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1.
Andrologia ; 51(6): e13272, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30907014

RESUMO

In recent years, genetic studies have yielded great progress in elucidating causes of male infertility. This investigation aims to identify frequent genetic abnormalities, that is, sex chromosome aneuploidies and Y-chromosome microdeletions among infertile men in Western Saudi Arabia. From a population of infertile patients, 88 male patients with either azoospermia or severe oligozoospermia (sperm concentration <5 million/ml) were selected. In addition to a thorough clinical workup, karyotypes and Y-chromosomal microdeletions were investigated. Among those 88 infertile patients, we detected six patients with Klinefelter syndrome, two with 47 XYY syndrome and two with Y-chromosome microdeletions AZFb,c. While the prevalence of sex chromosome aneuploidies was in the range of globally investigated populations, the microdeletions appeared to be less frequent in Western Saudi Arabia compared to other regions of the world. All genetically abnormal cases showed sperm concentration <1 million/ml, and hence, this appears to be the threshold for warranting genetic investigations in Western Saudi Arabia. Since Klinefelter and 47 XYY syndromes were only discovered late in life, upon an infertility investigation, sex chromosome aneuploidies due to their many-fold comorbidities require earlier medical attention. A neonatal screening programme is suggested for detection of these aneuploidies in Saudi Arabia for the general health benefit of these patients.


Assuntos
Aneuploidia , Infertilidade Masculina/epidemiologia , Síndrome de Klinefelter/epidemiologia , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/epidemiologia , Adulto , Deleção Cromossômica , Cromossomos Humanos Y/genética , Testes Genéticos/métodos , Necessidades e Demandas de Serviços de Saúde , Humanos , Incidência , Infertilidade Masculina/diagnóstico , Infertilidade Masculina/genética , Cariotipagem , Síndrome de Klinefelter/diagnóstico , Síndrome de Klinefelter/genética , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/organização & administração , Pessoa de Meia-Idade , Estudos Prospectivos , Arábia Saudita/epidemiologia , Aberrações dos Cromossomos Sexuais , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/diagnóstico , Transtornos do Cromossomo Sexual no Desenvolvimento Sexual/genética , Contagem de Espermatozoides
2.
Can J Urol ; 25(2): 9273-9280, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29680006

RESUMO

INTRODUCTION: To evaluate the efficacy and safety of intraprostatic injections of onabotulinumtoxinA (onaBoNT-A) to treat refractory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). MATERIALS AND METHODS: Prospective two-group controlled study. Treatment group included adult men with refractory category-III nonbacterial CP/CPPS who underwent transurethral intraprostatic injections of onaBoNT-A (200 U). Control group included comparable patients who underwent cystoscopy only. Primary outcome was the proportion of 6-point responders (≥ 6 points reduction of total score of National Institutes of Health-Chronic Prostatitis Symptom Index [NIH-CPSI]), at 3 months. Secondary outcomes included proportions of quality of life (QoL) responders (≤ 2 points in QoL domain), and global response assessment (GRA) responders (patients reporting moderately improved, or markedly improved), at 3 months. Other outcomes comprised changes from baseline NIH-CPSI scores, visual analog scale (VAS) sub-score of pain domain, PSA, prostate volume, post-void residual urine, and maximum flow rate. Significance was set at p < 0.05. RESULTS: Treatment group included 43 patients with mean age (SD) of 38.8 (7.3) years and mean duration of symptoms of 7.0 (2.9) years. At 3 months, the proportions of responders (NIH-CPSI 6-point, QoL, and GRA) were 72.1%, 69.8%, and 72.1%; which gradually declined to 37.2%, 25.7% and 27.9%, respectively, at 12 months. The baseline NIH-CPSI total score demonstrated -68.2% reduction at 3 months (-20.1 points; p < 0.0001); which gradually waned to -19% reduction (-5.6 points; p < 0.0001) at 12 months. Baseline VAS showed -79%, and -27.4% reductions at 3 and 12 months, respectively (p < 0.0001, each). None of control men has been 6-point, QoL nor GRA responder and none has demonstrated significant NIH-CPSI scores changes from baseline (p > 0.05, each). Compared to control, mean NIH-CPSI total scores of treated men at 1 and 3 months were significantly different (p < 0.001, each). CONCLUSION: OnaBoNT-A intraprostatic injections appeared to be effective and safe to ameliorate symptoms of refractory nonbacterial CP/CPPS; with pain most improved. The improvements gradually dwindled at 9-12 months.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Dor Crônica/tratamento farmacológico , Dor Pélvica/tratamento farmacológico , Prostatite/diagnóstico , Prostatite/tratamento farmacológico , Qualidade de Vida , Adulto , Doença Crônica , Dor Crônica/etiologia , Cistoscopia/métodos , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pélvica/etiologia , Estudos Prospectivos , Prostatite/complicações , Prostatite/microbiologia , Valores de Referência , Medição de Risco , Síndrome , Resultado do Tratamento
3.
Toxicol Lett ; 291: 77-85, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29654831

