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The effect of short term hydrochlorothiazide therapy on urinary calcium excretion was compared to that of low calcium and a combined low calcium and low sodium diet in 30 children with postglomerular hematuria. On basal conditions 9... more
The effect of short term hydrochlorothiazide therapy on urinary calcium excretion was compared to that of low calcium and a combined low calcium and low sodium diet in 30 children with postglomerular hematuria. On basal conditions 9 children were normocalciuric, 11 had absorptive, 10 renal hypercalciuria. The effect of thiazide treatment on the haematuria was also evaluated. Thiazide revealed to be more effective in reducing calcium excretion than low calcium diet alone in all groups (p less than 0.001 in normocalciuria; p less than 0.01 in both hypercalciuric groups). Combined low calcium--low sodium diet and thiazide treatment were equally effective in reducing calcium excretion in the hypercalciuric groups. On the first 3 days of thiazide treatment a slight increase of hematuria was observed; in the following period a significant decrease in the occurrence (p less than 0.01 in both hypercalciuric groups) and degree (p less than 0.01 in absorptive; p less than 0.02 in renal hypercalciuria) of hematuria was noted. These data furnish further evidence on the relation of hypercalciuria and post-glomerular hematuria.
The recombination after flash photolysis of carbon monoxide (CO) to protoheme (PH) in glycerol: water is studied over ten decades in time (1 ps to 10 ms). The rebinding consists of an initial nonexponential geminate phase followed by a... more
The recombination after flash photolysis of carbon monoxide (CO) to protoheme (PH) in glycerol: water is studied over ten decades in time (1 ps to 10 ms). The rebinding consists of an initial nonexponential geminate phase followed by a slower exponential bimolecular phase. The entire time course of this reaction between 260 and 300 K can be explained in a unified way using a simple, analytically tractable diffusion model involving just three parameters: the relative diffusion constant, the contact radius, and the intrinsic rate of reaction at contact.
AbstractAbstract In this study we compared the effects of hypertension on chronic rejection in a rat model of renal transplantation utilizing genetically normotensive (BBOK) and spontaneously hypertensive rats (SHR). SHR received either a... more
AbstractAbstract In this study we compared the effects of hypertension on chronic rejection in a rat model of renal transplantation utilizing genetically normotensive (BBOK) and spontaneously hypertensive rats (SHR). SHR received either a BBOK (BBOK → SHR) or an SHR (SHR → SHR) kidney; normotensive isografts served as controls. Before transplantation, SHR recipients were treated with hydralazine (50 mg/kg per day). To prevent acute rejection, an anti-CD4 antibody (3 mg/kg per day for 3 weeks) in combination with cyclosporin A (3 mg/kg per day for 1 week) was given to all groups. Six weeks after transplantation, blood pressure was measured, and the kidneys removed for histological and immunohistological analysis. SHR → SHR developed a significantly higher blood pressure than BBOK → SHR. Blood pressure in BBOK → BBOK was significantly lower than in the other two groups. The degree of glomerulosclerosis was similarly increased in allografted (BBOK → SHR) and SHR → SHR kidneys as compared with the BBOK → BBOK kidneys (P < 0.05). Infiltration of ED-1+ monocyte/macrophages and OX 19 pan-T-cells was most pronounced in allografts (BBOK → SHR) and was also increased in SHR → SHR as compared with BBOK → BBOK. Our results indicate that hypertension accelerates the morphological and immunohistological changes characteristic of grafts undergoing chronic rejection. However, our findings support the hypothesis that alloantigen-dependentfactors are of greater important.
