Late-adopted children grown up:A long-term longitudinal study on attachment patterns of adolescent adoptees and their adoptive mothers

This paper reports on a long-term follow-up of a longitudinal study conducted in Italy that assessed attachment patterns of late-adopted children (placed between 4 and 8 years old) and their adoptive mothers, in three phases: T1, at placement; T2, in childhood (7\u20138 months after adoption); and T3, in adolescence (current study). The following hypotheses were tested: 1) children\u2019 IWMs will shift from insecurity towards security in a long-term follow-up; and 2) there will be a significant association between adoptees\u2019 and adoptive mothers\u2019 IWMs in adolescence. Participants were 22 late-adopted adolescents (aged 11\u201316) and their adoptive mothers, all assessed in previous phases. Participants completed several measures of attachment, including the Separation-Reunion Procedure (T1, T2), Manchester Child Attachment Story Task (T2), Friends and Family Interview (T3), and Adult Attachment Interview (T1, T3). Late-adopted adolescents showed both an increase in attachment security and a decrease in disorganized attachment from childhood to adolescence. Adoptive mothers\u2019 (T3) secure states of mind were associated significantly to their adopted children attachment security in adolescence. These findings reinforce the importance of taking attachment into account for adoptive families from the beginning of adoption

Use of Mometasone furoate in prolonged treatment of experimental spinal cord injury in mice: A comparative study of three different glucocorticoids

Traumatic spinal cord injury (SCI) represents one of the most disabling injuries of the human body causing temporary or permanent sensory and/or motor system deficit, particularly hind limb locomotor function impairment. At present, steroidal inflammatory drugs, in particular methylprednisolone sodium succinate (MPSS) are the first line choice treatment of acute SCI. Despite progress in pharmacological, surgical and rehabilitative treatment approaches, SCI still remains a very complex medical and psychological challenge, with no curative therapy available. The aim of the present study was to compare the efficacy of MPSS in respect to other GCs such as dexamethasone (Dex) and mometasone furoate (MF) in an in vitro suitable model of LPS-induced inflammation in J774 cells as well as in an in vivo experimental mouse SCI (compression model). In both the in vitro and in vivo experiments, MF resulted surprisingly more potent than Dex and MPSS. In detail, mice sacrificed seven days after induction of SCI trauma resulted not only in tissue damage, cellular infiltration, fibrosis, astrocyte activation, iNOS expression, extracellular signal regulated kinase 1/2 phosphorylation in injured tissue, poly (ADP-ribose) polymerase 1 (PARP-1) activation but also apoptosis (Bax and Bcl-2 expression). All three GCs demonstrated the ability to modulate inflammatory, oxidative as well as apoptotic pathways, but MF demonstrated the best efficacy, while Dex and MPSS showed alternative potency with a different degree of protection. Therefore, we can conclude that MF is the best candidate for post-traumatic chronic treatment, since it ameliorates different molecular pathways involved in the damage's propagation to the surrounding areas of the injured spinal cord

The standardized herbal combination BNO 2103 contained in Canephron® N alleviates inflammatory pain in experimental cystitis and prostatitis

Background: Urinary tract infections are among the most common types of infections and give rise to inflammation with pain as one of the main symptoms. The herbal medicinal product Canephrod (R) N contains BNO 2103, a defined mixture of pulverized rosemary leaves, centaury herb, and lovage root, and has been used in the treatment of urinary tract infections for more than 25 years.Purpose: To test the hypothesis that BNO 2103 reduces pain in cystitis and prostatitis by virtue of anti-inflammatory properties, and to reveal potential mechanisms underlying the anti-inflammatory features.Study design: BNO 2103 was studied for anti-inflammatory and analgesic properties in three animal models in vivo, and the mode of action underlying the anti-inflammatory features was investigated in human leukocytes and cell-free assays in vitro.Methods: To assess the anti-inflammatory and analgesic efficacy of BNO 2103 we employed cyclophosphamide-induced cystitis and carrageenan-induced prostatitis in rats, and zymosan-induced peritonitis in mice. Human neutrophils and monocytes as well as isolated human 5-lipoxygenase and microsomal prostaglandin E-2 synthase-1-containing microsomes were utilized to assess inhibition of leukotriene and/or prostaglandin E-2 production by HPLC and/or ELISA.Results: When given orally, BNO 2103 reduced inflammation and hyperalgesia in experimental cystitis in rats, while individual components of BNO 2103 also reduced hyperalgesia. Furthermore, BNO 2103 reduced hyperalgesia in rats with carrageenan-induced prostatitis. Cell-based and cell-free studies implicate inhibition of prostaglandin E-2 and leukotriene B-4 biosynthesis as potential mechanisms underlying the analgesic and anti-inflammatory effects.Conclusion: Our data support the hypothesis that BNO 2103 reduces pain by virtue of its anti-inflammatory properties, possibly related to suppression of prostaglandin E-2 and leukotriene B-4 formation, and suggest that this combination has the potential to treat clinical symptoms such as inflammatory pain. Thus BNO 2103 may represent an alternative to reduce the use of antibiotics in urinary tract infections