RESUMO

Sphingolipids are critical regulators of tumor microenvironments and play an important role in estrogen-dependent cancers. Estrogen and estrogen metabolites were found to be involved in prostate cancer. Fingolimod (FTY720) is a sphingokinase-1 (SphK1) inhibitor with anticancer properties against various tumor cell types. Herein, we investigated the interference of FTY720 with the cross talk between sphingolipid metabolism and estrogen metabolism within prostate cancer cells. FTY720 showed cytotoxic antiproliferative effects against androgen-dependent and -independent prostate cancer cells with IC50 ranging from 3.0 ±â€¯0.3 to 6.8 ±â€¯1.7 µM. Exposure of prostate cancer cells to FTY720 resulted in a dramatic decrease in the concentration of estradiol, estrone, 4-hydroxyestradiol and 16α-hydroxyestrone compared to control cells. However, FTY720 significantly increased the concentration of 2-methoxyestrone and 2-methoxyestradiol within prostate cancer cells. This was mirrored by significant downregulating of the expression of estrogen and catechol estrogen-synthesizing enzymes (CYP19, CYP1A1 and CYP1B1) within prostate cancer cells. On the other hand, FTY720 significantly upregulated the expression of catechol estrogen-detoxifying enzyme (COMT). Additionally, FTY720 abolished estrogen-stimulated expression of ERα and basal expression of ERß within prostate cancer cells. Furthermore, FTY720 suppressed the expression of the ER-downstream regulated genes, CXCR4 and cyclin D1. Reciprocally, it was found that estradiol and catechol estrogens significantly induced the expression of SphK1 while methoxylated catechol estrogen suppressed its expression within prostate cancer cells in a dose-dependent manner. Current research has highlighted the hazardous influence of the estrogenic component to prostate cancer. We found that fingolimod (FTY720) could modulate the estrogenic micromilieu and interrupt its cross talk with sphingolipid metabolism.


Assuntos
Antineoplásicos/farmacologia , Estrogênios/metabolismo , Cloridrato de Fingolimode/farmacologia , Neoplasias da Próstata/metabolismo , Receptor Cross-Talk/efeitos dos fármacos , Esfingolipídeos/metabolismo , Apoptose/efeitos dos fármacos , Catecol O-Metiltransferase/biossíntese , Catecóis/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Masculino , Receptores de Estrogênio/efeitos dos fármacos , Microambiente Tumoral
4.
J Med Biol Eng ; 37(4): 474-483, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28867991

RESUMO

We introduce a novel diagnostic Visual Voiding Device (VVD), which has the ability to visually document urinary voiding events and calculate key voiding parameters such as instantaneous flow rate. The observation of the urinary voiding process along with the instantaneous flow rate can be used to diagnose symptoms of Lower Urinary Tract Dysfunction (LUTD) and improve evaluation of LUTD treatments by providing subsequent follow-up documentations of voiding events after treatments. The VVD enables a patient to have a urinary voiding event in privacy while a urologist monitors, processes, and documents the event from a distance. The VVD consists of two orthogonal cameras which are used to visualize urine leakage from the urethral meatus, urine stream trajectory, and its break-up into droplets. A third, lower back camera monitors a funnel topped cylinder where urine accumulates that contains a floater for accurate readings regardless of the urine color. Software then processes the change in level of accumulating urine in the cylinder and the visual flow properties to calculate urological parameters. Video playback allows for reexamination of the voiding process. The proposed device was tested by integrating a mass flowmeter into the setup and simultaneously measuring the instantaneous flow rate of a predetermined voided volume in order to verify the accuracy of VVD compared to the mass flowmeter. The VVD and mass flowmeter were found to have an accuracy of ±2 and ±3% relative to full scale, respectively. A VVD clinical trial was conducted on 16 healthy male volunteers ages 23-65.

