[Altered bone metabolism in db/db mice].

Bone and calcium metabolism was investigated in genetically obese, diabetic db/db mice and compared with that in a new hypoglycemic agent (AS-6) treated db/db mice and in their lean litter mates as controls. The 5-week-old db/db mice (serum Ca 9.88 +/- 0.22 mg/dl, glucose 258.6 +/- 13.3 mg/dl) were randomly divided into two groups. One group, together with their lean litter mates, was fed a commercial diet (CE-2). The other db/db group was fed CE-2 diet containing 0.1% of AS-6. Both groups were fed for 20 weeks. The serum glucose and calcium levels in db/db control groups (serum Ca 12.3 +/- 0.1 mg/dl, glucose 650.2 +/- 23.9 mg/dl) were higher than those in lean control groups (Ca 9.8 +/- 0.2 mg/dl, glucose 180.7 +/- 10.1 mg/dl). The wet, dry and ashed weights of the femur in db/db control were significantly lower and the length of femur in db/db control was significantly shorter than those of lean controls. These data suggest that retarded bone growth in db/db mice is related to progression of diabetes. Although, there was no change in Ca/P, Ca/ash and total perimeter in femurs, the cortical area in the femurs of db/db control mice (0.65 +/- 0.02 mm2) was significantly smaller than that of the femurs of lean control mice (0.74 +/- 0.02 mm2). The cortical bone thinning observed in the db/db control could have been caused by increased bone resorption. Treatment with AS-6 for 20 weeks resulted in a 48.6% decrease of serum glucose and 5.2% decrease of calcium as compared with db/db controls.(ABSTRACT TRUNCATED AT 250 WORDS)


[Serum lipids, lipoproteins and apolipoproteins in patients with senile dementia].

Serum lipid, lipoprotein, apolipoprotein, and sterol profiles were studied in 22 patients with senile dementia of the Alzheimer type (SDAT) and 29 patients with vascular dementia (VD). Levels of high density lipoprotein-cholesterol (HDL-C) were lower in both patients groups of SDAT and VD than in control group. Apolipoprotein AI and AII are two major proteins in HDL. In this study, apolipoprotein AI levels were normal, but apolipoprotein AII levels were lower in the patient groups, especially in the VD group, than in the control group. Lipoprotein(a) levels were higher in both patient groups, especially in the VD group. There were no differences of cholesterol, cholesterol precursors (desmosterol and lathosterol), and plant sterols (campesterol and beta-sitosterol) among the three groups. Murine apolipoprotein AII is a serum precursor of murine senile amyloid protein, and the apolipoprotein AII variant with proline-->glutamine substitution at position 5 in the serum of accelerated senescence-prone mice is identical to the murine senile amyloid fibril protein from amyloid-deposited tissues of these mice. In human SDAT and VD, the reason for the low level of apolipoprotein AII remains unclear.


[Silent lacunes in the elderly Parkinson's disease correlated with ambulatory blood pressure].

Lacunes on brain MRI, causal blood pressure, 24-hour ambulatory blood pressure and common carotid blood flow measured by the doppler method were studied in 31 elderly patients with Parkinson's disease (mean age 67.5 +/- 7.3 years). Nineteen patients with Parkinson's disease (61%) had at least one lacune. Patients with lacunes (P(+)) were significantly higher in age than patients without lacune (P(-)). The difference of casual blood pressure between patients in the two groups was not significant. On the other hand, the average of ambulatory blood pressure measurements during a 24-hour period was significantly higher in the P(+) group than in the P(-) group. The average of carotid blood flow was also significantly lower in the P(+) group than in the P(-) group, however, after adjustment for age, the difference between them became insignificant. In conclusion, the incidence of silent lacunes on brain MRI was fairly common in elderly patients with Parkinson's disease. A high average 24-hour ambulatory blood pressure was suggested to be one of the risk factors of lacunar stroke in elderly cases of Parkinson's disease. The concept of "combine type" in Parkinsonism was supposed to be suitable as well as in senile dementia of Alzheimer type.


[Prognostic analysis for postoperative complications of abdominal surgery in the elderly].

