Observation on the changes of clinical symptoms, blood and brain copper deposition in Wilson disease patients treated with dimercaptosuccinic acid for 2 years.

OBJECTIVE: To compare the clinical symptoms, brain copper deposition changes of Meso-2,3-dimercaptosuccinic acid (DMSA) and penicillamine therapy in patients with Wilson disease (WD) within 2 years. METHODS: 68 drug-naive patients with WD were enrolled. 10 WD patients treated with zinc gluconate alone were used as the control group. Neurological symptoms were scored using the modified Young Scale. Liver function tests, copper indices and sensitive weighted imaging (SWI) examination were collected. The values of corrected phase (CP) were collected. WD patients were treated with DPA (group 1) or DMSA (group 2) for two years, and followed up every 2 months. RESULTS: The ratio of neurological improvement in group 2 was higher than that in group 1 (P = 0.029). Higher rate of neurologic worsening was noticed in patients treated with DPA vs DMSA (P = 0.039). The post-treatment neurological score of DMSA group was lower than that of Zn group (P = 0.037). Hepatic function in 63.3% of patients was stable, while 16.7% was improved, and 20% was deteriorated, after DMSA therapy. Urinary copper levels were lower 1 month (p = 0.032), 4 months (p = 0.041), 12 months (p = 0.037) after initiation of treatment in group 2 than in group 1. At the first year of treatment, the CP values in globus pallidus and substantia nigra in group 2 were higher than those in group 1 (P = 0.034,0.039). At the second year of treatment, the CP values of substantia nigra in group 2 were higher (P = 0.041). Discontinuation was more common in patients on DPA therapy (P = 0 0.032). CONCLUSIONS: DMSA could remove metal from brain tissue faster than DPA. DMSA is effective for neurologic symptoms, while the outcome for hepatic symptoms is not entirely satisfactory. DMSA therapy is better tolerated than DPA.

A study of susceptibility-weighted imaging in patients with Wilson disease during the treatment of metal chelator.

OBJECTIVE: A randomized-controlled trial comparing study of the changes in brain sensitive-weighted imaging (SWI) of Wilson disease (WD) patients during the treatment with metal chelator was done. METHODS: 100 untreated WD patients (80 cases of cerebral type, 20 cases of hepatic type, age 20.13 ± 9.12 years old) and 20 normal controls were selected. Neurological symptoms were scored using the modified Young scale. Liver function tests and copper indices were collected. All study objects received SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. Cerebral-type WD patients were treated with D-penicillamine (DPA) (group 1) or Dimercaptopropane Sulfonate (DMPS) + Dimercaptosuccinic Acid (DMSA) (group 2). Hepatic-type WD patients were treated with DPA (group 3). All patients received annual neurological symptom score, liver function, copper indices, and SWI examination. RESULTS: At the first year of treatment, score of the modified Young scale in group 2 was lower than that in group 1 (P = 0.023) and lower than that before treatment (P = 0.040). After 2 years of treatment, the score of the modified Young scale in group 1 was lower than that before treatment (P = 0.012). At the second year after treatment, the urinary copper in group 2 was higher than that in group 1 (P = 0.014). Urinary copper was maintained at 200 µg/day in group 1 and 300 µg/day in group 2 after 3 years of treatment. At the first year of treatment, serum copper in group 1 was lower than that in group 2 (P = 0.032). At the first year of treatment, CP values of the pallidum and substantia nigra in group 2 were higher than those in group 1 (P = 0.026, 0.040). At the second year of treatment, CP value of substantia nigra in group 2 was higher than that in group 1 (P = 0.037). After 3 years of treatment, there was no difference in CP values between WD patients and normal controls. CONCLUSIONS: Therapy with DMPS and DMSA improves neurological symptoms of WD patients more quickly and leads to less aggravation, compared with therapy with DPA. The metal content in the brain of WD patients was at a low level after 3 years of treatment. DMPS and DMSA can remove metal from brain tissue faster than DPA.

Injury factors and pathological features of toxic milk mice during different disease stages.

