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1.
Rev. esp. geriatr. gerontol. (Ed. impr.) ; 55(5): 286-288, sept.-oct. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-192478

RESUMO

INTRODUCCIÓN: El síndrome de tormenta de citoquinas (STC) es una complicación muy grave de los pacientes con infección por SARS-CoV-2. El tratamiento y la evolución no están bien definidos. Nuestro objetivo es describir sus características clínicas, los tratamientos empleados y su evolución clínica. PACIENTES Y MÉTODO: Estudio retrospectivo observacional de pacientes consecutivos ingresados en el período comprendido entre el 23 de marzo y el 12 de abril de 2020 con infección por SARS-CoV-2 confirmada, con neumonía por estudio radiológico o tomografía de tórax, que cumplían criterios de STC y que recibieron tratamiento. Clasificamos a los pacientes en los que recibieron solo pulsos de glucocorticoides (GC), o pulsos de GC y tocilizumab. Determinamos niveles séricos de ferritina, PCR y dímeros-D. La variable final fue la supervivencia. RESULTADOS: Veintiún pacientes con una edad de 83 años (80-88 años). La ferritina media fue de 1.056 microg/L (317-3.553), la PCR de 115,8mg/dL (22-306) y los dímeros-D de 2,9mg/L (0,45-17,5). Todos los pacientes recibieron pulsos de GC y en 2 casos simultáneamente tocilizumab. El tiempo medio de seguimiento fue de 13,7 días (8-21). La mortalidad global fue del 38,1% (8/21pacientes). Los 2 pacientes que recibieron tocilizumab fallecieron. Los fallecidos presentaron niveles significativamente más elevados de ferritina (1.254 vs. 925microg/L; p = 0,045) y PCR (197,6 vs. 76mg/dL; p = 0,007). Al final del seguimiento se observó una disminución en los parámetros bioquímicos con ferritina de 727microg/L, PCR de 27mg/dl y dímeros-D de 1,18mg/L. En 13/21 pacientes (61,9%) el STC se controló sin necesidad de añadir otros tratamientos. CONCLUSIONES: La mortalidad del STC por SARS-CoV-2 es alta a pesar del tratamiento. Una mayor respuesta inflamatoria se asoció con una mayor mortalidad. Aunque parece que el uso precoz de pulsos de GC puede controlarlo, pudiendo disminuir la necesidad de uso de otros tratamientos, con el diseño del estudio y sus limitaciones, no se puede establecer esta conclusión


INTRODUCTION: Cytokine storm syndrome (CTS) is a serious complication of patients with SARS-CoV-2 infection. Treatment and evolution in octogenarians are not well defiREVned. Our objective is to describe its clinical characteristics, the treatments and its clinical evolution. PATIENTS AND METHOD: Retrospective observational study of consecutive patients admitted in the period between March 23 and April 12, 2020 with confirmed SARS-CoV-2 infection, with pneumonia by radiological study or chest tomography, whith STC criteria and who received treatment. We classified patients as those who received only glucocorticoid (GC) pulses, or GC and tocilizumab pulses. We determined serum levels of ferritin, CRP and D-dimers. The final variable was survival. RESULTS: 21 patients, (80-88 years). The mean ferritin was 1056 microg/L (317-3,553), CRP 115.8mg/dL (22-306) and D-dimers 2.9m/L (0.45-17.5). All patients received GC pulses and in 2 cases simultaneously tocilizumab. The mean follow-up time was 13.7 days (8-21). The overall mortality was 38.1% (8/21 patients). The 2 patients who received tocilizumab died. The deceased had significantly higher levels of ferritin (1,254 vs. 925microg/L; P=.045) and CRP (197.6 vs. 76mg / dL; P=.007). At the end of the follow-up, a decrease in the biochemical parameters was observed with ferritin of 727microg/L, CRP of 27mg/dl and D-dimers of 1.18mg/L. In 13/21 patients (61.9%), the CTS was controlled without the need to add other treatments. CONCLUSIONS: STC mortality from SARS-CoV-2 is high despite treatment. A greater inflammatory response was associated with a higher mortality. Although it seems that the early use of GC pulses could control it, and the use of other treatments such as tocilizumab shouldo be, with the study design and its limitations, this conclusion cannot be stablished


Assuntos
Humanos , Masculino , Feminino , Idoso de 80 Anos ou mais , Infecções por Coronavirus/imunologia , Pneumonia Viral/imunologia , Síndrome Respiratória Aguda Grave/imunologia , Vírus da SARS/patogenicidade , Citocinas/efeitos adversos , Inflamação/fisiopatologia , Glucocorticoides/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos Retrospectivos , Infecções por Coronavirus/epidemiologia , Epidemias , Mediadores da Inflamação/imunologia , Inflamação/imunologia , Ferritinas/efeitos dos fármacos , Linfo-Histiocitose Hemofagocítica/imunologia
4.
J Transl Med ; 18(1): 354, 2020 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933530

