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1.
Medicine (Baltimore) ; 100(35): e27067, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34477139

RESUMO

BACKGROUND: There is no clear information on the efficacy of corticosteroids, and splints in the treatment of patients with diabetes mellitus (DM). The aim of this study was to compare the outcomes of isolated corticosteroid injection therapy with splint treatment with corticosteroid injection in patients with and without DM. METHODS: 84 diabetics, and 84 healthy patients with a diagnosis of de Quervain's tenosynovitis were included in our study. The patients were randomly distributed into four subgroups with and without DM. Groups 1 and group 2 consisted of diabetic patients, while group 3 and group 4 consisted of healthy patients. Corticosteroid injections were administered to groups 1 and 3, and corticosteroid injection and splint treatment were administered to groups 2 and 4. RESULTS: There was no significant difference in terms of age, gender, dominant/non-dominant hand, pre-treatment Quick Disabilities of the Arm, Shoulder and Hand score and visual analog scale scores score between the four groups. Quick Disabilities of the Arm, Shoulder and Hand and visual analog scale scores in the four groups were found to be significantly better than pre-treatment at the 12th month. Finkelstein test results were positive in 37.5% of the patients in the first group, 35% of the patients in the second group, 20% of the patients in the third group and 9.5% of the patients in the fourth group. Groups 1 and 2 and, groups 3 and 4 were compared to evaluate the effect of the splint. While forearm-based thumb splint affected the results positively in healthy individuals, it was determined that it had no effect on the results in diabetic patients. CONCLUSION: Although corticosteroid treatment is effective in the treatment of de Quervain's tenosynovitis in healthy and diabetic individuals, the results are worse in diabetic patients than in healthy patients. In addition, the use of splint with corticosteroid injection in healthy individuals positively affects the results, while it does not affect the results in diabetic patients.


Assuntos
Corticosteroides/farmacologia , Doença de De Quervain/tratamento farmacológico , Contenções/normas , Tenossinovite/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Idoso , Análise de Variância , Doença de De Quervain/complicações , Doença de De Quervain/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Contenções/estatística & dados numéricos , Estatísticas não Paramétricas , Tenossinovite/complicações , Tenossinovite/fisiopatologia
2.
Viruses ; 13(7)2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34372616

RESUMO

Treatment options for COVID-19, a disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, are currently severely limited. Therefore, antiviral drugs that efficiently reduce SARS-CoV-2 replication or alleviate COVID-19 symptoms are urgently needed. Inhaled glucocorticoids are currently being discussed in the context of treatment for COVID-19, partly based on a previous study that reported reduced recovery times in cases of mild COVID-19 after inhalative administration of the glucocorticoid budesonide. Given various reports that describe the potential antiviral activity of glucocorticoids against respiratory viruses, we aimed to analyze a potential antiviral activity of budesonide against SARS-CoV-2 and circulating variants of concern (VOC) B.1.1.7 (alpha) and B.1.351 (beta). We demonstrate a dose-dependent inhibition of SARS-CoV-2 that was comparable between all viral variants tested while cell viability remains unaffected. Our results are encouraging as they could indicate a multimodal mode of action of budesonide against SARS-CoV-2 and COVID-19, which could contribute to an improved clinical performance.


Assuntos
Antivirais/farmacologia , Budesonida/farmacologia , COVID-19/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Corticosteroides/farmacologia , Animais , Antivirais/administração & dosagem , Budesonida/administração & dosagem , COVID-19/virologia , Chlorocebus aethiops , Glucocorticoides/farmacologia , Humanos , Células Vero , Replicação Viral/efeitos dos fármacos
3.
Theranostics ; 11(16): 7797-7812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335965

