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T Shiga

Publications and source records attributed to T Shiga.

At least 91 records · Page 5Linked to original sources
PubMed1996

Generation of nitric oxide and superoxide during reperfusion after focal cerebral ischemia in rats.

We investigated the levels of nitrosyl hemoglobin (HbNO) in rat jugular blood by electron spin resonance (ESR) spectroscopy during and after middle cerebral artery occlusion. The levels of plasma nitric oxide (NO) end products, nitrate plus nitrate, were compared with the levels of HbNO. Small amounts of HbNO were detected in sham-operated rats (n=4) and those subjected to 2 h of occlusion (n=4), whereas nitrite plus nitrate was increased only in the latter (P<0.01; vs.sham). Upon reperfusion after 2 h of occlusion both HbNO and nitrite plus nitrate clearly increased after 15 min (n=4) and 30 min (n=6) reperfusion (P<0.01; vs.occlusion). Administration of superoxide dismutase (5 mg/kg) significantly increased HbNO (P<0.05) but not plasma nitrate plus nitrate (n=5). The increase in HbNO suppressed by administration of NG-nitro-L-arginine methyl ester (20mg/kg; n=4,P<0.01), and this suppression could be reversed by L-arginine (200 mg/kg) (n=4). The present study clearly showed that the L-arginine-NO synthase pathway was activated during reperfusion after focal cerebral ischemia and indicated the involvement of a reaction between NO and superoxide during early reperfusion.

Animals↗
PubMed1996

Detection of nitric oxide production and its role in pancreatic ischemia-reperfusion in rats.

Partial ischemia of rat pancreas body and tail was obtained by occlusion of the celiac axis for 1 h after gastrectomy. The plasma level of nitrite plus nitrate in both systemic and portal venous blood after reperfusion was significantly higher than that after sham operation and ischemia alone. The elevation after reperfusion was significantly decreased by NG-nitro-L-arginine methyl ester (L-NAME). Simultaneous administration of L-arginine counteracted the L-NAME-induced decrease in the level of nitric oxide (NO) end products. Generation of NO was further demonstrated by nitrosylhemoglobin detection by electron spin resonance in the blood after reperfusion. On the other hand, the plasma level of lipase, a marker of damage to pancreatic exocrine tissue, was significantly increased after ischemia-reperfusion and further increased by administration of L-NAME. This increase in lipase correlated with a decrease in tissue blood flow in the pancreas. These results suggest that NO is generated during and may have a protective role in ischemia-reperfusion of the rat pancreas.

Animals↗
PubMed1996

O2 transfer from single microvessels to acinar cells in secretin-stimulated pancreas of rat.

O2 transfer from the inside to the outside of single microvessels in the resting and secretin-stimulated exocrine pancreas of rats was investigated by dual-spot microspectroscopy. Measurements of intravascular hemoglobin (Hb) concentration, O2 saturation of Hb, and velocity of flowing red blood cells were carried out in single microvessels at the edge of the exocrine pancreas of anesthetized rats. The rate of O2 release (Ro2) from a single microvessel wall was constant [approximately 2 nmol.cm-2.s-1] over a wide range of oxyhemoglobin inflow ([HbO2] inflow; 200-700 fmol/s) but decreased almost linearly with an [HbO2] inflow < 200 fmol/s, where [HbO2] inflow is defined as the product of inflowing oxyhemoglobin concentration ([HbO2]) and blood flow rate. When the exocrine pancreas was stimulated with secretin either by superfusion (> or = 0.3 nM) or by intravenous infusion (> or = 0.5 microgram.kg-1.h-1), the Ro2 as well as the pancreatic secretion increased about two times higher than the basal values. With secretin administration, it was found that 1) an inverse relationship between red blood cell velocity and intravascular Hb concentration held and thus 2) [HbO2] inflow was maintained within the basal level (i.e., 200-700 fmol/s). Furthermore, 3) the elevation of Ro2 from single microvessels was accomplished by the increased O2 extraction instead of the increased O2 supply in the microvessels.

Animals↗
PubMed1996

Effect of ACh and calmodulin inhibitor on O2 transfer from exocrine pancreatic microvessels of rats.

