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Biomedical subjects

H Sanada

Publications and source records attributed to H Sanada.

At least 19 recordsLinked to original sources

Antihypertensive and hormonal activity of MK 954 in spontaneously hypertensive rats.

MK 954 (DuP 753), a recently developed angiotensin II (Ang II) receptor antagonist, was administered orally for 2 weeks to spontaneously hypertensive (SHR) and Wistar-Kyoto rats (WKY). Whereas the basal levels of plasma Ang II were lower in SHR than in WKY, treatment with MK 954 markedly reduced blood pressure in SHR but not in WKY. Plasma renin activity, Ang I and Ang II were increased, while plasma aldosterone was decreased in both strains. These results no only indicate therapeutic efficacy of this agent in the chronic treatment of human hypertension, but also support the idea that the renin-angiotensin system plays an important role in the control of blood pressure in SHR.

Angiotensin I

Losartan, a specific angiotensin II receptor antagonist, increases angiotensin I and angiotensin II release from isolated rat hind legs: evidence for locally regulated renin-angiotensin system in vascular tissue.

The effect of Losartan (10(-9) to 10(-6) M) on angiotensins I and II release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal and bilaterally nephrectomized rats. Losartan increased dramatically both angiotensins I (Ang I) and II (Ang II) release in a dose-dependent fashion; the maximal percent increment in Ang I and Ang II release evoked by Losartan (10(-6) M) was about +380% and +160%, respectively, in normal rat hind legs. In nephrectomized animals, Losartan elicited a marked increase in both peptides dose-dependently. There was a highly positive correlation between the released amounts of Ang I and that of Ang II altered by Losartan in either normal (r = 0.954) or nephrectomized rats (r = 0.923). These results not only confirm the existence of a functional renin-angiotensin system in vascular tissues, but also suggest that the system is regulated by locally generated Ang II.

Angiotensin I

Effects of losartan, a nonpeptide angiotensin II receptor antagonist, on cardiac hypertrophy and the tissue angiotensin II content in spontaneously hypertensive rats.

Losartan, a recently developed nonpeptide angiotensin II (Ang II) receptor antagonist, was administered orally to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Cardiac weight and tissue Ang II, as well as plasma renin activity (PRA) and Ang II, were determined. Treatment with Losartan (10 mg/kg per day) lowered blood pressure markedly. Losartan reduced significantly the left ventricular weight by 11% compared with control rats. The left ventricular Ang II content was lowered by Losartan (18.6 +/- 0.9 pg/tissue; 21.9 +/- 0.9 pg/tissue, control, p less than 0.05), whereas PRA and plasma Ang II concentration were increased by the treatment. With the control and Losartan-treated animals, there was a significant positive correlation between the left ventricular weight and the tissue Ang II content (r = 0.563, p less than 0.05). These results provide evidence that cardiac tissue Ang II, rather than circulating Ang II, plays an important role in the pathophysiology of left ventricular hypertrophy of this animal model of human hypertension.

Analysis of Variance

Hypotensive activity of TCV-116, a newly developed angiotensin II receptor antagonist, in spontaneously hypertensive rats.

TCV-116, a recently developed angiotensin II (Ang II) receptor antagonist, was administered orally (1 mg/kg per day) to 10-week-old spontaneously hypertensive rats (SHR) for 2 weeks. Blood pressure and plasma components of the renin-angiotensin-aldosterone system were determined in these rats. TCV-116 produced a marked reduction in blood pressure without altering heart rate. Whereas plasma renin concentration (PRC), angiotensin I (Ang I) and angiotensin II (Ang II) all were significantly increased, plasma aldosterone was decreased by approximately 70% compared with control animals. These results not only indicate therapeutic efficacy of this agent in the chronic treatment of human hypertension, but support also the concept that the renin-angiotensin system plays an important role in the control of blood pressure in this animal model of human essential hypertension.

Angiotensin Receptor Antagonists

Proliferative activity of bile duct epithelium after bacterial infection in dogs.

