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Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.
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Álcoois Benzílicos , Clorobenzenos , Quinuclidinas , Humanos , Álcoois Benzílicos/administração & dosagem , Álcoois Benzílicos/efeitos adversos , Estudos Prospectivos , Clorobenzenos/efeitos adversos , Clorobenzenos/administração & dosagem , Quinuclidinas/efeitos adversos , Quinuclidinas/administração & dosagem , Idoso , Masculino , Feminino , China , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Pessoa de Meia-Idade , Povo Asiático , População do Leste AsiáticoRESUMO
Technical Specifications for Occupational Health Surveillance (GBZ 188-2014) is an important basis for judging suspected occupational diseases and occupational contraindications. There are crossing over or overlap between occupational contraindications and diagnostic criteria of poisoning damage. Occupational contraindications have different meanings with the degree and range of common diseases or symptoms and the frequency of physical examination during employment conflicts with the current standard. Based on the practice of occupational health examination in a large population, the present study analyzed relevant articles and put forward some suggestions for revision, in combination with clinical medicine, occupational health standards, and diagnostic standards of occupational diseases. The modification could provide a reference for the revision of Technical Specifications for Occupational Health Surveillance and the practice of occupational health examination.
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Doenças Profissionais , Serviços de Saúde do Trabalhador , Saúde Ocupacional , Medicina do Trabalho , Humanos , Local de Trabalho , Padrões de ReferênciaRESUMO
OBJECTIVE: To investigate the role of glucose-6-phosphate dehydrogenase (G6PD) in hepatitis B virus (HBV) replication and its possible mechanism of action. METHODS: Tissue microarray, quantitative real-time PCR, and Western blot were performed to analyze the differences in G6PD expression levels in the HBV-positive and HBV-negative liver tissues, HepG2.2.15 cells, and HepG2 cells. The siRNA transfection technique was used to knock down G6PD gene in HepG2.2.15 cells for 48 hours. Chemiluminescence was used for HBsAg and HBeAg quantification in supernatant, and quantitative real-time PCR was used to measure HBV DNA, type I interferon (IFN), and downstream IFN-stimulated genes. The t-test was used for comparison between groups. RESULTS: G6PD expression was significantly upregulated in the HBV-positive liver tissues and cells compared with HBV-negative liver tissues and cells, and the stain intensity and immunohistochemical scores were 89.69±54.92 and 31.90±18.62, respectively (P < 0.05). After G6PD expression in HepG2.2.15 cells was interfered by siRNA, the quantitative levels of HBV DNA, HBsAg, and HBeAg in supernatant were reduced significantly, and the mRNA expression levels of IFNα1, IFNß1, and five downstream IFN-stimulated genes (OAS1, ISG15, OAS3, EIF2α, and PKR) increased significantly (all P < 0.05). CONCLUSION: G6PD plays a vital role in HBV replication, and its mechanism of action in regulating HBV replication may be related to type I IFN signaling pathway.
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Glucosefosfato Desidrogenase/metabolismo , Vírus da Hepatite B/fisiologia , Fígado/enzimologia , Replicação Viral , DNA Viral/isolamento & purificação , Técnicas de Silenciamento de Genes , Células Hep G2 , Hepatite B , Antígenos de Superfície da Hepatite B/isolamento & purificação , Antígenos E da Hepatite B/isolamento & purificação , Humanos , Interferon Tipo I/metabolismo , Fígado/virologia , RNA Interferente Pequeno , Reação em Cadeia da Polimerase em Tempo Real , TransfecçãoRESUMO
The Cs technique has been widely used to provide soil redistribution estimates since the 1970s. However, most Cs-conversion models remain theoretical and largely unvalidated. Our objectives were to validate the four widely used conversion models, examine model parameter sensitivity, and evaluate the potential of using kriging to improve soil redistribution estimation. Soil loss was measured from a 1.6-ha plot since 1978. Winter wheat ( L.) was grown primarily under conventional tillage. Soil samples in a 10-m grid were taken from the plot to estimate the Cs inventory. Soil redistribution rates were estimated using four models and were further interpolated using ordinary kriging. The parameter sensitivity analyses at the 95% confidence limits showed that reference inventory had the most impact on estimated water erosion, followed by particle size correction for erosion and tillage depth, with minimal impacts from mass depth, bulk density, and particle size correction for deposition. Compared with the measured water erosion, the relative errors of the mean net water erosion estimates across the entire plot without and with kriging were 28 and -17% for the proportional model (PM), 141 and 106% for the simplified mass balance model, 133 and 100% for the improved mass balance model (MBM2), and 109% for the extended MBM2 with tillage erosion (MBM3). Results indicated that the PM performed better than the mass balance models under the study conditions and that kriging improved mean soil redistribution estimates. However, the full potential of the MBM2 and MBM3 needs to be further evaluated under conditions where loss of newly deposited Cs exists.
