Spectral signatures of mirror movements in the sensori-motor connectivity in kallmann syndrome.

Mirror movements (MM) might be observed in congenital and acquired neurodegenerative conditions but their anatomic-functional underpinnings are still largely elusive. This study investigated the spectral changes of resting-state functional connectivity in Kallmann Syndrome (hypogonadotropic hypogonadism with hypo/anosmia with or without congenital MM) searching for insights into the phenomenon of MM. Forty-four Kallmann syndrome patients (21 with MM) and 24 healthy control subjects underwent task (finger tapping) and resting-state functional MRI. The spatial pattern of task-related activations was used to mask regions and select putative motor networks in a spatially independent component analysis of resting-state signals. For each resting-state independent component time-course power spectrum, we extracted the relative contribution of four separate bands: slow-5 (0.01-0.027 Hz), slow-4 (0.027-0.073 Hz), slow-3 (0.073-0.198 Hz), slow-2 (0.198-0.25 Hz), and analyzed the variance between groups. For the sensorimotor network, the analysis revealed a significant group by frequency interaction (P = 0.002) pointing to a frequency shift in the spectral content among subgroups with lower slow-5 band and higher slow-3 band contribution in Kallmann patients with MM versus controls (P = 0.028) and with lower slow-5 band contribution between patients with and without MM (P = 0.057). In specific regions, as obtained from hand motor activation task analysis, spectral analyses demonstrated a lower slow-5 band contribution in Kallmann patients with MM versus both controls and patients without MM (P < 0.05). In Kallmann syndrome, the peculiar phenomenon of bimanual synkinesis is associated at rest with regionally and spectrally selective functional connectivity changes pointing to a distinctive cortical and subcortical functional reorganization. Hum Brain Mapp 39:42-53, 2018. © 2017 Wiley Periodicals, Inc.

Sniffin' Sticks and olfactory system imaging in patients with Kallmann syndrome.

BACKGROUND: The relationship between olfactory function, rhinencephalon and forebrain changes in Kallmann syndrome (KS) have not been adequately investigated. We evaluated a large cohort of male KS patients using Sniffin' Sticks and MRI in order to study olfactory bulb (OB) volume, olfactory sulcus (OS) depth, cortical thickness close to the OS, and olfactory phenotype. METHODS: Olfaction was assessed administering Sniffin' Sticks®, in 38 KS patients and 17 controls (by means of Screening 12 test®). All subjects underwent magnetic resonance imaging (MRI) to study OB volume, sulcus depth, and cortical thickness. RESULTS: Compared to controls, KS patients showed smaller OB volume (p<0.0001), reduced sulcus depth (p<0.0001), and thicker cortex in the region close to the OS (p<0.0001). Anosmic KS patients had smaller OB than controls and hyposmic KS patients; there was no difference between hyposmic KS patients and controls. OB volume correlated with Sniffin' Sticks score (r = 0.64; p < 0.001), OS depth (p<0.0001) and, inversely, with cortical thickness changes (p<0.0001). Sniffin' Sticks showed an inverse correlation with cortical thickness (r = -0.5; p<0.0001) and a trend toward a statistically significant correlation with OS depth. CONCLUSION: The present study provides further evidence of the strict relationship between olfaction and OB volume. The strong correlation between OB volume and the overlying cortical changes highlights the key role of rhinencephalon in forebrain embryogenesis.

Effect of various commercial buffers on sperm viability and capacitation.

