Fyhnbartlett5455
Data from the experiment conducted on rats demonstrated both an acute metabolic decrease in mesencephalic structures (SNpc and nucleus ruber) after a single injection of rotenone and secondary changes in cortical structures (S1 cortex and dorsal hippocampus) after chronic 7 day exposure. These changes reflect the general effect of rotenone on neuronal metabolic rate.This work aims to understand the properties of co-formers that form co-amorphous pharmaceutical materials and to predict co-amorphous system formation. A partial least square - discriminant analysis (PLS-DA) was performed using known co-amorphous systems described by 36 variables based on the properties of the co-former and the binding energy of the system. The PLS-DA investigated the propensity to form co-amorphous material of the active pharmaceutical ingredients mebendazole, carvedilol, indomethacin, simvastatin, carbamazepine and furosemide in combination with 20 amino acid co-formers. The variables that were found to favour the propensity to form co-amorphous systems appear to be a relatively large value for average molecular weight and the sum of the difference between hydrogen bond donors and hydrogen bond acceptors for both components, and a relatively small or negative value for excess enthalpy of mixing, excess enthalpy of hydrogen bonding and the difference in the Hansen parameter for hydrogen bonding of the coformer and the active pharmaceutical ingredient (API). To test the predictive power of this model, 29 potential co-formers were used to form either co-amorphous or crystalline two-component materials with mebendazole. Of these 29 two-component systems, the co-amorphous nature of a total of 26 materials was correctly predicted by the model, giving a predictive hit rate of 90 %.
Organochlorine pesticides such as DDT as well as postprandial hypertriglyceridemia have been linked with insulin resistance and diabetes mellitus. The cardiometabolic risk of PPhTg could also be due to its potential to increase the serum levels of this highly lipophilic pesticide. We studied the effect of postprandial triglyceride responses to a standard oral fat challenge on the levels of DDT and its metabolites in subjects with varying degree of glucose intolerance METHODS A standard fat challenge was performed in 60 subjects who were categorized as NGT, prediabetes, and NDDM based on an earlier OGTT. Fasting and postprandial levels of serum triglycerides, plasma DDT and its metabolites were estimated and compared in the 3 groups and their association with each other, and measures of glycemia and insulin resistance were also determined.
Peak Tg and TgAUC levels were significantly higher in NDDM group as compared to NGT and PD groups. TgAUC showed positive correlation with fasting plasma glucose (r=0.33, p=0.01), postprandial plasma glucose (r=0.39, p=0.002) and HOMA IR(r=0.63, p=0.001). ppDDE levels were found to be significantly higher in NDDM subjects compared with NGT group. ppDDE-AUC was significantly higher in the NDDM group compared with the other two study groups. Temsirolimus order Mean ppDDE levels also showed strong positive correlation with peak Tg (r=0.295 p=0.022), TgAUC (r=0.303 p=0.018), iPPTgAUC(r=0.57 p≤0.001) and iPPpeakTg(r=0.51 p≤0.001) as well as with FPG (r=0.269 p=0.038) PPPG (r=0.424 p=0.001) and HbA1c (r=0.321 p=0.012).
The findings of this study support the concept that the cardiometabolic risk associated with PPhTg may at least in part be related to the associated increase in serum levels of lipophilic OCPs like DDT.
The findings of this study support the concept that the cardiometabolic risk associated with PPhTg may at least in part be related to the associated increase in serum levels of lipophilic OCPs like DDT.
This study was performed to investigate the multi-targets mechanism of hydroxychloroquine (HCQ) in the treatment of rheumatoid arthritis (RA).
The predicted targets of HCQ and the proteins related to RA were returned from databases. Followed by protein-protein interaction (PPI) network, the intersection of the two group of proteins was studied. Furthermore, gene ontology (GO) and KyotoEncyclopediaofGenesandGenomes (KEGG) enrichment was used to analyse these proteins in a macro perspective. Finally, the candidate targets were checked by molecular docking.
The results suggested that HCQ in the treatment of RA was mainly associated with 4 targets that are smoothened homolog (SMO), sphingosine kinase (SPHK) 1, SPHK2 and gatty-acid amide hydrolase (FAAH), with their related 3276 proteins' network which regulate ErbB, HIF-1, NF-κB, FoxO, chemokines, MAPK, PI3K/Akt pathways and so forth. Biological process were mainly focused in the regulation of cell activation, myeloid leukocyte activation, regulated exocytosis and so forth. Molecular docking analysis showed that hydrogen bonding and π-π stacking were the main forms of chemical force.
Our research provides protein targets affected by HCQ in the treatment of RA. SMO, SPHK1, SPHK2 and FAAH involving 3276 proteins become the multi-targets mechanism of HCQ in the treatment of RA.
Our research provides protein targets affected by HCQ in the treatment of RA. SMO, SPHK1, SPHK2 and FAAH involving 3276 proteins become the multi-targets mechanism of HCQ in the treatment of RA.
International antibiotic awareness and stewardship campaigns use social media to disseminate campaign materials. Analysis of campaigns during 2016 and 2017 identified a wide range of hashtags in use, potentially leading to confusion and dilution of the campaign message. This study aimed to examine the impact of different hashtags on the dissemination of information during European Antibiotic Awareness Day and World Antibiotic Awareness Week, November 2018.
Tweets were prospectively extracted using Followthehashtag and analysed in Excel and R (14 400 tweets by 5 899 tweeters, with 60 222 retweets). Descriptive analysis and multivariable logistic regression analyses were adjusted for potential confounders.
There was a positive association between retweets received and inclusion of media, hashtag(s), mention of other tweeter(s), and number of followers. There was hashtag drift (e.g. the unofficial #WAAW2018 hashtag was used more frequently than the official campaign #WAAW18 hashtag). Analysis of five popular hashtags from the European and worldwide campaigns found a positive association between retweets and the unofficial hashtag #WAAW2018 and the long-established #AntibioticGuardian hashtag.