HelixComplex snail mucus as a potential technology against O3 induced skin damage

Mucus form H. aspersa muller has been reported to have several therapeutic proprieties, such as antimicrobial activity, skin protection and wound repair. In this study, we have analyzed H. aspersa mucus (Helixcomplex) bio-adhesive efficacy and its defensive properties against the ozone (O3) (0.5 ppm for 2 hours) exposure in human keratinocytes and reconstructed human epidermis models. Cytotoxicity, tissue morphology and cytokine levels were determined. We confirmed HelixComplex regenerative and bio-adhesive properties, the latter possibly via the characteristic mucopolysaccharide composition. In addition, HelixComplex was able to protect from O3 exposure by preventing oxidative damage and the consequent pro-inflammatory response in both 2D and 3D models. Based on this study, it is possible to suggest HelixComplex as a potentially new protective technology against pollution induced skin damage

Plasticity of the Anemonia viridis microbiota in response to different levels of combined anthropogenic and environmental stresses

Despite their recognized primary importance, marine coastal ecosystems around the globe are currently under threat, being subject to continuous local and global anthropogenic stressors. In this frame, understanding the response of coastal habitat-forming species to multiple stressors and their resilience is fundamental for the sustainable management of coastal ecosystems. In the present study, to provide some glimpses in this direction, we explored the response of the Anemonia viridis-associated microbiota to the combined anthropogenic stressors, which typically affect touristic hotspots at Mediterranean coastal sites. To this aim, two case studies have been carried out, the first in the Riccione coastal site (Italy, Center Mediterranean) and the second at Cap de Creus (Spain, North-western Mediterranean), where the A. viridis microbiota was assessed under the conditions of both high and low anthropogenic pressure. According to our findings, the A. viridis microbiota showed a relevant degree of plasticity in response to combined anthropogenic and environmental stressors, with changes that also mirrored variations in the surrounding seawater, thus indicating a close connection with the environment, from which potential symbiotic partners are selected. However, this potentially adaptive process also has a limitation, as observed in the highly anthropogenic impact site of Cap de Creus, where A. viridis-associated microbiota appeared completely unstructured, as demonstrated by an increased dispersion according to the Anna Karenina principle. This raises the question about the resilience of the A. viridis-associated microbiota under combined climate and anthropogenic threats, as well as of the anthropogenic factors driving the observed dysbiosis changes

Pharmacological modulation of mitochondrial calcium uniporter controls lung inflammation in cystic fibrosis

Mitochondria physically associate with the endoplasmic reticulum to coordinate interorganelle calcium transfer and regulate fundamental cellular processes, including inflammation. Deregulated endoplasmic reticulum–mitochondria cross-talk can occur in cystic fibrosis, contributing to hyperinflammation and disease progression. We demonstrate that Pseudomonasaeruginosainfection increases endoplasmic reticulum–mitochondria associations in cystic fibrosis bronchial cells by stabilizing VAPB-PTPIP51 (vesicle-associated membrane protein–associated protein B–protein tyrosine phosphatase interacting protein 51) tethers, affecting autophagy. Impaired autophagy induced mitochondrial unfolding protein response and NLRP3 inflammasome activation, contributing to hyperinflammation. The mechanism by which VAPB-PTPIP51 tethers regulate autophagy in cystic fibrosis involves calcium transfer via mitochondrial calcium uniporter. Mitochondrial calcium uniporter inhibition rectified autophagy and alleviated the inflammatory response in vitro and in vivo, resulting in a valid therapeutic strategy for cystic fibrosis pulmonary disease

Some of the Specific Crime Investigation Risk Disappearances of Persons

Nestanci osoba, osobito oni kod kojih postoje indicije da su nestale osobe žrtve ubojstava, u značajnoj mjeri zaokupljaju stručnu, ali i sveukupnu javnost. Traže se brze i učinkovite aktivnosti policije u razjašnjavanju takvih događaja i pronalaženje počinitelja. Takva kriminalistička istraživanja spadaju u red najsloženijih s obzirom na to da vrlo često u početku nema nedvojbenih dokaza da je uopće počinjeno kazneno djelo. Stoga će ovaj rad ukazati na neke stručne i organizacijske aspekte postupanja policije u takvim slučajevima.Disappearances of persons occupy the public and the media. Interest is particularly great when there is suspicion that the missing person is a victim of murder. Missing person\u27s family also expects from the police fast and efficient activities. These criminal investigations belong to the most complex because frequently in the beginning there is no clear evidence about the murder. The article therefore deals with the expert and organizational aspects of police proceedings

Considerazioni sui Linfomi non-Hodgkin cerebrali primitivi

Analisi di 6 casi di linfomi NH del SNC trattati presso la neurochirurgia di Ferrar

Antinociceptive action of NOP and opioid receptor agonists in the mouse orofacial formalin test

Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions, including pain transmission via selective activation of a specific receptor named NOP. The aim of this study was the investigation of the antinociceptive properties of NOP agonists and their interaction with opioids in the trigeminal territory. The orofacial formalin (OFF) test in mice was used to investigate the antinociceptive potential associated to the activation of NOP and opioid receptors. Mice subjected to OFF test displayed the typical biphasic nociceptive response and sensitivity to opioid and NSAID drugs. Mice knockout for the NOP gene displayed a robust pronociceptive phenotype. The NOP selective agonist Ro 65-6570 (0.1-1mgkg(-1)) and morphine (0.1-10mgkg(-1)) elicited dose dependent antinociceptive effects in the OFF with the alkaloid showing larger effects; the isobologram analysis of their actions demonstrated an additive type of interaction. The mixed NOP/opioid receptor agonist cebranopadol elicited potent (0.01-0.1mgkg(-1)) and robust antinociceptive effects. In the investigated dose range, all drugs did not modify the motor performance of the mice in the rotarod test. Collectively the results of this study demonstrated that selective NOP agonists and particularly mixed NOP/opioid agonists are worthy of development as innovative drugs to treat painful conditions of the trigeminal territory