RESUMO

BACKGROUND: Severe COVID-19 infection results in a systemic inflammatory response (SIRS). This SIRS response shares similarities to the changes observed during the peri-operative period that are recognised to be associated with the development of multiple organ failure. METHODS: Electronic patient records for patients who were admitted to an urban teaching hospital during the initial 7-week period of the COVID-19 pandemic in Glasgow, U.K. (17th March 2020-1st May 2020) were examined for routine clinical, laboratory and clinical outcome data. Age, sex, BMI and documented evidence of COVID-19 infection at time of discharge or death certification were considered minimal criteria for inclusion. RESULTS: Of the 224 patients who fulfilled the criteria for inclusion, 52 (23%) had died at 30-days following admission. COVID-19 related respiratory failure (75%) and multiorgan failure (12%) were the commonest causes of death recorded. Age ≥ 70 years (p < 0.001), past medical history of cognitive impairment (p ≤ 0.001), previous delirium (p < 0.001), clinical frailty score > 3 (p < 0.001), hypertension (p < 0.05), heart failure (p < 0.01), national early warning score (NEWS) > 4 (p < 0.01), positive CXR (p < 0.01), and subsequent positive COVID-19 swab (p ≤ 0.001) were associated with 30-day mortality. CRP > 80 mg/L (p < 0.05), albumin < 35 g/L (p < 0.05), peri-operative Glasgow Prognostic Score (poGPS) (p < 0.05), lymphocytes < 1.5 109/l (p < 0.05), neutrophil lymphocyte ratio (p ≤ 0.001), haematocrit (< 0.40 L/L (male)/ < 0.37 L/L (female)) (p ≤ 0.01), urea > 7.5 mmol/L (p < 0.001), creatinine > 130 mmol/L (p < 0.05) and elevated urea: albumin ratio (< 0.001) were also associated with 30-day mortality. On multivariate analysis, age ≥ 70 years (O.R. 3.9, 95% C.I. 1.4-8.2, p < 0.001), past medical history of heart failure (O.R. 3.3, 95% C.I. 1.2-19.3, p < 0.05), NEWS > 4 (O.R. 2.4, 95% C.I. 1.1-4.4, p < 0.05), positive initial CXR (O.R. 0.4, 95% C.I. 0.2-0.9, p < 0.05) and poGPS (O.R. 2.3, 95% C.I. 1.1-4.4, p < 0.05) remained independently associated with 30-day mortality. Among those patients who tested PCR COVID-19 positive (n = 122), age ≥ 70 years (O.R. 4.7, 95% C.I. 2.0-11.3, p < 0.001), past medical history of heart failure (O.R. 4.4, 95% C.I. 1.2-20.5, p < 0.05) and poGPS (O.R. 2.4, 95% C.I. 1.1-5.1, p < 0.05) remained independently associated with 30-days mortality. CONCLUSION: Age ≥ 70 years and severe systemic inflammation as measured by the peri-operative Glasgow Prognostic Score are independently associated with 30-day mortality among patients admitted to hospital with COVID-19 infection.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Pandemias , Pneumonia Viral/fisiopatologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/metabolismo , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Feminino , Mortalidade Hospitalar , Hospitalização , Hospitais de Ensino , Hospitais Urbanos , Humanos , Inflamação/fisiopatologia , Linfócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neutrófilos , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Prognóstico , Escócia/epidemiologia , Pesquisa Médica Translacional
5.
Fluids Barriers CNS ; 17(1): 55, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912226

RESUMO

Human coronaviruses are highly pathogenic viruses that pose a serious threat to human health. Examples include the severe acute respiratory syndrome outbreak of 2003 (SARS-CoV-1), the Middle East Respiratory Syndrome (MERS-CoV) outbreak of 2012, and the current SARS-CoV-2 (COVID-19) pandemic. Herein, we review the neurological manifestations of coronaviruses and discuss the potential pathogenic role of blood-brain barrier dysfunction. We present the hypothesis that pre-existing vascular damage (due to aging, cardiovascular disease, diabetes, hypertension or other conditions) facilitates infiltration of the virus into the central nervous system (CNS), increasing neuro-inflammation and the likelihood of neurological symptoms. We also discuss the role of a neuroinflammatory cytokine profile in both blood-brain barrier dysfunction and macrovascular disease (e.g. ischemic stroke and thromboembolism). Future studies are needed to better understand the involvement of the microvasculature in coronavirus neuropathology, and to test the diagnostic potential of minimally-invasive screening tools (e.g. serum biomarkers, fluorescein retinal angiography and dynamic-contrast MRI).