In order to evaluate the prognostic importance of the conditions before abdominal surgery for patients over 60 years of age. Multivariate analyses of postoperative complications were performed in 634 patients (comprising 525 cases of elective abdominal surgery and 109 cases of emergency abdominal surgery). The Mortality rate was significantly higher (p < 0.01) in the emergency group (11.9%) and relatively low among the elective abdominal surgery group (3.8%). In the emergency group, 13 patients died, and MOF (multiple organ failure) was found to be the direct cause of death in 11 (85%). Although, the majority (75%) of emergency operations were for benign disorders, the remainder (25%) had malignant tumors. It is noteworthy that among 25% of cases, obstructions and perforations due to large bowel cancers were found to be 59% and 19%, respectively. In the elective surgery group, postoperative pulmonary and cardiovascular complications were found in 11.6% and 9.6%, respectively. Death due to cardiovascular problems in rare (5%), however, postoperative pneumonia was the cause of death in 70% of all of postoperative death. Risk factors affecting postoperative pulmonary complications were malnutrition, advanced age, male sex, malignant disease, dementia, cerebrovascular disorders, impaired pulmonary function tests. Surprisingly, the risk factors were identical, except for impaired pulmonary function, for postoperative MRSA pneumonia. In our study, postoperative pulmonary death was not associated with impaired pulmonary function, and it appears to be rather affected by the presence of cerebrovascular disorders and malnutritional state. A poor nutritional states (< 40 according to Onodera's nutritional index) was present in over 50% of patients with cerbrovascular disorders and low ADL.(ABSTRACT TRUNCATED AT 250 WORDS)


[Neuropathological study of amyotrophic lateral sclerosis in relation to aging].

It has been assumed that amyotrophic lateral sclerosis (ALS) involves precocious senility as one of its pathogenetic aspects. The authors studied 55 autopsied cases of ALS in relation to age at death, ranging from 42 to 86. The materials consisted of 8 cases in the fifth decade, 8 in the sixth, 20 in the seventh, 12 in the eighth, and 7 in the ninth. The total duration of illness ranged from 6 months to 14 years. The most distinct relationship was observed in the anterior horn lesion of the cervical enlargement which became less severe with advancing age, irrespective of the length of illness. Fifth decade cases showed marked atrophy with severe neuronal loss and fibrillary gliosis in the anterior horn, while those in the ninth decade showed slight changes which were similar to age-matched controls. On the other hand, pyramidal tract degeneration did not show any correlation to age at death or to length of illness. Pyramidal tract degeneration was found in all younger age group cases, being always severe. In the older age groups, however, the degeneration varied extremely in degree from case to case. Some cases showed severe degeneration comparable with that in the younger age groups, while the others had no findings suggesting degeneration. In addition, cases on artificial respirators had a longer duration of illness, and more marked degeneration in the anterior horn, irrespective of age. Our study did not reveal that senile changes including senile plaques and neurofibrillary tangles were more marked in ALS cases. No clinicopathological correlation with dementia was recognized.(ABSTRACT TRUNCATED AT 250 WORDS)


[Immunological functions and clinical course of elderly patients with cerebrovascular diseases].

In the elderly, cerebrovascular diseases (CVD) are often complicated by severe infections such as pneumonia. This study aimed to examine the possible relationship at various timepoints of observation between immunological functions and the clinical course and to correlate the changes of immunological functions with CVD lesion side. The study was based on 25 right-handed patients (14 male and 11 female, mean age; male 69.0 years and female 74.9 years) with acute, focal neurological deficits of CVD (5 cerebral bleeding, 20 cerebral infarction; 11 right cerebral lesioned subjects, 14 left cerebral lesioned subjects). All patients were evaluated in terms of lymphocyte counts, T, B cell counts, T cell subsets, lymphocyte transformation and natural killer activity in peripheral blood as indices of immunological functions at various timepoints during the clinical course. Some of these immunological functions decreased within two months (acute stage) after onset of CVD, and some cases with decreased immunological functions developed complications of severe infection such as pneumonia. Patients who had both decreased immunological function and severe infection were 1 out of cases with 7 right cerebral lesions and 6 out of with 9 left cerebral lesions. This study suggests that the decreased immunological function in CVD subjects may be correlated with the site of the CVD lesion. In all left cerebral lesioned subjects, a reduction of immunological functions and a susceptibility to severe infection were not observed in the acute stage of CVD, however, some left cerebral lesion cases may be more closely related than in right cerebral lesion cases. The mechanism remains to be clarified.(ABSTRACT TRUNCATED AT 250 WORDS)


[Two autopsy cases of aortitis syndrome in the elderly].

Two autopsy cases of aortitis syndrome (Takayasu's aortitis) in the elderly are presented. Case 1 was an 81-year-old woman in whom hypertension was observed at age 37, and difference of right and left arm blood pressure was pointed out at age 65. She was referred to the authors' hospital at age 72. Chest X-ray and computed tomography of the thorax indicated atypical coarctation and diffuse calcification of the aorta. Case 2 was a 69-year-old woman in whom hypertension was pointed out at age 49, and blood pressure in the arms was found to differ from that in the legs at age 63. Chest X-ray and computed tomography showed diffuse calcification and marked narrowing of the descending aorta. Pathological examination revealed marked calcification in the thickened adventitia of the aorta with mild atherosclerotic change. Irregular fibrotic changes of the adventitia and degeneration of elastic fibers of the media of the aorta were noted in both cases, and were consistent with Takayasu's aortitis. This disorder is common in young women and only a small number of elderly cases are reported although its incidence is increasing. Diffuse calcification of the aorta with an absence of inflammatory signs, which is frequent in older patients, were observed in both case. Systemic hypertension is the most important risk factor with coarctation of the aorta in Takayasu's aortitis. Bypass surgery is recommended in young patients, however in elderly patients, it is generally avoided, in favor of medical control of hypertension.


