To investigate, if advanced glycation end products (AGEs) are involved in erectile dysfunction (ED) and also ALT-711, a cross-link breaker of AGEs, has the therapeutic potential against the ...development of ED in rats treated with high concentrated AGEs including food. For this purpose, 30 male Harlan Spraque-Dawley rats randomly were divided into three groups; (1) control rats treated with regular diet, (2) rats treated with high-level of AGE specific diet for 6 months, and (3) rats having AGE-diet treated with ALT-711 for the final 3 months of 6 months of AGE-diet period. Erectile response to cavernosal nerve stimulation (CNS), protein expression of neuronal nitric oxide synthase (nNOS) and levels of AGEs, Malondialdehyde (MDA), cyclic guanosine monophosphate (cGMP) were determined in penile tissues. Erectile responses to CNS and penile nNOS and cGMP content were significantly reduced, while AGEs and MDA were elevated in penises of Group-2. Treatment with ALT-711 reversed ED and depletion of both nNOS and cGMP. Additionally, ALT-711 treatment reduced penile tissue AGEs and MDA expression. In present study: rats without any co-morbidity such as diabetes mellitus (DM) and chronic renal failure (CRF) were treated with high-level AGEs containing food. Our results suggest that ALT-711 may be an interesting and promising approach in the treatment of AGEs-related ED.
Significant impairment in endothelial-derived nitric oxide is present in the diabetic corpus cavernosum. RhoA/Rho-kinase may suppress endothelial nitric oxide synthase (eNOS). Here, we tested the ...hypothesis that RhoA/Rho-kinase contributes to diabetes-related erectile dysfunction and down-regulation of eNOS in the streptozotocin (STZ-diabetic rat penis. Colocalization of Rho-kinase and eNOS protein was present in the endothelium of the corpus cavernosum. RhoA/Rho-kinase protein abundance and MYPT-1 phosphorylation at Thr-696 were elevated in the STZ-diabetic rat penis. In addition, eNOS protein expression, cavernosal constitutive NOS activity, and cGMP levels were reduced in the STZ-diabetic penis. To assess the functional role of RhoA/Rho-kinase in the penis, we evaluated the effects of an adeno-associated virus encoding the dominant-negative RhoA mutant (AAVTCMV19NRhoA) on RhoA/Rho-kinase and eNOS and erectile function in vivo in the STZ-diabetic rat. STZ-diabetic rats transfected with AAVCMVT19NRhoA had a reduction in RhoA/Rho-kinase and MYPT-1 phosphorylation at a time when cavernosal eNOS protein, constitutive NOS activity, and cGMP levels were restored to levels found in the control rats. There was a significant decrease in erectile response to cavernosal nerve stimulation in the STZ-diabetic rat. AAVT19NRhoA gene transfer improved erectile responses in the STZ-diabetic rat to values similar to control. These data demonstrate a previously undescribed mechanism for the down-regulation of penile eNOS in diabetes mediated by activation of the RhoA/Rho-kinase pathway. Importantly, these data imply that inhibition of RhoA/Rho-kinase improves eNOS protein content and activity thus restoring erectile function in diabetes.
Little is known about sperm health in male patients with familial Mediterranean fever (FMF). In this study, the authors aimed to search the frequency of sperm abnormalities of adolescent boys with ...FMF and also to investigate whether disease activity or colchicine treatment have negative effects on sperm parameters.
The male adolescents older than 14 years with a diagnosis of FMF were investigated retrospectively. Tel Hashomer and pediatric FMF clinical criteria were used for diagnosis of FMF. Patients who had semen analysis were included in the study.
Mean age at the diagnosis was 11.13 ± 3.82 years, and mean age at the study was 14.50 ± 0.70 years. The mean sperm concentration was found as 66.26 ± 41.02 million/ml (N > 15 million/ml), the mean total sperm count 113.42 ± 132.39 million (N > 39 million), and the mean sperm motility 51.78 ± 23.70% (N > 40%). Only 8 of 19 (42.1%) patients had normal sperm parameters. Sperm concentration was reduced in two cases, total sperm count was reduced in four patients, and motility was reduced in nine cases. The presence of FMF attacks under treatment was found to be a risk factor for decreased motility in the study group by multivariate regression analysis (odds ratio 0.076, 95% confidence interval 0.005–0.648, P = 0.031). Erythrocyte sedimentation rate at the time of diagnosis was high in patients with low sperm counts compared with those with normal sperm counts (56.00 ± 8.51 vs 24.35 ± 6.32, P: 0.03). Mean colchicine dose at the time of sperm analysis was higher in patients with low sperm motility than that with normal sperm motility (1.72 ± 0.18 vs 1.25 ± 0.08, P: 0.02).
