Publications (14)38.1 Total impact
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Article: Application of different scaffolds for bladder wall regeneration: the bladder as a natural bioreactor.
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ABSTRACT: We investigated the potential of different scaffolds for in vivo construction of bladder muscular and urothelial wall. Bladder wall was used as a bioreactor to create a model of the natural environment for cellular interactions, growth, and differentiation. Forty rabbits were divided into 10 groups. Different scaffolds were implanted between bladder mucosa and seromuscular layer. Scaffolds used in each group were one layer or a three-layered combination of tissue-engineered pericardium (TEP), biofilm, and polyglycolic acid (PGA). In all groups, a biopsy of full thickness of bladder was dissected. Muscular and urothelial layers were separated and minced into small fragments. Fragments were seeded above the urothelial layer and urothelial fragments were placed on the scaffold under the seromuscular layer. One group served as control and no scaffold was inserted between the separated bladder layers. After 2 and 6 weeks, biopsies were performed for histologic examinations (trichrome, smooth muscle α-actin, and pancytokeratin AE1/AE3, CD34, CD31). Histopathological examinations showed granulomatous reaction and severe inflammation in biofilm-containing groups. Samples with TEP alone and with PGA-coated TEP as scaffolds revealed more organized bladder wall in two different layers with mature urothelial and smooth muscle cells. The number of CD34+ cells and CD31+ microvessels increased continuously during 6 weeks. Our results demonstrated the effective role of PGA-coated TEP as a potential scaffold for muscular and urothelial fragment seeding in bladder wall acting as a natural bioreactor. Biodegradable scaffolds could be helpful in association with acellular matrices to optimize the cell attachment and in vivo bladder wall construction.Tissue Engineering Part A 11/2011; 18(7-8):882-7. · 4.64 Impact Factor -
Article: Vesicoureteral reflux and primary bladder neck dysfunction in children: urodynamic evaluation and randomized, double-blind, clinical trial on effect of α-blocker therapy.
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ABSTRACT: Primary bladder neck dysfunction has been under diagnosed as a treatable cause of vesicoureteral reflux. We evaluated the effect of prazosin administration on vesicoureteral reflux resolution and urodynamic parameters in children with idiopathic primary reflux and primary bladder neck dysfunction. A total of 62 children (mean ± SD age 7.9 ± 2.4 years) with documented vesicoureteral reflux and urodynamics proved primary bladder neck dysfunction were randomized to receive either 0.025 mg/kg α-blocker (prazosin, 40 patients) or placebo (22) nightly for 1 week with a subsequent increase to 2 divided doses. Patients were followed for 12 months with clinical evaluation and uroflowmetry performed every 2 months, and each patient underwent complete urodynamic study at 6-month intervals. In the placebo group no uroflowmetry or urodynamic parameter changed significantly at 1-year followup. A 60% decrease in reflux grade was observed in the treatment group compared to 17% in the placebo group. Mean maximal detrusor pressure, post-void residual and opening time were significantly decreased in both followup sessions in the prazosin group (p <0.05). Average flow rate improved from 4.30 to 12.80 ml per second at 6 months and to 13.10 ml per second at 12 months (both p <0.05). Special attention should be given to secondary causes of vesicoureteral reflux (such as primary bladder neck dysfunction, an underdiagnosed entity in children), since conventional treatment will most likely fail if these conditions are not addressed promptly. In this study prazosin was effective therapy for children with vesicoureteral reflux and primary bladder neck dysfunction.The Journal of urology 11/2010; 184(5):2128-33. · 4.02 Impact Factor -
Article: Autografting of Renal Progenitor Cells Ameliorates Kidney Damage in Experimental Model of Pyelonephritis
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ABSTRACT: Current therapies for pyelonephritic renal damage have severe limitations; stem cells may offer an exciting potential in regenerating nephrology. We aimed to investigate the feasibility of direct intrarenal injection of autologous renal progenitor cells (RPCs; originated from epithelial cells in Bowman's capsule) in chronic pyelonephritis rat model. Twenty-seven rats were divided into three groups. The control group (GI, n = 3) underwent sham subcapsular injection of isotonic saline. Pyelonephritis was induced in the right kidney of the remaining 24 rats and isotonic saline (GII, n = 12) or labeled autologous RPCs, obtained from a biopsy of left kidney (GIII, n = 12), were injected into the subcapsular space 6 weeks later. At 7, 14, 