[Analysis of nocturnal disturbed breathing in the elderly using desaturation index].

This study was conducted to examine the nocturnal ventilatory parameters and gas exchange in the elderly with nocturnal disturbed breathing. In order to facilitate analysis of ventilatory parameters with minimum manpower, we developed an unattended continuous nocturnal monitoring system for ventilation and arterial oxygen saturation. Using this system, nocturnal ventilatory parameters and gas exchange were investigated in our geriatric ward. We investigated 30 elderly subjects aged between 65 and 94 (mean age 77.8 +/- 6.5 years, male; female = 15:15). The subjects were free of severe cardiovascular and cerebrovascular disorders, and underwent 10 hours of continuous monitoring of ventilation and arterial oxygen saturation (SaO2). Number of significant desaturation (SDS; desaturation greater than 4% in SaO2 from the baseline value) and desaturation index (DI; sigma SDS(%) x duration (hour)) were calculated using the same system. The number of apnea episodes significantly correlated with DI and the number of SDS. DI also significantly correlated with lowest SaO2, while the number of SDS and the number of apneas were not found to be correlated with lowest SaO2. The number of SDS and the number of apnea episodes did not correlated with lowest SaO2. From the view point of gas exchange during the night, newly introduced DI is more comprehensive parameter when compared with the number of apneas or SDS. Subjects with a DI of over 0.5 were assigned to the group A (n = 8, mean age = 77.8) and the remaining subjects were assigned to group B (n = 22, mean age = 77.8). We compared the group A with the group B regarding nocturnal ventilatory parameters and SaO2.(ABSTRACT TRUNCATED AT 250 WORDS)


[Long-term nasogastric feeding and complications of acute gastric ulcer in two elderly patients].

Some elderly patients with chronic illness such as stroke, or Parkinsonism cannot take food orally because of dysphagia. In such cases, tube feeding can be used as a supplement to oral intake when malnutrition is present. This route allows for easier nursing care and decreases the frequency of aspiration pneumonia. Complications of tube feeding include nutrient deficiency states, pulmonary aspiration, gastrointestinal and metabolic disorders. We report two cases with complications of acute gastric ulcer which was thought to be induced with long-term tube feeding. Case 1 was a 61-year-old male patient with Parkinson's disease for ten years. L-DOPA had been administered with good control of his condition. However, his ability to swallow has deteriorated gradually. As he often suffered from aspiration pneumonia, nasogastric tube feeding was performed. After three years of tube feeding, he suddenly vomited much bloody material. He died from massive bleeding with acute gastric dilatation. Autopsy showed giant acute gastric ulcer covered with coagulated blood. UL3, 50 mm in maximum diameter, was observed in the middle portion of the greater curvature, where the top of tube probably came in contact with the gastric wall. Case 2 was an 83-year-old female patient with stroke and chronic heart failure. She had been hospitalized for about one year because of the intermittent deterioration of her cardiac condition. Furthermore, her inability to swallow increased during her hospitalization. She also suffered from aspiration pneumonia. Nasogastric tube feeding was performed to prevent aspiration pneumonia and malnutrition. She died of acute heart failure after twelve months. Autopsy revealed heart dilatation, old myocardial infarction and stroke. In addition, two acute gastric ulcers (UL3.10 and 30 mm in diameter) were recognized; one was in the upper portion of the greater curvature, the other in the lower portion of the greater curvature. The location of these gastric ulcers was unusual. Moreover, they coincided with location of top of the nasogastric tube. From these two cases, we conclude that in long-term tube feeding the tip of the tube often comes in contact with the gastric wall, and gastric ulcer could be produced by repeated mechanical stimulus of the wall. Reports of acute gastric ulcer induced by tube feeding have not been published previously. Therefore, we should pay much attention to this complication in the care of the elderly people with long-term tube feeding.


[Postprandial hypotension in the elderly with and without hypertension].