The inducible heat shock protein (HSP)72 plays a central role in antitumor immunomodulation. HSP72 expression was assessed on tumor samples of 43 patients with advanced and metastatic small cell lung cancer (SCLC) by immunohistochemistry... more
The inducible heat shock protein (HSP)72 plays a central role in antitumor immunomodulation. HSP72 expression was assessed on tumor samples of 43 patients with advanced and metastatic small cell lung cancer (SCLC) by immunohistochemistry and HSP72 [HSPA1B A(1267)G] polymorphism was determined. HSP72 expression of SCLC cells was significantly decreased in GG as compared to cells of AA or AG genotype patients, and was associated with significantly shorter survival in GG patients as compared to carriers of the A allele. Decreased HSP72 expression of SCLC cells associated with HSP72 GG genotype is a negative prognostic factor for survival in SCLC patients.
To evaluate the presence of autonomic neuropathy in childhood uremia, cardiovascular autonomic reflexes were examined in children with chronic renal failure. Cardiovascular autonomic reflexes of 10 uremic patients on chronic dialysis and... more
To evaluate the presence of autonomic neuropathy in childhood uremia, cardiovascular autonomic reflexes were examined in children with chronic renal failure. Cardiovascular autonomic reflexes of 10 uremic patients on chronic dialysis and 10 transplanted patients were compared to assess the effect of transplantation on autonomic neuropathy. Resting heart rate, heart rate changes induced by deep breathing, by Valsalva maneuver, and following standing up, and blood pressure change induced by handgrip test were examined. Of the 10 uremic children, 4 showed early involvement and 2 had definite involvement of autonomic neuropathy. Only 1 of the 10 transplanted patients showed early signs of autonomic neuropathy. Autonomic tests demonstrated predominantly parasympathetic dysfunction. In conclusion, cardiovascular autonomic neuropathy is not rare in children and adolescents and young adults with chronic renal failure. In contrast, the prevalence is very low in transplanted patients with similar uremic precedents. Efforts should be made to prevent or delay this uremia-related complication.
End-stage renal disease (ESRD) in children is associated with impaired neurocognitive function and development. However, data on factors associated with neurocognitive dysfunctions in children with kidney transplants are limited. We... more
End-stage renal disease (ESRD) in children is associated with impaired neurocognitive function and development. However, data on factors associated with neurocognitive dysfunctions in children with kidney transplants are limited. We conducted a cross-sectional analysis comparing cognitive functions (using the Woodcock-Johnson International Edition, WJIE) in 35 kidney transplant and 35 healthy control children. Data on laboratory measurements, comorbidities, and social characteristics were collected. Transplant children had significantly worse scores on the intelligence quotient (IQ) test compared with controls [Full Scale IQ score 85 (26) vs 107 (10), p &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001]. Lower maternal education level was significantly associated with lower WJIE cognitive test scores; however, no association was found between laboratory values and WJIE scores. Among children with kidney transplants, those with medical comorbid conditions had significantly lower Verbal Ability and Full Scale IQ scores. Earlier age of dialysis onset and a longer total time on dialysis (&amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;9 months) were associated with lower test scores. Age-standardized duration of hospitalization was inversely correlated with IQ (r = -0.46, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.01) and was an independent significant predictor (Beta = -0.38, p = 0.02) of IQ scores in transplanted children. Child kidney transplant recipients have neurocognitive function impairments that are associated with markers of socioeconomic status (SES) and factors related to disease severity.
Mechanisms of renal ischemia-reperfusion injury remain unresolved, and effective therapies are lacking. We previously showed that dehydroepiandrosterone protects against renal ischemia-reperfusion injury in male rats. Here, we... more
Mechanisms of renal ischemia-reperfusion injury remain unresolved, and effective therapies are lacking. We previously showed that dehydroepiandrosterone protects against renal ischemia-reperfusion injury in male rats. Here, we investigated the potential role ofσ1-receptor activation in mediating this protection. In rats, pretreatment with either dehydroepiandrosterone or fluvoxamine, a high-affinityσ1-receptor agonist, improved survival, renal function and structure, and the inflammatory response after sublethal renal ischemia-reperfusion injury. In human proximal tubular epithelial cells, stimulation by fluvoxamine or oxidative stress caused theσ1-receptor to translocate from the endoplasmic reticulum to the cytosol and nucleus. Fluvoxamine stimulation in these cells also activated nitric oxide production that was blocked byσ1-receptor knockdown or Akt inhibition. Similarly, in the postischemic rat kidney,σ1-receptor activation by fluvoxamine triggered the Akt-nitric oxide synthase...
