Biomedical subjects

Toshio Akimoto

Publications and source records attributed to Toshio Akimoto.

7 recordsLinked to original sources

PubMed2005

Arterial hypoxemia and intrapulmonary vasodilatation in rat models of portal hypertension.

BACKGROUND: Rats with chronic bile duct ligation (CBDL) and portal vein ligation (PVL) are used as models of portal hypertension. CBDL rats show hypoxemia with intrapulmonary vasodilatation (IPVD), and are recognized as a model of hepatopulmonary syndrome (HPS), while PVL rats are normoxemic. We investigated the differences in arterial oxygenation between these models, and the key factors leading to HPS. METHODS: Forty-eight Sprague-Dawley rats were prepared as CBDL or PVL models, or as Sham rats. Arterial oxygenation, hemodynamics (reference sample method), and IPVD were simultaneously evaluated in conscious and unrestrained animals, using (141)Ce- or (113)Sn-labeled microspheres (15 microm in diameter), respectively. Endothelin-1 (ET-1) and nitrate/nitrite (end products of nitric oxide; NOx) production by the lung tissue (increment across the lungs) was also determined. RESULTS: The extent of IPVD was similar in both models, but hypoxemia was only observed in CBDL rats. The ET-1 level and the increment in NOx were significantly increased in CBDL rats, and the increment was directly correlated with impairment of oxygenation. Blood flow through the bronchial arteries (anatomical shunting) was increased in CBDL rats, reaching more than three times the level in PVL rats or Sham rats. CONCLUSIONS: These results support the hypothesis that NO derived from the lung tissues contributes to hypoxemia, and IPVD appears to be a prerequisite for impaired oxygenation. The considerable increase of anatomical shunting may potentially contribute to impaired oxygenation in CBDL rats.

Animals↗

PubMed2005

Mapping of the cyclodextrin cavity using the cylindrical coordinate system.

This paper describes the mapping of the inner cavity of cyclodextrin and the guest molecule using the cylindrical coordinate system. Each cavity structure of alpha-, beta-, and gamma-cyclodextrin was examined using the coordinate system, in which, the Z-axis passes through the molecular axis; a normal of the plane that consists of 6, 7, or 8 C(1) atoms of glucose units was obtained using the least-squares methods and that passes through the center of C(1) atoms. The radius rho is the distance from the Z-axis to the solvent-accessible surface of a cavity. The psi-axis is defined such that the nearest C(1) atom of the glucose unit to the Z-axis is its origin. The atomic character of the inner surface of the cavity was also obtained and plotted in the same coordinates. The guest molecule was plotted with the same coordinate system as cyclodextrin to see atoms with large rho distance of the guest molecule on the solvent-accessible surface map of cyclodextrin. It was confirmed from the map that cyclodextrin molecules have an ellipsoidal shape, have pseudo-n-hold symmetry (n=6 to alpha, 7 to beta, and 8 to gamma) in relation to their molecular axis, and guest molecules are located in relatively hydrophobic regions. It was also confirmed that the maps of this system give insights into the complementary characters of structures between the host and the guest by plotting the guest molecule in the same coordinate system.

Carbohydrate Conformation↗

PubMed2005

Hemodynamic features of advanced cirrhosis due to chronic bile duct ligation.

AIM: The aim of the present study was to compare the hemodynamic features of portal hypertension in rats with early cirrhosis with those of rats with advanced cirrhosis following common bile duct ligation (CBDL). METHODS: A total of 53 male Sprague-Dawley rats were used. Hemodynamics were evaluated under conscious and unrestrained conditions 4 weeks and 8 weeks after CBDL, and 4 weeks after a sham operation. Arterial pressure and portal pressure were measured directly via catheters placed in the right femoral artery and main portal vein, respectively. The cardiac index and organ (splanchninc organs, brain, kidneys and lungs) blood flow were determined by the reference sample method using (141)Ce-labeled microspheres (15 mum in diameter). Arterial levels of endothelin-1 and nitrate/nitrite, as well as liver function variables, were also determined. RESULTS: Portal pressure was significantly higher 8 weeks after CBDL (15.8+/-2.1, n=8) than 4 weeks after CBDL (13.9+/-2.1 mmHg, n=12, p<0.05), and the hyperdynamic circulation of the early period was attenuated (p<0.05). Although hepatic artery blood flow 4 and 8 weeks after CBDL was higher than that after sham operation (p<0.05), portal territory blood flow was not increased. There was a significant positive correlation between portal pressure and portal territory blood flow 8 weeks after CBDL (r=0.822, n=8, p=0.012). In rats with anemia 4 weeks after CBDL, the hemoglobin concentration was negatively correlated with portal territory blood flow (r=-0.597, n=12, p=0.040). CONCLUSION: Portal pressure was higher 8 weeks after CBDL than 4 weeks after CBDL and increased with portal territory blood flow, suggesting that portal hypertension is maintained by a mechanism consistent with the forward flow theory. Anemia might exacerbate the hyperdynamic systemic circulation 4 weeks after CBDL.

