Biomedical subjects

Y Miyao

Publications and source records attributed to Y Miyao.

At least 37 records · Page 2Linked to original sources

PubMed1999

Plasma soluble intercellular adhesion molecule-1 levels in coronary circulation in patients with unstable angina.

It has been suggested that active inflammation plays an important role in the pathogenesis of acute coronary syndromes, including unstable angina. Intracellular adhesion molecule-1 (ICAM-1) is a major ligand on the endothelial cells for adherence of the activated polymorphonuclear leukocytes. Recently, it has been demonstrated that the soluble form of ICAM-1 has been detected in human serum and has been increased in many other inflammatory or autoimmune disorders. To evaluate the involvement of ICAM-1 in unstable angina, we examined plasma soluble ICAM-1 (sICAM-1) levels in coronary circulation. The plasma sICAM-1 levels in the coronary sinus and aortic root were simultaneously examined in 20 patients with unstable angina, 19 patients with stable exertional angina, and 16 control subjects. The plasma levels of sICAM-1 were measured by enzyme-linked immunosorbent assay. The mean plasma sICAM-1 levels (nanograms per milliliter) both in the coronary sinus and aortic root were significantly higher (p <0.01) in patients with unstable angina than in those with stable exertional angina and in control subjects (217+/-14 vs 126+/-8; 120+/-10 in the coronary sinus, 202+/-13 vs 125+/-9; 123+/-10 in the aortic root). Furthermore, the mean value was higher in the coronary sinus than in the aortic root in patients with unstable angina. There were no significant differences in the values between in the coronary sinus and aortic root in patients with stable exertional angina and control subjects. Thus, sICAM-1 release is increased, especially in coronary circulation in unstable angina.

Aged↗

PubMed1999

Improvement of endothelial vasomotor dysfunction by treatment with alpha-tocopherol in patients with high remnant lipoproteins levels.

OBJECTIVES: This study sought to examine whether oral intake of alpha-tocopherol, an antioxidant, could improve endothelium-dependent vasorelaxation in patients with high remnant lipoproteins levels. BACKGROUND: Remnant lipoproteins are known to be atherogenic and impair endothelium-dependent arterial relaxation, but the underlying mechanisms remain unclear. Oxidative stress is a common feature of various risk factors for atherosclerosis. METHODS: Flow-mediated vasodilation of the brachial artery during reactive hyperemia was examined by high resolution ultrasound technique before and at the end of 4 weeks treatment with oral administration of alpha-tocopherol acetate (300 IU/day) or placebo, which was randomly assigned, in 40 patients with high serum levels of remnants and in 30 patients with low remnants levels in the fasting state (>75th percentile and <25th percentile, respectively, of the distribution of remnants levels in 150 consecutive hospitalized patients). RESULTS: Before treatment, flow-mediated vasodilation was lower in patients with high remnants levels than in those with low levels (4.1 +/- 0.3% vs. 6.0 +/- 0.5%, p < 0.01). Treatment with alpha-tocopherol but not with placebo significantly increased flow-mediated dilation in patients with high remnants levels (7.5 +/- 0.4% after alpha-tocopherol vs. 4.2 +/- 0.4% after placebo, p < 0.01). In patients with low remnants levels, alpha-tocopherol was not effective. The beneficial effect with alpha-tocopherol in high remnants patients was associated with decrease in plasma levels of thiobarbituric acid reactive substances, an indicator of lipid peroxidation (6.6 +/- 0.3 nmol/ml before alpha-tocopherol vs. 4.6 +/- 0.3 after alpha-tocopherol, p < 0.05). CONCLUSIONS: Alpha-tocopherol improved impairment of endothelium-dependent vasodilation in patients with high remnants levels. The increase in oxidative stress may at least partly contribute to endothelial vasomotor dysfunction, in patients with high remnants levels.

Adult↗

PubMed1999

Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery.

