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1.
Ren Fail ; 43(1): 335-339, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33567947

RESUMO

The introduction of Bruton's tyrosine kinase inhibitor ibrutinib has made a significant progress in the treatment of chronic lymphocytic leukemia and other B-cell malignancies. Due to the reduction of cytokine release, it is effective in chronic graft-versus-host disease, and its use has also been suggested in autoimmune diseases and in prevention of COVID-19-associated lung damage. Despite this effect on the immune response, we report a severe hypersensitivity reaction in a 76-year-old male patient diagnosed with prolymphocytic leukemia. Four weeks after the ibrutinib start, non-oliguric acute kidney injury with proteinuria and microscopic hematuria developed and that was accompanied by lower limb purpuras and paresthesia. Renal biopsy revealed acute interstitial nephritis. Employing 1 mg/kg methylprednisolone administration, serum creatinine decreased from 365 µmol/L to 125 µmol/L at 11 days and the proteinuria-hematuria as well as the purpura, paresthesia resolved. Three months later at stabile eGFR of 56 ml/min/1.73 m2 methylprednisolone was withdrawn and a rituximab-venetoclax treatment was initiated without side effects. We conclude that despite the beneficial effect on cytokines response in Th1 direction, ibrutinib can cause acute interstitial nephritis. Early detection, discontinuation of ibrutinib, glucocorticoid administration may help to better preserve renal function, thereby lowering the risk of potential subsequent kidney injury.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Adenina/análogos & derivados , Nefrite Intersticial/induzido quimicamente , Piperidinas/efeitos adversos , Proteinúria/induzido quimicamente , Lesão Renal Aguda/tratamento farmacológico , Adenina/efeitos adversos , Idoso , Citocinas/efeitos dos fármacos , Glucocorticoides/uso terapêutico , Humanos , Rim/patologia , Leucemia Prolinfocítica/tratamento farmacológico , Masculino , Nefrite Intersticial/tratamento farmacológico , Inibidores de Proteínas Quinases , Proteinúria/tratamento farmacológico
2.
Methods Mol Biol ; 2201: 199-207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32975801

RESUMO

The discovery of opioid receptor expression on immune cells has originated a large research activity on the possible modulation by opioid drugs of immune system responses. In this chapter we describe an easy methodology useful to obtain information about the potential immunomodulatory activity of opioid drugs. An in vivo treatment schedule is used, and macrophages are studied for their ability to release different cytokines.


Assuntos
Citocinas/análise , Macrófagos/efeitos dos fármacos , Cultura Primária de Células/métodos , Analgésicos Opioides/imunologia , Analgésicos Opioides/farmacologia , Animais , Citocinas/efeitos dos fármacos , Fenômenos do Sistema Imunológico , Fatores Imunológicos/análise , Fatores Imunológicos/farmacologia , Imunomodulação/efeitos dos fármacos , Imunomodulação/imunologia , Macrófagos/metabolismo , Camundongos , Morfina/efeitos adversos , Morfina/metabolismo , Morfina/farmacologia , Receptores Opioides/imunologia
3.
Intern Med ; 60(3): 457-461, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33328409

RESUMO

We herein report a case of severe coronavirus disease 2019 (COVID-19) in which high-dose intravenous immunoglobulin (IVIg) treatment achieved significant clinical improvement of deterioration of pulmonary inflammation after temporary clinical improvement. In the present case, clinical and radiological deterioration occurred despite a decrease in viral load, suggesting that deterioration was caused by reactivation of proinflammatory factors, such as tumor necrosis factor-α and interleukin-6, rather than direct viral effects. IVIg treatment may provide not only immunosuppressive effects but also inhibition of proinflammatory cytokines, indicating that treatment including IVIg may be effective by inhibiting cytokine storm in severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.


