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1.
Chem Biol Interact ; 333: 109336, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33248029

RESUMO

Resin-based dental materials consist of filler particles and different monomers that are light cured in situ to re-establish dental function and aesthetics. Due to the degree of conversion of adhesive polymers, the monomers triethyleneglycol dimethacrylate (TEGDMA) and 2-hydroxyethyl methacrylate (HEMA) are released in relatively high amounts and are susceptible to degradation, acting as bioactive compounds and affecting cell and tissues. This study aimed to assess the effect of HEMA and TEGDMA exposure on metabolic activity, membrane integrity, and cell survival of human odontoblast-like cell (hOLCs). Exposure to resin monomers for 24 h induced major changes in cell membrane integrity, metabolic activity, and survival, which were measured by the calcein method and lactate dehydrogenase release. Increased and early reactive oxygen species (ROS) production was observed leading to degradative oxidation of membrane lipids identified as malondialdehyde production. Severe alteration in mitochondria occurred due to transmembrane mitochondrial potential collapse, possibly inducing activation of apoptotic cell death. hOLCs exposure to resin monomers modified the cell redox potential, with consequences on membrane permeability and integrity, including mitochondrial function. Lipid peroxidation appears to be a key phenomenon for the membrane structures oxidation after HEMA and TEGDMA exposure, leading to cell death and cytotoxicity. hOLCs respond early by differential induction of adaptive mechanisms to maintain cell homeostasis. Modulation of oxidative stress-induced response involves the regulation of genes that encode for antioxidant proteins such as catalase and heme oxygenase-1; regulation that functions as a critical protection mechanism against oxidative cell damage induced by HEMA and TEGDMA. Ascorbic acid as an antioxidant substance mitigates the oxidative damage associated with exposure to monomers.


Assuntos
Metacrilatos/efeitos adversos , Odontoblastos/citologia , Estresse Oxidativo/efeitos dos fármacos , Polietilenoglicóis/efeitos adversos , Ácidos Polimetacrílicos/efeitos adversos , Resinas Sintéticas/química , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Humanos , Mitocôndrias/efeitos dos fármacos , Odontoblastos/efeitos dos fármacos , Odontoblastos/metabolismo , Espécies Reativas de Oxigênio/metabolismo
2.
Zhonghua Zhong Liu Za Zhi ; 42(8): 617-623, 2020 Aug 23.
Artigo em Chinês | MEDLINE | ID: mdl-32867451

RESUMO

As a new type of anthracyclines, pegylated liposomal doxorubicin (PLD) is widely used in the treatment of a variety of malignant tumors, including soft tissue sarcoma, ovarian cancer, breast cancer, multiple myeloma, and so on. Compared with traditional anthracyclines, PLD can significantly decrease the incidences of adverse events such as cardiac toxicity and alopecia. However, the use of PLD will be accompanied with toxic side effects such as hand-foot syndrome, oral mucositis, and infusion reaction. This consensus will mainly focus on the mechanism, prevention and treatment of adverse events of PLD, in order to improve the therapeutic efficacy of PLD and life quality of patients.


Assuntos
Antibióticos Antineoplásicos/efeitos adversos , Doxorrubicina/análogos & derivados , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Síndrome Mão-Pé/complicações , Neoplasias/tratamento farmacológico , Estomatite/complicações , Antibióticos Antineoplásicos/uso terapêutico , Consenso , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Feminino , Humanos , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Guias de Prática Clínica como Assunto
3.
Pediatrics ; 146(2)2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32680878

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening syndrome classified into primary HLH and secondary HLH. Secondary HLH is always caused by autoimmune disease, infections, or cancer. The first-line therapy for secondary HLH is the HLH 2004 protocol, including dexamethasone, etoposide, and supportive therapy. However, up to 30% of patients, especially pediatric patients, remain unresponsive to first-line treatment, and the mortality rate reaches 50% in children with HLH. Furthermore, some children who have special conditions, such as an active virus infection, are not suitable for immunosuppressants treatment. Recently, several HLH-promoting cytokines have been identified, including interferon-γ, interleukin-2, and interleukin-6. Janus kinase 1 and 2 control the signaling of many cytokines, notably interferon-γ, interleukin-2, and interleukin-6. Janus kinase 1 and 2 inhibitors, such as ruxolitinib, have been successfully used to treat HLH in mice. Here, we report that a boy, diagnosed with HLH and high titer of hepatitis B virus-DNA copies, improved quickly, and the cytokine storm of HLH was alleviated after receiving ruxolitinib. Five days after ruxolitinib treatment, entecavir was introduced and serum titer results of hepatitis B virus-DNA returned negative. With 3 months of ruxolitinib treatment and following-up 1 year, the boy's situation maintained sustained remission. In this study, it is suggested that ruxolitinib might be a first-line drug, which could alleviate the cytokine storm of HLH. This treatment may be ushering in the age of glucocorticosteroid-free HLH treatment, which is particularly meaningful for children because it avoids the side effects of glucocorticosteroid.