To clarify the mechanism of postprandial hypotension in the elderly, blood pressure and humoral factors were measured before and after meal, water, and glucose ingestion in 20 healthy elderly. The elderly patients were divided into 10 normotensive and 10 hypertensive cases. A reduction in systolic BP after meals in the hypertensive group was significantly larger than that in the normotensive group (-12.0 +/- 4.1 vs. 4.0 +/- 3.2 mmHg, p < 0.05). Systolic BP in hypertensive group significantly decreased at 30, 45 and 60 minutes after meals compared to the value before meals. However, no significant reduction in systolic BP was observed in the normotensive group. A change in systolic BP after meal significantly correlated with that after glucose, but not with that after water ingestion, suggesting that glucose intake mainly contributes to the postprandial hypotension in the elderly. An increase in plasma renin activity and plasma catecholamine were observed after meals in the normotensive group, but not in the hypertensive group. An increase in systolic BP significantly correlated with an increase in PRA. It was suggested that an impairment of the sympathetic nervous system in the elderly with hypertension was involved in the mechanism of postprandial hypotension.


[Clinical characteristics of postinfarction left ventricular aneurysm with extensive calcification].

The authors experienced 4 cases of calcified postinfarction aneurysm of the left ventricle. They were all male, aged 55 to 71 (mean 64). Risk factor for coronary artery disease was only smoking in 2 patients, but there was none in the others. They had had acute anteroseptal or extensive anterior infarction at age 41-57 years (mean 49.3), and associated major cardiac events 10-22 years (mean 14.5) after acute myocardial infarction. Ventricular tachycardia, congestive heart failure and systemic thromboembolism were seen in 4, 2 and 1 patients respectively. However, none developed angina pectoris. In the 2 patients in whom signal-averaged electrocardiogram was performed, late potential was detected, so it was suspected that ventricular tachycardia could be due to reentry. Left ventricular end-diastolic pressure was elevated in all patients except one and ranged from 11 to 22 mmHg. Left ventricle was dilated in all cases and the end-diastolic volume index ranged from 143 to 503 ml/m2. The left ventricular ejection fraction ranged from 11 to 24%. However, in 2 of the 4 patients, the cardiac index was within normal limits, and evidence of congestive heart failure was absent. In 2 other patients with associated congestive heart failure, cardiac indices were 2.32, 1.56 l/min/m2 respectively. Coronary arteriogram showed a total occlusion in the left anterior descending (LAD) artery in all cases, and only the LAD artery was affected in 2 patients. In the remaining 2 patients, the right coronary arteries also were significantly stenotic or totally occluded, i.e., they had 2-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)


[An 88-year-old female case of hyperalphalipoproteinemia associated with deficiency of cholesteryl-ester transfer activity].

An 88-year-old female was admitted to our hospital for examination of hyperalphalipoproteinemia. The high level of her serum high-density lipoprotein cholesterol (HDL-C, 148 mg/dl) was due to cholesterol amount of HDL2-C but not HDL3-C, and serum cholesteryl ester transfer activity (CETA) was at a non-detectable level. Despite her age, apparent atherosclerotic changes were not observed. She may be the oldest case of hyperalphalipoproteinemia, possibly due to deficiency of serum CETA.


[Three cases of Chilaiditi's syndrome--hepatodiaphragmatic interposition of the colon].

Three cases of Chilaiditi's syndrome are reported. Case 1: A 56-year-old woman was admitted with dysphagia. She had been suffering from progressive systemic sclerosis for 16 years. Three years before the admission, dysphagia developed and dilatation and hypomotility of the esophagus were observed. Chest and abdominal x-ray films on admission showed severe dilatation of the intestine, pneumatosis cystoides intestinalis, abdominal free air, and Chilaiditi's syndrome. Chilaiditi's syndrome and other signs disappeared after conservative treatment. She died four months later due to cor pulmonale. Case 2: An 87-year-old man was admitted with constipation and left lower abdominal pain. Physical examination showed ascites. Chest and abdominal x-ray examination showed Chilaiditi's syndrome. Cytological examination of ascites revealed adenocarcinoma cells. Diagnosis of peritonitis carcinomatosa due to cancer of pancreatic tail was made. Chilaiditi's syndrome disappeared after removal of ascites. Case 3: A 71-year-old bedridden man who had urinary incontinence developed meterorism. Repeated chest x-ray examinations constantly showed Chilaiditi's syndrome. He died of pneumonia two years later. The pathogenesis of Chilaiditi's syndrome was discussed and the literature was reviewed.


[Successful treatment with vincristine for an elderly patient with idiopathic thrombocytopenic purpura].

A 77-year-old female was referred to our hospital in March 1991 because of a severe bleeding tendency. Her blood count on admission was as follows: Hb 7.5 g/dl, WBC 4.6 x 10(9)/l with normal differentiation and platelet 2 x 10(9)/l. One month prior to admission, her blood count was normal. Initially, acute idiopathic thrombocytopenic purpura (ITP) was suspected, because of the acute onset of the bleeding tendency and thrombocytopenia. High dose intravenous immunoglobulin (400 mg/kg/day for 5 days) and bolus methylprednisolone (1 g/day for 3 days then tapered) were administered, starting March 13. Her platelet count had increased immediately on March 20 to 40 x 10(9)/l. However, platelet count decreased to 4 x 10(9)/l in the following two weeks. Her clinical course differed from that of typical acute ITP. Because the treatment with prednisolone was not effective, it was changed to intravenous infusion of vincristine (VCR) at a weekly dose of 1 mg for 6 weeks. The treatment was extremely effective, and her platelet count reached over 200 x 10(9)/l. The treatment was discontinued. Three weeks later, her platelet count decreased to 15 x 10(9)/l, the administration of VCR was resumed, and her platelet count recovered again. Throughout her clinical course, no side effect of VCR was noticed except for mild hypesthesia of the fingertips. VCR therapy was considered to be an useful treatment in elderly patients with ITP.


