ERBB4 gene polymorphisms and the risk of prostate cancer in a sample of Iranian Population.

Genetic polymorphisms in ERBB4 are thought to be associated with cancer susceptibility. In the present study, we aimed to assess the impact of ERBB4 rs12052398 T>C, rs13393577 A>G, rs13424871 A>T, rs16847082 A>G and rs6147150 (12-bp I/D) polymorphisms on risk of prostate cancer (PCa) in a sample of Iranian population. In a case-control study, we enrolled 169 patients with pathologically confirmed PCa and 182 subjects with benign prostatic hyperplasia (BPH). No significant association was found among ERBB4 polymorphisms and risk of PCa. Subjects carrying TT/AA/AA/AG/ID, TC/AA/AA/AA/II, TT/AA/AT/AA/II and TT/AA/AT/AG/ID genotypes are associated with a decreased risk of PCa. Our findings suggest that haplotypes CAAAI and TAAAD (rs12052398, rs13393577, rs13424871, rs16847082 and rs6147150I) of the ERBB4 polymorphisms are associated with a significantly lower risk of PCa. Further studies with a larger sample sizes and diverse ethnicities are necessary to verify our findings.

Association of polymorphisms in PRKCI gene and risk of prostate cancer in a sample of Iranian Population.

The atypical protein kinase C iota (aPKCι) is an oncoprotein encoded by the PRKCI gene. It has been reported to play multifunctional roles in cellular maintenance, cell proliferation, survival, differentiation and apoptosis. In the present study we aimed to assess the impact of PRKCI rs546950 C>T and rs4955720 C>A polymorphisms on prostate cancer (PCa) risk in a sample of Iranian population. This case-control study was done on 169 patients with pathologically confirmed PCa and 182 benign prostatic hyperplasia (BPH). The PCR-RFLP method was used for detection rs546950 C>T and rs4955720 C>A polymorphisms. Our findings showed that rs546950 polymorphism of PRKCI decreased the risk of PCa in codominant (OR=0.35, 95%CI=0.19-0.64, P<0.001, CT vs CC) and dominant (OR=0.39, 95%CI=0.22-0.69, P=0.001, CT+TT vs CC) inheritance model tested. No significant association was found between rs4955720 C>A polymorphism and PCa. In the combined analysis of these two variants subjects carrying CT/CC, CT/CA, TT/AA and CT/AA significantly decreased the risk of PCa in comparison with rs546950 CC/rs4955720 CC genotype. Haplotype analysis indicated that rs546950T/rs4955720A decreased the risk of PCa compared to CC. In conclusion, the results revealed that PRKCI rs546950 variant decreased the risk of PCa in an Iranian population. Further studies with larger sample sizes and different ethnicities are required to confirm our findings.

The dilemma of hyperoxia following positive pressure mechanical ventilation: role of iron and the benefit of iron chelation with deferasirox.

BACKGROUND AND OBJECTIVE: Increased oxidative stress in patients under treatment with high concentrations of oxygen (hyperoxia) is considered to be one of the major mechanisms of lung injury, which is thought among different mediators, transition metal ion, iron, by generation of very reactive free radicals which play an important role. Disruption of normal iron homeostasis has been reported in hyperoxic conditions. We hypothesized that chelation of iron can reduce hyperoxia-induced lung injury. METHODS: Mechanically ventilated patients, who received oxygen with FiO2 >0.5 for at least 3 days, underwent bronchoscopy before and 72 hours after receiving "Deferasirox". Oxidative injury index and iron homeostasis markers were measured in lavage fluid and plasma. RESULTS: In 12 patients, the concentrations of 8-isoprostane (p=0.005), 8-oxoguanine (p=0.04), carbonyl proteins (p=0.04)--as markers of oxidative stress--decreased significantly in lavage fluid after intervention. Levels of iron-related proteins, ferritin (p=0.04) and transferrin (p=0.005) also decreased significantly in lavage fluid. CONCLUSION: Deferasirox--as an iron chelator--decrease oxidative injury index in hyperoxic condition and it could be consider safe and beneficial agent, along with other supportive measures in hyperoxia-induced lung injury for better toleration of oxygen therapy.

Effect of warm ischemia on graft outcome in laparoscopic donor nephrectomy.

PURPOSE: To assess the impact of warm ischemia time (WIT) on delayed graft function (DGF), graft loss, and graft function in laparoscopic donor nephrectomy (LDN). PATIENTS AND METHODS: We prospectively studied 100 kidney recipients from LDN donors from 2001 to 2003. For comparison of graft outcome with different extents of WIT, recipients were divided into three groups: group A received kidneys having 4 to 6 minutes, group B kidneys having >6 to 10 minutes, and group C kidneys having >10 minutes of WIT. The median follow-up was 415 days (range 11-791) days. RESULTS: The mean kidney WIT was 8.7 minutes (range 4-17 minutes). Graft outcome (DGF, graft loss, and median serum creatinine) was not significantly different in the three groups. CONCLUSIONS: Different extents of WIT in LDN, within the range of our study, were not associated with an adverse outcome in kidney transplantation.

