Higher risk of tuberculosis reactivation when anti-TNF is combined with immunosuppressive agents. A systematic review of randomized controlled trials

Objective. Treatment with tumour necrosis factor antagonists (anti-TNF) has been recognized as a risk factor for tuberculosis (TB) reactivation. Our aim was to evaluate risk of TB reactivation in rheumatologic and non-rheumatologic diseases treated with the same anti-TNF agents with and without concomitant therapies. Methods. We searched for randomized controlled trials (RCTs) evaluating infliximab, adalimumab, and certolizumab in both rheumatologic and non-rheumatologic diseases until 2012. Results were calculated as pooled rates and/or pooled odd ratios (OR). Results. Overall, 40 RCTs with a total of 14,683 patients (anti-TNF: 10,010; placebo: 4673) were included. TB reactivation was 0.26% (26/10,010) in the anti-TNF group and 0% (0/4673) in the control group, corresponding to an OR of 24.8 (95% CI 2.4-133). TB risk was higher when anti-TNF agents were combined with methotrexate or azathioprine as compared with either controls (24/4241 versus 0/4673; OR 54; 95% CI 5.3-88) or anti-TNF monotherapy (24/4241 versus 2/5769; OR 13.3; 95% CI 3.7-100). When anti-TNF was used as monotherapy, TB risk tended to be higher than placebo (2/5769 versus 0/4673; OR 4; 95% CI 0.2-15.7). Conclusions. TB risk with anti-TNF agents appeared to be increased when these agents were used in combination with methotrexate or azathioprine as compared with monotherapy regimen. TB risk seemed to be higher than placebo, even when monotherapy is prescribed

Targeting Food Allergy with Probiotics.

The dramatic increase in food allergy prevalence and severity globally is demanding effective strategies. Food allergy derives from a defect in immune tolerance mechanisms. Immune tolerance is modulated by gut microbiota composition and function, and gut microbiota dysbiosis has been associated with the development of food allergy. Selected probiotic strains could act on immune tolerance mechanisms. The mechanisms are multiple and still not completely defined. Increasing evidence is providing useful information on the choice of optimal bacterial species/strains, dosage, and timing for intervention. The increased knowledge on the crucial role played by gut microbiota-derived metabolites, such as butyrate, is also opening the way to a postbiotic approach in the stimulation of immune tolerance

Gut microbiota as target for innovative strategies against food allergy.

The dramatic increase in food allergy prevalence and severity globally requires effective strategies. Food allergy derives from a defect in immune tolerance mechanisms. Immune tolerance is modulated by gut microbiota function and structure, and microbiome alterations (dysbiosis) have a pivotal role in the development of food allergy. Environmental factors, including a low-fiber/high-fat diet, cesarean delivery, antiseptic agents, lack of breastfeeding, and drugs can induce gut microbiome dysbiosis, and have been associated with food allergy. New experimental tools and technologies have provided information regarding the role of metabolites generated from dietary nutrients and selected probiotic strains that could act on immune tolerance mechanisms. The mechanisms are multiple and still not completely defined. Increasing evidence has provided useful information on optimal bacterial species/strains, dosage, and timing for intervention. The increased knowledge of the crucial role played by nutrients and gut microbiota-derived metabolites is opening the way to a post-biotic approach in the stimulation of immune tolerance through epigenetic regulation. This review focused on the potential role of gut microbiome as the target for innovative strategies against food allergy

