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1.
Food Res Int ; 162(Pt A): 112062, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36461265

RESUMO

Consumption of tea residues dietary fiber (TRDF) contributed to the relief of hyperglycemia symptoms in type 2 diabetes (T2D). Given the properties of TRDF abundant in bound polyphenols, the research intended to evaluate the effect of the presence or absence of bound polyphenols in TRDF on the improvement of diabetic complications (liver and kidney injury, metabolic disorders) in T2D rats induced by high-fat diet and streptozocin injection. Our results revealed that the presence of bound polyphenols in TRDF was remarkably beneficial for the amelioration of liver and kidney damage caused by T2D, which was supported by significant differences in activities of serum glutamic oxaloacetic transaminase (AST) and glutamic-pyruvic transaminase (ALT), contents of inflammatory factors in liver and kidney, the levels of kidney oxidative stress, as well as histopathological status between TRDF and bound polyphenols removed-TRDF (TRDF-DF) groups. In addition, metabolomic analysis revealed that TRDF interventions could increase the levels of metabolites such as S-Adenosylmethionine, L-Homophenylalanine and Riboflavin, as well as differ in the regulation of the metabolic pathways including arachidonic acid metabolism and cysteine and methionine metabolism as compared to TRDF-DF without bound polyphenols. These results suggested that bound polyphenols ensured the health-promoting effects for T2D complications of TRDF.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Ratos , Animais , Chá , Polifenóis , Fibras na Dieta , Fígado
2.
Food Res Int ; 159: 111595, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35940761

RESUMO

This study investigated the impact of soluble dietary fiber (SDF) from untreated (U-SDF), fermented (F-SDF) and high temperature cooked (H-SDF) from tea residues on formation of acrylamide (AA) and 5-hydroxymethylfurfural (5-HMF) in biscuits. Both 3% F-SDF and 2% H-SDF can simultaneously inhibit AA and 5-HMF and SDFs increased the types of volatile compounds in biscuits. After the determination of the bound polyphenol compositions in SDFs by LC-QTOF-MS/MS, six polyphenols with different structural characteristics were selected to explore their contributions on the inhibitory effect of SDFs and structure-inhibitory capacity relationships in the "glucose-asparagine-linoleic acid" model system. It showed that the inhibitory activities of those polyphenols were greatly affected by the number of hydroxyl groups and methoxy groups on the benzene ring. Almost all polyphenols were also found to scavenge hydroxyl radicals generated in reactions. Thus, this study suggests that the bound polyphenols of SDFs play a key role in the inhibition of AA and 5-HMF.


Assuntos
Acrilamida , Polifenóis , Acrilamida/química , Fibras na Dieta , Furaldeído/análogos & derivados , Polifenóis/química , Espectrometria de Massas em Tandem , Chá
3.
Food Res Int ; 155: 111122, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35400409

RESUMO

Tea residues are rich in dietary fiber, which possesses excellent physicochemical and functional properties in vitro. However, the hypoglycemic effect and mechanism of dietary fiber from tea residues are not clear. The study aimed to investigate the potential hypoglycemic effect of dietary fiber obtained from tea residues fermentation (TRDF) and reveal its related mechanisms of action in terms of both intestinal flora and metabolomics. The type 2 diabetes (T2D) rat model induced by high-fat diet and streptozotocin injection was applied in this study. Four weeks of TRDF intervention could remarkably ameliorate hyperglycemia, severe oxidative stress and insulin resistance of diabetic rats. Additionally, there was a significant increase of short chain fatty acids (SCFAs) concentrations in feces of diabetic rats after TRDF intervention. Furthermore, TRDF played a positive role in relieving intestinal microbiota dysbiosis by enriching beneficial bacteria (S24-7 and Prevotellaceae) and inhibiting harmful bacteria (Desulfovibrionaceae and Clostridiaceae). Metabolomic analysis showed that TRDF improved the amino acid metabolism and citrate cycle. The study elaborated on the hypoglycemic effect and potential mechanisms of TRDF through multiple pathways of gut microbiota and metabolites, which could provide theoretical basis for TRDF as a dietary supplement to manage T2D.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Fibras na Dieta , Disbiose , Hipoglicemiantes/farmacologia , Metabolômica , RNA Ribossômico 16S/genética , Ratos , Chá/química
4.
Food Funct ; 13(5): 2710-2728, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35170607

