OM-85 is an immunomodulator of interferon-ß production and inflammasome activity.

The inflammasome-IL-1 axis and type I interferons (IFNs) have been shown to exert protective effects upon respiratory tract infections. Conversely, IL-1 has also been implicated in inflammatory airway pathologies such as asthma and chronic obstructive pulmonary disease (COPD). OM-85 is a bacterial extract with proved efficacy against COPD and recurrent respiratory tract infections, a cause of co-morbidity in asthmatic patients. We therefore asked whether OM-85 affects the above-mentioned innate immune pathways. Here we show that OM-85 induced interferon-ß through the Toll-like receptor adaptors Trif and MyD88 in bone marrow-derived dendritic cells. Moreover, it exerted a dual role on IL-1 production; on the one hand, it upregulated proIL-1ß and proIL-1α levels in a MyD88-dependent manner without activating the inflammasome. On the other hand, it repressed IL-1ß secretion induced by alum, a well-known NLRP3 activator. In vivo, OM-85 diminished the recruitment of inflammatory cells in response to peritoneal alum challenge. Our findings therefore suggest that OM-85 favors a protective primed state, while dampening inflammasome activation in specific conditions. Taken together, these data bring new insights into the mechanisms of OM-85 action on innate immune pathways and suggest potential explanations for its efficacy in the treatment of virus-induced airway diseases.

Emerging Major Histocompatibility Complex Class I-Related Functions of NLRC5.

Recent evidence demonstrates a key role for the nucleotide-binding oligomerization domain-like receptor (NLR) family member NLRC5 (NLR family, CARD domain containing protein 5) in the transcriptional regulation of major histocompatibility complex (MHC) class I and related genes. Detailed information on NLRC5 target genes in various cell types and conditions is emerging. Thanks to its analogy to CIITA (class II major MHC transactivator), a NLR family member known for over 20 years to be the master regulator of MHC class II gene transcription, also the molecular mechanisms underlying NLRC5 function are being rapidly unraveled. MHC class I molecules are crucial in regulating innate and adaptive cytotoxic responses. Whereas CD8+ T cells detect antigens presented on MHC class I molecules by infected or transformed cells, natural killer (NK) lymphocytes eliminate target cells with downregulated MHC class I expression. Data uncovering the relevance of NLRC5 in homeostasis and activity of these two lymphocyte subsets have been recently reported. Given the importance of CD8+ T and NK cells in controlling infection and cancer, it is not surprising that NLRC5 is also starting to emerge as a central player in these diseases. This chapter summarizes and discusses novel insights into the molecular mechanisms underlying NLRC5 activity and its relevance to pathological conditions. A thorough understanding of both aspects is essential to evaluate the clinical significance and therapeutic potential of NLRC5.

Strengthening of Porcelain Provided by Resin Cements and Flowable Composites.

This study evaluated the effect of mechanical properties of resin-based luting agents on the strength of resin-coated porcelain. The luting agents tested were two flowable resin composites (Filtek Z350 Flow and Tetric-N Flow), a light-cured resin cement (Variolink Veneer [VV]), and a dual-cured resin cement (Variolink II) in either light-cured (base paste) or dual-cured (base + catalyst pastes [VD]) mode. Flexural strength (σf) and modulus of elasticity (Ef) of the luting agents were measured in three-point bending mode (n=5). Porcelain discs (Vita VM7) were tested either untreated (control) or acid etched, silanized, and coated with the luting agents. Biaxial flexural strength (σbf) of the porcelain discs was tested using a ball-on-ring setup (n=30). The σbf of the resin-coated specimens was calculated at z-axial positions for multilayer specimens in the ball-on-ring test: position z = 0 (ceramic surface at the bonded interface) and position z = -t2 (luting agent surface above ring). The σf and Ef data were subjected to analysis of variance and the Student-Newman-Keuls test (α=0.05). A Weibull analysis was performed for σbf data. Weibull modulus (m) and characteristic strength (σ0) were calculated. Linear regression analyses investigated the relationship between mechanical properties of the luting agents and the strengthening of porcelain. VD had higher and VV had lower mechanical strength than the other materials. At z = 0, all resin-coated groups had higher σbf than the control group. No significant differences between the luting agents were observed for σbf and σ0. At z = -t2, VD had the highest σbf and σ0, whereas VV had the poorest results. No significant differences in m were observed across groups. A linear increase in flexural strength of the porcelain was associated with increased σf and Ef of the luting agents at position z = -t2. In conclusion, resin coating and use of luting agents with better physical properties generally improved the mechanical performance of porcelain.

