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Biomedical subjects

J Hoshino

Publications and source records attributed to J Hoshino.

At least 19 recordsLinked to original sources
PubMed2001

Lecithinized Cu, Zn-superoxide dismutase limits the infarct size following ischemia-reperfusion injury in rat hearts in vivo.

Covalent binding of 4 molecules of phosphatidylcholine palmitoyl to human recombinant superoxide dismutase (SOD) results in a compound (lecithinized SOD) that has a longer half-life and greater affinity to the cell membrane than unmodified SOD. We investigated whether lecithinized SOD played a protective role against myocardial ischemia-reperfusion injuries in rats. Rats underwent 45 min of myocardial ischemia by occluding the left coronary artery followed by 120 min of reperfusion. They were randomly assigned to receive either lecithinized SOD, polyethylene glycol conjugated SOD (PEG-SOD), unmodified SOD, free lecithin derivative, or PBS intravenously at 5 min prior to reperfusion. Myocardial infarct area assessed by TTC staining was smaller in lecithinized SOD group than PEG-SOD, unmodified SOD, free lecithin derivative or control group. Blood pressure and heart rate was similar in each group. ELISA demonstrated SOD level in the heart was significantly high in lecithinized SOD group, especially in the heart of ischemia at risk. Although serum SOD level of PEG-SOD was as high as lecithinized SOD, SOD level of the heart was low. These data suggested lecithinized SOD had a protective effect in myocardial ischemia-reperfusion injuries through its increased bioavailability.

Animals↗
PubMed2001

Left ventricle restoration in patients with non-ischemic dilated cardiomyopathy: risk factors and predictors of outcome and change of mid-term ventricular function.

OBJECTIVE: The partial left ventriculectomy (PLV) for end-stage dilated cardiomyopathy (DCM) which worked in some patients has been reported, although the hospital mortality is high. To reduce hospital mortality, we selected operative procedures of left ventricular (LV) restoration to improve the operative results. We analyzed the risk factors and predictors of outcome, and the mid-term changes of the LV function were determined. PATIENTS AND METHODS: Between December 1996 and September 2000, 74 patients with non-ischemic DCM received LV restoration. The age ranged from 14 to 76 years (mean, 49.0+/-14.0 years), and there were 63 men and 11 women. The etiology of the DCM was idiopathic DCM in 49 patients, and dilated hypertrophic cardiomyopathy in seven patients and others in 18. The preoperative New York Heart Association (NYHA) functional class was 29 in class III and 45 in class IV, in which 32 patients depended on inotropic support. PLV or septal anterior ventricular exclusion (SAVE) was selected depending on the akinetic lesion of the LV based on the intraoperative echo-test. Fifty-six patients received elective operations, and emergency operations were performed in 18 patients. The risk factors and predictors of outcome were analyzed in 74 patients, and in 35 patients who survived more than 1 year after receiving LV restoration, the mid-term cardiac function was examined by cardiac echogram and catheterization. RESULTS: PLV was performed in 62 patients and SAVE in 12 patients. Concomitant mitral surgery was performed in 66 patients (89%) and tricuspid annuloplasty in 42 patients (57%). There were 15 hospital deaths and 13 patients died after discharge from the hospital (cardiac deaths in nine and non-cardiac deaths in four). In the 46 late survivors, the NYHA class was I or II in 42 patients and III in four patients. Selection of the procedure of LV restoration (P<0.01), elective operation (P<0.05), and the preoperative volume of LV (endodiastolic volume index of <180 ml/m(2); P<0.05) were risk factors and predictors influencing hospital and late death. After the operation, the LV function improved significantly and the improvement was maintained at the mid-term period; the LV ejection fraction was 31.8+/-7.9% (P<0.01) at 1 year from 23.0+/-7.3% preoperatively, left ventricular diastolic diameter was 62.8+/-10.9 (P<0.01) from 81.7+/-8.2 mm and the LV endosystolic volume index was 88.5+/-45.8 (P<0.05) from 162.6+/-41.6 ml/m(2). CONCLUSIONS: The operative results improved with the selection of the procedures, with elective operation, and mitral plasty for less cardiac dilatation. The mid-term results of clinical status and LV function showed the effectiveness of the operation.