To clarify the relationship between proliferative activity in bile duct epithelia and bacterial infection in the dog, we induced obstructive cholestasis with a bacterial infection in two lobes of the liver. The bile duct branch draining the left lateral lobes of the liver was cannulated in all mongrel dogs. The dogs were divided into three groups and treated as follows: in group 1 the cannula was clamped after the injection of 10(7) Escherichia coli (aerobic bacteria) and 10(7) Bacteroides fragilis (anaerobic bacteria) cells; in group 2 the cannula was clamped after the injection of 10(7) E. coli cells; and in group 3 the cannula was clamped without the injection of any bacteria. Three months and 9 months later dogs from each group were killed, and their livers were examined. In the group 1 dogs papillary hyperplasia and severe dysplasia were noted in association with chronic cholangitis at 3 months and 9 months, respectively, after operation. In the group 2 dogs periductal fibrosis was severe, but epithelial papillary hyperplasia was less pronounced than in the group 1 dogs at each period. In the group 3 dogs no periductal fibrosis or epithelial papillary hyperplasia was seen at either 3 or 9 months postoperatively. These findings suggest that papillary hyperplasia and/or severe dysplasia of the bile duct epithelium may be caused by aerobic and anaerobic bacterial infection of the biliary tract in combination with bile stasis.

Animals

[Left atrial booster pump function in patients with hypertrophic cardiomyopathy and essential hypertension: evaluations based on left atrial pressure-volume relationship].

In patients with hypertrophic cardiomyopathy (HCM) and essential hypertension (HT), left ventricular dysfunction in early diastole which is associated with left atrial contraction plays an important role in left ventricular filling. To evaluate left atrial booster pump function, we analyzed left atrial preload (left atrial pressure at the end of diastasis; LAPd, left atrial volume index at the end of diastasis; LAVd), left atrial afterload (left ventricular end-diastolic pressure; LVEDP, left ventricular chamber stiffness constant; K), and left atrial ejection indices (left atrial ejection fraction during atrial contraction; LAEF, left atrial ejection volume index during atrial contraction; ACVI). The study subjects consisted of control subjects (n = 5), HT patients (n = 6), and HCM patients (n = 11). The left ventricular wall was significantly thicker in the HT and HCM groups. The left ventricular rapid filling volume index was less in the HT group, and significantly less in the HCM than in the control group. LAPd and LAVd were greater in the HT group than in the control group, and greater in the HCM group than in the HT group. LVEDP and K were greater in the HT group than in the control group, and significantly greater in the HCM group than in the other 2 groups. ACVI was greater in the HT group than in the control group, but in the HCM group, ACVI was significantly less than in the HT group and did not differ significantly from that in the control group. LAEF was significantly less in the HCM group than in the other 2 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Alterations of cytoplasmic enzyme activities of liver in rats fed on diets containing orotic acid with dietary fibers.

1. Rats were fed with diets containing orotic acid with dietary fibers to induce alteration of lipid metabolism and cytoplasmic enzyme activities in the livers. Concentrations of blood glucose, serum insulin and free fatty acids (FFA) were measured. 2. In CP (cellulose + orotic acid) group compared to basal (cellulose - orotic acid) or CBH (corn bran hemicellulose + cellulose + orotic acid) groups, glucose-6-phosphate dehydrogenase, pyruvate kinase and ATP citrate lyase activities and FFA concentration were decreased according to lipid accumulation of livers. 3. In the CBH group, glycerokinase activity was higher than basal group.

Animals

Natural evacuation versus irrigation.

The comparison of the influences of the natural evacuation method and the colostomy irrigation method on complaints, daily activities and psychosocial conditions revealed that colostomy irrigation, as compared to natural evacuation, imposes less distress on the patient, causes fewer skin problems and is less of a financial burden. In daily activities, irrigation causes fewer difficulties in comparison to natural evacuation in the areas of bathing and sleeping. Furthermore, the frequency of going outdoors remains at the same level as in pre-operative days and the patients are able to adjust to daily activities post-operatively. By comparing irrigation patients and natural evacuation patients from a psychosocial standpoint, irrigation patients hold a higher degree of self-esteem, have fewer anxieties and fewer worries than those using natural evacuation. The instruction of evacuation control, management of gas odor, and a great deal of psychosocial support needs to be given to natural evacuation patients.