Increased O-linked ß-N-acetylglucosamine glycosylation (O-GlcNAcylation) is a known contributor to diabetes; however its relevance in diabetic nephropathy is poorly elucidated. Here we studied the process and enzymes of O-GlcNAcylation... more
Increased O-linked ß-N-acetylglucosamine glycosylation (O-GlcNAcylation) is a known contributor to diabetes; however its relevance in diabetic nephropathy is poorly elucidated. Here we studied the process and enzymes of O-GlcNAcylation with a special emphasis on Akt-endothelial nitric oxide synthase (eNOS) and heat shock protein 72 (HSP72) signaling. Since tubular injury is the prominent site of diabetic nephropathy the effect of hyperglycemia was first measured in proximal tubular (HK-2) cells cultured in high glucose. The in vivo O-GlcNAcylation and protein levels of O-GlcNAc transferase (OGT), O-GlcNAcase (OGA), pAkt/Akt, peNOS/eNOS and HSP72 were assessed in streptozotocin-induced diabetic rat model. The effects of various renin-angiotensin-aldosterone system (RAAS)-inhibitors were also evaluated. In proximal tubular cells hyperglycemia-induced OGT expression led to increased O-GlcNAcylation which was followed by a compensatory increase of OGA. In parallel peNOS and pAkt levels decreased, while HSP72 increased. In diabetic rats elevated O-GlcNAcylation was accompanied by decreased OGT and OGA. RAAS-inhibitors ameliorated diabetes-induced kidney damage; prevented the elevation of O-GlcNAcylation and the decrement of pAkt, peNOS and HSP72. In conclusion hyperglycemia-induced elevation of O-GlcNAcylation contributes to the progression of DN via inhibition of Akt/eNOS phosphorylation and HSP72 induction. RAAS-blockers successfully inhibit this process suggesting a novel pathomechanism of their renoprotective action in the treatment of DN.
PurposeRetinopathy of prematurity (ROP), which is associated with abnormal retinal vessel development, is the leading cause of visual loss in preterm infants. Endothelial nitric oxide synthase (eNOS) is believed to play a central role in... more
PurposeRetinopathy of prematurity (ROP), which is associated with abnormal retinal vessel development, is the leading cause of visual loss in preterm infants. Endothelial nitric oxide synthase (eNOS) is believed to play a central role in both retinal angiogenesis and vasculogenesis. The aim of this study was to investigate functional genetic polymorphisms of eNOS in the pathogenesis of ROP.MethodseNOS T−786C and 27-bp repeat (eNOS, b: wild-type, a: mutant) genotypes were determined using allele-specific polymerase chain reaction in 105 low birth weight (LBW) preterm infants treated for ROP (treated group). A control group was set up and composed of 127 LBW infants with stage 1 or 2 ROP that did not not require treatment (untreated group).ResultsThe genotype distribution of eNOS 27-bp repeat polymorphism was found to significantly differ (p=0.015) between the two groups, whereas the genotype distribution of eNOS T−786C did not differ (p=0.984) between the groups. There was no difference in the distribution of either the “a” allele (p=0.153) nor of the C allele (p=0.867) in a groups comparison. Multiple logistic regression analysis revealed that male gender (p=0.046) and eNOS aa genotype (p=0.047 versus ab genotype and p=0.022 versus bb genotype) were significantly associated severe ROP that required treatment. The haplotype estimations based on the detected genotype distributions showed that the prevalence of aT and bT haplotypes was significantly increased in the group treated for ROP.ConclusionsFunctional eNOS 27-bp repeat polymorphism might be associated with the risk of severe ROP, however we found no association between the eNOS T−786C and the pathogenesis of ROP.
