[An outline of continuous ambulatory peritoneal dialysis (CAPD)].
Explore the source record for details and available documents.
Humans↗
Biomedical subjects
K Kubo
Publications and source records attributed to K Kubo.
[Clinical aspect of indication in CAPD therapy].
Explore the source record for details and available documents.
Cardiovascular Diseases↗
Actions of the novel thromboxane A2 receptor antagonist sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)-ethylidene]-6,11- dihydrodibenz[b,e]oxepine-1-carboxylate monohydrate on smooth muscle preparations.
The effects of KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)- ethylidene]-6,11-dihydrodibenz[b,e]oxepine-2-carboxylate monohydrate, CAS 127166-41-0) on smooth muscle preparations were examined. In isolated guinea-pig aorta, KW-3635 competitively inhibited the U-46619 (a thromboxane mimetic) induced contractions (pA2 = 7.74), the effect being more potent than those of sulotroban and daltroban. In canine saphenous vein, KW-3635 also antagonized the U-46619-induced contraction (pA2 = 8.11). In this preparation, solutroban and daltroban, but not KW-3635, exhibited intrinsic agonistic action. KW-3635, even at a high concentration of 10(-5) mol/l did not affect the norepinephrine- or KCl-induced contractions of guinea-pig or rat aorta, prostaglandin (PG)E2- or PGF2 alpha-induced contractions of guinea-pig ileum nor the PGE2-induced contraction of rat fundus. KW-3635 at concentrations higher than its thromboxane A2- (TxA2-)antagonistic one, non-competitively inhibited the PGF2 alpha-induced contractions of guinea-pig aorta (pD2' = 6.23), as was the case with daltroban. The inhibitory effect of KW-3635 (3 x 10(-6) mol/l) on U-46619-induced contractions of guinea-pig aorta persisted for longer than 2 h following washout of the tissue, whereas that of daltroban (10(-5) mol/l completely disappeared at 1 h after the washout. In anesthetized guinea-pigs, KW-3635 at doses of 10 to 1000 micrograms/kg (i.v.) inhibited U-46619 (1 microgram/kg i.v.)-induced pressor responses in a dose-dependent manner. The effect of KW-3635 (0.1 to 1 mg/kg i.v.) persisted for longer than 3 h. These results demonstrate that KW-3635 is a potent and specific TxA2 antagonist without agonistic action in vascular smooth muscles. KW-3635 is considered to be a promising candidate for the treatment of patients with disorders mediated via TxA2.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Protective effects of the novel thromboxane A2 receptor antagonist sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)-ethylidene]-6,11- dihydrodibenz[b,e]oxepine-2-carboxylate monohydrate against 9,11-dideoxy- 9 alpha, 11 alpha-epoxymethano-prostaglandin F2 alpha-induced sudden death in guinea-pigs and rats.
Injection of U-46619 (9,11-dideoxy-9 alpha, 11 alpha-epoxymethano- prostaglandinF2 alpha; 130 micrograms/kg i.v.) produced sudden death in anesthetized guinea-pigs and rats within 10-15 min. This sudden death is typified by a precipitous drop in mean arterial blood pressure (MABP) and a dramatic decrease in the circulating platelet counts. In guinea-pigs, KW-3635 (sodium(E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]-6,11- dihydrodibenz[b,e]oxepine-2-carboxylate monohydrate, CAS 127166-41-0) at doses of 0.1 mg/kg or greater dramatically protected animals against sudden death induced by injection of U-46619. Pretreatment with KW-3635 (0.3, 1.0 mg/kg i.v.) inhibited the decrease in circulating platelet counts and the decline in blood pressure associated with the i.v. injection of U-46619. Oral administration of KW-3635 (10, 30 mg/kg) also protected the animals from the U-46619-induced sudden death. The effect of KW-3635 was almost the same as that of daltroban, and was more potent than that of sulotroban. In rats, intravenous administration of KW-3635 at doses of 0.3 mg/kg or greater protected against sudden death. In contrast, acetylsalicylic acid a cyclooxygenase inhibitor, did not protect against sudden death induced by U-46619, indicating that the formation of endogenous thromboxane does not play a major role in the lethal effect of U-46619, and that the blockade of the lethal effects of U-46619 is specific for thromboxane receptor antagonists. Our data show that KW-3635 protects guinea-pigs and rats against U-46619-induced sudden death. Therefore, KW-3635 may be useful for the investigation of diseases where thromboxane is involved.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Beneficial effect of the novel thromboxane A2 receptor antagonist sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]-6,11- dihydrodibenz[b,e]oxepine-2-carboxylate monohydrate on collagen-induced coronary ischemia in guinea-pigs.
