Biomedical subjects

Serap Gur

Publications and source records attributed to Serap Gur.

4 recordsLinked to original sources

PubMed2006

The breakdown of preformed advanced glycation end products reverses erectile dysfunction in streptozotocin-induced diabetic rats: preventive versus curative treatment.

OBJECTIVES: Accumulation of advanced glycation end products (AGEs) has been linked to many of the complications of diabetes mellitus, including erectile dysfunction (ED). Furthermore, it has been demonstrated that inhibitors of AGE formation, such as aminoguanidine, can prevent ED in diabetic animals. However, it is unknown whether late administration of a putative cross-link breaker, ALT-711, can reverse diabetic ED. We therefore compared ALT-711 and aminoguanidine in their ability to reverse ED in diabetic rats. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly divided into four groups: (i) age-matched controls; (ii) streptozotocin (STZ)-induced diabetic rats (60 mg/kg; intraperitoneal injection); (iii) STZ diabetic rats treated with ALT-711 (3 mg/kg/day, intraperitoneal injection); and (iv) STZ diabetic rats treated with aminoguanidine (1 gm/L in drinking water) during the final 6 weeks of 12 weeks of induced diabetes. At the end of 12 weeks, erectile response to cavernous nerve stimulation (CNS) was determined. Neuronal nitric oxide synthase (nNOS) contents were measured in all penises, and AGE levels were determined both in penile tissues and in serum samples. RESULTS: Erectile responses to CNS and penile nNOS protein content were significantly reduced, while AGE levels were elevated in the penises and serum of untreated diabetic animals. Treatment with ALT-711, but not with aminoguanidine, reversed ED and nNOS depletion and reduced serum and penile tissue AGE levels. CONCLUSIONS: These results suggest that cross-link breakers, such as ALT-711, are the optimal therapeutic approach, compared with treatment with inhibitors of AGE formation, in the reversal of diabetes-related ED.

Animals↗

PubMed2005

Gene therapy for erectile dysfunction.

The past decade has seen an explosion of new information on the physiology of penile erection, pathophysiology of erectile dysfunction (ED), and development of new oral agents (e.g., three PDE5 inhibitors) to manage ED. Although all three selective PDE5 inhibitors are effective in the majority of ED cases, these oral medications have failed in certain disease states, such as diabetic ED, postprostatectomy ED, and severe veno-occlusive dysfunction. Only about 50% to 60% of these cases benefit from PDE5 inhibitor therapy, prompting the development of new approaches, including gene-based therapies for the treatment of ED. The penis is a convenient tissue target for gene therapy because of its external location and accessibility, the ubiquity of endothelial lined spaces, and low level of blood flow, especially in the flaccid state. Initially, gene therapy has been reserved for the treatment of life-threatening disorders including cancer, hereditary and acquired diseases. However, gene therapy is an attractive therapeutic possibility for the treatment of ED. Evolution of nitric oxide (NO), a small gaseous, lipophilic signaling molecule that is produced by nitric oxide synthase (NOS) activates guanylate cyclase (GC), resulting in increased cyclic guanosine monophosphate (cGMP) production, plays a significant role in our understanding of cavernosal smooth muscle physiology. Many gene therapy strategies have focused on the NO/GS/cGMP pathway. All three NOS isoforms, endothelial NOS (eNOS), neuronal NOS (nNOS), and iNOS have been used for gene therapy in order to modulate erectile response. Various viral and nonviral vectors have been used to date for the transfer of genetic material to the target cell or tissues with various degrees of success. Recently, second generation or "gutless" (helper-dependent) adenovirus vectors have been developed in order to reduce cellular toxicity and immune response, while increasing efficient gene therapy. Varieties of other gene therapy trials have also been undertaken for the treatment of ED and are the focus of this review.

Brain-Derived Neurotrophic Factor↗

PubMed2005

The relationship between the type of penile abnormality and penile vascular status in patients with peyronie's disease.

PURPOSE: We evaluated penile vascular status using penile duplex Doppler ultrasound (PDDU) according to the type of abnormality in men with Peyronie's disease (PD). MATERIALS AND METHODS: A total of 523 patients with PD were evaluated retrospectively. Each patient underwent PDDU following injections of 10 to 15 mug prostaglandin E1 intracavernously with accompanying visual sexual stimulation to evaluate penile blood flow. Abnormalities were divided into 7 groups. Objective evaluation of penile curvature was done with a protractor during maximum erection. Specific criteria were used to categorize patients into varying definitions of vascular status. The results were compared statistically among groups. RESULTS: Mean patient age +/- SEM was 54.2 +/- 1.5 years. The most frequently noted type of curvature was dorsal (43.5% of cases), followed by lateral (24.8%). Mean peak systolic velocity in the ventrolateral group was the highest, while the lowest peak systolic velocity was noted in the hourglass abnormality group. The hourglass group had the highest rate of pure arterial insufficiency, while veno-occlusive dysfunction was seen most commonly in the ventral curvature group. The ventrolateral group showed the most normal vascular status parameters. CONCLUSIONS: This study demonstrates there is a relationship between the type of curvature and penile hemodynamics. Although patients with PD in the hourglass abnormality group were the youngest, this abnormality was associated with the poorest penile vascular status. Patients with ventrolateral curvature had the best penile hemodynamics in our series. PDDU findings may direct the treating physician to different treatment options.

Diabetes Mellitus↗

PubMed2005

Poly(Adenosine diphosphate-ribose) polymerase inhibition preserves erectile function in rats after cavernous nerve injury.

PURPOSE: We investigated the involvement of poly(adenosine diphosphate-ribose) (PAR) polymerase (PARP) activation in the development of erectile dysfunction and the therapeutic benefit of the potent PARP inhibitor INO-1001 (Inotek Pharmaceuticals Corp., Beverly, Massachusetts) in a bilateral cavernous nerve crush injury (BCNCI) model in rats. MATERIALS AND METHODS: Sprague-Dawley rats were divided into 3 groups, namely sham treated, BCNCI plus vehicle and BCNCI plus the PARP inhibitor INO-1001. One week after surgical intervention all groups underwent in vivo cavernous nerve stimulation. PAR activation, nitrotyrosine and inducible nitric oxide synthase were evaluated by immunohistochemistry and serum levels of INO-1001 were measured by high performance liquid chromatography. Penile tissues were analyzed for levels of malondialdehyde and myeloperoxidase. Data sets were statistically compared in all groups. RESULTS: Neurogenic mediated erectile responses were evaluated. Mean intracavernous pressure (ICP), the ICP-to-blood-pressure ratio and total ICP were significantly decreased in BCNCI plus vehicle rats. These values were not statistically different between the sham and PARP inhibitor treated groups. There was a marked decrease in PAR staining in the treatment group. There was a substantial increase in malondialdehyde tissue levels but not myeloperoxidase in response to BCNCI, which was unchanged with PARP inhibitor treatment. There was a marked increase in tyrosine nitration in the treatment group. Up-regulation of nitric oxide synthase and increased tyrosine nitration were not observed in the penile tissues of the treatment group. CONCLUSIONS: These data demonstrate that BCNCI in a rat model causes increased PARP activation, resulting in severe erectile dysfunction. Treatment with the PARP inhibitor INO-1001 decreases the degree of nitrosative stress, prevents PARP activation and provides significant cavernous neuroprotection, which in turn preserves erectile function.

Adenosine Diphosphate Ribose↗