RESUMO
Objective To investigate the causes of false-positive results in the 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI-04) PET/CT imaging. Methods The imaging data of 547 patients undergoing 68Ga-FAPI-04 PET/CT examination in the Department of Nuclear Medicine of the Affiliated Hospital of Southwest Medical University from September 2020 to May 2021 were retrospectively collected.Two experienced nuclear medicine diagnostic physicians analyzed the clinical data,relevant imaging examinations,laboratory examinations,pathological results and follow-up results of the patients with false-positive results. Results The 68Ga-FAPI-04 PET/CT imaging of 547 patients showed false-positive results in 99 (18.1%) patients,including 56 males and 43 females.The postoperative pathological examination confirmed false-positive results in 13 patients,including 1 patient of thyroiditis,2 patients of pulmonary tuberculosis,1 patient of bone tuberculosis,2 patients of pulmonary inflammatory pseudotumor,1 patient of pulmonary sarcoidosis,1 patient of pulmonary benign fibroma,1 patient of organic pneumonia,2 patients of renal angiomyolipoma,1 patient of mass pancreatitis,and 1 patient of pancreatic mucinous cystadenoma.The medical history,relevant imaging examination,and long-term follow-up confirmed false-positive results in 86 patients.Specifically,the false-positive uptake in the neck,chest,abdomen,bone joint,and skin occurred in 8 (9.3%),13 (15.1%),5 (5.8%),57 (66.3%),and 3 (3.5%) patients,respectively.Inflammation-related uptake appeared in 83 (83.8%) patients with false-positive imaging results,of which arthritis (23 patients) and osteophyte (29 patients) were the most common.Sixteen (16.2%) patients showed the false-positive uptake related to fibroblasts. Conclusion 68Ga-FAPI-04 PET/CT imaging will show non-malignant tumor false-positive results,which are mainly associated with inflammation and fibroblasts.
Assuntos
Feminino , Masculino , Humanos , Radioisótopos de Gálio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Angiomiolipoma , Estudos Retrospectivos , Neoplasias Renais , Fibroblastos , Inflamação , Fluordesoxiglucose F18 , QuinolinasRESUMO
A strategy combining collision cross section(CCS) prediction and quantitative structure-retention relationship(QSRR) model for quinoline and isoquinoline alkaloids was established based on UHPLC-IM-Q-TOF-MS and applied to Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex. The strategy included the following three steps.(1) The molecular features were extracted by the "find features" algorithm.(2) The potential quinoline and isoquinoline alkaloids were screened by filtering the original characteristic ions extracted from Phellodendri Chinensis Cortex and Phellodendri Amurensis Cortex by the established CCS vs m/z prediction interval.(3) According to the retention time of candidate compounds predicted by QSRR model, the chemical constituents were identified in combination with the characteristic fragment ions and pyrolysis law of secondary mass spectrometry. With the strategy, a total of 80 compounds were predicted, and 15 were identified accurately. The strategy is effective for the identification of small analogs of traditional Chinese medicine.
Assuntos
Cromatografia Líquida de Alta Pressão , Algoritmos , Alcaloides , Isoquinolinas , QuinolinasRESUMO
Malaria, one of the major global public health events, is a leading cause of mortality and morbidity among children and adults in tropical and subtropical regions(mainly in sub-Saharan Africa), threatening human health. It is well known that malaria can cause various complications including anemia, blackwater fever, cerebral malaria, and kidney damage. Conventionally, cardiac involvement has not been listed as a common reason affecting morbidity and mortality of malaria, which may be related to ignored cases or insufficient diagnosis. However, the serious clinical consequences such as acute coronary syndrome, heart failure, and malignant arrhythmia caused by malaria have aroused great concern. At present, antimalarials are commonly used for treating malaria in clinical practice. However, inappropriate medication can increase the risk of cardiovascular diseases and cause severe consequences. This review summarized the research advances in the cardiovascular complications including acute myocardial infarction, arrhythmia, hypertension, heart failure, and myocarditis in malaria. The possible mechanisms of cardiovascular diseases caused by malaria were systematically expounded from the hypotheses of cell adhesion, inflammation and cytokines, myocardial apoptosis induced by plasmodium toxin, cardiac injury secondary to acute renal failure, and thrombosis. Furthermore, the effects of quinolines, nucleoprotein synthesis inhibitors, and artemisinin and its derivatives on cardiac structure and function were summarized. Compared with the cardiac toxicity of quinolines in antimalarial therapy, the adverse effects of artemisinin-derived drugs on heart have not been reported in clinical studies. More importantly, the artemisinin-derived drugs demonstrate favorable application prospects in the prevention and treatment of cardiovascular diseases, and are expected to play a role in the treatment of malaria patients with cardiovascular diseases. This review provides reference for the prevention and treatment of malaria-related cardiovascular complications as well as the safe application of antimalarials.
