Oxidation and reduction of nitrite ion in the TiO2 photo-induced catalytic reaction.

During a photo-induced catalytic reaction under near UV irradiation to an aqueous suspension of Ti4O2, about 95% of NO2- was oxidized to NO3-, but NH4+ was not detected. The oxidation was inhibited by the addition of mannitol or under anaerobic conditions. The nitration of HPA was observed in the presence of t-buthanol, suggesting the formation of ONOO. An ESR spectrum gave a triplet signal at g = 2.041,in the presence of NO2-, mannitol, FeSO4, and MGD, indicating the reduction of NO2- to NO.

Luminescence of Novel Neodymium Sulfonylaminate Complexes in Organic Media.

Luminescence of Nd(III) in an organic solvent having C-H bonds was achieved for the first time by complexing Nd(III) with long-chain perfluoroalkylated ligands such as bis(perfluorooctylsulfonyl)aminate (pos). The complex [Nd(pos)(3)] gave an emission quantum yield of 3.0+/-0.5 % in undeuterated acetone. The bulky pos ligands suppress the excitation of C-H vibrations, energy migration at diffusional collision, and the coordination of acetone molecules (see picture) to the Nd(III) center, which otherwise quench the luminescence.

[The usefulness of dynamic computed tomography scanning in predicting the outcome of acute stroke patients].

The aim of this study was to investigate whether brain dynamic computed tomography (CT) is useful in predicting clinical outcome. Thirty patients suffering from cerebral ischemia in the territory of the middle cerebral artery (MCA) underwent dynamic CT scanning within 6 hours of stroke onset. Regions of interest (ROIs) were placed in the bilateral MCA territories and three parameters, peak value (PV), time to peak (TP), and PV divided by TP, were calculated from time-density curves (TDCs) on ROIs. After conventional treatment using pharmacological agents, the 30-day clinical outcome was evaluated on the Glasgow outcome scale. To investigate the relationship between the disease-to-contralateral side ratio of each parameter's value and 30-day clinical outcome, TDCs were classified into the following four types; type 1, with TP ratio less than 1.1; type 2, with TP ratio ranging from 1.1 to 1.5 and PV/TP ratio more than 0.75; type 3, with TP ratio ranging from 1.1 to 1.5 and PV/TP ratio less than 0.75; and type 4, with TP ratio more than 1.5 and PV/TP ratio less than 0.3. Clinical outcome in patients with type 1 or 2 TDC was better than in patients with type 3 or 4 TDC (p < 0.01, Fisher's exact test). We can conclude that dynamic CT is a useful means for estimating the clinical prognosis of acute stroke patients after conventional treatment. Poor clinical outcome following conventional therapy is expected in patients with type 3 or 4 TDC in contrast to patients with type 1 or 2 TDC.

A case of Rathke's cleft cyst with apoplexy.

We report a case of Rathke's cleft cyst associated with cholesterin granuloma in an 8-year-old girl with apoplexy. She was admitted to our hospital in April 1996 because of repeated headache and deep ophthalmic pain, without any visual disturbance. Computed tomography (CT) of the pituitary demonstrated an intrasellar isodense mass extending to the suprasellar cistern. Magnetic resonance imaging (MRI) showed a high-intensity mass on both T1- and T2-weighted images. The preoperative diagnosis of this lesion was Rathke's cleft cyst associated with a craniopharyngioma and/or hemorrhage. Transsphenoidal microsurgery was performed, and a bloody coffee-like serous and mucinous-yellowish substance was evacuated. Curettage of the wall removed the yellowish hard mass and soft membranous tissue. Histological examination of this tumor revealed a Rathke's cleft cyst with cholesterin granuloma.

Differential cytoprotection by glycine against oxidant damage to proximal tubule cells.

