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1.
Reumatol Clin (Engl Ed) ; 17(9): 491-493, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34756308

RESUMO

SARS-COV-2 infection has spread worldwide since it originated in December 2019, in Wuhan, China. The pandemic has largely demonstrated the resilience of the world's health systems and is the greatest health emergency since World War II. There is no single therapeutic approach to the treatment of COVID-19 and the associated immune disorder. The lack of randomised clinical trials (RCTs) has led different countries to tackle the disease based on case series, or from results of observational studies with off-label drugs. We as rheumatologists in general, and specifically rheumatology fellows, have been on the front line of the pandemic, modifying our activities and altering our training itinerary. We have attended patients, we have learned about the management of the disease and from our previous experience with drugs for arthritis and giant cell arteritis, we have used these drugs to treat COVID-19.


Assuntos
Antivirais/uso terapêutico , Fatores Biológicos/uso terapêutico , COVID-19/tratamento farmacológico , Imunossupressores/uso terapêutico , Papel do Médico , Reumatologistas , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , COVID-19/complicações , COVID-19/epidemiologia , COVID-19/imunologia , Quimioterapia Combinada , Educação de Pós-Graduação em Medicina , Bolsas de Estudo , Saúde Global , Humanos , Hospedeiro Imunocomprometido , Infecções Oportunistas/complicações , Infecções Oportunistas/tratamento farmacológico , Infecções Oportunistas/imunologia , Equipe de Assistência ao Paciente/organização & administração , Padrões de Prática Médica , Doenças Reumáticas/complicações , Doenças Reumáticas/tratamento farmacológico , Doenças Reumáticas/imunologia , Reumatologistas/educação , Reumatologistas/organização & administração , Reumatologia/educação , Reumatologia/métodos , Reumatologia/organização & administração , Espanha/epidemiologia
2.
BioDrugs ; 35(6): 715-733, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34797516

RESUMO

BACKGROUND AND AIMS: Immunogenicity with formation of anti-drug antibodies (ADA) to biologics is an important reason for treatment failure in inflammatory bowel disease (IBD). Our aim was to assess the rate of ADA, the effect of combination therapy with immunomodulators on ADA and the influence of ADA on efficacy and safety of biologics for IBD treatment. METHODS: MEDLINE, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to April 2020 for trials of biologics that assessed immunogenicity. The overall certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). The primary outcome was rate of ADA. Secondary outcomes included efficacy and safety outcomes among patients with detectable versus undetectable ADA. For dichotomous outcomes, pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated. RESULTS: Data from 68 studies were analyzed and 33 studies (5850 patients) were included in the meta-analysis. Pooled ADA rates for biologic monotherapy were 28.0% for infliximab, 7.5% for adalimumab, 3.8% for golimumab, 10.9% for certolizumab, 6.2% for ustekinumab and 16.0% for natalizumab. Pooled ADA rates were 8.4% for vedolizumab and 5.0% for etrolizumab for combo- and monotherapy combined. In all biologics, ADA rates were underestimated by use of drug-sensitive ADA assays and higher dose and/or frequency. ADA rate was significantly reduced in patients treated with combination therapy for infliximab (RR 0.52; 95% CI 0.44-0.62), adalimumab (RR 0.31; 95% CI 0.14-0.69), golimumab (RR 0.29; 95% CI 0.10-0.83), certolizumab pegol (RR 0.30; 95% CI 0.14-0.67) and natalizumab (RR 0.20; 95% CI 0.11-0. 39). ADA to infliximab were associated with lower clinical response rates (RR 0.75; 95% CI 0.61-0.91) and higher rates of infusion reactions (RR 2.36; 95% CI 1.85-3.01). CONCLUSIONS: Differences in analytical methods to detect ADA hamper comparison of true ADA rates across biologics in IBD. Use of combination therapy with immunomodulators appeared to reduce ADA positivity for most biologics. For infliximab, ADA were associated with reduced drug efficacy and increased adverse events.