Adolescent↗
PubMed2001

Effects of chondroitin sulfate on colitis induced by dextran sulfate sodium in rats.

Chondroitin sulfate (CS) is currently marketed as a therapeutic drug for neurodynia, lumbago and arthrodynia. Recently, many clinical studies have demonstrated the therapeutic effects of orally administered CS against diseases with inflammation. Furthermore, these reports suggest CS plays an important role in the protection of the base of ulcers and has anti-inflammatory activity. We investigated the effects of CS against dextran sulfate sodium (DSS)-induced rat colitis. Rats were given 3% DSS solution for 10 days ad libitum. CS and 5-aminosalicylic acid (5-ASA) were orally administered daily. The doses of the CS groups were 20 or 100 mg/kg and that for the 5-ASA group was 100 mg/kg. Evaluations were made of bloody stools, areas of erosion and hematological data. CS improved the symptoms of bloody stools, erosion and increase of white blood cells. Especially, CS (100 mg/kg) group showed markedly more improvement than the 5-ASA group. We think that the major mechanism of the therapeutic effects of CS are the prevention of tissue damage by the protection of digestive mucosa and anti-inflammatory effects. Therefore, CS may have therapeutic value for alimentary tract diseases such as inflammatory bowel disease or ulcer.

Animals↗
PubMed2001

[Left ventriculoplasty for non-ischemic cardiomyopathy with severe heart failure in 70 patients].

OBJECTIVES: Treatment of cardiac failure due to non-ischemic cardiomyopathy by left ventriculoplasty using partial left ventriculectomy (Batista operation) or septal anterior ventricular exclusion was evaluated. METHODS: Left ventriculoplasty was performed in 70 patients (59 men and 11 women with a mean age of 51 years) from December 1996 to June 2000. Preoperative New York Heart Association (NYHA) functional class was IV in 43 patients including 29 receiving inotropic support, and class III in 27 patients. Nineteen patients required emergency surgery because of on-going shock and 51 patients were operated electively. Combined cardiac procedures were mitral valve reconstruction in 62 patients (45 replacements, 17 repairs), tricuspid annuloplasty in 37, and aortic valve replacement in 4. The initial 24 patients underwent typical Batista operation regardless of myocardial viability. The other 46 patients underwent selective ventriculoplasty to excise or exclude the weakest part according to the findings of the intraoperative echo-guided volume reduction test. RESULTS: The intraaortic balloon pump was used in 12 patients and the left ventricular assist device in 2 patients. Three (5.9%) of the 51 patients who underwent elective operation and 12 (63.2%) of the 19 patients with emergency operation died in the hospital, giving an overall hospital mortality of 21.4% (15/70). Hospital mortality was reduced from 33.3% (8/24) in the initial 24 patients to 15.2% (7/46) in the recent 46 patients with the volume reduction test. Mean ejection fraction increased from 22.2 +/- 6.7% to 29.6 +/- 6.0%. Diastolic dimension decreased from 81.1 +/- 9.5 to 69.8 +/- 19.2 mm. End-diastolic and systolic volume indices decreased from 199.0 +/- 47.9 to 124.1 +/- 34.9 ml/m2 and from 154.0 +/- 41.2 to 89.3 +/- 31.7 ml/m2, respectively, at one postoperative month in the 55 hospital survivors. The mean pulmonary capillary wedge pressure decreased from 25.6 +/- 7.8 to 13.6 +/- 4.5 mmHg. Serum brain natriuretic peptide decreased from 999 +/- 647 preoperatively to 547 +/- 362 pg/ml one month after the operation. Thirteen patients (18.6%) died in the late period mainly due to heart failure. Among the 42 survivors, 37 patients returned to NYHA functional class I-II, and cardiac events were rare after one postoperative year. Actuarial survivals at 3 years in elective and emergency operations were 71.9% and 33.3%, respectively. CONCLUSIONS: Left ventriculoplasty is acceptably safe for elective operation and clinical improvement can be obtained by proper surgical procedures and careful postoperative medical treatment.

