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BACKGROUND: In the rush to develop health technologies for the COVID-19 pandemic, the unintended consequence of digital health inequity or the inability of priority communities to access, use, and receive equal benefits from digital health technologies was not well examined. OBJECTIVE: This scoping review will examine tools and approaches that can be used during digital technology innovation to improve equitable inclusion of priority communities in the development of digital health technologies. The results from this study will provide actionable insights for professionals in health care, health informatics, digital health, and technology development to proactively center equity during innovation. METHODS: Based on the Arksey and O'Malley framework, this scoping review will consider priority communities' equitable involvement in digital technology innovation. Bibliographic databases in health, medicine, computing, and information sciences will be searched. Retrieved citations will be double screened against the inclusion and exclusion criteria using Covidence (Veritas Health Innovation). Data will be charted using a tailored extraction tool and mapped to a digital health innovation pathway defined by the Centre for eHealth Research roadmap for eHealth technologies. An accompanying narrative synthesis will describe the outcomes in relation to the review's objectives. RESULTS: This scoping review is currently in progress. The search of databases and other sources returned a total of 4868 records. After the initial screening of titles and abstracts, 426 studies are undergoing dual full-text review. We are aiming to complete the full-text review stage by May 30, 2024, data extraction in October 2024, and subsequent synthesis in December 2024. Funding was received on October 1, 2023, from the Centre for Health Equity Incubator Grant Scheme, University of Melbourne, Australia. CONCLUSIONS: This paper will identify and recommend a series of validated tools and approaches that can be used by health care stakeholders and IT developers to produce equitable digital health technology across the Centre for eHealth Research roadmap. Identified evidence gaps, possible implications, and further research will be discussed. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53855.
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COVID-19 , Equidad en Salud , Humanos , COVID-19/epidemiología , Telemedicina/organización & administración , Tecnología Digital , Salud DigitalRESUMEN
Artificial intelligence (AI) algorithms have the potential to revolutionize healthcare, but their successful translation into clinical practice has been limited. One crucial factor is the data used to train these algorithms, which must be representative of the population. However, most healthcare databases are derived from high-income countries, leading to non-representative models and potentially exacerbating health inequities. This review focuses on the landscape of health-related open datasets in Latin America, aiming to identify existing datasets, examine data-sharing frameworks, techniques, platforms, and formats, and identify best practices in Latin America. The review found 61 datasets from 23 countries, with the DATASUS dataset from Brazil contributing to the majority of articles. The analysis revealed a dearth of datasets created by the authors themselves, indicating a reliance on existing open datasets. The findings underscore the importance of promoting open data in Latin America. We provide recommendations for enhancing data sharing in the region.
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Artificial intelligence (AI) and machine learning (ML) have an immense potential to transform healthcare as already demonstrated in various medical specialties. This scoping review focuses on the factors that influence health data poverty, by conducting a literature review, analysis, and appraisal of results. Health data poverty is often an unseen factor which leads to perpetuating or exacerbating health disparities. Improvements or failures in addressing health data poverty will directly impact the effectiveness of AI/ML systems. The potential causes are complex and may enter anywhere along the development process. The initial results highlighted studies with common themes of health disparities (72%), AL/ML bias (28%) and biases in input data (18%). To properly evaluate disparities that exist we recommend a strengthened effort to generate unbiased equitable data, improved understanding of the limitations of AI/ML tools, and rigorous regulation with continuous monitoring of the clinical outcomes of deployed tools.
