[Dermatological diseases and sexuality. How to proceed?]. / Dermatologische Erkrankungen und Sexualität. Wie geht man vor?

A variety of dermatological diseases is associated with male or female sexual dysfunction. Some sexual disorders are caused organically; erectile dysfunction in men with systemic sclerosis may be due to penile vascular alterations and corporal fibrosis. Other dermatoses such as psoriasis are associated with risk factors (metabolic syndrome) for sexual disorders and may therefore indirectly induce erectile dysfunction. However, the majority of sexual dysfunctions in dermatological patients is caused by reduced self confidence and sexual self esteem leading to affected partnership and sexuality. Dermatologists should be trained in basic sexual medicine and ask their patients for sexual problems. They may not treat sexual disorders, but they should be identified as sympathetic physicians for these problems and should be able to refer the patient to specialists in sexual medicine.

Hebephilia as a sexual disorder.

BACKGROUND: The term "hebephilia" describes the sexual preference for minors at an early pubertal body age. For most clinicians the definition of hebephilia is not obvious and not integrated as a separate category in the DSM-5. METHOD: N = 222 self-motivated applicants from the community for the therapy program of the Prevention Project Dunkelfeld in Berlin were assessed concerning their sexual preference towards minors. RESULTS: Approximately two-thirds (n = 153) showed a sexual interest in early pubertal minors (15 % exclusively; 85 % non-exclusively). Approximately 95 % reported having sexually abused children and/or having used child abusive images at least once in their lifetime. Hebephiles reported a significantly higher level of clinically relevant distress and personality characteristics, as well as more offense-supportive attitudes compared to normative samples. CONCLUSION: Hebephilia can be differentiated from pedophilia in terms of sexual interest for the body age of the minor. Associated personal distress, deviant personality characteristics as well as sexual behavior problems suggest that hebephilia can fulfill the criteria of a sexual disorder which should be considered in classification systems (DSM, ICD).

Human face processing is tuned to sexual age preferences.

Human faces can motivate nurturing behaviour or sexual behaviour when adults see a child or an adult face, respectively. This suggests that face processing is tuned to detecting age cues of sexual maturity to stimulate the appropriate reproductive behaviour: either caretaking or mating. In paedophilia, sexual attraction is directed to sexually immature children. Therefore, we hypothesized that brain networks that normally are tuned to mature faces of the preferred gender show an abnormal tuning to sexual immature faces in paedophilia. Here, we use functional magnetic resonance imaging (fMRI) to test directly for the existence of a network which is tuned to face cues of sexual maturity. During fMRI, participants sexually attracted to either adults or children were exposed to various face images. In individuals attracted to adults, adult faces activated several brain regions significantly more than child faces. These brain regions comprised areas known to be implicated in face processing, and sexual processing, including occipital areas, the ventrolateral prefrontal cortex and, subcortically, the putamen and nucleus caudatus. The same regions were activated in paedophiles, but with a reversed preferential response pattern.

[Motility disorders of the esophagus]. / Motilitätsstörungen des Ösophagus.

Motility disorders of the esophagus comprise a heterogeneous spectrum of diseases. Primary malformations of the esophagus are now amenable to improved surgical and gastroenterological therapies; however, they often lead to persistent long-term esophageal dysmotility. Achalasia originates from impaired relaxation of the gastroesophageal sphincter apparatus. Systemic diseases may give rise to secondary disorders of esophageal motility. A number of visceral neuromuscular disorders show an esophageal manifestation but aganglionosis rarely extends into the esophagus. The growing group of myopathies includes metabolic and mitochondrial disorders with increasing levels of genetic characterization and incipient emergence of therapeutic strategies. Esophagitis with an infectious etiology causes severe dysmotility particularly in immunocompromised patients. Immunologically mediated inflammatory processes involving the esophagus are increasingly better understood. Finally, rare tumors and tumor-like lesions may impair esophageal motor function.

[Hebephilia as a sexual disorder]. / Hebephilie als sexuelle Störung.