Adolescent↗
PubMed2000

Renal artery stenosis associated with epidermal nevus syndrome.

Epidermal nevus syndrome is an unusual neurocutaneous disorder in which epidermal nevi are associated with abnormalities of the skeleton and central nervous system, including the eyes and somtimes the cardiovascular system. We treated a patient in whom the latter included renal artery stenosis. An 18-year-old man with epidermal nevi was diagnosed as having the syndrome based on the additional presence of scoliosis, an arachnoid cyst in the middle cranial fossa, and microphthalmos. Hypertension was diagnosed when the patient was 15 years old. The plasma renin activity (9.7 ng/ml/h) was elevated. Right renal artery stenosis was demonstrated by angiography, and the abdominal aorta was narrowed distal to the ostium of the superior mesenteric artery. The plasma renin activity in the right renal vein (16 ng/ml/h) was higher than contralaterally (10 ng/ml/h). Several cardiovascular manifestations have been reported as a complication of epidermal nevus syndrome. Hypertension in an individual with epidermal nevi and congenital anomalies should prompt a search for a vascular anomaly.

Adolescent↗
PubMed2000

Effect of enalapril on exhaled nitric oxide in normotensive and hypertensive subjects.

We investigated whether an angiotensin-converting enzyme (ACE) inhibitor increases the production of nitric oxide (NO) in exhaled air in normotensive and hypertensive subjects. In study 1, 8 normotensive male subjects received a single oral dose of enalapril (5 mg) or nitrendipine (10 mg) in a crossover manner. Exhaled air was collected at baseline, and at 2, 4, and 8 hours after administration of the drug. In study 2, 10 normotensive subjects (6 men and 4 women) and 10 hypertensive subjects (6 men and 4 women) received a single oral dose of enalapril (5 mg). Exhaled air was collected at baseline and at 2 and 4 hours after administration of the drug. In study 1, enalapril significantly increased the NO release rate from the lung in normotensive subjects (36.9+/-5.1 pmol/s at baseline versus 58.3+/-7.3 pmol/s at 4 hours, P<0.01). Nitrendipine did not change the NO release rate. In study 2, enalapril significantly increased the release of NO from the lung in normotensive subjects (40.4+/-6.0 pmol/s at baseline versus 70. 3+/-11.4 pmol/s at 4 hours, P<0.01) but not in hypertensive subjects. ACE inhibition increased NO production from the lung in normotensive subjects but not in hypertensive patients. The reduction of angiotensin II production and/or the accumulation of bradykinin in the pulmonary tissue may be responsible for increased NO production in components of the lung, such as the pulmonary vascular endothelium, bronchial epithelial cells, macrophages, nasopharyngeal cells, and neurons. However, the effects of ACE inhibition on NO production from the lung differ between hypertensive subjects and normotensive subjects.

Adult↗
PubMed2000

Renovascular hypertension observed in a patient with antiphospholipid-antibody syndrome.

The antiphospholipid-antibody syndrome is associated with an increased incidence of arterial and venous thrombosis. Although renal infarction has been observed in these patients, stenotic lesions of the renal artery associated with the antiphospholipid-antibody syndrome have not been reported. A 47-year-old male with a history of hypertension for 7 years developed blurred vision secondary to thrombotic occlusion of the central retinal artery. Laboratory and radiologic examinations revealed renal dysfunction, a positive anticardiolipin antibody, and narrowing of the right renal artery. Successful percutaneous transluminal renal artery angioplasty resulted in normalization of the blood pressure and recovery of renal function.