OBJECTIVE: To evaluate different injury factors and pathological characteristics of the brain at different disease stages in toxic milk (TX) mice, an animal model of Wilson's disease (WD). METHODS: Thirty TX mice (10 each at 3, 6 and 12 months old) and 30 age-matched C57 mice were used in this study. Corrected phase (CP) values were determined from susceptibility-weighted images. Myelin content was determined by measuring inhibition optical density values of Luxol fast blue-stained sections. Neurofilament protein 68 kDa (NF68), ß-amyloid precursor protein (ß-APP), and myelin basic protein (MBP) levels, as well as copper and iron content, in brain nuclei of the TX mouse were evaluated. Gene amplification ratios for catalase (CAT), GSH peroxidase (GSH-PX), nitric oxide synthase (NOS), and superoxide dismutase (SOD) in mouse brain were also determined. RESULTS: Compared with C57 mice, neuronal cell counts were decreased in 12-months-old TX mice (p = .011). Myelin content was decreased in the lenticular nucleus (p = .029), thalamus (p = .030), and brainstem (p = .034) of 6-months-old TX mice; decreases in the corresponding nuclei (p = .044, .037, and .032, respectively) were also found in 12-months-old TX mice. MBP values were lower in the lenticular nucleus and thalamus (p = .027 and .016, respectively) of 6-months-old TX mice and in the corresponding nuclei (p = .24 and .040) of 12-months-old TX mice. NF-68 values were lower in the lenticular nucleus and thalamus (p = .034 and .037, respectively) of 6-months-old TX mice and in the corresponding nuclei (p = .006 and .012) of 12-months-old TX mice. ß-APP values were higher in the thalamus of 6-months-old (p = .037) and 12-months-old (p = .012) TX mice. Iron content was higher in the lenticular nucleus, thalamus, and cerebellum (p = .044, .038, and .029, respectively) of 6-months-old TX mice and in the corresponding nuclei (p = .017, .024, and .029) of 12-months-old TX mice. The NOS gene amplification multiple was higher (p = .039), whereas the SOD1 gene amplification multiple was lower (p = .041) in 12-months-old TX mice. There was no correlation between metal content or oxidation index and pathological index. CONCLUSIONS: The pathological characteristics of the brains of TX mice may differ at different ages. Different pathogenic factors, including copper and iron deposition and abnormal oxidative stress, are present at different stages.

[Logistic regression analysis of risk factors of serious complications related with double-J ureteral stenting following percutaneous nephrolithotomy].

OBJECTIVE: To investigate the risk factors of the serious complications related with double-J ureteral stent placement following percutaneous nephrolithotomy (PCNL). METHODS: Clinical data were reviewed for 272 patients treated with PCNL and indwelling double-J stents between January, 2014 and April, 2016. The risk factors of serious complications were identified using univariate and multivariate logistic regression analysis. RESULTS: Serious complications of double-J ureteral stenting occurred in 63 patients (23.1%). Univariate and multivariate logistic regression analysis indicated that the ureter abnormalities (ß=1.735, P=0.000, OR=5.670), stent indwelling duration (ß=1.206, P=0.028, OR=3.340), gender (ß=0.895, P=0.016, OR=2.446), preoperative urinary tract infection (ß=0.849, P=0.020 , OR=2.338) and stent size (ß=0.847, P=0.011, OR=2.333) were all risk factors of serious complications related with the procedure. CONCLUSION: Male patients are exposed to a higher risk of serious complications following PCNL. Effective management of urinary tract infection and choice of appropriate stent size in cases of ureteral abnormalities help to reduce these complications. The double-J stent should be withdrawn as soon as possible in patients with good postoperative recovery.

Diffusion tensor imaging of the extracorticospinal network in the brains of patients with Wilson disease.

