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A J Becker

Publications and source records attributed to A J Becker.

At least 19 recordsLinked to original sources
PubMed2006

Frequent loss of chromosome 9, homozygous CDKN2A/p14(ARF)/CDKN2B deletion and low TSC1 mRNA expression in pleomorphic xanthoastrocytomas.

The molecular pathogenesis of pleomorphic xanthoastrocytoma (PXA), a rare astrocytic brain tumor with a relatively favorable prognosis, is still poorly understood. We characterized 50 PXAs by comparative genomic hybridization (CGH) and found the most common imbalance to be loss on chromosome 9 in 50% of tumors. Other recurrent losses affected chromosomes 17 (10%), 8, 18, 22 (4% each). Recurrent gains were identified on chromosomes X (16%), 7, 9q, 20 (8% each), 4, 5, 19 (4% each). Two tumors demonstrated amplifications mapping to 2p23-p25, 4p15, 12q13, 12q21, 21q21 and 21q22. Analysis of 10 PXAs with available high molecular weight DNA by high-resolution array-based CGH indicated homozygous 9p21.3 deletions involving the CDKN2A/p14(ARF)/CDKN2B loci in six tumors (60%). Interphase fluorescence in situ hybridization to tissue sections confirmed the presence of tumor cells with homozygous 9p21.3 deletions. Mutational analysis of candidate genes on 9q, PTCH and TSC1, revealed no mutations in PXAs with 9q loss and no evidence of TSC1 promoter methylation. However, PXAs consistently showed low TSC1 transcript levels. Taken together, our study identifies loss of chromosome 9 as the most common chromosomal imbalance in PXAs and suggests important roles for homozygous CDKN2A/p14(ARF)/CDKN2B deletion as well as low TSC1 mRNA expression in these tumors.

Adolescent↗
PubMed2005

[Therapy for organic erectile dysfunction].

Erectile dysfunction is a common disease of men. It is associated with various comorbidities and has a prevalence of about 50% in the 7th decade. Erectile dysfunction often affects the quality of life of the patient and his partner, and it is very important to offer adequate therapy that respects the individual circumstances of each patient. The mandatory diagnostic work-up includes a medical and psychosexual history, a physical examination and routine laboratory tests. Besides psychotherapy, oral pharmacotherapy with oral PDE-5 inhibitors (sildenafil, tadalafil, vardenafil) is the most effective therapy for erectile dysfunction and is superior to centrally acting drugs (yohimbine). In cases of failure or contraindication of oral pharmacotherapy, local pharmacotherapy is the second-line therapy. The third-line options are vacuum erectile devices and penile implants, and these have a high patient satisfaction. New therapeutic strategies such as anti-serotoninergic substrates and growth hormone offer a promising future for the therapy of erectile dysfunction but remain to be evaluated.

Erectile Dysfunction↗
PubMed2004

Expression analysis of metabotropic glutamate receptors I and III in mouse strains with different susceptibility to experimental temporal lobe epilepsy.

Increased hippocampal excitability constitutes a pathogenetic hallmark of pharmacoresistant human temporal lobe epilepsy (TLE). Metabotropic glutamate receptors (mGluRs) can be subdivided into three classes based on sequence homologies, mechanisms of signal transduction as well as pharmacological characteristics. Generally, class I mGluRs mediate neuronal excitation whereas activation of class II and III mGluRs decreases synaptic transmission. Changes in expression of class I and III mGluR subunits have been described in human TLE. It remains to be determined whether altered mGluR expression relates to differences in seizure susceptibility or hippocampal damage. Here, we examine the transcription levels of mGluRs class I (mGluR1 and 5) and III (mGluR4 and 7) in experimental TLE and correlate differential mGluR subunit expression with mouse-strain-dependent susceptibility to TLE induced by pilocarpine. Expression of mGluRs 1, 4, 5 and 7 was determined in epileptic dentate gyrus granule cells (DG) in CD1, C57BL/6 and FVB/N mice by real time RT-PCR. FVB/N mice appear significantly more vulnerable to pilocarpine-induced seizures than C57BL/6 and CD1 strains. RT-PCR analysis demonstrates an increased expression of inhibitory mGluR 4 and downregulation of excitatory mGluR 1 in epileptic CD1 mice and a decrease of the excitatory mGluRs 1 and 5 in C57BL/6 (p<0.05, n=6 each) but not in the FVB/N strain. These results correlate differential expression of excitatory class mGluR I and inhibitory class mGluR III to seizure susceptibility and hippocampal damage. Our data suggest mGluRs class I and III as interesting potential therapeutic targets to interfere with hippocampal epileptogenesis and hyperexcitability.