RESUMO

Rationale: Corticosteroid resistance (CR) is a serious drawback to steroid therapy in patients with ulcerative colitis (UC); the underlying mechanism is incompletely understood. Twist1 protein (TW1) is an apoptosis inhibitor and has immune regulatory functions. This study aims to elucidate the roles of TW1 in inducing and sustaining the CR status in UC. Methods: Surgically removed colon tissues of patients with ulcerative colitis (UC) were collected, from which neutrophils were isolated by flow cytometry. The inflammation-related gene activities in neutrophils were analyzed by RNA sequencing. A CR colitis mouse model was developed with the dextran sulfate sodium approach in a hypoxia environment. Results: Higher TW1 gene expression was detected in neutrophils isolated from the colon tissues of UC patients with CR and the CR mouse colon tissues. TW1 physically interacted with glucocorticoid receptor (GR)α in CR neutrophils that prevented GRα from interacting with steroids; which consequently abrogated the effects of steroids on regulating the cellular activities of neutrophils. STAT3 (Signal Transducer and Activator of Transcription-3) interacted with Ras protein activator like 1 to sustain the high TW1 expression in colon mucosal neutrophils of CR patients and CR mice. Inhibition of TW1 restored the sensitivity to corticosteroid of neutrophils in the colon tissues of a CR murine model. Conclusions: UC patients at CR status showed high TW1 expression in neutrophils. TW1 prevented steroids from regulating neutrophil activities. Inhibition of TW1 restored the sensitivity to corticosteroids in the colon tissues at the CR status.


Assuntos
Colite Ulcerativa/metabolismo , Resistência a Medicamentos/genética , Proteínas Nucleares/metabolismo , Proteína 1 Relacionada a Twist/metabolismo , Corticosteroides/farmacologia , Adulto , Animais , China , Colite , Colite Ulcerativa/genética , Colo/metabolismo , Dexametasona/farmacologia , Modelos Animais de Doenças , Feminino , Humanos , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Neutrófilos/metabolismo , Proteínas Nucleares/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína 1 Relacionada a Twist/genética
4.
Int J Mol Sci ; 22(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34299024

RESUMO

Temporomandibular joint osteoarthritis (TMJ OA) is a low-inflammatory disorder with multifactorial etiology. The aim of this review was to present the current state of knowledge regarding the mechanisms of action and the efficacy of hyaluronic acid (HA), corticosteroids (CS) and platelet-rich plasma (PRP) in the treatment of TMJ OA.: The PubMed database was analyzed with the keywords: "(temporomandibular joint) AND ((osteoarthritis) OR (dysfunction) OR (disorders) OR (pain)) AND ((treatment) OR (arthrocentesis) OR (arthroscopy) OR (injection)) AND ((hyaluronic acid) OR (corticosteroid) OR (platelet rich plasma))". After screening of 363 results, 16 studies were included in this review. Arthrocentesis alone effectively reduces pain and improves jaw function in patients diagnosed with TMJ OA. Additional injections of HA, either low-molecular-weight (LMW) HA or high-molecular-weight (HMW) HA, or CS at the end of the arthrocentesis do not improve the final clinical outcomes. CS present several negative effects on the articular cartilage. Results related to additional PRP injections are not consistent and are rather questionable. Further studies should be multicenter, based on a larger group of patients and should answer the question of whether other methods of TMJ OA treatment are more beneficial for the patients than simple arthrocentesis.


Assuntos
Corticosteroides/uso terapêutico , Ácido Hialurônico/uso terapêutico , Osteoartrite/tratamento farmacológico , Plasma Rico em Plaquetas/metabolismo , Transtornos da Articulação Temporomandibular/tratamento farmacológico , Adolescente , Corticosteroides/farmacologia , Adulto , Humanos , Ácido Hialurônico/farmacologia , Injeções Intra-Articulares , Osteoartrite/fisiopatologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Transtornos da Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/fisiopatologia
5.
Ann Hematol ; 100(10): 2453-2462, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34269838