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BACKGROUND: Subjective hearing loss (SHL) refers to an individual's self-assessment of their hearing loss. The association and underlying mechanisms between SHL and cognitive impairment still necessitate elucidation. OBJECTIVES: To validate potential mechanisms between SHL and cognitive impairment. DESIGN: Cross-section. SETTING: Shanghai, China. PARTICIPANTS: A total of 2369 individuals from communities and the cognitive disorder clinic. MEASUREMENTS: All participants were subjected to a comprehensive neuropsychological assessment, encompassing the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S). The participants' brain ß-amyloid (Aß) deposition status, plasma biomarkers associated with Alzheimer's disease (AD), and cardiovascular risk factors were also collected. RESULTS: In individuals with a heightened SHL, elevated HHIE-S score was linked to diminished cognitive and daily functioning as well as heightened levels of depressed mood. This correlation was observed in auditory memory performance but not in visual memory. The influence of SHL on cognitive function was mediated by depressed mood. SHL was associated with diabetes and smoking, whereas cognitive function was associated with hyperlipidemia and alcohol consumption. In individuals with positive brain Aß deposition, SHL demonstrated associations with cognitive function independent of plasma Aß42/40 ratio, P-tau181, neurofilament light chain, and APOE allele status. CONCLUSION: SHL has an independent effect on cognitive impairment. The findings do no provide evidence for the common cause mechanism. Instead, the findings support the presence of a cognitive resource mechanism and an impoverished environment mechanism, along with the potential for a pathological interaction mechanism.
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Peptídeos beta-Amiloides , Disfunção Cognitiva , Perda Auditiva , Humanos , Masculino , Feminino , Perda Auditiva/psicologia , Idoso , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/sangue , Estudos Transversais , China , Testes Neuropsicológicos , Pessoa de Meia-Idade , Biomarcadores/sangue , Fatores de Risco , Autoavaliação Diagnóstica , Encéfalo/metabolismo , DepressãoRESUMO
BACKGROUND: Large-scale preclinical Alzheimer's disease study based on ß-amyloid positron emission tomography (PET) has not been conducted in China. OBJECTIVES: Establish a cohort on Alzheimer's disease spectrum, especially the preclinical stages, and determine the factors influencing the acceptance of ß-amyloid PET scan screening in China. DESIGN: Longitudinal. SETTING: Shanghai, China. PARTICIPANTS: A total of 4386 participants were screened and 2451 participants who met enrollment criteria were eventually included in this report. MEASUREMENTS: The multidimensional data was collected, including comprehensive assessments, PET and magnetic resonance imaging scans, genetics, and plasma biomarkers. RESULTS: There were 571 participants in the normal cognition group, 625 participants in the subjective cognitive decline group, 155 participants in the objectively defined subtle cognitive decline group, 501 participants in the mild cognitive impairment group, 471 participants in Alzheimer's disease group, and 128 participants with cognitive impairment from other known causes. Significant differences in demographics, florbetapir PET, APOE, and neuropsychological tests were found among the groups. Eight hundred and seventeen participants (33.3%) completed the florbetapir PET scanning. Non-demented individuals with higher age, lower education years, male, with a family history of dementia, and higher self-report depression prefer to undergo PET scans. Acceptance of PET scans did not correlate with objectively assessed cognitive impairment. CONCLUSIONS: The Chinese Preclinical Alzheimer's Disease Study was designed to establish a large-scale cohort with comprehensive data collection. Our findings may help to understand the factors affecting the acceptance of ß-amyloid PET in urban areas of China and help us address the low acceptance challenge.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Tomografia por Emissão de Pósitrons , Humanos , Masculino , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/diagnóstico por imagem , Apolipoproteínas E , China , População do Leste Asiático , Tomografia por Emissão de Pósitrons/métodosRESUMO
