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1.
Tokai J Exp Clin Med ; 45(3): 126-130, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32901900

RESUMO

We present a case of osteomyelitis of the condyle secondary to bisphosphonate-related osteonecrosis of the jaw. A 77-year-old female was referred to our clinic with complaints of swelling in the left mandibular molar regions. The patient had been suffering from myeloperoxidase anti-neutrophil cytoplasmic antibody (MPOANCA) associated vasculitis and had been treated with glucocorticoids for 8 years, and oral bisphosphonates had been prescribed to prevent osteopenia secondary to glucocorticoids. Imaging examinations showed radiolucency of the left mandibular body. Based on the diagnosis of osteomyelitis of the mandibular body secondary to bisphosphonate-related osteonecrosis, the patient received antimicrobial therapy and was well-healed. However, the patient returned 8 weeks later complaining of acute left preauricular swelling. Computed tomography showed the destructive changes in the mandibular condyle. We speculated that the infection was caused by the local spread from osteomyelitis of the left mandibular body. The risk of jaw necrosis related to antiresorptive therapy is well known. In recent years, the number of older patients being administered glucocorticoids with bisphosphonates has increased; therefore, we must be attentive to the signs of infectious diseases of the jawbone in the aging because it can easily shift to osteomyelitis or osteonecrosis and spread infection through the marrow.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Arcada Osseodentária , Côndilo Mandibular , Osteomielite/etiologia , Idoso , Antibacterianos/administração & dosagem , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Feminino , Glucocorticoides/efeitos adversos , Humanos , Imagem por Ressonância Magnética , Côndilo Mandibular/diagnóstico por imagem , Osteomielite/diagnóstico por imagem , Osteomielite/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
2.
PLoS Med ; 17(9): e1003222, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32956407

RESUMO

BACKGROUND: Treatment with corticosteroids is recommended for Duchenne muscular dystrophy (DMD) patients to slow the progression of weakness. However, chronic corticosteroid treatment causes significant morbidities. Vamorolone is a first-in-class anti-inflammatory investigational drug that has shown evidence of efficacy in DMD after 24 weeks of treatment at 2.0 or 6.0 mg/kg/day. Here, open-label efficacy and safety experience of vamorolone was evaluated over a period of 18 months in trial participants with DMD. METHODS AND FINDINGS: A multicenter, open-label, 24-week trial (VBP15-003) with a 24-month long-term extension (VBP15-LTE) was conducted by the Cooperative International Neuromuscular Research Group (CINRG) and evaluated drug-related effects of vamorolone on motor outcomes and corticosteroid-associated safety concerns. The study was carried out in Canada, US, UK, Australia, Sweden, and Israel, from 2016 to 2019. This report covers the initial 24-week trial and the first 12 months of the VBP15-LTE trial (total treatment period 18 months). DMD trial participants (males, 4 to <7 years at entry) treated with 2.0 or 6.0 mg/kg/day vamorolone for the full 18-month period (n = 23) showed clinical improvement of all motor outcomes from baseline to month 18 (time to stand velocity, p = 0.012 [95% CI 0.010, 0.068 event/second]; run/walk 10 meters velocity, p < 0.001 [95% CI 0.220, 0.491 meters/second]; climb 4 stairs velocity, p = 0.001 [95% CI 0.034, 0.105 event/second]; 6-minute walk test, p = 0.001 [95% CI 31.14, 93.38 meters]; North Star Ambulatory Assessment, p < 0.001 [95% CI 2.702, 6.662 points]). Outcomes in vamorolone-treated DMD patients (n = 46) were compared to group-matched participants in the CINRG Duchenne Natural History Study (corticosteroid-naïve, n = 19; corticosteroid-treated, n = 68) over a similar 18-month period. Time to stand was not significantly different between vamorolone-treated and corticosteroid-naïve participants (p = 0.088; least squares [LS] mean 0.042 [95% CI -0.007, 0.091]), but vamorolone-treated participants showed significant improvement compared to group-matched corticosteroid-naïve participants for run/walk 10 meters velocity (p = 0.003; LS mean 0.286 [95% CI 0.104, 0.469]) and climb 4 stairs velocity (p = 0.027; LS mean 0.059 [95% CI 0.007, 0.111]). The vamorolone-related improvements were similar in magnitude to corticosteroid-related improvements. Corticosteroid-treated participants showed stunting of growth, whereas vamorolone-treated trial participants did not (p < 0.001; LS mean 15.86 [95% CI 8.51, 23.22]). Physician-reported incidences of adverse events (AEs) for Cushingoid appearance, hirsutism, weight gain, and behavior change were less for vamorolone than published incidences for prednisone and deflazacort. Key limitations to the study were the open-label design, and use of external comparators. CONCLUSIONS: We observed that vamorolone treatment was associated with improvements in some motor outcomes as compared with corticosteroid-naïve individuals over an 18-month treatment period. We found that fewer physician-reported AEs occurred with vamorolone than have been reported for treatment with prednisone and deflazacort, and that vamorolone treatment did not cause the stunting of growth seen with these corticosteroids. This Phase IIa study provides Class III evidence to support benefit of motor function in young boys with DMD treated with vamorolone 2.0 to 6.0 mg/kg/day, with a favorable safety profile. A Phase III RCT is underway to further investigate safety and efficacy. TRIAL REGISTRATION: Clinical trials were registered at www.clinicaltrials.gov, and the links to each trial are as follows (as provided in manuscript text): VBP15-002 [NCT02760264] VBP15-003 [NCT02760277] VBP15-LTE [NCT03038399].


