Clostridium botulinum Type E Toxins Bind to Caco-2 Cells by a Different Mechanism from That of Type A Toxins

Cultured Clostridium botulinum strains produce progenitor toxins designated as 12S, 16S, and 19S toxins. The 12S toxin consists of a neurotoxin (NTX, 7S) and a non-toxic non-hemagglutinin (NTNH). The 16S and 19S toxins are formed by conjugation of the 12S toxin with hemagglutinin (HA), and the 19S toxin is a dimer of the 16S toxin. Type A cultures produce all 3 of these progenitor toxins, while type E produces only the 12S toxin. The 7S toxin is cleaved into heavy (H) and light (L) chains by a protease(s) in some strains, and the H chain has 2 domains, the N-terminus (Hn) and C-terminus (Hc). It has been reported that type A toxins bind to the intestinal cells or cultured cells via either HA or Hc. In this study, we investigated the binding of type A and E toxins to Caco-2 cells using Western blot analysis. Both the type E 7S and 12S toxins bound to the cells, with the 7S toxin binding more strongly, whereas, in the type A strain, only the 16S/19S toxins showed obvious binding. Pre-incubation of the type E 7S toxin with IgG against recombinant type E Hc significantly inhibited the 7S toxin binding, indicating that Hc might be a main binding domain of the type E toxin

Drug Nanoparticle Formulation Using Ascorbic Acid Derivatives

Drug nanoparticle formulation using ascorbic acid derivatives and its therapeutic uses have recently been introduced. Hydrophilic ascorbic acid derivatives such as ascorbyl glycoside have been used not only as antioxidants but also as food and pharmaceutical excipients. In addition to drug solubilization, drug nanoparticle formation was observed using ascorbyl glycoside. Hydrophobic ascorbic acid derivatives such as ascorbyl mono- and di-n-alkyl fatty acid derivatives are used either as drugs or carrier components. Ascorbyl n-alkyl fatty acid derivatives have been formulated as antioxidants or anticancer drugs for nanoparticle formulations such as micelles, microemulsions, and liposomes. ASC-P vesicles called aspasomes are submicron-sized particles that can encapsulate hydrophilic drugs. Several transdermal and injectable formulations of ascorbyl n-alkyl fatty acid derivatives were used, including ascorbyl palmitate

EFFECT OF POSTURAL CHANGE ON THE AERODYNAMIC CHARACTERISTICS DURING TAKEOFF IN SKI JUMPING

The purpose of this study was to quantify the aerodynamic characteristics during takeoff using computational fluid dynamics (CFD). The CFD method adopted for this study is based on Large-Eddy Simulation. Body surface data were obtained by 3-D laser scanning of an active ski jumper. A model was generated by dividing the data into A 5 segments with joint mobility. Based on video analysis of the actual takeoff movement at a jumping hill, two sets of motion data were generated (world-class jumper A and less-experienced junior jumper B). The incoming velocity was set to 23.23 m/s. The aerodynamic force, flow velocity, and vortices for each model were compared between models. Comparison of the two models shows that aerodynamic forces acting upon models might be influenced by the airflow condition around the model's back. Expansion of the low air-speed domain of jumper B can be caused by a large trunk angle of attack (Meile et al., 2006). The trunk and upper arm motion might cause the flow structure difference of the wake. Two distinct vortexes generated by the arms produced a downwash flow in the wake of jumper A. It is considered that the positioning of the arms in a very low position strongly influences the flow structure. These results suggested that the vortexes generated by the arms seem to be very important for the aerodynamic lift generation

Intraprostatic Botulinum Neurotoxin Type A Injection for Benign Prostatic Hyperplasia:Preliminary Results with a Newly Purified Neurotoxin

Several studies have demonstrated the efficacy of intraprostatic injection of botulinum neurotoxin type A (BoNT/A) against symptomatic benign prostatic hyperplasia (BPH). The most commonly used BoNT/A product, Botox®, forms large complexes and composed of neurotoxin (NTX) as well as non-toxic components. We purified NTX lacking non-toxic components. We investigated the efficacy of this newly purified NTX for men with BPH. Ten male patients (mean age, 70.0 years) with BPH received 100 units (prostate volume [PV] ＜30ml) or 200 units (PV ｧ30ml) of NTX injected into the prostate via a minimally invasive outpatient technique. Evaluation included uroflowmetry, postvoid residual urine volume (PVR), PV, and International Prostate Symptom Score (IPSS) measured at baseline and 1, 3, 6, and 12 months post-treatment. The status of 7 of the 10 patients examined was found to have improved within 1 month of treatment. The mean IPSS decreased from 23.8±7.0 to 16.3±10.3 (p＝0.0093) at 1 month, to 14.9±8.2 (p＝0.0074) at 3 months, and to 16.9±7.3 (p＝0.018) at 12 months. The mean PV decreased from 47.8±21.2 to 39.2±19.5ml (p＝0.0076) at 3 months. The PVR improved at 3 and 6 months post-treatment. Intraprostatic NTX injection induces prostate shrinkage and is effective in men with BPH