Yoko Sotoda

Heterotopic Pancreas of the Esophagus Associated With a Rare Type of Esophageal Atresia

An infant with a rare type of esophageal/tracheal anomaly associated with heterotopic pancreas of the esophagus is herein reported. The upper pouch containing heterotopic pancreas reached 1.5 cm below the tracheal carina, and the distal esophagus connected to the trachea 2 cm above the tracheal carina and thus formed a partial duplication of the esophagus. Heterotopic pancreas of the esophagus is extremely rare, with only 7 cases previously reported. Here we report the combination of heterotopic pancreas and esophageal atresia with tracheoesophageal fistula.

Association between cardiometabolic index and atherosclerotic progression in patients with peripheral arterial disease.

BACKGROUND Cardiometabolic index (CMI), calculated as a product of waist-to-height ratio and triglycerides-to-HDL cholesterol ratio, is a new index for discriminating diabetes mellitus. Patients with peripheral arterial disease (PAD) are prone to have other atherosclerotic diseases such as coronary artery disease and stroke. The purpose of this study was to clarify the relationships between CMI and indicators of atherosclerotic progression in patients with PAD. METHODS The subjects were 63 outpatients with PAD. Relationships of CMI with variables related to atherosclerotic progression were investigated using multivariate linear regression analysis and analysis of covariance with adjustment for age, sex and histories of smoking and alcohol drinking. RESULTS Log-transformed CMI was significantly correlated with mean intima-media thickness of the common carotid artery (IMT) (standardized regression coefficient: 0.350, p < 0.01) and % decrease in ankle-brachial systolic pressure index (ABI) after treadmill exercise (standardized regression coefficient: 0.365, p < 0.01). Mean IMT and % decrease in ABI by treadmill exercise were significantly higher (p < 0.01) in the group of the 3rd tertile for CMI than in the group of its 1st tertile (mean ± SE: mean IMT (mm), 0.94 ± 0.06 (1st tertile) vs. 0.94 ± 0.06 (2nd tertile) vs. 1.19 ± 0.06 (3rd tertile); % decrease in ABI, 14.1 ± 3.4 [1st tertile] vs. 26.0 ± 3.5 [2nd tertile] vs. 30.0 ± 3.5 [3rd tertile]). CONCLUSION CMI was shown to be associated with the degrees of atherosclerosis in the common carotid artery and ischemia in leg arteries and is therefore a useful discriminator of atherosclerotic progression in patients with PAD.

Intracellular alkalinization augments capacitative Ca2+ entry in vascular smooth muscle cells

Agonist-induced Ca2+ influx of vascular smooth muscle cells is thought to be triggered by depletion of intracellular Ca2+ stores. This study investigated the effects of intracellular alkalinization on capacitative Ca2+ entry in A7r5 rat aortic smooth muscle cells. Intracellular alkalinization was induced by NH4Cl. Transplasmalemmal Ca2+ influx due to Ca2+ store depletion induced by thapsigargin, which was abolished by pretreatment of the cells with SKF-96365 but not affected by that with verapamil, was significantly increased by pretreatment with NH4Cl. Neither 5-hydroxytryptamine-induced inositol monophosphate accumulation nor intracellular Ca2+ release from its stores was affected by NH4Cl. These results suggest that intracellular alkalinization acts on the process(es) after depletion of Ca2+ stores and facilitates capacitative Ca2+ entry in vascular smooth muscle cells.

Intramuscular hemangioma in the right ventricle.

Intramuscular cardiac hemangiomas are extremely rare. We describe a 74-year-old man with a tumor occupying the apex of the right ventricle that was incidentally diagnosed by echocardiography. Computed tomography and coronary angiography showed that the tumor arose from the ventricular septum and that the feeding artery was a branch of the right coronary artery. The tumor was completely excised, and the postoperative course was uneventful. Histological examination revealed that the tumor was a cardiac hemangioma (intramuscular type). To our knowledge, this is only the second case report of an intramuscular cardiac hemangioma in the world literature.

Diverse effects of monensin on capacitative Ca2+ entry and release of stored Ca2+ in vascular smooth muscle cells.

The effects of monensin, an activator of Na(+)/H(+) exchanger (NHE), on capacitative Ca(2+) entry (CCE) were investigated using A7r5 cells. Capacitative Ca(2+) entry was induced by elevation of extracellular Ca(2+) concentrations of A7r5 cells in which stored Ca(2+) had been depleted by previous administration of thapsigargin. Capacitative Ca(2+) entry was abolished by pretreatment of the cells with SKF-96365 (1-[beta-(3-[4-methoxyphenyl]propoxy)-4-methoxyphenethyl]-1H-imidazole hydrochloride) but was not affected by pretreatment with verapamil. Monensin significantly increased capacitative Ca(2+) entry. On the other hand, 5-hydroxytryptamine-induced inositol monophosphate accumulation and subsequent intracellular Ca(2+) release from its stores were significantly inhibited by monensin, while thapsigargin-induced Ca(2+) release was not affected by monensin. These results suggest that monensin has diverse actions on capacitative Ca(2+) entry and agonist-induced release of stored Ca(2+) in vascular smooth muscle cells.

Involvement of decreased myo-inositol transport in lipopolysaccharide-induced depression of phosphoinositide hydrolysis in vascular smooth muscle

The mechanism underlying lipopolysaccharide (LPS)‐induced depression of phosphoinositide (PI) hydrolysis was investigated using rat aortas. In LPS‐pretreated aortas, the 5‐hydroxytryptamine‐stimulated accumulation of inositol monophosphate and incorporation of exogenous myo‐inositol into PIs were significantly less than those in control aortas. Both sodium‐myo‐inositol cotransporter (SMIT) and phosphatidylinositol transfer protein (PITP) genes were constituently expressed in rat aortas. The mRNA level of SMIT was remarkably lower in LPS‐pretreated aortas, while that of PITP mRNA was not affected by LPS. These results suggest that LPS‐induced depression of SMIT expression is involved in inhibition of agonist‐stimulated PI hydrolysis by LPS.