The effect of KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl) ethylidene]-6,11-dihydrodibenz[b,e] oxepine-2-carboxylate monohydrate, CAS 127166-41-0), a novel thromboxane A2 (TxA2) receptor antagonist, on collagen-induced coronary ischemia was studied in guinea-pigs. Under pentobarbital anaesthesia, intravenous injection (i.v.) of collagen (1 mg/kg) induced abnormal ECG changes such as ST-T changes, elevation of T-wave arrhythmia and cardiac arrest in severe cases. The changes of ECG (leads I, II and III) were recorded for 10 min following collagen injection. KW-3635 (25-50 mg/kg p.o.) remarkably improved the collagen-induced ischemic ECG changes. The effect of KW-3635 was more potent than those of daltroban, isbogrel and ticlopidine. Neither nifedipine nor propranolol had any effect. The plasma thromboxane B2 level in the KW-3635-treated animals was lower in comparison with those in both the control and daltroban-treated animals. These results suggest that TxA2 may play a role in this model of coronary ischemia and that KW-3635 is effective in the treatment of ischemic heart disease.
Animals↗
Enhancement of tissue-type plasminogen activator-induced thrombolysis and prevention of reocclusion by sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)- ethylidene]-6,11-dihydrodibenz[b,e]oxepine-2-carboxylate monohydrate in a canine model of femoral thrombosis.
The purpose of this study was to examine whether the blockade of thromboxane A2 (TxA2)/prostaglandin H2 (PGH2) receptor by the selective TxA2/PGH2 receptor antagonist KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)ethylidene]-6,11- dihydrodibenz[b,e]oxepine-2-carboxylate monohydrate, CAS 127166-41-0) is effective in enhancing tissue-type plasminogen activator (tPA)-induced thrombolysis and preventing reocclusion in a model of femoral artery thrombosis in anesthetized dogs. The thrombus was formed by inserting a copper coil into the femoral artery. Sodium heparin (100 U/kg i.v.) was administered shortly after the formation of thrombus. All dogs received i.v. tPA at a dose of 20 micrograms/kg/min starting 60 min after the formation of the occlusive thrombus for up to 60 min if necessary, to achieve reperfusion. After 30 min of thrombotic occlusion, the animals received vehicle (Group I, controls, n = 9) or KW-3635 (Group II, 0.3 mg/kg bolus i.v. + 0.3 mg/kg/h infusion, n = 9; Group III, 1 mg/kg bolus i.v. + 1 mg/kg/h infusion, n = 9) and the infusion of either vehicle or KW-3635 was continued thereafter throughout the experiment. The time to reperfusion in Group I was 37.3 +/- 5.2 min, while those in Group II and Group III were 25.3 +/- 6.2 min (p greater than 0.05) and 17.3 +/- 3.1 min (p less than 0.05), respectively. Reocclusion occurred within 4 h in 100% of Group I, whereas the incidence of reocclusion was reduced to 67% in Group II and to 0% in Group III. These data suggest that endogenous TxA2 generation is involved in lysis and rethrombosis during thrombolytic therapy by tPA.(ABSTRACT TRUNCATED AT 250 WORDS)
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
Antiplatelet effects of the novel thromboxane A2 receptor antagonist sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)-ethylidene]-6,11- dihydrodibenz[b,e] oxepine-2-carboxylate monohydrate.
The effects of KW-3635 (sodium (E)-11-[2-(5,6-dimethyl-1-benzimidazolyl)- ethylidene]-6,11-dihydrodibenz[b,e] oxepine-2-carboxylate monohydrate, CAS 127166-41-0) on platelet aggregation were examined. In human washed platelets, KW-3635 shifted the concentration-aggregation curves for U-46619, a thromboxane A2 (TxA2) mimetic, to the right. The pA2 value for KW-3635 was 8.8 +/- 0.10, while those for sulotroban and daltroban were 6.31 +/- 0.18 and 7.75 +/- 0.07, respectively. In human platelet rich plasma (PRP), KW-3635 at 10(-8) mol/l to 10(-6) mol/l inhibited the aggregations induced by U-46619 (1 mumol/l) or collagen (1.5 micrograms/ml). However, KW-3635 at up to 10(-5) mol/l did not affect the primary phase of platelet aggregation induced by adenosine diphosphate or epinephrine. KW-3635 at 10(-5) mol/l did not affect the antiaggregatory effects of the prostaglandins PGI2, PGE1 and PGD2. These results indicate that KW-3635 is a potent and selective TxA2 receptor antagonist. The TxA2 antagonistic effects of KW-3635 were compared with that of daltroban in PRP from various animals species. The effects of KW-3635 on platelet aggregation were species-dependent and KW-3635 exhibited the most prominent activity in human platelets. The activities of KW-3635 in mouse and rabbit PRP were much less potent. In PRP from guinea-pigs, dogs, cats and rats, KW-3635 exhibited moderate anti-aggregatory effects. In the guinea-pig PRP, KW-3635 at 10(-7) mol/l to 3 x 10(-6) mol/l inhibited both the platelet aggregation and the concomitant adenosine triphosphate secretion in a concentration-dependent manner, the effect being more potent than those of sulotroban and daltroban. In the experiments on the platelet aggregation ex vivo in guinea-pigs, KW-3635 at oral doses of 3 and 10 mg/kg inhibited the aggregations induced by U-46619 (1, 3 mumol/l), collagen (3, 6, 9 micrograms/ml) and arachidonate (50, 100 mumol/l). The effects lasted for longer than 7 h following oral administration. These results indicate that KW-3635 is a specific and orally active TxA2 receptor antagonist. KW-3635 is expected to be a drug useful for the treatment of patients with thrombotic disorders.
