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Biomedical subjects

T Sanada

Publications and source records attributed to T Sanada.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effect of an angiotensin II receptor antagonist, CV-11974, and its prodrug, TCV-116, on production of aldosterone.

In dispersed rabbit adrenocortical glomerulosa cells, a non-peptide angiotensin II (AT1) receptor antagonist, CV-11974 (10(-10)-10(-5) M), competitively inhibited angiotensin II- or angiotensin III-stimulated aldosterone production, whereas PD123177, an angiotensin AT2 receptor antagonist, did not. CV-11974 inhibited aldosterone production induced by 4 mM K+ but not by 12 mM K+. CV-11974 had no effect on adrenocorticotropic hormone-stimulated aldosterone or corticosterone production, but inhibited angiotensin II-stimulated corticosterone production. In the rat, TCV-116, the prodrug of CV-11974, (0.1 and 1 mg/kg, p.o.) markedly reduced the elevation of both plasma aldosterone concentration and blood pressure induced by i.v. infusion of angiotensin II. In spontaneously hypertensive rats, TCV-116 at daily p.o. doses of 0.1, 1 and 10 mg/kg for 2 weeks caused a dose-dependent reduction of blood pressure and plasma aldosterone concentration without affecting plasma corticosterone. Thus, TCV-116 inhibited the induction of aldosterone production by not only exogenous but also endogenous angiotensin II.

Administration, Oral↗
PubMed1994

Antihypertensive effects of a highly potent and long-acting angiotensin II subtype-1 receptor antagonist, (+-)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylate (TCV-116), in various hypertensive rats.

The antihypertensive effects of (+-)-(cyclohexyloxycarbonyloxy)ethyl2-ethoxy-1-[[2'-(1H- tetrazol-5- yl)biphenyl-4-yl]methyl]-1-H-benzimidazole-7-carboxylate (TCV-116), an angiotensin II (AII) subtype-1 receptor antagonist, were studied in various hypertensive and normotensive rats, using 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl-4- yl)methyl]-imidazole, potassium salt (losartan) as a reference compound. TCV-116 is a prodrug, which is converted in vivo to the active component, 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl)]methyl]-1H- benzimidazole-7-carboxylic acid (CV-11974). In spontaneously hypertensive rats (SHR) p.o. TCV-116 (0.1 mg/kg) demonstrated a sustained antihypertensive effect that lasted for more than 10 hr and the dose that reduced the blood pressure by an average of 25 mm Hg for 24 hr (ED25), was 0.68 mg/kg. Intravenous CV-11974 reduced the blood pressure with an ED25 of 0.0027 mg/kg. Repeated p.o. administration of TCV-116 (1 mg/kg) to SHR once daily for 2 weeks reduced the blood pressure by 30 to 50 mm Hg over 24 hr without any heart rate changes. The antihypertensive effects of TCV-116 correlated well with the inhibition of angiotensin II-induced contractile responses of aortic strips prepared ex vivo after p.o. administration of TCV-116. Oral TCV-116 had a sustained antihypertensive effect with ED25 of 0.03 and 0.23 mg/kg in two-kidney, one-clip and one-kidney, one-clip hypertensive rats, respectively, and was much more potent in SHR and renal-hypertensive rats than losartan.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin Receptor Antagonists↗
PubMed1993

Inhibition of rabbit aortic angiotensin II (AII) receptor by CV-11974, a new nonpeptide AII antagonist.

