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1.
Rev Assoc Med Bras (1992) ; 67(9): 1256-1260, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34816917

RESUMO

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of combined doxofylline and salbutamol in the treatment of acute exacerbation of chronic obstructive pulmonary disease. METHODS: A total of 68 acute exacerbation of chronic obstructive pulmonary disease patients were randomly divided into control group (34 cases) and experimental group (34 cases), who received the doxofylline treatment and combined doxofylline and salbutamol treatment for 1 week, respectively. During the treatment, the remission time of typical respiratory manifestations was recorded, and the adverse reactions were observed. At the end of treatment, the treatment efficacy was evaluated. Before and after treatment, the pulmonary function indexes and serological indicators were detected. RESULTS: After treatment, compared with control group, in experimental group, the effective rate of treatment was significantly increased (p<0.05), the remission time of typical respiratory manifestations was significantly shortened (p<0.05), the pulmonary function indexes were significantly improved (p<0.05), the serum high-sensitivity C-reactive protein and cystatin C levels were significantly decreased, respectively (p<0.05), and the serum prealbumin level was significantly increased (p<0.05). In addition, the adverse reaction rate had no significant difference between two groups (p>0.05). CONCLUSIONS: In the treatment of acute exacerbation of chronic obstructive pulmonary disease, the combined use of doxofylline and salbutamol can quickly relieve the respiratory symptoms, mitigate the pulmonary dysfunction, and reduce the inflammatory response, thus promoting the outcome of patients.


Assuntos
Albuterol , Doença Pulmonar Obstrutiva Crônica , Humanos , Pulmão , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Teofilina/efeitos adversos , Teofilina/análogos & derivados
2.
Pediatrics ; 148(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34599008

RESUMO

In this state-of-the-art review, we highlight the major advances over the last 5 years in neonatal acute kidney injury (AKI). Large multicenter studies reveal that neonatal AKI is common and independently associated with increased morbidity and mortality. The natural course of neonatal AKI, along with the risk factors, mitigation strategies, and the role of AKI on short- and long-term outcomes, is becoming clearer. Specific progress has been made in identifying potential preventive strategies for AKI, such as the use of caffeine in premature neonates, theophylline in neonates with hypoxic-ischemic encephalopathy, and nephrotoxic medication monitoring programs. New evidence highlights the importance of the kidney in "crosstalk" between other organs and how AKI likely plays a critical role in other organ development and injury, such as intraventricular hemorrhage and lung disease. New technology has resulted in advancement in prevention and improvements in the current management in neonates with severe AKI. With specific continuous renal replacement therapy machines designed for neonates, this therapy is now available and is being used with increasing frequency in NICUs. Moving forward, biomarkers, such as urinary neutrophil gelatinase-associated lipocalin, and other new technologies, such as monitoring of renal tissue oxygenation and nephron counting, will likely play an increased role in identification of AKI and those most vulnerable for chronic kidney disease. Future research needs to be focused on determining the optimal follow-up strategy for neonates with a history of AKI to detect chronic kidney disease.


Assuntos
Injúria Renal Aguda , Injúria Renal Aguda/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/terapia , Biomarcadores/urina , Cafeína/uso terapêutico , Humanos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Recém-Nascido , Recém-Nascido Prematuro , Rim/efeitos dos fármacos , Rim/fisiologia , Lipocalina-2/urina , Estudos Multicêntricos como Assunto , Consumo de Oxigênio , Terapia de Substituição Renal/instrumentação , Pesquisa , Fatores de Risco , Teofilina/uso terapêutico , Equilíbrio Hidroeletrolítico
3.
Nat Commun ; 12(1): 5993, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645808

RESUMO

Metabolic biomonitoring in humans is typically based on the sampling of blood, plasma or urine. Although established in the clinical routine, these sampling procedures are often associated with a variety of compliance issues, which are impeding time-course studies. Here, we show that the metabolic profiling of the minute amounts of sweat sampled from fingertips addresses this challenge. Sweat sampling from fingertips is non-invasive, robust and can be accomplished repeatedly by untrained personnel. The sweat matrix represents a rich source for metabolic phenotyping. We confirm the feasibility of short interval sampling of sweat from the fingertips in time-course studies involving the consumption of coffee or the ingestion of a caffeine capsule after a fasting interval, in which we successfully monitor all known caffeine metabolites as well as endogenous metabolic responses. Fluctuations in the rate of sweat production are accounted for by mathematical modelling to reveal individual rates of caffeine uptake, metabolism and clearance. To conclude, metabotyping using sweat from fingertips combined with mathematical network modelling shows promise for broad applications in precision medicine by enabling the assessment of dynamic metabolic patterns, which may overcome the limitations of purely compositional biomarkers.


