Protection of Liver Functions and Improvement of Kidney Functions by Twelve Weeks Consumption of Cuban Policosanol (Raydel^®) with a Decrease of Glycated Hemoglobin and Blood Pressure from a Randomized, Placebo-Controlled, and Double-Blinded Study with Healthy and Middle-Aged Japanese Participants

Policosanol consumption has been associated with treating blood pressure and dyslipidemia by increasing the level of high-density lipoproteins-cholesterol (HDL-C) and HDL functionality. Although policosanol supplementation also ameliorated liver function in animal models, it has not been reported in a human clinical study, particularly with a 20 mg doage of policosanol. In the current study, twelve-week consumption of Cuban policosanol (Raydel®) significantly enhanced the hepatic functions, showing remarkable decreases in hepatic enzymes, blood urea nitrogen, and glycated hemoglobin. From the human trial with Japanese participants, the policosanol group (n = 26, male 13/female 13) showed a remarkable decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from baseline up to 21% (p = 0.041) and 8.7% (p = 0.017), respectively. In contrast, the placebo group (n = 26, male 13/female 13) showed almost no change or slight elevation. The policosanol group showed a 16% decrease in γ-glutamyl transferase (γ-GTP) at week 12 from the baseline (p = 0.015), while the placebo group showed a 1.2% increase. The policosanol group exhibited significantly lower serum alkaline phosphatase (ALP) levels at week 8 (p = 0.012), week 12 (p = 0.012), and after 4-weeks (p = 0.006) compared to those of the placebo group. After 12 weeks of policosanol consumption, the ferric ion reduction ability and paraoxonase of serum were elevated by 37% (p p = 0.004) higher than week 0, while placebo consumption showed no notable changes. Interestingly, glycated hemoglobin (HbA1c) in serum was lowered significantly in the policosanol group 4 weeks after consumption, which was approximately 2.1% (p = 0.004) lower than the placebo group. In addition, blood urea nitrogen (BUN) and uric acid levels were significantly lower in the policosanol group after 4 weeks: 14% lower (p = 0.002) and 4% lower (p = 0.048) than those of the placebo group, respectively. Repeated measures of ANOVA showed that the policosanol group had remarkable decreases in AST (p = 0.041), ALT (p = 0.008), γ-GTP (p = 0.016), ALP (p = 0.003), HbA1c (p = 0.010), BUN (p = 0.030), and SBP (p = 0.011) from the changes in the placebo group in point of time and group interaction. In conclusion, 12 weeks of 20 mg consumption of policosanol significantly enhanced hepatic protection by lowering the serum AST, ALT, ALP, and γ-GTP via a decrease in glycated hemoglobin, uric acid, and BUN with an elevation of serum antioxidant abilities. These results suggest that improvements in blood pressure by consumption of 20 mg of policosanol (Raydel®) were accompanied by protection of liver function and enhanced kidney function

Intermittent Exercise at Lactate Threshold Induces Lower Acute Stress than Its Continuous Counterpart in Middle-to-Older Aged Men

This study aimed to compare the degree of exhaustion and trophic effects between continuous exercise (CE) and intermittent exercise (IE) at lactate threshold (LT) intensity. Seven healthy men (age: 43–69 years) performed the following three experimental tests in a randomized crossover order: (1) control; (2) CE, performed as a 20-min of cycling at LT intensity; and (3) IE, performed as 20 sets of a one-min bout of cycling at LT intensity with a 30-s rest between every two sets. Heart rate (HR), blood lactate concentration (LA), rating of perceived exertion (RPE), catecholamines, cortisol, growth hormone, insulin-like growth factor (IGF)-1, and brain-derived neurotrophic factor (BDNF) were measured. The sampling timing in each test was as follows: 10 min before the onset of exercise, at the 25%, 50%, and 100% time points of exercise, and at 10 min after exercise. IE was found to be accompanied by a lower degree of exhaustion than CE in measures of HR, LA, RPE, catecholamines, and cortisol. In terms of trophic effects, both of IGF-1 and BDNF increased in CE, while a marginal increase of BDNF was observed in IE. The results indicated that IE induces lower stress than CE, but may not be effective for inducing trophic effects

Effects of Home-Based Robotic Therapy Involving the Single-Joint Hybrid Assistive Limb Robotic Suit in the Chronic Phase of Stroke: A Pilot Study

