| 1681. |
- Diaz, Jessica M. Aguilar, et al.
(författare)
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New and Repurposed Drugs for the Treatment of Active Tuberculosis : An Update for Clinicians
- 2023
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Ingår i: Respiration. - : S. Karger. - 0025-7931 .- 1423-0356. ; 102:2, s. 83-100
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Forskningsöversikt (refereegranskat)abstract
- Although tuberculosis (TB) is preventable and curable, the lengthy treatment (generally 6 months), poor patient adherence, high inter-individual variability in pharmacokinetics (PK), emergence of drug resistance, presence of comorbidities, and adverse drug reactions complicate TB therapy and drive the need for new drugs and/or regimens. Hence, new compounds are being developed, available drugs are repurposed, and the dosing of existing drugs is optimized, resulting in the largest drug development portfolio in TB history. This review highlights a selection of clinically available drug candidates that could be part of future TB regimens, including bedaquiline, delamanid, pretomanid, linezolid, clofazimine, optimized (high dose) rifampicin, rifapentine, and para-aminosalicylic acid. The review covers drug development history, preclinical data, PK, and current clinical development.
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| 1682. |
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| 1683. |
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| 1684. |
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| 1685. |
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| 1686. |
- Díaz, Miguel, Högskoleadjunkt, et al.
(författare)
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Acute resveratrol supplementation in coronary artery disease : towards patient stratification
- 2020
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Ingår i: Scandinavian Cardiovascular Journal. - : Taylor & Francis. - 1401-7431 .- 1651-2006. ; :1, s. 14-19
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Resveratrol (RV) is a polyphenol with antioxidant, anti-inflammatory and cardio-protective properties. Our objective was to investigate whether acute supplementation with high doses of RV would improve flow-mediated dilation (FMD) and oxygen consumption (VO2) kinetics in older coronary artery disease (CAD) patients.DESIGN: We employed a placebo-controlled, single-blind, crossover design in which ten participants (aged 66.6 ± 7.8 years) received either RV or placebo (330 mg, 3x day-1) during three consecutive days plus additional 330 mg in the morning of the fourth day with a seven-day wash-out period in-between. On the fourth day, FMD of the brachial artery and VO2 on-kinetics were determined. Results; RV improved FMD in patients who had undergone coronary artery bypass grafting (CABG; -1.4 vs. 5.0%; p = 0.004), but not in those who had undergone percutaneous coronary intervention (PCI; 4.2 vs. -0.2%; NS).CONCLUSION: Acute high dose supplementation with RV improved FMD in patients after CABG surgery but impaired FMD in patients who underwent PCI. The revascularization method-related differential effects of RV may be due to its direct effects on endothelial-dependent dilator responses. Our findings have important implications for personalized treatment and stratification of older CAD patients.
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| 1687. |
- Díaz, Miguel, Högskoleadjunkt, et al.
(författare)
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Differential effects of resveratrol on the dilator responses of femoral arteries, ex vivo
- 2019
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Ingår i: Nitric oxide. - : Elsevier. - 1089-8603 .- 1089-8611. ; 92, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Resveratrol is a plant-derived phytoalexin with antioxidant, anti-inflammatory and cardio-protective properties and may be a promising therapeutic intervention strategy in cardiovascular disease. Here, we investigated the acute direct effects of trans-resveratrol (RV), on acetylcholine (ACh)-induced and flow-mediated dilation (FMD) of isolated pressurized femoral arteries of young (4-month-old) and old (26-month-old) mice. Vessel exposure to RV enhanced ACh (0.01-1.0 mM)-induced dilation (p < 0.05), but not FMD (@ 5-10 μL⋅min-1) (p < 0.05) in both young and old mice. After RV incubation, acute nitric oxide (NO) production by cultured endothelial cells was increased in response to 0.01 mM ACh, but reduced by flow (5-10 μL⋅min-1; p < 0.05). In isolated femoral arteries from endothelial nitric oxide synthase knockout (eNOS-/-) mice, RV had no overall effect on flow mediated dilation, but potentiated ACh induced dilation, that was completely abolished by potassium channel blockers, Apamin and Tram 34 (p < 0.01). We demonstrate that the non-metabolised form of RV stimulates ACh-induced dilation via the NO and EDHF pathways, but not FMD by interaction with the cyclo-oxygenase pathway. Our findings have important implications in the use of RV (for both young and aged) under 'normal' non-diseased physiological states.
