Synthesis and binding study of certain 6-arylalkanamides as molecular probes for cannabinoid receptor subtypes

Tetrahydrocannabinol and other mixed cannabinoid (CB) receptors CB(1)/CB(2) receptor agonists are well established to elicit antinociceptive effects and psychomimetic actions, however, their potential for abuse have dampened enthusiasm for their therapeutic development. In an effort to refine a semi-rigid structural framework for CB(2) receptors binding, we designed novel compounds based on aromatic moiety and flexible linker with various amides mimicking the outlook of the endogenous anandamide which could provide as CB(2) receptor ligand. In this direction, we developed and synthesized new aryl or arylidene hexanoic acid amides and aryl alkanoic acid diamide carrying different head groups. These new compounds were tested for their affinities for human recombinant CB receptors CB(1) and CB(2) and fatty acid amide hydrolase. Although, the preliminary screening of these compounds demonstrated weak binding activity towards CB receptor subtypes at 10 µmole, yet this template still could serve up as probes for further optimization and development of affinity ligand for CB receptors

Comparative toxicity of copper oxide bulk and nano particles in Nile Tilapia; Oreochromis niloticus: Biochemical and oxidative stress

Nile Tilapia; Oreochromis niloticus are commonly used in the assessment of aquatic environment quality and also considered as useful bio-indicators during environmental pollution monitoring. The LC50/96 h of copper oxide (bulk & nano) particles [CuO (BPs & NPs)] were 2205 & 150 mg/l, respectively. Two tested concentrations of CuO (BPs & NPs) were selected: the first concentration was equivalent to (1/10) (220.5 & 15 mg/l), and the second was equivalent to (1/20) (110.25 & 7.5 mg/l) LC50/96 h·CuO (BPs & NPs), respectively. While serum glucose, liver function tests (AST, ALT and ALP) and kidney function tests (creatinine and uric acid) showed a significant increase, serum total proteins, albumin, globulin and total lipids showed a significant decrease. Both liver and gill tissues of the studied fish showed a reduction in GSH content and an elevation in MDA and GPx activities. The present study also showed an elevation in liver CAT & SOD activities when exposed to both concentrations of CuO BPs and in the case of gills when exposed to both concentrations of CuO (BPs & NPs), although activity of these enzymes showed an inhibition in the liver when exposed to both concentrations of CuO NPs. The present study investigated whether CuO NPs are more toxic than CuO BPs

Ameliorative effects of vitamins-loaded flavoured nanophytosomes fortified with star anise volatile oil against CsA-Induced liver and kidney injury in rats: Application in functional ice cream

This study investigated the effect of flavoured nanophytosomes loaded with vitamins A, E, D, B complex, folic acid, and C, as well as zinc on the immunosuppressive cyclosporin A (CsA)-induced liver and kidney injury in male rats. The vitamins flavoured nanophytosomes (VFnPs) were characterized in terms of particle size, zeta potential, encapsulation efficiency. Ice cream was flavoured with star anise volatile oil to mask the VFnPs' flavour and unacceptable taste. The study found that treatment with CsA alone resulted in increased (P > 0.05) levels of creatinine, urea, and MDA, as well as the activities of AST and ALT, while the levels of SOD, CAT, GST, proteins, CD4, INF-ᵧ, IL-6, IL-1β, and TLR4 decreased (P > 0.05). However, the group that received CsA simultaneously with VFnPs showed a significant (P > 0.05) decrease in the levels of creatinine, urea, and MDA, as well as the activities of AST and ALT, and increased (P > 0.05) levels of SOD, CAT, GST, proteins, CD4, INF-ᵧ, IL-6, IL-1β, and TLR4. The increase in the ratio of VFnPs had little effect on the physiochemical and sensory evaluation of the ice cream. Finally, the study suggests that VFnPs could potentially protect against CsA-induced liver and kidney injury and serve as a promising natural therapy for treating such conditions

Accelerated surgery versus standard care in hip fracture (HIP ATTACK) : an international, randomised, controlled trial

Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4\u20139) in the accelerated-surgery group and 24 h (10\u201342) in the standard-care group (p<0\ub70001). 140 (9%) patients assigned to accelerated surgery and 154 (10%) assigned to standard care died, with a hazard ratio (HR) of 0\ub791 (95% CI 0\ub772 to 1\ub714) and absolute risk reduction (ARR) of 1% ( 121 to 3; p=0\ub740). Major complications occurred in 321 (22%) patients assigned to accelerated surgery and 331 (22%) assigned to standard care, with an HR of 0\ub797 (0\ub783 to 1\ub713) and an ARR of 1% ( 122 to 4; p=0\ub771). Interpretation: Among patients with a hip fracture, accelerated surgery did not significantly lower the risk of mortality or a composite of major complications compared with standard care. Funding: Canadian Institutes of Health Research