Assuntos
Barreira Hematoencefálica/fisiopatologia , Infecções por Coronavirus/fisiopatologia , Inflamação/fisiopatologia , Microvasos/fisiopatologia , Doenças do Sistema Nervoso/fisiopatologia , Pneumonia Viral/fisiopatologia , Betacoronavirus , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/virologia , Doenças Cardiovasculares/fisiopatologia , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Diabetes Mellitus/fisiopatologia , Encefalite/imunologia , Encefalite/fisiopatologia , Humanos , Inflamação/imunologia , Microvasos/imunologia , Doenças do Sistema Nervoso/imunologia , Pandemias , Pneumonia Viral/imunologia , Convulsões/imunologia , Convulsões/fisiopatologia , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/fisiopatologia , Tromboembolia/imunologia , Tromboembolia/fisiopatologia
6.
Mayo Clin Proc ; 95(8): 1710-1714, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32753145

RESUMO

Given the rapid spread of the coronavirus disease 2019 (COVID-19) pandemic and its overwhelming effect on health care systems and the global economy, innovative therapeutic strategies are urgently needed. The proposed primary culprit of COVID-19 is the intense inflammatory response-an augmented immune response and cytokine storm-severely damaging the lung tissue and rendering some patients' conditions severe enough to require assisted ventilation. Sex differences in the response to inflammation have been documented and can be attributed, at least in part, to sex steroid hormones. Moreover, age-associated decreases in sex steroid hormones, namely, estrogen and testosterone, may mediate proinflammatory increases in older adults that could increase their risk of COVID-19 adverse outcomes. Sex hormones can mitigate the inflammation response and might provide promising therapeutic potential for patients with COVID-19. In this article, we explore the possible anti-inflammatory effects of estrogen and testosterone and the anabolic effect of testosterone, with particular attention to the potential therapeutic role of hormone replacement therapy in older men and women with COVID-19.


Assuntos
Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Estrogênios/fisiologia , Pneumonia Viral/fisiopatologia , Testosterona/fisiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Estrogênios/uso terapêutico , Feminino , Terapia de Reposição Hormonal , Humanos , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Inflamação/virologia , Masculino , Pandemias , Pneumonia Viral/tratamento farmacológico , Testosterona/uso terapêutico
7.
Artigo em Inglês | MEDLINE | ID: mdl-32849309

RESUMO

COVID-19, caused by SARS-CoV-2, is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Several reports from around the world have identified obesity and severe obesity as one of the strongest risk factors for COVID-19 hospitalization and mechanical ventilation. Moreover, countries with greater obesity prevalence have a higher morbidity and mortality risk of developing serious outcomes from COVID-19. The understanding of how this increased susceptibility of the people with obesity to develop severe forms of the SARS-CoV-2 infection occurs is crucial for implementing appropriate public health and therapeutic strategies to avoid COVID-19 severe symptoms and complications in people living with obesity. We hypothesize here that increased ACE2 expression in adipose tissue displayed by people with obesity may increase SARS-CoV-2 infection and accessibility to this tissue. Individuals with obesity have increased white adipose tissue, which may act as a reservoir for a more extensive viral spread with increased shedding, immune activation and pro-inflammatory cytokine amplification. Here we discuss how obesity is related to a pro-inflammatory and metabolic dysregulation, increased SARS-CoV-2 host cell entry in adipose tissue and induction of hypercoagulopathy, leading people with obesity to develop severe forms of COVID-19 and also death. Taken together, it may be crucial to better explore the role of visceral adipose tissue in the inflammatory response to SARS-CoV-2 infection and investigate the potential therapeutic effect of using specific target anti-inflammatories (canakinumab or anakinra for IL-1ß inhibition; anti-IL-6 antibodies for IL-6 inhibition), anticoagulant or anti-diabetic drugs in COVID-19 treatment of people with obesity. Defining the immunopathological changes in COVID-19 patients with obesity can provide prominent targets for drug discovery and clinical management improvement.


Assuntos
Tecido Adiposo/fisiopatologia , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/mortalidade , Inflamação/fisiopatologia , Obesidade/complicações , Pneumonia Viral/mortalidade , Trombofilia/fisiopatologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Humanos , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Taxa de Sobrevida
8.
Lancet ; 396(10247): 345-360, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738956

RESUMO

Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. The disorder affects people of all ages and ethnicities, has a substantial psychosocial impact on patients and relatives, and is the leading cause of the global burden from skin disease. Atopic dermatitis is associated with increased risk of multiple comorbidities, including food allergy, asthma, allergic rhinitis, and mental health disorders. The pathophysiology is complex and involves a strong genetic predisposition, epidermal dysfunction, and T-cell driven inflammation. Although type-2 mechanisms are dominant, there is increasing evidence that the disorder involves multiple immune pathways. Currently, there is no cure, but increasing numbers of innovative and targeted therapies hold promise for achieving disease control, including in patients with recalcitrant disease. We summarise and discuss advances in our understanding of the disease and their implications for prevention, management, and future research.