BACKGROUND: The term "hebephilia" describes the sexual preference for the body scheme of pubescent minors (Tanner stages 2 and 3). For most clinicians the definition of hebephilia as a sexual disorder is not obvious. METHOD: In all assessed males included in the Prevention Project Dunkelfeld at the Institute for Sexual Medicine at the Charité between 2005 and 2011, who met the inclusion criteria and showed no evidence for exclusion criteria (n=222), the existence of a hebephilia was examined. RESULTS: Approximately two thirds of the present sample (n=153) showed responsiveness for the body scheme of pubescent minors. Of these, only 15% were exclusively attracted by the pubescent body scheme and 85% were cases of mixed types. Concerning the clinical aspects of the sexual preference disorder, about 95% reported child sexual abuse and/or having used child abusive images at least once in their lifetime. Additionally, hebephiles reported a higher level of clinical/psychological stress and more distinct personality characteristics in relation to a comparative sample. In terms of risk factors, hebephiles showed more offense-supportive attitudes compared to a male comparative sample. CONCLUSION: Hebephilia is a sexual disorder, but cannot be independently coded in the presently valid classification systems (DSM-IV-TR and ICD-10). Plans to separately include this in future in the DSM-5 represent an important step from a sexological point of view.

An Exploratory Study on the Central Nervous Correlates of Sexual Excitation and Sexual Inhibition.

The Sexual Inhibition/Sexual Excitation Scales (SIS/SES) measure sexual excitation and sexual inhibition proneness. We used SIS and SES scores of 62 heterosexual teleiophilic men (Mage 34.3, SD = 9.9) to predict brain activation levels during the presentation of male and female visual sexual stimuli in a magnetic resonance imaging (MRI) scanner. Statistical analyses revealed significant correlations. SES and SIS1 scores were positively associated with brain activation in various brain regions during the presentation of both male and female stimuli. SIS2 turned out to be a weaker predictor of brain activation, still revealing one significant correlation in the right lateral orbitofrontal cortex. Significant regions for SES and SIS1 were, among others, primary and supplementary motor areas, the caudate nucleus, the dorsal anterior cingulate cortex, anterior insula, and prefrontal areas. Our study can be seen as an exploratory investigation of SIS and SES with means of functional brain imaging. The results provide a promising contribution to the assertion of neurophysiological systems of sexual inhibition and excitation proneness.

Prevalence of erectile dysfunction among middle-aged men in a metropolitan area in Germany.

The comparison of results of previous studies on the prevalence of erectile dysfunction is hampered due to differences in study design and research instruments including definitions used. The aim of the study was to determine the prevalence of erectile dysfunction/erectile disorder (ED) using different definitions. An epidemiological cross-sectional study was conducted between May and November 2002 in Berlin, Germany. A total of 6000 men between 40 and 79 years of age were randomly selected by the Berlin Office of Vital Statistics and were sent a questionnaire by mail. The prevalence of ED was determined using five different methods. A total of 1915 questionnaires were eligible for analysis. The five different definitions yielded age-adjusted ED prevalence rates between 18 and 48%. Age was strongly correlated with all five definitions (P<0.001). These results indicate the need for standardized criteria when conducting future studies on ED and may aid in designing public health and clinical management strategies.

[Sexual medicine in daily practice : Germany-wide questionnaire of urologists]. / Sexualmedizin im ärztlichen Alltag : Bundesweite Umfrage unter Ärzten in der Urologie.

BACKGROUND: Sexual-related problems are very prevalent. Physicians of different disciplines are frequently contacted by men with those problems. OBJECTIVES: The aim of this study was to investigate the situation of sexual medicine in daily practice and to evaluate German urologists' need for further training in this field with a focus on gender-specific differences. MATERIALS AND METHODS: A five-page questionnaire included questions about sexual medicine in daily practice. A focus was set on physicians dealing with sexual medicine in daily practice and their need for further training in this field. In April/Mai 2015, questionnaires were sent per mail to 5955 urologists, urology residents and andrologists throughout Germany. The questionnaire was developed based on previously published studies and a pretest was performed to evaluate comprehensibility. A χ2 test was performed to determine significant gender-specific differences; for this propose response options were dichotomised. P values ≤0.05 were considered significant. RESULTS: The response rate was 16.0%, representing 955 questionnaires. A total of 50 questionnaires from non-urologists were excluded, so 905 questionnaires were analysed. The mean age was 47.7 ± 10.4 years, 78.9% were male, 97.0% had studied in Germany, 86.7% were specialists and 37.7% had further qualification in andrology. CONCLUSION: Our results emphasize the need for further training in sexual medicine, especially for female physicians. This study underlines the demand for advanced qualification in sexual medicine.