Assuntos
Síndrome da Liberação de Citocina/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Pirazóis/uso terapêutico , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Criança , Síndrome da Liberação de Citocina/etiologia , Quimioterapia Combinada , Febre/etiologia , Guanina/análogos & derivados , Guanina/uso terapêutico , Hepatite B Crônica/complicações , Hepatite B Crônica/congênito , Hepatite B Crônica/tratamento farmacológico , Humanos , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Janus Quinases/antagonistas & inibidores , Masculino , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Pirazóis/farmacologia , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Carga Viral
4.
Cardiovasc Drugs Ther ; 34(5): 651-657, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32444994

RESUMO

BACKGROUND: The high surgical risk in redo cardiac surgery is largely attributed to adhesions around the epicardium and the great vessels. BAX602 is an adhesion prevention reagent composed of two synthetic polyethylene glycols. Spraying BAX602 over the epicardium and the great vessels reportedly contributes to adhesion prevention after pediatric cardiac surgery. The present study aims to evaluate the safety and effectiveness of BAX602 spray in patients undergoing extracorporeal ventricular assist device implantation surgery to treat refractory congestive heart failure. METHODS AND DESIGN: This investigator-initiated, multicenter, pivotal, two-arm, open-label, randomized trial will include a total of 30 patients. The primary outcome measure is the severity of adhesions, which will be evaluated during re-sternotomy surgery performed 2-12 weeks after the primary extracorporeal ventricular assist device implantation surgery. The adhesion severity will be evaluated at five predefined sites using a four-grade adhesion evaluation score (0 = no adhesion; 1 = filmy and avascular adhesion; 2 = dense/vascular adhesion; 3 = cohesive adhesion). This measure will be summarized in two ways to evaluate the effect of BAX602: (1) the total score of the severity of adhesions at all five sites (ranging from 0 to 15), and (2) the total number of sites with dense/vascular or cohesive adhesions (ranging from 0 to 5). ETHICS AND DISSEMINATION: The study findings will be disseminated at regional, national, and international conferences and through peer-reviewed scientific journals. TRIAL REGISTRATION: The trial was registered in the UMIN Clinical Trials Registry (UMIN-CTR: UMIN000038998) on 6 January 2020.


Assuntos
Cardiopatias/prevenção & controle , Insuficiência Cardíaca/terapia , Coração Auxiliar , Polietilenoglicóis/administração & dosagem , Implantação de Prótese/instrumentação , Função Ventricular Esquerda , Adolescente , Adulto , Aerossóis , Idoso , Feminino , Cardiopatias/etiologia , Cardiopatias/patologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/síntese química , Desenho de Prótese , Implantação de Prótese/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Fatores de Tempo , Aderências Teciduais , Resultado do Tratamento , Adulto Jovem
5.
Thromb Haemost ; 120(5): 737-746, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32369845

RESUMO

Long-term safety and efficacy data of extended half-life factor IX (FIX) prophylaxis in children with hemophilia B (HB) are sparse. paradigm 5 is a multinational, open-label, single-arm, phase III trial assessing once-weekly (40 IU/kg) prophylactic nonacog beta pegol (N9-GP) in previously treated patients (PTPs) aged ≤ 12 years with HB (FIX activity ≤ 2%). Primary endpoint: incidence of anti-FIX inhibitory antibodies (≥ 0.6 Bethesda Units). We present a 5-year analysis (N = 25, including remaining patients with ≥ 5 years' follow-up) and compare with a 1-year analysis (≥ 52 weeks' exposure). The main phase enrolled 25 children; 22 entered the extension phase; 17 remained in trial at data cutoff. Median treatment period: 5.6 years/patient; median total number of N9-GP exposure days: 290.0/patient. No patients developed anti-FIX inhibitory antibodies. No other safety concerns, including thromboembolic events, were reported. Neurological examinations have not revealed any new abnormal findings. Sixteen (64.0%) patients remained free from spontaneous bleeds; all bleeds were mild/moderate in severity; 93.0% were controlled with 1 to 2 N9-GP injections. No intracranial hemorrhages were reported. Annualized bleeding rates (ABRs) were very low at 5 years (median/Poisson-estimated mean overall ABR: 0.66/0.99), having decreased from the 1-year analysis (1.00/1.44). Median/Poisson-estimated mean spontaneous ABRs for the 1- and 5-year analyses: 0.00/0.45 and 0.00/0.33. Mean FIX trough activity at 5 years: 17.9%. Mean polyethylene glycol plasma concentration reached steady state at 6 months, increasing slightly over time, in line with increased FIX trough activity. N9-GP administered for ≥ 5 years shows favorable long-term safety and efficacy in PTPs with HB (FIX activity ≤ 2%).