Assuntos
Criança , Adulto , Humanos , Antimaláricos/farmacologia , Doenças Cardiovasculares/tratamento farmacológico , Artemisininas/farmacologia , Quinolinas , Malária Cerebral/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Arritmias Cardíacas/tratamento farmacológicoRESUMO
El uso de moduladores de CFTR en pacientes con fibrosis quística post trasplante pulmonar es un tema todavía controversial. Varias publicaciones reportan los beneficios del modulador elexacaftor/tezacaftor/ivacaftor en los síntomas extrapulmonares de la fibrosis quística, especialmente enfermedad sinusal, síntomas gastrointestinales y diabetes. Un número alto de pacientes debe discontinuar el tratamiento por mala tolerancia, sin embargo, no se describen interacciones de importancia con el tratamiento inmunosupresor. Se debe considerar para su uso los riesgos versus beneficios en forma individual en cada paciente.
The use of CFTR modulators in patients with cystic fibrosis after lung transplantation is still a controversial issue. Several publications report the benefits of the use of the modulator elexacaftor/tezacaftor/ivacaftor on extrapulmonary symptoms of cystic fibrosis, especially sinus disease, gastrointestinal symptoms and diabetes. A high number of patients must discontinue treatment due to poor tolerance; however, no significant interactions with immunosuppressive treatment have been described. The individual risk-benefit of each patient should be considered for its use.
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Humanos , Fibrose Cística/tratamento farmacológico , Pirazóis/uso terapêutico , Piridinas/uso terapêutico , Quinolinas/uso terapêutico , Transplante de Pulmão , Regulador de Condutância Transmembrana em Fibrose Cística , Fibrose Cística/cirurgia , Combinação de Medicamentos , Benzodioxóis/uso terapêutico , Aminofenóis/uso terapêutico , Indóis/uso terapêuticoRESUMO
El montelukast se utiliza ampliamente en el tratamiento de sibilancias recurrentes y/o asma. Están descritas numerosas reacciones adversas medicamentosas (RAM) en niños relacionadas con montelukast; se destacan las neuropsiquiátricas. Realizamos un estudio observacional, retrospectivo, descriptivo, sobre RAM relacionadas con montelukast. Entre enero de 2012 y diciembre de 2017, en la Unidad de Neumonología Pediátrica se trataron con Montelukast 348 pacientes; de ellos, 20 presentaron RAM. Los síntomas más frecuentes fueron insomnio (n = 7), hiperactividad (n = 4), pesadillas (n = 3), dolor abdominal (n = 2) y parestesias en extremidades (n = 2). Se presentaron desde días hasta meses tras iniciar el tratamiento, y desaparecieron tras su suspensión. Se destacan dos pacientes con parestesias en extremidades, síntoma no descrito antes en niños. El 5,7 % de los pacientes tratados con montelukast presentaron RAM que requirieron suspender el tratamiento. Los trastornos del sueño fueron los más frecuentes.
Montelukast is widely used in recurrent wheezing and/or asthma treatment. Several adverse drug reactions (ADRs) have been described in children related to montelukast. Neuropsychiatric reactions are one of the most important. We designed an observational, retrospective, descriptive study on ADRs related to montelukast in the Pediatric Pulmonology Unit, Hospital Universitario Miguel Servet, Zaragoza, Spain. Between January 2012 and December 2017, in the Pediatric Pulmonology Unit, 348 patients were treated with Montelukast; of them, 20 presented RAM. The main symptoms described were insomnia (n = 7), hyperactivity (n = 4), nightmares (n = 3), abdominal pain (n = 2) and paraesthesia in extremities (n = 2). They appeared from the first days to months after the start of treatment and disappeared after stopping it. Two patients presented limb paresthesia, not described previously in children. The 5.7 % of our patients treated with montelukast had ADRs that required treatment discontinuation. Sleep disorders were the most frequent.