Objective: To summarize the clinical features and therapeutic outcomes of patients with hyperinsulinemic hypoglycemia (HH) auxiliarily diagnosed by 18F-DOPA positron emission tomography (PET) CT scanning. Methods: The clinical data of 123 patients who were diagnosed with hyperinsulinemic hypoglycemia by comprehensive clinical diagnostic procedures in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University between January 2016 and December 2020 were retrospectively analyzed. Clinical data such as gender, age of onset, province, concurrent serum insulin level measured during hypoglycemia, lesion type of pancreas by 18F-DOPA-PET CT scanning, genetic test results, and treatment were collected successively. The clinical features and therapeutic outcomes were compared between patients with focal and diffuse pancreatic lesions. T test, Rank sum test, and χ² test were used for comparison between groups. Results: A total of 123 patients with hyperinsulinemic hypoglycemia (72 males and 51 females), whose average age of onset was 3 days (ranging from 1 day to 4 860 days), were recruited from 24 provinces. The concurrent serum insulin level was 7.1 (0.4-303.0) mU/L during hypoglycemia. 18F-DOPA-PET CT scanning identified focal lesions in 25.2% (31/123) and diffuse lesions in 74.8% (92/123) of the patients; 64.2% (79/123) of the HH cases were found to have pathogenic gene variants, in which 88.6% (70/79) were found to have KATP channel related genes (61 in ABCC8 and 9 in KCNJ11 mutations). Thirty-seven patients (17 focal and 20 diffuse) received surgical treatment with a success rate of 67.6% (25/37). The effective rate of diazoxide for children with diffuse type was significantly higher than that of children with focal group (28.3% (26/92) vs. 9.7% (3/31), χ²=10.31, P=0.001). Conclusions: 18F-DOPA-PET CT scan can improve the success rate of surgery. Comprehensive diagnosis of the etiology of hyperinsulinemic hypoglycemia by genetic analysis and 18F-DOPA-PET CT scanning can result in better treatment and prognosis.
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Hiperinsulinismo Congênito , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Criança , Hiperinsulinismo Congênito/diagnóstico por imagem , Hiperinsulinismo Congênito/tratamento farmacológico , Hiperinsulinismo Congênito/genética , Di-Hidroxifenilalanina/análogos & derivados , Feminino , Humanos , Masculino , Tomografia por Emissão de Pósitrons , Estudos RetrospectivosRESUMO
AIM: To determine the clinical features of hepatic myelopathy (HM), a rare condition associated with chronic liver disease (CLD), in patients in the city of Harbin, China. METHODS: The medical files of 13 patients with HM were selected from 500 randomly chosen files of CLD patients registered in four Harbin hospitals. General information on all cases was summarised and clinical features were compared between HM positive patients (HM group) and HM negative CLD patients (control group). Detailed analysis of the clinical characteristics of HM positive patients was undertaken. RESULTS: The patients in the HM group ranged in age from 41-50 years, which did not differ significantly from the control group. However, the sex ratio in the HM group (12 males/1 female) was significantly higher (p<0.05) than in the control group (342 males/145 females).The most frequent underlying aetiology was post type B hepatitis (12 cases). All cases in the HM group had a history of relapsing hepatic encephalopathy (HE) before or after HM onset, and showed electroencephalographic (EEG) abnormalities; however, the results of spinal cord magnetic resonance imaging were negative, and cerebrospinal fluid analysis findings were normal. Except for clinical manifestations of bilateral lower limb spastic paralysis, the two groups did not differ significantly in regard to other symptoms or signs. Hypoproteinaemia (positive predictive value (PPV) 5.69%, negative predictive value (NPV) 99.65%), blood ammonia elevation (PPV 5.29%, NPV, 99.32%) and abnormal EEG (PPV 5.00%, NPV 100.00%) were sensitive and specific for HM diagnosis. CONCLUSION: In Harbin, HM is found mainly among middle aged men with CLD caused by viral hepatitis and accompanied by relapsing onset of HE. Bilateral lower limb spastic paralysis with hypoproteinaemia, blood ammonia elevation and/or abnormal EEG are significant diagnostic indicators of HM.