Activities of Daily Living

Left atrial afterload mismatch in hypertrophic cardiomyopathy.

To investigate left atrial (LA) booster pump function in hypertrophic cardiomyopathy (HC), LA and left ventricular pressure-volume loops were estimated in 5 control subjects, 6 patients with essential hypertension and 11 patients with HC. Investigation of LA preload revealed that LA pressure and volume immediately before LA contraction were both increased in patients with hypertension (10 +/- 5 mm Hg, 71 +/- 19 ml/m2) compared with control subjects (7 +/- 1 mm Hg, 59 +/- 6 ml/m2), and even more increased in patients with HC (16 +/- 7 mm Hg, 81 +/- 25 ml/m2). Investigation of LA afterload revealed that the left ventricular chamber stiffness constant was higher in patients with hypertension (0.035 +/- 0.015) than in control subjects (0.028 +/- 0.009), and even more increased in patients with HC (0.056 +/- 0.017). LA stroke work index was higher in patients with hypertension (116 +/- 34 mm Hg.ml) and HC (115 +/- 19 mm Hg.ml) than in control subjects (87 +/- 23 mm Hg.ml). Investigation of LA ejection revealed that LA stroke index was higher in patients with hypertension (24 +/- 5 ml/m2) than in control subjects (18 +/- 4 ml/m2) and patients with HC (18 +/- 2 ml/m2), and LA ejection fraction was lower in patients with HC (23 +/- 6%) than in control subjects (32 +/- 7%) and patients with hypertension (34 +/- 8%). In patients with HC, LA function curve showed a shift to the lower right, and LA stroke index was inversely correlated (r = -0.76) with LA afterload. This study suggests that LA booster pump failure due to LA afterload mismatch exists in HC.

Adult

Effects of dietary fat and protein on the activity of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase and the urinary excretion of niacin metabolites in rats.

The effects of dietary protein and soybean oil on the metabolism of L-tryptophan through the NAD pathway and the activity of alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD) [EC4.1.1.45] in rat liver and kidney were investigated. The animals were fed on the following niacin-free diets for 11 days: group 1, a fat-free 20% casein diet (20% Cas); group 2, a fat-free 40% casein diet (40% Cas); group 3, a 40% casein diet containing 20% soybean oil (40% Cas + 20% F). After feeding on each diet for 7 days, the urine was collected during 48 h. On day 9, L-tryptophan was force-fed and the urine was collected during 48 h. Niacin metabolites such as N-methylnicotinamide (MNA), N-methyl-2-pyridone-5-carboxamide (2-Py) and N-methyl-4-pyridone-3-carboxamide (4-Py) in the urine samples were analyzed by chromatography. The activity of ACMSD in the liver and kidney was assayed immediately after the last urine collection. The results indicate that the urinary excretion of the niacin metabolites in the 40% Cas group was lower than that of the 20% Cas group in spite of the more intake of tryptophan in the former group. On the other hand, in the 40% Cas+ 20% F group, tryptophan intake was lower and the excretion of the metabolites was significantly higher than that in the 40% Cas group. The hepatic ACMSD activity in the 40% Cas group was 5.8 times that of the 20% Cas group and that in the 40% Cas + 20% F group was one tenth that of the 20% Cas group. These results indicate that the ratio of the excreted metabolites to the tryptophan intake was reduced by the high dietary protein level, but increased by the addition of high soybean oil. The data analysis shows that the amount of urinary total niacin metabolites ([TNM]: MNA + 2-Py + 4-Py) could be expressed in the following equation in the rats fed on each diet: [TNM] = 0.090 ([Trp] -22.5.delta w) [1/(1 + 2.4 [ACMSD])], where [ACMSD] is the hepatic ACMSD activity, [Trp] the tryptophan intake, and delta w the body weight gain.

