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Biomedical subjects

J Yoshikawa

Publications and source records attributed to J Yoshikawa.

At least 181 records · Page 10Linked to original sources
PubMed1998

[Long-term results of mitral valve repair with artificial chordae tendineae].

The long-term results of mitral valve repair using artificial polytetrafluorethylene (PTFE) chordae were assessed in 61 consecutive patients with pure mitral regurgitation who underwent mitral valve repair with replacement of elongated or ruptured chordae tendineae between 1992 and 1996. There were 36 men and 25 women aged from 14 to 73 years (mean 52.1 +/- 13.8 years). The patients were followed up for between 1 to 73 months (mean 29.3 +/- 17.6 months). Fifty-five patients underwent mitral valve repair of the anterior leaflet and 6 repair of the posterior leaflet. There were two hospital and two late deaths. Actual survival rate at 5 years was 93.1%. Freedom from cardiac events at 5 years was 87.8%. Two patients required reoperation due to hemolysis. There were three occurrences of non-fatal thromboembolism. Although further investigation is necessary in a large population, expanded PTFE sutures are excellent for chordal replacement during mitral valve repair.

Adolescent↗
PubMed1998

[Serial changes in mitral regurgitation after mitral valve repair with artificial chordae tendineae: assessment by transesophageal echocardiography].

Serial changes in mitral regurgitation after anterior mitral valve repair were examined by transesophageal echocardiography (TEE) in 34 of 86 consecutive patients with pure mitral regurgitation who underwent anterior mitral valve repair from 1987 to 1996. The patients were divided into two groups: 15 patients undergoing mitral repair with polytetrafluoroethylene (PTFE; PTFE group) and 19 undergoing conventional mitral repair without PTFE (non-PTFE group). The PTFE group included 11 men and 4 women with a mean age of 52.1 years. They were followed for mean 22.8 +/- 12.0 months. The non-PTFE group included 12 men and 7 women with a mean age of 53.9 years. They were followed for mean 33.9 +/- 20.4 months. Mitral regurgitation jet areas were observed at the time of operation, 1 month after mitral valve repair, and in the late follow-up period. Regurgitation jet areas were 0.7 +/- 0.7, 1.1 +/- 0.9 and 2.5 +/- 2.1 cm2 in the PTFE group, and 1.1 +/- 1.3, 2.4 +/- 1.7, 4.7 +/- 2.9 cm2 in the non-PTFE group. The jet area was significantly smaller in the PTFE group than in the non-PTFE group at 1 month after operation and in the late follow-up period. Moderate to severe regurgitation was observed in two patients (13.3%) in the PTFE group, and eight patients (42.1%) in the non-PTFE group. Mitral valve repair with PTFE showed better results than conventional mitral valve repair without PTFE during the mean follow-up period of 23 months.

Adult↗
PubMed1998

[Automated cardiac output measurement by color Doppler echocardiography].

Recently, automated cardiac flow measurement (ACM) has been developed for measuring the volume flow rate of blood flow through the left ventricular outflow tract. Measurements of left ventricular cardiac output by the ACM method were compared with those by the thermal dilution method with a Swan-Ganz catheter in 27 patients (16 men and 11 women; aged 44 +/- 3 years) in whom clear two-dimensional and color Doppler images of the left ventricular outflow tract were obtained. The total time required for left ventricular stroke volume calculation by both ACM and pulsed Doppler methods was measured in 10 patients (six men and four women; aged 41 +/- 2 years). There was an excellent correlation in the measurements of cardiac output between the ACM and thermal dilution methods (y = 0.77x + 0.77, r = 0.84, SEE = 0.4 l/min). The total time required for left ventricular stroke volume calculation by the ACM method was significantly shorter than that by the pulsed Doppler method (92 +/- 10 vs 177 +/- 30 sec, p < 0.01). The ACM method is simple, quick, and accurate for the automated assessment of cardiac output.

Adult↗
PubMed1998

[Evaluation of patients with cerebral infarction using transesophageal echocardiography: atherosclerotic changes in the thoracic aorta and the branches of the aortic arch].