RESUMO

Dietary fiber intake is beneficial for the prevention of some chronic metabolic diseases. Considering the characteristic that dietary fiber from tea residues (TRDF) is rich in bound polyphenols, the study aimed to elucidate the interaction effect between dietary fiber components (TRDF-DF) and bound polyphenol components (TRDF-BP) on the anti-hyperglycemic activity of TRDF. A type 2 diabetes (T2D) rat model induced by high-fat diet and streptozotocin injection was applied in this study. The results showed that bound polyphenol components rather than dietary fiber components were essential for the anti-hyperglycemic activity of TRDF, as evidenced by remarkable differences in fasting blood glucose (FBG), the insulin resistance index (HOMA-IR) and the levels of serum oxidative stress between the TRDF and TRDF-DF groups, as well as the up-regulation of the expression of insulin signaling pathway-related proteins in the liver after TRDF and TRDF-BP administration. In addition, the synergistic effect between TRDF-BP and TRDF-DF components modulated gut microbiota dysbiosis and increased the content of short chain fatty acids (SCFAs) via enriching beneficial bacteria and inhibiting harmful bacteria. The role of TRDF-BP and TRDF-DF as well as their interaction effect on the anti-hyperglycemic activity of TRDF are elucidated, which can provide theoretical basis for TRDF as a dietary supplement to manage T2D.


Assuntos
Fibras na Dieta/farmacologia , Alimento Funcional , Hipoglicemiantes/farmacologia , Polifenóis/farmacologia , Chá , Animais , Diabetes Mellitus Tipo 2 , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/química , Masculino , Polifenóis/química , Ratos , Ratos Wistar , Relação Estrutura-Atividade
5.
Drug Des Devel Ther ; 15: 4827-4836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34880597

RESUMO

BACKGROUND: Betel nuts have long been used in traditional Chinese medicine. In our study, the bioactive components of betel nut were systematically investigated, and the main components and their target genes in the treatment of depression were predicted. METHODS: The metabolites of the kernels and peels were analyzed with a UPLC-MS/MS system. Mass spectrometry outcomes were annotated by MULTIAQUANT. "Compound-disease targets" were utilized to construct a pharmacology network. RESULTS: A total of 873 metabolites were identified, with a high abundance of flavonoids, alkaloids, and phenols. Moreover, the abundance of flavonoids, alkaloids, and phenols in the kernel was significantly higher than that in the peel. A high abundance of catechin, arginine, and phenylalanine was detected in the kernel, while a high abundance of arginine, arecoline, and aminobutyric acid was detected in the peel. Catechins and cyanoside were the most abundant flavonoids in the kernel and peel, respectively. Arecoline was the most abundant alkaloid. A total of 111 metabolites showed a significant difference between the kernels and peels. The relative abundance of 40 differential metabolites was higher than 100,000, including 14 primary metabolites, 12 flavonoids, 4 phenols, and 4 alkaloids. Among the 40 high abundance metabolites, 20 were higher in the kernel and 20 in the peel. In addition, the enrichment of metabolic pathways found that the kernel and peel of the fruit adopted different metabolic pathways for the synthesis of flavonoids and alkaloids. Network pharmacology prediction showed that 93 metabolites could target 141 depression-related genes. The main components of betel nut intervention in depression were predicted to include L-phenylalanine, protocatechuic acid, okanin, nicotinic acid, L-tyrosine, benzocaine, syringic acid, benzocaine, phloretic acid, cynaroside, and 3,4-dihydroxybenzaldehyde. CONCLUSION: Betel nuts are rich in natural metabolites, and some of these metabolites can participate in the intervention of depression. In addition, the metabolites showed distinct characteristics between the kernel and peel. Therefore, it is necessary to comprehensively and rationally use betel nuts.


