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2. Analysis of the finasteride treatment and its withdrawal in the rat hypothalamus and hippocampus at whole-transcriptome level

Author

Giatti, S, Cioffi, L, Diviccaro, S, Piazza, R, Melcangi, R, Giatti S., Cioffi L., Diviccaro S., Piazza R., Melcangi R. C., Giatti, S, Cioffi, L, Diviccaro, S, Piazza, R, Melcangi, R, Giatti S., Cioffi L., Diviccaro S., Piazza R., and Melcangi R. C.

Abstract

Purpose: As reported in patients treated for androgenetic alopecia with finasteride (i.e., a blocker of the enzyme 5 alpha-reductase) and in an animal model, side effects affecting sexual, psychiatric, neurological, and physical domains, may occur during the treatment and persist with drug suspension. The etiopathogenesis of these side effects has been poorly explored. Therefore, we performed a genome-wide analysis of finasteride effects in the brain of adult male rat. Methods: Animals were treated (i.e., for 20 days) with finasteride (1mg/rat/day). 24 h after the last treatment and 1 month after drug suspension, RNA sequencing analysis was performed in hypothalamus and hippocampus. Data were analyzed by differential expression analysis and Gene-Set Enrichment Analyses (GSEA). Results: Data obtained after finasteride treatment showed that 186 genes (i.e., 171 up- and 15 downregulated) and 19 (i.e., 17 up- and 2 downregulated) were differentially expressed in the hypothalamus and hippocampus, respectively. Differential expression analysis at the drug withdrawal failed to identify dysregulated genes. Several gene-sets were enriched in these brain areas at both time points. Conclusion: Some of the genes reported to be differentially expressed (i.e., TTR, DIO2, CLDN1, CLDN2, SLC4A5, KCNE2, CROT, HCRT, MARCKSL1, VGF, IRF2BPL) and GSEA, suggest a potential link with specific side effects previously observed in patients and in the animal model, such as depression, anxiety, disturbance in memory and attention, and sleep disturbance. These data may provide an important background for future experiments aimed at confirming the pathological role of these genes.

Published
2024

3. Neuroactive Steroid–Gut Microbiota Interaction in T2DM Diabetic Encephalopathy

Author

Diviccaro, S, Cioffi, L, Piazza, R, Caruso, D, Melcangi, R, Giatti, S, Diviccaro S., Cioffi L., Piazza R., Caruso D., Melcangi R. C., Giatti S., Diviccaro, S, Cioffi, L, Piazza, R, Caruso, D, Melcangi, R, Giatti, S, Diviccaro S., Cioffi L., Piazza R., Caruso D., Melcangi R. C., and Giatti S.

Abstract

The pathological consequences of type 2 diabetes mellitus (T2DM) also involve the central nervous system; indeed, T2DM patients suffer from learning and memory disabilities with a higher risk of developing dementia. Although several factors have been proposed as possible contributors, how neuroactive steroids and the gut microbiome impact brain pathophysiology in T2DM remain unexplored. On this basis, in male Zucker diabetic fatty (ZDF) rats, we studied whether T2DM alters memory abilities using the novel object recognition test, neuroactive steroid levels by liquid chromatography–tandem mass spectrometry, hippocampal parameters using molecular assessments, and gut microbiome composition using 16S next-generation sequencing. Results obtained reveal that T2DM worsens memory abilities and that these are correlated with increased levels of corticosterone in plasma and with a decrease in allopregnanolone in the hippocampus, where neuroinflammation, oxidative stress, and mitochondrial dysfunction were reported. Interestingly, our analysis highlighted a small group of taxa strictly related to both memory impairment and neuroactive steroid levels. Overall, the data underline an interesting role for allopregnanolone and microbiota that may represent candidates for the development of therapeutic strategies.

Published
2023

4. Paroxetine effects in adult male rat colon: Focus on gut steroidogenesis and microbiota

Author

Diviccaro, S, Giatti, S, Cioffi, L, Falvo, E, Piazza, R, Caruso, D, Melcangi, R, Diviccaro S., Giatti S., Cioffi L., Falvo E., Piazza R., Caruso D., Melcangi R. C., Diviccaro, S, Giatti, S, Cioffi, L, Falvo, E, Piazza, R, Caruso, D, Melcangi, R, Diviccaro S., Giatti S., Cioffi L., Falvo E., Piazza R., Caruso D., and Melcangi R. C.