Assuntos
Formação de Anticorpos , Doenças Inflamatórias Intestinais , Adalimumab/uso terapêutico , Fatores Biológicos , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Infliximab/uso terapêutico
3.
Medicine (Baltimore) ; 100(40): e27368, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34622837

RESUMO

BACKGROUND: Biological therapy is effective for the treatment of psoriasis and psoriatic arthritis; however, adverse effects related to immunosuppression, such as viral infections, have been reported. Amongst these infections, herpes zoster (HZ) is common. OBJECTIVE: To evaluate the risk of HZ in psoriasis and psoriatic arthritis patients treated with biological therapy. DATA SOURCES: A comprehensive literature search of PubMed, Embase, and Web of Science was performed using certain keywords until October 9, 2020. Nine studies were included after a detailed assessment. STUDY ELIGIBILITY CRITERIA: The eligibility criteria included randomized controlled trials (RCTs) and observational studies of patients with psoriasis or psoriatic arthritis treated with biological therapies; compared with non-biological therapies, non-biological systemic therapies, or controls; with the incidence of HZ reported in case and control groups. The Cochrane risk of bias tool and Newcastle-Ottawa scale were used to assess the quality of the RCTs and observational studies, respectively. Data were extracted from 9 eligible studies and then analyzed using Stata software (Version 12.0). RESULTS: The risk of HZ in biological therapies was higher than that in non-biological (odds ratios [OR]: 1.48; 95% confidence interval [CI]: 1.18-1.86; I2 = 0%) and non-biological systemic (OR: 1.32; 95% CI: 1.02-1.71; I2 = 0%) therapies. Furthermore, the risk of HZ associated with tumor necrosis factor-α inhibitors increased significantly (OR: 1.50; 95% CI: 1.11-2.02; I2 = 0%). Notably, infliximab (OR: 2.43; 95% CI: 1.31-4.50; I2 = 0%) and etanercept (OR: 1.65; 95% CI: 1.07-2.56; I2 = 0%) increased the risk of HZ, while adalimumab (OR: 1.21; 95% CI: 0.64-2.30; I2 = 0%), ustekinumab (OR: 2.20; 95% CI: 0.89-5.44; I2 = 0%), alefacept (OR: 1.46; 95% CI: 0.20-10.47; I2 = 0%), and efalizumab (OR: 1.58; 95% CI: 0.22-11.34; I2 = 0%) did not. LIMITATIONS: Few RCTs have reported HZ incidents; thus, our results require confirmation via large-scale RCTs. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Biological therapies, especially tumor necrosis factor-α inhibitors, may lead to the risk of HZ in psoriasis and psoriatic arthritis patients. Amongst these agents, infliximab and etanercept have been shown to significantly increase the risk of HZ. Additionally, younger age and female sex may be risk factors. SYSTEMATIC REVIEW REGISTRATION NUMBER: INPLASY202110027.


Assuntos
Antirreumáticos/efeitos adversos , Artrite Psoriásica/tratamento farmacológico , Fatores Biológicos/efeitos adversos , Herpes Zoster/induzido quimicamente , Adulto , Idoso , Antirreumáticos/administração & dosagem , Fatores Biológicos/administração & dosagem , Feminino , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco
4.
Molecules ; 26(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34641329

RESUMO

The antioxidant activity of food compounds is one of the properties generating the most interest, due to its health benefits and correlation with the prevention of chronic disease. This activity is usually measured using in vitro assays, which cannot predict in vivo effects or mechanisms of action. The objective of this study was to evaluate the in vivo protective effects of six phenolic compounds (naringenin, apigenin, rutin, oleuropein, chlorogenic acid, and curcumin) and three carotenoids (lycopene B, ß-carotene, and astaxanthin) naturally present in foods using a zebrafish embryo model. The zebrafish embryo was pretreated with each of the nine antioxidant compounds and then exposed to tert-butyl hydroperoxide (tBOOH), a known inducer of oxidative stress in zebrafish. Significant differences were determined by comparing the concentration-response of the tBOOH induced lethality and dysmorphogenesis against the pretreated embryos with the antioxidant compounds. A protective effect of each compound, except ß-carotene, against oxidative-stress-induced lethality was found. Furthermore, apigenin, rutin, and curcumin also showed protective effects against dysmorphogenesis. On the other hand, ß-carotene exhibited increased lethality and dysmorphogenesis compared to the tBOOH treatment alone.