28, and 60 days, dimercaptosuccinic acid scan was performed in three animals of each group at every interval and subsequently renal sections were obtained for the evaluation of tubular and glomerular regeneration and proliferation. Cell transplantation resulted in the reduction of tubular and glomerular atrophy after 2 weeks. The transplanted cells were observed in the reconstructed region of the kidneys as evidenced by the presence of fluorescently labeled cells both in tubules and glomeruli. We also observed significant decrease in interstitial fibrosis in the fourth week and there were higher amount of Ki-67-positive cells in GIII. Notably, the right renal tissue integrity was significantly improved in this group and revealed normal cortical function on day 60. Transplanting RPCs showed the potential for partial augmentation of kidney structure and function in pyelonephritis. Cellular repair was seen predominantly in the proximal tubule, the major site of injury in pyelonephritis. Our findings may pave the way toward the future regeneration of renal scarring of pyelonephritis in children.Cell Medicine. 12/2009; 1(3):115-122. -
Article: Biodegradable mini plate and screw: a secure method for internal fixation of symphysis pubis in animal model of pubic diastasis.
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ABSTRACT: To investigate short-term results of symphysis pubis reapproximation in a simulated animal model of pubic diastasis using biodegradable plate and screw, in comparison with animals with no fixation, in terms of inflammatory reaction, histologic changes, and three-dimensional pelvic bone CT (3D-CT) scan. Fifteen male goats were divided in 3 groups and underwent midline pubic symphysiotomy. In GI (n = 6), the pubes were brought together with sutures through the bone and fixed by placing a biodegradable plate and screws. In GII (n = 3), symphysis was brought together by inserting sutures. Animals' pubes received no fixation in GIII (n = 6). Three-dimensional CT scan was performed, after 3 months in GII, and at the third and sixth months in GI and GIII. Furthermore, tissue-implant interface was examined for tissue reaction and implant degradation. Pelvic bone 3D-CT scan in the biodegradable group revealed characteristic differences in pubic diastasis, iliac wing angle, and inter-triradiate distance compared with GII and GIII. Decreases of 21.8 +/- 0.7 mm, 7.28 +/- 0.4 mm, and 7.43 +/- 1.5 degrees were observed in pubic diastasis, inter-triradiate distance, and iliac wing angle, respectively, in biodegradable group in comparison with GIII in the sixth month. Neither clinical nor histologic evidence of inflammation due to insertion of biodegradable system was reported. Pubic bone adaptation with biodegradable plate and screws is a safe and reliable procedure for secure anterior pubic fixation in bladder exstrophy. Easy intraoperative handling, no long-term traction, biocompatibility, and no disturbance in skeletal growth are important prerequisites for introduction of this method of pubic approximation into clinical practice.Urology 12/2009; 75(3):676-81. · 2.43 Impact Factor -
Article: An antenatally diagnosed rhabdomyosarcoma of the bladder treated without extensive surgery.
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ABSTRACT: A female fetus was followed up from week 30 of gestation after bilateral hydroureteronephrosis and a large pelvic mass were detected on fetal imaging. At birth, the patient had high respiratory rate, a palpable bladder up to the umbilicus and a large pelvic mass, which compressed the anorectal wall. Fetal ultrasonography, fetal magnetic resonance urography, pelvic examination, full hematologic investigation, blood culture, abdominal and pelvic ultrasonography, voiding cystourethrography, abdominal and pelvic spiral CT, measurement of serum tumor marker levels, pathologic examination of the excised specimen, pelvic MRI. Botryoid subtype of rhabdomyosarcoma occupying most of the bladder and protruding through the urethra, with bilateral hydroureteronephrosis. Catheterization on the second day of life improved the patient's renal function, but her general condition remained unstable and surgical intervention was deferred. On the fourth day, gross hematuria and decreased urinary output were observed, which rapidly progressed to anuria, and she underwent transurethral resection of the protruding part of the tumor and bilateral cutaneous ureterostomy. Subsequently, she received chemotherapy with vincristine, actinomycin D and ifosfamide, and was followed up with serial imaging. At 18 months, MRI showed no evidence of residual tumor, and cystoscopic biopsy confirmed the absence of viable tumor; chemotherapy was stopped. She had no sign of recurrence 24 months after ending chemotherapy.Nature Reviews Urology 09/2009; 6(8):449-53. · 4.41 Impact Factor -
Article: Application of magnetic resonance urography in diagnosis of congenital urogenital anomalies in children.