OBJECTIVE: To evaluate damage to the extracorticospinal tract in Wilson disease (WD) patients using diffusion tensor imaging (DTI). METHODS: 70 patients with WD, including 50 with cerebral type and 20 with hepatic type, and 20 age-matched healthy controls were enrolled. Neurological symptoms were scored using the modified Young Scale. Patients with cerebral type WD were divided into four subgroups: those with (1) hypokinesia, (2) parkinsonism, (3) mouth and throat dystonia, and (4) psychiatric symptoms. All study subjects underwent DTI of the brain. Five regions of interest (ROIs) were chosen. Fractional anisotropy (FA) and fiber volumes between ROIs were determined, and the relationships between DTI metrics and clinical status were evaluated. RESULTS: FA values and fiber volumes between subcortical nuclei were lower in WD patients. Fiber volumes between the putamen (PU) and the globus pallidus (GP), substantia nigra (SN), and thalamus (TH); between the head of the caudate nucleus (CA) and the GP and TH; and between the TH and cerebellum were lower in group 1 than in the other groups of WD patients. Fiber volumes between the GP and the SN and TH were lower in group 2, and fiber volumes between the SN and TH were lower in group 3. DTI metrics differed between patients with the cerebral and hepatic types of WD. CONCLUSIONS: DTI can reconstruct the network of the extracorticospinal tract. Fiber projection between subcortical nuclei was abnormal in WD patients. Damage to fiber connections may correlate with neurological symptoms in WD patients.

[Comparison of laparoscopic pyelolithotomy and percutaneous nephrolithotomy for renal pelvic stones larger than 2.5 cm].

OBJECTIVE: To compare the safety, efficacy and complications of laparoscopic pyelolithotomy (LPL) and percutaneous nephrolithotomy (PCNL) for treatment of renal pelvic stones larger than 2.5 cm. METHODS: From 2011 to 2016, 32 patients underwent LPL and another 32 patients received PCNL for renal pelvic stones larger than 2.5 cm. The baseline characteristics of the patients, stone size, mean operative time, estimated blood loss, postoperative hospital stay, stone-free rate, postoperative analgesia, blood transfusion, and the intraoperative, early postoperative and long-term complications were compared between the two groups. RESULTS: The baseline characteristics and stone size were comparable between the two groups. The mean operative time of LPL and PCNL was 117∓23.12 and 118.16∓25.45 min, respectively (P>0.05). The two groups showed significant differences in the mean estimated blood loss (63∓11.25 vs 122∓27.78 mL, P<0.01) and blood transfusion rate (0 vs 6.2%, P<0.01) but not in postoperative hospital stay (4.5∓1.34 vs 4.8∓2.2 days, P>0.05), stone-free rate (93.1% vs 87.5%, P>0.05) or the postoperative analgesia time (1.7∓0.5 and 1.9∓0.6 days, P>0.05). The incidence of intraoperative complications were significant lower in LPL group than in PCNL group (6.2% vs 25.0%, P<0.01), but the incidences of early postoperative complications (25.0% vs 34.4%, P>0.05) and long-term postoperative complications (9.4% vs 12.5%, P>0.05) were similar between them. CONCLUSION: PCNL is the standard treatment for pelvic stones larger than 2.5 cm, but for urologists experienced with laparoscopic technique, LPL provides a feasible and safe option for management of such cases.

Effects of insulin-like growth factor-1 on the relaxation responses of the cavernous smooth muscle from aged rats.

OBJECTIVE: The aim of this study was determine whether intracavernosal injection (ICI) of insulin-like growth factor-1 (IGF-1) protein can improve corpus cavernosal smooth muscle relaxation in aging rats. MATERIALS AND METHODS: Ten young (4-month-old) and 30 old (24-month-old) Sprague-Dawley male rats were enrolled in the study. The old rats were divided into three groups: vehicle-only (n = 10), IGF-1 1 µg/kg (n = 10) and IGF-1 10 µg/kg treatment groups (n = 10). After 4 weeks of single IGF-1 injection treatment, strips of corporal tissue were precontracted with phenylephrine, and dose-response curves were generated to evaluate endothelial-dependent [acetylcholine (ACh)], endothelial-independent [sodium nitroprusside (SNP)] and electrical field stimulation (EFS) vasoreactivity. The changes in percentage of cavernosal smooth muscle and the concentration of nitric oxide (NO) in penile tissue were also evaluated. RESULTS: After IGF-1 treatment, the vasoreactivity was significantly improved in both the 1 µg/kg and the 10 µg/kg treatment groups compared with the vehicle-only group at 4 weeks in response to ACh, SNP and EFS (all p < 0.05). The percentage of cavernosal smooth muscle was increased in the IGF-1 treatment groups. The NO concentrations were increased after IGF-1 treatment. CONCLUSIONS: These data demonstrate that ICI of IGF-1 can improve vasoreactivity via endothelium-dependent and endothelial-independent mechanisms in the corpus cavernosum of the aging rat.

