During the years, many usnic acid (UA) conjugates have been synthesized to obtain potent endowed with biological properties. Since (
)-UA is less abundant in nature than (
)-enantiomer, it is ...difficult to source, thus precluding a deeper investigation. Among the lichens producing UA,
is a valuable (S)-UA source. In the present work, we report on a rapid HPLC-UV/PAD-CD protocol suitable for the analysis and the identification of the main secondary metabolites present in
extract. Best results were achieved using XBridge Phenyl column and acetonitrile and water, which were both added with formic acid as mobile phase in gradient elution. By combining analytical, spectroscopical, and chiroptical analysis, the most abundant analyte was unambiguously identified as (
)-UA. Accordingly, a versatile microwave-assisted extractive (MAE) protocol, assisted by a design of experiment (DoE), to quantitatively recover (
)-UA was set up. The best result in terms of UA extraction yield was obtained using ethanol and heating at 80 °C under microwave irradiation for 5 min. Starting from 100 g of dried
, 420 mg of (
)-UA were achieved. Thus, our extraction method resulted in a suitable protocol to produce (
)-UA from
for biological and pharmaceutical investigation or commercial purposes.
During the past several years, the frequency of discovery of new molecular entities based on γ- or δ-lactam scaffolds has increased continuously. Most of them are characterized by the presence of at ...least one chiral center. Herein, we present the preparation, isolation and the absolute configuration assignment of enantiomeric 2-(4-bromophenyl)-1-isobutyl-6-oxopiperidin-3-carboxylic acid (
-
). For the preparation of racemic
-
, the Castagnoli-Cushman reaction was employed. (Semi)-preparative enantioselective HPLC allowed to obtain enantiomerically pure
-
whose absolute configuration was assigned by X-ray diffractometry. Compound (+)-(
)-
represents a reference compound for the configurational study of structurally related lactams.
The aim of this study was to compare sociodemographic characteristics, patterns of drug use, and risky sexual behaviour among female and male users of crack cocaine.
Between 2012 and 2013, we ...conducted a cross-sectional study of 919 crack cocaine users (783 men and 136 women) in Central Brazil using face-to-face interviews. Blood samples were collected to test for syphilis. The Chi-Square Automatic Interaction Detector (CHAID) was used to explore the differences between genders. We implemented two models: the first model included previous incarceration and variables related to patterns of drug use, and the second model included variables related to sexual risky behaviours and syphilis exposure.
Women consumed more crack cocaine than men on a regular basis; however, poly-drug use was more common among men. More women than men reported exchanging sex for money and/or drugs and inconsistent condom use during sexual intercourse; women also reported more sexual partners. In addition, the frequency of sexual violence was higher for women than men. A higher proportion of women than men were positive for syphilis (27.2% vs. 9.2%; p < 0.001). The CHAID decision tree analysis identified seven variables that differentiated the genders: previous incarceration, marijuana use, daily crack cocaine consumption, age at first illicit drug use, sexual violence, exchange of sex for money and/or drugs, and syphilis exposure.
Our findings demonstrate a difference in patterns of crack cocaine consumption and sexual risky behaviours between genders, thus indicating a need for gender-specific interventions in this population.
The association of situs inversus totalis and left ventricular noncompaction is very rare and poses several and unique challenges if endo‐epicardial ablation has to be performed, both for anatomical ...access to the target area and for arrhythmia complexity. We report a case of incessant ventricular tachycardia with endo‐epicardial involvement that required ablation in both surfaces to obtain final noninducibility
The metabolism of α-tocopherol (α-TOH, vitamin E) shows marked interindividual variability, which may influence the response to nutritional and therapeutic interventions with this vitamin. Recently, ...new metabolomics protocols have fostered the possibility to explore such variability for the different metabolites of α-TOH so far identified in human blood, i.e., the "vitamin E metabolome", some of which have been reported to promote important biological functions. Such advances prompt the definition of reference values and degree of interindividual variability for these metabolites at different levels of α-TOH intake. To this end, a one-week oral administration protocol with 800 U RRR-α-TOH/day was performed in 17 healthy volunteers, and α-TOH metabolites were measured in plasma before and at the end of the intervention utilizing a recently validated LC-MS/MS procedure; the expression of two target genes of α-TOH with possible a role in the metabolism and function of this vitamin, namely pregnane X receptor (PXR) and the isoform 4F2 of cytochrome P450 (CYP4F2) was assessed by immunoblot in peripheral blood leukocytes. The levels of enzymatic metabolites showed marked interindividual variability that characteristically increased upon supplementation. With the exception of α-CEHC (carboxy-ethyl-hydroxychroman) and the long-chain metabolites M1 and α-13'OH, such variability was found to interfere with the possibility to utilize them as sensitive indicators of α-TOH intake. On the contrary, the free radical-derived metabolite α-tocopheryl quinone significantly correlated with the post-supplementation levels of α-TOH. The supplementation stimulated PXR, but not CYP4F2, expression of leucocytes, and significant correlations were observed between the baseline levels of α-TOH and both the baseline and post-supplementation levels of PXR. These findings provide original analytical and molecular information regarding the human metabolism of α-TOH and its intrinsic variability, which is worth considering in future nutrigenomics and interventions studies.