5.
J Biochem Mol Toxicol ; 30(12): 608-613, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27492265

RESUMO

Onabotulinumtoxin A (onabotA) is gaining wide medical use in children. The present study was planned to investigate the influence of its injection on the maturing testicular structures in rats. Immature rats were injected in the bilateral cremaster muscles by onabotA with three doses of (10, 20, and 40 U/kg) three times in a 2-week interval. The effect of these injections on fertility indices was examined. Levels of antisperm antibodies and several apoptosis parameters were also investigated. DNA content in form of ploidy and histopathological alterations were assessed. OnabotA-injected groups showed decreased sperm count and semen quality, while sperm vitality, morphology, and testosterone levels were not significantly affected. Furthermore, DNA flow cytometric analysis confirmed delayed sperm maturation. Apoptosis markers were significantly increased by the injections. In conclusion, onabotA injection in growing rats adversely affected sperm count and maturation. OnabotA testicular effects are mediated, at least partly, by apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Toxinas Botulínicas Tipo A/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Apoptose/genética , Caspase 3/genética , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Injeções Intramusculares , Masculino , Ploidias , Ratos , Ratos Sprague-Dawley , Análise do Sêmen , Maturidade Sexual/genética , Espermatozoides/citologia , Espermatozoides/metabolismo , Testículo/citologia , Testículo/metabolismo , Testosterona/sangue , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Receptor fas/genética , Receptor fas/metabolismo
6.
Sci Rep ; 5: 15639, 2015 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-26492952

RESUMO

Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight &prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-ß (ER-ß) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone-induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-ß/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation.


Assuntos
Metformina/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Testosterona/efeitos adversos , Animais , Masculino , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , Ratos
7.
Life Sci ; 121: 10-5, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25433128

RESUMO

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-ß-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-ß 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.


Assuntos
Estrogênios/metabolismo , Leptina/farmacologia , Próstata/citologia , Próstata/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Neoplasias da Próstata/metabolismo
8.
Urology ; 84(5): 1081-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25214202

RESUMO

OBJECTIVE: To examine the hypotheses that clinical varicoceles affect baseline serum total testosterone levels (T) and varicocelectomy improves T. MATERIALS AND METHODS: This prospective, nonrandomized, controlled study involved 4 groups of adult men. Varicocele-infertile treatment group (VIT) included 66 men who underwent varicocelectomy. Thirty-three varicocele-infertile control men (VIC) and 33 varicocele-fertile control men (VFC) were only observed. Normal-control (NC) group included 33 fertile men without varicocele. Varicocele groups were stratified into baseline hypogonadal (T <300 ng/dL) or eugonadal (T ≥300 ng/dL) subgroups. Main outcome measurements were between-group baseline T differences; and within-group T changes at 6- and 12-month follow-ups of men with varicocele. P <.05 was considered significant. RESULTS: Means (standard deviations) of baseline T in VIT, VIC, VFC, and NC were 347.4 (132.1), 339.7 (125.8), 396.6 (164.9), and 504.8 (149.7) ng/dL, respectively. The baseline T levels of varicocele groups were comparable, whereas they were significantly low compared with NC group. At 6-month follow-up, VIT demonstrated significant T improvements (mean change = 44.7 ng/dL; 12.9%; P <.0001). T changes were more remarkable among baseline hypogonadals (mean change = 93.7 ng/dL; 40.1%; P <.0001) compared with eugonadals (mean change = 8.6 ng/dL; 2.01%; P = .1223). These improvements were persistent at 12-month follow-up. Contrariwise, VIC and VFC exhibited nonsignificant T changes. Postvaricocelectomy T changes correlated significantly and inversely with baseline T (r = -0.689; P <.0001). This correlation was stronger and more significant among hypogonadals (r = -0.528; P = .004) than eugonadals (r = -0.400; P = .013). T improvements also exhibited significant positive correlations with preoperative and postoperative sperm concentrations. CONCLUSION: Baseline T was significantly low in men with varicocele compared with normal men. Varicocelectomy yielded significant T improvements among hypogonadal men but insignificant changes in eugonadals. T changes correlated strongly and significantly with baseline T and sperm concentrations.