Assuntos
Monitoramento Biológico/métodos , Café/metabolismo , Metabolômica/métodos , Suor/química , Adulto , Monitoramento Biológico/normas , Biotransformação , Cafeína/análise , Cafeína/metabolismo , Ácido Clorogênico/análise , Ácido Clorogênico/metabolismo , Cromatografia Líquida , Feminino , Dedos , Humanos , Masculino , Metabolômica/normas , Pessoa de Meia-Idade , Análise de Componente Principal , Espectrometria de Massas em Tandem , Teobromina/análise , Teobromina/metabolismo , Teofilina/análise , Teofilina/metabolismo
4.
Shokuhin Eiseigaku Zasshi ; 62(4): 119-124, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34470940

RESUMO

A simultaneous determination method for caffeine, theobromine, and theophylline in chocolate was developed. Three compounds were ultrasonically extracted twice (15 min at 50℃) in an acetonitrile-water (1 : 1, v/v). The extract was purified using Oasis HLB SPE cartridge, and the purified processed by LC-MS. The method exhibited recoveries of 97.4-100.2%, RSDs of repeatability of 1.0-2.8%, and RSDs of within-laboratory reproducibility of 2.0-7.9%. This method was simpler and more selective than existing methods, and was practical for caffeine, theobromine, and theophylline analysis in chocolate.


Assuntos
Chocolate , Teobromina , Cafeína , Cromatografia Líquida , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem , Teofilina
5.
Food Res Int ; 148: 110587, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507732

RESUMO

Epigallocatechin gallate (EGCg) and methylxanthines are representative bioactive compounds in tea leaves, the strong affinity between them will elicit destruction of tea quality. In order to elucidate the mechanism of complexation between EGCg and methylxanthines, we compared the bindings of theophylline and caffeine to EGCg by nuclear magnetic resonance (NMR), molecular docking and isothermal titration calorimetry (ITC). The results revealed that the stoichiometries of caffeine to EGCg and theophylline to EGCg were both 1:1. Caffeine and theophylline were captured in the hydrophobic space formed by aromatic rings of EGCg. The affinity between EGCg and caffeine was stronger than that between EGCg and theophylline, which could be partially attributed to the two extra CH-π interactions between N7-Me of caffeine and aromatic rings of EGCg. Furthermore, the results of ITC were agreed well with NMR and molecular docking, indicating that ITC was possible to accurately evaluate the complexation.


Assuntos
Cafeína , Catequina , Catequina/análogos & derivados , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Teofilina , Termodinâmica
6.
Talanta ; 234: 122658, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364467

RESUMO

The Cytochrome P450 CYP1A2 is a central enzyme in the metabolism of drugs and xenobiotics. The overall activity of this enzyme is influenced by a complex array of biochemical, dietary, and genetic factors. One of the simplest ways to probe the overall output of CYP1A2 is to measure the ratio between the concentration of a precursor and a product of its activity. With the growing interest in the Paraxanthine/Caffeine ratio, the need arises to develop improved analytical methods specifically optimized for the rapid and sensitive determination of paraxanthine and caffeine in biological samples. We report a new optimized method for the determination of caffeine and paraxanthine in various human matrices. The method involved direct determination following protein precipitation based on ultra high performance liquid chromatographic separation with tandem mass spectrometric detection (UHPLC-ESIMS/MS). The method offers an improvement in the detection limit over previously published methods by at least 10-fold (0.1 pg), rapid chromatographic separation (ca. 5 min), the utilization of a green chromatographic solvent (5% v/v ethanol), direct determination with little sample preparation, and the employment of isotopically labeled internal standards and qualifier ions to ensure accuracy. Method validation in urine, saliva, and plasma was performed by spiking at various concentration levels where the recovery and repeatability were within ±15% and ±10%, respectively. The method was applied to investigate the levels of caffeine and paraxanthine in volunteers following controlled caffeine administration and to investigate the inter- and intra-individual variability in the paraxanthine/caffeine ratio in volunteers following an unrestricted caffeine diet. In conclusion, the developed UHPLC-ESIMS/MS method is optimized specifically for the simultaneous determination of the paraxanthine/caffeine ratio in multiple biological matrices, offers several advantages over the current methods, and is well suitable for application in large clinical studies.