Algorithms

Effect of aging on endothelin-induced prostaglandin I2 release in isolated hind legs of the spontaneously hypertensive rat.

We evaluated the effect of aging on spontaneous release of prostaglandin I2 (PGI2; measured as 6-keto-PGF1a) as well as on endothelin-induced release of PGI2 from isolated hind legs perfused with Krebs-Ringer solution in 5-week-old, 10-week-old and 40-week-old Wistar-Kyoto rats (WKY) and age-matched spontaneously hypertensive rats (SHR). The spontaneous release of PGI2 was stable up to 40 minutes for both strains. The amount of the spontaneous release of PGI2 tended to fall with advancing age in WKY, while it remained unchanged in SHR. Porcine endothelin-1 (pET-1) added to the perfusion medium (2 x 10(-12)-2 x 10(-10) M) increased PGI2 release in a dose-dependent fashion in both strains regardless of age. However, the maximal increase of PGI2 release evoked by endothelin (2 x 10(-10) M) was significantly greater in 40-week-old SHR compared with age-matched WKY. These results not only suggest that there exists a much greater reservoir of vascular PGI2 synthesis in SHR, but also imply that the enhanced release of PGI2 in response to endothelin, the most potent vasoconstrictor known, may function as a factor or a modulator to attenuate endothelin-induced vasoconstriction in senescent SHR.

6-Ketoprostaglandin F1 alpha

Effects of dietary pyrazinamide, tryptophan, or nicotinic acid and gamma-ray irradiation on levels of NAD and NADP in various organs of mice.

The effects of large amounts of tryptophan, pyrazinamide, or nicotinic acid in diets on the contents of total NAD (NAD + NADH) and NADP (NADP + NADPH) of various organs were investigated in mice with or without gamma-irradiation. Female C3H/HeN mice were fed one of the following 4 kinds of experimental diets for one week: 1) control diet (20% casein diet containing 3 mg niacin per 100g diet); 2) diet supplemented by 0.5% L-tryptophan (T-diet); 3) diet supplemented by 0.5% L-tryptophan (T-diet); 4) diet supplemented by 0.1% nicotinic acid (NA-diet). Half of the mice in each group were subsequently irradiated with 8 Gy of gamma-ray (60 Co) after 4 h of fasting. Then, the contents of total NAD and NADP in thymus, spleen, kidney, liver, and blood were determined in all animals. The results indicated that NAD content of spleen was higher in PT-group (21.5%) and NA-group (23.2%) than in that of control group. In thymus, however, NAD content of only the PT-group was significantly greater (13.1%) than control. NAD level of kidney was also significantly higher (32.6%) in PT-group. By gamma-irradiation, NAD contents of thymus and spleen of all groups tended to be decreased, but those of kidney and liver were not always reduced. In the latter two organs, significant NAD reduction was shown only in kidney of PT-group and in liver of PT- and NA-groups. Even after irradiation, NAD levels of spleen and thymus in PT- and NA-groups tended to be kept higher than those in irradiated control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Two-dimensional echocardiographic and left ventriculographic evaluations of left ventricular diverticula].

