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1.
N Engl J Med ; 383(11): 1009-1017, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32905673

RESUMO

BACKGROUND: When patients with a tracheostomy tube reach a stage in their care at which decannulation appears to be possible, it is common practice to cap the tracheostomy tube for 24 hours to see whether they can breathe on their own. Whether this approach to establishing patient readiness for decannulation leads to better outcomes than one based on the frequency of airway suctioning is unclear. METHODS: In five intensive care units (ICUs), we enrolled conscious, critically ill adults who had a tracheostomy tube; patients were eligible after weaning from mechanical ventilation. In this unblinded trial, patients were randomly assigned either to undergo a 24-hour capping trial plus intermittent high-flow oxygen therapy (control group) or to receive continuous high-flow oxygen therapy with frequency of suctioning being the indicator of readiness for decannulation (intervention group). The primary outcome was the time to decannulation, compared by means of the log-rank test. Secondary outcomes included decannulation failure, weaning failure, respiratory infections, sepsis, multiorgan failure, durations of stay in the ICU and hospital, and deaths in the ICU and hospital. RESULTS: The trial included 330 patients; the mean (±SD) age of the patients was 58.3±15.1 years, and 68.2% of the patients were men. A total of 161 patients were assigned to the control group and 169 to the intervention group. The time to decannulation was shorter in the intervention group than in the control group (median, 6 days [interquartile range, 5 to 7] vs. 13 days [interquartile range, 11 to 14]; absolute difference, 7 days [95% confidence interval, 5 to 9]). The incidence of pneumonia and tracheobronchitis was lower, and the duration of stay in the hospital shorter, in the intervention group than in the control group. Other secondary outcomes were similar in the two groups. CONCLUSIONS: Basing the decision to decannulate on suctioning frequency plus continuous high-flow oxygen therapy rather than on 24-hour capping trials plus intermittent high-flow oxygen therapy reduced the time to decannulation, with no evidence of a between-group difference in the incidence of decannulation failure. (REDECAP ClinicalTrials.gov number, NCT02512744.).


Assuntos
Remoção de Dispositivo , Oxigenoterapia , Sucção , Traqueostomia , Estado Terminal , Feminino , Humanos , Análise de Intenção de Tratamento , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Oxigenoterapia/métodos , Fatores de Tempo , Desmame do Respirador
2.
Molecules ; 27(17)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36080263

RESUMO

The feasibility of using dwarf kiwi fruits (Actinia arguta Miq.) as a healthy and sustainable food, compared to other types of commercial kiwi fruits, was evaluated in the present study. The overall antioxidant capacity of these fruits was assessed by either extraction-dependent methods (ABTS, ORAC) or the direct method called Quick, Easy, New, CHEap, Reproducible (QUENCHER) (DPPH, FRAP, Folin-Ciocalteu), applied for the first time to analyze kiwi fruits. With this methodology, all the molecules with antioxidant capacity are measured together in a single step, even those with high molecular weight or poor solubility in aqueous extraction systems, such as antioxidant dietary fiber. The effect of kiwi extracts on physiological and induced intracellular reactive oxygen species (ROS) production on IEC-6 cells was also analyzed, as well as total phenolic content (TPC) by Fast Blue BB, flavonols, hydroxycinnamic acids, and hydroxybenzoic acids. A. arguta fruits showed the highest values in all the antioxidant assays, being remarkably higher than the other kiwi species for Q-FRAP and Q-DPPH. Dwarf kiwi showed the highest potential in reducing physiological ROS and the highest values of TPC (54.57 mgGAE/g), being hydroxybenzoic acids the main phenolic family found (2.40 mgGAE/g). Therefore, dwarf kiwi fruits are a natural source of antioxidants compared to conventional kiwi fruits, being a sustainable and healthy alternative to diversify fruits in the diet.


