Benidipine has effects similar to losartan on the central blood pressure and arterial stiffness in mild to moderate essential hypertension

Background Central blood pressure (BP) is pathophysiologically more important than peripheral BP for the pathogenesis of cardiovascular disease.Arterial stiffness is also a good predictor of cardiovascular morbidity and mortality.The effects of benidipine,a unique dual L-/T-type calcium channel blocker,on central BP have not been reported.This study aimed to compare the effect of benidipine and losartan on the central BP and arterial stiffness in mild to moderate essential hypertensives.Methods This 24 weeks,multi-center,open label,randomized,active drug comparative,parallel group study was designed as a non-inferiority study.The eligible patients (n=200) were randomly assigned to receive benidipine (n=101)or losartan (n=99).Radial artery applanation tonometry and pulse wave analysis were used to measure the central BP,pulse wave velocity (PWV) and augmentation index (Alx).We also measured the metabolic and inflammatory markers.Results After 24 weeks,the central BP decreased significantly from baseline by (16.8+14.0/10.5+9.2) mmHg (1mmHg =0.133 kPa) (systolic/diastolic BP; P ＜0.001) in benidipine group and (18.9+14.7/12.1+10.2) mmHg (P ＜0.001)in losartan group respectively.Both benidipine and losartan groups significantly lowered peripheral BP (P ＜0.001) and Alx (P ＜0.05),but there were no significant differences between the two groups.The mean aortic,brachial and femoral PWV did not change in both groups after 24-week treatment.There were no significant changes of the blood metabolic and inflammatory biomarkers in each group.Conclusion Benidipine is as effective as losartan in lowering the central and peripheral BP,and improving arterial stiffness.     

Phospholipid micelle-based magneto-plasmonic nanoformulation for magnetic field-directed,imaging-guided photo-induced cancer therapy

We present a magnetoplasmonic nanoplatform combining gold nanorods (GNR) and iron-oxide nanoparticles within phospholipid-based polymeric nanomicelles (PGRFe). The gold nanorods exhibit plasmon resonance absorbance at near infrared wavelengths to enable photoacoustic imaging and photothermal therapy, while the Fe₃O₄ nanoparticles enable magnetophoretic control of the nanoformulation. The fabricated nanoformulation can be directed and concentrated by an external magnetic field, which provides enhancement of a photoacoustic signal. Application of an external field also leads to enhanced uptake of the magnetoplasmonic formulation by cancer cells in vitro. Under laser irradiation at the wavelength of the GNR absorption peak, the PGRFe formulation efficiently generates plasmonic nanobubbles within cancer cells, as visualized by confocal microscopy, causing cell destruction. The combined magnetic and plasmonic functionalities of the nanoplatform enable magnetic field-directed, imaging-guided, enhanced photo-induced cancer therapy.From the Clinical EditorIn this study, a nano-formulation of gold nanorods and iron oxide nanoparticles is presented using a phospholipid micelle-based delivery system for magnetic field-directed and imaging-guided photo-induced cancer therapy. The gold nanorods enable photoacoustic imaging and photothermal therapy, while the Fe₃O₄ nanoparticles enable magnetophoretic control of the formulation. This and similar systems could enable more precise and efficient cancer therapy, hopefully in the near future, after additional testing.     

Protective effect of a marine polyphenol,dieckol against carbon tetrachloride-induced acute liver damage in mouse

In this study, the hepatoprotective effect of dieckol on carbon tetrachloride (CCl₄) induced hepatic damages in ICR mice liver was investigated. Mice were randomly divided into 4 groups such as saline treated (negative control), CCl₄ treated (positive control), CCl₄ + dieckol (5 mg/kg mouse) and CCl₄ + dieckol (25 mg/kg mouse), respectively. The body weights and survival rates of mice, followed by dieckol treatments were significantly increased compared to the positive control. The level of GOT, GPT and MDA in the serum of the dieckol treated groups were reduced dose dependently than the control, significantly. The antioxidant enzymes including CAT, and GSH-px levels were increased significantly compared to the positive control. However, no significant differences were observed on hepatic histophathological analysis in dieckol treated groups dose dependently. Down-regulation of Bax and up-regulation of Bcl-xl protein expressions were observed in liver tissues of the dieckol administered groups. These results suggested that, dieckol can be developed as a therapeutic agent for liver disease by oxidative stress.     

Characterization of the Phase II metabolites of rutaecarpine in rat by liquid chromatography-electrospray ionization-tandem mass spectrometry

From the authors’ previous studies on the Phase I metabolism of rutaecarpine, nine metabolites formed were identified as products of hydroxylation on the aromatic rings in rat liver microsomes. In order to determine the possible metabolic fate of rutaecarpine, the Phase II metabolites of rutaecarpine were characterized in the present study by using liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS). When male Sprague–Dawley rats were treated intravenously with 4?mg?kg^?1 rutaecarpine, 16 different Phase I and II metabolites were identified in urine including four sulfate and four glucuronide conjugates. Phase I metabolites of rutaecarpine were identified as four mono-hydroxylated metabolites (M2–5) and four isobaric di-hydroxylated metabolites (M6–9). These metabolites were identical to the in vitro metabolites except one, which was hydroxylated in the aliphatic moiety. In addition, Phase II metabolites were identified as conjugated with sulfate (S1–4) and glucuronide (G1–4). In faeces, 11 different metabolites were identified. The metabolites M8 and glucuronide conjugated (G1–4) were not detected. Structures of all metabolites were confirmed with CID fragmentation spectra of MS², MS³ and retention times by LC/ESI-MS.     

