Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between Azelnidipine and amlodipine on glucose tolerance and endothelial function - a crossover trial (AGENT)

<p>Abstract</p> <p>Background</p> <p>Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice.</p> <p>Methods</p> <p>Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT.</p> <p>Results</p> <p>Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (<it>P </it>< 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both <it>P </it>< 0.05). Serum levels of high-sensitivity C-reactive protein (<it>P </it>= 0.067) and interleukin-6 (<it>P </it>= 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (<it>P </it>= 0.016).</p> <p>Conclusions</p> <p>These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension.</p

The Effects of Transdermal Nicotine Patches on the Cardiorespiratory and Lactate Responses During Exercise from Light to Moderate Intensity: Implications for Exercise Prescription during Smoking Cessation

Background and objectivesExercise can help ease withdrawal symptoms of smokers. However, there is little information about the physiological responses, such as cardiorespiratory and lactate (La) responses, during exercise from light to moderate intensity combined with transdermal nicotine patches (TNPs) in smokers. This study aimed to investigate the effect of TNPs on the cardiorespiratory and La responses during exercise at light to moderate intensity.Materials and MethodsFourteen young men (8 non-smokers, 6 current smokers) aged 20 to 26 years participated in this study. They performed an incremental graded submaximal exercise test using an electromagnetic cycle ergometer set from 30 to 210 W with (TNP condition) or without a TNP (control condition) in a random order. The TNP was applied to the left arm 8–10 h prior to starting the exercise to achieve the peak level of blood nicotine concentration. Heart rate (HR), rate of perceived exertion (RPE), oxygen consumption (VO2), ventilation (VE), and blood La at rest and during exercise were measured and analyzed. ResultsThe HR at rest was significantly higher in the TNP condition than in the control condition (TNP; 74.7 ± 13.8 bpm, control; 65.3 ± 10.8 bpm, p < 0.001). There was no interaction (condition × exercise intensity) between any of the variables, and VO2, VE, RPE, and La during exercise were not significantly different between the conditions. However, HR during exercise was 6.7 bpm higher on average in the TNP condition. Conclusions: The HR during exercise was greater at light to moderate intensity with a TNP. Our study results will guide clinicians or health professionals when prescribing exercise programs combined with TNPs for healthy young smokers

Association between the tissue accumulation of advanced glycation end products and exercise capacity in cardiac rehabilitation patients

Background Advanced glycation end products (AGEs) are associated with aging, diabetes mellitus (DM), and other chronic diseases. Recently, the accumulation of AGEs can be evaluated by skin autofluorescence (SAF). However, the relationship between SAF levels and exercise capacity in patients with cardiovascular disease (CVD) remains unclear. This study aimed to investigate the association between the tissue accumulation of AGEs and clinical characteristics, including exercise capacity, in patients with CVD. Methods We enrolled 319 consecutive CVD patients aged >= 40 years who underwent early phase II cardiac rehabilitation (CR) at our university hospital between November 2015 and September 2017. Patient background, clinical data, and the accumulation of AGEs assessed by SAF were recorded at the beginning of CR. Characteristics were compared between two patient groups divided according to the median SAF level (High SAF and Low SAF). Results The High SAF group was significantly older and exhibited a higher prevalence of DM than the Low SAF group. The sex ratio did not differ between the two groups. AGE levels showed significant negative correlations with peak oxygen uptake and ventilator efficiency (both P <0.0001). Exercise capacity was significantly lower in the high SAF group than in the low SAF group, regardless of the presence or absence of DM (P <0.05). A multivariate logistic regression analysis showed that SAF level was an independent factor associated with reduced exercise capacity (odds ratio 2.10; 95% confidence interval 1.13-4.05; P = 0.02). Conclusion High levels of tissue accumulated AGEs, as assessed by SAF, were significantly and independently associated with reduced exercise capacity. These data suggest that measuring the tissue accumulation of AGEs may be useful in patients who have undergone CR, irrespective of whether they have DM

Effects of Ingesting Food Containing Heat-Killed <i>Lactococcus lactis</i> Strain Plasma on Fatigue and Immune-Related Indices after High Training Load: A Randomized, Double-Blind, Placebo-Controlled, and Parallel-Group Study