Gray matter anomalies in pedophiles with and without a history of child sexual offending.

Pedophilia is a psychiatric disorder that is inter-related with but distinct from child sexual offending (CSO). Neural alterations reportedly contribute to both pedophilia and CSO, but until now, no study has distinguished the brain structural anomalies associated with pedophilia from those specifically associated with CSO in pedophilic men. Using high-resolution T1-weighted brain images and voxel-based morphometry, we analyzed the gray matter (GM) volume of the following 219 men recruited at four acquisition sites in Germany: 58 pedophiles with a history of CSO, 60 pedophiles without any history of CSO and 101 non-pedophilic, non-offending controls to control for the effects of age, education level, verbal IQ, sexual orientation and the acquisition site. Although there were no differences in the relative GM volume of the brain specifically associated with pedophilia, statistical parametric maps revealed a highly significant and CSO-related pattern of above vs below the 'normal' GM volume in the right temporal pole, with non-offending pedophiles exhibiting larger volumes than offending pedophiles. Moreover, regression analysis revealed that the lower GM volume of the dorsomedial prefrontal or anterior cingulate cortex was associated with a higher risk of re-offending in pedophilic child molesters. We believe our data provide the first evidence that CSO in pedophilia rather than pedophilia alone is associated with GM anomalies and thus shed new light on the results of previous studies on this topic. These results indicate the need for new neurobehavioral theories on pedophilia and CSO and may be potentially useful for treatment or prevention approaches that aim to reduce the risk of (re)offending in pedophilia.

[Biopsychosocial understanding of human sexuality. Prerequisite for diagnostics and treatment in sexual medicine]. / Biopsychosoziales Verständnis menschlicher Geschlechtlichkeit. Vorausetzung für sexualmedizinische Diagnostik und Therapie.

Sexual medicine is a subdiscipline of clinical medicine that deals with human sexuality and disorders. Sexuality eludes a unilateral definition. As a biologically, psychologically, and socially determined experience dimension of the human being, its individual form depends on biological factors and developments in the person's life. Moreover, sexuality exhibits different dimensions--lust, reproduction, and relationship--that are indeed closely interrelated. For this reason, directing therapy at only one of these dimensions is not adequate. All human beings are programmed toward fulfillment of elementary biopsychosocial needs such as acceptance, closeness, warmth, and security. If these basic needs are shortchanged in terms of fulfillment, all sorts of restrictions in the quality of life ensue, even to the point of resultant disorders of sexual function. Treatment then approaches the roots when it does not center on the sexual dysfunction but rather on the underlying frustrated relationship of the partners. Syndyastic sexual therapy is an important treatment method in sexual medicine.

[Influence of neurological diseases on partnership and sexuality. Particularly in view of multiple sclerosis and Parkinson's disease]. / Der Einfluss neurologischer Erkrankungen auf Partnerschaft und Sexualität. Unter besonderer Berücksichtigung der Multiplen Sklerose und des Morbus Parkinson.

A great number of neurological diseases exert a direct impact on sexuality, due to lesions in the central and peripheral nervous system and due to different neurological symptoms and their treatment (for example medication). The psychosocial basic needs for acceptance, intimacy, and security, which can be best fulfilled by sexual communication, attain essential importance in the situation of disease-induced helplessness. This implies that not only the experience of sexual pleasure and the functioning of reproduction can be influenced, but the partnership, too. A holistic treatment approach always requires the consideration of partnership aspects.

[Sex therapy for male sexual dysfunction]. / Sexualtherapie bei sexuellen Funktionsstörungen des Mannes.

