The rs1800471 Polymorphism of TGFB1 Gene, Serum TGF-Beta1 Level and Chronic Kidney Disease Progression.

The aim of the study was to investigate whether rs1800471 polymorphism in TGFB1 gene is associated with the development and progression of non-diabetic chronic kidney disease. Moreover, we examined the serum TGF-beta1 concentration and its association with that polymorphism and progression of the disease. We applied two different methodological approaches. Firstly, a family based study was carried out, comprised of 109 patients with non-diabetic chronic kidney disease and their 218 healthy parents, using the transmission/disequilibrium test. The rs1800471 polymorphism and serum TGF-beta1 level were determined in all subjects. Serum TGF-beta1 concentration was also measured in 40 healthy controls. Secondly, we performed a case-control orientated study to determine whether rs1800471 polymorphism and other factors influence the progression of renal impairment. We found no relationships between rs1800471 polymorphism allele transfer and the incidence or progression of non-diabetic chronic kidney disease. We found, however, that the serum TGF-beta1 was significantly higher in patients than in controls. In conclusion, rs1800471 polymorphism in TGFB1 gene does not have an impact on the development and progression of non-diabetic chronic kidney disease caused by primary glomerulopathy and chronic interstitial nephritis. The increased serum TGF-beta1 concentration in such patients suggests its role in the pathomechanism of the disease. Circulating TGF-beta1 level is determined in a multifactorial way, not by rs1800471 polymorphism in TGFB1 gene.

Phenotypic spectrum of epidermolysis bullosa associated with α6ß4 integrin mutations.

BACKGROUND: Integrin α6ß4 is a transmembrane receptor and a key component of the hemidesmosome anchoring complex. It is involved in cell-matrix adhesion and signalling in various tissues. Mutations in the ITGA6 and ITGB4 genes coding for α6ß4 integrin compromise dermal-epidermal adhesion and are associated with skin blistering and pyloric atresia (PA), a disorder known as epidermolysis bullosa with PA (EB-PA). OBJECTIVES: To elucidate the molecular pathology of skin fragility in eight cases, disclose the underlying ITGA6 and ITGB4 mutations and study genotype-phenotype correlations. METHODS: DNA was isolated from ethylenediaminetetraacetic acid-blood samples, and the coding exons and exon-intron boundaries of ITGA6 and ITGB4 were amplified by polymerase chain reaction (PCR), and directly sequenced. Skin samples were submitted to immunofluorescence mapping with antibodies to adhesion proteins of the dermal-epidermal junction. Primary keratinocytes were isolated, and used for RNA and protein extraction, reverse transcription PCR and immunoblotting. Ultrastructural analysis of the skin was performed in one patient. RESULTS: We disclose 10 novel mutations, one in ITGA6 and nine in ITGB4. Skin cleavage was either intraepidermal or junctional. Lethal outcome and PA correlated with loss-of-function mutations in two cases. Solely mild skin involvement was associated with deletion of the C-terminus of ß4 integrin. Combinations of missense, nonsense or frameshift mutations caused severe urinary tract involvement in addition to skin fragility in five cases. CONCLUSIONS: The present study reveals novel ITGA6 and ITGB4 gene mutations and supports previous reports showing that the phenotype may lack PA and be limited to skin and nail involvement. In four out of six cases of EB-PA, life expectancy was not impaired. A high frequency of urinary tract involvement was found in this study, and represented the main cause of morbidity. Low levels of ß4 integrin expression were compatible with hemidesmosomal integrity and a mild skin phenotype.

28 years of functioning of the ileal ureter - own experience and systematic review.