The angiotensin II (AII) antagonistic action of CV-11974 (2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl] benzimidazole-7-carboxylic acid) was investigated in an AII-receptor binding assay using rabbit aortic membranes and an AII-induced contraction assay using rabbit aortic strips. A single class of [125I]AII-(Sar1,Ile8) binding sites was found in the membranes with a dissociation constant (Kd) of 0.15 nM and a receptor concentration (Bmax) of 86.9 fmol/mg protein. CV-11974 markedly reduced Kd without affecting Bmax. The specific binding of [125I]AII-(Sar1,Ile8) in this preparation was inhibited completely by CV-11974 [the inhibition constant (Ki) = 0.64 nM], DuP 753 [an angiotensin II type I (AT1) receptor-selective antagonist] (Ki = 51 nM) and EXP3174 (an active metabolite of DuP 753) (Ki = 6.8 nM), but was not affected by PD123177 (an AT2 receptor-selective antagonist). These results suggest that the single binding site in rabbit aortic membranes is an AT1 receptor subtype. The affinity of CV-11974 to these AT1 receptors was approximately 80 and 10 times higher than that of DuP 753 and EXP3174, respectively. CV-11974 showed no appreciable affinity for the AT2 receptors found in bovine cerebellum. In the in vitro functional study, CV-11974 markedly reduced the AII-induced maximal contractile response of rabbit aortic strips (pD'2 = 9.97). In contrast, Compound 7-H, which lacks the carboxyl group at the benzimidazole ring of CV-11974, inhibited the contraction in a competitive manner. The inhibition by CV-11974 was long lasting. These results suggest that CV-11974 is a potent and long-acting AT1 receptor-selective, competitive antagonist. The carboxyl group at the benzimidazole ring plays an important role in the interaction between CV-11974 and the AT1 receptor.

Angiotensin II↗
PubMed1993

Effect of U74006F on neurologic function and brain edema after fluid percussion injury in rats.

The effect of the 21-aminosteroid U74006F, an inhibitor of iron-dependent lipid peroxidation, on neurologic outcome and cerebral edema was evaluated in adult male Sprague-Dawley rats subjected to a fluid percussion temporal brain injury followed by 45 min of hypoxia (PaO2 = 30.0 mm Hg). The rats were divided randomly into five groups. Bolus injections of a control drug or U74006F (1.0, 3.0, 10.0, or 30.0 mg/kg) were given 3 min and 3 h after the injury. Twenty-four hours after the injury, the neurologic status was evaluated, the rats were killed, and brain water content was determined by microgravimetry. U74006F did not significantly reduce brain water content at any dose level, nor did it affect rotorod walking or activity scores. However, rats treated with U74006F at a dose of 10.0 mg/kg had significantly better motor function scores (p < 0.05) than rats in the control group. These findings demonstrate the usefulness of U74006F as a cerebroprotective agent in this model of experimental head injury.

Animals↗
PubMed1993

Pharmacological profile of a highly potent and long-acting angiotensin II receptor antagonist, 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4- yl]methyl]-1H-benzimidazole-7-carboxylic acid (CV-11974), and its prodrug, (+/-)-1-(cyclohexyloxycarbonyloxy)-ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5- yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate (TCV-116).

The angiotensin II (AII) antagonistic action of 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl-1H-benzi mid azole-7 - carboxylic acid (CV-11974) was examined in in vitro assay systems, including AII receptor binding assay using membrane fractions of bovine adrenal cortex or rabbit aorta and AII-induced contraction assay using rabbit aortic strips, and CV-11974 and its prodrug, (+/-)1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H- benzimidazole-7-carboxylate (TCV-116), were examined in an in vivo system of AII-induced pressor response in conscious rats. DuP 753 or EXP3174 (the main active metabolite of DuP 753) was used as the reference compound. CV-11974 inhibited the binding of [125I] AII to the bovine adrenal cortical membrane and rabbit aortic membrane with IC50 values of 1.12 x 10(-7) and 2.86 x 10(-8) M, respectively. Similar results were obtained with EXP3174. CV-11974 interacted with AII in these membrane fractions with subtype 1 receptor in a competitive manner. CV-11974 at 10(-5) M did not affect the binding of [125I]AII to subtype 2 (AT2) receptor in bovine cerebellum. CV-11974 selectively inhibited the AII-induced contraction of rabbit aortic strips in a noncompetitive manner (pD' 2, 9.97); it had no effects on the contraction induced by norepinephrine, KCl, serotonin, prostaglandin F2 alpha or endothelin. EXP3174 showed a pD'2 value of 8.95 for the AII-induced contraction. CV-11974 given intravenously and TCV-116 given orally inhibited the AII-induced pressor response in rats with ID50 values of 0.033 mg/kg and 0.069 mg/kg, respectively. These effects of CV-11974 and TCV-116 were 12 and 48 times more potent than those of EXP3174 and DuP 753, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex↗
PubMed1992

[A case of repetitive monomorphic ventricular tachycardia].