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Humanos , Masculino , Feminino , Recém-Nascido , Lactente , Pré-Escolar , Criança , Adolescente , Quinolinas/efeitos adversos , Sulfetos/efeitos adversos , Antiasmáticos/efeitos adversos , Antagonistas de Leucotrienos/efeitos adversos , Ciclopropanos/efeitos adversos , Acetatos/efeitos adversos , Asma/tratamento farmacológico , Transtornos do Sono-Vigília/induzido quimicamente , Estudos RetrospectivosRESUMO
45.7% of Chinese patients with advanced lung adenocarcinoma were reported to harbour sensitizing epidermal growth factor receptor (EGFR) mutations. Limited therapeutic options are left for non-small cell lung cancer (NSCLC) harbouring sensitizing EGFR mutations after failure of EGFR-tyrosine kinase inhibitor (TKI) therapy and chemotherapy, finding effective options for them is an unmet clinic need. Herein we reported a case that till January 12, 2021, an 82-year-old female with sensitizing EGFR-mutant advanced lung adenocarcinoma received a surprising progression-free survival (PFS) benefit of over 21 months from the combination therapy of pembrolizumab and anlotinib after her failure of treatments of osimertinib, chemotherapy and anlotinib-monotherapy. .
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Idoso de 80 Anos ou mais , Feminino , Humanos , Adenocarcinoma de Pulmão/genética , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Pulmonar de Células não Pequenas/genética , Receptores ErbB/genética , Indóis , Neoplasias Pulmonares/genética , Mutação , QuinolinasRESUMO
Three compounds, including scolosprine C(1), uracil(2) and hypoxanthine(3), were isolated and purified from the ethyl acetate fraction of centipede by silica gel normal-phase column chromatography, reversed-phase medium pressure preparation chromatography, and high-pressure semi-preparative HPLC. The structure was elucidated through a combination of spectroscopic analyses [such as nuclear magnetic resonance(NMR) and mass spectrometry(MS)] and literature review. Among them, compound 1 was a new quinoline alkaloid. In previous reports, we have described the isolation and structure elucidation of one new and two known quinoline alkaloids. In this paper, we would report the isolation and structure elucidation of scolosprine C in detail.
Assuntos
Animais , Alcaloides , Artrópodes , Quilópodes , QuinolinasRESUMO
Abstract INTRODUCTION: Artemisinin-based combination therapy (ACT), such as artemisinin-piperaquine (AP), dihydroartemisinin-piperaquine (DP), and artemether-lumefantrine (AL), is the first-line treatment for malaria in many malaria-endemic areas. However, we lack a detailed evaluation of the cardiotoxicity of these ACTs. This study aimed to analyze the electrocardiographic effects of these three ACTs in malaria patients. METHODS: We analyzed the clinical data of 89 hospitalized patients with falciparum malaria who had received oral doses of three different ACTs. According to the ACTs administered, these patients were divided into three treatment groups: 27 treated with AP (Artequick), 31 with DP (Artekin), and 31 with AL (Coartem). Electrocardiograms and other indicators were recorded before and after the treatment. The QT interval was calculated using Fridericia's formula (QTcF) and Bazett's formula (QTcB). RESULTS: Both QTcF and QTcB interval prolongation occurred in all three groups. The incidence of such prolongation between the three groups was not significantly different. The incidence of both moderate and severe prolongation was not significantly different between the three groups. The ΔQTcF and ΔQTcB of the three groups were not significantly different. The intra-group comparison showed significant prolongation of QTcF after AL treatment. CONCLUSIONS: Clinically recommended doses of DP, AL, and AP may cause QT prolongation in some malaria patients but do not cause torsades de pointes ventricular tachycardia or other arrhythmias.
