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Biomedical subjects

Jun Watanabe

Publications and source records attributed to Jun Watanabe.

107 records · Page 6Linked to original sources
PubMed2003

Characteristics and 1-year prognosis of medically treated patients with chronic heart failure in Japan.

The study was designed to characterize patients with chronic heart failure (CHF) in Japan in terms of the etiologies and prognosis. CHF was defined by ejection fraction (EF >or=50%), left ventricular diastolic dimension (LVDD >or=55 mm) or a past history of congestive heart failure. Among the 721 recruited patients, the most frequent etiology for CHF was dilated cardiomyopathy (DCM) in patients aged less than 59 years, and valvular heart disease (VHD) in those aged 70 years or more. The 1-year crude mortality was 8% overall and 12% in patients with myocardial infarction (MI). Sudden death accounted for 40% of the total deaths among all patients, and 60% in patients with MI. Multivariate logistic regression analysis showed that brain natriuretic peptide (BNP) was a consistent prognostic marker in CHF patients with a variety of etiologies. Total death and hospitalization because of heart failure were significantly less frequent in patients with BNP less than 100 pg/ml. In conclusion, the etiologies of Japanese CHF appear to be more diverse than those of other Western countries, but BNP is an excellent prognostic marker despite the etiological diversity. Sudden, unexpected death in CHF patients is also a serious problem in Japan. A nation-wide epidemiologic study should be done to characterize Japanese CHF.

Aged↗
PubMed2003

Polyphenols from some foodstuffs as inhibitors of ovalbumin permeation through caco-2 cell monolayers.

Some spices showed high inhibitory activity against ovalbumin permeation through Caco-2 cell monolayers. Pimentol from allspice, rosmarinic acid and luteolin-7-O-beta-glucuronide from thyme, quercetin-3-O-beta-glucuronide from coriander and rutin from tarragon were identified as the active principles. A structure-activity relationship study among the active isolates and their related compounds indicated that the presence of a catechol structure played an important role in the inhibitory activity of each compound.

Anti-Allergic Agents↗
PubMed2003

Varieties of right ventricular diastolic function in patients with non-obstructive hypertrophic cardiomyopathy.

We examined whether differences in the location of myocardial hypertrophy influence the right ventricular diastolic function in patients with non-obstructive hypertrophic cardiomyopathy using cineangiography. Biplane right ventriculography was performed in 34 subjects (normal = 14, asymmetric septal hypertrophy = 9, apical hypertrophy = 11) during cardiac catheterization. In patients with asymmetric septal hypertrophy, compared with apical hypertrophy and normal groups, the indices of the right ventricular diastolic function including right ventricular peak filling rate and filling fraction of rapid filling phase were lower and the time to peak filling rate was prolonged. But in patients with apical hypertrophy, these indices were not significantly different compared with normal. There were no differences in right ventricular ejection fraction and cardiac index among the three groups. These data suggest that the location of the myocardial hypertrophy of the left ventricle is a significant factor affecting the right ventricular diastolic filling in non-obstructive hypertrophic cardiomyopathy.

Adult↗
PubMed2003

Are novel scavenger-like receptors involved in the hepatic uptake of heparin?

Heparin is an anionic macromolecular drug. It has been widely used as an anticoagulant, and numerous efforts to clarify the mechanism of its disposition in the body have been made to help expand its clinical applications, using its newly found biological activities, as well as to further improve its use in anticoagulant therapy. It has now been shown that heparin is taken up extensively not only by Kupffer cells but also by parenchymal cells in the liver, the major distribution organ, and a receptor-mediated endocytotic mechanism, which is shared by heparin analogs and various anionic macromolecules, is responsible for heparin uptake in both types of cells. Although the characteristics of the receptors for heparin in both cells have lots of similarities to those of scavenger receptors, the receptors in parenchymal cells do not accept acetylated low density lipoprotein (Ac-LDL) as a ligand, which is the only striking difference between them and major scavenger receptors. Although the receptors in Kupffer cells, which accept Ac-LDL as a ligand, may belong to class A scavenger receptors, this remains to be established. We therefore conclude at present that it is likely that novel scavenger-like receptors for heparin (heparin receptors) or unidentified scavenger receptors are responsible for heparin uptake in the liver.

Journal Article↗
PubMed2003

Incidence and characteristics of pulmonary thromboembolism in Japan 2000.