Abstract

Paroxetine, a selective serotonin reuptake inhibitor (SSRI), is prescribed to treat psychiatric disorders, although an off-label SSRI use is also for functional gastrointestinal disorders. The mutual correlation between serotonin and peripheral sex steroids has been reported, however little attention to sex steroids synthesized by gut, has been given so far. Indeed, whether SSRIs, may also influence the gut steroid production, immediately after treatment and/or after suspension, is still unclear. The finding that gut possesses steroidogenic capability is of particular relevance, also for the existence of the gut-microbiota-brain axis, where gut microbiota represents a key orchestrator. On this basis, adult male rats were treated daily for two weeks with paroxetine or vehicle and, 24 h after treatment and at 1 month of withdrawal, steroid environment and gut microbiota were evaluated. Results obtained reveal that paroxetine significantly affects steroid levels, only in the colon but not in plasma. In particular, steroid modifications observed immediately after treatment are not overlap with those detected at withdrawal. Additionally, paroxetine treatment and its withdrawal impact gut microbiota populations differently. Altogether, these results suggest a biphasic effect of the drug treatment in the gut both on steroidogenesis and microbiota.

Published
2022

5. Gut microbiota composition is altered in a preclinical model of type 1 diabetes mellitus: Influence on gut steroids, permeability, and cognitive abilities

Author

Diviccaro, S, Falvo, E, Piazza, R, Cioffi, L, Herian, M, Brivio, P, Calabrese, F, Giatti, S, Caruso, D, Melcangi, R, Diviccaro, Silvia, Falvo, Eva, Piazza, Rocco, Cioffi, Lucia, Herian, Monika, Brivio, Paola, Calabrese, Francesca, Giatti, Silvia, Caruso, Donatella, Melcangi, Roberto Cosimo, Diviccaro, S, Falvo, E, Piazza, R, Cioffi, L, Herian, M, Brivio, P, Calabrese, F, Giatti, S, Caruso, D, Melcangi, R, Diviccaro, Silvia, Falvo, Eva, Piazza, Rocco, Cioffi, Lucia, Herian, Monika, Brivio, Paola, Calabrese, Francesca, Giatti, Silvia, Caruso, Donatella, and Melcangi, Roberto Cosimo

Abstract

Sex steroid hormones are not only synthesized from the gonads but also by other tissues, such as the brain (i.e., neurosteroids) and colon (i.e., gut steroids). Gut microbiota can be shaped from sex steroid hormones synthesized from the gonads and locally interacts with gut steroids as in turn modulates neurosteroids. Type 1 diabetes mellitus (T1DM) is characterized by dysbiosis and also by diabetic encephalopathy. However, the interactions of players of gut-brain axis, such as gut steroids, gut permeability markers and microbiota, have been poorly explored in this pathology and, particularly in females. On this basis, we have explored, in streptozotocin (STZ)induced adult female rats, whether one month of T1DM may alter (I) gut microbiome composition and diversity by 16S next-generation sequencing, (II) gut steroid levels by liquid chromatography-tandem mass spectrometry, (III) gut permeability markers by gene expression analysis, (IV) cognitive behavior by the novel object recognition (NOR) test and whether correlations among these aspects may occur. Results obtained reveal that T1DM alters gut beta-, but not alpha-diversity. The pathology is also associated with a decrease and an increase in colonic pregnenolone and allopregnanolone levels, respectively. Additionally, diabetes alters gut permeability and worsens cognitive behavior. Finally, we reported a significant correlation of pregnenolone with Blautia, claudin-1 and the NOR index and of allopregnanolone with Parasutterella, Gammaproteobacteria and claudin-1. Altogether, these results suggest new putative roles of these two gut steroids related to cognitive deficit and dysbiosis in T1DM female experimental model.

Published
2023

7. Gut Steroids and Microbiota: Effect of Gonadectomy and Sex

Author

Diviccaro, S., Fitzgerald, J.A., Cioffi, L., Falvo, E., Crispie, F., Cotter, P.D., O'Mahony, S.M., Giatti, S., Caruso, D., and Melcangi, R.