Atherosclerotic disease of the aortic arch is thought to be a potential source of cerebral emboli, but this disease in the branch of the aortic arch has not been extensively explored. This study assessed atherosclerotic lesions in the thoracic aorta and the branches of the aortic arch using transesophageal echocardiography in patients with cerebral infarction, and simultaneously searched for potential cardiac sources for emboli. Thrombi were detected in the left atrial appendage in nine of 54 patients with cerebral infarction and these patients were excluded. The remaining 45 patients with cerebral infarction (31 males and 14 females aged 68.5 +/- 7.4 years) and 35 normal subjects (21 males and 14 females aged 69.2 +/- 9.5 years) were evaluated. The thickness of the wall was measured in the branches of the aortic arch (brachiocephalic trunk, left common carotid artery and left subclavian artery) as well as the thoracic aorta (ascending aorta, aortic arch and descending aorta). Atherosclerotic lesions were defined as increased echogenicity of the intima (intimal thickening), calcification, protruded plaque, ulceration or plaque with cystic lesion. The thicknesses of the wall in the aortic arch (3.84 +/- 1.25 vs 2.71 +/- 1.33 mm, p < 0.01), left common carotid artery (2.67 +/- 1.10 vs 2.16 +/- 0.91 mm, p < 0.05) and the left subclavian artery (2.52 +/- 0.67 vs 2.15 +/- 0.88 mm, p < 0.05) were significantly greater in patients than in the normal subjects. The incidence of plaque or ulceration was significantly increased in patients with cerebral infarction compared with the normal subjects in the aortic arch (76% vs 43%, p < 0.05) and left common carotid artery (44% vs 17%, p < 0.05). Transesophageal echocardiography can detect possible sources of emboli in the branches of the aortic arch as well as the thoracic arch in patients with cerebral infarction.

Aged↗
PubMed1998

Relation between the kinetics of thallium-201 in myocardial scintigraphy and myocardial metabolism in patients with acute myocardial infarction.

OBJECTIVE: To investigate the relations between myocardial metabolism and the kinetics of thallium-201 in myocardial scintigraphy. METHODS: 46 patients within six weeks after the onset of acute myocardial infarction underwent resting myocardial dual isotope, single acquisition, single photon emission computed tomography (SPECT) using radioiodinated 15-iodophenyl 3-methyl pentadecaenoic acid (BMIPP) and thallium-201, exercise thallium-201 SPECT, and positron emission tomography (PET) using nitrogen-13 ammonia (NH3) and [F18]fluorodeoxyglucose (FDG) under fasting conditions. The left ventricle was divided into nine segments, and the severity of defects was assessed visually. RESULTS: In the resting SPECT, less BMIPP uptake than thallium-201 uptake was observed in all of 40 segments with reverse redistribution of thallium-201, and in 21 of 88 segments with a fixed defect of thallium-201 (p < 0.0001); and more FDG uptake than NH3 uptake (NH3-FDG mismatch) was observed in 35 of 40 segments with reverse redistribution and in 38 of 88 segments with fixed defect (p < 0.0001). Less BMIPP uptake in the resting SPECT was observed in 49 of 54 segments with slow stress redistribution in exercise SPECT, and in nine of 17 segments with rapid stress redistribution (p < 0.0005); NH3-FDG mismatch was observed in 42 of 54 segments with slow stress redistribution and in five of 17 segments with rapid stress redistribution (p < 0.0005). CONCLUSIONS: Thallium-201 myocardial scintigraphy provides information about not only myocardial perfusion and viability but also about myocardial metabolism in patients with acute myocardial infarction.

Adult↗
PubMed1998

[Assessment of coronary flow reserve in patients with hypertrophic cardiomyopathy using transthoracic color Doppler echocardiography].