Lactococcus lactis strain Plasma (LC-Plasma) is a unique lactic acid bacterium that activates plasmacytoid dendritic cells (pDCs). We evaluated the effect of LC-Plasma on fatigue indices and dendritic cells activity in athletes after 14 days’ continuous exercise load. Thirty-seven participants were divided into two groups and consumed placebo (PL) or LC-Plasma capsules (containing 100 billion cells) daily for 14 days. Maturation markers on dendritic cells, blood parameters, physiological indices, and fatigue-related indices were recorded on days 1 and 15 (before and after exercise). Cumulative days of symptoms relating to physical conditions were also recorded during the continuous exercise period. We observed that CD86 as a maturation marker on pDCs was significantly higher and that cumulative days of fatigue were significantly fewer in the LC-Plasma group than in the Placebo group on day 15. We also conducted 2 h ergometer exercise on day 15 to evaluate fatigue. The results showed that autonomic fatigue parameters (LF/HF) were significantly lower in the LC-Plasma group. These results suggest that LC-Plasma supplementation alleviates fatigue accumulation and increases pDC activity caused by a continuous high training load

Efficacy of heat-killed Lactococcus lactis JCM 5805 on immunity and fatigue during consecutive high intensity exercise in male athletes: a randomized, placebo-controlled, double-blinded trial

BACKGROUND: Lactococcus lactis JCM 5805 (LC-Plasma) is a unique lactic acid bacteria (LAB) which activates plasmacytoid dendritic cells (pDC). We aimed to evaluate the effect of LC-Plasma on dendritic cell (DC) activity and subjective indices of upper respiratory tract infections (URTI) and fatigue in athletes under high intensity exercise. METHODS: We conducted a randomized, placebo-controlled, double-blinded trial. Fifty-one male subjects belonging to a university sports club were randomized into placebo (n = 25) and LC-Plasma (n = 26) groups. Individuals ingested placebo capsules containing cornstarch or LC-Plasma capsules containing 100 billion cells of heat-killed LC-Plasma per day for 13 days. During the intervention period, subjects performed high intensity exercise according to their sports club training regime. Blood and saliva sampling were obtained at days 1 and 14, and physical conditions were recorded in a diary. We investigated expression of maturation markers on DCs, muscle damage and stress markers and used student’s t test adjusted by Bonferoni’s method for multiple comparison between groups. These data were presented as mean ± SD. We also investigated cumulative days of symptoms regarding infections and fatigue and used Chi-square test for comparison between groups. These data were presented as cumulative number. RESULTS: CD86 as maturation marker on pDC was significantly increased in the LC-Plasma group at day 14 (Placebo: 296 ± 70 vs. LC-Plasma: 365 ± 115; Mean Fluorescent Intensity; p = 0.013). Cumulative days of URTI were significantly lower in the LC-Plasma group (Placebo: URTI positive 56, URTI negative 256 vs. LC-Plasma: URTI positive 39, URTI negative 299; days; p = 0.028) and symptoms like sneeze or running nose were significantly lower in the LC-Plasma group (Placebo: Symptom positive 52, Symptom negative 258, vs. LC-Plasma: Symptom positive 36, Symptom negative 301; days; p = 0.032). Moreover, the cumulative days of fatigue were significantly fewer in the LC-Plasma group (Placebo: Symptom positive 128, Symptom negative 182, vs. LC-Plasma: Symptom positive 110, Symptom negative 225; days; p = 0.032). Markers of muscle damage and stress markers were not significantly different between groups. CONCLUSION: We consider that heat-killed LC-Plasma supplementation relieves morbidity and symptoms of URTI via activation of pDC and decreases fatigue accumulation during consecutive high intensity exercise in athletes. However, LC-Plasma ingestion did not affect markers of muscle damage and stress. TRIAL REGISTRATION: UMIN-CTR, UMIN000020372. Registered 28 December 2015

Arabidopsis R1R2R3-Myb proteins are essential for inhibiting cell division in response to DNA damage

Inhibition of cell division is an active response to DNA damage that enables cells to maintain genome integrity. However, how DNA damage arrests the plant cell cycle is largely unknown. Here, we show that the repressor-type R1R2R3-Myb transcription factors (Rep-MYBs), which suppress G2/M-specific genes, are required to inhibit cell division in response to DNA damage. Knockout mutants are resistant to agents that cause DNA double-strand breaks and replication stress. Cyclin-dependent kinases (CDKs) can phosphorylate Rep-MYBs in vitro and are involved in their proteasomal degradation. DNA damage reduces CDK activities and causes accumulation of Rep-MYBs and cytological changes consistent with cell cycle arrest. Our results suggest that CDK suppressors such as CDK inhibitors are not sufficient to arrest the cell cycle in response to DNA damage but that Rep-MYB-dependent repression of G2/M-specific genes is crucial, indicating an essential function for Rep-MYBs in the DNA damage response