Animals↗
PubMed2004

The reelin pathway components disabled-1 and p35 in gangliogliomas--a mutation and expression analysis.

Focal epilepsies in young patients are frequently associated with differentiated glioneuronal tumours. Dysplastic neurones represent a characteristic neuropathological feature of gangliogliomas, the most common entity encountered in this group. Here, we have analysed two major components of the reelin pathway involved in neuronal migration and cortical development, that is, p35 and disabled-1 (dab1), in gangliogliomas. Genomic structures of human dab1 and p35 were identified 'in silico' using the HTGS databank, NCBI BLAST 2.1. DNA sequence analysis was carried out in gangliogliomas obtained from 29 epilepsy patients vs. peripheral blood DNA from non-affected control individuals (n = 100). Gene expression of dab1 and p35 was determined by real-time RT-PCR (reverse transcriptase polymerase chain reaction) in gangliogliomas (n = 14) vs. non-neoplastic central nervous system tissue (n = 20). The human dab1 gene contains 13 coding exons and is located on chromosome 1p31-32. A single coding exon constitutes the human p35 gene, which is located on chromosome 17q11.2. A novel homologueous genomic region on chromosome 2 has to be taken into account for future studies on p35. One ganglioglioma patient showed a unique polymorphism in the p35 gene. The single base exchange (C to A) at nucleotide 904 of the p35 cDNA (GenBank X80343, start ATG, codon 302) results in a leucine-isoleucine amino acid substitution. No mutations of the dab1 and p35 genes in gangliogliomas were observed. However, significantly lower levels of dab1 and p35 gene transcripts were detected in gangliogliomas compared to controls (dab1 28.24%, t-test P < 0.001; p35 21.28%, t-test P < 0.001, in gangliogliomas vs. controls). Our data suggest that mutational events of dab1 and p35 are not involved in the molecular pathogenesis of gangliogliomas. A potential functional role of these developmentally regulated genes for the formation of epileptogenic glioneuronal lesions remains to be elucidated.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Growth hormone, somatomedins and men's health.

According to current basic science as well as the clinical literature, human growth hormone has become an important topic in the field of anti-aging medicine. It is well known that the administration of human growth hormone compensates for the dwarfism syndrome in growth hormone-deficient children and growth hormone is also established as a substitution therapy for adults with pituitary deficiency. The effects mediated by growth hormone comprise an increase in muscle mass, a decrease in body fat, improved physical condition, oxygen consumption and overall quality of life, an improvement of the ratio of high-density lipoprotein to low-density lipoprotein, as well as an increase in bone density. Due to the insulin antagonistic effect of growth hormone as well as its insulin-like growth factor-1-mediated mitogenic effect, there is reason to doubt the safety of administering growth hormone outside the framework of approved indications. In an ongoing study, we are evaluating whether growth hormone and somatomedins might be of importance in the regulation of male sexual performance, including penile erection.

Adult↗
PubMed2001

Plasma levels of cyclic guanosine-3',5'-monophosphate in the cavernous and systemic blood of healthy males during different functional conditions of the penis.

