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Biomedical subjects

Tetsumi Irie

Publications and source records attributed to Tetsumi Irie.

13 recordsLinked to original sources
PubMed2006

Effect of 2,6-di-O-methyl-alpha-cyclodextrin on hemolysis and morphological change in rabbit's red blood cells.

The effects of 2,6-di-O-methyl-alpha-cyclodextrin (DM-alpha-CyD) on hemolysis and morphological changes in rabbit's red blood cells (RBC) were examined, compared with those of alpha-cyclodextrin (CyD) and 2-hydoxypropyl-alpha-cyclodextrin (HP-alpha-CyD). The hemolytic activity of alpha-CyDs increased in the order of HP-alpha-CyD<alpha-CyD<DM-alpha-CyD. The three alpha-CyDs induced morphological changes of RBC from discocyte to stomatocyte. At the same concentration (3mM) of alpha-CyDs, DM-alpha-CyD and alpha-CyD released phospholipids, rather than cholesterol, and DM-alpha-CyD markedly released proteins from RBC membranes, compared to alpha-CyD and HP-alpha-CyD. The treatment of RBC with DM-alpha-CyD lowered the extent of a fluorescent sphingomyelin analogue from lipid rafts of RBC membranes in a concentration-dependent manner. These results suggest that DM-alpha-CyD has higher hemolytic and morphological change activity than alpha-CyD and HP-alpha-CyD through more extraction of phospholipids including sphingomyelin and proteins, not cholesterol, from RBC membranes than alpha-CyD and HP-alpha-CyD.

Animals↗
PubMed2006

[Plasma levobupivacaine concentrations following epidural administration of levobupivacaine conjugated with or without maltosyl-beta-cyclodextrin].

BACKGROUND: To investigate the pharmacokinetics of complexation of levobupivacaine with maltosyl-beta-cyclodextrin, the plasma concentrations of levobupivacaine were measured following epidural administration of levobupivacaine conjugated with maltosyl-beta-cyclodextrin or levobupivacaine alone in a rabbit model. METHODS: Rabbits were randomly divided into two groups, levobupivacaine (1%) group (n = 6) and levobupivacaine (1%) conjugated with maltosyl-beta-cyclodextrin (100 mM) group (n = 6). One ml of each solution was randomly injected through an epidural catheter placed at L5-6. The plasma levobupivacaine concentrations were measured before and 5, 10, 15, 30, 60, 120, 240, 360, and 480 min after injection. RESULTS: The plasma levobupivacaine concentrations were significantly higher in the levobupivacaine conjugated with maltosyl-beta-cyclodextrin group than in levobupivacaine group at 5 min (1,465 +/- 311, 1,033 +/- 347 ng x ml(-1)), 10 min (1,068 +/- 237, 731 +/- 191), and 15 min (958 +/- 311, 605 +/- 118). There were no differences in area under the curve (1,551 +/- 387, 1,176 +/- 154 ng x hr x ml(-1)) and elimination half life (100 +/- 54, 78 +/- 37 min) between the two groups. CONCLUSIONS: The results of this study indicated that the absorption of levobupivacaine conjugated with maltosyl-beta-cyclodextrin from the epidural space and the elimination from the blood were similar to plain levobupivacaine.

Anesthesia, Epidural↗
PubMed2005

Population pharmacokinetics of theophylline in very premature Japanese infants with apnoea.

OBJECTIVE: To estimate the population pharmacokinetics of theophylline in very premature infants using the non-linear mixed effects modelling. METHOD: A total of 167 serum concentration measurements obtained from routine theophylline monitoring of 107 very premature Japanese infants were collected. RESULTS: The final pharmacokinetic parameters were CL (mL/h) = [6.98 . body weight (BW) (kg)(2.17) + 0.244 . post-conceptional age (weeks)] . 1.24(oxygen support), Vd (L) = 0.492 . BW (kg) and F = 0.660, respectively. Clearance was increased by 24% for patients receiving oxygen support. The inter-individual variabilities in clearance and apparent volume of distribution were 15.6% and 80.4%, respectively, and the residual variability was 34.2% as a coefficient of variation. CONCLUSION: Application of the findings in this study to patient care may permit selection of an appropriate initial maintenance dosage to achieve target theophylline concentrations, thus enabling the clinician to achieve the desired therapeutic effect in very premature Japanese infants.