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ABSTRACT: Magnetic resonance urography (MRU) has become a useful adjuvant in evaluating urogenital anomalies. In present study, we evaluated the ability of MRU in diagnosis of different congenital urogenital anomalies when the results of conventional imaging modalities were inconclusive. A total of 90 children were included in this series. The children were evaluated with T2-weighted and contrast-enhanced T1-weighted MRU sequences. The results were compared with findings obtained with ultrasonography, intravenous urography, renal nuclide scan, and voiding cystourethrography. MRU was requested in these children because conventional imaging modalities were equivocal or a co-existing urogenital anomaly was suspected. Only those cases that underwent surgery were included in this study and the surgical findings were set as the reference standard in statistical evaluation. The records of 61 boys with mean (range) age of 2.3 years (2 months-12 years) and 29 girls with mean (range) age of 3.3 years (3 months-12 years) were reviewed. The final diagnosis was ureteropelvic junction obstruction (n = 25), vesicoureteral junction obstruction (n = 16), ureterocele (n = 19), ectopic kidney (n = 11), posterior urethral valve (n = 17), and polycystic kidney (n = 2). The overall sensitivity of MRU, intravenous urography, renal nuclide scan, ultrasonography, and voiding cystourethrography in diagnosis of the aforementioned anomalies were 86, 63, 50, 44, and 41%, respectively. MRU was much more sensitive than other imaging modalities in diagnosis of end-ureteral dilation (100%) and ureterocele (89%). MRU provides a reliable noninvasive technique for imaging of the congenital anomalies in the urinary tract of children with T2-weighted MRU sequences providing unenhanced static-water images of the urinary tract as well as depicting adjacent soft-tissue lesions, and T1-weighted MRU technique imitating conventional intravenous urography. Both MRU sequences can be combined for a comprehensive examination of the urinary tract.Pediatric Surgery International 10/2008; 24(9):979-86. · 1.25 Impact Factor -
Article: Vitamin E administration at the onset of fever prevents renal scarring in acute pyelonephritis.
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ABSTRACT: We evaluated the protective effects of antioxidant at the onset of fever on renal damage in a rat model of acute pyelonephritis. Twenty rats were allocated to four groups. In groups 1 to 3, the animals were given direct inoculation of Escherichia coli into the right kidney, and group four served as control. All rats in groups 1 to 3 were given once-daily intraperitoneal injections of ceftriaxon for five consecutive days, beginning on the third day after inoculation. The animals' body temperatures were monitored; as soon as body temperature reaches 38 degrees C, the rats in group 2 were given allopurinol co-treatment, whereas, in group 3, vitamin E co-treatment was started at fever onset. Both kidneys were excised 6 weeks later, for the evaluation of histopathologic changes, apoptotic damage, and concentrations of transforming growth factor-beta (TGF-beta). Only minimal changes were found in control samples. Pathologic scores of inflammation and fibrosis in group 1 were higher than in the vitamin E and allopurinol groups (P < 0.05). Apoptosis index was also decreased in groups 2 and 3, compared to group 1 (P < 0.05). There was no significant difference in average TGF-beta levels between study groups. These findings suggest that administration of vitamin E or allopurinol following the onset of fever can reduce renal damage in pyelonephritis.Pediatric Nephrology 09/2008; 23(9):1503-10. · 2.52 Impact Factor -
Article: Transurethral autologous myoblast injection for treatment of urinary incontinence in children with classic bladder exstrophy.