Twenty cases of left ventricular diverticula were gleaned from 4,300 consecutive angiocardiographic records (13 males and seven females whose age ranged from 17 to 78 years with a mean of 52 +/- 16 years). Their findings were compared with those of 16 patients with left ventricular aneurysms due to myocardial infarction. In only one patient was a diverticulum first detected by two-dimensional echocardiography before left ventriculography was performed. None of the patient had an associated midline thoracoabdominal defect. Five patients had premature ventricular beats, two of whom had ventricular tachycardia. Three patients complicated mitral valve prolapse and three atrial septal defect. Of the 20 patients, four each had two diverticula, as opposed to 16 others who each had a single diverticulum. The diameter of the diverticula ranged from eight to 70 mm. The sites of 14 diverticula were along the inferior wall; five in the anterior wall; four in the apex. Morphologically 15 diverticula were bulky outpouchings, six were tongue-like, and three hammocking. All diverticula exceeding 15 mm in diameter and originated near the mitral ring could always be detected in the short-axis view of two-dimensional echocardiography. However, those originating in the apex or of a tongue-like configuration could rarely by detected. Comparative two-dimensional echocardiographic analyses of 16 diverticula, 16 left ventricular aneurysms, and 16 normal left ventricular walls disclosed that the left ventricular aneurysmal wall had a higher echo intensity, but the diverticula had the same wall echo intensity as the normal left ventricular wall. Left ventricular end-diastolic wall thickness in an aneurysm (7.6 +/- 1.5 mm) was lower (p less than 0.01) than the normal left ventricular wall (11.1 +/- 1.3 mm), but it did not differ from the normal left ventricular wall in any case of diverticulum (10.2 +/- 1.5 mm). The percent wall thickening ratio in aneurysms (-3.6 +/- 10.7%) was lower (p less than 0.01) than the normal left ventricular wall (39.8 +/- 10.9%), but it did not differ from the normal left ventricular wall in diverticula (45.8 +/- 16.6%). Regional fractional shortening in the diverticula (41.3 +/- 9.2%) did not differ from that in the normal left ventricular wall (34.5 +/- 5.2%). In conclusion, a small diverticulum without a midline thoracoabdominal defect is not rare, and two-dimensional echocardiography is the diagnostic method of choice in many cases based on the echo features described above.

Adolescent

[A case of bilateral coronary artery to pulmonary artery fistulas associated with hepatic arteriovenous fistula].

A 55-year-old man, previously treated for primary hypothyroidism, was admitted for evaluation of atypical chest pain. On physical examination, the pulse rate was 60 and blood pressure was 132/84 mmHg. Heart sounds were normal and no murmur was heard. Abdominal palpation showed no abnormal finding, and bruit was not heard. The electrocardiogram was normal and stress-induced ischemia was not found. The chest X-ray showed no sign of pulmonary hyperaemia or mass lesion, and central shadow was normal (CTR = 44%). During right heart catheterization, the pressures were normal in the cardiac chambers, pulmonary artery, and wedge position. A significant increase in oxygen saturation was disclosed at pulmonary artery level (10%) and the upper site of the inferior vena cava (22%). Coronary arteriography found coronary artery fistulas from the left main trunk, the left anterior descending artery, the left circumflex, and the right coronary artery to the pulmonary trunk. The left and right ventriculograms were normal. The digital subtraction angiography of celiac artery showed hepatic arteriovenous fistula. Ultrasonography and computed tomography found no mass lesion of the liver. Since combination of the bilateral coronary artery with pulmonary artery fistula, and hepatic arteriovenous fistula is very rare, the present case is worth noting for the investigation of the pathogenesis of congenital arteriovenous fistulas.

Arterio-Arterial Fistula

[Chemotherapy of chronic myelogenous leukemia--VP(M) regimen initiated during its chronic phase, and evaluation of MCNU in the phase of blastic crisis].

Seventy-four patients in the chronic phase of Ph1-positive chronic myelogenous leukemia (CML) have been treated with busulfan or other alkylating agents in a conventional way. During its chronic phase, 24 of these 74 cases had received additional intermittent therapy every 4 to 6 months, consisting of vincristine 2 mg or vindesine 3 mg per week, prednisolone 20-30 mg per day and partly 6 mercaptopurine 50 to 100 mg, combined with allopurinol 200 to 300 mg per day for 2 to 3 weeks. The 50% survival of these patients using the Kaplan-Meier's method was 73.7 months and 5-year survival was 69.6%, against 40.5 months and 14.4%, respectively, in the remaining patients. Nine patients in the blastic or accelerated phase of Ph1-positive CML have been treated with new regimens including MCNU. All cases had been refractory for usual types of induction chemotherapy. The new regimen consisted of MCNU 50-100 mg, combined with vindesine or 6-MP plus allopurinol or prednisolone. Five out of 9 cases attained complete remission and 1 partial remission. The major adverse effect of this regimen was slight liver damage. MCNU could be regarded as an useful agent in the blastic phase as well as in the chronic phase of CML.

Adolescent