OBJECTIVES: We examined whether endothelial dysfunction occurs when acute hyperglycemia is induced by oral glucose loading. BACKGROUND: Endothelial dysfunction has been shown to occur in patients with diabetes mellitus (DM), and chronic hyperglycemia is implicated as a cause of endothelial dysfunction. However, in many patients with Type 2 DM and in those with impaired glucose tolerance (IGT), fasting blood glucose may be within normal limits, and hyperglycemia occurred only post-prandially. METHODS: With ultrasound technique, we measured flow-mediated endothelium-dependent vasodilation during oral glucose tolerance test in 58 subjects: (17 patients with normal glucose tolerance [NGT], 24 with IGT, and 17 with type 2 DM). In addition, we measured the levels of thiobarbituric acid reactive substances (TBARS) and nitrite/nitrate. RESULTS: Flow-mediated vasodilation decreased after glucose loading (NGT: 7.53+/-0.40, 4.24+/-0.28 and 6.35+/-0.40, in fasting, at 1- and 2-h, respectively, IGT: 6.50+/-0.48, 1.40+/-0.41** and 4.00+/-0.47*, respectively; DM: 4.77+/-0.37, 1.35+/-0.38** and 1.29+/-0.29%**, respectively; *p < 0.01 vs. fasting, **p < 0.005 vs. fasting). The TBARS concentration increased in parallel with plasma glucose level in each group (NGT: 1.43+/-0.07, 2.03+/-0.12 and 1.80+/-0.12, respectively; IGT: 1.65+/-0.11, 2.46+/-0.12** and 1.94+/-0.08*, respectively; DM: 1.73+/-0.07, 2.34+/-0.08** and 2.47+/-0.09** nmol/ml, respectively; *p < 0.05 vs. fasting, **p < 0.01 vs. fasting). Glucose loading did not change nitrite/nitrate concentration in any of the groups. CONCLUSIONS: Hyperglycemia in response to oral glucose loading rapidly suppresses endothelium-dependent vasodilation, probably through increased production of oxygen-derived free radicals. These findings strongly suggest that prolonged and repeated post-prandial hyperglycemia may play an important role in the development and progression of atherosclerosis.

Acute Disease↗

PubMed1999

Monoclonal antibody ONS-M21 recognizes integrin alpha3 in gliomas and medulloblastomas.

The monoclonal antibody ONS-M21 recognizes an antigen found on the surface of glioma and medulloblastoma cells but does not react with the antigens of normal brain tissue. We purified and identified the 140-kDa protein by means of an antibody-binding affinity column. This 140-kDa antigen has sequences homologous to the amino-terminal region and five parts of the internal domain of integrin alpha3. When the integrin alpha3-related sequences was amplified and used to analyse the mRNA of glioma and medulloblastoma surgical specimens, the transcription level of integrin alpha3 mRNA appeared to be quantitatively correlated with the grade of malignancy. These findings suggest that the ONS-M21 antibody, which reacts with integrin alpha3, might be useful in the diagnosis of gliomas and medulloblastomas.

Amino Acid Sequence↗

PubMed1999

Interstitial invasion of well-differentiated hepatocellular carcinoma and subsequent tumor growth.

Pathological processes of interstitial invasion of hepatocellular carcinoma (HCC) were investigated in 125 autopsy and seven surgical cases, where selection focused on those occurring in well-differentiated HCC. The invasive pattern of well-differentiated HCC was characterized by the formation of streaks of tumor cell cords running along connective tissue fibers, referred to as a streak pattern. These cell cords were unaccompanied by reticulin frameworks and type IV collagen, which are consistent components of HCC parenchyma. The typical streak pattern was observed only in HCC cases and could be useful in differential diagnosis. Following progressive accumulation or proliferation of the tumor cells within the interstitium, many capillaries appeared between the cell cords while collagen fibers tended to disappear. The tumor cell cords then showed branching and were accompanied by reticulin frameworks, type IV collagen and sinusoidal blood spaces. In the setting of interstitial invasion of well-differentiated HCC, it is suggested that interstitial tissue is converted into HCC parenchyma via the aforementioned steps.