Assuntos
Atividade Motora/efeitos dos fármacos , Distrofia Muscular de Duchenne/tratamento farmacológico , Pregnadienodiois/uso terapêutico , Corticosteroides/efeitos adversos , Criança , Pré-Escolar , Progressão da Doença , Glucocorticoides/efeitos adversos , Humanos , Masculino , Prednisona/uso terapêutico , Pregnadienodiois/metabolismo , Resultado do Tratamento , Caminhada/fisiologia
4.
Medicine (Baltimore) ; 99(34): e21671, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846782

RESUMO

BACKGROUND: Concerns exist regarding the analgesia effect and safety of multiple versus single doses dexamethasone in unicompartmental knee arthroplasty. There is an urgent need of studies that efficiently control for confounding, conduct comprehensive and consecutive observation of potential risks of the dexamethasone administration, and investigate its clinical applicability. We thus further designed a randomized controlled study to assess the different dose of dexamethasone on postoperative pain and complications in patients undergoing unicompartmental knee arthroplasty. METHODS: This randomized, prospective, controlled study was carried out between January 2018 and August 2019. It was approved by the institutional review board in our hospital (HBRM2020013). A total of 80 patients were randomly assigned to each group: the study group (n = 40) and the control group (n = 40). All surgical procedures were performed by a similar orthopedic surgeon. In the study group, patients received intravenously 20 mg dexamethasone (4 mL, Tianjin Kingyork group Co., Ltd., China) just after the anesthesia, and repeated at 24 hours after the surgery. Patients in the control group received intravenously 10 mg dexamethasone solution (2 mL) just after the anesthesia, and repeated at 24 hours after the surgery. CRP, IL-6, VAS pain scores at rest and walking, the VAS scores of nausea, and the incidence of postoperative vomiting and nausea (POVN) were recorded at 24, 48, and 72 hours postoperatively. CONCLUSION: We hypothesized that patients receiving multiple doses of dexamethasone was associated with better outcomes compared with patients receiving single dose of dexamethasone. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5770).


Assuntos
Artroplastia do Joelho , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Dor Pós-Operatória/tratamento farmacológico , Náusea e Vômito Pós-Operatórios/dietoterapia , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Artroplastia do Joelho/métodos , Dexametasona/efeitos adversos , Glucocorticoides/efeitos adversos , Humanos , Estudos Prospectivos , Resultado do Tratamento
6.
Circ J ; 84(10): 1887, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32779609
7.
J Hosp Med ; 15(8): 489-493, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32804611

RESUMO

The efficacy of glucocorticoids in COVID-19 is unclear. This study was designed to determine whether systemic glucocorticoid treatment in COVID-19 patients is associated with reduced mortality or mechanical ventilation. This observational study included 1,806 hospitalized COVID-19 patients; 140 were treated with glucocorticoids within 48 hours of admission. Early use of glucocorticoids was not associated with mortality or mechanical ventilation. However, glucocorticoid treatment of patients with initial C-reactive protein (CRP) ≥20 mg/dL was associated with significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08-0.70), while glucocorticoid treatment of patients with CRP <10 mg/dL was associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI, 1.39-5.03). Whether glucocorticoid treatment is associated with changes in mortality or mechanical ventilation in patients with high or low CRP needs study in prospective, randomized clinical trials.


Assuntos
Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Glucocorticoides/uso terapêutico , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Respiração Artificial/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Índice de Massa Corporal , Proteína C-Reativa/análise , Criança , Pré-Escolar , Comorbidade , Grupos de Populações Continentais , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Estudos Prospectivos , Fatores de Tempo , Adulto Jovem
8.
Brasília; CONITEC; jul. 2020.
Não convencional em Português | BRISA/RedTESA | ID: biblio-1121202

