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1.
Pharm Res ; 36(11): 155, 2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31485804

RESUMO

PURPOSE: The purpose of this study was to determine the impact of food on gastric pH and the ability of over the counter betaine hydrochloride (BHCl) acid to reacidify gastric pH after food-induced elevations in gastric pH. METHODS: This open-label cross over clinical study (NCT02758015) included 9 subjects who were randomly assigned to one of 16 possible, 4-period cross-over sequences to determine the impact and relationship of food and gastric pH with acid supplementation. Subjects were administered various doses (1500 mg, 3000 mg and 4500 mg) of betaine hydrochloride (BHCl) to determine the ability of acid supplementation to reacidify gastric pH after the elevation of gastric pH caused by the ingestion of food. RESULTS: Following the administration of food and the resulting elevation in gastric pH, time to return to baseline gastric pH levels without acid supplementation was 49.7 ± 14.0 min. Administering 4500 mg of BHCl acid in capsules was able to reacidify gastric pH levels back to baseline following the administration of food in approximately 17.3 ± 5.9 min. AUCpH of each treatment were similar and not statistically different. Mean max pH following the administration of food was 3.20 ± 0.55. CONCLUSION: The ability of food to elevate and maintain gastric pH levels in the presence of acid supplementation was made evident throughout the study. A 4500 mg dose of BHCl was required to reacidify gastric pH after the administration of food. This study details the difficulty faced by clinicians in dosing a poorly soluble, weakly basic drug to patients receiving acid reducing agents where administration with food is recommended to avoid gastric side effects. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02758015.


Assuntos
Betaína/uso terapêutico , Alimentos , Absorção Gástrica , Ácido Gástrico/metabolismo , Fármacos Gastrointestinais/uso terapêutico , Preparações Farmacêuticas/metabolismo , Administração Oral , Adolescente , Adulto , Estudos Cross-Over , Feminino , Interações Alimento-Droga , Determinação da Acidez Gástrica , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
2.
Stud Health Technol Inform ; 264: 79-82, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437889

RESUMO

The W3C project, "Linking Open Drug Data" (LODD), linked several publicly available sources of drug data together. So far, French data, like marketed drugs and their summary of product characteristics, were not integrated and remained difficult to query. In this paper, we present Romedi (Référentiel Ouvert du Médicament), an open dataset that links French data on drugs to international resources. The principles and standard recommendations created by the W3C for sharing information were adopted. Romedi was connected to the Unified Medical Language System and DrugBank, two central resources of the LODD project. A SPARQL endpoint is available to query Romedi and services are provided to annotate textual content with Romedi terms. This paper describes its content, its services, its links to external resources, and expected future developments.


Assuntos
Preparações Farmacêuticas , Web Semântica , França , Armazenamento e Recuperação da Informação , Internet , Linguagem , Semântica , Unified Medical Language System
4.
Stud Health Technol Inform ; 264: 873-877, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438049

RESUMO

Poor communication of medication administration instructions is a preventable cause of medication nonadherence. The Universal Medication Schedule (UMS) framework improves adherence by providing a simplified set of dose timing rules. However, this framework does not readily generalize to individuals with varying daily routines. We propose a point-of-care solution for enhancing guideline-based electronic prescribing and personalizing dose schedules. We describe a JSON-based approach to encode and execute standard treatment guidelines to support electronic prescribing as well as an algorithm for optimizing medication administration schedules based on a patient's daily routine. We evaluated the structure and accuracy of our JavaScript Object Notation (JSON) formalism focusing on Kenya's hypertension treatment guidelines. Our experiments compare the medication schedules generated by our algorithm with those generated by pharmacists. Our findings show that treatment guidelines can be efficiently represented and executed using the JSON formalism, and that different medication administration schedules can be generated automatically and optimized for patients' daily routines.


Assuntos
Prescrição Eletrônica , Preparações Farmacêuticas , Humanos , Quênia , Adesão à Medicação , Farmacêuticos
5.
J Forensic Leg Med ; 67: 28-36, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398663

RESUMO

The application of forensic entomotoxicology in investigations of death by poisoning has gained popularity as insects serves as an alternative specimen (evidence) when conventional toxicological samples have degraded or are no longer available. Successful detection, identification, and quantification of drugs and toxic substances from insects have been demonstrated through various research experiments. In the present review paper, role of insects as toxicological sample, its collection and preservation, analysis using various instrumental techniques, and trends in the use of analytical techniques have been discussed. Limitations hindering the growth of this field and the way forward for future studies have been highlighted. In addition, the effect of poisons on insects used for postmortem interval estimation has been described.


