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Biomedical subjects

F Scheller

Publications and source records attributed to F Scheller.

At least 19 recordsLinked to original sources

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↗

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↗

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↗

Development of a creatinine ELISA and an amperometric antibody-based creatine sensor with a detection limit in the nanomolar range.

Creatinine-specific antibodies have been generated and used for highly sensitive and specific immunochemical creatinine determinations. Creatinine was derivatized at N3 and coupled to KLH carrier protein. On the basis of this immunogen, monoclonal antibodies were developed by hybridoma technology. Antibodies from various clones have been characterized with BIAcore 2000 with respect to the dissociation constant and specificity. Antibodies of clone B90-AH5 exhibited the lowest dissociation constant (0.74 microM) and the highest specificity for creatinine and were chosen for the development of a competitive ELISA and an amperometric creatinine sensor. The creatinine sensor was constructed by fixing a creatinine-modified membrane on the top of a platinum working electrode which was then incorporated into a stirred electrochemical measuring cell. For creatinine determination the creatinine-containing sample was incubated with B90-AH5 and anti-IgG(mouse)-glucose oxidase conjugate and applied to the measuring cell. After a washing step glucose was added and the produced hydrogen peroxide was registered at Eappl = +600 mV vs Ag/AgCl. The measuring range was 0.01-10 microg/mL. The highest sensitivity for creatinine was achieved at 330 ng/mL (3 microM) and the lower detection limit at 4.5 ng/mL (40 nM). This is far below the relevant clinical range, which is 5-17 microg/mL (44-150 microM) and allows a reliable determination of very low creatinine concentrations in serum, where standard methods cannot be applied. After each measurement the sensor was regenerated with 10 mM HCl without any loss in binding activity.

Antibodies, Monoclonal↗

Cavernous and systemic testosterone levels in different phases of human penile erection.

OBJECTIVES: To examine changes in testosterone levels in the cavernous and peripheral blood during different phases of erection because, although the determination of systemic testosterone levels has been well established in the diagnostic workup of erectile dysfunction, the exact role of testosterone in adult male sexual function remains unclear. METHODS: Blood samples were drawn simultaneously from the corpus cavernosum and the cubital vein of 54 healthy and normally potent volunteers during four different stages of the cavernous erectile tissue (flaccidity, tumescence, rigidity, and detumescence). Penile erections were induced by audiovisual and tactile stimulation, and testosterone levels were determined by radioimmunoassay. RESULTS: The mean testosterone level in the corpus cavernosum plasma during the flaccid state was 2.9 +/- 1.2 ng/mL. During tumescence and rigidity, the testosterone levels in the cavernous blood significantly increased, to 4.3 +/- 1.3 ng/mL and 4. 4 +/- 1.4 ng/mL, respectively. During detumescence, the cavernous testosterone levels dropped to 3.5 +/- 1.4 ng/mL. The changes in the testosterone levels in the peripheral plasma were less pronounced. A significant increase was also found in the peripheral testosterone levels from flaccidity (4.1 +/- 1.1 ng/mL) to tumescence (4.4 +/- 1. 4 ng/mL). No further increase in testosterone occurred during the phase of rigidity. From rigidity to detumescence, the peripheral testosterone levels dropped to 4.1 +/- 1.2 ng/mL. CONCLUSIONS: Penile erection was found to be accompanied by a significant increase in cavernous and systemic testosterone plasma levels. The estimated difference between the systemic and cavernous testosterone levels during penile flaccidity, when blood flow through the cavernous body is minimized, might be a diagnostic tool to evaluate the amount of bioavailable testosterone and the activity of testosterone receptors in the corpus cavernosum smooth musculature.

Adult↗

Plasma levels of cavernous and systemic norepinephrine and epinephrine in men during different phases of penile erection.

PURPOSE: Knowledge of the functional anatomy, hemodynamics, neurophysiology and pharmacology of penile erection has improved tremendously during the last 2 decades. However, only few in vivo studies on human peripheral neurotransmission have been carried out up until now. Therefore, we conducted a study to examine plasma levels of catecholamines norepinephrine (NE) and epinephrine (E) in the peripheral and cavernous blood of healthy men during penile flaccidity and in different phases of erection. MATERIALS AND METHODS: Blood samples were drawn simultaneously from the corpus cavernosum (CC) and the cubital vein (P) in 53 healthy volunteers with normal erectile function, in four different functional states of the cavernous erectile tissue (flaccidity = 1, tumescence = 2, rigidity = 3, detumescence = 4). Penile erections were induced by audiovisual and tactile stimulation and the plasma concentrations of NE and E were determined by means of a radioimmunoassay (RIA). RESULTS: A significant (p <0.001) reduction of NE in CC plasma was found from flaccidity (362 + or - 173 pg./ml.) to rigidity (248 + or - 122 pg./ml.), followed by an increase in the detumescence phase (336 + or - 199 pg./ml.), (p <0.001). In contrast, changes in NE levels in the peripheral plasma were less pronounced from 1P (202 + or - 102 pg./ml.) to 3P (229 + or - 118 pg./ml.), (p = 0.006) and from 3P to 4P (222 + or - 127 pg./ml.), respectively (p = 0.370). The most pronounced increase in cavernous E levels were observed from flaccidity (47 + or - 41 pg. /ml.) to tumescence (130 + or - 106 pg./ml.) (p <0.001). Cavernous E levels dropped significantly from 113 + or - 67 pg./ml. during rigidity to 76 + or - 57 pg./ml. + or - during detumescence (p <0.001). The course of peripheral plasma levels of E was similar to that in the cavernous blood. Mean peripheral E level was 69 + or - 55 pg./ml. in the state of penile flaccidity, reaching 98 + or - 78 pg./ml. in tumescence and 82 + or - 64 pg./ml. in rigidity (p <0.001), respectively, and finally decreasing to 62 + or - 46 pg./ml. in detumescence. CONCLUSION: Penile erection, based on the relaxation of cavernous and arterial smooth muscle, is accompanied by a significant reduction of NE in cavernous blood, while E levels rose in peripheral and cavernous blood during developing erection.