Assuntos
Alcaloides/análise , Antidepressivos/análise , Areca/química , Flavonoides/análise , Fenóis/análise , Alcaloides/metabolismo , Alcaloides/uso terapêutico , Antidepressivos/metabolismo , Antidepressivos/uso terapêutico , Cromatografia Líquida de Alta Pressão , Biologia Computacional , Depressão/tratamento farmacológico , Flavonoides/metabolismo , Flavonoides/uso terapêutico , Humanos , Metabolômica , Farmacologia em Rede , Fenóis/metabolismo , Fenóis/uso terapêutico , Espectrometria de Massas em Tandem
6.
PLoS One ; 16(10): e0258489, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648581

RESUMO

Betel nut chewing (BNC) is prevalent in South Asia and Southeast Asia. BNC can affect host health by modulating the gut microbiota. The aim of this study is to evaluate the effect of BNC on the gut microbiota of the host. Feces samples were obtained from 34 BNC individuals from Ledong and Lingshui, Hainan, China. The microbiota was analyzed by 16S rRNA gene sequencing. BNC decreased the microbial α-diversity. Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria were the predominant phyla, accounting for 99.35% of the BNC group. The Firmicutes-to-Bacteroidetes ratio was significantly increased in the BNC group compared to a control group. The abundances of the families Aerococcaceae, Neisseriaceae, Moraxellaceae, Porphyromonadaceae, and Planococcaceae were decreased in the BNC/BNC_Male/BNC_Female groups compared to the control group, whereas the abundances of Coriobacteriaceae, Streptococcaceae, Micrococcaceae, Xanthomonadaceae, Coxiellaceae, Nocardioidaceae, Rhodobacteraceae, and Succinivibrionaceae were increased. In general, the gut microbiome profiles suggest that BNC may have positive effects, such as an increase in the abundance of beneficial microbes and a reduction in the abundance of disease-related microbes. However, BNC may also produce an increase in the abundance of disease-related microbes. Therefore, extraction of prebiotic components could increase the beneficial value of betel nut.


Assuntos
Areca/química , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Adolescente , Adulto , Areca/metabolismo , Bactérias/genética , Bactérias/isolamento & purificação , Bacteroidetes/genética , Bacteroidetes/isolamento & purificação , China , Análise Discriminante , Fezes/microbiologia , Feminino , Firmicutes/genética , Firmicutes/isolamento & purificação , Humanos , Análise dos Mínimos Quadrados , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/química , Análise de Componente Principal , Proteobactérias/genética , Proteobactérias/isolamento & purificação , RNA Ribossômico 16S/análise , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Adulto Jovem
7.
BMC Infect Dis ; 19(1): 689, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382930

RESUMO

BACKGROUND: Isoniazid (INH) represents the cornerstone for the treatment of cases infected with Mycobacterium tuberculosis (MTB) strains. Several molecular mechanisms have been shown to be the major causes for INH resistance, while the dynamic change of mutations conferring INH resistance among MTB strains during the past decade is still unknown in China. METHODS: In this study, we carried out a comparative analysis of the INH minimal inhibitory concentration (MIC) distribution, and investigate the dynamic change of molecular characteristics among INH-resistant MTB strains between 2005 and 2015. RESULTS: The proportion of INH resistance (39.0%, 105/269) in 2015 was significantly higher than in 2005 (30.0%, 82/273; P = 0.03). Among 269 isolates collected in 2015, 76 (28.3%, 76/269) exhibited high-level INH-resistance (MIC≥32 mg/L), which was significantly higher than that in 2005 (20.5%, 56/273, P = 0.04). In addition, a significantly higher percentage of INH-resistant isolates carried inhA promoter mutations in 2015 (26.7%) versus that in 2005 (14.6%, P = 0.04), while no significant difference was observed in the rates of isolates containing katG mutations between 2005 (76.8%) and 2015 (70.5%, P = 0.33). Notably, the proportion of MTB isolates with inhA mutations (26.7%, 28/105) for patients who had previous exposure to protionamide (PTH) was higher than that for patients who had no previous exposure to PTH (21.4%, 6/28). CONCLUSIONS: In conclusion, our results demonstrated that the proportion of INH-resistant MTB isolates significantly increased during the last decade, which was mainly attributed to an increase of high-level INH-resistant MTB. In addition, prior exposure to PTH may be associated with the increased frequency of INH-resistant tuberculosis strains with inhA mutations in China.