Assuntos
Entomologia , Comportamento Alimentar , Toxicologia Forense/métodos , Envenenamento/diagnóstico , Mudanças Depois da Morte , Animais , Depressores do Sistema Nervoso Central/análise , Besouros , Dípteros , Etanol/análise , Humanos , Larva , Extração Líquido-Líquido , Praguicidas/análise , Preparações Farmacêuticas/análise , Extração em Fase Sólida , Xenobióticos
6.
Ceska Slov Farm ; 68(3): 119-124, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31431020

RESUMO

The problem of magnesium deficiency is an urgent issue of modern humanity. The population of many countries has a tendency to reduce the intake of this element in the daily diet. Its level decreases due to stress, inappropriate lifestyle, increased excretion from the body because of influence of medicines, etc. Therefore, creation of magnesium-containing medicines is a perspective scientific area. Currently at the pharmaceutical market, combination drugs with a multi-therapeutic effect are preferred. We have developed a technology for the preparation of the combined oral solution named Maglycimet, which consists of the following active pharmaceutical ingredients: magnesium aspartate, magnesium glutamate, glycine, methylcobalamin. Technological parameters of the solution preparation were established. Temperature modes and the loading order of main and auxiliary substances were studied and determined. The valuable point of the preparation of this medicine was to obtain the salts magnesium aspartate and magnesium glutamate directly in the reaction mixture. Based on the theoretical and experimental studies, technological parameters for the preparation of these salts were chosen. In this experimental study, the main indicators of the quality of the solution at the preparation stage were evaluated: organoleptic properties, pH, density, quantitative content of magnesium, glycine, methylcobalamin. The results indicated the significance of further research for subsequent industrial production of the developed medicine by Ukrainian manufacturers.


Assuntos
Magnésio , Preparações Farmacêuticas/química , Sais , Tecnologia Farmacêutica
7.
Stud Health Technol Inform ; 264: 452-456, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437964

RESUMO

Misspellings in clinical free text present potential challenges to pharmacovigilance tasks, such as monitoring for potential ineffective treatment of drug-resistant infections. We developed a novel method using Word2Vec, Levenshtein edit distance constraints, and a customized lexicon to identify correct and misspelled pharmaceutical word forms. We processed a large corpus of clinical notes in a real-world pharmacovigilance task, achieving positive predictive values of 0.929 and 0.909 in identifying valid misspellings and correct spellings, respectively, and negative predictive values of 0.994 and 0.333 as assessments where the program did not produce output. In a specific Methicillin-Resistant Staphylococcus Aureus use case, the method identified 9,815 additional instances in the corpus for potential inaffective drug administration inspection. The findings suggest that this method could potentially achieve satisfactory results for other pharmacovigilance tasks.


Assuntos
Preparações Farmacêuticas , Farmacovigilância , Algoritmos , Linguagem , Staphylococcus aureus Resistente à Meticilina
8.
Pharm Res ; 36(10): 148, 2019 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-31414302

RESUMO

Medications have been used during space missions for more than half a century, yet our understanding of the effects of spaceflight on drug pharmacokinetics and pharmacodynamics is poor. The space environment induces time-dependent alterations in human physiology that include fluid shifts, cardiovascular deconditioning, bone and muscle density loss, and impaired immunity. This review presents the current knowledge on the physiological effects of spaceflight that can translate into altered drug disposition and activity and eventually to inadequate treatment. It describes findings from studies in astronauts along with mechanistic studies in animal models and in vitro systems. Future missions into deeper space and the emergence of commercial spaceflight will require a more detailed understanding of space pharmacology to optimize treatment in astronauts and space travelers.


