Search PubMed⌕ Search

Biomedical subjects

N Aoki

Publications and source records attributed to N Aoki.

At least 379 records · Page 21Linked to original sources

Protective effects of a novel nonglucocorticoid 21-aminosteroid (U74006F) during traumatic shock in rats.

The purpose of this study was to investigate the effect of the nonglucocorticoid steroid U74006F in the pathogenesis of a murine traumatic shock model. Pentobarbital-anesthetized (40 mg/kg) rats were subjected to Noble-Collip drum trauma and developed a lethal shock state characterized by a decreased mean arterial blood pressure (MABP) to 67 +/- 2 mm Hg and survival time (1.5 +/- 0.2 h). In contrast, sham trauma rats exhibited a MABP of 122 +/- 4 mm Hg at 5 h postanesthesia. Administration of U74006F at doses of 22.5 mg/kg at 15 to 20 min following trauma significantly maintained a higher MABP and prolonged survival compared to those trauma rats receiving only the vehicle for U74006F (0.002 N HCl). U74006F at 15 and 22.5 mg/kg prolonged survival time to 2.6 +/- 0.3 (p less than 0.05) and 3.1 +/- 0.6 h (p less than 0.02), respectively. U74006F also significantly attenuated the plasma accumulation of cathepsin D (p less than 0.02 to p less than 0.01) and free amino-nitrogen compounds (p less than 0.01) compared to the rats receiving only vehicle. Additionally, U74006F at 15 and 22.5 mg/kg blunted the production of the cardiotoxic peptide, myocardial depressant factor (MDF) (p less than 0.01 to p less than 0.001). Moreover, U74006F is a steroid without significant glucocorticoid or mineralocorticoid activity. These results suggest that U74006F may be useful as a therapeutic agent in traumatic shock.

Animals↗

Effects of interleukin-6 and granulocyte colony-stimulating factor on the proliferation of leukemic blast progenitors from acute myeloblastic leukemia patients.

The effects of recombinant human interleukin-6 (rh IL-6), which has homology with rh granulocyte colony-stimulating factor (rh G-CSF) at the amino acid sequence level, and rh G-CSF on normal human bone marrow cells, fresh leukemic blast progenitors from 16 acute myeloblastic leukemia (AML) patients, and G-CSF-dependent human AML cell line (OCI/AML 1a) were investigated. rh G-CSF stimulated the proliferation of leukemic blast progenitors from 13 out of 16 AML patients tested. rh IL-6 stimulated the proliferation of blasts from eight AML patients and enhanced the G-CSF-dependent proliferation of the fresh AML blasts from two out of eight patients tested. On the other hand, rh IL-6 suppressed the blast colony formation from two AML patients and OCI/AML 1a cells and also reduced the G-CSF-dependent proliferation of the blast progenitors from one of the two patients and the cell line, rh IL-6 had no effect on the colony formation of normal granulocyte-macrophage colony-forming units (CFU-GM) with or without rh G-CSF. Differentiation-induction by rh IL-6 was not observed in the fresh AML blasts but was observed in OCI/AML 1a. The effect of IL-6 on the blast colony formation and G-CSF-dependent blast cell growth was complicated and heterogenous among the AML cases; IL-6 stimulated blast colony formation in some cases and suppressed it in others. The heterogeneity of the response was supposed to be derived from the heterogeneity of the characteristics of AML cells. Although G-CSF simply stimulated the blast colony formation, IL-6 had a bimodulatory effect on the proliferation of leukemic blast progenitors from AML patients. IL-6 might be involved in the regulation of the proliferation of AML cells in vivo as well as in vitro.

Adolescent↗

Beneficial effects of two forms of NO administration in feline splanchnic artery occlusion shock.

We studied the effects of nitric oxide (NO) solution and acidified sodium nitrite (NaNO2), which produces NO, in splanchnic artery occlusion (SAO) shock in cats. NO is thought to be endothelium-derived relaxing factor (EDRF), a labile substance having several potentially valuable biological effects. Anesthetized cats subjected to total occlusion of the celiac, superior mesenteric, and inferior mesenteric arteries for 120 min, followed by reperfusion, usually died approximately 60 min after reperfusion. NO infusion significantly improved survival time in SAO-shock cats compared with those receiving vehicle (P less than 0.005). Administration of NO also attenuated the increase in plasma activities of the lysosomal hydrolase cathepsin D (P less than 0.05), total amino-nitrogen (P less than 0.001), and of the cardiotoxic peptide, myocardial depressant factor (MDF) (P less than 0.001). SAO-shock cats treated with NaNO2 at pH 2.0 also exhibited lower plasma cathepsin D (P less than 0.001), amino-nitrogen (P less than 0.05), and MDF activities (P less than 0.01), and survival time was also significantly improved (P less than 0.02). The same dose of NaNO2 infused at pH 7.4 failed to exert any significant protective effect. These results indicate that NO exerts beneficial effects in SAO shock in cats and suggest that exogenously administered NO may be a potentially useful therapeutic agent in splanchnic ischemic shock, probably via a cytoprotective rather than a vasodilator effect.