Abnormal coronary flow pattern and coronary vasodilator reserve have been identified in patients with hypertrophic cardiomyopathy (HCM) using invasive techniques. The characteristics of coronary flow velocity and coronary flow reserve were evaluated by noninvasive-recording of coronary flow velocity in the distal portion of the left anterior descending coronary artery in 7 patients with HCM and 7 normal subjects using transthoracic color Doppler echocardiography. Coronary flow velocity was measured at rest and during intravenous infusion of adenosine triphosphate (0.15 mg/kg/min). Diastolic peak velocity, diastolic mean velocity, the time from the beginning of diastole to peak velocity (TVP) and velocity half time from peak velocity was measured in each group. Coronary flow reserve was obtained as the ratio of hyperemic mean velocity to resting mean velocity. TVP was significantly prolonged in the patients with HCM compared with the normal subjects (159 +/- 38 vs 103 +/- 54 msec, p < 0.05). Velocity half time was significantly shorter in the patients with HCM compared with the normal subjects (304 +/- 138 vs 451 +/- 109 msec, p < 0.05). Although diastolic mean velocity during hyperemia was not different between the 2 groups (62 +/- 8 vs 70 +/- 19 cm/sec), diastolic mean velocity at rest was significantly higher in the patients with HCM than in the normal subjects (39 +/- 6 vs 26 +/- 7 cm/sec, p < 0.01). Therefore, coronary flow reserve was significantly lower in the patients with HCM than in the normal subjects (1.6 +/- 0.4 vs 2.7 +/- 0.4, p < 0.001). There was a good correlation between diastolic mean velocity and the ratio of interventricular septal to posterior left ventricular wall thickness (y = 0.024x + 0.46, r = 0.75). Transthoracic assessment of coronary flow velocity using color Doppler echocardiography reveals that coronary flow reserve is reduced in patients with HCM because of increased baseline resting diastolic mean velocity.

Cardiomyopathy, Hypertrophic↗
PubMed1998

Chemical, metabolic and immunological characterization of gangliosides of human glioma cells.

The patterns of ganglioside profiles were studied in 10 human glioma and one melanoma cell lines. Ganglio-series gangliosides, GM3 (NeuAc alpha2-3Gal beta1-4Glc beta1-Cer) and GM2 (GalNAc beta 1-4 (NeuAc alpha2-3)Gal beta1-4Glc beta 1-1Cer), and a neolacto-series ganglioside, sialylparagloboside (SPG) (NeuAc alpha 2-3Gal beta1-4GlcNAc beta1-3Gal beta1-4Glc beta1-1Cer), were the predominant constituents. The activities of the two key enzymes, GM3 synthetase and lactotriaosyl ceramide (Lc3Cer) synthetase, alone did not account for the ganglioside profile. Metabolic labeling with the use of [3H]glucosamine-HCl showed more pronounced difference in the synthetic rate of each ganglioside type, in which GM2 was the most strongly labeled in 7 out of the 10 glioma cell lines. On quantifying the chemical content of GM3 and GM2, the GM3/GM2 molar ratio of above 2.0 was arbitrarily classified into GM3 dominant type (KG-1C and Mewo); the ratio below 0.5 was designated as GM2 dominant type (H4, U138MG, U373MG, T98G and A172); and the ratio between 0.5 and 2.0 was regarded as GM3 and GM2-co-dominant type (U87MG, Hs683, SW1088 and U118MG). Subsequently, the capabilities of the antibody binding to these gangliosides were examined in native forms in the cell membrane and in chemically-isolated forms. The intensity of reaction against chemically isolated GM3 and GM2 gangliosides was dependent on the quantity, and GM2 was more reactive than GM3; however, the reactivities on the cell surface did not correlate with the chemical content indicating other factors to influence their immunoreactivities.

Antibodies, Monoclonal↗
PubMed1997

Automated assessment of mitral regurgitant volume and regurgitant fraction by a newly developed digital color Doppler velocity profile integration method.