Assuntos
Testosterona/sangue , Varicocele/complicações , Varicocele/cirurgia , Adulto , Estudos de Casos e Controles , Humanos , Infertilidade Masculina/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Contagem de Espermatozoides , Resultado do Tratamento , Procedimentos Cirúrgicos Urogenitais , Procedimentos Cirúrgicos Vasculares , Adulto Jovem
9.
Naunyn Schmiedebergs Arch Pharmacol ; 387(12): 1131-40, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25164963

RESUMO

The current study aimed to investigate the potential role of the anti-inflammatory effects of silymarin (SIL) in inhibiting experimentally induced benign prostatic hyperplasia (BPH) in rats. Rats were injected testosterone (3 mg/kg/day, subcutaneously (s.c.)) for 2 weeks. In the treatment group, SIL (50 mg/kg, per orally (p.o.)) was administered daily to rats concomitantly with testosterone. Rats were killed 72 h after the last testosterone injection. Then, prostate tissues were dissected out, weighed, and subjected to histological, immunohistochemical, and biochemical examinations. Rats treated with testosterone showed marked increase in prostate weight and prostate weight/body weight with histopathological picture of inflammation and hyperplasia as well as increased collagen deposition. Co-treatment with SIL significantly alleviated these pathological changes. Further, SIL attenuated testosterone-induced nuclear factor-kappa B (NF-κB), cyclooxygenase-II (COX-II), and inducible nitric oxide synthase (iNOS) upregulation, and blunted testosterone-mediated increase in nitric oxide level and messenger RNA (mRNA) expression of interleukin-6 (IL-6) and IL-8. Testosterone-induced downregulation of phosphatase and tensin homolog (PTEN) and upregulation of hypoxia-inducible factor 1α (HIF-1α) were alleviated by SIL. Our findings highlight the anti-inflammatory properties of SIL as a crucial mechanism of its preventive actions against experimental BPH. This can be attributed to, at least partly, attenuating the expression of NF-kB and the subsequent inflammatory cascade, ameliorating the expression of PTEN, and mitigating that of HIF-1α. These data warrant further investigations for the potential use of SIL in the management of BPH.


Assuntos
Mediadores da Inflamação/metabolismo , Hiperplasia Prostática/tratamento farmacológico , Silimarina/farmacologia , Testosterona/farmacologia , Animais , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Hiperplasia Prostática/patologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacos
10.
Mediators Inflamm ; 2014: 640746, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24829522

RESUMO

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'-ß-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-ß1 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.


Assuntos
Fatores Imunológicos/uso terapêutico , Cebolas/química , Extratos Vegetais/uso terapêutico , Hiperplasia Prostática/tratamento farmacológico , Animais , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Ratos , Ratos Wistar , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
11.
Toxicol Appl Pharmacol ; 275(2): 182-8, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24440444

RESUMO

Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicular function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/efeitos adversos , Testículo/efeitos dos fármacos , Animais , Peso Corporal , Colesterol/sangue , Criptorquidismo/induzido quimicamente , Criptorquidismo/patologia , Infertilidade/induzido quimicamente , Infertilidade/patologia , Isoenzimas/metabolismo , L-Lactato Desidrogenase/metabolismo , Masculino , NF-kappa B/genética , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/patologia , Testosterona/sangue , Triglicerídeos/sangue
12.
Low Urin Tract Symptoms ; 6(3): 162-6, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26663598

