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1.
Zebrafish ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608227

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder that is clinically assessed by motor symptoms associated with the loss of midbrain dopaminergic neurons affecting the quality of life for over 8.5 million people worldwide. The neurotoxin 6-hydroxydopamine (6-OHDA) has been used to chemically induce a PD-like state in zebrafish larvae by several laboratories; however, highly variable concentration, methodology, and reagents have resulted in conflicting results suggesting a need to investigate these issues of reproducibility. We propose a protocol that addresses the differences in methodology and induces changes in 6 days postfertilization (dpf) larvae utilizing a 24-h exposure at 3 dpf with 30 µM 6-OHDA. Despite ∼50% lethality, no morphological or development differences in surviving fish are observed. Definition of our model is defined by downregulation of the expression of th1 by reverse transcriptase-quantitative polymerase chain reaction, a marker for dopaminergic neurons and a reduction in movement. Additionally, we observed a downregulation of pink1 and an upregulation of sod1 and sod2, indicators of mitochondrial dysfunction and response to reactive oxygen species, respectively.

2.
J Vis Exp ; (205)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38587389

RESUMO

In recent years, a number of technologies have emerged to purify biogas into biomethane. This purification entails a reduction in the concentration of polluting gases such as carbon dioxide and hydrogen sulfide to increase the content of methane. In this study, we used a microalgal cultivation technology to treat and purify biogas produced from organic waste from the swine industry to obtain ready-to-use biomethane. For cultivation and purification, two 22.2 m3 open-pond photobioreactors coupled with an absorption-desorption column system were set up in San Juan de los Lagos, Mexico. Several recirculation liquid/biogas ratios (L/G) were tested to obtain the highest removal efficiencies; other parameters, such as pH, dissolved oxygen (DO), temperature, and biomass growth, were measured. The most efficient L/Gs were 1.6 and 2.5, resulting in a treated biogas effluent with a composition of 6.8%vol and 6.6%vol in CO2, respectively, and removal efficiencies for H2S up to 98.9%, as well as maintaining O2 contamination values of less than 2%vol. We found that pH greatly determines CO2 removal, more so than L/G, during cultivation because of its participation in the photosynthetic process of microalgae and its ability to vary pH when solubilized due to its acidic nature. DO, and temperature oscillated as expected from the light-dark natural cycles of photosynthesis and the time of day, respectively. Biomass growth varied with CO2 and nutrient feeding as well as reactor harvesting; however, the trend remained primed for growth.


Assuntos
Biocombustíveis , Microalgas , Animais , Suínos , Lagoas , Dióxido de Carbono/análise , Bactérias , Biomassa
4.
Rev Esp Geriatr Gerontol ; 59(3): 101481, 2024 Feb 28.
Artigo em Espanhol | MEDLINE | ID: mdl-38422785

RESUMO

INTRODUCTION: It is necessary to analyze the aging process in institutionalized older people. For this purpose, a descriptive and analytical epidemiological study was carried out in nursing homes for older adults before the COVID-19 pandemic. OBJECTIVE: Provide an in-depth insight into cognitive (MEC), emotional (Geriatric Depression Scale), and functional (Barthel Scale) status within the older adult participants. METHOD: A sample of 973 participants analyzed the relationship between cognitive status, vulnerability to depression, and autonomous performance in Daily Day Activities (DDA) to predict the impact of the comorbidity of these variables. Therefore, in addition to the general distribution of the sample in the previously mentioned dimensions, differences were analyzed according to gender, age, educational level, and geographic area. RESULTS: The results confirm the hypothesis that a more impaired cognitive state is associated with higher levels of depression and lower functional capacity. The MEC scores have positive and highly significant correlations with Barthel and Yesavage. The relationship between dementia and autonomy is observed for both sexes, while the relationship between dementia and depression is only observed in women. The educational level influences the MEC scores (the more education, the better performance) and the Barthel scores (the less education, the greater dependency). Statistically significant differences were also found depending on the area of residence location. CONCLUSIONS: The more deteriorated cognitive state will be associated with a higher level of depression and lower functional capacity in daily life activities.

