Molecular Characterization of Microrna Interference and Aristolochic Acid Intoxication Found in Upper Tract Urothelial Carcinoma in Patients with Balkan Endemic Nephropathy: A Systematic Review of the Current Literature.

The term "aristolochic acid nephropathy" (AAN) is used to include any form of toxic interstitial nephropathy that is caused either by ingestion of plants containing aristolochic acids (AA) or by the environmental contaminants in food such as in Balkan endemic nephropathy (BEN). Aristolochic acid (AA) intoxication is strongly associated with the development of upper tract urothelial carcinoma (UTUC); however, the underlying molecular mechanism remains to be defined. MicroRNAs (miRNA) regulate several biological processes, including cell proliferation, differentiation, and metabolism, acting as oncogenes or tumor suppressors. A unique miRNA expression profile suggested that miRNAs could function as regulators in UTUC developmental processes. This review aimed to summarize data available in the literature about underlying molecular mechanisms leading to the expression of miRNAs in AA-UTUC patients with BEN. Strong correlation in AA-UTUC has a distinctive gene alteration pattern, AL-DNA adducts, and a unique tumor protein (TP53) mutational spectrum AAG to TAG (A: T→T: A) transversion in codon 139 (Lys → Stop) of exon 5 activates the p53 tumor suppressor protein. Further, p53 protein is responsible not only for the expression of miRNAs but also acts as a target molecule for miRNAs and plays a crucial function in the AA-UTUC pathogenicity through activation of cyclin-dependent kinase (CyclinD1) and cyclin protein kinase 6(CDK6) to support cell cycle arrest. This study, proposed a molecular mechanism that represented a possible unique relationship between AA intoxication, miRNAs expression, and the progression of UTUC in patients with BEN.

Radiological and material characterization of high volume fly ash concrete.

The main goal of research presented in this paper was the material and radiological characterization of high volume fly ash concrete (HVFAC) in terms of determination of natural radionuclide content and radon emanation and exhalation coefficients. All concrete samples were made with a fly ash content between 50% and 70% of the total amount of cementitious materials from one coal burning power plant in Serbia. Physical (fresh and hardened concrete density) and mechanical properties (compressive strength, splitting tensile strength and modulus of elasticity) of concrete were tested. The radionuclide content (226Ra, 232Th and 40K) and radon massic exhalation of HVFAC samples were determined using gamma spectrometry. Determination of massic exhalation rates of HVFAC and its components using radon accumulation chamber techniques combined with a radon monitor was performed. The results show a beneficial effect of pozzolanic activity since the increase in fly ash content resulted in an increase in compressive strength of HVFAC by approximately 20% for the same mass of cement used in the mixtures. On the basis of the obtained radionuclide content of concrete components the I -indices of different HVFAC samples were calculated and compared with measured values (0.27-0.32), which were significantly below the recommended 1.0 index value. The prediction was relatively close to the measured values as the ratio between the calculated and measured I-index ranged between 0.89 and 1.14. Collected results of mechanical and radiological properties and performed calculations clearly prove that all 10 designed concretes with a certain type of fly ash are suitable for structural and non-structural applications both from a material and radiological point of view.

A rare case of isolated kidney cysticercosis.

A rare case of isolated kidney cysticercosis is presented. Clinical signs and diagnostic findings are unspecific. They are discussed and a conservative therapeutic approach is suggested.

Mechanical properties and tissue reinforcement of polypropylene grafts used for pelvic floor repair--an experimental study.

PURPOSE: Although grafts can be made from the same materials, the final weave of the product may play a role in the ultimate outcomes or complications. The aim of this experimental study is to evaluate and compare the mechanical properties of the meshes and their influence on biological characteristics as well. METHODS: Full-thickness abdominal wall defect with respect to the peritoneum was primary repaired in 144 male Wister rats using the overlay technique. Monofilament, multifilament and coated polypropylene grafts were used for the repairs. Graft shrinkage, thickness and tensile strength of the explants were analysed after 3 and 6 weeks. RESULTS: Monofilament grafts showed the highest shrinkage level of 11.97-18% during the investigated period. The thickness of monofilament explants increased gradually, with a maximum of 25.35% after 6 weeks. Multifilament and collagen explants did swell more rapidly in the third week, decreasing thereafter to 19.63-23.04% above the pre-implantation values after 6 weeks. The tensile strength showed a gradual increase over the course of the experiment in all groups. CONCLUSION: After graft stabilisation, all samples had similar strength, regardless of the significant differences in the pre-implantation values of graft strength.