RESUMO

BACKGROUND: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by decreased platelet count. While corticosteroids are a useful first-line therapy for ITP patients, their long-term effectiveness is limited, and the determinants of corticosteroid sensitivity in ITP patients remain largely unknown. Sirtuin 1 (SIRT1), a member of the mammalian sirtuin family, is related to the anti-inflammatory effects of corticosteroids. Here, we investigate the contribution of the SIRT1 single-nucleotide polymorphisms (SNPs) rs12778366 and rs4746720 to ITP susceptibility. METHODS: We recruited 330 ITP patients and 309 healthy controls from Han population, and performed genotyping of SIRT1 rs12778366 and rs4746720 using a MassARRAY system. The results were validated in another 55 ITP patients from ethnic minorities. RESULTS: Using clinical data of patients and controls from Han polulation, including corticosteroid sensitivity, susceptibility, refractoriness, and severity, our results revealed that the CC/TC genotypes of SIRT1 rs12778366 were associated with a 2.034-fold increased risk of corticosteroid resistance compared to the homozygous major TT genotype (dominant, CC/TC vs. TT, OR = 2.034, 95% CI = 1.039-3.984, p = 0.038). In contrast, the CC/CT genotype of SIRT1 rs4746720 showed a 0.560-fold decreased risk of corticosteroid resistance (dominant, 95% CI = 0.321-0.976, OR = 0.560, p = 0.041). The C allele substitute in SIRT1 rs12778366 was significantly associated with the corticosteroid sensitivity of ITP patients (p = 0.021). The similar results were obtained in minority ITP patients. CONCLUSION: This study indicates that SIRT1 rs12778366 and rs4746720 may be genetic factors related to corticosteroid sensitivity in ITP patients.


Assuntos
Corticosteroides/uso terapêutico , Polimorfismo de Nucleotídeo Único , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Sirtuína 1/genética , Corticosteroides/farmacologia , Adulto , Resistência a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/efeitos dos fármacos , Púrpura Trombocitopênica Idiopática/genética , Resultado do Tratamento
6.
Mycoses ; 64(8): 817-822, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34091966

RESUMO

OBJECTIVES: To investigate the occurrence of Trichosporon asahii fungemia among critically ill COVID-19 patients. METHODS: From 1 July to 30 September 2020, cases of T asahii fungemia (TAF) in a Brazilian COVID-19 referral centre were investigated. The epidemiology and clinical courses were detailed, along with a mycological investigation that included molecular species identification, haplotype diversity analysis and antifungal susceptibility testing. RESULTS: Five critically ill COVID-19 patients developed TAF in the period. All five patients had common risk conditions for TAF: central venous catheter at fungemia, previous exposure to broad-spectrum antibiotics, prior echinocandin therapy and previous prolonged corticosteroid therapy. The average time of intensive care unit hospitalisation previous to the TAF episode was 23 days. All but one patient had voriconazole therapy, and TAF 30-day mortality was 80%. The five T asahii strains from the COVID-19 patients belonged to 4 different haplotypes, mitigating the possibility of skin origin and cross-transmission linking the 5 reported episodes. The antifungal susceptibility testing revealed low minimal inhibitory concentrations for azole derivatives. CONCLUSIONS: Judicious prescription of antibiotics, corticosteroids and antifungals needs to be discussed in critically ill COVID-19 patients to prevent infections by hard-to-treat fungi like T asahii.


Assuntos
Corticosteroides/administração & dosagem , Antifúngicos/administração & dosagem , Basidiomycota/isolamento & purificação , COVID-19/complicações , Superinfecção/complicações , Tricosporonose/complicações , Corticosteroides/farmacologia , Idoso , Antifúngicos/farmacologia , Basidiomycota/classificação , Basidiomycota/efeitos dos fármacos , Basidiomycota/genética , Brasil/epidemiologia , COVID-19/epidemiologia , Candidemia/complicações , Feminino , Fungemia/complicações , Haplótipos , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Filogenia , Fatores de Risco , Superinfecção/epidemiologia , Tricosporonose/epidemiologia
7.
J Infect Dis ; 224(6): 934-937, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34157110

