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6.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-33004527

RESUMEN

The respiratory tract and its resident immune cells face daily exposure to stress, both from without and from within. Inhaled pathogens, including severe acute respiratory syndrome coronavirus 2, and toxins from pollution trigger a cellular defence system that reduces protein synthesis to minimise viral replication or the accumulation of misfolded proteins. Simultaneously, a gene expression programme enhances antioxidant and protein folding machineries in the lung. Four kinases (PERK, PKR, GCN2 and HRI) sense a diverse range of stresses to trigger this "integrated stress response". Here we review recent advances identifying the integrated stress response as a critical pathway in the pathogenesis of pulmonary diseases, including pneumonias, thoracic malignancy, pulmonary fibrosis and pulmonary hypertension. Understanding the integrated stress response provides novel targets for the development of therapies.


Asunto(s)
Inflamación/metabolismo , Enfermedades Pulmonares/metabolismo , Estrés Oxidativo/fisiología , Biomarcadores/metabolismo , Humanos
7.
Eur Respir Rev ; 29(157)2020 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-33004529

RESUMEN

Novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has rapidly spread throughout the world, resulting in a pandemic with high mortality. There are no effective treatments for the management of severe COVID-19 and current therapeutic trials are focused on antiviral therapy and attenuation of hyper-inflammation with anti-cytokine therapy. Severe COVID-19 pneumonia shares some pathological similarities with severe bacterial pneumonia and sepsis. In particular, it disrupts the haemostatic balance, which results in a procoagulant state locally in the lungs and systemically. This culminates in the formation of microthrombi, disseminated intravascular coagulation and multi-organ failure. The deleterious effects of exaggerated inflammatory responses and activation of coagulation have been investigated in bacterial pneumonia and sepsis and there is recognition that although these pathways are important for the host immune response to pathogens, they can lead to bystander tissue injury and are negatively associated with survival. In the past two decades, evidence from preclinical studies has led to the emergence of potential anticoagulant therapeutic strategies for the treatment of patients with pneumonia, sepsis and acute respiratory distress syndrome, and some of these anticoagulant approaches have been trialled in humans. Here, we review the evidence from preclinical studies and clinical trials of anticoagulant treatment strategies in bacterial pneumonia and sepsis, and discuss the importance of these findings in the context of COVID-19.


Asunto(s)
Anticoagulantes/uso terapéutico , Betacoronavirus , Coagulación Sanguínea/fisiología , Infecciones por Coronavirus/sangre , Neumonía Bacteriana/sangre , Neumonía Viral/sangre , Sepsis/sangre , Biomarcadores/sangre , Infecciones por Coronavirus/tratamiento farmacológico , Infecciones por Coronavirus/epidemiología , Humanos , Pandemias , Neumonía Viral/tratamiento farmacológico , Neumonía Viral/epidemiología
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 6131-6134, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-33019370

RESUMEN

Point-of-care diagnostic devices aid in the early and rapid detection of immunological markers leading to better medical outcomes. Lateral flow immunoassays (LFIA) are fast assays that provide both qualitative and semi-quantitative results on site. Sample preparation for LFIA tests is usually done manually with multiple mixing steps and is prone to errors. The iQuant Auto is an entirely automated system that can handle sample preparation, effective transfer to lateral flow test membrane, and subsequent result estimation. The system uses a pneumatic system for fluid handling and sample preparation, and an image-based fluorescence reader for reaction visualization. The device works with test specific milli-fluidic lateral flow kit called iQPrep Kit, which has integrated reagent storage areas and valves for fluid control. The test kit can be manufactured using standard manufacturing techniques and can be produced at scale cheaply. The iQPrep Kit can be modified to test for various markers like HbA1c, Vitamin D, and TSH, while the hardware for sample preparation and the fluorescence reader remains the same. The device has a minimalist and intelligible graphical interface aiding smooth operation by less skilled people at resource-limited settings. Standard reference cartridges of different volume ratios were used to validate the functionality of the instrument. The intra- instrument coefficient of variation (CoV) of the mobile kit reader was found to be less than 0.62%. The positional accuracy of the system to ensure precise kit engagement with the other auxiliary systems was checked, and the CoV was 0.16%. The fluid handling capabilities were tested, and it was found that an average fluid loss of 10 µl results due to the liquid adherence to fluid channel walls and valve interfaces. The iQuant Auto is an easily operable, total analysis system for immunodiagnostics.


