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1.
Artigo em Inglês | MEDLINE | ID: mdl-34341094

RESUMO

BACKGROUND AND OBJECTIVES: We sought to define the risk of severe coronavirus disease 2019 (COVID-19) infection requiring hospitalization in patients with CNS demyelinating diseases such as MS and the factors that increase the risk for severe infection to guide decisions regarding patient care during the COVID-19 pandemic. METHODS: A pilot cohort of 91 patients with confirmed or suspected COVID-19 infection from the Northeastern United States was analyzed to characterize patient risk factors and factors associated with an increased severity of COVID-19 infection. Univariate analysis of variance was performed using the Mann-Whitney U test or analysis of variance for continuous variables and the χ2 or Fisher exact test for nominal variables. Univariate and stepwise multivariate logistic regression identified clinical characteristics or symptoms associated with hospitalization. RESULTS: Our cohort demonstrated a 27.5% hospitalization rate and a 4.4% case fatality rate. Performance on Timed 25-Foot Walk before COVID-19 infection, age, number of comorbidities, and presenting symptoms of nausea/vomiting and neurologic symptoms (e.g., paresthesia or weakness) were independent risk factors for hospitalization, whereas headache predicted a milder course without hospitalization. An absolute lymphocyte count was lower in hospitalized patients during COVID-19 infection. Use of disease-modifying therapy did not increase the risk of hospitalization but was associated with an increased need for respiratory support. DISCUSSION: The case fatality and hospitalization rates in our cohort were similar to those found in MS and general population COVID-19 cohorts within the region. Hospitalization was associated with increased disability, age, and comorbidities but not disease-modifying therapy use.


Assuntos
COVID-19 , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central , Hospitalização/estatística & dados numéricos , Fatores Imunológicos/uso terapêutico , Sistema de Registros/estatística & dados numéricos , Respiração Artificial/estatística & dados numéricos , Adulto , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/terapia , Estudos de Coortes , Comorbidade , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/tratamento farmacológico , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/epidemiologia , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Mortalidade , New England/epidemiologia , Projetos Piloto , Fatores de Risco , Índice de Gravidade de Doença
2.
Clin Oral Investig ; 25(9): 5149-5169, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34342763

RESUMO

OBJECTIVES: The aim of this systematic review was to assess the efficacy and safety of topical non-steroidal immunomodulators (TNSIs) for oral lichen planus (OLP) treatment. MATERIALS AND METHODS: A search strategy designed for this purpose retrieved 1156 references. After analysis of titles and abstracts, 75 studies were selected for full-text analysis. Only randomized controlled clinical trials were selected, resulting in 28 studies included for qualitative and quantitative analysis. RESULTS: The meta-analysis showed similar benefits in clinical response and symptom resolution between tacrolimus 0.1% and pimecrolimus 1% in comparison to topical steroids (TS). Pimecrolimus showed superior efficacy of clinical response but not for symptom resolution compared to placebo. Tacrolimus and pimecrolimus showed better performance preventing symptom relapse, while pimecrolimus also prevented clinical relapse better than TS. Cyclosporine was superior to placebo; however, TS showed better efficacy of clinical response. Thalidomide and retinoid were assessed in only one trial each, and both showed similar efficacy to TS. Rapamycin also presented similar clinical response to TS; however, the later showed greater reduction of symptoms. Mycophenolate mofetil 2% mucoadhesive was no better than placebo. No serious adverse effects have been reported. Cyclosporine showed a higher frequency and variety of adverse effects. CONCLUSIONS: Topical tacrolimus and pimecrolimus are safe and effective alternatives for OLP treatment. CLINICAL RELEVANCE: TS are usually the first choice for OLP treatment. Because some oral lesions may have a low response to treatment with TS, more topical therapeutic options, such as TNSIs, should be considered before systemic steroids are used.