Antigens, CD34↗

PubMed1999

Plasma adrenomedullin as an indicator of prognosis after acute myocardial infarction.

OBJECTIVE: To elucidate whether prognosis after acute myocardial infarction can be predicted by measuring plasma adrenomedullin, a novel vasorelaxant peptide. PATIENTS AND DESIGN: Plasma adrenomedullin concentrations on day 2 after myocardial infarction were measured in 113 patients with myocardial infarction with other clinical and haemodynamic variables related to mortality. RESULTS: During a mean follow up period of 25 months, 16 patients died of cardiac causes. Plasma adrenomedullin concentrations on day 2 increased significantly in patients with myocardial infarction compared with controls (mean (SD), 12.3 (8.8) v 4.9 (1.0) pmol/l, p < 0.001). Plasma adrenomedullin correlated negatively with left ventricular ejection fraction on admission (r = -0.47, p < 0.001), although it did not significantly correlate with any other haemodynamic variable. By univariate Cox proportional hazards analysis, plasma adrenomedullin, age, coronary reperfusion, maximum creatine kinase concentrations, pulmonary congestion, pulmonary capillary wedge pressure, cardiac index, and left ventricular ejection fraction were all significantly related to mortality. Among the non-invasive variables, only plasma adrenomedullin was an independent predictor of mortality after myocardial infarction (p < 0.05). The Kaplan-Meier survival curves based on the median plasma adrenomedullin concentration (10.3 pmol/l) showed that patients with high plasma adrenomedullin had a higher mortality than those with low plasma adrenomedullin (p < 0.01). CONCLUSIONS: Plasma adrenomedullin on day 2 after myocardial infarction is strongly associated with long term mortality, and thus may complement standard prognostic indicators.

Adrenomedullin↗

PubMed1999

Does coronary artery morphology predict favorable results of intracoronary thrombolysis in patients with unstable angina pectoris?

The efficacy of intracoronary thrombolysis (ICT) for unstable angina pectoris (UAP) has been limited, despite the similar pathogenesis between UAP and acute myocardial infarction. To ascertain the subset of UAP suitable for ICT, the clinical responses to ICT were assessed in patients with UAP. Eighty-2 patients with medically refractory angina were divided into 2 groups according to the coronary artery morphology of the culprit lesion before ICT: (1) lesions with acute cut off and/or filling defects (AC) and (2) lesions with a tapered shape (TA). The TIMI flow grade was determined from coronary angiograms before and immediately after ICT. The diameter stenosis (%DS) and minimal lumen diameter (MLD) of the culprit lesion were determined using quantitative coronary angiographic analysis before and immediately after ICT. In addition, inhospital cardiac event rates including urgent/emergency coronary angioplasty or bypass surgery, nonfatal myocardial infarction or cardiac death were compared between the 2 groups. Multivariate logistic regression analysis was performed using 13 clinical factors contributing to successful ICT. The results showed that all 3 coronary angiographic parameters (TIMI flow, %DS, and MLD) significantly improved in the AC group (p<0.01, p<0.01 and p<0.05, respectively), whereas none of these parameters improved in the TA group. The inhospital cardiac event rate after ICT was significantly higher in the TA group (76%) than in the AC group (48%; p=0.016). Odds ratio predicting successful ICT was 7.09 (p<0.01) for the AC lesion, and 2.54 (p<0.01) for new angina. In conclusion the AC lesions are more commonly associated with coronary thrombosis that responds to ICT than are the TA lesions. Thus, the coronary angiographic morphology may be an important predictor for a successful ICT in patients with medically refractory UAP.

Aged↗

PubMed1999

Role of cytokines and adhesion molecules in ischemia and reperfusion in patients with acute myocardial infarction.