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ABSTRACT: The application of autologous myoblasts is an area of active research that may represent an improved alternative for the treatment of urinary incontinence. In this study we investigated the effectiveness of autologous myoblast injection for the treatment of urinary incontinence in children with classic bladder exstrophy. Seven boys and 1 girl with persistent urinary incontinence were entered in the study. All children had undergone staged bladder repair and bladder neck reconstruction, and 5 patients had received 1 to 3 transurethral injections of bulking agent. Autologous myoblasts were isolated from abdominal muscle biopsy and cultured before endourethral injection. After the procedure patients underwent pelvic floor electrical stimulation and continued pelvic floor exercises that had been started at least 1 year before injection. The clinical outcomes (based on a 24-hour voiding diary), and cystometric and urodynamic studies were evaluated. Followup ranged from 12 to 18 months (average 15.3). There was a significant, time dependent improvement in urinary continence. At final followup all 7 boys (88% of patients) were socially dry (daytime dryness more than 3 hours), including 3 (38%) who were completely dry. Urodynamic studies revealed an increase in mean bladder capacity (p <0.001), detrusor leak point pressure (p <0.001) and average maximum urinary flow (p <0.01). All 7 boys (vs only 2 patients preoperatively) achieved normal voiding with demonstrable voiding detrusor contraction in the presence of a compliant stable bladder (p <0.05). Our results suggest that transurethral autologous myoblast injection is a valid option for the treatment of structural urinary incontinence in children with classic bladder exstrophy. However, favorable preoperative urodynamic profiles and postoperative pelvic floor electrical stimulation may have contributed to the outcome in this series.The Journal of urology 09/2008; 180(3):1098-105. · 4.02 Impact Factor -
Article: Comparison of magnetic resonance urography with ultrasound studies in detection of fetal urogenital anomalies.
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ABSTRACT: Prenatal ultrasonography detects the vast majority of urogenital anomalies, but in some cases the diagnosis remains in doubt. We assessed the potential of magnetic resonance urography (MRU) in the evaluation of different urogenital anomalies in fetuses when ultrasound study was equivocal. We retrospectively reviewed the medical records of 46 fetuses in whom the presence of urogenital anomalies was suspected at ultrasound studies, but remained inconclusive. Fetal MRU was performed within the same week as ultrasound studies. All patients underwent MRU, comprising overview, fast, thick-slab, heavily T2-weighted sequences, followed by focused, high-resolution T2-weighted sequences obtained in sagittal, axial and coronal planes. T1-weighted sequences were obtained in selected cases for assessment of the gastrointestinal tract. All MRU results were compared with ultrasound findings. Sensitivity of each imaging modality was estimated based on definite diagnoses made after birth or abortion. The mean (range) gestational age was 27 (18-36)weeks. The final diagnosis was ureteropelvic junction obstruction in 12, ureteral dilation (due to vesicoureteral junction obstruction) in five, ureterocele in five, posterior urethral valve in 16, multicystic dysplastic kidney in six, mesenteric cyst in one and abdominoscrotal hydrocele in one. Overall diagnostic sensitivity of fetal MRU was 96% compared to sonography with 58% sensitivity (p<0.05). Fetal MRU studies provided additional information to sonography in 17 (37%) cases, and were especially more sensitive in evaluation of ureteral anatomy. Fetal MRU can accurately diagnose a wide variety of urinary tract disorders and must be regarded as a valuable complementary tool to ultrasound in the assessment of the urinary system, particularly in cases of inconclusive ultrasound findings. The present study had a selection bias, as only fetuses with possible anomalies proposed by sonography were referred for MRU; however, this is the population that probably benefits most from MRU studies.Journal of pediatric urology 02/2008; 4(1):32-9. · 1.38 Impact Factor -
Article: Comparison of different techniques for hemostasis in a rabbit model of hypospadias repair.