Assuntos
Humanos , Malária Falciparum/tratamento farmacológico , Artemisininas/efeitos adversos , Malária/tratamento farmacológico , Antimaláricos/efeitos adversos , Quinolinas , Combinação de Medicamentos , Eletrocardiografia , Artemeter/uso terapêutico , Combinação Arteméter e Lumefantrina/uso terapêuticoRESUMO
BACKGROUND@#Despite the recommendation of inhaled corticosteroids (ICSs) plus long-acting beta 2-agonist (LABA) and leukotriene receptor antagonist (LTRA) or ICS/LTRA as stepwise approaches in asthmatic children, there is a lack of published systematic review comparing the efficacy and safety of the two therapies in children and adolescents aged 4 to 18 years. This study aimed to compare the safety and efficacy of salmeterol/fluticasone (SFC) vs. montelukast (MON), or combination of montelukast and fluticasone (MFC) in children and adolescents aged 4 to 18 years with bronchial asthma.@*METHODS@#A systematic search was conducted in MEDLINE, EMBASE, the Cochrane Library, China BioMedical Literature Database, Chinese National Knowledge Infrastructure, VIP Database for Chinese Technical Periodical, and Wanfang for randomized controlled trials (RCTs) published from inception to May 24, 2021. Interventions are as follows: SFC vs. MON, or combination of MFC, with no limitation of dosage or duration. Primary and secondary outcome measures were as follows: the primary outcome of interest was the risk of asthma exacerbation. Secondary outcomes included risk of hospitalization, pulmonary function, asthma control level, quality of life, and adverse events (AEs). A random-effects (I2 ≥ 50%) or fixed-effects model (I2 < 50%) was used to calculate pooled effect estimates, comparing the outcomes between the intervention and control groups where feasible.@*RESULTS@#Of the 1006 articles identified, 21 studies met the inclusion criteria with 2643 individuals; two were at low risk of bias. As no primary outcomes were similar after an identical treatment duration in the included studies, meta-analysis could not be performed. However, more studies favored SFC, instead of MON, owing to a lower risk of asthma exacerbation in the SFC group. As for secondary outcome, SFC showed a significant improvement of peak expiratory flow (PEF)%pred after 4 weeks compared with MFC (mean difference [MD]: 5.45; 95% confidence interval [CI]: 1.57-9.34; I2 = 95%; P = 0.006). As for asthma control level, SFC also showed a higher full-controlled level (risk ratio [RR]: 1.51; 95% CI: 1.24-1.85; I2 = 0; P < 0.001) and higher childhood asthma control test score after 4 weeks of treatment (MD: 2.30; 95% CI: 1.39-3.21; I2 = 72%; P < 0.001) compared with MFC.@*CONCLUSIONS@#SFC may be more effective than MFC for the treatment of asthma in children and adolescents, especially in improving asthma control level. However, there is insufficient evidence to make firm conclusive statements on the use of SFC or MON in children and adolescents aged 4 to 18 years with asthma. Further research is needed, particularly a combination of good-quality long-term prospective studies and well-designed RCTs.@*PROSPERO REGISTRATION NUMBER@#CRD42019133156.
Assuntos
Adolescente , Criança , Humanos , Acetatos , Administração por Inalação , Corticosteroides/uso terapêutico , Albuterol/uso terapêutico , Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Ciclopropanos , Quimioterapia Combinada , Fluticasona/uso terapêutico , Quinolinas , Xinafoato de Salmeterol/uso terapêutico , SulfetosRESUMO
Abstract Introduction The types of allergic rhinitis are roughly classified based on the causative antigens, disease types, predilection time, and symptom severity. Objective To examine the clinical typing and individualized treatment approach for allergic rhinitis and to determine the optimal treatment method for this disease using various drug combination therapies. Methods A total of 108 participants with allergic rhinitis were divided into three groups based on symptoms. Subsequently, each group was further categorized into four subgroups based on the medications received. The efficacy of the treatments was evaluated using the visual analog scale VAS scores of the total and individual nasal symptoms, decline index of the symptom score, histamine and leukotriene levels, and mRNA and protein expression levels of histamine 1 and cysteinyl leukotriene 1 receptors. Results Loratadine + mometasone furoate and loratadine + mometasone furoate + montelukast significantly improved the sneezing symptom and reduced the histamine levels compared with the other combination therapies (p < 0.05). Meanwhile, montelukast + mometasone furoate and montelukast + mometasone furoate + loratadine considerably improved the nasal obstruction symptom and decreased the leukotriene D4 levels compared with the other combination therapies (p < 0.05). Conclusion Clinical symptom evaluation combined with experimental detection of histamine and leukotriene levels can be an objective and accurate method to clinically classify the allergic rhinitis types. Furthermore, individualized treatment based on allergic rhinitis classification can result in a good treatment efficacy.