Assuntos
Líquen Plano Bucal , Administração Tópica , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Líquen Plano Bucal/tratamento farmacológico , Esteroides , Resultado do Tratamento
3.
Int J Mol Sci ; 22(15)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34360566

RESUMO

Disruptions in the human gut microbiome have been associated with a cycle of hepatocyte injury and regeneration characteristic of chronic liver disease. Evidence suggests that the gut microbiota can promote the development of hepatocellular carcinoma through the persistence of this inflammation by inducing genetic and epigenetic changes leading to cancer. As the gut microbiome is known for its effect on host metabolism and immune response, it comes as no surprise that the gut microbiome may have a role in the response to therapeutic strategies such as immunotherapy and chemotherapy for liver cancer. Gut microbiota may influence the efficacy of immunotherapy by regulating the responses to immune checkpoint inhibitors in patients with hepatocellular carcinoma. Here, we review the mechanisms by which gut microbiota influences hepatic carcinogenesis, the immune checkpoint inhibitors currently being used to treat hepatocellular carcinoma, as well as summarize the current findings to support the potential critical role of gut microbiome in hepatocellular carcinoma (HCC) immunotherapy.


Assuntos
Carcinoma Hepatocelular/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Imunidade , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Neoplasias Hepáticas/imunologia , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/microbiologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/microbiologia
4.
Biomolecules ; 11(8)2021 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-34439920

RESUMO

In 2019, COVID-19 emerged as a severe respiratory disease that is caused by the novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The disease has been associated with high mortality rate, especially in patients with comorbidities such as diabetes, cardiovascular and kidney diseases. This could be attributed to dysregulated immune responses and severe systemic inflammation in COVID-19 patients. The use of effective antiviral drugs against SARS-CoV-2 and modulation of the immune responses could be a potential therapeutic strategy for COVID-19. Studies have shown that natural phenolic compounds have several pharmacological properties, including anticoronavirus and immunomodulatory activities. Therefore, this review discusses the dual action of these natural products from the perspective of applicability at COVID-19.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Flavonoides/uso terapêutico , Fatores Imunológicos/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Inibidores de Proteases/uso terapêutico , Animais , Antivirais/química , Antivirais/farmacologia , Coronavirus/efeitos dos fármacos , Flavonoides/química , Flavonoides/farmacologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia
5.
Pan Afr Med J ; 38: 372, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367451

RESUMO

Rituximab (RTX), a chimeric monoclonal anti-CD20 antibody has become part of the standard therapy for patients with CD20-expressing B-cell lymphoma and rheumatoid arthritis. After encouraging results with open studies in systemic lupus erythematosus (SLE), RTX has not shown its effectiveness in randomized controlled trials. However, its efficacy has been validated in renal, hematological, and neuropsychiatric disorders. Understanding the history of RTX in SLE would be instructive in the hydroxychloroquine (HCQ) saga in COVID-19. Three steps would be necessary and sufficient before definitively closing the debate: 1) determine the effective and safe dose of HCQ, as well as the minimum duration of treatment in COVID-19; 2) define the profile of patients in whom HCQ would be more likely to be effective (especially in asymptomatic patients and/or at the onset of the first signs of the disease) and 3) conduct one or more multicentre RCT to evaluate the efficacy and safety of HCQ in COVID-19 in SSA.


Assuntos
COVID-19/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Rituximab/uso terapêutico , Humanos
6.
Int J Mol Sci ; 22(15)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34360803