[Influences of three surgical approaches to urethral stricture on the erectile function of the patients].

OBJECTIVE: To evaluate the impacts of three different surgical approaches to urethral stricture on the erectile function of the patients. METHODS: This study included 126 male patients with urethral stricture, 35 treated by substitution urethroplasty (group A), 52 by anastomotic urethroplasty (group B), and 39 by internal urethroplasty (group C). We evaluated the pre- and postoperative erectile function of the patients using IIEF-5 scores by telephone calls and interviews. We also monitored their nocturnal penile tumescence (NPT). RESULTS: The IIEF-5 scores in groups A, B and C were 13.5 +/- 4.5, 11.1 +/- 4.8 and 14.5 +/- 4.41 respectively after surgery, all significantly decreased as compared with 17.1 +/- 2.6, 17.1 +/- 3.0 and 17.6 +/- 2.2 preoperatively (P < 0.05). CONCLUSION: All the three surgical approaches can reduce IIEF-5 scores in patients with urethral stricture, but anastomotic urethroplasty may induce a higher incidence of erectile dysfunction than the other two approaches.

Characterizing brain mineral deposition in patients with Wilson disease using susceptibility-weighted imaging.

AIMS: The aim of this study was to evaluate the feasibility of characterizing the brain-mineral deposition in patients with Wilson disease (WD) using susceptibility-weighted imaging (SWI). MATERIALS AND METHODS: The study enrolled 30 WD patients and 20 age-matched healthy controls. Neurological symptoms were scored using the modified Young Scale. The hepatic function indices, serum and urinary copper content, and serum iron content were determined. All study objects received the magnetic resonance imaging (MRI) and SWI test of the brain. The values of corrected phase (CP) were calculated on SWI. The relationship between CP values and the clinical status were evaluated. RESULTS: The serum iron content of WD patients was higher than the normal. The CP values of substantia nigra, caudate nucleus, and globus pallidus of WD were lower than the normal values, while the CP value of substantia nigra was the lowest. No correlations were determined between the CP values and the iron and copper parameters. There was negative correlation between the scores of dysarthria and the CP values of the globus pallidus. There was negative correlation between the scores of tremor and the CP values of caudate nucleus. Some regions, which had high signals on T2-weighted image, had low signals on SWI. CONCLUSIONS: There might be abnormal iron metabolism in patients with WD. The decreased CP values might reflect a deposition of both copper and iron. SWI may be more sensitive than the ordinary MRI. The mineral deposition may contribute to the neural symptoms.

shRNA constructs targeting IGFBP-3 alleviate age related erectile dysfunction in the rat.

PURPOSE: We investigated whether injecting shRNA constructs targeting IGFBP-3 in the penis of old rats would improve erectile function. MATERIALS AND METHODS: The most validated IGFBP-3 shRNA plasmid vector (pGPU6/GFP/Neo-shIGFBP-3) was prepared and injected in penile corpus cavernosum tissue. A total of 30 old (age 24 months) male Sprague Dawley® rats were randomly divided into 3 groups, including 10 each that received phosphate buffered saline only (100 µl), pGPU6/GFP/Neo-shNC (100 µg) and the most validated plasmid constructs pGPU6/GFP/Neo-shIGFBP-3 (100 µg). At 4 weeks the erectile response was measured as intracavernous pressure. The percent of smooth muscle in corpus cavernosum tissue was evaluated. Nitric oxide synthase activity and the cGMP concentration in penile tissue were also analyzed. IGFBP-3 was estimated in penile tissue by Western blot, real-time reverse transcriptase-polymerase chain reaction and immunohistochemistry. RESULTS: pGPU6/GFP/Neo-shIGFBP-3 corrected the impaired erectile response in aged rats compared with the response in those injected with phosphate buffered saline and pGPU6/GFP/Neo-shNC (each p <0.01). The percent of cavernous smooth muscle was increased in the pGPU6/GFP/Neo-shIGFBP-3 group. Nitric oxide synthase activity and the cGMP concentration were also significantly increased in rats treated with pGPU6/GFP/Neo-shIGFBP-3. IGFBP-3 shRNA effectively reduced IGFBP-3 mRNA and protein expression in penile corpus cavernosum tissue. CONCLUSIONS: Decreasing IGFBP-3 expression by plasmid expressed shRNA improved erectile function in aged rats. The therapy may modulate smooth muscle integrity and increase the cGMP concentration. This may be a new direction for treating erectile dysfunction in clinical practice.