Assuntos
Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Isoniazida/uso terapêutico , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/epidemiologia , Adulto , Idoso , Proteínas de Bactérias/genética , China/epidemiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Oxirredutases/genética , Prevalência , Regiões Promotoras Genéticas , Tuberculose/tratamento farmacológico , Tuberculose/microbiologia , Adulto Jovem
8.
Clin Infect Dis ; 69(3): 405-413, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-30321294

RESUMO

BACKGROUND: The increase in multidrug-resistant tuberculosis (MDR-TB) severely hampers tuberculosis prevention and control in China, a country with the second highest MDR-TB burden globally. The first nationwide drug-resistant tuberculosis surveillance program provides an opportunity to comprehensively investigate the epidemiological/drug-resistance characteristics, potential drug-resistance mutations, and effective population changes of Chinese MDR-TB. METHODS: We sequenced 357 MDR strains from 4600 representative tuberculosis-positive sputum samples collected during the survey (70 counties in 31 provinces). Drug-susceptibility testing was performed using 18 anti-tuberculosis drugs, representing the most comprehensive drug-resistance profile to date. We used 3 statistical and 1 machine-learning methods to identify drug-resistance genes/single-nucleotide polymorphisms (SNPs). We used Bayesian skyline analysis to investigate changes in effective population size. RESULTS: Epidemiological/drug-resistance characteristics showed different MDR profiles, co-resistance patterns, preferred drug combination/use, and recommended regimens among 7 Chinese administrative regions. These factors not only reflected the serious multidrug co-resistance and drug misuse but they were also potentially significant in facilitating the development of appropriate regimens for MDR-TB treatment in China. Further investigation identified 86 drug-resistance genes/intergenic regions/SNPs (58 new), providing potential targets for MDR-TB diagnosis and treatment. In addition, the effective population of Chinese MDR-TB displayed a strong expansion during 1993-2000, reflecting socioeconomic transition within the country. The phenomenon of expansion was restrained after 2000, likely attributable to the advances in diagnosis/treatment technologies and government support. CONCLUSIONS: Our findings provide an important reference and improved understanding of MDR-TB in China, which are potentially significant in achieving the goal of precision medicine with respect to MDR-TB prevention and treatment.


Assuntos
Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Genoma Bacteriano , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adolescente , Adulto , Idoso , Antituberculosos/farmacologia , Teorema de Bayes , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mutação , Mycobacterium tuberculosis/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Escarro/microbiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Sequenciamento Completo do Genoma , Adulto Jovem
9.
Infect Genet Evol ; 72: 151-158, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30292007

RESUMO

Selective pressure from antibiotic use is one of the most important risk factors associated with the development of drug resistance in Mycobacterium tuberculosis (MTB). However, the mechanisms underlying drug resistance at the molecular level remain partly unclear. Therefore, the purpose of this study was to investigate the potential functional effect of novel mutations arising from anti-tuberculosis treatment. We analyzed two multidrug-resistant TB (MDR-TB) isolates from the same patient; one collected before and one almost a year after commencing MDR-TB treatment. The post-treatment isolate exhibited elevated ethambutol resistance. We sequenced the whole genomes of the two clinical isolates and detected six novel polymorphisms affecting the genes Rv1026, nc0021, Rv2155c, Rv2437, and Rv3696c, and the intergenic region between Rv2764c and Rv2765. Metabolomics approach was used to reveal the effect of the found variation on the metabolic pathways of MTB. Partial least squares-discriminant analysis showed a clear differentiation between the two isolates, involving a total of 175 metabolites. Pathway analysis showed that these metabolites are mainly involved in amino sugar and nucleotide sugar metabolism, ß-alanine metabolism, sulfur metabolism, and galactose metabolism. The increased ethambutol resistance exhibited by the post-treatment MDR-TB strain could speculatively be linked to the identified genetic variations, which affected the synthesis of a number of metabolites associated with sources of carbon and energy. This may have been the main factor underlying the increased ethambutol resistance of this isolate.