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
[Massive osteolysis of the skull--case report and review of the literature].
The authors describe a rare case of massive osteolysis of the skull, along with a brief review of the literature. A 11 year-old female was admitted with a complaint of a painless depression in the right parietal region, which had been slowly enlarging for several years. Skull x-ray films revealed a radiolucent area with irregular and non-sclerotic margin in the right parietal bone. Plain CT showed an osteolytic lesion involving the outer table and diploë with absence of new bone formation. On 99mTc scintigrams, there were no abnormal accumulation in the whole skeletal system including the skull. Blood examinations including serum calcium, phosphate, and alkaline phosphatase were entirely normal. In the differential diagnosis of lytic skull lesion, the long, inactive course without any corroborative local or systemic evidence of illness, and the absence of new bone formation on radiological examinations clinch the diagnosis of massive osteolysis.
Alkaline Phosphatase↗
[A case of sphenoid ridge meningioma presenting as subarachnoid hemorrhage].
The authors present a case of sphenoid ridge meningioma presenting as subarachnoid hemorrhage. A 56-year-old man came to our hospital with a complaint of severe headache developed during evacuation of the bowels. Computed tomogram on admission revealed a mass lesion of high density, which was homogeneously enhanced with contrast media, in the medial part of the left sphenoid ridge, but no evidence of the intracranial hemorrhage. Nevertheless, the cerebrospinal fluid obtained by lumbar puncture was bloody, indicating the occurrence of subarachnoid hemorrhage. Cerebral angiograms showed no abnormality except for the downward displacement of the suprachnoidal segment of the left internal carotid artery. During the operation, the adhesion between the tumor and the cortical vein was observed and the subarachnoid hemorrhage was recognized exclusively around the vein. These findings indicates that the present hemorrhage may be derived from the vein. In the previous reports of meningioma associated with intracranial hemorrhage, the origin of hemorrhage and the pathophysiological mechanism for hemorrhage have been speculated from both operative and histological findings. In consideration of these speculations, we discussed the possible mechanism for the breakdown of the cortical vein in the present case.
Humans↗
[A study of psychopathology in phobia and obsessive-compulsive disorder: through the treatment of exposure and response prevention by transcutaneous electrical stimulation].
For the treatment of phobia and obsessive-compulsive disorder (OCD), we developed a method of exposure (in vivo or in imagination) and response prevention by transcutaneous electrical stimulation (TES), in which weak electrical stimuli (3-4V, about 5Hz) are applied to the palm ("Rokyu" in acupuncture treatment) or vertex ("Hyakue") of a patient tolerating dysphoria induced in a state of imagination or in real life. TES was very effective in about 80% of 32 patients treated (Seishin Igaku, 1989). Through the treatment of severe cases with TES, several new findings regarding the psychopathology and etiologic mechanism of phobia or OCD were recently obtained. 1) In relatively simple cases treated with TES, anxiety and fear were extinguished within a few minutes by simultaneous close-up normal thoughts. Antagonism may thus possibly be present between a self integration mechanism and pathological mental structure, and TES may discontinuously dysfunctions this antagonism in the manner of a changeover switch. In severe cases, anxiety and fear were not immediately abolished by TES, but strong resistance and fear appeared with increase in TES. Thus, multilevel pathological mental structure are possibly present in severe cases. Moreover, one obsessive-compulsive patient suddenly restored totally free senses after 10 months of TES treatment and stated that he had been found for 10 years by a rule demanding obsessive checking. A certain more decisive principle may then have been present in his pathological mental structure. Based on the above, the pathological mental structure in these phobia and OCD may be concluded to have been dissociated from the self integration mechanism, intensified as the mechanism dealing specifically with anxiety, and finally became resistant to self integration due to the simultaneous close-up of a decisive principle. As for the mechanism of TES action, the following change provides some indication: that is, when TES was applied to the patient under exposure in a state of imagination, strong anxiety was initially induced, and then disappeared after several minutes. This may indicate that TES activates not only a pathological mental structure but also normal mental structure. Thus, while TES may be elevating the energy of anxiety, filling the pathological mental structure, by exposure and response prevention, it is efficiently inducing this anxiety towards the self integration mechanism. 2) On the basis of the above concept, an attempt was made to explain the etiologic mechanism of phobia or OCD. In many cases, the disease is evoked by a trivial provoking trigger after persistent conflict and psychic fatigue.(ABSTRACT TRUNCATED AT 400 WORDS)
Adult↗
Impaired muscle energy metabolism in uremia as monitored by 31P-NMR.
