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排序方式: 共有820条查询结果,搜索用时 15 毫秒
41.
Sunil Veeravalli Bilal A. Omar Lyndsey Houseman Matthew Hancock Sandra G. Gonzalez Malagon Flora Scott Azara Janmohamed Ian R. Phillips Elizabeth A. Shephard 《Biochemical pharmacology》2014
Flavin-containing monooxygenases (FMOs) of mammals are thought to be involved exclusively in the metabolism of foreign chemicals. Here, we report the unexpected finding that mice lacking Fmos 1, 2 and 4 exhibit a lean phenotype and, despite similar food intake, weigh less and store less triglyceride in white adipose tissue (WAT) than wild-type mice. This is a consequence of enhanced whole-body energy expenditure, due mostly to increased resting energy expenditure (REE). This is fuelled, in part, by increased fatty acid β-oxidation in skeletal muscle, which would contribute to depletion of lipid stores in WAT. The enhanced energy expenditure is attributed, in part, to an increased capacity for exercise. There is no evidence that the enhanced REE is due to increased adaptive thermogenesis; instead, our results are consistent with the operation in WAT of a futile energy cycle. In contrast to FMO2 and FMO4, FMO1 is highly expressed in metabolic tissues, including liver, kidney, WAT and BAT. This and other evidence implicates FMO1 as underlying the phenotype. The identification of a novel, previously unsuspected, role for FMO1 as a regulator of energy homeostasis establishes, for the first time, a role for a mammalian FMO in endogenous metabolism. Thus, FMO1 can no longer be considered to function exclusively as a xenobiotic-metabolizing enzyme. Consequently, chronic administration of drugs that are substrates for FMO1 would be expected to affect energy homeostasis, via competition for endogenous substrates, and, thus, have important implications for the general health of patients and their response to drug therapy. 相似文献
42.
《Diabetes & Metabolic Syndrome: Clinical Research & Reviews》2022,16(3):102437
Background and aimsThis study aimed to assess the effects of vildagliptin on the prevention of cardiovascular diseases in Thai patients with type 2 diabetes mellitus using the Thai Cardiovascular Risk Score.MethodsAll patients with type 2 diabetes mellitus who used vildagliptin at a secondary hospital in Thailand were screened and recruited. The relevant variables were obtained from patient medication charts at the first visit on which the patients were prescribed vildagliptin and from the 6-month, 12-month, and 18-month post-treatment visits. The Thai Cardiovascular Risk Score was calculated and monitored as a primary outcome, whereas changes in separate cardiometabolic parameters were assessed as secondary outcomes.ResultsOf the 321 patients screened, only 95 were recruited for the analysis. The average 10-year cardiovascular risks of patients increased from 19.65% at baseline to 20.74%, 20.69%, and 23.78% at 6, 12, and 18 months post treatment, respectively. However, a better trend of reduction in cardiovascular risk was observed in patients with a high baseline cardiovascular risk. The glucose-lowering effects of vildagliptin were significantly observed 12 months of treatment onwards, but non-significant changes were found in lipid and blood pressure levels as well as body mass index.ConclusionVildagliptin provided a promising glucose-lowering effect in Thai patients with type 2 diabetes mellitus. However, the mean 10-year cardiovascular risk did not significantly decrease. However, a negative correlation between cardiovascular risk reduction and baseline cardiovascular risk was observed in this study. Low sample size was a major limitation of this study. 相似文献
43.
J.M.A. Alcantara G. Sanchez-Delgado B. Martinez-Tellez E. Merchan-Ramirez I. Labayen J.R. Ruiz 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2018,28(9):929-936
Background & aims
Achieving high inter-day reliability is a key factor to analyze the magnitude of change in RMR, for instance after an intervention. The aims of this study were: i) to determine the congruent validity of RMR and respiratory quotient (RQ) with two breath by breath commercially available metabolic carts [CCM Express (CCM) and Ultima CardiO2 (MGU)]; and ii) to analyze the inter-day reliability of RMR and RQ measurements.Methods & results
Seventeen young adults participated in the study. RMR measurements were performed during two consecutive 30-min periods, on two consecutive days with both metabolic carts. The 5-min period that met the steady state criteria [Coefficient of variance (CV) < 10% for VO2, VCO2, and VE, and CV<5% for RQ] and with the lowest CV average was included in further analysis. RMR values were higher with the MGU than with the CCM on both days (two-way ANOVA, P = 0.021), however, no differences were found on RQ values obtained by both metabolic carts (P = 0.642). Absolute inter-day RMR differences obtained with the MGU were higher than those obtained with the CCM (219 ± 185 vs. 158 ± 154 kcal/day, respectively, P = 0.002; 18.3 ± 17.2% vs. 13.5 ± 15.3%, respectively, P = 0.046). We observed a significant positive association of absolute inter-day differences in RMR obtained with both metabolic carts (β = 0.717; R2 = 0.743; P < 0.001).Conclusions
The CCM metabolic cart provides lower RMR values and seems more reliable than the MGU in our sample of young adults. Our findings also suggest that a great part of inter-day variability is explained by the individuals. 相似文献44.