The relaxation of cavernous arterial and trabecular smooth muscle is dependent upon the stimulation of guanylyl cyclase activity by nitric oxide (NO), which is released from nerve terminals and endothelial cells within the cavernous tissue, and the subsequent accumulation of cyclic guanosine-3',5'-monophosphate (cGMP) in the intracellular space. The present study was undertaken to determine whether or not plasma levels of cGMP in the systemic and cavernous blood of healthy male subjects change from penile flaccidity to tumescence, rigidity and detumescence. Fifteen adult healthy males were exposed to visual and tactile erotic stimuli to elicit penile tumescence and rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein in the respective penile stages, and cGMP was determined in plasma aliquots by means of a radioimmunoassay. Mean systemic and cavernous plasma levels of cGMP in the blood samples obtained from the healthy volunteers ranged from 1.2-1.7 pmol/ ml. cGMP levels in the systemic circulation and in the cavernous blood did not change during developing erection, rigidity and detumescence. No significant differences were found between cGMP plasma levels in the systemic and cavernous blood in the different penile stages. Our results may reflect the fact that the stimulation of NO production in healthy males during sexual arousal and developing penile erection either does not yield substantial quantities of cGMP or that the rate of cGMP-extrusion from cavernous smooth muscle cells into the extracellular space accounts only for a minor fraction of plasma cGMP. Moreover, basal levels of cGMP in the blood flushing the lacunar spaces of the cavernous body in the state of developing erection may conceal any local release of cGMP that may occur within the penile erectile tissue. Thus, we conclude that the quantification of cGMP is of no use in the evaluation of the physiologic mechanisms of penile erection in vivo.

Adult↗
PubMed2001

Phosphodiesterase 1 inhibition in the treatment of lower urinary tract dysfunction: from bench to bedside.

Anticholinergic drugs are currently the therapy of choice to treat urgency and urge incontinence. However, muscarinergic receptor blockers with adequate selectivity for detrusor smooth muscle are not available. Also, in contrast to the normal detrusor, the unstable detrusor neurotransmission seems to be at least partially regulated by non-cholinergic (NANC) pathways. These factors may explain the common side effects and the limited clinical efficacy of these compounds. Specific modulation of intracellular second messenger pathways offers the possibility of organ selective manipulation of tissue function, specifically contraction and relaxation of smooth musculature. Because of their central role in the intracellular regulation of smooth muscle tone phosphodiesterases (PDEs) are an attractive pharmacological targets. The PDE 5 specific inhibitor sildenafil (Viagra) has revolutionized the treatment of patients with erectile dysfunction. Numerous other PDE inhibitors are currently under investigation for the treatment of various disorders. We investigated the role of PDEs in human detrusor smooth muscle. Our data demonstrate the presence of five PDE isoenzymes in human detrusor and suggest, for the first time, that the cAMP pathway and the calcium/calmodulin-stimulated PDE (PDE 1) are of functional importance in the intracellular regulation in this tissue in vitro. In addition. initial clinical data with the PDE 1 inhibitor vinpocetine in patients not responding to standard anticholinergic therapy indicate a possible role for vinpocetine in the treatment of urgency, urge incontinence and, possibly, low compliance bladder and interstitial cystitis. The results of a larger randomized, double-blind, placebo-controlled, multicenter trial with vinpocetine show a tendency in favor of vinpocetine over placebo; however, statistically significant results were documented for one parameter only. This might be due to the rather low dosage chosen and the small sample size. Further studies are necessary and currently underway to delineate the optimal dosage, indications and patient population. Modulation of intracellular key enzymes effecting second messenger metabolism, i.e. isoenzyme-selective PDE inhibition is a novel approach which possibly avoids the limitations of anticholinergic therapy in patients with lower urinary tract dysfunction.

Humans↗
PubMed2001

Possible role of bradykinin and angiotensin II in the regulation of penile erection and detumescence.