[Yimusake Tablet: safe and efficacious for premature ejaculation].

OBJECTIVE: To objectively evaluate the efficacy and safety of Yimusake Tablet in the treatment of premature ejaculation (PE) through a multi-centered large-sample trial. METHODS: We conducted a multi-centered, open, fixed-dose, and self-compared clinical trial among 300 patients with diagnosed PE. The trial lasted 12 weeks, including 4 weeks without any medication and 8 weeks of treatment with Yimusake Tablet, 2 pills (1 g) per night. We observed the intravaginal ejaculation latency time (IELT) before and after treatment, evaluated the safety of medication, and performed a questionnaire investigation on the patients' satisfaction. RESULTS: Of the 300 PE patients, 288 accomplished the clinical trial. The patients ranged in age from 22 to 60 years, averaging at 31.6 years. The mean IELT of the patient was 62.5 seconds at baseline, 168.9 seconds after 4 weeks of treatment with Yimusake Tablet, and 222.2 seconds after 8 weeks of medication. Among the 157 patients with normal erectile function (IIEF >21), the mean IELT was 71.4 seconds before treatment, 147.4 seconds after 4 weeks of medication, and 172.5 seconds after 8 weeks of medication. The patients' satisfaction was significantly increased after treatment. Those complicated by mild to moderate erectile dysfunction achieved different degrees of improvement in the IIEF-5 score, with a mean increase of 3.8. Only a few patients experienced mild adverse events, including constipation, dry mouth, nose bleeding, abdominal pain, and lumbosacral pain, which were all relieved without drug withdrawal. CONCLUSION: Yimusake Tablet is a safe and effective medicine for the treatment of PE.

[Impact of aging on the secretion of insulin-like growth factor-1 in the corpus cavernosum smooth muscle cells of rats in vitro].

OBJECTIVE: To observe the secretion of insulin-like growth factor-1 (IGF-1) in corpus cavernosum smooth muscle cells (CCSMCs) in rats of different ages and explore the possible relationship of IGF-1 with aging-related erectile dysfunction (ED). METHODS: We primarily cultured CCSMCs of rats aged 4, 12 and 24 months, and identified them by immunohistochemistry. We quantitatively cultured the CCSMCs in 6-well culture plates, determined the levels of IGF-1 secreted from the CCSMCs by enzyme immunoassay (EIA) and analyzed the effect of age on the IGF-1 level. RESULTS: CCSMCs were successfully cultured in vitro. The level of IGF-1 secreted from the CCSMCs was decreased with the increase of age, with 7.1 ng/10(5) cells in the 4-month-old group, 2.2 ng/10(5) cells in the 12-month group, and 1.9 ng/10(5) cells in the 24-month group, with statistically significant differences among the three groups (P < 0.01). CONCLUSION: The secretion of IGF-1 is reduced with the increase of age, and the decreased expression of IGF-1 might be associated with aging-related ED.

A randomized controlled trial of postoperative tumor lysate-pulsed dendritic cells and cytokine-induced killer cells immunotherapy in patients with localized and locally advanced renal cell carcinoma.