Assuntos
Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/metabolismo , Medicina Aeroespacial , Animais , Astronautas , Gravitação , Humanos , Farmacocinética , Voo Espacial , Ausência de Peso/efeitos adversos
9.
Einstein (Sao Paulo) ; 17(4): eGS4621, 2019 Jul 01.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31271589

RESUMO

OBJECTIVE: To calculate the cost and assess the results on implementing technological resources that can prevent medication errors. METHODS: A retrospective, descriptive-exploratory, quantitative study (2007-2015), in the model of case study at a hospital in the Brazilian Southeastern Region. The direct cost of each technology was calculated in the drug chain. Technological efficacy was observed from the reported series of the indicator incidence of medication errors. RESULTS: Thirteen technologies were identified to prevent medication errors. The average cost of these technologies per year in the prescription stage was R$ 3.251.757,00; in dispensing, R$ 2.979.397,10; and in administration, R$ 4.028.351,00. The indicator of medication error incidence decreased by 97.5%, gradually between 2007 to 2015, ranging from 2.4% to 0.06%. CONCLUSION: The average cost per year of the organization to implement preventive technologies in the drug chain totaled up R$ 10.259.505,10. There was an average investment/year of R$ 55,72 per patient and its association with smaller indicator of incidence of medication errors confirms a satisfactory result in this reported series regarding such investment.


Assuntos
Erros de Medicação/economia , Erros de Medicação/prevenção & controle , Sistemas de Medicação no Hospital/economia , Brasil , Análise Custo-Benefício , Sistemas de Informação Hospitalar , Humanos , Segurança do Paciente/economia , Preparações Farmacêuticas , Serviço de Farmácia Hospitalar , Estudos Retrospectivos , Tecnologia
10.
Expert Opin Drug Metab Toxicol ; 15(8): 633-658, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31274340

RESUMO

Introduction: In quantitative modeling, the resolving of underpredictions and overpredictions of hepatic clearance (CLh) makes a top priority for pharmacokinetic modelers. Clearly, the 'protein-mediated hepatic uptake' is a violation of 'the free drug hypothesis', but the lack of its consideration in CLh-predictive approaches may be one of the reasons to explain the discrepancies between predicted and observed values. Areas covered: We first review the two 'albumin-facilitated hepatic uptake' models that were recently challenged to improve the in vitro-to-in vivo extrapolation (IVIVE) of CLh by reducing the underprediction bias, particularly in the absence of albumin (ALB) in vitro compared to the presence of ALB in vivo. Second, we identify three types of interactions related to the ALB-bound drug moiety (i.e., ALB-lipids, ALB-proteins, and ALB-ligand allosteric interactions) that may be behind the 'ALB-mediated hepatic uptake' mechanism(s) for highly bound drugs. Main keywords used in our search are IVIVE; albumin; allostery; protein-mediated uptake; hepatic clearance; polarized hepatocytes. Expert opinion: Understanding the implication of these interactions and the enzyme/transporter interplay for each drug would help selecting the appropriate IVIVE model. Therefore, we have proposed a tree of decision for guidance. The next step is to improve the 'ALB-facilitated hepatic uptake' models to cover the remaining uncertainties.


Assuntos
Albuminas/metabolismo , Hepatócitos/metabolismo , Modelos Biológicos , Transporte Biológico , Humanos , Lipídeos/química , Fígado/metabolismo , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/metabolismo , Farmacocinética , Ligação Proteica , Proteínas/metabolismo
11.
Chem Commun (Camb) ; 55(63): 9241-9250, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31328738

RESUMO

The field of chemical biology has introduced several approaches, typically using chemical probes, to measure the direct binding interaction of a small molecule with its biological target in cells. The use of these direct target engagement assays in pharmaceutical development can support mechanism of action hypothesis testing, rank ordering of compounds, and iterative improvements of chemical matter. This Feature Article highlights a newer application of these approaches: the quantification of target engagement in animal models to support late stage preclinical development and the nomination of a drug candidate to clinical trials. Broadly speaking, these efforts can be divided between compounds that covalently and reversibly interact with protein targets; recent examples for both categories are discussed for a range of targets, along with their limitations. New, promising technologies are also highlighted, in addition to the application of target engagement determination to new therapeutic modalities.