5.
Sci Rep ; 13(1): 14295, 2023 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-37652965

RESUMO

The PHQ-9 questionnaire is a screening test worldwide used to measure depression. But it cannot be used in Costa Rica, due to the fact that it has not previously been validated for its population. The present study aims to show the validation of the PHQ-9 questionnaire and its variants (PHQ-2, PHQ-4, PHQ-8) in a population sample of adults residing in Costa Rica. A sample was collected (n = 1162) using a self-administered questionnaire. Confirmatory Factor Analysis (CFA), Receiver Operating Characteristic (ROC) curve, and Multiple Group Confirmatory Factor Analysis (MGCFA) were tested. One factor was found that explained 73.33% of the variance with excellent internal consistency (α = 0.928). Goodness-of-fit measures were adequate (RMSEA = 0.107; CFI = 0.948), as was diagnostic power at a cut-off of 10 (78.60 for Sensitivity and 27.95 for 1-Specificity). External validation indices were good (r = 0.843 with GAD-7, r = - 0.647 with RS14, and r = 0.301 with FCV19S), and the model showed invariance by sex (∆χ2 = 27.90; df = 27; p < 0.001). Additionally, new cut-off points were proposed for PHQ-9 and its variants for Costa Rican male, female, and general populations. The PHQ-9 and its variants (PHQ-2, 4, and 8) are valid tools for detecting depression (and anxiety for PHQ-4) in Costa Rican population. In addition, new cut-off points differentiated by sex are proposed.


Assuntos
Ansiedade , Questionário de Saúde do Paciente , Humanos , Feminino , Masculino , Costa Rica , Transtornos de Ansiedade , Análise Fatorial
6.
Appl Biochem Biotechnol ; 195(7): 4321-4335, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36689159

RESUMO

Suitability of microalgae valorization mainly depends on its biochemical composition. Overall, among all microalgal derivatives, pigments currently stand out as the major added-value component. While it is well recognized that microalgal growth conditions strongly affect biomass composition, final tuning of already grown microalgae has been scarcely studied. Herein, pigment crude extract and debris biomass composition of an already grown microalgal consortium was evaluated after a short-term exposure (90 min) to different levels of irradiance (15, 50, 120 µmol m-2 s-1) and sulfide concentrations (0, 3.2, 16 mg L-1). Although lipid, protein, and carbohydrate contents of debris biomass were not decisively modified by the short-term exposures, pigments content of the crude extracts were strongly modified after 90-min exposure at given sulfide and irradiance conditions. Particularly, a higher content of chlorophyll a, chlorophyll b, and total carotenoids was estimated at an optimal sulfide concentration of 5 mg L-1, and the higher irradiance of 120 µmol m-2 s-1. Contrarily, the average irradiation level of 50 µmol m-2 s-1 and the absence of sulfide stimulated the production of phycoerythrin and phycocyanin which could be increased by 65 and 50%, respectively. Thus, a final qualitative and quantitative tuning of pigment content is plainly achievable on grown microalgal biomass, in a reduced exposure time, at given irradiance or sulfide conditions.


Assuntos
Microalgas , Clorofila A/metabolismo , Microalgas/metabolismo , Ficoeritrina , Ficocianina , Carotenoides/metabolismo , Biomassa
7.
Drug Alcohol Depend ; 242: 109714, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36463764

