Modulation of thyroidal radioiodine uptake by theophylline

Diagnostic and therapeutic use of radioiodine in the management of thyroid disorders depends on the ability of thyroid cells to concentrate radioiodine, a process regulated by thyrotropin and dependent on the intracellular increase in cAMP. We tested the ability of theophylline, a drug known to increase intracellular cAMP via inhibition of phosphodiesterase, to modulate the thyroidal radioiodine uptake in FRTL-5 cells, in mice and in humans. In FRTL-5 cells, theophylline increased the uptake of radioactive iodine and intracellular cAMP only at low concentrations (1 microM). In mice, theophylline increased slightly the radioiodine uptake, although this increase varied from 1.5- to 6.6-fold. In humans, theophylline decreased slightly the radioiodine uptake, a decrease that became more pronounced with time after radioiodine administration. These studies suggest that theophylline modulates the radioiodine uptake in a dose-dependent fashion, although the modulation is mild and probably not applicable to the clinical setting.     

不同时间犬缺血心肌对^99Tc^m-MIBI摄取比值的观察

目的：观察犬冠状动脉左旋支狭窄后心肌细胞对^99碍^m-甲氧基异丁基异腈（^99Tc^m-MIBI）摄取与时间变化之间的关系。方法：建立犬冠状动脉左旋支狭窄模型（12只），分别注射^99Tc^m-MIBI，剂量为185MBq（5mCi）。注射1h和4h后，各处死6只犬，取出心脏，于左室侧壁（缺血区）和前壁（正常区）分别取心肌组织约100rag，用1计数器测定其放射性计数，换算成每克组织放射性计数值，求出侧壁与前壁放射性比值。结果：注射后1h犬左心室缺血区与正常区组织放射性计数比值为0．726±O．054，4h为0．673±0．080，两者之间比较差鼻无昂薯件（t=1．3452．P〉0．05）．结论．砸长时问不能摇高按血心肌对辨^99Tc^m-MIBI梧取比．     

Influence of climbing style on physiological responses during indoor rock climbing on routes with the same difficulty

The objectives of this study were to (1) continuously assess oxygen uptake and heart rate; (2) quantify the extent to which maximal whole-body cardiorespiratory capacity is utilized during climbing on four routes with the same difficulty but different steepness and/or displacement. Fifteen expert climbers underwent a maximal graded exercise test (MT), on a treadmill, in order to assess their maximal physiological capacity. After MT, four sport routes, equal in difficulty rating but different in steepness and/or displacement, were climbed. Oxygen uptake and heart rate were continuously measured. Respiratory exchange ratio (RER) was calculated. Blood lactate concentration and rating of perceived exertion (RPE) were taken before and directly after climbing. Data were expressed as peak values (HRpeak, VO₂peak and RERpeak) and as averages over the entire climb (HRavg, VO₂avg and RERavg). During climbing, higher HRpeak and HRavg were found in routes with a vertical upward displacement in comparison to traversing routes with a horizontal displacement. The average absolute and relative oxygen uptake was significantly lower in the traversing route in comparison with the three other routes. The traverse is done at a lower percent of the running maximum. Comparing four routes with the same difficulty but different steepness and/or displacement shows that (1) routes with an upward displacement causes the highest peak and average heart rate; (2) routes with a vertical displacement on overhanging wall is physiologically the most demanding; (3) the traverse is physiologically the less demanding.     

Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction

Background

Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure–volume loop analysis in HFPEF.

Methods

26 HFPEF patients who showed an increase in LV stiffness by pressure–volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin < 100 μg/l or ferritin of 100–299 μg/l in combination with transferrin saturation < 20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies.

Results

Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p < 0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r = − 0.636, p < 0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency.

Conclusion

In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID.     

Pinealectomy reduces hepatic and muscular glycogen content and attenuates aerobic power adaptability in trained rats

The current study emphasizes the crucial role of the pineal gland on the effects of chronic training in different tissues focusing on carbohydrate metabolism. We investigated the maximal oxygen uptake (aerobic power), muscle and liver glycogen content, and also the enzymes involved in the carbohydrate metabolism of rat adipose tissue. Pinealectomized and sham-operated adult male Wistar rats were distributed into four groups: pinealectomized (PINX) untrained, pinealectomized trained, control untrained and control trained. The maximal oxygen uptake capability was assayed before and after the training protocol by indirect open circuit calorimetry. The rats were killed after 8 wk of training. Blood samples were collected for glucose and insulin determinations. The glycogen content was assayed in the liver and muscle. Maximal activities of epididymal adipose tissue enzymes (hexokinase, pyruvate kinase, lactate dehydrogenase, citrate synthase and malic enzyme) as well as adipocyte size were determined. The exercise training in control animals promoted an increase in the aerobic power and in liver glycogen content but caused a reduction in the malic enzyme activity in adipose tissue. However, PINX trained animals, in contrast to trained controls, showed a decrease in the aerobic power and in liver and muscle glycogen content, as well as an increase in the activity of the adipocyte enzymes involved in carbohydrate metabolism. In conclusion, these data show that the pineal gland integrity is necessary for the homeostatic control of energy metabolism among adipose, muscle and hepatic tissues. The pinealectomized animals showed alterations in adaptive responses of the maximal oxygen uptake to training. Therefore, the pineal gland must be considered an influential participant in the complex adaptation to exercise and is involved in the improvement of endurance capacity.     