Formulations for Intermittent Release of Parathyroid Hormone (1-34) and Local Enhancement of Osteoblast Activities

The objective of these studies was to develop simple, implantable devices that intermittently release PTH(1-34) and thus could be used for locally stimulating bone formation. The formulations were based on the association polymer system of cellulose acetate phthalate and Pluronic F-127. Release profiles for intermittent devices showed five discrete peaks, whereas sustained devices exhibited zero-order kinetics. Osteoblastic activity was greater for cells intermittently treated with PTH(1-34) compared to sustained exposure. These controlled release devices delivering PTH(1-34) in an intermittent manner may be useful for affecting osteoblast activities in a localized area.     

The Longevity Properties of 1,2,3,4,6-Penta-O-Galloyl-β-D-Glucose from Curcuma longa in Caenorhabditis elegans

Here in this study, we isolated 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) from Curcuma longa L. and elucidated the lifespanextending effect of PGG using Caenorhabditis elegans model system. In the present study, PGG demonstrated potent lifespan extension of worms under normal culture condition. Then, we determined the protective effects of PGG on the stress conditions such as thermal and oxidative stress. In the case of heat stress, PGG-treated worms exhibited enhanced survival rate, compared to control worms. In addition, PGG-fed worms lived longer than control worms under oxidative stress induced by paraquat. To verify the possible mechanism of PGG-mediated increased lifespan and stress resistance of worms, we investigated whether PGG might alter superoxide dismutase (SOD) activities and intracellular ROS levels. Our results showed that PGG was able to elevate SOD activities of worms and reduce intracellular ROS accumulation in a dose-dependent manner.     

Differences in leg length discrepancy and weight distribution between the healthy and unhealthy sides of hemiplegic stroke patients

Weight distribution is often measured for the evaluation of balance. The present study was designed to evaluate the correlation between leg length discrepancy (LLD) and balance as measured by weight distribution after stroke. Twenty-two patients who were hemiplegic after stroke (twelve men and ten women) participated in this weight-distribution measurement and the LLD measurement study. A tape measure was used to measure LLD between the unhealthy and healthy sides. The balance was measured in three different positions (weight distribution while standing quietly, while sit to standing, and while in a maximal weight-shifting position) using the Messen Tairuieren Dokumentieren system. The degree of weight distribution on the unhealthy side was less than on the healthy side in all the positions. The functional and anatomical leg length discrepancy in the lower limb of the unhealthy side was longer than that of the healthy side. In all positions, these LLDs were significantly correlated with balance on the unhealthy side compared with that on healthy side. The present study in part found that after stroke, hemiplegic patients could become more unbalanced because of asymmetry in weight distribution and decreased limits of stability caused by leg length discrepancy.     

Hempseed oil induces reactive oxygen species- and C/EBP homologous protein-mediated apoptosis in MH7A human rheumatoid arthritis fibroblast-like synovial cells

Ethnopharmacological relevance

The medicinal efficacy of hempseed (Cannabis sativa L.), which is rich in polyunsaturated fatty acids, in atopic dermatitis, inflammation, and rheumatoid arthritis (RA) has been suggested for centuries. Hempseed has been used as a treatment for these diseases in Korean and Chinese folk medicine. The aim of the study is to investigate the effects of hempseed oil (HO) on MH7A human RA fibroblast-like synovial cells.

Materials and methods

MH7A cells were used to study the anti-rheumatoid effects of hempseed (Cannabis sativa L., cv. Cheungsam/Cannabaceae) oil by investigating cell viability, apoptosis, lipid accumulation, oxidative stress, and endoplasmic reticulum (ER) stress-induced apoptosis.

Results

HO treatment reduced the survival rate of MH7A cells and promoted apoptotic cell death in a time- and dose-dependent manner. Both lipid accumulation and the level of intracellular reactive oxygen species (ROS) increased in HO-treated MH7A cells. Co-treatment with the antioxidant Tiron effectively abrogated the cytotoxic effects of HO; the ROS level was reduced, cell viability was recovered, and apoptotic cell death was significantly diminished. Moreover, HO-treated cells exhibited increased expression of the major ER stress markers, glucose-regulated protein 78 and C/EBP homologous protein (CHOP). The siRNA-mediated knockdown of CHOP prevented HO-induced apoptosis.

Conclusions

Our results suggest that HO treatment induced lipid accumulation, ROS production, CHOP expression, and apoptosis in MH7A cells, and that CHOP functions as an anti-rheumatoid factor downstream of HO in MH7A cells.