Resumo Introdução A rinite alérgica é basicamente classificada de acordo com os antígenos causadores, tipos de doença, peridiocidade e gravidade dos sintomas. Objetivo Avaliar os tipos clínicos e a abordagem terapêutica individualizada para cada tipo de rinite alérgica e determinar o método de tratamento ideal utilizando várias terapias de combinação de fármacos. Método Um total de 108 participantes com rinite alérgica foram divididos em três grupos com base nos sintomas. Posteriormente, cada grupo foi subsequentemente categorizado em quatro subgrupos com base nos medicamentos recebidos. A eficácia dos tratamentos foi avaliada utilizando os escores da escala visual analógica EVA dos sintomas nasais totais e individualmente, índice de declínio do escore de sintomas, níveis de histamina e leucotrienos e níveis de expressão de mRNA e proteína dos receptores de histamina 1 e cisteinil-leucotrieno 1. Resultados As associações entre loratadina + furoato de mometasona, assim como a de loratadina + furoato de mometasona + montelucaste melhoraram significativamente o sintoma de espirros e reduziram os níveis de histamina em comparação às outras terapias combinadas (p < 0,05). Por outro lado, a associação montelucaste + furoato de mometasona, assim como a associação montelucaste + furoato de mometasone + loratadina melhoraram consideravelmente o sintoma de obstrução nasal e diminuíram os níveis de leucotrieno D4 em comparação com as outras combinações (p < 0,05). Conclusão A avaliação clínica dos sintomas combinada com a detecção experimental dos níveis de histamina e leucotrieno pode ser um método objetivo e preciso para classificar clinicamente os tipos de rinite alérgica. Além disso, o tratamento individualizado baseado na classificação da rinite alérgica pode resultar no aumento da eficácia do tratamento.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Histamina/sangue , Leucotrieno D4/sangue , Quimioterapia Combinada/métodos , Medicina de Precisão/métodos , Rinite Alérgica/sangue , Quinolinas/uso terapêutico , Espirro , RNA Mensageiro/genética , Receptores Histamínicos H1/genética , Obstrução Nasal/tratamento farmacológico , Resultado do Tratamento , Loratadina/uso terapêutico , Receptores de Leucotrienos/genética , Antialérgicos/uso terapêutico , Rinite Alérgica/diagnóstico , Rinite Alérgica/tratamento farmacológico , Furoato de Mometasona/uso terapêutico , Acetatos/uso terapêutico , Mucosa NasalRESUMO
Abstract INTRODUCTION: The drugs currently available for leishmaniasis treatment have major limitations. METHODS: In vitro and in vivo studies were performed to evaluate the effect of a quinoline derivative, Hydraqui (7-chloro-4-(3-hydroxy-benzilidenehydrazo)quinoline, against Leishmania amazonensis. In silico analyses of absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters were performed. RESULTS: Hydraqui showed significant in vitro anti-amastigote activity. Also, Hydraqui-treated mice exhibited high efficacy in lesion size (48.3%) and parasitic load (93.8%) reduction, did not cause hepatic and renal toxicity, and showed appropriate ADMET properties. CONCLUSIONS: Hydraqui presents a set of satisfactory criteria for its application as an antileishmanial agent.
Assuntos
Animais , Feminino , Quinolinas/uso terapêutico , Leishmania mexicana/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Antiprotozoários/uso terapêutico , Quinolinas/química , Leishmaniose Cutânea/parasitologia , Modelos Animais de Doenças , Carga Parasitária , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Anlotinib hydrochloride is the only anti-angiogenic, multi-targeted tyrosine kinase inhibitor, which has been approved for non-small cell lung cancer and small cell lung cancer in China. In order to provide guidance for clinical practitioners to use anlotinib hydrochloride safely and efficiently, the Chinese Association for Clinical Oncologists, the Expert Committee of Vascular Targeted Therapy of Chinese Society of Clincal Oncology and the Cancer Targeted Therapy Professional Committee of China Anti-Cancer Association co-organized experts and integrated multiple evidences of Anlotinib Hydrochloride, from both clinical trial, post-marketed clinical data and the associated experiences of experts accumulated in clinical practice, etc. The present consensus covers the clinical data of anlotinib hydrochloride applied in advanced non-small cell lung cancer and small cell lung cancer, and the safety management recommendations.