Sperm abnormalities of male patients with FMF is not infrequent, and it is linked to both inflammation due to uncontrolled disease and colchicine therapy.Table The laboratory finding and colchicine dose of FMF patients with normal and abnormal semen parameters (n = 19)VariableSperm concentrationaTotal sperm countbMotilitycNormalLowPNormalLowPNormalLowPMean CRP0.12 ± 0.020.89 ± 0.550.280.95 ± 0.630.27 ± 0.090.921.35 ± 0.930.21 ± 0.040.32Mean ESR2.50 ± 0.509.06 ± 2.210.369.27 ± 2.505.00 ± 1.780.8310.40 ± 3.616.11 ± 1.440.76Mean SAA7.28 ± 4.4249.66 ± 35.530.5051.06 ± 41.4523.22 ± 16.010.6873.84 ± 61.9313.38 ± 7.270.56Mean colchicine dose (mg/day)1.50 ± 1.211.25 ± 0.250.461.37 ± 0.771.88 ± 0.420.321.25 ± 0.081.72 ± 0.180.02CRP, C-reactive protein; ESR, erythrocyte sedimentation rate; SAA, serum amyloid A.aNormal sperm concentration >15 million.bNormal total count >39 million.cNormal motility rate >40%.
Recently, the relationship between advanced glycation end products (AGEs) and erectile dysfunction (ED) has been reported. The present study aimed to investigate whether a combination of an AGE ...cross-link breaker (alagebrium/ALT-711) and sildenafil could enhance the erectile capacity in streptozotocin (STZ) diabetic rats. Additionally, we assessed the effect of that treatment option on some molecules that have been suggested to have crucial roles in AGE-related ED pathways. Four groups of animals were utilized: (1) age-matched control rats, (2) STZ-induced diabetic rats (40 mg kg(-1) i.p.), (3) STZ rats+sildenafil (5 mg kg(-1) p.o.), (4) STZ rats treated with a combination of sildenafil (5 mg kg(-1) p.o)+alagebrium/ALT-711 (10 mg kg(-1) p.o.) for the final 1 month of the 2 months of diabetes period. At 2 months after i.p. injection of STZ, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Penile tissue AGEs, MDA (malondialdehyde), cyclic guanosine monophosphate (cGMP) (ELISA), endothelial nitric oxide (NO) synthase (eNOS), inducible NO synthase (iNOS) (western blot), nuclear factor (NF)-κB, mitogen-activated protein (MAP) kinase (immunohistochemistry) and apoptosis (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling) analyses were performed in all groups of rats. STZ diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve) after CNS when compared with control rats (P<0.05). The increase in both ICP and area under the erectile curve of STZ diabetic rats treated with a combination of sildenafil+alagebrium/ALT-711 as well as in STZ diabetic rats treated with sildenafil alone was significantly greater than STZ diabetic rats. Additionally, combination treatment decreased AGE, MDA, iNOS, NF-κB, MAP kinase and apoptosis levels, whereas it preserved cGMP contents in diabetic penile tissue. Decreased AGE, MDA, iNOS, NF-κB, MAP kinase and increased cGMP levels at the combination (sildenafil+alagebrium/ALT-711) therapy group increased both the peak ICP and total ICP to CNS in the STZ diabetic rats, which was similar to the response observed in control rats. These results may explain the role of AGEs in diabetes-related ED and the effect of an AGE cross-link breaker alagebrium/ALT-711+sildenafil therapy on some critical molecules related to AGE-related ED pathways.
Summary
Environmental exposure to pesticides may cause serious health risks including fertility and reproductive function. The aim of this study was to highlight whether there is a relationship ...between exposure to abamectin and male fertility parameters of farmworkers. Twenty male farmworkers who were using abamectin and 20 men not exposed to pesticides were recruited as experimental and control groups, respectively. Semen analysis, molecular markers of sperm maturity and serum reproductive hormone levels were evaluated. In experimental group, high plasma abamectin levels were detected. These men have decreased sperm motility. Moreover, diminished molecular markers of sperm maturity, such as decreased hyaluronic acid (HA) binding of sperm, increased numbers of aniline blue positive sperm and increased percentage of creatine kinase (CK) positive sperm, were observed in abamectin‐exposed men. Their serum testosterone, LH and FSH levels did not change significantly. We conclude that exposure to abamectin may impair male fertility by effecting semen quality.
Summary
Erectile dysfunction (ED) is the most common male sexual problem worldwide. The association between ED and components of metabolic syndrome (MtS) is well established. This study examined neck ...circumference (NC) as a possible indicator of MtS and also of ED. Ninety‐two patients were included and divided into two groups. Group 1 consisted of 47 patients with ED and Group 2 consisted of 45 healthy volunteers. Questionnaires, differences in anthropometric and laboratory measurements between patients with ED and the control group, and a cut‐off value for NC were investigated. The mean NC in ED patients was higher in Group 1 than in Group 2 (P = 0.001), and Group 1 also demonstrated more MtS criteria than Group 2 (P < 0.001). The cut‐off point of NC was defined as 34.75 cm for ED and MtS. The cut‐off values of waist circumference for ED and MtS were 105.5 and 102.5 cm respectively. In the light of these findings, NC may be a new component of MtS in ED patients. Additionally, NC may be a novel indicator of central obesity and ED. We suggest that NC values of 35 cm and over may predict ED in patients with MtS.