A high prevalence and incidence of sexual dysfunctions as well as the availability of orally effective medications cause a rising interest in professional help. In diagnosing and treating sexual disorders, a holistic, biopsychosocial understanding of sexuality and a thorough analysis of the specific needs of the couple are of the utmost importance. Furthermore, the typical physician-patient relationship has to be transformed into a physician-couple relationship wherever possible. Sex therapy, then, focuses on the universal psychosocial fundamental needs and their relevance for the complaints of the couple. In this way the main focus of attention is shifted from the sexual dysfunction to the communicative meaning of sexuality within the relationship and to the quality of the partnership as a whole. Thus the sexual problem is put into a new perspective and sexual functions are relieved from the pressure of performance anxiety. Simultaneously intimacy and mutual satisfaction are promoted. The possibility of obtaining an additional qualification in sexual medicine (since 1997 in postgraduate, curricular trainings) is offering new opportunities for urologists to integrate aspects of sexual medicine into their clinical practice and thus to propose a more extensive form of therapy to their patients. This paper reflects the process of this integration, illustrating it with respective case reports; it stresses the necessity of a holistic approach to the treatment of sexual dysfunctions, also in regard to the economic advantages of a biopsychosocially oriented sex therapy.

Nonpolar interactions in the modification of an essential sulfhydryl of sorbitol dehydrogenase by N-alkylmaleimides.

A series of N-alkylmaleimides varying in chainlength from N-methyl- to N-octylmaleimide inclusive was shown to effectively inactivate sheep liver sorbitol dehydrogenase at pH 7.5 and 25 degrees C. The apparent second-order rate constants for inactivation increased with increasing chainlength of the N-alkylmaleimide used. Positive chainlength effects were also indicated by the Kd values for the N-ethyl and N-heptyl derivatives obtained from studies of the saturation kinetics observed for inactivation of the enzyme at high concentrations of these maleimides. The complete inactivation of sorbitol dehydrogenase was demonstrated to occur through the selective covalent modification of one cysteine residue per subunit of enzyme. The stoichiometry of enzyme inactivation was supported on the one hand by fluorescence titration with fluorescein mercuric acetate of the native and the inactivated enzyme, and, on the other hand, by the simultaneous inactivation of the enzyme with selective modification of one sulfhydryl per subunit by N-[p-(2-benzoxazolyl)phenyl]maleimide. Protection of the enzyme from N-alkylmaleimide inactivation was observed with the binding of NADH, whereas both NAD and sorbitol were ineffective as protecting ligands. Diazotized 3-aminopyridine adenine dinucleotide, in contrast to previous studies of this reagent with yeast alcohol dehydrogenase and rabbit muscle glycerophosphate dehydrogenase, did not function as a site-labeling reagent for sorbitol dehydrogenase.

Selective induction of peroxisomal enzymes by the hypolipidemic drug bezafibrate. Detection of modulations by automatic image analysis in conjunction with immunoelectron microscopy and immunoblotting.

Quantitative immunoelectron microscopy in conjunction with quantitative analysis of immunoblots have been used to study the effects of bezafibrate (BF), a peroxisome-proliferating hypolipidemic drug, upon six different enzyme proteins in rat liver peroxisomes (Po). Antibodies against following peroxisomal enzymes: catalase, urate oxidase, alpha-hydroxy acid oxidase, acyl-CoA oxidase, bifunctional enzyme (hydratase-dehydrogenase) and thiolase, were raised in rabbits, and their monospecificities were confirmed by immunoblotting. Female Sprague-Dawley rats were treated for 7 days with 250 mg/kg/day bezafibrate and liver sections were incubated with the appropriate antibodies followed by the protein A-gold complex. The labeling density for each enzyme was estimated by automatic image analysis. In parallel experiments immunoblots prepared from highly purified peroxisome fractions of normal and BF-treated rats were incubated with the same antibodies. The antigens were visualized by an improved protein A-gold method including an anti-protein A step and silver amplification. The immunoblots were also quantitated by an image analyzer. The results revealed a selective induction of beta-oxidation enzymes by bezafibrate with thiolase showing the most increase followed by bifunctional protein and acyl-CoA oxidase. The labeling density for catalase and alpha-hydroxy acid oxidase was reduced, confirming fully the quantitative analysis of immunoblots which in addition revealed reduction of uricase. These observations demonstrate that hypolipidemic drugs induce selectively the beta-oxidation enzymes while other peroxisomal enzymes are reduced. The quantitative immunoelectron microscopy with automatic image analysis provides a versatile, highly sensitive and efficient method for rapid detection of modulations of individual proteins in peroxisomes.

