The Impact of Tofogliflozin on Physiological and Hormonal Function, Serum Electrolytes, and Cardiac Diastolic Function in Elderly Japanese Patients with Type 2 Diabetes Mellitus

The sodium glucose transporter 2 (SGLT2) inhibitor tofogliflozin is a glucose-lowering drug that causes the excretion of surplus glucose by inhibiting SGLT2. Because of tofogliflozin’s osmotic diuresis mechanism, patients’ serum electrolytes, body fluid levels, and cardiac function must be monitored. We retrospectively analyzed the cases of 64 elderly Japanese patients with type 2 diabetes mellitus (T2DM) who received tofogliflozin for 3 months. Their HbA1c, serum electrolytes (sodium, potassium, chloride), hematocrit, brain natriuretic peptide (cardiac volume load marker) and renin and aldosterone (RAA; an index of regulatory hormones involved in body fluid retention) were continuously monitored during the investigation period. Renal function and cardiac function (by echocardiography) were assessed throughout the period. HbA1c significantly decreased (β1=−0.341, p<0.0001, linear regression analysis [LRA]). Most of the hormonal, electrolyte, and physiological parameters were maintained throughout the study period. In these circumstances, E/e’ tended to decrease (β1=−0.382, p=0.13, LRA). Compared to the baseline, E/e’ was significantly decreased at 1 and 3 months (p<0.01, p<0.05). In the higher E/e’ group (E/e’≥10, n=34), E/e’ decreased significantly (β1=−0.63, p<0.05, LRA). ΔE/e’ was correlated with body-weight change during treatment (r=0.64, p<0.01). The 3-month tofogliflozin treatment improved glycemic control and diastolic function represented by E/e’ in T2DM patients, without affecting serum electrolytes, renal function, or RAA. No negative impacts on the patients were observed. Three-month tofogliflozin treatment lowered glucose and improved cardiac diastolic function

Cigarette smoking, genetic polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study

Background: It is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism. Methods: We used data from the Fukuoka Colorectal Cancer Study, a population-based case-control study, including 685 cases and 778 controls who gave informed consent to genetic analysis. Interview was conducted to assess lifestyle factors, and DNA was extracted from buffy coat. Results: In comparison with lifelong nonsmokers, the odds ratios (OR) of colorectal cancer for &lt;400, 400-799 and ≥800 cigarette-years were 0.65 (95 % confidence interval [CI], 0.45-0.89), 1.16 (0.83-1.62) and 1.14 (0.73-1.77), respectively. A decreased risk associated with light smoking was observed only for colon cancer, and rectal cancer showed an increased risk among those with ≥400 cigarette-years (OR 1.60, 95 % CI 1.04-2.45). None of the polymorphisms under study was singly associated with colorectal cancer risk. Of the gene-gene interactions studied, the composite genotype of CYP1A1*2A or CYP1A1*2C and GSTT1 polymorphisms was associated with a decreased risk of colorecta

Polyphosphoric acid treatment promotes bone regeneration around titanium implants

This study was conducted to evaluate the effect of polyphosphoric acid (PPA) treatment on bone regeneration around titanium (Ti) implants in vivo. Adsorption of PPA by Ti was achieved by immersing Ti implants (2 mm in diameter, 4 mm in length) in different concentrations of PPA solution (0, 1 and 10 wt%) for 24 h at 37 degrees C after proper Ti surface cleaning. The treated Ti implants were implanted on 8-week-old-male rat (n = 30) tibiae. Two or four weeks after implantation, all animals were deeply anaesthetized and underwent perfusion fixation. Ten specimens in each condition were further immersed in the same fixative for 1 week and eventually embedded in polyester resin. Afterwards, undecalcified sections were ground to a thickness of approximately 70 microm parallel to the long axis of the implant. The sections were stained with basic fuchsine and methylene blue and then examined by light microscopy. For quantitative evaluation of bone regeneration around the implants, the bone-implant contact ratio (BICR) was determined. Polyphosphoric acid treatment of the Ti implant surface significantly enhanced direct bone contact to the Ti surface. Especially, the BICRs of the 1 wt% PPA-treated Ti implants were significantly higher than those of the control untreated Ti implants, both 2 and 4 weeks after implantation. At 4 weeks, 10 wt% PPA-treated implants also significantly increased the BICR as compared to that of the untreated Ti implants. These results suggest that PPA treatment promotes osteoconductivity of Ti in vivo.status: publishe

DUSP-1 Induced by PGE2 and PGE1 Attenuates IL-1&beta;-Activated MAPK Signaling, Leading to Suppression of NGF Expression in Human Intervertebral Disc Cells

The molecular mechanism of discogenic low back pain (LBP) involves nonphysiological nerve invasion into a degenerated intervertebral disc (IVD), induced by nerve growth factor (NGF). Selective cyclooxygenase (COX)-2 inhibitors are mainly used in the treatment of LBP, and act by suppressing the inflammatory mediator prostaglandin E2 (PGE2), which is induced by inflammatory stimuli, such as interleukin-1&beta; (IL-1&beta;). However, in our previous in vitro study using cultured human IVD cells, we demonstrated that the induction of NGF by IL-1&beta; is augmented by a selective COX-2 inhibitor, and that PGE2 and PGE1 suppress NGF expression. Therefore, in this study, to elucidate the mechanism of NGF suppression by PGE2 and PGE1, we focused on mitogen-activated protein kinases (MAPKs) and its phosphatase, dual-specificity phosphatase (DUSP)-1. IL-1&beta;-induced NGF expression was altered in human IVD cells by MAPK pathway inhibitors. PGE2 and PGE1 enhanced IL-1&beta;-induced DUSP-1 expression, and suppressed the phosphorylation of MAPKs in human IVD cells. In DUSP-1 knockdown cells established using small interfering RNA, IL-1&beta;-induced phosphorylation of MAPKs was enhanced and prolonged, and NGF expression was significantly enhanced. These results suggest that PGE2 and PGE1 suppress IL-1&beta;-induced NGF expression by suppression of the MAPK signaling pathway, accompanied by increased DUSP-1 expression

Characteristics of Patients with and without Postoperative Cognitive Dysfunction.

<p>Continuous variables are presented as mean ± SD and categorical variables are presented as frequency (percentage). CABG  =  coronary artery grafting; CPB  =  cardiopulmonary bypass.</p

Prevalence of Gray Matter Loss in the Medial Temporal Lobe, Intracranial and Carotid Artery Stenosis, and Atherosclerosis of the Ascending Aorta.

<p>MTL  =  medial temporal lobe; MRI  =  magnetic resonance imaging; MRA  =  magnetic resonance angiography.</p

Voxel-based based specific regional analysis for Alzheimer's disease (VSRAD) analysis in a 78-year-old woman before aortic valve replacement (A) and a 68-year-old man before mitral valve repair (B).

<p>VSRAD provides a color-scaled Z score map ranging from 2.0 to 6.0 with overlaid orthogonal sections of an anatomically standardized brain template. (A) Axial VSRAD and its enlarged image at 20 mm. Gray matter was lost in the medial temporal lobe. The Z score was 3.1. (B) In contrast, there was no gray matter change in the medial temporal lobe preoperatively. Z score was 0.3.</p