Biomedical subjects

M Waki

Publications and source records attributed to M Waki.

134 records · Page 8Linked to original sources

PubMedDate not supplied

Effect of topically applied iganidipine dihydrochloride, a novel calcium antagonist, on optic nerve head circulation in rabbits.

PURPOSE: To study the effect of topically applied iganidipine dihydrochloride (iganidipine), a novel water-soluble calcium channel blocker, on blood flow in the optic nerve head (ONH), intraocular pressure, and systemic blood pressure in rabbits. METHODS: After 0.1% iganidipine (20 microL) was instilled into normal eyes, the change in ONH blood flow was measured using a hydrogen gas clearance flowmeter. Iganidipine (0.0001% to 0.1%) was instilled into eyes with impaired ocular circulation before or after the intravitreal injection of endothelin-1, and the change in ONH blood flow was measured. Changes in intraocular pressure and blood pressure after instillation of 0.1% iganidipine were measured. In all experiments, physiological saline was instilled into the contralateral eye as a control. RESULTS: Iganidipine significantly increased the ONH blood flow in normal eyes with the maximum increment of 31.7% at 45 minutes after instillation. Preinstillation of 0.01% and 0.1% iganidipine significantly inhibited the decrease in ONH blood flow in the eyes with impaired circulation. Moreover, ONH blood flow recovered with postinstillation of 0.1% iganidipine. These effects were persistent. Instillation of 0.1% iganidipine did not change either the intraocular pressure or the blood pressure. CONCLUSION: The instillation of iganidipine persistently increased and maintained the ONH blood flow in rabbit eyes with normal and impaired ocular circulation.

Administration, Topical↗

PubMedDate not supplied

Effects of soy protein diet on the expression of adipose genes and plasma adiponectin.

Many studies have reported the cholesterol-lowering, anti-lipogenic, anti-obesity and anti-hypertensive effects of soy protein. Adipose tissue-specific plasma protein, adiponectin, has anti-atherogenic and anti-insulin-resistance properties. Here, we investigated the effects of soy protein diet on body fat composition, plasma glucose, lipid and adiponectin levels and expression of genes involved in glucose and fatty acid metabolism in obese KK-A y mice. Body weights and adipose tissue weights of mesenteric, epididymal, and brown fat were lower in mice on calorie-restricted diet containing soy protein isolate. Plasma cholesterol, triglyceride, free fatty acid, and glucose levels were also decreased by this diet. Body fat content and plasma glucose levels in mice on a soy protein isolate diet were still lower than those treated with an isocaloric casein-protein-diet. Among the genes related to glucose and fatty acid metabolism, adiponectin mRNA levels in adipose tissue and adiponectin plasma concentrations were elevated in mice on a calorie-restricted diet, although there were no significant differences between soy protein and casein protein groups. Our results indicate that that soy protein diet decreased body fat content and plasma glucose levels more effectively than isocaloric casein-protein diet in obese mice.

Adiponectin↗

PubMedDate not supplied

Involvement of oxygen free radicals in experimental retinal ischemia and the selective vulnerability of retinal damage.

Protective effects of CV-3611, a free radical scavenger, on retinal ischemic injury in the rat and on glutamate-induced cytotoxicity in a cell line were evaluated. Transient retinal ischemia was induced by raising intraocular pressure of rats to 110 mm Hg for 45 min, and the electroretinogram (ERG) was measured to evaluate retinal function. No ERG could be recorded immediately after reperfusion, and thereafter the ERG gradually recovered. Recovery of the a-wave latency and the amplitudes of the a and b waves in the CV-3611-treated (10 mg/kg, p.o.) group were significantly better than those in the control group up to 24 h after reperfusion. In both the control and CV-3611 group, the b wave showed better recovery than the a wave up to 6 h after reperfusion, while the relationship was reversed after 24-hour reperfusion. Glutamate (10 mM)-induced cytotoxicity in the N18-RE-105 cell, a neural retina-neuroblastoma hybridoma, was quantified by measuring lactate dehydrogenase. Three and 10 microM of CV-3611 significantly attenuated the glutamate-induced cytotoxicity in N18-RE-105 cells. Thus, the radical scavenger (CV-3611) promoted the recovery of retinal function after ischemia-reperfusion injury and ameliorated glutamate-induced cytotoxicity. These results suggest that oxygen free radicals play an important role in the early phase of retinal ischemic injury. Moreover, differential recovery processes of the a and b waves after ischemia suggest that the selective vulnerability of the retina to ischemia could change functionally during the period of reperfusion.