RESUMO

INTRODUÇÃO: A artrite psoriaca (AP), doenca articular inflamatoria associada a psoriase, pertencente ao grupo das espondiloartrites, reune manifestacoes cutaneas e articulares. Tem uma prevalencia de aproximadamente 1 a 2 por 1.000 na populacao em geral. Cerca de 30% dos pacientes com psoriase desenvolvem AP. No exame fisico, estao presentes dor oriunda do estresse, sensibilidade das linhas articulares e derrames nas articulacoes afetadas, geralmente em uma distribuicao assimetrica. O tratamento preconizado no Protocolo Clinico e Diretrizes Terapeuticas de Artrite Psoriaca e disponivel no SUS e a base de anti-inflamatorios nao esteroidais, glicocorticoides, medicamentos modificadores do curso da doenca (MMCD) sinteticos e biologicos e Inibidor de citocinas anti-interleucina (IL)-17. TECNOLOGIA: Citrato de tofacitinibe (XeljanzR). PERGUNTA: Tofacitinibe e eficaz e seguro para o tratamento da artrite psoriaca ativa moderada a grave em pacientes adultos que nao responderam ou sao intolerantes ao tratamento previo com MMCD sinteticos ou biologicos? EVIDÊNCIAS CIENTÍFICAS: Foram selecionados dois estudos fase III, ensaios clinicos randomizados avaliando eficacia e seguranca do tofacitinibe em pacientes tratados previamente com medicamentos modificadores da doenca sinteticos e anti-TNF. No estudo com pacientes tratados previamente com anti-TNF, ACR50 em 3 meses foi de 15% para placebo, 30% para tofacitinibe de 5mg( p = 0,003), e 28% para tofacitinibe de 10 mg (p = 0,007). Ja no estudo de pacientes tratados previamente com MMCD sinteticos em 3 meses as taxas de resposta foram 10% para placebo, 30 % para tofacitinibe 5mg e 42% para tofacitinibe 10 mg (p < 0,001 para as duas comparacoes. AVALIAÇÃO ECONÔMICA: Foi apresentada uma analise de custo-miniminizacao, uma vez que os estudos de comparacao indireta do tofacitinibe com seus comparadores demonstraram efetividade semelhante. O custo anual do tratamento por paciente, considerando-se apenas o preco do tofacitinibe proposto pelo demandante, foi de R$ 11.074,10. Em relacao aos seus comparadores, se incorporado, pode gerar uma reducao de custos que variou de -R$ 1.336,74 (em relacao ao Adalimumabe) a -R$ 14.940,94 (em relacao ao Imfliximabe). AVALIAÇÃO DE IMPACTO ORÇAMENTÁRIO: Em todos os cenarios propostos o uso do tofacitinibe gerou economia de recursos. O impacto orcamentario do tofacitinibe ao custo proposto pelo demandante em 1 ano foi de ­R$ 41,4 milhoes , variando nos cenarios entre ­R$ 9,1 milhoes a ­R$ 64,1 milhoes e em 5 anos foi de ­R$ 240,6 milhoes variando nos cenarios entre ­R$ 52,8 milhoes a ­R$ 372,1 milhoes. A estimativa da populacao pelo metodo demanda aferida contemplou toda populacao com AP, e nao apenas a populacao com AP moderada a grave, fazendo com que estes valores estejam superestimados. MONITORAMENTO DO HORIZONTE TECNOLÓGICO: Foram detectadas no horizonte seis potenciais tecnologias para o tratamento de pacientes com artrite psoriaca ativa moderada a grave com resposta inadequada ou intolerantes ao tratamento previo com MMCD sinteticos ou biológicos. CONSIDERAÇÕES: O citrato de tofacitinibe e uma tecnologia ja incorporada no SUS para outras indicacoes. As poucas evidencias cientificas disponiveis, possivelmente em virtude do recente registro desta nova indicacao junto as agencias reguladoras, e que atenderam a pergunta estruturada aqui proposta, demonstraram que o medicamento possui eficacia semelhante aos MMCD biologicos a um custo inferior. Sua administracao por via oral favorece a adesao ao tratamento na maioria dos casos, alem de reduzir custos anuais de tratamento. Deve ser usado em associacao aos MMCD sinteticos. A evidencia atualmente disponivel sobre eficacia e seguranca do tofacitinibe para tratamento de artrite psoriaca e baseada em apenas 2 ensaios clinicos randomizados, estudos fase III, com risco de vies incerto e grau de recomendacao fraco a favor da tecnologia. RECOMENDAÇÃO PRELIMINAR DA CONITEC: Os membros do plenario presentes na 85a reunião ordinaria, realizada nos dias 04 e 05 de fevereiro de 2020, indicaram que o tema fosse submetido a consulta publica com recomendacao preliminar favoravel a incorporacao ao SUS de tofacitinibe para tratamento de artrite psoriaca ativa moderada a grave em pacientes adultos que nao respondem ou sao intolerantes ao tratamento previo com medicamentos modificadores do curso da doenca (MMCD) sinteticos ou biologicos. Considerou-se que as evidencias apresentadas demonstram que o tofacitinibe possui eficacia semelhante aos medicamentos ja disponiveis no SUS, alem de ser um medicamento oral, o que poderia favorecer a adesao ao tratamento. Alem disso, a sua incorporacao geraria economia de recursos em cenarios que contemplam os demais medicamentos biologicos atualmente incorporados ao SUS para a mesma condicao clinica. A materia foi disponibilizada em consulta publica. CONSULTA PÚBLICA: Houve 103 contribuicoes, 18 tecnico-cientificas e 85 de experiencia ou opiniao, sobre a recomendacao preliminar da Conitec. Apenas 2 contribuicoes foram contrarias, porem sem nenhuma argumentacao. Nao foram adicionadas referencias que alterassem as analises da evidencia. RECOMENDAÇÃO FINAL: Os membros da Conitec presentes na 88a reuniao ordinaria, no dia 07 de julho de 2020, deliberaram por unanimidade, recomendar a incorporacao do citrato de tofacitinibe para o tratamento de pacientes adultos com artrite psoriaca ativa moderada a grave intolerantes ou com falha terapeutica aos medicamentos modificadores do curso da doença sinteticos ou biologicos, conforme o Protocolo Clinico e Diretrizes Terapeuticas do Ministerio da Saude. Foi assinado o Registro de Deliberacao no 529/2020. DECISÃO: incorporar o citrato de tofacitinibe para o tratamento de pacientes adultos com artrite psoriaca ativa moderada a grave intolerantes ou com falha terapeutica aos medicamentos modificadores do curso da doenca sinteticos ou biologicos, conforme o Protocolo Clinico e Diretrizes Terapeuticas do Ministerio da Saude, no ambito do Sistema Unico de Saude - SUS, conforme Portaria no 28, publicada no Diario Oficial da Uniao no 160, secao 1, pagina 117, em 20 de agosto de 2020.