OBJECTIVE: The incidence of pulmonary thromboembolism (PTE) is much lower in Japan than in the United States. The number of deaths from PTE, however, has gradually increased. The present study was designed to investigate the incidence and characteristics of PTE in Japan. METHODS AND MATERIALS: We sent 5,582 questionnaires to inquire about the number of new cases of PTE between August 1, 2000 and September 30, 2000. RESULTS: We received 1,702 replies and 205 new cases were registered. The number of new cases per year was 4,022 (95% confidence interval: 3,704-4,305) and the incidence was 32 (95% confidence interval: 29.2-33.9) patients per 1,000,000 people per year. Main risk factors were immobilization, surgery, trauma, and malignancy. The mortality within a month and 6 months was 16% and 20%, respectively. Half of the deaths within a month occurred on the diagnosis day. CONCLUSION: The results showed that the incidence of PTE in Japan 2000 tended to increase compared with that in 1996, but it was still much lower than that in the United States.

Age Distribution↗
PubMed2002

Investigation of transport mechanism of pentazocine across the blood-brain barrier using the in situ rat brain perfusion technique.

To characterize pentazocine (PTZ) transport across the blood-brain barrier (BBB), the cerebrovascular permeability-surface area product (PS(inf)) of PTZ was determined by a well-established in situ rat brain perfusion technique. The uptake kinetics of PTZ by the rat brain exhibited saturability, which indicates the simultaneous mechanisms of carrier-mediated transport and passive diffusion. The kinetic parameters were estimated as follows: maximal influx rate (V(max)), 27.2 +/- 5.2 nmol/s/g brain; apparent Michaelis constant (K(m)) for the saturable component of PTZ uptake, 2.9 +/- 0.5 mM; nonsaturable uptake rate constant (K(d)), 1.5 +/- 0.3 microL/s/g brain. BBB transport of PTZ was significantly inhibited by cationic drugs such as diphenhydramine, propranolol, and eptazocine (a narcotic-antagonist analgesic), but not by choline, suggesting that the PTZ transport system is shared by cationic drugs. Furthermore, co-perfusion of verapamil caused a significant (two-fold) increase in the BBB permeability to PTZ. This finding indicates that PTZ may be a substrate of the endogenous BBB efflux transport system, P-glycoprotein. These findings demonstrate that the primary mechanism governing the uptake of PTZ by the brain is carrier-mediated transport, not passive diffusion.

Animals↗
PubMed2002

Effect of angiotensin converting enzyme inhibition on myocardial phosphoinositide metabolism visualised with 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol in myocardial infarction in the rat.

We recently reported that myocardial phosphoinositide (PI) metabolism can be visualised by 1-[1-11C]-butyryl-2-palmitoyl-rac-glycerol (11C-DAG) in rats with myocardial infarction (MI). Angiotensin II, the receptors for which are expressed predominantly in infarcted areas with active fibrogenesis rather than in non-infarcted regions, is involved in the upstream signalling systems of PI metabolism and plays an important role in the process of left ventricular (LV) remodelling after MI. We therefore hypothesised that the distribution of 11C-DAG after MI may be affected by the inhibition of angiotensin converting enzyme, which is one of the most important factors in the development of LV remodelling after MI. Rats were injected with 11C-DAG after 3 or 10 weeks of treatment with captopril or no treatment following coronary artery ligation, and quantitative autoradiography was performed. Cells occupying the infarcted region were identified by immunohistochemistry. Compared with untreated rats, treatment with captopril for 3 weeks after MI elicited a reduction in the 11C-DAG uptake in the infarcted region (P<0.05) but not in the non-infarcted region, and was associated with a 22% decrease in the heart weight/body weight ratio. The thallium-201 distribution in the infarcted area was similarly low in the rats with and rats without the 3-week captopril treatment after MI. Abundant macrophages and myofibroblasts occupied the infarcted area in both rats with and rats without the captopril treatment for 3 weeks after MI. The 11C-DAG radioactivity in the infarcted region in the untreated rats was lower 10 weeks after MI than 3 weeks after MI (P<0.01). This finding was in agreement with the results of immunohistochemistry demonstrating that the number and size of macrophages and myofibroblasts were remarkably reduced in rats 10 weeks after MI compared with 3 weeks after MI. Captopril treatment for 10 weeks after MI did not decrease the 11C-DAG radioactivity in the infarcted area further. These data suggest that 11C-DAG is useful for visually detecting regions with activated PI metabolism after MI, and that captopril reduces PI metabolism in the infarcted region in the relatively early phase of MI, which might contribute to the attenuation of ventricular remodelling.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Normal and oxidized low density lipoproteins accumulate deep in physiologically thickened intima of human coronary arteries.