RESUMO

Emerging data from open-label randomized trials without placebo controls suggest potential mortality benefits for combining corticosteroids with the interleukin 6 receptor antagonist tocilizumab in severe coronavirus disease 2019. Conversely, dual immunomodulation may weaken antiviral responses and delay viral clearance, allowing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to expand its population and accrue genetic diversity within individual hosts. Generating a pool of hosts with genetically diverse viral populations while introducing new selective pressures in the form of vaccination-induced immunity could accelerate the process of antigenic drift in SARS-CoV-2. However, clinical trials to date have largely disregarded viral outcomes, and data on viral kinetics in response to immunomodulation are scarce. Coadministration of antiviral agents with immunomodulation could serve as a potential strategy to aid viral clearance and reduce the risk of genetic diversification.


Assuntos
Anticorpos Monoclonais Humanizados/farmacologia , COVID-19/tratamento farmacológico , Dexametasona/farmacologia , SARS-CoV-2/efeitos dos fármacos , Corticosteroides/farmacologia , Antivirais/farmacologia , Combinação de Medicamentos , Humanos , Fatores Imunológicos
8.
BMC Cancer ; 21(1): 754, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187419

RESUMO

BACKGROUND: Corticosteroid therapy (CST) prior to biopsy may hinder histopathological diagnosis in primary central nervous system lymphoma (PCNSL). Therefore, preoperative CST in patients with suspected PCNSL should be avoided if clinically possible. The aim of this study was thus to analyze the difference in the rate of diagnostic surgeries in PCNSL patients with and without preoperative CST. METHODS: A multicenter retrospective study including all immunocompetent patients diagnosed with PCNSL between 1/2004 and 9/2018 at four neurosurgical centers in Austria was conducted and the results were compared to literature. RESULTS: A total of 143 patients were included in this study. All patients showed visible contrast enhancement on preoperative MRI. There was no statistically significant difference in the rate of diagnostic surgeries with and without preoperative CST with 97.1% (68/70) and 97.3% (71/73), respectively (p = 1.0). Tapering and pause of CST did not influence the diagnostic rate. Including our study, there are 788 PCNSL patients described in literature with an odds ratio for inconclusive surgeries after CST of 3.3 (CI 1.7-6.4). CONCLUSIONS: Preoperative CST should be avoided as it seems to diminish the diagnostic rate of biopsy in PCNSL patients. Yet, if CST has been administered preoperatively and there is still a contrast enhancing lesion to target for biopsy, surgeons should try to keep the diagnostic delay to a minimum as the likelihood for acquiring diagnostic tissue seems sufficiently high.


Assuntos
Corticosteroides/uso terapêutico , Corticosteroides/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Retrospectivos , Adulto Jovem
9.
PLoS One ; 16(6): e0252576, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34081722

RESUMO

Inhaled Corticosteroids (ICS) are commonly prescribed to patients with severe COPD and recurrent exacerbations. It is not known what impact ICS cause in terms of COVID-19 positivity or disease severity in COPD. This study examined 27,810 patients with COPD from the Cleveland Clinic COVID-19 registry between March 8th and September 16th, 2020. Electronic health records were used to determine diagnosis of COPD, ICS use, and clinical outcomes. Multivariate logistic regression was used to adjust for demographics, month of COVID-19 testing, and comorbidities known to be associated with increased risk for severe COVID-19 disease. Amongst the COPD patients who were tested for COVID-19, 44.1% of those taking an ICS-containing inhaler tested positive for COVID-19 versus 47.2% who tested negative for COVID-19 (p = 0.033). Of those who tested positive for COVID-19 (n = 1288), 371 (28.8%) required hospitalization. In-hospital outcomes were not significantly different when comparing ICS versus no ICS in terms of ICU admission (36.8% [74/201] vs 31.2% [53/170], p = 0.30), endotracheal intubation (21.9% [44/201] vs 16.5% [28/170], p = 0.24), or mortality (18.4% [37/201] vs 20.0% [34/170], p = 0.80). Multivariate logistic regression demonstrated no significant differences in hospitalization (adj OR 1.12, CI: 0.90-1.38), ICU admission (adj OR: 1.31, CI: 0.82-2.10), need for mechanical ventilation (adj OR 1.65, CI: 0.69-4.02), or mortality (OR: 0.80, CI: 0.43-1.49). In conclusion, ICS therapy did not increase COVID-19 related healthcare utilization or mortality outcome in patients with COPD followed at the Cleveland Clinic health system. These findings should encourage clinicians to continue ICS therapy for COPD patients during the COVID-19 pandemic.