Assuntos
/terapia , Imunoglobulinas Intravenosas/administração & dosagem , Insuficiência Respiratória/terapia , /isolamento & purificação , /complicações , Síndrome da Liberação de Citocina/prevenção & controle , Citocinas/efeitos dos fármacos , Humanos , Ivermectina/uso terapêutico , Pulmão/diagnóstico por imagem , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Carga Viral
5.
PLoS One ; 15(9): e0238918, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32970698

RESUMO

Inflammatory bowel disease (IBD) is a disease that causes inflammation throughout the digestive tract. Repeated inflammation and frequent relapses cause intestinal damage and expose the patient to a higher risk. In this work, we proposed an immune therapy model for effective treatment strategy through mathematical modeling for patients with IBD. We evaluated the ability of the patient's immune system to recover during treatment. For this, we defined the interval of healthy individual, and examined the frequency of compartments such as T cells and cytokines considered in the model maintain the normal state. Based on the fact that each patient has a unique immune system, we have shown at the same drug works differently, depending on the individual immune system characteristics for every patient. It is known that IBD is related to an imbalance between pro- and anti- inflammatory cytokines as the cause of the disease. So the ratios of pro- to anti- inflammatory cytokines are used as an indicator of patient's condition and inflammation status in various diseases. We compared the ratios of pro- to anti- inflammatory cytokine according to patient's individual immune system and drugs. Since the effects of biological drugs are highly dependent on the patient's own immune system, it is essential to define the immune system status before selecting and using a biological drug.


Assuntos
Citocinas/metabolismo , Imunoterapia/métodos , Doenças Inflamatórias Intestinais/imunologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Citocinas/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Modelos Teóricos
6.
Crit Care Resusc ; 22(3): 227-236, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32900329

RESUMO

OBJECTIVE: The systemic inflammatory response syndrome (SIRS) is a dysregulated response that contributes to critical illness. Adjunctive acetylsalicylic acid (ASA) treatment may offer beneficial effects by increasing the synthesis of specialised proresolving mediators (a subset of polyunsaturated fatty acid-derived lipid mediators). DESIGN: Pilot, feasibility, multicentre, double-blind, randomised, placebo-controlled trial. SETTING: Four interdisciplinary intensive care units (ICUs) in Australia. PARTICIPANTS: Critically ill patients with SIRS. INTERVENTIONS: ASA 100 mg 12-hourly or placebo, administered within 24 hours of ICU admission and continued until ICU day 7, discharge or death, whichever came first. MAIN OUTCOME MEASURES: Interleukin-6 (IL-6) serum concentration at 48 hours after randomisation and, in a prespecified subgroup of patients, serum lipid mediator concentrations measured by mass spectrometry. RESULTS: The trial was discontinued in December 2017 due to slow recruitment and after the inclusion of 48 patients. Compared with placebo, ASA did not decrease IL-6 serum concentration at 48 hours. In the 32 patients with analysis of lipid mediators, low-dose ASA increased the concentration of 15-hydroxyeicosatetraenoic acid, a proresolving precursor of lipoxin A4, and reduced the concentration of the proinflammatory cytochrome P-dependent mediators 17-HETE (hydroxyeicosatetraenoic acid), 18-HETE and 20-HETE. In the eicosapentaenoic acid pathway, ASA significantly increased the concentration of the anti-inflammatory mediators 17,18-DiHETE (dihydroxyeicosatetraenoic acid) and 14,15-DiHETE. CONCLUSIONS: In ICU patients with SIRS, low-dose ASA did not significantly alter serum IL-6 concentrations, but it did affect plasma concentrations of certain lipid mediators. The ability to measure lipid mediators in clinical samples and to monitor the effect of ASA on their levels unlocks a potential area of biological investigation in critical care. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN 12614001165673).


Assuntos
Aspirina/administração & dosagem , Estado Terminal , Citocinas/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Síndrome de Resposta Inflamatória Sistêmica/tratamento farmacológico , Austrália , Método Duplo-Cego , Estudos de Viabilidade , Humanos , Interleucina-6/sangue , Lipídeos , Resultado do Tratamento
7.
Am J Trop Med Hyg ; 103(4): 1493-1495, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32748768

RESUMO

Mucosal leishmaniasis (ML) affects predominantly the nose and occurs usually weeks or months after the cure of the primary cutaneous lesion. The pathology of ML is characterized by an exaggerated inflammatory reaction with infiltration of lymphocytes, macrophages, and plasma cells. There is also a paucity of parasites and a strong delayed-type hypersensitivity reaction. Herein, we report a case of a young man who had a large ulcer in his left leg and complained of dysphagia. In nasofibrolaryngoscopy, there were nodular lesions in the oropharynx and rhinopharynx. The skin lesion biopsy showed a chronic inflammation with amastigotes inside macrophages, and DNA of Leishmania braziliensis confirmed the diagnosis of ML in tissue biopsied from the pharynx. The leishmaniasis skin test was negative. Cytokine evaluation showed lack of production of interferon (IFN)-γ, interleukin (IL)-1ß, and IL-17 with enhancement of these cytokine levels after cure.