Assuntos
Fator IX/administração & dosagem , Hemofilia B/tratamento farmacológico , Hemostáticos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adolescente , Fatores Etários , Ásia , Criança , Pré-Escolar , Esquema de Medicação , Europa (Continente) , Fator IX/efeitos adversos , Fator IX/farmacocinética , Hemofilia B/sangue , Hemofilia B/diagnóstico , Hemorragia/sangue , Hemorragia/diagnóstico , Hemorragia/prevenção & controle , Hemostáticos/efeitos adversos , Hemostáticos/sangue , Hemostáticos/farmacocinética , Humanos , Lactente , América do Norte , Segurança do Paciente , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacocinética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/sangue , Proteínas Recombinantes/farmacocinética , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
6.
Int J Mol Sci ; 21(8)2020 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-32316632

RESUMO

Drought stress is a major obstacle to agricultural production. Tibetan wild barley with rich genetic diversity is useful for drought-tolerant improvement of cereals. MicroRNAs (miRNAs) play critical roles in controlling gene expression in response to various environment perturbations in plants. However, the genome-wide expression profiles of miRNAs and their targets in response to drought stress are largely unknown in wild barley. In this study, a polyethylene glycol (PEG) induced drought stress hydroponic experiment was performed, and the expression profiles of miRNAs from the roots of two contrasting Tibetan wild barley genotypes XZ5 (drought-tolerant) and XZ54 (drought-sensitive), and one cultivated barley Tadmor (drought-tolerant) generated by high-throughput sequencing were compared. There were 69 conserved miRNAs and 1574 novel miRNAs in the dataset of three genotypes under control and drought conditions. Among them, seven conserved miRNAs and 36 novel miRNAs showed significantly genotype-specific expression patterns in response to drought stress. And 12 miRNAs were further regarded as drought tolerant associated miRNAs in XZ5, which mostly participate in gene expression, metabolism, signaling and transportation, suggesting that they and their target genes play important roles in plant drought tolerance. This is the first comparation study on the miRNA transcriptome in the roots of two Tibetan wild barley genotypes differing in drought tolerance and one drought tolerant cultivar in response to PEG treatment. Further results revealed the candidate drought tolerant miRNAs and target genes in the miRNA regulation mechanism in wild barley under drought stress. Our findings provide valuable understandings for the functional characterization of miRNAs in drought tolerance.


Assuntos
Hordeum/crescimento & desenvolvimento , MicroRNAs/genética , Polietilenoglicóis/efeitos adversos , Sequenciamento Completo do Exoma/métodos , Secas , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Hordeum/classificação , Hordeum/efeitos dos fármacos , Hordeum/genética , MicroRNAs/química , Modelos Moleculares , Conformação de Ácido Nucleico , Proteínas de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , RNA de Plantas/genética
7.
PLoS One ; 15(4): e0230893, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32275726

RESUMO

BACKGROUND AND AIMS: Sustained off-treatment immune control is achievable in a proportion of patients with chronic hepatitis B treated with peginterferon alfa-2a. We evaluated on-treatment predictors of hepatitis B surface antigen (HBsAg) clearance 3 years after peginterferon alfa-2a treatment and determined the incidence of hepatocellular carcinoma. METHODS: A prospective, international, multicenter, observational study in patients with chronic hepatitis B who have been prescribed peginterferon alfa-2a (40KD) in a real-world setting. The primary endpoint was HBsAg clearance after 3 years' follow-up. RESULTS: The modified intention-to-treat population comprised 844 hepatitis B e antigen (HBeAg)-positive patients (540 [64%] completed 3 years' follow-up), and 872 HBeAg-negative patients (614 [70%] completed 3 years' follow-up). At 3 years' follow-up, HBsAg clearance rates in HBeAg-positive and HBeAg-negative populations, respectively, were 2% (16/844) and 5% (41/872) in the modified intention-to-treat population and 5% [16/328] and 10% [41/394] in those with available data. In HBeAg-positive patients with data, Week 12 HBsAg levels <1500, 1500-20,000, and >20,000 IU/mL were associated with HBsAg clearance rates at 3 years' follow-up of 11%, 1%, and 5%, respectively (Week 24 predictability was similar). In HBeAg-negative patients with available data, a ≥10% decline vs a <10% decline in HBsAg at Week 12 was associated with HBsAg clearance rates of 16% vs 4%. Hepatocellular carcinoma incidence was lower than REACH-B (Risk Estimation for Hepatocellular Carcinoma in Chronic Hepatitis B) model predictions. CONCLUSIONS: Sustained off-treatment immune control is achieved with peginterferon alfa-2a in a real-world setting. HBsAg clearance 3 years after completion of peginterferon alfa-2a can be predicted on the basis of on-treatment HBsAg kinetics.