Assuntos
Corticosteroides/uso terapêutico , COVID-19/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Administração por Inalação , Corticosteroides/administração & dosagem , Corticosteroides/farmacologia , Agonistas de Receptores Adrenérgicos beta 2/efeitos adversos , Adulto , Idoso , COVID-19/complicações , Teste para COVID-19 , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/uso terapêutico , Nebulizadores e Vaporizadores , Pandemias , Doença Pulmonar Obstrutiva Crônica/complicações , Sistema de Registros , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade
10.
Bull Cancer ; 108(6): 635-642, 2021 Jun.
Artigo em Francês | MEDLINE | ID: mdl-33888298

RESUMO

Immunotherapy, which consists in using molecules targeting the immune system, has existed for many years in oncology (vaccines, interleukins, monoclonal antibodies) but has recently expanded due to the development of immune checkpoint inhibitors. These monoclonal antibodies help to restore the immunity against cancer by specifically targeting some immune checkpoints such as CTLA-4, PD-1 and PD-L1. Furthermore, in oncology, it is common to use systemic corticosteroids in the management of symptoms linked to the natural history of the disease (pain, spinal cord compression, cerebral edema) and toxicities linked to anticancer treatment. The impact of corticosteroids on the efficacy of immune checkpoint inhibitors is still poorly understood and they should be used cautiously. According to previously published studies, there seems to be a deleterious effect of corticosteroid therapy on the efficacy of immune checkpoint inhibitors when administered before or at the initiation of immunotherapy, while this effect does not seem present when corticosteroids are administered to patients already undergoing immunotherapy. The aim of this work is to analyze the existing data evaluating the impact of corticosteroid use of on the efficacy of immune checkpoint inhibitors.


Assuntos
Corticosteroides/farmacologia , Antígeno B7-H1 , Antígeno CTLA-4 , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia Adotiva , Cromatina/efeitos dos fármacos , Interações Medicamentosas , Humanos , Transcrição Genética/efeitos dos fármacos , Resultado do Tratamento
11.
Int Forum Allergy Rhinol ; 11(7): 1041-1046, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33728824

RESUMO

The frequent association between coronavirus disease 2019 (COVID-19) and olfactory dysfunction is creating an unprecedented demand for a treatment of the olfactory loss. Systemic corticosteroids have been considered as a therapeutic option. However, based on current literature, we call for caution using these treatments in early COVID-19-related olfactory dysfunction because: (1) evidence supporting their usefulness is weak; (2) the rate of spontaneous recovery of COVID-19-related olfactory dysfunction is high; and (3) corticosteroids have well-known potential adverse effects. We encourage randomized placebo-controlled trials investigating the efficacy of systemic steroids in this indication and strongly emphasize to initially consider smell training, which is supported by a robust evidence base and has no known side effects.