Apnea↗
PubMed2005

[Pitfalls in homogeneous assays for HDL-c and LDL-c in serum].

Between 1994 and 2004, homogenous assays for HDL-C and LDL-C based on different determination principles were developed to replace complicated conventional precipitation methods. Nowadays, most laboratories employ homogenous assays. However, due to differences in principles and reactivity, measurements made by different assays do not necessarily match in some cases. HDL-C determinations may vary depending on duration and conditions of serum storage for the CDC-DCM and the homogenous assay methods, due to their different principles of determination. In patients with cholestasis, apoE-rich HDL, Lp-X and Lp-Y are occasionally observed. In these cases, the reactivity of homogenous assays for HDL-C varies markedly among the manufacturers. Furthermore, because the specific gravities of Lp-X and Lp-Y are comparable to that of LDL, these lipoproteins are grouped as LDL by ultracentrifugation, and this is a source of confusion in clinical settings. The American CDC assesses the accuracy of cholesterol assays by the BQ method, which measures the total of IDL, the narrowly-defined LDL, and Lp(a). However, of the various homogenous assays for LDL-C, reactivities to IDL and Lp (a) differ, and as a result, it is possible that type III hyperlipidemia characterized by increased IDL may be misdiagnosed.

Arteriosclerosis↗
PubMed2004

Applicability of (SBE)7m-beta-CD in controlled-porosity osmotic pump tablets (OPTs).

The purpose of this study was to investigate the general application of a controlled-porosity osmotic pump tablet (OPT) utilizing (SBE)7m-beta-CD as both a solubilizer and an osmotic agent for drugs with varying physical properties. OPTs utilizing (SBE)7m-beta-CD were prepared for five poorly soluble and two highly water-soluble drugs. The Japanese Pharmacopoeia dissolution method was used to study the drug and (SBE)7m-beta-CD release from the OPTs. The drug concentration in the OPT core after the OPT was placed in the release medium for two hours was assayed gravimetrically and by HPLC. An appropriate composition ratio (ACR) of (SBE)7m-beta-CD to drug at which drug release from the OPT was complete and pH-independent within the physiological pH range of the GI tract was determined for each drug. The ACR values correlate to the drug concentration in the OPT core when the OPTs were placed in the release medium for two hours. The release profiles of prednisolone (a poorly water-soluble drug) and sodium chloride (a water-soluble compound) from the OPTs were almost the same as that of (SBE)7m-beta-CD. Also, the release rate of each drug per unit membrane surface area from the OPTs was similar, regardless of the differences in drug solubility. The present results confirmed that (SBE)7m-beta-CD serves as both a solubility modulator and as an osmotic pumping agent for OPTs, from which the release rate of both water-soluble and poorly water-soluble drugs can be controlled.

Adjuvants, Pharmaceutic↗
PubMed2004

Decrease of fertilizing ability of mouse spermatozoa after freezing and thawing is related to cellular injury.

In general, the fertilizing ability of cryopreserved mouse spermatozoa is less than that of fresh spermatozoa. This ability is especially low in C57BL/6, the main strain used for the production of transgenic mice. To solve this problem, the relationship between cell damage and fertilizing ability in cryopreserved mouse spermatozoa was examined in this study. Sperm motility analysis revealed no significant difference among the motilities of cryopreserved C57BL/6J, BALB/cA, and DBA/2N sperm (67.6%, 43.4%, and 60.0%, respectively) after thawing. However, the results of in vitro fertilization (IVF), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) showed a strong correlation between the frequency of aberrant spermatozoa (FAS) and fertilization rates (FR; C57BL/6J: FAS, 83.7%; FR, 17.0%; BALB/cA: FAS, 67.2%; FR, 24.2%; and DBA/2N: FAS, 10.2%; FR, 93.6%), and damage to spermatozoa was localized particularly in the acrosome of the head and mitochondria.

Acrosome↗
PubMed2004

Involvement of thromboxane A2 (TXA2) in the early stages of oleic acid-induced lung injury and the preventive effect of ozagrel, a TXA2 synthase inhibitor, in guinea-pigs.