BACKGROUND: It remains a challenge to inhibit the local recurrence or distant metastasis of localized or locally advanced renal cell carcinoma (RCC) after surgical resection. We investigated the feasibility, safety and efficacy of immunotherapy using autologous tumor lysate (TL)-pulsed dendritic cells (DCs) and cytokine-induced killer (CIK) cells in patients with localized or locally advanced RCC. METHODS: From January 2001 to July 2009, we collected 137 patients that met the selection criteria and randomly divided them into three groups. After surgery, immunotherapy with TL-pulsed DCs-CIK cells (DC-CIK group) and interferon (IFN)-α (IFN-α group) was performed in 46 patients, respectively. The other 45 patients received no postoperative adjuvant therapy (the control group). The changes in the numbers of T lymphocyte subsets, including CD4(+)CD25(high) regulatory T cells (Treg), were determined before the operation and after immunotherapy. The overall survival was compared among the three groups. RESULTS: An increase of the CD4(+)/CD8(+) ratio and a decrease of CD4(+)CD25(high) cells were observed after TL-pulsed DC-CIK cells or IFN-a immunotherapy. All patients tolerated the TL-pulsed DC-CIK cells immunotherapy very well, and side effects in the DC-CIK group were less than in the IFN-α group. The metastasis and recurrence rates were significantly decreased after TL-pulsed DC-CIK cells or IFN-α immunotherapy compared with the control group (P < 0.01). The Log-rank test showed that the overall survival rates were significantly higher in the DC-CIK group and IFN-α group than that in the control group (P < 0.01), but there was no difference between the DC-CIK group and IFN-α group (P > 0.05). CONCLUSION: Postoperative immunotherapy with TL-pulsed DC-CIK cells may prevent recurrence/metastasis and increase the overall survival rate after surgery in localized or locally advanced RCC.

Presence of tumour-infiltrating FOXP3+ lymphocytes correlates with immature tumour angiogenesis in renal cell carcinomas.

BACKGROUND: FOXP3+ regulatory T cells (Tregs) inhibit effector T cell functions and are implicated in tumour progression. However, together with microvessel density (MVD) they remain controversial prognostic predictors for renal cell carcinoma (RCC), and potential associations have yet to be determined. The objective of this study was to determine the prognostic significance of Tregs and MVD and their potential relationship in RCCs. DESIGN: Paraffin-embedded tissues from 62 RCC patients were analysed using immunohistochemistry to detect FOXP3+ lymphocytes, and double immunohistochemistry to detect different microvessel types in the tumour interior, rim and normal kidney tissue, and their correlation with clinicopathological characteristics. Survival analysis was also performed. RESULTS: The presence of FOXP3+ cells in the tumour interior or the rim showed no correlation with death from RCC and other pathological characteristics. Negative correlations were noted between the immature MVD in the tumour interior or the rim and tumour size, tumour stage and overall survival; however, there was no correlation with the nuclear grade or pathological type. A positive correlation between FOXP3+ Tregs and immature MVD (r=0.363, P=0.014) and mature MVD (r=0.383, P=0.009) was confirmed in the tumour interior. However, there was no correlation between FOXP3+ Tregs and mature MVD (r=0.281, P=0.076) or immature MVD (r=0.064, P=0.692) in the tumour rim. CONCLUSIONS: In this study, a positive correlation between the presence of FOXP3+ Tregs and immature and mature MVD in RCC was confirmed, which suggests a link between suppression of immunity, tumour angiogenesis and poor prognosis.

[Insulin-like growth factor-1 gene therapy improves the levels of mRNA and protein of endothelial nitric oxide synthase in aging related erectile dysfunction in rats].