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Current methods to evaluate a journal's impact rely on the downstream citation mapping used to generate the Impact Factor. This approach is a fragile metric prone to being skewed by outlier values and does not speak to a researcher's contribution to furthering health outcomes for all populations. Therefore, we propose the implementation of a Diversity Factor to fulfill this need and supplement the current metrics. It is composed of four key elements: dataset properties, author country, author gender and departmental affiliation. Due to the significance of each individual element, they should be assessed independently of each other as opposed to being combined into a simplified score to be optimized. Herein, we discuss the necessity of such metrics, provide a framework to build upon, evaluate the current landscape through the lens of each key element and publish the findings on a freely available website that enables further evaluation. The OpenAlex database was used to extract the metadata of all papers published from 2000 until August 2022, and Natural language processing was used to identify individual elements. Features were then displayed individually on a static dashboard developed using TableauPublic, which is available at www.equitablescience.com. In total, 130,721 papers were identified from 7,462 journals where significant underrepresentation of LMIC and Female authors was demonstrated. These findings are pervasive and show no positive correlation with the Journal's Impact Factor. The systematic collection of the Diversity Factor concept would allow for more detailed analysis, highlight gaps in knowledge, and reflect confidence in the translation of related research. Conversion of this metric to an active pipeline would account for the fact that how we define those most at risk will change over time and quantify responses to particular initiatives. Therefore, continuous measurement of outcomes across groups and those investigating those outcomes will never lose importance. Moving forward, we encourage further revision and improvement by diverse author groups in order to better refine this concept.
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Artificial Intelligence (AI) represents a significant milestone in health care's digital transformation. However, traditional health care education and training often lack digital competencies. To promote safe and effective AI implementation, health care professionals must acquire basic knowledge of machine learning and neural networks, critical evaluation of data sets, integration within clinical workflows, bias control, and human-machine interaction in clinical settings. Additionally, they should understand the legal and ethical aspects of digital health care and the impact of AI adoption. Misconceptions and fears about AI systems could jeopardize its real-life implementation. However, there are multiple barriers to promoting electronic health literacy, including time constraints, overburdened curricula, and the shortage of capacitated professionals. To overcome these challenges, partnerships among developers, professional societies, and academia are essential. Integrating specialists from different backgrounds, including data specialists, lawyers, and social scientists, can significantly contribute to combating digital illiteracy and promoting safe AI implementation in health care.
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Inteligencia Artificial , Curriculum , Humanos , Escolaridad , Redes Neurales de la Computación , Aprendizaje AutomáticoRESUMEN
Introduction In January, the National Institutes of Health (NIH) implemented a Data Management and Sharing Policy aiming to leverage data collected during NIH-funded research. The COVID-19 pandemic illustrated that this practice is equally vital for augmenting patient research. In addition, data sharing acts as a necessary safeguard against the introduction of analytical biases. While the pandemic provided an opportunity to curtail critical research issues such as reproducibility and validity through data sharing, this did not materialise in practice and became an example of 'Open Data in Appearance Only' (ODIAO). Here, we define ODIAO as the intent of data sharing without the occurrence of actual data sharing (eg, material or digital data transfers).Objective Propose a framework that states the main risks associated with data sharing, systematically present risk mitigation strategies and provide examples through a healthcare lens.Methods This framework was informed by critical aspects of both the Open Data Institute and the NIH's 2023 Data Management and Sharing Policy plan guidelines.Results Through our examination of legal, technical, reputational and commercial categories, we find barriers to data sharing ranging from misinterpretation of General Data Privacy Rule to lack of technical personnel able to execute large data transfers. From this, we deduce that at numerous touchpoints, data sharing is presently too disincentivised to become the norm.Conclusion In order to move towards Open Data, we propose the creation of mechanisms for incentivisation, beginning with recentring data sharing on patient benefits, additional clauses in grant requirements and committees to encourage adherence to data reporting practices.
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COVID-19 , Humanos , Estados Unidos , Pandemias , Reproducibilidad de los Resultados , National Institutes of Health (U.S.) , Difusión de la Información/métodosRESUMEN
BACKGROUND/AIM: Renin-angiotensin system (RAS) is present in a diverse type of cells and plays an important role in lung physiology and pathophysiology. Angiotensin converting enzymes (ACE) are part of the RAS system. There are still controversies about the association of I/D polymorphisms of ACE1 with COVID-19 severity. The goal of the study was to determine whether there is an association of the I/D polymorphism with severity of COVID-19 in Mexican patients. PATIENTS AND METHODS: The study included voluntary participants: 53 healthy individuals negative to RT-PCR COVID-19 (control), and 165 patients positive to COVID-19. Severity was defined by the need of hospitalization, invasive ventilation, shock, or multiple organ failure. The patient group consisted of 28 asymptomatic, 82 with mild, and 55 with severe COVID-19. I/D polymorphism was determined by PCR. Rutinary laboratory tests were performed in all the participants. RESULTS: DD polymorphism was significantly associated with severe COVID-19, independently of comorbidities, or any other variable. Receiver operator characteristic curves demonstrated association of low total cholesterol, low high-density lipoproteins, and high c-reactive protein with severity of COVID-19. CONCLUSION: The DD polymorphism was associated with the course of the infection and severity of COVID-19 in a sample of Mexican patients.