[A case of amnesic stroke caused by left hippocampal infarction].

A 78-year-old woman was admitted to our hospital because of acute onset amnesia in March 1991. Neurological examination revealed right homonymous hemianopsia and clumsiness of the right hand. Magnetic resonance imaging (MRI) demonstrated abnormal intensity areas in the left hippocampus, parahippocampal gyrus, fimbria of the hippocampus and the occipital lobe. Immediate memory and long-term memory were relatively well-preserved, but short-term memory was severely disturbed. Her memory disturbance persisted for more than 9 months and she eventually developed an "amnesic stroke". According to the MRI findings, the "amnesic stroke" was produced by infarction of the left hippocampus, parahippocampal gyrus and fimbria of the hippocampus. We emphasized that in this case an "amnesic stroke" was caused by infarction of the left hippocampal lesions.


[Non-Hodgkin's lymphoma in an elderly patient complicated by cyclophosphamide-induced allergic hepatic dysfunction].

A 77-year-old male presented at our Department of Urology in August 1990 with a gradually enlarging swelling in the right scrotum. On August 21, right high orchietomy was performed. This was diagnosed histologically as non-Hodgkin's lymphoma (diffuse large cell type), and the patient was transferred to our department on September 11 for further examination and treatment. As enlargement of the lymph nodes around the abdominal aorta was evident, it was diagnosed as stage IIA according to the Ann Arbor Classification. Beginning on September 21, three courses of COP-BLAM therapy (CPM, VCR, PDN, BLM, ADR, PCZ) were administered (the third course started on November 8) to achieve complete remission. Hepatic dysfunction appeared, however, from November 16, and by November 19, GOT and GPT increased to 6700 and 2120, respectively, with aggravation of jaundice. PDN therapy was instituted, and GOT and GPT improved gradually, but jaundice did not improve. On December 22, laparoscopy was performed, and liver biopsy produced histologic findings of drug-induced hepatitis. Further, lymphoblastic response was positive for CPM. Hepatic failure occurred on December 29, and plasma exchange was performed, but it failed to improve the condition, and the patient died on January 15. We described a case of non-Hodgkin's lymphoma complicated by hepatic dysfunction, probably induced by CPM, in an elderly patient who died to hepatic failure.


[A case of choreoathetoid movements induced by anticholinergic drugs, trihexyphenidyl HCl and dosulepin HCl].

We report a 72-year-old woman who showed marked orolingual dyskinesia and choreoathetoid movements of the neck, with rolling and nodding of the head. She had been treated for postural tremor and other complaints with multiple drugs, including trihexyphenidyl HCl (THP) 6 mg/day for about two years. Moreover, two months before admission to our hospital, a doctor added tricyclic antidepressant, dosulepin HCl (DL) because of her state of anxiety. Two weeks following DL administration, the persistent dyskinesia described above appeared. Suspecting the dyskinesia to be induced by anticholinergics, we withdrew THP, which decreased the intensity of the dyskinesia. Then, when DL was ceased the dyskinesia almost completely disappeared, slightly recurring only during calculating, when excited or writing. In order to confirm that anticholinergics were the cause of the dyskinesia, we administered THP 6 mg/day again. In a few days the same dyskinesia reappeared, disappearing following THP withdrawal. In this case the overlap of anticholinergics might have resulted in the dyskinesia, because both THP and DL have anticholinergic effects. It should be stressed that inappropriate administration of anticholinergics could cause severe dyskinesia in the elderly.


[A case of recurrent cerebral hemorrhage considered to be cerebral amyloid angiopathy by cerebrospinal fluid examination].

A 73-year-old man was admitted with gait disturbance and dysarthria. He showed right-side cerebellar ataxia. Computed tomography of brain showed left thalamic bleeding. Nine months later, he was admitted again because of seizure and consciousness disturbance. He had a history of diabetes mellitus and gout for five years, but no hypertension. On physical examination the lungs and heart were normal. On neurological examination, he showed stupor,pupils and eye position were normal. He showed right hemiparesis and urinary incontinence. The deep tendon reflexes were (+) at the upper limbs and (2+) at the right knee and ankle. Blood pressure was 162/88 mmHg and glucose was 275 mg/dl. Other laboratory data were normal. Brain CT showed hemorrhage of the left frontal lobe. The cystatin C level in cerebrospinal fluid was 68 ng/ml. Therefore we suspected cystatin C deposit amyloid angiopathy. In this case, thalamic hemorrhage was initially thought to be amyloid angiopathy. In cases of cerebral hemorrhage in the elderly without hypertension, we must be considered amyloid angiopathy.