Assuntos
Humanos , Artrite Psoriásica/tratamento farmacológico , Anti-Inflamatórios não Esteroides/efeitos adversos , Interleucinas/antagonistas & inibidores , Antirreumáticos/efeitos adversos , Janus Quinases/antagonistas & inibidores , Glucocorticoides/efeitos adversos , Avaliação da Tecnologia Biomédica , Sistema Único de Saúde , Brasil , Análise Custo-Benefício/economia
9.
Lancet ; 396(10246): 267-276, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711802

RESUMO

BACKGROUND: Patients with inflammatory diseases, such as rheumatoid arthritis, often receive glucocorticoids, but long-term use can produce adverse effects. Evidence from randomised controlled trials to guide tapering of oral glucocorticoids is scarce. We investigated a scheme for tapering oral glucocorticoids compared with continuing low-dose oral glucocorticoids in patients with rheumatoid arthritis. METHODS: The Steroid EliMination In Rheumatoid Arthritis (SEMIRA) trial was a double-blind, multicentre, two parallel-arm, randomised controlled trial done at 39 centres from six countries (France, Germany, Italy, Russia, Serbia, and Tunisia). Adult patients with rheumatoid arthritis receiving tocilizumab and glucocorticoids 5-15 mg per day for 24 weeks or more were eligible for inclusion if they had received prednisone 5 mg per day for 4 weeks or more and had stable low disease activaity, confirmed by a Disease Activity Score for 28 joints-erythrocyte sedimentation rate (DAS28-ESR) of 3·2 or less 4-6 weeks before and on the day of randomisation. Patients were randomly assigned 1:1 to either continue masked prednisone 5 mg per day for 24 weeks or to taper masked prednisone reaching 0 mg per day at week 16. All patients received tocilizumab (162 mg subcutaneously every week or 8 mg/kg intravenously every 4 weeks) with or without csDMARDs maintained at stable doses during the entire 24-week study. The primary outcome was the difference in mean DAS28-ESR change from baseline to week 24, with a difference of more than 0·6 defined as clinically relevant between the continued-prednisone group and the tapered-prednisone group. The trial is registered with ClinicalTrials.gov, NCT02573012. FINDINGS: Between Oct 21, 2015, and June 9, 2017, 421 patients were screened and 259 (200 [77%] women and 59 [23%] men) were recruited onto the trial. In all 128 patients assigned to the continued-prednisone regimen, disease activity control was superior to that in all 131 patients assigned to the tapered-prednisone regimen; the estimated mean change in DAS28-ESR from baseline to week 24 was 0·54 (95% CI 0·35-0·73) with tapered prednisone and -0·08 (-0·27 to 0·12) with continued prednisone (difference 0·61 [0·35-0·88]; p<0·0001), favouring continuing prednisone 5 mg per day for 24 weeks. Treatment was regarded as successful (defined as low disease activity at week 24, plus absence of rheumatoid arthritis flare for 24 weeks and no confirmed adrenal insufficiency) in 99 (77%) patients in the continued-prednisone group versus 85 (65%) patients in the tapered-prednisone group (relative risk 0·83; 95% CI 0·71-0·97). Serious adverse events occurred in seven (5%) patients in the tapered-prednisone group and four (3%) patients in the continued-prednisone group; no patients had symptomatic adrenal insufficiency. INTERPRETATION: In patients who achieved low disease activity with tocilizumab and at least 24 weeks of glucocorticoid treatment, continuing glucocorticoids at 5 mg per day for 24 weeks provided safe and better disease control than tapering glucocorticoids, although two-thirds of patients were able to safely taper their glucocorticoid dose. FUNDING: F Hoffmann-La Roche.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Indução de Remissão/métodos , Administração Intravenosa , Administração Oral , Adulto , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Reumatoide/etnologia , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , França/epidemiologia , Alemanha/epidemiologia , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Injeções Subcutâneas , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Federação Russa/epidemiologia , Sérvia/epidemiologia , Tunísia/epidemiologia
10.
Respir Physiol Neurobiol ; 280: 103492, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32659271