The Hu antigens are composed of a family of neuronal-specific, RNA-binding proteins encoded by at least three distinct genes. All three gene products, HuD, HuC/ple21, and Hel-N1, are human homologues of Elav, a Drosophila protein required... more
The Hu antigens are composed of a family of neuronal-specific, RNA-binding proteins encoded by at least three distinct genes. All three gene products, HuD, HuC/ple21, and Hel-N1, are human homologues of Elav, a Drosophila protein required for neuronal development and maintenance. Although the three proteins are very similar in structure, they are differentiated by alternative splicing of their mRNAs. We report here that the Hu antigens bind avidly to the AU-rich element resident in many mRNAs that regulate cell proliferation. This interaction suggests that the Hu antigens promote neuronal differentiation by suppressing the neuroblast cell cycle. Such a mechanism provides a plausible model for the role of the Hu antigens in tumorigenesis, neuronal differentiation, and paraneoplastic neurologic disorders.
Computer simulations of a simple model of a reversible diffusion-influenced reaction are used to test various approximate theoretical treatments. The model is a random walk in continuous time of N particles on a one-dimensional lattice.... more
Computer simulations of a simple model of a reversible diffusion-influenced reaction are used to test various approximate theoretical treatments. The model is a random walk in continuous time of N particles on a one-dimensional lattice. The particles can be trapped reversibly at the origin. They move independently, except that only one particle at a time can occupy the origin. The theory is formulated in general terms using master equations for the probability distribution of occupancy numbers of different lattice sites. The general theoretical problem is not solved, although some exact consequences are presented. Several approximation schemes are described and tested by comparison with the simulations.
Atypical hemolytic uremic syndrome (aHUS) is a rare disorder caused by dysregulation of the complement alternative pathway, and associated with mutations in genes of complement components and regulators. In the recent years several... more
Atypical hemolytic uremic syndrome (aHUS) is a rare disorder caused by dysregulation of the complement alternative pathway, and associated with mutations in genes of complement components and regulators. In the recent years several studies have been published describing these mutations, however, no data is available from the Central and Eastern European region. In this study we present a detailed genetic analysis of our 30 patients, hospitalized with the diagnosis of aHUS in the past 7 years. We analyzed the genetic variants of genes CFH, CFI, CD46, THBD, CFB and C3; furthermore the possible effect of mutations that may alter the function or level of factor H protein was also investigated. We identified 27 (12 novel and 15 previously described) potentially disease-causing mutations in the candidate genes in 23 patients. Genetic analysis of family members revealed that in most cases the disease develops in individuals with multiple genetic risk factors, which may explain the low penetrance of the mutations. Here we showed that two novel mutations (p.W198R, p.P1161T) and a previously reported one (p.R1215Q) in CFH caused impaired regulation as indicated by increased lysis in hemolytic test, while four CFH mutations (p.V609D, p.S722X, p.T1216del and p.C448Y) were associated with decreased factor H protein level in serum as determined by allele-specific immunoassay. These results further point to the necessity of complete genetic workup of patients with aHUS and to the importance of functional characterization of novel variations.
Depression is highly prevalent in diabetes (DM). Brain-derived neurotrophic factor (BDNF) which is mainly regulated by the endoplasmic reticulum chaperon sigma-1 receptor (S1R) plays a relevant role in the development of depression. We... more
Depression is highly prevalent in diabetes (DM). Brain-derived neurotrophic factor (BDNF) which is mainly regulated by the endoplasmic reticulum chaperon sigma-1 receptor (S1R) plays a relevant role in the development of depression. We studied the dose-dependent efficacy of S1R agonist fluvoxamine (FLU) in the prevention of DM-induced depression and investigated the significance of the S1R-BDNF pathway. We used streptozotocin to induce DM in adult male rats that were treated for 2 weeks p.o. with either different doses of FLU (2 or 20 mg/bwkg) or FLU + S1R antagonist NE100 (1 mg/bwkg) or vehicle. Healthy controls were also enrolled. Metabolic, behaviour, and neuroendocrine changes were determined, and S1R and BDNF levels were measured in the different brain regions. In DM rats, immobility time was increased, adrenal glands were enlarged, and thymuses were involuted. FLU in 20 mg/bwkg, but not in 2 mg/bwkg dosage, ameliorated depression-like behaviour. S1R and BDNF protein levels were decreased in DM, while FLU induced SIR-BDNF production. NE100 suspended all effects of FLU. We suggest that disturbed S1R-BDNF signaling in the brain plays a relevant role in DM-induced depression. The activation of this cascade serves as an additional target in the prevention of DM-associated depression.