RESUMO

BACKGROUND: This systematic review summarized published literature on county-level predictors of drug overdose mortality in the United States (US). METHODS: Peer-reviewed studies and doctoral dissertations published in English between 1990 and July 19, 2022 were identified from PubMed, Web of Science, ProQuest Dissertations & Theses, PsycINFO, CINAHL, and EconLit. Eligible studies examined at least one county-level predictor of drug overdose mortality in US counties. Two reviewers independently completed screening, quality assessment (with an adapted National Institutes of Health Quality Assessment Tool), and data extraction. Results were qualitatively summarized and grouped by predictor categories. RESULTS: Of 56 studies included, 42.9% were subnational, and 53.6% were limited to opioid overdose. In multiple studies, measures related to opioid prescribing, illness/disability, economic distress, mining employment, incarceration, family distress, and single-parent families were positively associated with drug overdose mortality outcomes, while measures related to cannabis dispensaries, substance use treatment, social capital, and family households were negatively associated with drug overdose mortality outcomes. Both positive and negative associations were documented for smoking, uninsurance, healthcare professional shortage status, physicians per capita, unemployment, income, poverty, educational attainment, racial composition, and rurality. Findings within studies also differed by subpopulation (by race/ethnicity, gender, age, or rurality) and the type of drugs involved in overdose. CONCLUSIONS: The findings of this review provide relatively mixed evidence regarding many county-level predictors of overdose mortality, several of which also vary between subpopulations, supporting the importance of additional research to elucidate pathways through which the county context may shape risk of fatal overdose.


Assuntos
Overdose de Drogas , Transtornos Relacionados ao Uso de Substâncias , Humanos , Estados Unidos , Analgésicos Opioides , Padrões de Prática Médica , Etnicidade
8.
Sci Rep ; 12(1): 20996, 2022 12 05.
Artigo em Inglês | MEDLINE | ID: mdl-36470938

RESUMO

Since the beginning of the COVID-19 pandemic, the need to implement protocols that respond to the mental health demands of the population has been demonstrated. The PASMICOR programme started in March 2020, involving a total of 210 requests for treatment. Out of those subjects, the intervention was performed in 53 patients with COVID-19 without history of past psychiatric illness, 57 relatives and 60 health professionals, all of them within the area of Salamanca (Spain). Interventions were carried out by professionals of the public mental health service mostly by telephone. Depending on clinical severity, patients received basic (level I) or complex psychotherapeutic care combined with psychiatric care (level II). The majority of attended subjects were women (76.5%). Anxious-depressive symptoms were predominant, although sadness was more frequent in patients, insomnia in relatives and anxiety and fear in health professionals. 80% of the sample, particularly most of the health professionals, required a high-intensity intervention (level II). Nearly 50% of the people treated were discharged after an average of 5 interventions. Providing early care to COVID-19 patients, relatives and professionals by using community mental health resources can help to reduce the negative impact of crises, such as the pandemic, on the most affected population groups.


Assuntos
COVID-19 , Humanos , Feminino , Masculino , COVID-19/epidemiologia , Pandemias , Seguimentos , Saúde Mental , SARS-CoV-2
9.
Artigo em Inglês | MEDLINE | ID: mdl-35270404

RESUMO

The SARS-CoV-2 health emergency has led to a restructuring of health care systems and the reassignment of medical specialists from their usual duties to attend COVID-19 patients. The aim of this paper is to describe the levels of insomnia, anxiety, depression, and the impact on quality of life of doctors who were on the frontline of COVID-19 during the first two waves of the pandemic. Self-report surveys were conducted on said physicians during both waves, with 83 and 61 responses in the first and second waves, respectively. The reported presence of insomnia was frequent (71.8%), although it decreased in the second survey. Anxiety was moderate, decreasing from 57.1% to 43.1% between measurements. Overall, depression rates decreased between the two surveys. Substance use was found to have an indirect correlation with personal and professional satisfaction. In the light of the unforeseeable evolution of the pandemic and the medium- to long-term repercussions on professionals, we believe the adaptation of health resources is crucial to meet the new unpredictable mental health needs of this group.