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Hepatopatias/complicações , Doenças da Medula Espinal/etiologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Feminino , Humanos , Hepatopatias/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Doenças da Medula Espinal/epidemiologia , Doenças da Medula Espinal/terapia , Resultado do TratamentoRESUMO
OBJECTIVE: MYC-induced long non-coding RNA (MINCR) has been shown to be a long noncoding RNA that facilitates the progression of a number of malignancies, including hepatocellular carcinoma (HCC). However, few studies have explored the expression and role of MINCR in HCC. In this study, we aimed to investigate the clinical significance of MINCR in HCC. PATIENTS AND METHODS: MINCR expression levels in 161 pairs of HCC tissues and pair-matched adjacent normal tissues were examined by qRT-PCR. The correlation between clinicopathological features and MINCR expression was analyzed by x2 test. Differences in patient survival were determined using the Kaplan-Meier method and a log-rank test. The significance of survival variables was analyzed using the Cox multivariate proportional hazards model. RESULTS: Our results showed that MINCR was significantly upregulated in HCC tissues, compared with paired adjacent nontumor tissue samples. MINCR upregulation was correlated with TNM stage (p = 0.005) and histological grade (p = 0.001). The results of Kaplan-Meier method and log-rank test indicated that the 5-years overall survival of the high MINCR group was significantly lower than that of low MINCR group (p = 0.0035). Univariate and multivariate analysis results indicated that MINCR was an independent prognostic factor in HCC (p < 0.05). CONCLUSIONS: We firstly provided the possibility that evaluating MINCR in HCC tissues may have prognostic and predictive value in the clinical management of HCC patients.
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Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Fatores de Risco , Fatores de Tempo , Regulação para CimaRESUMO
Stationary phase retention in a synchronous coil planet centrifuge or high-speed counter-current chromatography (CCC) relies on the interplay of hydrostatic (tangential and normal centrifugal) and hydrodynamic (Archimedean screw and mobile phase drag) forces. By offering a set of quantitative or semi-quantitative theoretical frameworks, this work has resolved fundamental questions such as "in the absence of mobile phase flow, how is the distribution of the two phases in a CCC column determined?" and "for Type-J CCC, do the helical and the spiral columns lead to similar performance?"
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Distribuição Contracorrente/instrumentação , Distribuição Contracorrente/métodos , Modelos TeóricosRESUMO
Retention properties of polyethylene glycol-phosphate aqueous two-phase systems in a spiral coil (5 mm I.D.) on Type-J synchronous counter-current chromatographic devices have been compared for the elution mode where the lower phase is the mobile phase and flows from the inside head terminal. This was achieved with the aid of digital imaging under stroboscopic illumination, an image analysis and measurement of the displaced volume of the stationary phase. For the spiral coil, high and stable stationary phase retention at mobile phase flow rates up to 64 ml/min has been obtained. Wave-like disturbance of the interface near the proximal point was observed and analyses have been made for possible use in protein separation.