Tolerogenic effect elicited by protein fraction derived from different hypoallergic formulas in PBMCs from children with cow milk allergy

are available for the dietary treatment of cow’s milk allergy (CMA). Safety and nutritional profile of these formulas have been well evaluated, but the potential tolerogenic activity elicited by their protein fraction is still largely undefined. We aimed to comparatively evaluate the tolerogenic effect elicited by protein fraction derived from different hypoallergenic formulas available for the dietary treatment of CMA METHODS: Four hypoallergenic formulas were compared: extensively whey formula (EHWF), extensively hydrolyzed casein formula (EHCF), hydrolyzed rice formula (RHF), amino acid based formula (AAF). Formulas were reconstituted in water according to manufacturer’s instructions, and subjected to in vitro infant gut simulated digestion using a sequential gastric and duodenal static model. Resulting protein fractions were purified using C18 reversed phase pre-packed cartridges (Sep-Pak, Waters, Milford, MA, USA),recovered in 70% acetonitrile/0.1% trifluoroacetic acid and finally vacuum-dried. Tolerogenic effects were was evaluated in peripheral blood mononuclear cells (PBMCs) from 6 patients, with challenge-proven IgE-mediated CMA (age range 1-5 yrs, all Caucasians), stimulated with different doses of digested protein fractions (from 0.25 to 250 μg/ml) or -lactoglobulin (BLG;100μg/ml) or bovine serum albumin (BSA;100μg/ml) as positive and negative control respectively. The production of Th2 (IL-4, IL-5, IL-13) and Th1 (IL-10, IFN-γ) cytokines were assessed by ELISA. Modulatory action was also evaluated on immune (IL-33) and non-immune tolerogenic factors (mucin 5AC, tight-junction proteins ZO-1 and occludin) in human enterocytes (Caco-2 cells) by ELISA and Real Time PCR, respectively. RESULTS: Th2 cytokines were unaffected by the exposure to protein fraction from all study formulas, whereas only protein fraction from EHCF was able to positively modulate IL-10, IL-33, mucin 5AC, ZO-1 and occludin expression. All protein fraction from study formulas were able to increase INF-γ expression in PBMCs. CONCLUSION: The results suggest a different regulatory action on immune and non-immune tolerogenic mechanisms elicited by protein fraction from different hypoallergenic formulas

The potential role of advanced glycation end products in food allergy pathogenesis

prevalence has dramatically increased in the last two decades. Among dietary factors, it has been hypothesized that advanced glycation endproducts(AGEs), present at high level in junk food, could be involved in FA pathogenesis. AGEs are a heterogeneous group of compounds deriving from sugars(sweets and beverages), autoclaved/processed foods, microwaved foods, more roasted/barbecued meat. To evaluate the AGEs levels in FA children compared with healthy controls and subjects with respiratory allergy. Methods: We evaluated paediatric patients with challenge-proven FA, children with respiratory allergy(RA) and age and sex-matched healthy controls. Subcutaneous AGEs levels were evaluated through the AGE reader. Food-frequency questionnaires were evaluated in all study subjects. In vitro studies were performed on human enterocytes(Caco-2 cells) stimulated with 200 mg/ml of BSA-AGE for 24and48 hours to evaluate effects on gut barrier function: mucin2(mucus production), transpithelial electrical resistance(TEER), ZO-1, occludin expression(intestinal permeability). The direct effects elicited on peripheral blood mononuclear cells (PBMCs) after the treatment with 200 mg/ml of BSA-AGE for 48hours, 4and 7days of treatment were also evaluated. RESULTS: 115 subjects were evaluated and subdivided into 3 groups: group 1 patients with FA (n=31); group 2 patients with RA (n=18), group 3 healthy controls (n=66). The consumption of food containing AGEs was higher in subjects with FA compared to RA children and healthy controls (p<0.05). FA and RA children presented significant higher subcutaneous AGEs levels compared to healthy controls (p<0.05). Linear regression analysis confirmed a significant positive correlation between subcutaneous levels of AGEs and consumption of food containing AGEs. Human enterocytes exposed to BSA-AGE treatment showed a reduction of TEER, of Muc2 and tight junction proteins (Occludin and ZO-1). Moreover, the treatment with BSA-AGE on human PBMCs stimulates pro-inflammatory cytokines TNF-α and Th2 cytokines(IL-5 and IL-13)production , but it was unable to modulate IL-10 production. Finally, after7days of treatment with BSAAGE, we found a low percentage of proliferating CD4+T. CONCLUSIONS: Current hypotheses and models of FA do not adequately explain the dramatic increase observed in the last years