The stem cell self-renewal gene, Musashi 1, is highly expressed in tumor and non-tumor samples of human bladder.

CONTEXT: The stem cell model for cancer assumes that a key event in tumorigenesis is the deregulation of genes involved in the regulation of stem cell self-renewal. The Musashi family is an evolutionarily conserved group of neural RNA-binding proteins. In mammals, the family consists of two individual genes, Musashi 1 (MSI1) and MSI2, encoding the Musashi 1 and Musashi 2 proteins. Musashi 1 is involved in the regulation of self-renewal of stem cells. Recently, its over-expression has also been reported in a variety of human tumors. AIMS: To investigate a potential expression of the stem cell self-renewal gene, Musashi 1, in human bladder cancer, we examined its gene expression in a series of tumor and non-tumor tissue samples of bladder. MATERIALS AND METHODS: Relative expression of MSI1 was determined by the real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) in 70 surgical samples of bladder. RESULTS: Using specific primers for MSI1 and TBP (as an internal control) for qRT-PCR technique, we found a relatively high expression level of MSI1 in all examined tumor and non-tumor bladder tissue specimens. However, our data did not show any correlation between the level of gene expression and tumor/non-tumor states of the samples (P>0.05). CONCLUSIONS: All together, our data demonstrated that Musashi 1 is highly and un-differentially expressed in both examined tumoral and apparently normal bladder tissues.

Preparation and evaluation of sustained release calcium alginate beads and matrix tablets of acetazolamide.

The aim of this study was to develop sustained release dosage forms of acetazolamide (ACZ) preparing its calcium alginate beads and matrix tablets. ACZ was incorporated into calcium alginate beads using microencapsulation method. Two methods were applied to prolong ACZ release rate. In the first method, the drug was incorporated into calcium alginate beads either alone or with various polymers in internal phase. The second method involved the preparation of matrix tablet from the beads benefiting direct compression method with or without various polymers in external phase. The release rate of these prepared formulations and an innovator's sustained-release capsule (Diamox®) were assessed. In-vitro dissolution studies revealed that the matrix tablets prepared by the second method containing NaCMC could sustain ACZ release properly and the drug released until 9 h. It was also found that several parameters such as concentration of sodium alginate, calcium chloride and ACZ; type and concentration of polymers; syringe needle size as well as distance between needle tip and surface of the calcium chloride could affect the properties of beads, matrix tablets and subsequently release profile. Preparation of polymer free beads, incorporation of polymers in internal phase of the beads and direct compression of the beads did not give sustained release property. Whereas, incorporation of NaCMC in the external phase of the beads in matrix tablets or in combination with alginate powder in directly compressed conventional tablets could produce dosage form with sustained release property similar to reference formulation.

Laparoscopic partial nephrectomy for tumours >4 cm compared with smaller tumours: perioperative results.

OBJECTIVE: The use of laparoscopic partial nephrectomy (LPN) in patients with tumours >4 cm remains to be further evaluated. We report our experience with LPN in tumours >4 cm compared with tumours ≤4 cm. MATERIALS AND METHODS: This is a retrospective study of data from all LPN patients operated from 2003 to 2008. Inclusion criteria were a single organ confined contrast enhancing mass/Bosniac III-IV cyst. Hospital admission records were used to extract operative and follow-up data. Patients were grouped into group A: ≤4 cm (32 patients, 53% of total), and group B: >4 cm (28 patients, 47% of total). RESULTS: A total of 60 patients (mean ± SD age, 47.4 ± 13.4 years; M/F, 36/24) were included. Mean ± SD tumour size was 31.5 ± 7.3 mm and 51.6 ± 10.9 mm in groups A and B, respectively. (P < 0.001) Malignant pathology was present in 22 (69%) and 16 patients (57%) in groups A and B, respectively. (P > 0.05) There was no statistically significant difference in age, gender, pre-operative creatinine, estimated glomerular filtration rate (eGFR), and other investigated pre-operative characteristics between study groups. (all P > 0.05) Nor any difference was observed regarding operative and pathologic (warm ischaemia time, operation duration, transfusion, positive margins, and malignant histology) as well as post-operative variables (re-hospitalization, post-operative complications, hospital stay, or eGFR changes). CONCLUSION: The results of this study supports the feasibility and comparability of operative and post-operative early complications for LPN when applied to tumours >4 cm in selected patients compared with tumours ≤4 cm.

The indirect role of site distribution in high-grade dysplasia in adenomatous colorectal polyps.