Adult↗

Possible role of human growth hormone in penile erection.

PURPOSE: Treatment with recombinant human growth hormone in adult patients with growth hormone deficiency increases nitric oxide and cyclic guanosine monophosphate (cGMP). We examined the functional in vitro effects of recombinant human growth hormone on tissue tension and cyclic nucleotide levels of human corpus cavernosum and detected changes in growth hormone in the cavernous and peripheral blood during different phases of penile erection. MATERIALS AND METHODS: Relaxant responses of human corpus cavernosum were investigated using the organ bath technique. Tissue levels of cGMP were determined by a specific radioimmunoassay after dose dependent exposition of isolated human corpus cavernosum strips to recombinant human growth hormone. In 35 healthy potent volunteers blood samples were obtained simultaneously from the corpus cavernosum and cubital vein during different functional conditions of the penis, including flaccidity, tumescence, rigidity and detumescence. Penile erection was induced by audiovisual and tactile stimulation. Serum growth hormone was determined by an immunoradiometric assay. RESULTS: Recombinant human growth hormone elicited dose dependent relaxation of human corpus cavernosum strips in vitro. The relaxing potency of recombinant human growth hormone was paralleled by its ability to elevate intracellular levels of cGMP. In vivo the peripheral growth hormone serum profile of the respective penile conditions did not significantly differ from those of cavernous serum. The main increase in growth hormone to greater than 90% was determined during developing penile tumescence, followed by a transient decrease afterward. CONCLUSIONS: These results suggest that penile erection may probably be induced by growth hormone through its cGMP stimulating activity on human corpus cavernosum smooth muscle.

Adult↗

Laccase of Coriolus zonatus: isolation, purification, and some physicochemical properties.

Laccase is one of the lignolytic enzymes found in liquid cultures of the fungus Coriolus zonatus in defined medium. The enzyme was isolated from culture liquid and characterized. Laccase from C. zonatus is a single-chain protein with a molecular mass of 60 kDa. Carbohydrate moiety of enzyme consisted of mannose, galactose and N-acetyl-glucosamine in a ratio of 6:2:0.6, respectively, and comprised 10% of the entire molecule. Isoelectric point was detected at pH 4.6. Laccase was found to have a pH optimum of 4.9 and temperature optimum of 55 degrees C. Substrate specificity studies were conducted with catechol, K-ferrocyanide, hydroquinone, and sinapinic acid as substrates. The highest efficiency of catalysis was observed with sinapic acid as the substrate. The kinetic constants kcat and Km of this reaction were 624 s-1 and 7 microM, respectively.

Journal Article↗

Biosensor based on an enzyme modified electrode for highly-sensitive measurement of polyphenols.

The use of glucose dehydrogenase from Acinetobacter calcoaceticus for highly sensitive measurement of polyphenols, based on bioelectrocatalytic analyte recycling, has been demonstrated. A polyphenol (analyte) is oxidized on the surface of a glassy carbon electrode at an anodic potential and is regenerated by immobilized glucose dehydrogenase (GDH) in the presence of glucose, resulting in an amplified response. The dynamic properties of the enzyme-modified glassy carbon electrode allow the convenient monitoring of subnanomolar analyte concentration. The detection limits for p-aminophenol and norepinephrine are 0.2 nM and 0.5 nM, respectively.

Acinetobacter↗

Enzyme electrodes and their application.

Starting from the state of the art, principles for improving the analytical characteristics of enzyme electrodes are discussed. Coupling of appropriate amperometric electrode processes with enzyme systems, e.g. urease or aminopeptidases, results in a simplification of operation. Optimal sample frequencies are realized on the basis of enzyme membranes, with both a small characteristic diffusion time and a high enzyme activity, applied in a well-designed sample-processing system. Coupled enzyme reactions of the sequence or competition type are successfully used for extension to new analytes, e.g. inhibitors, cofactors or alternative substrates. Cyclization of the analyte enhances the sensitivity of enzyme electrodes to the nanomolar concentration range. Enzymic anti-interference layers are a tool for improving the sensor specificity. The operational characteristics of enzyme electrodes are thus adaptable to any given analytical problem.

Biotechnology↗

[Elimination of saccharose from the blood and its renal excretion following transfusion of buffy coat-free erythrocyte concentrates containing disaccharides].

The elimination of sucrose from the blood and its renal excretion was analysed in 108 patients after applying a total of 394 transfusion units (TE), resuspended, buffy-coat-free erythrocyte concentrates (EK) containing 23 mmol of sucrose per TE. In transfusing 3 TE even 90% of the sucrose were eliminated from the blood during the application time and up to 99% within 3 h, nearly 80% were excreted through the kidneys within 12 h. Elimination and excretion were delayed with impaired kidney function. With respect to intravasal elimination of sucrose bilaterally nephrectomized patients have to rely on hemodialysis. Side-effects of sucrose due to extended intravasal and interstitial duration could not be observed in those patients affected with decreased kidney efficiency and after massive transfusions.

Aged↗