Gut Microbiome as Target for Innovative Strategies Against Food Allergy

The dramatic increase in food allergy prevalence and severity globally requires effective strategies. Food allergy derives from a defect in immune tolerance mechanisms. Immune tolerance is modulated by gut microbiota function and structure, and microbiome alterations (dysbiosis) have a pivotal role in the development of food allergy. Environmental factors, including a low-fiber/high-fat diet, cesarean delivery, antiseptic agents, lack of breastfeeding, and drugs can induce gut microbiome dysbiosis, and have been associated with food allergy. New experimental tools and technologies have provided information regarding the role of metabolites generated from dietary nutrients and selected probiotic strains that could act on immune tolerance mechanisms. The mechanisms are multiple and still not completely defined. Increasing evidence has provided useful information on optimal bacterial species/strains, dosage, and timing for intervention. The increased knowledge of the crucial role played by nutrients and gut microbiota-derived metabolites is opening the way to a post-biotic approach in the stimulation of immune tolerance through epigenetic regulation. This review focused on the potential role of gut microbiome as the target for innovative strategies against food allergy

Butyrate as bioactive human milk protective component against food allergy

Background: Food allergy (FA) is a growing health problem worldwide. Effective strategies are advocated to limit the disease burden. Human milk (HM) could be considered as a protective factor against FA, but its mechanisms remain unclear. Butyrate is a gut microbiota-derived metabolite able to exert several immunomodulatory functions. We aimed to define the butyrate concentration in HM, and to see whether the butyrate concentration detected in HM is able to modulate the mechanisms of immune tolerance. Methods: HM butyrate concentration from 109 healthy women was assessed by GS-MS. The effect of HM butyrate on tolerogenic mechanisms was assessed in in vivo and in vitro models. Results: The median butyrate concentration in mature HM was 0.75&nbsp;mM. This butyrate concentration was responsible for the maximum modulatory effects observed in all experimental models evaluated in this study. Data from mouse model show that in basal condition, butyrate up-regulated the expression of several biomarkers of gut barrier integrity, and of tolerogenic cytokines. Pretreatment with butyrate significantly reduced allergic response in three animal models of FA, with a stimulation of tolerogenic cytokines, inhibition of Th2 cytokines production and a modulation of oxidative stress. Data from human cell models show that butyrate stimulated human beta defensin-3, mucus components and tight junctions expression in human enterocytes, and IL-10, IFN-γ and FoxP3 expression through epigenetic mechanisms in PBMCs from FA children. Furthermore, it promoted the precursors of M2 macrophages, DCs and regulatory T cells. Conclusion: The study's findings suggest the importance of butyrate as a pivotal HM compound able to protect against FA

Civiltà della Campania. Anno II, n. 2 (febbraio-marzo 1975)

A. II, n. 2 (febbraio-marzo 1975): M. Parrilli, All’Unesco Ravello e Castellabate, P. 3 ; L’anno santo in Campania, P. 7; B. Gatta, Videre Petrum, P. 8; B. Lucrezi, Gli itinerari sacri, P. 12 ; Il Duomo di Salerno: novecento anni di fede e storia », P. 24 ; R. Causa, Santuari nel Nocerino, P. 26 ; G. Giordano, Pacem in maribus, P. 32 ; R. Virtuoso, L’ambiente e il ruolo del turismo, P. 40 ; S. Pavia, I centri storici, P. 32 ; R. Di Stefano, Villa Campolieto, P. 48 ; R. De Simone, Feste popolari, P. 56 ; E. Corsi, II riassetto di Ischia, P. 60 ; C. Nazzaro, Rosmarino col pomodoro, P. 65 ; G. Doria, Il napoletano che cammina, P. 66 ; M. Stefanile, Raffaele Viviani, P. 68 ; A. Fratta, Amedeo Maiuri: una vita per l’archeologia, P. 80 ; E. Fiore, Gli Incontri del Cinema, P. 86 ; G. Blasi, Petrosino l’antipadrino, P. 90 ; I. Santoro, Il mistero di Velia di, P. 93 ; R. Senatore, La rinascita del Borgo Scacciaventi di, P. 97 ; P. Andria, Salerno: S. Pietro a Corte, P. 100 ; U. Abundo, Amalfi sempre di, P. 102 ; V. Gramignazzi Serrone, S. Agata dei Goti, P. 106 ; Attività congressuali in Campania, P. 108 ; Notiziario, P. 10

