Screening of endocrine organ-specific humoral autoimmunity in 47,XXY Klinefelter's syndrome reveals a significant increase in diabetes-specific immunoreactivity in comparison with healthy control men.

The aim of this study was to evaluate the frequency of humoral endocrine organ-specific autoimmunity in 47,XXY Klinefelter’s syndrome (KS) by investigating the autoantibody profile specific to type 1 diabetes (T1DM), Addison’s disease (AD), Hashimoto thyroiditis (HT), and autoimmune chronic atrophic gastritis (AG). Sixty-one adult Caucasian 47,XXY KS patients were tested for autoantibodies specific to T1DM (Insulin Abs, GAD Abs, IA-2 Abs, Znt8 Abs), HT (TPO Abs), AD (21-OH Abs), and AG (APC Abs). Thirty-five of these patients were not undergoing testosterone replacement therapy TRT (Group 1) and the remaining 26 patients started TRT before the beginning of the study (Group 2). KS autoantibody frequencies were compared to those found in 122 control men. Six of 61 KS patients (9.8 %) were positive for at least one endocrine autoantibody, compared to 6.5 % of controls. Interestingly, KS endocrine immunoreactivity was directed primarily against diabetes-specific autoantigens (8.2 %), with a significantly higher frequency than in controls (p = 0.016). Two KS patients (3.3 %) were TPO Ab positive, whereas no patients were positive for AD- and AG-related autoantigens. The autoantibody endocrine profile of untreated and treated KS patients was not significantly different. Our findings demonstrate for the first time that endocrine humoral immunoreactivity is not rare in KS patients and that it is more frequently directed against type 1 diabetes-related autoantigens, thus suggesting the importance of screening for organ-specific autoimmunity in clinical practice. Follow-up studies are needed to establish if autoantibody-positive KS patients will develop clinical T1D

Immunoglobulins in Human Seminal Plasma

Single radial immunodiffusion has been used to evaluate immunoglobulins and secretory piece (SP) in human seminal plasma. Samples were collected from 90 healthy volunteers, 202 subjects submitted to vasectomy for contraceptive purposes, tested at various intervals after surgery, and 725 patients grouped according to selected andrological disorders. Results may be summarized as follows. In normal subjects IgG and IgA were constantly present (mean values +/- SD: 8.14 +/- 2.82 mg/dl; 1.91 +/- 1.03 mg/dl, respectively) while IgM were detected in trace amounts (from 0.7 to 3.3 mg/dl) in 10% of subjects, and negligible or absent in the remaining subjects. In vasectomized subjects IgG and IgA showed a significant increase only in the first 3 months after vasectomy, probably due to surgery. In andrological patients Ig showed an increase in cases with antisperm antibodies (A b) and in those with infections of genital tract and positive semen culture. On the basis of these findings and the secretory piece assay data the importance appears to be stressed of the local immunocompetent system at least in some andrological diseases

Structural variants of chromosome 9: a possibile association with hypogonadotropic hypogonadism

We report two cases of structural variations of chromosome 9 associated with hypogonadotropic hypogonadism and azoospermia in adolescent boys. One patient also had a partially imperforated urethral meatus. Histological examination revealed that both had hypotrophic and underdeveloped testes. There was no LH and FSH response to LH-RH stimulation nor was there any response to naloxone tests. Basal and HCG stimulated plasma testosterone values were below normal prepubertal levels. As the administration of gonadotrophins did not improve the clinical and hormonal findings, alternative androgen therapy was necessary to achieve secondary sexual characteristics. Although they reached a good level of androgenization, their testes were still very small and azoospermia remained, as confirmed by repeated semen analyses. A possible association between chromosome 9 polymorphisms and hypothalamo-pituitary axis abnormalities is suggested. It is hypothesized that structural variants of chromosome 9 are not unrelated occurrences. Furthermore, and in view of the fact that they can lead to a high risk of azoospermia and infertility, such variants call for clinical investigatio

Gram staining applied to Human spermatozoa: a simple method for studyng chromatin condensation status

Gram staining applied to human spermatozoa from fertile donors is described. The stain revealed populations of Gram-positive and Gram-negative spermatozoa. Data showed a significant and progressive decrease in the percentage of Gram-positive spermatozoa at different times during the chromatin decondensation procedure (SDS-BSA and SDS-EDTA). No significant correlation could be found between Gram staining and other functional tests used for spermatozoa; only the aniline blue staining test showed a poor correlation. Our study demonstrates that normal spermatozoa with regular chromatin condensation appear Gram-positive, while spermatozoa with altered chromatin condensation appear Gram-negative

the tempio della consolazione in todi integrated geomatictechniques for a monument description including structuraldamage evolution in time