Assuntos
Corticosteroides/farmacologia , COVID-19 , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Transtornos do Olfato , COVID-19/complicações , COVID-19/fisiopatologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Saúde Global , Humanos , Conduta do Tratamento Medicamentoso/normas , Determinação de Necessidades de Cuidados de Saúde , Transtornos do Olfato/tratamento farmacológico , Transtornos do Olfato/epidemiologia , Transtornos do Olfato/etiologia , Mucosa Olfatória/efeitos dos fármacos , Mucosa Olfatória/virologia , Remissão Espontânea , Projetos de Pesquisa , SARS-CoV-2/patogenicidade
13.
Thorax ; 76(4): 326-334, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33542087

RESUMO

BACKGROUND: Severe asthma is a chronic lung disease characterised by inflammation, airway hyperresponsiveness (AHR) and airway remodelling. The molecular mechanisms underlying uncontrolled airway smooth muscle cell (aSMC) proliferation involved in pulmonary remodelling are still largely unknown. Small G proteins of the Rho family (RhoA, Rac1 and Cdc42) are key regulators of smooth muscle functions and we recently demonstrated that Rac1 is activated in aSMC from allergic mice. The objective of this study was to assess the role of Rac1 in severe asthma-associated airway remodelling. METHODS AND RESULTS: Immunofluorescence analysis in human bronchial biopsies revealed an increased Rac1 activity in aSMC from patients with severe asthma compared with control subjects. Inhibition of Rac1 by EHT1864 showed that Rac1 signalling controlled human aSMC proliferation induced by mitogenic stimuli through the signal transducer and activator of transcription 3 (STAT3) signalling pathway. In vivo, specific deletion of Rac1 in SMC or pharmacological inhibition of Rac1 by nebulisation of NSC23766 prevented AHR and aSMC hyperplasia in a mouse model of severe asthma. Moreover, the Rac1 inhibitor prevented goblet cell hyperplasia and epithelial cell hypertrophy whereas treatment with corticosteroids had less effect. Nebulisation of NSC23766 also decreased eosinophil accumulation in the bronchoalveolar lavage of asthmatic mice. CONCLUSION: This study demonstrates that Rac1 is overactive in the airways of patients with severe asthma and is essential for aSMC proliferation. It also provides evidence that Rac1 is causally involved in AHR and airway remodelling. Rac1 may represent as an interesting target for treating both AHR and airway remodelling of patients with severe asthma.


Assuntos
Remodelação das Vias Aéreas , Asma/metabolismo , Miócitos de Músculo Liso/metabolismo , Hipersensibilidade Respiratória , Proteínas rac1 de Ligação ao GTP/metabolismo , Corticosteroides/farmacologia , Aminoquinolinas/administração & dosagem , Aminoquinolinas/farmacologia , Animais , Biópsia , Líquido da Lavagem Broncoalveolar/citologia , Estudos de Casos e Controles , Proliferação de Células , Modelos Animais de Doenças , Eosinófilos/metabolismo , Células Caliciformes/metabolismo , Humanos , Camundongos , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
14.
Transplantation ; 105(6): 1143-1155, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33534529

RESUMO

We discuss what therapeutic regimen might be acceptable/successful in the first clinical trial of genetically engineered pig kidney or heart transplantation. As regimens based on a calcineurin inhibitor or CTLA4-Ig have proved unsuccessful, the regimen we administer to baboons is based on induction therapy with antithymocyte globulin, an anti-CD20 mAb (Rituximab), and cobra venom factor, with maintenance therapy based on blockade of the CD40/CD154 costimulation pathway (with an anti-CD40 mAb), with rapamycin, and a corticosteroid. An anti-inflammatory agent (etanercept) is administered for the first 2 wk, and adjuvant therapy includes prophylaxis against thrombotic complications, anemia, cytomegalovirus, and pneumocystis. Using this regimen, although antibody-mediated rejection certainly can occur, we have documented no definite evidence of an adaptive immune response to the pig xenograft. This regimen could also form the basis for the first clinical trial, except that cobra venom factor will be replaced by a clinically approved agent, for example, a C1-esterase inhibitor. However, none of the agents that block the CD40/CD154 pathway are yet approved for clinical use, and so this hurdle remains to be overcome. The role of anti-inflammatory agents remains unproven. The major difference between this suggested regimen and those used in allotransplantation is the replacement of a calcineurin inhibitor with a costimulation blockade agent, but this does not appear to increase the complications of the regimen.