Although acute myocardial infarction (AMI) may involve both plaque rupture and ischemia-reperfusion injury, the pathogenesis of these phenomena is unclear. To elucidate the pathogenesis of AMI, serial measurements of platelet activating factor (PAF), interleukin-6 and cell adhesion molecules were made in patients with AMI. The PAF levels were measured upon hospital admission and at 24 and 72h in 8 patients with AMI. Serum levels of interleukin-6, soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule- 1 (sVCAM- 1) were measured upon admission and at 24 h and 4 weeks in 30 patients with AMI and 15 patients with stable effort angina. PAF levels were higher in patients with AMI than in normal volunteers; the increased levels lasting at least 72h. In contrast, interleukin-6 increased at 24h. sE-selectin was elevated at admission and sVCAM-1 increased later. sE-selectin levels upon admission in patients with additional ST-segment elevation after reperfusion were significantly higher than those in patients without ST-elevation. In patients with AMI, the time-course of changes in blood levels of cytokines varied according to the individual substances. Although it is unclear what is the precise role of each of the cytokines in the pathophysiology of AMI, sE-selectin may be possibly related to the reperfusion injury in the infarcted myocardium.

Acute Disease↗

PubMed1999

Application of a rigid endoscope to the microsurgical management of 54 cerebral aneurysms: results in 48 patients.

OBJECT: To enhance visual confirmation of regional anatomy, endoscopy was introduced during microsurgery for cerebral aneurysms. The risks and benefits are analyzed in the present study. METHODS: The endoscopic technique was used during microsurgery for 54 aneurysms in 48 patients. Forty-three aneurysms were located in the anterior circulation and 11 were in the posterior circulation. Thirty-eight aneurysms (70.4%) had not ruptured. All ruptured aneurysms in the present series produced Hunt and Hess Grade I or II subarachnoid hemorrhage. After initial exposure achieved with the aid of a microscope, the rigid endoscope was introduced to confirm the regional anatomy, including the aneurysm neck and adjacent structures. The necks of 43 aneurysms were clipped using microscopic control or simultaneous microscopic/endoscopic control. After clipping, the positions of the clip and nearby structures were inspected using the endoscope. Use of the neuroendoscope provided useful information that further clarified the regional anatomy in 44 cases (81.5%) either before or after neck clipping. In nine cases (16.7%), these details were available only with the use of the endoscope. In five cases (9.3%), the surgeons reapplied the clip on the basis of endoscopic information obtained after the initial clipping. There were two cases in which surgical complications were possibly related to the endoscopic procedures (one patient with asymptomatic cerebral contusion and another with transient oculomotor palsy). CONCLUSIONS: It is the authors' impression that the use of the endoscope in the microsurgical management of cerebral aneurysms enhanced the safety and reliability of the surgery. However, there is a prerequisite for the surgeon to be familiar with this instrumentation and fully prepared for the risks and inconveniences of endoscopic procedures.

Adult↗

PubMed1999

[Creative activities in home care for terminally-ill cancer patients at a rural municipal hospital].

Karuizawa Hospital is a rural, small town municipal hospital with 60 beds, located in Nagano Prefecture in central Japan. The terminal stages of patients who were treated in our department of surgery but later died of cancer are reviewed. In the five year period extending from April, 1994 through March, 1999 sixty patients died from cancer. Of them, 34 people died in their own home and 26 in our hospital. The annual ratio of patients who died at home to those who died in the hospital are analyzed, as well as whether these ratios differed according to the location of the patient's cancer. The identity of the patients' main home caregiver was sought, as well as how many days the patients resided at home until they passed away, and how frequently doctors or nurses visited their home. Some of the doctors' attempts to gain informed consent are described. Based on the findings, the authors recommend an end to the practice of first revealing the name and details of a patient's disease to his/her family. It was also found that documented information is useful in order to promote smooth relationships among patients, family members, and the doctor.

Home Care Services, Hospital-Based↗

PubMed1999

Sustained elevation of plasma brain natriuretic peptide levels associated with progressive ventricular remodelling after acute myocardial infarction.