Non-linear cardiac output dynamics during ramp-incremental cycle ergometry

Published literature asserts that cardiac output (=O₂×1/C_(a-v)O₂) increases as a linear function of oxygen uptake with a slope of approximately 5–6 during constant work rate exercise. However, we have previously demonstrated that C_(a-v)O₂ has a linear relationship as a function of O₂ during progressively increasing work rate incremental exercise. Therefore, we hypothesized that may indeed have a non-linear relationship with respect to O₂ during incremental, non-steady state exercise. To investigate this hypothesis, we performed five maximal progressive work rate exercise studies in healthy human subjects. was determined every minute during exercise using measured breath-by-breath O₂, and arterial and pulmonary artery measurements of PO₂, hemoglobin saturation, and content. was plotted as a function of O₂ and the linear and non-linear (first order exponential and hyperbolic) fits determined for each subject. Tests for linearity were performed by assessing the significance of the quadratic terms added to the linear relation using least squares estimation in linear regression. Linearity was inadequate in all cases (group P<0.0001). We conclude that cardiac output is a non-linear function of O₂ during ramp-incremental exercise; the pattern of non-linearity suggests that while the kinetics of are faster than those of O₂ they progressively slow as work rate (and O₂) increases.     

Intestinal mucosa permeability following oral insulin delivery using core shell corona nanolipoparticles

Chitosan nanoparticles (NC) have excellent capacity for protein entrapment, favorable epithelial permeability, and are regarded as promising nanocarriers for oral protein delivery. Herein, we designed and evaluated a class of core shell corona nanolipoparticles (CSC) to further improve the absorption through enhanced intestinal mucus penetration. CSC contains chitosan nanoparticles as a core component and pluronic F127-lipid vesicles as a shell with hydrophilic chain and polyethylene oxide PEO as a corona. These particles were developed by hydration of a dry pluronic F127-lipid film with NC suspensions followed by extrusion. Insulin nested inside CSC was well protected from enzymatic degradation. Compared with NC, CSC exhibited significantly higher efficiency of mucosal penetration and, consequently, higher cellular internalization of insulin in mucus secreting E12 cells. The cellular level of insulin after CSC treatment was 36-fold higher compared to treatment with free insulin, and 10-fold higher compared to NC. CSC significantly facilitated the permeation of insulin across the ileum epithelia, as demonstrated in an ex vivo study and an in vivo absorption study. CSC pharmacological studies in diabetic rats showed that the hypoglycemic effects of orally administrated CSC were 2.5-fold higher compared to NC. In conclusion, CSC is a promising oral protein delivery system to enhance the stability, intestinal mucosal permeability, and oral absorption of insulin.     

性激素对3T3-L1前脂肪细胞和脂肪细胞胰岛素敏感性的影响

目的观察不同浓度雌、雄激素对3T3-L1前脂肪细胞葡萄糖转运的影响,探讨性激素在胰岛素抵抗形成中的意义。方法体外培养3T3-L1前脂肪细胞,并诱导其分化成熟,利用2-脱氧-[3H]-D-葡萄糖掺入法,研究不同浓度的17β雌二醇、睾酮对胰岛素刺激的前脂肪细胞和脂肪细胞葡萄糖摄取能力的影响。结果10-8mol/L的17β雌二醇即能够抑制3T3-L1前脂肪细胞胰岛素刺激状态下的葡萄糖转运,且呈现明显的浓度依赖性抑制;而睾酮为10-8mol/L时3T3-L1前脂肪细胞胰岛素刺激状态下的葡萄糖转运并无明显影响,在浓度达到10-7mol/L开始出现抑制效应,浓度越高抑制效应越明显。结论性激素可以调节3T3-L1前脂肪细胞的胰岛素敏感性。     

峰值氧耗量对非射血分数减低的心力衰竭患者预后评估的价值

目的:探讨心肺运动试验重要参数对非射血分数减低心力衰竭(HFr EF)预后评价的价值。方法:前瞻性入组2014年1月到2018年6月,我院诊断为非HFr EF患者,记录患者再入院及死亡事件,最后进行生存分析。结果:入选124例患者,平均随访(24±5)个月,10例患者死亡,32例患者因心力衰竭再住院治疗。心力衰竭组患者峰值氧耗量劣于正常健康对照组[(17.4±2.7)vs.(31.5±3.2)m L·kg^-1·min^-1,P<0.05]。事件组峰值氧耗量低于无事件组[(13.9±2.1)vs.(19.2±3.5)m L·kg^-1·min^-1,P<0.05]。多因素分析表明:峰值氧耗量是预测非HFr EF患者预后的指标(HR=0.81,95%CI:0.76~0.92,P<0.002)。结论:峰值氧耗量可以很好预测非HFr EF患者预后。