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Biomedical subjects

Y Kawashima

Publications and source records attributed to Y Kawashima.

At least 55 records · Page 3Linked to original sources
PubMed2000

Utilization of poly(DL-lactide-co-glycolide) nanoparticles for preparation of mini-depot tablets by direct compression.

PURPOSE: The objectives of this study were to prepare the long-acting matrix tablets by direct compression of the mixture of drug and poly(DL-lactide-co-glycolide) (PLGA) nanoparticles and to clarify the effects of such factors as polymer species, mixing ratio of nanoparticles with different molecular weights, and the tablet weight on the drug release and to discuss the mechanism of drug release from matrix tablets. In addition, mini-matrix tablets were prepared to investigate the possibility of application as an implantable dosage form. METHODS: PLGA nanoparticles were prepared by the modified spontaneous emulsion solvent diffusion method. The matrix tablets were prepared by direct compression of mixtures of drug and nanoparticles, and then the release properties, swelling properties and changes in molecular weight of PLGA during the release test were evaluated. RESULTS: The drug showed the biphasic release patterns from all matrix tablets; i.e. a portion of the drug was released rapidly (the initial release phase), the release stopped for a long period (the lag time), and then the residual drug was released (the second release phase). Matrix tablets with various biphasic release patterns could be prepared by altering the molecular weight or copolymer ratio of PLGA. The addition of nanoparticles of low molecular weight PLGA to those of high molecular weight reduced the release rate at the initial release phase, but that at the second release phase was almost entirely unaffected by mixing ratio. Also, the release patterns could be changed by altering the tablet weight and size, but the amounts released per unit of surface area were the same. Hydration analysis suggested that the initial release rates were correlated well with the swelling properties of tablets. CONCLUSION: This system had advantages in terms of simplicity in design and predictability of drug release rate and may be useful as an implantable dosage form.

Delayed-Action Preparations↗
PubMed2000

Induction by perfluorinated fatty acids with different carbon chain length of peroxisomal beta-oxidation in the liver of rats.

The potency of the induction of peroxisomal beta-oxidation was compared between perfluorinated fatty acids (PFCAs) with different carbon chain lengths in the liver of male and female rats. In male rats, perfluoroheptanoic acid (PFHA) has little effect, although perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) potentially induced the activity. By contrast, PFHA and PFOA did not induce the activity of peroxisomal beta-oxidation in the liver of female rats while PFNA and PFDA effectively induced the activity. The induction of the activity by these PFCAs was in a dose-dependent manner, and there is a highly significant correlation between the induction and hepatic concentrations of PFCAs in the liver regardless of their carbon chain lengths. These results strongly suggest that the difference in their chemical structure is not the cause of the difference in the potency of the induction. Hepatic concentrations of PFOA and PFNA was markedly higher in male compared with female rats. Castration of male rats reduced the concentration of PFNA in the liver and treatment with testosterone entirely restored the reduction. In contrast to the results obtained from the in vivo experiments, the activity of peroxisomal beta-oxidation was induced by PFDA and PFOA to the same extent in cultured hepatocytes prepared from both male and female rats. These results, taken together, indicate that difference in accumulation between PFCAs in the liver was responsible for the different potency of the induction of peroxisomal beta-oxidation between PFCAs with different carbon chain lengths and between sexes.

Acyl-CoA Oxidase↗
PubMed2000

Prevalence of anorexia nervosa and bulimia nervosa in a geographically defined area in Japan.

OBJECTIVE: Little has been understood regarding the frequency of eating disorders in Japan. This study was designed to identify the prevalence of anorexia nervosa (AN) and bulimia nervosa (BN) in Japan. METHOD: We asked doctors in all of the relevant medical facilities (130 hospitals and 1,326 clinics) in Niigata Prefecture to report patients with DSM-IV-diagnosed eating disorders who appeared or were admitted between 20-24 October 1997. The response rate was 94.4%. RESULTS: The estimated point prevalences of AN and BN were 4.79 and 1.02, respectively, per 100,000 females. Specifically for the age group of 15-29 years, the prevalence of AN was 17.10 and that of BN 5.79. DISCUSSION: The prevalence of AN and BN in Japan is lower than that for European Caucasian populations. This result may be due to cultural and ethnic differences and/or it may be a transient phenomenon.

