Serum insulin is associated with right ventricle function parameters and lung volumes in subjects free of cardiovascular disease.
- 作者列表："Krüchten RV","Lorbeer R","Rospleszcz S","Storz C","Askani E","Kulka C","Rathmann W","Peters A","Karrasch S","Bamberg F","Schlett C","Mujaj B
Background:Diabetes mellitus is an established risk factor for cardiovascular diseases. Even impaired levels of glucose and insulin might harm organ function prior to diabetes onset. Whether serum glucose or insulin plays a direct role in cardiac dysfunction or lung volume reduction remains unclear. The aim was to investigate the relationship between glucose and insulin with the right ventricle and lung volumes within KORA-MRI FF4 study. Methods:From the KORA-MRI FF4 cohort study 337 subjects (mean age 55.7 ± 9.1 years; 43% women) underwent a whole-body 3T MRI scan. Cardiac parameters derived from a cine-steady-state free precession sequence using cvi42. MRI-based lung volumes derived semi-automatically using an in-house algorithm. Fasting serum glucose, fasting insulin levels, and HOMA index were calculated in all study subjects. Linear regression analyses were performed to assess the relationships between glucose and insulin levels with right ventricle volumes and lung volumes adjusted for age, sex, BMI, and cardiovascular risk factors. Results:In univariate and multivariate-adjusted models, high serum insulin was inversely associated with end-diastolic volume (β = -12.43, P < 0.001), end-systolic volume (β = -7.12, P < 0.001), stroke volume (β = -5.32, P < 0.001), but not with ejection fraction. The association remained significant after additional adjustment for lung volumes. Similarly, serum insulin was inversely associated with lung volume (β = -0.15, P = 0.04). Sensitivity analysis confirmed results after excluding subjects with known diabetes. Conclusions:Serum insulin was inversely associated with right ventricle function and lung volumes in subjects from the general population free of cardiovascular disease, suggesting that increased insulin levels may contribute to subclinical cardiopulmonary circulation impairment.
背景: 糖尿病是心血管疾病的危险因素。即使葡萄糖和胰岛素水平受损也可能在糖尿病发作前损害器官功能。血清葡萄糖或胰岛素是否在心功能障碍或肺体积减少中起直接作用仍不清楚。目的是在KORA-MRI FF4研究中研究葡萄糖和胰岛素与右心室和肺容量之间的关系。 方法: 来自KORA-MRI FF4队列研究的337名受试者 (平均年龄55.7 ± 9.1岁; 43% 名女性) 接受了全身3t MRI扫描。使用cvi42从电影稳态自由进动序列导出的心脏参数。使用内部算法半自动导出基于MRI的肺容积。计算所有研究对象的空腹血糖、空腹胰岛素水平和HOMA指数。进行线性回归分析，以评估葡萄糖和胰岛素水平与右心室容积和肺容积之间的关系，调整年龄，性别，BMI和心血管危险因素。 结果: 在单变量和多变量校正模型中，高血清胰岛素与舒张末期容积 (β = -12.43，P <0.001) 、收缩末期容积 (β = -7.12，P <0.001) 、每搏输出量 (β = -5.32，P <0.001) 、但与射血分数无关。在对肺容量进行额外调整后，该相关性仍然显著。类似地，血清胰岛素与肺体积呈负相关 (β = -0.15，P = 0.04)。在排除已知患有糖尿病的受试者后，敏感性分析证实了结果。 结论: 在无心血管疾病的普通人群中，血清胰岛素与右心室功能和肺容量呈负相关，提示胰岛素水平升高可能导致亚临床心肺循环障碍。
METHODS::The ATP binding-cassette superfamily corresponds the mostly transmembrane transporters family found in humans. These proteins actively transport endogenous and exogenous substrates through biological membranes in body tissues, so they have an important role in the regulation of many physiological functions necessary for human homeostasis, as well as in response regulation to several pharmacological substrates. The development of multidrug resistance has become one of the main troubles in conventional chemotherapy in different illnesses including cancer, being the increased efflux of antineoplastic drugs the main reason for this multidrug resistance, with a key role of the ABC superfamily. Likely, the interindividual variability in the pharmacological response among patients is well known, and may be due to intrinsically factors of the disease, genetic and environmental ones. Thus, the understanding of this variability, especially the genetic variability associated with the efficacy and toxicity of drugs, can provide a safer and more effective pharmacological treatment, so ABC genes are considered as important regulators due to their relationship with the reduction in pharmacological response. In this review, updated information about transporters belonging to this superfamily was collected, the possible role of these transporters in cancer, the role of genetic variability in their genes, as well as some therapeutic tools that have been tried to raise against main transporters associated with chemoresistance in cancer.
METHODS:BACKGROUND:Cholinergic neurotransmission regulates neuroinflammation in Parkinson disease (PD). RESEARCH DESIGN AND METHODS:The authors conducted a delayed-start study of donepezil for cognitive decline in non-demented PD patients. The study consisted of a 96-week randomized placebo-controlled double-blind phase 1, followed by a 24-week donepezil extension phase 2. The primary outcome measure was a change in the Mini-Mental State Examination (MMSE) at week 120. RESULTS:A total of 98 patients were randomly allocated to the early-start (donepezil-to-donepezil) and delayed-start (placebo-to-donepezil) groups. Mean (SD) of the baseline MMSE was 27.6 (2.0) and 28.0 (2.1), respectively. MMSE change at week 120 was better in the early-start group than in the delayed-start group, but the difference was not significant. The MMSE declined in apolipoprotein ε4 carriers, but not in non-carriers, and the factor interaction (intervention × ε4 genotype) was highly significant (P < 0.001). Analyzed with the interaction, the difference was significant (group difference 1.95 [0.33 to 3.57], P = 0.018). The MMSE decline slope in phase 1 was significantly better in the early-start group than in the delayed-start group (P = 0.048). CONCLUSIONS:Cognitive function deteriorated in ε4 carriers, but not in non-carriers, and early-start donepezil may postpone cognitive decline in the former.
METHODS::Since the discovery of dental pulp stem cells, a lot of teams have expressed an interest in dental pulp regeneration. Many approaches, experimental models and biological explorations have been developed, each including the use of stem cells and scaffolds with the final goal being clinical application in humans. In this review, the authors' objective was to compare the experimental models and strategies used for the development of biomaterials for tissue engineering of dental pulp with stem cells. Electronic queries were conducted on PubMed using the following terms: pulp regeneration, scaffold, stem cells, tissue engineering and biomaterial. The extracted data included the following information: the strategy envisaged, the type of stem cells, the experimental models, the exploration or analysis methods, the cytotoxicity or viability or proliferation cellular tests, the tests of scaffold antibacterial properties and take into account the vascularization of the regenerated dental pulp. From the 71 selected articles, 59% focused on the "cell-transplantation" strategy, 82% used in vitro experimentation, 58% in vivo animal models and only one described an in vivo in situ human clinical study. 87% used dental pulp stem cells. A majority of the studies reported histology (75%) and immunohistochemistry explorations (66%). 73% mentioned the use of cytotoxicity, proliferation or viability tests. 48% took vascularization into account but only 6% studied the antibacterial properties of the scaffolds. This article gives an overview of the methods used to regenerate dental pulp from stem cells and should help researchers create the best development strategies for research in this field.