Assuntos
Leishmania braziliensis/isolamento & purificação , Leishmaniose Mucocutânea , Antiprotozoários/uso terapêutico , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/etiologia , Humanos , Leishmania braziliensis/efeitos dos fármacos , Leishmaniose Mucocutânea/diagnóstico , Leishmaniose Mucocutânea/tratamento farmacológico , Leishmaniose Mucocutânea/patologia , Macrófagos/parasitologia , Masculino , Antimoniato de Meglumina/uso terapêutico , Pessoa de Meia-Idade , Nasofaringe/parasitologia , Nasofaringe/patologia , Orofaringe/parasitologia , Orofaringe/patologia , Pele/parasitologia , Pele/patologia
9.
Life Sci ; 257: 118058, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32653518

RESUMO

SARS-CoV-2 is a new member of coronaviruses that its sudden spreading put the health care system of most countries in a tremendous shock. For controlling of the new infection, COVID-19, many efforts have been done and are ongoing to defeat this virus in the combat field. In this review, we focused on how the immune system behaves toward the virus and the relative possible consequences during their interactions. Then the therapeutic steps and potential vaccine candidates have been described in a hope to provide a better prospective of effective treatment and preventive strategies to the novel SARS-CoV in near future.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Betacoronavirus/patogenicidade , Coronavirus/imunologia , Coronavirus/patogenicidade , Infecções por Coronavirus/patologia , Citocinas/efeitos dos fármacos , Citocinas/imunologia , Citocinas/metabolismo , Humanos , Pandemias , Pneumonia Viral/patologia , Vacinação/métodos
10.
Br J Anaesth ; 125(3): 267-274, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32660717

RESUMO

BACKGROUND: Anaesthetic agents are likely to alter circulating cytokine concentrations. Because preceding studies have not been able to exclude the contribution of surgical trauma, perioperative stress, or both to circulating cytokine concentrations, the effects of anaesthesia remain unclear. The aim of this study was to quantify serum cytokines in healthy volunteers administered i.v. anaesthetic agents in the absence of surgical trauma and perioperative stress. METHODS: Serum samples obtained during previous standardised studies from healthy volunteers were compared before and 6-8 h after induction of anaesthesia with propofol (n=31), propofol/remifentanil (n=30), dexmedetomidine (n=17) or dexmedetomidine/remifentanil (n=15). Anaesthetic regimens were standardised and volunteers did not undergo any surgical intervention. Serum concentrations of interleukin (IL)2, IL4, IL6, IL10, IL17, IL18, IL21, IL22, IL23, C-X-C motif ligand 8, interferon gamma, E-selectin, L-selectin, major histocompatibility complex class I chain-polypeptide-related sequence (MIC)A, MICB, Granzyme A, and Granzyme B were quantified using a multiplexed antibody-based assay (Luminex). RESULTS: Samples were obtained from volunteers of either sex aged 18-70 yr. After anaesthesia with propofol alone, concentrations of IL4 (P=0.012), IL6 (P=0.027), IL21 (P=0.035), IL22 (P=0.002), C-X-C motif ligand 8 (P=0.004), MICB (P=0.046), and Granzyme A (P=0.045) increased. After anaesthesia with propofol and remifentanil, IL17 (P=0.013), interferon gamma (P=0.003), and MICA (P=0.001) decreased, but IL6 (P=0.006) and L-selectin (P=0.001) increased. After dexmedetomidine alone, IL18 (P=0.002), L-selectin (P=0.017), E-selectin (P=0.002), and Granzyme B (P=0.023) decreased. After dexmedetomidine with remifentanil no changes were observed. CONCLUSIONS: In healthy volunteers not undergoing surgery, different i.v. anaesthesia regimens were associated with differential effects on circulating cytokines.