Adolescent↗
PubMed2000

Left ventricular myocardial remodeling and contractile state in chronic aortic regurgitation.

BACKGROUND: In chronic aortic regurgitation, eccentric hypertrophy, with combined concentric hypertrophy of the left ventricle, is an important adaptive response to volume overload, which in itself is a compensatory mechanism for permitting the ventricle to normalize its afterload and to maintain normal ejection performance (physiologic hypertrophy). However, progressive dilatation of the left ventricle leads to depressed left ventricular (LV) contractility and myocardial structural changes, including cellular hypertrophy and interstitial fibrosis (pathological hypertrophy). HYPOTHESIS: The study was undertaken to determine the relationship between left ventricular myocardial structure and contractile function in 14 patients with chronic aortic regurgitation by cardiac catheterization and endomyocardial biopsies. METHODS: Myocardial cell diameter and percent interstitial fibrosis were obtained from biopsy samples. Contractile function was evaluated from the ratio of end-systolic wall stress to end-systolic volume index (ESS/ESVI) and the ejection fraction-end-systolic stress (EF-ESS) relationship, which was obtained from 30 normal control subjects. RESULTS: Myocardial cell diameter correlated significantly with the ESVI (r = 0.72, p < 0.005), ejection fraction (r = -0.58, p < 0.05), and ESS/ESVI (r = -0.58, p < 0.05). The percent interstitial fibrosis also correlated inversely with ESS/ESVI (r = -0.71, p < 0.005). Compared with very few patients with an ESVI < 70 ml/m2, the majority of patients with ESVI > or = 70 ml/m2 had a cell diameter of > or = 30 microns and a percent interstitial fibrosis of > or = 10%. The nine patients who had depressed contractile function, as assessed from the EF-ESS relationship, had a higher percent interstitial fibrosis (p < 0.05) than five patients showing a normal EF-ESS relationship, despite the fact that there was no significant difference in myocardial cell diameter between them. Thus, advanced cellular hypertrophy and excessive interstitial fibrosis were significantly and independently associated with myocardial contractile dysfunction and appeared to be responsible for ventricular remodeling. CONCLUSION: Our findings suggest that in many patients with aortic regurgitation, eccentric hypertrophy changes its nature from physiologic to nonphysiologic during the earlier stages in the course of the disease rather than during the stage described previously.

Adolescent↗
PubMed2000

Immunolocalization of TGF-beta1, -beta2, and -beta3, and TGF-beta receptors in human lens capsules with lens implants.

PURPOSE: To establish the alteration in expression pattern of transforming growth factor (TGF)-betas and their receptors during repair of lens capsules after cataract surgery, we immunohistochemically located TGF-beta isoforms and their receptors in human lens capsules before and after cataract surgery. METHODS: Ten post-cataract surgery capsular specimens were obtained during vitrectomy. Three sections of the anterior capsules were obtained during cataract surgery. A whole lens capsular bag immediately after lens extraction was obtained during vitrectomy. Cryosections of these specimens were processed for immunohistochemical analysis for TGF-beta1, TGF-beta2, TGF-beta3, TGF-beta receptor type I (TbetaR-I), type II (TbetaR-II) and type III (TbetaR-III), and were observed under light micros-copy. RESULTS: Lens epithelial cells (LECs) lining the inner surface of the anterior capsules exhibited immunoreactivity for TGF-beta2 and TbetaR-II. Immunoreactivity for TGF-beta1, -beta3, TbetaR-I and TbetaR-III was negative. In the whole capsular bag specimen, equatorial LECs were positive for TGF-beta1 and -beta2, but not for -beta3. In post-cataract surgery specimens, antibodies for each TGF-beta isoform labelled either the LECs or ECM accumulated on the capsules. Post-surgical LECs expressed TbetaR-I and TbetaR-II, and had also TbetaR-III in seven of the nine specimens examined. CONCLUSION: Expression pattern of TGF-beta s in quiescent LECs showed regional heterogeneity. Anterior LECs exhibited TGF-beta2 immunoreactivity, while equatorial LECs were positive for TGF-beta1 and -beta2. Quiescent LECs expressed TbetaR-II. LECs proliferating around IOLs expressed proteins of each TGF-beta isoform and each TbetaR. TGF-beta s were also localized in the ECM on capsules undergoing repair. TGF-beta3, TbetaR-I and TbetaR-III are up-regulated in LECs after cataract surgery.