Assuntos
Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Etambutol , Metabolômica , Mutação , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , Metabolismo dos Carboidratos/efeitos dos fármacos , Metabolismo dos Carboidratos/genética , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Etambutol/farmacologia , Etambutol/uso terapêutico , Humanos , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/genética , Testes de Sensibilidade Microbiana , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Sequenciamento Completo do Genoma
10.
J Glob Antimicrob Resist ; 14: 17-22, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29476986

RESUMO

OBJECTIVES: This study aimed to describe trends in antituberculosis drug prescribing for inpatients from 2011-2015 in a Chinese national tuberculosis (TB) hospital. METHODS: This retrospective study, performed in March 2016, reviewed the medical records of all inpatients from Beijing Chest Hospital diagnosed with TB between 2011-2015. Medication used for TB treatment during the inpatient period was recorded. RESULTS: A total of 11465 inpatients were enrolled in the study. The most frequently prescribed drug for inpatients was isoniazid (71.2%; 8164/11465), followed by ethambutol (67.5%; 7738/11465), pyrazinamide (59.7%; 6839/11465) and rifampicin (40.0%; 4589/11465). In addition, amikacin (16.5%; 1889/11465), levofloxacin (33.0%; 3789/11465), para-aminosalicylic acid (12.4%; 1422/11465) and clarithromycin (3.5%; 406/11465) were the most common drugs used in the treatment of inpatients for Group II, III, IV and V drugs, respectively. A significant increasing trend in prescribing was found for rifampicin, pyrazinamide, capreomycin, moxifloxacin, prothionamide, para-aminosalicylic acid, cycloserine, clofazimine and linezolid, respectively, whilst there was a significant decreasing trend in the rate of prescribing of ethambutol, amikacin, levofloxacin, amoxicillin/clavulanic acid and clarithromycin during the 5-year study period (Ptrend<0.01). CONCLUSIONS: These data demonstrate that prescription of anti-TB drugs varied greatly across clinical diagnostic categories, treatment history and drug susceptibility profiles of TB patients. The World Health Organization (WHO)-endorsed standard regimen should be more extensively employed under conditions where drug susceptibility testing is unavailable in order to guide clinicians to formulate a suitable treatment regimen for TB patients.


Assuntos
Antituberculosos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , China , Hospitais de Doenças Crônicas/estatística & dados numéricos , Humanos , Pacientes Internados , Isoniazida/uso terapêutico , Linezolida/uso terapêutico , Prontuários Médicos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Estudos Retrospectivos , Rifampina/uso terapêutico
11.
Artigo em Inglês | MEDLINE | ID: mdl-29378718

RESUMO

We performed a multicenter, prospective, randomized study to investigate the efficacy and safety of clofazimine (CLO) for treatment of extensively drug-resistant tuberculosis (XDR-TB) in China. Forty-nine patients infected with XDR-TB were randomly assigned to either the control group or the CLO group, both of which received 36 months of individually customized treatment. The primary endpoint was the time to sputum culture conversion on solid medium. Clinical outcomes of patients were evaluated at the time of treatment completion. Of the 22 patients in the experimental group, 7 (31.8%) met the treatment criterion of "cure" and 1 (4.5%) "complete treatment," for a total of 8 (36.4%) exhibiting successful treatment outcomes without relapse. In the control group, 6 patients (22.2%) were cured and 6 (22.2%) completed treatment by the end of the study. Statistical analysis revealed no significant difference in successful outcome rates between the CLO group and the control group. The average sputum culture conversion time for the experimental group was 19.7 months, which was not statistically different from that for the control group (20.3 months; P = 0.57). Of the 22 patients in the CLO group, 12 (54.5%) experienced adverse events after starting CLO treatment. The most frequently observed adverse event was liver damage, with 31.8% of patients (7/22 patients) in the CLO group versus 11.1% (3/27 patients) in the control group exhibiting this adverse event. Our study demonstrates that inclusion of CLO in background treatment regimens for XDR-TB is of limited benefit, especially since hepatic disorders arise as major adverse events with CLO treatment. (This study is registered with the Chinese Clinical Trial Registry [ChiCTR, www.chictr.org.cn] under identifier ChiCTR1800014800.).