Assuntos
Antioxidantes/administração & dosagem , Fatores Biológicos/administração & dosagem , Carotenoides/administração & dosagem , Polifenóis/administração & dosagem , Peixe-Zebra/embriologia , terc-Butil Hidroperóxido/efeitos adversos , Animais , Antioxidantes/farmacologia , Apigenina/administração & dosagem , Apigenina/farmacologia , Fatores Biológicos/farmacologia , Carotenoides/farmacologia , Curcumina/administração & dosagem , Curcumina/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Embrião não Mamífero/efeitos dos fármacos , Desenvolvimento Embrionário/efeitos dos fármacos , Flavanonas/administração & dosagem , Flavanonas/farmacologia , Licopeno/administração & dosagem , Licopeno/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Polifenóis/farmacologia , Xantofilas/administração & dosagem , Xantofilas/farmacologia , beta Caroteno/administração & dosagem , beta Caroteno/efeitos adversos , beta Caroteno/farmacologia
5.
PLoS One ; 16(10): e0258607, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648570

RESUMO

Staphylococcus aureus and Methicillin-resistant S. aureus (MRSA) remains one of the major concerns of healthcare associated and community-onset infections worldwide. The number of cases of treatment failure for infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, Acrophialophora levis, a thermophilous fungus species, showed antibacterial activity, namely against S. aureus and clinical MRSA strains. The ethyl acetate extract of culture filtrate was found to display significant activity against S. aureus and MRSA with a minimum inhibitory concentration (MIC) of 1 µg/mL and 4 µg/mL, respectively. Scanning electron micrographs demonstrated drastic changes in the cellular architecture of metabolite treated cells of S. aureus and an MRSA clinical isolate. Cell wall disruption, membrane lysis and probable leakage of cytoplasmic are hallmarks of the antibacterial effect of fungal metabolites against MRSA. The ethyl acetate extract also showed strong antioxidant activity using two different complementary free radicals scavenging methods, DPPH and ABTS with efficiency of 55% and 47% at 1 mg/mL, respectively. The total phenolic and flavonoid content was found to be 50 mg/GAE and 20 mg/CAE, respectively. More than ten metabolites from different classes were identified: phenolic acids, phenylpropanoids, sesquiterpenes, tannins, lignans and flavonoids. In conclusion, the significant antibacterial activity renders this fungal strain as a bioresource for natural compounds an interesting alternative against resistant bacteria.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Fatores Biológicos/farmacologia , Staphylococcus aureus Resistente à Meticilina/ultraestrutura , Sordariales/química , Acetatos/química , Antibacterianos/química , Antioxidantes/química , Fatores Biológicos/química , Flavonoides/isolamento & purificação , Hidroxibenzoatos/isolamento & purificação , Índia , Lignanas/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Sesquiterpenos/isolamento & purificação , Taninos/isolamento & purificação
6.
Immunol Allergy Clin North Am ; 41(4): 639-652, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34602234

RESUMO

Biologics are protein-based pharmaceuticals derived from living organisms or their proteins. We discuss the mechanism of action for currently approved biologics and a give summary of the studies on immune suppression from biologics. Most of these studies have been conducted with rheumatology patients, and many in adults. Their relevance for children is explored and existing gaps in data for children are highlighted.


Assuntos
Fatores Biológicos , Produtos Biológicos , Adulto , Produtos Biológicos/uso terapêutico , Criança , Humanos
7.
Molecules ; 26(19)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34641295

RESUMO

Due to sedentary lifestyle and harsh environmental conditions, gorgonian coral extracts are recognized as a rich source of novel compounds with various biological activities, of interest to the pharmaceutical and cosmetic industries. The presented study aimed to perform chemical screening of organic extracts and semi-purified fractions obtained from the common Adriatic gorgonian, sea fan, Eunicella cavolini (Koch, 1887) and explore its abilities to exert different biological effects in vitro. Qualitative chemical evaluation revealed the presence of several classes of secondary metabolites extended with mass spectrometry analysis and tentative dereplication by using Global Natural Product Social Molecular Networking online platform (GNPS). Furthermore, fractions F4 and F3 showed the highest phenolic (3.28 ± 0.04 mg GAE/g sample) and carotene (23.11 ± 2.48 mg ß-CA/g sample) content, respectively. The fraction F3 inhibited 50% of DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) and ABTS (2,2'-azino-bis (3-ethylbenzthiazolin-6-yl) sulfonic acid) radicals at the concentrations of 767.09 ± 11.57 and 157.16 ± 10.83 µg/mL, respectively. The highest anti-inflammatory potential was exhibited by F2 (IC50 = 198.70 ± 28.77 µg/mL) regarding the inhibition of albumin denaturation and F1 (IC50 = 254.49 ± 49.17 µg/mL) in terms of soybean lipoxygenase inhibition. In addition, the most pronounced antiproliferative effects were observed for all samples (IC50 ranging from 0.82 ± 0.14-231.18 ± 46.13 µg/mL) against several carcinoma cell lines, but also towards non-transformed human fibroblasts pointing to a generally cytotoxic effect. In addition, the antibacterial activity was tested by broth microdilution assay against three human pathogenic bacteria: Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. The latter was the most affected by fractions F2 and F3. Finally, further purification, isolation and characterization of pure compounds from the most active fractions are under investigation.