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of Botulinum Toxin A (BoNTA) intradetrusor injections in patients with neurogenic detrusor overactivity. METHODS: All patients provided clinical history and voiding diary, submitted to clinical examination, urine culture; serum creatinine; imaging, including plain abdominal X-rays, abdomino-pelvic ultrasonography and voiding cystourethrogram; and urodynamic tests (CMG) . They were managed by intradetrusor injections of BoNTA. For the typical patient, 300 units of BoNTA were injected through 30 injections of 10 u/mL intradetrusally into equally spaced sites of the bladder wall, excluding the trigone, under cystoscopic guidance. Patients were commenced clean intermittent catheterizations (CICs) every 4-6 h post-injection. Follow up included voiding diaries, abdomino-pelvic ultrasonography, serum creatinine and CMG, were completed for all patients at 6 and 12 weeks. This study used IBM SPSS Version 20.0 for statistical analysis. RESULTS: Forty-five patients (28 males and 17 females) with a mean age of 19.6 years were subjected to BoNTA intradetrusor injections. A good clinical response (dry patient either completely or more than 50% of the period between CICs) was observed in 68.9 and 66.7% of the patients after 6 and 12 weeks of follow up, respectively. In the group that responded well, the mean bladder volume increased post-injection by 48.2% and the mean maximum intravesical pressure decreased to 35.3 cm H2 O, a 33.4% improvement. No patients had side-effects related to BoNTA or to the procedure, and no patients experienced a deterioration of their renal functions. CONCLUSIONS: Intradetrusor BoNTA injections provide a good clinical response. The urodynamic parameters significantly improved in patients with neurogenic detrusor overactivity.

13.
IUBMB Life ; 65(8): 716-29, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23847086

RESUMO

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-ß (ER-ß) 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-ß abundance.


Assuntos
Antineoplásicos/uso terapêutico , Ácidos Cafeicos/uso terapêutico , Paclitaxel/uso terapêutico , Álcool Feniletílico/análogos & derivados , Neoplasias da Próstata/tratamento farmacológico , Taxoides/uso terapêutico , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Docetaxel , Sinergismo Farmacológico , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Humanos , Concentração Inibidora 50 , Masculino , Álcool Feniletílico/uso terapêutico
14.
Toxicol Lett ; 220(3): 247-58, 2013 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-23685341

RESUMO

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-ß-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-ß (ERß) 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.


Assuntos
Transformação Celular Neoplásica/induzido quimicamente , Estradiol/análogos & derivados , Estrogênios de Catecol/farmacologia , Próstata/efeitos dos fármacos , Neoplasias da Próstata/induzido quimicamente , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Ensaio Cometa , Dano ao DNA , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Estradiol/farmacologia , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Citometria de Fluxo , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Receptor IGF Tipo 1/metabolismo
15.
Toxicol Lett ; 219(2): 160-9, 2013 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-23500659

RESUMO

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-ß. 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-ß 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.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Fitoestrógenos/farmacologia , Hiperplasia Prostática/prevenção & controle , Silimarina/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Imuno-Histoquímica , Masculino , NF-kappa B/biossíntese , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/biossíntese , Próstata/patologia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/patologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/biossíntese , Receptores Androgênicos/efeitos dos fármacos , Receptores de Estrogênio/biossíntese , Receptores de Estrogênio/efeitos dos fármacos , Testosterona/farmacologia
16.
Res Rep Urol ; 5: 11-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24400230

RESUMO

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/m(2) and 74 (54%) were obese with body mass index ≥ 30 kg/m(2). 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.

17.
Res Rep Urol ; 5: 91-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24400240

RESUMO

OBJECTIVE: To establish a possible association between obesity, measured by waist circumference (WC) and body mass index (BMI), and voiding and sexual functions in a random cohort of Saudi men. MATERIALS AND METHODS: An outpatient men's health clinic was set up at King Abdulaziz University Hospital in Jeddah, Saudi Arabia and men were invited to discuss their sexual and urinary functions. The data collected included age, WC, weight, height, blood pressure, history of diabetes, hypertension, and smoking. The International Prostate Symptom Score (IPSS) and the International Inventory of Erectile Function (IIEF-5) questionnaire were used to assess urinary tract symptoms and sexual function, respectively. Serum testosterone, prostate-specific antigen and cholesterol levels were measured and documented. Data were analyzed using the Statistical Package for the Social Sciences. RESULTS: We recruited 113 participants. The mean WC and BMI of the men were 104 ± 14.599 cm and 29.706 kg/m(2), respectively. Thirty-seven men (32.7%) had an IPSS ≥ 8 points. Sexual disorders were reported in 19 men; 16 men had erectile dysfunction, while three had premature ejaculation. Of the whole cohort, 37 men were diabetic, of which 15 (40.5%) had an IPSS ≥ 8 and 13 (35%) were either overweight or obese. CONCLUSION: Increased WC and BMI were associated with diabetes mellitus and large percentages of voiding and sexual disorders.