Tert-butyl hydroperoxide (tBHP) injured freshly isolated proximal tubules in an Fe-dependent fashion that was ameliorated by a lipophilic antioxidant, diphenyl-p-phenylenediamine (DPPD), but was only minimally affected by glycine. Menadione-induced injury was Fe-independent and was unaffected by DPPD, but was strongly blocked by glycine. Fe was highly toxic when intracellular loading was facilitated by concomitant treatment with hydroxyquinoline (HQ). This toxicity was blocked by DPPD or chelating the Fe, but not by glycine. All of the lesions were characterized by severe depletion of glutathione and other soluble thiols. Menadione induced large increases in protein associated with the Triton-insoluble cytoskeleton and decreases in protein thiol content, consistent with extensive cross linking, but did not increase thiobarbituric acid reactive substances (TBARS). tBHP and HQ + Fe had either no effect or only moderate, delayed effects on cytoskeletal proteins, but induced substantial increases of TBARS. Glycine did not the alter changes in cytoskeletal proteins, thiols, or TBARS produced by any of the agents. Protection against tBHP toxicity by deferoxamine and DPPD was accompanied by substantial suppression of TBARS accumulation. Superimposition of hypoxia during tBHP exposure reduced TBARS accumulation and restored cytoprotective activity to glycine. Thus, in contrast to its consistently strong cytoprotection against a number of other insults, glycine is only variably cytoprotective against oxidant lesions in freshly isolated proximal tubules. Extensive oxidative crosslinking of proteins is compatible with maintenance of glycine cytoprotection against lethal membrane damage. Fe-induced injury to proximal tubules associated with lipid peroxidation as manifested by TBARS formation is a relatively glycine-insensitive insult.

Calcium dependence of integrity of the actin cytoskeleton of proximal tubule cell microvilli.

To better define the role of Ca2+ in pathophysiological alterations of the proximal tubule microvillus actin cytoskeleton, we studied freshly isolated tubules in which intracellular free Ca2+ was equilibrated with highly buffered, precisely defined medium Ca2+ levels using a combination of the metabolic inhibitor, antimycin, and the ionophore, ionomycin, in the presence of glycine, to prevent lethal membrane damage and resulting nonspecific changes. Increases of Ca2+ to > or = 10 microM were sufficient to initiate concurrent actin depolymerization, fragmentation of F-actin into forms requiring high-speed centrifugation for recovery, redistribution of villin to sedimentable fractions, and structural microvillar damage consisting of severe swelling and fragmentation of actin cores. These observations implicate Ca(2+)-dependent, villin-mediated actin cytoskeletal disruption in tubule cell microvillar damage under conditions conceivably present during pathophysiological states. However, despite prior evidence for cytosolic free Ca2+ increases of the same order of magnitude and similar structural microvillar alterations, Ca(2+)- and villin-mediated events did not appear to account for the initial microvillar damage that occurs during ATP depletion induced by antimycin alone or hypoxia.

The selective endothelin ETA receptor antagonist FR139317 inhibits neointimal thickening in the rat.

Endothelin is known as a potent mitogenic mediator. We tested the in vivo ability of FR139,317((R)2-[(R)-2-[(S)-2-[[1-(hexahydro- 1H-azepinyl)]carbonyl]amino-4-methylpentanoyl] amino-3-[3-(1-methyl-1 H-indoyl)]propionyl]amino-3-(2-pyridyl)propionic acid), a selective antagonist of the endothelin ETA receptor subtype, to inhibit neointimal thickening following photochemically induced injury of the endothelium of rat femoral artery. FR139,317 (32 mg/kg s.c., twice a day) was administered for 3 weeks after the injury. FR139,317 significantly decreased the neointimal area (76.3%) without changing the medial area. Therefore, it is suggested that endothelin may play an important role, via mainly endothelin ETA receptors, in neointima formation in injured artery.

Contribution of actin cytoskeletal alterations to ATP depletion and calcium-induced proximal tubule cell injury.