Assuntos
Cafeína , Citocromo P-450 CYP1A2 , Biomarcadores , Cromatografia Líquida de Alta Pressão , Humanos , Teofilina
7.
Biomed Khim ; 67(4): 352-359, 2021 Jul.
Artigo em Russo | MEDLINE | ID: mdl-34414894

RESUMO

Chronic obstructive pulmonary disease (COPD) is characterized by reduced sensitivity of cells to the anti-inflammatory effects of glucocorticoids (GCs). Azithromycin and a low dose theophylline have a significant impact on molecular mechanisms leading to corticosteroid resistance. The aim of this study was to evaluate the ability of azithromycin and theophylline to enhance the anti-inflammatory effects of GCs on the production of cytokines by NK and NKT-like blood cells of COPD patients. Whole blood cells from COPD patients (n=21) were incubated in the presence of budesonide (10 nM), azithromycin (10 µg/mL), theophylline (1 µM), or their combinations and stimulated with phorbol myristate acetate (50 ng/mL). Intracellular production of proinflammatory cytokines in NK (CD3-CD56+) and NKT-like (CD3+CD56+) blood cells was analyzed by flow cytometry. Budesonide reduced synthesis of interleukin 4 (IL-4), CXCL8, tumor necrosis factor α (TNFα) by NK and NKT-like cells, as well as production of interferon γ (IFNγ) by NK cells. Azithromycin suppressed production of IL-4 and CXCL8 by NK and NKT-like cells, and theophylline inhibited IL-4 synthesis by these lymphocytes. The combination of azithromycin and budesonide had a more pronounced inhibitory effect on the production of IL-4 and CXCL8 by NK and NKT-like cells than the effect of these drugs alone. The combination of theophylline and budesonide suppressed synthesis of IL-4 and CXCL8 by NK and NKT-like cells, as well as the production of TNFα and IFNγ by NK cells stronger than budesonide alone. The obtained results demonstrate the benefits for the combined use of GCs with theophylline at a low dose or azithromycin to suppress the inflammatory process in patients with COPD.


Assuntos
Glucocorticoides , Doença Pulmonar Obstrutiva Crônica , Azitromicina/farmacologia , Citocinas , Humanos , Células Matadoras Naturais , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Teofilina/farmacologia
8.
Medicine (Baltimore) ; 100(34): e27091, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449512

RESUMO

ABSTRACT: The relationship between chronic obstructive pulmonary disease (COPD) and reflux esophagitis (RE) was controversial. We investigated the factors influencing RE development in patients with COPD and evaluated the association between RE and AECOPD.Patients with COPD who underwent esophagogastroduodenoscopy from January 2003 to December 2013 in St. Paul's Hospital, the Catholic University of Korea (Seoul, Korea) were enrolled retrospectively. The grade of RE was based on the Los Angeles classification and minimal change esophagitis. Body mass index, smoking history, medical history, AECOPD, pulmonary function test data, endoscopic findings, and comorbidities were reviewed.Of a total of 218 patients with COPD, 111 (50.9%) were diagnosed with RE. None of age, sex, smoking history, or the severity of airflow limitation was associated with RE. AECOPD was not related to either the presence or severity of RE. There was no significant correlation between RE grade by Los Angeles classification and severity of airflow limitation (P = .625). Those who had RE used theophylline (P = .003) and long-acting muscarinic antagonists (P = .026) significantly more often than did controls. The use of theophylline (OR 2.05; 95% CI, 1.16-3.65, P = .014) was associated with an increased incidence of RE.The use of theophylline might increase the risk of RE in COPD patients. RE may not be associated with airflow limitation or AECOPD.


