Oral Delivery of Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Bioencapsulated in Plant Cells Attenuates Pulmonary Hypertension

Emerging evidences indicate that diminished activity of the vasoprotective axis of the renin–angiotensin system, constituting angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to the pathogenesis of pulmonary hypertension (PH). However, long-term repetitive delivery of ACE2 or Ang-(1-7) would require enhanced protein stability and ease of administration to improve patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect against gastric enzymatic degradation and facilitates long-term storage at room temperature. Besides, fusion to a transmucosal carrier helps effective systemic absorption from the intestine on oral delivery. We hypothesized that bioencapsulating ACE2 or Ang-(1-7) fused to the cholera nontoxin B subunit would enable development of an oral delivery system that is effective in treating PH. PH was induced in male Sprague Dawley rats by monocrotaline administration. Subset of animals was simultaneously treated with bioencapsulaed ACE2 or Ang-(1-7) (prevention protocol). In a separate set of experiments, drug treatment was initiated after 2 weeks of PH induction (reversal protocol). Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) prevented the development of monocrotaline-induced PH and improved associated cardiopulmonary pathophysiology. Furthermore, in the reversal protocol, oral ACE2 or Ang-(1-7) treatment significantly arrested disease progression, along with improvement in right heart function, and decrease in pulmonary vessel wall thickness. In addition, a combination therapy with ACE2 and Ang-(1-7) augmented the beneficial effects against monocrotaline-induced lung injury. Our study provides proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary disease therapeutics

Oral Delivery of Angiotensin-Converting Enzyme 2 and Angiotensin-(1-7) Bioencapsulated in Plant Cells Attenuates Pulmonary Hypertension

Emerging evidences indicate that diminished activity of the vasoprotective axis of the renin–angiotensin system, constituting angiotensin-converting enzyme 2 (ACE2) and its enzymatic product, angiotensin-(1-7) [Ang-(1-7)] contribute to the pathogenesis of pulmonary hypertension (PH). However, long-term repetitive delivery of ACE2 or Ang-(1-7) would require enhanced protein stability and ease of administration to improve patient compliance. Chloroplast expression of therapeutic proteins enables their bioencapsulation within plant cells to protect against gastric enzymatic degradation and facilitates long-term storage at room temperature. Besides, fusion to a transmucosal carrier helps effective systemic absorption from the intestine on oral delivery. We hypothesized that bioencapsulating ACE2 or Ang-(1-7) fused to the cholera nontoxin B subunit would enable development of an oral delivery system that is effective in treating PH. PH was induced in male Sprague Dawley rats by monocrotaline administration. Subset of animals was simultaneously treated with bioencapsulaed ACE2 or Ang-(1-7) (prevention protocol). In a separate set of experiments, drug treatment was initiated after 2 weeks of PH induction (reversal protocol). Oral feeding of rats with bioencapsulated ACE2 or Ang-(1-7) prevented the development of monocrotaline-induced PH and improved associated cardiopulmonary pathophysiology. Furthermore, in the reversal protocol, oral ACE2 or Ang-(1-7) treatment significantly arrested disease progression, along with improvement in right heart function, and decrease in pulmonary vessel wall thickness. In addition, a combination therapy with ACE2 and Ang-(1-7) augmented the beneficial effects against monocrotaline-induced lung injury. Our study provides proof-of-concept for a novel low-cost oral ACE2 or Ang-(1-7) delivery system using transplastomic technology for pulmonary disease therapeutics

話し合いでの「不同意コミュニケーション」における「配慮」の様相 -接触場面での物事を決める話し合いの分析から-

departmental bulletin pape

待遇コミュニケーション学の位置づけ -語用論との関係-

departmental bulletin pape

話し合いにおける「不同意コミュニケーション」に関する考察 -日本語母語話者同士の談話資料を基にして-

departmental bulletin pape

Determination of Dopamine in the Presence of Ascorbic Acid using Poly (Acridine red) Modified Glassy Carbon Electrode

Poly (acridine red) modified glassy carbon electrode was used for the detection of dopamine in the presence of ascorbic acid in a pH 7.4 phosphate buffer solutions (PBS) by cyclic voltammetry and differential pulse voltammetry. The major difficulty of the overlapped oxidation potential of ascorbic acid could be overcome through the distinct attractive ability of poly (acridine red) film to cationic dopamine and anionic ascorbic acid. The results showed that the dopamine anodic peak current and the concentration of dopamine had a linear relationship in the range of 1.0×10-7 ~ 1.0×10-4 mol dm-3. The detection limit (S/N=3) obtained by differential pulse voltammetry was 1.0×10-9 mol dm-3. The relative standard deviation of 10 successive scans was 2.07 % for 1.0×10-6 mol dm-3 DA. Ascorbic acid had hardly interference with the determination of dopamine. The proposed method exhibits good recovery and reproducibility

Sensitive Detection of Haloperidol and Hydroxyzine at Multi-Walled Carbon Nanotubes-Modified Glassy Carbon Electrodes

Haloperidol (i.e. HPD) and hydroxyzine (i.e. HXY), two effective and important tranquilizers with low redox activity, were found to generate an irreversible anodic peak at about +0.86 V (vs. SCE) or two anodic peaks at about +0.83 and +0.91 V in 0.05 M NaH2PO4-Na2HPO4 (pH=7.0) buffer solution with a multi-walled carbon nanotubes-modified glassy carbon electrode (i.e. MWNTs/GC), respectively. Their sensitive and quantitative measurement based on the first two anodic peaks was established under the optimum conditions. The anodic peak current was linear to HPD and HXY concentration from 1×10-7 to 2.5 ×10-5 M and 5×10-8 to 2.5 ×10-5 M, the detection limits obtained were 8×10-9 and 5×10-9 M, separately. The modified electrode exhibited some excellent characteristics including easy regeneration, high stability, good reproducibility and selectivity. The method proposed was successfully applied to the detection of HPD and HXY in drug tablets and proved to be reliable compared with ultraviolet spectrophotometry. The modified electrode was characterized by electrochemical methods