Animals↗

PubMedDate not supplied

A 1-year follow-up study on the effect of atenolol on serum beta 2-microglobulin level in hypertensive diabetic patients.

Hypertensive diabetic patients are particularly prone to renal function impairment. A total of nine out-patients with diabetes and hypertension were, therefore, entered into this single-blind uncontrolled study on the effects of 50 mg/day atenolol on reducing blood pressure and preserving normal kidney functioning. Treatment and evaluations were continued for 12 months. Serum beta 2-microglobulin concentration was used as the index for measuring renal impairment. Atenolol significantly reduced heart rate, systolic and diastolic blood pressure, and serum beta 2-microglobulin concentrations compared with baseline. Plasma glucose and glycosylated haemoglobin levels were unchanged, and blood urea nitrogen levels were increased slightly (non-significant). Serum creatinine showed a tendency (non-significant) to reflect the changes in beta 2-microglobulin concentration. Ways in which atenolol may act to improve kidney functioning are suggested. It is concluded that atenolol is a favourable choice for the treatment of hypertension in diabetic patients with normally functioning kidneys since, even in long-term use, normal renal functioning is preserved.

Atenolol↗

PubMedDate not supplied

Opioid activities of morphiceptin-like peptides latent in various natural proteins.

The Tyr-Pro-Phe peptide sequence, an N-terminal tripeptide fragment of opioid peptide morphiceptin, was searched on the database SEQDB (Peptide Institute, Osaka). More than 30 proteins were drawn in a list with 15 amino acid varieties at the position adjacent to Phe. Seven morphiceptin-like peptides with the H-Tyr-Pro-Phe-Xxx-NH2 sequence, where Xxx denotes the selected amino acids (Ala, Asp, Gly, Gln, Lys, Thr and Tyr), have been synthesized. Together with the side-chain protected analogs [Asp(OBzl), Lys(Z), and Thr(Bzl)], they have been evaluated for opioid activities. For the mu opioid receptors to which morphiceptin binds specifically and selectively, analogs with Xxx = Asp, Lys, Ala, Thr, Gln, Tyr and Gly showed a considerably weaker binding affinity than morphiceptin. In contrast, the Thr(Bzl) derivative demonstrated an affinity ten times greater than morphiceptin. Because of an extremely weak affinity for the delta receptors, its mu-selectivity became very high (260-fold). The present results and the increased activity of [Val4]morphiceptin (Sakaguchi et al., 36) indicate that the mu receptors tolerate the hydrophobic or aromatic residue at the site corresponding to position 4 of morphiceptin. When the circular dichroism (CD) spectra are compared between active and inactive analogs, no significant difference is found in both water and methanol. This suggests that the activity of morphiceptin analogs with the Tyr-Pro-Phe sequence is mainly determined by the structural characters of the amino acid residue in position 4 rather than by the molecular conformation. The results suggested a possible formation of morphiceptin-like peptides in various protein digests.

Amino Acid Sequence↗

PubMedDate not supplied

Design and synthesis of dimeric analogs of neurokinin A and B: effect of dimerization of COOH-terminal heptapeptides on receptor selection.