Amines↗

Leukocyte-dependent and leukocyte-independent mechanisms of impairment of endothelium-mediated vasodilation.

Leukocytes release cytokines and oxygen derived free radicals upon activation. Both superoxide (O2) and tumor necrosis factor (TNF) inhibit endothelium-dependent vasodilation in the intact circulation as well as in isolated blood vessels. Superoxide inactivates endothelium-derived relaxing factor (EDRF) rapidly, whereas TNF required 2 h to block EDRF release due to synthesis of adhesive proteins on the surface of neutrophils and/or the expression of their ligands on endothelial cells. Thus, vasodilation to acetylcholine is markedly attenuated by either O2 or TNF, whereas the vasodilation to NaNO2 at pH 2.0 or to nitroglycerin is not affected. Superoxide dismutase restores acetylcholine responses to myocardial ischemia followed by reperfusion, whereas cycloheximide restores acetylcholine responses to TNF. This occurs both in the isolated perfused rat heart (perfused without plasma or blood cells) and in isolated perfused cat carotid arteries. EDRF may be important in preserving integrity of vital tissues during ischemic states.

Acetylcholine↗

Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the cat.

Myocardial ischemia and reperfusion have been shown to impair coronary vasorelaxation to endothelium-dependent vasodilators. To examine the time course of this dysfunction, occlusion of the left anterior descending (LAD) coronary artery (90 minutes) was followed by reperfusion for 0, 2.5, 5, 20, 180, or 270 minutes. Coronary arterial rings from the ischemic LAD and control left circumflex (LCx) arteries were tested for responsiveness to the endothelium-dependent receptor-mediated vasodilator, acetylcholine (ACh), and the endothelium-dependent nonreceptor-mediated vasodilator, A23187, as well as the endothelium-independent vasodilator, NaNO2. ACh relaxation was not impaired after 90 minutes of ischemia without reperfusion. However, 2.5 minutes of reperfusion resulted in depressed ACh responses (36 +/- 10% of control) that was further reduced to 16 +/- 6% at 20 minutes, and remained comparably depressed at every time thereafter. A23187 vasodilator responses were also attenuated after reperfusion, although the reduced response occurred later (that is, at 20 minutes). There was no significant decrease in response to NaNO2 in the LAD at any time or to any vasodilator in LCx control rings. Treatment with recombinant human superoxide dismutase (hSOD, 5 mg/kg/hr, that is, 15,545 SOD units/kg/hr), starting 10 minutes before reperfusion, preserved the vasodilator response to ACh (82 +/- 6%) and A23187, but treatment with the hydroxyl ion scavenger N-(2-mercapto proprionyl)-glycine (MPG) (8 mg/kg/hr) only protected the A23187 response. No damage to the surface of the endothelium was observed by scanning electron microscopy at any time point. Myocardial cell damage increased with time of reperfusion as assessed by increasing plasma CK activities and amounts of necrotic tissue indexed to area at risk. Significant myocardial injury occurred at 3 hours after reperfusion. These findings suggest that endothelial dysfunction resulting in reduced endothelium-derived relaxing factor release occurs before the development of myocardial cell necrosis and may be due to oxygen-derived free radicals produced rapidly on reperfusion.

Animals↗

Endothelium and myocardial protecting actions of taprostene, a stable prostacyclin analogue, after acute myocardial ischemia and reperfusion in cats.

The effects of taprostene, a synthetic prostacyclin analogue, were investigated in a 6-hour model of myocardial ischemia (MI) with reperfusion in anesthetized cats. Taprostene (100 ng/kg/min) was infused intravenously starting 30 minutes postocclusion of the left anterior descending coronary artery followed by reperfusion 1 hour later, and the cats were observed for an additional 4.5 hours. Taprostene infusion resulted in significantly lower plasma creatine phosphokinase activities at every time from 3 to 6 hours for the MI + taprostene group compared with the MI + vehicle group and were not significantly different when compared with sham MI controls. The areas at risk, expressed as a percentage of the total left ventricular weights, were not significantly different between the MI groups. However, the necrotic area expressed as a percentage of the myocardial area at risk was significantly lower in the taprostene-treated cats compared with the untreated MI group (p less than 0.01). Cardiac myeloperoxidase activities indicated that significantly fewer neutrophils were attracted to the area at risk and to the ischemic zone of the MI + taprostene cats when compared with the MI cats given only the vehicle. Data from isolated left anterior descending coronary artery ring preparations removed from hearts after 6 hours of ischemia indicated that the endothelium was damaged by ischemia-reperfusion injury in the untreated cats. However, endothelial dysfunction was not observed in circumflex coronary arteries of ischemic cats or in coronary rings isolated from MI + taprostene cats. Thus, taprostene exerted a significant cardioprotection in cats subjected to ischemia and reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Rebleeding from intracranial dissecting aneurysm in the vertebral artery.

