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P Drescher

Publications and source records attributed to P Drescher.

35 records · Page 2Linked to original sources
PubMed1995

Contrast medium induced renal vasoconstriction, role of alpha receptors.

Standard imaging techniques for evaluation of renal and renovascular disease require the application of radiocontrast medium. The use of high osmolar, ionic radio contrast medium is however associated with adverse effects including acute renal insufficiency. Renal vasoconstriction seems to play an important role in the pathomechanism of this side effect. The cellular mechanisms however remain unsolved. Alpha 1-adrenoceptors and their subtypes are the crucial link between sympathetic stimulation and renal vasoconstriction. We investigated the role of alpha 1-receptors and the alpha 1A and alpha 1B subtypes in the renal artery and in sodium/meglumine diatrizoate induced renal artery smooth muscle contraction. Alpha 1-receptor induced rabbit renal artery contraction was produced by stimulation with the specific agonist phenylephrine which was antagonized dose-dependently and reversibly by the alpha 1-blockers prazosin, terazosin and YM 617. The alpha 1A-receptor was the prevalent receptor subtype in rabbit renal artery. This was identified by applying the specific alpha 1A-receptor antagonist 5-methylurapidil and the irreversible alpha 1B-receptor antagonist chloroethyllonidine. These two inhibited the PE induced contraction by 96% and 66%, respectively. Sodium/meglumine diatrizoate elicited renal artery contraction at 25% of the phenylephrine control. This contraction was not influenced by alpha 1-blockers indicating the absence of an alpha 1-receptor mediated process.

Adrenergic alpha-Agonists↗
PubMed1994

Smooth muscle contractility in prostatic hyperplasia: role of cyclic adenosine monophosphate.

The role of cyclic 3'-5' adenosine monophosphate (cAMP) on alpha 1-adrenoceptor (alpha 1-receptor) induced smooth muscle contractions in symptomatic benign prostatic hyperplasia (BPH) was investigated. Application of the selective alpha 1-receptor agonist phenylephrine (PE) induced fully reversible contractions in a dose-dependent fashion. Phosphodiesterase (PDE) inhibitors blocking the degradation of cAMP suppressed the PE induced contractions as follows: theophylline (1 mM), 91.1 +/- 1.4%; papaverine (0.5 mM), 822.8 +/- 3.2%; milrinone (0.5 mM), 68.2 +/- 0.6%. Forskolin (50 microM), which elevates cAMP through direct activation of adenylatecyclase (AC), inhibited the PE induced contractions by 82.4 +/- 3.6%. To further increase the intracellular cAMP concentration ([cAMP]i), the membrane permeable cAMP analogue N6-2'-O-dibutyryladenosine derivative (dBcAMP; 1 mM) was applied and reduced the PE evoked contractions by 69.8 +/- 2.3%. We conclude that elevation of [cAMP]i is an important step in inducing smooth muscle relaxation.

Bucladesine↗
PubMed1994

Reduced levels of IE2 gene expression and shutdown of early and late viral genes during latent infection of the glioblastoma cell line U138-MG with selectable recombinants of human cytomegalovirus.

To establish stable culture conditions which support persistence of the human cytomegalovirus (HCMV) genome in a latent state, the expression of the bacterial neomycin phosphotransferase (neo) from HCMV recombinants was used for selection. Different cell lines were infected with HCMV recombinants. The human glioblastoma line U138-MG was rendered resistant to G418 and retained the viral genome. More than 90% of the cells expressed the viral IE1 protein of 72 kDa for a culture period of 18 months. Many fewer cells expressed IE2-encoded proteins. No late gene expression or infectious virus was detectable. IE2 gene expression in latently infected cells appeared to be restricted at the level of RNA accumulation. Treatment with TPA or retinoic acid led to enhanced expression of the IE2 gene and the early genes encoding pp65 (UL83) and p52 (UL44). Superinfection with wild-type HCMV led to replication of neo-recombinant virus, indicating that replication-competent virus had been retained in latently infected U138-MG and that the cells had kept their permissive phenotype. Latent HCMV infection in U138-MG cells provides a useful model system for studying the role of particular viral and cellular genes in latent and permissive infections.

Cytomegalovirus↗
PubMed1994

G-proteins in alpha 1-adrenoceptor mediated prostatic smooth muscle contraction.