Assuntos
Antozoários/química , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Fatores Biológicos/farmacologia , Animais , Antibacterianos/química , Antibacterianos/isolamento & purificação , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Fatores Biológicos/química , Fatores Biológicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Células Hep G2 , Humanos , Células MCF-7 , Espectrometria de Massas , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pseudomonas aeruginosa , Metabolismo Secundário , Staphylococcus aureus/efeitos dos fármacos
8.
Breast Cancer Res Treat ; 190(3): 403-413, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34596798

RESUMO

PURPOSE: Neurotensin receptor-1 (NTS1) is increasingly recognized as a potential target in diverse tumors including breast cancer, but factors associated with NTS1 expression have not been fully clarified. METHODS: We studied NTS1 expression using the Tissue MicroArray (TMA) of primary breast tumors from Institut Bergonié. We also studied association between NTS1 expression and clinical, pathological, and biological parameters, as well as patient outcomes. RESULTS: Out of 1419 primary breast tumors, moderate to strong positivity for NTS1 (≥ 10% of tumoral cells stained) was seen in 459 samples (32.4%). NTS1 staining was cytoplasmic in 304 tumors and nuclear in 155 tumors, a distribution which appeared mutually exclusive. Cytoplasmic overexpression of NTS1 was present in 21.5% of all breast tumors. In multivariate analysis, factors associated with cytoplasmic overexpression of NTS1 in breast cancer samples were higher tumor grade, Ki67 ≥ 20%, and higher pT stage. Cytoplasmic NTS1 was more frequent in tumors other than luminal A (30% versus 17.3%; p < 0.0001). Contrastingly, the main "correlates" of a nuclear location of NTS1 were estrogen receptor (ER) positivity, low E&E (Elston and Ellis) grade, Ki67 < 20%, and lower pT stage. In NTS1-positive samples, cytoplasmic expression of NTS1 was associated with shorter 10-year metastasis-free interval (p = 0.033) compared to NTS1 nuclear staining. Ancillary analysis showed NTS1 expression in 73% of invaded lymph nodes from NTS1-positive primaries. CONCLUSION: NTS1 overexpression was found in about one-third of breast tumors from patients undergoing primary surgery with two distinct patterns of distribution, cytoplasmic distribution being more frequent in aggressive subtypes. These findings encourage the development of NTS1-targeting strategy, including radiopharmaceuticals for imaging and therapy.


Assuntos
Neoplasias da Mama , Receptores de Neurotensina , Fatores Biológicos , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Feminino , Humanos , Compostos Radiofarmacêuticos , Receptores de Neurotensina/genética
9.
Molecules ; 26(19)2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34641422