C-reactive protein (CRP) is a well-known acute phase protein. The concentration of CRP in serum is increased in response to inflammatory stimuli. Increased levels serve to identify organic disease, to monitor disease activity and to... more
C-reactive protein (CRP) is a well-known acute phase protein. The concentration of CRP in serum is increased in response to inflammatory stimuli. Increased levels serve to identify organic disease, to monitor disease activity and to assist differential diagnosis. The aim of the authors&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; cross-sectional study was to determine CRP distribution of the healthy Hungarian population. 207 (79 male, 128 female; mean age: 4 +/- 68 years) healthy blood donors were enrolled for the study. The following parameters were registered: sex, age, body mass index, smoking habits, diabetes mellitus and blood pressure. Serum samples were assayed for total serum cholesterol, triglyceride, erythrocyte sedimentation rate, hemoglobin and for white blood cell count. CRP was measured by ultrasensitive, particle enhanced immunoturbidimetric assay. CRP levels were less than 5 mg/L in 81% of the blood donors. Mean level of CRP in the study population was 3.57 mg/L (SD +/- 5.33); the distribution was comparable to the data of already published studies. Comparing laboratory parameters and the risk status stratified according to CRP levels (less or more than 5 mg/L) significant differences were found in BMI (p = 0.0015), in total serum cholesterol (p = 0.0136), in triglyceride (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), in erythrocyte sedimentation rate (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001), in white blood cell (p = 0.0007) and granulocyte count (p = 0.0014). Significant correlation was found between age and the concentration CRP (r = 0.22; p = 0.0011). The CRP measurement by ultrasensitive method is suitable for cardiovascular risk estimation in apparently healthy men and women. Risk prediction adapted for the Hungarian situation may be stimulated by these data.
ABSTRACT
ABSTRACT
The distribution of inorganic phosphate ions in urine is calculated with known stability constants, measured pH and electrolyte concentrations. The distribution of phosphate ions in the urine of healthy children is considerably different... more
The distribution of inorganic phosphate ions in urine is calculated with known stability constants, measured pH and electrolyte concentrations. The distribution of phosphate ions in the urine of healthy children is considerably different from that of hypercalciuremic children. Before and after oral calcium-loading test, the most significant difference is in the molar fraction of CaHPO4.
Phosphate retention is commonly associated with chronic renal failure. Previously we presented a technique to calculate the distribution of phosphate constituents in body fluids. We studied it in pre- and postdialysis serum of 62... more
Phosphate retention is commonly associated with chronic renal failure. Previously we presented a technique to calculate the distribution of phosphate constituents in body fluids. We studied it in pre- and postdialysis serum of 62 patients. After hemodialysis, there was some decrease in the concentration of each constituent, with significant changes in the molar fraction of H2PO4- and CaHPO4. There is a significant negative correlation between the molecular mass of the constituent (X) and the effect of dialysis (Y): urea and H2PO4- 50%; NaHPO4-, HPO4(2-), and creatinine 41-44%; MgHPO4 39%, and CaHPO4 28%. Y = 69.7 - 0.26x, r = -0.833, p less than 0.001. This limited removal of CaHPO4 may contribute to the vascular calcification and peripheral ischemic necrosis of chronic uremic patients.

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