Recent development of the automated cardiac flow measurement (ACFM) method has provided automated measurement of stroke volume and cardiac output by spatial and temporal integration of digital Doppler velocity profile data. The purpose of this study was to evaluate the clinical usefulness of the ACFM method using digital color Doppler velocity profile integration in the assessment of mitral regurgitant volume and regurgitant fraction from measurements of both aortic outflow and mitral inflow volumes. We calculated both aortic outflow and mitral inflow volumes from the apical approach with the ACFM and pulsed Doppler (PD) methods in 20 patients with isolated mitral regurgitation. Mitral regurgitant volume and regurgitant fraction were calculated by the following equation: mitral regurgitant volume = (mitral inflow volume) - (aortic outflow volume), % regurgitant fraction = (mitral regurgitant volume)/(mitral inflow volume) x 100. Mitral regurgitant volume and regurgitant fraction were compared with that determined by the PD method. Mitral regurgitant volume measurement by the ACFM method showed a good correlation with that measured by the PD method (r = 0.90, y = 0.77x + 11.6, SEE = 9.0 ml); the mean differences between PD and ACFM measurements was -1.7 +/- 12.5 ml. Regurgitant fraction estimated by the ACFM method correlated well with that of the PD method (r = 0.92, y = 0.98x + 2.1, SEE = 8.8%). The mean difference for the measurement of regurgitant fraction between the PD and ACFM methods was 0.8 +/- 6.6%. Total time required for mitral regurgitant volume calculation in 1 cardiac cycle by the ACFM method was significantly shorter than that of the PD method (126 +/- 15 seconds vs 228 +/- 36 seconds, p <0.01). In conclusion, the newly developed ACFM method is simple, quick, and accurate in the automated assessment of mitral regurgitant volume and regurgitant fraction.

Adult↗
PubMed1997

Phasic coronary flow characteristics in patients with constrictive pericarditis: comparison with restrictive cardiomyopathy.

BACKGROUND: Phasic coronary flow characteristics have been reported in patients with aortic valve disease and hypertrophic cardiomyopathy. The purpose of this study was to assess the differences in coronary flow characteristics between patients with constrictive pericarditis and those with restrictive cardiomyopathy. METHODS AND RESULTS: The study populations consisted of 7 case patients with constrictive pericarditis, 8 with restrictive cardiomyopathy, and 11 control subjects with chest pain and normal coronary arteries. Five minutes after injection of 3 mg of isosorbide dinitrate, phasic coronary flow velocity patterns were analyzed in the proximal segment of the angiographically normal left anterior descending coronary artery at rest using a 0.014-in, 15-MHz Doppler guidewire. Coronary flow reserve was obtained from the ratio of adenosine-induced (0.14 mg x kg(-1) x min(-1) I.V.) hyperemic/baseline time-averaged peak velocity. Although in case patients with constrictive pericarditis and restrictive cardiomyopathy maximal hyperemic time-averaged peak velocity (21+/-8 and 31+/-17 versus 60+/-19 cm/s, respectively; P<.001) and coronary flow reserve (1.3+/-0.4 and 1.6+/-0.6 versus 3.6+/-0.4, respectively, P<.001) were significantly lower than in control subjects, there were no significant differences in these indexes between the two groups of case patients. Velocity half-time of diastolic flow velocity corrected by square root(RR), which indicates deceleration of diastolic flow, in the groups of case patients with constrictive pericarditis and restrictive cardiomyopathy was significantly less than that in control subjects (6.2+/-2.6 and 10.6+/-1.5 versus 16.9+/-2.7, respectively; P<.001); this was also significantly smaller in constrictive pericarditis than restrictive cardiomyopathy (P<.001). This index <9.5 could distinguish constrictive pericarditis from restrictive cardiomyopathy with a sensitivity of 86% and a specificity of 88%. Furthermore, time from the beginning of diastole to diastolic peak velocity corrected by square root(RR) indicating acceleration of diastolic flow velocity in constrictive pericarditis was significantly less than that in restrictive cardiomyopathy and control subjects (2.8+/-1.2 versus 4.8+/-0.8 and 4.4+/-0.6, respectively; P<.001). CONCLUSIONS: Although coronary flow reserve is limited in both constrictive pericarditis and restrictive cardiomyopathy because of restriction of hyperemic response, rapid acceleration and more rapid deceleration of diastolic flow velocity are more characteristic in constrictive pericarditis than in restrictive cardiomyopathy.