Adult↗
PubMed2000

Beneficial effects of novel nitric oxide donor (FK409) on pulmonary ischemia-reperfusion injury in rats.

BACKGROUND: Nitric oxide (NO) seems to play an important role in tissue injury during reperfusion of the lung. FK409 is the first spontaneous NO donor that increases plasma guanosine 3':5'-cyclic monophosphate. It is reported that FK409 prevented myocardial infarction following occlusion and reperfusion in rat coronary arteries. In this study, we evaluated the effects of FK409 on pulmonary ischemia-reperfusion injury in an in situ warm ischemia model of rats. METHODS: Animals were divided into 2 groups: the FK409 study group that was administered FK409 (0.4 mg/kg) before reperfusion and the control group, administered a saline vehicle only. Following a thoracotomy, the bronchus, pulmonary artery and vein were separately clamped for 1 hour. Arterial oxygen tension (PaO2), arterial oxygen saturation (SaO2), and endothelin-I (ET-I) were measured after 2 hours of reperfusion. Histologic and immunohistochemical studies were performed; polymorphonuclear neutrophils (PMNs) were counted after 2 hours of reperfusion. RESULTS: PaO2, SaO2, ET-I after 2 hours of reperfusion and the 7-day survival rate were significantly (p < 0.05) better in the FK409 group than the control group. Histologic damage was reduced in the FK409 group compared with the control group. PMN infiltration was also significantly (p < 0.05) lower in the FK409 group than in the control group. CONCLUSION: FK409 seems to protect against ischemia-reperfusion injury of the lung. This effect may be related to a homeostatic effect on pulmonary vascular beds and prevention of PMN sequestration.

Animals↗
PubMed2000

Optimal end point of FR167653 administration and expression of interleukin-8 messenger RNA on extended liver resection with ischemia in dogs.

BACKGROUND: FR167653 is a potent suppressant of interleukin-1 and tumor necrosis factor production. We previously reported that FR167653 inhibited the expression of interleukin-1 messenger RNA (mRNA) after ischemia-reperfusion and provided a protective effect against ischemia-reperfusion injury after extended liver resection. In this study we investigated the optimal end point of FR167653 administration and the inhibition of interleukin-8 (IL-8) mRNA expression caused by the administration of FR167653 during extended liver resection with ischemia in a dog model. STUDY DESIGN: The right portal pedicle was clamped for 60 minutes but the left portal vein was left patent to avoid portal congestion. After reperfusion 75% of the liver was resected. EXPERIMENT I: Adult mongrel dogs were divided into three groups: the control group (n = 9); the FR-2 group (n = 6), which received FR167653 through the portal vein starting 30 minutes before the onset of ischemia until 2 hours after reperfusion; and the FR-6 group (n = 6), which received FR167653 starting 30 minutes before ischemia until 6 hours after reperfusion. Hepatic venous blood was collected to measure liver enzymes. Liver specimens were harvested for histologic study 6 hours after reperfusion and polymorphonuclear neutrophils were counted. EXPERIMENT II: The expression of IL-8 was measured by reverse-transcriptase polymerase chain reaction. RESULTS: Aspartate aminotransferase and alanine aminotransferase levels after reperfusion and hyaluronic acid levels 6 hours after reperfusion were significantly (p < 0.05) lower in the FR-2 and FR-6 groups than in the control group. There were no significant differences between the FR-2 and FR-6 groups after reperfusion. Histologically liver tissue damage was mild in the FR-2 and FR-6 groups, and polymorphonuclear neutrophil infiltration was significantly lower in the FR-2 and FR-6 groups than in the control group. The 3-day survival rate was statistically (p < 0.05) better in the FR-2 and FR-6 groups than in the control group. IL-8 mRNA expression was inhibited in the FR-treated group. CONCLUSIONS: FR167653 should be administered until shortly after reperfusion and need not be administered for many hours after reperfusion. FR167653 inhibits IL-8 mRNA production and inhibits polymorphonuclear neutrophil infiltration.