Effects of acetylcholine (ACh) and calmodulin (CaM) inhibitor, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7), on the rate of O2 release (Ro2) from single exocrine pancreatic microvessels of anesthetized rats were investigated with dual-spot microspectroscopy. The surface of the pancreas was superfused with Krebs-Henseleit buffer containing various concentrations of ACh and/or W-7. Superfusion of ACh (> or = 20 microM) elevated Ro2 as well as pancreatic secretion approximately 2.5 times higher than that of control level, whereas superfusion of W-7 (> or = 100 microM) reduced approximately 50%. In both cases, O2 inflow in single microvessels, as quantified by oxyhemoglobin inflow into the microvessels, was maintained at control level. On the other hand, superfusion of both ACh and W-7 did not modify Ro2 and pancreatic secretion, despite significant reduction in O2 inflow. These results indicate that 1) the ACh-induced elevation of O2 release from single microvessels is accomplished by increased O2 extraction instead of increased O2 inflow in the microvessels, and 2) the activity of a W-7-sensitive Ca2+ binding protein, most likely CaM, is responsible for half of the microvascular O2 transfer and of the pancreatic exocrine secretion.

Acetylcholine↗
PubMed1996

[Effect of intra-operative fluid on renal function during hypotensive anesthesia with trimethaphan].

During induced hypotensive anesthesia in 26 cases with trimethaphan, either Ringer's lactate solution (LR group) or 2/3 lactate-saline solution (2/3 LS group) was infused at the same rate. Urine volume, creatinine clearance (Ccr), FENa, urinary gamma-GTP index and urinary Na/K ratio were determined before hypotension, during hypotension and after the operation. During hypotension, FENa and urine Na/K ratio decreased in both groups. In 2/3 LS group, these remained low after the operation compared with the values before hypotension and in LR group. These results suggest that LR solution might depress an endocrine response which is induced by hypotensive anesthesia. As urine volume and Ccr were unchanged by hypotension, and infusion of colloid solution (Hespander) could not increase these figures, circulating blood volume might not be decreased during hypotensive anesthesia. Since urinary gamma-GTP index increased slightly during hypotension or after the operation, there might have been a slight epithelial cell damage of tubules with hypotensive anesthesia.

Adult↗
PubMed1995

Effects of superoxide dismutase on nitric oxide production during reperfusion after focal cerebral ischemia is rats.

To assess the interaction of nitric oxide (NO) and superoxide during reperfusion after cerebral ischemia, we studied the dose effects of superoxide dismutase (SOD) on the levels of nitrosyl hemoglobin and plasma nitrite + nitrate which were increased at 30 min reperfusion after 2 h middle cerebral artery occlusion in rats. SOD was administered at 10 min before reperfusion. With 1, 5 and 10 mg/Kg of SOD, plasma nitrite + nitrate level was decreased by 25 mg/kg of SOD. The same amount of apo enzyme was without effect. These results suggest effect of superoxide in the NO level released during reperfusion after cerebral ischemia.

Animals↗
PubMed1995

Generation of nitric oxide as a rejection marker in rat pancreas transplantation.

In clinical pancreas transplantation, no reliable marker for the early diagnosis of acute rejection has been reported. This is one reason why the graft survival rate of pancreas transplantation alone is much lower than that of other organs, such as hearts, livers, and kidneys. We designed an experiment to investigate acute rejection of pancreas allografts in hyperglycemic rats by measurement of blood glucose levels and nitric oxide (NO) products (nitrite plus nitrate, and nitrosyl hemoglobin). As recipients, Lewis rats were rendered hyperglycemic by intravenous injection of streptozotocin before transplantation. F344 rats were used as donors of pancreas allografts. Lewis rats were also used as donors of syngeneic pancreas grafts. After transplantation, the blood glucose level returned to a normal level and rejection was defined as the recurrence of hyperglycemia. The mean survival time of pancreas allografts was 14 +/- 0.7 days. The plasma level of nitrite plus nitrate in allografted rats peaked on postoperative day 7. Electron spin resonance spectra of NO bound to hemoglobin were detected in the blood from allografted rats with a peak on postoperative day 7, whereas NO bound to hemoglobin was not detected in the blood from recipients of syngeneic grafts at any sampling time. The results show that NO was synthesized in the earlier period than the elevation of the blood glucose level during rejection after pancreas transplantation in rats.