Diffuse intimal thickening (DIT) that develops as a physiologic adaptation in the arterial wall has been implicated to have a predilection for atherosclerosis. We histologically investigated the lipid accumulation process in the human coronary DIT by focusing on the localization of normal and oxidized low-density lipoproteins (LDLs). Immunohistochemistry for apolipoprotein B 100 (a major apolipoprotein of LDL) and 8-iso-prostaglandin F(2alpha) (an oxidative product in LDL) showed substantial accumulation of oxidized relative to normal LDLs in the deep layers of DIT (52/139 segments). Subendothelial deposition of normal rather than oxidized LDLs, known as an early event of fatty streak formation, was less frequently found (13/139 segments). In contrast with fibrofatty lesions, lipid accumulation localized deep in DIT was characterized by fine lipid droplets scattered in the preserved tissue and by its association with neither macrophage accumulation nor apoptosis in the constituent cells. On the other hand, the deep intimal location of lipid accumulation clearly coincided with increased type I and type III collagen and elastic fibers but rarely with sulfated proteoglycans including decorin, which were all strongly expressed in advanced lesions. This lipid accumulation was found only in sites with DIT of more than 200 micro m, occasionally extending to the inner media and involving neovessel formation around it. The presence of deep intimal lipid accumulation was associated with reduced endothelium-dependent relaxation to substance P in isolated coronary rings. These results suggest that normal and oxidized LDLs accumulate preferably in the nutritional border zone of established DIT involving local extracellular matrix alterations but independently of inflammatory or apoptotic processes. This may contribute to the functional and morphologic abnormalities seen in human coronary atherogenesis that progresses slowly with age.

Adult↗
PubMed2002

Investigation on the influx transport mechanism of pentazocine at the blood-brain barrier in rats using the carotid injection technique.

The influx transport mechanism of pentazocine (PTZ) at the blood-brain barrier (BBB) was investigated in rats using the carotid injection technique. The uptake kinetics of PTZ into the rat brain exhibited saturability, which occurred by both nonsaturable and carrier-mediated transport processes. The in vivo kinetic parameters were estimated as follows: the maximal uptake rate (Jmax), 3.6 +/- 1.2 micromol/min/g brain and the apparent Michaelis constant (K1), 3.7 +/- 1.7 mM for the saturable component of PTZ into the brain, and the nonsaturable uptake rate constant (Kd), 0.06 +/- 0.04 ml/min/g brain. The uptake of PTZ by the brain was strongly inhibited by lidocaine, imipramine and propranolol, and also by H1-antagonists such as mepyramine, diphenhydramine. In addition, narcotic-antagonist analgesic (buprenorphine, butorphanol or eptazocine) and an opioid antagonist (naloxone) significantly inhibited PTZ transport. These results suggest that PTZ permeates into the brain via a carrier-mediated transport system, which may widely recognize the cationic drugs.

Animals↗
PubMed2002

Dissolution tests for self-setting calcium phosphate cement-containing nifedipine.

Nifedipine-containing calcium phosphate cement (CPC) was prepared, and nifedipine (NF) release from this preparation was evaluated by the shaking method (SK), Japanese Pharmacopoeia XIV (JPXIV) paddle method (PD), and JPXIV flow-through cell method (FT). The release of NF from the CPC preparation continued for 7 d or longer by all these methods. This suggests that the release of NF can be controlled by preparing NF-containing CPC. The release pattern of NF from CPC in these tests was found to follow the Higuchi equation. However, the Higuchi constant differed among the three dissolution tests, probably because the apparent tortuosity of capillary system (tau) varied.

Calcium Channel Blockers↗
PubMed2002

Evaluation of heart-rate turbulence as a new prognostic marker in patients with chronic heart failure.

The significance of heart-rate turbulence (HRT) in patients with chronic heart failure (CHF) was evaluated to examine whether it is sensitive to the risk of ventricular tachycardia (VT). HRT is reported to predict the prognosis after myocardial infarction (MI), but its prognostic value in patients with CHF remains unknown. HRT was measured in 50 CHF patients (left ventricular ejection fraction <50% and/or left ventricular end-diastolic diameter >55 mm, 34 cardiomyopathy, 16 post-MI) and 21 patients without obvious heart diseases (control). HRT slope and HRT onset were measured by the original definitions using digitized Holter ECG recordings. Cardiac pump function was assessed by echocardiography. The value of the HRT slope was significantly lower in CHF than in control (3.7 +/- 1.7 vs 16.4 +/- 5.3, mean +/- SD, p < 0.01). The value of the HRT onset in patients with CHF was significantly higher than that in control patients (-1.1 +/- 1.9 vs -3.6 +/- 1.7, mean +/- SD, p < 0.05). The HRT slope and onset in CHF patients with VT were nearly identical to those without VT. The HRT slope appears to be a powerful prognostic marker that shows significant differences between CHF subgroups when divided by clinical events; that is, CHF death and CHF hospitalization. However, it has limited value for predicting fatal ventricular arrhythmias.