The actin cytoskeleton of rabbit proximal tubules was assessed by deoxyribonuclease (DNase) binding, sedimentability of detergent-insoluble actin, laser-scanning confocal microscopy, and ultrastructure during exposure to hypoxia, antimycin, or antimycin plus ionomycin. One-third of total actin was DNase reactive in control cells prior to deliberate depolymerization, and a similar proportion was unsedimentable from detergent lysates during 2.5 h at 100,000 g. Tubules injured by hypoxia or antimycin alone, without glycine, showed Ca(2+)-dependent pathology of the cytoskeleton, consisting of increases in DNase-reactive actin, redistribution of pelletable actin, and loss of microvilli concurrent with lethal membrane damage. In contrast, tubules similarly depleted of ATP and incubated with glycine showed no significant changes of DNase-reactive actin or actin sedimentability for up to 60 min, but, nevertheless, developed substantial loss of basal membrane-associated actin within 15 min and disruption of actin cores and clubbing of microvilli at durations > 30 min. These structural changes that occurred in the presence of glycine were not prevented by limiting Ca2+ availability or pH 6.9. Very rapid and extensive cytoskeletal disruption followed antimycin-plus-ionomycin treatment. In this setting, glycine and pH 6.9 decreased lethal membrane damage but did not ameliorate pathology in the cytoskeleton or microvilli; limiting Ca2+ availability partially protected the cytoskeleton but did not prevent lethal membrane damage. The data suggest that both ATP depletion-dependent but Ca(2+)-independent, as well as Ca(2+)-mediated, processes can disrupt the actin cytoskeleton during acute proximal tubule cell injury; that both types of change occur, despite protection afforded by glycine and reduced pH against lethal membrane damage; and that Ca(2+)-independent processes primarily account for prelethal actin cytoskeletal alterations during simple ATP depletion of proximal tubule cells.

[Surgical treatment of subaortic stenosis].

We reviewed 10 cases with subaortic stenosis (SAS) who underwent surgical repairs in our hospital. They were divided into 3 groups. Group I-A included patients with discrete SAS which had been detected before the initial operation. Group I-B included patients with discrete SAS which became apparent following the initial operations. Group II patients included SAS except the discrete type. Surgical treatment of each group was discussed. In group IA, there were no early deaths nor late deaths. There was 1 reoperation due to restenosis. Group IB had 3 cases which included VSD with CoA, Taussig-Bing anomaly, and common atrioventricular canal with VSD. In the Taussig-Bing anomaly case, an arterial switch (Lecompte maneuver) was performed 3 years ago. SAS was successfully relieved with the right ventriculotomy and VSD patch incision. Group II had 3 cases. There were 2 operative deaths and 1 late death. SAS was relieved by, in two cases, Stansel anastomosis with BT shunt and, in the last one, palliative arterial switch operation. It was extremely difficult to detect SAS in group II, when SAS had rapidly progressed following PAB in neonate and early infant. Our present policy is that PAB would be performed if there is no apparent SAS before the initial operation. SAS should be relieved as soon as possible if it is apparent at the postoperative period. Either Stansel anastomosis with BT shunt or palliative arterial switch operation would be the best choice in such a difficult case.

[Two cases of coronary artery fistula with coronary artery aneurysm].

Two cases of coronary artery fistula with coronary artery aneurysm were reported. Coronary angiography showed dilated right coronary artery with the formation of aneurysm drained to the right atrium and to the right ventricle respectively. The inflow ostium from the coronary artery to the aneurysm were closed from inside adding aneurysmorraphy. Postoperative clinical courses were uneventful and residual shunts were not detected by angiography. We reported these cases with literature.

[Right-sided infective endocarditis with ventricular septal defect].

Two patients underwent surgical treatment for right-sided infective endocarditis with ventricular septal defect. In both cases, blood cultures showed Peptostreptococcus, and the operation was performed at non-active phase after antibiotics therapy. The case 1 was a 7-year-old girl who was observed a vegetation on the chorda of the anterior paillary muscle by echocardiography. The defect was directly closed and the vegetation was excised. The case 2 was 22-year-old female who had been diagnosed of VSD in her infancy. A high fever continued and echocardiography revealed a vegetation attached to the septal tricuspid leaflet. Partial excision of the leaflet and autopericard patch plasty was performed, and the VSD was directly closed. Postoperatively intravenous antibiotic therapy was given for periods of 6 weeks, and clinical course were uneventful in both cases. Local excision of vegetation and leaflet repair by autopericard patch plasty should be performed in cases with localized vegetation and minor valvular regurgitation.

