Identification and characterization of aquaporin-2 water channel mutations causing nephrogenic diabetes insipidus with partial vasopressin response

Congenital nephrogenic diabetes insipidus (NDI) is a rare disease caused most often by mutations in the vasopressin V2 receptor (AVPR2). We studied a family which included a female patient with NDI with symptoms dating from infancy. The patient responded to large doses of desmopressin (dDAVP) which decreased urine volume from 10 to 4 I/day. Neither the parents nor the three sisters were polyuric. The patient was found to be a compound heterozygote for two novel recessive point mutations in the aquaporin-2 (AQP2) gene: L22V in exon 1 and C181W in exon 3. Residue Cys181 in AQP2 is the site for inhibition of water permeation by mercurial compounds and is located near to the NPA motif conserved in all aquaporins. Osmotic water permeability (Pf) in Xenopus oocytes injected with cRNA encoding C181W-AQP2 was not increased over water control, while expression of L22V cRNA increased the Pf to approximately 60% of that for wild-type AQP2. Co-injection of the mutant cRNAs with the wild-type cRNA did not affect the function of the wild-type AQP2. Immunolocalization of AQP2-transfected CHO cells showed that the C181W mutant had an endoplasmic reticulum-like intracellular distribution, whereas L22V and wild-type AQP2 showed endosome and plasma membrane staining. Water permeability assays showed a high Pf in cells expressing wild-type and L22V AQP2. This study indicates that AQP2 mutations can confer partially responsive NDI.      

ATG16L1 and NOD2 polymorphisms enhance phagocytosis in monocytes of Crohn’s disease patients

AIM:To investigate if the presence of relevant genetic polymorphisms has effect on the effectual clearance of bacteria by monocytes and granulocytes in patients with Crohn’s disease(CD).METHODS:In this study,we assessed the differential responses in phagocytosis by measuring the phagocytic activity and the percentage of active phagocytic monocytes and granulocytes in inflammatory bowel disease patients as well as healthy controls.As both autophagy related like 1(ATG16L1)and immunityrelated guanosine triphosphatase gene are autophagy genes associated with CD and more recently nucleo-tide-binding ligomerization domain-containing protein2(NOD2)has been identified as a potent inducer of autophagy we genotyped the patients for these variants and correlated this to the phagocytic reaction.The genotyping was done with restriction fragment length polymorphisms analysis and the phagocytosis was determined with the pHrodo?Escherichia coli Bioparticles Phagocytosis kit for flowcytometry.RESULTS:In this study,we demonstrate that analysis of the monocyte and granulocyte populations of patients with CD and ulcerative colitis showed a comparable phagocytic activity(ratio of mean fluorescence intensity)between the patient groups and the healthy controls.CD patients show a significantly higher phagocytic capacity(ratio mean percentage of phagocytic cells)compared to healthy controls(51.91%±2.85%vs 37.67%±7.06%,P=0.05).The extend of disease was not of influence.However,variants of ATG16L1(WT:2.03±0.19 vs homozygoot variant:4.38±0.37,P<0.009)as well as NOD2(C-ins)(heterozygous variant:42.08±2.94 vs homozygous variant:75.58±4.34(P=0.05)are associated with the phagocytic activity in patients with CD.CONCLUSION:Monocytes of CD patients show enhanced phagocytosis associated with the presence of ATG16L1 and NOD2 variants.This could be part of the pathophysiological mechanism resulting in the disease.     

Evaluation of Efficacy of Microwave Irradiation in Disinfecting Dental Gypsum Casts: An Ex Vivo Study

The aim of this study is to assess the efficacy of microwave irradiation in disinfecting gypsum casts and also to compare its efficacy with validated method of chemical disinfection. The present study is an ex vivo study conducted on a sample of five irreversible hydrocolloid impressions in vitro and on ten patients gypsum casts in vivo following standard impression techniques to check the efficacy of microwave oven irradiation and compare its efficacy with standard chemical method of disinfection. Results were analysed using Mann–Whitney test and Wilcoxon signed rank test. Untreated gypsum casts showed cfu/ml counts with a median log value of 6, while microwave-irradiated ones had median cfu/ml counts of 0. Casts poured from chemically disinfected impressions demonstrated cfu/ml counts with a median log value of 5. Microwave irradiation was found to be effective in disinfecting gypsum casts when compared to chemical disinfectant in disinfecting dental impressions.     