Assuntos
Actinidia , Actinidia/química , Antioxidantes/química , Dieta , Frutas/química , Hidroxibenzoatos/análise , Fenóis/análise , Extratos Vegetais/química , Espécies Reativas de Oxigênio/análise
3.
Br J Clin Pharmacol ; 87(10): 3949-3960, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33759250

RESUMO

AIMS: Emodepside is an anthelmintic, originally developed for veterinary use. We investigated in healthy subjects the safety, and pharmacokinetics of a liquid service formulation (LSF) and immediate release (IR) tablet of emodepside in 2 randomised, parallel-group, placebo-controlled, Phase I studies. METHODS: Seventy-nine subjects in 10 cohorts in the single ascending dose study and 24 subjects in 3 ascending-dose cohorts in the multiple ascending dose study were enrolled. Emodepside as LSF was administered orally as single 1-40-mg doses and for 10 days as 5 or 10 mg once daily and 10-mg twice daily doses, respectively. Pharmacokinetics and safety were assessed up to 21 and 30 days, respectively. In addition, IR tablets containing 5 or 20 mg emodepside were tested in the single ascending dose study. RESULTS: Emodepside as LSF was rapidly absorbed under fasting conditions, with dose-proportional increase in plasma concentrations at doses from 1 to 40 mg. Terminal half-life was > 500 hours. In the fed state, emodepside was absorbed more slowly but overall plasma exposure was not significantly affected. Compared to the LSF, the rate and extent of absorption was significantly lower with the tablets. CONCLUSIONS: Overall, emodepside had acceptable safety and tolerability profiles, no major safety concerns, after single oral administration of 20 mg as LSF and after multiple oral administration over 10 days at 5 and 10 mg OD and at 10 mg twice daily. For further clinical trials, the development of a tablet formulation overcoming the limitations observed in the present study with the IR tablet formulation is considered.


Assuntos
Oncocercose Ocular , Oncocercose , Administração Oral , Área Sob a Curva , Depsipeptídeos , Relação Dose-Resposta a Droga , Interações Alimento-Droga , Meia-Vida , Voluntários Saudáveis , Humanos , Masculino , Oncocercose/tratamento farmacológico
4.
Eur J Pediatr ; 180(1): 291-294, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32653937

RESUMO

Oral immunotherapy is a common treatment in cow's milk protein allergy. The Department of Pediatric Allergology at the Children's Hospital of Zaragoza performed a retrospective analysis of 335 infants under 1 year of age diagnosed with IgE-mediated cow's milk and early treated. Clinical evaluation, skin prick test, and serum-specific IgE level control were performed before starting and after finishing treatment. Upon completion of treatment, more than 98% of patients became tolerant to milk and no one presented serious adverse reactions. Nowadays, the remaining non-tolerant patients (1.8%) can take milk or derivatives daily-as prophylaxis-to a certain maximum dose and still remain asymptomatic. After immunotherapy, both positive skin prick tests and a progressive decrease in specific IgE levels were found, as desensitization to milk increased.Conclusion: Oral immunotherapy is a safe and effective treatment against allergy to cow's milk proteins in infants. Such treatment should be offered to the children's families from the first moment of diagnosis. What is known: • Cow's milk proteins are responsible for the earliest IgE-mediated allergic reactions in children. • Oral immunotherapy (OIT) is commonly used as cow's milk allergy treatment and it is proposed at different ages. What is new: • OIT it is an effective and safe method with no severe reactions at early ages. • The number of reaching successful treatments is awesome so we believe that immunity response can be molded at the first months of life, so the probability of success with infants is greater than in older children.


Assuntos
Hipersensibilidade a Leite , Animais , Bovinos , Criança , Feminino , Humanos , Imunoglobulina E , Imunoterapia , Lactente , Hipersensibilidade a Leite/diagnóstico , Hipersensibilidade a Leite/terapia , Proteínas do Leite , Estudos Retrospectivos , Testes Cutâneos
5.
Int J Mol Sci ; 22(24)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34948364

RESUMO

Curcumin (Cur) is an anti-inflammatory polyphenol that can be complexed with polymeric cyclodextrin (CD) to improve solubility and bioavailability. The aim of the present work was to prepare a CurCD hydrogel to treat inflammatory skin conditions. Epichlorohydrin-ß-CD (EpißCD) was used as polymeric CD. To characterize the binary system, solid-state and in-solution studies were performed. Afterwards, an experimental design was performed to optimize the hydrogel system. Finally, the CurEpißCD hydrogel system was tested for anti-inflammatory activity using a HaCat psoriasis cell model. Co-grinded Cur/EpißCD binary system showed a strong interaction and Curcumin solubility was much improved. Its combination with Pluronic® F-127/hyaluronate hydrogel demonstrated an improvement in release rate and Curcumin permeation. After testing its anti-inflammatory activity, the system showed a significant reduction in IL-6 levels. Hydrogel-containing CurEpißCD complex is a great alternative to treat topical inflammatory diseases.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Curcumina/administração & dosagem , Portadores de Fármacos/química , Epicloroidrina/química , beta-Ciclodextrinas/química , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Curcumina/química , Curcumina/farmacologia , Liberação Controlada de Fármacos , Humanos , Psoríase/tratamento farmacológico , Solubilidade
6.
AAPS PharmSciTech ; 22(3): 103, 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712964

