41 research outputs found
Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I–II essential hypertension: a randomized, double-blind clinical study
Azilsartan is a novel angiotensin receptor blocker being developed for hypertension treatment. This 16-week, multicenter, randomized, double-blind study compared the efficacy and safety of azilsartan (20–40 mg once daily by forced titration) and its ability to provide 24-h blood pressure (BP) control, with that of candesartan cilexetil (candesartan; 8–12 mg once daily by forced titration) in 622 Japanese patients with grade I–II essential hypertension. Efficacy was evaluated by clinic-measured sitting BP, and by ambulatory BP monitoring (ABPM) at week 14. Participants (mean age: 57 years, 61% males) had a mean baseline sitting BP of 159.8/100.4 mm Hg. The mean change from baseline in sitting diastolic BP at week 16 (primary endpoint) was −12.4 mm Hg in the azilsartan group and −9.8 mm Hg in the candesartan group, demonstrating a statistically significant greater reduction with azilsartan vs. candesartan (difference: −2.6 mm Hg, 95% confidence interval (CI): −4.08 to −1.22 mm Hg, P=0.0003). The week 16 (secondary endpoint) mean change from baseline in sitting systolic BP was −21.8 mm Hg and −17.5 mm Hg, respectively, a significant decrease with azilsartan vs. candesartan (difference: −4.4 mm Hg, 95% CI: −6.53 to −2.20 mm Hg, P<0.0001). On ABPM, the week 14 mean changes from baseline in diastolic and systolic BP were also significantly greater with azilsartan over a 24-h period, and during the daytime, night-time and early morning. Safety and tolerability were similar among the two groups. These data demonstrate that once-daily azilsartan provides a more potent 24-h sustained antihypertensive effect than that of candesartan but with equivalent safety
Application of CR4-targeting antitumor immunoadjuvant for an advanced dendritic cell therapy
Highly Effective Non-Viral Antitumor Gene Therapy System Comprised of Biocompatible Small Plasmid Complex Particles Consisting of pDNA/Polyethylenimine "Max"/Anionic Polysaccharide Ternary Complexes
Long-Term Trypsin Treatment Promotes Stem Cell Potency of Canine Adipose-Derived Mesenchymal Stem Cells
Involvement of endogenous prostaglandin E2 in tubular epithelial regeneration through inhibition of apoptosis and epithelial-mesenchymal transition in cisplatin-induced rat renal lesions
In the kidney, prostaglandin (PG) E2 is the
main PG, playing important roles in maintaining
homeostasis or development of pathological settings.
Roles of PGE2 in renal lesions remain to be clarified.
The expression patterns of PGE2 synthesis enzymes such
as cyclooxygenase (COX)-1, COX-2 and microsomal
PGE synthase (mPGES)-1, and PGE2 receptors (EP2 and
EP4) were examined in cisplatin-induced rat renal
failure. The immunoexpressions for COX-1, mPGES-1
and EP4 receptor were increased exclusively in the
affected renal tubules, but those of COX-2 and EP2
receptor were not detected; increased expression of
COX-1 was confirmed at mRNA level. Using rat renal
epithelial cell line (NRK-52E), the effects of PGE2 on
cell proliferation were investigated. The addition of
PGE2 or 11-deoxy-PGE1 (EP4 receptor agonist) to
NRK-52E increased the cell number, indicating the
effects of PGE2 via EP4 receptor. Furthermore, 11-
deoxy-PGE1-treated NRK-52E cells underwent the
G0/G1 arrest and decreased apoptosis. NRK-52E treated
with transforming growth factor (TGF)-ß1, an inducer of
epithelial-mesenchymal transition (EMT), in the
presence of 11-deoxy-PGE1 decreased the mRNA
expression of α-smooth muscle actin (a marker of
myofibroblasts). Collectively, the present study shows
that COX-1 plays more important roles than dose COX-
2 in cisplatin-induced rat renal failure; the product,
PGE2, may regulate renal epithelial regeneration via EP4
receptor through inhibition of apoptosis and EMT
Three Cases of Idiopathic Sterile Pyogranulomatous Inflammation of Epidural Fat in Miniature Dachshunds
Highly Effective Non-Viral Antitumor Gene Therapy System Comprised of Biocompatible Small Plasmid Complex Particles Consisting of pDNA/Polyethylenimine "Max"/Anionic Polysaccharide Ternary Complexes
We have reported that ternary complexes of plasmid DNA with conventional linear polyethylenimine (l-PEI) and certain polyanions were very stably dispersed, and, with no cryoprotectant, they could be freeze-dried and re-hydrated without the loss of transfection ability. These properties enabled the preparation of a concentrated suspension of very small pDNA complex, by preparing the complexes at highly diluted conditions, followed by condensation via lyophilization-and-rehydration procedure. Recently, a high potency linear polyethylenimine having no residual protective groups, i.e., Polyethylenimine “Max” (PEI “Max”), is available, which has been reported to induce much higher gene expression than conventional l-PEI. We tried to prepare the small DNA/PEI “Max”/polyanion complexes by a similar freeze-drying method. Small complex particles could be obtained without apparent aggregation, but transfection activity of the rehydrated complexes was severely reduced. Complex-preparation conditions were investigated in details to achieve the freeze-dried DNA/PEI “Max”/polyanion small ternary complexes with high transfection efficiency. DNA/PEI “Max”/polyanion complexes containing cytokine-coding plasmids were then prepared, and their anti-tumor therapeutic efficacy was examined in tumor-bearing mice
Generation of Footprint-Free Canine Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells Using Sendai Virus Vector
Mouse Model for the Equilibration Interaction between the Host Immune System and Human T-Cell Leukemia Virus Type 1 Gene Expression
To study the involvement of immune responses against Tax of human T-cell leukemia virus type 1 (HTLV-1) in the growth of and gene suppression in Tax-expressing tumor cells in vivo, we established a model system involving C57BL/6J mice and a syngeneic lymphoma cell line, EL4. When mice were immunized by DNA-based immunization with Tax expression plasmids, solid tumor formation upon subcutaneous inoculation of EL4 cells expressing green fluorescent protein-fused Tax (Gax) under the control of the HTLV-1 enhancer was strongly inhibited, and in vitro analysis showed that DNA immunization elicited cytotoxic T-lymphocyte (CTL) responses but not production of antibodies to Tax protein. Since EL4/Gax cells inoculated into DNA-immunized mice were not completely eradicated but were maintained as small solid tumors for a long period, there appeared to be a certain equilibrium between CTL activity and the growth of Gax-expressing cells. With such a balance, expression of the Gax gene in EL4/Gax cells was strongly suppressed. These results suggested that gene expression under the control of the HTLV-1 long terminal repeat and Tax is silenced in vivo, resulting in an equilibrium between viral expression and the host immune system. Such a balance would represent a status of persistent infection by HTLV-1 in virus-infected individuals during the latency period