Asunto(s)
Inmunoensayo , Pruebas Inmunológicas , Sistemas de Atención de Punto , Biomarcadores , Humanos , Tiempo de Protrombina , Juego de Reactivos para Diagnóstico
9.
Sci Rep ; 10(1): 16496, 2020 10 05.
Artículo en Inglés | MEDLINE | ID: mdl-33020546

RESUMEN

This study aimed to analyze aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio in COVID-19 patients. After exclusion, 567 inpatients were included in this study and separated into two groups according to their AST/ALT ratio on admission. Death was regarded as poor prognosis in this study. Of 567 patients, 200 (35.3%) had AST/ALT ≥ 1.38. Of the 200 patients, older age (median age 60 years), myalgia (64 [32%] cases), fatigue (91 [45.5%] cases), some comorbidities and outcomes were significantly different from patients with AST/ALT < 1.38. They also had worse chest computed tomography (CT) findings, laboratory results and severity scores. Levels of platelet count (OR 0.995, 95% CI [0.992-0.998]) and hemoglobin (OR 0.984, 95% CI [0.972-0.995]) were independently associated with AST/ALT ≥ 1.38 on admission. Furthermore, a high AST/ALT ratio on admission was an independent risk factor for poor prognosis (OR 99.9, 95% CI [2.1-4280.5]). In subsequent monitoring, both survivors and non-survivors showed decreased AST/ALT ratio during hospitalization. In conclusion, high AST/ALT ratio might be the indication of worse status and outcomes in COVID-19 patients.


Asunto(s)
Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Infecciones por Coronavirus/sangre , Neumonía Viral/sangre , Adulto , Factores de Edad , Anciano , Biomarcadores/sangre , Comorbilidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/patología , Fatiga/epidemiología , Femenino , Hemoglobinas/análisis , Humanos , Masculino , Persona de Mediana Edad , Mialgia/epidemiología , Pandemias , Admisión del Paciente/estadística & datos numéricos , Recuento de Plaquetas , Neumonía Viral/epidemiología , Neumonía Viral/patología , Análisis de Supervivencia
12.
Curr Opin Ophthalmol ; 31(6): 508-513, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33009084

RESUMEN

PURPOSE OF REVIEW: The aim of this article is to summarize up-to-date research on the effects of obstructive sleep apnea (OSA) on retinal vascular conditions. RECENT FINDINGS: OSA is associated with the development of diabetic retinopathy, retinal vein occlusion, and central serous chorioretinopathy. The severity of OSA and biomarkers such as the apnea-hypopnea index (AHI) correlate with the severity of retinal disease. Dysregulation of circadian locomotor output cycles kaput (CLOCK) genes that govern circadian rhythm is associated with development of proliferative retinal disease. SUMMARY: OSA and retinal vascular disease have a high cost burden on the healthcare system. OSA creates systemic changes and hypoxic conditions that may incite or exacerbate retinal vascular diseases. Retinal changes may be the first clinical manifestation of otherwise undiagnosed OSA, so it is important to refer patients with new-onset retinal vascular disease for appropriate sleep testing.


