Biomedical subjects

U Hartmann

Publications and source records attributed to U Hartmann.

At least 19 recordsLinked to original sources

PubMed2003

Specificity of the neuroendocrine response to orgasm during sexual arousal in men.

We have demonstrated that sexual activity produces transient sympathoadrenal activation and a pronounced, long-lasting increase in prolactin in men and women. However, by analyzing endocrine alterations at 10-min intervals, a precise assignment of these changes to the pre-, peri- and postorgasmic periods was not possible. Thus, the current study aimed to accurately differentiate the endocrine response to sexual arousal and orgasm in men using an automatic blood collection technique with 2-min sampling intervals. Blood was drawn continuously before, during and after orgasm over a total period of 40 min in 10 healthy subjects and were compared with samples obtained under a control condition. Sexual activity induced transient increases of plasma epinephrine and norepinephrine levels during orgasm with a rapid decline thereafter. In contrast, prolactin levels increased immediately after orgasm and remained elevated throughout the experiment. Although oxytocin was acutely increased after orgasm, these changes were not consistent and did not reach statistical significance. Vasopressin, LH, FSH and testosterone plasma concentrations remained unaltered during sexual arousal and orgasm. These data confirm that prolactin is secreted after orgasm and, compared with oxytocin, seems to represent a more reliable and sustained marker for orgasm in man. The results further reinforce a role for prolactin either as a neuroendocrine reproductive reflex or as a feedback mechanism modulating dopaminergic systems in the central nervous system that are responsible for appetitive behavior.

Adolescent↗

PubMed2002

[Sexuality in the elderly].

Disturbance of sexual function and sexual perceptions in the aging often have a significant negative impact on overall quality of life. Epidemiological data on this phenomenon are sparse. Recently, however, more investigations have been undertaken to improve diagnostic and therapeutic approaches. First scientific concepts are now emerging that will allow better patients care in the future.

Adult↗

PubMed2002

Absence of orgasm-induced prolactin secretion in a healthy multi-orgasmic male subject.

In several studies we have recently demonstrated that orgasm induces prolactin secretion in healthy males and females. This suggests that prolactin may form a feedback regulator of the refractory period following orgasm. To examine this position we investigated the prolactin response of a healthy multi-orgasmic male subject. Blood was drawn continuously during masturbation-induced orgasm. The prolactin response of the case-subject was compared with that of nine healthy adult men with a normal refractory period. The case-subject showed no prolactin response to three orgasms. Data from this multi-orgasmic subject support the hypothesized role of plasma prolactin in contributing to sexual-satiation mechanisms.

Adult↗

PubMed2001

Endocrine response to masturbation-induced orgasm in healthy men following a 3-week sexual abstinence.

This current study examined the effect of a 3-week period of sexual abstinence on the neuroendocrine response to masturbation-induced orgasm. Hormonal and cardiovascular parameters were examined in ten healthy adult men during sexual arousal and masturbation-induced orgasm. Blood was drawn continuously and cardiovascular parameters were constantly monitored. This procedure was conducted for each participant twice, both before and after a 3-week period of sexual abstinence. Plasma was subsequently analysed for concentrations of adrenaline, noradrenaline, cortisol, prolactin, luteinizing hormone and testosterone concentrations. Orgasm increased blood pressure, heart rate, plasma catecholamines and prolactin. These effects were observed both before and after sexual abstinence. In contrast, although plasma testosterone was unaltered by orgasm, higher testosterone concentrations were observed following the period of abstinence. These data demonstrate that acute abstinence does not change the neuroendocrine response to orgasm but does produce elevated levels of testosterone in males.

Adult↗

PubMed2001

Evaluation of potential organ culture media for eye banking using a human corneal endothelial cell growth assay.