Synthetic cannabinoid JWH-018 impairs object recognition memory in mice: behavioral and electrophysiological evidence

Introduction: JWH-018 (1-pentyl-3-(1-naphthoyl) indole) is a synthetic CB1 and CB2 agonist illegally marketed in 'Spice' and “herbal blend” for its psychoactive effects similar to those produced by Cannabis. In rodents JWH-018 reproduces the typical effects of THC as hypothermia, analgesia, hypolocomotion and akinesia, while its effects on memory functions are still unknowns. Behavioral and in vitro electrophysiological studies were undertaken to investigated the effects of acute JWH-018 administration on novel object recognition memory and hippocampal LTP formation in CD-1 male mice. Methods and Results: The novel object recognition task is a one-trial learning paradigm allowing the assessment of acquisition, consolidation or retrieval of (object) information separately. JWH-018 (0.1-1 mg/Kg i.p.) dose-dependently impaired both short (2 hours after training section) and long (24 hours after training section) memory retention in mice by CB1 receptor stimulation, since JWH-018 effect was prevented by the selective CB-1 receptor antagonist AM251 (3 mg/Kg). Electrically evoked Schaffer area fEPSP has been extracellularly recorded from stratum radiatum of mouse dorsal hippocampal transversal slices. A stimulus–response curve was recorded before and after JWH-018 contact. At this time, an LTP stimulation paradigm was applied. JWH-018 (10-1000 nM) dose-dependently reduced LTP in hippocampal slices and abolished it at higher concentrations (300 and 1000 nM). Conclusion: These results show that JWH-018 impairs cognitive function in mice possibly by impairing hippocampal memory formation. This aspect should be carefully investigated since chronic consumption of THC impairs cognitive function not only in animal models but in particular in human consumers by altering brain neurodevelopment (http://www.dronet.org/monografia.php?monografie=93)

Pharmacological profile of nociceptin/orphanin FQ receptors interacting with G-proteins and β-arrestins 2

Nociceptin/orphanin FQ (N/OFQ) controls several biological functions by selectively activating an opioid like receptor named N/OFQ peptide receptor (NOP). Biased agonism is emerging as an important and therapeutically relevant pharmacological concept in the field of G protein coupled receptors including opioids. To evaluate the relevance of this phenomenon in the NOP receptor, we used a bioluminescence resonance energy transfer technology to measure the interactions of the NOP receptor with either G proteins or β-arrestin 2 in the absence and in presence of increasing concentration of ligands. A large panel of receptor ligands was investigated by comparing their ability to promote or block NOP/G protein and NOP/arrestin interactions. In this study we report a systematic analysis of the functional selectivity of NOP receptor ligands. NOP/G protein interactions (investigated in cell membranes) allowed a precise estimation of both ligand potency and efficacy yielding data highly consistent with the known pharmacological profile of this receptor. The same panel of ligands displayed marked differences in the ability to promote NOP/β-arrestin 2 interactions (evaluated in whole cells). In particular, full agonists displayed a general lower potency and for some ligands an inverted rank order of potency was noted. Most partial agonists behaved as pure competitive antagonists of receptor/arrestin interaction. Antagonists displayed similar values of potency for NOP/Gβ1 or NOP/β-arrestin 2 interaction. Using N/OFQ as reference ligand we computed the bias factors of NOP ligands and a number of agonists with greater efficacy at G protein coupling were identified

CUSTOM-MADE CRANIAL VALUT RECONSTRUCTION: A RETROSPECTIVE STUDY

None of several materials used to reconstruct skull defects is fully satisfactory, due to biological and physical properties. In large defects or in defects with more complex geometries, the preoperative prefabrication of a custom polymethylmethacrylate (PMMA) implant based on a three dimensional model could be the best choice. From January 2007 to December 2010 PMMA custom made cranioplasty have been implanted in 44 patients (22M/22F; age range 17-82) at the Neurosurgery Unit of the Arcispedale S. Anna of the University Hospital of Ferrara, Italy. The causes of primary operation were 25 (56.8%) cerebral hemorrhages, 15 (34.1%) traumas, 3 (6.8%) tumors and 1 (2.3%) infection, respectively. Hypertension was a co-morbidity factor in 13 (29.5%) patients. Cranial vault reconstruction was performed after a mean period of 9 months. The variables analyzed were causes of craniotomy (hemorrhages, traumas, tumors and infections), co-morbidity factor (i.e. hypertension), sites (1 frontal, 8 fronto-temporal, 32 fronto-temporo-parietal, 2 temporo-parietal and 1 temporo-occipito-parietal) and dimension of the defect (maximum diameter smaller than 9 cm, 9 ≤ x < 12 cm, equal or greater than 12 cm). Each patient obtained an good aesthetic result. In two cases the reconstruction was removed in the follow-up period: one case of infected reconstruction and case of mobility of the prothesis. PMMA custom-made devices from processing of CT images can be used for produce cranial prothesies which have a low rate of infection and mobilit