Assuntos
Dermatite Atópica/epidemiologia , Dermatite Atópica/fisiopatologia , Inflamação/fisiopatologia , Linfócitos T/imunologia , Adolescente , Asma/epidemiologia , Criança , Pré-Escolar , Comorbidade , Dermatite Atópica/prevenção & controle , Dermatite Atópica/terapia , Eczema/patologia , Hipersensibilidade Alimentar/epidemiologia , Predisposição Genética para Doença/genética , Carga Global da Doença , Humanos , Lactente , Transtornos Mentais/epidemiologia , Microbiota/fisiologia , Terapia de Alvo Molecular/métodos , Fototerapia/métodos , Prevalência , Prurido/patologia , Qualidade de Vida , Rinite Alérgica/epidemiologia , Linfócitos T/patologia
9.
Paediatr Respir Rev ; 35: 81-87, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32792288

RESUMO

The rapid spread of SARS-CoV-2 infection globally coupled with the relatively high case-fatality rate has led to immediate need for therapeutic intervention to prevent and treat COVID-19 disease. There is accumulating evidence that morbidity and mortality in COVID-19 may be exacerbated by a dysregulated host immune response resulting in significant hyperinflammation and cytokine release. The aim of this review is to describe the basis for the immune dysregulation caused by SARS-CoV-2 infection and to examine current investigations into immunomodulatory therapies aimed at targeting the excessive host immune response.


Assuntos
Infecções por Coronavirus/imunologia , Síndrome da Liberação de Citocina/imunologia , Fatores Imunológicos/uso terapêutico , Pneumonia Viral/imunologia , Síndrome de Resposta Inflamatória Sistêmica/imunologia , Corticosteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Complexo Antígeno-Anticorpo/imunologia , Betacoronavirus , Criança , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/terapia , Síndrome da Liberação de Citocina/fisiopatologia , Síndrome da Liberação de Citocina/terapia , Humanos , Imunização Passiva/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Inflamação/imunologia , Inflamação/fisiopatologia , Inflamação/terapia , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Inibidores de Janus Quinases/uso terapêutico , Pandemias , Pneumonia Viral/fisiopatologia , Pneumonia Viral/terapia , Receptores de Interleucina-6/antagonistas & inibidores , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Síndrome de Resposta Inflamatória Sistêmica/terapia
11.
Life Sci ; 258: 118166, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739471

RESUMO

In this paper, a model is proposed of the pathophysiological processes of COVID-19 starting from the infection of human type II alveolar epithelial cells (pneumocytes) by SARS-CoV-2 and culminating in the development of ARDS. The innate immune response to infection of type II alveolar epithelial cells leads both to their death by apoptosis and pyroptosis and to alveolar macrophage activation. Activated macrophages secrete proinflammatory cytokines and chemokines and tend to polarise into the inflammatory M1 phenotype. These changes are associated with activation of vascular endothelial cells and thence the recruitment of highly toxic neutrophils and inflammatory activated platelets into the alveolar space. Activated vascular endothelial cells become a source of proinflammatory cytokines and reactive oxygen species (ROS) and contribute to the development of coagulopathy, systemic sepsis, a cytokine storm and ARDS. Pulmonary activated platelets are also an important source of proinflammatory cytokines and ROS, as well as exacerbating pulmonary neutrophil-mediated inflammatory responses and contributing to systemic sepsis by binding to neutrophils to form platelet-neutrophil complexes (PNCs). PNC formation increases neutrophil recruitment, activation priming and extraversion of these immune cells into inflamed pulmonary tissue, thereby contributing to ARDS. Sequestered PNCs cause the development of a procoagulant and proinflammatory environment. The contribution to ARDS of increased extracellular histone levels, circulating mitochondrial DNA, the chromatin protein HMGB1, decreased neutrophil apoptosis, impaired macrophage efferocytosis, the cytokine storm, the toll-like receptor radical cycle, pyroptosis, necroinflammation, lymphopenia and a high Th17 to regulatory T lymphocyte ratio are detailed.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/fisiopatologia , Síndrome do Desconforto Respiratório do Adulto/fisiopatologia , Células Epiteliais Alveolares/imunologia , Células Epiteliais Alveolares/patologia , Animais , Betacoronavirus/imunologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Humanos , Imunidade Inata , Inflamação/etiologia , Inflamação/imunologia , Inflamação/fisiopatologia , Inflamação/terapia , Ativação de Macrófagos , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/patologia , Ativação de Neutrófilo , Pandemias , Ativação Plaquetária , Pneumonia Viral/complicações , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Síndrome do Desconforto Respiratório do Adulto/etiologia , Síndrome do Desconforto Respiratório do Adulto/imunologia , Síndrome do Desconforto Respiratório do Adulto/terapia , Trombofilia/etiologia , Trombofilia/imunologia , Trombofilia/fisiopatologia , Trombofilia/terapia
12.
Life Sci ; 258: 118164, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32739467