Assuntos
Esofagite Péptica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Broncodilatadores/efeitos adversos , Comorbidade , Endoscopia do Sistema Digestório , Esofagite Péptica/induzido quimicamente , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antagonistas Muscarínicos/efeitos adversos , República da Coreia , Testes de Função Respiratória , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores Sexuais , Fumar/epidemiologia , Teofilina/efeitos adversos
9.
Int J Chron Obstruct Pulmon Dis ; 16: 2375-2383, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34429595

RESUMO

Objective: To evaluate the effect of doxofylline on reducing the inflammatory response in mechanically ventilated rats with chronic obstructive pulmonary disease (COPD). Methods: A total of 40 eight-week-old male Sprague Dawley rats were randomly divided into four groups of 10 rats each: a control group (group C), a model group (group M), a model + natural saline group (group N), and a doxofylline group (group D). Then mechanical ventilation, drug intervention, and the extraction of the experimental material were performed in each group. Pulmonary tissue samples were taken after 120 minutes of mechanical ventilation and the pulmonary histopathological changes and the wet/dry (W/D) weight ratio of the pulmonary tissue were identified. The levels of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) were detected using an enzyme-linked immunosorbent assay, and the expression levels of c-Jun-N-terminal kinase (JNK) and phosphorylated c-Jun N-terminal kinase (p-JNK) were detected using immunohistochemistry. Results: Compared with group C, the pulmonary histopathology in groups M, N, and D showed typical changes associated with COPD. Furthermore, the W/D weight ratio and levels of TNF-α, JNK, and p-JNK in the pulmonary tissue increased in groups M, N, and D (P < 0.05), while the levels of IL-10 decreased (P < 0.05). Compared with group M, no statistically significant changes in the above indicators were detected in the pulmonary tissue of group N (P > 0.05). Compared with group N, the W/D weight ratio and levels of TNF-α, JNK, and p-JNK in the pulmonary tissue decreased in group D (P < 0.05), while the levels of IL-10 increased (P < 0.05). Conclusion: Doxofylline might attenuate pulmonary inflammatory responses in mechanically ventilated rats with COPD, and the JNK/stress-activated protein kinase signaling pathway is involved in doxofylline's inhibition of inflammatory responses in the pulmonary tissue of rats with COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Animais , Pulmão , Masculino , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Ratos , Ratos Sprague-Dawley , Respiração Artificial , Teofilina/análogos & derivados , Fator de Necrose Tumoral alfa
10.
Ultrason Sonochem ; 77: 105675, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34298309

RESUMO

In this paper, the ultrasound-assisted solvent-mediated polymorphic transformation of theophylline was explored in detail. The induction time and reconstruction time were significantly decreased by ultrasound, thereby decreasing the total transformation time and promoting the transformation process. The ultrasound-promoted efficiency of nucleation was different in three alcoholic solvents, which was difficult to explain by traditional kinetic effects. To resolve the above confusion, binding energies calculated by Density Functional Theory were applied to explore the relationship between the ultrasound-promoted efficiency of nucleation and solute-solvent interactions. Then, a possible molecular self-assembly nucleation pathway affected by ultrasound was proposed: the ultrasound could change and magnify the crucial effect of the specific sites of solute-solvent interactions in the nucleation process. Finally, the transformation kinetics with different effective ultrasonic energies was quantitatively analyzed by Avrami-Erofeev model, indicating that the dissolution element in the rate-limiting step was gradually eliminated by higher ultrasonic energy. Fortunately, the elusive crystal form V could be easily obtained by the ultrasound-assisted polymorph transformation. This proved to be a robust method to produce high purity form V of theophylline. The outcome of this study demonstrated that the proper ultrasonic irradiation had the potential to produce specific polymorphs selectively.