OBJECTIVE: To explore the effects of gene transfer of insulin like growth factor-1 (IGF-1) on the penis of senile rats and the altered levels of mRNA and protein of endothelial nitric oxide synthase (eNOS). METHODS: Ten young (4 months) and 20 senile (24 months) Sprague-Dawley male rats were selected. The senile rats were divided into 2 groups: phosphate buffer solution (PBS)-only (n = 10) and 100 µg IGF-1 plasmid treatment group (n = 10). After a 4-week injection of IGF-1, the responses of intracavernous pressure (ICP) with electrical stimulation to the cavernous nerve and systemic mean arterial pressure (MAP) were evaluated. In the control and transfected senile rats, the levels of eNOS mRNA and protein were examined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot respectively. RESULTS: The ICP/MAP and total ICP were significantly higher in the young control group versus the PBS-only group at Week 4 (P < 0.05). The ICP/MAP and total ICP were significantly higher in the young control group and the 100 µg IGF-1 treatment group versus the PBS-only group at Week 4 (P < 0.05). The levels of mRNA and protein of eNOS were higher in the 100 µg IGF-1 treatment group versus the PBS-only group at Week 4 (0.62 ± 0.16 vs 0.25 ± 0.08, 0.71 ± 0.19 vs 0.27 ± 0.09, both P < 0.05, respectively). CONCLUSION: The gene therapy of IGF-1 can ameliorate erectile functions and improve the levels of mRNA and protein of eNOS in senile rats.

[Growth factors and gene therapy for erectile dysfunction].

Growth factors have a universal bioactivity. Gene therapy is a new strategy in dealing with erectile dysfunction (ED). This paper presents an overview on the value of growth factors, particularly the vascular epithelial growth factor (VEGF) and insulin-like growth factor 1 (IGF-1), in the treatment of ED.

Higher expression of mRNA and protein of insulin-like growth factor binding protein-3 in old rat penile tissues: implications for erectile dysfunction.

INTRODUCTION: Previous studies have confirmed the gene transfer of insulin-like growth factor-1 (IGF-1) and the IGF-1 protein can improve the erectile function in aging rats. IGF binding protein (BP)-3 can regulates the availability of IGF-I. The higher expression of IGFBP-3 may play an important role in erectile dysfunction (ED). AIM: The study aimed to investigate the mRNA and protein expression of IGFBP-3 in young and old rat penile tissues and assess the alteration of the penile structure and the NO-guanosine 3',5'-cyclic-monophosphate (cGMP) signaling pathways-related marker in ED associated with aging. MAIN OUTCOME MEASURES: The main outcome measures for this study were the expression of IGFBP-3, morphological changes, NO-cGMP signaling pathways-related marker, erectile responses were determined. METHODS: Traditional reverse transcriptase polymerase chain reaction (RT-PCR) and real-time PCR were performed to examine the mRNA expression of the IGFBP-3. The Western blot was used to confirm the protein expression. Immunohistochemistry was also performed to identify the cellular localization of the encoded protein. The percentage of smooth muscle in corpus cavernosum tissue, the activity of nitric oxide synthase (NOS), and concentration of cGMP in penile tissue were also analyzed. RESULTS: The expression levels of IGFBP-3 of mRNA and protein were greatly increased in aging rats compared with young control rats, which is confirmed by traditional RT-PCR, real-time PCR, and Western blot (P < 0.01, respectively). Increased IGFBP-3 protein was localized to the epithelium of the urethra, penile endothelium, and smooth muscle in the corpus cavernosum. Significant depletion of the smooth muscle density relative to the connective tissue was also observed in the penis of the aged rats, and the lower activity of NOS and lower concentration of cGMP was also demonstrated accompanied with a significant reduction in the intracavernous pressure. CONCLUSIONS: Our data suggest that the increased mRNA and protein expression of IGFBP-3 in old rats may play a role in ED.

Single-centre study comparing standard apical dissection with a modified technique to facilitate vesico-urethral anastomosis during laparoscopic radical prostatectomy.

A modified apical dissection of the prostate to improve the efficiency of vesico-urethral anastomosis (VUA) in laparoscopic radical prostatectomy (LRP) was reported. A total of 42 patients were randomly selected and enrolled in this study. A standard LRP was performed in 21 patients (group 1), whereas a novel, modified apical dissection of the prostate in LRP was performed in another 21 patients (group 2). Surgical data, total operative time, VUA time, extravasation rate, catheterisation time, occurrence of anastomotic strictures, and the early and late continence rates were analysed statistically. No differences in clinical or pathological characteristics were determined between the two groups. The total operative time, VUA time, blood loss and catheterisation time were lower in group 2, which received the novel, modified technique compared with group 1, which received the standard technique to dissect the apex of the prostate (P < 0.01 for each variable). Regarding the extravasation rate and the occurrence of anastomotic strictures, no significant differences were found between the two groups (P > 0.05 for each). After catheter removal, a statistically significant difference in the continence rates was present at 3 and 30 days post operation in the two groups (P < 0.01, respectively). At 90 days post operation, the difference, although still present, was no longer statistically significant (P > 0.05). The novel, modified apical dissection of the prostate facilitates the VUA and significantly improves the efficacy of the procedure and early restoration of continence.