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COVID-19 , Humanos , COVID-19/genética , Lípidos/sangre , Polimorfismo Genético , Sistema Renina-Angiotensina/genéticaRESUMEN
Cardiovascular (CV) diseases are the major cause of death in industrialized countries. The main function of the CV system is to deliver nutrients and oxygen to all tissues. During most CV pathologies, oxygen and nutrient delivery is decreased or completely halted. Several mechanisms, including increased oxygen transport and delivery, as well as increased blood flow are triggered to compensate for the hypoxic state. If the compensatory mechanisms fail to sufficiently correct the hypoxia, irreversible damage can occur. Thus, hypoxia plays a central role in the pathogenesis and pathophysiology of CV diseases. Hypoxia inducible factors (HIFs) orchestrate the gene transcription for hundreds of proteins involved in erythropoiesis, glucose transport, angiogenesis, glycolytic metabolism, reactive oxygen species (ROS) handling, cell proliferation and survival, among others. The overall regulation of the expression of HIF-dependent genes depends on the severity, duration, and location of hypoxia. In the present review, common CV diseases were selected to illustrate that HIFs, and proteins derived directly or indirectly from their stabilization and activation, are related to the development and perpetuation of hypoxia in these pathologies. We further classify CV diseases into acute and chronic hypoxic states to better understand the temporal relevance of HIFs in the pathogenesis, disease progression and clinical outcomes of these diseases. We conclude that HIFs and their derived factors are fundamental in the genesis and progression of CV diseases. Understanding these mechanisms will lead to more effective treatment strategies leading to reduced morbidity and mortality.
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Breast cancer (BC) is the leading cause of cancer death in women worldwide, with a higher mortality reported in undeveloped countries. Ideal adjuvant therapeutic strategies require the continuous monitoring of patients by regular blood tests to detect circulating cancer cells, in order to determine whether additional treatment is necessary to prevent cancer dissemination. This circumstance requires a non-complex design of tumor cell biosensor in whole blood with feasibility for use in poor regions. In this work we have evaluated an inexpensive and simple technique of relative bioimpedance measurement, assisted by magnetic nanoparticles, as a potential biosensor of BC cells in suspension. Measurements represent the relative impedance changes caused by the magnetic holding of an interphase of tumor cells versus a homogenous condition in the frequency range of 10-100 kHz. The results indicate that use of a magnet to separate tumor cells in suspension, coupled to magnetic nanoparticles, is a feasible technique to fix an interphase of tumor cells in close proximity to gold electrodes. Relative impedance changes were shown to have potential value as a biosensor method for BC cells in whole blood, at frequencies around 20 kHz. Additional studies are warranted with respect to electrode design and sensitivity at micro-scale levels, according to the proposed technique.