Comparative environmental assessment of natural and recycled aggregate concrete.

Constant and rapid increase in construction and demolition (C&D) waste generation and consumption of natural aggregate for concrete production became one of the biggest environmental problems in the construction industry. Recycling of C&D waste represents one way to convert a waste product into a resource but the environment benefits through energy consumption, emissions and fallouts reductions are not certain. The main purpose of this study is to determine the potentials of recycled aggregate concrete (concrete made with recycled concrete aggregate) for structural applications and to compare the environmental impact of the production of two types of ready-mixed concrete: natural aggregate concrete (NAC) made entirely with river aggregate and recycled aggregate concrete (RAC) made with natural fine and recycled coarse aggregate. Based on the analysis of up-to-date experimental evidence, including own tests results, it is concluded that utilization of RAC for low-to-middle strength structural concrete and non-aggressive exposure conditions is technically feasible. The Life Cycle Assessment (LCA) is performed for raw material extraction and material production part of the concrete life cycle including transport. Assessment is based on local LCI data and on typical conditions in Serbia. Results of this specific case study show that impacts of aggregate and cement production phases are slightly larger for RAC than for NAC but the total environmental impacts depend on the natural and recycled aggregates transport distances and on transport types. Limit natural aggregate transport distances above which the environmental impacts of RAC can be equal or even lower than the impacts of NAC are calculated for the specific case study.

[Endometriosis in cesarean section surgical scar].

INTRODUCTION: Endometriosis is the presence of endometrial glands and stroma outside of uterine cavity. It may occur in the abdominal wall scar after the operation in which uterus was opened. In cesarean section scar it occurs in 0.4%. It is in 2/3 patients characterised with triad of: tumor, periodic pain associated with menses and history of cesarean section. The mechanism of endometriosis occuring in the cesarean scar is felt to be secondary to iatrogenic transplantation of endometrium or extrauterine decidual tissue into the incision during the cesarean section. CASE OUTLINE: Forty years old patient with tumor 4,5x4 cm that appeared in abdominal wall scar one year after second cesarean section, followed by periodic pain and macroscopic changes associated with menses. First diagnosis was granuloma in the surgical scar, but as she had periodic simptoms, diferential diagnosis was endometriosis. Hormonal therapy with contraceptiv drugs was ordered. As it was no improvement she was operated. The surgical excision of the tumor including fascia and muscle tissue was done. Sample revealed endometrium after histopathologic examination. Patient was complitely recoverd and without relepse of simptoms during followup to date. CONCLUSION: When there is a tumor in the cesarean section scar or scar after the operation in which uterus or ovarial tube was opened, followed with periodical pain and macroscopic changes associated with menses, endometriosis should be considered. Surgical excision of the tumor is sufficient and patohistological examination confirms diagnosis.

The history of urinary diversion.

The earliest attempt to divert urine flow from the ureters to the intestine, was performed in 1851 by John Simon. In the absence of antibiotics, ureterosigmoidostomy and its modifications during the 19th and early 20th century have been associated with high rate of surgical and metabolic complications. In 1910, Robert Coffey demonstrated a new method for ureterointestinal anastomosis, which renovated primary enthusiasm in ureterosigmoidostomy and it gained broad popularity during the next forty years. In 1950, Ferris and Odel reported 80% incidence of hyperchloremic metabolic acidosis following ureterosigmoidostomy. Based on further investigations by Lapides in 1951, Parsons, Powel and Pyrah in 1952, and Stamey in 1956, which clearly demonstrated that hyperchloremic metabolic acidosis is inevitable complication of ureterosigmoidostomy, this urinary diversion lost its popularity. In 1950's ileal conduit, popularized by Bricker, became the gold standard for the subsequent 35 years. Early attempts for continent urinary diversion occurred form 1888, by Guido Tizzoni and Alfonso Poggi, while the first reservoir-type ileal loop urinary diversion was performed by Cuneo in 1911. By better understanding of principles of detubularization, based on works of Kock and principles of clean intermittent catheterization, established by Lapides, interest in continent urinary diversion has increased. Up to date, various continent cutaneous stomal reservoirs, sigmoidorectal pouches and orthotopic bladder substitutes have been described. Regarding encouraging improvements in biocompatible materials, alloplastic bladder replacement could be the next step for the future in bladder replacement surgery.