Angioplasty, Balloon, Coronary↗
PubMed2000

Effects of antihypertensive therapy on blood pressure and left ventricular hypertrophy in patients with severe hypertension.

The mechanisms responsible for regression of left ventricular (LV) mass with antihypertensive therapy in patients with severe hypertension remain unclear. This study was designed to examine whether systolic and diastolic blood pressures are associated with changes in LV mass. Eighteen patients with essential hypertension whose average seated diastolic blood pressure was >or = 110 mm Hg were enrolled in the study. All patients were administered antihypertensive therapy and underwent M-mode echocardiography before and after 6 months of treatment. In all patients, antihypertensive treatment significantly reduced systolic blood pressure from 175 +/- 21 mm Hg at baseline to 143 +/- 22 mm Hg at 6 months (p < 0.001), and diastolic blood pressure from 116 +/- 7 mm Hg at baseline to 92 +/- 20 mm Hg at 6 months (p < 0.001). LV mass index at 6 months was significantly reduced compared to its baseline value (p < 0.05). Change (value at 6 months-value at baseline) in systolic and diastolic blood pressures correlated positively with the change in LV mass index (r = 0.61, p < 0.01 and r = 0.71, p < 0.001, respectively). The patients were divided into responders. whose LV mass regressed by > or = 10% (n = 9), and nonresponders, whose LV mass regressed by < 10% (n = 9). Systolic (p < 0.001) and diastolic (p < 0.001) blood pressures. interventricular septal thickness (p< 0.05), posterior wall thickness (p < 0.001), and LV mass index (p < 0.001) were significantly decreased in the responders, but not in the nonresponders, at 6 months compared with those at baseline. Systolic (p < 0.05) and diastolic (p < 0.05) blood pressures in nonresponders were significantly higher than those in the responders at 6 months. The changes in systolic and diastolic blood pressures did not correlate with the change in LV mass index in the responders or the nonresponders. The regression of LV mass is strongly affected by reducing blood pressure. This is the first study using antihypertensive therapy to demonstrate that a change in blood pressure correlates positively with changes in LV mass index in severely hypertensive patients.

Adult↗
PubMed1999

Lecithinized superoxide dismutase induces vasodilation; evidence of direct contribution of superoxide anions to modulating vascular tone.

The purpose of this study was to examine the role of superoxide anions in modulating the vascular tone. The effects of unmodified and lecithinized superoxide dismutase (SOD) on vascular tone were determined in aortic ring preparations of mice. In lecithinized SOD, 4 molecules of a phosphatidylcholine derivative were covalently bound to each dimer of recombinant human copper-zinc SOD to facilitate tissue accumulation. Unmodified SOD did not change vascular tone. However, lecithinized SOD induced dose-dependent vasodilation of aortic ring preparations. The pretreatment with NG-nitro-L-arginine methylester (L-NAME) 10(-4) mol/L abolished the vasodilation induced by lecithinized SOD. The results of this study indicate that superoxide anions play a prominent role in modulating the vascular tone by enhancing the breakdown of nitric oxide.

Acetylcholine↗
PubMed1998

Antihypertensive agents prevent nephrosclerosis and left ventricular hypertrophy induced in rats by prolonged inhibition of nitric oxide synthesis.