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Técnicas Biosensibles , Neoplasias de la Mama/diagnóstico , Espectroscopía Dieléctrica , Nanopartículas de Magnetita , Neoplasias de la Mama/patología , Línea Celular Tumoral , Electricidad , Femenino , Humanos , Microscopía ConfocalRESUMEN
INTRODUCTION: Spectral analysis of heart rate variability is a noninvasive method for evaluating autonomic cardiovascular dysfunction under various clinical conditions, such as in dialysis patients, in whom an imbalance between the sympathetic and parasympathetic nervous system appears to be an important risk factor for sudden cardiovascular death and arrhythmia. ⢠OBJECTIVE: We compared the effect of icodextrin-based dialysis solution, an option that allows for better metabolic and fluid overload control, with that of glucose-based dialysis fluid on sympathetic and parasympathetic activity in the heart, as assessed by heart rate variability, in diabetic patients on peritoneal dialysis (PD). ⢠METHODS: This secondary analysis uses data from a randomized controlled trial in diabetic PD patients with high or high-average peritoneal transport using icodextrin-based (ICO group, n = 30) or glucose-based (GLU group, n = 29) solutions for the long dwell. All patients underwent 24-hour electrocardiographic Holter monitoring at baseline, and at 6 and 12 months of follow-up. ⢠RESULTS: We observed no significant differences between the groups in most of the variables analyzed, although values were, in general, below reference values. In the ICO group, total power and both low- and high-frequency power in normalized units increased, but the percentage of RR intervals with variation of more than 50 ms declined over time; in the GLU group, all those values declined. Plasma catecholamine levels were higher at baseline and declined over time. ⢠CONCLUSIONS: These results indicate a partial recovery of sympathetic activity in the ICO group, probably because of better extracellular fluid control and lower exposure to glucose with the use of icodextrin-based dialysis solutions.
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Diabetes Mellitus Tipo 2/fisiopatología , Soluciones para Diálisis/farmacología , Glucanos/farmacología , Glucosa/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Diálisis Peritoneal , Muerte Súbita Cardíaca , Femenino , Humanos , Icodextrina , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Surgically induced adhesions complicate up to 100% of abdominal surgeries. Food and Drug Administration-approved treatments are generally not only less effective than desired but they also have major contraindications. Oxychlorine species, including chlorine dioxide (ClO2), suppress scar formation in infected wounds without affecting keratinocytes while reducing fibroblast proliferation. The aim of the present study was to evaluate the effect of oxychlorine solutions containing ClO2 on adhesion formation. METHODS: Male Wistar rats were subjected to Buckenmaier model of surgical adhesions and treated with either oxychlorine solutions containing ClO2 (40-150 ppm) or isotonic saline solution. To increase the severity of adhesions, peritonitis was produced by intraperitoneal administration of a diluted nonlethal dose of feces (50 mg/kg). Wound strength of the healed wound was measured to evaluate the effects of oxychlorine solutions. In addition, an oxychlorine solution of lesser efficacy (at 100 ppm) was compared with three available anti-adhesion materials. RESULTS: Reproducibility of the model was validated in 26 rats. Oxychlorine solutions containing ClO2 (40-110 ppm) significantly reduced postsurgical adhesion formation without affecting the strength of the healed wound. Higher concentrations (120 and 150 ppm) had no effect. Fecal peritonitis significantly increased, and solutions with ClO2 at 110 ppm significantly reduced adhesion formation. The effect of the oxychlorine solution was significantly greater than that of Interceed, Guardix, Seprafilm, and isotonic saline solution. CONCLUSIONS: ClO2-containing oxychlorine solutions could be an innovative strategy for the suppression of surgical adhesion formation, with the additional advantage of contributing antiseptic properties.
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Compuestos de Cloro/farmacología , Óxidos/farmacología , Adherencias Tisulares/prevención & control , Animales , Relación Dosis-Respuesta a Droga , Hipoxia/complicaciones , Masculino , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Adherencias Tisulares/etiologíaRESUMEN
Oxidative stress (OS) induced by acute exercise is reduced by chronic exercise. Ozone (O(3)) exposure produces OS. The aim of this study was to determine if aerobic exercise (AE) reduced OS produced by O(3). A pilot experiment was performed with male Wistar rats submitted to AE (trained to swim 90 min/day). Adaptation to exercise was demonstrated three weeks after training by means of changes in reduced nitrates (NO(x)) in plasma. Therefore, two-week training was chosen for the following experiments. Six of twelve trained rats were exposed to O(3) (0.5 ppm, 4 h/day, one hour before exercise). Two groups of sedentary animals (n = 6 each) were used as controls, one of which was exposed to O(3). At the end of the experiments NO(x), 8-isoprostane (8-IP), malondialdehyde (MDA), superoxide dismutase (SOD) activity, and carbonyls (CBs) were measured in plasma. CBs did not change in any group. O(3)-induced OS was manifested by reduced NO(x) and SOD activity, as well as increased 8-IP and MDA. Exercise significantly blocked O(3) effects although SOD was also decreased by exercise (a greater drop occurring in the O(3) group). It is concluded that AE protects against OS produced by O(3) and the effect is independent of SOD.