Alanine Transaminase↗
PubMed2000

Spray-dried lactose composite particles containing an ion complex of alginate-chitosan for designing a dry-coated tablet having a time-controlled releasing function.

PURPOSE: The properties of novel spray-dried lactose composite particles suitable for the coating filler of a dry-coated tablet having a long induction period in drug release were investigated. METHODS: To prepare spray-dried composite particles containing alginate-chitosan complex (SD(L/AL-CS)), an aqueous solution of lactose and sodium alginate and the acetic acid solution of chitosan were concomitantly fed into the rotary atomizer of a spray-dryer. The formation of the alginate-chitosan complex was confirmed by measuring the weight of insoluble portion in the mixture of sodium alginate and chitosan solutions. The dissolution properties of the dry-coated tablet were measured with the JP specified paddle method. RESULTS: The micromeritic properties of SD(L/AL-CS) were compared to those of the SD composite particles of lactose-sodium alginate, having a good compacting property. The drug release profiles of dry-coated tablet with SD(L/AL-CS) contained a long induction period followed by a rapid drug release phase in the artificial intestinal fluid. The induction period for drug release to occur was increased with an increase in the degree of deacetylation of chitosan and in the amount of chitosan in the formulation. The prolongation of induction period was attributed to the formation of an insoluble ion complex between sodium alginate and chitosan in the composite particles, which could form a rigid gel structure on the tablet surface. CONCLUSIONS: A time-controlled release tablet was designed with the composite particles of lactose containing the alginate-chitosan ion complex. The induction period of the dry-coated tablet could be prolonged in order to deliver the drug to the colon by controlling the type and amount of chitosan formulated in the composite particles.

Alginates↗
PubMed2000

Inhibition of complement-mediated haemolysis in paroxysmal nocturnal haemoglobinuria by heparin or low-molecular weight heparin.

Complement (C')-mediated haemolysis in paroxysmal nocturnal haemoglobinuria (PNH) is mainly due to the deficiency of glycosyl phosphatidylinositol-anchored membrane proteins with C'-regulatory activities CD55 and CD59 in PNH-affected red blood cells (RBCs). Hydrophobic insertion of C5b-7 to RBC membranes, initiating the formation of a membrane attack complex, readily results in lysis of PNH RBCs due to the deficiency of CD59. We studied the significance of the electrostatic interactions between C5b-6 and RBC membranes preceding the insertion of C5b-7. In vitro, C'-mediated lysis of PNH RBCs (assessed by sucrose haemolytic assay) was inhibited by heparin, low-molecular weight heparin (LMWH) or protamine, indicating the significance of the electrostatic interactions between C' components and RBC membranes in the process of C'-mediated haemolysis. Neuraminidase-treated PNH RBCs became resistant to C' activation, suggesting that the sialic acid moieties on RBC membranes are involved in the interactions of RBC with C' components. By using biotin-labelled C7, we demonstrated that LMWH as well as heparin inhibited the insertion of C5b-7 to RBCs, although they did not inhibit the incorporation of C7 into membrane-associated C5b-6. Neither heparin nor LMWH could inhibit the procoagulant alteration of PNH RBC membranes induced by C' activation even at concentrations which inhibited the haemolysis completely. Because LMWH inhibited the C'-mediated lysis of PNH RBCs in vitro at the range which induced a limited prolongation of activated partial thromboplastin time of normal plasma, we consider that LMWH may be useful for both the inhibition of haemolysis and the prevention of thrombosis, which often follow a haemolytic attack in PNH.

Anticoagulants↗
PubMed2000

Expression of involucrin by ocular surface epithelia of patients with benign and malignant disorders.