RESUMO

In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China. Later described as COVID-19 (coronavirus disease 2019), this infection caused by a virus from the Coronaviridae family (SARS-CoV-2) has spread globally. Effective therapies for this new disease are urgently needed. In this short communication, we will evaluate the use of corticosteroids as an adjunctive pharmacological therapy in the management of COVID-19 and describe its pros and cons in light of the latest available evidence.


Assuntos
Anti-Inflamatórios/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Citocinas/antagonistas & inibidores , Glucocorticoides/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Anti-Inflamatórios/efeitos adversos , Betacoronavirus/fisiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Citocinas/sangue , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Esquema de Medicação , Glucocorticoides/efeitos adversos , Humanos , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia
11.
Nat Commun ; 11(1): 3593, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32681096

RESUMO

During pregnancy, maternal endocrine signals drive fetal development and program the offspring's physiology. A disruption of maternal glucocorticoid (GC) homeostasis increases the child's risk of developing psychiatric disorders later in life. We here show in mice, that the time of day of antenatal GC exposure predicts the behavioral phenotype of the adult offspring. Offspring of mothers receiving GCs out-of-phase compared to their endogenous circadian GC rhythm show elevated anxiety, impaired stress coping, and dysfunctional stress-axis regulation. The fetal circadian clock determines the vulnerability of the stress axis to GC treatment by controlling GC receptor (GR) availability in the hypothalamus. Similarly, a retrospective observational study indicates poorer stress compensatory capacity in 5-year old preterm infants whose mothers received antenatal GCs towards the evening. Our findings offer insights into the circadian physiology of feto-maternal crosstalk and assign a role to the fetal clock as a temporal gatekeeper of GC sensitivity.


Assuntos
Relógios Circadianos/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Exposição Materna/efeitos adversos , Transtornos Mentais/etiologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Ansiedade , Comportamento/efeitos dos fármacos , Feminino , Glucocorticoides/administração & dosagem , Humanos , Recém-Nascido Prematuro/psicologia , Masculino , Transtornos Mentais/metabolismo , Transtornos Mentais/fisiopatologia , Transtornos Mentais/psicologia , Gravidez , Complicações na Gravidez/tratamento farmacológico , Cuidado Pré-Natal , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo
12.
Life Sci ; 257: 118044, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622944

RESUMO

AIMS: High-dose glucocorticoid (GC) administration causes osteoporosis. Many previous studies from our group and other groups have shown that melatonin participates in the regulation of osteoblast proliferation and differentiation, especially low concentrations of melatonin, which enhance osteoblast osteogenesis. However, the role of melatonin in glucocorticoid-induced osteoblast differentiation remains unknown. MATERIALS AND METHODS: An examination of the expression of osteoblast differentiation markers (ALP, OCN, COLL-1), as well as alkaline phosphatase staining and alkaline phosphatase enzymatic activity assay to measure osteoblast differentiation and quantifying Alizarin red S staining to measure mineralization, were performed to determine the effects of dexamethasone (Dex) and melatonin on the differentiation of MC3T3-E1 cells. We used immunofluorescence staining to detect the expression of Runx2 in melatonin-treated MC3T3-E1 cells. The expression of mRNA was determined by qRT-PCR, and protein levels were measured by western blotting. KEY FINDINGS: In the present study, we found that 100 µM Dex significantly reduced osteoblast differentiation and mineralization in MC3T3-E1 cells and that 1 µM melatonin attenuated these inhibitory effects. We found that only inhibition of PI3K/AKT (MK2206) and BMP/Smad (LDN193189) signalling abolished melatonin-induced differentiation and mineralization. Meanwhile, MK2206 decreased the expression of P-AKT and P-Smad1/5/9 and LDN193189 decreased the expression of P-Smad1/5/9 but had no obvious effect on P-AKT expression in melatonin-treated and Dex-induced MC3T3-E1 cells. SIGNIFICANCE: These findings suggest that melatonin rescues Dex-induced inhibition of osteoblast differentiation in MC3T3-E1 cells via the PI3K/AKT and BMP/Smad signalling pathways and that PI3K/AKT signalling may be the upstream signal of BMP/Smad signalling.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Melatonina/metabolismo , Osteoblastos/metabolismo , Animais , Biomineralização/efeitos dos fármacos , Proteína Morfogenética Óssea 2/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Calcificação Fisiológica/efeitos dos fármacos , Linhagem Celular , Dexametasona/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glucocorticoides/efeitos adversos , Glucocorticoides/farmacologia , Melatonina/farmacologia , Camundongos , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Smad/metabolismo
14.
Medicine (Baltimore) ; 99(29): e21220, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702891