Effects of surface treatments, thermocycling, and cyclic loading on the bond strength of a resin cement bonded to a lithium disilicate glass ceramic.

SUMMARY Objectives : The aim of this present study was to investigate the effect of two surface treatments, fatigue and thermocycling, on the microtensile bond strength of a newly introduced lithium disilicate glass ceramic (IPS e.max Press, Ivoclar Vivadent) and a dual-cured resin cement. Methods : A total of 18 ceramic blocks (10 mm long × 7 mm wide × 3.0 mm thick) were fabricated and divided into six groups (n=3): groups 1, 2, and 3-air particle abraded for five seconds with 50-µm aluminum oxide particles; groups 4, 5, and 6-acid etched with 10% hydrofluoric acid for 20 seconds. A silane coupling agent was applied onto all specimens and allowed to dry for five seconds, and the ceramic blocks were bonded to a block of composite Tetric N-Ceram (Ivoclar Vivadent) with RelyX ARC (3M ESPE) resin cement and placed under a 500-g static load for two minutes. The cement excess was removed with a disposable microbrush, and four periods of light activation for 40 seconds each were performed at right angles using an LED curing unit (UltraLume LED 5, Ultradent) with a final 40 second light exposure from the top surface. All of the specimens were stored in distilled water at 37°C for 24 hours. Groups 2 and 5 were submitted to 3,000 thermal cycles between 5°C and 55°C, and groups 3 and 6 were submitted to a fatigue test of 100,000 cycles at 2 Hz. Specimens were sectioned perpendicular to the bonding area to obtain beams with a cross-sectional area of 1 mm(2) (30 beams per group) and submitted to a microtensile bond strength test in a testing machine (EZ Test) at a crosshead speed of 0.5 mm/min. Data were submitted to analysis of variance and Tukey post hoc test (p≤0.05). Results : The microtensile bond strength values (MPa) were 26.9 ± 6.9, 22.2 ± 7.8, and 21.2 ± 9.1 for groups 1-3 and 35.0 ± 9.6, 24.3 ± 8.9, and 23.9 ± 6.3 for groups 4-6. For the control group, fatigue testing and thermocycling produced a predominance of adhesive failures. Fatigue and thermocycling significantly decreased the microtensile bond strength for both ceramic surface treatments when compared with the control groups. Etching with 10% hydrofluoric acid significantly increased the microtensile bond strength for the control group.

[Our experience in the surgery of bile ducts]. / La nostra esperienza in tema di chirurgia delle vie biliari

After a brief review of modern techniques for correct diagnosis and therapy of bile duct pathology, a personal series of 955 operations (between 1-XI-1972 and 30-X-1975) is presented. The need for routine peroperative control of VBP and the usefulness of respecting the papilla where it is anatomo-functionally undamaged are stressed. Personal experience shows that the most rational methodology is after papillotomy the application of a prepapillary Kehr incision through a choledochotomy because this presents fewer complications than the transpapillary Kehr incision in calculosis or stenosis of the VBP where bile duct suture is not advisable. With regard to bilio-digestive anastomosis, indications and limitations are discussed and it is suggested that where the patient's general and local states permit, choledochojejunal anastomosis should permit, choledochojejunal anastomosis should be used, with choledocho-duodenostomy only in special cases. Cholecysto-gastro and cholecystoduodenostomy should be reserved for patients in very serious conditions.