A wide variety of sperm preparation protocols are currently available for assisted conception. They include density gradient separation and washing methods. Both aim at isolating and capacitating as much motile sperm as possible for subsequent oocyte fertilization. The aim of this study was to examine the effects of four commercial sperm washing buffers on sperm viability and capacitation. Semen samples from 48 healthy donors (normal values of sperm count, motility, morphology, and volume) were analyzed. After separation (density gradient 40/80%), sperm were incubated in various buffers then analysed for reactive oxygen species (ROS) production, viability, tyrosine phosphorylation (Tyr-P), cholera toxin B subunit (CTB) labeling, and the acrosome reaction (AR). The buffers affected ROS generation in various ways resulting either in rapid cell degeneration (when the amount of ROS was too high for cell survival) or the inability of the cells to maintain correct functioning (when ROS were too few). Only when the correct ROS generation curve was maintained, suitable membrane reorganization, evidenced by CTB labeling was achieved, leading to the highest percentages of both Tyr-P- and acrosome-reacted-cells. Distinguishing each particular pathological state of the sperm sample would be helpful to select the preferred buffer treatment since both ROS production and membrane reorganization can be significantly altered by commercial buffers.

Effect of astaxanthin on human sperm capacitation.

In order to be able to fertilize oocytes, human sperm must undergo a series of morphological and structural alterations, known as capacitation. It has been shown that the production of endogenous sperm reactive oxygen species (ROS) plays a key role in causing cells to undergo a massive acrosome reaction (AR). Astaxanthin (Asta), a photo-protective red pigment belonging to the carotenoid family, is recognized as having anti-oxidant, anti-cancer, anti-diabetic and anti-inflammatory properties and is present in many dietary supplements. This study evaluates the effect of Asta in a capacitating buffer which induces low ROS production and low percentages of acrosome-reacted cells (ARC). Sperm cells were incubated in the presence or absence of increasing concentrations of Asta or diamide (Diam) and analyzed for their ROS production, Tyr-phosphorylation (Tyr-P) pattern and percentages of ARC and non-viable cells (NVC). Results show that Asta ameliorated both sperm head Tyr-P and ARC values without affecting the ROS generation curve, whereas Diam succeeded in enhancing the Tyr-P level but only of the flagellum without increasing ARC values. It is suggested that Asta can be inserted in the membrane and therefore create capacitation-like membrane alteration which allow Tyr-P of the head. Once this has occurred, AR can take place and involves a higher numbers of cells.

Effects of tadalafil on platelets and endothelium in patients with erectile dysfunction and cardiovascular risk factors: a pilot study.

Activation of endothelial cells and platelets is an initial step toward the development of cardiovascular disease. Erectile dysfunction (ED) may be an early manifestation of endotheliopathy. We evaluated the effects of tadalafil on cyclic nucleotides (cGMP and cAMP) and soluble adhesion molecules (E- and P-selectin [ES and PS]). The patients were divided into 2 groups on the basis of the presence (10 patients) or absence (9 patients) of cardiovascular risk factors (dyslipidemia, hypertension, and smoking). Nitric oxide (NO) was unmeasurable in all the patients. Tadalafil administration induced a significant increase in cGMP levels in both groups (P < .01). In contrast, cAMP significantly increased (P < .05) and PS decreased (P < .01) only in patients without cardiovascular risk factors. Tadalafil induced a beneficial effect on platelet activation in patients with ED without cardiovascular risk factors; this effect was not mediated by NO.

Effects of extracellular adenosine 5'-triphosphate on human sperm motility.

Extracellular adenosine 5'-triphosphate (ATP) previously has been shown to increase the fertilization percentage in human in vitro fertilization (IVF) performed for male factor infertility. The objective of this study is to determine the effects of extracellular adenosine 5'-triphosphate (ATPe) on human sperm function by examining its effects on end points of sperm capacitation. Sperm obtained from healthy volunteers with normal semen parameters, asthenozoospermic men, and cryopreserved samples were incubated in medium with or without 2.5 mM ATPe. The effects of ATPe on acrosomal exocytosis, protein tyrosine phosphorylation, and sperm motility parameters were quantified. Although ATPe did not affect acrosomal exocytosis or protein tyrosine phosphorylation in sperm from healthy donors, it significantly altered several motility parameters, with the largest effects manifested in increased curvilinear velocity and percentage hyperactivation. ATPe similarly affected sperm selected for poor motility and thawed cryopreserved sperm but to a lesser extent than its effects on sperm with normal motility. ATPe increased straight-line velocity and linearity of sperm obtained from asthenozoospermic men. Human sperm motility characteristics are altered by ATPe; this finding may explain its previously reported beneficial effect on human IVF. These results suggest that ATPe could constitute a new therapeutic modality in the treatment of male infertility.