RESUMO

The aim of cancer immunotherapy is to reactivate autoimmune responses to combat cancer cells. To stimulate the immune system, immunomodulators, such as adjuvants, cytokines, vaccines, and checkpoint inhibitors, are extensively designed and studied. Immunomodulators have several drawbacks, such as drug instability, limited half-life, rapid drug clearance, and uncontrolled immune responses when used directly in cancer immunotherapy. Several strategies have been used to overcome these limitations. A simple and effective approach is the loading of immunomodulators onto gold-based nanoparticles (GNPs). As gold is highly biocompatible, GNPs can be administered intravenously, which aids in increasing cancer cell permeability and retention time. Various gold nanoplatforms, including nanospheres, nanoshells, nanorods, nanocages, and nanostars have been effectively used in cancer immunotherapy. Gold nanostars (GNS) are one of the most promising GNP platforms because of their unusual star-shaped geometry, which significantly increases light absorption and provides high photon-to-heat conversion efficiency due to the plasmonic effect. As a result, GNPs are a useful vehicle for delivering antigens and adjuvants that support the immune system in killing tumor cells by facilitating or activating cytotoxic T lymphocytes. This review represents recent progress in encapsulating immunomodulators into GNPs for utility in a cancer immunotherapeutic regimen.


Assuntos
Ouro/uso terapêutico , Fatores Imunológicos/uso terapêutico , Imunoterapia , Nanopartículas Metálicas/uso terapêutico , Neoplasias , Humanos , Neoplasias/imunologia , Neoplasias/terapia , Linfócitos T Citotóxicos/imunologia
7.
Int J Mol Sci ; 22(15)2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-34361041

RESUMO

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6'-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.


Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Gliose/tratamento farmacológico , Hipocampo/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Talidomida/análogos & derivados , Animais , Lesões Encefálicas Traumáticas/complicações , Cognição , Gliose/etiologia , Hipocampo/metabolismo , Fatores Imunológicos/farmacologia , Masculino , Memória , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Talidomida/farmacologia , Talidomida/uso terapêutico
8.
Artigo em Inglês | MEDLINE | ID: mdl-34452974

RESUMO

BACKGROUND AND OBJECTIVES: Since the onset of the COVID-19 pandemic, a growing number of reports have described cases of acute disseminated encephalomyelitis (ADEM) and acute hemorrhagic leukoencephalitis (AHLE) following infection with COVID-19. Given their relatively rare occurrence, the primary objective of this systematic review was to synthesize their clinical features, response to treatments, and clinical outcomes to better understand the nature of this neurologic consequence of COVID-19 infection. METHODS: Patients with a history of COVID-19 infection were included if their reports provided adequate detail to confirm a diagnosis of ADEM or AHLE by virtue of clinical features, radiographic abnormalities, and histopathologic findings. Cases purported to be secondary to vaccination against COVID-19 or occurring in the context of a preexisting relapsing CNS demyelinating disease were excluded. Case reports and series were identified via PubMed on May 17, 2021, and 4 additional cases from the authors' hospital files supplemented the systematic review of the literature. Summary statistics were used to describe variables using a complete case analysis approach. RESULTS: Forty-six patients (28 men, median age 49.5 years, 1/3 >50 years old) were analyzed, derived from 26 case reports or series originating from 8 countries alongside 4 patient cases from the authors' hospital files. COVID-19 infection was laboratory confirmed in 91% of cases, and infection severity necessitated intensive care in 67%. ADEM occurred in 31 cases, whereas AHLE occurred in 15, with a median presenting nadir modified Rankin Scale score of 5 (bedridden). Anti-MOG seropositivity was rare (1/15 patients tested). Noninflammatory CSF was present in 30%. Hemorrhage on brain MRI was identified in 42%. Seventy percent received immunomodulatory treatments, most commonly steroids, IV immunoglobulins, or plasmapheresis. The final mRS score was ≥4 in 64% of patients with adequate follow-up information, including 32% who died. DISCUSSION: In contrast to ADEM cases from the prepandemic era, reported post-COVID-19 ADEM and AHLE cases were often advanced in age at onset, experienced severe antecedent infection, displayed an unusually high rate of hemorrhage on neuroimaging, and routinely had poor neurologic outcomes, including a high mortality rate. Findings are limited by nonstandardized reporting of cases, truncated follow-up information, and presumed publication bias.