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Estrés Oxidativo/efectos de los fármacos , Ozono/farmacología , Condicionamiento Físico Animal , Animales , Dinoprost/análogos & derivados , Dinoprost/metabolismo , Masculino , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
Antioxidants are among the most popular health-protecting products, sold worldwide without prescription. Indeed, there are many reports showing the benefits of antioxidants but only a few questioning the possible harmful effects of these "drugs". The normal balance between antioxidants and free radicals in the body is offset when either of these forces prevails. The available evidence on the harmful effects of antioxidants is analyzed in this review. In summary, a hypothesis is presented that "antioxidant-induced stress" results when antioxidants overwhelm the body's free radicals.
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Antioxidantes/efectos adversos , Estrés Oxidativo/efectos de los fármacos , Ensayos Clínicos como Asunto , Progresión de la Enfermedad , Ejercicio Físico/fisiología , Radicales Libres/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/farmacología , Superóxidos/metabolismoRESUMEN
Pain is a symptom associated with alterations of the musculoskeletal system and frequently needs to be treated by the orthopedist. The purpose of this review is to analyze the mechanisms involved in the pain sensation and the various treatments that have been applied in orthopedics to control pain. Since it is known that the analgesic response is not the same in all patients, aspects that affect the pain sensation were assessed, such as the placebo effect, patients sex and genomic factors. The treatment varieties analyzed included drug therapy, considering the drugs, their pharmaceutical presentations and the route of administration most frequently used in orthopedics; and acupuncture, which has proven to be effective in special cases.
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Analgesia , Enfermedades Musculoesqueléticas/complicaciones , Manejo del Dolor , Analgesia por Acupuntura , Analgésicos/uso terapéutico , Humanos , Dolor/etiologíaRESUMEN
The effects of nitric oxide in biological systems depend on its steady-state concentration and where it is being produced. The organ where nitric oxide is produced is relevant, and within the organ, which types of cells are actually contributing to this production seem to play a major determinant of its effect. Subcellular compartmentalization of specific nitric oxide synthase enzymes has been shown to play a major role in health and disease. Pathophysiological conditions affect the cellular expression and localization of nitric oxide synthases, which in turn alter organ cross talk. In this study, we describe the compartmentalization of nitric oxide in organs, cells, and subcellular organelles and how its localization relates to several relevant clinical conditions. Understanding the complexity of the compartmentalization of nitric oxide production and the implications of this compartmentalization in terms of cellular targets and downstream effects will eventually contribute toward the development of better strategies for treating or preventing pathological events associated with the increase, inhibition, or mislocalization of nitric oxide production.
