Effects of age on responses to isometric exercise. Isometric handgrip in noninvasive screening for cardiovascular disease.

Isometric handgrip (IHG) imposes an acutely increased afterload on the left ventricle. Utilizing systolic time intervals, we studied various responses to IHG, measured as changes from resting values with near-maximum IHG, in old normal (ON) subjects, young normal (YN) subjects, and old patients with hypertensive heart disease (HHD) and patients with coronary artery disease (CAD). There were no differences in responses to IHG between ON and patients with HHD or patients with CAD. However, there were clear differences between the responses of ON and YN subjects. Increase in heart rate (HR) was much more prominent in YN (ON vs. YN = +11.6 +/- 2.6 vs. +15.6 +/- 5.7 beats per minute p less than 0.001). Pre-ejection period (PEP) end isovolumic contraction time (IVCT) increased in ON but decreased in YN (PEP + 6.2 +/- 1.7 vs. -11.0 +/- 3.7 msec., p less than 0.001; IVCT +8.1 +/- 2.2 vs. -13.8 +/- 3.4 msec., p less than 0.001. Shortening of LVET was much more marked in YN (-6.5 +/- 4.1 VS. -63.3 +/- 9.9 msec. p less than 0.001), but this was entirely due to the HR differences since there was no difference in ejection time index (+ 5.1 +/- 3.4 vs. -0.4 +/- 7.3 msec. p greater than 0.5). IHG produced no significant differences between ON and YN in the timing of the "mitral" component of the first heart sound (q-Im), in the ratio PEP/LVET, or in pulse transmission time (PTT). By contrast, resting control PTT was markedly short in ON, especially those with CAD. Resting PTT in ON was 27.1 +/- 2.6 msec.; in YN 43.7 +/- 1.4 msec.; in CAD patients 20.7 +/- 1.3 msec. We conclude that even near-maximal IHG does not seem to be an adequate noninvasive screening test for cardiovascular disease in that age alone seems to have the most significant influence on the responses.     

Resting and exercise left ventricular function in patients with hypertrophic cardiomyopathy

Left ventricular ejection fraction (EF) at rest and during exercise was measured in 19 patients with hypertrophic cardiomyopathy (HCM) by means of radionuclide angiography. The results were compared to those in 20 normal subjects. Based on hemodynamic data, patients with HCM were divided into three groups. In group I, no demonstrable left ventricular outflow obstruction, there were five patients; their mean EF increased from 68% +/- 8.9 (+/- SD) at rest to 74% +/- 9.2 during exercise (p less than 0.05). In group II, latent obstruction, there were six patients; their mean EF at rest (75.2% +/- 8.2) and at peak exercise (78.7% +/- 6.7) was not statistically different (p greater than 0.05). Group III, obstruction present at rest, consisted of eight patients; EF at rest (82.6% +/- 8.5) decreased significantly during exercise (75.6% +/- 7.7, p less than 0.01). In normal subjects resting EF was 66.3% +/- 7.6; it increased to 76.4% +/- 7 (p less than 0.001). Exercise duration and heart rate-blood pressure product were lower in groups II and III. Thus there are significant differences in left ventricular systolic function both at rest and during exercise between these three major hemodynamic subgroups. These findings emphasize the importance of such a hemodynamic classification of HCM.     

Arginine-stabilized mPEG-PDLLA (50/50) polymeric micelles of docetaxel by electrostatic mechanism for tumor-targeted delivery

Abstract

Arginine-stabilized, docetaxel-loaded polymeric micelles (AR-DTX-PM) were prepared to enhance the physical stability of micelles and control the degradation of docetaxel (DTX). Amphiphilic diblock copolymers, methoxy-(Polyethylene Glycol)-block-Poly (D, L-lactide) (mPEG-PDLLA) were synthesized and used for the formulation of lyophilized DTX-PM powders. The micelles were found to have diameters of 20–30?nm with narrow polydispersity, and the entrapment efficiency was 90–100%. The accumulative release of AR-DTX-PM was higher than that of glucose-dispersed DTX-PM (Glu-DTX-PM). The results of both physical and chemical stability studies showed that the concentration of arginine required for optimum stability was 2.0?mg/ml. Preliminary investigation of the mechanisms of stabilization by arginine suggested that it is due to the electrostatic interaction as well as hydrogen bonds between DTX and arginine. The acute toxicity studies demonstrated that AR-DTX-PM was better tolerated in beagle dogs than DTX injection. However, the pharmacokinetic studies revealed no significant difference in C_max and AUC of AR-DTX-PM compared to DTX injection. When AR-DTX-PM was administrated at a dose of 30?mg/kg, the antitumor effect was stronger than that of commercial DTX injection at 10?mg/kg, and the increase of administration dose did not cause higher toxicity. The in vivo imaging test showed that the residence time of AR-DTX-PM at tumor sites was longer than its commercial formulation. In a word, it is expected that AR-DTX-PM can reduce systemic toxicity while retaining antitumor efficacy in cancer patients.     