Assuntos
Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Internacionalidade , Polietilenoglicóis/uso terapêutico , Adulto , Feminino , Antígenos de Superfície da Hepatite B/metabolismo , Antígenos E da Hepatite B/metabolismo , Hepatite B Crônica/metabolismo , Humanos , Interferon-alfa/efeitos adversos , Masculino , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Segurança , Resultado do Tratamento
8.
PLoS One ; 15(4): e0231888, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343708

RESUMO

BACKGROUND AND AIMS: Inadequate bowel preparation (BP) is an unfavorable factor that influence the success of colonoscopy. Although standard education (SE) given to patients are proved useful to avoid inadequate BP. Studies concerning the effects of reinforced education (RE) on the quality of BP were inconsistent. The aim of this updated meta-analysis of randomized controlled trial was to compare the quality of BP between patients receiving RE in addition to SE and those receiving SE alone. METHODS: MEDLINE, EMBASE, Web of Science and the Cochrane Library were systemically searched to identify the relevant studies published through April 2019. The primary outcome was the rate of adequate BP. Subgroup analyses were conducted. Secondary outcomes included BP score, adenoma detection rate (ADR), polyp detection rate (PDR), insertion time, withdrawal time, adverse events, >80% purgative intake and diet compliance. Dichotomous variables were reported as odds ratio (OR) with 95% confidence interval (CI). Continuous data were reported as mean difference (MD) with 95%CI. Pooled estimates of OR or MD were calculated using a random-effects model. Statistical heterogeneity was accessed by calculating the I2 value. A P value less than 0.05 was considered significant. RESULTS: A total of 18 randomized controlled trails (N = 6536) were included in this meta-analysis. Patients who received RE had a better BP quality than those only receiving SE (OR 2.59, 95%CI: 2.09-3.19; P<0.001). A higher ADR (OR 1.35; 95%CI: 1.06-1.72; P = 0.020) and PDR (OR 1.24, 95%CI: 1.02-1.50; P = 0.030), shorter insertion (MD -0.76; 95%CI: -1.48-(-0.04); P = 0.040) and withdrawal time (MD -0.83; 95%CI: -1.83-(-0.28); P = 0.003), less nausea/vomiting (OR 0.78; 95%CI: 0.64-0.97; P = 0.020) and abdominal distension (OR 0.72; 95%CI: 0.68-0.92; P = 0.020) were achieved in the RE group. More patients had >80% purgative intake (OR 2.17; 95%CI, 1.09-4.32; P = 0.030) and were compliant with diet restriction (OR 2.38; 95%CI: 1.79-3.17; P<0.001) in the RE group. CONCLUSION: RE significantly improved BP quality, increased ADR and PDR, decreased insertion and withdrawal time and adverse events.


Assuntos
Colonoscopia , Educação de Pacientes como Assunto , Adenoma/patologia , Humanos , Laxantes/administração & dosagem , Laxantes/efeitos adversos , Náusea/etiologia , Razão de Chances , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Pólipos/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto
9.
Acta Oncol ; 59(6): 713-722, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32141389

RESUMO

Background: Previously, we showed that reintroduction of the same (first-line) chemotherapy at progression could only partially make up for the loss in efficacy as compared to continuously delivered first-line chemotherapy. Here, we report the probability of starting second-line study chemotherapy in the Stop&Go trial, and the progression-free survival (PFS) and overall survival (OS) of patients who received both the first- and second-line treatment in an intermittent versus continuous schedule.Methods: First-line chemotherapy comprised paclitaxel plus bevacizumab, second-line capecitabine or non-pegylated liposomal doxorubicin, given per treatment line as two times four cycles (intermittent) or as eight consecutive cycles (continuous).Results: Of the 420 patients who started first-line treatment within the Stop&Go trial (210:210), a total of 270 patients continued on second-line study treatment (64% of all), which consisted of capecitabine in 201 patients and of non-pegylated liposomal doxorubicin in 69 patients, evenly distributed between the treatment arms. Median PFS was 3.7 versus 5.0 months (HR 1.07; 95% CI: 0.82-1.38) and median OS 10.9 versus 12.4 months (HR 1.27; 95% CI: 0.98-1.66) for intermittent versus continuous second-line chemotherapy. Second-line PFS was positively influenced by prior hormonal therapy for metastatic disease and longer first-line PFS duration, while triple-negative tumor status had a negative influence. Patients with a shorter time to progression (TTP) in first-line (≤10 months) had a higher probability of starting second-line treatment if they received intermittent compared to continuous chemotherapy (OR 1.97; 95% CI: 1.02-3.80).Conclusion: We recommend continuous scheduling of both the first- and second-line chemotherapy for advanced breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Neoplasias da Mama/mortalidade , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Esquema de Medicação , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Intervalo Livre de Progressão , Receptor ErbB-2 , Fatores de Tempo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico
10.
Intern Med ; 59(12): 1559-1563, 2020 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-32188815

