Phthalimido-alkyl-1H-1,2,3-triazole derivatives 3a–d and 4a–d were efficiently synthesized using 1,3-dipolar cycloaddition reaction. Anti-inflammatory activity and toxicity studies were performed. ...The results demonstrated that all the tested compounds reduced carrageenan-induced paw edema and indicated no lethality for toxicity against Artemia salina and acute toxicity in vivo (LD50 up to 1 g kg −1). Furthermore, the structure of phthalimide linked to phenyl group proved to be more active than the compounds containing benzothiazole moiety. Structural modifications such as removal of the phthalimide group and subsequent acetylation, to exemplify a non-cyclic amide, demonstrate that the phthalimide and triazole moieties are important for design of potent candidates with anti-inflammatory drug proprieties. Docking into the cyclooxygenase-2 (COX-2) confirms the importance of the phthalimide and triazole groups in the anti-inflammatory activity. The histopathological studies showed that the compounds 3a–d and 4a–d did not cause serious pathological lesions liver or kidneys.
Reactive oxygen species (ROS) are involved in neuropathic pain, a complicated condition after nerve tissue lesion. Vitamin D appears to improve symptoms of pain and exhibits antioxidant properties. ...We investigated the effects of oral administration of vitamin D3, the active form of vitamin D, on nociception, the sciatic functional index (SFI), and spinal cord pro-oxidant and antioxidant markers in rats with chronic constriction injury (CCI) of the sciatic nerve, a model of neuropathic pain. Vitamin D3 (500 IU/kg per day) attenuated the CCI-induced decrease in mechanical withdrawal threshold and thermal withdrawal latency (indicators of antinociception) and SFI. The vitamin prevented increased lipid hydroperoxide levels in injured sciatic nerve without change to total antioxidant capacity (TAC). Vitamin D3 prevented increased lipid hydroperoxide, superoxide anion generation (SAG), and hydrogen peroxide (H2O2) levels in the spinal cord, which were found in rats without treatment at 7 and 28 days post-CCI. A significant negative correlation was found between mechanical threshold and SAG and between mechanical threshold and H2O2 at day 7. Vitamin D3 also prevented decreased spinal cord total thiols content. There was an increase in TAC in the spinal cord of vitamin-treated CCI rats, compared to CCI rats without treatment only at 28 days. No significant changes were found in body weight and blood parameters of hepatic and renal function. These findings demonstrated, for first time, that vitamin D modulated pro-oxidant and antioxidant markers in the spinal cord. Since antinociception occurred in parallel with oxidative changes in the spinal cord, the oxidative changes may have contributed to vitamin D-induced antinociception.
BACKGROUND AND PURPOSE Bones are widely innervated, suggesting an important role for the sympathetic regulation of bone metabolism, although there are controversial studies. We investigated the ...effects of propranolol in a model of experimental periodontal disease.
EXPERIMENTAL APPROACH Rats were assigned as follows: animals without ligature; ligated animals receiving vehicle and ligated animals receiving 0.1, 5 or 20 mg·kg−1 propranolol. After 30 days, haemodynamic parameters were measured by cardiac catheterization. Gingival tissues were removed and assessed for IL‐1β, TNF‐α and cross‐linked carboxyterminal telopeptides of type I collagen (CTX) by elisa, or intercellular adhesion molecule 1 (ICAM‐1), receptor activator of NF‐κ B ligand (RANKL) and osteoprotegerin (OPG) by Western blot analysis. Sections from the mandibles were evaluated for bone resorption. Also, we analysed the ability of propranolol to inhibit osteoclastogenesis in vitro.
RESULTS Propranolol at 0.1 and 5 mg·kg−1 reduced the bone resorption as well as ICAM‐1 and RANKL expression. However, only 0.1 mg·kg−1 reduced IL‐1β, TNF‐α and CTX levels as well as increased the expression of OPG, but did not alter any of the haemodynamic parameters. Propranolol also suppressed in vitro osteoclast differentiation and resorptive activity by inhibiting the nuclear factor of activated T cells (NFATc)1 pathway and the expression of tartrate‐resistant acid phosphatase (TRAP), cathepsin K and MMP‐9.
CONCLUSIONS AND IMPLICATIONS Low doses of propranolol suppress bone resorption by inhibiting RANKL‐mediated osteoclastogenesis as well as inflammatory markers without affecting haemodynamic parameters.
Tin dioxide (SnO2) has intrinsic characteristics that do not favor its photocatalytic activity. However, we evidenced that surface modification can positively influence its performance for CO2 ...photoreduction in the gas phase. The hydroxylation of the SnO2 surface played a role in the CO2 affinity decreasing its reduction potential. The results showed that a certain selectivity for methane (CH4), carbon monoxide (CO), and ethylene (C2H4) is related to different SnO2 hydrothermal annealing. The best performance was seen for SnO2 annealed at 150 °C, with a production of 20.4 μmol g−1 for CH4 and 16.45 μmol g−1 for CO, while for SnO2 at 200 °C the system produced more C2H4, probably due to a decrease of surface −OH groups.