Adult↗
PubMed1997

Comparison of coronary flow reserve between focal and diffuse vasoconstriction induced by ergonovine in patients with vasospastic angina.

Decreased coronary flow reserve has been reported in patients with ergonovine-induced coronary vasoconstriction by the thermodilution method. To assess the difference of coronary flow reserve between patients with focal and diffuse vasospasm, after the vasospasm is discontinued by injection 3 mg of isosorbide dinitrate, phasic flow velocities of the diseased coronary artery were recorded at rest and during hyperemia (140 microg/kg/min of adenosine infusion intravenously) using a 0.014-inch, 15-MHz Doppler guidewire in 26 patients with ergonovine-induced coronary vasospasm (0.2-mg ergonovine injection intravenously), including 12 patients with focal (>90% stenosis), 14 patients with diffuse vasospasm (>50%), and 11 controls with normal coronary arteries without vasospasm. Although time-averaged peak velocity in cases with diffuse and focal vasospasm was not significantly different compared with that in controls at baseline (22 +/- 7, 18 +/- 5 vs 20 +/- 7 cm/s, respectively, NS), it was significantly lower in patients with diffuse vasospasm than in cases with focal vasospasm and in controls during hyperemia (43 +/- 13 vs 64 +/- 18, 61 +/- 19 cm/s, respectively, p <0.01). As a result, coronary flow reserve obtained from the ratio of hyperemic/baseline time-averaged peak velocity was significantly lower in patients with diffuse vasospasm than that in controls (1.9 +/- 0.4 vs 3.1 +/- 0.4, p <0.01), although it was not significantly different between the subjects with focal vasospasm and controls (3.5 +/- 0.7 vs 3.1 +/- 0.4, NS). Thus, coronary flow reserve is maintained normally in patients with focal vasospasm and limited in those with diffuse vasospasm. Microvascular impairment could exist further in cases with diffuse vasospasm, although similar endothelial dysfunction of the epicardial coronary artery is observed in focal and diffuse vasospasm.

Adult↗
PubMed1997

Assessment of flail mitral leaflets by dynamic three-dimensional echocardiographic imaging.

To evaluate the usefulness of dynamic 3-dimensional images obtained by multiplane transesophageal echocardiography (TEE) in the diagnosis of the involved leaflets in patients with a flail mitral leaflet, 23 patients who underwent mitral valve repair were examined with multiplane TEE. In all patients, the involved lesions diagnosed by dynamic 3-dimensional images coincided with those confirmed at the time of operation; dynamic 3-dimensional images by multiplane transesophageal probe are useful in the evaluation of the involved sites in patients with a flail mitral leaflet.

Adult↗
PubMed1997

Differences in expression of sarcoplasmic reticulum Ca2+-ATPase and Na+-Ca2+ exchanger genes between adjacent and remote noninfarcted myocardium after myocardial infarction.

Although cardiac failure can develop over time after myocardial infarction, the mechanism responsible for this is still unknown. The change of intracellular Ca2+ transport protein, such as sarcoplasmic reticulum (SR) Ca2+-ATPase (SR-Ca2+), Na+-Ca2+ exchanger (Na+-Ca2+), or cardiac phenotypic modulation of contractile protein in noninfarcted myocardium may have a important role. However, the time course in gene expression of sarcoplasmic reticulum (SR) Ca2+-ATPase (SR-Ca2+), Na+-Ca2+ exchanger (Na+-Ca2+), and contractile protein in the adjacent and remote noninfarcted myocardium after myocardial infarction has not been examined. At 1, 3 weeks and 3 months after myocardial infarction, hemodynamics were measured and mRNA of the left ventricle was analyzed. Left ventricular end-diastolic volume and weight increased both with time. Ascites became apparent at 3 months after infarction. SR-Ca2+ mRNA levels in the adjacent noninfarcted myocardium were 0.7- (P<0.01), 0.9- (N.S.), and 0.7-fold (P<0.01) of control, and Na+-Ca2+ mRNA levels were 2.1- (P<0.01), 1.4- (P<0.01), and 0.8-fold (P<0.01) of control, at 1, 3 weeks and 3 months after infarction, respectively. beta-Myosin heavy chain (MHC) mRNA was increased to 2.1- (P<0.01), 1.5- (P<0.01), and 1.4-fold (P<0.01), and alpha-skeletal actin was increased to 2.4- (P<0.01), 3.8- (P<0.01), and 1.6-fold (P<0.01) control levels, at 1 week, 3 weeks and 3 months, respectively. In contrast, alpha-MHC mRNA level was decreased at 1 week and 3 months after infarction. alpha-cardiac actin mRNA level did not change over time after infarction. In the remote non-infarcted myocardium, beta-MHC, alpha-skeletal actin, and Na+-Ca2+ mRNA levels were increased, but SR-Ca2+, alpha-MHC, and alpha-cardiac actin mRNA did not change after infarction. These findings suggest that: (1) intracellular Ca2+ handling system after myocardial infarction may be different between adjacent and remote non-infarcted myocardium: and that (2) both decreased gene expression of SR Ca2+-ATPase and Na+-Ca2+ exchanger in the adjacent non-infarcted myocardium may progress cardiac dysfunction.