The pharmacological characterization of FK 739, a new angiotensin II-receptor antagonist.

The pharmacological properties of FK 739, a new angiotensin II-receptor antagonist, were examined. FK 739 inhibited the specific binding of [125I]-angiotensin II to rat aortic smooth muscle cell membrane with an IC50 value of 8.6 nM, but did not displace the specific binding of [125I]-angiotensin II to bovine cerebellum membrane. In isolated helical strips of rabbit aorta, FK 739 shifted the concentration-response curve of angiotensin II-induced contraction in parallel to the right, and the values of the slope and pA2 were 1.06 and 8.45, respectively. In in vivo studies, oral administration of FK 739 at 10 mg/kg significantly inhibited the angiotensin I-induced pressor response in normotensive rats and dogs, and it caused a fall of mean blood pressure in renal hypertensive rats and dogs. In spontaneously hypertensive rats, FK 739 at 32 and 100 mg/kg significantly decreased the mean blood pressure in a dose-dependent manner. Additionally, we studied whether FK 739 would cause side effects such as dry cough, like other ACE inhibitors did. Oral administration of FK 739 (10 and 32 mg/kg) did not affect the capsaicin-induced bronchial edema. On the other hand, captopril (10 mg/kg) significantly enhanced capsaicin-induced bronchial edema. These results indicate that FK 739 is a potent and competitive antagonist for AT1-type receptors, and suggest that FK 739 might be a safe and useful agent for the treatment of hypertension in clinical trials.

Pharmacological profile of FR139317, a novel, potent endothelin ETA receptor antagonist.

The effects of FR139317 on the cardiovascular system were investigated in cultured cells, isolated organs and whole animals. FR139317 inhibited the specific binding of [125]endothelin(ET)-1 to porcine aortic microsomes in a concentration-dependent, monophasic fashion with an IC50 of 0.53 nM. In contrast, FR139317 showed low affinity for [125I]ET-1 specific binding sites in porcine kidney (IC50, 4.7 microM). In isolated rabbit aorta, FR139317 shifted the ET-1-induced concentration-contractile response curve to the right with a pA2 value of 7.2 and lacked agonist activity. A single (i.v.) bolus dose of FR139317 completely inhibited the pressor response to ET-1 in vivo, but had no effect on the initial depressor response in conscious normotensive rats. These data indicate that FR139317 is a potent, highly specific ETA receptor antagonist. In addition, FR139317 also inhibited ET-1 induced [3H]thymidine incorporation in cultured vascular smooth muscle cells from rat aorta (IC50, 4.1 nM), suggesting that ET-1-induced mitogenesis is mediated only by the ETA receptor. FR139317 could become a useful tool for investigating the physiological and pharmacological actions of ET.

Subtype selectivity of a novel endothelin antagonist, FR139317, for the two endothelin receptors in transfected Chinese hamster ovary cells.

We investigated the receptor-binding properties and the antagonist activities of FR139317, a novel endothelin (ET) antagonist, in transfected Chinese hamster ovary cells permanently expressing the two ET receptor subtypes (ETA and ETB). In displacement analysis using membrane preparations derived from the receptor-expressing cells, FR139317 showed a high affinity for ETA (Ki = 1 nM) and a lower affinity for ETB (Ki = 7.3 microM). FR139317 inhibited ETA-mediated phosphatidylinositol hydrolysis and arachidonic acid release and produced a parallel shift in the dose-response curve for ET-1, with respective pA2 values of 8.2 and 7.7. In contrast, FR139317 had no inhibitory effects on these ET-1-induced responses in ETB-expressing cells. FR139317 itself showed no stimulatory effects on phosphatidylinositol hydrolysis and arachidonic acid release in ETA- and ETB-expressing cells. Thus, FR139317 is a potent, competitive, and highly selective antagonist for ETA. This compound should be a powerful tool for investigation of the physiological properties of ETA and exploration of its role in diseases.