Assuntos
Antituberculosos/uso terapêutico , Clofazimina/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Adulto , Idoso , Antituberculosos/efeitos adversos , China , Clofazimina/efeitos adversos , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos
12.
Artigo em Inglês | MEDLINE | ID: mdl-29311073

RESUMO

Cycloserine (Cs) is recommended by the World Health Organization as a second-line drug to treat multidrug-resistant tuberculosis (MDR-TB); however, its efficacy has never been sufficiently evaluated. To gain some insights into the value of cycloserine for MDR-TB treatment, in vitro bacteriostatic effect was determined and patient validations were performed prospectively. The in vitro activity of Cs against 104 wild-type Mycobacterium tuberculosis strains was determined, and serum Cs concentrations were measured for 73 MDR TB patients 2 h after administration. The treatment outcomes for 27 MDR-TB patients who had baseline isolates and were treated with Cs-containing regimens were followed up. The MICs for 90% of the recruited 104 wild-type strains were below 32 µg/ml. Eighteen out of 52 patients had peak serum concentrations (Cmax) below 20 µg/ml at the dosage of 500 mg daily, while 13 out of 21 patients had peak serum concentrations higher than 35 µg/ml at the dosage of 750 mg daily. The percentage of favorable treatment outcomes among patients with a Cmax/MIC ratio of ≥1 was statistically significantly higher than that among the group with a Cmax/MIC ratio of <1 (P = 0.022). The epidemiological cutoff value for Cs susceptibility testing was 32 µg/ml. A high percentage of patients receiving the recommended dosage of 10 mg/kg for Cs administration could not acquire desirable blood concentrations; therefore, adjusting the dosage according to drug concentration monitoring is necessary. The Cmax/MIC ratio might be a good indicator for predicting the treatment outcome for patients with MDR-TB or extensively drug-resistant TB (XDR-TB) who are being administered Cs-containing regimens.


Assuntos
Antituberculosos/sangue , Antituberculosos/uso terapêutico , Ciclosserina/sangue , Ciclosserina/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/sangue , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Pequim , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/patogenicidade , Fatores de Risco , Adulto Jovem
13.
J Infect ; 75(5): 433-440, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28804028

RESUMO

OBJECTIVES: The objective of this study was to explore the prevalence and primary clinical outcomes of extensively drug-resistant tuberculosis plus addition resistance to all drug tested (XDR-TB-Plus) between 2011 and 2015 in Beijing Chest Hospital. METHODS: We retrospectively reviewed the drug susceptibility testing (DST) results of clinical Mycobacterium tuberculosis (MTB) strains from TB patients seeking health care in the National Clinical Center for Tuberculosis, between 2011 and 2015. The medical records of patients classified as XDR-TB-Plus were reviewed, including demographic characteristics, treatment regimen, and treatment outcome. RESULTS: Of 9544 MTB isolates, there were 3376 (35.4%), 842 (8.8%) and 61 (0.64%) isolates identified as multidrug resistant tuberculosis (MDR-TB), extensively drug resistant tuberculosis (XDR-TB) and XDR-TB-Plus, respectively. The proportion of XDR-TB showed significant increase from 6.3% in 2011 to 9.1% in 2015 (Chi-square trend 5.94, P = 0.015). Similarly, the proportion of XDR-TB-Plus seemed to increase from 0.46% in 2011 to 0.74% in 2015, while the increasing trend was not significant (Chi-square trend 1.50, P = 0.221). The most frequently prescribed anti-TB drug was moxifloxacin (18/29, 62.1%), followed by protionamide (16/29, 55.2%), clofazimine (15/29, 51.7%), and pyrazinamide (15/29, 51.7%). Patients receiving regimens containing linezolid (LZD) were almost 27 times more likely to have favorable treatment outcome compared with those receiving regimens without LZD [odds ratios = 27.00; 95% CI = 2.50-291.19; P = 0.003]. CONCLUSIONS: In conclusion, our data have demonstrated that the proportion of XDR-TB has significantly increased over the past five years in Beijing Chest Hospital. In addition, the XDR-TB-Plus patients were more likely to reach favorable clinical outcome under the treatment of regimen containing LZD.