Previous studies have shown that levels of plasma brain natriuretic peptide (BNP) increase in an early phase of acute myocardial infarction. However, the relations between plasma BNP levels and left ventricular remodelling, which occurs long after acute myocardial infarction, are not fully understood. Venous plasma BNP levels were measured 2, 7, 14, 30, 90 and 180 days after the onset of acute myocardial infarction in 21 patients. Left ventricular end-diastolic volume index (EDVI, ml/m2) in acute (5 days) and chronic (6 months) phases were assessed by electron-beam computed tomography using Simpson's method. The remodelling group (n=9) was defined by an increase in EDVI >/=5 ml/m2 relative to the baseline value. Plasma BNP levels on days 2, 7, 14, 30 and 90 were significantly higher in the remodelling group than in the non-remodelling group (n=12, P<0.05). Sustained elevation of plasma BNP levels was noted from day 2 (61+/-12 pmol/l) to day 90 (55+/-12 pmol/l) and significantly decreased on day 180 (24+/-3 pmol/l) in the remodelling group. In contrast, plasma BNP levels significantly decreased from day 2 (25+/-4 pmol/l) to day 90 (9+/-1 pmol/l) and reached a steady level thereafter in the non-remodelling group. Plasma BNP levels on day 7 correlated positively with an increase in EDVI (r=0.70, P<0.001) from the acute to chronic phase. More importantly, the sustained elevation of plasma BNP (percentage decrease smaller than 25%) from day 30 to day 90 identified patients in the remodelling group with a sensitivity of 100% and a specificity of 83%. In conclusion, not only the high levels of plasma BNP in an acute phase, but also the sustained elevation of plasma BNP in a chronic phase, may be associated with progressive ventricular remodelling occurring long after acute myocardial infarction.

Adult↗

PubMed1998

Vitamin E administration improves impairment of endothelium-dependent vasodilation in patients with coronary spastic angina.

OBJECTIVES: We examined the effects of oral administration of vitamin E, an antioxidant, on endothelium-dependent vasodilation in patients with coronary spastic angina. BACKGROUND: We have recently reported that endothelium-dependent vasodilation is impaired in patients with coronary spastic angina (CSA). Furthermore, it is known that oxidative stress may play an important role in the impairment of endothelium-dependent vasodilation in cardiovascular diseases. METHODS: With the ultrasound technique, flow-dependent vasodilation of the brachial arteries during reactive hyperemia was examined before and after treatment for a month with either oral administration of vitamin E (alpha-tocopherol acetate, 300 mg/day) or placebo, which is randomly assigned, in patients with CSA (n=60). RESULTS: Before treatment, patients with CSA had impaired flow-dependent vasodilation, lower plasma levels of alpha-tocopherol and higher plasma levels of thiobarbituric acid reactive substances (TBARS), as compared with age- and sex-matched control subjects (n=60) (flow-dependent vasodilation: 3.1+/-1.8 vs. 7.1+/-2.5%, p < 0.001; alpha-tocopherol levels: 8.9+/-1.8 vs. 10.8+/-1.8 microg/ml, p < 0.001). In patients with CSA, treatment with vitamin E restored flow-dependent vasodilation (3.1+/-1.7 vs. 8.3+/-2.0%, p < 0.001), and this improvement was associated with the decreases in plasma TBARS levels and anginal attacks. CONCLUSIONS: The results indicate that vitamin E treatment improved endothelium-dependent vasodilation and decreased plasma TBARS levels in patients with CSA. Thus, increased oxidative stress may contribute to endothelial dysfunction and anginal attacks in patients with CSA.

Adult↗

PubMed1998

Internalization with high targeting potential of mouse monoclonal antibody ONS-M21 recognizing human malignant glioma antigen.

In order to evaluate the targeting potential of mouse monoclonal antibody ONS-M21 recognizing a human astrocytoma- and medulloblastoma-associated antigen, the internalization ability of this antibody and the selective cytotoxicity in the toxin-conjugated form were examined. Internalization assay with 125I-labeled ONS-M21 showed that about 20% of the total radioactivities was detected in the cellular fraction of human medulloblastoma cell line ONS-76 cells and that the reaction reached a plateau level in 30 min. To examine the selective delivery capacity of a high molecular substance in place of 125I, an immunotoxin was prepared with ricin A chain and ONS-M21 via disulfide bonds. A cytotoxic effect against ONS-76 cells was found with [3H]thymidine incorporation assay using the immunotoxin, but not against antigen-negative HuH-7 and SW480 cells. These results suggest that ONS-M21 could effectively deliver toxins, chemotherapeutic agents or radionuclei to malignant glioma specifically.