The Tempio della Consolazione in Todi (16th cent.) has always been one of the most significant symbols of the Umbrian landscape. Since the first times after its completion (1606) the structure has exhibited evidences of instability, due to foundation subsiding and/or seismic activity. Structural and geotechnical countermeasures have been undertaken on the Tempio and its surroundings from the 17th century until recent times. Until now a truly satisfactory analysis of the overall deformation and attitude of the building has not been performed, since the existing surveys record the overhangs of the pillars, the crack pattern or the subsidence over limited time spans. Describing the attitude of the whole church is in fact a complex operation due to the architectural character of the building, consisting of four apses (three polygonal and one semicircular) covered with half domes, which surround the central area with the large dome. The present research aims to fill the gap of knowledge with a global study based on geomatic techniques for an accurate 3D reconstruction of geometry and attitude, integrated with a historical research on damage and interventions and a geotechnical analysis. The geomatic survey results from the integration of different techniques: GPS-GNSS for global georeferencing, laser scanning and digital photogrammetry for an accurate 3D reconstruction, high precision total station and geometric leveling for a direct survey of deformations and cracks, and for the alignment of the laser scans. The above analysis allowed to assess the dynamics of the cracks occurred in the last 25 years by a comparison with a previous survey. From the photographic colour associated to the point cloud was also possible to map the damp patches showing on the domes intrados, mapping their evolution over the last years

Methylene blue MMX® tablets for chromoendoscopy. Bioavailability, colon staining and safety in healthy volunteers undergoing a full colonoscopy.

Abstract Methylene blue-MMX® tablets are proposed as an aid for detection and visualisation of adenomas and carcinomas in patients undergoing colonoscopy, by improving their detection rate and highlighting the presence of the intestinal dysplastic lesions. Single total doses of 100 and 200 mg were administered to healthy volunteers undergoing a bowel cleansing preparation and a full colonoscopy to investigate the colonic staining. The pharmacokinetics of methylene blue and the safety after exposure to the tablets were also investigated. With 200 mg, the best staining, assessed as the sum of acceptable and good staining, was achieved in the ascending colon and rectosigmoid (75% subjects each), the transverse and the descending colon (approximately 63% each). Absence of staining or overstaining were reported for no colonic region of interest in any subject. Similar results were observed in the 100 mg dose group. Methylene blue blood concentrations reached a peak (Cmax) in a median time (Tmax) of 12 h with 100 mg and 16 h with 200 mg. AUC0-t was 10.7 ± 6.7 μg/mLxh after 100 mg and 25.2 ± 7.4 μg/mLxh after 200 mg. Half-life ranged between 9 and 22 h after the lower dose and between 6 and 26 h after the higher dose. The cumulative urinary excretion was about 28% after 100 mg and about 39% after 200 mg up to 60 h post-dose. The overall frequency of adverse events after single dose of the test product administered along with a bowel cleansing preparation was 39%, but only one was related to the test product: abnormal transaminases. The most frequent adverse event was a transient polyuria (17%). One serious adverse event (gastrointestinal haemorrhage) led the subject to study discontinuation and hospitalisation and another subject withdrew the study due to one adverse event (haematemesis). Either event was not related to methylene blue

Hypothalamo-pituitary axis and puberty

Puberty is a complex process that culminates in the acquisition of psychophysical maturity and reproductive capacity. This elaborate and fascinating process marks the end of childhood. Behind it lies a complex, genetically mediated neuroendocrine mechanism through which the gonads are activated thanks to the fine balance between central inhibitory and stimulating neuromodulators and hormones with both central and peripheral action. The onset of puberty involves the reactivation of the hypothalamic-pituitary-gonadal (HPG) axis, supported by the initial “kiss” between kisspeptin and the hypothalamic neurons that secrete GnRH (the GnRH “pulse generator”). This pulsatile production of GnRH is followed by a rise in LH and, consequently, in gonadal steroids. The onset of puberty varies naturally between individuals, and especially between males and females, in the latter of whom it is typically earlier. However, pathological variations, namely precocious and delayed puberty, are also possible. This article reviews the scientific literature on the physiological mechanisms of puberty and the main pathophysiological aspects of its onset