96 research outputs found
DRUG DESIGN, SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF NOVEL MULTIMODAL INDOLE-FUSED TRICYCLIC DERIVATIVES TARGETING CANNABINOID-MODULATED G PROTEIN-COUPLED RECEPTORS AND CHOLINESTERASES
No full textDue to the multi-factorial nature of most neurological disorders, developing multi-target compounds is still considered among the effective approaches to developing neuroprotective drugs. Despite the scientific advances in the areas of neurochemistry, genetics, molecular and cell biology, there is still no effective treatment available that can delay the onset or slow the progression of neurodegenerative diseases, like Alzheimer’s disease (AD) and memory impairments. In the context of the challenging multitarget-directed-ligand (MTDL) design strategy of novel therapeutic agents for treating AD and related syndromes, progress has been made in the medicinal chemistry of drugs acting within and beyond the endocannabinoid system. Endogenous lipids, such as palmitoylethanolamide, that act simultaneously at GPCRs, ion channels, and PPARs can be taken as templates.
In this Ph.D. thesis study, starting from the structures of small-molecules inhibiting well-established AD-related targets, such as cholinesterases (AChE and BChE) and N-methyl-D-aspartate (NMDA) receptor, the synthesis has been carried out of novel rationally designed tricyclic indole-fused derivatives which interestingly proved to act as modulators (antagonists and/or inverse agonists) of the cannabinoid-related GPCRs GPR18 and GPR55, in some cases endowed with additional BChE-selective inhibition. The desired outcome is the combination of the anticholinesterase activity with the modulation of these poorly studied receptors, for a synergistic effect against neuroinflammation and neurodegeneration. Structure−activity relationships were analyzed, and selectivity versus cannabinoid (CB) and CB-like receptors was assessed. Chemical synthesis and analysis, radioligand binding and functional assays, enzymes’ inhibition kinetics and molecular modeling studies, in addition to allowing us to select candidates for in vivo pharmacological evaluation, provided us with useful medicinal chemistry information enabling the optimization of MTDLs against neurological disorders, potentially more effective than the currently available
Travelling-wave resonant four-wave mixing breaks the limits of cavity-enhanced all-optical wavelength conversion
No full textWave mixing inside optical resonators, while experiencing a large enhancement of the nonlinear interaction efficiency, suffers from strong bandwidth constraints, preventing its practical exploitation for processing broad-band signals. Here we show that such limits are overcome by the new concept of travelling-wave resonant four-wave mixing (FWM). This approach combines the efficiency enhancement provided by resonant propagation with a wide-band conversion process. Compared with conventional FWM in bare waveguides, it exhibits higher robustness against chromatic dispersion and propagation loss, while preserving transparency to modulation formats. Travelling-wave resonant FWM has been demonstrated in silicon-coupled ring resonators and was exploited to realize a 630-μm-long wavelength converter operating over a wavelength range wider than 60 nm and with 28-dB gain with respect to a bare waveguide of the same physical length. Full compatibility of the travelling-wave resonant FWM with optical signal processing applications has been demonstrated through signal retiming and reshaping at 10 Gb s(-1)
Evaluation of the Effects of Undenatured Type II Collagen (UC-II) as Compared to Robenacoxib on the Mobility Impairment Induced by Osteoarthritis in Dogs
No full textOsteoarthritis (OA) is a chronic disease that requires a multimodal therapeutic approach. The aim of this study was to evaluate the effects of undenatured type II collagen (UC-II) as compared to robenacoxib in dogs affected by OA. Our hypothesis was that the two compounds would be similar (non-inferiority) in improving mobility. To test this hypothesis, a complete orthopedic examination, x-ray and the Liverpool Osteoarthritis in Dogs (LOAD) survey were performed in dogs affected by OA before and after the treatments. The study was designed as a clinical, randomized, controlled and prospective study. Sixty client-owned dogs were randomized in the R group (n = 30, robenacoxib 1 mg/kg/day for 30 days) and in the UC-II group (n = 30, UC-II 1 tablet/day for 30 days). Thirty days after the beginning of the treatment (T30), the dogs were reassessed for the LOAD, MOBILITY and CLINICAL scores. Based on the data obtained from the study, a significant reduction in LOAD and MOBILITY scores was recorded between T0 and T30 with a similar magnitude among the two groups (R = 31.5%, p < 0.001; UC-II = 32.7%, p = 0.013). The results of this study showed that UC-II and robenacoxib were able to similarly improve mobility of dogs affected by OA
Molecular detection of avian pathogens in poultry red mite (Dermanyssus gallinae) in Algerian layer farms as a potential predictive tool
No full text: The poultry red mite Dermanyssus gallinae is a hematophagous ectoparasite of layer hens. Infestations with poultry red mites pose an increasing threat to the egg production industry, causing serious problems to animal health and welfare, directly or indirectly as a vector of several infectious agents. In this study, we aimed to investigate common avian pathogens in mites. The mite samples were collected from 58 poultry farms in 7 regions accounting for more than 70 % of the national egg production in Algeria. The presence of 13 avian pathogens was detected using DNA and RNA samples from mites collected. Results revealed significant associations between PRM and potential pathogens such as Escherichia coli, Salmonella enterica, fowlpox virus, and gallid herpesvirus 1. Pathogen detection in Dermanyssus gallinae could serve as an early diagnostic or a risk analysis tool for infectious diseases in poultry farms, facilitating effective disease management strategies. Despite further research being necessary to address uncertainties, such a strategy could be used to enhance the integrated management of poultry health