OBJECTIVES: To examine the functional effects of bradykinin (BK) and angiotensin II (AN II) on isolated human cavernous tissue and to detect any changes in the AN II levels in cavernous and peripheral blood samples taken from healthy volunteers at different functional conditions of the penile erectile tissue. Metabolites of the renin-angiotensin system and endothelium-derived vasoactive substances are known to be involved in the regulation of arterial vascular tone. The human corpus cavernosum (HCC), consisting of endothelial and smooth muscle cells, can be regarded as a compartment comparable to the vascular system. METHODS: The relaxing and contracting properties of BK and AN II on isolated HCC were investigated using the organ bath technique. Tissue levels of adenosine-3,5-cyclic monophosphate (cAMP) and guanosine-3,5-cyclic monophosphate (cGMP) were determined using specific radioimmunoassays, after exposing isolated HCC strips in a dose-dependent manner to BK, forskolin, and sodium nitroprusside. Blood samples were drawn simultaneously from the corpus cavernosum and cubital vein of 34 healthy volunteers at stages of penile flaccidity, tumescence, rigidity, and detumescence. Penile erection was induced by audiovisual and tactile stimulation. AN II levels were determined using a radioimmunoassay. RESULTS: In vitro, BK, forskolin, and sodium nitroprusside elicited dose-dependent relaxation of norepinephrine-induced tension of isolated HCC, and AN II evoked dose-dependent contraction of the HCC strips. The relaxing potency of BK was paralleled by its ability to elevate the intracellular levels of cAMP and cGMP. In vivo, the AN II levels in the cavernous plasma increased from 21.8 +/- 4.6 pg/mL in the flaccidity phase to 27.9 +/- 10 pg/mL in the detumescence phase. In the peripheral plasma, the AN II levels were 17.2 +/- 6.2 to 19.5 +/- 6.5 pg/mL in the respective penile stages. Thus, the mean AN II levels in the cavernous blood were about 30% higher than in the blood samples taken from the cubital vein. In the cavernous blood, the increase in the AN II plasma levels in the detumescence phase (27.9 +/- 10 pg/mL) was statistically significant. CONCLUSIONS: Our results suggest that penile cavernous smooth muscle tone is partially balanced by kinin-induced relaxation and AN II-induced contraction. Since the tissue and plasma levels of both peptides are regulated by the activity of the angiotensin-converting enzyme, there might be a rationale for the use of angiotensin-converting enzyme inhibitors in the treatment of erectile dysfunction associated with arterial hypertension.

Adult↗
PubMed2001

Cavernous and systemic testosterone plasma levels during different penile conditions in healthy males and patients with erectile dysfunction.

OBJECTIVES: To determine the testosterone plasma levels in the cavernous and peripheral blood taken during different penile conditions from patients with erectile dysfunction (ED) and to evaluate whether these courses are different from those detected in the blood of healthy males. Although the determination of the systemic testosterone concentration (TC) has been fairly well established in the diagnostic workup of ED, the exact role of testosterone in adult male sexual function remains unclear. METHODS: Blood samples were drawn simultaneously from the corpus cavernosum and cubital vein of 54 healthy males with normal erectile function and 46 patients with ED during the penile stages of flaccidity, tumescence, rigidity (reached by the healthy males only), and detumescence. Tumescence and rigidity were induced by audiovisual and tactile stimulation. The TC was determined by means of a radioimmunoassay. RESULTS: In the flaccid phase, the TC in the cavernous blood taken from the healthy volunteers was 2.9 +/- 1.2 ng/mL. The TC significantly increased during tumescence (4.3 +/- 1.3 ng/mL) and rigidity (4.4 +/- 1.4 ng/mL), P <0.001. In the detumescence phase, the TC decreased appreciably to 3.5 +/- 1.4 ng/mL. In the systemic blood, the increase from flaccidity (4.1 +/- 1.1 ng/mL) to tumescence (4.4 +/- 1.4 ng/mL) was found to be less pronounced but, nevertheless, significant (P = 0.001). No further increase was detected during rigidity. From rigidity to detumescence, the systemic TC dropped to 4.1 +/- 1.2 ng/mL. In the patients with ED, the mean increase in systemic and cavernous testosterone levels from flaccidity (cubital vein 3.0 +/- 1.0 ng/mL, corpus cavernosum 2.6 +/- 1.0 ng/mL) to tumescence (cubital vein 3.2 +/- 1.1 ng/mL, corpus cavernosum 3.0 +/- 1.0 ng/mL) was less pronounced. Nevertheless, the course of testosterone detected in the systemic and cavernous plasma of the patients during flaccidity, tumescence, and detumescence resembled that registered in the healthy controls. In the flaccid phase, the mean cavernous TC in the healthy subjects was found to be 30% lower than the level in the peripheral blood; in the patients with ED, this difference was only 13%. CONCLUSIONS: In the healthy males, the penile erection was accompanied by an increase in the cavernous and peripheral TC. The difference between the peripheral and cavernous TC in the healthy subjects and patients with ED in the flaccid phase, when the blood flow through the cavernous body is minimized, might be a diagnostic tool to evaluate the amount of bioavailable testosterone, as well as the density of testosterone receptors, in the cavernous smooth musculature.