Biogenesis of peroxisomes: sequential biosynthesis of the membrane and matrix proteins in the course of hepatic regeneration.

The biogenesis of peroxisomes was investigated in the model of regenerating rat liver after partial hepatectomy (PH), using analytical differential centrifugation in combination with immunoblotting and in vivo pulse labeling as well as immunoelectron microscopy. The total activity of catalase decreased sharply after PH, returning gradually over several days to normal levels. In the 16 to 32-h period the enzyme activity started to increase first in the heavy mitochondrial fraction, shifting at 28 h to the crude peroxisomal and at 32 h to the microsomal fraction, suggesting de novo formation of peroxisomes by budding or fragmentation from larger aggregates. Whereas most peroxisomal matrix proteins were reduced during the 16 to 32-h period after PH, the 26 and 70 kDa peroxisomal membrane proteins were increased. Moreover, in vivo pulse labeling studies with radioactive leucine showed significantly higher levels of specific activity in the peroxisomal membrane than in the matrix subfractions at 16 h with increasing labeling of the matrix at 32 h after PH. These findings suggest that de novo formation of peroxisomes in regenerating rat liver is initiated by the synthesis of membrane proteins and is followed by that of the matrix components.

Immunocytochemical localization of a urate oxidase immunoreactive protein in the plasma membranes and membranes of the secretory/endocytic compartments of digestive gland cells of the mussel Mytilus galloprovincialis.

The subcellular compartmentalization of urate oxidase (UOX) in the digestive glands of mussels, Mytilus galloprovincialis Lmk, was studied by means of immunoblotting and immunocytochemistry, using an antibody raised in rabbit against rat liver UOX. Western blot analysis of subcellular fractions revealed an immunoreactive polypeptide with a molecular weight similar to the corresponding mammalian hepatic protein. This crossreactive polypeptide of 32 kDa was particle-bound yet not peroxisome-associated. In paraffin sections the antiserum specifically labeled the plasma membrane of the digestive gland epithelial cells and discrete regions within the perinuclear and apical portions of the digestive tubules and duct cells. By electron microscopy gold particles representing antigenic sites were found on the microvilli and the lateral plasma membrane as well as the membranes of the secretory/ endocytic compartments, that is, the Golgi complex, secretory and some endocytic vesicle membranes. Since the peroxisomal UOX-antibody exhibits a comparable immunoreactivity towards a urate-transporter channel protein in rat kidney proximal tubules and has been used for its molecular cloning (Leal-Pinto et al., 1997, J. Biol. Chem. 272, 617-625), we suggest that the membrane protein identified in mussel digestive glands could represent a homologous urate-transporter protein.

Suppression of peroxisomal lipid beta-oxidation enzymes of TNF-alpha.

TNF-alpha is a potent cytokine which induces marked hyperlipidemia. Because of the important role of peroxisomes in lipid metabolism we investigated the effects of human recombinant TNF-alpha upon rat liver peroxisomal enzymes. Sixteen hours after the administration of a single dose of 25 micrograms of TNF-alpha to male rats the activity of peroxisomal fatty acyl-CoA oxidase was reduced by 50%. This was confirmed also by immunoblotting and by quantitative immunoelectron microscopy which in addition revealed substantial reduction of the trifunctional protein (hydratase-dehydrogenase-isomerase) in peroxisomes. These observations suggest that the suppression of peroxisomal beta-oxidation may contribute to the perturbation of the isomerase) in peroxisomes. These observations suggest that the suppression of peroxisomal beta-oxidation may contribute to the perturbation of the lipid metabolism induced by TNF-alpha.

TNF-alpha downregulates the peroxisome proliferator activated receptor-alpha and the mRNAs encoding peroxisomal proteins in rat liver.