SnO2 nanoparticles are synthesized and applied in the CO2 photoreduction process. The synthesis methodology produces strongly bonded ‐OH groups, which influences the process of reducing the CO2 potential as well as its affinity. The hydroxyl groups act as charge mediators, reducing the potential for CO2 reduction. The semiconductors show selectivity to C1 hydrocarbons and the sample subjected to higher annealing shows selectivity for C2 products.
A large proportion of older persons in developing countries do not have access to pension, which also constrains their ability to afford healthcare services and entails extensive challenges to the ...well-being of older people. This study aimed to analyze the financial preparedness of different age groups for retirement in Brazil. Data were derived from a survey to empirically validate the proposed relationships between preparedness for retirement and resilience for the future (financial well-being (FWB) outcomes) on the one hand and among demographic and socioeconomic aspects, behaviors and attitudes, knowledge and experience, and “key” psychological factors on the other hand. The sample consisted of 412 individuals aged between 22 and 79 years. FWB was measured using the financial capability and well-being model and regressed on a number of sociodemographic and psychological variables using linear regression analyses. The results demonstrated that preparedness for retirement was strongly related to older age. Additionally, age was correlated with resilience for the future close to zero, which indicates no relationship. Knowledge and the psychological factors of self-control and confidence were positively and strongly related to better financial behavior for all age groups. In addition, grit and resilience for the future were positively related to better financial behavior in the older age group. Furthermore, the variables of retirement contribution were seemingly not viewed as important to the older group compared with their young and mature counterparts. Multidimensional interventions, especially targeting behaviors and psychological patterns, could, therefore, be recommended in advance to young and mature groups to prepare them to secure their old age and achieve FWB.
Adenosine Receptor Type 2A (A
AR) plays a role in important processes, such as anti-inflammatory ones. In this way, the present work aimed to search for compounds by pharmacophore-based virtual ...screening. The pharmacokinetic/toxicological profiles of the compounds, as well as a robust QSAR, predicted the binding modes via molecular docking. Finally, we used molecular dynamics to investigate the stability of interactions from ligand-A
AR. For the search for A
AR agonists, the UK-432097 and a set of 20 compounds available in the BindingDB database were studied. These compounds were used to generate pharmacophore models. Molecular properties were used for construction of the QSAR model by multiple linear regression for the prediction of biological activity. The best pharmacophore model was used by searching for commercial compounds in databases and the resulting compounds from the pharmacophore-based virtual screening were applied to the QSAR. Two compounds had promising activity due to their satisfactory pharmacokinetic/toxicological profiles and predictions via QSAR (Diverset 10002403 pEC
= 7.54407; ZINC04257548 pEC
= 7.38310). Moreover, they had satisfactory docking and molecular dynamics results compared to those obtained for Regadenoson (Lexiscan
), used as the positive control. These compounds can be used in biological assays (in vitro and in vivo) in order to confirm the potential activity agonist to A
AR.
Abstract
The CO
2
photoreduction process to produce light hydrocarbons is known to be influenced by the presence of CuO nanoparticles, but the actual role of this material, whether as a catalyst or a ...reactant, has not yet been revealed. In this work, we investigate the role of CuO nanoparticles produced by a solvothermal method as a catalyst in CO
2
-saturated water reaction media under UV light, considering the effects of different electrolytes (Na
2
C
2
O
4
, KBrO
3
, and NaOH) and temperatures on nanoparticle phase and activity. The electrolyte strongly influenced product selectivity (NaOH led to evolution of CH
4
, Na
2
C
2
O
4
to CO, and KBrO
3
to O
2
) and induced CuO phase change. A long-term analysis of these processes indicated that during the initial steps, CuO acted as a reactant, rather than as a catalyst, and was converted to CuCO
3
.Cu(OH)
2
, while the as-converted material acted as a catalyst in CO
2
photoreduction, with conversion values comparable to those reported in the literature.
•WHO and ILO are developing joint estimates of work-related burden of disease and injury.•We systematically reviewed effect of occupational exposure to noise on CVD.•We found 17 eligible studies with ...534,688 participants in 11 countries/3 WHO regions.•We are very uncertain about the effect of occupational exposure to noise on CVD.
The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large number of individual experts. Evidence from mechanistic data suggests that occupational exposure to noise may cause cardiovascular disease (CVD). In this paper, we present a systematic review and meta-analysis of parameters for estimating the number of deaths and disability-adjusted life years from CVD that are attributable to occupational exposure to noise, for the development of the WHO/ILO Joint Estimates.
We aimed to systematically review and meta-analyse estimates of the effect of any (high) occupational exposure to noise (≥85 dBA), compared with no (low) occupational exposure to noise (<85 dBA), on the prevalence, incidence and mortality of ischaemic heart disease (IHD), stroke, and hypertension.
