In a previous study, we showed that a novel anticancer drug, 1-(3-C-ethynyl-
β
-D-
ribo
-pentofuranosyl)cytosine (TAS106, ECyd) increased the antitumour efficacy of X-irradiation. However, its ...effects on hypoxic cells in tumours remain unclarified. Here, we show that TAS106 enhances the induction of apoptosis in X-irradiated human gastric adenocarcinoma MKN45 and MKN28 cells under hypoxia
in vitro
. At the same time, the accumulation of HIF-1
α
observed under hypoxia was shown to be decreased to the level of normoxia in the presence of 0.1
μ
M
TAS106. To study the function of HIF-1
α
protein in apoptosis of hypoxic cells, we employed an HIF-1
α
reductive approach using its specific antisense oligodeoxynucleotide. The reduction of HIF-1
α
gene expression dramatically enhanced X-ray-induced apoptosis in hypoxic cells. In
in vivo
experiments in which MKN45 cells were transplanted into severe combined immunodeficient (SCID) mice, TAS106 (0.5 mg kg
−1
) suppressed HIF-1
α
expression and subsequently reduced the area of the hypoxic region in the tumour and enhanced the induction of apoptosis in the hypoxic region when combined with 2 Gy of X-irradiation. These results suggest the possibility that TAS106 acts as a potent radiosensitiser through the inhibition of HIF-1
α
expression and can be a useful agent against radiotherapy-resistant hypoxic cells in solid tumours.
Abstract
Background
Although hyperuricemia is known as a risk factor for hypertension, the optimal range of serum uric acid (SUA) for preventing hypertension has not been established, especially in a ...healthy population.
Methods
This is a 5-year cohort study to clarify the optimal SUA for hypertension. Subjects consisted of Japanese adults between 30 and 85 years of age were enrolled in the study at our Center for Preventive Medicine, and available at enrollment (2004) and at 5-year follow-up (2009). We excluded the study subjects who were hypertensive, diabetic, dyslipidemic, had a history of gout or hyperuricemia on medications, or if they had chronic kidney disease as estimated glomerular filtration rate <60 ml/min/1.73m2. Linear and logistic regression analyses were used to examine the relationship between each 1 mg/dL of serum uric acid range and development of hypertension with multiple adjustments for age, smoking, drinking habits, body mass index and baseline systolic blood pressure.
Results
Of 13,070 subjects enrolled at this step, we included 6,476 subjects (46.9±10.1 years old, 34.6% men) without comorbidities. The cumulative incidences of hypertension over 5 years were 5.9% in women and 12.1% in men. The lowest cumulative incidences of hypertension were 2.6% in 2.0–3.0 mg/dL of serum uric acid in women and 6.9% in 4.0–5.0 mg/dL in men. In contrast, the highest uric acid range showed highest cumulative incidence of hypertension both in women (28.6% in 8.0–9.0 mg/dL) and men (21.0% in ≥9.0 mg/dL). Hypouricemic (<2.0 mg/dL) subjects had higher cumulative incidences of hypertension than subjects with 2.0–3.0 mg/dL of serum uric acid levels, we excluded these subjects in multivariable logistic analysis. The odds ratio of 1 mg/dL increase of serum uric acid for developing hypertension was 1.395 (95% CI, 1.182–1.648) in women and 1.139 (95% CI, 1003–1.294) in men after multiple adjustments.
Conclusion
The optimal serum uric acid range for preventing hypertension was 2.0–3.0 mg/dL in women and 4.0–5.0 mg/dL in men. Higher uric acid levels increase cumulative incidence of hypertension.
Acknowledgement/Funding
None
Abstract
Background
Some recent studies showed that hyperfiltration is a risk for cardiovascular disease. However, the mechanism is still unknown. This longitudinal study tested the hypothesis that ...hyperfiltration could be a risk for hypertension.
Methods
This study retrospectively included Japanese healthy adults between 30 and 85 years of age who had medical check-up at our Center for Preventive Medicine, both at enrollment (2004) and at 5-year follow-up (2009). We excluded the subjects with hypertension, diabetes mellitus, dyslipidemia, hyperuricemia, or chronic kidney disease (estimated glomerular filtration <60 mL/min/1.73 m2) at the baseline. We divided this study subjects into three categories of eGFR (60–80 (reference), 80–100, and 100≤mL/min/1.73 m2), and defined hyperfiltration as more than 100 mL/min/1.73 m2 of eGFR. We used logistic regression analyses to examine risk factors for development of hypertension with multiple adjustments for age, sex, smoking, drinking habits, body mass index, and eGFR categories.
Results
In this study, 6045 subjects without comorbidities (mean age of 47±10 years, 1,842 men) were followed for 5 years. Of those, 450 subjects had developed hypertension. After multiple adjustments, hyperfiltration is a risk for development of hypertension (OR: 1.374; 95% confidence incidence (CI), 1.013–1.864), as well as aging (OR: 1.063; 95% CI, 1.052–1.073), higher BMI (OR: 1.244; 95% CI, 1.200–1.289), and drinking habits (OR: 1.387, 95% CI, 1.117–1.721).
Conclusion
Hyperfiltration carries a significant risk for developing hypertension in Japanese individual without comorbidities. We should take account for hyperfiltration as a risk for hypertension, as well as chronic kidney diseases.