18.
Springerplus ; 2: 537, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-25674400

RESUMO

OBJECTIVES: To examine the link between increased body mass index and benign prostatic hyperplasia (BPH) related complications, namely: acute urinary retention (AUR), Bladder stones and Bladder diverticula. PATIENTS: We reviewed the medical records of BPH patients who underwent prostatectomy over three years period from 2010-2012. Prostatectomy was either done in the gold standard transurethral resection of the prostate (TURP) or using green light laser selective photo-vaporization (PVP). Age, PSA, Prostate Volume (PV) as measured by ultrasonography, patients' weight & height, BPH related complications mainly AUR, bladder stones, and bladder diverticula were all taken in account. The BMI was calculated as weight in kg divided by square height in meters. The BMI was divided in 4 categories according to WHO classification: underweight if BMI ≤18.50 kg/m2; normal weight if BMI = 18.50-24.9 kg/m2; overweight: BMI ≥25 kg/m2; and obese BMI if ≥30 kg/m2. STATISTICAL ANALYSIS: done using the SPSS package version 16. Chi-square test was used for comparison between groups where p-value was considered significant if <0.05 and ANOVA test was used for comparison between multiple variables. RESULTS: 197 patients were included in this study, of those 95(48%) underwent TURP and 102(52%) underwent PVP. The two groups were found to be similar in mean age and PSA, and significantly different in prostate volume and operating room (O.R.) time. CONCLUSIONS: Although the mean weight for patients undergoing prostatectomy in this study was in the overweight range, yet only 59/197(30%) patients with increased BMI presented with AUR. In this particular cohort of patients undergoing prostatectomy there was no significant differences in the development of AUR, bladder stone and diverticulum formation between patients with increased BMI (overweight and obese) and those with normal BMI. Further studies are recommended to explore the influence of increased BMI on BPH-related complications.

20.
Can Urol Assoc J ; 7(3-4): E193-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22630338

RESUMO

OBJECTIVE: We evaluated the safety and efficacy of photoselective vaporization of the prostate (PVP) using GreenLight 120-W lithium triborate (LBO) laser to treat symptomatic small-to-medium sized benign prostatic hyperplasia (BPH). METHODS: This prospective non-controlled observational study included symptomatic BPH men ≥50 years with international prostate symptom score (IPSS) ≥14, prostate volume (PV) ≤80 cc and maximum flow rate (Q-max) ≤15 mL/s. PVP was performed using the GreenLight 120-W LBO laser machine. Patients were assessed at baseline and postoperatively at discharge, 2 weeks, and 3, 6 and 12 months. We measured changes in IPSS, PV, PSA, Q-max, post-void residual (PVR), hemoglobin (Hb), serum sodium (Na+) and reported complications. Statistical significance was p < 0.05. RESULTS: The study included 103 men with mean age of 67 (±standard deviation)±9.7 years. Thirty patients were on indwelling urethral catheters for refractory urinary retention and 12 on ongoing anticoagulants. The mean baseline IPSS, PV, PSA, Q-max and PVR parameters significantly improved at follow-up (p < 0.001; each). Mean measurements at baseline versus at six months were: IPSS 25.6 ± 4.2 vs. 7.4±2.3; PV 44.6 ± 9.2 vs. 21.6 ± 6.3 cc (51.6% reduction); Q-max 5.8 ± 3.4 vs. 20.4 ± 4.8 mL/s; PVR 110 ± 40 vs. 35 ± 9 cc. Mean baseline Hb and serum Na+ declined non-significantly (p > 0.05) at discharge and at 2 weeks. No patient needed a blood transfusion. Secondary procedures were needed in 2 patients for urethral and bladder neck strictures. The re-treatment rate for residual adenoma was 0.97%. CONCLUSION: PVP using the GreenLight 120-W LBO laser to treat small-to-medium sized symptomatic BPH demonstrated significant improvements in efficacy parameters and high safety profile within 12 months of follow-up. The procedure entails good hemostasis with minimal blood loss even in patients receiving ongoing anticoagulants.

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