Assuntos
COVID-19/complicações , Encefalomielite Aguda Disseminada/etiologia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encefalomielite Aguda Disseminada/mortalidade , Encefalomielite Aguda Disseminada/fisiopatologia , Encefalomielite Aguda Disseminada/terapia , Glucocorticoides/uso terapêutico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Unidades de Terapia Intensiva , Leucoencefalite Hemorrágica Aguda/etiologia , Leucoencefalite Hemorrágica Aguda/mortalidade , Leucoencefalite Hemorrágica Aguda/fisiopatologia , Leucoencefalite Hemorrágica Aguda/terapia , Imageamento por Ressonância Magnética , Plasmaferese , SARS-CoV-2 , Índice de Gravidade de Doença
9.
Int J Med Mushrooms ; 23(5): 1-11, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34347990

RESUMO

Since December 2019, a de novo pattern of pneumonia, later named coronavirus disease 2019 (COVID-19), has caused grave upset throughout the global population. COVID-19 is associated with several comorbidities; thus, preventive and therapeutic strategies targeting those comorbidities along with the causative agent, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), seem imperative. In this state-of-the-art review, edible and medicinal mushrooms are featured in the treatment of SARS-CoV-2, COVID-19 pathomanifestations, and comorbid issues. Because this is not an original research article, we admit our shortcomings in inferences. Yet we are hopeful that mushroom-based therapeutic approaches can be used to achieve a COVID-free world. Among various mushroom species, reishi or lingzhi (Ganoderma lucidum) seem most suitable as anti-COVID agents for the global population.


Assuntos
Agaricales/química , Antivirais/uso terapêutico , Produtos Biológicos/uso terapêutico , COVID-19/prevenção & controle , COVID-19/terapia , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Antivirais/administração & dosagem , Produtos Biológicos/administração & dosagem , COVID-19/imunologia , COVID-19/fisiopatologia , Síndrome da Liberação de Citocina/prevenção & controle , Síndrome da Liberação de Citocina/terapia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Camundongos , Reishi/química , SARS-CoV-2/imunologia , SARS-CoV-2/patogenicidade
10.
Rheumatology (Oxford) ; 60(8): 3868-3871, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-34340243

RESUMO

OBJECTIVES: Henoch-Schönlein purpura (HScP) may present in children with severe, occasionally refractory, gastrointestinal (GI) involvement. The use of corticosteroids (CSs) is commonplace in the management of the disease, but to date no standardized protocol is available and, although rare, resistance to CS therapy may be challenging to clinicians. IVIG has been proposed as an effective alternative to CSs, but to date no controlled trial has been conducted to ascertain their real efficacy. We share our personal experience of successful IVIG treatment in two cases of GI HScP, comparing it with similar experiences reported in literature. METHODS: Retrospective clinical data collection, comparison with available literature. RESULTS: We describe two children with severe HScP GI vasculitis refractory to high-dose intravenous CSs that responded rapidly to IVIG administration, with complete recovery within a few days. Patient characteristics and response to IVIG administration were comparable to those of other previously reported cases. CONCLUSION: Our observation confirms that IVIG may be useful in the treatment of CS-resistant HScP-related GI vasculitis in children, and highlights the need for more structured research, including a randomized trial against CSs, in order to ascertain their real effectiveness.


Assuntos
Glucocorticoides/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Enteropatias/tratamento farmacológico , Púrpura de Schoenlein-Henoch/tratamento farmacológico , Adolescente , Pré-Escolar , Ensaios Clínicos Controlados como Assunto , Resistência a Medicamentos , Humanos , Masculino
11.
Nutrients ; 13(7)2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34371920