An intravenous injection of oleic acid into animals can produce a lung injury with hypoxaemia and pulmonary vascular hyper-permeability. Although oleic acid lung injury is used as a model of acute respiratory distress syndrome (ARDS), the precise mechanisms of the lung injury are still unclear. We have investigated whether thromboxane A(2) (TXA(2)) participated in the lung injury and have evaluated the efficacy of ozagrel, a TXA(2) synthase inhibitor, on the lung injury in guinea-pigs. Oleic acid injection increased the plasma level of TXB(2), a stable metabolite of TXA(2), and the time-course of plasma TXB(2) was similar to that of the decreased partial oxygen pressure of arterial blood (Pao(2)) induced with oleic acid. Ozagrel administered intravenously 30 min before oleic acid injection prevented the decrease in Pao(2) and pulmonary vascular hyper-permeability. It also prevented increases in lactate dehydrogenase activity, a measure of lung cell injury, TXB(2 )and its weight ratio to 6-keto prostaglandin F(1alpha) in bronchoalveolar lavage fluid. Although ozagrel administered simultaneously with oleic acid ameliorated the decrease in Pao(2), post treatment showed little effect. We suggest that TXA(2) participated in the oleic acid lung injury, as an "early phase" mediator, and rapidly-acting TXA(2) synthase inhibitors were effective in the prevention of acute lung injury.

6-Ketoprostaglandin F1 alpha↗
PubMed2004

Preventive effect of tranilast on oleic acid-induced lung injury in guinea pigs.

Acute respiratory distress syndrome or acute lung injury (ARDS)/(ALI) involve the severe lung injury with pulmonary vascular hyper-permeability and hypoxemia induced by inflammatory reactions. Since ARDS/ALI carries high mortality, the development of new drugs against ARDS/ALI is required. We examined the effect of tranilast, an anti-allergic drug, on vascular hyper-permeability in the lungs and airways, and on hypoxemia, in oleic acid (OA)-induced acute lung injury, an animal model of ARDS/ALI. The increase in pulmonary and airway vascular permeability and the decrease in partial oxygen pressure of arterial blood induced by an intravenous injection of OA were drastically ameliorated by the oral administration of tranilast in a dose-dependent manner. This is the first report to prove that tranilast prevents pulmonary and airway vascular permeability and hypoxemia induced by OA. These results suggest that tranilast may be a candidate drug for the treatment of ARDS/ALI.

Animals↗
PubMed2003

Effects of alpha 1-acid glycoprotein on erythrocyte deformability and membrane stabilization.

The effects of alpha(1)-acid glycoprotein (AGP) on human erythrocyte membrane were examined in vitro. Bovine and dog AGP, in addition to human AGP or asialo human AGP were used, and the collected data were compared with that for human serum albumin (HSA). A new technique developed by Kikuchi was used to investigate erythrocyte deformability. The addition of AGPs including human AGP facilitated the passage of human erythrocytes with an average diameter of 7.2 microm suspended in phosphate buffered saline (PBS) through a 5 microm wide microchannel; hemolysis was suppressed after the passage. The stabilizing effects of AGPs on membrane were evaluated. Human AGP prevented hemolysis induced by hypotonic phosphate buffer solution. The effects of human AGP on the oxidative changes in erythrocytes exposed to oxygen radicals were investigated. Human AGP protected erythrocytes from H(2)O(2) and prevented the oxidation of dihydrorhodamine 123 to rhodamine 123 from H(2)O(2). We propose that the antioxidant activity of human AGP is due to the binding of free radicals. In all studies, the effects of human AGP on erythrocytes might not be a function of the negative charge associated with sialyl residues, because the presence of N-acetylneuraminic acid had no effect. However, human AGP may promote microcirculation and antioxidant activity compared with HSA. No species differences in the physiological function of AGP were found. These results suggest that an increase in the AGP content of serum above the normal value found under pathological conditions facilitates the passage of erythrocytes through capillaries, stabilizes erythrocyte membranes and protects against oxidative stress, all of which are favorable for microcirculation.