Acute Disease↗
PubMed1995

The development of interneurons in the chick embryo spinal cord following in vivo treatment with retinoic acid.

To investigate the role of retinoic acid (RA) in the development of interneurons in the spinal cord, we examined the expression of cellular retinoic acid binding protein type I (CRABP I). The earliest developing interneurons in the chick spinal cord can be divided into two major groups: circumferential (C) neurons and primitive longitudinal (PL) neurons. In brachial segments, both types of interneurons began to express CRABP I at stage (st.) 13+ of the V. Hamburger and H.L. Hamilton (1951, J. Morphol. 88:49-92) stage series, which is before the onset of axonogenesis. Subsequently, with the onset of axonal outgrowth, C neurons and PL neurons expressed CRABP I in their cell bodies, axons, and growth cones. The expression of CRABP I was developmentally regulated. CRABP I immunoreactivity gradually decreased after st. 36 (embryonic day [E] 10) such that no interneurons expressed this protein by E21. The transient expression of CRABP I during a period of intensive axonal growth suggested that RA may be involved in the development of interneurons. To test this idea, we implanted an all-trans RA-containing ion exchange bead into either rostral segments of the spinal cord at st. 12-13 or into caudal segments at st. 15-16, all stages that are well before the appearance of CRABP-I-positive neurons in these segments. In the RA-treated spinal cord, increased numbers of pyknotic cells were found predominantly in dorsal regions, presumably reflecting the death of neuroepithelial cells, C neurons and premigratory neural crest cells. Surviving C neurons in the RA-treated spinal cord extended their axons ventrally toward the floor plate as in control embryos. PL neurons also projected their axons rostrally or caudally in the RA-treated spinal cord, similarly to control embryos. However, the proportion of caudally projecting PL neurons was significantly increased in segments rostral to the RA-containing bead. These results suggest that RA may regulate the survival and axonal orientation (directionality) of subpopulations of spinal interneurons.

Animals↗
PubMed1995

Platelet-activating factor-induced loss of vascular responsiveness to noradrenaline in pithed rats: involvement of nitric oxide.

The role of nitric oxide and cyclo-oxygenase products in the platelet-activating factor (PAF)-induced hyporesponsiveness to noradrenaline was investigated in pithed rats. Infusion of PAF (30 ng/kg/min) for 60 min reduced the mean arterial blood pressure and impaired the pressor responses to noradrenaline (10 ng/kg, 100 ng/kg, 1 microgram/kg). Administration of NG-monomethyl-L-arginine (L-NMMA, 30 mg/kg) restored the reduced MABP and the impaired responses to their original levels. Indomethacin (5 mg/kg) had no significant effect on the PAF-induced hyporesponsiveness. Administration of 30 mg/kg L-NMMA caused hypertension in the PAF vehicle-treated animals and reduced the pressor response to 1 microgram/kg noradrenaline. Administration of 3 mg/kg L-NMMA had no significant effect on the responsiveness to noradrenaline. These results suggest that nitric oxide contributes to the PAF-induced hyporesponsiveness to noradrenaline and that cyclo-oxygenase products do not play a major role in this hyporesponsiveness.

Analysis of Variance↗
PubMed1995

Increase in plasma nitric oxide end products following rat cortical injury.

The changes in plasma nitric oxide (NO) end products, nitrite (NO2-) and nitrate (NO3-), were studied following cortical injury in rats. At 3 days after stereotactic cortical injury (day 3), plasma NO end products were significantly increased (P < 0.01), and decreased by day 7. This increase on day 3 was inhibited by a selective inhibitor of inducible NO synthase (NOS), aminoguanidine (100 mg/kg, i.p. on days 1 and 2, P < 0.001). The present study first demonstrated the temporary increase in plasma NO end products, which is attributable to the inducible NOS activation after cerebral injury.

Animals↗
PubMed1995

Chronopharmacology of enalapril in hypertensive patients.