RESUMO

We herein report a case of migratory aortitis after the administration of granulocyte-colony-stimulating factor (G-CSF) to a 65-year-old woman with a history of pancreatic cancer. She was being administered pegfilgrastim and developed aortitis around the aortic arch. Although it resolved within two weeks, she again developed aortitis around the descending aorta, presenting as migratory aortitis, after pegfilgrastim was resumed. We further experienced three additional cases of G-CSF-induced aortitis that also showed spontaneous resolution, suggesting no or short-term use of immunosuppression. Aortitis due to G-CSF can present as migratory aortitis, since aortitis can quickly resolve and inflammation can recur at a different location.


Assuntos
Aortite/induzido quimicamente , Aortite/patologia , Filgrastim/efeitos adversos , Polietilenoglicóis/efeitos adversos , Idoso , Aorta Torácica/patologia , Feminino , Granulócitos , Humanos , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/tratamento farmacológico
11.
J Oncol Pharm Pract ; 26(7): 1785-1790, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32188319

RESUMO

INTRODUCTION: Granulocyte colony-stimulating factor (G-CSF) is widely used as a neutrophil supportive therapy in breast cancer chemotherapy. Common adverse events of G-CSF include bone pain, headache, and fatigue; however, reports of G-CSF-associated vasculitis are few. CASE REPORT: A 66-year-old woman who had undergone surgery for breast cancer received adjuvant chemotherapy with prophylactic use of pegfilgrastim (peg-G). She developed peg-G-associated vasculitis 11 days after initially receiving peg-G.Management and outcome: Although various blood and culture tests were required to rule out other vasculitis syndromes and infections, her symptoms spontaneously disappeared without any treatment other than discontinuation of the causal drug. DISCUSSION: G-CSF-associated vasculitis is occasionally accompanied by severe complications such as aortic dissection and aneurysm formation. This case report is important to draw attention towards this rare and difficult-to-diagnosis adverse event of peg-G.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Filgrastim/efeitos adversos , Polietilenoglicóis/efeitos adversos , Vasculite/induzido quimicamente , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante , Feminino , Filgrastim/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Polietilenoglicóis/administração & dosagem
12.
Dermatitis ; 31(2): 140-143, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32091464

RESUMO

BACKGROUND: Allergic contact dermatitis (ACD) caused by (meth)acrylates used in nail products is being increasingly reported in nail technicians and consumers. OBJECTIVES: The aim of the study was to assess the incidence of sensitization to (meth)acrylates in technicians and users of nail products with ACD, referred for patch testing in a tertiary center, during the last 10 years. METHODS: All patients with ACD, who reported a profession associated with cosmetic nail procedures or use of such services and were referred for patch tests in our department between January 2009 and December 2018, were identified. The incidence of positive sensitization to (meth)acrylates was assessed. RESULTS: Contact allergy to 1 or more (meth)acrylates was found in 116 (74.4%) of 156 nail technicians or nail product users, all women. One hundred thirty-eight (88.5%) were occupationally exposed, and 18 (11.5%) were consumers. In addition, there was a statistically significant increase in (meth)acrylate ACD during 2014-2018 (100/127 cases [79%]) when compared with 2009-2013 (16/29 cases [55%]). The most common sensitizer among the 156 allergic individuals was ethylene glycol dimethacrylate, which was positive in 113 cases (72.4%), and among patients with acrylate-positive patch test, the rate was 97.4%. CONCLUSIONS: Our experience confirms the worldwide changing landscape of rising (meth)acrylate sensitization in nail technicians and nail products users with ACD. Efforts to improve prevention are needed, and clinicians should have a high index for suspicion in this occupational group.


Assuntos
Acrilatos/efeitos adversos , Alérgenos/efeitos adversos , Cosméticos , Dermatite Alérgica de Contato/epidemiologia , Dermatite Ocupacional/epidemiologia , Metacrilatos/efeitos adversos , Unhas , Adolescente , Adulto , Idoso , Dermatite Alérgica de Contato/etiologia , Dermatite Ocupacional/etiologia , Feminino , Grécia/epidemiologia , Humanos , Incidência , Metilmetacrilato/efeitos adversos , Pessoa de Meia-Idade , Testes do Emplastro , Polietilenoglicóis/efeitos adversos , Ácidos Polimetacrílicos/efeitos adversos , Adulto Jovem
13.
Nat Microbiol ; 5(4): 642-650, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32042128