RESUMO

The topical use of rosmarinic acid (RA) in skin inflammatory pathologies is restricted due to its poor water solubility, poor permeability, and chemical instability. In this study, RA-loaded transethosomes-in-Carbopol® formulations have been developed to evaluate its anti-inflammatory activity on imiquimod-induced psoriasis-like skin inflammation in mice. In vitro release profiles demonstrated sustained behavior due to the retentive action of gel and the entrapment of RA into the vesicles. However, the low viscosity of the combined formulation increased the drug release rate. Animal evaluation of anti-inflammatory activity demonstrated that transethosomes-in-gel containing dexamethasone (Dex-TE-Gel), as positive control, showed effect in all the pro-inflammatory parameters evaluated, evidencing that these drug-loaded nanocarriers have been effectively reached the site of action. In addition, transethosomes-in-gel containing RA (RA-TE-Gel) formulations produced a great reduction in the punch edema (P < 0.001) and in TNF-α and IL-6 (P < 0.05). However, non-significant differences were obtained for IL-1ß, IL17, and MPO. Despite the protecting effect of Carbopol® and transethosomes on oxidation index and antioxidant activity of RA over the 7 days of treatment, however, a degradation process of this antioxidant to caffeic acid may be the cause of these in vivo results. We have also checked that the pH existing into the intercellular space of damaged cells (pH 6.8) may be affecting. Therefore, our results suggest that RA-TE-Gel could act as an effective RA formulation for skin delivery; further studies will help to understand the loss of activity at the cellular level.


Assuntos
Cinamatos/administração & dosagem , Cinamatos/uso terapêutico , Depsídeos/administração & dosagem , Depsídeos/uso terapêutico , Psoríase/tratamento farmacológico , Administração Cutânea , Animais , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Portadores de Fármacos , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Géis , Camundongos , Camundongos Endogâmicos BALB C , Viscosidade , Ácido Rosmarínico
7.
Int Ophthalmol ; 41(9): 2973-2979, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33864578

RESUMO

PURPOSE: To study the indications and clinical outcomes, in a real-word setting, of amniotic membrane extract eye drops (AMEED) use for ocular surface disease (OSD). METHODS: A retrospective study of patients treated with topical AMEED between January 2018 and January 2020 was conducted. Patients were classified in two groups according to specific OSD-dry eye disease (DED) and wound healing delay (WHD) groups. Demographics, comorbidities, treatment duration and clinical outcomes were analysed. RESULTS: A total of 50 eyes of 36 patients with or without previous treatments were included. Patients in the DED group presented more systemic comorbidities (83 vs 22%; p < 0.001) and spent more mean time under AMEED treatment (10 vs 7.2 months average) than the WHD group (p = 0.0104). In four patients, long-term treatment (more than 24 months) was reported. Global similar symptomatic improvement was reported for both groups (DED 88.9% vs WHD 100%; p = 0.486), with the WHD group especially consisting in general relief (78%) and the DED group reporting more pain improvement (44%) (p = 0.011). Regarding patients with autologous serum as a previous treatment, no statistical differences were found in subjective or objective improvement. An overall success was achieved in 94.4% of the cases and no adverse events were found. CONCLUSION: AMEED administration is a promising mean to treat OSD such as dry eye, persistent epithelial defect and corneal ulcers. Although AMEED may be effective in the treatment of severe DED and persistent epithelial defect or corneal ulcers, conclusions are limited owing to the absence of controlled clinical trials.