Assuntos
Citocinas/sangue , Citocinas/efeitos dos fármacos , Dexmedetomidina/farmacologia , Hipnóticos e Sedativos/farmacologia , Propofol/farmacologia , Remifentanil/farmacologia , Adolescente , Adulto , Idoso , Analgésicos Opioides/farmacologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Adulto Jovem
11.
Postgrad Med ; 132(7): 604-613, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32496926

RESUMO

Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading worldwide. Antiviral therapy is the most important treatment for COVID-19. Among the drugs under investigation, anti-malarials, chloroquine (CQ) and hydroxychloroquine (HCQ), are being repurposed as treatment for COVID-19. CQ/HCQ were shown to prevent receptor recognition by coronaviruses, inhibit endosome acidification, which interferes with membrane fusion, and exhibit immunomodulatory activity. These multiple mechanisms may work together to exert a therapeutic effect on COVID-19. A number of in vitro studies revealed inhibitory effects of CQ/HCQ on various coronaviruses, including SARS-CoV-2 although conflicting results exist. Several clinical studies showed that CQ/HCQ alone or in combination with a macrolide may alleviate the clinical symptoms of COVID-19, promote viral conversion, and delay disease progression, with less serious adverse effects. However, recent studies indicated that the use of CQ/HCQ, alone or in combination with a macrolide, did not show any favorable effect on patients with COVID-19. Adverse effects, including prolonged QT interval after taking CQ/HCQ, may develop in COVID-19 patients. Therefore, current data are not sufficient enough to support the use of CQ/HCQ as therapies for COVID-19 and increasing caution should be taken about the application of CQ/HCQ in COVID-19 before conclusive findings are obtained by well-designed, multi-center, randomized, controlled studies.


Assuntos
Antivirais/uso terapêutico , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antivirais/farmacologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/metabolismo , Cloroquina/farmacologia , Coronavirus Humano 229E/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Glicosilação , Humanos , Hidroxicloroquina/farmacologia , Imunidade Inata , Técnicas In Vitro , Síndrome do QT Longo/induzido quimicamente , Ativação Linfocitária/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Pandemias , Peptidil Dipeptidase A/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Espécies Reativas de Oxigênio , Vírus da SARS/efeitos dos fármacos , Transdução de Sinais , Linfócitos T , Receptores Toll-Like/efeitos dos fármacos , Receptores Toll-Like/metabolismo , Resultado do Tratamento , Internalização do Vírus/efeitos dos fármacos
13.
Sci Rep ; 10(1): 7727, 2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32382026

RESUMO

It is now accepted that red blood cells (RBCs) from healthy individuals regulate T-cell activity through modulating cytokine interactions, and that stored RBCs or RBCs from inflammatory cohorts are dysfunctional. Our study aimed to investigate how changes in RBCs that have been intentionally modified can affect T-cell activity as a mechanistic test of this modification. Exposure to a cancer cell line in culture was used to alter the cytokine profile of intact RBCs and the effect of these modified RBCs (ccRBCs) on T-cells was evaluated using flow cytometry. We used RBCs from healthy volunteers and quantified cytokines in RBC lysates and conditioned media using Luminex technology. During in vitro cancer cell exposure, RBCs sequestered a variety of cytokines including IL-8, bFGF, and VEGF. Although unmodified RBCs (oRBCs) stimulated proliferation of T-cells (Jurkat cells and peripheral blood mononucleated cells), ccRBCs augmented this proliferative response (3.5-fold and 1.9-fold more respectively). Unlike oRBCs, T-cells stimulated with ccRBCs were no longer protected from phytohemagglutinin-P-driven overexpression of GATA-3 and T-bet and these T-cells were induced to secrete a variety of cytokines including IL-17 and MCP-3. This study supports the hypothesis that RBCs are capable of binding and releasing cytokines in blood, and that modification of these cells can then also affect the T-cell response.


Assuntos
Proliferação de Células/genética , Citocinas/genética , Eritrócitos/metabolismo , Linfócitos T/imunologia , Comunicação Celular/genética , Proliferação de Células/efeitos dos fármacos , Citocinas/efeitos dos fármacos , Transfusão de Eritrócitos , Eritrócitos/imunologia , Citometria de Fluxo , Voluntários Saudáveis , Humanos , Células Jurkat , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/genética , Neoplasias/química , Neoplasias/patologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
14.
Medicine (Baltimore) ; 99(19): e20172, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384509