Assuntos
Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , China , Consenso , Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêuticoRESUMO
Painful diabetic neuropathy (PDN) is a diabetes mellitus complication. Unfortunately, the mechanisms underlying PDN are still poorly understood. Adenosine triphosphate (ATP)-gated P2X7 receptor (P2X7R) plays a pivotal role in non-diabetic neuropathic pain, but little is known about its effects on streptozotocin (STZ)-induced peripheral neuropathy. Here, we explored whether spinal cord P2X7R was correlated with the generation of mechanical allodynia (MA) in STZ-induced type 1 diabetic neuropathy in mice. MA was assessed by measuring paw withdrawal thresholds and western blotting. Immunohistochemistry was applied to analyze the protein expression levels and localization of P2X7R. STZ-induced mice expressed increased P2X7R in the dorsal horn of the lumbar spinal cord during MA. Mice injected intrathecally with a selective antagonist of P2X7R and P2X7R knockout (KO) mice both presented attenuated progression of MA. Double-immunofluorescent labeling demonstrated that P2X7R-positive cells were mostly co-expressed with Iba1 (a microglia marker). Our results suggest that P2X7R plays an important role in the development of MA and could be used as a cellular target for treating PDN.
Assuntos
Animais , Masculino , Camundongos , Acetamidas/farmacologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Neuropatias Diabéticas/etiologia , Hiperalgesia/etiologia , Camundongos Endogâmicos C57BL , Quinolinas/farmacologia , Receptores Purinérgicos P2X7/fisiologia , Medula Espinal/fisiologia , Estreptozocina/farmacologiaRESUMO
Montelukast sodium is an effective and well-tolerated anti-asthmatic drug. Long non-coding RNAs (lncRNAs) are involved in the treatment of asthma. Therefore, this study aimed to investigate the effect of montelukast sodium on children with cough-variant asthma (CVA) and the role of lncRNA prostate cancer gene expression marker 1 (PCGEM1) in drug efficacy. The efficacy of montelukast sodium was evaluated by assessing the release of inflammatory factors and pulmonary function in CVA children after a 3-month treatment. An ovalbumin (OVA)-sensitized mouse model was developed to simulate asthmatic conditions. PCGEM1 expression in clinical peripheral blood samples and lung tissues of asthmatic mice was determined. Asthmatic mice experienced nasal inhalation of PCGEM1 overexpression with simultaneous montelukast sodium to investigate the roles of PCGEM1 in asthma treatment. The NF-κB axis after PCGEM1 overexpression was detected to explore the underling mechanisms. Consequently, montelukast sodium contributed to reduced levels of pro-inflammatory factors and improved pulmonary function in CVA children. PCGEM1 was poorly expressed in OVA-sensitized asthmatic mice and highly expressed in CVA children with response to the treatment. PCGEM1 overexpression enhanced the anti-inflammatory effects and promoted effects on pulmonary function of montelukast sodium in CVA children and OVA-sensitized asthmatic mice. Furthermore, PCGEM1 inhibited the activation of the NF-κB axis. This study demonstrated the anti-inflammatory and lung-protective effects of montelukast sodium on CVA, which was strengthened by overexpression of PCGEM1. Findings in this study highlighted a potential anti-asthmatic target of montelukast sodium.