Assuntos
Âmnio , Síndromes do Olho Seco , Âmnio/transplante , Humanos , Soluções Oftálmicas , Extratos Vegetais , Estudos Retrospectivos
8.
Sensors (Basel) ; 19(10)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091820

RESUMO

Correcting atmospheric turbulence effects in light with Adaptive Optics is necessary, since it produces aberrations in the wavefront of astronomical objects observed with telescopes from Earth. These corrections are performed classically with reconstruction algorithms; between them, neural networks showed good results. In the context of solar observation, the usage of Adaptive Optics on solar differs from nocturnal operations, bringing up a challenge to correct the image aberrations. In this work, a convolutional approach is given to address this issue, considering SCAO configurations. A reconstruction algorithm is presented, "Shack-Hartmann reconstruction with deep learning on solar-prototype" (proto-HELIOS), to correct on fixed solar images, achieving an average 85.39% of precision in the reconstruction. Additionally, results encourage to continue working with these techniques to achieve a reconstruction technique for all the regions of the sun.

9.
AAPS PharmSciTech ; 20(7): 294, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31432298

RESUMO

Liposomes with their capacity to anchor gold nanoparticles (AuNPs) onto their surface are used in the treatment of several pathologies such as cancer. The objective of this work was the optimization of the vesicle composition by using cationic agents in order to reinforce the anchoring process of AuNPs, and for the study of the influence of local temperature and vesicle size on drug release. A Plackett-Burman design was conducted to determine the optimal composition for the anchoring of AuNPs. A comprehensive study of the influence of lipid bilayer composition on the surface charge, size, and polydispersity index (PdI) of liposomes was carried out. Afterwards, in vitro release studies by dialysis were performed and several release parameters were evaluated as a function of temperature. Cholesterol was fixed as the rigid agent and Didodecyldimethylammonium bromide (DDAB) was selected as the cationic lipid into the liposome bilayer. Photomicrographs revealed that DDAB facilitated the anchoring of AuNPs onto the liposomal surface. The anchoring of AuNPs also enhanced the amount and rate of calcein released, especially in extruded samples, at several incubating temperatures. In addition, it was observed that both the anchoring of AuNPs and the calcein release were improved by increasing the surface of the vesicles. The contributions of liposome composition (DDAB inclusion, incubation temperature, anchoring of AuNPs) and size and surface availability of the vesicles on calcein release could be used to design improved lipid nanostructures for the controlled release of anticancer drugs.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Compostos de Amônio Quaternário/administração & dosagem , Liberação Controlada de Fármacos , Humanos , Bicamadas Lipídicas/química , Lipossomos/química , Compostos de Amônio Quaternário/química
10.
Mar Drugs ; 16(10)2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30308980

RESUMO

Microalgae represent a source of bio-active compounds such as carotenoids with potent anti-inflammatory and antioxidant properties. We aimed to investigate the effects of fucoxanthin (FX) in both in vitro and in vivo skin models. Firstly, its anti-inflammatory activity was evaluated in LPS-stimulated THP-1 macrophages and TNF-α-stimulated HaCaT keratinocytes, and its antioxidant activity in UVB-irradiated HaCaT cells. Next, in vitro and ex vivo permeation studies were developed to determine the most suitable formulation for in vivo FX topical application. Then, we evaluated the effects of a FX-containing cream on TPA-induced epidermal hyperplasia in mice, as well as on UVB-induced acute erythema in hairless mice. Our results confirmed the in vitro reduction of TNF-α, IL-6, ROS and LDH production. Since the permeation results showed that cream was the most favourable vehicle, FX-cream was elaborated. This formulation effectively ameliorated TPA-induced hyperplasia, by reducing skin edema, epidermal thickness, MPO activity and COX-2 expression. Moreover, FX-cream reduced UVB-induced erythema through down-regulation of COX-2 and iNOS as well as up-regulation of HO-1 protein via Nrf-2 pathway. In conclusion, FX, administered in a topical formulation, could be a novel natural adjuvant for preventing exacerbations associated with skin inflammatory pathologies as well as protecting skin against UV radiation.