A comparative study of clinical value of single B-mode ultrasound guidance and B-mode combined with color doppler ultrasound guidance in mini-invasive percutaneous nephrolithotomy to decrease hemorrhagic complications.

OBJECTIVES: To compare the clinical value of single B-mode ultrasonography and B-mode combined with color Doppler ultrasonography in the guidance of mini-invasive percutaneous nephrolithotomy (m-PCNL) to decrease the incidence of hemorrhagic complications. METHODS: A total of 297 patients with renal stones who had undergone m-PCNL were retrospectively categorized into 2 groups. Group 1 (187 patients) underwent m-PCNL with single B-mode ultrasound guidance and group 2 (110 patients) underwent m-PCNL with combined B-mode and color Doppler ultrasound guidance. The clinical characteristics of the patients, intraoperative and postoperative characteristics, complications, especially hemorrhagic complications, and blood transfusion rate were recorded and compared. RESULTS: No statistically significant differences in age, height, weight, stone burden, operative time, stone-free rate, or length of postoperative hospital stay were found between the 2 groups. In group 2, a statistically significant decrease in the transfusion rate was found compared with group 1 (P <.05). In group 1, 5 patients (2.6%) required a blood transfusion, 2 (1.1%) developed a renal arteriovenous fistula and required embolotherapy, 2 (1.1%) developed hemorrhage and required embolotherapy after surgery, 16 (8.6%) developed capillary hemorrhage during surgery but had no hemorrhage postoperatively. However, no serious hemorrhagic complications were found in group 2. Only 3 patients (2.7%) developed capillary hemorrhage during surgery, and no hemorrhage occurred postoperatively. CONCLUSIONS: Using combined B-mode and color Doppler ultrasound guidance during in m-PCNL resulted in the real-time detection and avoidance of the renal blood vessels during puncture and decreased the incidence of hemorrhagic complications, especially in the patients with a solitary and compensative kidney.

Modified apical dissection of the prostate improves early continence in laparoscopic radical prostatectomy: technique and initial results.

OBJECTIVES: Incontinence after radical retropubic prostatectomy (RRP) is one of the greatest worries for all patients. One of the possible reasons for this urinary incontinence is a postoperative deficiency of the external striated urethral sphincter (EUS) complex and continence nerves. This study evaluated the application of a modified simple technique to dissection of the apical prostate in laparoscopic radical prostatectomy (LRP) and assessed the rate of urinary continence. METHODS: A total of 104 patients were randomly selected using envelopes and enrolled in this study. A standard LRP was performed in 52 patients (standard LRP group) and a modified technique for simple dissection of the apical prostate in LRP was performed in another 52 patients (modified LRP group). The urethra was dissected and transected at the apex of the prostate, proximal to the nerve-distributing rhabdosphincter using sharp scissors to avoid damage to the EUS complex and continence nerves. In all patients, a pad test was performed on 3, 30 and 90 days postoperatively and correlated with urinary continence. Continence was defined as zero pads or a liner used for security reasons only. RESULTS: After catheter removal, the continence rates were regained in 66, 85 and 96% of patients in the modified LRP group compared with 28, 55 and 91% of the patients in the standard LRP group at 3, 30 and 90 days, respectively. A statistically significant difference was present at 3 and 30 days (p < 0.01, respectively). At 90 days, the difference, although still present, was not statistically significant (p > 0.05). CONCLUSIONS: In this preliminary study, the technique of simplified apical dissection of the prostate in LRP appears to be an easy and feasible technique in early recovery of urinary continence. Further long-term and larger sample studies are necessary to elucidate the modified technique in LRP on early restoration of urinary continence.