Effects of Elevated beta-Estradiol Levels on the Functional Morphology of the Testis - New Insights

Elevated estradiol levels are correlated with male infertility. Causes of hyperestrogenism include diseases of the adrenal cortex, testis or medications affecting the hypothalamus-pituitary-gonadal axis. The aim of our study was to elucidate the effects of estradiol treatment on testicular cellular morphology and function, with reference to the treatment regimen received. Testes samples (n = 9) were obtained post-orchiectomy from male-to-female transsexuals within the age range of 26–52 years. Each patient had a minimum of 1–6 years estradiol treatment. For comparison, additional samples were obtained from microscopically unaltered testicular tissue surrounding tumors (n = 7). The tissues obtained were investigated by stereomicroscopy, histochemistry, scanning electron microscopy (SEM) and immunohistochemistry. Our studies revealed that estradiol treatment significantly decreased the diameter of the seminiferous tubules (p < 0.05) and induced fatty degeneration in the surrounding connective tissue. An increase in collagen fiber synthesis in the extracellular matrix (ECM) surrounding the seminiferous tubules was also induced. Spermatogenesis was impaired resulting in mainly spermatogonia being present. Sertoli cells revealed diminished expression of estrogen receptor alpha (ERα). Both Sertoli and Leydig cells showed morphological alterations and glycoprotein accumulations. These results demonstrate that increased estradiol levels drastically impact the human testis

Replacement of the Cobalt Center of Vitamin B 12 by Nickel: Nibalamin and Nibyric Acid Prepared from Metal‐Free B 12 Ligands Hydrogenobalamin and Hydrogenobyric Acid

The (formal) replacement of Co in cobalamin (Cbl) by NiII generates nibalamin (Nibl), a new transition‐metal analogue of vitamin B12. Described here is Nibl, synthesized by incorporation of a NiII ion into the metal‐free B12 ligand hydrogenobalamin (Hbl), itself prepared from hydrogenobyric acid (Hby). The related NiII corrin nibyric acid (Niby) was similarly synthesized from Hby, the metal‐free cobyric acid ligand. The solution structures of Hbl, and Niby and Nibl, were characterized by spectroscopic studies. Hbl features two inner protons bound at N2 and N4 of the corrin ligand, as discovered in Hby. X‐ray analysis of Niby shows the structural adaptation of the corrin ligand to NiII ions and the coordination behavior of NiII. The diamagnetic Niby and Nibl, and corresponding isoelectronic CoI corrins, were deduced to be isostructural. Nibl is a structural mimic of four‐coordinate base‐off Cbls, as verified by its ability to act as a strong inhibitor of bacterial adenosyltransferase

Zinc Substitution of Cobalt in Vitamin B12: Zincobyric acid and Zincobalamin as Luminescent Structural B12-Mimics

Replacing the central cobalt ion of vitamin B12 by other metals has been a long‐held aspiration within the B12‐field. Herein, we describe the synthesis from hydrogenobyric acid of zincobyric acid (Znby) and zincobalamin (Znbl), the Zn‐analogues of the natural cobalt‐corrins cobyric acid and vitamin B12, respectively. The solution structures of Znby and Znbl were studied by NMR‐spectroscopy. Single crystals of Znby were produced, providing the first X‐ray crystallographic structure of a zinc corrin. The structures of Znby and of computationally generated Znbl were found to resemble the corresponding CoII‐corrins, making such Zn‐corrins potentially useful for investigations of B12‐dependent processes. The singlet excited state of Znby had a short life‐time, limited by rapid intersystem crossing to the triplet state. Znby allowed the unprecedented observation of a corrin triplet (ET=190 kJ mol−1) and was found to be an excellent photo‐sensitizer for 1O2 (ΦΔ=0.70)

The Hydrogenobyric Acid Structure Reveals the Corrin Ligand as an Entatic State Module Empowering B12‐Cofactors for Catalysis

The B12 cofactors instill a natural curiosity regarding the primordial selection and evolution of their corrin ligand. Surprisingly, this important natural macrocycle has evaded molecular scrutiny, and its specific role in predisposing the incarcerated cobalt-ion for organometallic catalysis has remained obscure. Herein, we report the biosynthesis of the cobalt-free B12 corrin moiety, hydrogenobyric acid (Hby), a compound crafted through pathway redesign. Detailed insights from single crystal X-ray and solution structures of Hby have revealed a distorted helical cavity, redefining the pattern for binding cobalt-ions. Consequently, the corrin ligand coordinates cobalt-ions in de-symmetrized ‘entatic’ states, thereby promoting the activation of B12-cofactors for their challenging chemical transitions. The availability of Hby also provides a route to the synthesis of transition metal analogs of B12

The intermolecular anthracene-transfer in a regiospecific antipodal C60 difunctionalization

We analyze the mechanism of the topochemically controlled difunctionalization of C60 and anthracene, where an anthracene molecule is transferred from one C60 monoadduct to another one under exclusive formation of equal amounts of C60 and the difficult to make antipodal C60 bisadduct. Our herein disclosed dispersion corrected DFT studies show the anthracene transfer to take place in a synchronous retro Diels-Alder/Diels-Alder reaction: an anthracene molecule dissociates from one fullerene under formation of an intermediate, while already undergoing stabilizing interactions with both neighboring fullerenes, facilitating the reaction kinetically. In the intermediate, a planar anthracene molecule is sandwiched between two neighboring fullerenes and forms equally strong "double-decker" type pi-pi stacking interactions with both of these fullerenes. Analysis with the distorsion interaction model shows that the anthracene unit of the intermediate is almost planar with minimal distorsions. This analysis sheds light on the existence of noncovalent interactions engaging both faces of a planar polyunsaturated ring and two convex fullerene surfaces in an unprecedented \u27inverted sandwich\u27 structure. Hence, it sheds light on new strategies to design functional fullerene based materials.<br /

