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排序方式: 共有106条查询结果,搜索用时 140 毫秒
1.
Ashwinipriyadarshini Megur Daiva Baltriukien Virginija Bukelskien Aurelijus Burokas 《Nutrients》2021,13(1)
For years, it has been reported that Alzheimer’s disease (AD) is the most common cause of dementia. Various external and internal factors may contribute to the early onset of AD. This review highlights a contribution of the disturbances in the microbiota–gut–brain (MGB) axis to the development of AD. Alteration in the gut microbiota composition is determined by increase in the permeability of the gut barrier and immune cell activation, leading to impairment in the blood–brain barrier function that promotes neuroinflammation, neuronal loss, neural injury, and ultimately AD. Numerous studies have shown that the gut microbiota plays a crucial role in brain function and changes in the behavior of individuals and the formation of bacterial amyloids. Lipopolysaccharides and bacterial amyloids synthesized by the gut microbiota can trigger the immune cells residing in the brain and can activate the immune response leading to neuroinflammation. Growing experimental and clinical data indicate the prominent role of gut dysbiosis and microbiota–host interactions in AD. Modulation of the gut microbiota with antibiotics or probiotic supplementation may create new preventive and therapeutic options in AD. Accumulating evidences affirm that research on MGB involvement in AD is necessary for new treatment targets and therapies for AD. 相似文献
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Frederico G. S. Toledo William F. Martin Linda Morrow Carine Beysen Daiva Bajorunas Ying Jiang Bernard L. Silverman David McDonnell Mark N. Namchuk John W. Newcomer Christine Graham 《Neuropsychopharmacology》2022,47(3):696
A combination of olanzapine and samidorphan (OLZ/SAM) received US Food and Drug Administration approval in May 2021 for the treatment of adults with schizophrenia or bipolar I disorder. OLZ/SAM provides the efficacy of olanzapine, while mitigating olanzapine-associated weight gain. This exploratory study characterized the metabolic profile of OLZ/SAM in healthy volunteers to gain mechanistic insights. Volunteers received once-daily oral 10 mg/10 mg OLZ/SAM, 10 mg olanzapine, or placebo for 21 days. Assessments included insulin sensitivity during an oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, other measures of glucose/lipid metabolism, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance. In total, 60 subjects were randomized (double-blind; placebo, n = 12; olanzapine, n = 24; OLZ/SAM, n = 24). Olanzapine resulted in hyperinsulinemia and reduced insulin sensitivity during an OGTT at day 19, changes not observed with OLZ/SAM or placebo. Insulin sensitivity, measured by hyperinsulinemic-euglycemic clamp, was decreased in all treatment groups relative to baseline, but this effect was greatest with olanzapine and OLZ/SAM. Although postprandial (OGTT) glucose and fasting cholesterol concentrations were similarly increased with olanzapine or OLZ/SAM, other early metabolic effects were distinct, including post-OGTT C-peptide concentrations and aspects of energy metabolism. Forty-nine subjects (81.7%) experienced at least 1 AE, most mild or moderate in severity. OLZ/SAM appeared to mitigate some of olanzapine’s unfavorable postprandial metabolic effects (e.g., hyperinsulinemia, elevated C-peptide) in this exploratory study. These findings supplement the body of evidence from completed or ongoing OLZ/SAM clinical trials supporting its role in the treatment of schizophrenia and bipolar I disorder.Subject terms: Medical research, Developmental biology 相似文献
4.
Dr Richard H. Karas Moti L. Kashyap Robert H. Knopp Laurence H. Keller Daiva R. Bajorunas Michael H. Davidson 《Am J Cardiovasc Drugs》2008,8(2):69-81
INTRODUCTION: High-dose HMG-CoA reductase inhibitors (statins) fail to prevent approximately two-thirds of cardiovascular events. This fact has focused increased attention on treating abnormalities of non-high-density lipoprotein-cholesterol (non-HDL-C), HDL-C, and triglycerides in national guidelines and has intensified interest in combination therapy. METHODS: The OCEANS study (Open-label evaluation of the safety and efficacy of a Combination of niacin ER and simvAstatin in patieNts with dySlipidemia; ClinicalTrials.gov identifier: NCT00080275) evaluated the safety and efficacy of a combination of niacin extended release and simvastatin (NER/S; SIMCOR) over 52 weeks in 520 patients with mixed dyslipidemia. After a >or=4-week run-in phase of diet modification and simvastatin 40 mg/day, median baseline values (mg/dL) were: non-HDL-C = 141, low-density lipoprotein-cholesterol (LDL-C) = 110, HDL-C = 45, and triglyceride = 151. Patients were randomized to an 8- or 12-week niacin titration scheme to a maximum NER/S dosage of 2,000/40 mg/day. RESULTS: Differences between titration groups in tolerability, safety, and efficacy were minimal; therefore, all results are for pooled titration groups. The safety of NER/S was consistent with the safety profile of each individual component. Treatment with NER/S was well tolerated: 71% of patients experienced flushing and 92% of flushing episodes were mild or moderate in intensity. Overall, 61% of patients experienced flushing episodes that were rated as mild or moderate in intensity. Flushing decreased over time: <40% of those who had flushing during titration experienced flushing during the final 12 weeks. A total of 20% of patients discontinued treatment because of a treatment-related adverse event, including 7% who discontinued because of flushing. Median changes from baseline (following the simvastatin 40 mg/day run-in phase) to 24 weeks were: non-HDL-C = -27.3%, LDL-C = -25.0%, HDL-C = +23.9%, and triglycerides = -35.9% (all p < 0.0001 vs baseline). In lipid-treatment-naive patients, NER/S 2,000/40 mg/day decreased non-HDL-C, LDL-C, and triglycerides by approximately 50% and increased HDL-C by approximately 25% when week-24 lipid values were compared with lipid values obtained prior to the simvastatin 40 mg/day run-in. All three therapeutic lipid targets (LDL-C [risk-adjusted goal], HDL-C >or=40 mg/dL, and triglycerides <150 mg/dL) were achieved concurrently by 65% of patients treated with NER/S. CONCLUSION: Treatment with NER/S 2,000/40 mg/day is well tolerated, has no unanticipated adverse events, and provides additional, clinically relevant improvements in multiple lipid parameters beyond statin monotherapy. 相似文献
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Molecular characterization of isoniazid-resistant Mycobacterium tuberculosis clinical isolates in Lithuania 总被引:1,自引:0,他引:1 下载免费PDF全文
Bakonyte D Baranauskaite A Cicenaite J Sosnovskaja A Stakenas P 《Antimicrobial agents and chemotherapy》2003,47(6):2009-2011
Mutations at codon 315 of the katG gene were detected in 312 of 364 (85.7%) isoniazid-resistant Mycobacterium tuberculosis isolates. Seven of 52 (13.5%) isoniazid-resistant isolates with the wild-type Ser315 codon and 10 of 52 (19.2%) isoniazid-resistant isolates with a mutated katG allele had mutation -15C-->T in the promoter of the mabA-inhA operon. 相似文献
6.