The role of signal transducing guanine-nucleotide binding proteins (G-proteins) in alpha 1-receptor mediated smooth muscle contractions was investigated in human hyperplastic prostatic tissue. The selective alpha 1-receptor agonist phenylephrine (PE) evoked dose dependent contractions antagonized by the alpha 1-receptor blockers prazosin (EC50 10 nM) and YM617 (EC50 3 nM). Application of nifedipine (1-10,000 nM), a blocker of voltage-dependent L-type Ca(2+)-channels (VDCC), inhibited the PE evoked contraction up to 65.4%. Pretreating the tissue strips with pertussis toxin (PTX, exotoxin from Bordetella pertussis; 5-25 micrograms/ml), inactivating a subpopulation of G-proteins, inhibited the PE induced contractions up to 73.9%. PTX pretreatment had no effect on contractions elicited by 125 mM K+. Application of nifedipine to PTX pretreated tissue led to an additional inhibition of 13.7%. Our findings demonstrate the involvement of PTX-sensitive G-proteins in the signal transduction pathway of alpha 1-receptor induced contractions of prostatic smooth muscle. The remaining contractility of PTX pretreated tissue suggests additional participation of PTX insensitive mechanisms in alpha 1-receptor mediated prostatic smooth muscle contractions.

Adrenergic alpha-Antagonists↗
PubMed1994

Isolation and biological activity of aspidospermine and quebrachamine from an Aspidosperma tree source.

The indolealkaloids aspidospermine and quebrachamine have been isolated in crystalline form by a relatively rapid fractionation from the extract of a powdered material designated "Quebracho" derived from an Aspidosperma tree species. We present a novel isocratic LC method that provides baseline resolution of these two compounds and of the structurally related yohimbine in less than 15 min. Gas chromatography-mass spectrometry was employed to identify these compounds as well as several minor derivatives of aspidospermine during and after the purification process. Aspidospermine and quebrachamine like yohimbine have been found to possess adrenergic blocking activities for a variety of urogenital tissues.

Alkaloids↗
PubMed1994

Smooth muscle tone regulation in rabbit cavernosal and spongiosal tissue by cyclic AMP- and cyclic GMP-dependent mechanisms.

The relaxing effects of several specific and nonspecific inhibitors of phosphodiesterases (PDE) on rabbit isolated corpus cavernosum (CC) and spongiosum (CS) were investigated. Preparations were mounted in organ baths, and isometric tension was recorded. The results were compared with the effects of direct administration of analogs of the second messenger cyclic nucleotides and the effects of forskolin, a direct stimulator of adenylate cyclase, and the nitric oxide donor 3-morpholinosydnonimine (SIN 1). All drugs relaxed the phenylephrine-induced contractions in CC and CS in a dose-dependent fashion. In CC and CS, type III (SK&F 95654) and type V (zaprinast and dipyramidole) PDE inhibitors, as well as the nonspecific inhibitors papaverine and trequinsin, showed no differences in IC50. The type IV inhibitor rolipram relaxed CC and CS at significantly lower concentrations (p < 0.005) than any other PDE inhibitor, and in CC the type III and IV inhibitor zardaverine was more potent (p < 0.05) than SK&F 95654. SIN 1 stimulates guanylate cyclase and effectively inhibits contractions in CC and CS. Activation of adenylate cyclase by forskolin also was highly effective (p < 0.005). It is concluded that PDE inhibition constitutes an effective relaxing mechanism in rabbit CC and CS. The marked effects of the different types of PDE inhibitors support the importance of cyclic guanosine 3',5'-monophosphate and cyclic adenosine 3',5'-monophosphate in smooth muscle relaxation in erectile tissue.

Animals↗
PubMed1994

Alpha-1 receptor mediated smooth muscle regulation in benign prostatic hyperplasia.