We have studied the effects of TNF-alpha on the mRNAs coding for the peroxisome proliferator activated receptor alpha (PPAR-alpha), and for catalase (Cat), acyl-CoA oxidase (AOX), multifunctional enzyme (PH), and beta-actin in rat liver. Total RNA was isolated from livers of male SD-rats 16 h after administration of a single dose of 25 microg TNF-alpha and mRNAs were analyzed by a novel dot blot RNase protection assay. The mRNAs for PPAR-alpha and for Cat, AOX and PH were significantly reduced by TNF-treatment. In addition, the level of PPAR-alpha protein was also decreased after TNF. In contrast, the mRNA for beta-actin was markedly increased implying that the effect of TNF on PPAR-alpha and the peroxisomal mRNAs is highly selective. This effect may have important implications in perturbation of the lipid metabolism induced by TNF-alpha.

Impairment of peroxisomal structure and function in rat liver allograft rejection: prevention by cyclosporine.

BACKGROUND: During allograft rejection, cytokines and lipid mediators contribute to cell injury and organ failure. Peroxisomes play a crucial role in lipid metabolism, including the degradation of lipid mediators by peroxisomal beta-oxidation. Therefore, we investigated the alterations of hepatic peroxisomes after allogeneic rat liver transplantation. METHODS: MHC-incompatible Dark Agouti (RT1a) donor rats and Lewis (RT1(1)) recipient rats were used for allogeneic transplantation. For immunosuppression, a group of these animals received cyclosporine (CsA) intraperitoneally (1 mg/kg body weight per day). Lewis rats were used for isogeneic transplant combination. Ten days after transplantation, livers were investigated using morphometrical methods for determination of peroxisomal diameter and volume density. The activities of peroxisomal catalase (CAT) and acyl-coenzyme A oxidase (AOX) were determined, and the corresponding proteins were evaluated by quantitative immunocytochemistry and immunoblotting. The expressions of mRNAs encoding CAT and AOX were investigated by Northern blotting. RESULTS: The volume density and diameter of peroxisomes were significantly decreased in allogeneic transplanted livers but were unchanged in CsA-treated animals. Both the activities of CAT and AOX and their protein levels were significantly reduced in liver allografts. Moreover, the corresponding mRNA levels of CAT and AOX were decreased significantly in liver allografts, whereas CsA treatment led to an increase of those mRNAs. Isogeneic transplanted livers showed only a slight reduction of the corresponding enzyme values. CONCLUSIONS: Peroxisomes are severely affected both morphologically and functionally after allogeneic liver transplantation. These results suggest that impairment of peroxisomal lipid beta-oxidation could contribute to the pathogenesis of the rejection process by decreased catabolism of lipid mediators involved in the regulation of the inflammatory response. CsA, in addition to its immunosuppressive effects, may contribute to allograft survival by maintenance of those important peroxisomal functions.

Light microscopic morphometric analysis of peroxisomes by automatic image analysis: advantages of immunostaining over the alkaline DAB method.

The feasibility of light microscopic post-embedding immunocytochemistry for morphometry of peroxisomes using automatic image analysis was investigated and compared with the classical alkaline DAB method. Perfusion-fixed rat liver tissue was either embedded in LR White or incubated in the alkaline diaminobenzidine (DAB) medium for cytochemical visualization of catalase. Sections from the LR White-embedded material were incubated with a monospecific antibody against catalase, followed by protein A-gold and silver intensification. Determination of peroxisomal volume density in sections of different thickness revealed that the values increased with section thickness in DAB-stained sections but were unaffected in immunostained preparations. Moreover, the absolute value for volume density of peroxisomes, as determined by light microscopy in immunostained sections, was quite close to the value obtained by analysis of electron microscopic preparations. Finally, morphometric analysis of bezafibrate-induced peroxisome proliferation revealed that the ratio of proliferation obtained by light microscopy in immunostained sections was very close to the results obtained by electron microscopic morphometry. The main advantage of post-embedding immunostaining for light microscopic morphometry is that it restricts the immunocytochemical reaction product to the surface of the section, thus making it independent of section thickness.