We describe two patients with rebleeding from intracranial vertebral artery dissecting aneurysms during the acute stage. One patient had excellent results after emergency surgery. A review of recent reports including 60 patients with this disorder revealed a rebleeding rate of 30%, mostly during the acute stage. This suggests that a ruptured dissecting aneurysm in the vertebral artery is at risk for rebleeding during the acute stage, similar to a saccular aneurysm in the same location.

Aortic Dissection↗

Chronic subdural hematoma in infancy. Clinical analysis of 30 cases in the CT era.

The cases of 30 infants with chronic subdural hematoma treated surgically between 1978 and 1987 (after the introduction of computerized tomography) were reviewed. This series was limited to infants presenting with increased intracranial pressure, neurological deficits, or developmental retardation. Nineteen patients were male and 11 were female, ranging in age from 1 to 14 months (average 6.1 months). The surgical treatment was initiated with percutaneous subdural tapping which was repeated periodically, if indicated, for 2 weeks. If the patients failed to respond to subdural tapping, subdural-peritoneal shunting was installed. The follow-up periods were from 3 months to 9 years 8 months (average 4 years 10 months). Computerized tomography at that time disclosed disappearance or minimal collection of subdural fluid in 28 cases (93%) and a significant collection (greater than 5 mm) in two (7%). Neurological examination revealed that the patients were "normal" in 17 cases (57%), "mildly or moderately disabled" in nine (30%), and "severely disabled" in four (13%). The majority of disabled patients had lesions secondary to infantile acute subdural hematoma, child abuse, or hemorrhagic diathesis. These results indicate that the treatment protocol in the present series is acceptable for the elimination of subdural hematoma. Together, early diagnosis and treatment of the etiological conditions causing the lesion are indispensable for obtaining a satisfactory neurological outcome.

Chronic Disease↗

[Combination therapy with aztreonam and clindamycin on severe infections accompanying neutropenic patients with hematological disorders].

We studied effectiveness and safety of combination therapy of aztreonam (AZT) (2-6 g/day) and clindamycin (CLDM) (1,200-2,400 mg/day) on severe infections in neutropenic patients with hematological diseases. We administered AZT and CLDM to 250 consecutive patients and analyzed the results of a total of 212 cases for evaluation except 38 cases of exclusions and dropouts. Hematological malignancies constituted the dominating underlying diseases which represented 90.6% of all underlying diseases. The overall clinical efficacy of the combination therapy with AZT and CLDM was 65.6% and the following results were obtained for different categories: sepsis, 64.7%; suspected sepsis, 66.4%; and pneumonia 54.5%. Even severe patients with less than 100/microliters of neutrophil counts showed good responses with an efficacy rate at 57.4%. Side effects were observed in only 7 cases (2.8%). We concluded that the combination therapy with AZT and CLDM would be useful as empiric therapy against various infections in febrile neutropenic patients with hematological diseases.

Adult↗

Haematopoietic suppressing activity of gamma-interferon in serum and bone marrow of aplastic anaemia patients.

To determine the mechanism by which haematopoiesis is suppressed in aplastic anaemia, the effect of the sera from 6 patients on the granulopoietic precursors (colony-forming units in culture; CFU-C) was studied in vitro. Addition of the sera from 2 patients significantly suppressed CFU-C. The suppressive effect of the sera on CFU-C was inhibited by the addition of 1.5 NU/ml of anti-gamma-IFN antibody. In another patient, anti-gamma-IFN antibody increased autologous CFU-C although the serum of the patient did not suppress CFU-C. Serum gamma-IFN levels of all patients were under 2 IU/ml. The above findings suggest that humoral factors inhibit haematopoiesis in some patients with aplastic anaemia, and that gamma-IFN plays a role as an inhibitor even at a low concentration.

Adolescent↗

[A case of large basal ganglia AVM totally removed by staged operation].

Large basal ganglia AVMs have been deemed inoperable because of their location in critical structures. Nonetheless, the unfavorable natural history of an untreated ruptured AVM in a young patient induced us to approach these lesions. We presented a case of a large basal ganglia AVM totally removed by a three-staged operation. A 26-year-old man who had twice experienced intracranial hemorrhage was admitted for examination. On admission, mild left hemiparesis, hypesthesia and left hemianopsia were disclosed. CT scan showed the AVM was located in the posterior thalamus with the hematoma cavity laterally. Right carotid and vertebral angiograms demonstrated a large AVM, 5cm in diameter, supplied by the anterior choroidal artery (AchoA), the lateral lenticulostriate arteries (I-LSAs), the lateral posterior choroidal artery (LPchoA) and the thalamo-perforating artery. Drainage was via the internal cerebral vein and the basal vein of Rosenthal. MRI demonstrated more clearly the anatomical relationship of the nidus and surrounding structures. The patient underwent a three staged operation. At the first operation AchoA was interrupted in the inferior horn of the lateral ventricle (IHL) via the hematoma cavity using the trans-sylvian approach. The anterior part of the nidus was dissected with all except one of the I-LSAs being disconnected. At the next operation by occipital interhemispheric approach, some feeders from the posterior cerebral artery were coagulated and disconnected. The medial and posterior part of the nidus was dissected from the thalamus along with the choroid plexus of the trigone of the lateral ventricle.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