RESUMO

High mobility group box-1 (HMGB1) protein is a diverse, single polypeptide moiety, present in mammalian eukaryotic cells. In response to stimuli, this nuclear protein is actively secreted in to the extracellular compartment or passively released by the necrotic cells, in order to mediate inflammatory responses, by forming complexes with IL-1α, IL-1ß, LPS and other moieties, and binding to RAGE, TLR and other receptor ligands, initiating downstream, signaling processes. This molecule acts as a proinflammatory cytokine and contributes to the progression of diseases like, acute lung injury, autoimmune liver damage, graft rejection immune response and arthritis. Small concentrations of HMGB1 are released during apoptosis, which facilitates oxidative regulation on Cys106, and propagates immune inactivating tolerogenic signals in the body. The review portrays the role of HMGB1 in rheumatoid arthritis, evidently supported by pre-clinical and clinical investigations, demonstrating extensive HMGB1 expression in synovial tissue and fluid as well as serum, excessive expression of transduction receptor signaling molecules, bone remodeling and uncontrolled expression of bone destroying osteoclastogenesis, resulting in destruction of articular cartilage, bone deformation and synovial proliferation, alleviating the pathogenesis in RA disease. Moreover, the review highlights the therapeutic regime targeting HMGB1, facilitating inhibition of its actions and release into the extracellular compartment, to ameliorate the destructive events that prevail in rheumatoid arthritis.


Assuntos
Artrite Reumatoide/patologia , Proteína HMGB1/metabolismo , Animais , Apoptose/efeitos dos fármacos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Artrite Reumatoide/fisiopatologia , Remodelação Óssea/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Cartilagem Articular/fisiopatologia , Proteína HMGB1/análise , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Terapia de Alvo Molecular , Osteogênese/efeitos dos fármacos
13.
Ecotoxicol Environ Saf ; 204: 111036, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32784013

RESUMO

Human exposure to methylmercury (MeHg) due to contaminated fish intake as part of a high-fat (HFD), high-carbohydrate diets is a reality today for many populations. HFD is associated with hypertension and hyperlipidemia, primary cardiovascular disease (CVD) risk factors. Some studies suggest that MeHg induces those risk factors. We evaluated the effect of MeHg exposure in mice fed with HFD or control diet for eight weeks. In the last experimental 15 days, the half group received a MeHg solution (20 mg/L) replacing water. Blood pressure (BP), heart rate, lipoprotein concentrations, and paraoxonase activity were evaluated. Liver cholesterol, triacylglycerol, and IBA-1+ cells, as well as transcriptional levels of genes related to lipid metabolism and inflammatory response, were also assessed. HFD and both MeHg groups presented increased BP and total cholesterol (TC). In the liver, HFD but not MeHg was related to an increase in TC. Also, MeHg intoxication reduced paraoxonase activity regardless of diet. MeHg intoxication and HFD increased steatosis and the number of IBA-1+ cells and modified some gene transcripts associated with lipid metabolism. In conclusion, we demonstrated that MeHg effects on CVD risk factors resemble those caused by HFD.


Assuntos
Pressão Arterial/efeitos dos fármacos , Aterosclerose/epidemiologia , Dieta Hiperlipídica/efeitos adversos , Poluentes Ambientais/efeitos adversos , Fígado/efeitos dos fármacos , Compostos de Metilmercúrio/efeitos adversos , Estado Nutricional , Animais , Aterosclerose/induzido quimicamente , Fígado Gorduroso/metabolismo , Feminino , Inflamação/induzido quimicamente , Inflamação/fisiopatologia , Lipoproteínas/metabolismo , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fatores de Risco
14.
Ir Med J ; 113(5): 81, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32603576