We investigated the ability of the angiotensin converting enzyme (ACE) inhibitor imidapril hydrochloride, and of the calcium channel blocker amlodipine besilate, to prevent nephrosclerosis and left ventricular hypertrophy (LVH) in rats with hypertension induced by chronic inhibition of nitric oxide (NO). Male Wistar rats were given distilled water (control), NG-nitro-L-arginine methyl ester (L-NAME) 500 mg/L, L-NAME plus imidapril 10 mg/L or 100 mg/L, or L-NAME plus amlodipine 50 mg/L or 100 mg/L in the drinking water (n = 10-12). We then collected 24-h urine samples at 2, 4, and 6 weeks, obtained blood samples at 6 weeks, and histologically examined the kidney and heart. L-NAME markedly reduced the levels of NO metabolites in serum and urine while increasing the tail-cuff blood pressure, the urinary albumin level (1.90 +/- 0.65 v 0.05 +/- 0.02 mg/day/100 g in control), and the area of the left ventricular wall (83.3 +/- 3.0 v 69.8 +/- 1.8 mm2 in control). Nephrosclerosis and myocardial interstitial fibrosis were documented histologically. The plasma renin activity was significantly higher in rats treated with L-NAME than in the control rats. The concomitant administration of imidapril (10 mg/L) with L-NAME completely normalized the tail-cuff pressure, the LVH (70.8 +/- 1.8 mm2), the albuminuria (0.05 +/- 0.01 mg/day/100 g), and the histologic changes. Amlodipine (50 mg/L) also ameliorated the L-NAME-induced effects, but to a lesser extent. Thus, the chronic inhibition of NO synthesis in rats produced nephrosclerosis and LVH that were effectively prevented by giving imidapril at a dose lower than that of amlodipine. We conclude that ACE inhibitors can prevent nephrosclerosis and LVH even in the presence of a reduction in NO production, implying that in rats the inhibition of the renin-angiotensin system is more effective than the blockade of calcium channels in preventing hypertensive tissue injury.

Amlodipine↗
PubMed1998

Antagonism of ANG II type 1 receptors protects the endothelium during the early stages of renal hypertension in rats.

The degree of involvement of the renin-angiotensin system in endothelial dysfunction was investigated by using a one-kidney, one-clip (1K,1C) model of renal hypertension. Male Wistar rats received 0.02% enalapril, 0.02% losartan, or tap water for 1 day before and for 48 h after the induction of renal artery stenosis or sham operation. The aorta of 1K,1C rats showed increased contraction and decreased relaxation responses produced by norepinephrine and acetylcholine, respectively, vs. control responses. Exposure to 10(-5) mol/l NG-monomethyl-L-arginine acetate augmented the contractile responses to norepinephrine to a greater extent in control rats than in the 1K,1C rats. The increased contraction and decreased relaxation responses to these agonists in the 1K,1C rats were normalized by enalapril or losartan. The addition of HOE-140 to the bath did not alter these normalized responses. Results suggest that angiotensin II causes endothelial dysfunction and reduces nitric oxide levels in 1K,1C rats. Such endothelial dysfunction enhanced the norepinephrine-induced contraction during the early-stage hypertension in 1K,1C rats.

Acetylcholine↗
PubMed1998

Production of superoxide and nitric oxide by alveolar macrophages in the bleomycin-induced interstitial pneumonia mice model.

To elucidate the potential role of superoxide (O2-) and nitric oxide (NO) in the pathogenesis of interstitial pneumonia, the quantity of O2- and NO produced by the alveolar macrophages (AM) were determined in the bleomycin (BLM)-induced interstitial pneumonia mouse model. The production of O2- and NO increased on days 7, 14 and 21 after BLM injection. Strong expression of peroxynitrite (ONOO-) was seen in AM by using immunostaining for nitrotyrosine. The hydroxyproline contents increased on day 21 after BLM injection. O2- and NO are thought to play an important role in the pathology of fibrosis.

Animals↗
PubMed1997

Flow-mediated vasodilation of a conduit artery in relation to downstream peripheral tissue blood flow during reactive hyperemia in humans.