Uremic patients often complain of fatigue and muscle weakness. In order to elucidate the abnormalities of energy metabolism in the muscles of such patients, we measured the concentrations of phosphocreatine (PCr), inorganic phosphate (Pi) and adenosine triphosphate (ATP) as well as the intracellular pH in skeletal muscles by 31P-NMR at rest, during aerobic and anaerobic exercise and during recovery in 15 uremic patients (7 non-dialyzed patients and 8 dialyzed patients) and 6 control subjects. At rest, there was no difference in intracellular pH between the uremic patients and controls, but the concentrations of PCr and ATP in the skeletal muscle were lower in the uremic patients. However, during aerobic exercise, the uremic patients showed a rapid decrease in intracellular pH and a delay in its recovery. They also revealed an increased PCr utilization during aerobic exercise and its delayed resynthesis during recovery. During anaerobic exercise, the uremic patients, especially non-dialyzed patients, displayed a slower decrease in pH than the controls and a delay in its recovery. An increased PCr utilization during anaerobic exercise and a delayed resynthesis during recovery were also demonstrated. These findings suggest that the aerobic and anaerobic energy productions in uremic patients are impaired and that the energy production of the muscle depends on anaerobic glycolysis during exercise. Hemodialysis apparently facilitates recovery of the inhibited enzyme activities of oxidative phosphorylation and glycolysis in uremic patients.
Adenosine Triphosphate↗
[Evaluation of cardiac function during KCl-induced paralytic attack in the patients with normokalemic periodic paralysis].
Some reports have been written about hypokalemic periodic paralysis dealing with cardiac dysfunction and arrhythmia during the paralytic attack. However, no reports have been written about the cardiac function during the attack in cases of normokalemic periodic paralysis. So, we investigated cardiac function in two patients with normokalemic periodic paralysis. A 3.0 g dose of KCl was administered orally to the patients (1 male, 1 female) and 10 healthy volunteers (5 males, 5 females). Cardiac function by using ejection time (ET)/pre-ejection period (PEP), grasping power, and the level of plasma catecholamine were measured during the paralytic attack. Changes in the patients were compared with those in the volunteers. Next, a 3.0 g dose of KCl was administered to the patient, followed by intravenous dosing of 10% NaCl (50 ml) after which ET/PEP and grasping power measured. Lastly, a 60 mg dose of diltiazem, a 10 mg dose of nifedipine or a 80 mg dose of verapamil were administered, followed by a 3.0 g dose of KCl after which ET/PEP and grasping power were measured again. Thirty minutes after the administration of KCl, the grasping power decreased remarkably, from 32.0 kg to 17.0 kg in the male patient and from 30.0 kg to 20.0 kg in the female patient. By contrast, the ET/PEP showed a clear increase, from 3.47 to 6.17 in the male patient and from 2.84 to 5.45 in the female patient. Grasping power of the volunteers, however, did not change remarkably (avg. 40.3 kg before vs. 40.9 kg after in the males and avg. 26.9 kg before vs. 26.0 kg after in the females) and ET/PEP of the volunteers did not change remarkably (avg. 3.37 before vs. 3.17 after in the males and avg. 3.30 before vs. 3.43 after in the females). No significant changes were found in the levels of plasma catecholamine during the paralytic attack.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[Lung lymph composition and flow in experimental pulmonary edema].
Explore the source record for details and available documents.
Animals↗
Hyaluronidase assay using fluorogenic hyaluronate as a substrate.