We present a case treated with aprindine and metoprolol combined with a DDD type pacemaker for repetitive monomorphic ventricular tachycardia. A 50-year-old man was admitted because of palpitation and near syncope attack. Electrocardiogram showed repetitive monomorphic ventricular tachycardias (RBBB LAD type) and R-R interval of about 440 msec and I degree A-V block in sinus rhythm. Electrophysiologic study disclosed that overdrive pacing in HRA suppressed ventricular tachycardias. Left ventriculography revealed a dilated left ventricular and decreased contractility. Antiarrhythmic agents such as quinidine sulfate, procainamide, disopyramide, mexiletine, lidocaine and propranolol were not effective. But, the combination of propranolol and aprindine decreased the rate of the ventricular tachycardia. With aprindine 60 mg/day and metoprolol 60 mg/day combined with the atrioventricular sequential pacing at 85/min, ventricular tachycardia completely disappeared.

Aprindine↗
PubMed1991

Surface coil spectroscopic imaging: time and spatial evolution of lactate production following fluid percussion brain injury.

Detailed temporal and spatial distributions of lactate production are presented for graded fluid-percussion brain injury in the rat. A one-dimensional proton spin-echo spectroscopic imaging (1D SESI) technique, performed with a surface coil, is presented and evaluated. This technique, which represents a practical compromise, provides spatially localized proton nuclear magnetic resonance (NMR) brain spectra from a series of small voxels (less than 0.15 cm3) in less than 10 min, thus enabling both spatial and temporal monitoring of lactate production. These high-resolution lactate maps are correlated with hyperintense regions observed in T2-weighted images taken 10 h after impact, which, in turn, correlate with histology. The data demonstrate that, following severe trauma there is delayed production and propagation of lactate to regions of the brain that are remote from the trauma site. The extent of lactate production depends on the severity of impact. More significantly, the data show that following severe trauma, local lactate concentrations exceed 15 mumol/g, the concentration that has been claimed as the threshold for brain injury. Therefore high lactate levels cannot be ruled out a priori as a possible factor in brain injury following severe head trauma.

Animals↗
PubMed1990

[Relationships between the degree of lesion and that of vocal dysfunction in vocal fold polyp].

Relationships between the degree of lesion and that of vocal dysfunction were investigated in 122 cases of vocal fold polyp. A normalized size of polyps and glottic gap were correlated to the results of phonatory ability tests, stroboscopic investigations, acoustic analyses, and perceptual evaluations. There was no significant correlation between the size and the gap. The size of polyp was negatively correlated to fundamental frequency, whereas it was positively correlated to roughness of voice, asymmetry of vocal fold vibration, irregularity of vocal fold vibration, pitch perturbation quotient, amplitude perturbation quotient, and normalized noise energy. The glottic gap showed negative correlations to maximum phonation time and sound pressure level, and positive correlations to mean airflow rate and fundamental frequency.

Adult↗
PubMed1990

[The correlation between plasma atrial natriuretic polypeptide levels (ANP) and cardio-pulmonary function during the perioperative period of esophageal cancer].