Arterial conduit vessels dilate in response to increased blood flow stimuli. Our objective was to determine precisely how a change in large arterial diameter results in a change in peripheral tissue blood flow. Using high-resolution ultrasound Doppler echography, we measured the diameter of the right femoral artery at rest, during reactive hyperemia, and after administration of 2.5 mg of sublingual isosorbide dinitrate in 10 healthy young men. Reactive hyperemia was induced by distal circulatory arrest followed by reperfusion of the leg ipsilateral (right) or contralateral (left) to the side of arterial diameter measurements. Femoral arterial blood flow was calculated by simultaneous measurement of femoral arterial diameter and blood velocity. The change in skin blood flow was also analyzed simultaneously by laser Doppler flowmetry. Reactive hyperemia induced a 2-fold increase in femoral arterial blood velocity 30 sec after cuff release. During this flow augmentation, the femoral artery dilated. The peak of skin blood flow was coincident with the peak of femoral arterial vasodilation. The time required for the return of arterial diameter to baseline was longer than that for blood flow in both the conduit artery and the peripheral skin tissue. Equivalent cuff occlusion and release of the contralateral limb had no effect on ipsilateral arterial diameter. Isosorbide dinitrate induced dilation in all subjects, despite the absence of a significant increase in blood velocity. These results indicate that the human femoral artery dilates in response to increased blood velocity, and that the flow-mediated vasodilation of a large conduit artery is involved in the adjustments of blood flow in the downstream peripheral tissue.

Adult↗
PubMed1997

Effect of lecithinized-superoxide dismutase on the rat colitis model induced by dextran sulfate sodium.

Lecithinized-superoxide dismutase (PC-SOD), which is synthesized with a lecithin derivative bound covalently to recombinant human Cu,Zn-SOD, has a longer half-life in blood and higher cell affinity than unmodified SOD. The effects of PC-SOD were evaluated using the rat ulcerative colitis model induced by 3% dextran sulfate sodium. Intravenous injection of rats with 0.5 or 1 mg/kg of PC-SOD suppressed the progression of bloody stools, the formation of erosion, and the infiltration of the colon with inflammatory cells. Furthermore, it also reduced the increase of leukocytes in blood. Thus, PC-SOD may have therapeutic potential in the treatment of ulcerative colitis.

Animals↗
PubMed1997

Effect of lecithinized-superoxide dismutase on the interstitial pneumonia model induced by bleomycin in mice.

Superoxide anion (O2-) acts as an exacerbation factor in interstitial pneumonia. Lecithinized-superoxide dismutase (PC-SOD), which is synthesized with a lecithin derivative bound covalently to recombinant human Cu,Zn-SOD, has a longer half-life in plasma and higher affinity to cell membranes than unmodified SOD. The effect of PC-SOD was evaluated using the bleomycin-induced interstitial pneumonia mouse model. Treatment with PC-SOD at 10 mg/kg significantly reduced the hydroxyproline content and fibrosis score. Namely, PC-SOD suppressed the progression of pulmonary fibrosis on the bleomycin-induced interstitial pneumonia mouse model. PC-SOD may be a potential drug for interstitial pneumonia therapy.

Animals↗
PubMed1996

Rate of nitric oxide release in the lung and factors influencing the concentration of exhaled nitric oxide.

The level of nitric oxide (NO) in exhaled air fluctuates in normal individuals depending on the physiological conditions. We evaluated the effects of duration of exhalation and breath-holding on the exhaled concentrations of NO in 16 normal human volunteers. Exhaled gas corresponding to vital capacity was collected in 6-liter Tedlar bags and analyzed by chemiluminescence. The NO concentration in exhaled gas increased significantly in proportion to the duration of exhalation [P = 0.009 +/- 0.011 (SD)] and was increased after breath-holding. There was no significant difference in the exhaled NO concentration among 10-s phases of a 30-s exhalation, as determined from multiple breath collections. The NO released from the airways is presumably unaffected by fluctuation of exhalation speed. The NO release rate, calculated from a single regression analysis between the NO concentration and the duration of exhalation, was 39 +/- 29 pmol/s, a value which was about fourfold greater in nine patients with bronchial asthma.

Adult↗