RESUMO

Although Clostridium difficile is widely considered an antibiotic- and hospital-associated pathogen, recent evidence indicates that this is an insufficient depiction of the risks and reservoirs. A common thread that links all major risk factors of infection is their association with gastrointestinal disturbances, but this relationship to C. difficile colonization has never been tested directly. Here, we show that disturbances caused by diarrhoeal events trigger susceptibility to C. difficile colonization. Using survey data of the human gut microbiome, we detected C. difficile colonization and blooms in people recovering from food poisoning and Vibrio cholerae infections. Carriers remained colonized for year-long time scales and experienced highly variable patterns of C. difficile abundance, where increased shedding over short periods of 1-2 d interrupted week-long periods in which C. difficile was undetectable. Given that short shedding events were often linked to gastrointestinal disturbances, our results help explain why C. difficile is frequently detected as a co-infecting pathogen in patients with diarrhoea. To directly test the impact of diarrhoea on susceptibility to colonization, we developed a mouse model of variable disturbance intensity, which allowed us to monitor colonization in the absence of disease. As mice exposed to avirulent C. difficile spores ingested increasing quantities of laxatives, more individuals experienced C. difficile blooms. Our results indicate that the likelihood of colonization is highest in the days immediately following acute disturbances, suggesting that this could be an important window during which transmission could be interrupted and the incidence of infection lowered.


Assuntos
/efeitos dos fármacos , Infecções por Clostridium/microbiologia , Diarreia/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Laxantes/efeitos adversos , Polietilenoglicóis/efeitos adversos , Actinobacteria/genética , Actinobacteria/crescimento & desenvolvimento , Actinobacteria/isolamento & purificação , Animais , Bacteroidetes/genética , Bacteroidetes/crescimento & desenvolvimento , Bacteroidetes/isolamento & purificação , Infecções por Clostridium/complicações , Contagem de Colônia Microbiana , Diarreia/induzido quimicamente , Diarreia/complicações , Modelos Animais de Doenças , Fezes/microbiologia , Firmicutes/genética , Firmicutes/crescimento & desenvolvimento , Firmicutes/isolamento & purificação , Fusobactérias/genética , Fusobactérias/crescimento & desenvolvimento , Fusobactérias/isolamento & purificação , Humanos , Masculino , Camundongos , Proteobactérias/genética , Proteobactérias/crescimento & desenvolvimento , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S/genética
14.
BMC Plant Biol ; 20(1): 84, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085729

RESUMO

BACKGROUND: Membrane lipid composition associates closely with membrane stability and fluidity under water stress. In this study, lipidomic analyses based on electrospray ionization mass spectrometry (ESI-MS/MS) were carried out to explore dynamic changes of membrane lipids in term of molecular species caused by PEG (Polyethylene glycol-6000)-induced water stress in wheat seedlings. RESULTS: Among the main phospholipids, phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG) are primary degradation targets, and PC was degraded in the largest degree. Membrane ion leakage dramatically increased later than the significant reduction of these phospholipids, indicating that the loss of membrane integrity lagged behind severe phospholipid degradation. Monogalactosyldiacylglycerol (MGDG) increased firstly and decreased later, while digalactosyldiacylglycerol (DGDG) ratcheted up with stress. DGDG/MGDG increased after stress for 3 days, and unsaturation of DGDG was promoted with stress. Variation trends of galactolipids differed among molecular species. The time when MGDG (34:3), DGDG (34:3) began to decline approached to the time when non-stomatal limitation impaired photosynthesis. While the two predominant molecular species MGDG (36:6) and DGDG (36:6) began to decline later. So we speculated that MGDG (34:3), DGDG (34:3) might be key components in photosynthesis apparatus and participate in photosynthesis directly. While the two predominant molecular species, MGDG (36:6) and DGDG (36:6) might locate in thylakoid lipid bilayer matrix and play roles in stabilizing the membrane. The research provides new insights into the dynamic response of lipid metabolism to PEG-induced water stress. CONCLUSION: In wheat plants under water stress, the major molecular species of PC, PE and PG were degraded, MGDG and DGDG molecular species had differing degradation time courses.


Assuntos
Secas , Lipídeos de Membrana/metabolismo , Folhas de Planta/metabolismo , Triticum/fisiologia , Polietilenoglicóis/efeitos adversos , Plântula/metabolismo , Estresse Fisiológico/genética
16.
PLoS One ; 15(2): e0229517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32106270