Activated Corrosion Products Evaluations for Occupational Dose Mitigation in Nuclear Fusion Facilities

Activated corrosion products generation in primary heat transfer systems of nuclear fusion facilities is a relevant radiological source term for occupation dose assessments. The formation of the Chalk River Undefined Deposit, already well known in nuclear fission power plants, represents a significant safety issue in fusion applications due to the intense high energy neutron fluences (about 14 MeV in Deuterium-Tritium operation). The activated corrosion products formation is a multi-physical problem. The combined synergy of activation, corrosion, dissolution, erosion, ejection, precipitation, and transport phenomena induces the contamination of coolant loop regions located outside the bio-shield, where scheduled worker operation might take place. The following manuscript shows how activated corrosion products are evaluated for the nuclear fusion power plant design under investigation by the Safety and Environment Work Package (WPSAE) of the Eurofusion Consortium (i.e., the European Demonstration power plant, EU-DEMO). The major issues in activated corrosion products estimations are here exposed and the main results for mass and activity inventories are briefly shown for some main Primary Heat Transfer Systems of EU-DEMO

SAR Studies on Curcumin's Pro-inflammatory Targets: Discovery of Prenylated Pyrazolocurcuminoids as Potent and Selective Novel Inhibitors of 5-Lipoxygenase.

The anticarcinogenic and anti-inflammatory properties of curcumin have been extensively investigated, identifying prostaglandin E2 synthase (mPGES)-1 and 5-lipoxygenase (5-LO), key enzymes linking inflammation with cancer, as high affinity targets. A comparative structure-activity study revealed three modifications dissecting mPGES-1/5-LO inhibition, namely (i) truncation of the acidic, enolized dicarbonyl moiety and/or replacement by pyrazole, (ii) hydrogenation of the interaryl linker, and (iii) (dihydro)prenylation. The prenylated pyrazole analogue 11 selectively inhibited 5-LO, outperforming curcumin by a factor of up to 50, and impaired zymosan-induced mouse peritonitis along with reduced 5-LO product levels. Other pro-inflammatory targets of curcumin (i.e., mPGES-1, cyclooxygenases, 12/15-LOs, nuclear factor-κB, nuclear factor-erythroid 2-related factor-2, and signal transducer and activator of transcription 3) were hardly affected by 11. The strict structural requirements for mPGES-1 and 5-LO inhibition strongly suggest that specific interactions rather than redox or membrane effects underlie the inhibition of mPGES-1 and 5-LO by curcumin

A non-invasive approach to monitor chronic lymphocytic leukemia engraftment in a xenograft mouse model using ultra-small superparamagnetic iron oxide-magnetic resonance imaging (USPIO-MRI).

This work was supported by: Associazione Italiana Ricerca sul Cancro (AIRC) [Grant 5 x mille n.9980, (to M.F., F.M. and A. N.)]; AIRC I.G. [n. 14,326 (to M.F.)], [n.10136 and 16,722 (A.N.)], [n.15426 (to F.F.)]. AIRC and Fondazione CaRiCal co-financed Multi Unit Regional Grant 2014 [n.16695 (to F.M.)]. Italian Ministry of Health 5 × 1000 funds (to F.F). A.G R. was supported by Associazione Italiana contro le Leucemie-Linfomi-Mielomi (AIL) Cosenza - Fondazione Amelia Scorza (FAS). S.M. C.M., F.V., L. E., S. B., were supported by AIRC.Peer reviewedPostprin

The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP).