Assuntos
Modelos Animais , Preparações Farmacêuticas/metabolismo , Animais , Interações de Medicamentos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacocinética , Preparações Farmacêuticas/química , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacocinética
13.
BMC Bioinformatics ; 20(Suppl 13): 383, 2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31337333

RESUMO

BACKGROUND: Drug repurposing has been motivated to ameliorate low probability of success in drug discovery. For the recent decade, many in silico attempts have received primary attention as a first step to alleviate the high cost and longevity. Such study has taken benefits of abundance, variety, and easy accessibility of pharmaceutical and biomedical data. Utilizing the research friendly environment, in this study, we propose a network-based machine learning algorithm for drug repurposing. Particularly, we show a framework on how to construct a drug network, and how to strengthen the network by employing multiple/heterogeneous types of data. RESULTS: The proposed method consists of three steps. First, we construct a drug network from drug-target protein information. Then, the drug network is reinforced by utilizing drug-drug interaction knowledge on bioactivity and/or medication from literature databases. Through the enhancement, the number of connected nodes and the number of edges between them become more abundant and informative, which can lead to a higher probability of success of in silico drug repurposing. The enhanced network recommends candidate drugs for repurposing through drug scoring. The scoring process utilizes graph-based semi-supervised learning to determine the priority of recommendations. CONCLUSIONS: The drug network is reinforced in terms of the coverage and connections of drugs: the drug coverage increases from 4738 to 5442, and the drug-drug associations as well from 808,752 to 982,361. Along with the network enhancement, drug recommendation becomes more reliable: AUC of 0.89 was achieved lifted from 0.79. For typical cases, 11 recommended drugs were shown for vascular dementia: amantadine, conotoxin GV, tenocyclidine, cycloeucine, etc.


Assuntos
Reposicionamento de Medicamentos/métodos , Preparações Farmacêuticas/química , Área Sob a Curva , Interações de Medicamentos , Humanos , Preparações Farmacêuticas/metabolismo , Proteínas/química , Proteínas/metabolismo , Curva ROC , Aprendizado de Máquina Supervisionado
14.
Expert Opin Ther Pat ; 29(8): 653-662, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31298053

RESUMO

Introduction: The Ecuadorian Institute of Intellectual Property (IEPI) granted several compulsory licenses between 2011 and 2017. In 2009, the President of Ecuador signed a decree that was intended to facilitate the request of compulsory licenses (CL) in the country, not only for Enfarma EP but for any privately owned local company in order to produce more accessible medicines. Areas covered: The national and international regulatory framework of pharmaceutical patents and the local applicability of CL in Ecuador. The authors also analyzed the results of requesting unplanned and epidemiologically unnecessary CL at a national level. Finally, the authors reviewed the effects of requesting, granting or denying CL on price per unit in the last 7 years of available data. Expert opinion: The authors think that compulsory licenses are useful tools when negotiating drug prices or when the demand cannot be satisfied due to economic constrain within the local health system. However, the authors' experience suggests that Ecuador did not have an established and reliable production system neither an adequate plan before requesting CL, therefore the positive effects of this measure were not clearly established.


Assuntos
Custos de Medicamentos/legislação & jurisprudência , Indústria Farmacêutica/legislação & jurisprudência , Licenciamento/economia , Indústria Farmacêutica/economia , Equador , Acesso aos Serviços de Saúde , Humanos , Propriedade Intelectual , Patentes como Assunto/legislação & jurisprudência , Preparações Farmacêuticas/economia , Preparações Farmacêuticas/provisão & distribução
15.
Sci Total Environ ; 690: 683-695, 2019 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-31301508

RESUMO

Pharmaceuticals and personal care products (PPCPs) are known as an emerging class of water contaminants due to their potential adverse effects on aquatic ecosystems. In this study, we conducted the first nationwide survey to understand the distribution and environmental risk of 72 PPCPs in surface waterways of Sri Lanka. Forty-one out of 72 targeted compounds were detected with total concentrations ranging between 5.49 and 993 ng/L in surface waterways in Sri Lanka. The highest level of PPCP contamination was detected in an ornamental fish farm. Sulfamethoxazole was found with the highest concentration (934 ng/L) followed by N,N-diethyl-meta-toluamide (202 ng/L) and clarithromycin (119 ng/L). Diclofenac, mefenamic acid, ibuprofen, trimethoprim, and erythromycin were detected ubiquitously throughout the country. Our data revealed that hospital and domestic wastewater, and aquaculture activities potentially contribute to the presence of PPCPs in Sri Lankan waterways. The calculated risk quotients indicated that several locations face medium to high ecological risk to aquatic organisms from ibuprofen, sulfamethoxazole, diclofenac, mefenamic acid, tramadol, clarithromycin, ciprofloxacin, triclocarban, and triclosan. The aforementioned compounds could affect aquatic organisms from different trophic levels like algae, crustacean and fish, and also influence the emergence of antibiotic resistant bacteria. These findings emphasize that a wide variety of pharmaceuticals have become pervasive environmental contaminants in the country. This data will serve to expand the inventory of global PPCP pollution. Further monitoring of PPCPs is needed in Sri Lanka in order to identify PPCP point sources and to implement strategies for contaminant reduction in wastewater to protect the aquatic ecosystem, wildlife, and human health.