Assuntos
Eritema/tratamento farmacológico , Hiperplasia/tratamento farmacológico , Pomadas/farmacologia , Pele/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Xantofilas/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Eritema/metabolismo , Feminino , Humanos , Hiperplasia/metabolismo , Interleucina-6/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , L-Lactato Desidrogenase/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Pelados , Óxido Nítrico Sintase Tipo II/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Pele/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/efeitos dos fármacos
11.
Drug Dev Ind Pharm ; 44(1): 135-143, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28967285

RESUMO

This work was aimed at determining the feasibility of artificial neural networks (ANN) by implementing backpropagation algorithms with default settings to generate better predictive models than multiple linear regression (MLR) analysis. The study was hypothesized on timolol-loaded liposomes. As tutorial data for ANN, causal factors were used, which were fed into the computer program. The number of training cycles has been identified in order to optimize the performance of the ANN. The optimization was performed by minimizing the error between the predicted and real response values in the training step. The results showed that training was stopped at 10 000 training cycles with 80% of the pattern values, because at this point the ANN generalizes better. Minimum validation error was achieved at 12 hidden neurons in a single layer. MLR has great prediction ability, with errors between predicted and real values lower than 1% in some of the parameters evaluated. Thus, the performance of this model was compared to that of the MLR using a factorial design. Optimal formulations were identified by minimizing the distance among measured and theoretical parameters, by estimating the prediction errors. Results indicate that the ANN shows much better predictive ability than the MLR model. These findings demonstrate the increased efficiency of the combination of ANN and design of experiments, compared to the conventional MLR modeling techniques.


Assuntos
Química Farmacêutica/métodos , Lipossomos/química , Redes Neurais de Computação , Algoritmos , Modelos Lineares , Análise de Regressão
12.
J Microencapsul ; 35(4): 357-371, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29889613

RESUMO

The aim of this study was to evaluate the stability of levodopa liposomes co-loaded with three different antioxidants (curcumin, ascorbic acid, and superoxide dismutase (SOD)). For this purpose, multilamellar liposomes were prepared. Curcumin was added into the lipid bilayer while ascorbic acid and SOD were placed into the aqueous phase. The influence of preparation technique and surface charge were also investigated. Vesicles were characterised and free radical scavenging potential was determined. From stability study, ascorbic acid showed better stabilising effect. These co-loaded liposomes also exhibited potential radical scavenging activity where ascorbic acid played a key role. From the study of different preparation techniques and charge, we concluded that cationic liposomes made by Thin Layer Evaporation following extrusion offered the best physicochemical and stability properties. A dual mechanism of these liposomes implies the chemical stabilisation of levodopa (dose reduction) and the antioxidant effect, with a preventive effect on Parkinson's disease.


Assuntos
Antioxidantes/química , Antiparkinsonianos/administração & dosagem , Ácido Ascórbico/química , Curcumina/química , Levodopa/administração & dosagem , Lipossomos/química , Superóxido Dismutase/química , Antiparkinsonianos/química , Dopaminérgicos/administração & dosagem , Dopaminérgicos/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Levodopa/química , Bicamadas Lipídicas/química
13.
Plant Cell ; 26(3): 1134-50, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24610723

RESUMO

Strigolactones (SLs) are phytohormones that play a central role in regulating shoot branching. SL perception and signaling involves the F-box protein MAX2 and the hydrolase DWARF14 (D14), proposed to act as an SL receptor. We used strong loss-of-function alleles of the Arabidopsis thaliana D14 gene to characterize D14 function from early axillary bud development through to lateral shoot outgrowth and demonstrated a role of this gene in the control of flowering time. Our data show that D14 distribution in vivo overlaps with that reported for MAX2 at both the tissue and subcellular levels, allowing physical interactions between these proteins. Our grafting studies indicate that neither D14 mRNA nor the protein move over a long range upwards in the plant. Like MAX2, D14 is required locally in the aerial part of the plant to suppress shoot branching. We also identified a mechanism of SL-induced, MAX2-dependent proteasome-mediated degradation of D14. This negative feedback loop would cause a substantial drop in SL perception, which would effectively limit SL signaling duration and intensity.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Hidrolases/metabolismo , Lactonas/metabolismo , Transdução de Sinais , Sequência de Aminoácidos , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Dados de Sequência Molecular , Proteólise , Homologia de Sequência de Aminoácidos , Transcrição Gênica
14.
Mar Drugs ; 16(1)2017 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-29295585

