Water-Soluble and Low Molecular Weight Chitosan-Based Plasmid DNA Delivery

Purpose. Chitosan, a natural cationic polysaccharide, is a candidate non-viral vector for gene delivery because of its high positive charges and low cytotoxicity. In this study, low molecular weight chitosan (LMWC, molecular weight of 22 kDa) was characterized and evaluated as a gene carrier. Methods. Plasmid/LMWC complex was analyzed in 1% agarose gel electrophoresis. To confirm that the LMWC protected plasmids from nuclease, DNase I protection assays were performed. pSV--galactosidase plasmid/LMWC complex was transfected into 293T cells and transfection efficiency was evaluated by -galactosidase assay. Cytotoxicity of LMWC was determined by MTT assay. Results. Unlike high molecular weight chitosan (HMWC), LMWC is highly water soluble, and can form complex with plasmids in physiological buffer. The plasmid DNA was completely retarded at a weight ratio of 1:2 (plasmid:LMWC) in 1% agarose gel. DNase I protection assay showed that plasmids were protected from DNase I over 60 min. The most efficient transfection was obtained at a weight ratio of 1:3 (plasmid:LMWC). The transfection efficiency of LMWC was significantly higher than naked DNA and higher than poly-L-lysine (PLL). MTT assay showed that LMWC was less cytotoxic than PLL. Conclusions. LMWC is non-toxic and has higher transfection efficiency than PLL. Therefore, LMWC will be useful in the development of safe gene carriers.     

Optimal Control Strategy of Plasmodium vivax Malaria Transmission in Korea

ObjectiveTo investigate the optimal control strategy for Plasmodium vivax malaria transmission in Korea.MethodsA Plasmodium vivax malaria transmission model with optimal control terms using a deterministic system of differential equations is presented, and analyzed mathematically and numerically.ResultsIf the cost of reducing the reproduction rate of the mosquito population is more than that of prevention measures to minimize mosquito-human contacts, the control of mosquito-human contacts needs to be taken for a longer time, comparing the other situations. More knowledge about the actual effectiveness and costs of control intervention measures would give more realistic control strategies.ConclusionMathematical model and numerical simulations suggest that the use of mosquito-reduction strategies is more effective than personal protection in some cases but not always.     

Differences in postoperative outcomes, function, and cosmesis: open versus robotic thyroidectomy

Background  

Robotic thyroidectomy using a gasless transaxillary approach, first described in 2008, has become popular. This study compared outcomes, including postoperative distress and patient satisfaction, for patients undergoing robotic thyroidectomy with those for patients treated by conventional open thyroidectomy.     

Resveratrol enhances 5-hydroxytryptamine type 3A receptor-mediated ion currents: the role of arginine 222 residue in pre-transmembrane domain I

Resveratrol, which is found in grapes, red wine, and berries, has many beneficial health effects, such as anti-cancer, neuro-protective, anti-inflammatory, and life-prolonging effects. However, the cellular mechanisms by which resveratrol acts are relatively unknown, especially in terms of possible regulation of receptors involved in synaptic transmission. 5-Hydroxytryptamine type 3A (5-HT(3A)) receptor is one of several ligand-gated ion channels involved in fast synaptic transmission. In the present study, we investigated the effect of resveratrol on mouse 5-HT(3A) receptor channel activity. 5-HT(3A) receptor was expressed in Xenopus oocytes, and the current was measured using a two-electrode voltage clamp technique. Treatment of resveratrol itself had no effect on the oocytes injected with H(2)O as well as on the oocytes injected with 5-HT(3A) receptor cRNA. In the oocytes injected with 5-HT(3A) receptor cRNA, co- or pre-treatment of resveratrol with 5-HT potentiated 5-HT-induced inward peak current (I(5-HT)) with concentration-, reversible, and voltage-independent manners. The EC(50) of resveratrol was 28.0±2.4 μM. The presence of resveratrol caused a leftward shift of 5-HT concentration-response curve. Protein kinase C (PKC) activator or inhibitor had no effect on resveratrol action on I(5-HT). Site-directed mutations of pre-transmembrane domain 1 (pre-TM1) such as R222A, R222D, R222E, R222K, and R222T abolished or attenuated resveratrol-induced enhancement of I(5-HT), indicating that resveratrol might interact with pre-TM1 of 5-HT(3A) receptor. These results indicate that resveratrol might regulate 5-HT(3A) receptor channel activity via interaction with the N-terminal domain and these results further show that resveratrol-mediated regulation of 5-HT(3A) receptor channel activity might be one of cellular mechanisms of resveratrol action.     

Ginsenosides attenuate kainic acid-induced synaptosomal oxidative stress via stimulation of adenosine A(2A) receptors in rat hippocampus

Treatment with ginsenosides attenuated KA-induced seizures and oxidative stress in the synaptosome, and reduced synaptic vesicles at the presynaptic terminals dose-dependently. The adenosine A(2A) receptor antagonist 1,3,7-trimethyl-8-(3-chlorostyryl) xanthine reversed the ginsenoside-mediated pharmacological actions. Neither the adenosine A(1) receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine nor the adenosine A(2B) receptor antagonist alloxazine affected the ginsenoside-mediated pharmacological actions. Our results suggest that ginsenosides block KA-induced synaptosomal oxidative stress, associated with hippocampal degeneration, through activation of adenosine A(2A) receptors.     

Age and body weight adjusted warfarin initiation program for ischaemic stroke patients

Background:  Despite its proven effect, anticoagulation is not recommended to the acute ischaemic stroke due to the risk of bleeding complications. The purpose of this study is development of individualized warfarin initiation program for acute or subacute stroke patients.
Methods:  Among stroke patients who regularly visited out-patient clinics, we included patients who have continuously taken the same dose of warfarin as the prothrombin time remained at target International Nomarlized Ratio (INR). We assessed potential variables that affect the maintenance dose of warfarin. Using these variables, we developed an individualized warfarin initiation program.
Results:  The median warfarin maintenance dose (interquartile range) in the 321 included patients was 4 (3–5) mg per day. Age (adjusted R ² = 0.221, P  <   0.001) and body weight (added to age, adjusted R ² = 0.238, P  =   0.008) were significant predicting factors of the dose. We classified the maintenance doses into high (HG), standard, and low group (LG) based on the distribution of maintenance doses. Decision tree analysis categorized younger (≤55 years old) and heavier (≥55 kg) patients into HG, and very old (≥80 years old) or low body weight (<55 kg among those >56 years old) patients into LG. We recommend 7 mg of warfarin as a standard initial dose, but 10 mg was recommended for HG patients and 5 mg for LG.
Conclusion:  We expect that this individualized program may reduce the time to target INR without excessive anticoagulation. Further prospective studies are needed to reveal the efficacy and safety of applying this program for acute stroke patients.