Exploitation of rubbery electrospun nanofibrous mat for fracture toughness improvement of structural epoxy adhesive bonded joints

The improvement of the fracture toughness of adhesive joints is a key factor in many structural applications. The ability of nylon electrospun nanofibrous mat to act as an adhesive carrier and reinforcing web in adhesive bonding has been demonstrated by the Authors in previous works. It has been shown that the impregnation method developed and refined during the previous studies allow generating high-quality pre-preg nanomats out of a 2k unfilled epoxy resin. By applying this methodology, in the present work, rubbery nanofibrous mats have been adopted for the first time to reinforce and increase the fracture toughness of adhesive joints. Rubbery nanofibers were produced by electrospinning of nitrile butadiene rubber (NBR) and poly(ε-caprolactone) (PCL). The addition of the semi-crystalline polymer (PCL) is exploited to maintain the nanofibrous morphology, which the rubber alone (NBR) would not be able to ensure due to its low glass transition temperature (Tg). The nanofibers thus obtained have been integrated into a two-component high strength epoxy resin for structural applications. S235 steel adherends for Double Cantilever Beam (DCB) tests have been manufactured and sandblasted to improve adhesion. An optimization of the sandblasting parameters (distance, pressure, angle and time) has been carried out evaluating the shear strength and the fracture surfaces on S235 steel Single Lap Joints (SLJ). Finally, DCB tests have been performed to compare the mode I fracture toughness with and without the rubbery electrospun nanomats

Plant-derived peptides rubiscolin-6, soymorphin-6 and their c-terminal amide derivatives: pharmacokinetic properties and biological activity

The aim of this work is to investigate the pharmacokinetic properties, antinociceptive and antioxidant activities of rubiscolin-6, soymorphin-6 and their C-terminal amides; The four peptides were synthesized following Fmoc-SPPS strategy to give the final peptides in excellent overall yields and purity following analytical RP-HPLC analysis. None of them shows antioxidant activity and α-tyrosinase inhibition in vitro. All compounds are able to activate G-protein coupled receptor at the δ-opioid receptor (DOR) at 100 μM concentration however, rubiscolin-6-amide exhibits significative antinociceptive effect after i.c.v. administration in the tail flick test (TF) and s.c. administration in the formalin test (FT). Rubiscolin-6 shows the best in vitro intestinal bioavailability in CaCo2 cell monolayer and stability to the brush border exopeptidases in the apical compartment. In silico experiments show the interaction of rubiscolin-6 and rubiscolin-6 amide at the binding cavity of DOR compared with the crystallographic ligand TIPP-NH2

Soy-enriched bread, a pilot study to determine its beneficial effects in menopause.

Menopause is the last step in the reproductive history of a woman. The ovaries stop producing hormones and the body reacts by lowering its functions, including the cognitive one. Phytoestrogens are plant products with the estrogen-like activity which are able to mimic many of estrogen’s functions. The aim of the present experiment was to study the effects of 30 days of regular consumption of soy-enriched bread containing a known amount of phytoestrogens (genistein and daidzein) in climacteric or menopausal women. Thirty women at different stages of menopause (climacteric, within 5 years of menopause, more than 5 years of menopause) were asked to include 200 g/die of bread containing 40 mg of phytoestrogens in their diet. The effect of the regular consumption of this bread on common menopausal symptoms and cognitive parameters was determined before and after 30 days through questionnaires and experimental tests. Phytoestrogens were measured in the urine. Twenty-five women completed the study. Independence of the menopause stage, there was a significant increase of phytoestrogens in the urine and a decrease of the classical symptoms (i.e., hot flushes). Moreover, the women showed a significant improvement in attentional performance tests, the quality of life index and pain intensity. Phytoestrogens would be an important supplement in aging women due to their ability to induce estrogen-like effects without the potential side effects of estrogens. Their presence in soy-enriched bread, a food commonly present in meals, avoids consideration of their consumption as a drug

Intra-articular therapy with infliximab in psoriatic arthritis: efficacy and safety in refractory monoarthritis