An endothelin ETA receptor antagonist, FR139317, ameliorates cerebral vasospasm in dogs.

The role of endothelin in the pathogenesis of cerebral vasospasm after subarachinoid hemorrhage was investigated by evaluating the effect of FR139317, a novel potent ETA receptor antagonist, on the vasospasm in a canine two-hemorrhage model. Intracisternal administration of FR139317 (0.1 mg) significantly reduced the vasoconstriction of the basilar artery at day 7 (control group, n = 6, 61.6 +/- 4.0%, FR139317 treated group, n = 6, 75.9 +/- 1.5% of basal diameter, p < 0.01). In normal anesthetized dogs, the intracisternal administration of FR139317 did not affect the basal diameter of the basilar artery, blood pressure or heart rate. These results suggest that endothelin plays an important role in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage, and that FR139317 could be a valuable tool for preventing vasospasm after subarachnoid hemorrhage.

Nilvadipine as a neuroprotective calcium entry blocker in a rat model of global cerebral ischemia. A comparative study with nicardipine hydrochloride.

The effects of two dihydropyridine type calcium entry blockers, nilvadipine and nicardipine hydrochloride (nicardipine), on the liberation of free fatty acids (FFAs) were investigated using an experimental model of global cerebral ischemia in rats, and were compared with their pharmacokinetic properties. Nilvadipine, but not nicardipine, at a dose of 100 micrograms/kg i.v., significantly attenuated the liberation of FFAs, particularly docosahexaenoic and arachidonic acid. Furthermore, the brain concentration of nilvadipine was higher than that of nicardipine after equivalent dosing. The results of the present study demonstrate that pharmacokinetic differences between these two calcium entry blockers might explain the difference in their pharmacological efficacy.

WS009 A and B, new endothelin receptor antagonists isolated from Streptomyces sp. no. 89009. II. Biological characterization and pharmacological characterization of WS009 A and B.

WS009 A and B, produced by Streptomyces sp. No. 89009, were found to be competitive and specific antagonists against endothelin (ET)-1 receptors in in vitro studies and also active in in vivo studies. Furthermore, WS009 A and B were specific antagonists for vascular ET-1 receptors (ETA receptors) and significantly prevented the accumulation of intracellular inositol 1,4,5-triphosphate (IP3) in endothelin treated rat aorta tissues.

[Dural arteriovenous malformation in the falx with subarachnoid hemorrhage].

A case of falx dural arteriovenous malformation was reported. A 62 year old man was admitted to Nakamura City Hospital on August 15, 1989, with severe headache as his chief complaint. On admission, his consciousness was lethargic. CT scan showed subarachnoid hemorrhage with ventricular perforation and hematoma of the corpus callosum. Angiograms demonstrated a dural arteriovenous malformation (DAVM) in the frontal falx, which was fed by bilateral middle meningeal arteries and the left anterior falx artery and drained into the superior sagittal sinus via the dural vein. Bifrontal craniotomy was performed. At first, bilateral middle meningeal arteries were coagulated, and the frontoparietal dura was excised widely. Then, the falx was cut at the crista galli. The DAVM was found in the falx, including a vascular sac embedded in the brain tissue. The DAVM was coagulated as much as possible. Carotid angiograms revealed complete disappearance of the DAVM, 4 months after the operation. Although angiograms performed after only one month still showed a small residual DAVM. On reviewing the literature we found only 5 patients with the DAVM in the falx. In 6 cases including our own, intracranial hemorrhage occurred in 4 cases (3 cases were subarachnoid hemorrhage). Vascular sacs were seen in 4 cases, and drainage to the pial vein was noted in 3 cases. It seemed to be rare that the DAVM drained into the dural vein. In our particular case, operative findings showed the DAVM drained into the dural vein without the pial vein, and intracranial hemorrhage was attributed to rupture of the vascular sac.