0001); positive family anamnesis for diabetes mellitus type 2 (P < .0001); body mass index at the time of transplantation, ≥ 30 kg/m(2) (P = .0236); prediabetes before transplantation (P < .0009); and proteinuria, >0.15 g/d (P < .0002). In the 5-year analysis, we identified patients who were diagnosed with NODAT after the 1st year. We identified age ≥ 50 years at the time of transplantation to be an independent risk factors for NODAT. CONCLUSIONS: It is advisable to carry out the oral glucose tolerance test even in patients with physiologic levels of fasting glycemia.

Hydrodynamic Trapping of Swimming Bacteria by Convex Walls.

Swimming bacteria display a remarkable tendency to move along flat surfaces for prolonged times. This behavior may have a biological importance but can also be exploited by using microfabricated structures to manipulate bacteria. The main physical mechanism behind the surface entrapment of swimming bacteria is, however, still an open question. By studying the swimming motion of Escherichia coli cells near microfabricated pillars of variable size, we show that cell entrapment is also present for convex walls of sufficiently low curvature. Entrapment is, however, markedly reduced below a characteristic radius. Using a simple hydrodynamic model, we predict that trapped cells swim at a finite angle with the wall and a precise relation exists between the swimming angle at a flat wall and the critical radius of curvature for entrapment. Both predictions are quantitatively verified by experimental data. Our results demonstrate that the main mechanism for wall entrapment is hydrodynamic in nature and show the possibility of inhibiting cell adhesion, and thus biofilm formation, using convex features of appropriate curvature.

[Prevalence of diabetic retinopathy and distal symmetrical diabetic polyneuropathy, and glomerular filtration screening upon the diagnosis of type 2 diabetes mellitus - a cohort study]. / Prevalencia diabetickej retinopatie, distálnej symetrickej diabetickej polyneuropatie a screening glomerulárnej filtrácie v case dia-gnózy diabetes mellitus 2. typu -  kohortná stúdia.

The prospective cohort study analyzes the prevalence of microvascular complications at the time of dia-gnosis type 2 diabetes (DM 2). We were monitoring 200 outpatients (117 men and 83 women, aged from 30 to 92 years) with newly diagnosed and previously untreated type 2 diabetes mellitus during the period of August 2007 -  August 2011 accidentally sending GP or internists. Prevalence of diabetic retinopathy in men was 0.85% and in women 1.2%. The prevalence of diabetic distal symetric polyneuropathy in men was 53% and in women 62%. The median of glomerular filtration based on a simplified MDRD 4 equation (according to the study Modification of Diet in Renal Disease) was 1.27 ± 0.6 ml/ s/ 1.73 m2 for men and 1.05 ± 0.32 ml/ s/ 1.73 m2 for women. At baseline, 16.6% of men and 46.2% of women enrolled in our cohort study had glomerular filtration rate < 1 ml/ s/ 1.73 m2.

[The value of ECG assessment in pulmonary embolism diagnostics]. / Význam hodnotenia EKG v diagnostike plúcnej embólie.

Acute pulmonary embolism is one of the most frequent and risky cardiovascular diseases. Despite accessability of different examinig methods and rich clinical experience, pulmonary embolism is demanding disease especially in diagnostics. The reason might be in clinical picture, that is not typical everytime and leads to incorrect choice of diagnostic methods, that delay the disease assessment. Regarding this, precise evaluation of every each symptom and basal, resp. supplemental examinations is important step to rapid and right assessment of this diagnose.

[Metabolic syndrome and prediabetic states]. / Metabolický syndróm a prediabetické stavy.

Metabolic syndrome is defined as cluster of independent risk factors of coronary heart disease and type 2 diabetes mellitus including prediabetic glucose metabolism disorders associated with insulin resistance as impaired fasting glucose, impaired glucose tolerance and/ or borderline increasing of glycosylated haemoglobin; central obesity, atherogenic dyslipidaemia with increasing of triglyceride levels and decreasing of high density lipoprotein levels and hypertension. In diagnosis of prediabetic states there are used fasting glycaemia, 2 hours glycaemia during oral glucose tolerant test and HbA1c level, which importance in diagnostic is discussed. In DM2 prevention there is important mainly physical activity at least 30 min daily. In the case of pharmacotherapy there was confirmed efficiency of metformin, which could be used in states with high risk of DM2 conversion and some antihypertensive drugs, mainly sartans. In the case of treatment of dyslipidaemia by statins there is moderate increased risk of DM2 in prediabetic states, but cardiovascular benefit from treatment some times exceeds this risk.

[Paraneoplastic hypoglyacemia]. / Paraneoplastická hypoglykémia -  popis prípadu a prehlad problematiky.