A significant age shift of the human parvovirus B19 antibody prevalence among young adults in Japan observed in a decade.

A seroepidemiological study on human parvovirus (B19) in Japan was undertaken with serum samples randomly collected from healthy Japanese populations (416 in 1973, 675 in 1984 and 508 in 1987/88). All samples were tested for anti-B19 IgG antibody by the indirect antigen-capture ELISA. The antibody prevalence for ages 0-9 years old in 1984 was significantly higher (16%) than that in 1973 (2%), whereas those for ages 20-29 years and 30-39 years were significantly lower in 1984 (20% and 56%) than in 1973 (67% and 80%) (p < 0.005). After the erythema infectiosum (EI) outbreak in 1986/87, the antibody prevalences for ages 5-9, 10-14 and 15-19 years were 40-85% in Fukuoka, 0-10% in Gunma, and 21-41% in Chiba reflecting each EI incidence in these three prefectures, whereas those for ages 20-29 years remained low (< 20%). These data indicate that B19 virus was transmitted mainly among children and no significant incidence of B19 virus infection in adults has occurred since 1973, resulting in a notable shifting of B19 susceptibility toward older ages including child-bearing females.


Assessment of the molluscicidal activities of Tribromosalan, Cartap and Chlorothalonil against Oncomelania hupensis.

Molluscicidal activities of Tribromosalan, Cartap and Chlorothalonil were evaluated in the laboratory and the field against Oncomelania hupensis, the intermediate host of Schistosoma japonicum in China. The three chemicals were very effective against O. hupensis in the laboratory. The molluscicidal activities found in the field trials suggest that Tribromosalan and Cartap may be used as practical molluscicides. Dosage of 10 g/m2 of Tribromosalan in spring only and 20 g/m2 of Cartap in both spring and autumn would be recommendable as practical mollusciciding doses for the control of O. hupensis.


Isolation of spotted fever group rickettsia from Apodemus speciosus in an endemic area in Japan.

A spotted fever group rickettsia was isolated from Apodemus mice captured near the site where a person had been infected in Miyazaki Prefecture. Antigenic characteristics of the isolate designated as strain TO-1 were compared with those of Rickettsia japonica (strain YH) and Rickettsia montana (ATCC VR611) by the indirect fluorescent antibody test with 14 serum specimens obtained from Apodemus speciosus, immune rat antisera against the strains TO-1 and YH, and three patients' sera. The titers of these sera measured with strain TO-1 were identical to those with strain YH, suggesting the antigenic similarity between these two organisms. It was also suggested that Apodemus speciosus is likely to be an important vertebrate host for a spotted fever group rickettsia in Japan.


[Radionuclide study of left ventricular function and regional myocardial perfusion in patients with a DDD pacemaker].

In order to determine the influence of right ventricular artificial pacing on left ventricular function, particularly on diastolic specificity and regional myocardial perfusion, 99mTc multigated blood pool study and 201Tl myocardial SPECT at rest were performed on 12 patients with a DDD pacemaker implanted due to atrio-ventricular block at various degrees and on 7 normal adults without pacemaker as controls. Studies were performed on the pacing group during both ventricular pacing (VP) and atrio-ventricular sequential pacing (AVSP) at a rate of 80 beats/min. Although global left ventricular ejection fraction (LVEF) showed no significant differences between the control group (63.7 +/- 9.1%) and the pacing group, or between during AVSP (57.8 +/- 9.6%) and during VP (55.8 +/- 10.0%), global early diastolic peak filling rate (EDPFR) in the pacing group were significantly lower during AVSP (0.90 +/- 0.52 counts/second/end-diastolic counts) than during VP (1.55 +/- 0.52) (p less than 0.01), which were both found to be lower than those seen in control group (2.37 +/- 0.48 (p less than 0.01). Functional images disclosed regional prolongation of left ventricular ejection time (ET) in septal and apical areas of the left ventricle adjacent to the pacing site in 7 of the 12 patients (58.3%) during AVSP and in 3 of them (25%) during VP, and also revealed regional decrease in EDPFR in the similar areas in all of the patients during both modes, being more remarkable during AVSP than during VP. On 201Tl myocardial SPECT at rest, regional perfusion impairment was observed in septum, apex and the infero-posterior wall on the septal side adjacent to the pacing site in 8 of 10 patients (80%) during AVSP and in 6 of 9 patients (66.7%) during VP. These results suggest that a change in electrical conduction by right ventricular pacing may disturb regional myocardial relaxation, probably resulting in a regional impairment of myocardial perfusion.