PURPOSE: Keratinization of the ocular surface epithelium is associated with various disorders impairing vision. We immunohistochemically determined whether the ocular surface epithelia express involucrin, and whether its expression pattern may differ in benign vs. malignant disorders. Expression of cytokeratins was also examined to provide further information relative to the epithelial differentiation. METHODS: We evaluated 17 specimens; 6 specimens of the normal ocular surface epithelia, 3 specimens from cases of conjunctival intraepithelial neoplasia (CIN), 6 of conjunctival squamous cell carcinoma (SCC) and 2 of conjunctivae from cases of superior limbic keratoconjunctivitis (SLK). RESULTS: Corneal epithelium exhibited intracellular immunoreactivity for involucrin. Four of the 6 specimens of bulbar conjunctival epithelium showed involucrin immunoreactivity in the perimembranous region, whereas the fornical conjunctiva was negative. Cornified envelope in SLK specimens was positive for involucrin. The CIN showed its immunoreactivity in the perimembranous region in all levels of the hyperproliferative epithelium without keratinization, i.e., similar to the bulbar conjunctiva. The neoplastic cells of well-differentiated SCC showed involucrin in the perimembranous region, and those of moderately- to poorly-differentiated SCC have involucrin in their cytoplasm. The expression pattern of cytokeratins was unrelated to grade of malignancy in ocular SCC. CONCLUSION: The epithelia of normal subjects and of CIN expresses involucrin without keratinization. In contrary, the keratinized SLK epithelium markedly expresses involucrin in the cornified envelope. The subcellular immunolocalization of involucrin in the ocular SCC may help in evaluating the differentiation, i.e., malignancy, of neoplastic cells.

Adult↗
PubMed2000

Matrix metalloproteinases and tissue inhibitors of metalloproteinases of fibrous humans lens capsules with intraocular lenses.

PURPOSE: We located immunohistochemically the matrix metalloproteinases (MMP) -1, -2, -3 and -9 and the tissue inhibitors of matrix metalloproteinases (TIMP) -1 and -2 in the fibrous capsule of patients with intraocular lenses (IOLs). METHODS: During vitreoretinal surgery in 10 patients we obtained post-cataract surgery lens capsules with or without an IOL. The mean interval between the previous cataract operation and the extraction of the specimens was 35.2 months (range: 2-120 months). Circular sections of the anterior capsule with lens epithelial cells (LECs) were also obtained during cataract surgery. Specimens were processed for immunohistochemical identification of MMPs and TIMPs by light microscopy. RESULTS: While all the members of MMPs and TIMPs were not detected in the normal anterior capsules, they were detected in the ECM and/or LECs on the lens capsules extracted within 18 months after IOL implantations in all of the 4 patients, but were not observed in specimens obtained 18 months or longer postoperatively. In LECs of 1 capsule specimen 10 years postoperatively, MMP-1, but not other MMPs and TIMPs, was detected. CONCLUSIONS: MMPs and TIMPs were detected in the ECM and/or LECs on post-cataract surgery capsules. These proteins may be remodeling the newly deposited ECM and regulating LEC behavior on residual lens capsules in the early phase of healing after cataract surgery.

Adult↗
PubMed2000

Mucoadhesive DL-lactide/glycolide copolymer nanospheres coated with chitosan to improve oral delivery of elcatonin.

The purpose of this work was to develop a novel mucoadhesive DL-lactide/glycolide copolymer (PLGA) nanosphere system to improve peptide absorption and prolong the physiological activity following oral administration. The desired PLGA nanospheres with elcatonin were prepared by the emulsion solvent diffusion method to coat the surface of the resultant nanospheres with a mucoadhesive polymer such as chitosan, poly(acrylic acid), and sodium alginate. Their mucoadhesive properties were evaluated by measuring the nanospheres adsorbed to a rat everted intestinal sac (in vitro). The chitosan-coated nanospheres showed higher mucoadhesion to the everted intestinal tract in saline than the other polymer-coated nanospheres. There was no mucoadhesion site-specificity of the chitosan-coated nanospheres between duodenal, jejunal, and ileal sacs. The payload of drug in the chitosan-coated nanospheres was successfully increased by using the solvent diffusion method in oil. The pattern of drug release of the resultant nanospheres did not differ markedly from that of uncoated nanospheres. The chitosan-coated nanospheres with elcatonin were administered intragastrically to fasted Wistar rats. The chitosan-coated nanosphere reduced significantly the blood calcium level compared with elcatonin solution and uncoated nanospheres, and the reduced calcium level was sustained for a period of 48 hr. Even under nonfasting conditions, the mucoadhesion of chitosan-coated nanospheres was unaltered and the reduction in blood Ca levels was maintained satisfactorily.

Acrylic Resins↗