Intimal hyperplasia of experimental autologous vein graft in hyperlipidemic rabbits with poor distal run-off

Poor distal runoff and hyperlipidemia are factors affecting the fate of an implanted graft. In the present study, combined effects of poor distal runoff and hyperlipidemia on intimal hyperplasia (IH) of the vein graft were examined in a newly developed poor distal runoff model in rabbits. A poor distal runoff model was prepared in the right hindlimb of 30 rabbits. These animals were divided into two groups, depending on the diet provided; normolipidemic diet group (Group NL, n = 14) and hyperlipidemic 1% cholesterol diet group (Group HL, n = 16). Four weeks after preparing the poor runoff model, the femoral vein was implanted into the ipsilateral femoral artery. At 2, 4 and 6 weeks, the grafts were harvested. IH of the graft was measured and macrophages in the IH were examined immunohistochemically. Intimal cell proliferation was also determined by bromodeoxyuridine (BrdU) incorporation. IH of the vein graft was significantly accelerated in cases of poor distal runoff and hyperlipidemia. There were no macrophages in the IH in the NL group. In the HL group, macrophages infiltrated the outer layer of IH, sometimes just above the internal elastic lamina, and increased with time. In the poor distal runoff limbs at 6 weeks, macrophages also appeared in the subendothelial layer but were absent in that layer in the controls. Intimal cell proliferation expressed as the Brd U labeling index (LI) was maximum at 2 weeks. In the HL group, BrdU LI of 1H in the poor distal runoff limb was higher than in the control at 2 and 4 weeks. Throughout the experiments, BrdU Us in the HL group were significantly higher than in the NL. Hyperlipidemia accelerates intimal cell proliferation to a greater extent, then does 1H. In cases of a poor distal runoff, the enhancement of cell proliferation by hyperlipidemia is augmented. These responses, in the presence of a hyperlipidemia, may be closely related to the migration of macrophages.     

The administration of pitavastatin augments creatinine clearance associated with reduction in oxidative stress parameters: acute and early effects

Background

Chronic kidney disease (CKD) is a serious health problem worldwide. Therapies that can halt the progression of CKD are limited, and the identification of new strategies for CKD treatment is therefore important. Pitavastatin, one of the newest statins introduced to the market, has been shown to exhibit some beneficial effects on renal and endothelial function.

Method

We enrolled 12 healthy volunteers for our study. With or without pitavastatin administration, creatinine clearance (Ccr), urinary albumin excretion, lipid status, and oxidative stress markers were evaluated in acute and early phases after administration of the drug.

Results

A single pitavastatin administration increased Ccr and reduced oxidative stress parameters, such as 8-OHdG levels and isoprostane production, within 6 h, without altering lipid status in healthy participants. A two-week treatment with pitavastatin lowered total and LDL cholesterol and triglycerides but not HDL cholesterol at 7 and 14 days. This change in lipid profile is associated with enhanced Ccr and the suppression of oxidative stress parameters. Urinary albumin excretion was reduced after either acute or chronic administration of pitavastatin, although this effect was not yet significant.

Conclusion

We found that pitavastatin augmented Ccr and reduced oxidative stress parameters in healthy subjects. These data suggest that pitavastatin affects renal outcomes in both lipid status-dependent and -independent manners. These observations suggest that pitavastatin treatment could be beneficial for CKD patients.     

Cellular origin of microfibrils explored by monensin-induced perturbation of secretory activity in embryonic primary cultures

Fibrillin is a primary component of elastin-associated microfibrils. Since microfibrils are distributed rather ubiquitously in embryonic tissues, attention has focused on the types of cells responsible for producing fibrillin. To clarify this issue, we employed monensin-induced perturbation of secretory activity in embryonic primary cultures, as this would allow examination of both the secreted protein and the formation of extracellular fibrils in the same culture. Micromasses of avian limb bud mesoderm, its ectodermal covering and several explants from other sources were cultured in the presence and absence of monensin, and evaluated immunohistochemically using antibodies against fibrillin and cell lineage markers. The results indicated that monensin perturbation induced intracellular accumulation of fibrillin and prevented the formation of microfibrils. It was shown specifically that not only mesodermally derived fibrogenic cells and myogenic cells of skeletal and smooth muscle cell lineage, but also epithelial-type cells such as endothelial and ectodermal cells, are producers of fibrillin. This dual cellular origin of fibrillin at the ectomesenchymal interface is considered significant for understanding the formation and remodeling of microfibrils originating from the basal lamina.     