Asunto(s)
Oftalmopatías/complicaciones , Apnea Obstructiva del Sueño , Biomarcadores , Ritmo Circadiano , Humanos , Polisomnografía , Enfermedades de la Retina/complicaciones , Apnea Obstructiva del Sueño/diagnóstico , Apnea Obstructiva del Sueño/etiología , Apnea Obstructiva del Sueño/fisiopatología
13.
Curr Opin Ophthalmol ; 31(6): 521-531, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33009085

RESUMEN

PURPOSE OF REVIEW: Ocular sarcoidosis is one of the most common causes of uveitis worldwide. The diagnosis and treatment of patients with ocular sarcoidosis remains challenging in some cases. It is important for clinicians to keep up to date with new diagnostic and treatment tools for this disease. RECENT FINDINGS: The International Workshop on Ocular Sarcoidosis diagnostic criteria were first proposed in 2009 and revised in 2017. The new criteria contained two parts: ocular presentation and systemic investigation. The diagnostic value of liver enzymes was reduced in the new criteria, whereas the value placed of lymphopenia and the CD4/CD8 ratio in bronchoalveolar lavage fluid were increased. Despite not being included in the criteria, recent studies have also highlighted the diagnostic value of serum soluble interleukin-2 receptors. Recent ophthalmologic imaging also provides useful insights for the differential diagnosis.Many new treatments for ocular sarcoidosis have been developed in recent years. The introduction of biological immunomodulatory agents for uveitis treatment represents a big improvement. Antitumor necrosis factor-alpha antibodies, including adalimumab, have been proven to be effective for treating ocular sarcoidosis. Many studies have also suggested that other biological agents could be effective and well tolerated. Newer intravitreal dexamethasone and fluocinolone implants have been developed. Patients treated with these implants have experienced good and sustained control of their intraocular inflammation. SUMMARY: Diagnosis and treatment options for ocular sarcoidosis have changed over time. However, challenges still exist in some difficult patients. Future studies should focus on finding more sensitive biomarkers and developing more effective immunomodulatory treatments with longer efficacy and less side effects.


Asunto(s)
Oftalmopatías/diagnóstico , Oftalmopatías/tratamiento farmacológico , Sarcoidosis/diagnóstico , Sarcoidosis/tratamiento farmacológico , Biomarcadores/análisis , Diagnóstico Diferencial , Endoftalmitis/diagnóstico , Humanos
14.
Urol Clin North Am ; 47(4): 523-536, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33008501

RESUMEN

Personalized medicine uses a patient's genotype, environment, and lifestyle choices to create a tailored diagnosis and therapy plan, with the goal of minimizing side effects, avoiding lost time with ineffective treatments, and guiding preventative strategies. Although most precision medicine strategies are still within the laboratory phase of development, this article reviews the promising technologies with the greatest potential to improve the diagnosis and treatment options for male infertility, including sperm cell transplantation, genomic editing, and new biomarker assays, based on the latest proteomic and epigenomic studies.


Asunto(s)
Genómica , Infertilidad Masculina/genética , Infertilidad Masculina/terapia , Medicina de Precisión/métodos , Biomarcadores/sangre , Terapia Combinada , Predicción , Humanos , Infertilidad Masculina/diagnóstico , Masculino , Proteómica , Medición de Riesgo , Resultado del Tratamiento
16.
Rev Soc Bras Med Trop ; 53: e20190356, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33027411

RESUMEN

INTRODUCTION: This study aimed to evaluate and compare with healthy control subjects the levels of indirect inflammatory markers such as mean platelet volume (MPV), platelet to lymphocyte ratio (PLR), and neutrophil to lymphocyte ratio (NLR) in adults and children with brucellosis. METHODS: White blood cell, neutrophil, lymphocyte, and platelet counts, and C-reactive protein (CRP) levels were retrospectively recorded for all participants. RESULTS: NLR and neutrophil counts were significantly higher in adult patients compared to those in pediatric patients. CONCLUSIONS: Indirect inflammatory markers such as NLR, PLR, MPV, red distribution width, and CRP levels may be helpful for follow-up of brucellosis.