Assuntos
Teofilina/química , Ondas Ultrassônicas , Cristalização , Cinética , Modelos Moleculares , Conformação Molecular , Solubilidade , Solventes/química
12.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298966

RESUMO

Theophylline, a typical representative of active pharmaceutical ingredients, was selected to study the characteristics of experimental and theoretical solubility measured at 25 °C in a broad range of solvents, including neat, binary mixtures and ternary natural deep eutectics (NADES) prepared with choline chloride, polyols and water. There was a strong synergistic effect of organic solvents mixed with water, and among the experimentally studied binary systems, the one containing DMSO with water in unimolar proportions was found to be the most effective in theophylline dissolution. Likewise, for NADES, the addition of water (0.2 molar fraction) resulted in increased solubility compared to pure eutectics, with the highest solubilisation potential offered by the composition of choline chloride with glycerol. The ensemble of Statistica Automated Neural Networks (SANNs) developed using intermolecular interactions in pure systems has been found to be a very accurate model for solubility computations. This machine learning protocol was also applied as an extensive screening for potential solvents with higher solubility of theophylline. Such solvents were identified in all three subgroups, including neat solvents, binary mixtures and ternary NADES systems. Some methodological considerations of SANNs applications for future modelling were also provided. Although the developed protocol is focused exclusively on theophylline solubility, it also has general importance and can be used for the development of predictive models adequate for solvent screening of other compounds in a variety of systems. Formulation of such a model offers rational guidance for the selection of proper candidates as solubilisers in the designed solvents screening.


Assuntos
Colina/química , Aprendizado de Máquina , Modelos Químicos , Solventes/química , Teofilina/química , Água/química , Solubilidade
13.
J Vet Pharmacol Ther ; 44(6): 902-909, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34173985

RESUMO

Theophylline is used in canine medicine for the management of chronic bronchitis and bradyarrhythmias, yet no species-validated commercial products are available. This study reports the single-dose and multidose pharmacokinetics and safety of a modified, compounded theophylline (MCT) product readily available from a well-established, USP-compliant compounding pharmacy, which may be a suitable and reliable source for theophylline for dogs. Eleven dogs underwent serial plasma theophylline measurement following 10 mg/kg MCT PO. After a 7 days washout, dogs received 10 mg/kg MCT PO q12h and serial plasma theophylline quantification was repeated after the ninth dose. Dogs were monitored for potential adverse effects. For the nine dogs that completed the study, plasma theophylline concentrations were between 5 and 30 µg/ml for 91 +/- 15% of the dosing interval. There was no significant difference in half-life between single-dose and multidose administration. The most common adverse effects reported were mild and included agitation, excitement, and increased activity. The results of this study support the use of 10 mg/kg MCT administered twice daily as a starting dosage in dogs. This regimen appears safe, achieves appropriate plasma drug concentrations in most dogs, and does not cause significant changes in pharmacokinetic properties at steady state. Because compounded drugs do not undergo consistent testing for identity, quality, strength, purity, and stability, results of research described in reports using compounded products may not be reproducible.


Assuntos
Bronquite Crônica , Doenças do Cão , Animais , Bronquite Crônica/veterinária , Cães , Meia-Vida , Teofilina/efeitos adversos
14.
Mater Sci Eng C Mater Biol Appl ; 126: 112148, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34082959

RESUMO

A comprehensive study of release kinetics of a hydrophilic drug from bio-aerogels based on pectin was performed. Pectin aerogels were made by polymer dissolution, gelation (in some cases this step was omitted), solvent exchange and drying with supercritical CO2. Theophylline was loaded and its release was studied in the simulated gastric fluid during 1 h followed by the release in the simulated intestinal fluid. Pectin concentration, initial solution pH and concentration of calcium were varied to tune the properties of aerogel. The kinetics of theophylline release was monitored and correlated with aerogel density, specific surface area, and aerogel swelling and erosion. Various kinetic models were tested to identify the main physical mechanisms governing the release.


Assuntos
Pectinas , Teofilina , Dessecação , Portadores de Fármacos , Géis
15.
Talanta ; 232: 122417, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074405

RESUMO

Biosensors are of interest for the quantitative detection of small molecules (metabolites, drugs and contaminants for instance). To this end, fluorescence is a widely used technique that is easily associated to aptamers. Light-up aptamers constitute a particular class of oligonucleotides that, specifically induce fluorescence emission when binding to cognate fluorogenic ligands such as malachite green (MG). We engineered a dual aptasensor for theophylline (Th) based on the combination of switching hairpin aptamers specific for MG on the one hand and for Th on the other hand, hence their names: malaswitch (Msw) and theoswitch (Thsw). The two aptaswitches form a loop-loop or kissing Msw-Thsw complex only in the presence of theophylline, allowing binding of MG, subsequently generating a fluorescent signal. The combination of the best Msw and Thsw variants, MswG12 and Thsw19.1, results in a 20-fold fluorescence enhancement of MG at saturating theophylline concentration. This aptasensor discriminates between theophylline and its analogues caffeine and theobromine. Kissing aptaswitches derived from light-up aptamers constitute a novel sensing device.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Corantes de Rosanilina , Teofilina
18.
BMJ Case Rep ; 14(5)2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952564

