Biomedical subjects

U Jonas

Publications and source records attributed to U Jonas.

At least 55 records · Page 3Linked to original sources

PubMed2001

The portrait of James Israel by the German impressionist Max Liebermann: a selected pictorial view on the early twentieth century development of surgical urology in Berlin.

On the occasion of his retirement from the position as head of the Jewish Hospital in Berlin in 1917, the famous kidney surgeon James Israel (1848-1926) was portrayed by Max Liebermann (1847-1935). At that time both men were leading members of their professions--medicine and fine arts--and represented the Jewish community in Berlin. Private contacts between the surgeon and the artist had been established when Liebermann and his wife needed surgical treatment themselves some years before. Liebermann's later friendship with the surgeon Ferdinand Sauerbruch (1875-1951) culminated in one of the best-known portraits of a member of the medical profession. This biographical article from the history of medicine and fine arts reflecting the relation of these men provides a special view of the development of urological surgery in Berlin at the beginning of the twentieth century.

Berlin↗

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

Tolterodine: an overview.

Tolterodine has emerged as a new anticholinergic drug to treat detrusor instability in recent years. This substance and its major metabolite DD01 exhibit a favourable effect-to-side-effect ratio for the bladder. Several clinical studies demonstrated the drug's efficacy in reducing the symptoms of an overactive bladder (urgency, urge incontinence and high micturition frequency) and in increasing functional bladder volume. With a clinical effectiveness comparable to oxybutynin, the side effect-profile measures up favourably to oxybutynin. Consequently, though some limitations need to be addressed, tolterodine can be regarded as the drug of first choice to treat overactive bladders in a variety of patient groups: the young (and otherwise healthy), the elderly, as well as in patients with renal and hepatic insufficiency. A new extended release formula of tolterodine has been launched that may improve patients' compliance.

Animals↗

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

Tolterodine once-daily: superior efficacy and tolerability in the treatment of the overactive bladder.

OBJECTIVES: To evaluate the efficacy and tolerability of a new extended-release (ER), once-daily, capsule formulation of tolterodine, relative to placebo and the existing immediate-release (IR), twice-daily, tablet formulation, for treatment of the overactive bladder. METHODS: This was a double-blind, multicenter, randomized, placebo-controlled trial. One thousand five hundred twenty-nine patients (81% women) with urinary frequency (eight or more micturitions every 24 hours) and urge incontinence (five or more episodes per week) were randomized to oral therapy with tolterodine ER 4 mg once daily (n = 507), tolterodine IR 2 mg twice daily (n = 514), or placebo (n = 508) for 12 weeks. Efficacy was assessed at the end of the treatment period on the basis of the micturition diary variables. Tolerability and safety were assessed by evaluating the adverse events, electrocardiogram parameters, laboratory values, and treatment withdrawals. RESULTS: Tolterodine ER 4 mg once daily (P = 0.0001) and tolterodine IR 2 mg twice daily (P = 0.0005) both significantly reduced the mean number of urge incontinence episodes per week compared with placebo. The median reduction in these episodes as a percentage of the baseline values was 71% for tolterodine ER, 60% for tolterodine IR, and 33% for placebo. The ER formulation was 18% more effective than the IR formulation (P <0.05). Treatment with both formulations of tolterodine was also associated with statistically significant improvements in all other micturition diary variables compared with placebo. For both formulations, the mean decreases in micturition frequency (P <0.0079) and pad usage (P <0.0145) were significant, and the mean volume voided per micturition increased (P = 0.0001). The rate of dry mouth (of any severity) was 23% for tolterodine ER, 30% for tolterodine IR, and 8% for placebo. The overall dry mouth rate for patients taking tolterodine ER was 23% lower than for tolterodine IR (P <0.02), and the rate of severe dry mouth in the ER group was only 1.8%. The rates of withdrawal were comparable for the two active groups and the placebo group. No safety concerns were noted. CONCLUSIONS: Tolterodine ER 4 mg once daily is effective and well tolerated in the treatment of overactive bladder with no safety concerns. Tolterodine ER demonstrated an improved efficacy for reducing urge incontinence episodes and a lower frequency of dry mouth compared with the existing IR twice-daily formulation.