Subjects
Ribosomal, Male, 16S, gut microbiota, branched- and short-chain fatty acids, gastrointestinal tract, mucosa, pregnenolone, sex dimorphism, sex steroids, stool, Animals, Castration, Female, Gas Chromatography-Mass Spectrometry, Pregnanolone, Progesterone, RNA, Ribosomal, 16S, Rats, Microbiota, Pregnenolone, Settore MED/13 - Endocrinologia, Settore BIO/10 - Biochimica, RNA
Abstract

Sex steroids, derived mainly from gonads, can shape microbiota composition; however, the impact of gonadectomy and sex on steroid production in the gut (i.e., gut steroids), and its interaction with microbiota composition, needs to be clarified. In this study, steroid environment and gut steroidogenesis were analysed by liquid chromatography tandem mass spectrometry and expression analyses. Gut microbiota composition as branched- and short-chain fatty acids were determined by 16S rRNA gene sequence analysis and gas chromatography flame ionisation detection, respectively. Here, we first demonstrated that levels of pregnenolone (PREG), progesterone (PROG), and isoallopregnanolone (ISOALLO) were higher in the female rat colon, whereas the level of testosterone (T) was higher in males. Sexual dimorphism on gut steroidogenesis is also reported after gonadectomy. Sex, and more significantly, gonadectomy, affects microbiota composition. We noted that a number of taxa and inferred metabolic pathways were associated with gut steroids, such as positive associations between

Published
2022

9. Family Pediatrician and Public Health collaboration, an alliance to increase vaccination coverage: an experience with MenB vaccination in Italy.

Author

D’Avino, A., Aloi, G., Argo, G., Bozza, L., Canale, P., Carlomagno, F., Carpino, A., Castaldo, E., Castiglione, O., Chianese, P., Cioffi, L., Coppola, G., Costigliola, C., D’Onofrio, A., de Franchis, R., De Giovanni, M., De Magistris, T., De Prosperis, A., Ercolini, P., and Esposito, A.

Subjects
NEISSERIA meningitidis, VACCINATION, PEDIATRICIANS, BOOSTER vaccines, ROTAVIRUS vaccines
Abstract

Background. Invasive Meningococcal Disease is a severe disease mainly affecting infants and young children. Most infections are caused by serogroups A, B, C, W, X, and Y. In the last 10 years, serogroup B has been the main cause of Invasive Meningococcal Disease in Europe. Recent data resulting from an observational study conducted in Italy show a significant reduction in the number of Invasive Meningococcal Disease cases due to Neisseria meningitidis B after the introduction of vaccine 4CMenB. Thus, the Naples Team of Federation of Italian Primary Care Pediatricians and the Public Health Department started an active collaboration focused on vaccination process management (named “Progetto Via”) with the aim of increasing Meningococcal B vaccination coverage. Study design. Source of data is the regional platform “GE.VA.”. Every Primary care Pediatrician uses daily to record vaccination activity. This platform is integrated with data entered by operators of the District/ Vaccination Center. Methods. Time: January 2019 – December 2019. The Federation of Italian Primary Care Pediatricians/ Naples organized a meeting to identify six coordinators. The pediatricians could choose to counsel in their own offices and send children to the vaccination center or to counsel and vaccinate directly in their own clinics. Results. A total of 78 pediatricians took part in the project: 46 did only counseling and 32 did both counseling and vaccination in their medical clinic. Data obtained show an overall average vaccination coverage growth of about 13% in the first 4 months of the survey, and a further growth of about 11% in the following seven months, with a total growth in the entire period of 24%. The pediatricians’ counseling is essential to recover non-compliant subjects, considering both the relationship of trust with the families and the visits already scheduled as an ideal moment for vaccinations’ status check. Conclusions. The project highlights how an effective collaboration between family pediatricians and the Local Health Authority becomes valuable in getting closer to reach the Ministerial goal of 95%. Vaccination coverage increased significantly when family pediatricians supported the activity of vaccine centers in distress in many regional situations. The trust relationship, the hourly availability and the capillary network of family pediatricians’ clinics were key elements for the success of this project and were also recognized by parents. [ABSTRACT FROM AUTHOR]

Published
2022
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11. PediaVirus chatline: all together against COVID-19