Paraneoplastic hypoglyacemia (PH) is a relatively rare phenomenon, which may be caused by insulinomas or nonislet cell tumours (NICT). Both types are among the major "fasting" hypoglyacemia as opposed to reactive postprandial hypoglyacemia. The most common group of nonislet cell tumours causing hypoaglycemia are large mesenchymal tumours, which account for over 50 % of all neoplasms associated with hypoglyacemia. Neuroglycopenic symptoms in patients with NICT may be present for months or years before the actual diagnosis of the underlying disease. Differentiation and correct diagnosis of this type of disease leads to significant improvement in the quality of life of these patients.

[Syncope as first and only sign of left atrial myxoma]. / Synkopa ako prvý a jediný príznak myxómu lavej predsiene.

Myxoma is the most frequent primary heart tumor. It is localised in the left atrium in majority of cases, but each of heart chambers may be affected. Left atrial myxoma becomes symptomatic in case it leads into mitral valve obstruction, systemic embolisation or it manifests with unspecific systemic symptoms. Echocardiography is a golden standard of myxoma diagnostics. We present a case of 61-years old woman patient in whom exercise induced syncope was the first and only sign of far gone left atrial myxoma with left ventricle inflow tract obstruction, leading to mitral pseudostenosis.

HER-2 [Ile655Val] polymorphism in association with breast cancer risk: a population-based case-control study in Slovakia.

Breast cancer belongs to the most frequent types of cancer affecting women and it occurs at any age. Around 1600-1800 women are getting ill annually in the Slovak republic. One of the most important factors in connection with cancer genesis refers to changes in specific genes. HER-2 proto-oncogene belongs to low penetrating genes, which increase susceptibility to breast cancer genesis. Clinical studies demonstrated an association between polymorphism at codon 655 of this gene and increased risk for breast cancer development. The aim of this case-control based prospective study was to determine the distribution of HER-2 genotype and its association with risk factors of breast cancer in the population of women in Slovak republic. HER-2 genotypes were determined with PCR-RFLP method. The DNA was isolated from white blood cell nuclei. The frequency of Val allele in the cancer group was 29.79% and was higher than in the control group 15.84% (p<0.05). The presence of the heterozygote (Ile/Val) genotype was identified in 46.81% of patients in the case group and in 28.33% in healthy individuals, and the homozygote (Val/Val) genotype in 6.38% and 1.67, respectively (p<0.01). The risk of breast cancer development for carriers of one valine (Val) allele in genotype was two-times lower (OR=2.47) than for carriers of two Val alleles (OR=5.73) (p<0.05). Risk of cancer genesis for Val allele carriers was higher in multiparas (OR=2.90), among women with positive family history of breast cancer (OR=5.0), BMI>24 (kg/m2), and late menopause (OR=1.5). Contraceptives in anamnesis contrariwise showed tend to decrease the risk in Val allele carriers (OR=0.3). In conclusion, this study revealed relatively high frequency of the Val allele among the women population of the Slovak republic. Ile655Val polymorphism of HER-2 gene was associated with a statistically significantly increased risk of breast cancer all above in homozygotes for Val allele.

[Glomerulonephritides, histology forms, way of treatment and therapeutic effect in our patients]. / Glomerulonefritídy, histologické formy, spôsob terapie a terapeutická odozva u nasich pacientov.

Authors present a group of patients in the article who were monitored at a nephrology outpatient department of the University Hospital in Martin between years 1997 and 2001 for nephritic or nephrotic syndrome. Indications, contraindications and ways of histology examinations of kidneys in their department are discussed in the beginning of the work. Than prevalence of individual types of glomerulonephritides as well as way and length of therapy based on histology picture are discussed in the monitored group of patients. In the end results of therapeutic response are presented. Among other things, authors came to a conclusion that it is the least possible to manage the disease when histology results show sclerotisation of glomerules and in cases of frequent relapses in prolipherative forms of glomerulonephritides.

Labeling phosphorylated LHCII with microspheres for tracking studies and force measurements.

We report a method to selectively label phosphorylated, membrane proteins with microscopic particles. This technology is particularly useful in single particle studies. In such studies, the particles may serve to visualize protein diffusion and/or as 'handles' to study the force of interaction between the labeled protein and the membrane matrix. In the latter kind of experiments, forces can be applied and measured by calibrated optical tweezers. Optical tweezers were used in this work to test the strength of the particle labeling. Labeling a single protein with a particle produces a long-lived, distinct tag and is particularly useful for proteins in photosynthetic membranes, which contain endogenous fluorophores that would render single fluorescent proteins difficult to detect.

Increased platelet glycoprotein V levels in patients with coronary and peripheral atherosclerosis--the influence of aspirin and cigarette smoking.