BACKGROUND: To evaluate the ability of different commercially available cell culture media to induce proliferation and morphological changes in primary cultures of human corneal endothelial cells (HCEC). This screening model was used in an attempt to establish a rational basis for the development of well-defined, serum-free preservation media for long-term organ culture of human donor corneas. METHODS: A total of 11 different culture media enriched with 0%, 2%, 5%, and 10% fetal calf serum (FCS) were compared. The test media were divided into three groups: Group 1: Media based on minimal essential medium (MEM), currently used for long-term corneal organ culture in European eye banks; Group 2: F99-based media, enriched for growth of corneal endothelial cells at serum-reduced conditions; and Group 3: Media designed for growth of special cell types or for short-term corneal organ culture. The growth-promoting capacity of each test medium was quantified using an HCEC proliferation assay, whereas changes in cell morphology were evaluated by phase-contrast microscopy. RESULTS: The morphological characteristics of HCEC were best maintained in the group of F99-based media, which also induced the highest level of cell proliferation under serum-reduced conditions. Specifically, the medium F99-Sr (F99 enriched with ascorbic acid, insulin, bFGF, transferrin, selenium, and lipids) induced a two- to three-fold higher HCEC density at both 0% and 2% FCS when compared to all other test media, and it also maintained the most endothelial cell-like morphology. Also, at higher serum concentrations (5% and 10% FCS), the cell growth was most prominent in F99-Sr, as well as in the medium SFM that originally was designed for serum-free growth of vascular endothelial cells. CONCLUSION: This study suggests that the media F99-Sr and SFM should be further tested and refined as potential new storage solutions for long-term corneal organ culture at physiological temperatures.

Aged↗

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

The scanning near-field optical microscope as a tool for proteomics.

The identification of the entire genetic code of human DNA is more or less completed. With this knowledge, research in identifying the real information lying in the genes, will begin. This information is contained in the proteins, which are the main biological actors in the cell. For this reason proteins will be targeted in biological investigations in the future. The structure, affinity and reactivity of each identified protein has to be determined, which is a primary goal in the field of proteomics. This will require new and better strategies to identify protein-protein interaction. Our approach, based on the detection and visualization of single proteins by scanning near-field optical microscopy (SNOM), has allowed us to visualize various fixed and fluorochrome-labelled proteins at the nanometer scale. Subsequently SNOM may then be developed to efficiently detect the specific behavior of a certain protein in response to other biomolecules.

Bacterial Proteins↗

PubMed2001

Coitus-induced orgasm stimulates prolactin secretion in healthy subjects.

Previous data have indicated that orgasm produces marked alterations in plasma prolactin concentrations in men and women. Thus, the current study aimed to extend these data by examining prolactin response to coitus in healthy males and females. Ten pairs of healthy heterosexual couples participated in the study. Blood was drawn continuously for 20 min before, during, and until 60 min following sexual intercourse and orgasm. Plasma was subsequently analysed for prolactin concentrations. Coitus-induced orgasm produced a marked elevation of plasma prolactin in both males and females. Plasma prolactin concentrations remained elevated 1 h following orgasm. These data, together with previous evidence that masturbation-induced orgasm produces pronounced, long-lasting increases in plasma prolactin concentrations in both males and females, suggest a role for acute prolactin alterations in modifying human sexual desire following orgasm.

Adult↗

PubMed2001

Proteoglycans in the nervous system--the quest for functional roles in vivo.

Large numbers of different proteoglycans are expressed in tightly regulated spatio-temporal patterns by both the nerve cells (neurons) and the supporting glial cells of the nervous system. Several of these proteoglycans have been shown by studies in vitro to affect the migration of neural precursor cells, the elongation and pathfinding of neurites and the formation and stabilization of synapses. Such processes are important for the accurate wiring of the nervous system, and so it has been postulated that proteoglycans play an essential role during neural development. However, with few exceptions, the phenotypes of null mutations in mice and some human genetic diseases have provided little support for this view. Here we will review recent data from both in vitro and in vivo studies analyzing the function of proteoglycans in the nervous system in order to provide possible explanations for their apparent lack of function.