RESUMO

Chronic inflammatory skin diseases such as psoriasis have a significant impact on society. Currently, the major topical treatments have many side effects, making their continued use in patients difficult. Microalgae have emerged as a source of bio-active molecules such as glycolipids with potent anti-inflammatory properties. We aimed to investigate the effects of a glycolipid (MGMG-A) and a glycolipid fraction (MGDG) obtained from the microalga Isochrysis galbana on a TPA-induced epidermal hyperplasia murine model. In a first set of experiments, we examined the preventive effects of MGMG-A and MGDG dissolved in acetone on TPA-induced hyperplasia model in mice. In a second step, we performed an in vivo permeability study by using rhodamine-containing cream, ointment, or gel to determinate the formulation that preserves the skin architecture and reaches deeper. The selected formulation was assayed to ensure the stability and enhanced permeation properties of the samples in an ex vivo experiment. Finally, MGDG-containing cream was assessed in the hyperplasia murine model. The results showed that pre-treatment with acetone-dissolved glycolipids reduced skin edema, epidermal thickness, and pro-inflammatory cytokine production (TNF-α, IL-1ß, IL-6, IL-17) in epidermal tissue. The in vivo and ex vivo permeation studies showed that the cream formulation had the best permeability profile. In the same way, MGDG-cream formulation showed better permeation than acetone-dissolved preparation. MGDG-cream application attenuated TPA-induced skin edema, improved histopathological features, and showed a reduction of the inflammatory cell infiltrate. In addition, this formulation inhibited epidermal expression of COX-2 in a similar way to dexamethasone. Our results suggest that an MGDG-containing cream could be an emerging therapeutic strategy for the treatment of inflammatory skin pathologies such as psoriasis.


Assuntos
Glicolipídeos/administração & dosagem , Glicolipídeos/uso terapêutico , Haptófitas/química , Hiperplasia/prevenção & controle , Dermatopatias/prevenção & controle , Administração Tópica , Animais , Sobrevivência Celular/efeitos dos fármacos , Citocinas/análise , Citocinas/biossíntese , Composição de Medicamentos , Feminino , Glicolipídeos/farmacocinética , Humanos , Hiperplasia/induzido quimicamente , Hiperplasia/patologia , Queratinócitos/efeitos dos fármacos , Camundongos , Pomadas , Pele/patologia , Absorção Cutânea , Dermatopatias/induzido quimicamente , Dermatopatias/patologia , Acetato de Tetradecanoilforbol
15.
JAMA ; 316(15): 1565-1574, 2016 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-27706464

RESUMO

Importance: High-flow conditioned oxygen therapy delivered through nasal cannulae and noninvasive mechanical ventilation (NIV) may reduce the need for reintubation. Among the advantages of high-flow oxygen therapy are comfort, availability, lower costs, and additional physiopathological mechanisms. Objective: To test if high-flow conditioned oxygen therapy is noninferior to NIV for preventing postextubation respiratory failure and reintubation in patients at high risk of reintubation. Design, Setting, and Participants: Multicenter randomized clinical trial in 3 intensive care units in Spain (September 2012-October 2014) including critically ill patients ready for planned extubation with at least 1 of the following high-risk factors for reintubation: older than 65 years; Acute Physiology and Chronic Health Evaluation II score higher than 12 points on extubation day; body mass index higher than 30; inadequate secretions management; difficult or prolonged weaning; more than 1 comorbidity; heart failure as primary indication for mechanical ventilation; moderate to severe chronic obstructive pulmonary disease; airway patency problems; or prolonged mechanical ventilation. Interventions: Patients were randomized to undergo either high-flow conditioned oxygen therapy or NIV for 24 hours after extubation. Main Outcomes and Measures: Primary outcomes were reintubation and postextubation respiratory failure within 72 hours. Noninferiority margin was 10 percentage points. Secondary outcomes included respiratory infection, sepsis, and multiple organ failure, length of stay and mortality; adverse events; and time to reintubation. Results: Of 604 patients (mean age, 65 [SD, 16] years; 388 [64%] men), 314 received NIV and 290 high-flow oxygen. Sixty-six patients (22.8%) in the high-flow group vs 60 (19.1%) in the NIV group were reintubation (absolute difference, -3.7%; 95% CI, -9.1% to ∞); 78 patients (26.9%) in the high-flow group vs 125 (39.8%) in the NIV group experienced postextubation respiratory failure (risk difference, 12.9%; 95% CI, 6.6% to ∞) [corrected]. Median time to reintubation did not significantly differ: 26.5 hours (IQR, 14-39 hours) in the high-flow group vs 21.5 hours (IQR, 10-47 hours) in the NIV group (absolute difference, -5 hours; 95% CI, -34 to 24 hours). Median postrandomization ICU length of stay was lower in the high-flow group, 3 days (IQR, 2-7) vs 4 days (IQR, 2-9; P=.048). Other secondary outcomes were similar in the 2 groups. Adverse effects requiring withdrawal of the therapy were observed in none of patients in the high-flow group vs 42.9% patients in the NIV group (P < .001). Conclusions and Relevance: Among high-risk adults who have undergone extubation, high-flow conditioned oxygen therapy was not inferior to NIV for preventing reintubation and postextubation respiratory failure. High-flow conditioned oxygen therapy may offer advantages for these patients. Trial Registration: clinicaltrials.gov Identifier: NCT01191489.