A SHORT INTRODUCTION: Irreversible ureteral damage is a rare and challenging problem for pediatric urologists. Ileal replacement has become one of the limited surgical options for ureteral reconstruction. Only a few papers have examined the results of the ileal ureter and renal function outcomes. Furthermore, there are even fewer papers showing patients with the intestinal ureter, which is used to drain urine from a solitary kidney in early childhood. AN OBJECTIVE: To perform a systematic review and analyze available cases of the long-term function of the "neoureter" and differences in the surgical approach. To present the case of a 29-year-old female with a history of ileal replacement of the ureter in a solitary kidney which was performed in this patient at the age of 14 months. STUDY DESIGN: PubMed and Scopus were used to search for eligible articles. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were strictly followed. Based on the titles, abstracts, and full-text reviews, 77 articles were analyzed, of which only 23 were directly related to pediatric cases of our interest. Medical records of the female patient, who has been treated in our center since 1991, were retrospectively described and reviewed. RESULTS: Of 23 papers, we identified 75 cases of children who underwent ureteral substitution. The outcomes of the procedure are satisfactory and acceptable. The presented case of the female patient shows a good therapeutic option. CONCLUSION: Ileal ureteral reconstruction is a safe and effective therapeutic option (even in a long-term follow-up). Despite many problems and complications, it allows preservation of renal and bladder function and social dryness.

[Resistance to therapy in primary nephrotic syndrome: effect of MDR1 gene activity]. / Odpornosc na leczenie w przebiegu pierwotnego zespolu nerczycowego: wplyw aktywnosci genu MDR1.

MDR1 gene encodes for a transmembranous glycoprotein, gp-170, which acts as a drug export pump and is also a cyclosporine(CsA)-binding protein. This study aimed at evaluating MDR1 expression in NS sensitive(S) and resistant(R) to therapy (steroids/S/, cyclophosphamide/C/, CsA) patients. Twenty six boys, 13 girls aged 3-8 years were included to the study. MDR1 was analysed using: 1) evaluation of gp-170 activity according to DiC2/3/ [3,3-Diethyloxa-carbocyanine Iodide] by means of flow cytometry and as 2) mRNA expression of MDR1 determined by RT-PCR. The analysis was performed in the lymphocyte subset CD4/CD45RA presenting suppressor-inducer activity. Negative control, Jurkat-T-cell line, not expressing the MDR1 phenotype, was transfected with viral expression vector containing a full-length cDNA for the human MDR1 gene. We found that: in SR-NS the high expression of MDR1 was associated mainly with the suppressor-inducer T-cells (CD45RA+CD4+) and was subsequently enhanced during an ineffective treatment with C and/or CsA. C-R-NS and CsA-R-NS were partially reversible by S- and R-Verapamil; this was in vitro confirmed by inhibition of export pump activity, gp-170. SS-NS, C-S-NS and CsA-S-NS presented the low expression and activity of MDR1 comparing to R-children (p < 0.001) and healthy controls (p < 0.00001). Resistance to therapy in NS patients seems to be resulted from the enhanced expression of MDR1 gene and subsequent high activity of export pump P-gp-170. Calcium channel blockers may reverse the MRD1-related resistance in the therapy of NS. Analysis of MDR1 may help to detect of suspected therapy resistance in NS.

[Studies on the behavior of some immunologic parameters after local, endoscopic autohemotherapy in children treated for vesicoureteral reflux]. / Badania nad zachowaniem sie okreslonych parametrów immunologicznych po miejscowej, endoskopowej autohemoterapii u dzieci leczonych z powodu odplywu pecherzowo-moczowodowego.

Evaluation of the effect of autologous blood injection into muscular layer on the immune system in children who were treated endoscopically for vesicoureteral reflux. There were 29 children examined after before and endoscopic autohemoinjection. The examination included determination of basic immunoglobulin levels in serum (IgA, IgG, IgM). Also the human lymphocyte subpopulations were determined. Initial and final values were compared, average values and standard deviations for respective age groups were determined. Autologous blood used for injections in endoscopic treatment of vesicoureteral reflux stimulates immune system, especially in young children.

[Comparative study of anatomical changes and function in kidneys after reconstructive surgery of the urinary tract using scintigraphic and other imaging examinations]. / Ocena porównawcza zmian anatomicznych i czynnosciowych nerek po operacjach rekonstrukcyjnych dróg moczowych w badaniu scyntygraficznym i innych badaniach obrazowych.