OBJECTIVE
To describe our experience of inguinal exploration in patients who had a reasonable chance of having a benign testicular lesion.
PATIENTS AND METHODS
From 1995 to 2002, 11 patients (mean ...age 43 years, range 27–63) with testicular masses that were suspected to be benign underwent inguinal exploration.
RESULTS
In nine of the 11 patients, frozen‐section analysis and the final pathological results were similar, and two underwent inguinal orchidectomy. In seven patients the testicle was spared. Finally, because of an uncertain pathological diagnosis and patient age, two patients underwent orchidectomy.
CONCLUSIONS
Inguinal exploration and testicular‐sparing surgery are reasonable options in patients with peripheral intratesticular lesions, on the basis of preoperative ultrasonographic characteristics, and if there is a possibility of the mass being benign because of age, race, physical examination and tumour markers.
Erectile dysfunction associated with diabetes mellitus is caused in part by disordered endothelial smooth muscle relaxation, neuropathy, and a decrease in cavernosal nitric oxide synthase (NOS) ...activity. The purpose of this study was to determine whether a combination of sildenafil and adenoviral gene transfer of endothelial NOS (eNOS) could enhance the erectile response in diabetic rats. Five groups of animals were utilized: (1) age-matched control rats, (2) streptozotocin (STZ)-induced diabetic rats (60 mg/kg i.p.), (3) STZ-rats + sildenafil (2 mg/kg i.v.), (4) STZ-rats transfected with AdCMVbetagal or AdCMVeNOS, and (5) STZ-rats transfected with AdCMVeNOS +sildenafil (2 mg/kg i.v.). At 2 months after i.p. injection of STZ, groups 4 and 5 were transfected with the adenoviruses and 1-2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Cyclic 3',5'-guanosine monophosphate (cGMP) levels were assessed in the cavernosal tissue. STZ-diabetic rats had a significant decrease in erectile function as determined by the peak intracavernosal pressure (ICP) and total ICP (area under the erectile curve; AUC) after CNS when compared to control rats. STZ-diabetic rats+AdCMVeNOS had a peak ICP and AUC, which were similar to control animals. STZ-diabetic rats administered sildenafil demonstrated a significant increase in peak ICP at the 5 and 7.5 V settings, while the AUC was significantly increased at all voltage (V) settings. The increase in both ICP and AUC of STZ-diabetic rats transfected with AdCMVeNOS at all V settings was greater than STZ-diabetic rats transfected with AdCMVbetagal. STZ-diabetic rats transfected with AdCMVeNOS and administered sildenafil had a significant increase in total ICP that was greater than eNOS gene therapy alone. Cavernosal cGMP levels were significantly decreased in STZ-diabetic rats, but were increased after transfection with AdCMVeNOS to values greater than control animals. In conclusion, overexpression of eNOS and cGMP in combination with sildenafil significantly increased both the peak ICP and total ICP to CNS in the STZ-diabetic rat, which was similar to the response observed in control rats. Moreover, the total erectile response was greater in STZ-diabetic rats receiving eNOS gene therapy plus sildenafil than STZ-rats receiving sildenafil or eNOS gene therapy alone.
Superoxide anion may contribute to erectile dysfunction (ED) in diabetes mellitus by reducing cavernosal nitric oxide (NO) bioavailability. The purpose of this study was to determine if gene transfer ...of extracellular superoxide dismutase (EC-SOD) can reduce superoxide anion formation and determine if this reactive oxygen species may contribute to diabetes-related ED in an experimental model of diabetes.
Three groups of animals were utilized: (1) control; (2) streptozotocin (STZ)-diabetic rats 60 mg/kg intraperitoneally (ip) intracavernosally injected with AdCMVbetagal (negative control); and (3) STZ-rats intracavernosally injected with AdCMVEC-SOD. Two months after ip injection of STZ, groups 2 and 3 were transfected with the adenoviruses and 2 days after transfection, all animals underwent cavernosal nerve stimulation (CNS) to assess erectile function. Confocal microscopy for superoxide anion and von Willebrand Factor (vWF) was performed in the STZ-diabetic rat. Superoxide anion production, total SOD activity, and cyclic guanosine monophosphate (cGMP) levels were measured in each experimental group of rats.
Confocal microscopy demonstrated superoxide in smooth muscle and endothelial cells of the STZ-rat cavernosum and colocalized with vWF in the endothelium. Higher superoxide anion levels and decreased cGMP levels were found in the penis of STZ-rats at a time when erectile function was reduced. Two days after administration of AdCMVEC-SOD, superoxide anion levels were significantly lower in the penis of STZ-rats. Total SOD activity and cavernosal cGMP was increased in the penis of EC-SOD-transfected rats. STZ-rats transfected with AdCMVEC-SOD had a peak intracavernosal pressure (ICP) and total ICP to CNS that was similar to control rats.
These data demonstrate that in vivo adenoviral gene transfer of EC-SOD can reduce corporal superoxide anion levels and raise cavernosal cGMP levels by increasing NO bioavailability thus restoring erectile function in the STZ-diabetic rat.
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