Administration, Oral↗

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

Smooth muscle electromyography.

This article addresses smooth muscle physiology, electromechanical and pharmacomechanical coupling, computed-based interpretations, and the role of electromyography in the diagnosis of erectile dysfunction.

Discriminant Analysis↗

PubMed2001

The history of erectile dysfunction management.

This article describes the evolution or revolution in the management of erectile dysfunction over the centuries. In recent history there has been a rapid movement away from a predominant role for the specialist towards the primary care physician. The physician is increasingly faced with the need to individualize therapy to meet patient expectations.

Erectile Dysfunction↗

PubMed2001

Efficacy of sacral nerve stimulation for urinary retention: results 18 months after implantation.

PURPOSE: We investigate the efficacy of sacral neurostimulation in patients with idiopathic urinary retention in a prospective, randomized multicenter trial. MATERIALS AND METHODS: A total of 177 patients with urinary retention refractory to standard therapy were enrolled in the study. Greater than 50% improvement in baseline voiding symptoms during a 3 to 7-day percutaneous test stimulation qualified a patient for surgical implantation of an InterStim parallel system. Of the patients who qualified for implantation 37 were randomly assigned to a treatment and 31 to a control group. Patients in the treatment group underwent early surgical implantation of the sacral nerve stimulation system, while implantation was delayed in the control group for 6 months. Followup evaluations, including voiding diary analysis and temporary deactivation of the stimulator at 6 months, were conducted at 1, 3, 6, 12 and 18 months after implantation in the treatment group, and after 3 and 6 months in the control group. RESULTS: Compared to the control group, patients implanted with the InterStim system had statistically and clinically significant reductions in the catheter volume per catheterization (p <0.0001). Of the patients treated with implants 69% eliminated catheterization at 6 months and an additional 14% had a 50% or greater reduction in catheter volume per catheterization. Therefore, successful results were achieved in 83% of the implant group with retention compared to 9% of the control group at 6 months. Temporary inactivation of sacral nerve stimulation therapy resulted in a significant increase in residual volumes (p <0.0001) but effectiveness of sacral nerve stimulation was sustained through 18 months after implant. CONCLUSIONS: Results of this prospective, randomized clinical study demonstrate that sacral nerve stimulation is effective for restoring voiding in patients with retention who are refractory to other forms of treatment.

Adult↗

PubMed2001

Expression of different phosphodiesterase genes in human cavernous smooth muscle.

PURPOSE: Knowledge of intracellular signal propagation in smooth muscle tone regulation is of major importance in the understanding of the physiology of penile erection, and the development of new and selective pharmacological agents for the treatment of related disorders. Since phosphodiesterases (PDE) are key enzymes of the signaling pathway, we elucidate their presence and potential functional relevance in human cavernous tissue. MATERIALS AND METHODS: To identify PDE messenger RNA in human cavernous tissue, we constructed primers for 14 published PDE isoforms. Expression of the genes was then analyzed by reverse transcriptase polymerase chain reaction under standard conditions and by subsequent sequencing. RESULTS: Messenger RNA was detected in human corpus cavernosum for the human phosphodiesterase isoenzymes and isoforms PDE1A, PDE1B, PDE1C, PDE2A, PDE3A, PDE4A, PDE4B, PDE4C, PDE4D, PDE5A, PDE7A, PDE8A and PDE9A. CONCLUSIONS: A total of 13 PDE genes were expressed in human cavernous tissue, indicating a role of these enzymes in penile erection regulation. The intracellular mechanisms of hydrolyzing cyclic adenosine monophosphate and cyclic guanosine monophosphate by PDEs are more complex than assumed previously. These findings open up new possibilities in the development of drugs for the treatment of erectile dysfunction.

Base Sequence↗

PubMed2001

Dehalogenation of chlorinated hydroxybiphenyls by fungal laccase.