RESUMO

BACKGROUND: Concerns exist regarding the analgesia effect and safety of epidural steroid injection (ESI) after discectomy. There is an urgent need of studies that efficiently control for confounding, conduct comprehensive and consecutive observation of potential risks of ESI, and investigate its clinical applicability. We thus further designed a randomized controlled study to assess the efficacy of ESI on postoperative pain and complications in patients undergoing unilateral lumbar microdiscectomy. METHODS: This prospective, blinded randomized controlled trial was conducted at our single hospital. This study was approved by the Committee at the No.2 People's Hospital of Yibin. All procedures were performed by a single surgeon and informed consent was obtained from each patient. Ninty eligible patients diagnosed at our institution with herniated lumbar disc during a period from June 2020 to July 2021 will be assessed. Group 1 was a mixture of 1 mL of 0.5% bupivacaine and 10 mg of triamcinolone acetonide in 1 mL. Group 2 was a mixture of 1 mL of 0.5% bupivacaine and 1 mL of normal saline. The primary outcome measure was the amount of morphine consumption from a patient-controlled analgesia pump at 12, 24, and 48 hours after surgery. The following secondary outcomes were also assessed: postoperative pain score, back pain score, functional disability, and adverse effect. CONCLUSIONS: We hypothesized that the ESI was associated with lower pain score, morphine consumption, and hospital stay, with no significant difference in complications for ESI application after lumbar discectomy in lumbar disc herniation when compared with placebo. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5683).


Assuntos
Discotomia , Glucocorticoides/uso terapêutico , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares , Analgesia Controlada pelo Paciente , Método Duplo-Cego , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Injeções Epidurais , Medição da Dor , Dor Pós-Operatória , Período Pós-Operatório , Estudos Prospectivos , Resultado do Tratamento
15.
Medicine (Baltimore) ; 99(27): e20824, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629668

RESUMO

INTRODUCTION: Glucocorticoids (GCs), especially low-dose GCs, are commonly prescribed for rheumatoid arthritis (RA), although the risk/benefit ratio is controversial. A randomized, double-blind clinical trial was performed to evaluate the efficacy and safety of low-dose oral GCs combined with methotrexate (MTX) and hydroxychloroquine (HCQ) in early RA (ERA). METHODS: Eighty untreated ERA patients were randomized into the trial (GCs + MTX + HCQ) and control (placebo + MTX + HCQ) groups, for 1-year treatment. Therapeutic evaluation indices were American College of Rheumatology (ACR) 20 of ACR, disease activity score (DAS) 28- erythrocyte sedimentation rate (ESR), visual analog scale scores, joint function, health assessment questionnaire-disability index score, morning stiffness duration, C-reaction protein and ESR. The clinical indicators were evaluated pre-treatment and at 1st, 3th, 6th and 12th month of treatment. The MRI data of single joint (ie, the most swollen joint) for each patient were acquired with a revised OMERACT RAMRIS Scoring System before and after treatment. The correlation analysis was adopted to confirm whether the efficacy of GC treatment is related to the time of RA onset. The side effects (eg, gastrointestinal reactions, liver dysfunction, upper respiratory tract infection, leukocyte reduction) were also monitored. RESULTS: At 1st month, 55% and 20% cases in the experimental and control groups achieved ACR20 response, respectively, indicating a significant difference (χ = 16.157, P < .001). This trend continued until 6th month. At 12th month, the number of patients achieved ACR20 response was similar in both groups. At 1st to 6th month, DAS28- ESR scores in the experimental group were significantly lower than control values (all p < .05). The experimental group showed improved inflammation, quality of life and radiological symptoms. Bone erosion remained unchanged in the experimental group, while worsening in control group. Correlation coefficients between RA duration and DAS28-ESR score were 0.496, 0.464, 0.509, and 0.550 at 1st, 3th, 6th, and 12th month, respectively. No differences were found in adverse events between the 2 groups. CONCLUSIONS: Low-dose GCs combined with MTX and HCQ significantly achieves disease remission indexed by ACR20 and DAS28-ESR, and improves clinical and radiological outcomes in ERA patients at the early stage, with superiority over placebo + MTX + HCQ, without enhancing adverse reactions.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Glucocorticoides/uso terapêutico , Hidroxicloroquina/uso terapêutico , Metotrexato/uso terapêutico , Adulto , Antirreumáticos/administração & dosagem , Antirreumáticos/efeitos adversos , Sedimentação Sanguínea , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Masculino , Metotrexato/administração & dosagem , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de Doença
16.
J Pharmacol Sci ; 143(4): 300-306, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32534995