Assuntos
Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Histocompatibilidade , Imunossupressores/farmacologia , Transplante Heterólogo , Corticosteroides/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Anticorpos Heterófilos/metabolismo , Soro Antilinfocitário/farmacologia , Antígenos CD40/antagonistas & inibidores , Antígenos CD40/imunologia , Antígenos CD40/metabolismo , Quimioterapia Combinada , Venenos Elapídicos/farmacologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Xenoenxertos , Humanos , Imunossupressores/toxicidade , Papio , Medição de Risco , Fatores de Risco , Rituximab/farmacologia , Sirolimo/farmacologia , Sus scrofa , Transplante Heterólogo/efeitos adversos
15.
Infect Immun ; 89(9): e0066520, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-33526567

RESUMO

Immunotherapy has become a new paradigm in oncology, improving outcomes for several types of cancer. However, there are some aspects about its management that remain uncertain. One of the key points that needs better understanding is the interaction between immunotherapy and gut microbiome and how modulation of the microbiome might modify the efficacy of immunotherapy. Consequently, the negative impact of systemic antibiotics and corticosteroids on the efficacy of immunotherapy needs to be clarified.


Assuntos
Corticosteroides/farmacologia , Antibacterianos/farmacologia , Interações entre Hospedeiro e Microrganismos , Inibidores de Checkpoint Imunológico/uso terapêutico , Microbiota , Neoplasias/tratamento farmacológico , Probióticos , Corticosteroides/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunomodulação/efeitos dos fármacos , Interações Microbianas/efeitos dos fármacos , Interações Microbianas/imunologia , Microbiota/efeitos dos fármacos , Neoplasias/etiologia , Resultado do Tratamento
16.
Food Chem Toxicol ; 150: 112087, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33640537

RESUMO

Coronavirus disease-19 (COVID-19) is a complex disease that causes illness ranging from mild to severe respiratory problems. It is caused by a novel coronavirus SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) that is an enveloped positive-sense single-stranded RNA (+ssRNA) virus belongs to coronavirus CoV family. It has a fast-spreading potential worldwide, which leads to high mortality regardless of lows death rates. Now some vaccines or a specific drug are approved but not available for every country for disease prevention and/or treatment. Therefore, it is a high demand to identify the known drugs and test them as a possible therapeutic approach. In this critical situation, one or more of these drugs may represent the only option to treat or reduce the severity of the disease, until some specific drugs or vaccines will be developed and/or approved for everyone in this pandemic. In this updated review, the available repurpose immunotherapeutic treatment strategies are highlighted, elucidating the crosstalk between the immune system and SARS-CoV-2. Despite the reasonable data availability, the effectiveness and safety of these drugs against SARS-CoV-2 needs further studies and validations aiming for a better clinical outcome.


Assuntos
Antivirais/farmacologia , Inflamação/etiologia , SARS-CoV-2/efeitos dos fármacos , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/imunologia , COVID-19/virologia , Citocinas/metabolismo , Humanos , Inflamação/tratamento farmacológico , Inflamação/imunologia , Interferons/farmacologia , Interferons/uso terapêutico , Inibidores de Janus Quinases/farmacologia , Inibidores de Janus Quinases/uso terapêutico , SARS-CoV-2/imunologia
17.
Sci Rep ; 11(1): 747, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436915

RESUMO

To evaluate the effect of postoperative corticosteroids on surgical outcome and autotaxin (ATX) levels after microhook ab interno trabeculotomy combined with cataract surgery (µLOT-CS), prospective, consecutive non-randomized case series comparing outcomes of 30 eyes with primary open angle glaucoma was performed. The aqueous ATX, intraocular pressure (IOP) and glaucoma medications were monitored for 3 months postoperatively. An in-vivo mouse µLOT model was generated. In vitro, ATX and fibrotic changes induced by dexamethasone (Dex) treatment following scratch (S) in cultured human trabecular meshwork (hTM) cells were assessed by immunofluorescence, immunoenzymatic assay, and RT-qPCR. Postoperative ATX at 1 week and the number of antiglaucoma medications at 3 months were significantly lower in non-steroid group, and steroid use was the only variable significantly associated with postoperative medications at 3 months in multiregression analyses. In vitro, ATX activity was significantly upregulated in the Dex + S group, and αSMA was significantly upregulated in the Dex and Dex + S groups. Fibronectin and COL1A1 were significantly upregulated in the S group. µLOT-CS decreased IOP and medications in the overall cohort, and non-use of postoperative steroids resulted in a smaller number of postoperative medications. Limiting postoperative steroids in µLOT may minimize IOP elevation and postoperative fibrosis.