We have investigated the transformation of chlorinated hydroxybiphenyls by laccase produced by Pycnoporus cinnabarinus. The compounds used were transformed to sparingly water-soluble colored precipitates which were identified by gas chromatography-mass spectrometry as oligomerization products of the chlorinated hydroxybiphenyls. During oligomerization of 2-hydroxy-5-chlorobiphenyl and 3-chloro-4-hydroxybiphenyl, dechlorinated C---C-linked dimers were formed, demonstrating the dehalogenation ability of laccase. In addition to these nonhalogenated dimers, both monohalogenated and dihalogenated dimers were identified.

Basidiomycota↗

PubMed2001

Long-term effectiveness of sacral nerve stimulation for refractory urge incontinence.

OBJECTIVES: To evaluate the long-term efficacy of sacral nerve stimulation for refractory urinary urge incontinence. STUDY DESIGN AND METHODS: Urge incontinent patients qualified for surgical implantation of a neurostimulator system after trial screening with percutaneous test stimulation. Surgical implantation of the InterStim System (Medtronic Inc., Minneapolis, Minn., USA) was performed in cases where a >50% reduction in incontinence symptoms was documented during the 3- to 7-day test stimulation period. The InterStim System consists of an implantable pulse generator, a transforamenally placed quadripolar lead, and an extension that connects these two devices for unilateral stimulation of the S3 or S4 sacral nerve. Efficacy for 96 implanted patients was based on urinary symptom changes as quantified in voiding diaries collected at baseline and annually after surgical implantation. RESULTS: As compared to baseline, the group of 96 implanted patients demonstrated significant reductions in urge incontinent symptoms at an average of 30.8+/-14.8 (range 12-60) months with respect to the number of urge incontinent episodes per day, severity of leaking, and the number of absorbent pads/diapers replaced per day due to incontinence (all p<0.0001, respectively). Gender, pretreatment variables, and age were not found to be relevant factors that affected these results. 11 of the 96 patients underwent device explant due to lack of efficacy, pain or bowel dysfunction. These data were conservatively included in the efficacy results. No permanent injuries associated with the devices or therapy were reported. CONCLUSION: Sacral nerve stimulation is an effective treatment for refractory urge incontinence with sustained long-term benefit through an average of 30.8 months.

Adult↗

PubMed2001

Male lower urinary tract symptoms and related health care seeking in Germany.

OBJECTIVES: To investigate the prevalence of lower urinary tract symptoms (LUTS) and LUTS- related health care issues in the male population between the ages of 50 and 80 in Germany. METHODS: 8,973 randomly chosen men in the age group of interest received by mail a self-administered questionnaire addressing voiding symptoms and bother, common health status, and social demographic as well as health care resources related issues. RESULTS: Of 6,031 (67.2%) returned questionnaires, 5,404 (60.2%) were properly filled out and entered into the database. Of these, 5,004 (56%) completed all IPSS questions. 3,539 (70.7%) of the men presented with no or mild LUTS (IPSS 0--7), 1,465 (29,3%) with moderate to severe voiding symptoms (IPSS >7), respectively. From logistic regression analysis it appears that mainly bother from voiding symptoms as well as incomplete emptying and week stream induced a visit to the doctor. Of men with moderate symptoms (IPSS 8--19), 40% did not report any bother. CONCLUSION: LUTS is a common condition among German elderly males. In general, bother from LUTS seem to have more effects on health care seeking behavior than symptoms themselves or physical health status. Bother scores may discriminate between those individuals with moderate symptoms (IPSS 8--19), who may be followed through watchful waiting instead of active therapy.

Aged↗

PubMed2001

Twelve-month treatment of overactive bladder: efficacy and tolerability of tolterodine.