Assuntos
Quinolinas/uso terapêutico , Asma/tratamento farmacológico , Antiasmáticos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Tosse/tratamento farmacológico , RNA Longo não Codificante/metabolismo , Acetatos/uso terapêutico , Asma/sangue , Tosse/sangue , Modelos Animais de Doenças , Camundongos Endogâmicos BALB CRESUMO
Abstract Purpose To determine the nephroprotective effect of NAC and Montelukast Sodium administration against the development of renal damage associated with long warm renal ischemia. Methods Twenty-seven rats were randomly divided into 3 study groups, which received NAC, montelukast and placebo, and 3 rats were included in the sham-treated control group. Medications were given 3 days before the procedure. DMSA renal scintigraphy was performed before and after surgery. The right renal pedicle was occluded for 45 min to induce ischemia and then subjected to reperfusion for 6 h (I/R groups). Results On pathological examination, the mean pathological scores of the montelukast and NAC groups were significantly lower than those of the placebo group. (p <0.05). In biochemical examination, significant differences were found in all parameter levels between the placebo group and the montelukast and NAC groups. (p <0.05) When postoperative DMSA renal scintigraphy measurements and renal function levels were compared, significant differences were found between the montelukast and NAC groups and the placebo and sham groups. Conclusion The administration of NAC and montelukast sodium was seen to have a nephroprotective effect against the development of renal damage associated with warm renal ischemia.
Assuntos
Animais , Ratos , Acetilcisteína/farmacologia , Quinolinas/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Acetatos/farmacologia , Sulfetos , Tomografia Computadorizada por Raios X , Ratos Wistar , Succímero , Ciclopropanos , Rim/irrigação sanguíneaRESUMO
OBJECTIVE@#To study the association of cytoplasmic phospholipase A2 (PLA2G4) rs932476 polymorphism with the development of bronchial asthma and the response to montelukast, a leukotriene receptor antagonist, in children.@*METHODS@#A total of 128 children with bronchial asthma were enrolled as case group, and 100 healthy children were enrolled as control group. The genotype and allele frequencies of PLA2G4 rs932476 were compared between the two groups. The children in the case group were administered with montelukast except routine treatment for 2 months, and the changes in serum levels of leukotriene B4 (LTB4), interleukin-4 (IL-4), immunoglobulin E (IgE), and interferon gamma (IFN-γ), pulmonary function and fractional exhaled nitric oxide (FeNO) after treatment were observed.@*RESULTS@#There were no significant differences in the genotype and allele frequencies of PLA2G4 rs932476 between the case and control groups, as well as between the groups with different severities of asthma (P>0.05). After treatment, the children with AA genotype had a significantly higher overall response rate than those with GG genotype. After treatment, the case group had significant reductions in the serum levels of IgE and IL-4 and a significant increase in the level of IFN-γ (P<0.05). After treatment, the children with GG genotype had a higher serum level of IL-4 and a lower level of IFN-γ than those with AA genotype. After treatment, the case group had significant increases in pulmonary function parameters, and the children with AA genotype had significantly higher parameters than those with GG genotype. The case group had a significant reduction in the level of FeNO, and the children with AA genotype had a significantly lower level than those with GG genotype after treatment. The case group had a significantly higher serum level of LTB4 than the control group before treatment (P<0.05). After treatment the case group had a significant reduction in the serum level of LTB4 (P<0.05). The children with GG genotype had a significantly higher level of LTB4 than those with AA genotype after treatment (P<0.05).@*CONCLUSIONS@#PLA2G4 rs932476 polymorphism is not associated with the susceptibility and severity of bronchial asthma in children, but it may has certain influence on children's response to the leukotriene receptor antagonist montelukast, possibly by affecting the level of LTB4.
Assuntos
Criança , Humanos , Acetatos , Asma , Antagonistas de Leucotrienos , QuinolinasRESUMO
Abstract INTRODUCTION: Concern regarding the cardiotoxicity of antimalarials has been renewed because of their potential to cause QT/QTc interval prolongation related to torsade de pointes (TdP). Artemisinin-piperaquine (AP) is considered an effective artemisinin-based combination therapy (ACT) for malaria. METHODS: This study involved a retrospective analysis of clinical data of 93 hospitalized malaria patients who had received AP orally. Electrocardiograms (ECGs) were obtained at specific time points in the original study. RESULTS: Some cases of QT prolongation were observed. However, no TdP was found. CONCLUSIONS: AP may cause QT interval prolongation in some malaria patients but may not lead to TdP.