Introduction. Robotic therapy has drawn attention in the rehabilitation field including home-based rehabilitation. A previous study has reported that home-based therapy could be more effective for increasing upper limb activity than facility-based therapy. The single-joint hybrid assistive limb (HAL-SJ) is an exoskeleton robot developed according to the interactive biofeedback theory, and several studies have shown its effectiveness for upper limb function in stroke patients. A study of home-based robotic therapy has shown to enhance rehabilitation effectiveness for stroke patient with a paretic upper limb. However, home-based therapy involving a HAL-SJ in stroke patients with paretic upper limbs has not been investigated. The present study aimed to investigate paretic upper limb activity and function with home-based robotic therapy involving a HAL-SJ in stroke patients. Materials and Methods. A home-based robotic therapy program involving a HAL-SJ was performed for 30 min per session followed by standard therapy for 30 min per session, 2 times a week, for 4 weeks (i.e., completion of all 8 sessions involved 8 h of rehabilitation), at home. After the intervention, patients were followed up by telephone and home visits for 8 weeks. The paretic upper limb activity and function were assessed using the Motor Activity Log (MAL; amount of use (AOU)), arm triaxial accelerometry (laterality index (LI)), the Fugl–Meyer assessment (FMA), and the action research arm test (ARAT), at baseline and week 4 and week 12 after the start of training. Results. The study included 10 stroke patients (5 men; mean age, 61.1 ± 7.1 years). The AOU scores and LI significantly improved at week 4 after the start of training (p<0.05). However, no significant changes were observed in the LI at week 12 (p=0.161) and the FMA scores at both week 4 and week 12 (p=0.059 and p=0.083, respectively). The ARAT scores significantly improved at both week 4 and week 12 (p<0.05). Conclusion. Home-based robotic therapy combined with conventional therapy could be a valuable approach for increasing paretic upper limb activity and maintaining paretic upper limb function in the chronic phase of stroke

Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Phosphate Accelerates Cellular Cholesterol Efflux in THP-1 Cells

Cholesterol efflux is a major atheroprotective function of high-density lipoproteins (HDLs) which removes cholesterol from the foam cells of lipid-rich plaques in Type 2 diabetes. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin phosphate increases plasma glucagon-like peptide-1 (GLP-1) concentrations and is used to treat Type 2 diabetes. GLP-1 plays an important role in regulating insulin secretion and expression via the GLP-1 receptor (GLP-1R), which is expressed in pancreatic islets as well as freshly isolated human monocytes and THP-1 cells. Here, we identified a direct role of GLP-1 and DPP-4 inhibition in HDL function. Cholesterol efflux was measured in cultivated phorbol 12-myristate 13-acetate-treated THP-1 cells radiolabeled with 3H-cholesterol and stimulated with liver X receptor/retinoid X receptor agonists. Contrary to vildagliptin, sitagliptin phosphate together with GLP-1 significantly (p < 0.01) elevated apolipoprotein (apo)A1-mediated cholesterol efflux in a dose-dependent manner. The sitagliptin-induced increase in cholesterol efflux did not occur in the absence of GLP-1. In contrast, adenosine triphosphate-binding cassette transporter A1 (ABCA1) mRNA and protein expressions in the whole cell fraction were not changed by sitagliptin in the presence of GLP-1, although sitagliptin treatment significantly increased ABCA1 protein expression in the membrane fraction. Furthermore, the sitagliptin-induced, elevated efflux in the presence of GLP-1 was significantly decreased by a GLP-1R antagonist, an effect that was not observed with a protein kinase A inhibitor. To our knowledge, the present study reports for the first time that sitagliptin elevates cholesterol efflux in cultivated macrophages and may exert anti-atherosclerotic actions that are independent of improvements in glucose metabolism. Our results suggest that sitagliptin enhances HDL function by inducing a de novo HDL synthesis via cholesterol efflux

Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Phosphate Accelerates Cellular Cholesterol Efflux in THP-1 Cells

Cholesterol efflux is a major atheroprotective function of high-density lipoproteins (HDLs) which removes cholesterol from the foam cells of lipid-rich plaques in Type 2 diabetes. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin phosphate increases plasma glucagon-like peptide-1 (GLP-1) concentrations and is used to treat Type 2 diabetes. GLP-1 plays an important role in regulating insulin secretion and expression via the GLP-1 receptor (GLP-1R), which is expressed in pancreatic islets as well as freshly isolated human monocytes and THP-1 cells. Here, we identified a direct role of GLP-1 and DPP-4 inhibition in HDL function. Cholesterol efflux was measured in cultivated phorbol 12-myristate 13-acetate-treated THP-1 cells radiolabeled with 3H-cholesterol and stimulated with liver X receptor/retinoid X receptor agonists. Contrary to vildagliptin, sitagliptin phosphate together with GLP-1 significantly (p &lt; 0.01) elevated apolipoprotein (apo)A1-mediated cholesterol efflux in a dose-dependent manner. The sitagliptin-induced increase in cholesterol efflux did not occur in the absence of GLP-1. In contrast, adenosine triphosphate-binding cassette transporter A1 (ABCA1) mRNA and protein expressions in the whole cell fraction were not changed by sitagliptin in the presence of GLP-1, although sitagliptin treatment significantly increased ABCA1 protein expression in the membrane fraction. Furthermore, the sitagliptin-induced, elevated efflux in the presence of GLP-1 was significantly decreased by a GLP-1R antagonist, an effect that was not observed with a protein kinase A inhibitor. To our knowledge, the present study reports for the first time that sitagliptin elevates cholesterol efflux in cultivated macrophages and may exert anti-atherosclerotic actions that are independent of improvements in glucose metabolism. Our results suggest that sitagliptin enhances HDL function by inducing a de novo HDL synthesis via cholesterol efflux