RESUMO

We report a case of severe amnestic syndrome following theophylline overdose. A woman in her early 30s was admitted to hospital where she developed status epilepticus following an intentional overdose of theophylline and lansoprazole. She developed a profound acidosis and required intubation in the intensive care unit. Following extubation the patient was noted to have a severe amnestic syndrome with poor short-term memory. A work-up to exclude infectious, autoimmune and paraneoplastic causes for encephalitis was undertaken. Cerebrospinal fluid analysis was normal and autoimmune encephalitis titres were negative. Initial MRI brain imaging demonstrated hyperintensities of the mesial temporal lobes bilaterally. Follow-up imaging at 4 months identified further interval reduction but persistent hippocampal hyperintensities. Theophylline toxicity with corresponding amnestic syndrome and hippocampal hyperintensities has been rarely reported. We believe this case with persistent abnormal Montreal Cognitive Assessment Score at 12 months correlates with persistent hippocampal abnormalities seen on imaging.


Assuntos
Encefalite , Doença de Hashimoto , Feminino , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Teofilina
19.
Chem Commun (Camb) ; 57(44): 5418-5421, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33949481

RESUMO

Ligand-induced activation of CRISPR/Cas9 function is achieved based on a synergic approach through the integration of the theophylline aptamer into protein-unrecognized regions of guide RNA. This design of allosteric regulation opens a new window towards the broad involvement of RNA aptamers for conditional control of CRISPR/Cas9 function.


Assuntos
Sistemas CRISPR-Cas , RNA Guia/metabolismo , Teofilina/metabolismo , Sistemas CRISPR-Cas/genética , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas/genética , RNA Guia/química , Teofilina/química
20.
PLoS One ; 16(5): e0251348, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34029327

RESUMO

BACKGROUND: A synergism has been reported between theophylline and corticosteroids, wherein theophylline increases and restores the anti-inflammatory effect of inhaled corticosteroids (ICS) by enhancing histone deacetylase-2 (HDAC) activity. Several studies have explored the efficacy of low-dose theophylline plus ICS therapy on chronic obstructive pulmonary disease (COPD) but the results are discrepant. METHOD: We conducted searches in electronic database such as PubMed, Web Of Science, Cochrane Library, and Embase to find out original studies. Stata/SE 15.0 was used to perform all data analysis. RESULT: A total of 47,556 participants from 7 studies were included in our analysis and the sample size of each study varied from 24 to 10,816. Theophylline as an add-on therapy to ICS was not associated with the reduction of COPD exacerbations (HR: 1.08, 95% CI: 0.97 to 1.19, I2 = 95.2%). Instead, the theophylline group demonstrated a higher hospitalization rate (HR: 1.12, 95% CI: 1.10 to 1.15, I2 = 20.4%) and mortality (HR: 1.19, 95% CI: 1.14 to 1.25, I2 = 0%). Further, the anti-inflammatory effect of low-dose theophylline as an adjunct to ICS on COPD was controversial. Besides, the theophylline group showed significant improvement in lung function compared with the non-theophylline group. CONCLUSION: Based on current evidence, low-dose theophylline as add-on therapy to ICS did not reduce the exacerbation rate. Instead, the hospitalization rate and mortality increased with theophylline. Thus, we do not recommend adding low-dose theophylline to ICS therapy in COPD patients. TRIAL REGISTRATION: PROSPERO Registration CRD42021224952.


Assuntos
Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Teofilina/farmacologia , Teofilina/uso terapêutico , Administração por Inalação , Animais , Broncodilatadores/farmacologia , Broncodilatadores/uso terapêutico , Quimioterapia Combinada/métodos , Hospitalização , Humanos
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