The pharmacokinetics and pharmacodynamics of enalapril, an angiotensin converting enzyme inhibitor, are reported to vary with the time of administration. The present study was undertaken to examine whether the effect of enalapril on plasma bradykinin (BK), substance P and prostaglandin E2 (PGE2), which are likely to be involved in the mechanism of enalapril-induced cough, might also be affected by its time of administration. Enalapril 5 mg or placebo was given orally at 10:00 h (day trial) or 22:00 h (night trial) to 12 patients with essential hypertension. Serum concentrations of total drug (enalapril + enalaprilat, its active metabolite) during the day and night trials did not differ significantly at any time. However, serum enalaprilat tended to be higher and its maximum concentration greater in the day trial than in the night trial. Blood pressure 24 h after administration of enalapril was reduced at 22:00 h, but not at 10:00 h. Plasma BK tended to increase following enalapril administration at 10:00 h, but not at 22:00 h. Remarkable increases in plasma BK were observed in two patients in the day trial and one of them also complained of cough. However, no such increase in plasma BK or subsequent adverse effect were recorded in the night trial. Plasma substance P and PGE2 did not change significantly following enalapril administration either in the day or night trial. The results suggest that the response of BK to enalapril is affected by the time of administration. In patients who complain of cough during treatment with enalapril during the daytime, this adverse effect might be diminished or eliminated by a switch to night-time administration.

Adult↗
PubMed1995

Expressing kidney uptake during 99Tcm-MAG3 renography in terms of administered activity.

In a study of gamma-camera renography, a digitized time-activity curve, or renogram, was standardized in terms of absolute renal uptake. The algorithm for standardization of the renogram was based on a gamma-camera uptake method employed by Gates and Schlegel et al. All count rates for the background-corrected renograms were converted to percent renal uptake per injected dose per minute (%RU). The maximum value for the scale on the y-axis was set at 20% RU. The renograms were generated from 66 kidneys in 35 patients (27 males, 8 females) aged 19-80 years. Using the newly developed computer program, the shape of the renograms was considered abnormal between 8/52 (15%) and 10/53 (19%) kidneys, depending on the observer, all of which were classified as normal when displayed conventionally. All the renograms for 4 patients with one poorly functioning kidney, and between 8 (28%) and 10 (32%) renograms for 31 patients with two poorly performing kidneys, exceeded the maximum g-axis value of 20% RU. Expression of the renograms based on absolute uptake is helpful in avoiding the potential problem of two poorly functioning kidneys, which may be considered near-normal in terms of count rate. The maximum value on the y-axis in 99Tcm-MAG3 renography should be fixed between 25 and 30% RU, while the actual amplitude of the standardized renogram may depend on the method used for quantification.

Adult↗
PubMed1995

Ethanol induces heterogeneous reduction of cytochrome aa3 within perfused rat liver lobule assessed using microspectroscopy.

The redox state of cytochrome aa3 was measured at microspots (20 microns diameter) within the lobule of perfused rat livers, using reflectance microspectroscopy, and the effect of ethanol infusion on sublobular distribution of the redox states was evaluated. A sigmoidal relationship was observed between oxygen delivery and the reduction of cytochrome aa3 in both the periportal and pericentral regions of the liver lobule when the influent O2 concentration was decreased in a graduated manner. This sigmoidal curve was shifted to the more reduced state by ethanol infusion, with ethanol (25-100 mM) increasing the degree of cytochrome aa3 reduction in a dose-dependent manner according to the distance from the periportal region along a sinusoid. This increase was spatially heterogeneous within a liver lobule. These data indicate that ethanol accelerates cytochrome aa3 reduction, with a distinct gradient of reduction along sinusoids but a heterogeneous distribution within the liver lobule.

Animals↗
PubMed1995

[Imaging of infectious and inflammatory foci using 111In-DTPA-IgG].

We performed radionuclide scanning after intravenous administration of 80 MBq of 111In-labeled non-specific polyclonal human immunoglobulin G (111In-DTPA-IgG). Serial scintigrams were acquired at 6, 24, 48, and 72 hr after injection in 10 patients suspected of having inflammation and/or infection. In 5 patients, the results of scintigraphy were verified with intraoperative cultures or biopsy. The values were as follow: sensitivity: 100% (4/4); specificity 50% (3/6); accuracy: 70% (7/10); positive predictive value: 57.1% (4/7); and negative predictive value: 100% (3/3). The results indicate that 111In-DTPA-IgG scintigraphy is certainly a promising method for the detection of inflammation and/or infection.