The spread of microorganisms causing health-care associated infection (HAI) is contributed to by their intrinsic tolerance to a variety of biocides, used as antiseptics or disinfectants. The natural ...monomeric stilbenoid resveratrol (RV) is able to modulate the susceptibility to the chlorhexidine digluconate (CHX) biocide in Acinetobacter baumannii. In this study, a panel of reference strains and clinical isolates of Gram-negative bacteria, Gram-positive bacteria and yeasts were analyzed for susceptibility to CHX and benzalkonium chloride (BZK) and found to be tolerant to one or both biocides. The carbonyl cyanide m-chlorophenylhydrazine protonophore (CCCP) efflux pump inhibitor reduced the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CHX and BZK in the majority of strains. RV reduced dose-dependently MIC and MBC of CHX and BZK biocides when used as single agents or in combination in all analyzed strains, but not CHX MIC and MBC in Pseudomonas aeruginosa, Candida albicans, Klebsiella pneumoniae, Stenotrophomonas maltophilia and Burkholderia spp. strains. In conclusion, RV reverts tolerance and restores susceptibility to CHX and BZK in the majority of microorganisms responsible for HAI. These results indicates that the combination of RV, CHX and BZK may represent a useful strategy to maintain susceptibility to biocides in several nosocomial pathogens.
Lack of therapeutic adherence is a relevant problem in clinical practice and it can be assessed via validated tools such as the Test of Adherence to Inhalers (TAI). Education on the correct use of ...inhaler devices has been associated with improvement in adherence. Many studies highlighted the pivotal role of pharmacists in promoting therapeutic adherence in the management of respiratory diseases.
To evaluate the effectiveness on adherence and clinical parameters of an educational intervention administered by clinical pharmacists (CPs) to patients with asthma on long-term inhalation therapy.
A prospective comparative study involving 34 community pharmacies in Italy (23 intervention, 11 control). Enrolled subjects were evaluated for adherence to inhalation therapy by TAI, asthma control by “Asthma Control Test” (ACT), and lung function at baseline and after 2 months. The educational intervention at baseline was based on TAI results and administered by specifically trained pharmacists.
A total of 242 consecutive subjects (167 intervention, 75 control) were enrolled. There was a significant improvement in TAI score, ACT and lung function parameters (p-value<0.001) in the intervention group between baseline and the follow-up visit. Patients with baseline ACT≥20 maintained disease control more frequently in the intervention group compared to the control arm (95% vs 79.5%, p = 0.004).
Conclusions through administration of TAI-driven educational interventions addressing both technical and psychological issues, trained CPs can help improve adherence to treatment and asthma control.
•Adherence to inhalers in asthma is reported to be poor and affects asthma control.•Educational intervention by clinical pharmacists is effective in improving both adherence and asthma control.•Our results suggest that clinical pharmacists should be included in the multidisciplinary work-up of asthmatics.
The presence of tektite-like glasses from a geographically restricted area in Belize (Central America) has been known for several decades. We comprehensively studied 18 such Belize glasses by a ...variety of petrographic and geochemical methods, including major and trace element analysis, radiogenic isotopic composition (Rb-Sr, Sm-Nd, and Re-Os), water content, oxidation state, and cosmogenic radionuclides. The aims were to determine their compositional variation, their mode of formation and possible source rocks, and their relation to known tektites, and to search for evidence of an extraterrestrial component.
In terms of petrography, the samples are similar to tektites from the four “classical” strewn fields, with the presence of lechatelierites, schlieren, and vesicles; these are also widely accepted indicators of an impact origin. No close similarities to volcanic glasses are evident. Water contents are very low, and iron oxidation states are mostly reduced, in both cases similar to observations for other tektites. The geochemical and isotopic data presented, such as Cr, Co and Ni elemental abundances and interelement ratios, as well as trace element patterns are typical for local and regional volcanics from the active Central American Arc. Particular similarities to material comparable to volcanic rocks from Honduras or Guatemala are noted. This is confirmed by Sr-Nd isotope signatures of the Belize glasses, showing close similarities to Central American volcanics in general, and Honduran and Guatemalan volcanic, in particular. Osmium concentrations and 187Os/188Os ratios are comparable to arc volcanics from world-wide locations, but - in a few of the samples - elevated Ir concentrations, near-chondritic Pt/Ir and 187Os/188Os ratios can also be interpreted with the admixture of a minor meteoritic component to some of the Belize samples. 10Be concentrations are consistent with values typical of both, young or deeply buried soils and with values for Central American volcanics, which carry subducted 10Be.
Geochemical data clearly indicate a source different from that of the Australasian tektites. Both isotope data sets for the Belize glasses indicate a close relationship to local arc lavas, especially those from Guatemala and Honduras, suggesting that the glasses were not deposited very far from their source. The main evidence that the Belize glasses are of impact origin are their petrographic characteristics and low water content. The evidence from 10Be is consistent with, but does not require, a model of formation for the Belize glasses by an impact on loosely consolidated surface sediments exposed to rain. A probable meteoritic component is low and heterogeneously distributed.
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