Erectile Dysfunction↗
PubMed2001

Plasma levels of angiotensin II during different penile conditions in the cavernous and systemic blood of healthy men and patients with erectile dysfunction.

OBJECTIVES: To detect changes in plasma levels of angiotensin II (Ang II) under different functional conditions of the penile erectile tissue in the cavernous and systemic blood of patients with erectile dysfunction (ED) and compare them with the course of Ang II in healthy male subjects. It has been shown that the mammalian corpus cavernosum produces and secretes physiologically relevant amounts of the vasoconstrictive peptide Ang II and that intracavernosal injection of Ang II terminates penile erection in the dog. Thus, we speculated whether a dysregulation in the secretion or degradation of Ang II might contribute to the manifestation of ED. METHODS: Thirty-four healthy adult men and 48 patients with ED of either organogenic or psychogenic etiology were exposed to visual and tactile erotic stimuli to elicit penile tumescence and, in the group of healthy subjects, rigidity. Whole blood was simultaneously aspirated from the corpus cavernosum and the cubital vein during the different functional conditions of the penis. Ang II plasma levels were measured using a radioimmunoassay. RESULTS: In healthy men, the Ang II levels in the cavernous plasma increased from 22.1 +/- 7.1 pg/mL in the phase of penile rigidity to 27.9 +/- 10 pg/mL in the detumescence phase. In the peripheral plasma, the Ang II levels were 17.2 +/- 6.2 to 19.5 +/- 6.5 pg/mL over the respective penile stages. The courses of Ang II registered in the patients were similar to those detected in the healthy men. In the patients and healthy men, systemic Ang II levels were found to be lower than the concentrations detected in the cavernous blood. In the group of organogenic patients, the Ang II levels during penile flaccidity in the systemic and cavernous blood were higher than those registered in the blood samples taken from the healthy men. CONCLUSIONS: Our results suggest that cavernous smooth muscle tone is, in part, balanced by Ang II-induced contraction and that Ang II might be involved in the initiation of penile detumescence in men. That Ang II plasma levels are generally elevated in the systemic and cavernous blood of patients with an organogenic etiology of ED may hint at the significance of Ang II in the pathophysiology of ED. Since the tissue and plasma levels of Ang II are regulated by the activity of angiotensin-converting enzyme, there might be a rationale for the use of angiotensin-converting enzyme inhibitors in the treatment of vasculogenic ED.

Adult↗
PubMed2001

Mutational analysis of TSC1 and TSC2 genes in gangliogliomas.