Dimeric analogs of neurokinin A and neurokinin B COOH-terminal heptapeptides were synthesized in order to examine the effect of ligand dimerization on the receptor selection. Dimerization was carried out at the NH2-terminus of peptides with succinic acid, yielding succinyl bis[Asp-Ser-Phe-Val-Gly-Leu-Met-NH2] (D-NKA4-10) and succinyl bis[Asp-Phe-Phe-Val-Gly-Leu-Met-NH2] (D-NKB4-10). In the assay using rat vas deferens (RVD), it was found that the deletion of the NH2-terminal tripeptide from native neurokinin A or B enhances the activity 1.5- to 8-fold, resulting in formation of NK-2 receptor specific ligands NKA4-10 and NKB4-10. When dimeric analogs of these shortened peptides, namely D-NKA4-10 and D-NKB4-10, were examined in RVD and guinea pig ileum (GPI), they were fairly potent in GPI, but not in RVD. Under conditions in which the NK-1 receptors in GPI were desensitized with NK-1 specific substance P methyl ester, dimers reduced the activity drastically, while the corresponding monomers exhibited unchanged activity. These results suggest that dimerization of the COOH-terminal heptapeptide of neurokinins changes the receptor selection of peptides from NK-2 to NK-1, and that the NK-1 receptor has a structure favorable to a dimeric peptide ligand.

Amino Acid Sequence↗

PubMedDate not supplied

Long-term serum lipid lowering, behavior modification, and weight loss in obese women.

Reduced calorie intake, changes in the composition of foods ingested, and increased physical activity are the usual initial recommended therapies for the obesity that often accompanies hypercholesterolemia and other hyperlipidemias. Collectively resulting in weight loss, these behavioral changes are known to produce short-term (< or = 7- to 9-mo) reductions in serum cholesterol and other lipids. In contrast, previous long-term (> or = 1-yr) investigations fail to disclose a cholesterol-lowering effect of weight loss, although the subjects in these studies were not hypercholesterolemic. The aim of our investigation was to examine the long-term changes in serum lipids that occurred in a representative cohort of healthy obese (n = 45, body mass index mean +/- SD 39.0 +/- 8.6 kg/m2) women after they completed a 15-wk conventional behavior-modification program. The serum cholesterol level of this cohort was elevated at baseline (6.18 +/- 1.41 mM, > or = 75th percentile). At the time of follow-up (17.0 +/- 7.0 mo), there were significant decreases in body weight (-16.7 kg, p < 0.001) and reductions in serum total (-0.53 mM, p < 0.01) and low-density lipoprotein (-0.35 mM, p < 0.05) cholesterol. Serum triglyceride levels also decreased significantly (-0.38 mM, p < 0.001), and serum high-density lipoprotein levels remained unchanged; the ratio of high-density lipoprotein total cholesterol increased significantly (p < 0.05) relative to baseline levels. Multiple stepwise regression analysis indicated that the best predictor of percentage change in each respective lipid was its own baseline level.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMedDate not supplied

Comparative blood compatibility of polyether vs polycarbonate urethanes by epifluorescent video microscopy.

The segmented polyether urethanes (PEUs) have been used in implantable medical devices due to excellent mechanical properties, acceptable blood compatibility, and good biostability. However, recent studies demonstrate that the polyether soft segment of PEU is susceptible to oxidative degradation in vivo due to scission of the polyether group. Recently, polycarbonate urethanes (PCUs) having no ether linkage in the soft segment have been developed, and show improved stability against oxidative degradation over PEUs. The current study evaluates blood compatibility of these PCUs in comparison with PEUs using epifluorescent video microscopy (EVM) combined with a parallel plate flow cell. The authors selected two PCUs, Corethane 80A (Corvita Corporation, Miami, FL) and PCU(1560), and two PEUs, Pellethene 2363-80AE (Dow Chemical Japan, Tokyo, Japan) and Tecoflex EG80A (Thermedics, Inc., Woburn, MA), all of which have similar hard segment compositions (MDI or HMDI:1,4-butanediol(BD)) and the same hardness of 80A. The EVM measured the amount of platelet coverage on the surfaces using human whole blood perfused at a wall shear rate of 100/sec for 20 min. Complement activation (C3a) also was measured. Both PEUs, especially Pellethane, showed significantly higher platelet adhesion than the PCUs (p < 0.05). There were no significant differences in platelet adhesion between the two PCUs. As for C3a measurements, Tecoflex showed higher complement activation than the others. Based on these results, it is recommended that PEUs should be replaced by ether free PCUs for use in implantable blood contacting devices such as artificial hearts and pacemaker lead insulators.

Biocompatible Materials↗