Hisham A. Mosli

Vesicoureteral Reflux in Patients with Double Pigtail Stents

A prospective study of 30 renal units in 27 patients with double pigtail ureteral stents seen at our hospital was done. The aim of the study was to confirm or rule out the occurrence of vesicoureteral reflux radiologically, and to define its degree in stented patients. During the filling phase of the cystourethrogram, reflux occurred in 19 of the 30 renal units (63%). Of those 19 renal units the reflux was grade 1/4 in 15 (79%), while in 4 (21%) it was of higher grades (2 to 3/4). During the voiding phase of the cystourethrogram reflux was observed in 24 of 30 renal units (80%). Of those 24 renal units reflux was of high grade (2 to 4/4) in 20 (83%), while it was low grade (1/4) in 4 (17%). In the presence of a double pigtail stent the ureteral peristaltic waves were sluggish and averaged 1 to 2 waves per minute in the 15 patients observed fluoroscopically for 1 minute after voiding. We conclude that in the majority of patients with double pigtail ureteral stents vesicoureteral reflux occurs at a low grade during vesical filling and at a high grade during voiding. Also, the stents adversely affect the ureteral peristaltic activities.

Caffeic acid phenethyl ester synergistically enhances docetaxel and paclitaxel cytotoxicity in prostate cancer cells

Evidence is growing for the beneficial role of selective estrogen receptor modulators (SERM) in prostate diseases. Caffeic acid phenethyl ester (CAPE) is a promising component of propolis that possesses SERM activity. This study aimed at investigating the modulatory impact of CAPE on docetaxel (DOC) and paclitaxel (PTX) cytotoxicity in prostate cancer cells and exploring the possible underlying mechanisms for this chemomodulation. CAPE significantly increased DOC and PTX potency in PC‐3, DU‐145 and LNCaP prostate cancer cells. Combination index calculations showed synergistic interaction of CAPE/DOC and CAPE/PTX cotreatments in all the tested cell lines. Subsequent mechanistic studies in PC‐3 cells indicated that cyclin D1 and c‐myc were significantly reduced in the combined treatment groups with concurrent increase in p27kip. DNA‐ploidy analysis indicated a significant increase in the percentage of cells in pre‐G1 in CAPE/DOC and CAPE/PTX cotreatments. Decreased Bcl‐2/Bax ratio together with increased caspase‐3 activity and protein abundance were observed in the same groups. Estrogen receptor‐β (ER‐β) and its downstream tumor suppressor forkhead box O1 levels were significantly elevated in CAPE and combination groups compared to DOC or PTX‐alone. ER‐α and insulin‐like growth factor‐1 receptor protein abundance were reduced in the same groups. CAPE significantly reduced AKT, ERK and ER‐α (Ser‐167) phosphorylation in PC‐3 cells. CAPE‐induced inhibition of AKT phosphorylation was more prominent (1.7‐folds higher) in cells expressing ER‐α such as PC‐3 compared to LNCaP. In conclusion, CAPE enhances the antiproliferative and cytotoxic effects of DOC and PTX in prostate cancer cells. This can be, at least partly, attributed to CAPE augmentation of DOC and PTX proapoptotic effects in addition to CAPE‐induced alterations in ER‐α and ER‐β abundance.

Role of the phytoestrogenic, pro-apoptotic and anti-oxidative properties of silymarin in inhibiting experimental benign prostatic hyperplasia in rats.

Androgen and estrogen play an important role in the pathogenesis of benign prostatic hyperplasia (BPH). Estrogen exerts its action through two distinct estrogen receptors (ERs) either ER-α or ER-β. The phytoestrogenic property of silymarin (SIL) has been previously characterized. Thus, this study examined the protective effect of SIL against testosterone-induced BPH in rats. In an initial dose-response study, SIL in a dose of 50mg/kg was the most effective in preventing the rise in prostate weight, prostate weight/body weight ratio and histopathologic changes induced by testosterone. Testosterone significantly decreased ER-β and increased ER-α and AR expressions as compared to the control group and these effects were significantly ameliorated by SIL. Furthermore, SIL significantly protected against testosterone-provoked decline in mRNA expression of P21(WAF1/Cip1) and Bax/Bcl-xl ratio as well as caspase-3 activity. SIL minimized the number of proliferating cell nuclear antigen (PCNA) positive cells as compared to testosterone-treated group. Moreover, SIL significantly blunted the inducible NF-κB expression and restored the oxidative status to within normal values in the prostatic tissues. Collectively these findings elucidate the effectiveness of SIL in preventing testosterone-induced BPH in rats. This could be attributed, at least partly, to its phytoestrogenic, pro-apoptotic and anti-oxidative properties.