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| 1688. |
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| 1689. |
- Díaz-Navarro, S., et al.
(författare)
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Sex estimation using long bones in the largest burial site of the Copper Age : Linear discriminant analysis and random forest
- 2024
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Ingår i: Journal of Archaeological Science. - : Elsevier. - 2352-409X .- 2352-4103. ; 58
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Tidskriftsartikel (refereegranskat)abstract
- Sex estimation of the individuals in a sample is fundamental for any bioarchaeological study to define a particular demographic assemblage or to classify isolated remains. Long bones are an excellent alternative for sex estimation when the most dimorphic anatomical parts are not preserved or are highly altered. Here we propose a set of discriminant functions and classification models to estimate the sex of prehistoric individuals using linear discriminant analysis and machine learning approaches. Different osteometric variables were taken from the humeri, ulnae, radii, femurs and tibias of a sample of 109 articulated skeletons buried in the collective tomb of Camino del Molino (Region of Murcia, SE-Spain), dated to the 3rd millennium BC. Sex was estimated based on standard anthropological methods and ancient DNA analysis of a control sample. Fifty-two discriminant functions with prediction thresholds higher than 0.8 on the ROC curve were obtained using independent (22) and combined variables (30). The best LDA models for sex prediction were those based on proximal epiphyseal widths or their combination with other variables, reaching values close to 0.98 on the ROC curve. The random forest-based model obtained an accuracy of 0.94 and confirmed the importance of epiphyseal widths in sex classification. This analysis is more comprehensive than univariate LDA, as it allows for ranking the importance of bones in sex discrimination and considers correlations between long bones rather than treating them as independent observations. In contrast, applying LDA to each bone makes it easier to predict the sex of other coeval collections that do not have such a complete sample. This work aims to overcome the scarcity of methods that can be applied to sex estimation of the large volume of isolated remains from Camino del Molino and for other Mediterranean skeletal series from the Late Prehistory with high biological affinity and that share similar environmental conditions.
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| 1690. |
- Diaz, Oscar E., et al.
(författare)
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Perfluorooctanesulfonic acid modulates barrier function and systemic T-cell homeostasis during intestinal inflammation
- 2021
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Ingår i: DMM Disease Models and Mechanisms. - : The Company of Biologists. - 1754-8411 .- 1754-8403. ; 14:12, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- The intestinal epithelium is continuously exposed to deleterious environmental factors that might cause aberrant immune responses leading to inflammatory disorders. However, what environmental factors might contribute to disease are poorly understood. Here, to overcome the lack of in vivo models suitable for screening of environmental factors, we used zebrafish reporters of intestinal inflammation. Using zebrafish, we interrogated the immunomodulatory effects of polyfluoroalkyl substances, which have been positively associated with ulcerative colitis incidence. Exposure to perfluorooctanesulfonic acid (PFOS) during 2,4,6-trinitro-benzene sulfonic acid (TNBS)-induced inflammation enhanced the expression of proinflammatory cytokines as well as neutrophil recruitment to the intestine of zebrafish larvae, which was validated in the TNBS-induced colitis mouse model. Moreover, PFOS exposure in mice undergoing colitis resulted in neutrophil-dependent increased intestinal permeability and enhanced PFOS translocation into the circulation. This was associated with a neutrophil-dependent expansion of systemic CD4+ T cells. Thus, our results indicate that PFOS worsens inflammation-induced intestinal damage with disruption of T-cell homeostasis beyond the gut and provides a novel in vivo toolbox to screen for pollutants affecting intestinal homeostasis.
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