Adult↗
PubMed1995

[Response-oriented salvage chemotherapy with mitoxantrone, etoposide and enocitabine for previously treated acute myeloid leukemia. Tohoku Leukemia Study Group].

Twenty-two patients with previously treated acute myeloid leukemia (AML) received salvage chemotherapy with mitoxantrone, 5 mg/m2/d on days 1 to 3, etoposide, 70 mg/m2/d on days 1 to 5, and enocitabine, 170 mg/m2/d on days 1 to 7 (BHAC-ME). Additional mitoxantrone, etoposide (both for up to 2 days) and enocitabine (for up to 7 days) were given if the bone marrow obtained on day 8 was not severely hypoplastic. Mitoxantrone and etoposide had been previously administered in 14 and 15 patients, respectively. Seven patients had primary resistance; 14 patients had first relapse (4 early and 10 late): and 2 patients had second relapse. Overall, seven patients (31%) achieved a complete remission; 7/14 with first relapse, and 0/8 with primary resistance or second relapse. Four patients, 3 with primary resistance and 1 with first relapse, died of infectious complication in aplasia. First relapse patients who had been previously treated both with mitoxantrone and etoposide, had a lower CR rate than the other first relapse patients [2/8 (25%) vs 5/6 (86%)], although patient characteristics such as duration of first CR, initial karyotype, and performance status, were similar between the two groups. We conclude that response-oriented BHAC-ME regimen is still active in first relapse AML patients unless they have received both mitoxantrone and etoposide previously.

Acute Disease↗
PubMed1995

Influence of aging on the oxidative and conjugative metabolism of propranolol.

The influence of aging on the hepatic metabolism of propranolol, i.e. conjugation, side-chain oxidation and ring oxidation, was investigated in 32 in-patients aged 30 to 84 yrs. Plasma propranolol concentration and main urinary metabolites [propranolol glucuronide (PPLG), naphthoxylactic acid (NLA), and 4-hydroxypropranolol (40HP)] were determined after a single oral dose of 20 mg propranolol. There were significant correlations between age and 1) maximum propranolol concentration, 2) area under the plasma concentration-time curve, and 3) elimination half-life. The apparent oral clearance of propranolol was inversely correlated with age. Partial metabolic clearance (PMC) to 40HP (ring oxidation) and PMC to NLA (side-chain oxidation) were significantly correlated with age, while PMC to PPLG was not. These observations suggest that there are age-related reductions in two oxidizing capacities, while there is no significant influence of aging on the conjugating capacity. The age-related reduction in oral clearance of propranolol may be mainly caused by the decline in the capacity of two different oxidation pathways.

Adrenergic beta-Antagonists↗
PubMed1994

Effects of NG-nitro-L-arginine and/or L-arginine on experimental pulmonary metastasis in mice.

Effects of NG-nitro-L-arginine methyl ester (L-NAME; an inhibitor of nitric oxide (NO) synthase) and/or L-arginine (substrate of NO synthase) on pulmonary metastasis of murine melanoma and Lewis lung carcinoma cells were investigated. L-NAME, L-arginine or both L-NAME and L-arginine was injected i.p. into mice 5, 3, and 1 h before and 1, 3, 5, and 7 h after the injection of tumor cells into mice via a tail vein. The administration of L-NAME (9.3 mumol/mouse) alone or L-arginine alone (46.5 or 186 mumol/mouse) potentiated pulmonary metastasis of highly and poorly metastatic B16 melanoma cells. L-NAME alone also increased the number of pulmonary metastasis of Lewis lung carcinoma cells, but L-arginine (185 mumol/mouse) did not. However, the combination of L-NAME and L-arginine increased the number of pulmonary metastasis of both the melanoma and Lewis lung carcinoma cells synergistically. L-NAME or L-arginine administration enhanced the retention of B16 melanoma cells in the lungs examined 24 h after the tumor cell injection. Synergistic effect of L-NAME and L-arginine was also seen in the tumor cell retention. The present results suggest that the metastatic potentials of the tumor cells do not simply correlate to NO production in vivo.

Animals↗