Anti-inflammatory and antiproliferative activities of date palm pollen (Phoenix dactylifera) on experimentally-induced atypical prostatic hyperplasia in rats

BackgroundAtypical prostatic hyperplasia (APH) is a pseudoneoplastic lesion that can mimic prostate adenocarcinoma because of its cytologic and architectural features. Suspension of date palm pollen (DPP) is an herbal mixture that is widely used in folk medicine for male infertility. The aim of the present study was to evaluate the effect of DPP suspension and extract on APH-induced rats.MethodsAPH was induced in adult castrated Wistar rats by both s.c. injection of testosterone (0.5 mg/rat/day) and smearing citral on shaved skin once every 3 days for 30 days. Saw palmetto (100mg/kg), DPP suspension (250, 500 and 1000 mg/kg), and lyophilized DPP extract (150,300 and 600 mg/kg) were given orally daily for 30 days. All medications were started 7 days after castration and along with testosterone and citral.ResultsThe histopathological feature in APH-induced prostate rats showed evidence of hyperplasia and inflammation. Immunohistochemical examination revealed that the expressions of IL-6, IL-8, TNF-α, IGF-1 and clusterin were increased, while the expression of TGF-β1 was decreased that correlates with presence of inflammation. Moreover, histopathological examination revealed increased cellular proliferation and reduced apoptosis in ventral prostate. Both saw palmetto and DPP treatment has ameliorated these histopathological and immunohistochemical changes in APH-induced rats. These improvements were not associated with reduction in the prostatic weight that may be attributed to the persistence of edema.ConclusionDPP may have a potential protective effect in APH-induced Wistar rats through modulation of cytokine expression and/or upregulation of their autocrine/paracrine receptors.

In situ extracorporeal shock wave lithotripsy (ESWL) for the management of primary ureteric calculi in children

Lithotripsy was used to treat 19 children (3 to 16 years of age) with primary ureteric calculi. No attempts were made to mobilize the stones to the kidney. Stones were located in the upper ureter in seven patients, middle ureter in three, and lower ureter in nine. Stone size ranged from 5 to 25 mm (average, 10.4 mm). All treatments were performed in the outpatient unit. Two children required general anesthesia, and 17 received intravenous sedation. The mean amount of energy used was 17.8 kV, and the average number of shock waves was 5,489. Before commencement of lithotripsy, two patients needed ureteric catheterization, and two had placement of double pigtail catheters. Of the 18 children who had adequate follow-up, 17 (94.4%) were completely stone-free, without any complication. The authors conclude that in situ extracorporeal shock wave lithotripsy is a safe and effective method for the treatment of primary ureteric calculi in children.

Leptin influences estrogen metabolism and accelerates prostate cell proliferation

AIM The present study was designed to investigate the effect of leptin on estrogen metabolism in prostatic cells. MAIN METHODS Malignant (PC-3) and benign (BPH-1) human prostate cells were treated with 17-β-hydroxyestradiol (1 μM) alone or in combination with leptin (0.4, 4, 40 ng/ml) for 72 h. Cell proliferation assay, immunocytochemical staining of estrogen receptor (ER), liquid chromatography-tandem mass spectrometry method (LC-MS) and semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) were used. KEY FINDINGS Cell proliferation assay demonstrated that leptin caused significant growth potentiation in both cells. Immunocytochemical staining showed that leptin significantly increased the expression of ER-α and decreased that of ER-β in PC-3 cells. LC-MS method revealed that leptin increased the concentration 4-hydroxyestrone and/or decreased that of 2-methoxyestradiol, 4-methoxyestradiol and 2-methoxyestrone. Interestingly, RT-PCR showed that leptin significantly up-regulated the expression of aromatase and cytochrome P450 1B1 (CYP1B1) enzymes; however down-regulated the expression of catechol-o-methyltransferase (COMT) enzyme. SIGNIFICANCE These data indicate that leptin-induced proliferative effect in prostate cells might be partly attributed to estrogen metabolism. Thus, leptin might be a novel target for therapeutic intervention in prostatic disorders.