Assuntos
COVID-19 , Médicos , Ansiedade/epidemiologia , Ansiedade/psicologia , COVID-19/epidemiologia , Depressão/epidemiologia , Depressão/psicologia , Humanos , Satisfação Pessoal , Qualidade de Vida/psicologia , SARS-CoV-2 , Qualidade do Sono
10.
Molecules ; 27(4)2022 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-35208995

RESUMO

Lubricants are materials able to reduce friction and/or wear of any type of moving surfaces facilitating smooth operations, maintaining reliable machine functions, and reducing risks of failures while contributing to energy savings. At present, most worldwide used lubricants are derived from crude oil. However, production, usage and disposal of these lubricants have significant impact on environment and health. Hence, there is a growing pressure to reduce demand of this sort of lubricants, which has fostered development and use of green lubricants, as vegetable oil-based lubricants (biolubricants). Despite the ecological benefits of producing/using biolubricants, availability of the required raw materials and agricultural land to create a reliable chain supply is still far from being established. Recently, biomass from some microalgae species has attracted attention due to their capacity to produce high-value lipids/oils for potential lubricants production. Thus, this multidisciplinary work reviews the main chemical-physical characteristics of lubricants and the main attempts and progress on microalgae biomass production for developing oils with pertinent lubricating properties. In addition, potential microalgae strains and chemical modifications to their oils to produce lubricants for different industrial applications are identified. Finally, a guide for microalgae oil selection based on its chemical composition for specific lubricant applications is provided.


Assuntos
Biomassa , Lubrificantes , Microalgas , Materiais Biocompatíveis/química , Reatores Biológicos , Biotecnologia , Lubrificantes/química , Lubrificantes/isolamento & purificação , Lubrificação , Microalgas/química , Microalgas/crescimento & desenvolvimento , Fotossíntese
11.
JBRA Assist Reprod ; 26(1): 22-27, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-34415121

RESUMO

OBJECTIVE: To compare the clinical pregnancy rate among patients undergoing direct in vitro fertilization vs. in vitro fertilization after two cycles of intrauterine insemination in couples with unexplained infertility. METHODS: Comparative cross-sectional, retrospective study from 2016 to 2019, from the Centro Mexicano de Fertilidad Doctor Alberto Kably. The patients with unexplained infertility were divided into two groups, direct in vitro fertilization and a group of in vitro fertilization after intrauterine insemination, and we compared the rate of pregnancy and live births in both cases. RESULTS: 89 couples with unexplained infertility were included, the in vitro fertilization after intrauterine insemination group (n=46) and direct in vitro fertilization group (n=43). The direct in vitro fertilization group resulted in a higher clinical pregnancy rate throughout the study compared to the other group (55.8% vs. 34.8%, OR 2.37; 95% CI 1.008 - 5.57, p=0.046). However, there was no difference in the rate of live newborns (p=0.12). When analyzing the data by cycle, we noticed a statistical difference in both, the clinical pregnancy rate in the direct in vitro fertilization group (38.7% vs. 16.7%, OR 3.2; 95% CI 1.50-6.62), as well as the rate of live newborns (32.3 % vs. 14.6%, OR 2.79; 95% CI 1.28-6.07, p=0.008). CONCLUSIONS: In the in vitro fertilization group, as first-line treatment for unexplained infertility, the patients had a higher pregnancy rate.


Assuntos
Fertilização In Vitro , Infertilidade , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Infertilidade/epidemiologia , Infertilidade/terapia , Inseminação Artificial , Gravidez , Taxa de Gravidez , Estudos Retrospectivos
12.
Rev. colomb. cir ; 36(3): 481-486, 20210000. fig, tab
Artigo em Espanhol | LILACS | ID: biblio-1254307