Animals↗

PubMed1998

Prevalence of verotoxin-producing Escherichia coli harbored in the intestine of cattle in Japan.

The production of verotoxin was examined in 2152 Escherichia coli isolates from 387 cattle in Japan from 1992 to 1994. The toxin was detected in 263 isolates from 94 cattle (detection rate: 24.3%). Verotoxin-producing E. coli (VTEC) was isolated from the cattle in 15 out of 17 prefectures, and the strains were divided into 33 serotypes. E. coli O157:H7 was isolated from 7 out of 387 cattle (detection rate: 1.8%) in four prefectures. These results suggest that VTEC is widely distributed in Japan and include a wide variety of serotypes.

Animals↗

PubMed1998

Correlation of residual stenosis immediately after coronary angioplasty with long-term prognosis.

This study evaluated the correlation of residual stenosis after percutaneous transluminal coronary angioplasty with the long-term prognosis. Among consecutive 1,230 patients who underwent coronary angioplasty in the National Cardiovascular Center in Osaka, Japan, 894 patients had de novo lesions. Of these, the 70 patients with acute myocardial infarctions and 105 with unstable angina who had emergency coronary angioplasties were excluded from the study. Among the remaining 719 patients, successful dilatation of the main target vessel was achieved in 592 patients, who then comprised the study group. They were divided into three groups according to their residual stenosis (RS) immediately after coronary angioplasty: group A, RS < 15% (n=208); group B, 15% < or = RS < or = 35% (n=286), and group C, 35% < RS < 50% (n=98). The duration of follow-up was 1,668, 1,660, and 1,680 days in group A, B, and C, respectively. The groups A, B, and C were not significantly different in terms of age, history of myocardial infarction, left ventricular ejection fraction, number of diseased vessels and target vessels, and risk factors such as hypertension, hyperlipidemia, and diabetes mellitus. Primary end point of follow-up was defined as death from any cause and the second end point was occurrence of cardiac events. Kaplan-Meier survival analysis showed significant differences among the three groups. Moreover, survival curves seem to be dependent on the degree of post-procedural residual stenosis. Multivariate analysis using a Cox proportional hazard regression model showed that age, ejection fraction, and residual stenosis were independent determinants of event-free, cardiac, and total survival. Residual stenosis immediately after coronary angioplasty is an independent contributor to long-term clinical prognosis in patients treated with successful balloon coronary angioplasty.

Analysis of Variance↗

PubMed1998

Plasma brain natriuretic peptide is a biochemical marker for the prediction of progressive ventricular remodeling after acute myocardial infarction.

To investigate the relation between plasma brain natriuretic peptide (BNP) and progressive ventricular remodeling, we measured plasma BNP and atrial natriuretic peptide (ANP) in 30 patients with acute myocardial infarction on days 2, 7, 14, and 30 after the onset. Left ventricular end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and ejection fraction (EF) on admission and 1 month after the onset were assessed by left ventriculography. Changes in EDVI (deltaEDVI), ESVI (deltaESVI), and EF (deltaEF) were obtained by subtracting respective acute-phase values from corresponding chronic-phase values. Plasma ANP on days 2 and 7 showed only weak correlations with deltaEDVI (r = 0.48 and 0.54; both p < 0.01), whereas plasma BNP on day 7 more closely correlated with deltaEDVI (r = 0.77; p < 0.001). When study patients were divided into two groups according to plasma BNP on day 7, the group with BNP higher than 100 pg/ml showed greater increases in left ventricular volume and less improvement in EF compared with the other group with BNP lower than 100 pg/ml (deltaEDVI = 10.4 +/- 8 vs -3.4 +/- 9 ml/m2, deltaESVI = 6.2 +/- 7 vs -4.9 +/- 5 ml/m2, and deltaEF = 1.0% +/- 4% vs 4.9% +/- 5%; p < 0.05, respectively). Multiple regression analysis revealed that only plasma BNP on day 7, but not ANP, peak creatine phosphokinase level, left ventricular end-diastolic pressure, or acute-phase EF, correlated independently with deltaEDVI (p < 0.01). These results suggest that plasma BNP may be a simple and useful biochemical marker for the prediction of progressive ventricular remodeling within the first 30 days of acute myocardial infarction.