[The utility of quantitative 99mTc-GSA liver scintigraphy in the evaluation of hepatic functional reserve: comparison with 99mTc-PMT and 99mTc-Sn colloid].

Using data from 17 patients with liver cirrhosis and 3 patients with fatty liver, we have compared the utility of 3 hepatic imaging agents in the evaluation of hepatic functional reserve. Evaluated here were 99mTc-galactosyl human serum albumin (GSA) which is a new ligand for hepatic binding protein, 99mTc-N-pyridoxyl-5-methyl tryptophan (PMT) of a hepatobiliary agent, and 99mTc-Sn colloid. In each patient, we performed these 3 imaging studies within a week and also examined hepatic function tests (indocyanine green test, hepaplastin test, choline-esterase, etc). In each imaging study, serial images and dynamic data were obtained after the injection of 99mTc-GSA (185 MBq/3 mg), 99mTc-PMT (185 MBq), or 99mTc-Sn colloid (185 MBq). Using the obtained dynamic data, we analyzed the liver kinetics of the 3 agents based on 1 compartment model with 3 parameters (hepatic clearance, hepatic excretion rate, non-specific volume of distribution). From fitting the liver and heart data to this model, three unknown parameters were determined. Patlak plot was also applied in order to estimate liver uptake rate. Both curve fitting and Patlak plot could determine appropriate parameters in every study. In 99mTc-GSA, a nonlinear 3 compartment model was also applied in order to estimate hepatic blood flow, liver receptor density, and affinity of receptor-GSA binding separately. Using the obtained parameters, we analyzed the correlations between the parameters and the results of hepatic function tests. In all of the parameters, those obtained from 99mTc-GSA imaging showed the most significant statistical correlation with the results of hepatic function tests. From the present results, 99mTc-GSA imaging was concluded to be the best for evaluation of hepatic functional reserve.


[Pulmonary clearance of 99mTc-DTPA aerosol in patients with progressive systemic scleroderma].

Alveolar epithelial permeability was assessed in 32 patients with progressive systemic scleroderma (PSS), using 99mTc-DTPA aerosol. Immediately after the inhalation of 99mTc-DTPA aerosol for 3 to 6 minutes under normal tidal breathing, lung was imaged sequentially for 30 minutes from the posterior by a gamma camera and exponential fitting was processed on the time activity curve. T1/2 (min) was used as a parameter for the evaluation of permeability of alveolar epithelium. Patients with collagen disease showed shorter T1/2 (T1/2 = 43.7 +/- 23.8 min) than the normal volunteers (T1/2 = 76.8 +/- 8.7 min). No significant difference was observed between patients with or without interstitial changes on the chest CT. Significant correlation was not observed between T1/2 and %VC or %DLco. In 8 cases, studies were repeated in the interval of 3 to 19 months. Improvement of T1/2 was seen in 4 cases, independent of CT findings. These results suggest that 99mTc-DTPA aerosol clearance study provides information independent from other lung examinations, and may be useful for the assessment of lung interstitial changes in patients with PSS.


[Estimation of perioperative myocardial infarction in patients under aorto-coronary bypass grafts with plasma level of myosin light chain I and 201Tl SPECT].

After aorto-coronary bypass grafts surgery plasma level of myosin light chain I, determined with monoclonal antibodies to myosin light chain I (LC-I), were studied in 12 patients (pts) without electrocardiographical perioperative myocardial infarction. Rest 201Tl myocardial images were collected before and after surgery. LC-I increased and reached peak levels (15 +/- 7 ng/ml) at 91 +/- 29 minutes after the aortic declamp. From peak levels LC-I rapidly decreased with fast half-time disappearance (1.4 +/- 0.9 hours). In 5 pts of 12 pts LC-I recovered to normal range and MB reached maximum levels (34 +/- 23 IU/L) at 18 +/- 9 hours after declamp. In 4 pts 201Tl images showed improvement and in one 201Tl images showed no changes. In 7 pts of 12 pts LC-I decreased to minimum levels (2.7 +/- 0.6 ng/ml) at 12 +/- 6 hours and then gradually increased to peak levels (5.6 +/- 0.9 ng/ml) on day 3 +/- 0.9. MB reached maximum level (61 +/- 20 IU/L) at 3.2 +/- 1 hours. In 201Tl images 3 pts showed suspected new lesion, 2 pts showed no changes and 2 pts showed improvement. No correlation was noted between peak LC-I level and duration of aortic declamp. No significant relation was suspected between early LC-I peak and irreversible myocardial cell injury. From close relationship between aortic declamp and appearance of LC-I peak, it was concluded that LC-I, accumulated during aortic clamp, was washed out by aortic declamp. Relation was suspected between early LC-I peak and myocardial injury during myocardial protection.(ABSTRACT TRUNCATED AT 250 WORDS)


[Diffusely increased uptake in the skull in normal bone scans].