RESUMO

BACKGROUND: Chinese herbal bath has long been used in the curative treatment of psoriasis vulgaris. However, there is no unified standard protocol for Chinese herbal bath. Many factors affect the curative effect of Chinese herbal bath, such as water temperature, bath concentration, and soaking time. Most studies involving Chinese herbal bath has described the bath generally, and few studies have investigated the factors that might contribute to the efficacy of Chinese herbal bath. Here we describe a protocol to evaluate the efficacy and safety of various bathwater temperatures and herbal concentrations on psoriasis vulgaris, and their effect on serum vascular endothelial growth factor (VEGF), tumor necrosis factor α (TNF-α), interleukin 23 (IL-23), and interleukin 17 (IL-17). These data could be useful for optimizing Chinese herbal bath treatments. METHODS: In this randomized controlled trial, we planned to recruit 288 hospitalized atients with psoriasis vulgaris aged 18 to 65 years. All participants who meet the inclusion criteria will be randomly assigned to the observation group, the control group, or the basic treatment group. The observation group will be divided into 6 sub-groups according to water temperatures and bath concentrations, designated as observation groups 1 to 6. Thirty-six participants will be assigned to each group. The basic treatment group will be given co-qingdai capsule, po 2 g tid; compound glycyrrhizin tablet, po 75 mg tid; AA Skincare jojoba Oil, us.ext qd. The observation group will be given a Chinese herbal bath at the same time as the basic treatment. The control group will be given ozone hydrotherapy at the same time as the basic treatment. The entire treatment course will last for 2 weeks. The following parameters will be compared in each group, before and 2 weeks after treatment: the psoriasis area and severity index score (PASI), pruritus score, clinical efficacy, and dermatology life quality index score (DLQI); serum levels of serum VEGF, TNF-α, IL-23, and IL-17; and confocal laser scanning microscope images. CONCLUSION: This study will evaluate the efficacy and safety of various Chinese herbal bath conditions (water temperatures and herbal concentrations) on the treatment of psoriasis vulgaris, which will provide an important reference for the operation of Chinese herbal bath. TRIAL REGISTRATION NUMBER: ChiCTR1900027468.


Assuntos
Citocinas/efeitos dos fármacos , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Psoríase/terapia , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Adolescente , Adulto , Idoso , Terapia Combinada , Relação Dose-Resposta a Droga , Método Duplo-Cego , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Ácido Glicirrízico/uso terapêutico , Humanos , Masculino , Medicina Tradicional Chinesa/efeitos adversos , Pessoa de Meia-Idade , Temperatura , Fatores de Tempo , Adulto Jovem
16.
Medicine (Baltimore) ; 99(20): e20161, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443332

RESUMO

INTRODUCTION: Psoriasis vulgaris (PV) is a chronic, painful, disfiguring, and disabling dermatological disease, which affects the physical and mental health of patients and impacts their quality of life. Current conventional systemic therapies can be costly, present risks of side effects, have limited efficacy and commonly recur following treatment cessation. Some Chinese herbal medicine therapies have shown therapeutic benefits for psoriasis vulgaris, including relieving symptoms and improving quality of life, and a potential of reducing relapse rate. However, explicit evidence has not yet been obtained. METHODS AND ANALYSIS: This is a pilot randomized controlled trial with the objective of investigating the effect of Jia Wei Liang Xue Xiao Feng San granules on relapse rate of recurrent PV and the correlation between Psoriasis area severity index (PASI) and key psoriasis-related cytokine changes and the number of cells. A total of 102 participants were recruited for this study, including 72 patients with recurrent PV, 15 healthy volunteers and 15 patients with psoriasis vulgaris who have recovered for more than 1 year. A total of 72 patients, with recurrent PV, will be randomized (1:1) to receive the oral Chinese herbal medicine Jia Wei Liang Xue Xiao Feng San or the oral Acitretin Capsule treatments for a period of 8 weeks. After this period, participants whose PASI scores improvement reached more than 75%, will undergo a 52-week follow-up phase.The primary outcome measures are as follows:The secondary study outcomes will include:This trial may provide a novel regimen for recurrent PV patients if the granules decrease recurrence rate without further adverse effects. ETHICS AND DISSEMINATION: The ethics approval was provided by the Sichuan Traditional Chinese medicine regional ethics review committee. The ethics approval number is 2018KL-055. The design and the results of the study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR1900022766).