Assuntos
Humanos , Masculino , Feminino , Adulto , Quinolinas/efeitos adversos , Síndrome do QT Longo/induzido quimicamente , Malária Falciparum/tratamento farmacológico , Artemisininas/efeitos adversos , Antimaláricos/efeitos adversos , Quinolinas/uso terapêutico , Síndrome do QT Longo/diagnóstico , Estudos Retrospectivos , Artemisininas/uso terapêutico , Quimioterapia Combinada , Eletrocardiografia , Pessoa de Meia-Idade , Antimaláricos/uso terapêuticoRESUMO
@#<p><strong>Background:</strong> Infection with Mycobacterium tuberculosis, the causative agent of TB, is responsible for one of the global epidemics. Thus, new drugs are needed that do not confer cross-resistance with currently administered front-line therapeutics. Quinoline-based natural products and synthetic derivatives have been extensively explored for antitubercular activity.<br /><strong>Objective:</strong> The main goal of this study was to prepare a collection of benzylated 8-hydroxyquinoline derivatives through synthesis and assess their antitubercular activity along with a molecular docking study to clarify their biological mechanism of action.<br /><strong>Methodology:</strong> The benzylated 8-hydroxyquinoline derivatives were synthesized using Williamson synthesis methods. Antitubercular activity was assessed against fast replicating M. tuberculosis H??Rv using Microplate Alamar Blue Assay (MABA) and non-replicating cultures using Low-Oxygen Recovery Assay (LORA). Molecular docking studies were carried out against enoyl-acyl carrier protein reductase (InhA).<br /><strong>Results:</strong> Five benzylated 8-hydroxyquinoline derivatives were synthesized in moderate yields and characterized using NMR spectroscopy. MABA and LORA assays indicate compounds 3-5 as the most inhibitory derivatives with MIC90's ranging from 6.38 to 54.28 ?M. Molecular docking against InhA showed modest 90 binding energies for compounds 4 (-8.5 kcal/mol) and 5 (-8.6 kcal/mol).<br /><strong>Conclusion:</strong> Findings suggest a rationale for the further evolution of this promising series of antitubercular quinoline small molecules. Structure-activity analysis shows that an 8-benzyl moiety with chlorine atom/s is important for improved activity against replicating and non-replicating M. tb. H??Rv. This is also supported by our in silico studies.</p>
Assuntos
Mycobacterium tuberculosis , Quinolinas , Simulação de Acoplamento MolecularRESUMO
OBJECTIVE@#To study the clinical effect of different combinations of fluticasone propionate (Flu), montelukast sodium (Mon) and ketotifen (Ket) in the treatment of children with cough variant asthma (CVA).@*METHODS@#A total of 280 children with CVA who were admitted to the department of respiratory medicine from June 2015 to January 2018 were randomly divided into Flu+Mon+Ket, Flu+Mon, Flu+Ket, Mon+Ket, Flu, Mon and Ket groups, with 40 children in each group. The children in each group were given corresponding drug(s), and the course of treatment was 3 months for all groups. The condition of cough, cough symptom score, pulmonary function and adverse drug reactions were evaluated after 2 and 3 months of treatment. The children were followed up to observe recurrence.@*RESULTS@#After treatment, cough symptom score tended to decrease in all 7 groups, with increases in percentage of forced expiratory volume in 1 second (FEV1%) and percentage of predicted peak expiratory flow (PEF%). After 2 months of treatment, the Flu+Mon+Ket group had a significantly lower cough symptom score and significantly higher FEV1% and PEF% than the other groups (P0.05). There was a low incidence rate of adverse events in all 7 groups, and there was no significant difference among the 7 groups (P>0.05). The Ket group had a significantly higher recurrence rate of cough than the other groups (P0.0024).@*CONCLUSIONS@#For children with CVA, a combination of Flu, Mon and Ket has a better clinical effect than a combination of two drugs and a single drug at 2 months of treatment and is safe. After 3 months of treatment, Flu or Mon alone has a similar effect to drug combination. Ket alone has a poor clinical effect and a high recurrence rate after drug withdrawal.
Assuntos
Criança , Humanos , Acetatos , Androstadienos , Antiasmáticos , Asma , Tratamento Farmacológico , Tosse , Tratamento Farmacológico , Combinação de Medicamentos , Fluticasona , Cetotifeno , QuinolinasRESUMO
ABSTRACT Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.