Objective: To evaluate efficacy and safety of intra-articular therapy (IA) with infliximab (IFX), in patients with psoriatic arthritis (PsA) and refractory monoarthritis. Methods: Four male and 1 female aged from 25 to 71 years and disease duration from 1 to 25 years, affected by PsA (CASPAR criteria) were observed . All patients were treated with immunomodulators (methotrexate, leflunomide, cyclosporin A), 3/5 with concomitant steroids, 4/5 with NSAID’s. Only 1 patient were treated with IFX 5 mg/kg IV every 6 weeks. Before the IFX injection an amount of synovial fluid was aspired from the inflamed site and the anti-TNF injection was echographic guided. Patients were evaluated at regular intervals through clinical and echographic examination and retreated in case of flare. Results: At follow-up visit after 7 days, in all patients treated with the first injection was detected total regression of the inflammation and no new inflamed synovial fluid was observed; power doppler examination shows reduction of local vascularization. Two patients experienced full remission after 6 months and only one injection, 1 patient (arthritis of the wrist) was in remission after 2 injections (3 months of interval). In 2 patients with knee arthritis and important synovial hypertrophy good results obtained after the first injection were not maintained afterwards and second injection was ineffective: these patients were evaluated for surgical intervention. Conclusions: Local injections of IFX were safe and well tolerated in all patients. The efficacy in short term was observed in all cases; our supposition is that presence of synovial hypertrophy is cause of worsening

Evaluation of XD 10 Polyamide Electrospun Nanofibers to Improve Mode I Fracture Toughness for Epoxy Adhesive Film Bonded Joints

The demand for ever-lighter structures raises the interest in bonding as a joining method, especially for materials that are difficult to join with traditional welding and bolting techniques. Structural adhesives, however, are susceptible to defects, but can be toughened in several ways: by changing their chemical composition or by adding fillers, even of nanometric size. Nanomaterials have a high surface area and limited structural defects, which can enhance the mechanical properties of adhesives depending on their nature, quantity, size, and interfacial adhesion. This work analyzes the Mode I fracture toughness of joints bonded with METLBOND® 1515-4M epoxy film and XantuLayr electrospun XD 10 polyamide nanofibers. Two joint configurations were studied, which differed according to the position of the nanomat within the adhesive layer: one had the nanofibers at the substrate/adhesive interfaces, and the other had the nanofibers in the center of the adhesive layer. Double cantilever beam joints were manufactured to evaluate the Mode I fracture toughness of the bonding with and without nano-reinforcement. The nanofibers applied at the substrate/adhesive interface improved the Mode-I fracture toughness by 32%, reaching the value of 0.55 N/mm. SEM images confirm the positive contribution of the nanofibers, which appear stretched and pulled out from the matrix. No fracture toughness variation was detected in the joints with the nanofibers placed in the middle of the adhesive layer

Integration of nylon electrospun nanofibers into structural epoxy adhesive joints

The fracture toughness is a key parameter in the development of bonded joints for several structural applications. Adhesives are commonly toughened with fillers or modifying the resin chemical composition. Many studies also suggest that resin toughening could be achieved through electrospun polymer nanomat. In previous works, the Authors proved that nylon nanomats can be used as an adhesive carrier and reinforcing web for the adhesive layer. This allowed developing a laboratory route to produce high-quality prepregs of electrospun nylon carrier using medium viscosity, two-component, unfilled epoxy adhesive. By applying the same methodology, in the present work, electrospun nylon prepregs were produced using a high strength and high toughness 2k structural epoxy adhesive to toughen the joint. The wet nanoreinforced strips were placed between S235 steel sandblasted adherents and oven-cured to obtain Double Cantilever Beam (DCB) joints. DCB tests have been performed to compare the mode-I fracture toughness with and without the nanofibrous mat. Unlike previous works with medium-low toughness epoxies, this time the fracture toughness is reduced after the integration of an electrospun nano-reinforcement. From the Scanning Electron Microscope (SEM) images it seems that the nanomat hinders the ductile failure mechanism which instead develops in the neat resin

Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity .