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ABSTRACT: We compared the cellular and ultrastructural changes in the urethral wall following application of different hemostasis techniques in a rabbit model of hypospadias surgery. Rabbits were allocated into 5 groups. In group 1 animals underwent surgery without application of any hemostasis technique; in group 2 continuous penile tourniquet was applied for 30 minutes; in group 3, 3 intermittent periods of 10-minute penile tourniquet were applied with 3-minute intervals of reperfusion; in group 4 epinephrine was injected to maintain a 30-minute period of hemostasis; and in group 5 epinephrine vehicle (normal saline) was injected during the procedure. Early urothelium ultrastructural damage was studied 1 hour postoperatively with electron microscopy. Apoptotic damage and histopathological changes were determined 48 hours following the procedure. Late onset complications were assessed with retrograde urethrography and evaluation of tissue fibrosis at 8 weeks postoperatively. Electron microscope studies demonstrated urothelium ultrastructural damage in all hemostasis groups compared to controls. However, the changes were most prominent in group 4. The apoptosis index of urethral wall myocytes in groups 1 and 5 was significantly lower compared to other groups. Moreover, the number of apoptotic myocytes in epinephrine injected animals was significantly higher than in the continuous or intermittent tourniquet group as well as the normal saline injected group. At 8 weeks postoperatively collagen deposition in the urethral wall of rabbits in group 4 was higher than that in group 1. Although urethrocutaneous fistula was found in only 1 rabbit in group 4, the difference was not significant. Hemostasis techniques applied for maintaining a bloodless surgical field during hypospadias repair may lead to ischemia/reperfusion tissue damage in the urethral wall. Our findings suggest that epinephrine injection may result in more prominent cellular changes compared to tourniquet techniques. However, further experimental and human studies are required to draw a firm conclusion.The Journal of urology 01/2008; 178(6):2555-60. · 4.02 Impact Factor -
Article: The urethral valve of Guérin and lacuna magna: clinical presentations and urodynamic findings.
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ABSTRACT: We described the clinical presentations, radiological findings, urodynamic patterns and endoscopic management in a series of patients with symptomatic lacuna magna (LM). The medical records of 14 boys diagnosed as LM were reviewed, retrospectively. The presence of LM was first diagnosed based on clinical history, physical exam, and radiological findings; then confirmed by urethroscopy. Urodynamic study was performed in 10 boys before and after the procedure. Transurethral incision and fulguration of the valve was performed in all patients. The mean (range) age of patients was 3.1 years (6 months to 8 years). The boys presented with dysuria (n = 9), postvoid dribbling (n = 4), hematuria (n = 3), bloody spotting (n = 3), enuresis (n = 4), and glanular irritation and pain (n = 6). The post-operative period was uneventful in all patients. The symptoms were relieved and repeat radiological exam showed complete resolution of LM in all children by the 3rd post-surgical month. Before the procedure, main urodynamic abnormalities in children were high P(detmax) and detrusor instability that significantly improved within 3-6 months after treatment. Despite evidence suggesting that a LM is a frequent, normal anatomical variant, the valve may cause symptoms such as intermittent hematuria, dysuria, and bloody spotting of underwear. The lesion may be associated with obstructive urodynamic patterns in some children. Endoscopic treatment of patients effectively relieves the symptoms and corrects the urodynamic abnormalities.Pediatric Surgery International 10/2007; 23(9):873-8. · 1.25 Impact Factor -
Article: Myocyte apoptosis in primary obstructive megaureters: the role of decreased vascular and neural supply.