RESUMO

Introducción. La prevención de las complicaciones en el manejo de la apendicitis aguda sigue siendo un reto para el cirujano pediatra; por lo que es de gran importancia comparar las opciones de manejo quirúrgico, para saber si es posible prevenir dichos resultados, que finalmente llevan a un aumento en el uso de recursos necesarios para tratar a un paciente. El objetivo de este estudio fue comparar las complicaciones postoperatorias y los costos de la laparoscopia transumbilical asistida y la laparoscopia multipuerto, en pacientes pediátricos en un hospital general de cuarto nivel de la ciudad de Bogotá, D.C., Colombia, entre octubre de 2011 y enero de 2019. Métodos. Estudio observacional, descriptivo, retrospectivo, de corte transversal, con muestreo no probabilístico a conveniencia, en el que se incluyeron los pacientes entre 0 y 16 años de edad, con historia clínica completa y diagnóstico postquirúrgico de apendicitis aguda, los cuales fueron intervenidos mediante cirugía laparoscópica transumbilical asistida o por multipuerto. Se hizo un análisis descriptivo univariado y bivariado. Resultados. De los 850 pacientes operados en ese periodo, la técnica quirúrgica más usada fue multipuerto (n=528, 62,1%) y se presentaron complicaciones en 59 (6,94%) de los pacientes. El diagnóstico postquirúrgico más frecuente fue apendicitis no perforada (n=762, 89,6%). Al comparar los dos grupos se encontró un valor de p de 0,9685 para la edad, 0,5364 para el diagnóstico postquirúrgico, 0,1127 para las complicaciones postoperatorias y 0,0085 para el costo. Discusión. El costo de hospitalización y las complicaciones de los pacientes a quienes se les practicó apendicectomía transumbilical asistida es similar a la técnica por multipuerto


Introduction. The prevention of complications in the management of acute appendicitis remains a challenge for the pediatric surgeon. Therefore, it is of great importance to compare the surgical management options, to know if it is possible to prevent these results, which ultimately lead to an increase in the use of resources necessary to treat a patient. The objective of this study was to compare the postoperative complications and costs of assisted transumbilical laparoscopy and multiport laparoscopy in pediatric patients. Method. Observational, descriptive, retrospective, cross-sectional study with non-probabilistic convenience sampling, where patients between 0 and 16 years old with a complete medical history, with a postsurgical diagnosis of acute appendicitis, who underwent assisted transumbilical surgery or by multiport performed at a fourth level general hospital in Bogotá, Colombia, between October 2011 and January of 2019. A descriptive univariate and bivariate analysis was performed. Results. Of the 850 patients operated on in this period, the most used surgical technique was multiport (n=528; 62.1%) and complications occurred in 59 (6.94%) of the patients. The most frequent postsurgical diagnosis was non-perforated appendicitis (n=762; 89.6%). Comparing the two groups, a p-value of 0.9685 was found for age, 0.5364 for postsurgical diagnosis, 0.1127 for postoperative complications, and 0.0085 for cost. Discussion. The cost of hospitalization and complications for patients who underwent assisted transumbilical appendectomy is similar to the multiport technique


Assuntos
Humanos , Apendicite , Procedimentos Cirúrgicos Minimamente Invasivos , Apendicectomia , Complicações Pós-Operatórias , Custos e Análise de Custo
13.
J Environ Manage ; 279: 111813, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33338770

RESUMO

Microalgae-bacteria consortium based technology using a High Rate Algal Pond (HRAP) interconnected to an Absorption Bubble Column (ABC) has emerged as an environmentally friendly promising option to upgrade biogas. However, the oxygenic photosynthesis of microalgae induces oxygen contamination in upgraded biogas, which could limit its further applications. Several strategies were proposed to favor the oxygen desorption and oxygen uptake in parts and accessories of the upgrading system. The effect of the volumetric ratio liquid recirculation rate/biogas rate (L/G = 5.0, 1.0 y 0.5) was evaluated in conjunction with the application of a novel accessory called Open Trickling Column (OTC). The O2 content in upgraded biogas was around 2.1%v, attaining CO2 removal efficiencies around 90%, at L/G ratio of 1.0 during diurnal and nocturnal periods. The inclusion of an OTC at the previous L/G, enhanced 54% the removal of O2 by stripping and uptake compared with the basal condition. Mass balances of H2S and methane showed that L/G > 1.0 favored the complete oxidation of H2S but promoted the loss of methane in dissolved form. Additionally the effect of increasing linear velocity of liquid broth in the lab-scale HRAP (from 15 cm s-1 to 20 cm s-1) showed to improve the O2 stripping with a consequential increase of biomass concentration under steady-state (from 0.7 to 1.4 g L-1) besides achieving O2 content in the upgraded biogas around 1.5%v.