Asunto(s)
Brucelosis , Volúmen Plaquetario Medio , Adulto , Biomarcadores , Niño , Humanos , Persona de Mediana Edad , Recuento de Plaquetas , Estudios Retrospectivos , Adulto Joven
17.
Rev Med Liege ; 75(10): 644-648, 2020 Oct.
Artículo en Francés | MEDLINE | ID: mdl-33030839

RESUMEN

The diagnosis of heart failure can sometimes be challenging for the clinician because presentation circumstances and heart failure phenotypes are varied. The identification and validation of sensitive and specific biomarkers for this condition are still a subject of intensive research. Among them, natriuretic peptides (ANP, BNP, NTproBNP) are widely used and validated as markers of heart failure. Their appropriate use and correct interpretation, however, require knowledge of their indications, specificities and limitations. The European Society of Cardiology has recently issued recommendations in this regard. This article summarizes them in order to facilitate the understanding and the use of natriuretic peptides in clinical practice. It also discusses their use in the etiological diagnosis of pleural effusions caused by heart failure.


Asunto(s)
Insuficiencia Cardíaca , Derrame Pleural , Biomarcadores , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Péptidos Natriuréticos , Sensibilidad y Especificidad
18.
Signal Transduct Target Ther ; 5(1): 219, 2020 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-33024082

RESUMEN

Convalescent plasma (CP) transfusion has been indicated as a promising therapy in the treatment for other emerging viral infections. However, the quality control of CP and individual variation in patients in different studies make it rather difficult to evaluate the efficacy and risk of CP therapy for coronavirus disease 2019 (COVID-19). We aimed to explore the potential efficacy of CP therapy, and to assess the possible factors associated with its efficacy. We enrolled eight critical or severe COVID-19 patients from four centers. Each patient was transfused with 200-400 mL of CP from seven recovered donors. The primary indicators for clinical efficacy assessment were the changes of clinical symptoms, laboratory parameters, and radiological image after CP transfusion. CP donors had a wide range of antibody levels measured by serology tests which were to some degree correlated with the neutralizing antibody (NAb) level. No adverse events were observed during and after CP transfusion. Following CP transfusion, six out of eight patients showed improved oxygen support status; chest CT indicated varying degrees of absorption of pulmonary lesions in six patients within 8 days; the viral load was decreased to a negative level in five patients who had the previous viremia; other laboratory parameters also tended to improve, including increased lymphocyte counts, decreased C-reactive protein, procalcitonin, and indicators for liver function. The clinical efficacy might be associated with CP transfusion time, transfused dose, and the NAb levels of CP. This study indicated that CP might be a potential therapy for severe patients with COVID-19.


Asunto(s)
Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Antivirales/administración & dosificación , Betacoronavirus/patogenicidad , Infecciones por Coronavirus/terapia , Neumonía Viral/terapia , Adulto , Anciano , Antivirales/uso terapéutico , Betacoronavirus/inmunología , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/diagnóstico por imagen , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/patología , Progresión de la Enfermedad , Femenino , Humanos , Inmunización Pasiva/métodos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/diagnóstico por imagen , Neumonía Viral/inmunología , Neumonía Viral/patología , Polipéptido alfa Relacionado con Calcitonina/sangre , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X , Carga Viral
19.
Beijing Da Xue Xue Bao Yi Xue Ban ; 52(5): 821-827, 2020 Oct 18.
Artículo en Chino | MEDLINE | ID: mdl-33047714

RESUMEN

OBJECTIVE: To evaluate the sub-acute oral effect of titanium dioxide (TiO2) nanoparticles on the oxidation/antioxidation biomarkers and inflammatory cytokines in blood, liver, intestine, and colon in rats. METHODS: Twenty four 4-week-old clean-grade Sprague Dawley (SD) rats were randomly devided into 4 groups by body weight (n=6, control, low, middle, and high), in which the rats were orally exposed to TiO2 nanoparticles at doses of 0, 2, 10 and 50 mg/kg body weight/day for 28 consecutive days separately. Food intake, body weight and abnormal behaviors during the experiment were recorded. The rats were euthanized on the 29th day. The blood was collected via abdominal aortic method and centrifuged to collect the serum. Tissues from liver, intestine and colon were collected and homogenated. Then enzyme-linked immunosorbent assay (ELISA) and microwell plate methods were used to detect oxidation/antioxidation biomarkers including superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GSH-Px), total mercapto (T-SH), glutathione disulfide (GSSG), malomdialdehvde (MDA) and inflammatory cytokines including interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the serum, liver, intestine and colon in the rats. RESULTS: Compared with the control group, no significant differences in body weight, food intake and organ coefficients were observed in all the three groups after TiO2 gavage. No significant changes in GSH, GSH-Px, T-SH, and IL-6 were observed. Compared with the control group, significant increase of SOD activity in serum in high dose group, signi-ficant increase of GSSG concentration in intestine in middle and high dose group and significant increase of MDA concentration in liver in low and high dose group were observed. Compared with the control group, a significant increase of TNF-α in liver in middle and high dose group was observed. CONCLUSION: TiO2 nanoparticle can increase antioxidant enzymes activities in blood, increase oxidative biomarkers in liver and intestine, increase inflammatory cytokines in liver in rats after a 28-day sub-acute orally administration. Among blood, liver, intestine, and colon, liver is most sensitive to the toxicity induced by TiO2 nanoparticles, followed by intestine, blood, and colon in sequence.