Assuntos
Corticosteroides/farmacologia , Catarata/terapia , Glaucoma de Ângulo Aberto/cirurgia , Diester Fosfórico Hidrolases/metabolismo , Malha Trabecular/efeitos dos fármacos , Trabeculectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Estresse Mecânico , Resultado do Tratamento
19.
Sci Rep ; 11(1): 1015, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441909

RESUMO

Since the start of the novel coronavirus 2019 (COVID-19) pandemic, corticosteroid use has been the subject of debate. The available evidence is uncertain, and knowledge on the subject is evolving. The aim of our cohort study was to evaluate the association between corticosteroid therapy and hospital mortality, in patients hospitalized with COVID-19 after balancing for possible confounders. One thousand four hundred forty four patients were admitted to our hospital with a positive RT-PCR test for SARS-CoV-2, 559 patients (39%) were exposed to corticosteroids during hospital stay, 844 (61%) were not exposed to corticosteroids. In the cohort of patients exposed to corticosteroids, 171 (30.6%) died. In the cohort of patients not exposed to corticosteroids, 183 (21.7%) died (unadjusted p < 0.001). Nonetheless, exposure to corticosteroids was not associated with in-hospital mortality after balancing with overlap weight propensity score (adjusted p = 0.25). Patients in the corticosteroids cohort had a reduced risk of ICU admission (adjusted p < 0.001). Treatment with corticosteroids did not affect hospital mortality in patients with COVID-19 after balancing for confounders. A possible advantage of corticosteroid therapy was to reduce Intensive Care Unit admission, which could be useful in reducing pressure on Intensive Care Units in times of limited resources, as during the COVID-19 pandemic.


Assuntos
Corticosteroides/farmacologia , COVID-19/tratamento farmacológico , COVID-19/mortalidade , Mortalidade Hospitalar , Corticosteroides/uso terapêutico , Idoso , Estudos de Coortes , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Resultado do Tratamento
20.
Am J Hematol ; 96(3): 367-378, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33393136

RESUMO

The introduction of novel agents over the last decade has rapidly expanded the therapeutic landscape of multiple myeloma (MM) for both transplant-eligible and transplant-ineligible patients. The assessment of minimal residual disease (MRD) by next-generation flow cytometry or next-generation sequencing is established as a powerful predictor of long-term outcomes. The use of MRD in response-adapted clinical trials may provide opportunities to identify candidates for treatment escalation and de-escalation. Agents with proven activity in the relapsed and refractory setting are being studied in the management of high-risk newly diagnosed MM (NDMM). Here, we summarize the most recent clinical trials that have led to the current paradigms in the management of NDMM. We also discuss how novel agents could be incorporated in the newly diagnosed setting and potential clinical trial designs that could leverage MRD information with the goal of treatment optimization.


Assuntos
Mieloma Múltiplo/terapia , Terapias em Estudo , Corticosteroides/administração & dosagem , Corticosteroides/farmacologia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Bortezomib/administração & dosagem , Bortezomib/farmacologia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Gerenciamento Clínico , Drogas em Investigação/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Humanos , Fatores Imunológicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Neoplasia Residual , Oligopeptídeos/administração & dosagem , Oligopeptídeos/farmacologia , Inibidores de Proteases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Talidomida/administração & dosagem , Talidomida/farmacologia
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