CONTEXT: Tolterodine is a bladder-selective antimuscarinic agent designed for the treatment of overactive bladder. Traditional antimuscarinic therapies are poorly tolerated due to a high incidence of anticholinergic adverse events and consequently few patients remain on long term therapy. OBJECTIVE: To evaluate the long term efficacy and tolerability of tolterodine in patients with symptoms of overactive bladder. DESIGN: Twelve-month open-label extension of 4 randomised, placebo-controlled, double-blind, multinational, multicentre trials of 4 weeks' duration. PATIENTS: 714 patients (aged 18 to 92 years) with symptoms of overactive bladder who completed the double-blind portion of the studies. INTERVENTION: Tolterodine 2 mg twice daily for up to 12 months. MAIN OUTCOME MEASURES: Micturition diary variables: number of micturitions per 24 hours, number of urge incontinence episodes per 24 hours, mean urine volume voided per micturition. Safety variables: adverse events, study discontinuation rate. RESULTS: A total of 441 patients (62%) completed 12 months' open-label treatment with tolterodine, which significantly reduced the number of micturitions per 24 hours [mean change -2.4, 95% confidence interval (CI) -2.7 to -2.2, median change -20%, p < 0.0001] and number of urge incontinence episodes per 24 hours (mean change -1.3, 95% CI -1.6 to -1.0, median change -74%, p < 0.0001), while the mean volume voided per micturition was significantly increased (+33 ml, 95% CI +28 to +38, median change +18%; p < 0.0001). 41% of patients reported dry mouth (27% mild, 10% moderate, 3% severe). Dosage reduction to 1 mg twice daily was required in 23% of patients. 15% of patients withdrew from the study due to adverse events, with 5% having associated dry mouth. CONCLUSIONS: The high percentage of patients completing 12 months' treatment indicates that tolterodine is an effective and well tolerated agent for long term treatment of overactive bladder.

Adolescent↗

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

Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate.

PURPOSE: Current pharmacological concepts in the treatment of benign prostatic hyperplasia are aimed at the static and dynamic component of the disease. Mainly alpha-blocking agents are used to reduce the adrenergic tone of prostatic myocytes, thus, increasing urine flow through the prostatic urethra by reducing urethral resistance. With the introduction of the phosphodiesterase (PDE) 5 inhibitor sildenafil the concept of PDE inhibition has gained tremendous interest in the field of urology. We characterized PDE isoenzymes from human prostatic tissue by molecular biology and protein chemistry, and investigated the effects of various PDE inhibitors compared with standard pharmacological agents on adrenergic tension in isolated human prostatic strips. MATERIALS AND METHODS: PDE isoenzymes were characterized by reverse transcriptase-polymerase chain reaction and anion exchange chromatography. Using the organ bath technique we determined the relaxing effects of the PDE inhibitors papaverine, vinpocetine (Biomol GmbH, Hamburg, Germany), erythro-9-[2-hydrox-3-nonyl]adenine hydrochloride (Tocris Cookson, Ltd., Bristol, United Kingdom) rolipram (Schering AG, Berlin, Germany), zaprinast (Rhône-Poulenc Rorer, Ltd., Dagenham, United Kingdom) and sildenafil (Pfizer, Ltd., Sandwich, United Kingdom), the adenylate cyclase activating agent forskolin (ICN Biomedicals, Aurora, Ohio) and the nitric oxide donor sodium nitroprusside on adrenergic tension in prostatic strips isolated from the transition zone. RESULTS: Reverse transcriptase-polymerase chain reaction revealed messenger RNA transcripts encoding for PDE 1, 2, 4, 5, 7, 8, 9 and 10 in the various anatomical regions of the human prostate, including the peripheral, central and transition zones. Except for complementary DNA encoding for PDE 1C, complementary DNA fragments encoding for PDE 1A, 1B, 2A, 4A, 4B, 4C, 4D, 5A, 7A, 8A, 9A and 10A were found at almost even ratios in the different histological regions of the prostate. The hydrolytic activities of PDE 4 and 5 were present in the cytosolic fraction of prostatic tissue, whereas in the particulate fraction only the hydrolytic activity of PDE 4 was detected. Adrenergic tension in prostatic strip preparations was reversed by forskolin, sodium nitroprusside, and inhibitors of PDE 4 and 5. CONCLUSIONS: Our results demonstrate the presence and functional relevance of PDE isoenzymes 4 and 5 in human prostatic tissue. These studies support the possible use of inhibitors of PDE 4 and 5 for treating urinary obstruction secondary to benign prostatic hyperplasia.

Humans↗

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↗