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The alteration of the gut microbiota mediated by proton pump inhibitor (PPI) drugs could be involved in the clinical response associated with immunotherapy [immunocheckpoint inhibitors (ICIs)] in cancer patients. Due to the current controversy in the scientific evidence, it has been proposed to evaluate the correlation between the concomitant use of PPIs and the effectiveness of immunotherapy in a real clinical practice setting. Single-center retrospective cohort study that included patients treated with anti-PD-1 or anti-CTLA4, including nivolumab, pembrolizumab, atezolizumab, or the combination ipilimumab-nivolumab in metastatic neoplastic disease. The clinical effectiveness of ICI, measured in progression-free survival (PFS) and overall survival (OS), was compared between the PPI-use versus PPI-no-use group. PPI-use group was associated with lower PFS [hazard ratio (HR):1.89 (1.38-2.59), P<0.001] and OS [HR: 2.02 (1.45-2.82), P<0.001] versus PPI-no-use group. However, this difference was not observed for pembrolizumab PFS [HR: 1.38 (0.93-2.39), P=0.160] and OS [HR: 1.41 (0.81-2.44), P=0.187]. The study showed significantly lower PFS and OS in the chronic PPI-use group (P<0.001), recent PPI-use group (P<0.001) and concomitant PPI-use group (P=0.001, 0.007) versus PPI-no-use group. However, late PPI use >30 days after the onset of ICI has no significant effect on the efficacy of treatment [HR: 0.92 (0.49-1.70), P=0.791; HR: 1.10 (0.59-2.05), P=0.756]. The concomitant use of PPIs in immunotherapy is associated with worse clinical outcomes compared with the group without PPI use. In addition, the study shows how the late use of PPIs does not have a significant effect on clinical benefit.
RESUMO
Biodegradable films based on agar with glycerol (GLY) as a plasticizer were developed by incorporating hydroalcoholic garlic extract (HGE) on the film surface. The effect of GLY content (0, 15, or 30 wt%) and different concentrations of HGE (0, 0.5, 1, or 1.5 µg/mL) on the physicochemical and transport properties of the films was evaluated. The optical (color and transparency), mechanical (tensile test), transport (diffusion and water vapor transmission rate), thermal (thermogravimetric analysis) structural (infrared spectroscopy and X-ray diffraction), and morphological (scanning electron microscope) properties were analyzed. The impregnation of HGE increased the transparency values and decreased the luminosity, tensile strength, elastic modulus, and crystallinity of the agar films. The formulation of 30 wt% GLY with 1.5 µg/mL HGE, identified as 30 GLY [1.5], showed a similar thermal stability that of a neat agar film. The agar films with 30 wt% GLY showed the lowest diffusion coefficient and water vapor transmission rate, indicating that volatile compounds are slowly released. From the results the formulation 30 GLY [1.5] could be used as a film to transport and to release HGE which is supported by a biodegradable matrix and this system has a potential use as insect semiochemical for plague control.
Assuntos
Ágar/química , Fenômenos Químicos , Alho/química , Feromônios/química , Extratos Vegetais/química , Algoritmos , Biodegradação Ambiental , Modelos Teóricos , Vapor , Resistência à Tração , Termogravimetria , Difração de Raios XRESUMO
The electro-Fenton degradation of Triclosan in aqueous solution was studied using a cylindrical reactor in which polarized carbon cloth electrodes and a cation exchange resin were employed. Using a factorial design of experiments approach, the effect of four variables (considering two levels for each one), was measured on four response parameters that reflect the electrooxidation efficiency of the electrochemical reactor. The results revealed that in all cases triclosan degradation was very efficient (above 95%) and that while there is a reasonable effect of all variables and their interactions, the one with the strongest influence on the process is the nature and magnitude of the ionic strength of the electrolytic solution. In this way, while the presence of a buffer species in this solution can keep the pH in a value that affects the generation of â¢OH radicals from the Fenton mixture, a high ionic strength solution can promote the elimination of Fe ionic species from the reactor by decreasing resin Fe retention due to competition effects of other ions for the binding sites of the substrate. HPLC experiments of the effluent solutions, also revealed that the degradation by-products of triclosan were dependent on the nature and ionic strength of the electrolytic solution in the electro-Fenton process under study. Finally, comparison of the different operation modes, also suggested that electro-adsorption of Fe cationic species in the negatively polarized cathode surface, is the main factor that controls Fe ion retention within the reactor.
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BACKGROUND: Ocimum micranthum Willd is a plant used in traditional medicine practiced in the region of the Yucatan peninsula. In particular, it is used for the treatment of cutaneous infections and wound healing, however there are currently no existing scientific studies that support these applications. The aim of the present study was to evaluate the antimicrobial and the in vitro proliferative activity (on healthy mammalian cell lines) of the essential oil and extracts (aqueous and ethanolic) of this plant. METHODS: The minimal inhibitory concentration (MIC) of essential oil and aqueous and ethanolic extracts of Ocimum micranthum leaves against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Candida albicans was determined using the microdilution technique. The in vitro proliferative activity of human fibroblast (hFB) and Chinese hamster ovary (CHO-K1) cells treated with these extracts was evaluated using the MTT test. The hFB cell line was also evaluated using Trypan Blue assay. RESULTS: Candida albicans was more susceptible to the ethanolic extract and the aqueous extract (MIC value of 5 µL/mL and 80 µL/mL respectively). In the case of Staphylococcus aureus, Bacillus subtilis, and Pseudomonas aeruginosa, the MIC of the aqueous and ethanolic extract was 125 µL/mL. The aqueous extract showed a significant (p < 0.05) antiproliferative effect on hFB cells at a concentration of 4%, with cell proliferation percentage values of 73.56% and 20.59% by MTT method and Trypan Blue assay, respectively; the same effect was observed for the ethanolic extract at concentration from 0.06% to 0.25% using MTT method and at a concentration from 0.125% to 0.25% using Trypan Blue assay. In CHO-K1 cells an antiproliferative effect was observed at a concentration of 8% of aqueous extract and from 0.06% to 0.25% of ethanolic extract using the MTT method. CONCLUSION: These assays showed that low concentrations of essential oil and extracts of Ocimum micranthum leaves are sufficient to cause an antiproliferative effect on the hFB cell line but do not produce an antimicrobial effect against the microorganisms evaluated. More studies are necessary to improve understanding of the mechanism of action of the compounds implicated in the bioactivities shown by the crude extracts.
Assuntos
Anti-Infecciosos/farmacologia , Inibidores do Crescimento/farmacologia , Ocimum/química , Óleos Voláteis/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Bactérias/efeitos dos fármacos , Células CHO , Proliferação de Células/efeitos dos fármacos , Cricetinae , Cricetulus , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fungos/efeitos dos fármacos , Inibidores do Crescimento/química , Inibidores do Crescimento/isolamento & purificação , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Folhas de Planta/químicaRESUMO
Se presenta un nuevo proceder quirúrgico en coordinación con el médico de la familia para viabilizar en un solo tiempo quirúrgico la corrección de las estructuras bucales de soporte a las prótesis estomatológicas. Se analizan los resultados en 181 pacientes operados por este novedoso procedimiento