RESUMO

Background Recent research has indicated that vitamin D may have immune supporting properties through modulation of both the adaptive and innate immune system through cytokines and regulation of cell signalling pathways. We hypothesize that vitamin D status may influence the severity of responses to Covid-19 and that the prevalence of vitamin D deficiency in Europe will be closely aligned to Covid-19 mortality. Methods We conducted a literature search on PubMed (no language restriction) of vitamin D status (for older adults) in countries/areas of Europe affected by Covid-19 infection. Countries were selected by severity of infection (high and low) and were limited to national surveys or where not available, to geographic areas within the country affected by infection. Covid-19 infection and mortality data was gathered from the World Health Organisation. Results Counter-intuitively, lower latitude and typically 'sunny' countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency. These countries have also been experiencing the highest infection and death rates in Europe. The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean 25(OH)D concentrations, low levels of deficiency and for Norway and Finland, lower infection and death rates. The correlation between 25(OH)D concentration and mortality rate reached conventional significance (P=0.046) by Spearman's Rank Correlation. Conclusions Optimising vitamin D status to recommendations by national and international public health agencies will certainly have benefits for bone health and potential benefits for Covid-19. There is a strong plausible biological hypothesis and evolving epidemiological data supporting a role for vitamin D in Covid-19.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Deficiência de Vitamina D/epidemiologia , 25-Hidroxivitamina D 2/sangue , Betacoronavirus , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Suplementos Nutricionais , Europa (Continente)/epidemiologia , Política de Saúde , Humanos , Inflamação/fisiopatologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Prevalência , Índice de Gravidade de Doença , Vitamina D/fisiologia
15.
Circ Arrhythm Electrophysiol ; 13(8): e008627, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32654514

RESUMO

BACKGROUND: During acute infections, the risk of malignant ventricular arrhythmias is increased, partly because of a higher propensity to develop QTc prolongation. Although it is generally believed that QTc changes almost exclusively result from concomitant treatment with QT-prolonging antimicrobials, direct effects of inflammatory cytokines on ventricular repolarization are increasingly recognized. We hypothesized that systemic inflammation per se can significantly prolong QTc during acute infections, via cytokine-mediated changes in K+ channel expression. METHODS: We evaluated (1) the frequency of QTc prolongation and its association with inflammatory markers, in patients with different types of acute infections, during active disease and remission; (2) the prevalence of acute infections in a cohort of consecutive patients with Torsades de Pointes; (3) the relationship between K+ channel mRNA levels in ventricles and peripheral blood mononuclear cells and their changes in patients with acute infection over time. RESULTS: In patients with acute infections, regardless of concomitant QT-prolonging antimicrobial treatments, QTc was significantly prolonged but rapidly normalized in parallel to CRP (C-reactive protein) and cytokine level reduction. Consistently in the Torsades de Pointes cohort, concomitant acute infections were highly prevalent (30%), despite only a minority (25%) of these cases were treated with QT-prolonging antimicrobials. KCNJ2 K+ channel expression in peripheral blood mononuclear cell, which strongly correlated to that in ventricles, inversely associated to CRP and IL (interleukin)-1 changes in acute infection patients. CONCLUSIONS: During acute infections, systemic inflammation rapidly induces cytokine-mediated ventricular electrical remodeling and significant QTc prolongation, regardless concomitant antimicrobial therapy. Although transient, these changes may significantly increase the risk of life-threatening ventricular arrhythmia in these patients. It is timely and warranted to transpose these findings to the current coronavirus disease 2019 (COVID-19) pandemic, in which both increased amounts of circulating cytokines and cardiac arrhythmias are demonstrated along with a frequent concomitant treatment with several QT-prolonging drugs. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
Doenças Transmissíveis/metabolismo , Citocinas/metabolismo , Parada Cardíaca/metabolismo , Frequência Cardíaca , Ventrículos do Coração/metabolismo , Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Torsades de Pointes/metabolismo , Potenciais de Ação , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/efeitos adversos , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/fisiopatologia , Feminino , Parada Cardíaca/epidemiologia , Parada Cardíaca/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/fisiopatologia , Humanos , Inflamação/epidemiologia , Inflamação/fisiopatologia , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Canais de Potássio Corretores do Fluxo de Internalização/genética , Prevalência , Fatores de Risco , Transdução de Sinais , Fatores de Tempo , Torsades de Pointes/epidemiologia , Torsades de Pointes/fisiopatologia , Adulto Jovem
16.
Nutr Hosp ; 34(3): 622-630, 2020 Jul 13.
Artigo em Espanhol | MEDLINE | ID: mdl-32603180

RESUMO

Introduction: The current COVID-19 pandemic mainly affects older people, those with obesity or other coexisting chronic diseases such as type-2 diabetes and high blood pressure. It has been observed that about 20 % of patients will require hospitalization, and some of them will need the support of invasive mechanical ventilation in intensive care units. Nutritional status appears to be a relevant factor influencing the clinical outcome of critically ill patients with COVID-19. Several international guidelines have provided recommendations to ensure energy and protein intake in people with COVID-19, with safety measures to reduce the risk of infection in healthcare personnel. The purpose of this review is to analyze the main recommendations related to adequate nutritional management for critically ill patients with COVID-19 in order to improve their prognosis and clinical outcomes.