The present study examined the influence of subtotal esophagectomy through r-thoracal and abdominal approach on plasma atrial natriuretic polypeptide (ANP) and postoperative cardiopulmonary function using the Swan-Ganz Catheter in patients with thoracic esophageal cancer. The cardiac output (CO), left ventricular stroke work index (LVSWI), pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), and plasma atrial natriuretic polypeptide levels (ANP) were measured during the perioperative period till the 3rd day. Subjects were divided into 2 groups by preoperative PVR values, those over 100 dynes.sec.cm-5 (PVR group), and those less than 100 dynes.sec.cm-5 (N group). Significant correlations were observed between ANP and CO (r = -0.63, P = 0.028), PVR (r = 0.66, P = 0.018), LVSWI (r = -0.71, P = 0.0009) and SVR (r = 0.71, P = 0.009) at 3 hours after operation. And the correlations between ANP and CO (r = 0.54, P = 0.049), PVR (r = -0.69, P = 0.019) and LVSWI (r = 0.65, P = 0.031) were observed on the 2nd POD. Moreover, the patients indicating high PVR values preoperatively showed significantly higher PVR values than those seen in the N group during the postoperative days. Postoperative complications were significantly seen in the PVR group. Primary water and sodium balance tended to be the higher accumulation in the PVR group than those of the N group, and the cardiovascular parameters in the PVR group revealed hypodynamic characteristics in the early period after the operation. With these results, it is suggested that perioperative fluid therapy and respiratory management should be performed more strictly in the PVR group.

Adult↗
PubMed1990

[Effect of postoperative hypertonic sodium infusion in the patients with total gastrectomy for gastric cancer].

In 17 patients with gastric cancer undergoing total gastrectomy, the effect of postoperative hypertonic sodium infusion were studied. The subjects were divided into 2 groups by concentration in the postoperative infusions. Group 1(Na group): over 5.0 mEq/Kg/day of sodium were infused in the postoperative days (POD). (End of operation to POD-4), Group 2 (Control group): 2.0-2.5 mEq/Kg/day of sodium (End of Op. to POD-1), 1.5-2.0 mEq/Kg/day (POD-2-4). 2.0-2.5 mEq/Kg/day were infused after POD-5 in both groups. In the Na group, NAG-Index, FENa and BUN were higher than those of control group. And cumulative primary Na balance (from end of operation to POD-5) indicated positive balance in Na group, and negative in control group. Furthermore, the cumulative infused sodium dose correlated with cumulated urinary sodium dose, potassium dose and cumulative NAG dose (from end of operation to POD-5). Significant difference was observed between two groups in urinary nitrogen. These findings suggest that the sodium dose in the postoperative infusion were suitable with 2.0-2.5 mEq/Kg/day.

Adult↗
PubMed1989

Improved surgical technique for epidermoid cysts of the vocal fold.

An improved surgical technique for epidermoid cysts of the vocal fold is presented. This technique employs a specially designed double-bladed elevator. Following betamethasone injection around the cyst, an incision is made posterior to the cyst at its mediolateral midpoint. The incision is extended anteriorly over the cyst with the use of a double-bladed elevator. The cyst then is elevated carefully from the surrounding tissue and removed. A single incision line on the upper aspect of the vocal fold should be the result. Eight patients were operated on with the present technique. The voice was improved postoperatively in all patients. The voice improvement was reflected objectively in stroboscopic findings, maximum phonation time, airflow rate, fundamental frequency and intensity of phonation, and results of acoustic analyses of voice.

Adult↗
PubMed1989

[Significance of right precordial ST elevation in experimental right ventricular infarction].

We produced experimental isolated right ventricular infarction (RVI) with closed chest method, and examined ECG changes of right precordial leads and changes of cardiac output (C. O) in 19 dogs. As a result, ECG showed ST depressions in leads, II, III, aVF and V2-V6 and ST elevations in a VR lead in all 15 cases of the proximal occlusion of right coronary artery (RCA). In 10 of 15 dogs ST elevations in some right precordial leads occurred, and the sensitivity of ST elevation in single right precordial lead was 60% (V5R), 53% (V4R) and 47% (V3R and V1), respectively for the detection of RVI. When left circumflex artery (LCX) was occluded, ST elevation in V4R lead after RCA occlusion was blocked. Therefore, it is thought that the sensitivity of ST elevation in right precordial lead may be lower than expectation in identifying RVI. Concerning anterior chest leads, none of 15 dogs with RVI showed ST elevations in leads V2-V6 in this study. If ST elevations in right precordial leads did not appear, variation of C.O was small and C.O reduced in proportion to the extension of ST elevations in right precordial leads.