Symptoms in benign prostatic hyperplasia (BPH) are partially caused by an increased prostatic smooth muscle tone. This tone depends on extra- and intracellular Ca2+ stores and is regulated by various second messenger pathways. We investigated the role of intracellular Ca2+ stores and cyclic 3'-5' adenosine monophosphate (cAMP) in BPH. Contractions elicited by the specific alpha 1-receptor agonist phenylephrine (PE) were inhibited by the selective alpha 1-receptor antagonists prazosin and YM 617. To elucidate the contribution of intracellular Ca2+ stores to the alpha 1-receptor induced contraction nifedipine, a blocker of voltage dependent L-type Ca2+ channels (VDCC) was applied and found to inhibit the PE induced contractions up to 65%. To further confirm the participation of intracellular Ca2+ stores, we applied ryanodine (10 microM) which reduced the alpha 1-receptor mediated contractions up to 80%. The remaining contraction was sensitive to nifedipine. The cAMP pathway mediating smooth muscle relaxation by regulating intracellular Ca2+ concentrations ([Ca2+]i) was also investigated. Nonspecific phosphodiesterase (PDE) inhibitors such as papaverine (0.5 mM) and theophylline (1 mM) and the specific PDE inhibitor milrinone (0.5 mM), all of which prevent degradation of cAMP, suppressed the PE induced contractions by 82%, 91% and 68%, respectively. Forskolin (50 microM), an activator of adenylylecyclase (AC), inhibited the PE induced contractions by 83%. The membrane permeable cAMP analog, N6-2'-0-dibutyryladenosine derivative (dBcAMP) also reduced the PE induced response by 70%.

Adrenergic alpha-Antagonists↗
PubMed1994

Long-term results of therapy with intracavernousal injections and penile venous surgery in chronic erectile dysfunction.

A follow up study of 603 patients with chronic erectile failure was carried out concerning the long term effects of intracavernous injection therapy with papaverine/phentolamine (n = 172 evaluable) and venous surgery (n = 134 evaluable). Injection therapy was effective in 95.8% of injections. Side effects included prolonged erections in 0.15% of injections and fibrotic palpable indurations in 3.4%. Acceptance of therapy was high among patients and their partners and improvement of self image or partnership was reported in 77.8% and 79.5% respectively. Results of venous surgery were not satisfactory. Only 19.4% of patients achieved sufficient spontaneous erections and 35.1% needed adjuvant injections. Spongiosolysis yielded better results. Patients with neurological impairment, diabetes mellitus, postoperative onset of erectile dysfunction and age above 40 years showed poorer surgical results. Venous surgery should only be offered to a highly selected group of patients.

Adult↗
PubMed1993

Role of intracellular Ca2+ stores in smooth muscle contractions of the guinea pig vas deferens.

Guinea pig vas deferens was used as an animal model for alpha-1 adrenoceptor (alpha 1-receptor) mediated contractions in human hyperplastic prostatic tissue. The selective alpha 1-receptor agonist, phenylephrine (PE), induced fully reversible, dose-dependent contractions antagonized by increasing concentrations of the alpha 1-receptor blockers prazosin (1-100 nM) and YM 617 (0.1-10 nM). Removal of extracellular Ca2+ reduced PE-evoked contractions in a time-dependent manner. Nifedipine (1-1000 nM), a blocker of voltage-dependent L-type Ca2+ channels (VDCC), inhibited the PE-induced response by up to 65%. Removal of extracellular Ca2+ abolished the alpha 1-agonist reactivity in a time-dependent fashion. To elucidate the participation of intracellular Ca2+ stores in alpha 1-receptor-mediated contractions, the tissue was pretreated with ryanodine (10 microM) or thapsigargin (0.1 microM), established inhibitors of Ca2+ release from intracellular pools. Both substances reduced the PE contractions by up to 80%. Nifedipine suppressed the remaining contractions completely. This provides evidence that Ca2+ influx through VDCC and Ca2+ release from intracellular stores contribute to alpha 1-receptor-mediated contractions in the guinea pig vas deferens and may be important in obstructive benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗
PubMed1993

[New imaging methods in thoracic diagnosis. A study to evaluate digital storage screen radiography, the slit technique ("AMBER"), asymmetric ("InSight") and conventional film-screen techniques].

New methods have been introduced in recent years in chest imaging to achieve high image quality simultaneously in the mediastinum and in the lung field. In this study the clinical value is assessed for four techniques: digital storage phosphor radiography, slit-technique ("AMBER"), asymmetrical film/screen ("InSight") and conventional film/screen. 43 patients were examined with these techniques within one day. Seven readers of four universities graded the image quality according to ten criteria of the mediastinum and the lung field. The slit-technique ("AMBER") showed the best image quality in both areas. Compared to conventional film/screen, storage phosphor radiography and asymmetrical film/screen ("InSight") yield better image quality only in the mediastinum.

Adult↗
PubMed1992

[Detection of a pheochromocytoma in the urinary bladder wall].