45.
Enrique Galve Eduardo Alegría Alberto Cordero Lorenzo Fácila Jaime Fernández de Bobadilla Carla Lluís-Ganella Pilar Mazón Carmen de Pablo Zarzosa José Ramón González-Juanatey 《Revista espa?ola de cardiología》2014
Cardiovascular disease develops in a slow and subclinical manner over decades, only to manifest suddenly and unexpectedly. The role of prevention is crucial, both before and after clinical appearance, and there is ample evidence of the effectiveness and usefulness of the early detection of at-risk individuals and lifestyle modifications or pharmacological approaches. However, these approaches require time, perseverance, and continuous development. The present article reviews the developments in 2013 in epidemiological aspects related to prevention, includes relevant contributions in areas such as diet, weight control methods (obesity is now considered a disease), and physical activity recommendations (with warnings about the risk of strenuous exercise), deals with habit-related psychosocial factors such as smoking, provides an update on emerging issues such as genetics, addresses the links between cardiovascular disease and other pathologies such as kidney disease, summarizes the contributions of new, updated guidelines (3 of which have recently been released on topics of considerable clinical importance: hypertension, diabetes mellitus, and chronic kidney disease), analyzes the pharmacological advances (largely mediocre except for promising lipid-related results), and finishes by outlining developments in the oft-neglected field of cardiac rehabilitation. This article provides a briefing on controversial issues, presents interesting and somewhat surprising developments, updates established knowledge with undoubted application in clinical practice, and sheds light on potential future contributions. 相似文献
46.
47.
Peter Stein Jolene K. Berg Linda Morrow David Polidori Eunice Artis Sarah Rusch Nicole Vaccaro Damayanthi Devineni 《Metabolism: clinical and experimental》2014
Objective
Canagliflozin is a sodium glucose co-transporter 2 inhibitor approved for treating patients with type 2 diabetes. This study evaluated renal and non-renal effects of canagliflozin on postprandial plasma glucose (PG) excursion in patients with type 2 diabetes inadequately controlled with metformin.Materials/Methods
Patients (N = 37) were randomized to a four-period crossover study with 3-day inpatient stays in each period and 2-week wash-outs between periods. Patients received Treatments (A) placebo/placebo, (B) canagliflozin 300 mg/placebo, (C) canagliflozin 300 mg/canagliflozin 300 mg, or (D) canagliflozin 300 mg/canagliflozin 150 mg on Day 2/Day 3 in one of four treatment sequences (similar urinary glucose excretion [UGE] expected for Treatments B–D). A mixed-meal tolerance test (MMTT) was given 20 minutes post-dose on Day 3 of each period.Results
A single dose of canagliflozin 300 mg reduced both fasting and postprandial PG compared with placebo, with generally similar effects on fasting PG and UGE observed for Treatments B–D. An additional dose of canagliflozin 300 mg (Treatment C), but not 150 mg (Treatment D), prior to the MMTT on Day 3 provided greater postprandial PG reduction versus placebo (difference in incremental glucose AUC0–2h, − 7.5% for B vs A; − 18.5% for C vs A; − 12.0% [P = 0.012] for C vs B), leading to modestly greater reductions in total glucose AUC0–2h with Treatment C versus Treatment B or D. Canagliflozin was generally well tolerated.Conclusions
These findings suggest that a non-renal mechanism (ie, beyond UGE) contributes to glucose lowering for canagliflozin 300 mg, but not 150 mg. 相似文献48.
Per Marits Ann-Charlotte Wikström Dusan Popadic Ola Winqvist Sarah Thunberg 《Clinical immunology (Orlando, Fla.)》2014,153(2):332-342
The golden standard for functional evaluation of immunodeficiencies is the incorporation of [3H]-thymidine in a proliferation assay stimulated with mitogens. Recently developed whole blood proliferation assays have the advantage of parallel lymphocyte lineage analysis and in addition provide a non-radioactive alternative. Here we evaluate the Flow-cytometric Assay for Specific Cell-mediated Immune-response in Activated whole blood (FASCIA) in a comparison with [3H]-thymidine incorporation in four patients with severe combined immunodeficiency. The threshold for the minimum number of lymphocytes required for reliable responses in FASCIA is determined together with reference values from 100 healthy donors when stimulated with mitogens as well as antigen specific stimuli. Finally, responses against PWM and SEA + SEB stimuli are conducted with clinically relevant immunomodulatory compounds. We conclude that FASCIA is a rapid, stable and sensitive functional whole blood assay that requires small amounts of whole blood that can be used for reliable assessment of lymphocyte reactivity in patients. 相似文献
49.
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