Animals↗

PubMed2005

Viability and plasma vitamin K levels in the common bile duct-ligated rats.

The common bile duct-ligated (CBDL) rat, which is widely used as a model of human cirrhosis, rapidly develops secondary biliary cirrhosis (SBC) within 4 weeks. The CBDL rat shows poor viability, however, a detailed examination of the causes of its death has not been made. In this study, we investigated the outcome of bile duct ligation in detail and attempted to extend the life span of this model by feeding the animals a diet supplemented with nutrients. Survival rate, blood chemistry, blood cell counts, plasma levels of K vitamins and liver histology were compared among CBDL rats fed a standard diet and an enriched diet. Sham-operated rats were used as a control. Six out of 18 CBDL rats fed the standard diet died within 32 days of operation. The cause of death was massive internal hemorrhage in various organs or body cavities. All CBDL rats fed the enriched diet survived more than 31 days, but the viability of CBDL rats was not significant between those fed the standard diet and the enriched diet. The degree of anemia correlated significantly with the prolongation of prothrombin time. Plasma vitamin K1 levels in CBDL rats were significantly lower than those in sham-operated rats, but vitamin K2 levels were similar. We suggest that massive hemorrhage, which was the direct cause of death, is caused by the impairment of hemostasis resulting from vitamin K deficiency. The enriched diet with vitamin K nutritional supplements seemed to contribute to the prolongation of the life span of CBDL rats.

Animals↗

PubMed2004

Molecular mechanism of dielectrically controlled optical resolution (DCR).

We have recently found the first example of dielectrically controlled optical resolution (DCR). By adjusting the dielectric constant of the solvent used in the resolution process, each optical isomer of (R,S)-alpha-amino-epsilon-caprolactam can be selectively obtained using N-tosyl-(S)-phenylalanine as a chiral selector. The molecular mechanism of DCR has been investigated by comparing the molecular and crystal structures of the optical selector, its target substrate and their diastereomeric salts. Strong hydrophobic interactions between the phenyl rings of the optical selector govern the molecular aggregation of the selectors and form a hydrophilic layer in which molecular recognition takes place. The recognition site in the hydrophilic layer can inherently identify both of the isomers. The dielectric constant of the solvent used in the discrimination process controls the intermolecular interaction which determines the isomer to be selected. The molecular mechanism of DCR disclosed in this study strongly suggests that DCR is not a specific but a general phenomenon. This method can be applicable to a large variety of optical resolution processes.

Caprolactam↗

PubMed2003

Intrapulmonary vascular dilatation and nitric oxide in hypoxemic rats with chronic bile duct ligation.

BACKGROUND/AIMS: Nitric oxide (NO) has been suggested as the major cause of pulmonary vascular dilatation and hypoxemia in hepatopulmonary syndrome (HPS). The aim of this study was to assess the effect of NO on arterial oxygenation in rats with common bile duct ligation (CBDL rats), a model of HPS. METHODS: Arterial blood gases were measured in 44 CBDL rats and 44 Sham rats under unrestrained conditions. Intrapulmonary shunting was assessed with (141)Ce-labeled microspheres (15-mum diameter) and serum nitrate/nitrite levels were measured by HPLC. The effect of NOS inhibition on A-aDO(2) was studied using L-NAME. RESULTS: A decrease of PaO(2) below 82.7 mmHg (the mean value-2sigma in Sham rats) was seen in 43% of CBDL rats. Intrapulmonary shunting was greater in CBDL rats than in Sham rats (P<0.001). A correlation between the extent of shunting and A-aDO(2) was found in all animals studied (r=0.89, P<0.001, n=16). Serum levels of nitrate/nitrite increased significantly across the lungs, and the increase was significantly correlated with A-aDO(2) in the total population of animals studied. Administration of L-NAME to CBDL rats achieved a significant improvement of A-aDO(2). CONCLUSIONS: These results suggest that pulmonary vascular dilatation due to NO leads to hypoxemia in CBDL rats.

Animals↗

PubMed2002

Detection of Corynebacterium kutscheri from the oral cavity of rats.

A simple and useful method for the detection of C. kutscheri from the oral cavity of living rats was devised. In 10 sacrificed rats from two naturally and subclinically infected conventional colonies, 10(4.28) or 10(3.84) CFU/ml C. kutscheri were isolated from upper incisor swab extractions, while 10(1.38) or 10(1.58) and < 10 or 10(1.56) CFU/ml from the upper soft palate and pharynx, respectively. In another survey with 26 living animals, which were reared on the same rack, organisms were detected from the upper incisor and gingival swabs in 15 of 26 rats (57.7%). The results were reproducible at a second survey 10 days later. No organisms were isolated from any sites of the orally negative rats. These results indicated that culture of swab specimens from the upper incisors and gingivae of incisors is useful for the detection of C. kutscheri infection in living rats.

Animals↗