Antioxidant and anti-inflammatory effects of a diet supplemented with sesamin on hepatic ischemia-reperfusion injury in rats

BACKGROUND/AIMS: The antioxidant and anti-inflammatory properties of sesamin (a non-fat constituent of sesame oil) have been attributed to an increased accumulation of dihomo-y-linolenic acid, a precursor of 1-series prostaglandins, and the decreasing production of proinflammatory 2-series prostaglandins and 4-series leukotrienes by inhibiting the delta-5 desaturase activity. We investigated the effects of a diet containing sesamin on hepatic ischemia-reperfusion injury in rats. METHODOLOGY: After feeding rats either a basal diet (control group) or a diet supplemented with sesamin (sesamin group) for 14 days, the rats underwent 60 minutes of partial hepatic ischemia and 3 hours of reperfusion. The phospholipid fatty acid composition of both liver and lung tissue specimens were then analyzed. The plasma levels of leukotriene B4 and PCOOH (phosphatidylcholine hydroperoxide) were also determined. RESULTS: The consumption of the dietary sesamin resulted in a significant increase in the dihomo-y-linolenic acid content in the tissue phospholipids of the liver and lung specimens. The amounts of polyunsaturated fatty acids in the lungs subjected to the ischemia-reperfusion injury were well preserved in the animals from the sesamin group. Despite a lack of differences in the levels of arachidonic acid, the plasma levels of leukotriene B4 in the rats fed dietary sesamin (88 +/- 15 pg) tended to be lower (P = 0.07) than those fed the control diet (110 +/- 20 pg). Furthermore, the plasma concentrations of PCOOH in the sesamin group (130 +/- 62 pmol) were also significantly lower (P < 0.05) than those in the control group (223 +/- 33 pmol). CONCLUSIONS: These findings indicate that a diet containing sesamin may thus reduce hepatic ischemia-reperfusion injury by inducing both antioxidant and anti-inflammatory activities.     

Autonomic imbalance as a property of symptomatic Brugada syndrome.

The autonomic properties in 27 patients with the electrocardiographic morphology of Brugada syndrome were investigated using 24-h Holter monitoring: 10 patients had a history of ventricular fibrillation (VF; Br-VF group) and 17 did not (Br-N group); there were 26 healthy subjects enrolled in this study. All subjects underwent normal Holter data monitoring and power spectral analysis. Few extrasystoles were observed in either group, and the mean heart rate (HR), maximum HR, and total heart beats over 24 h were obtained. All of these measurements were significantly lower in the Br-VF group than in the Br-N and healthy subject groups. The RR interval variability was analyzed over 512 beats every 10 min. The high-frequency component (0.15-0.40 Hz; HF), low-frequency component (0.04-0.15 Hz; LF) and the LF/HF ratio were analyzed over 24 h. The HF was significantly higher and LF/HF ratio lower in the Br-VF group than in the healthy subjects. The HF was also significantly higher than in the Br-N group. During the night (00.00-05.00 h), the HF was significantly higher in the Br-VF group, and the LH/HF lower. During the day (12.00-17.00 h), the HF was significantly higher in the Br-VF group, but there was no difference in the LF/HF. These results indicate that high vagal tone and low sympathetic tone are specific properties of symptomatic Brugada syndrome.     

Aerobic Exercise Attenuates the Loss of Skeletal Muscle during Energy Restriction in Adults with Visceral Adiposity

ObjectiveTo evaluate the effects of energy restriction with or without aerobic exercise on thigh muscle mass and quality in adults with visceral adiposity.Methods75 males and females were randomly assigned to the groups ‘diet only’ (DO; n = 42) or ‘diet plus aerobic exercise’ (D/Ex; n = 33) for 12 weeks. The target energy intake in both groups was 25 kcal/kg of ideal body weight. Subjects in the D/Ex group were instructed to exercise for ≥300 min/week at lactate threshold. Computed tomography was used to measure thigh muscle cross-sectional area (CSA), normal-density muscle area (NDMA), and visceral fat area.ResultsTotal body weight (DO: −6.6 ± 3.6%; D/Ex: −7.3 ± 4.6%) and visceral fat (DO: −16.0 ± 13.8%; D/Ex: −23.1 ± 14.7%) decreased significantly in both groups; however, the changes were not significantly different between the two groups. The decrease in muscle CSA was significantly greater in the DO group (-5.1 ± 4.5%) compared with the D/Ex group (-2.5 ± 5.0%). NDMA decreased significantly in the DO (-4.9 ± 4.9%) but not in the D/Ex group (-1.4 ± 5.0%).ConclusionAerobic exercise attenuated the loss of skeletal muscle during energy restriction in adults with visceral adiposity.Key Words: Aerobic exercise, Skeletal muscle, Normal density muscle, Visceral adiposity, Energy restriction