RESUMO

Drug and therapies currently used to treat human bone diseases have a lot of severe side effects. Liquiritigenin is a flavonoid extracted from Glycyrrhiza glabra roots which has been reported to have positive effects in vitro on osteoblasts activity and bone mineralization as well as inhibitory effect on osteoclasts differentiation and activity in vitro. The present study was aimed to evaluate the in vivo effects of liquiritigenin on bone structure and metabolism in physiological and pathological conditions using Danio rerio as experimental animal model. Treatments with liquiritigenin were performed on embryos to evaluate the osteogenesis during skeletal development. Other treatments were performed on adult fish affected by glucocorticoid-induced osteoporosis to assay the therapeutic potential of liquiritigenin in the reversion of bone-loss phenotype in scale model. Liquiritigenin treatment of zebrafish embryo significantly enhances the osteogenesis during development in a dose-dependent manner. In addition, liquiritigenin inhibits the formation of the osteoporotic phenotype in adult zebrafish model of glucocorticoid-induced osteoporosis preventing osteoclast activation in scales. Interestingly, liquiritigenin does not counteract the loss of osteoblastic activity in scales. The liquiritigenin exhibits in vivo anti-osteoporotic activity on adult fish scale model. It can be considered a good candidate to develop new drugs against osteoporosis.


Assuntos
Flavanonas/farmacologia , Flavanonas/uso terapêutico , Glucocorticoides/efeitos adversos , Osteoclastos/efeitos dos fármacos , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Animais , Modelos Animais de Doenças , Osteogênese/efeitos dos fármacos , Estimulação Química , Peixe-Zebra
17.
Medicine (Baltimore) ; 99(22): e20121, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32481378

RESUMO

INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of azithromycin (AZI) combined with glucocorticoid (GC) in the treatment of children with refractory Mycoplasma pneumoniae. METHODS: Computer search for PubMed, EMbase, Cochrane Library, China Biomedical Literature Database (CBMdisc), China Knowledge Network (CNKI), Wanfang, VIP (VIP), and a randomized controlled trial (RCT) of AZI combined with GC in the treatment of children with refractory Mycoplasma pneumoniae pneumonia test (RCT), the search time limit is built until March 20, 2019. Two researchers independently performed literature screening, data extraction, and literature risk bias, and meta-analysis was performed using RevMan 5.3 software. RESULTS: A total of 12 RCTs were included, including 1130 patients. Meta-analysis showed that AZI combined with GC therapy significantly improved the total effective rate of the disease compared with the conventional treatment group (odds ratio [OR] = 6.37; 95% confidence interval [CI] 4.03, 10.07; P < .00001; I = 0%), effectively shortened the antipyretic time (SMD = -2.29; 95% CI -2.70, -1.88; P < .0001); promoted lung inflammation absorption (SMD = -1.89; 95% CI -2.38, -1.40; P < .0001), reduced cough time (SMD = -2.39; 95% CI -2.80, -1.99; P < .0001); shortened hospital stay (SMD = -2.19; 95% CI -3.21, -1.17; P < .0001); improved imaging findings (OR = 5.38; 95% CI 1.09, 26.51, P = .04); reduced inflammation index (SMD = -3.15; 95% CI -4.93, -1.36; P = .004); improved immune function (SMD = 1.29; 95% CI -0.02, 2.60; P < .0001); had no significant adverse reactions (OR = 1.18; 95% CI 0.71, 1.98; P = .53). CONCLUSIONS: According to the current limited research evidence, the addition of GCs to the conventional treatment of refractory Mycoplasma pneumoniae in children can improve the clinical efficacy to a certain extent, and the safety is better. However, due to the quality and quantity of the included literature, the conclusions of this study need to be confirmed by more high-quality studies.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Glucocorticoides/uso terapêutico , Mycoplasma pneumoniae , Pneumonia por Mycoplasma/tratamento farmacológico , Antibacterianos/efeitos adversos , Azitromicina/efeitos adversos , Criança , Tosse/tratamento farmacológico , Tosse/microbiologia , Quimioterapia Combinada , Febre/tratamento farmacológico , Febre/microbiologia , Glucocorticoides/efeitos adversos , Humanos , Tempo de Internação , Pneumonia por Mycoplasma/complicações , Pneumonia por Mycoplasma/diagnóstico por imagem
19.
J Allergy Clin Immunol ; 146(2): 300-306, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32561389