Background. In the last two decades, obesity has assumed the form of a pandemic, often related to the development of cardiovascular diseases (CVD) and strokes. There is a worldwide emergency that requires the development of novel and safer anti-obesity treatments. Rimonabant, a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), associated with lifestyle modifications was successfully engaged in the control of obesity by reducing appetite and weight gain. Though this drug has shown to be effective to control body weight and to manage obesity, it has been withdrawn from the market due to its important side effects. Thus, a novel drug able to provide the same therapeutic efficacy without the dangerous side efficacy without the dangerous side effects is an urgent need. We report a series of lonidamine joined Leu, tert-Leu and Val amino acids with different C-terminal functional groups (LONI1-4,11, Figure 1) designed as hybrids of Fubinaca family compounds and Rimonabant, as novel compounds endowed with orexant/anorexant activity. Methods. We evaluated the orexant/anorexant activity of LONI1-4,11 in the feeding test using CD-1 male mice after intraperitoneal (i.p.) administration (10 mg/kg). For a LONI11 formalin test and a tail flick test after an administration by the subcutaneous (s.c.,30–100 μg/20 µL) and intracerebroventricular (i.c.v.,10 µg/10 μL) routes, respectively, were also carried out in mice to investigate the antinociceptive property at the central and peripheral levels. Furthermore, Zymosan-induced edema (s.c., 100 µg/20 μL) and hyperalgesia (s.c., 100 µg/20 μL) assays were also performed to estimate the anti-inflammatory activity of LONI11 in mice model. Results. We observed a significant orexant effect for LONI11 and an intense anorexant effect for LONI2 and LONI4 (Figure 2). LONI11 at the doses of 10 µg/10 μL and 100 µg/20 μL produced a slight antinociceptive effect after i.c.v. and s.c. injections, respectively, in tail flick test (Figure 3, left panel) and in formalin test (Figure 3, right panel). In zymosan-induced edema (Figure 4, left panel) and hyperalgesia (Figure 4, right panel), LONI11 reduced the percent of paw volume increase and paw latency after s.c. administration, also suggesting a possible peripheral anti-inflammatory activity. Conclusions. These results could be useful as a starting point to optimize the pharmacological properties of rimonabant/Fubinaca hybrids and to better understand the molecular mechanism below their biological profile. An understanding of all the neuroendocrine networks and their roles in the hypothalamus to regulate the feeding behaviour could lead to the development of novel and safer approaches to manage the main nutritional disorders

Pharmacological activities of plant-derived opioid peptides rubiscolin-6, soymorphin-6 and their c-terminal amide derivatives.

Background. Rubiscolin-6 (amino acid sequence: YPLDLF) is an opioid peptide derived from the plant enzyme Rubisco and Soymorphin-6 (peptide sequence: YPFVVA) is an opioid peptide derived from the enzymatic digestion of soy proteins. In this work we investigated the pharmacological activities of Rubiscolin-6, Soymorphin-6 and their new C-terminal amides in vitro using cells expressing the human recombinant delta and mu opioid receptors and in vivo using the mouse tail flick and formalin tests. Methods. In in vitro experiments, we evaluated the capability of Rubiscolin-6, Soymorphin-6 and their new C-terminal amides to activate the mu- and delta-human recombinant receptors permanently transfected in CHO cells. In such cells, the expression of a chimeric G protein that forces the opioid receptors to couple with the calcium pathway allows measuring receptor activation with an automated calcium mobilization assay. In in vivo experiments, the tail flick test was used to determinate antinociceptive response induced by a thermal stimulus and compounds were injected at 10 µg/10µL for intracerebroventricular (i.c.v.) administrations. In the formalin test, which measured the response to inflammatory pain, compounds were administered subcutaneously in the dorsal surface of the right hind paw of the mouse at the dose of 100 µg/20 µL. Results. In the calcium mobilization assay, Rubiscolin-6 C-amide, Soyamorphin-6 and Soyamorphin-6 C-amide stimulated calcium mobilization in mu expressing cells only at micromolar concentrations while Rubiscolin-6 was completely inactive. In cells expressing the delta receptor, all compounds showed an incomplete concentration response curve, being active only at micromolar concentrations. The pharmacological parameters obtained with these ligands in CHO cells are summarized in Table 1. In the tail flick test, Rubiscolin-6 induced a significant but transient antinociceptive effect whereas Rubiscolin-6 C-amide induced a statistically significant, prolonged antinociceptive effect (Figure 1, left panel). Soymorphin-6 and Soymorphin-6 C-amide exerted significant antinociceptive until 30 min after the administration (Figure 1, right panel). In the formalin test, Rubiscolin-6 was not able to change the nociceptive effect of formalin whereas Rubiscolin-6 C-amide reduced formalin-induced nociception in both test phases (Figure 2, left panel). Soymorphin-6 and Soymorphin-6 C-amide did not change the nociceptive effects of formalin (Figure 2, right panel). Conclusions. In conclusion, we found Rubiscolin-6 derivative C-terminal amide able to exert strong antinociceptive effect after central and subcutaneous administration despite its low agonist potency at opioid receptors. These results push us to further investigate Rubiscolin-6 amide mechanism of action in other experimental paradigms and design other derivatives more active in animal models of pain and inflammation