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Distribuição Contracorrente/instrumentação , Distribuição Contracorrente/métodos , Polímeros/química , Solventes/químicaRESUMO
OBJECTIVE: To assess tooth whiteness clinically using an image analysis system and a whiteness algorithm to compare with visual shade matching. METHODOLOGY: Images of the maxillary anterior teeth of 20 subjects were obtained using an image analysis system adapted for tooth whiteness measurement. Red, green, and blue values from each image, and Commision Internationale de l'Eclairage whiteness index (CIE WI) values were calculated. A visual shade match was also carried out using a Vitapan 3D Master 26-tab shade guide. RESULTS: The range of CIE WI values for image analysis and visual shade matching was 32.86-85.91 and 32.68-79.84, respectively. Limits of agreement between methods were +17.71 and -14.60 CIE WI units. The 95% confidence interval of the difference was calculated as -0.176 to +3.083. A two-tailed Student t-test with a 95% confidence level showed significant differences (p = 0.028) between the paired CIE WI values of each tooth for the two measurement techniques. As the accuracy and reliability of the image analysis system was found to be high in previous in vitro studies, the differences between the two methods were probably related to the inherent subjectivity of visual shade matching. CONCLUSION: The adapted digital image analysis system could be used as an alternative to, or in conjunction with visual shade matching.
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Cor , Colorimetria/métodos , Dente/química , Adulto , Intervalos de Confiança , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Fotografia Dentária/instrumentação , Fotografia Dentária/métodosRESUMO
AIM: The aim of this study was to assess the reliability and validate a customized image analysis system, designed for use within clinical trials of general dental hygiene and whitening products, for the measurement of stain levels on extracted teeth and to compare it with reflectance spectrophotometry. METHOD: Twenty non-carious extracted teeth were soaked in an artificial saliva, brushed for 1 min using an electric toothbrush and a standard toothpaste, bleached using a 5.3% hydrogen peroxide solution and cycled for 6 h daily through a tea solution. CIE L* values were obtained after each treatment step using the customized image analysis system and a reflectance spectrophotometer. A statistical analysis was carried out in SPSS. RESULTS: Fleiss' coefficient of reliability for intra-operator repeatability of the image analysis system and spectrophotometry was 0.996 and 0.946 respectively. CIE L* values were consistently higher using the image analysis compared with spectrophotometry, and t-tests for each treatment step showed significant differences (P < 0.05) for the two methods. Limits of agreement between the methods were -27.95 to +2.07, with a 95% confidence of the difference calculated as -14.26 to -11.84. The combined results for all treatment steps showed a significant difference between the methods for the CIE L* values (P < 0.05). CONCLUSION: The image analysis system has proven to be a reliable method for assessment of changes in stain level on extracted teeth. The method has been validated against reflectance spectrophotometry. This method may be used for pilot in vitro studies/trials of oral hygiene and whitening products, before expensive in vivo tests are carried out.
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Processamento de Imagem Assistida por Computador , Fotografia Dentária , Descoloração de Dente/patologia , Calorimetria , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectrofotometria , Chá , Clareamento DentalRESUMO
Objective: To study the feasibility of (18)F-fluoro-L-dihydroxyphenylalanine positron emission tomography/Computed tomography ((18)F-DOPA PET/CT) scanning in the localization and differential diagnosing of focal versus diffuse form of pancreas lesions in patients with hyperinsulinemic hypoglycemia (HH). Method: Twenty-four patients were diagnosed with HH between January, 2016 and February, 2017 in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University using an integrated clinical and biochemical diagnostic protocol, domestic (18)F-DOPA PET/CT imaging technique were applied after MRI and ultrasound failed to detect pancreas lesions. Pancreas (18)F-DOPA standardized uptake values (SUV) were measured, and pancreas' lesions were dually analyzed via visual method and pancreas percentage SUV method. Among these patients, 9 patients received surgical pancreatic lesion resections, the correlations among surgical outcomes, histopathological findings and (18)F-DOPA PET/CT scan results were analyzed. Result: Seven patients were detected with focal form of pancreas lesions, the mean peak of SUV was 4.7±1.7(2.6-7.1), and 17 patients were found to have diffuse form lesions after (18)F-DOPA-PET/CT scanning. Among the 24 cases, 9 patients (7 showed focal and 2 showed diffuse (18)F-DOPA PET/CT pancreatic uptake)were euglycemic without any medical support after surgery; the resected pancreatic tissue histopathological results were consistent with that of PET/CT imaging. Only one patient, who responded to medical treatment before surgery, had temporary hyperglycemia after operation. Conclusion: Domestic (18)F-DOPA PET/CT could successfully locate and differentiate the pancreatic lesions and thus improve the success of surgery.