RESUMO

AIMS: To analyze the efficacy and safety of sofosbuvir (SOF)-based regimens in Thai patients with chronic hepatitis C virus infection who had pre-existing significant liver fibrosis. PATIENTS AND METHODS: This was a retrospective cohort study, conducted between 1 June 2018 and 31 May 2019 at Rajavithi Hospital, Bangkok, Thailand. All patients completed 12 weeks of SOF-based regimens and had follow-up for at least 12 weeks after therapy discontinuation. The primary outcome was sustained virological response (SVR) 12 weeks after the end of therapy. RESULT: A total of 185 patients were included, with 52, 63 and 70 taking SOF+Ledipasvir (SOF+LDV), SOF+LDV+ribavirin (RBV) and SOF+Pegylated interferon (Peg-IFN)+RBV (SOF+Peg-IFN+RBV) respectively. Genotype (GT) 1 was predominant at 40.0%, followed by GT3 at 37.8%, and GT6 at 22.2%. Overall 95.1% of patients in this study achieved SVR (n = 176/185), and the only factor associated with SVR was HCV genotype (p = 0.001). GT6 patients had lower SVR rates compared to GT1 and GT3 patients (82.9%, 98.6%, and 98.6% respectively) while there was no association between SVR and other factors (p >0.05) such as gender, age, BMI, underlying cirrhosis, baseline HCV viral load, or prior treatment history. No serious adverse events were reported in the present study. CONCLUSION: Sofosbuvir-based regimens in the treatment of patients with chronic HCV infection were highly efficacious with excellent safety and tolerability profiles in a real-world setting; however, further research is required to establish whether or not such a regimen is an adequate treatment for all genotype 6 patients.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Sofosbuvir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Estudos de Coortes , Quimioterapia Combinada , Feminino , Fluorenos/administração & dosagem , Fluorenos/efeitos adversos , Genótipo , Hepacivirus/genética , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2/administração & dosagem , Interferon alfa-2/efeitos adversos , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Estudos Retrospectivos , Ribavirina/administração & dosagem , Ribavirina/efeitos adversos , Sofosbuvir/administração & dosagem , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Tailândia , Fatores de Tempo , Resultado do Tratamento , Uridina Monofosfato/administração & dosagem , Uridina Monofosfato/efeitos adversos , Uridina Monofosfato/análogos & derivados
17.
Int J Clin Pharmacol Ther ; 58(5): 268-273, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32101521

RESUMO

OBJECTIVE: This work aims to evaluate the therapeutic survey of adverse events during antiviral treatment of hepatitis in the three major University Hospitals in Abidjan. MATERIALS AND METHODS: A retrospective cross-sectional descriptive study of 203 patients from August 1, 2015, to July 31, 2018, enumerated adverse events during antiviral treatments, drugs used for their management, and their clinical or biological impact. RESULTS: The following was seen: hematological disorders during treatment with pegylated interferon α-2a (88.61%) and ribavirin (77.55%), pain syndrome when using pegylated interferon α-2a (90.5%), and digestive disorders while taking sofosbuvir (60.71%) and daclatasvir (66.67%). Hematological disorders were managed with filgrastim for neutropenia and oral iron or blood transfusion for anemia and/or thrombocytopenia. Pain syndrome was treated with paracetamol. As for digestive disorders, they were most often managed with activated charcoal. CONCLUSION: Correction of the adverse events was made either using causal treatment or using symptomatic drugs. However, some drugs, in particular hematopoietic factors, have been less used due to their costs.


Assuntos
Antivirais/efeitos adversos , Hepatite C Crônica/tratamento farmacológico , Antivirais/uso terapêutico , Costa do Marfim , Estudos Transversais , Quimioterapia Combinada , Genótipo , Hospitais Universitários , Humanos , Imidazóis/efeitos adversos , Imidazóis/uso terapêutico , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Estudos Retrospectivos , Ribavirina/efeitos adversos , Ribavirina/uso terapêutico , Sofosbuvir/efeitos adversos , Sofosbuvir/uso terapêutico , Resultado do Tratamento
18.
Gynecol Oncol ; 156(3): 535-544, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31924332