We present the case of a 23-year old female patient with clinical signs and biochemical results of a pheochromocytoma. Abdominal ultrasound gave no hints on localisation. Angiography demonstrated a richly vasculated tumour in the region of the superior urinary bladder. Computed tomography (CT) was able to localise the tumour but could not differentiate the tumour origin in bladder or uterus. The selective venous catheter blood sampling confirmed the localisation of the norepinephrine producing pheochromocytoma in the inferior pelvic region. Intraoperative diagnosis turned out to be an extra-adrenal pheochromocytoma of unknown tumour status in the dorsal bladder wall.

Adult↗
PubMed1989

[Current developments in the radiologic diagnosis of the adrenal glands].

Cross-sectional imaging techniques have dramatically improved the diagnosis of adrenal disease. In most patients with endocrine-active adrenal disease, CT is the only imaging test needed to establish the correct diagnosis. Adrenal venography with blood sampling may provide important additional information in patients with Conn adenoma. Magnetic resonance imaging and (IMBG) scintigraphy appear to be the best imaging tests for the localization of multiple or extra-adrenal pheochromocytomas. Inactive adrenal tumors detected incidentally are a problem as for as diagnosis is concerned, since inactive adrenal adenomas have to be differentiated from carcinomas and metastases. MRI is rarely helpful in these cases. For patients with a known primary tumor, the authors recommend CT-guided biopsy. In all other cases a follow-up study often reveals that the adrenal tumor detected is benign.

Adrenal Gland Diseases↗
PubMedDate not supplied

Ca2+ and cyclic adenosine monophosphate involvement in radiographic contrast medium-induced renal vasoconstriction.

PURPOSE: To investigate the role of extracellular Ca2+ and cyclic 3'-5' adenosine monophosphate (cAMP), a known second messenger promoting smooth muscle relaxation, in preventing renal vasoconstriction induced by radiographic contrast medium (RCM). MATERIALS AND METHODS: Isometric contractions of rabbit renal artery were elicited by potassium chloride and increasing concentrations of meglumine/sodium diatrizoate. To determine the contribution of extracellular Ca2+, nifedipine, a blocker of voltage-dependent L-type Ca2+ channels (VDCC), was applied. The contribution of cAMP was investigated by applying the nonspecific phosphodiesterase (PDE) inhibitors papaverine and theophylline and the specific PDE inhibitor milrinone, all of which prevent degradation of cAMP. Forskolin, an activator of cAMP by stimulating adenylyl cyclase (AC), was also investigated. RESULTS: RCM elicited contractions that were 24.5% of the KCl control contraction, which was reduced by nifedipine (100 mumol/L) by 34.7%. Papaverine, theophylline, and milrinone inhibited RCM-induced contractions by 69.8%, 64.3%, and 43.7%, respectively. Forskolin reduced the response by 82.2%. CONCLUSION: Ca2+ influx through VDCC partially contributes to RCM-induced renal artery vasoconstriction. Intracellular cAMP appears to be an important second messenger pathway for prevention of this response. These findings emphasize the role of second messenger systems involved in adverse RCM effects and the potential prevention of these effects.

Animals↗
PubMedDate not supplied

Renal transplant evaluation with MR angiography and MR imaging.

Magnetic resonance (MR) angiography is a widely used, noninvasive tool for evaluating the aorta and its branches. It is particularly useful in renal transplant recipients because it provides anatomic detail of the transplant artery without nephrotoxic effects. Volume rendering is underutilized in MR angiography, but this technique affords high-quality three-dimensional MR angiograms, especially in cases of tortuous or complex vascular anatomy. An imaging protocol was developed that includes gadolinium-enhanced MR angiography of the transplant renal artery with volume rendering and multiplanar reformation postprocessing techniques. Axial T2-weighted and contrast material-enhanced T1-weighted MR images are also obtained to examine the renal parenchyma itself and to evaluate for hydronephrosis or peritransplant fluid collections. This imaging protocol allows rapid global assessment of the renal transplant arterial system, renal parenchyma, and peritransplant region. It can also help detect or exclude many of the various causes of renal transplant dysfunction (eg, stenosis or occlusion of a transplant vessel, peritransplant fluid collections, ureteral obstruction). Conventional angiography can thus be avoided in patients with normal findings and reserved for those with MR angiographic evidence of stenosis.

Adult↗