RESUMO

Terminalia catappa L. (tropical almond) is a nutritious fruit found mainly in the tropics. This study is aimed to establish the naturally biotransformed molecules and identify the probiotic agents facilitating the fermentation. The aqueous extracts from both the unfermented and fermented T. catappa nuts were subjected to gas chromatography/mass spectrometry (GC/MS) analysis. Syringol (6.03%), glutamine (1.71%), methyl laurate (1.79%), methyl palmitate (1.53%), palmitic acid (5.20%), palmitoleic acid (2.80%), and methyl oleate (2.97%) were detected in the unfermented nuts of the T. catappa. Additionally, two of these natural compounds (palmitic acid (4.19%) and palmitoleic acid (1.48%)) survived the fermentation process to emerge in the fermented seeds. The other natural compounds were biotransformed into 2,3-butanediol (1.81%), butyric acid (16.20%), propane-1,3-diol (19.66%), neoheptanol (2.89%), 2-piperidinone (6.63%), palmitoleic acid (1.18%), formamide, n-(p-hydroxyphenethyl)- (2.80%), and cis-vaccenic acid (1.69%) that newly emerged in the fermented seeds. The phytochemical compounds are likely carbon sources for the organisms facilitating the biotransformed molecules and product production. Four (4) potential probiotic bacteria strains, namely, Probt B1a, Probt B2a, Probt B4a, and Probt B4b, were isolated from the fermented nut. Enterococcus faecum, and Enterococcus faecalis were the organisms identified as driving the fermentation of the seeds. All strains were gram-positive, catalase-negative, and non-hemolytic, which suggests their harmless nature. N-(p-hydroxyphenethyl)-) was associated with fermentation for the first time, and neoheptanol was discovered as the main alcoholic molecule formed during the fermentation of the seeds. This fermentation is a handy tool for bio-transforming compounds in raw food sources into compounds with nutritious and therapeutic potentials.


Assuntos
Fatores Biológicos/química , Fermentação , Frutas/química , Nozes/química , Extratos Vegetais/química , Probióticos/química , Terminalia/química , Enterococcus faecalis/crescimento & desenvolvimento , Enterococcus faecium/crescimento & desenvolvimento , Sementes/química
10.
PLoS One ; 16(10): e0258800, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34665824

RESUMO

BACKGROUND: Diabetes mellitus (DM) and chronic kidney disease (CKD) are common causes of morbidity and mortality. Flaxseed contains several bioactive compounds that have been shown to possess anti-inflammatory and antioxidative properties. The aim of the present study was to investigate the possible effect of flaxseed in diabetic rats with adenine-induced CKD. METHODS: Male Wister rats (n = 48) were randomly divided into seven equal groups and treated for 33 consecutive days as follows: G1: control. G2 adenine, G3: streptozotocin (STZ), G4: flaxseed, G5: adenine+flaxseed, G6: STZ+flaxseed, G7: adenine+STZ+flaxseed). DM or CKD were experimentally induced by a single intraperitoneal injection of streptozotocin (STZ) or by adenine via oral gavage, respectively. RESULTS: Rats fed adenine alone exhibited several changes including decreased body weight, increased food and water intake and urine output, increased urinary albumin/creatinine ratio. They also showed an increase in plasma urea and, creatinine, indoxyl sulfate, neutrophil gelatinase-associated lipocalin and cystatin C, and a decrease in renalase activity. These were associated with significant changes in inflammatory and oxidative biomarkers, e.g., increase in 8-isoprostane, 8 -hydroxy -2-deoxy guanosine and decrease in antioxidant enzymes, as well as increase in interleukins 1ß and 6, and NF-κB, and a decrease in interlukin-10. Histopathologically, there was increased tubular necrosis and fibrosis. Concomitant administration of adenine and STZ further worsened the renal damage induced by adenine alone. Flaxseed significantly ameliorated the changes caused by adenine and STZ, given either singly or in combination. CONCLUSION: These findings suggest that flaxseed is a potential therapeutic agent in attenuating the progression of CKD in diabetes.


Assuntos
Anti-Inflamatórios/administração & dosagem , Fatores Biológicos/administração & dosagem , Diabetes Mellitus Experimental/tratamento farmacológico , Linho/química , Insuficiência Renal Crônica/tratamento farmacológico , Sementes/química , Adenina/efeitos adversos , Animais , Anti-Inflamatórios/farmacologia , Fatores Biológicos/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Modelos Animais de Doenças , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Insuficiência Renal Crônica/induzido quimicamente , Estreptozocina/efeitos adversos , Resultado do Tratamento
12.
Tuberk Toraks ; 69(3): 433-436, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34581170