In this work, a simple, reproducible, and inexpensive fabrication route for moldless micropatterning of a colloidal assembly on a conducting substrate surface is actualized by means of ...electrophoretic deposition (EPD) technique. A synergetic combination of photolithography and EPD is employed for fabricating micropatterns of barium titanate (BaTiO
3
) nanoparticles on an indium-tin-oxide (ITO) coated glass slide or a Pt/ITO substrate. At first, high quality resist molds with various micropatterns are fabricated on ITO glass slide by photolithography technique, which is used for providing a controlled local electric field during the EPD process. Then, BaTiO
3
nanoparticles suspension is prepared in KCl aqueous solution and is demonstrated the BaTiO
3
nanoparticles are negative charged in the suspension. At last, EPD of various BaTiO
3
micropatterns is accomplished successfully on the anodic ITO glass slide or Pt/ITO substrate using the micropatterned ITO glass slide as the cathode, indicating that it is a simple and potential route for micropatterning of colloidal assembly on a non-modified conducting substrate by virtue of EPD process.
Abstract
Background
To improve the prognosis of patients with out-of-hospital cardiac arrest (OHCA), the rate of high-quality cardiopulmonary resuscitation (CPR) and immediate use of automated ...external defibrillators (AEDs) by citizens must be further increased. Japanese government launched certified CPR courses for citizens throughout Japan in 1994 and the number of citizens certified on the course is increasing. However, the impact of the number of citizens officially certified for the courses on the rate of CPR implementation by citizens and the outcomes in patients with OHCA is unclear.
Methods
From a prospective, nationwide, population-based registry of patients with OHCA in Japan, we identified 350,444 patients from 2005 through 2020 with bystander-witnessed OHCA with 72,069 ventricular-fibrillation (VF) and the other non-VF cardiac arrests. The association between the number of citizens certified for the CPR courses and the rate of CPR implementation by citizens throughout Japan was analyzed by Poisson distribution and Cochran–Armitage test for trend. The primary outcome was survival at 1 month. The secondary outcomes were favorable neurologic outcome at 1 month. The associations between the CPR attempted by citizens categorized into three (chest-compression-only CPR, chest compression with rescue breathing, and use of AEDs with chest compression and rescue breathing) and outcomes were determined by multivariable mixed logistic regression analyses.
Results
Cumulative number of citizens certified for the CPR courses increased from 717,808 in 2005 to 34,938,322 in 2020, which reached to 27.8% of total Japanese population. Annual course receivers were also linearly increased during the period (Incidence Rate Ratios 1.03, p<0.001). Similarly, the rate of patients receiving CPR by citizens increased linearly from 40.6% in 2005 to 56.8% in 2020 (P for trend<0.001). In the multivariable mixed logistic regression analyses, higher CPR activity by citizens were significantly associated with better 1-year survival in both VF and non-VF patients even after adjusted for covariates VF = chest compression: odds ratio (OR) 1.17; 95% confidence interval (CI) 0.98–1.39; P =0.078; chest compression with rescue breathing: OR 1.22; 95% CI 1.02–1.49; P =0.030; use of AEDs with chest compression and rescue breathing: OR 1.54; 95% CI 1.54–1.92; P <0.001 vs no CPR, non-VF= chest compression: OR 1.19; 95% CI 0.76–1.87; P =0.45; chest compression with rescue breathing: OR 2.26; 95% CI 1.34–3.82; P =0.020 vs non-CPR. Similar results were also found in neurological outcomes in 1 month.
Conclusions
The rate of CPR implementation by citizens throughout Japan has continuously and linearly increased in these 15 years in proportion to the increase in the number of citizens certified for the government-organized CPR courses. Higher CPR activity by citizens were significantly associated with better 1-year survival and favorable functional status in both VF and non-VF patients.
Epidemiologic and clinical studies have suggested that urate-lowering therapy may slow the progression of chronic kidney disease (CKD). However, definitive evidence is lacking.
Randomized, ...double-blind, placebo-controlled trial.
467 patients with stage 3 CKD and asymptomatic hyperuricemia at 55 medical institutions in Japan.
Participants were randomly assigned in a 1:1 ratio to receive febuxostat or placebo for 108 weeks.
The primary end point was the slope (in mL/min/1.73m2 per year) of estimated glomerular filtration rate (eGFR). Secondary end points included changes in eGFRs and serum uric acid levels at 24, 48, 72, and 108 weeks of follow-up and the event of doubling of serum creatinine level or initiation of dialysis therapy.
Of 443 patients who were randomly assigned, 219 and 222 assigned to febuxostat and placebo, respectively, were included in the analysis. There was no significant difference in mean eGFR slope between the febuxostat (0.23±5.26mL/min/1.73m2 per year) and placebo (−0.47±4.48mL/min/1.73m2 per year) groups (difference, 0.70; 95% CI, −0.21 to 1.62; P=0.1). Subgroup analysis demonstrated a significant benefit from febuxostat in patients without proteinuria (P=0.005) and for whom serum creatinine concentration was lower than the median (P=0.009). The incidence of gouty arthritis was significantly lower (P=0.007) in the febuxostat group (0.91%) than in the placebo group (5.86%). Adverse events specific to febuxostat were not observed.
GFR was estimated rather than measured, and patients with stages 4 and 5 CKD were excluded.
Compared to placebo, febuxostat did not mitigate the decline in kidney function among patients with stage 3 CKD and asymptomatic hyperuricemia.
Funded by Teijin Pharma Limited.
Registered at the UMIN (University Hospital Medical Information Network) Clinical Trials Registry with study number UMIN000008343.
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