Modified Mainz pouch II (Sigma Rectum pouch) urinary diversion: 12 years experience.

OBJECTIVE: To analyze the outcome of Mainz Pouch II urinary diversion related to complications and life quality. PATIENTS AND METHODS: From 1995 to 2006, a total of 67 patients (60 male and 7 female, mean age 58.4 years, range 48 to 70) who underwent modified ureterosigmoidostomy (Mainz Pouch II) procedure have been retrospectively analyzed. The mean follow-up was 18 (1 - 72) months and it was available for 56 patients (84%). Early and late postoperative complications as well as quality of life after surgery were analyzed. An clinical questionairre has been used for examination specific urinary diversion items. RESULTS: Early postoperative complications (<30 days) we-re detected in 9 patients (13%) and late complications (>30 days) in 19 patients (28%). Early complications consisted of urine leakage of moderate degree in 5 (7%) and ileus requiring surgical revision in 4 (6%) patients. The late complications included acute pyelonephritis in 12 patients (18%) and uretero-sigmoidal anastomotic site stenosis in 7 (11%). Ureterosigmoidal anastomotic site stenosis was detected in 7 patients with 7 renoureteric units (RU). In 4 RU, metal Strecker stent was successfully applied. In 3 RU, permanent nephrostomy catheter was applied. Oral alkalizing agents were applied in 22 patients (33%) due to metabolic acidosis. Two patients died due to severe acidosis. Continent rate was 96%. The mean voiding frequency during the day and night was 5.2+/-1.8 and 2.7+/-0.5, respectively. Global life quality was bad for 3 (8%), acceptable for 15 (38%) and good for 22 (54%) patients. CONCLUSION: The Mainz Pouch II urinary diversion is simple and safe procedure regarding complications rate, continence and quality of life. It is good alternative to other forms of continent urinary diversion. Patient selection and compliance following by meticulous follow-up are of utmost importance for successful operative outcome.

Symptoms and urodynamics after unsuccessful transurethral prostatectomy.

The aim of this study is to make symptomatic and urodynamic evaluation of the patients after unsuccessful primary transurethral prostatectomy (TURP). Symptom score was not significantly different before and after TURP. Voiding symptoms were improved but storage symptoms were impaired as well as a quality of life. Free flow was fairly improved after prostatectomy as well as obstruction grade. Detrusor instability and residual obstruction were the most frequently recognized factors for voiding disturbances. Secondary TURP, or bladder neck incision are indicated in only 25% of patients so it should be performed more cautiously.

Trapping of the double-J stent in the urinary tract eight years after extracorporeal shock wave lithotripsy.

We report a case of the 'forgotten' D-J stent in the urinary tract for eight years. In spite of years D-J stent spent in the urinary tract, and the great burden of the new-formed stones, residual renal function still exist. One year after treatment patient is stone free, infection free, with the mild renal failure.

beta2-microglobulin in patients with urothelial cancer.