Assuntos
Microalgas , Biocombustíveis , Biomassa , Dióxido de Carbono/análise , Metano , Oxigênio , Fotobiorreatores , Tecnologia
14.
Rev Int Androl ; 19(4): 285-288, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-33358454

RESUMO

INTRODUCTION: Hyperprolactinaemia is an unusual cause of erectile dysfunction, yet erectile dysfunction is a common complaint in patients with hyperprolactinaemia. We present a patient with erectile dysfunction without symptoms suggesting hyperprolactinaemia. MATERIALS AND METHODS: Patient consulted with erectile dysfunction for the past 10 years. Decreased time and quality of erection with an IIEF score of 14/30. Lab reports: prolactin 90.2 ng/ml, FSH 1.6 mlU/ml, LH 1.8 UI/L, total testosterone .491 ng/ml. Brain MRI: lateral pituitary micro adenoma, 5mm in diameter. RESULTS: Patient in treatment with cabergoline 1mg per week, after treatment noticed improvement in erectile dysfunction and sexual desire. Actual prolactin 15.4 ng/ml. CONCLUSIONS: Up to 5% of patients with erectile dysfunction are diagnosed with a pituitary adenoma. Erectile dysfunction caused by pituitary neoplasms is a multifactorial disease and elevated prolactin has consequences on testosterone, LH, FSH, and dopamine precursor levels.


Assuntos
Disfunção Erétil/tratamento farmacológico , Hormônio Foliculoestimulante/uso terapêutico , Neoplasias Hipofisárias/complicações , Prolactinoma/complicações , Adulto , Cabergolina/uso terapêutico , Disfunção Erétil/diagnóstico , Disfunção Erétil/etiologia , Hormônio Foliculoestimulante/sangue , Humanos , Masculino , Prolactina/sangue , Prolactinoma/diagnóstico , Testosterona/sangue , Resultado do Tratamento
16.
Artigo em Inglês | MEDLINE | ID: mdl-32759705

RESUMO

Healthcare services are facing challenges in increasing their efficiency, quality of care, and coping with surges in demand. To this end, some hospitals have implemented lean healthcare. The aim of this systematic review is to evaluate the effects of lean healthcare (LH) interventions on inpatient care and determine whether patient flow and efficiency outcomes improve. The review was performed according to PRISMA. We used six databases to search for studies published from 2002 to 2019. Out of 5732 studies, 39 measuring one or more defined outcomes were included. Hospital length of stay (LOS) was measured in 23 studies, 16 of which reported a reduction, turnover time (TOT) decreased in six out of eight studies, while the turnaround time (TAT) and on-time starts (OTS) improved in all five and seven studies, respectively. Moreover, eight out of nine studies reported an earlier discharge time, and the boarding time decreased in all four cases. Meanwhile, the readmission rate did not increase in all nine studies. Lastly, staff and patient satisfaction improved in all eight studies. Our findings show that by focusing on reducing non-value-added activities, LH contributed to improving patient flow and efficiency within inpatient care.


Assuntos
Hospitalização , Qualidade da Assistência à Saúde , Gestão da Qualidade Total , Estudos de Coortes , Hospitais , Humanos , Pacientes Internados , Tempo de Internação
17.
J Alzheimers Dis ; 76(4): 1527-1539, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32716353