Assuntos
Betacoronavirus , Infecções por Coronavirus/dietoterapia , Cuidados Críticos/métodos , Estado Terminal , Desnutrição/dietoterapia , Pandemias , Pneumonia Viral/dietoterapia , Doenças Cardiovasculares/epidemiologia , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Proteínas na Dieta/administração & dosagem , Nutrição Enteral/efeitos adversos , Nutrição Enteral/métodos , Gastroenteropatias/complicações , Humanos , Inflamação/epidemiologia , Inflamação/fisiopatologia , Desnutrição/diagnóstico , Desnutrição/etiologia , Desnutrição/prevenção & controle , Metanálise como Assunto , Micronutrientes/administração & dosagem , Avaliação Nutricional , Necessidades Nutricionais , Apoio Nutricional , Obesidade/epidemiologia , Pneumonia Viral/complicações , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto , Síndrome da Realimentação/prevenção & controle , Respiração Artificial , Sarcopenia/epidemiologia
17.
Paediatr Respir Rev ; 35: 20-24, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32653469

RESUMO

Since the initial description in 2019, the novel coronavirus SARS-Cov-2 infection (COVID-19) pandemic has swept the globe. The most severe form of the disease presents with fever and shortness of breath, which rapidly deteriorates to respiratory failure and acute lung injury (ALI). COVID-19 also presents with a severe coagulopathy with a high rate of venous thromboembiolism. In addition, autopsy studies have revealed co-localized thrombosis and inflammation, which is the signature of thromboinflammation, within the pulmonary capillary vasculature. While the majority of published data is on adult patients, there are parallels to pediatric patients. In our experience as a COVID-19 epicenter, children and young adults do develop both the coagulopathy and the ALI of COVID-19. This review will discuss COVID-19 ALI from a hematological perspective with discussion of the distinct aspects of coagulation that are apparent in COVID-19. Current and potential interventions targeting the multiple thromboinflammatory mechanisms will be discussed.


Assuntos
Lesão Pulmonar Aguda/sangue , Infecções por Coronavirus/sangue , Inflamação/sangue , Pneumonia Viral/sangue , Trombose/sangue , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/fisiopatologia , Anticoagulantes/uso terapêutico , Antitrombinas/uso terapêutico , Betacoronavirus , Transtornos da Coagulação Sanguínea/sangue , Transtornos da Coagulação Sanguínea/imunologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Capilares/imunologia , Capilares/fisiopatologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/fisiopatologia , Endotélio Vascular/imunologia , Endotélio Vascular/fisiopatologia , Inibidores do Fator Xa/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/fisiopatologia , Pandemias , Ativação Plaquetária , Inibidores da Agregação de Plaquetas/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/fisiopatologia , Embolia Pulmonar/sangue , Embolia Pulmonar/imunologia , Embolia Pulmonar/fisiopatologia , Trombina/imunologia , Trombina/metabolismo , Trombose/tratamento farmacológico , Trombose/imunologia , Trombose/fisiopatologia
18.
PLoS One ; 15(7): e0236035, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673354

RESUMO

PURPOSE: Systemic inflammation and coronary microvascular dysfunction (CMD) may be causal drivers of heart failure with preserved ejection fraction (HFpEF). We tested the hypothesis that subclinical inflammation is associated with non-endothelial dependent CMD and diastolic dysfunction. METHODS: In a cross-sectional study of 336 women with angina but no flow limiting coronary artery stenosis (180 with diabetes) and 95 asymptomatic controls, blood samples were analysed for 90 biomarkers of which 34 were part of inflammatory pathways. CMD was assessed as coronary flow velocity reserve (CFVR) by transthoracic Doppler echocardiography and defined as CFVR<2.5. We used E/e' as an indicator of diastolic function in age-adjusted linear regressions to assess correlations between biomarkers, CFVR and diastolic function. RESULTS: CMD was found in 59% of participants whereas only 4% fulfilled strict criteria for diastolic dysfunction. Thirty-five biomarkers, 17 of them inflammatory, were negatively correlated with CFVR and 25, 15 inflammatory, were positively correlated with E/e'. A total of 13 biomarkers, 9 inflammatory, were associated with both CFVR and E/e'. CFVR and E/e' were only correlated in the subgroup of patients with CMD and signs of increased filling pressure (E/e'>10) (p = 0.012). CONCLUSION: This is the first study to link a large number of mainly inflammatory biomarkers to both CMD and E/e', thus confirming a role of inflammation in both conditions. However, despite a high prevalence of CMD, few patients had diastolic dysfunction and the data do not support a major pathophysiologic role of non-endothelial dependent CMD in diastolic dysfunction.