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Hiperinsulinismo Congênito/complicações , Di-Hidroxifenilalanina/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Criança , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética , Pâncreas , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios XRESUMO
Metabolic homeostasis, or low-level metabolic steady state, has long been taken for granted in metabolic engineering, and research priority has always been given to understand metabolic flux control and regulation of the reaction network. In the past, this has not caused concerns because the metabolic networks studied were invariably associated with living cells. Nowadays, there are needs to reconstruct metabolic networks, and so metabolic homeostasis cannot be taken for granted. For metabolic steady state, enzyme feedback control has been known to explain why metabolites in metabolic pathways can avoid accumulation. However, we reasoned that there are further contributing mechanisms. As a new methodology developed, we separated cofactor intermediates (CIs) from non-cofactor intermediates, and identified an appropriate type of open systems for operating putative reaction topologies. Furthermore, we elaborated the criteria to tell if a multi-enzyme over-all reaction path is of in vivo nature or not at the metabolic level. As new findings, we discovered that there are interactions between the enzyme feedback inhibition and the CI turnover, and such interactions may well lead to metabolic homeostasis, an emergent property of the system. To conclude, this work offers a new perspective for understanding the role of CIs and the presence of metabolic homeostasis in the living cell. In perspective, this work might provide clues for constructing non-natural metabolic networks using multi-enzyme reactions or by degenerating metabolic reaction networks from the living cell.
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As part of an overall aim to base the feeding of substrates to cultured animal cells on their actual metabolic needs, we have developed a stoichiometric approach centred on the macronutrients in the medium. Heat flux records the overall metabolic activity and therefore was the sensitive indicator of changing metabolic requirement. Analyses were made of the experimental measurements on two engineered cell lines in batch culture, the 2C11-12 macrophage hybridoma cell capable of the respiratory burst and the CHO320 constitutively producing human interferon-gamma. The crux was to construct simplified stoichiometric equations for the growth reactions to represent metabolic activity as it changed with time. Beforehand, it was essential to select the appropriate components for the equations. The choice was then justified by constructing enthalpy balances in which the ratio of heat flux to enthalpy flux must be close to unity for validation. By combining the stoichiometric approach with heat flow measurements, it was shown both theoretically and experimentally that the set of stoichiometric coefficients constituting a validated growth equation has a one-to-one corresponding relationship to the metabolic activity of the average cell population. Thus, a strategy was established for feeding the cells at any one time with the correct ratio of the major substrates, glucose and glutamine, in response to metabolic requirements that change with time.
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Técnicas de Cultura de Células , Divisão Celular , Hibridomas/metabolismo , Macrófagos/metabolismo , Animais , Reatores Biológicos , Calorimetria , Linhagem Celular , Meios de Cultura , Engenharia Genética , Hibridomas/citologia , Interferon gama/biossíntese , Macrófagos/citologia , Camundongos , Explosão Respiratória , TermodinâmicaRESUMO
A microtitre assay has been developed using hydroxyapatite-coated wells and Streptococcus sanguis NCTC 10904 at 10(7) cells per ml. A number of models representing toothpaste and mouthwash usage were adopted to detect the anti-adherent efficacy of a polyvinylmethylether maleic acid copolymer (PVM/MA), polyoxypropylene/polyoxyethylene block copolymer (PO/EO), two casein-derived peptides and selected silicones. The results not only confirmed the anti-adherence property of the selected components but also indicated possible molecular interactions leading to the observed performance. To account for the diversity of oral microbial cells in vivo, a further testing system was developed. This involved submerging a hydroxyapatite disc in a mixed culture of human salivary microbial cells, and exposing it to different treatments using the active component either in an aqueous dispersion or in a toothpaste. The effect of toothpastes containing PO/EO, dimethicone copoyol or PVM/MA was investigated over a 4-h incubation with microflora. These tests showed that in a toothpaste formulation the anti-adherent efficacy may be reduced when compared with an aqueous dispersion containing the same or nearly the same concentration of the active component.