RESUMO

Nutraceuticals, including vitamin D, vitamin A, zinc, lactoferrin, polyphenols coenzyme Q, magnesium, and selenium, are implicated in the modulation of the complex molecular pathways involved in the immune response against viral pathogens. A common element of the activity of nutraceuticals is their ability to enhance the innate immune response against pathogens by acting on the major cellular subsets and inducing the release of pro-inflammatory cytokines and antimicrobial peptides. In some cases, this action is accompanied by a direct antimicrobial effect, as evidenced in the specific case of lactoferrin. Furthermore, nutraceuticals act through complex molecular mechanisms to minimize the damage caused by the activation of the immune system against pathogens, reducing the oxidative damage, influencing the antigen presentation, enhancing the differentiation and proliferation of regulatory T cells, driving the differentiation of lymphocyte subsets, and modulating the production of pro-inflammatory cytokines. In this paper, we review the main molecular mechanisms responsible for the immunomodulatory function of nutraceuticals, focusing on the most relevant aspects for the prevention and treatment of viral infections.


Assuntos
Antivirais/uso terapêutico , Suplementos Nutricionais , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Animais , Antivirais/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Sistema Imunitário/virologia , Fatores Imunológicos/efeitos adversos , Resultado do Tratamento , Viroses/imunologia , Viroses/metabolismo , Viroses/virologia , Vírus/imunologia , Vírus/patogenicidade
12.
Washington; Pan American Health Organization; 25 ed; Aug. 26, 2021. 346 p. tab..
Não convencional em Inglês | PIE | ID: biblio-1284280

RESUMO

The vast amount of data generated by clinical studies of potential therapeutic options for COVID-19 presents important challenges. The new data must be interpreted quickly so that prescribers can make optimal treatment decisions with as little harm to patients as possible, and so that medicines manufacturers can scale up production rapidly and bolster their supply chains. Rapid interpretation of fresh data will save lives by ensuring that successful drugs can be administered to as many patients as possible as quickly as possible. This publication, the 25th edition of the database of evidence on potential therapeutic options for COVID-19, examines 137 therapeutic options. This information will help investigators, policymakers, and prescribers navigate the flood of relevant data to ensure that management of COVID-19, at both individual and population levels, is based on the best available knowledge. This resource will be continually updated as more research is released into the public space.


Assuntos
Humanos , Antivirais/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , COVID-19/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Ensaios Clínicos como Assunto
13.
Washington; Pan American Health Organization; 24 ed; Aug. 5, 2021. 345 p. tab..
Não convencional em Inglês | PIE | ID: biblio-1284281

RESUMO

The vast amount of data generated by clinical studies of potential therapeutic options for COVID-19 presents important challenges. The new data must be interpreted quickly so that prescribers can make optimal treatment decisions with as little harm to patients as possible, and so that medicines manufacturers can scale up production rapidly and bolster their supply chains. Rapid interpretation of fresh data will save lives by ensuring that successful drugs can be administered to as many patients as possible as quickly as possible. This publication, the 25th edition of the database of evidence on potential therapeutic options for COVID-19, examines 137 therapeutic options. This information will help investigators, policymakers, and prescribers navigate the flood of relevant data to ensure that management of COVID-19, at both individual and population levels, is based on the best available knowledge. This resource will be continually updated as more research is released into the public space.


Assuntos
Humanos , Antivirais/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , COVID-19/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Ensaios Clínicos como Assunto
14.
Nutrients ; 13(7)2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34371956