RESUMO

As the COVID-19 pandemic continues, case reports have been published where patients with severe asthma using biological agents survived with a mild course of illness and encouraged the continuation of biological therapies in patients with severe asthma. However, contrary to previous information, a more severe course of COVID-19 has recently been reported in severe asthmatics using biological therapy compared to the general population. To evaluate the COVID-19 rate and disease severity in severe asthmatics using biological agents. A retrospective study was conducted in patients with severe asthma treated with biological agents. Data concerning whether the subjects had contracted COVID-19 and the severity of the disease were evaluated. Eihgty-four severe asthmatics using biological agents (omalizumab or mepolizumab) aged 48.3 ± 10.6 years (mean ± standard deviation) with female/male ratio: 53 (63.1%)/31 (36.9%) were included in the study. Among participants 13 (15.5%) had contracted COVID-19. The course of COVID-19 was mild in five (38.5%) and moderate in eight patients (61.5%), while none of the patients had a severe course of COVID-19. Mechanical ventilation or intensive care follow-up was not required in any of the six patients (46.2%) who were treated as inpatients. All participants survived COVID-19 in full recovery and no deaths occurred in the cases. A higher rate of COVID-19 was found in patients with severe asthma using biologics compared to those reported in previous reports. However, all patients with COVID-19 have a mild to moderate disease course.


Assuntos
Antiasmáticos , Asma , COVID-19 , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Asma/epidemiologia , Fatores Biológicos/uso terapêutico , Feminino , Humanos , Masculino , Pandemias , Estudos Retrospectivos , SARS-CoV-2 , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Tohoku J Exp Med ; 255(1): 57-60, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34588346

RESUMO

Pediatric inflammatory bowel disease is associated with growth failure due to chronic inflammation, nutrient disorder, and the side effects of drugs, such as corticosteroids. Biological agents are therapeutic drugs that significantly improve the prognosis of patients with inflammatory bowel disease. The effectiveness of ustekinumab has been reported in the management of adult patients with inflammatory bowel disease. There are very few reports regarding the effectiveness and safety of ustekinumab in pediatric patients with inflammatory bowel disease, especially those who are biologically naive. A 10-year-old girl presented with chronic abdominal pain, diarrhea, and weight loss. Colonoscopy showed a longitudinal ulcer and cobblestone appearance in the ileum and discontinuous inflammation of the colon; therefore, she was diagnosed with Crohn's disease. She was prescribed a fat-restricted diet, elemental diet, 5-aminosalicylic acid, transient prednisolone, and ustekinumab. She achieved clinical and endoscopic remission based on the weighted Pediatric Crohn's Disease Activity Index, fecal calprotectin, and colonoscopy findings at week 75. This patient developed no adverse events, such as infusion reaction or susceptibility to infection over the 75 weeks. The use of ustekinumab as the first biological agent may be an effective and safe treatment for pediatric Crohn's disease.


Assuntos
Doença de Crohn/terapia , Ustekinumab/uso terapêutico , Fatores Biológicos/uso terapêutico , Criança , Colonoscopia , Terapia Combinada , Doença de Crohn/diagnóstico por imagem , Dieta com Restrição de Gorduras , Feminino , Alimentos Formulados , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Humanos , Mesalamina/administração & dosagem , Prednisolona/administração & dosagem , Indução de Remissão , Resultado do Tratamento , Ustekinumab/administração & dosagem
14.
Clin Pharmacol Ther ; 110(5): 1311-1317, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34472087

RESUMO

The relevance of biological therapies for an increasing number of conditions is on the rise. Following the expiry of the initial period of market exclusivity, many of these successful therapies have seen the arrival of biosimilars on the market. The clear identification of the precise medicine responsible for an adverse drug reaction (ADR) report is an important element for pharmacovigilance, allowing timely detection of potential product-specific safety signals. We looked at the identifiability of biologicals up to the level of commercial product name in ADR reports received from European clinical practice between 2011 and December 2019. A good level of identification (91.5%) was observed overall, but at the same time a downward trend was observed in the last 5 years. This reduction in the level of identifiability of biological products (originators and biosimilars) at the commercial name level in general was driven by five widely used substances, whereas the identification of all other biologics stayed consistent over time (at over 90%). We observed that those five substances were used mostly within oncology. The introduction of the first biosimilar in the market did not appear to affect their identifiability. These results show that although the general level of identification at the commercial product name level in ADRs in Europe is robust and generally stable over time, decreasing trends can be down to a few commonly used substances, which need to be monitored to reverse the trend.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Fatores Biológicos/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , União Europeia , Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/normas , Fatores Biológicos/normas , Medicamentos Biossimilares/normas , Bases de Dados Factuais/estatística & dados numéricos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , União Europeia/estatística & dados numéricos , Humanos , Farmacovigilância , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Rituximab/efeitos adversos
15.
Int J Mol Sci ; 22(18)2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34576324