Amyloid beta-Protein Precursor↗

PubMed2001

A dose-escalation study to assess the efficacy and safety of sildenafil citrate in men with erectile dysfunction.

OBJECTIVE: To assess the efficacy and safety of sildenafil citrate (Viagra, Pfizer Inc., USA) in a double-blind, placebo-controlled, dose-escalation study over a period of 26 weeks in men with erectile dysfunction of a broad spectrum of aetiology. PATIENTS AND METHODS: In all, 315 patients from five countries were randomized to receive treatment with placebo (156 men) or sildenafil (159 men). Significant concomitant medical conditions were hypertension (20%), a history of pelvic surgery (19%), diabetes mellitus (15%), and ischaemic heart disease (10%). Patients randomized to treatment received a starting dose of 25 mg of sildenafil or matching placebo, which could be increased to 50 mg and then to 100 mg of sildenafil, based on efficacy and tolerability. Assessments of efficacy comprised the 15-item International Index of Erectile Function (IIEF), including question three (ability to achieve an erection) and question four (ability to maintain an erection), a partner questionnaire, an overall efficacy question, and event-log data. RESULTS: After 12 weeks of treatment, 26%, 32% and 42% of patients were taking 25, 50 and 100 mg of sildenafil, respectively. A similar distribution of doses was reported after 26 weeks of treatment. Treatment with sildenafil significantly improved the patients' abilities to achieve and maintain an erection compared with treatment with placebo (P < 0.001). Scores for four of the five sexual function domains of the IIEF (erectile function, orgasmic function, intercourse satisfaction and overall satisfaction) also improved significantly (P < 0.001). There was a significant improvement in the mean score for the erectile function domain, regardless of the aetiology of erectile dysfunction (P < 0.001). After 12 weeks and 26 weeks of treatment, 82% and 79% of patients receiving sildenafil reported improved erections, compared with 24% and 23% of patients receiving placebo, respectively (P < 0.001). Treatment-related adverse events were mild to moderate and occurred in 27% of patients receiving sildenafil, compared with 8% of patients receiving placebo. CONCLUSION: Sildenafil is an effective and well-tolerated treatment for men with erectile dysfunction of a broad spectrum of aetiology.

Administration, Oral↗

PubMed2001

Evaluation of potential organ culture media for eye banking using human donor corneas.

AIM: To evaluate the ability of different commercially available cell culture solutions to preserve human donor corneas during 3 weeks of "closed system" organ culture at physiological temperature. This screening was performed in an attempt to establish a rational basis for the development of a serum-free organ culture medium for eye banking. METHODS: 72 normal human donor corneas were organ cultured for 21 days at 31 degrees C in eight different test media (nine corneas in each group). The basic culture solutions included: minimal essential medium (MEM), MEM with stabilised L-glutamine, M199, DIF-1000, SFM, F99, and F99 with ascorbic acid, insulin, bFGF, transferrin, selenium, and lipids (termed F99-Sr). All media were supplemented with 2% fetal calf serum (FCS), except for MEM, which was also studied at 8% FCS. The evaluation parameters included: (1) the endothelial cell loss as evaluated using trypan blue staining; (2) the ability of keratocytes and endothelial cells to incorporate tritiated uridine into RNA as evaluated using autoradiography and digital image analysis; (3) the leakage of immunogenic keratan sulphate as assessed using ELISA; and (4) changes in storage medium pH, glucose, and lactate content. RESULTS: SFM induced the lowest endothelial cell loss of 14% (SD 2%) and the highest RNA synthesis rates of all test solutions supplemented with 2% FCS. Corneas stored in SFM also showed the least leakage of keratan sulphate and the highest glucose consumption and lactate production. In five media (MEM with 2% FCS, MEM with stabilised L-glutamine, M199, F99, and F99-Sr), comparable and intermediate potentials for organ culture were observed with endothelial cell loss of 16-19%. By contrast, 29% (4%) of the endothelium was lost after storage in DIF-1000. Interestingly, the use of 8% FCS (in MEM) had a marked protective effect on the endothelium, which showed the highest RNA synthetic activity combined with a cell loss of only 11% (4%), compared with 19% (6%) at 2% FCS (p<0.05). CONCLUSION: Among the present test solutions, SFM appears to be the most prominent candidate for a new corneal organ culture medium and should be further tested and possibly refined to effectively substitute serum addition.