Gangliogliomas constitute the most frequent tumour entity in patients with temporal lobe epilepsy. The characteristic histopathological admixture of glial and neuronal elements, the focal nature and their differentiated phenotype and benign biological behaviour suggest an origin from a developmentally compromised or dysplastic precursor lesion. The present study analysed TSC1 and TSC2 genes as potential candidates involved in the pathogenesis of this intriguing neoplasm. Recent data suggest that both genes play a role in cortical differentiation and growth control. DNA sequence analysis of TSC1 and TSC2 was studied in 20 patients with gangliogliomas. Fifteen of these tumours (75%) carried polymorphisms in the TSC2 gene. The frequency of these polymorphisms was significantly increased in intron 4 (12.5%) and exon 41 (15%) compared to control individuals (8.1 and 6.5%, respectively, n = 100). A somatic mutation in intron 32 of the TSC2 gene was encountered in one patient. In the TSC1 gene, seven polymorphisms occurred as a combination of base exchanges in exon 14 and intron 13. No mutations were observed in this gene. Laser microdissection and harvesting of individual neuronal and glial elements identified the intron 32 mutation within the glial portion but not in dysplastic neurones of the tumour. The data demonstrate numerous polymorphisms as well as a novel TSC2 mutation in gangliogliomas from patients with chronic epilepsies. The selective detection of the TSC2 mutation within the glial component of a ganglioglioma suggests that the glioma portion has undergone clonal evolution in this case.

Brain Neoplasms↗
PubMed2001

Distinct expression pattern of microtubule-associated protein-2 in human oligodendrogliomas and glial precursor cells.

Microtubule-associated protein 2 (MAP2), a protein linked to the neuronal cytoskeleton in the mature central nervous system (CNS), has recently been identified in glial precursors indicating a potential role during glial development. In the present study, we systematically analyzed the expression of MAP2 in a series of 237 human neuroepithelial tumors including paraffin-embedded specimens and tumor tissue microarrays from oligodendrogliomas, mixed gliomas, astrocytomas, glioblastomas, ependymomas, as well as dysembryoplastic neuroepithelial tumors (DNT), and central neurocytomas. In addition, MAP2-immunoreactive precursor cells were studied in the developing human brain. Three monoclonal antibodies generated against MAP2A-B or MAP2A-D isoforms were used. Variable immunoreactivity for MAP2 could be observed in all gliomas with the exception of ependymomas. Oligodendrogliomas exhibited a consistently strong and distinct pattern of expression characterized by perinuclear cytoplasmic staining without significant process labeling. Tumor cells with immunoreactive bi- or multi-polar processes were mostly encountered in astroglial neoplasms, whereas the small cell component in neurocytomas and DNT was not labeled. These features render MAP2 immunoreactivity a helpful diagnostic tool for the distinction of oligodendrogliomas and other neuroepithelial neoplasms. RT-PCR, Western blot analysis, and in situ hybridization confirmed the expression of MAP2A-C (including the novel MAP2+ 13 transcript) in both oligodendrogliomas and astrocytomas. Double fluorescent laser scanning microscopy showed that GFAP and MAP2 labeled different tumor cell populations. In embryonic human brains, MAP2-immunoreactive glial precursor cells were identified within the subventricular or intermediate zones. These precursors exhibit morphology closely resembling the immunolabeled neoplastic cells observed in glial tumors. Our findings demonstrate MAP2 expression in astrocytic and oligodendroglial neoplasms. The distinct pattern of immunoreactivity in oligodendrogliomas may be useful as a diagnostic tool. Since MAP2 expression occurs transiently in migrating immature glial cells, our findings are in line with an assumed origin of diffuse gliomas from glial precursors.

Adult↗
PubMed2001

Systemic and cavernous plasma levels of endothelin (1-21) during different penile conditions in healthy males and patients with erectile dysfunction.

The role of the sympathetic adrenergic nerves in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic transmitters are involved in this process. The peptide endothelin-1 (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated by various authors that ET-1 might be involved in the pathophysiology of erectile dysfunction. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels registered in systemic and cavernous blood cavities taken from healthy males and patients with ED during different penile conditions (flaccidity, tumescence/rigidity, detumescence). Thirty-two healthy adult males and 25 patients were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET-1/-2 was determined in plasma aliquots by means of an enzyme-linked immunoassay (ELISA). Mean systemic and cavernous plasma level of ET-1/-2 in blood samples obtained from the volunteers was 0.2-0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernous blood during penile tumescence, rigidity and detumescence. In the group of patients, mean plasma ET-1/-2 levels in the phase of penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernous blood (flaccidity: 0.52+/-0.38 fmol/ml vs. 0.48+/-0.46 fmol/ml, respectively; detumescence: 0.53+/-0.33 fmol/ml vs. 0.27+/-0.11 fmol/ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and psychogenic etiology of ED. In the phase of detumescence, the mean ET-1/-2 level was lower in the cavernous blood cavities taken from the patients than in the samples obtained from the healthy males. Our study revealed a difference in the profiles of ET-1/-2 registered in the cavernous blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seems to be of no physiological significance, our data counteract the hypothesis of an ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding an involvement of ET-1 in the pathophysiology of erectile dysfunction.