Animals↗
PubMed2003

Preventive effect of phosphoenolpyruvate on hypoxemia induced by oleic acid in Guinea pigs.

Oleic acid-induced hypoxemia is an animal model of acute respiratory distress syndrome (ARDS). Increased capillary permeability is a cause of hypoxemia in lung injury. Endothelial cells form a major capillary barrier, and disruption of the barrier appears to involve a decreased level of ATP in the cells. Phosphoenolpyruvate (PEP) is an endogenous substance that is one of the ATP precursors and can cross some cell membranes via anion exchanger. We examined the effect of PEP on oleic acid-induced lung injury in guinea pigs. An intravenous injection of oleic acid (15 microl/kg) caused severe hypoxemia. Pretreatment with PEP at a dose of 2, 20, or 200 micromol/kg attenuated the oleic acid-induced decrease in the arterial partial pressure of oxygen in a dose-dependent manner. Furthermore, PEP attenuated the oleic acid-induced increase in vascular permeability in the proximal and distal bronchi, as indicated by the extravascular leakage of Evans Blue dye. The combination of PEP with ATP (4 micromol/kg) showed no additional inhibitory effect on oleic acid-induced lung injury, compared with PEP alone. We suggest that PEP is a promising candidate to prevent hypoxemia in acute lung injuries associated with increased vascular permeability, such as ARDS.

Animals↗
PubMed2003

Oxidative stress in early stage of acute lung injury induced with oleic acid in guinea pigs.

Changes in several biomarkers in bronchoalveolar lavage fluid (BALF) during an early stage of lung injury induced with oleic acid were examined in guinea pigs. In addition, a possible contribution of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and xanthine oxidase to the oxidative changes in the lung injury was investigated. An intravenous injection of oleic acid increased the levels of lipid peroxidation products, lactate dehydrogenase, and total proteins, decreased the ratio of glutathione to glutathione disulfide in the BALF, and also affected the levels of other oxidative biomarkers such as superoxide dismutase and catalase in the BALF in a dose-dependent manner. Diphenyleneiodonium chloride, a NADPH oxidase inhibitor, inhibited the oxidative changes in the BALF and the decrease in partial pressure of oxygen in artery induced with oleic acid, while allopurinol, a xanthine oxidase inhibitor, had no inhibitory effects. The results demonstrate that oxidative stress would be an important mechanism of oleic acid-induced lung injury, and indicate that the NADPH oxidase-dependent pathway contributes significantly to the generation of reactive oxygen species in oleic acid-induced lung injury.

Animals↗
PubMed2002

Involvement of calmodulin inhibition in analgesia induced with low doses of intrathecal trifluoperazine.

We examined which of the known properties of trifluoperazine, including calmodulin inhibition, are involved in its analgesic effect. Furthermore, we tried to find any possible interaction between opioidergic system and calmodulin inhibition-induced analgesia. Intrathecal trifluoperazine (1, 10, 100 microg) showed a biphasic effect in the formalin test; i.e., analgesia at relatively low doses (1, 10 microg) and hyperalgesia at a high dose (100 microg). No analgesic effects were observed after intrathecal injection of sulpiride (1, 10, 100 microg), atropine (0.1, 1, 10 microg), phentolamine (0.1, 1, 10 microg) and brompheniramine (0.1, 1, 10 microg). Meanwhile, intrathecal calmidazolium (10, 50, 250 microg) induced a dose-dependent analgesia. Histamine (1 microg), physostigmine (1 microg), bromocriptine (1 microg) and norepinephrine (1 microg) did not affect trifluoperazine-induced analgesia. Calcium (20 microg) attenuated the antinociceptive effect of trifluoperazine and inhibited the analgesic effect of calmidazolium. Finally, naloxone (2 mg/kg) decreased trifluoperazine-induced antinociception but did not have any effects on calmidazolium-induced analgesia. We concluded that calmodulin inhibition may be involved in the analgesia produced by trifluoperazine. With increasing doses of trifluoperazine, the algesic effect seems to overcome the analgesic effect. It is also suggested that the opioidergic system does not interact with calmodulin inhibition-induced analgesia even though this system has a possible role in trifluoperazine-induced analgesia.

Analgesia↗