BACKGROUND: The appropriate application of Endoscopic modalities for polypectomy depends on the likelihood that the adenoma in question harbors invasive cancer. While prior studies have evaluated polyp size and morphology in assessing the risk of malignancy, in recent decay some authorities have paid more attention to dysplasia. All in all, the relative risk of cancer based on polyp distribution in correlation with dysplasia has not been statistically studied which is done in our study. METHODS AND MATERIALS: Between June 2001 and March 2004, the distribution of 130 adenomatous polyps was compared with synchronous invasive or in situ cancer. Factors such as Patient age, Patients gender, location of lesion, size of polyp, histological subtype of adenoma on biopsy, degree of dysplasia, synchronous cancer, color of polyp, and number of polyps were included in the data collection. RESULTS: Multivariate logistic regression test was used to evaluate the association between malignancy and various clinical variables. It revealed histological subtype, high grade of dysplasia and size to be independent predictor of malignancy. However; left-sided location and histological subtype to be independent risk factor for high-grade dysplasia. CONCLUSION: Lesions greater than 1 cm in diameter with high-grade dysplasia after splenic flexure should be managed as presumptive malignancies with segmental colon resection. In intermediate-risk lesions the physician should decide individually.

CatSper gene expression in postnatal development of mouse testis and in subfertile men with deficient sperm motility.

BACKGROUND: The search for Ca2+ channels residing in sperm has led to the recent cloning and characterization of a novel gene, named CatSper, which codes for a unique Ca2+ channel expressed exclusively in the testis. It plays an essential role in sperm motility, penetration into the oocyte, and ultimately in male fertility. In this study, we assessed the temporal profile of CatSper gene expression during mouse testis development and performed a semi-quantitative evaluation of expression levels in a group of subfertile men which lack sperm motility. METHODS: A small piece of testicular tissue obtained by either multi-site testicular biopsy or orchidectomy was used for semi-quantitative RT-PCR of CatSper and beta2-microglobulin (beta2m, as an internal control) genes. RESULTS: Our results reveal that: (i) the expression of mouse CatSper is developmentally regulated with a direct correlation between CatSper expression and mouse sexual maturation. CatSper gene expression is first detected at 3 weeks of age and coincides with the appearance of round spermatids in the developing mouse testis. (ii) There is a significant reduction in the level of CatSper gene expression (up to 3.5-fold difference) among patients which lack sperm motility as compared with patients whose infertility cannot be ascribed to a deficiency in motility (used as a control). CONCLUSIONS: The data obtained in this study support a potential role for CatSper in sperm motility and fertility in mouse and human. CatSper is therefore implicated as a potential target to explore the molecular mechanisms of male infertility.

PCNL in the management of lower pole caliceal calculi.

INTRODUCTION: Several therapeutic methods are used in the management of lower pole caliceal calculi. This survey has been conducted to evaluate the safety and efficacy of percutaneous nephrolithotomy in the management of lower pole calculi. MATERIALS AND METHODS: Fifty-five patients, 43 males and 12 females with a mean age of 41.5 (range 11 to 75) years, who had suffered from lower pole caliceal calculi and treated by standard percutaneous nephrolithotomy (PCNL) between 1997 and 2001, were enrolled in this study. The stones were classified as follows: small (less than 25 mm), intermediate (25 to 34 mm) and large (more than 35 mm). Mean follow-up was 6.2 months (range 2 weeks to 34 months). RESULTS: The stones were completely extracted by one session PCNL in 43 patients (79%). Repeat PCNL was needed in one patient and another method was used for stone extraction in another patient. Regarding the size of stone, 88%, 79%, and 74% of small, intermediate, and large stones were completely extracted, respectively. No major complication was noted. CONCLUSION: PCNL has high success rate in patients with stones larger than 2 cm and its morbidity would be low, provided that it is performed by skilled surgeons.

A comparison between laparoscopic and open pyeloplasty in patients with ureteropelvic junction obstruction.

INTRODUCTION: Our aim was to compare clinical and radiological outcomes, complications, and hospital stay in laparoscopic and open pyeloplasty. MATERIALS AND METHODS: From February 2002 to February 2003, 69 patients with ureteropelvic junction obstruction (UPJO) were assigned into two groups. Thirty-seven patients underwent transperitoneal laparoscopic pyeloplasty and 32 underwent open surgical pyeloplasty. Clinical symptoms were assessed before and after surgery, subjectively. Radiological assessment was also done three months postoperatively. RESULTS: Mean operative time was 3.2 hours and 2.2 hours in laparoscopic and open pyeloplasty groups, respectively. Intraoperative bleeding was trivial in both groups and no complication or conversion to open surgery occurred. Postoperative complication rates were 24% and 6% in laparoscopic and open pyeloplasty groups, respectively. Mean hospital stay was similar (6.2 days) in the two groups. Mean follow-up was 16.5 months versus 11.4 months. Clinical and radiological success rates were 89% and 83.8% for laparoscopy group versus 96.5% and 87% for open pyeloplasty group. Due to recurrence of stricture, repeated surgery was performed in 4 patients of laparoscopy and 1 of open pyeloplasty groups. CONCLUSION: Laparoscopic pyeloplasty is a less invasive method with less pain, cosmetic advantages, no long incision, and outcome comparable with open surgery. Hospital stay is also not longer than that in open surgeries. Hence, laparoscopic pyeloplasty can be a substitute for skilled surgeons.