Lung cancer in patients over 70

The validity of the surgical treatment has been established by the investigation of immediate and late results of the treatment of 118 patients with lung cancer aged from 70 to 84. The postoperative lethality was 17,8%, the 5-year survival being 25,8% of the patients discharged from the hospital. No biologically specific features of lung carcinoma in patients older than 70 were found which could promise longer life of such patients without surgery.     

Substitution of a lengthy defect of the ureter for the vermiform appendix

The authors share their experiences with the substitution of the ureter for the appendix in three patients. In two of them the lengthy constriction of the pelvic portion of the ureter resulted from postirradiation alterations, in the other--from a gunshot wound of the lumbar area. The sufficient length and diameter of their appendix on a mobile mesentery allowed its being used for the substitution of the ureter. The results of operations were successful and without postoperative complications in all cases.     

Treatment of epithelial tumors of the upper urinary tracts

The authors present the results of different operative treatments of tumors of the upper urinary tracts (UUT). A total of 116 patients with UUT tumors were examined and treated from 1990 to 2002 (age 19-80 years, mean age 61.3+/- 1.3 years; males 82, females 34). Tumors of the renal pelvis and the ureter were detected in 76 (65.5%) and 40 (34.5%) patients, respectively (8.0 and 4.3% of a total number of patients with tumors of the kidneys and UUT). 107 (92.2%) patients were operated. Nephroureterectomy and ureterectomy with resection of the urinary bladder were performed in 73 (68.2%) patients, TUR of the urinary bladder wall, ureteral ostium with pelvic part of the ureter and nephroureterectomy (including endovideosurgery) in 22 (20.6%), nephroureterocystectomy in 4 (3.7%), resection of the pelvic ureter with Boari's operation in 5 (4.7%), nephroscopy, ureteroscopy with removal of urothelial tumor in 3 (2.8%) patients. Postoperative complications (most of them infectious-inflammatory) developed in 10 (9.3%) patients. Lethality was 0.9%. Tumor recurrences occurred in 27 (25.2%) patients within 5-year follow-up. 15 (14.0%) patients were reoperated. 5-year survival reached 67.0%. Conventional and radical method of treating patients with tumors of the renal pelvis and ureter is nephroureterectomy with urinary bladder resection and its modification. In invasion of the tumor in the muscular layer of the bladder wall surgery should be extended and supplemented with cystectomy. Conservative surgical interventions are indicated in tumors of the sole kidney, bilateral process, benign or surface tumor of the urothelium.     

Surgical treatment of long ureteral strictures

The paper reviews experience, specific features and outcomes of surgical treatment of 115 patients (60 males, 55 females) with long strictures and defects of the ureter. Renal and ureteral malformations, acquired strictures were detected in 14 (12.2%) and 101 (87.8%), respectively. The following reconstructive operations were made in 102 patients: ureterocalicoanastomosis by Neuvert (n = 3), specially designed original plastic repair of the lumbar ureter (n = 3), ureterolysis (n = 7), indirect ureterocystoanastomosis (n = 39), appendicoureteroplasty (n = 2), intestinal plastic reconstruction of the ureters and urinary bladder (n = 43), autotransplantation of the kidney (n = 3). Postoperative complications developed in 13 (11.3%) patients. No lethal outcomes occurred. Urinary tracts improved hemodynamics in all the patients. Recovery of ureteral passage in its long strictures necessitates atypical surgery. These were listed above. The proposed method of lumbar ureter replacement by mobilization and raising urinary bladder wall together with relevant ostium and pelvic ureter is perspective.