As platelet hyperactivity is important in atherosclerosis and smoking, we hypothesized higher levels of soluble platelet membrane glycoprotein V (gpV) in 95 patients with peripheral artery disease (PAD) and 92 with coronary artery disease (CAD) compared to 99 healthy controls, and examined the effects of aspirin and of smoking two cigarettes on soluble gpV and platelet function. Soluble gpV (ELISA) was significantly raised in, but not between, both PAD and CAD patients, compared to controls (p < 0.05). In multivariate analysis, systolic blood pressure, smoking and atherosclerosis (all p < 0.01) were significant influences on soluble gpV in the whole study cohort. There was a weak correlation between soluble gpV and another platelet marker, soluble P selectin (p = 0.048). Acute smoking in 14 subjects increased platelet aggregability and beta-thromboglobulin, but not soluble gpV: there were no changes in 11 non-smokers. Five days consumption of aspirin (325 mg daily) by 14 subjects did not influence levels of soluble gpV. Our data indicate that soluble gpV may be a useful new marker of platelet activation in atherosclerosis, but may be influenced by smoking status and blood pressure.

[Latent autoimmune (type 1) diabetes mellitus in patients originally classified as type 2. Divergence of etiologic markers]. / Latentný autoimunitný (typ-1) diabetes mellitus u pacientov pôvodne klasifikovaných ako typ-2. Divergencia etiologických markerov.

BACKGROUND: To assess the prevalence of markers of autoimmune insulitis (AII) in patients classified originally as having Type-2 diabetes mellitus (Type-2 DM). 386 patients subdivided according to the BMI, C-peptide and type of treatment. METHODS AND RESULTS: Age, BMI, C-peptide, Glutamic acid decarboxylase autoantibodies (GADA), HLA-DR/,-DQ alleles. Prevalence of GADA varied from < 5% in obese patients with normal/increased C-peptide to > 30% in non-obese patients with low C-peptide. In majority of GADA positive patients, the Type-1 DM high-risk HLA-DRB1*, HLA-DQB1* alleles have been found. Among them HLA-DRB1*0302 and HLA-DRB1*0201 were more frequent than HLA-DRB1*040x and HL:A-DQB1*0302. CONCLUSIONS: Significant fraction of patients classified initially as Type-2 DM may have in fact Type-1 DM. Such patients can be recognized on the basis of assessment of serological (GADA) and immuno-genetical (HLA-DR/,-DQ alleles) markers. In some patients clinical, metabolic, immune, and immunogenetic markers may disagree. This divergence stresses multifactorial genesis of diabetes. Moreover, it can also suggest that both autoimmune insulitis and insulin resistance may coexist in parallel.

[A multicompartmental and multifactorial model of production of plasminogen activator inhibitor (PAI-1). II. Clinical study in patients with insulin resistance]. / Multikompartmentový a multifaktoriálny model produkcie inhibítora plazminogénového aktivátora (PAI-1). II. Klinické stúdie u chorých s inzulínovou rezistenciou.

PAI-1 levels are closely associated with insulin resistance (IR) syndrome, including patients with obesity, hypertension, hypertriglyceridaemia and type 2 diabetes mellitus (DM). Clinical studies demonstrated PAI-1 correlations with insulin (IRI), triglycerides (TG) and body mass index (BMI) values, but these relations have not been confirmed in all studies. In obesity PAI-1 levels correlate with IRI and BMI in the relation to increased adipocyte PAI-1 production, which is dependent on stimulative insulin action. In the case of endothelial hyperproduction in patients with IR elevated PAI-1 levels correlate with TG values. Insulin inhibits induced endothelial PAI-1 production. PAI-1 levels in patients with IR represent cumulative production in described tissues.

Chloride ion binding to bacteriorhodopsin at low pH: an infrared spectroscopic study.

Bacteriorhodopsin (bR) and halorhodopsin (hR) are light-induced ion pumps in the cell membrane of Halobacterium salinarium. Under normal conditions bR is an outward proton transporter, whereas hR is an inward Cl- transporter. There is strong evidence that at very low pH and in the presence of Cl-, bR transports Cl- ions into the cell, similarly to hR. The chloride pumping activity of bR is connected to the so-called acid purple state. To account for the observed effects in bR a tentative complex counterion was suggested for the protonated Schiff base of the retinal chromophore. It would consist of three charged residues: Asp-85, Asp-212, and Arg-82. This quadruplet (including the Schiff base) would also serve as a Cl- binding site at low pH. We used Fourier transform infrared difference spectroscopy to study the structural changes during the transitions between the normal, acid blue, and acid purple states. Asp-85 and Asp-212 were shown to participate in the transitions. During the normal-to-acid blue transition, Asp-85 protonates. When the pH is further lowered in the presence of Cl-, Cl- binds and Asp-212 also protonates. The binding of Cl- and the protonation of Asp-212 occur simultaneously, but take place only when Asp-85 is already protonated. It is suggested that HCl is taken up in undissociated form in exchange for a neutral water molecule.