RESUMO

OBJECTIVE: This phase 3 study aimed to compare overall survival (OS) of women with platinum-sensitive, recurrent ovarian cancer (ROC) treated with third-line trabectedin (T) + pegylated liposomal doxorubicin (PLD) vs. PLD monotherapy. METHODS: Women with advanced-relapsed epithelial ovarian cancer were randomly assigned 1: 1 to intravenous infusions of either T + PLD (trabectedin 1.1 mg/m2 for 3 h; PLD 30 mg/m2 for 1.5 h, every 3 weeks) or PLD (50 mg/m2 for 1.5 h, every 4 weeks). Primary endpoint was OS. Secondary endpoints included investigator-assessed progression free survival (PFS) and objective response rates (ORR). At randomization, patients were stratified by time from last dose of first-line platinum therapy to disease progression, ECOG grade 0 or 1, BRCA1/2 germline mutational status, and prior PLD therapy. Exploratory endpoints included OS, PFS, and ORR in the stratified subgroups (PFI, ECOG, BRCA1/2 status, and prior PLD therapy). This trial is registered with ClinicalTrials.gov, number NCT01846611. RESULTS: 576 patients were randomized (T + PLD, n = 289; PLD, n = 287). Median OS was 23.8 months with T + PLD vs. 22.2 months with PLD (HR:0.92, 95%CI:0.73-1.18; p = 0.52). Median PFS was 7.52 vs. 7.26 months (HR:0.93, 95%CI:0.76-1.15; p = 0.52); ORR was 46% vs. 35.9% (OR:1.52, 95%CI:1.07-2.16; p = 0.01). Patients with BRCA1/2 mutations had median OS of 34.2 months with T + PLD vs. 20.9 months with PLD (HR:0.54, 95%CI:0.33-0.90; p = 0.016). Patients with BRCA1/2 mutations had median PFS of 10.1 months with T + PLD vs. 7.6 months with PLD (HR:0.72, 95%CI:0.48-1.08; p = 0.039). Patients with BRCA1/2 mutations and a 6-12 months platinum-free interval (PFI), median OS was 31.5 vs. 14.9 months, respectively (HR:0.37, 95%CI:0.17-0.82; p = 0.011). Grade 3-4 AEs were higher in T + PLD (79%) vs. PLD (54%). CONCLUSION: Combination of T and PLD did not show favorable OS benefit nor safety; however, patients with germline BRCA1/2 mutations and/or a PFI of 6-12 months appear to have clinically relevant survival benefit with T + PLD. No new safety signals were identified.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Intervalo Livre de Progressão , Taxa de Sobrevida , Trabectedina/administração & dosagem , Trabectedina/efeitos adversos , Resultado do Tratamento , Adulto Jovem
19.
Expert Opin Investig Drugs ; 29(2): 125-133, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31899984

RESUMO

Introduction: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and is strongly associated with obesity and insulin resistance. NAFLD refers to a spectrum of disorders ranging from asymptomatic hepatic steatosis (nonalcoholic fatty liver, NAFL) to nonalcoholic steatohepatitis (NASH), which increases the risk of developing more severe forms of liver disease such as progressive fibrosis, cirrhosis, and liver cancer. Currently, there are no food and drug administration (FDA) approved drugs to treat NASH. Pegbelfermin (BMS-986036) is a PEGylated fibroblast growth factor 21 (FGF21) analogue that is under investigation for the treatment of NASH.Areas covered: We reviewed the (pre)clinical pegbelfermin studies and compared these with other studies that assessed FGF21 and FGF21 analogues in the treatment of NASH.Expert opinion: With no FDA approved treatments available for NASH, there is an urgent need for novel therapies. Pegbelfermin is a systemic treatment with pleiotropic effects on various tissues. Short-term adverse effects are limited, but more research is required to study potential long-term safety issues. In a phase 2a trial, pegbelfermin has shown promising improvements in several NASH related outcomes. However, clinical trials demonstrating long-term benefits on hard outcomes such as liver histology, cirrhosis development, or survival are required for further validation.


Assuntos
Fatores de Crescimento de Fibroblastos/análogos & derivados , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Polietilenoglicóis/uso terapêutico , Animais , Progressão da Doença , Drogas em Investigação/efeitos adversos , Drogas em Investigação/farmacologia , Drogas em Investigação/uso terapêutico , Fatores de Crescimento de Fibroblastos/efeitos adversos , Fatores de Crescimento de Fibroblastos/farmacologia , Fatores de Crescimento de Fibroblastos/uso terapêutico , Humanos , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Obesidade/complicações , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/farmacologia
20.
Blood ; 135(13): 987-995, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-31977001

RESUMO

Administering asparaginase has always been problematic in adults because most general oncologists who treat adults are not familiar with its usage and toxicity. The toxicity profile of the drug is unique and is not observed with any other chemotherapy agent. Furthermore, asparaginase is almost exclusively used in acute lymphoblastic leukemia (ALL), which is a very rare cancer in adults. Currently, the long-acting pegylated form (pegasparaginase) is the only Escherichia coli-derived asparaginase available in the United States. The use of pediatric regimens is likely to lead to more adult patients receiving multiple doses of pegasparaginase. However, oncologists who treat adults may be reluctant to use pegasparaginase or may unnecessarily discontinue administering it because of certain adverse effects. As a result, the clinical benefit of multiple doses of pegasparaginase will be missed. Despite the fact that pegasparaginase is associated with unique toxicities, the majority are nonfatal, manageable, and reversible. Here, we describe real-life cases of adults with ALL who were treated with pediatric-inspired regimens that incorporated pegasparaginase to illustrate the management of several pegasparaginase-associated adverse effects and guide whether and how to continue the drug.


Assuntos
Antineoplásicos/efeitos adversos , Asparaginase/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Polietilenoglicóis/efeitos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Humanos , Polietilenoglicóis/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
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