Effects of Elevated beta-Estradiol Levels on the Functional Morphology of the Testis - New Insights

Elevated estradiol levels are correlated with male infertility. Causes of hyperestrogenism include diseases of the adrenal cortex, testis or medications affecting the hypothalamus-pituitary-gonadal axis. The aim of our study was to elucidate the effects of estradiol treatment on testicular cellular morphology and function, with reference to the treatment regimen received. Testes samples (n = 9) were obtained post-orchiectomy from male-to-female transsexuals within the age range of 26–52 years. Each patient had a minimum of 1–6 years estradiol treatment. For comparison, additional samples were obtained from microscopically unaltered testicular tissue surrounding tumors (n = 7). The tissues obtained were investigated by stereomicroscopy, histochemistry, scanning electron microscopy (SEM) and immunohistochemistry. Our studies revealed that estradiol treatment significantly decreased the diameter of the seminiferous tubules (p < 0.05) and induced fatty degeneration in the surrounding connective tissue. An increase in collagen fiber synthesis in the extracellular matrix (ECM) surrounding the seminiferous tubules was also induced. Spermatogenesis was impaired resulting in mainly spermatogonia being present. Sertoli cells revealed diminished expression of estrogen receptor alpha (ERα). Both Sertoli and Leydig cells showed morphological alterations and glycoprotein accumulations. These results demonstrate that increased estradiol levels drastically impact the human testis

Can surgical reconstruction of vaginal and ligamentous laxity cure overactive bladder symptoms in women with pelvic organ prolapse?

Objective: To examine the extent and intensity of the coexistence of overactive bladder (OAB) symptoms in women with pelvic organ prolapse (POP) and to evaluate the likelihood of OAB symptom improvement after surgical POP reconstruction over a period of 2 years. Patients and Methods: The effectiveness of the transvaginal, single-incision 'Elevate' technique for anatomical cure of anterior/apical and posterior/apical vaginal prolapse has been previously reported in a prospective, multicentre study. This technique uses mesh arms attached to the sacrospinous ligaments to recreate apical ligamentous support. Using the same sample population as that used in the multicentre study (n = 281), we conducted the present sub-analysis focusing on estimating the extent of comorbidity between POP and OAB symptoms, as well as the effects of subsequent pelvic floor reconstruction on OAB symptoms over a long period. Assessments of POP and OAB symptom severity before and after surgery at 6, 12 and 24 months were obtained using the Pelvic Floor Distress Inventory (PFDI) questionnaire. Results: Preoperatively, 70% of all POP patients reported moderate to severe OAB symptoms, with almost half (49.5%) noting severe OAB bother ('quite a bit bothersome') for one or more of the classic OAB symptom domains on the PFDI: 'daytime urinary frequency'; 'urinary urgency'; 'urinary urgency incontinence'; and/or 'nocturia'. In fact, across all four OAB symptom domains evaluated, there were significantly more severe symptoms ('quite a bit bothersome') than moderate ('moderately bothersome') or mild ('somewhat bothersome'): 26-31%, 13-21%, and 17-19% of patients, respectively. In patients with symptomatic POP >stage 2, there was no relationship between further degree of prolapse and presence of severity of OAB symptoms; however, patients with POP stage 2 had significantly more complaints regarding the items 'daytime urinary frequency' and 'urinary urgency incontinence' compared with those with stage 3-4 POP. Pelvic floor reconstructive surgery resulted in significant improvement in all OAB symptoms, which seemed to be stable over time. The cure rate of moderate-to-severe OAB complaints ranged between 60% and 80%, which was a durable improvement noted throughout 24 months. Conclusion: Results showed that POP was to a high degree accompanied by moderate-to-severe OAB complaints. Significant long-lasting improvements in bothersome OAB symptoms occurred after adequate surgical reconstruction of anterior/apical and posterior/apical vaginal support

The impact of sacrospinous ligament fixation on pre-existing nocturia and co-existing pelvic floor dysfunction symptoms

Introduction and hypothesis: To evaluate whether nocturia and coexisting pelvic floor symptoms in women with pelvic organ prolapse (POP) can be improved by ligamentous fixation of apical vaginal prolapse to the sacrospinous ligament. Methods: We evaluated the PROPEL study data from 281 women with pelvic organ prolapse stage > 2. Bothersome nocturia and coexisting pelvic floor symptoms were assessed with the Pelvic Floor Disorder Inventory (PFDI) questionnaire preoperatively and at 6, 12 and 24 months after successful vaginal prolapse repair. Women with successful reconstruction (POP-Q stage < 1 at all compartments throughout the 2-year follow-up), defined as anatomical “responders,” were compared to the anatomical “non-responders.” Results: Among the patients completing all PFDI questions (N = 277), anatomical responders and non-responders were the groups of interest for our analysis. We found the occurrence rates of “moderate” or “quite a bit” of nocturia was significantly reduced after surgery in all subgroups (48.7% at baseline vs. 19.5% after 24 months). The occurrence of nocturia was halved for responders compared to non-responders (45.4% and 48.3% at baseline vs. 14% and 29.5% after 24 months). Anatomical non-responders still had a relevant improvement of POP-Q stages, especially in the apical compartment. Prevalence rates of co-existing over- and underactive bladder, fecal incontinence, defecation disorders and pain symptoms were also significantly reduced postoperatively. Conclusion: Nocturia can be associated with symptomatic POP, with improvements seen following vaginal ligamentous prolapse repair. We caution providers, however, when advising patients of the possible resolution of nocturia following POP reconstruction, that all other traditional etiologies of nocturia must first be ruled out