Assuntos
Cosméticos/análise , Monitoramento Ambiental , Preparações Farmacêuticas/análise , Poluentes Químicos da Água/análise , Aquicultura , Medição de Risco , Sri Lanka , Sulfametoxazol , Triclosan , Águas Residuárias
17.
Nihon Yakurigaku Zasshi ; 154(1): 28-34, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31308347

RESUMO

Drug metabolism is an important determinant to control pharmacokinetics, drug response and drug toxicity. Large variabilities are observed in expression or activity of drug-metabolizing enzymes such as cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT). Therefore, understanding of the causes for the variation of drug metabolism potencies is essential for efficient drug development and promotion of safe use of medicines. The expression of drug-metabolizing enzymes is controlled by transcriptional regulation by nuclear receptors and transcriptional factors, and by epigenetic regulation such as DNA methylation and histone acetylation. In addition to such regulatory mechanisms, recent studies revealed that microRNAs (miRNAs) significantly contribute to post-transcriptional regulation of drug-metabolizing enzymes. miRNAs are endogenous ~22-nucleotide non-coding RNAs that regulate gene expression through the translational repression and degradation of mRNAs. More recently, it has been clarified that the presence of pseudogenes or single nucleotide polymorphisms as well as RNA editing event affect miRNA-dependent regulation. It is unwavering fact that miRNAs significantly contribute to inter- and intra-individual differences in the expression of drug-metabolizing enzymes. In this review, we introduce current knowledge of miRNA-mediated regulation of drug metabolism.


Assuntos
Inativação Metabólica , MicroRNAs/genética , Preparações Farmacêuticas/metabolismo , Epigênese Genética , Edição de Genes , Regulação da Expressão Gênica , Humanos , Polimorfismo de Nucleotídeo Único , Receptores Citoplasmáticos e Nucleares
18.
Adv Exp Med Biol ; 1140: 99-109, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347043

RESUMO

Mass spectrometry imaging (MSI) of tissue samples is a promising analytical tool that has quickly become associated with biomedical and pharmacokinetic studies. It eliminates several labor-intensive protocols associated with more classical imaging techniques, and provides accurate, histological data at a rapid pace. Because mass spectrometry is used as the readout, MSI can be applied to almost any molecule, especially those that are biologically relevant. Many examples of its utility in the study of peptides and proteins have been reported; here we discuss its value in the mass range of small molecules. We explore its success and potential in the analysis of lipids, medicinals, and metal-based compounds by featuring representative studies from mass spectrometry imaging laboratories around the globe.


Assuntos
Lipídeos/análise , Espectrometria de Massas , Metais/análise , Preparações Farmacêuticas/análise , Humanos
19.
Adv Exp Med Biol ; 1140: 299-316, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31347055

RESUMO

The pharmaceutical and clinical industries are imperative for the maintenance of global health and welfare and require accurate, reproducible, and high throughput analyses. Technological advancements, such as the development and implementation of liquid chromatography-tandem mass spectrometry (LC-MS), have allowed for improvements in these areas, however there is still room for development. One way in which current analyses may be improved is by the implementation of ion mobility technology. Ion mobility has the capability to produce much more comprehensive data sets, by providing separation of isomers, as well as improving throughput, with separations being performed as fast as 60 ms. Here we will discuss the potential for ion mobility to assist in the two specific areas of glycosylation monitoring of biological drugs, and vitamin D analysis, as representatives of ion mobility's potential in both the pharmaceutical and clinical industries, respectively, as well as the current hurdles of ion mobility adoption in both fields.