Asunto(s)
Antioxidantes , Nanopartículas , Animales , Biomarcadores , Citocinas , Estrés Oxidativo , Ratas , Ratas Sprague-Dawley , Titanio
20.
Ann Biol Clin (Paris) ; 78(5): 499-518, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-33026346

RESUMEN

The French society of clinical biology "Biochemical markers of COVID-19" has set up a working group with the primary aim of reviewing, analyzing and monitoring the evolution of biological prescriptions according to the patient's care path and to look for markers of progression and severity of the disease. This study covers all public and private sectors of medical biology located in metropolitan and overseas France and also extends to the French-speaking world. This article presents the testimonies and data obtained for the "Overseas and French-speaking countries" sub-working group made up of 45 volunteer correspondents, located in 20 regions of the world. In view of the delayed spread of the SARS-CoV-2 virus, the overseas regions and the French-speaking regions have benefited from feedback from the first territories confronted with COVID-19. Thus, the entry of the virus or its spread in epidemic form could be avoided, thanks to the rapid closure of borders. The overseas territories depend very strongly on air and/or sea links with the metropolis or with the neighboring continent. The isolation of these countries is responsible for reagent supply difficulties and has necessitated emergency orders and the establishment of stocks lasting several months, in order to avoid shortages and maintain adequate patient care. In addition, in countries located in tropical or intertropical zones, the diagnosis of COVID-19 is complicated by the presence of various zoonoses (dengue, Zika, malaria, leptospirosis, etc.).


Asunto(s)
Servicios de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/terapia , Salud Global/estadística & datos numéricos , Neumonía Viral/diagnóstico , Neumonía Viral/epidemiología , Neumonía Viral/terapia , Medicina del Viajero/organización & administración , Adulto , África/epidemiología , Anciano , Anciano de 80 o más Años , Bélgica/epidemiología , Betacoronavirus/fisiología , Biomarcadores/análisis , Biomarcadores/sangre , Cambodia/epidemiología , Niño , Servicios de Laboratorio Clínico/organización & administración , Servicios de Laboratorio Clínico/estadística & datos numéricos , Trazado de Contacto/métodos , Trazado de Contacto/estadística & datos numéricos , Infecciones por Coronavirus/transmisión , Diagnóstico Diferencial , Femenino , Francia/epidemiología , Hospitalización/estadística & datos numéricos , Humanos , Recién Nacido , Islas/epidemiología , Lenguaje , Laos/epidemiología , Louisiana/epidemiología , Masculino , Personal de Laboratorio Clínico/organización & administración , Personal de Laboratorio Clínico/estadística & datos numéricos , Persona de Mediana Edad , Pandemias , Neumonía Viral/transmisión , Estudios Retrospectivos , Encuestas y Cuestionarios , Análisis de Supervivencia , Medicina del Viajero/métodos , Medicina del Viajero/estadística & datos numéricos , Enfermedad Relacionada con los Viajes , Clima Tropical , Medicina Tropical/métodos , Medicina Tropical/organización & administración , Medicina Tropical/estadística & datos numéricos , Vietnam/epidemiología
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