RESUMO

The coronavirus disease 2019 (COVID-19) (caused by severe acute respiratory syndrome coronavirus 2) pandemic has massively distorted our health care systems and caused catastrophic consequences in our affected communities. The number of victims continues to increase, and patients at risk can only be protected to a degree, because the virulent state may be asymptomatic. Risk factors concerning COVID-19-induced morbidity and mortality include advanced age, an impaired immune system, cardiovascular or pulmonary diseases, obesity, diabetes mellitus, and cancer treated with chemotherapy. Here, we discuss the risk and impact of COVID-19 in patients with mastocytosis and mast cell activation syndromes. Because no published data are yet available, expert opinions are, by necessity, based on case experience and reports from patients. Although the overall risk to acquire the severe acute respiratory syndrome coronavirus 2 may not be elevated in mast cell disease, certain conditions may increase the risk of infected patients to develop severe COVID-19. These factors include certain comorbidities, mast cell activation-related events affecting the cardiovascular or bronchopulmonary system, and chemotherapy or immunosuppressive drugs. Therefore, such treatments should be carefully evaluated on a case-by-case basis during a COVID-19 infection. In contrast, other therapies, such as anti-mediator-type drugs, venom immunotherapy, or vitamin D, should be continued. Overall, patients with mast cell disorders should follow the general and local guidelines in the COVID-19 pandemic and advice from their medical provider.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Gerenciamento Clínico , Mastocitose Cutânea/tratamento farmacológico , Mastocitose Sistêmica/tratamento farmacológico , Pandemias , Pneumonia Viral/epidemiologia , Betacoronavirus/imunologia , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/patologia , Difosfonatos/uso terapêutico , Prova Pericial , Glucocorticoides/efeitos adversos , Antagonistas dos Receptores Histamínicos/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Mastócitos/efeitos dos fármacos , Mastócitos/imunologia , Mastócitos/patologia , Mastocitose Cutânea/diagnóstico , Mastocitose Cutânea/epidemiologia , Mastocitose Cutânea/patologia , Mastocitose Sistêmica/diagnóstico , Mastocitose Sistêmica/epidemiologia , Mastocitose Sistêmica/patologia , Agonistas Mieloablativos/efeitos adversos , Pneumonia Viral/diagnóstico , Pneumonia Viral/patologia , Medicina de Precisão/métodos , Fatores de Risco , Vitamina D/uso terapêutico
20.
Int J Nanomedicine ; 15: 3605-3620, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32547017

RESUMO

Purpose: Osteonecrosis of the femoral head (ONFH) is a chronic and irreversible disease that eventually develops into a joint collapse and results in joint dysfunction. Early intervention and treatment are essential for preserving the joints and avoiding hip replacement. In this study, a system of human umbilical mesenchymal stem cells-supermagnetic iron oxide nanoparticles (NPs) @polydopamine (SCIOPs) was constructed. The magnetic targeting system gathers in the lesion area, inhibits the apoptosis of bone cells, enhances osteogenic effect, and effectively treats ONFH under external magnetic field. Materials and Methods: The supermagnetic iron oxide NPs @polydopamine (SPION@PDA NPs) were characterized by transmission electron microscopy and zeta potential, respectively. The effects of SPION@PDA NPs on the viability, proliferation, and differentiation of stem cells were detected by the CCK8 method, flow cytometry, and staining, respectively. The serum inflammatory indicators were detected by Luminex method. The bone mass of the femoral head was analyzed by micro computed tomography. The expression of apoptosis and osteoblast-related cytokines was detected by Western blotting. The osteogenesis of the femoral head was detected by histological and immunohistochemical sections. Results: The SCIOPs decreased the pro-inflammatory factors, and the micro CT showed that the bone repair of the femoral head was enhanced after treatment. The hematoxylin and eosin sections also showed an increase in the osteogenesis in the femoral head. Western blotting results showed and increased expression of anti-apoptotic proteins Akt and Bcl-2, decreased expression of apoptotic proteins caspase-3 and Bad, and increased expression of osteogenic proteins Runx-2 and Osterix in the femoral head. Conclusion: Under the effect of magnetic field and homing ability of stem cells, SCIOPs inhibited the apoptosis of osteoblasts, improved the proliferation ability of osteoblasts, and promoted bone repair in the femoral head through the Akt/Bcl-2/Bad/caspase-3 signaling pathway, thereby optimizing the tissue repair ability.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/terapia , Glucocorticoides/efeitos adversos , Fenômenos Magnéticos , Nanopartículas de Magnetita/química , Células-Tronco Mesenquimais/citologia , Transdução de Sinais , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Feminino , Hemólise/efeitos dos fármacos , Humanos , Indóis/química , Nanopartículas de Magnetita/toxicidade , Nanopartículas de Magnetita/ultraestrutura , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteogênese/efeitos dos fármacos , Polímeros/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Microtomografia por Raio-X , Proteína de Morte Celular Associada a bcl/metabolismo
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