Assuntos
Química Farmacêutica/métodos , Cromatografia Líquida , Espectrometria de Massas em Tandem , Glicosilação , Isomerismo , Preparações Farmacêuticas/análise , Vitamina D/análise
20.
Zhonghua Yi Xue Za Zhi ; 99(24): 1898-1903, 2019 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-31269587

RESUMO

Objective: To investigate the effect of different drugs on tracheal stenosis caused by transforming growth factor-ß/rapamycin target protein (TGF-ß/mTOR) signaling pathway. Methods: Thirty rabbits were randomly divided into normal control group, normal saline group, penicillin group, budesonide group and erythromycin group. The normal control group was not treated,and tracheal stenosis models were established in the other groups. From the 1st to 10th day after modeling, each group was respectively administered with normal saline (0.75 ml/kg, 2 times/d), intramuscular injection of penicillin (40 000 U/kg, 2 times/d), gastric administration of erythromycin (12.5 mg/kg, 2 times/d), inhalation of budesonide (0.05 mg/kg, 2 times/d). Rabbits were sacrificed on the 11th day after surgery, and tracheal specimens were collected to measure the degree of tracheal stenosis. Relative mRNA expression level of interleukin-6 (IL-6), transforming growth factor-ß (TGF-ß), Type Ⅰ collagen (COL-1), Type Ⅲ collagen (COL-3), and Sirtuin 1 (SIRT-1) were detected by Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR); protein expression of mTOR, phosphorylated protein kinase B (p-AKT), vascular endothelial growth factor (VEGF),SIRT-1 were detected by immunohistochemical analysis; protein expression of nuclear factor κB (NF-κB),phosphorylated nuclear factor κB (p-NF-κB),protein kinase B (AKT),p-AKT,mTOR were detected by Western blotting. Results: The degree of stenosis of normal control group was (14.02±2.86)%, saline group was (64.14±3.21)%, penicillin group was (49.11±2.96)%, budesonide group was (39.52±2.09)%, erythromycin group was (32.60±4.27)%. The differences between any two groups were statistically significant (all P<0.05). Except between erythromycin group and normal control group, the differences in relative expression of IL-6 mRNA between any two groups (1.00±0.00, 9.02±1.50, 4.25±0.87, 2.53±0.17, 1.31±0.56) was statistically significant (all P<0.05), and the differences in relative expression of TGF-ß mRNA among all groups (1.00±0.00, 6.92±0.84, 3.83±0.44, 2.13±0.25, 1.40±0.15) were statistically significant (all P<0.05). The relative expression of SIRT-1 mRNA among all the groups (1.000±0.000, 0.209±0.042, 0.375±0.034, 0.555±0.028, 0.667±0.032) was statistically significant different (all P<0.05); except between erythromycin group and budesonide group,the protein levels of SIRT-1 among all other groups (16.93±2.28, 4.77±1.45, 7.70±0.61, 10.76±1.04, 11.03±1.10) were statistically significant different (all P<0.05). The protein levels of mTOR (9.28±4.56, 58.18±8.12, 44.75±5.56, 32.82±5.99, 24.73±3.56) and p-AKT (16.57±4.86, 61.79±6.66, 42.98±5.99, 32.79±5.34, 24.00±4.40) determined through immunohistochemistry of all groups were statistically significant different (all P<0.05). The protein levels of NF-κB, p-NF-κB, AKT, p-AKT and mTOR determined through Western blotting had the same trend as that of determined through immunohistochemistry. The protein expression of NF-κB,AKT and mTOR in saline group were significantly higher than other groups; those protein expression of erythromycin group was lower than budesonide group and penicillin group. Except between the erythromycin group and the normal control group, the protein expression of mTOR in other groups was statistically significant different (all P<0.05). Conclusion: Penicillin,erythromycin and budesonide can alleviate inflammation by increasing SIRT-1, alleviate tracheal scar hyperplasia induced by TGF-beta/mTOR pathway, and reduce the degree of tracheal stenosis in rabbits.


Assuntos
Constrição Patológica , Animais , Broncopatias , Preparações Farmacêuticas , Coelhos , Transdução de Sinais , Serina-Treonina Quinases TOR , Fator de Crescimento Transformador beta , Fator A de Crescimento do Endotélio Vascular
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