Animals↗
PubMed1997

Endothelin production in cultured vascular smooth muscle cells--modulation by the atrial, brain, and C-type natriuretic peptide system.

We examined the regulatory mechanisms of endothelin-1 (ET-1) production in cultured rat vascular smooth muscle cells (VSMC) with a special focus on the roles of protein kinase C (PKC)- and cyclic guanosine-3',5'-monophosphate (GMP)-mediated signaling systems. Effects of atrial, brain, and C-type natriuretic peptides (ANP, BNP, and CNP) on angiotensin II (Ang II)-, and arginine vasopressin (AVP)-induced production of ET-1 were examined in cultured rat aortic VSMC. Ang II and AVP stimulated ET-1 production in a concentration-dependent manner through angiotensin subtype 1 (AT1) and vasopressin subtype 1 (V1) receptors, respectively. The stimulatory effects of Ang II and AVP were markedly abolished in PKC-depleted cells. Rat ANP (1-28), rat BNP-45, and rat CNP-22 potently inhibited Ang II- and AVP-stimulated ET-1 production in a concentration-dependent manner, respectively. The inhibitory effect by CNP on ET-1 production was paralleled by an increase in the cellular level of cyclic GMR.8-Bromo cyclic GMP reduced the stimulated ET-1 production by Ang II and AVP. These results indicate that Ang II and AVP stimulate ET-1 production in cultured rat VSMC through AT1 and V1 receptors by a mechanism probably involving activation of PKC, and that ANP, BNP, and CNP inhibit this stimulated production through a cyclic GMP-dependent process.

Angiotensin II↗
PubMed1997

Improvement of erythrocyte deformability by cholesterol-lowering therapy with pravastatin in hypercholesterolemic patients.

Erythrocyte deformation is an important regulatory factor of the microcirculation. The present study was designed to examine whether erythrocyte deformability is altered in hypercholesterolemic patients and, if so, whether cholesterol-lowering therapy affects this parameter in these patients. The erythrocyte deformability of 37 hypercholesterolemic patients was evaluated before and after 1 year of therapy with pravastatin, an inhibitor of hepatic hydroxymethyl glutaryl coenzyme A reductase, under various shear stresses (4.7, 9.5, 23.6, 47.3, 118.1, and 236.2 dyne/cm2) using laser diffractometry. At study entry, erythrocyte deformability under 4.7 and 9.5 dyne/cm2 shear stress, which is actually observed in human vessels, was reduced compared with that in 20 age-matched normocholesterolemic subjects and was inversely correlated with serum cholesterol and low-density lipoprotein (LDL) cholesterol. Pravastatin therapy for 1 year, which reduced serum cholesterol from 288 +/- 28 to 223 +/- 20 mg/dL, significantly improved erythrocyte deformability by approximately 20%. There was a significant relation between the improvement of erythrocyte deformability and the reduction of serum cholesterol or LDL cholesterol. The results suggest that erythrocyte deformability is reduced in hypercholesterolemic patients, and that long-term cholesterol-lowering therapy can improve reduced erythrocyte deformability, which may contribute to the improvement of organ perfusion.