Assuntos
Extubação , Ventilação de Alta Frequência/métodos , Ventilação de Alta Frequência/estatística & dados numéricos , Ventilação não Invasiva , Oxigenoterapia/métodos , Insuficiência Respiratória/prevenção & controle , APACHE , Idoso , Estado Terminal , Feminino , Insuficiência Cardíaca/terapia , Humanos , Tempo de Internação , Masculino , Oxigenoterapia/instrumentação , Oxigenoterapia/estatística & dados numéricos , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Fatores de Risco
16.
ScientificWorldJournal ; 2014: 279614, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25525616

RESUMO

This study examines the relationship between subclinical ketosis (SCK) in dairy cows and the butyric acid content of the silage used in their feeding. Twenty commercial farms were monitored over a period of 12 months. The feed at each farm and the silages used in its ration were sampled monthly for proximal analysis and for volatile fatty acid analysis. A total of 2857 urine samples were taken from 1112 cows to examine the ketonuria from about 30 days prepartum to 100 postpartum. Wide variation was recorded in the quality of silages used in the preparation of diets. Approximately 80% of the urine samples analyzed had no detectable ketone bodies, 16% returned values indicative of slight SCK, and the remainder, 4%, showed symptoms of ketosis. Most of the cases of hyperkenuria were associated with the butyric acid content of the silage used (r2=0.56; P<0.05). As the metabolizable energy content of the feed was similar, no relationship was observed between the proportion of cows with SCK and the energy content of the feed. In our study, the probability of dairy cows suffering SCK is higher when they are eating feed made from silage with a high butyric acid content (35.2 g/kg DM intake).


Assuntos
Ácido Butírico/análise , Indústria de Laticínios , Cetose/veterinária , Silagem/análise , Animais , Bovinos , Dieta/veterinária , Corpos Cetônicos/urina , Cetose/urina
17.
Food Funct ; 15(2): 838-852, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38164088

RESUMO

Olacein (OLA), one of the main secoiridoids derived from extra virgin olive oil (EVOO), has been shown to modulate oxidative and inflammatory responses in various pathological conditions; however, its potential benefit in joint disorders such as rheumatoid arthritis (RA) is unknown. Therefore, this study was designed to evaluate the preventive role of the effects of an OLA-supplemented diet in the murine model of collagen-induced arthritis (CIA), delving into the possible mechanisms and signaling pathways involved. Animals were fed an OLA-enriched preventive diet for 6 weeks prior to CIA induction and until the end of the experimental time course. On day 43 after the first immunization, mice were sacrificed: blood was collected, and paws were histologically and biochemically processed. Dietary OLA prevented collagen-induced rheumatic bone, joint and cartilage conditions. Circulating matrix metalloproteinase (MMP)-3 and proinflammatory cytokine (IL-6, IL-1ß, TNF-α, IL-17) levels were significantly decreased in the joint, as well as MMP-9 and cathepsin-K (CatK) expression in secoiridoid-fed animals. In addition, dietary OLA was able to decrease COX-2, mPGES-1 and iNOS protein expressions and, also, PGE2 levels. The mechanisms possibly involved in these protective effects could be related to the activation of the Nrf-2/HO-1 axis and the inhibition of proinflammatory signaling pathways, including JAK-STAT, MAPKs and NF-κB, involved in the production of inflammatory and oxidative mediators. These results support the interest of OLA, as a nutraceutical intervention, in the management of RA.