Assuntos
Antituberculosos/uso terapêutico , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Adulto , China/epidemiologia , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Prevalência , Estudos Retrospectivos , Resultado do Tratamento
14.
J Pineal Res ; 46(3): 248-54, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19317793

RESUMO

Acute renal dysfunction is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study was designed to evaluate the potential protective effect of melatonin on CPB-induced renal damage in a rat model. Forty male Sprague-Dawley rats were randomly divided into four groups: sham, control (CPB + placebo), low dose of melatonin (CPB + 10 mg/kg melatonin) and high dose of melatonin (CPB + 20 mg/kg melatonin). Blood samples were collected at the beginning, at the end of CPB, and at 0.5, 1, 2, 3, and 24 hr postoperation. Serum creatinine and blood urea nitrogen levels were assayed. Rats were killed 24 hr after surgery, the histologic appearance of the kidney and malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT) and superoxide dismutase (SOD) contents were determined. The expression levels of hemeoxygenase-1 (HO-1) protein and gene were determined using western blotting and real-time PCR, respectively. In the control group, CPB surgery significantly increased urea, creatinine levels in serum, MDA and MPO levels in tissues, while decreasing SOD and CAT activities in tissues. Histopathologic findings of the control group confirmed that there was renal impairment by cast formation and tubular necrosis in the tubular epithelium. These changes were markedly reversed in both low dose of melatonin and high dose of melatonin groups. Furthermore, HO-1 gene transcript and protein were significantly upregulated in the kidney tissues after melatonin treatment compared with the placebo treatment. Our findings show that melatonin was effective in preventing CPB-induced renal damage probably through its antioxidant function and upregulation of HO-1.


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Heme Oxigenase-1/metabolismo , Nefropatias/tratamento farmacológico , Melatonina/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Expressão Gênica , Heme Oxigenase-1/genética , Rim/efeitos dos fármacos , Rim/ultraestrutura , Nefropatias/etiologia , Nefropatias/prevenção & controle , Masculino , Malondialdeído/metabolismo , Melatonina/uso terapêutico , Peroxidase/metabolismo , Distribuição Aleatória , Ratos , Estatísticas não Paramétricas , Superóxido Dismutase/metabolismo , Regulação para Cima
15.
Pediatr Transplant ; 12(5): 550-6, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18466197

RESUMO

Recent in vitro data suggested that n-3 fatty acids could inhibit the activation of PPAR gamma. This study was designed to test the hypothesis that fish oil ameliorates CAV development via activating PPAR gamma in an inbred rat model of heart transplantation. Animals were divided into four groups: isograft, control (CsA + vehicle), LFO-treated group (CsA + 0.3% v/w fish oil), and HFO-treated group (CsA + 0.6% v/w fish oil). CsA was administered at 1.5 mg/kg/day for two wk postoperatively. Recipients were treated with fish oil or vehicle daily for eight wk. The histopathological and immunohistochemical examination, activity of NF-kappaB and PPAR gamma, intragraft chemokine levels, and chemokine receptor expression were analyzed. Both LFO and HFO significantly decreased the CAV score, inhibited recruitment of T lymphocytes and macrophages, elevated the activity of PPAR gamma, inhibited the activity of NF-kappaB, reduced levels of intragraft MCP-1 and IP-10 as well as downregulated expression of chemokine receptors CCR2. CXCR3 expression was not affected. Our results demonstrated that fish oil might attenuate CAV development, possibly through activating PPAR gamma and subsequently inhibiting the NF-kappaB activation, the chemokines secretion, as well as the CCR2 expression.


