Heme oxygenase-1 (HO-1) is induced by a variety of conditions associated with oxidative stress. We demonstrated that mildly oxidized LDL markedly induces HO-1 in human aortic endothelial and smooth muscle cell cocultures and that its induction results in the attenuation of monocyte chemotaxis resulting from treatment with mildly oxidized LDL in vitro. To elucidate the role of HO-1 in the development of atherosclerotic lesions in vivo, we modulated HO-1 expression in LDL-receptor knockout mice fed high-fat diets. During 6-week high-fat diet trials, intraperitoneal injections of hemin (H group) or hemin and desferrioxamine (HD group) to induce HO-1, Sn-protoporphyrin IX to inhibit HO-1 (Sn group), and saline as control (C group) were performed. Both the H and HD groups showed significantly less mean atherosclerotic lesions in the proximal aorta compared with the C group, whereas the Sn group showed larger lesion compared with the C group. Modulation of HO expression and HO activities were confirmed by Northern blot analysis and HO activity assay. Immunohistochemical studies revealed significant HO-1 expression in atherosclerotic lesions, where oxidized phospholipids also localized. Major cell types expressing HO-1 were macrophages and foam cells in the lesions. HO modulations affected plasma lipid hydroperoxide (LPO) levels and nitrite/nitrate levels. These results suggest that HO-1, induced under hyperlipidemia, functioned as an intrinsic protective factor against atherosclerotic lesion formation, possibly by inhibiting lipid peroxidation and influencing the nitric oxide pathway.

Background-Heme oxygenase-1 (HO-1) is proposed to have a variety of adaptive responses against oxidative stress. To examine the function of HO-1 against atherogenesis in vivo, we observed the effects of HO-1 inhibition on atherosclerotic lesion formation in Watanabe heritable hyperlipidemic rabbits (WHHL). Methods and Results-During 4 weeks of a 1% cholesterol diet, intravenous injections of Sn-protoporphyrin IX to inhibit HO-1 (S group, nϭ10) and saline as a control (C group, nϭ10) were given to 3-month-old WHHL rabbits. The percentages of en face atherosclerotic lesion areas in total descending aorta by Sudan IV staining (EFA) and the ratio of intima to media in microscopic atherosclerotic lesions in the ascending aortas (I/M) were calculated. Two different quantitative methods revealed significantly greater atherosclerotic lesions in the S group than the C group (EFA, PϽ0.001; I/M, PϽ0.005). HO-1 expression in atherosclerotic lesions was confirmed by Northern blot and immunohistochemical analyses. The dominant cell types expressing HO-1 were macrophages and foam cells, in which oxidized phospholipids were also accumulated. HO inhibition increased plasma and tissue lipid peroxide levels without affecting plasma lipid composition. Conclusions-These results suggest the possibilities that HO-1 has antiatherogenic properties in vivo and that the antiatherogenic properties of HO-1 are conducted through the prevention of lipid peroxidation.

The transradial approach for catheterization is becoming increasingly more popular. At present, the choice of the right or left radial artery depends on the operator's preference. We examined how the laterality influenced the effectiveness of the approach. Employing Judkins-type catheters, we performed coronary angiography in 232 patients with the left approach and in 205 patients with the right approach. Although access time did not differ between the two groups of patients, the duration of catheter manipulation was shorter in the left- than in the right-approach group (11.7 +/- 5.9 vs. 9.8 +/- 4.4 min; P < 0.001). Because of the shorter duration of catheter manipulation, the total procedural duration was shorter in the left-approach group (13.7 +/- 6.4 vs. 11.4 +/- 4.8 min; P < 0.001). The fluoroscopy time was shorter in the left- than in the right-approach group (3.7 +/- 2.5 vs. 5.0 +/- 3.3 min; P < 0.001). The amount of contrast material did not differ between the groups (79 +/- 27 vs. 83 +/- 25 ml). The rate of guidewire usage to engage the coronary ostium was higher in the right- than in the left-approach group because of the severe tortuosity of the right subclavian artery (20/205 vs. 0/232; P < 0.001). Thus, for operators with significant experience, the left radial approach may provide increased procedural efficacy for coronary angiography compared to the right radial approach.