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Óxido Nítrico Sintasa/metabolismo , Fracciones Subcelulares/enzimología , Animales , Asma/fisiopatología , Compartimento Celular , Activación Enzimática , Regulación Enzimológica de la Expresión Génica , Semivida , Humanos , Isoenzimas/metabolismo , Hígado/enzimología , Hepatopatías/fisiopatología , Pulmón/enzimología , Músculo Esquelético/enzimología , Enfermedades Musculares/fisiopatología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa de Tipo I/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Neumonía/fisiopatología , Transporte de Proteínas/fisiología , Transducción de Señal/efectos de los fármacosRESUMEN
Larrea tridentata also known as Creosote bush, Larrea, chaparral, greasewood or gobernadora has been used in the folk medicine for the treatment of several illnesses. The primary product that is present at high concentrations in the leaves from this plant is nordihydroguaiaretic acid (NDGA) which is a powerful antioxidant. On the other hand, potassium dichromate (K(2)Cr(2)O(7))-induced nephrotoxicity is associated with oxidative stress. The aim of this work was to study the effect of NDGA on K(2)Cr(2)O(7)-induced nephrotoxicity and oxidative stress. Nephrotoxicity was induced by a single injection of K(2)Cr(2)O(7) (15 mg/Kg). A group of K(2)Cr(2)O(7)-treated rats was administered NDGA by mini osmotic pumps (17 mg/Kg/day). The results show that NDGA was able to ameliorate the structural and functional renal damage evaluated by histopathological analysis and by measuring proteinuria, urinary excretion of N-acetyl-beta-d-glucosaminidase, serum creatinine, and serum glutathione peroxidase activity. In addition, immunostaining of 4-hydroxy-2-nonenal and 3-nitrotyrosine, markers of oxidative and nitrosative stress, respectively, was ameliorated by the NDGA treatment. These data strongly suggest that the antioxidant properties of NDGA are involved in its renoprotective effect in K(2)Cr(2)O(7)-treated rats.
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Riñón/efectos de los fármacos , Masoprocol/farmacología , Estrés Oxidativo/efectos de los fármacos , Dicromato de Potasio/toxicidad , Animales , Femenino , Inmunohistoquímica , Ratas , Ratas WistarRESUMEN
This study evaluates experimentally an induction based non-invasive technique for detection of changes of fluid volume through phase shift measurements as a possible method for volumetric brain edema monitoring. An induction coil - spherical head model was build and tested. The model involves two different diameter coils coaxially centered on a two-compartment glass sphere head model centrally placed with respect to the coils. Three different fluid volumes of physiological saline in 20 ml increments were used to simulate different edema levels. Phase shift of the impedance coils as a function of relative fluid volume was measured at five frequencies (40, 50, 100, 200 and 300 MHz) by a commercial vector network analyzer. The results show significant phase shift increase as a function of frequency and fluid volume. The experiments with the coil-spherical head system suggest that the tested technique has the potential to become a practical configuration for non-invasive volumetric brain edema monitoring.
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Edema Encefálico/diagnóstico , Edema Encefálico/patología , Monitoreo Fisiológico/instrumentación , Análisis Espectral/instrumentación , Encéfalo/patología , Simulación por Computador , Conductividad Eléctrica , Impedancia Eléctrica , Fenómenos Electromagnéticos , Diseño de Equipo , Cabeza/patología , Humanos , Modelos Estadísticos , Modelos Teóricos , Monitoreo Fisiológico/métodos , Oscilometría , Pletismografía de Impedancia , Análisis Espectral/métodosRESUMEN
BACKGROUND: This work investigates the potential value of combined splanchnic perfusion and tissue injury measurements as a guide to resuscitation therapy during an experimental model of septic shock in anesthetized pigs. MATERIALS AND METHODS: An endotoxic shock model in 22 male pigs was developed by intravenous infusion of lipopolysaccharide. Three experimental groups were designed: a control group, a therapy group whose intervention was guided by haemodynamic variables, and a therapy group whose intervention was guided by splanchnic tissue indicators. The control group was allowed to progress into septic shock without intervention. The animals were subjected to resuscitation protocols with fluids and catecholamines depending on their responses, either to haemodynamic variables in one treatment group, or to measurements of pHi combined with an ischemic injury classification given by gastric impedance spectroscopy in the other treatment group. Resuscitation protocols were designed to promote changes in haemodynamic responses as well as splanchnic perfusion. A Kaplan-Meier survival analysis was estimated in each group. RESULTS: Survival in both treatment groups was significantly better than in the control group. There was no significant difference in the survival outcome between treatment groups. CONCLUSION: Splanchnic tissue indicators have the potential of being used as complementary tools for guiding the appropriate treatment of septic shock. The results justify the need for further studies in order to determine the best use of gastric tonometry and spectroscopic impedance information in clinical practice.