Adult↗
PubMed1997

Renoprotective effects of a combined endothelin type A/type B receptor antagonist in experimental malignant hypertension.

We previously showed that plasma endothelin-1 (ET-1) concentration was increased in deoxycorticosterone acetate (DOCA)-salt-induced malignant hypertension in spontaneously hypertensive rats (SHR). In contrast, in normal SHR, this value is similar to that seen in Wistar-Kyoto (WKY) rats. The purpose of this study was to examine the effects of the new combined ET type A/type B (ETA/B) receptor antagonist, TAK-044, on the development of hypertension in this model of malignant hypertension. TAK-044 10 mg/kg, which effectively blocks both ETA and ETB receptors, was administered intraperitoneally once per day for 4 weeks in DOCA-salt SHR, and the effects on ET-1 and other parameters were compared with the same values in untreated WKY rats, untreated DOCA-salt SHR, and hydralazine-treated DOCA-salt SHR. DOCA-salt caused marked increases in blood pressure, blood urea nitrogen (BUN), serum creatinine, and plasma ET-1 concentrations in SHR. Both TAK-044 and hydralazine significantly suppressed the increase in blood pressure in DOCA-salt SHR to the same extent. Both treatments also suppressed the increase in BUN and serum creatinine, but this attenuation was less marked with hydralazine than with TAK-044. Neither TAK-044 nor hydralazine affected plasma ET-1 concentration in this model. TAK-044 significantly reduced kidney weight in DOCA-salt SHR, whereas the decrease seen with hydralazine was less marked. Prevention of DOCA-salt-induced renal structural injury (mesangial hypercellularity, glomerular sclerotic changes, and tubulointerstitial damage) in this model was clearly greater with TAK-044 treatment than with hydralazine treatment. These results suggest that endogenous ET-1 may, at least in part, contribute to renal functional and structural damage in malignant DOCA-salt SHR. Our results raise the possibility of renoprotective effects of ETA/B receptor blockers in certain forms of malignant hypertension.

Animals↗
PubMed1997

Increased levels of nitric oxide derivatives in induced sputum in patients with asthma.

BACKGROUND: Nitric oxide (NO) plays an important role as an inflammatory mediator in the airways. However, because direct measurement of endogenous NO has been difficult in vivo, the exact pathologic roles of NO in human airway inflammation have remained unclear. OBJECTIVE: This study was designed to determine whether NO may be harmful by amplifying allergic inflammation in asthmatic airways. METHODS: In this study we examined the concentration of stable end products of NO, nitrite and nitrate, in induced sputum in 18 patients with asthma and 10 normal control subjects and evaluated the relationship between levels of NO derivatives in sputum and cellular and biochemical profiles, the degree of airflow obstruction, and the cytotoxic activities for epithelial cells. RESULTS: The concentration of NO derivatives in induced sputum was significantly higher in patients with asthma than in normal control subjects (1086 +/- 325 mumol/L, 577 +/- 115 mumol/L; p < 0.05). Percentages of eosinophil counts and eosinophil cationic protein levels in sputum were also significantly higher in patients with asthma. Moreover, percentages of eosinophil counts and eosinophil cationic protein levels in sputum in patients with asthma were significantly correlated with the concentration of NO derivatives in sputum (r = 0.63, p < 0.01; r = 0.56, p < 0.05, respectively). In addition, we found that the concentration of NO derivatives in sputum in patients with asthma was significantly correlated with the degree of airflow obstruction (FEV1/forced vital capacity) (r = -0.62, p < 0.01) and with percentages of shedding epithelial cells (r = 0.61, p < 0.01). CONCLUSION: We have shown that a higher concentration of NO derivatives was found in induced sputum of patients with asthma as compared with normal subjects. The clinical implication of our findings is that measurement of NO derivatives in induced sputum may be useful for assessing allergic inflammation in airways.

Adult↗