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Aderência Bacteriana/efeitos dos fármacos , Streptococcus sanguis/efeitos dos fármacos , Cremes Dentais/farmacologia , Durapatita , Humanos , Maleatos/farmacologia , Testes de Sensibilidade Microbiana , Poloxaleno/farmacologia , Polietilenos/farmacologia , Saliva/microbiologia , Simeticone/farmacologia , Streptococcus sanguis/fisiologia , Cremes Dentais/químicaRESUMO
BACKGROUND AND PURPOSE: The thermogenesis of BAT is believed to be controlled through some pathways initiated in the brain, though the changes in brain activity among different states of BAT-positive subjects are still unclear. We hypothesized that some significant differences of regional cerebral metabolism between various groups were related to the BAT activities regardless of temperature changes. MATERIALS AND METHODS: Relative regional cerebral glucose metabolism was compared between 15 healthy subjects with activated BAT and 30 healthy controls without activated BAT by using a brain FDG-PET scan. A follow-up PET scan was performed to assess metabolic changes of the brain when BAT activity was eliminated by heat exposure. RESULTS: Compared with controls, BAT-positive subjects exhibited lower activity in the inferior parietal lobule, limbic system, and frontal lobe and higher activity in the precuneus before heat exposure. Compared with the BAT elimination status, subjects with activated BAT showed a decreased metabolism in the parietal lobe, frontal lobe, culmen, cingulate gyrus, and sublobar region. Compared with controls, BAT-positive subjects after BAT inactivation had significant hypometabolic areas in the temporal lobe and limbic lobe and hypermetabolic areas in the parietal lobe. CONCLUSIONS: Our findings illustrate that changes of regional cerebral metabolism are related to BAT activities regardless of temperature changes. This before-after controlled study supports the finding that the brain responses appear to be active in modulating the metabolic function of BAT activity.
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Tecido Adiposo Marrom/fisiologia , Encéfalo/metabolismo , Glucose/metabolismo , Adulto , Regulação da Temperatura Corporal , Encéfalo/diagnóstico por imagem , Feminino , Fluordesoxiglucose F18 , Temperatura Alta , Humanos , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Tomografia Computadorizada por Raios XRESUMO
Unlike the existing 2-D pseudo-ring model for helical columns undergoing synchronous type-J planetary motion of counter-current chromatograph (CCC), the 3-D "helix" model developed in this work shows that there is a second normal force (i.e. the binormal force) applied virtually in the axial direction of the helical column. This force alternates in the two opposite directions and intensifies phase mixing with increasing the helix angle. On the contrary, the 2-D spiral column operated on the same CCC device lacks this third-dimensional mixing force. The (principal) normal force quantified by this "helix" model has been the same as that by the pseudo-ring model. With ß>0.25, this normal centrifugal force has been one-directional and fluctuates cyclically. Different to the spiral column, this "helix" model shows that the centrifugal force (i.e. the hydrostatic force) does not contribute to stationary phase retention in the helical column. Between the popular helical columns and the emerging spiral columns for type-J synchronous CCC, this work has thus illustrated that the former is associated with better phase mixing yet poor retention for the stationary phase whereas the latter has potential for better retention for the stationary phase yet poor phase mixing. The methodology developed in this work may be regarded as a new platform for designing optimised CCC columns for analytical and engineering applications.