Background
Evidence-informed decision making is accepted in Canada and worldwide as necessary for the provision of effective health services. This process involves: 1) clearly articulating a practice-based issue; 2) searching for and accessing relevant evidence; 3) appraising methodological rigor and choosing the most synthesized evidence of the highest quality and relevance to the practice issue and setting that is available; and 4) extracting, interpreting, and translating knowledge, in light of the local context and resources, into practice, program and policy decisions. While the public health sector in Canada is working toward evidence-informed decision making, considerable barriers, including efficient access to synthesized resources, exist. 相似文献7.
Pain experience during saline‐contrast sonohysterography differs between premenopausal and postmenopausal women 下载免费PDF全文
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Bartkiene E Juodeikiene G Vidmantiene D 《International journal of food sciences and nutrition》2012,63(6):722-729
The use of soya and flaxseed flours fermented with Pediococcus acidilactici for wheat sourdough bread production was investigated. The protein digestibility, biogenic amine contents of soya and flaxseed sourdoughs, texture and sensory features of bread were studied. The fermentation with P. acidilactici significantly improved soya and flaxseed protein extraction and increased protein digestibility on an average by 13.5%. The concentrations of histamine (3.8?±?2.3 and 4.0?±?0.2?mg/kg), tyramine (4.6?±?0.7 and 19.3?±?1.8?mg/kg) and putrescine (66.4?±?1.3 and 11.3?±?3.0?mg/kg) do not present a health risk for consumers due to their relatively low levels in fermented plant products. The flaxseed sourdoughs influenced a 17.5% higher specific volume and a 4.6% lower crumb hardness of bread than those of soya sourdoughs, and did not disimprove sensory properties of bread. However, the fermented soya additives decreased acceptability of bread because of intensive taste and odour. 相似文献
10.
Emkey R Koltun W Beusterien K Seidman L Kivitz A Devas V Masanauskaite D 《Current medical research and opinion》2005,21(12):1895-1903
OBJECTIVE: Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered with extended interval dosing. Patient preferences were assessed for once-monthly versus once-weekly bisphosphonate treatment using a previously developed, open-label, cross-over trial design. RESEARCH DESIGN AND METHODS: This was a 6-month, prospective, randomized, open-label, multi-center study with a two-period and two-sequence cross-over treatment design. After screening, eligible patients (postmenopausal women with osteoporosis) were randomized to once-monthly ibandronate 150 mg followed by once-weekly alendronate 70 mg for a total of 6 months (Sequence A) or once-weekly alendronate followed by once-monthly ibandronate for a total of 6 months (Sequence B). The primary objective was to evaluate patient-reported preference for either the once-monthly ibandronate regimen or the once-weekly alendronate regimen based on responses to a preference questionnaire. RESULTS: A total of 342 patients were enrolled into this study (Sequence A, 170; Sequence B, 172). In the primary analysis of patient preference, 71.4% of women selected once-monthly ibandronate and 28.6% of women selected once-weekly alendronate. Overall, 66.1% preferred the once-monthly ibandronate regimen to the once-weekly alendronate regimen (26.5%) and 7.4% of participants stated no preference for either regimen. The preference rate for once-monthly ibandronate was statistically significant (p < 0.0001). 'Ease of following a treatment regimen for a long time' was the most common reason given for patient preference for both the once-monthly ibandronate (61%, 169/276) and once-weekly alendronate (25%, 70/276) regimens. Additionally, 17% (47/276) of patients who preferred once-monthly ibandronate chose 'it is easier to tolerate side effects' as did 4.3% (12/276) of patients who preferred alendronate. Significantly more women found once-monthly ibandronate to be more convenient (p < 0.0001). CONCLUSIONS: Significantly more women with postmenopausal osteoporosis preferred once-monthly ibandronate therapy to once-weekly alendronate therapy, and found the once-monthly regimen to be more convenient. Ease of following a treatment regimen for a long time was the most common reason given for the patients' preferences. 相似文献