RESUMO

BACKGROUND: Iron nanoparticles, mainly in magnetite phase (Fe3O4 NPs), are released to the environment in areas with high traffic density and braking frequency. Fe3O4 NPs were found in postmortem human brains and are assumed to get directly into the brain through the olfactory nerve. However, these pollution-derived NPs may also translocate from the lungs to the bloodstream and then, through the blood-brain barrier (BBB), into the brain inducing oxidative and inflammatory responses that contribute to neurodegeneration. OBJECTIVE: To describe the interaction and toxicity of pollution-derived Fe3O4 NPs on primary rat brain microvascular endothelial cells (rBMECs), main constituents of in vitro BBB models. METHODS: Synthetic bare Fe3O4 NPs that mimic the environmental ones (miFe3O4) were synthesized by co-precipitation and characterized using complementary techniques. The rBMECs were cultured in Transwell® plates. The NPs-cell interaction was evaluated through transmission electron microscopy and standard colorimetric in vitro assays. RESULTS: The miFe3O4 NPs, with a mean diameter of 8.45±0.14 nm, presented both magnetite and maghemite phases, and showed super-paramagnetic properties. Results suggest that miFe3O4 NPs are internalized by rBMECs through endocytosis and that they are able to cross the cells monolayer. The lowest miFe3O4 NPs concentration tested induced mid cytotoxicity in terms of 1) membrane integrity (LDH release) and 2) metabolic activity (MTS transformation). CONCLUSION: Pollution-derived Fe3O4 NPs may interact and cross the microvascular endothelial cells forming the BBB and cause biological damage.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Lesões Encefálicas/induzido quimicamente , Células Endoteliais/efeitos dos fármacos , Nanopartículas Magnéticas de Óxido de Ferro , Nanopartículas/toxicidade , Transporte Biológico/efeitos dos fármacos , Barreira Hematoencefálica/lesões , Barreira Hematoencefálica/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Células Cultivadas , Endocitose/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos
18.
Int J Mol Sci ; 21(15)2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32722468

RESUMO

Salicylic acid (SA) is an important signaling molecule involved in plant defense. While many proteins play essential roles in SA signaling, increasing evidence shows that responses to SA appear to involve and require lipid signals. The phospholipid-generated signal transduction involves a family of enzymes that catalyze the hydrolysis or phosphorylation of phospholipids in membranes to generate signaling molecules, which are important in the plant cellular response. In this review, we focus first, the role of SA as a mitigator in biotic/abiotic stress. Later, we describe the experimental evidence supporting the phospholipid-SA connection in plant cells, emphasizing the roles of the secondary lipid messengers (phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid (PA)) and related enzymes (phospholipase D (PLD) and phospholipase C (PLC)). By placing these recent finding in context of phospholipids and SA in plant cells, we highlight the role of phospholipids as modulators in the early steps of SA triggered transduction in plant cells.


Assuntos
Ácidos Fosfatídicos/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Células Vegetais/metabolismo , Ácido Salicílico/farmacologia , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Fosfolipase D/metabolismo , Proteínas de Plantas/metabolismo
19.
Clin Cancer Res ; 26(10): 2346-2353, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-31937615

RESUMO

PURPOSE: Ruxolitinib with lenalidomide and dexamethasone shows antimyeloma effects in vitro and in vivo. MUC1 leads to lenalidomide resistance in multiple myeloma cells, and ruxolitinib blocks its expression. Thus, ruxolitinib may restore sensitivity to lenalidomide. Therefore, a phase I trial was conducted to determine the safety and efficacy of ruxolitinib with lenalidomide and methylprednisolone for patients with relapsed/refractory multiple myeloma (RRMM) who had been treated with lenalidomide/steroids and a proteasome inhibitor and showed progressive disease at study entry. PATIENTS AND METHODS: A traditional 3+3 dose escalation design was used to enroll subjects in four cohorts with planned total enrollment of 28 patients. Subjects received ruxolitinib twice daily, lenalidomide daily on days 1-21 of a 28-day cycle, and methylprednisolone orally every other day. Primary endpoints were safety, clinical benefit rate (CBR), and overall response rate (ORR). RESULTS: Twenty-eight patients were enrolled. The median age was 67 years and received a median of six prior treatments including lenalidomide and steroids to which 93% were refractory. No dose-limiting toxicities occurred. The CBR and ORR were 46% and 38%, respectively. All 12 responding patients were refractory to lenalidomide. Grade 3 or grade 4 adverse events (AE) included anemia (18%), thrombocytopenia (14%), and lymphopenia (14%). Most common serious AEs included sepsis (11%) and pneumonia (11%). CONCLUSIONS: This phase I trial demonstrates that a JAK inhibitor, ruxolitinib, can overcome refractoriness to lenalidomide and steroids for patients with RRMM. These results represent a promising novel therapeutic approach for treating multiple myeloma (ClinicalTrials.gov number, NCT03110822).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 2/antagonistas & inibidores , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Nitrilas , Pirazóis/administração & dosagem , Pirazóis/efeitos adversos , Pirimidinas , Taxa de Sobrevida
20.
Ginecol. obstet. Méx ; 88(4): 244-251, ene. 2020. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1346182