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Resucitación , Choque Séptico/fisiopatología , Análisis Espectral/métodos , Estómago/fisiopatología , Animales , Hemodinámica , Concentración de Iones de Hidrógeno , PorcinosRESUMEN
The ability of estradiol to affect phenylephrine-induced contraction and the subsequent increase in resting tone, associated with capacitative Ca(2+) entry across the plasma membrane, was evaluated in rat aortic rings incubated in Ca(2+)-free solution. The incubation with estradiol (1-100 nM, 5 min) inhibited both the phenylephrine-induced contraction and the IRT. Neither cycloheximide (1 microM; inhibitor of protein synthesis) nor tamoxifen (1 microM; blocker of estrogenic receptors) modified the effects of estradiol. Estradiol (100 microM) also blocked the contractile response to serotonin (10 microM) but not to caffeine (10 mM). In addition, estradiol (100 microM) inhibited the contractile responses to cyclopiazonic acid (1 microM; selective Ca(2+)-ATPase inhibitor) associated with capacitative Ca(2+) influx through non-L-type Ca(2+) channels. Finally, estradiol inhibited the Ca(2+)-induced increases in intracellular free Ca(2+) (after pretreatment with phenylephrine) in cultured rat aorta smooth muscle cells incubated in Ca(2+)-free solution. In conclusion, estradiol interfered in a concentration-dependent manner with Ca(2+)-dependent contractile effects mediated by the stimuli of alpha(1)-adrenergic and serotonergic receptors and inhibited the capacitative Ca(2+) influx through both L-type and non-L-type Ca(2+) channels. Such effects are in essence nongenomic and not mediated by the intracellular estrogenic receptor.
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Aorta/efectos de los fármacos , Calcio/metabolismo , Estradiol/farmacología , Fenilefrina/farmacología , Vasoconstrictores/farmacología , Vasodilatación/fisiología , Animales , Aorta/anatomía & histología , Aorta/metabolismo , Cafeína/farmacología , Células Cultivadas , Cicloheximida/farmacología , Relación Dosis-Respuesta a Droga , Estradiol/análogos & derivados , Antagonistas de Estrógenos/farmacología , Femenino , Fulvestrant , Indoles/farmacología , Masculino , Músculo Liso Vascular/citología , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/citología , Miocitos del Músculo Liso/metabolismo , Inhibidores de Fosfodiesterasa/farmacología , Bloqueadores de los Canales de Potasio/farmacología , Progesterona/farmacología , Inhibidores de la Síntesis de la Proteína/farmacología , Ratas , Ratas Wistar , Serotonina/farmacología , Tamoxifeno/farmacología , Testosterona/farmacología , Tetraetilamonio/farmacología , Vasodilatadores/farmacologíaRESUMEN
The antioxidant nordihydroguaiaretic acid (NDGA) has recently become well known as a putative anticancer drug. In this paper, it was evaluated the in vitro peroxynitrite (ONOO(-)), singlet oxygen ((1)O(2)), hydroxyl radical (OH(v)), hydrogen peroxide (H(2)O(2)), superoxide anion and hypochlorous acid (HOCl) scavenging capacity of NDGA. It was found that NDGA scavenges: (a) ONOO(-) (IC(50) = 4 +/- 0.94 microM) as efficiently as uric acid; (b) (1)O(2) (IC(50) = 151 +/- 20 microM) more efficiently than dimethyl thiourea, lipoic acid, N-acetyl-cysteine and glutathione; (c) OH(v) (IC(50) = 0.15 +/- 0.02 microM) more efficiently than dimethyl thiourea, uric acid, trolox, dimethyl sulfoxide and mannitol, (d) (IC(50) = 15 +/- 1 microM) more efficiently than N-acetyl-cysteine, glutathione, tempol and deferoxamine and (e) HOCl (IC(50) = 622 +/- 42 microM) as efficiently as lipoic acid and N-acetyl-cysteine. NDGA was unable to scavenge H(2)O(2). In an in vivo study in rats, NDGA was able to prevent ozone-induced tyrosine nitration in lungs. It is concluded that NDGA is a potent in vitro scavenger of ONOO(-), (1)O(2), OH(v), and HOCl and is able to prevent lung tyrosine nitration in vivo.