beta2-Microglobulin (beta2-mi) is found on the surface of most nucleated cells, and in cancer patients its increased production and liberation into the blood has been described. We studied serum and urinary levels of beta2-mi in 29 patients with urinary bladder cancer (UBC) and 38 patients with upper-tract urothelial cancer (UTUC). A statistically significant (P < 0.01) increase in serum beta2-mi levels was demonstrated in patients with UTUC as compared with controls, whereas urinary excretion of beta2-mi was increased (P < 0.05) in both UTUC and bladder cancer patients. beta2-Mi production was studied in a 72-h culture of peripheral blood mononuclear cells (PBMC) under basal conditions and after stimulation with concanavalin A (Con A) or phytohemagglutinin (PHA). Basal production of beta2-mi by control unstimulated PBMC was 89.3 +/- 5; that of PHA-stimulated PBMC, 189 +/- 22 microg/10(6) cells; and that of Con A-stimulated PBMC, 210 +/- 32 microg/10(6) cells. beta2-Mi production by PBMC of cancer patients was not statistically significantly different from the control value, ruling out the possibility of an increased production by lymphocytes in these patients. Increased production of beta2-mi was demonstrated in 48-h ureteral and urinary bladder-cancer cell cultures, ranging from 440 to 2,600 microg. Serum beta2-mi was found to be increased to values of over 2.7 mg/l in 4 UBC and 12 UTUC patients with normal serum creatinine levels. Tumor surgery in those patients with increased serum beta2-mi resulted in normalization of the serum beta2-mi levels; urinary beta2-mi excretion was not significantly changed by surgery. This study establishes that increased serum levels of beta2-mi found in patients with urothelial cancer and normal glomerular function might be due to the increased production by tumor cells. However, activation of the immune response by mononuclear cells to the neoplasm cannot be excluded.

Tissue polypeptide antigen and carcinoembryonic antigen lack diagnostic accuracy in urothelial carcinoma.

Carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA) levels in serum and urine from 25 patients with bladder cancer and 42 patients with cancer of the renal pelvis/ureter have been evaluated as an aid for clinical diagnosis of urothelial cancer. The tumour CEA content varied markedly, from values obtained in normal urothelium up to 822 and 7306 ng/g wet tissue in cancer of the renal pelvis/ureter and bladder cancer, respectively. Serum and urine CEA levels were found not to correlate with the tumour CEA content. Serum CEA levels were found increased over 5 microg/L in up to 16% of bladder cancer patients, but only in 4.8% in renal pelvis/ureter cancer. Urine of cancer patients contained usually normal CEA levels. Increased serum TPA levels were found in 48% and 35.7% of patients with bladder cancer and cancer of renal pelvis/ureter, respectively. Urine TPA levels were significantly increased in both, patients with bladder cancer (p<0.001) and cancer of renal pelvis/ureter (p<0.01). The median values of urine TPA were 59, 1095 and 1325 U/L, in controls, patients with bladder cancer and cancer of renal pelvis/ureter, respectively. However, considering previously described increase of TPA in inflammatory diseases of urinary tract and in renal failure patients, results of urinary TPA obtained in the diagnostic workup of urothelial cancer should be cautiously interpreted. This study shows that serum and urine levels of CEA and TPA have no diagnostic accuracy required for clinical diagnosis of urothelial cancer.

Elevated tumour markers in patients with Balkan endemic nephropathy.

Balkan nephropathy (BEN) is commonly associated with urothelial cancer. Urothelial cancer is manifested in the advanced stage of disease. The aim of this study was to facilitate early detection of urothelial cancer in BEN patients and their family members living in an endemic region by using tumour markers, carcinoembryonic antigen (CEA) and tissue polypeptide antigen (TPA), and a putative marker, ferritin. Fifteen BEN patients with normal renal function, 17 with renal failure (BEN-RF), 13 healthy members of their families (HFM), 14 patients with glomerulonephritis (GN) and 12 healthy controls (C) were studied. Serum CEA levels in BEN patients were within normal limits, however, in BEN-RF patients they were significantly increased over HFM (p<0.05). Serum TPA levels in BEN and BEN-RF patients were significantly higher than in the C and HFM groups (p<0.05). Urinary CEA was not significantly different between the groups studied. Urinary TPA levels in HFM (median 125 U/l, BEN (236 U/l) and BEN-RF (275 U/l) were significantly increased over C (30 U/l), however, TPA levels were increased also in GN patients (437 U/l). None of the BEN patients studied developed urothelial cancer during the ten years' follow-up. Markedly elevated urinary TPA-like levels in all patients studied (HFM, BEN, BEN-RF, GN) suggest that urinary TPA may not be a reliable tumour marker. However, the clinical relevance of high TPA levels in BEN patients should be evaluated.