RESUMO

Resumen OBJETIVO: Evaluar el efecto del doble disparo en pacientes con un ciclo previo con menos de 65% de ovocitos maduros respecto de los ovocitos capturados, en una población con respuesta normal a la inducción de la ovulación con hCG recombinante o urinaria. MATERIALES Y MÉTODOS: Estudio de cohorte, prospectivo, efectuado en pacientes con diagnóstico de infertilidad, en tratamiento con fertilización in vitro, evaluadas en el Centro Mexicano de Fertilidad (Hospital Ángeles Lomas) entre 2017 y 2019. El tratamiento se llevó a cabo en la misma paciente, en cuyo ciclo previo convencional con esquema de antagonista e inducción de la ovulación con hCG tuvo respuesta ovárica subóptima y captura ovocitaria con menos de 65% en fase M2 (Grupo 1). Posteriormente se les indicó un segundo ciclo con el mismo esquema de gonadotropinas e inducción de la ovulación con doble disparo: acetato de triptorelina 1 mg + 5000 UI de hCG urinaria 40 y 34 horas previas a la captura (Grupo 2). Se evaluaron el porcentaje y la cantidad de ovocitos capturados en fase M2. RESULTADOS: Se registraron 34 pacientes en quienes se llevaron a cabo 68 ciclos. La cantidad de ovocitos capturados fue mayor en el grupo 2 (agonista de GnRH + hCG urinaria; p = 0.03). El doble disparo aumentó el porcentaje de ovocitos maduros (65.4 ± 21.3 vs 74.6 ± 20.2; p = 0.07). CONCLUSIONES: La técnica de doble disparo es valiosa para el tratamiento de pacientes con captura de ovocitos deficiente, aun con desarrollo folicular normal y concentraciones de estradiol adecuadas y óptimas de hCG el día de la captura. Se requieren estudios prospectivos de gran tamaño para dilucidar la recomendación mencionada de la técnica de "doble disparo".


Abstract OBJECTIVE: To evaluate the effect of double trigger in patients with a previous cycle with less than 65% of mature oocytes compared to the captured oocytes, in a normorresponding population with induction of ovulation with recombinant or urinary hCG. MATERIALS AND METHODS: A prospective cohort study, conducted in patients diagnosed with infertility, treated with in vitro fertilization, evaluated at the Mexican Fertility Center (Hospital Angeles Lomas) between 2017 and 2019. The treatment was carried out in the same patient, in whose previous conventional cycle with antagonist scheme and induction of ovulation with hCG had suboptimal ovarian response and oocyte capture with less than 65% in M2 phase (Group 1). Subsequently, a second cycle was performed with the same scheme of gonadotropins and induction of ovulation with double shot: 1 mg triptorelin acetate + 5000 IU of urinary hCG 40 and 34 hours prior to capture (Group 2 or double trigger). Percentage and quantity of oocytes captured in M2 phase were evaluated. RESULTS: 34 patients were registered, in whom 68 cycles were performed. The number of oocytes captured was greater in group 2 (agonist of GnRH + urinary hCG; p = 0.03). The double shot increased the percentage of mature oocytes 65.4 ± 21.3 vs 74.6 ± 20.2 (p = 0.07). CONCLUSIONS: The double trigger technique is valuable for the treatment of patients with poor oocyte capture, even with normal follicular development and adequate and optimal hCG estradiol concentrations on the day of capture. Large prospective studies are required to elucidate the aforementioned recommendation of the "double shot" technique.

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