Evaluation of clinical efficacy of undenatured type II collagen supplementation compared to cimicoxib and their association in dogs affected by natural occurring osteoarthritis
No full textThe aim of the study was to evaluate the clinical efficacy of 30 days treatment of undenatured type II collagen (UC-II (R)), compared to cimicoxib and to their combination, in osteoarthritic dogs. Client-owned dogs were enrolled in a clinical, randomized, controlled and prospective study. Posture, lameness, pain, range of motion and x-ray of affected joint(s) were evaluated and scored based on severity (CLINICAL score). The Liverpool Osteoarthritis in Dogs survey was used to score the owner evaluation of dog's mobility (LOAD score and MOBILITY score). Osteoarthritis (OA) stage was defined through the Canine Osteoarthritis Staging tool (COAST). After diagnosis (T0), all patients were randomly assigned to different treatment groups: C group = cimicoxib 2 mg/kg/day orally OS, F group = UC-II (R) 1 tablet per day OS; C + F group = cimicoxib-UC-II (R) at the same previous dosages; CTR group = dogs who didn't received any treatment. All treatments were administered for 30 days. Seventy-six dogs completed the study. LOAD score was recorded significant lower after treatment for each group, with a reduction in percentage of 29.5% for C, 31.4% for F, 21.1% for C + F. LOAD score was lower in C(P = 0.04), F(P = 0.001) and C + F(P = 0.009) group at T30 than CTR group. MOBILITY and CLINICAL scores were significantly lower in all groups at T30, when compared to T0. MOBILITY score was lower than CTR in C(P = 0.02) and F(P = 0.01); CLINICAL score was lower in C + F(P = 0.016). The present findings prove that the treatment with UC-II (R), cimicoxib and their combination provide significant reduction in clinical signs associated with OA
Precise fabrication of coupled ring-resonator structures
No full textWe report improvements in fabrication precision obtained in coupled ring-resonator slow-wave structures on an SOI platform. Optical delay lines were formed by using a cascade of coupled resonant cavities to slow the propagation of light through the combined effects of resonance and increased optical path length. Mismatch between the resonance frequencies of individual rings has the additional effect of broadening the spectrum - and such mismatch can compromise the correct operation of the fabricated device structures. Single-ring resonator, bus-coupled ring resonator all-pass filters and directly coupled ring resonators in apodised structures have been fabricated, in order to assess the variability of the process
Dermanyssus gallinae: the long journey of the poultry red mite to become a vector
No full textThe possibility that Dermanyssus gallinae, the poultry red mite, could act as a vector of infectious disease-causing pathogens has always intrigued researchers and worried commercial chicken farmers, as has its ubiquitous distribution. For decades, studies have been carried out which suggest that there is an association between a wide range of pathogens and D. gallinae, with the transmission of some of these pathogens mediated by D. gallinae as vector. The latter include the avian pathogenic Escherichia coli (APEC), Salmonella enterica serovars Enteritidis and Gallinarum and influenza virus. Several approaches have been adopted to investigate the relationship between D. gallinae and pathogens. In this comprehensive review, we critically describe available strategies and methods currently available for conducting trials, as well as outcomes, analyzing their possible strengths and weaknesses, with the aim to provide researchers with useful tools for correctly approach the study of the vectorial role of D. gallinae
Travelling-wave resonant four-wave mixing on a silicon chip
No full textWe demonstrate that travelling-wave four-wave
mixing in coupled resonators overcomes the bandwidth
limitations of wavelength conversion in single resonators,
preserving the efficiency enhancement: 28-dB gain over silicon
waveguides of the same length is here achieved
(1)H-NMR metabolomic profile of healthy and osteoarthritic canine synovial fluid before and after UC-II supplementation
No full textThe aim of the study was to compare the metabolomic synovial fluid (SF) profile of dogs affected by spontaneous osteoarthritis (OA) and supplemented with undenatured type II collagen (UC-II), with that of healthy control dogs. Client-owned dogs were enrolled in the study and randomized in two different groups, based on the presence/absence of OA (OA group and OA-free group). All dogs were clinically evaluated and underwent SF sampling for (1)H-Nuclear Magnetic Resonance spectroscopy ((1)H-NMR) analysis at time of presentation. All dogs included in OA group were supplemented with UC-II orally administered for 30 days. After this period, they were reassessed (OA-T30). The differences in the (1)H-NMR metabolic SFs profiles between groups (OA-free, OA-T0 and OA-T30) were studied. The multivariate statistical analysis performed on SFs under different conditions (OA-T0 vs OA-T30 SFs; OA-T0 vs OA-free SFs and OA-T30 vs OA-free SFs) gave models with excellent goodness of fit and predictive parameters, revealed by a marked separation between groups. β-Hydroxybutyrate was identified as a characteristic compound of osteoarthritic joints, showing the important role of fat metabolism during OA. The absence of β-hydroxybutyrate after UC-II supplementation suggests the supplement’s effectiveness in rebalancing the metabolism inside the joint. The unexpectedly high level of lactate in the OA-free group suggests that lactate could not be considered a good marker for OA. These results prove that (1)H-NMR-based metabolomic analysis is a valid tool to study and monitor OA and that UC-II improves clinical symptoms and the SF metabolic profile in OA dogs
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