RESUMO

Acetylsalicylic acid (aspirin) exhibits a broad range of activities, including analgesic, antipyretic, and antiplatelet properties. Recent clinical studies also recommend aspirin prophylaxis in women with a high risk of pre-eclampsia, a major complication of pregnancy characterized by hypertension. We investigated the effect of aspirin on mesenteric resistance arteries and found outdiscovered the molecular mechanism underlying this action. Aspirin (10-12-10-6 M) was tested on pregnant rat mesenteric resistance arteries by a pressurized arteriography. Aspirin was investigated in the presence of several inhibitors of: (a) nitric oxide synthase (L-NAME 2 × 10-4 M); (b) cyclooxygenase (Indomethacin, 10-5 M); (c) Ca2+-activated K+ channels (Kca): small conductance (SKca, Apamin, 10-7 M), intermediate conductance (IKca, TRAM34, 10-5 M), and big conductance (BKca, paxilline, 10-5 M); and (d) endothelial-derived hyperpolarizing factor (high KCl, 80 mM). Aspirin caused a concentration-dependent vasodilation. Aspirin-vasodilation was abolished by removal of endothelium or by high KCl. Furthermore, preincubation with either apamin plus TRAM-34 or paxillin significantly attenuated aspirin vasodilation (p < 0.05). For the first time, we showed that aspirin induced endothelium-dependent vasodilation in mesenteric resistance arteries through the endothelial-derived hyperpolarizing factor (EDHF) and calcium-activated potassium channels. By activating this molecular mechanism, aspirin may lower peripheral vascular resistance and be beneficial in pregnancies complicated by hypertension.


Assuntos
Aspirina/uso terapêutico , Fatores Biológicos/metabolismo , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Animais , Fatores Biológicos/genética , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Ratos , Ratos Sprague-Dawley
17.
Curr Opin Rheumatol ; 33(5): 431-445, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397605

RESUMO

PURPOSE OF REVIEW: Given the role of inflammation in severe forms of COVID-19, glucocorticoids and disease-modifying antirheumatic drugs (DMARDs) have been assessed as potential COVID-19 therapies. RECENT FINDINGS: Randomized controlled trials (RCTs) have shown that glucocorticoids reduce mortality in severe COVID-19. RCTs of DMARDs have shown mixed results varying on intervention and inclusion criteria. DMARDs, including colchicine or biologic agents, may improve COVID-19 outcomes in specific patient populations. SUMMARY: Glucocorticoids are an effective treatment for the management of severe COVID-19. Further studies are needed to better define the patient populations who could benefit from DMARD use, as well as provide guidance regarding the timing of these interventions.


Assuntos
Antirreumáticos , Artrite Reumatoide , COVID-19 , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fatores Biológicos/uso terapêutico , COVID-19/tratamento farmacológico , Humanos , SARS-CoV-2
18.
J Cosmet Dermatol ; 20(10): 3098-3102, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34365714

RESUMO

BACKGROUND: Since March 2020, the coronavirus disease 2019 (COVID-19) pandemic has been ongoing all around the world with a wide range of clinical course including asymptomatic cases to severe and fatal respiratory tract disease. Patients on immunosuppressive treatments were predicted to be more susceptible to COVID-19. AIMS: It was aimed to assess treatment continuity, the course of psoriasis and the course and clinical features of COVID-19 in patients treated with biological agents for psoriasis at the early initial period of COVID-19 pandemic. PATIENTS/METHODS: Patients treated with biological agents for psoriasis at our institute were contacted by phone between 1 and 10 July 2020 and fulfilled a questionnaire about their continuity to psoriasis treatments, clinical course of psoriasis, and any suspicion/diagnosis of COVID-19. RESULTS: A total of 106 patients, 41 females and 65 males, were enrolled. Mean age of the patients was 46.1 ± 12.1 years (range: 19-77). Median duration of psoriasis was 18 years (min-max: 1 month-51 years). Twenty-four patients (22.6%) were using tumor necrosis alpha inhibitors (ETA:1, IFX:19, ADA:4), whereas 82 patients (77.4%) were using interleukin (IL) 12/23 or IL-17 inhibitors (UST:48, SECU:30, IXE:4). Seventy-six patients (71.7%) continued the treatment, whereas 30 patients (28.3%) interrupted the treatment voluntarily. Twenty out of 30 patients (66.6%) who interrupted the treatment had an exacerbation of psoriasis. None of the patients were diagnosed with COVID-19 in the study period. CONCLUSION: Patients with psoriasis who received biological therapy continued their treatment at a high rate during the early period of the COVID-19 pandemic. No COVID-19 diagnosis was made among patients whether they continued or discontinued treatment. Recurrence and exacerbation of psoriasis in a significant proportion of patients who interrupted treatment and absence of COVID-19 diagnosis in each group support the importance and safety of continuity of biological treatments for psoriasis in COVID-19 era.