Adult↗
PubMed2002

An active compound against allergen absorption in hypoallergenic wheat flour produced by enzymatic modification.

Hypoallergenic wheat flour produced by modification with cellulase and actinase showed inhibitory activity against ovalbumin permeation in an in vitro model by using the Caco-2 cell monolayer. The activity was found in the cellulase preparation used for producing the flour. An active compound was isolated by HPLC and identified as Trp-Ser-Asn-Ser-Gly-Asn-Phe-Val-Gly-Gly-Lys by 1H-NMR data and Edman degradation. The undecapeptide, some oligopeptides with the N-terminal sequences and Trp ethyl ester showed activity at 10(-7) M, acetyl Trp being active at 10(-2) M. These data suggest that the Trp residue without a free carboxyl group would be required for the inhibitory activity of ovalbumin absorption through the intestinal tract.

Absorption↗
PubMed2002

Post-endsystolic active shortening in the non-ischemic region impairs left ventricular pressure fall in acute ischemic heart.

To investigate the relation between the impairment of isovolumic relaxation and the regional wall motion in acute ischemia, the left ventricular pressure fall and regional myocardial motion were examined in the relaxation phase in dogs during both acute coronary artery occlusion (n = 12) and a regional coronary flow reduction (n = 6). Fifteen to 40 seconds after complete coronary artery occlusion or in the stable state after a regional coronary flow reduction by 70 to 90% of the control state, a shortening of the non-ischemic region at the early isovolumic relaxation phase (the post-endsystolic shortening) appeared, combined with lengthening of the ischemic region. In these situations, the logarithmic plots of the left ventricular pressure fall was composed of two components (time constant of early part [Ta] and at latter part [Tb]). Ta was greater than Tb (64.3 +/- 13.8 milliseconds vs. 36.6 +/- 10.4 milliseconds at 15 seconds after coronary occlusion, p < 0.01; 67.6 +/- 22.9 milliseconds vs. 45.1 +/- 17.5 milliseconds at flow reduction, p < 0.01) and the time constant at control (p < 0.01). These findings suggested that post-endsystolic shortening in the non-ischemic region played a role in a the non-uniformity of the left ventricular contraction and contributed to the impairment of the left ventricular pressure fall in acute regional ischemia, especially in early isovolumic relaxation.

Acute Disease↗
PubMed2002

Metabolic extraction of nifedipine during absorption from the rat small intestine.

Nifedipine is one of drugs that have been suggested to undergo significant first-pass metabolism by cytochrome P450 (CYP) 3A in the intestine, based mainly on pharmacokinetic analyses of in vivo observations. To further substantiate this suggestion, we examined the metabolic extraction of nifedipine from the rat small intestine, using intestine perfused in situ by a single-pass technique and microsomes in vitro. When the intestinal lumen was perfused with nifedipine solution (30 microM) at the flow rate of 0.15 mL/min and steady-state was achieved, the fraction that disappeared from the intestinal lumen (F(a)) and the fraction absorbed into the mesenteric venous blood (F(a,b)) was 0.26 and 0.13, respectively. Thus, F(a,b) was 50% smaller than F(a), indicating a significant extraction of nifedipine during passage through the intestinal mucosa. When ketoconazole (40 microM), a specific inhibitor of CYP3A, was added to the perfusion solution, F(a,b) was increased to a level comparable with F(a), while F(a) remained unchanged, suggesting the complete inhibition of metabolic extraction by CYP3A. A similar result was obtained for cyclosporin A (40 microM), another specific CYP3A inhibitor. In intestinal microsomes, the metabolic degradation of nifedipine (1 microM) was almost completely inhibited by ketoconazole (10 microM) and cyclosporin A (10 microM), consistent with the results in the perfused intestine. It was also found in intestinal microsomes that anti-rat CYP3A2 antibody can inhibit nifedipine metabolism completely. Thus, the present study demonstrates that nifedipine undergoes significant extraction during passage through the intestinal mucosa, and provides substantial evidence that CYP3A2 is responsible for that.

Journal Article↗