Serum levels of some acute phase proteins in kidney and urinary tract urothelial cancers.

Early diagnosis of kidney and urothelial cancer requires some new sensitive and specific methods. In this study the diagnostic use of serum alpha 1-acid glycoprotein (alpha 1-AG), coeruloplasmin, alpha 1-antitrypsin (alpha 1-AT), alpha 2-macroglobulin (alpha 2-MG) and albumin in patients with kidney, urinary bladder and upper tract urothelial cancer was evaluated. In kidney cancer patients the serum levels of alpha 1-AG, coeruloplasmin and alpha 1-AT were significantly increased over the controls (p < 0.001), however, albumin was decreased (p < 0.005). Sensitivity was relatively high for alpha 1-AG (85%), albumin (85%) and alpha 1-AT (77%). In patients with urinary tract urothelial cancer alpha 1-AG, alpha 1-AT and coeruloplasmin were also increased but not as much as in kidney cancer. Sensitivity of alpha 1-AG (63%), albumin (75%) and alpha 1-AT (66%) was also lower than in kidney cancer. This study has established the relative importance of alpha 1-AT and albumin determination in patients with kidney as well as with urothelial cancer.

Prediction of unfavourable symptomatic outcome of transurethral prostatectomy in patients with the relative indication for operation.

A total of 48 patients with BPH were studied before and after TURP. Initial diagnostic evaluation consisted of clinical examination, IPSS, uroflowmetry, cystometry, and "pressure-flow" study. Contribution of the important urodynamic measurements for the favourable symptomatic outcome was evaluated. There was significantly better result in patients with severe symptoms preoperatively (p = 0.03), low preoperative Qmax (p = 0.03), and presence of obstruction (p = 0.004), especially in patients with normal or strong detrusor contraction. Preoperative volume of residual urine as well as detrusor instability were not important for the symptomatic outcome. IPSS and uroflowmetry should not be treated as optional diagnostic tests. They improved the percentage of patients with an excellent symptomatic outcome from 62.5% to 90% (p = 0.04). "Pressure-flow" study is the reliable method for the achievement of excellent symptomatic outcome, but not significantly better than uroflowmetry and IPSS together. "Pressure-flow" study should be performed only in inconclusive preoperative cases.

[Idiopathic thrombosis of the renal vein]. / Idiopatska tromboza vene renalis.

Renal vein thrombosis (TVR) is not a common disease especially when is not associated with renal parenchymal nephropathy. TVR has no characteristic symptoms, so it is often late recognised. The main procedures for diagnosis of TVR are: echotomography, CT and phlebography. All these procedures, although very informative, have certain limits in the clinical use. Therapy of TVR trombolytic, anticoagulant or surgical: thrombectomy or nephrectomy. In cases where the underlying parenchymal disease exists, aggresive therapeutic approach is not recommended, but in acute idiopathic TVR immediate recanalisation of the renal vein is the most effective.

Cytokine levels in patients with urinary tract cancer.

It is known that cytokine exert cytotoxic effect on certain tumor cell lines, as well as that cytokines production might be influenced by tumor cells. Therefore, serum and urine levels of TNF and IL-1 were determined by RIA in 20 patients with upper urinary tract cancer, 26 with urinary bladder cancer, and compared with those of 52 healthy blood bank donors. Serum levels of TNF in cancer patients were found moderately increased, and those of IL-1 unchanged. Conversely, urinary excretion of TNF was shown decreased in both upper urinary tract and urinary bladder cancer patients, while IL-1 excretion was not significantly changed. Tumor grade was not found to influence serum and urine levels of the cytokines studied. Unstimulated and PHA- and Con A-stimulated production of TNF by peripheral blood mononuclear cells was within the normal range, suggesting that other sources such as tumor cells have to be considered for the increase in the serum level. Basal production of IL-1 was lowered in patients with upper urothelial cancer. Further investigation are required to ascertain and reveal the possible mechanism of the decreased urinary excretion associated with increased serum levels of TNF in urinary tract cancer.