Reduced Insulin Sensitivity Is Related to Less Endogenous Dopamine at D2/3 Receptors in the Ventral Striatum of Healthy Nonobese Humans

Background:

Food addiction is a debated topic in neuroscience. Evidence suggests diabetes is related to reduced basal dopamine levels in the nucleus accumbens, similar to persons with drug addiction. It is unknown whether insulin sensitivity is related to endogenous dopamine levels in the ventral striatum of humans. We examined this using the agonist dopamine D_2/3 receptor radiotracer [¹¹C]-(+)-PHNO and an acute dopamine depletion challenge. In a separate sample of healthy persons, we examined whether dopamine depletion could alter insulin sensitivity.

Methods:

Insulin sensitivity was estimated for each subject from fasting plasma glucose and insulin using the Homeostasis Model Assessment II. Eleven healthy nonobese and nondiabetic persons (3 female) provided a baseline [¹¹C]-(+)-PHNO scan, 9 of which provided a scan under dopamine depletion, allowing estimates of endogenous dopamine at dopamine D_2/3 receptor. Dopamine depletion was achieved via alpha-methyl-para-tyrosine (64mg/kg, P.O.). In 25 healthy persons (9 female), fasting plasma and glucose was acquired before and after dopamine depletion.

Results:

Endogenous dopamine at ventral striatum dopamine D_2/3 receptor was positively correlated with insulin sensitivity (r(7)=.84, P=.005) and negatively correlated with insulin levels (r(7)=-.85, P=.004). Glucose levels were not correlated with endogenous dopamine at ventral striatum dopamine D_2/3 receptor (r(7)=-.49, P=.18). Consistently, acute dopamine depletion in healthy persons significantly decreased insulin sensitivity (t(24)=2.82, P=.01), increased insulin levels (t(24)=-2.62, P=.01), and did not change glucose levels (t(24)=-0.93, P=.36).

Conclusion:

In healthy individuals, diminished insulin sensitivity is related to less endogenous dopamine at dopamine D_2/3 receptor in the ventral striatum. Moreover, acute dopamine depletion reduces insulin sensitivity. These findings may have important implications for neuropsychiatric populations with metabolic abnormalities.     

Correlation between 25-hydroxyvitamin D level and arterial elasticity in middle-aged and elderly cadres in Guiyang,China: A retrospective observational study

There is evidence that serum 25-hydroxyvitamin D [25-(OH) D] levels may be associated with cardiovascular disease and its risk factors. This study aimed to investigate the relationship between 25-(OH) D levels and blood pressure (BP), blood lipids, and arterial elasticity in middle-aged and elderly cadres in China.In this retrospective study, we included 401 civil servants and cadres aged >42 years who underwent medical examinations at Guiyang Municipal First People''s Hospital, China in 2018. The participants were assigned to deficiency (≤20 ng/mL), insufficiency (20–30 ng/mL), and sufficiency (≥30 ng/mL) groups according to 25-(OH) D levels in their blood. Demographics, brachial–ankle pulse wave velocity (baPWV), BP, ankle–brachial index (ABI), and blood lipids were compared among groups. The associations between 25-(OH) D and other parameters were evaluated using linear regression analysis.Median (range) 25-(OH) D levels in the deficiency (n = 162), insufficiency (n = 162), and sufficiency (n = 77) groups were 15.32 (2.93–19.88), 25.12 (20.07–29.91), and 33.91 (30.23–82.42) ng/mL, respectively. There were significant differences in systolic BP, pulse pressure, baPWV (left and right sides), ABI (left side), high-density lipoprotein-cholesterol, and triglycerides (TGs; all P < .05) among groups. Multivariate linear regression revealed that TG, left baPWV, and right baPWV were significantly negatively correlated with 25-(OH) D levels (all P < .05).In this study, 25-(OH) D levels were found to be associated with TG, left baPWV, and right baPWV values. 25-(OH) D deficiency may be associated with reduced arterial elasticity.     

Physical performance and life quality in postmenopausal women supplemented with vitamin D: a two-year prospective study

Aim:

To investigate the effects of calcium and vitamin D supplementation on bone turnover marker levels, muscle strength and quality of life in postmenopausal Chinese women.

Methods:

A total of 485 healthy postmenopausal Chinese women (63.44±5.04 years) were enrolled in this open-label, 2-year, prospective, community-based trial. The participants were divided into group A, B, C, which were treated with calcium (600 mg/d) alone, calcium (600 mg/d) and cholecalciferol (800 IU/d) or calcium (600 mg/d) and calcitriol (0.25 μg/d), respectively, for 2 years. Serum levels of 25-hydroxyvitamin D, parathyroid hormone, β-CTX and P1NP were measured, and the muscle strength and quality of life were assessed at baseline and at 12- and 24-month follow-ups.

Results:

Four hundred and sixty one participants completed this study. Serum levels of 25-hydroxyvitamin D were significantly increased in group C, but not changed in groups A and B at 24-month follow-up. Serum levels of parathyroid hormone, bone turnover marker β-CTX and bone formation marker P1NP were significantly decreased in group C, while serum levels of β-CTX were increased in group A at 24-month follow-up. The participants in group C maintained the grip strength, while those in groups A and B exhibited decreased grip strength at 24-month follow-up. The quality of life for the participants in groups B and C remained consistent, but that in group A was deteriorated at 24-month follow-up.

Conclusion:

Supplementation with calcitriol and calcium modifies the bone turnover marker levels, and maintains muscle strength and quality of life in postmenopausal Chinese women, whereas supplementation with cholecalciferol and calcium prevents aging-mediated deterioration in quality of life.