The reducing terminal of hyaluronate was labeled with a fluorogenic reagent, 2-aminopyridine. The pyridylaminohyaluronate was incubated with testicular hyaluronidase for 1 h. After incubation, 4 vol of ethanol was added to the incubation mixture, followed by centrifugation. The fluorescence of the supernatant containing the degradation products of hyaluronidase digestion was then determined by fluorospectrophotometry (excitation wavelength, 320 nm; emission wavelength, 400 nm). It was found that the increase of the pyridylamino products was linearly correlated with enzyme concentration (up to 0.1 national formulary unit), incubation time (up to 60 min), and substrate concentration (up to 2.5 microM). The fluorogenic substrate was also applicable for the determination of crude hyaluronidase. This simple, rapid, and sensitive hyaluronidase assay was made possible by the use of pyridylaminohyaluronate as a substrate.
Aminopyridines↗
Extracellular depolymerization of hyaluronic acid in cultured human skin fibroblasts.
The chain length of [3H]hyaluronic acid synthesized by cultivating human skin fibroblasts in the presence of [3H]glucosamine was investigated. [3H]Hyaluronic acid obtained from the matrix fraction was excluded from a Sepharose CL-2B column irrespective of the incubation period, whereas that from the medium was depolymerized into a constant chain length (Mr = 40,000). The reducing and non-reducing terminals of the depolymerized hyaluronic acid were N-acetylglucosamine and glucuronic acid, respectively. Prolonged incubation produced no oligosaccharides as shown by examination of hyaluronidase digests, suggesting the presence of a novel endo-beta-N-acetylglucosaminidase in cultured human skin fibroblasts.
Cells, Cultured↗
[Oxidant-induced lung injury].
Explore the source record for details and available documents.
Animals↗
Characterization of the substrate-induced conformational change of N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine-labeled sarcoplasmic reticulum Ca2(+)-ATPase by using different kinds of substrate.
Cys-674 of the sarcoplasmic reticulum Ca2(+)-ATPase was labeled with N-iodoacetyl-N'-(5-sulfo-1-naphthyl)ethylenediamine without a loss of the catalytic activity, and changes in the fluorescence intensity upon addition of seven kinds of substrate were followed by the stopped-flow method. The steady-state fluorescence intensity and anisotropy were also determined. When Ca2+ was present, the fluorescence intensity and anisotropy decreased greatly upon addition of any substrate used. The observed affinity for each substrate agreed with the previously observed affinity of the catalytic site. The fluorescence drop induced by the adenine nucleotides, ATP and adenosine 5'-(beta, gamma-methylene)triphosphate (a nonhydrolyzable ATP analog), was much faster than that induced by other substrates. The ATP-induced fluorescence drop preceded phosphoenzyme formation when the ATP concentration was high, but the fluorescence drop coincided with phosphoenzyme formation when it was slowed by reducing ATP concentrations. The fluorescence drop induced by ITP or acetyl phosphate was slow even at high concentrations of the substrate, and it coincided with phosphoenzyme formation. When Ca2+ was absent, the fluorescence intensity and anisotropy decreased only slightly upon addition of any substrate other than the adenine nucleotides. They decreased substantially upon addition of the adenine nucleotides, but the kinetics of this fluorescence drop were quite different from that of the fluorescence drop induced by any substrate in the presence of Ca2+. These results show that the conformational change, which makes the bound label less constrained, is induced by substrate binding to the catalytic site of the Ca2(+)-activated enzyme. This change precedes phosphoenzyme formation in the catalytic cycle and is greatly accelerated by the adenine moiety of the substrate.
Animals↗
Isolation of a neuropeptide corresponding to the N-terminal 27 residues of the pituitary adenylate cyclase activating polypeptide with 38 residues (PACAP38).
A novel neuropeptide with 38 residues (PACAP38) was isolated from ovine hypothalamic tissues using the pituitary adenylate cyclase activation in rat pituitary cell cultures as a parameter of the biological activity (Miyata et al, Biochem. Biophys. Res. Commun. 164, 567-574, 1989). From the side fractions obtained during the purification of PACAP38, a shorter form peptide with 27 residues corresponding to the N-terminal 27 amino acids of PACAP38 and amidated C-terminus was isolated and named as PACAP27. Synthetic PACAP27 showed a biological activity of adenylate cyclase stimulation comparable to PACAP38. Moreover PACAP27 which shows a considerable homology with vasoactive intestinal polypeptide (VIP) demonstrated a similar vasodepressor activity as VIP, but the adenylate cyclase stimulating activity was about 1000 times greater than VIP.
Adenylyl Cyclases↗