Assuntos
Exaustão por Calor/imunologia , Temperatura Alta/efeitos adversos , Imunidade Celular/efeitos dos fármacos , Psoríase/tratamento farmacológico , Linfócitos T Auxiliares-Indutores/imunologia , Acitretina/administração & dosagem , Acitretina/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Imunidade Celular/fisiologia , Ceratolíticos/administração & dosagem , Ceratolíticos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Psoríase/psicologia , Qualidade de Vida , Recidiva , Índice de Gravidade de Doença , Adulto Jovem
17.
Muscle Nerve ; 62(2): 272-283, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32369618

RESUMO

BACKGROUND: The exact mechanisms underlying neuroinflammation and how they contribute to amyotrophic lateral sclerosis (ALS) pathogenesis remain unclear. One possibility is the secretion of neurotoxic factors, such as lipocalin-2 (LCN2), that lead to neuronal death. METHODS: LCN2 levels were measured in human postmortem tissue using Western blot, quantitative real time polymerase chain reaction, and immunofluorescence, and in plasma by enzyme-linked immunosorbent assay. SH-SY5Y cells were used to test the pro-inflammatory effects of LCN2. RESULTS: LCN2 is increased in ALS postmortem motor cortex, spinal cord, and plasma. Furthermore, we identified several LCN2 variants in ALS patients that may contribute to disease pathogenesis. Lastly, while LCN2 treatment caused cell death and increased pro-inflammatory markers, treatment with an anti-LCN2 antibody prevented these responses in vitro. CONCLUSIONS: LCN2 upregulation in ALS postmortem samples and plasma may be an upstream event for triggering neuroinflammation and neuronal death.


Assuntos
Esclerose Amiotrófica Lateral/genética , Inflamação/metabolismo , Lipocalina-2/genética , Córtex Motor/metabolismo , Medula Espinal/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Esclerose Amiotrófica Lateral/metabolismo , Esclerose Amiotrófica Lateral/fisiopatologia , Western Blotting , Estudos de Casos e Controles , Morte Celular , Linhagem Celular Tumoral , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Humanos , Técnicas In Vitro , Lipocalina-2/antagonistas & inibidores , Lipocalina-2/metabolismo , Lipocalina-2/farmacologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real
18.
Exp Parasitol ; 213: 107888, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32259552

RESUMO

Silymarin (SIL) represents a natural mixture of polyphenols showing an array of health benefits. The present study, carried out on a model cestode infection induced by Mesocestoides vogae tetrathyridia in the ICR strain of mice, was aimed at investigating the impact of SIL as adjunct therapy on the activity of praziquantel (PZQ) in relation to parasite burden, immunity and liver fibrosis within 20 days post-therapy. In comparison with PZQ alone, co-administration of SIL and PZQ stimulated production of total IgG antibodies to somatic and excretory-secretory antigens of metacestodes and modified the expression patterns of immunogenic molecules in both antigenic preparations. The combined therapy resulted in the elevation of IFN-γ and a decline of TNF-α and TGF-ß1 in serum as compared to untreated group; however, SIL attenuated significantly the effect of PZQ on IL-4 and stimulated PZQ-suppressed phagocytosis of peritoneal macrophages. In the liver, SIL boosted the effect of PZQ on gene expression of the same cytokines in a similar way as was found in serum, except for down-regulation of PZQ-stimulated TNF-α. Compared to PZQ therapy, the infiltration of mast cells into liver after SIL co-administration was nearly abolished and correlated with suppressed activities of genes for collagen I, collagen III and α-SMA. In conclusion, co-administration of SIL modified the effects of PZQ therapy on antigenic stimulation of the immune system and modulated Th1/Th2/Tregs cytokines. In liver this was accompanied by reduced fibrosis, which correlated with significantly higher reduction of total numbers of tetrathyridia after combined therapy as compared with PZQ treatment.