Adult↗

PubMed1998

Pharmacokinetics and pharmacodynamics of FK143, a nonsteroidal inhibitor of steroid 5 alpha-reductase, in healthy volunteers.

The pharmacokinetics and pharmacodynamics of FK143, a new nonsteroidal inhibitor of steroid 5 alpha-reductase, were investigated in healthy volunteers, with use of plasma FK143 concentrations and serum dihydrotestosterone levels as an index for pharmacologic effects. The area under the plasma concentration-time curve from zero to infinity [AUC(0-infinity)] and maximum plasma concentration [Cmax] were increased dose proportionally after oral administration (100 to 500 mg) while subjects were in the fed state. The AUC(0-infinity) and Cmax after 500 mg oral administration during fed conditions were significantly larger than those during the fasted state, suggesting an increase of the absorption of FK143. Dihydrotestosterone concentrations after a single administration of FK143 (100 to 500 mg) during fed conditions decreased to about 65% of predose values and thereafter slowly recovered to the same levels as predose values at 168 hours. A combined pharmacokinetic-pharmacodynamic model was constructed with use of changes in dihydrotestosterone concentrations. The pharmacokinetic-pharmacodynamic profiles of FK143 after repeated administration were predictable with use of the pharmacokinetic-pharmacodynamic parameters obtained after a single administration of FK143.

5-alpha Reductase Inhibitors↗

PubMed1998

Vitamin C attenuates abnormal vasomotor reactivity in spasm coronary arteries in patients with coronary spastic angina.

OBJECTIVES: This study sought to examine effect of vitamin C, an antioxidant, on the abnormal vasomotor reactivity in spasm coronary arteries. BACKGROUND: Oxygen free radicals generated in the arterial walls have been shown to cause endothelial vasomotor dysfunction. METHODS: Responses of the epicardial arterial diameters of the left coronary arteries to the intracoronary infusion of acetylcholine (ACh) (10 and 50 microg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of vitamin C (10 mg/min) or saline as a placebo in 32 patients with coronary spastic angina and in 34 control subjects. RESULTS: Vitamin C infusion suppressed the constrictor response of the epicardial diameter to ACh in spasm coronary arteries but had no significant effect in the control coronary arteries (percent change in distal diameter in response to 10 microg/min of ACh [constriction (-), dilation (+), mean +/- SEM] before vitamin C: -8.2 +/- 2.9% in spasm arteries, +8.4 +/- 2.9%* in control arteries; during vitamin C: +0.2 +/- 3.8%* in spasm arteries, +7.2 +/- 1.3%* in control arteries [*p < 0.01 vs. spasm arteries before vitamin CI). The coronary sinus-arterial difference in plasma thiobarbituric acid reactive substances during ACh infusion, an indicator of lipid peroxidation in coronary circulation, was higher in patients with coronary spastic angina than in control subjects (p < 0.01) but was suppressed in patients with coronary spastic angina to comparable levels in control subjects by combined infusion of vitamin C. Saline infusion had no effect. CONCLUSIONS: The results indicate that vitamin C attenuates vasomotor dysfunction in epicardial coronary arteries in patients with coronary spastic angina. Oxygen free radicals may at least in part play a role in the abnormal coronary vasomotor reactivity in response to ACh in spasm coronary arteries.

Acetylcholine↗