Civiltà della Campania. Anno III, n. 4 (gennaio-marzo 1976)

A. III, n. 4 (gennaio-marzo 1976): Ricordo di Alfonso, P. 3 ; A. Gatto, Un sodalizio d’arte sotto lo stesso cielo, P. 4 ; R. Causa, Itinerari nell’arte catalana, P. 12 ; B. Gatta, Un altro inglese che ama Garibaldi, P. 18 ; A. Garzya, Napoli e Bisanzio, P. 26 ; S. Ferraretti, Il grande Archivio Napoletano, P. 32 ; B.G., L’Abate Galiani tra Napoli e Parigi, P. 34 ; M. Stefanile, Campania a tavola, P. 36 ; D. Rea, Pulcinella: il mistero di una maschera, P. 44 ; L. Compagnone, Il piccolo teatro di Raffaele Petra, P. 56 ; V. Ricciuti, Quando il cinema si chiamava Napoli, P. 58 ; R. Cantarella, C’era una volta una piccola città, P. 62 ; E. Mallardo, La cattedrale di Avellino, P. 66 ; V. Gramignazzi-Serrone, S. Guglielmo al Goleto, P. 70 ; F. de Ciuceis, I fasti del San Carlo, P. 78 ; L. Orsini, Faito una selva nel cielo, P. 82 ; S. Ferraro, Archeologia a Sorrento, P. 86 ; G. Blasi, Un parco negli Alburni, P. 88 ; D. Lanzara, Il convento di Ischia, P. 92 ; Notiziario, P. 93

Civiltà della Campania. Anno II, n. 3 (agosto-ottobre 1975)

A. II, n.3 (agosto-ottobre 1975): Il messaggio dell’Assessore Emilio de Feo, P. 3 ; M. Parrilli, Continuità nel turismo regionale, P. 3 ; Napoli nei secoli, P. 5 ; G. Galasso, Tumulti ed elezioni del ’600, P. 6 ; N. Cilento, Nella città medioevale, P. 18 ; B. Gatta, Capri tra Napoleone e Murat, P. 24 ; R. Causa, Gioacchino Toma a Napoli, P. 30 ; A. Assante, Napoli e il suo porto, P. 34 ; G. Grimaldi, Messaggio di fede dell’Anno Santo, P. 40 ; R. Vlad, Musica all’aperto, P. 50 ; M. Stefanile, Viaggio nella storia di Amalfi, P. 52 ; D. Rea, Mappa minore, P. 60 ; M. Prisco , Incontro con la Badia, P. 68 ; P. Amos e A. Gambardella, Il villaggio di Albori, P. 74 ; R. Virtuoso, Giovanni Cuomo ritorna tra i giovani, P. 76 ; V. Panebianco, Il turismo venuto dalla storia, P. 80 ; A.P. Carbone, Le grotte di Pertosa, P. 84 ; F. de Ciuceis, Il mare di Caserta, P. 88 ; E. Tirone, Riti settennali a Guardia Sanframondi, P. 92 ; F. Calabro, Turismo e cultura a Capri, P. 98 ; F. de Ciuceis, Settembre al Borgo, P. 102 ; I. Santoro, Teggiano citta museo, P. 104 ; Notiziario, P. 108