Adult↗
PubMed2001

Systemic and cavernosal plasma levels of endothelin (1-21) during different penile conditions in healthy males and patients with erectile dysfunction.

The role of the sympathetic adrenergic nerves in mediating the constant tone of penile flaccidity and returning the erect penis to its flaccid state is fairly well established. However, it is not yet known whether additional nonadrenergic transmitters are involved in this process. The peptide endothelin-l (ET-1) may be one of the factors contributing to such a control. Moreover, it has been speculated that ET-1 might be involved in the pathophysiology of penile erection. The present study was undertaken to determine whether or not there is a difference in the courses of ET-1/-2 plasma levels recorded in systemic and cavernosal blood taken from healthy males and patients with erectile dysfunction (ED) during different penile conditions (flaccidity, tumescence/rigidity, detumescence). The study groups comprised 33 healthy adult males and 25 patients. The subjects were exposed to visual and tactile erotic stimuli in order to elicit penile tumescence and, in the group of healthy volunteers, rigidity. Whole blood was aspirated from the corpus cavernosum and the cubital vein, and ET- 1/-2 was determined in plasma aliquots by means of an enzyme-linked immunosorbent assay (ELISA). Mean systemic and cavernosal plasma levels of ET- 1/-2 in blood samples obtained from the volunteers was 0.2-0.7 fmol/ml. In the healthy males, no changes in ET-1/-2 levels were observed in the systemic and cavernosal blood during penile tumescence, rigidity and detumescence. In the patients, mean plasma ET-1/-2 levels during penile flaccidity and detumescence were found to be higher in the systemic circulation than in the cavernosal blood (flaccidity 0.52 +/- 0.38 fmol/ml vs 0.48 +/- 0.46 fmol/ml, respectively: detumescence 0.53 +/- 0.33 fmol/ml vs 0.27 +/- 0.11 fmol/ ml, respectively). No differences in the plasma courses of ET-1/-2 were found between patients with an organogenic and those with a psychogenic aetiology of ED. During detumescence, the mean ET-1/-2 level was lower in the cavernosal blood taken from the patients than in the samples obtained from the healthy males. Our study revealed a difference in the profiles of ET-l/-2 in the cavernosal blood of healthy subjects and patients with erectile dysfunction. Nevertheless, since this difference seemed to be of no physiological significance, our findings contradict the hypothesis of the ultimate importance of ET-1 in the control of penile flaccidity and detumescence and do not support speculations regarding the involvement of ET-1 in the pathophysiology of erectile dysfunction.

Adult↗
PubMed2000

Initial clinical experience with the selective phosphodiesterase-I isoenzyme inhibitor vinpocetine in the treatment of urge incontinence and low compliance bladder.

Current pharmacological treatment modalities for urge incontinence and low compliance bladder are limited by a low clinical efficacy and the significant side effects of the standard drugs available. Previous in vitro studies indicated a possible functional relevance of the intracellular phosphodiesterase (PDE)-1 isoenzyme in the regulation of human detrusor smooth muscle contractility. We therefore investigated the effect of the PDE-1 inhibitor vinpocetine in nonresponders to standard pharmacological therapy. In 11/19 patients (57.9%) clinical symptoms and/or urodynamic parameters were improved. Although these initial data are preliminary, they represent the first evidence that isoenzyme-selective PDE inhibition may be a novel approach to the treatment of lower urinary tract disorders.

Compliance↗