A protocol was developed and published, applying the Navigation Guide as an organizing systematic review framework where feasible. We searched electronic academic databases for potentially relevant records from published and unpublished studies up to 1 April 2019, including International Trials Register, Ovid MEDLINE, PubMed, Embase, Lilacs, Scopus, Web of Science, and CISDOC. The MEDLINE and Pubmed searches were updated on 31 January 2020. We also searched grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews and included study records; and consulted additional experts.
We included working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (<15 years) and unpaid domestic workers. We included randomized controlled trials, cohort studies, case-control studies and other non-randomized intervention studies with an estimate of the effect of any occupational exposure to noise on CVD prevalence, incidence or mortality, compared with the theoretical minimum risk exposure level (<85 dBA).
At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. We prioritized evidence from cohort studies and combined relative risk estimates using random-effect meta-analysis. To assess the robustness of findings, we conducted sensitivity analyses (leave-one-out meta-analysis and used as alternative fixed effects and inverse-variance heterogeneity estimators). At least two review authors assessed the risk of bias, quality of evidence and strength of evidence, using Navigation Guide tools and approaches adapted to this project.
Seventeen studies (11 cohort studies, six case-control studies) met the inclusion criteria, comprising a total of 534,688 participants (39,947 or 7.47% females) in 11 countries in three WHO regions (the Americas, Europe, and the Western Pacific). The exposure was generally assessed with dosimetry, sound level meter and/or official or company records. The outcome was most commonly assessed using health records. We are very uncertain (low quality of evidence) about the effect of occupational exposure to noise (≥85 dBA), compared with no occupational exposure to noise (<85 dBA), on: having IHD (0 studies); acquiring IHD (relative risk (RR) 1.29, 95% confidence interval (95% CI) 1.15 to 1.43, two studies, 11,758 participants, I2 0%); dying from IHD (RR 1.03, 95% CI 0.93–1.14, four studies, 198,926 participants, I2 26%); having stroke (0 studies); acquiring stroke (RR 1.11, 95% CI 0.82–1.65, two studies, 170,000 participants, I2 0%); dying from stroke (RR 1.02, 95% CI 0.93–1.12, three studies, 195,539 participants, I2 0%); having hypertension (0 studies); acquiring hypertension (RR 1.07, 95% CI 0.90–1.28, three studies, four estimates, 147,820 participants, I2 52%); and dying from hypertension (0 studies). Data for subgroup analyses were missing. Sensitivity analyses supported the main analyses.
For acquiring IHD, we judged the existing body of evidence from human data to provide “limited evidence of harmfulness”; a positive relationship is observed between exposure and outcome where chance, bias, and confounding cannot be ruled out with reasonable confidence. For all other included outcomes, the bodies of evidence were judged as “inadequate evidence of harmfulness”. Producing estimates for the burden of CVD attributable to occupational exposure to noise appears to not be evidence-based at this time.
10.1016/j.envint.2018.09.040.
CRD42018092272.
The fermentation profile, chemical composition, and microbial populations of alfalfa silages treated with microbial inoculants (MI) at different fermentation periods (T) were evaluated in tropical ...conditions. A 4×6 factorial arrangement was used in a randomized design with 3 replicates. Fresh alfalfa was treated with (1) no treatment (CTRL), (2) commercial inoculant (CIN), (3) Pediococcus acidilactici (strain 10.6, S1), and (4) Pediococcus pentosaceus (strain 6.16, S2). An inoculant application rate of 106 cfu/g of fresh forage was used. The fermentation periods were 1, 3, 7, 14, 28, and 56 d. Alfalfa was harvested 82 d after sowing at the early flowering stage, chopped into 1.5-cm particle size, and ensiled in 25×35cm vacuum-sealed plastic bags. The numbers of lactic acid bacteria, enterobacteria, mold, and yeast in alfalfa before ensiling were 5.42, 5.58, 4.82, and 4.8 log cfu/g, respectively. Silage chemical composition was evaluated only at 56 d. All parameters were affected by the interaction MI × T, except the concentrations of lactic and propionic acids. Alfalfa silage treated with S1 or S2 had lower pH values than CTRL from the first day until 28 d. However, the inoculants resulted in similar pH after 56 d, and these values were lower than the CTRL. The highest concentration of lactic acid was observed in the silage treated with S1 and S2 at 7 and 14 d of ensiling. The concentration of acetic acid was lower in the silages treated with S1 and S2 than the CTRL and CIN at 3 and 28 d of fermentation. There was no effect of MI or MI × T interaction on the microbial populations. However, the number of enterobacteria decreased over the fermentation period until 14 d and increased slightly after this time point. The chemical composition of alfalfa silage was not affected by MI at 56 d of ensiling. The strain P. pentosaceus 6.16 was the most efficient in dominating the fermentation process by decreasing the pH more quickly and increasing the concentration of lactic acid, suggesting its potential use as a silage inoculant.
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