RESUMO

We examined the immunomodulatory and anti-inflammatory effects of asiatic acid (AA) in atopic dermatitis (AD). AA treatment (5-20 µg/mL) dose-dependently suppressed the tumor necrosis factor (TNF)-α level and interleukin (IL)-6 protein expression in interferon (IFN)-γ + TNF-α-treated HaCaT cells. The 2,4-dinitrocholrlbenzene (DNCB)-induced AD animal model was developed by administering two AA concentrations (30 and 75 mg/kg/d: AD + AA-L and AD + AA-H groups, respectively) for 18 days. Interestingly, AA treatment decreased AD skin lesions formation and affected other AD characteristics, such as increased ear thickness, lymph node and spleen size, dermal and epidermal thickness, collagen deposition, and mast cell infiltration in dorsal skin. In addition, in the DNCB-induced AD animal model, AA treatment downregulated the mRNA expression level of AD-related cytokines, such as Th1- (TNF-α and IL-1ß and -12) and Th2 (IL-4, -5, -6, -13, and -31)-related cytokines as well as that of cyclooxygenase-2 and CXCL9. Moreover, in the AA treatment group, the protein level of inflammatory cytokines, including COX-2, IL-6, TNF-α, and IL-8, as well as the NF-κB and MAPK signaling pathways, were decreased. Overall, our study confirmed that AA administration inhibited AD skin lesion formation via enhancing immunomodulation and inhibiting inflammation. Thus, AA can be used as palliative medication for regulating AD symptoms.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Fatores Imunológicos/farmacologia , Triterpenos Pentacíclicos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Linhagem Celular , Sobrevivência Celular , Colágeno/análise , Citocinas/genética , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Derme/patologia , Dinitroclorobenzeno , Modelos Animais de Doenças , Epiderme/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Imunomodulação , Tecido Linfoide/patologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Triterpenos Pentacíclicos/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
15.
Arch. argent. pediatr ; 119(4): S198-S211, agosto 2021. tab, ilus
Artigo em Espanhol | LILACS, BINACIS | ID: biblio-1281043

RESUMO

La pandemia ocasionada por el nuevo coronavirus (SARS-CoV-2), declarada por la Organización Mundial de la Salud OMS) en marzo de 2020, afecta a un reducido número de pacientes pediátricos, quienes presentan, en su mayoría, compromiso respiratorio leve y evolución favorable. Sin embargo, en niños previamente sanos, comenzó a observarse un aumento de casos definidos como síndrome inflamatorio multisistémico (SIM-C) o similar a Kawasaki (Kawasaki-like) asociado a la enfermedad por el nuevo coronavirus (COVID-19) (KL-C) que evolucionan al shock y requieren internación en la unidad de cuidados intensivos.Los cuadros de SIM-C y los KL-C se caracterizan por fiebre, signos de inflamación, síntomas gastrointestinales y disfunción cardiovascular; las formas graves de presentación tienen mayor incidencia de hipotensión y/o shock. En el laboratorio se observan marcadores de inflamación, hipercoagulabilidad y daño miocárdico. El tratamiento farmacológico de primera línea consiste en la administración de inmunoglobulina por vía intravenosa más ácido acetilsalicílico por vía oral.Se recomienda un abordaje multidisciplinario para un diagnóstico certero y un tratamiento temprano y eficaz para disminuir la morbimortalidad.


The pandemic caused by the SARS-CoV-2 virus declared by the WHO in March 11th 2020, affects a small number of pediatric patients, who mostly present mild respiratory compromise and favorable evolution.However began to be observed in previously healthy children, an increase in cases defined as "Multisystemic Inflammatory Syndrome" (MIS-C) or "Kawasaki-like" post-COVID 19 (KL-C) that evolve to shock and require hospitalization in the Pediatric Intensive Care Unit.MIS-C and KL-C are characterized by fever; signs of inflammation, gastrointestinal symptoms, and cardiovascular dysfunction, associated with sever forms of presentation with higher incidence of hypotension and/or shock. In the laboratory, markers of inflammation, hypercoagulability and myocardial damage are observed. First-line drug treatment consists of intravenous immunoglobulin plus oral acetylsalicylic acid.A multidisciplinary approach is recommended for an accurate diagnosis and an early and effective treatment, in order to reduce morbidity and mortality.


Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/terapia , COVID-19/diagnóstico , COVID-19/terapia , Terapia Respiratória/métodos , Imunoglobulinas Intravenosas/uso terapêutico , Terapia Combinada , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia , Cuidados Críticos/métodos , Diagnóstico Precoce , Diagnóstico Diferencial , Teste para COVID-19 , COVID-19/fisiopatologia , Fatores Imunológicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico
17.
J Autoimmun ; 123: 102687, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34311142

RESUMO

The impact of SARS-CoV-2 infection in patients with autoimmune/auto-inflammatory rheumatic diseases (AARD) under immunomodulatory treatment has been a focus of interest during the COVID-19 pandemic. In this observational study, demographic data, disease related features and comorbidities, COVID-19 manifestations and outcome as well as antibody responses to SARS-CoV-2 were recorded among 77 consecutive patients with underlying AARD infected by SARS-CoV-2. Analysis of data was performed using univariate and multivariate models. Most patients (68.8%) had a mild COVID-19 course. The predominant clinical manifestations were fatigue (58.4%), low grade fever (45.4%) and upper respiratory tract symptoms (68.8%). About a quarter of patients required hospitalization (23.3%) and the mortality rate was 1.3%. Regarding COVID-19 severity, prior treatment with corticosteroids, mycophenolate mofetil or rituximab was more common in patients who developed a more serious disease course (60.0 vs 29.9%, p = 0.003, 40.0 vs 7.5%, p = 0.003, 10.0 vs 0.0%, p = 0.009, respectively). When disease related features and comorbidities were considered in multivariate models, older age and lung disease in the context of the AARD were found to be independent predictive factors for hospitalization (OR [95%]: 1.09 [1.03-1.15] and 6.43 [1.11-37.19]). Among COVID-19 related features, patients with shortness of breath and high-grade fever were more likely to get hospitalized (OR [95%]: 7.06 [1.36-36.57], 12.04 [2.96-48.86]), while anosmia was independently associated with lower hospitalization risk (OR [95%]: 0.09 [0.01-0.99]). Though the majority of AARD patients displayed a mild COVID-19 course, certain underlying disease features and COVID-19 related manifestations should prompt alertness for the physician to identify patients with AARD at high risk for severe COVID-19 and need for hospitalization.


Assuntos
Doenças Autoimunes/epidemiologia , COVID-19/epidemiologia , Doenças do Tecido Conjuntivo/epidemiologia , SARS-CoV-2 , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/biossíntese , Infecções Assintomáticas/epidemiologia , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Comorbidade , Doenças do Tecido Conjuntivo/tratamento farmacológico , Doenças do Tecido Conjuntivo/imunologia , Estado Terminal , Feminino , Grécia/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Hipotireoidismo/epidemiologia , Hospedeiro Imunocomprometido , Imunoglobulina G/biossíntese , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Inflamação , Pneumopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Literatura de Revisão como Assunto , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/epidemiologia , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Avaliação de Sintomas
18.
Science ; 373(6554): 510-516, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34326232

RESUMO

Type 1 diabetes (T1D) is an autoimmune disease in which T cells attack and destroy the insulin-producing ß cells in the pancreatic islets. Genetic and environmental factors increase T1D risk by compromising immune homeostasis. Although the discovery and use of insulin have transformed T1D treatment, insulin therapy does not change the underlying disease or fully prevent complications. Over the past two decades, research has identified multiple immune cell types and soluble factors that destroy insulin-producing ß cells. These insights into disease pathogenesis have enabled the development of therapies to prevent and modify T1D. In this review, we highlight the key events that initiate and sustain pancreatic islet inflammation in T1D, the current state of the immunological therapies, and their advantages for the treatment of T1D.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Fatores Imunológicos/uso terapêutico , Imunoterapia , Imunidade Adaptativa , Animais , Anti-Inflamatórios/uso terapêutico , Autoanticorpos/sangue , Linfócitos B/imunologia , Citocinas/imunologia , Citocinas/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Humanos , Imunidade Inata , Células Secretoras de Insulina/fisiologia , Interleucina-2/uso terapêutico , Linfócitos T/imunologia
19.
J Immunol Res ; 2021: 9934134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307694