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ABSTRACT: We compared myocyte apoptosis index, microvessel density and nerve supply as well as muscular and collagen composition in the obstructed ureteral endings of children with primary obstructive megaureter and normal controls. Tissue specimens were obtained during ureteral reimplantation in 16 patients with primary obstructive megaureter. For the control group normal ureteral endings were taken at autopsy from 19 age and sex matched children. In all specimens we determined the myocyte apoptosis index, number of CD31 positive microvessels, alpha-actin positive muscular component and number of nerve terminals. The collagen fibers were also specifically stained. The myocyte apoptosis index was higher in obstructed vesicoureteral junctions (10.14%+/-1.03%) compared to controls (2.11%+/-0.21%, p<0.001). Mean number of vascular elements per microscopic field was lower in ureteral endings of patients with obstructive megaureter compared to controls (p<0.001). The number of nerve endings was also significantly lower in obstructed ureteral endings. There was a negative correlation between the number of microvessels and myocyte apoptosis index in both study groups. In obstructed megaureters the number of nerve endings was also negatively correlated with myocyte apoptosis index but positively correlated with the number of microvessels. In obstructed vesicoureteral junctions the proportion of muscular component was lower and the proportion of collagen fibers was higher compared to normal controls. Positive correlation was found between the myocyte apoptosis index and the percentage of collagenous component in both study groups. Congenital defective vascular development may result in myocyte apoptosis, and reduction of neural elements and muscular components in obstructed vesicoureteral junctions. Subsequent substitution of connective tissue may lead to functional obstruction in primary obstructive megaureter.The Journal of Urology 07/2007; 178(1):259-64; discussion 264. · 3.75 Impact Factor -
Article: Time-dependent neovasculogenesis and regeneration of different bladder wall components in the bladder acellular matrix graft in rats.
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ABSTRACT: To determine the time-dependent regeneration of different cellular components in the bladder acellular matrix graft (BAMG) and the involvement of hematopoietic stem cells in BAMG vascular regeneration. Thirty-three male Sprague Dawley rats underwent partial cystectomy and the acellular matrices were grafted to the remaining host bladder. At 4, 7, 14, 30, 60, 90, and 180 d after grafting, animals were sacrificed and their bladders were excised and paraffin-embedded. Tissue sections were stained for determination of CD3, CD20, CD34, CD31, CD68, smooth muscle cell (SMC) alpha-actin, and neurofilament protein as well as elastin fibers and collagen typing. Cystometric evaluation of grafted bladders was also performed 3 mo after procedure. In acellular matrices, there was no expression of cellular markers and type-1 collagen fibers were predominant. One month after surgery, all grafted matrices were completely lined with urothelium. Polymorphonuclear cells and lymphocytes densely infiltrated BAMG during the first 2 wk after grafting; however the inflammation resolved by the first post-surgical mo. CD34+ endothelial progenitor cells (EPCs) were found in all grafts 4 d after surgery. The number of CD34+ cells increased continuously and peaked 2 mo after grafting. The increment in number of CD31+ microvessels in grafted matrices followed that of CD34+ cells and reached 144.5% of control values at third post-surgical mo. The mean number of CD34+ and CD31+ cells returned to control ranges by 6 mo after grafting. Expression of SMC alpha-actin was first visualized on day 4 and alpha-actin intensity reached to control values 6 mo after grafting. Neural elements appeared 1 wk after grafting and just 60% of normal intensity was achieved by the sixth post-surgical mo; however complete nerve bundles were found in all grafted matrices after 1 mo. Cystometric studies revealed higher bladder capacity and compliance but lower maximum intravesical pressure in grafted bladders in comparison with controls, 3 mo after surgery. Our results demonstrate the effective cellular regeneration in BAMG and propose a considerable role for the CD34+ EPCs in the neo-vasculogenesis of the grafts.Journal of Surgical Research 06/2007; 139(2):189-202. · 2.25 Impact Factor -
Article: Protective effects of Swertia longifolia Boiss. and its active compound, swerchirin, on paracetamol-induced hepatotoxicity in mice.
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ABSTRACT: Aerial parts of Swertia longifolia Boiss. (Gentianaceae), which grows in the north of Iran, were screened for hepatoprotective activity against paracetamol (acetaminophen)-induced hepatotoxicity in Swiss mice. Pretreatment with total plant extract and swerchirin, the major component of the plant, significantly reduced the elevation of biochemical parameters, AST (aspartate aminotransferase), ALT (alanine aminotransferase) and ALP (alkaline phosphatase), the enzymes that are increased by liver damage (P < 0.001). Our results indicated that total plant extract and swerchirin were hepatoprotective in the range of 6-50 mg kg(-1) orally.Journal of Pharmacy and Pharmacology 02/2006; 58(2):277-80. · 2.17 Impact Factor
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2007
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Tehran University of Medical Sciences
- Department of Urology
Tehrān, Ostan-e Tehran, Iran
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