Animals↗
PubMed1988

Risk factors in relation to postoperative complications in patients undergoing esophagectomy or gastrectomy for cancer.

To clarify the risk factors contributing to postoperative complications in the elderly patients (over 70 years) undergoing esophagectomy and/or gastrectomy, 364 patients with primary cancer seen were evaluated. As a result, some characteristic patterns of stress response in the elderly could be detected as follows: the disorders of the vital organs were more important indices for the development of postoperative complications rather than age, and a reduction in the maximum response of the stress hormones to surgical procedures in aged patients was noted; moreover, the functional variability of target organ in the aged group was confirmed. Studies on the hormonal response to surgery suggest that the restriction of fluid replacement is advisable until the third postoperative day, maintaining the host on the dry side, to prevent cardiopulmonary complications. As the nutritional status in the patients with esophageal and gastric cancer goes from bad to worse with the advancing clinical stages, adequate perioperative nutrition is imperative to prevent complications such as anastomotic leakage, wound dehiscence, and/or infections. For the treatment of anastomotic leaks after esophagectomy and esophagogastrectomy, more than 45 kcal/kg/d must be provided, and the serum albumin level must be restored to 3.5 g/dL in order to achieve spontaneous healing of small anastomotic leakages.

Adult↗
PubMed1988

Influence of culture medium pH and proteinase inhibitors on extracellular proteinase activity and cell growth of Sporothrix schenckii.

Sporothrix schenckii produces two extracellular proteinases in albumin- or collagen-supplemented unbuffered liquid medium. Proteinase I had an optimal pH of 6.0, and its activity was strongly inhibited by chymostatin. Proteinase II had an optimal pH of 3.5, and its activity was strongly inhibited by pepstatin. Speculating that these two proteinases are key enzymes for fungal growth, we investigated the influences of culture medium pH and either or both of the proteinase inhibitors pepstatin and chymostatin on the cell growth of S. schenckii. In buffered medium at a pH of 3.5, an optimal pH for proteinase II, only proteinase II activities were observed, while at pH 6.0, an optimal pH for proteinase I, only proteinase I activities were observed. However, there was no cell growth inhibition. These results suggested that the regulation of the production of the two proteinases is dependent on environmental pH. The addition of pepstatin or chymostatin to the culture medium did not inhibit the cell growth of S. schenckii, but the addition of both inhibitors at a concentration of 10 micrograms/ml strongly inhibited growth. These results suggested that at least one of the two proteinases was expressed to allow fungal growth in albumin-supplemented media. The indirect fungistatic action of the proteinase inhibitors, which inhibit proteolysis, may be applied to a topical therapeutic agent in vivo.

Chymotrypsin↗
PubMed1988

[A case report of brain metastasis due to an advanced gastric cancer].

In April 1984, a 49-year-old male underwent a partial gastrectomy for advanced gastric cancer. At that time, many metastatic foci were found, for example, in the rib, the lumbar vertebrae, the cervical vertebrae, and in the abdominal lymph nodes. Approximately one year later, he suddenly became disturbed and lost consciousness. A metastatic brain tumor was diagnosed. To destroy this tumor the patient received a course of irradiation therapy with a total dose of 45 gys directed toward head. Several months later, however, recurrence of the tumor was detected at the same intracranial region. Thus, a course of therapy, employing a combination of FT-207 and ACNU, was initiated against the recurrent tumor. Though the tumor was not eliminated, the patient manifested few of the prior symptoms. This state has continued for several months, with the patient having survived for three years after his gastrectomy. The following report will present the details of this case.

Brain Neoplasms↗