BACKGROUND AND PURPOSE: Leukotrienes (LTs) are inflammatory mediators produced via the 5-lipoxygenase (5-LOX) pathway and are linked to diverse disorders, including asthma, allergic rhinitis and cardiovascular diseases. We recently identified the benzimidazole derivative BRP-7 as chemotype for anti-LT agents by virtual screening targeting 5-LOX-activating protein (FLAP). Here, we aimed to reveal the in vitro and in vivo pharmacology of BRP-7 as an inhibitor of LT biosynthesis. EXPERIMENTAL APPROACH: We analysed LT formation and performed mechanistic studies in human neutrophils and monocytes, in human whole blood (HWB) and in cell-free assays. The effectiveness of BRP-7 in vivo was evaluated in rat carrageenan-induced pleurisy and mouse zymosan-induced peritonitis. KEY RESULTS: BRP-7 potently suppressed LT formation in neutrophils and monocytes and this was accompanied by impaired 5-LOX co-localization with FLAP. Neither the cellular viability nor the activity of 5-LOX in cell-free assays was affected by BRP-7, indicating that a functional FLAP is needed for BRP-7 to inhibit LTs, and FLAP bound to BRP-7 linked to a solid matrix. Compared with the FLAP inhibitor MK-886, BRP-7 did not significantly inhibit COX-1 or microsomal prostaglandin E2 synthase-1, implying the selectivity of BRP-7 for FLAP. Finally, BRP-7 was effective in HWB and impaired inflammation in vivo, in rat pleurisy and mouse peritonitis, along with reducing LT levels. CONCLUSIONS AND IMPLICATIONS: BRP-7 potently suppresses LT biosynthesis by interacting with FLAP and exhibits anti-inflammatory effectiveness in vivo, with promising potential for further development

Mycobacterium tuberculosis -Induced Upregulation of the COX-2/mPGES-1 Pathway in Human Macrophages Is Abrogated by Sulfasalazine

Macrophages are the primary human host cells of intracellular Mycobacterium tuberculosis ( M.tb ) infection, where the magnitude of inflammatory reactions is crucial for determining the outcome of infection. Previously, we showed that the anti-inflammatory drug sulfasalazine (SASP) significantly reduced the M.tb bactericidal burden and histopathological inflammation in mice. Here, we asked which genes in human inflammatory macrophages are affected upon infection with M.tb and how would potential changes impact the functional state of macrophages. We used a flow cytometry sorting system which can distinguish the dead and alive states of M.tb harbored in human monocyte-derived macrophages (MDM). We found that the expression of cyclooxygenase-2 and microsomal prostaglandin E 2 synthase (mPGES)-1 increased significantly in tagRFP + MDM which were infected with alive M.tb . After exposure of polarized M1-MDM to M.tb (H37Rv strain)-conditioned medium (MTB-CM) or to the M.tb -derived 19-kD antigen, the production of PGE 2 and pro-inflammatory cytokines increased 3- to 4-fold. Upon treatment of M1-MDM with SASP, the MTB-CM-induced expression of COX-2 and the release of COX products and cytokines decreased. Elevation of PGE 2 in M1-MDM upon MTB-CM stimulation and modulation by SASP correlated with the activation of the NF-κB pathway. Together, infection of human macrophages by M.tb strongly induces COX-2 and mPGES-1 expression along with massive PGE 2 formation which is abrogated by the anti-inflammatory drug SASP

Optical Response of CVD-Grown ML-WS2 Flakes on an Ultra-Dense Au NP Plasmonic Array

The combination of metallic nanostructures with two-dimensional transition metal dichalcogenides is an efficient way to make the optical properties of the latter more appealing for opto-electronic applications. In this work, we investigate the optical properties of monolayer WS2 flakes grown by chemical vapour deposition and transferred onto a densely-packed array of plasmonic Au nanoparticles (NPs). The optical response was measured as a function of the thickness of a dielectric spacer intercalated between the two materials and of the system temperature, in the 75–350 K range. We show that a weak interaction is established between WS2 and Au NPs, leading to temperature- and spacer-thickness-dependent coupling between the localized surface plasmon resonance of Au NPs and the WS2 exciton. We suggest that the closely-packed morphology of the plasmonic array promotes a high confinement of the electromagnetic field in regions inaccessible by the WS2 deposited on top. This allows the achievement of direct contact between WS2 and Au while preserving a strong connotation of the properties of the two materials also in the hybrid system