We performed a comparative evaluation of anatomical and functional changes in kidneys after urinary tract reconstructive procedures and in patients with history of urinary tract infections using renal scintigraphy and other imaging techniques. Statistically significant differences in the prevalence of pathological findings in imaging between these groups were shown. When children after the RVU are taken into account renal scintigraphy supplies us with objective and precise data about the renal scarring degree. In this group repeated renal scintigraphy should be warranted. After the reconstructive procedures due to hydronephrosis the images from ultrasonography and renal scintigraphy correlate well. Ultrasonography is a golden standard for screening these patients. Statistically significant higher degree of renal scarring in renal scintigraphy in patients after urinary tract infections without urinary tract defect proves the important role of infections in the pathogenesis of these changes. Children with recurrent symptomatic urinary tract infections should be submitted to renal scintigraphy imaging on regularly basis, as a risk group of higher chronic pyelonephritis prevalence.

[Pediatric differences in the activity of endothelin 1 in physiology and pathology]. / Odrebnosci pediatryczne w zachowaniu sie poziomu endoteliny 1 w stanach fizjologii i patologii.

In the paper authors gathered hitherto existing opinions concerning endothelin, its structure, biological role and mechanisms of action. A special attention was paid to children and the activity of endothelin in physiology and pathology in various stages of development.

[Diagnostic and therapeutic errors in the early period of anorexia nervosa in children]. / Bledy diagnostyczne i terapeutyczne we wczesnym okresie anorexia mentalis u dzieci.

In the years 1976-1988 in the Department of Paediatrics and Haematology, Silesian Medical Academy in Zabrze 22 children aged 12 to 17 years were diagnosed and treated for mental anorexia. The purpose of the analysis was evaluation of diagnostic and therapeutic errors made in primary health care units referring the patients to the Department. The most frequent errors were: misdiagnosis, symptomatic treatment and absence of psychotherapy.

[Complications of renal oligobiopsy with regard to highly selective renal artery embolization as a method treatment--case report]. / Powiklania oligobiopsji nerek z uwzglednieniem wysoce selektywnej embolizacji tetnicy nerkowej jako metody terapeutycznej--opis przypadku.

This report describes complications after renal oligobiopsy performed for verifying the diagnosis of glomerulonephritis (minimal change disease) in 16-year old boy treated since 2 years of age. Macroscopic hematuria with intracystic clotting and hematuria in lower renal pole occurred after the procedure. These complications were caused by arteriovenous fistula which was treated by high selective renal artery embolization.

[Toxic epidermal necrolysis (syndrome Lyell) versus Stevens-Johnson syndrome]. / Toksyczna nekroliza naskórka (zespól Lyella) a zespól Stevensa-Johnsona.

The paper presents new data concerning etiopathogenesis, clinical course and treatment of Lyell syndrome and Stevens-Johnson syndrome. An attempt of differential diagnosis involving etiological, clinical and histopathological differences was performed.

Nephrotic origin hyperlipidemia, relative reduction of vitamin E level and subsequent oxidative stress may promote atherosclerosis.

BACKGROUND: The relation between nephrotic syndrome and atherosclerosis has not yet been fully clarified, although the high levels of low-density lipoprotein cholesterol usually found in this syndrome may give rise to atherosclerosis. This study was intended to test the disturbances of antioxidant/oxidant status in children with nephrotic syndrome (NS). METHODS: 8 children in the active stage (AS) of NS, 7 children during the remission stage (REM) of NS, and 14 control subjects (CTRL) were enrolled into the study. The levels of plasma total cholesterol (TC), HDL-cholesterol (HDL-chol), LDL-cholesterol (LDL-chol), triglycerides (TG), vitamin E and 7-ketocholesterol (7KCH) before and after plasma saponification were measured. RESULTS: A significant increase in the concentrations of TC, LDL-chol, vitamin E and total 7KCH in AS patients have been found. These patients had also a lower vitamin E/LDL-chol ratio. These changes have not been observed in the remission stage of nephrotic syndrome. Higher amounts of electronegatively charged-(oxidized) LDL particles as well as different oxysterols in AS patients have also been demonstrated. CONCLUSION: The study revealed significant disturbances in oxidant status during NS leading to plasma accumulation of oxidized LDL and cholesterol oxidation products that exert cytotoxicity and are known to induce atherosclerosis. We suggest that this may constitute an important link between nephrotic syndrome and atherosclerosis.