Assuntos
Aldeídos , Artrite Experimental , Artrite Reumatoide , Fenóis , Camundongos , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Azeite de Oliva/efeitos adversos , NF-kappa B/metabolismo , Dieta , Iridoides
18.
Healthcare (Basel) ; 11(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37957983

RESUMO

Work-related stress is a significant problem in many work environments and can have negative consequences for both employees and organisations. This review aimed to identify which elements of biophilic design in the workplace affect workers' stress response. To enable this, a literature search was conducted using PsycINFO, Scopus, and Medline. The search was limited to articles published from 2012 to June 2023. This review only integrated quantitative data, incorporating twelve records for qualitative synthesis. The selected studies suggest that strategies such as access to outdoor environments or the creation of outdoor areas are effective in reducing stress in the workplace. If these are not feasible, the examined research advocates the use of virtual means to recreate such relaxation or break spaces. Furthermore, aspects of interest for future research were identified, such as multisensory stimulation, including the sense of smell, the exploration of views with natural elements, the creation of shelters, or the study of biomorphic forms.

19.
Antioxidants (Basel) ; 12(6)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37372034

RESUMO

Systemic lupus erythematosus (SLE) is a chronic immune-inflammatory disease characterized by multiorgan affectation and lowered self-tolerance. Additionally, epigenetic changes have been described as playing a pivotal role in SLE. This work aims to assess the effects of oleacein (OLA), one of the main extra virgin olive oil secoiridoids, when used to supplement the diet of a murine pristane-induced SLE model. In the study, 12-week-old female BALB/c mice were injected with pristane and fed with an OLA-enriched diet (0.01 % (w/w)) for 24 weeks. The presence of immune complexes was evaluated by immunohistochemistry and immunofluorescence. Endothelial dysfunction was studied in thoracic aortas. Signaling pathways and oxidative-inflammatory-related mediators were evaluated by Western blotting. Moreover, we studied epigenetic changes such as DNA methyltransferase (DNMT-1) and micro(mi)RNAs expression in renal tissue. Nutritional treatment with OLA reduced the deposition of immune complexes, ameliorating kidney damage. These protective effects could be related to the modulation of mitogen-activated protein kinases, the Janus kinase/signal transducer and transcription activator of transcription, nuclear factor kappa, nuclear-factor-erythroid-2-related factor 2, inflammasome signaling pathways, and the regulation of miRNAs (miRNA-126, miRNA-146a, miRNA-24-3p, and miRNA-123) and DNMT-1 expression. Moreover, the OLA-enriched diet normalized endothelial nitric oxide synthase and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-1 overexpression. These preliminary results suggest that an OLA-supplemented diet could constitute a new alternative nutraceutical therapy in the management of SLE, supporting this compound as a novel epigenetic modulator of the immunoinflammatory response.

20.
Foods ; 12(12)2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37372638

RESUMO

Hawthorn (Crataegus monogyna Jacq.) and whitebeam (Sorbus aria (L.) Crantz) are wild species traditionally used as ethnic foods in the Mediterranean area. Their red berries, and mainly the peels, may be used as ingredients due to their color (replacing other synthetic colorants) or functional properties. Some previous studies analyze all edible fruits, but there is very little literature on the composition and properties of the pulpless epidermis of the fruits of C. monogyna and no literature concerning the fruits of S. aria. Total phenolic compounds (TPC) and families of hydroxybenzoic acids, hydroxycinnamic acids, flavonols, and total monomeric anthocyanins were determined in the epidermis of C. monogyna and S. aria fruits. The in vitro antioxidant capacity was also determined using QUENCHER (Quick-Easy-New-CHEap-Reproducible) methodology. Anthocyanins profiles were analyzed in hydroalcoholic extracts through HPLC/MS. C. monogyna fruits presented higher content of TPC than S. aria, with hydroxybenzoic acids (2870.6 mg GAE/100g dw) as the major family, followed by flavonols (771.4 mg QE/100 g dw) and hydroxycinnamic acids (610.3 FAE/100 g dw). Anthocyanins were found in 251.7 mg cyanidin-3-glucoside/100 g dw, characterized by the content of cyanidin-O-hexoxide and peonidin-O-hexoxide. The levels of these compounds correlated with higher values of a* parameter (higher intensity of reddish color). These fruits also showed higher antioxidant capacity by Q-Folin-Ciocalteu and Q-FRAP. S. aria peels had fewer phenolic compounds, particularly anthocyanins (33.7 mg cyanidin-3-glucoside/100 g dw), containing different cyanidin derivatives. From these results, new insights about the composition of the epidermis of these wild fruits are provided, and their potential as ingredients for the food industry is corroborated.

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