Nitric oxide-dependent and -independent inhibition by lipopolysaccharide of phosphoinositide hydrolysis in vascular smooth muscle

The present study was designed in order to clarify the mechanisms of diminished phosphoinositide (PI) hydrolysis by lipopolysaccharide (LPS) in blood vessels. In vitro pretreatment of rat aortic strips with LPS (1 microg/ml) for 10 or 24 hrs inhibited 5-hydroxytryptamine (5-HT, 100 microM)-induced inositol monophosphate accumulation in a time-dependent manner. Coincubation of the aortas with N(G)-monomethyl-L-arginine (LNMMA, 1 mM) completely prevented the early diminution of 5-HT-stimulated PI hydrolysis after 10-hr exposure to LPS but did not affect the delayed diminution after 24-hr exposure. Coincubation with cycloheximide (1 microM) did not prevent the delayed LPS-induced diminution of phosphoinositide hydrolysis. Tetraethylammonium (10 mM) did not restore the diminished phosphoinositide hydrolysis after 24-hr exposure to LPS, suggesting that the diminution is not due to K+ channel activation. Sodium fluoride (10 mM)-induced inositol monophosphate accumulation was also decreased in the aortic strips after LPS incubation for 24 hrs, and this decrease was not prevented by coincubation with LNMMA. LPS incubation time-dependently increased nitric oxide (NO) production in the aortas, which was completely inhibited by LNMMA or cycloheximide. These results suggest that NO is mainly involved in the inhibitory action of LPS on stimulated-PI hydrolysis in the early stage, while in the later stage, a factor(s) besides NO causes attenuation of the stimulated-PI hydrolysis.

Association of Serum Uric Acid Levels with Leg Ischemia in Patients with Peripheral Arterial Disease after Treatment

Aim: We investigated the relationships of serum uric acid levels with the progression of atherosclerosis in patients with peripheral arterial disease (PAD) after treatment. Methods: Subjects were male patients diagnosed with PAD. Atherosclerosis at the common carotid artery was evaluated based on its intima-media thickness (IMT). Leg arterial flow was evaluated by measuring ankle-brachial index (ABI) and exercise-induced decrease in ABI. Results: Among various risk factors including age, blood pressure, adiposity, estimated glomerular filtration rate, and blood lipid, blood glucose, uric acid, fibrinogen and C-reactive protein levels, only uric acid levels showed significant correlations with ABI [Pearsons correlation coefficient, −0.292 (p < 0.01)] and leg exercise-induced decrease in ABI [Pearsons correlation coefficient, 0.236 (p < 0.05)]. However, there was no significant correlation between uric acid levels and maximum or mean IMT. Odds ratios of subjects with the 3rd tertile versus subjects with the 1st tertile for uric acid levels were significantly higher than the reference level of 1.00 for low ABI [4.44 (95% confidence interval, 1.45–13.65, p < 0.01)] and for high % decrease in ABI after exercise [4.31 (95% confidence interval, 1.34–13.82, p < 0.05)]. The associations of uric acid levels with the indicators of leg ischemia were also found after adjustment for age, history of revascularization therapy, diabetes, smoking, alcohol consumption, body mass index, triglyceride levels, and renal function. Conclusion: Uric acid levels are associated with the degree of leg ischemia in patients with PAD. Further interventional studies are needed to determine whether the correction of uric acid levels is effective in preventing the progression of PAD.

Recent Knowledge of Smoking and Peripheral Arterial Disease in Lower Extremities

Peripheral arterial disease (PAD) is an atherosclerotic obstructive disease of the arteries in lower extremities. Patients with PAD show high rates of mortality from coronary artery disease (CAD) and stroke. Smoking as well as diabetes is an important risk factor for PAD. A lesion of PAD in the lower extremities tends to be more proximal in smokers than in nonsmokers and to be more distal in patients with diabetes than in nondiabetics. By a systematic review, the odds ratio for PAD of smokers vs nonsmokers has been reported to be in the range of 1.7-7.4. Previous epidemiological studies suggest a stronger association of smoking with PAD than that with CAD. Nitric oxide (NO) is an important molecule suppressing the progression of atherosclerosis, but this function is compromised by smoking. Smoking decreases the bioactivity of NO and the expression level of NO synthase. In addition, smoking results in deteriorations of risk factors for atherosclerosis such as decreases in blood HDL (high-density lipoprotein) cholesterol and tissue plasminogen activator levels and increases in the levels of blood triglycerides, LDL (low-density lipoprotein) cholesterol, fibrinogen and the von Willebrand factor. Thus, smoking increases blood coagulability and deteriorates the blood lipid profile, resulting in thrombogenetic proneness and dyslipidemia. Smoking also increases the generation of atherogenic oxidized LDL in blood and decreases antiatherogenic prostacyclin production in the vascular endothelium. Smoking cessation is important for the prevention and therapy of PAD, and to this end, counseling by physicians and nicotine replacement therapy are useful and strongly recommended for patients with PAD.

Peripheral Arterial Disease

Peripheral arterial disease (PAD) is characterized by an impaired blood supply to the lower extremities, and the prevalence of PAD increases with age. Patients with PAD show intermittent claudication and ischemic ulcers, depending on the degree of ischemia in the lower extremities, and in addition, are often complicated with cardiovascular disease represented by coronary artery disease. Accordingly, the rate of mortality due to cardiovascular disease and the total mortality rate are known to be higher in patients with PAD compared with individuals without PAD.