Assuntos
Antioxidantes/administração & dosagem , Infecções por Cestoides/tratamento farmacológico , Citocinas/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Mesocestoides/efeitos dos fármacos , Praziquantel/administração & dosagem , Silimarina/administração & dosagem , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR
19.
Invest Ophthalmol Vis Sci ; 61(4): 48, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32347916

RESUMO

Purpose: We characterized the effects of Honokiol (HNK) on Aspergillus fumigatus-caused keratomycosis and the underlying mechanisms. HNK is known to have anti-inflammatory and antifungal properties, but the influence on fungal keratitis (FK) remains unknown. Methods: In ex vivo, minimum inhibitory concentration and Cell Count Kit-8 assay were carried out spectrophotometrically to provide preferred concentration applied in vivo. Time kill assay pointed that HNK was fungicidal and fungistatic chronologically. Adherence assay, crystal violet staining, and membrane permeability assay tested HNK effects on different fungal stages. In vivo, clinical scores reflected the improvement degree of keratitis outcome. Myeloperoxidase (MPO) assay, flow cytometry (FCM), and immunohistofluorescence staining (IFS) were done to evaluate neutrophil infiltration. Plate count detected HNK fungicidal potentiality. RT-PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA) verified the anti-inflammatory activity of HNK collaboratively. Results: In vitro, MIC90 HNK was 8 µg/mL (no cytotoxicity), and Minimal Fungicidal Concentration (MFC) was 12 µg/mL for A. fumigatus. HNK played the fungistatic and fungicidal roles at 6 and 24 hours, respectively, inhibiting adherence at the beginning, diminishing biofilms formation, and increasing membrane permeability all the time. In vivo, HNK improved C57BL/6 mice outcome by reducing disease severity (clinical scores), neutrophil infiltration (MPO, FCM, and IFS), and fungal loading (plate count). RT-PCR, Western blot, and ELISA revealed that HNK downregulated mRNA and protein expression levels of Toll-like receptor-2 (TLR-2), high mobility group box 1 (HMGB1), IL-1ß, and TNF-α. Conclusions: Our study suggested HNK played antifungal and anti-inflammatory roles on keratomycosis by reducing survival of fungi, infiltration of leucocytes, and expression of HMGB1, TLR-2, and proinflammatory cytokines, providing a potential treatment for FK.


Assuntos
Anti-Infecciosos/farmacologia , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/isolamento & purificação , Compostos de Bifenilo/farmacologia , Infecções Oculares Fúngicas/tratamento farmacológico , Lignanas/farmacologia , Animais , Aspergilose/diagnóstico , Western Blotting , Citocinas/efeitos dos fármacos , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Infecções Oculares Fúngicas/microbiologia , Feminino , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Reação em Cadeia da Polimerase em Tempo Real/métodos , Receptor 2 Toll-Like/efeitos dos fármacos , Resultado do Tratamento
20.
Chemosphere ; 254: 126717, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32339795

RESUMO

Pantropical spotted dolphins are apex predators and have a long lifespan, which makes them susceptible to chemical pollutants such as polybrominated diphenyl ethers (PBDEs), which are associated with immunotoxicity in wildlife. However, the effects of PBDEs and their mechanism of immunotoxicity in dolphins is largely unknown. Previously, we established fibroblast cell lines obtained from pantropical spotted dolphins (PSD-LWHT) as an in vitro model for assessing the toxicological implications of chemical pollutants in dolphins. In this study, we used the novel immortalized fibroblast cell line to explore the potential immune stimulation effect of PBDEs via prostaglandins signaling pathways to better understand the immunotoxicity pathway of PBDEs in dolphins. BDE-47, -100, and -209 exposure generally resulted in an increase in inflammatory cytokine expression, PGE2 levels, and COX-2 gene expression but BDE-209 resulted in a suppression in IL-10 production. Both protein and mRNA expression of COX-2 and PTGES increased significantly following exposure to the PBDEs. The results suggested BDE-100 and -209 increased prostaglandin E2 (PGE2) production via increased expression of COX-2 and PTGES expression. Only BDE-100 increased expression level of the prostaglandin E2 receptor EP4 while BDE-47 and BDE-209 decreased its expression. This probably explained why suppressive effect on the expression level of anti-inflammatory cytokines were only found in exposure with BDE-47 and BDE-209 rather than BDE-100. The results showed that PBDEs stimulate innate immune response by triggering PGE2-EPs-cAMP-cytokines signaling.


Assuntos
Éteres Difenil Halogenados/farmacologia , Imunidade Inata/efeitos dos fármacos , Prostaglandinas/metabolismo , Stenella/metabolismo , Animais , Linhagem Celular , Ciclo-Oxigenase 2/metabolismo , Citocinas/efeitos dos fármacos , Citocinas/metabolismo , Éteres Difenil Halogenados/imunologia , Bifenil Polibromatos/farmacologia , Poluentes Químicos da Água/farmacologia
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