Alterations of gut microbiota composition in post-finasteride patients: a pilot study.

PURPOSE: Post-finasteride syndrome (PFS) has been reported in a subset of patients treated with finasteride (an inhibitor of the enzyme 5alpha-reductase) for androgenetic alopecia. These patients showed, despite the suspension of the treatment, a variety of persistent symptoms, like sexual dysfunction and cognitive and psychological disorders, including depression. A growing body of literature highlights the relevance of the gut microbiota-brain axis in human health and disease. For instance, alterations in gut microbiota composition have been reported in patients with major depressive disorder. Therefore, we have here analyzed the gut microbiota composition in PFS patients in comparison with a healthy cohort. METHODS: Fecal microbiota of 23 PFS patients was analyzed by 16S rRNA gene sequencing and compared with that reported in ten healthy male subjects. RESULTS: Sexual dysfunction, psychological and cognitive complaints, muscular problems, and physical alterations symptoms were reported in more than half of the PFS patients at the moment of sample collection. The quality sequence check revealed a low library depth for two fecal samples. Therefore, the gut microbiota analyses were conducted on 21 patients. The α-diversity was significantly lower in PFS group, showing a reduction of richness and diversity of gut microbiota structure. Moreover, when visualizing ß-diversity, a clustering effect was found in the gut microbiota of a subset of PFS subjects, which was also characterized by a reduction in Faecalibacterium spp. and Ruminococcaceae UCG-005, while Alloprevotella and Odoribacter spp were increased compared to healthy control. CONCLUSION: Gut microbiota population is altered in PFS patients, suggesting that it might represent a diagnostic marker and a possible therapeutic target for this syndrome.

Steroidogenic machinery in the adult rat colon.

Gastrointestinal function is known to be regulated by steroid molecules produced by the gonads, the adrenal glands and the gut microbiota. However, we have a limited knowledge on the functional significance of local steroid production by gastrointestinal tract tissue. On this basis, we have here evaluated, as a first methodological approach, the expression of steroidogenic molecules and the local levels of key steroids in the male rat colon. Our findings indicate that the colon tissue expresses molecules involved in the early steps of steroidogenesis and in the consecutive synthesis and metabolism of steroid hormones, such as progesterone, testosterone and 17ß-estradiol. In addition, the levels of the steroid hormone precursor pregnenolone and the levels of active metabolites of progesterone and testosterone, such as dihydroprogesterone, tetrahydroprogesterone, dihydrotestosterone and 17ß-estradiol, were higher in colon than in plasma. Higher levels of the androgen metabolite 3α-diol were detected in the colon in comparison with another non-classical steroidogenic tissue, such as the cerebral cortex. These findings suggest the existence of local steroid synthesis and metabolism in the colon, with the production of active steroid metabolites that may impact on the activity of the enteric nervous system and on the composition of the gut microbiota.

Sex dimorphism in an animal model of multiple sclerosis: Focus on pregnenolone synthesis.

Neuroactive steroids, molecules produced from cholesterol in steroidogenic cells (i.e., peripheral glands and nervous system) are physiological modulators and protective agents of nervous function. A possible role for neuroactive steroids in the sex-dimorphic clinical manifestation, onset and progression of Multiple Sclerosis (MS) has been recently suggested. To explore this possibility, we assessed the synthesis of the first steroidogenic product (pregnenolone; PREG) in the spinal cord of experimental autoimmune encephalomyelitis rats, a MS model. Data obtained indicate that the synthesis of PREG in the spinal cord is altered by the pathology in a sex-dimorphic way and depending on the pathological progression. Indeed, in male spinal cord the synthesis was already decreased at the acute phase of the disease (i.e., 14 days post induction - dpi) and maintained low during the chronic phase (i.e., 45 dpi), while in females this effect was observed only at the chronic phase. Substrate availability had also a role in the sex-dimorphic kinetics. Indeed, at the chronic phase, male animals showed a reduction in the levels of free cholesterol coupled to alteration of cholesterol metabolism into oxysterols; these effects were not observed in female animals. These findings suggest that the comprehension of the neurosteroidogenic processes could be relevant to better understand the sexual dimorphism of MS and to possibly design sex-oriented therapeutic strategies based on neuroactive steroids.

Sensing the quantum behaviour of magnetic nanoparticles by electron magnetic resonance.

We have investigated Magnetic Nanoparticles (MNPs) of spinel type iron oxide (of approximately 8 nm) mineralized in the internal cavity of the bioreactor ferritin nanocage. In particular, we have used Electron Magnetic Resonance, EMR, spectroscopy and taken advantage of the capacity of the protein shells to control the size of the MNPs. EMR measurements in perpendicular and parallel configurations have been recorded at various temperatures. A model based on the giant spin is used to interpret the experimental results. The analysis indicates that the observed quantum behaviour has to be ascribed to the whole MNP and that the thermal population of excited spin states has a strong influence in the EMR behaviour of MNPs.

Gene variants associated to malignant thyroid disease in familial adenomatous polyposis: a novel APC germline mutation.

BACKGROUND AND AIM: Familial adenomatous polyposis (FAP) is an autosomal inherited syndrome characterized by hundreds to thousands colorectal adenomatous polyps with oncological transformation lifetime risk of 100%. FAP is mainly associated with mutations in APC (autosomal dominant inheritance) or MUTYH (autosomal recessive inheritance) genes. Affected individuals are at increased risk of developing extra-intestinal tumors. Lifetime risk of developing thyroid carcinoma has been described in previous reports of about 2-12%, mainly in females, and the mean age is below 30 yr. About 95% of cancers are papillary thyroid carcinomas (PTC), mostly multifocal. The aim of this study was to evaluate the frequency of PTC among our series of FAP patients and to assess the type of gene mutation associated with the disease. METHODS: Fifty-four subjects from 36 FAP families were selected (29 females/25 males) and the mean age (±SD) at diagnosis was 28.8±10.8 yr. All patients underwent blood examination for thyroid hormones and antibodies, germline mutational analysis of APC and/or MUTYH genes, thyroid ultrasound, and endocrinological evaluation. RESULTS: In 13/54 (24.1%) subjects, an eumetabolic thyroid disease was found: plurinodular disease in 7/54 (13.0%); single nodule in 4/54 (7.4%); in 2/54 patients (3.7%), we found a malignant nodule characterized after total thyroidectomy as a classical PTC. Both patients were female and showed a classic FAP phenotype. Mutational analysis revealed in the first patient the APC germline mutation 3183_87del ACAAA and in the second patient the del9-10 (del9080dup11) novel APC variant; the first mutation has been already reported in association with PTC; to our knowledge the second mutation has never been previously reported in association with FAP. CONCLUSIONS: In the population examined, the estimated prevalence of thyroid malignant diseases was 3.7%. In both patients, the identified APC gene pathogenetic variants mapped within the 5' region of the gene, previously reported as a PTC-associated mutational hot spot. Both patients had classic FAP phenotype and genetic analysis revealed two pathogenetic APC mutations: c.3183_87delACAAA, a recurrent pathogenetic variant and del9-10 (del9080dup11), a novel, not previously described genomic rearrangement. In agreement with previous studies, the morpho-functional surveillance of thyroid in FAP series should be recommended. A better insight into the overall genotype-phenotype correlation of APC gene mutations would be helpful for the identification of at-risk individuals.