Assuntos
Produtos Biológicos , COVID-19 , Psoríase , Adulto , Idoso , Atitude , Fatores Biológicos/uso terapêutico , Produtos Biológicos/uso terapêutico , Teste para COVID-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Psoríase/tratamento farmacológico , Psoríase/epidemiologia , SARS-CoV-2 , Adulto Jovem
19.
J Med Econ ; 24(1): 1134-1142, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34415224

RESUMO

AIM: The purpose of this manuscript was to illustrate the impact of the place in the treatment sequence on the cost and cost-effectiveness of different biologics for patients with moderate-to-severe plaque psoriasis. MATERIALS AND METHODS: We developed a treatment sequence model and focused on seven different biological treatment options and 840 combinations of treatment sequences. The model converted cost of treatment to a cost per responder by dividing treatment cost by expected number of patients achieving PASI100 after 52 weeks of treatment. We used Spanish ex-factory price levels, dosing recommendations and real-world data on drug survival to calculate the treatment costs. RESULTS: The most cost-effective treatment sequence was brodalumab-risankizumab-guselkumab-ixekizumab, with a cost per responder of €139,281 during the first five years of treatment. In comparison, if brodalumab was not recommended as first-line therapy, total costs would increase by 7.4% to €149,616. If brodalumab was not recommended as any of the first four lines of treatment, total costs would increase by 13.1% to €157,527 relative to the most cost-effective treatment sequence. CONCLUSIONS: A sequential therapy model may improve efficiency in the treatment of psoriasis. According to our results, brodalumab as the first-line therapy in Spain leads to the most cost-effective treatment sequence.


Assuntos
Psoríase , Fatores Biológicos , Terapia Biológica , Humanos , Psoríase/tratamento farmacológico , Índice de Gravidade de Doença , Espanha
20.
Sci Rep ; 11(1): 16393, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385564

RESUMO

Immune response to biologics treatment, while widely reported, yet fails to correlate with clinical outcomes and assay to assay comparison is often not possible. Hence, we developed a new peptide based-detection assay to stratify pediatric patients with juvenile idiopathic arthritis (JIA) or chronic non-infectious uveitis (CNU) and monitor anti-drug antibodies (ADAbs) formed as part of an immune response to treatment with the fully human monoclonal therapeutic antibody Adalimumab. Adalimumab derived synthetic peptides were optimized for maximum immunogenicity and were tested by SP-ELISA on a development cohort of 18 JIA and CNU treated patients. The two best performing peptides able to differentiate patient groups were selected for evaluation with a larger scale ELISA testing on a total of 29 sera from pediatric patients with JIA or CNU. The results of this peptide-based assay were compared to an in-house developed SPR biosensor ADAbs assay and a commercially available bridging ELISA. The first peptide, termed HC3, was able to positively detect ADAbs in 7 out of the 29 sera, while the second peptide, called LC3, was able to detect ADAbs in 11 out of 29 sera in the evaluation group. Following statistical data evaluation, it has been found that the detection of ADAbs using the peptide-based ELISA assay positively correlates with disease progression and remission. Two synthetic peptides derived from Adalimumab may provide a beneficial tool to clinicians for monitoring patient response to such treatment and taking informed decisions for treatment alternatives.


Assuntos
Adalimumab/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite Juvenil/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Imunidade/efeitos dos fármacos , Peptídeos/uso terapêutico , Uveíte/tratamento farmacológico , Sequência de Aminoácidos , Antirreumáticos/uso terapêutico , Fatores Biológicos/uso terapêutico , Criança , Estudos de Coortes , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino
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