Author

Iafusco, M, Ciampa, C, De Maddi, F, Palamone, G, Quarantiello, F, De Luca, G, Iannello, C, Pisano, S, Nocerino, A, Russo, R, Orlando, F, Iafusco, D, Aiello, A, Amorosi, W, Arena, S, Aschettino, M, Basile, P, Battista, A, Bozza, L, Cafiero, M, Caldore, M, Capuano, V, Carbone, Mg, Carbone, V, Casaburo, F, Cavaliere, P, Cerciello, L, Cervone De Martino, M, Cesiro, G, Ciampa, L, Ciao, C, Cimaduomo, L, Cioffi, L, Cirillo, C, Confetto, S, Coppola, G, Crisci, A, Cuzzolin, M, D’Avino, A, De Rosa, I, De Rosa, S, De Siena, M, Del Giudice, G, Del Zotti, F, Della Rotonda, G, D’Errico, U, Di Benedetto, L, Di Prisco, A, Di Stasio, F, Dinardo, M, Donadio, P, Emiliano, M, Esposito, A, Esposito, C, Esposito, L, Esposito, Sl, Fabiani, I, Federico, A, Ferrara, D, Ferraro, E, Filippi, A, Fiorinastro, F, Foria, G, Fusco, A, Gambardella, A, Gicchino, Mf, Giuliano, M, Grano, S, Greco, P, Iacono, A, Iafusco, F, Iannello, G, Iervolino, C, Illiano, G, Imperatore, C, Indolfi, C, Indolfi, P, Iovino, A, Iuliano, R, Kosova, P, Lieto, A, Liotta, L, Lisbino, M, Lodato, G, Loffredo, G, Maida, W, Maione, R, Maiorino, C, Marigliano, Ae, Marinelli, G, Marrone, G, Minervino, G, Napoli, M, Nappo, V, Narciso, V, Nardo, S, Noviello, D, Opallo, A, Orbinato, F, Ottaviano, C, Pace, M, Palma, R, Palmentieri, P, Palmieri, L, Palmieri, S, Parrella, G, Parrotta, G, Pellegrini, F, Peluso, C, Pesole, F, Petito, A, Pezzolla, L, Pignatelli, A, Pinto, L, Piroli, C, Piscopo, A, Pullano, F, Raineri, L, Rigante, Donato, Rivezzi, G, Rocco, C, Rocco, D, Rostan, E, Russo, N, Sannino, C, Sarno, C, Savanelli, L, Serra, S, Sibilio, M, Spera, M, Speranza, P, Stagni, A, Stanco, A, Torino, M, Uccello, A, Ummarino, M, Ummarino, D, Viano, V, Vigorita, S, Villani, S, Viola, R, Vitale, A, Vitiello, R, Vuillemieur, P, and Zanfardino, A

Subjects
Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA, Covid-19
Published
2020

18. Mirizzi Syndrome In Laparoscopic Era

Author

Cioffi L, Belli A, Russo G, D’Agostino A, Fantini C, Belli G., LIMONGELLI, Paolo, Cioffi, L, Limongelli, Paolo, Belli, A, Russo, G, D’Agostino, A, Fantini, C, and Belli, G.

Published
2012

20. Hepatopancreatoduodenectomy For Gallbladder Cancer

Author

Belli A, Cioffi L, Russo G, D’Agostino A, Fantini C, Belli G., LIMONGELLI, Paolo, Belli, A, Limongelli, Paolo, Cioffi, L, Russo, G, D’Agostino, A, Fantini, C, and Belli, G.

Published
2012

38. EVOLUZIONE DI MIELOPATIA SPONDILOGENA CERVICALE

Author

D’Avanzo R., Natale M., Bocchetti A., Squillante D., D’Avanzo C., Cioffi L., Guarnieri G., ROTONDO, Michele, SCUOTTO, Assunta, SUN, D’Avanzo, R., Scuotto, Assunta, Natale, M., Bocchetti, A., Squillante, D., D’Avanzo, C., Cioffi, L., Guarnieri, G., and Rotondo, Michele

Published
2003

39. LONG THERM STUDY ON THYMECTOMY FOR TREATMENT OF MIASTHENIA

Author

AMATO, BRUNO, COMPAGNA, RITA, PERSICO, GIOVANNI, lervolino E. M., Persico M., Cioffi L., Villa F. ., Amato, Bruno, Lervolino, E. M., Persico, M., Cioffi, L., Compagna, Rita, Villa, F. ., and Persico, Giovanni

Published
2000

48. The Intrasacral Meningocele

Author

Rinaldi, F., primary, Cioffi, L., additional, Cioffi, F.A., additional, Krasagakis, G., additional, Columbano, L., additional, and Bernini, F.P., additional

Published
2005
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