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

Epitope spreading and a varying but not disease-specific GAD65 antibody response in Type I diabetes. The Childhood Diabetes in Finland Study Group.

AIMS/HYPOTHESIS: The aim of this study was to analyse the conformational and linear epitope profiles of glutamic acid decarboxylase antibody (GAD65-ab)-positive sera to find disease-specific epitope profiles and to study, whether GAD65-ab epitope recognition changes or spreads during the prediabetic period and, thus, can provide markers to differentiate early from later stages of progression to diabetes. METHODS: Sera from subjects before (n = 21), at onset (n = 44), or at increased risk of Type I (insulin-dependent) diabetes mellitus (n = 20) and from patients with stiff-man syndrome (SMS, n = 18) or polyendocrine autoimmune syndrome (PAS, n = 21) were analysed for conformational and linear GAD65 epitope recognition by an immunohistochemical blocking test based on human monoclonal GAD65-ab (MICA 1-10) and western blotting of a GAD65 epitope-cDNA-library. RESULTS: A redundant reactivity of many GAD65-ab positive sera to three major conformational (EP-1, EP-2, EP-3) and two dominant linear epitope clusters (amino acid 1-124 and 535-585) was observed in diabetes, polyendocrine autoimmune syndrome and stiff-man syndrome and no disease-specific epitopes or epitope-profiles were detected. Epitope recognition broadened with higher titres and with the vulnerability of patients to acquire additional autoimmune diseases apart from diabetes. Low GAD65-ab serum titres (< 1200 arbitrary units) and EP-1 recognition in the absence of EP-2 binding characterised the early immune response. Changing epitope profiles combined stable recognition of EP-1 with gain or loss of reactivity to C-terminal epitopes during follow-up. CONCLUSION/INTERPRETATION: A maturing autoantibody response, which could spread from EP-1-recognition to other regions of GAD65, resulted in titre-related rather than disease-specific epitope profiles which were not sufficient to predict whether GAD65-ab positive subjects will progress to Type I diabetes, autoimmune polyendocrine syndrome or stiff-man syndrome.

Adolescent↗

PubMed2000

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↗

PubMed2000

Neuroendocrine response to film-induced sexual arousal in men and women.

The psychoneuroendocrine responses to sexual arousal have not been clearly established in humans. However, we have demonstrated previously that masturbation-induced orgasm stimulates cardiovascular activity and induces increases in catecholamines and prolactin in blood of both males and females. We presently investigated the role of orgasm in producing these effects. Therefore, in this study parallel analysis of prolactin, adrenaline, noradrenaline, and cortisol concentrations, together with cardiovascular variables of systolic/diastolic blood pressure and heart rate were undertaken during film-induced sexual arousal in nine healthy adult men and nine healthy adult women. Blood was drawn continuously via an indwelling cannula and connected tubing system passed through a mini-pump. In parallel, the cardiovascular parameters were recorded continuously via a computerised finger-cuff sensor. Subjective sexual arousal increased significantly in both men and women during the erotic film, with sexual arousal eliciting an increase in blood pressure in both males and females, and plasma noradrenaline in females only. In contrast, adrenaline, cortisol and prolactin levels were unaffected by sexual arousal. These data further consolidate the role of sympathetic activation in sexual arousal processes. Furthermore, they demonstrate that increases in plasma prolactin during sexual stimulation are orgasm-dependent, suggesting that prolactin may regulate a negative-feedback sexual-satiation mechanism.

Adult↗