Assuntos
Angina Pectoris/epidemiologia , Circulação Coronária , Vasos Coronários/fisiopatologia , Diástole , Inflamação/fisiopatologia , Volume Sistólico , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Pectoris/etiologia , Angina Pectoris/metabolismo , Angina Pectoris/patologia , Biomarcadores/metabolismo , Estudos de Casos e Controles , Estudos Transversais , Feminino , Seguimentos , Humanos , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico
19.
Rev Cardiovasc Med ; 21(2): 225-240, 2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32706211

RESUMO

In spite of medical advances, cardiovascular disease remains a significant concern, imposing a great burden upon the economy and public health of nations by causing the highest morbidity and mortality cases globally. Moreover, it is well established that inflammation is closely linked to the pathogenesis of cardiovascular diseases. Hence, targeting inflammation seems to be a promising strategy in reducing cardiovascular risks. Currently, the importance of natural products in modern medicine is well recognised and continues to be of interest to the pharmaceutical industry. Phenolic acids are a class of phytochemical compounds that are well-known for their health benefits. They consists of various phytochemical constituents and have been widely studied in various disease models. Research involving both animals and humans has proven that phenolic acids possess cardioprotective properties such as anti-hypertensive, anti-hyperlipidemia, anti-fibrotic and anti-hypertrophy activity. Furthermore, numerous studies have proven that phenolic acids in phytochemical constituents such as gallic acid, caffeic acid and chlorogenic acid are promising anti-inflammatory agents. Hence, in this review, we outline and review recent evidence on the role of phenolic acids and their anti-inflammatory significance in studies published during the last 5 years. We also discuss their possible mechanisms of action in modulating inflammation related to cardiovascular disease.


Assuntos
Anti-Inflamatórios/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Sistema Cardiovascular/efeitos dos fármacos , Dieta , Hidroxibenzoatos/administração & dosagem , Mediadores da Inflamação/metabolismo , Inflamação/prevenção & controle , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Sistema Cardiovascular/metabolismo , Sistema Cardiovascular/fisiopatologia , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Transdução de Sinais
20.
Med Hypotheses ; 143: 110111, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32721805

RESUMO

Patients with SARS-CoV-2 infections experience lymphopenia and inflammatory cytokine storms in the severe stage of the disease, leading to multi-organ damage. The exact pattern of immune system changes and their condition during the disease process is unclear. The available knowledge has indicated that the NF-kappa-B pathway, which is induced by several mediators, has a significant role in cytokine storm through the various mechanisms. Therefore, identifying the state of the immune cells and the dominant mechanisms for the production of cytokines incorporated in the cytokine storm can be a critical step in the therapeutic approach. On the other hand, some studies identified a higher risk for diabetic patients. Diabetes mellitus exhibits a close association with inflammation and increases the chance of developing COVID-19. Patients with diabetes mellitus have shown to have more virus entry, impaired immunity response, less viral elimination, and dysregulated inflammatory cytokines. The parallel analysis of COVID-19 and diabetes mellitus pathogenesis has proposed that the control of the inflammation through the interfering with the critical points of major signaling pathways may provide the new therapeutic approaches. In recent years, the role of Dipeptidyl Peptidase 4 (DPP4) in chronic inflammation has been proved. Numerous immune cells express the DPP4 protein. DPP4 regulates antibody production, cytokine secretion, and immunoglobulin class switching. DPP4 inhibitors like sitagliptin reduce inflammation intensity in different states. Following the accumulating data, we hypothesize that sitagliptin might reduce COVID-19 severity. Sitagliptin, an available DPP4 inhibitor drug, showed multidimensional anti-inflammatory effects among diabetic patients. It reduces the inflammation mostly by affecting on NF-kappa-B signaling pathway. Under the fact that inflammatory mediators are active in individuals with COVID-19, blocking the predominant pathway could be helpful.


Assuntos
Infecções por Coronavirus/complicações , Complicações do Diabetes/tratamento farmacológico , Inflamação/fisiopatologia , Pneumonia Viral/complicações , Fosfato de Sitagliptina/farmacologia , Infecções por Coronavirus/tratamento farmacológico , Citocinas , Complicações do Diabetes/virologia , Diabetes Mellitus/tratamento farmacológico , Dipeptidil Peptidase 4/metabolismo , Humanos , Resistência à Insulina , Modelos Teóricos , Subunidade p50 de NF-kappa B/metabolismo , Pandemias , Pneumonia Viral/tratamento farmacológico , Transdução de Sinais
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