Assuntos
Dieta , Ácidos Graxos Ômega-3/metabolismo , Regulação da Expressão Gênica , Transplante de Coração/métodos , PPAR gama/metabolismo , Doenças Vasculares/terapia , Animais , Quimiocinas/metabolismo , Óleos de Peixe , Transplante de Coração/efeitos adversos , Imuno-Histoquímica , NF-kappa B/metabolismo , Ratos , Receptores CCR2/metabolismo , Receptores de Quimiocinas/metabolismo , Transplante Homólogo , Doenças Vasculares/etiologia
16.
Eur J Pharmacol ; 580(3): 416-24, 2008 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-18053982

RESUMO

Hepatic injury after cardiac surgery was considered to be a consequence of cardiopulmonary bypass (CPB). This study tested the hypothesis that melatonin could attenuate the hepatic injury in a rat CPB model. Male Sprague-Dawley rats were randomly divided into four groups: sham-operation group, control group (given an equal volume of vehicle), low dose melatonin (10 mg/kg) treated group and high dose melatonin (20 mg/kg) treated group. Blood samples were collected at the beginning, at the cessation of CPB, and at 30 min, 1, 2, 3 and 24 h post-operation. Liver samples were harvested at 24 h after operation. The serum indices of the liver enzymes and systemic inflammation, as well as oxidative stress indices and the Ca++-ATPase activity of liver tissues were determined. In the control animals, the indices of liver enzymes, tumor necrosis factor-alpha (TNF-alpha) increased after operation, and liver inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), myeloperoxidase (MPO) increased as well. However, the activities of liver antioxidative enzymes and the concentration of glutathione (GSH) decreased remarkably. Results in melatonin group showed that melatonin reversed all the biochemical changes, but there was no significant difference between the melatonin-treated groups. In addition, histological findings further supported these results. All results indicated that application of exogenous melatonin during operation preserves liver function by reducing oxidative stress and the systemic inflammatory response.


Assuntos
Ponte Cardiopulmonar/efeitos adversos , Hepatopatias/prevenção & controle , Melatonina/farmacologia , Complicações Pós-Operatórias/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Dióxido de Carbono/sangue , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Concentração de Íons de Hidrogênio/efeitos dos fármacos , Infusões Intravenosas , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Hepatopatias/etiologia , Hepatopatias/fisiopatologia , Testes de Função Hepática , Masculino , Malondialdeído/metabolismo , Melatonina/administração & dosagem , Infiltração de Neutrófilos/efeitos dos fármacos , Óxido Nítrico Sintase/metabolismo , Oxigênio/sangue , Peroxidase/metabolismo , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/sangue
17.
World J Gastroenterol ; 12(31): 5068-70, 2006 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-16937509

RESUMO

AIM: To study the effect of combined indwelling catheter, hemofiltration, respiration support and traditional Chinese medicine (e.g. Dahuang) in treating abdominal compartment syndrome of fulminant acute pancreatitis. METHODS: Patients with fulminant acute pancreatitis were divided randomly into 2 groups of combined indwelling catheter celiac drainage and intra-abdominal pressure monitoring and routine conservative measures group (group 1) and control group (group 2). Routine non-operative conservative treatments including hemofiltration, respiration support, gastrointestinal TCM ablution were also applied in control group patients. Effectiveness of the two groups was observed, and APACHE II scores were applied for analysis. RESULTS: On the second and fifth days after treatment, APACHE II scores of group 1 and 2 patients were significantly different. Comparison of effectiveness (abdominalgia and burbulence relief time, hospitalization time) between groups 1 and 2 showed significant difference, as well as incidence rates of cysts formation. Mortality rates of groups 1 and 2 were 10.0% and 20.7%, respectively. For patients in group 1, celiac drainage quantity and intra-abdominal pressure, and hospitalization time were positively correlated (r = 0.552, 0.748, 0.923, P<0.01) with APACHE II scores. CONCLUSION: Combined indwelling catheter celiac drainage and intra-abdominal pressure monitoring, short veno-venous hemofiltration (SVVH), gastrointestinal TCM ablution, respiration support have preventive and treatment effects on abdominal compartment syndrome of fulminant acute pancreatitis.


Assuntos
Cateteres de Demora , Síndromes Compartimentais/complicações , Síndromes Compartimentais/terapia , Gastroenteropatias/complicações , Gastroenteropatias/terapia , Pancreatite/complicações , Pancreatite/terapia , Doença Aguda , Cateterismo/métodos , Hospitalização , Humanos , Medicina Tradicional Chinesa , Resultado do Tratamento
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