Treatment of polycystic ovary syndrome with spironolactone plus licorice.

OBJECTIVE: The aim of the study was to compare the effect of spironolactone (antagonist of mineralocorticoid and androgen receptors) versus spironolactone plus licorice (agonist of mineralocorticoid receptors and mild inhibitor of androgen synthesis) on plasma renin activity, aldosterone and androgen levels in women with polycystic ovary syndrome (PCOS). STUDY DESIGN: Thirty-two women with PCOS were divided into two groups: 16 received 100 mg spironolactone and 16 spironolactone plus 3.5 g of licorice a day. Blood pressure, body mass index, serum electrolytes, plasma renin activity, plasma aldosterone and cortisol, serum testosterone, and urinary tetrahydrocortisol/tetrahydrocortisone ratio were measured before and during treatment. RESULTS: Mean blood pressure was significantly reduced during spironolactone treatment, while it was unchanged in women receiving spironolactone plus licorice. Twenty percent of women treated with spironolactone and none treated with the addition of licorice complained of symptoms related to volume depletion. Consistently, the activation of the renin-aldosterone system was significantly lower during spironolactone plus licorice than with spironolactone alone. The prevalence of metrorrhagia was lower in the combined therapy. CONCLUSIONS: In patients with PCOS the mineralocorticoid properties of licorice can reduce the prevalence of side effects related to the diuretic activity of spironolactone.

Identification of the mineralocorticoid receptor in human spermatozoa.

Aldosterone seems to play a role in the regulation of the electrolyte content of sperm and in the motility of spermatozoa. The aim of the study was to evaluate the presence of the mineralocorticoid receptor (MR) in human ejaculated spermatozoa. We have assayed MR on spermatozoa of freshly ejaculated sperm from healthy donors. The identification of MR was made by using immunohistochemistry and immunofluorescence analyses, while MR mRNA expression was evaluated by real-time PCR assay. The immunohistochemical and immunofluorescence analyses showed positive staining both in the midpiece and in the tail of the spermatozoa. Relative quantification of MR by using real-time PCR shows that the mRNA expression of MR in spermatozoa is lower than in mononuclear leukocytes (positive controls). Sequencing showed complete identity between the sequence obtained from spermatozoa and the human MR cDNA sequence. Further studies should be performed in order to elucidate a possible physiological role of aldosterone in regulating electrolyte concentration, and the pro-oxidant effect of excess aldosterone in this new target tissue.

Licorice reduces serum testosterone in healthy women.

UNLABELLED: Licorice has been considered a medicinal plant for thousands of years. The most common side effect is hypokalemic hypertension, which is secondary to a block of 11beta-hydroxysteroid dehydrogenase type 2 at the level of the kidney, leading to an enhanced mineralocorticoid effect of cortisol. We have investigated the effect of licorice on androgen metabolism in nine healthy women 22-26 years old, in the luteal phase of the cycle. They were given 3.5 g of a commercial preparation of licorice (containing 7.6% W.W. of glycyrrhizic acid) daily for two cycles. They were not on any other treatment. Plasma renin activity, serum adrenal and gonadal androgens, aldosterone, and cortisol were measured by radioimmunoassay. Total serum testosterone decreased from 27.8+/-8.2 to 19.0+/-9.4 in the first month and to 17.5+/-6.4 ng/dL in the second month of therapy (p<0.05). It returned to pre-treatment levels after discontinuation. Androstenedione, 17OH-progesterone, and LH levels did not change significantly during treatment. Plasma renin activity and aldosterone were depressed during therapy, while blood pressure and cortisol remained unchanged. CONCLUSIONS: Licorice can reduce serum testosterone probably due to the block of 17-hydroxysteroid dehydrogenase and 17-20 lyase. Licorice could be considered an adjuvant therapy of hirsutism and polycystic ovary syndrome.