Immunomodulatory Effect of Red Onion (Allium cepa Linn) Scale Extract on Experimentally Induced Atypical Prostatic Hyperplasia in Wistar Rats

Red onion scales (ROS) contain large amounts of flavonoids that are responsible for the reported antioxidant activity, immune enhancement, and anticancer property. Atypical prostatic hyperplasia (APH) was induced in adult castrated Wistar rats by both s.c. injection of testosterone (0.5 mg/rat/day) and by smearing citral on shaved skin once every 3 days for 30 days. Saw palmetto (100 mg/kg) as a positive control and ROS suspension at doses of 75, 150, and 300 mg/kg/day were given orally every day for 30 days. All medications were started 7 days after castration and along with testosterone and citral. The HPLC profile of ROS methanolic extract displayed two major peaks identified as quercetin and quercetin-4′-β-O-D-glucoside. Histopathological examination of APH-induced prostatic rats revealed evidence of hyperplasia and inflammation with cellular proliferation and reduced apoptosis Immunohistochemistry showed increased tissue expressions of IL-6, IL-8, TNF-α, IGF-1, and clusterin, while TGF-β1 was decreased, which correlates with the presence of inflammation. Both saw palmetto and RO scale treatment have ameliorated these changes. These ameliorative effects were more evident in RO scale groups and were dose dependent. In conclusion, methanolic extract of ROS showed a protective effect against APH induced rats that may be attributed to potential anti-inflammatory and immunomodulatory effects.

Local inflammation influences oestrogen metabolism in prostatic tissue.

Whats known on the subject? and What does the study add?

Catechol estrogens induce proliferation and malignant transformation in prostate epithelial cells

In the current study, the non-transformed prostatic epithelial cells (BPH-1) were exposed to the catechol estrogens (CE) 2-hydroxyestradiol (2-OHE2) or 4-hydroxyestradiol (4-OHE2), or the parent hormone 17-β-estradiol (E2) at an equimolar concentration (1μM) for a period of 6 weeks. It was found that both 2-OHE2 and 4-OHE2 have more potent proliferation-enhancing effect than E2. Exposure to 2-OHE2, 4-OHE2 or E2 resulted in a significant increase in the protein abundance of cyclin D1 and c-myc. The treated cells exhibited a shift toward the proliferative phase as indicated by FACScan. BPH-1 cells treated with 4-OHE2 showed increased abundance of estrogen receptor-α (ERα) and its downstream IGF-1R. Reduced abundance of estrogen receptor-β (ERβ) and its downstream tumor suppressor FOXO-1 were observed in cells exposed to E2, 2-OHE2 and, to a greater extent, 4-OHE2. Comet assay revealed that CE, especially 4-OHE2, elicited significant genotoxic effects as compared to E2. 4-OHE2 showed greater ability to neoplastically transform BPH-1 cells as indicated by increased colony forming capacity in soft agar and matrix invasion. In conclusion, in vitro exposure to CE could neoplastically transform human prostatic epithelial cells. Further, 4-OHE2 is more carcinogenic to prostate epithelial cells than the parent hormone E2.

Kidney stone composition in overweight and obese patients: a preliminary report

Objective To report preliminary information on urinary stone composition in patients who are either overweight or obese with kidney stone disease. Methods A cohort of patients (n = 138) with nephrolithiasis were prospectively followed from January 2011 for 18 months. Of those, 64 (46%) were found to be overweight with body mass index ≥ 25 kg/m2 and 74 (54%) were obese with body mass index ≥ 30 kg/m2. Stone characteristics including size, location, and composition were studied in detail, and patients’ age, weight, height, and gender were all documented. The stone size and location were studied radiologically while semiquantitative stone analysis was carried out using the DiaSys method, which involves titrimetric determination of calcium, colorimetric determination/visual assessment of oxalate, phosphate, magnesium, ammonium, uric acid, and cystine, and qualitative determination of carbonate. Results Eighteen stones were collected from overweight and obese patients. Those obtained were either spontaneously passed (n = 2), fragments passed following shockwave lithotripsy (n = 11), extracted ureteroscopically (n = 2), or extracted by percutaneous nephrolithotomy (n = 3). About 95% of the stones contained calcium oxalate and more than half contained uric acid. Conclusion This report confirms that kidney stones are mainly composed of calcium oxalate and uric acid in overweight and obese patients with nephrolithiasis.