RESUMO

Background: Regulation of the immune system is critical for fighting against viral infections. Both suppression and hyperactivity of the immune system result in failure of treatment. The present study was designed to show the effects of immune system-related medications on mortality and length of stay (LOS) in a cohort of Iranian patients with coronavirus disease 2019 (COVID-19). Methods: A data mining study was performed on 6417 cases of COVID-19 covered by 17 educational hospitals of Iran University of Medical Sciences, Tehran. Association of a researcher-designed drug list with death and LOS was studied. For death outcome, logistic regression was used reporting odds ratio (OR) with 95% confidence interval (CI). For LOS, right censored Poisson regression was used reporting incidence rate ratio (IRR) with 95% CI. Results: Among the corticosteroids, prednisolone was a risk factor on death (OR = 1.41, 95%CI = 1.03 - 1.94). This association was increased after adjustment of age interactions (OR = 3.45, 95%CI = 1.01 - 11.81) and was removed after adjustment of ICU admission interactions (OR = 2.64, 95%CI = 0.70 - 9.92). Hydroxychloroquine showed a protecting effect on death (OR = 0.735, 95%CI = 0.627 - 0.862); however, this association was removed after adjustment of age interactions (OR = 0.76, 95%CI = 0.41 - 1.40). Among the antivirals, oseltamivir showed a protecting effect on death (OR = 0.628, 95%CI = 0.451 - 0.873); however, this association was removed after adjustment of age interactions (OR = 0.45, 95%CI = 0.11 - 1.82). For reduction of LOS, the only significant association was for hydroxychloroquine (IRR = 0.85, 95%CI = 0.79 - 0.92). Conclusion: The results of such data mining studies can be used in clinics until completing the evidence. Hydroxychloroquine may reduce mortality in some specific groups; however, its association may be confounded by some latent variables and unknown interactions. Administration of corticosteroids should be based on the conditions of each case.


Assuntos
COVID-19/tratamento farmacológico , COVID-19/imunologia , Pandemias , SARS-CoV-2 , Adjuvantes Imunológicos/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , COVID-19/mortalidade , Criança , Pré-Escolar , Estudos de Coortes , Mineração de Dados , Feminino , Humanos , Sistema Imunitário/efeitos dos fármacos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Lactente , Recém-Nascido , Irã (Geográfico)/epidemiologia , Tempo de Internação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
20.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281285

RESUMO

Sjögren's syndrome (SS), a chronic inflammatory disease involving the salivary and lacrimal glands, presents symptoms of sicca as well as systemic manifestations such as fatigue and musculoskeletal pain. Only a few treatments have been successful in management of SS; thus treatment of the disease is challenging. Metformin is the first-line agent for type 2 diabetes and has anti-inflammatory potential. Its immunomodulatory capacity is exerted via activation of 5' adenosine monophosphate-activated protein kinase (AMPK). Metformin inhibits mitochondrial respiratory chain complex I which leads to change in adenosine mono-phosphate (AMP) to adenosine tri-phosphate (ATP) ratio. This results in AMPK activation and causes inhibition of mammalian target of rapamycin (mTOR). mTOR plays an important role in T cell differentiation and mTOR deficient T cells differentiate into regulatory T cells. In this manner, metformin enhances immunoregulatory response in an individual. mTOR is responsible for B cell proliferation and germinal center (GC) differentiation. Thus, reduction of B cell differentiation into antibody-producing plasma cells occurs via downregulation of mTOR. Due to the lack of suggested treatment for SS, metformin has been considered as a treatment strategy and is expected to ameliorate salivary gland function.


Assuntos
Metformina/uso terapêutico , Síndrome de Sjogren/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Humanos , Fatores Imunológicos/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Transdução de Sinais/efeitos dos fármacos , Síndrome de Sjogren/etiologia , Síndrome de Sjogren/fisiopatologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/imunologia , Serina-Treonina Quinases TOR/metabolismo
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