Monocrotaline (MT), a pyrrolizidine alkaloid, causes pulmonary hypertension (PH) in rats and is widely utilized to analyze the pathophysiology of PH. However, a murine PH model with which transgenic animals may be used has not been established. To establish a murine MT-induced PH model, we administered different amounts of MT and determined the extent of right ventricular (RV) overload and PH. We also examined the expression of heme oxygenase-1 (HO-1), a potential antistress protein in MT-treated animals, and evaluated the functional role of HO-1 by administering an HO-1 inhibitor. Significant pulmonary inflammation and RV hypertrophy were observed when mice were given 600 mg/kg weight of MT weekly for 8 weeks. In addition, elevated RV pressure and induction of HO-1 in lung and RV were observed with this dose of MT. Interestingly, inhibition of HO activity promoted inflammatory changes in the lung and the resultant RV hypertrophy. HO-1 may play defensive roles against murine MT-induced pulmonary inflammation and the resultant RV overload.

Glycated albumin is a useful marker of glycemic control considering infant complications during pregnancy. This study also suggests that evaluating both glycated hemoglobin and glycated albumin levels can lead to better glycemic control in pregnant women.

Some neonatal hypoglycemias have genetic origins. For instance, mutation in forkhead box protein A2 (FOXA2), located on chromosome 20p11.21, has recently been reported to cause hyperinsulinemic hypoglycemia and hypopituitarism. Here, we report a case of hyperinsulinemic hypoglycemia and GH deficiency (GHD) with 20p11.23-p11.21 deletion, which included FOXA2. The boy was diagnosed with hyperinsulinemic hypoglycemia during the neonatal period and subsequently administered diazoxide for treatment. His blood glucose levels gradually stabilized, and the diazoxide dosage was slowly reduced and ultimately fully weaned. The patient was discharged at the age of 29 d. Unfortunately, the patient experienced recurrent hypoglycemia at 3 mo, and diazoxide administration was re-initiated. Further examination, including chromosomal microarray analysis, revealed a 2.48-Mb 20p11.23-p11.21 deletion that encompassed FOXA2. In addition, severe GHD was detected, and magnetic resonance imaging of the brain revealed pituitary stalk interruption. Accordingly, GH replacement therapy was started at 0.175 mg/kg/wk, and blood glucose levels were stabilized. Our report suggests that there are pathological conditions that can cause both hyperinsulinemic hypoglycemia and hypopituitarism and reaffirms the importance of evaluating not only insulin and congenital metabolic disorders but also pituitary function in patients with hypoglycemia.

GA is useful for predicting pregnancy outcomes in mothers with diabetes and must be maintained at low levels to prevent complications in infants.

SummaryThe ability of carbon dioxide microbubbles (MB-CO 2 ) to inactivate Lactobacillus fructivorans suspended in physiological saline and unpasteurised sake at ambient temperature and a pressure lower than 2.0 MPa was investigated. The number of L. fructivorans cells in physiological saline solution containing 15% ethanol showed a 6-log reduction following MB-CO 2 treatment at 40°C and 2.0 MPa for 50 min. The effectiveness of the treatment increased concomitantly with temperature, pressure and ethanol concentration of the sample solution but was unaffected by the glucose concentration in the sample solution. Furthermore, the number of L. fructivorans cells showed a 5-log reduction in sake after MB-CO 2 treatment at 40°C and 2.0 MPa for 60 min. Sensory evaluation revealed no significant difference between MB-CO 2 -treated sake and unpasteurised sake. These results indicated that MB-CO 2 treatment was highly effective for the inactivation of L. fructivorans and might become a practical method for pasteurising sake at ambient temperature.