Diffusely increased skull uptake (a hot skull) is often seen in patients with bone metastases and metabolic diseases. This finding is also, however, noticed in normal bone scans of aged women. To determine whether the hot skull could be considered a normal variant in elderly women and is associated to menopause, we studied 282 normal bone scans (166 women and 116 men without metabolic and hormonal disease; age range 11 to 84 yr). We divided the patients into eight age groups--ages 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, and 80-89 yrs. Measurements of skull uptake were obtained from anterior total body views using contrast-to-noise ratio (CNR). CNR for the skull was calculated using the following equation: (counts skull - counts femur)/square root of counts skull+counts femur, where the denominator signifies a measure of the noise and the numerator represents the contrast between the skull and the midfemur. Counts skull and femur are the number of average counts per one pixel recorded over the skull and midfemur, respectively. The sex dependent difference in skull uptake began to develop in the age group 30-39 yrs (p less than 0.05). The skull showed greater activity in women than in men for age groups from 30-39 to 80-89 yrs. In the age groups 50-59 and 60-69, the difference was particularly large (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


[Assessment of myocardial viability with 201Tl myocardial SPECT 24 hours after injection].

Recently many investigators reported that conventional stress-redistribution myocardial scintigraphy with 201Tl underestimated the presence of ischemic but viable myocardium. We studied the usefulness of 24 hour 201Tl myocardial single photon emission computed tomography (SPECT) to assess myocardial viability and investigated the factors affect to the quality of 24 hour SPECT images. Study patients were consisted with 70 patients with old myocardial infarction (OMI), 72 patients with angina pectoris without OMI (AP) and 43 patients with angiographically proven normal coronary arteries. To obtain SPECT images, 10 minute and 4 hour imagings were sampled 30 seconds per projection. Twenty-four hour imaging was sampled 60 seconds per projection. Twenty-four hour images were visually interpreted as good, moderate and poor quality. Then study patients were divided into 2 groups, group A with good 24 hour images and group B with moderate or poor 24 hour images. One hundred and fifty-eight patients (85.4%) of study patients had 24 hour SPECT images on a good quality. Only 4 patients (2.2%) had poor quality SPECT. All of these 4 patients had broad myocardial infarction. In patients with OMI 61 patients (87.1%), in AP 63 patients (87.5%) and in normal 35 patients (81.4%) had a good 24 hour SPECT. Total sampling counts and myocardial ROI counts were significantly higher in group A than in group B. Body weight was significantly higher and there were more male patients in group B than in group A. Late redistribution was seen in 20 patients (28.5%) with OMI and in 11 patients (15.3%) with AP.(ABSTRACT TRUNCATED AT 250 WORDS)


[Evaluation of coronary hemodynamics and exercise 201Tl-myocardial scintigraphy in patients with vasospastic angina].

To clarify the coronary hemodynamics and myocardial perfusion in patients with vasospastic angina, we performed exercise-201Tl-myocardial scintigraphy (planar and SPECT) in 72 patients and left coronary digital subtraction angiography (DSA) in 37 patients without significant organic coronary artery stenosis. Coronary artery spasm was documented by coronary angiography in all patients. Fifty-four patients (75%) developed exercise-induced 201Tl-myocardial perfusion defect on SPECT. 201Tl pulmonary uptake (L/H) was significantly increased in patients with vasospastic angina. Especially, L/H was higher in patients with multiple small perfusion defect on 201Tl-SPECT, so that exercise-induced left ventricular dysfunction existed in patients with vasospastic angina and especially in cases with multiple small perfusion defect on 201Tl-SPECT. The left coronary circulation time (CCT) was prolonged in patients with vasospastic angina. The mechanism of prolonged CCT is still unknown, but we suspected that prolonged CCT was induced by increased peripheral coronary vascular resistance in patients with vasospastic angina. It was concluded that the peripheral coronary circulation was disturbed in patients with vasospastic angina, but its abnormal coronary circulation had no relation to location of spasm-induced vessels. We concluded that impaired coronary microcirculation was taken a part of pathophysiology in vasospastic angina.


[Discrepancy between 123I-IMP SPECT and X-ray CT in chronic cerebrovascular disease].

The discrepancy between the low accumulation area (LAA) seen on 123I-IMP SPECT and the low density area (LDA) on X-ray CT was evaluated in 76 cases with chronic cerebrovascular disease. In 19 patients, LAA was larger than LDA beyond the vascular territory. Brain angiogram showed either obstruction or stenosis of the major arteries in as many as 59 percentages of this discrepancy group. In many patients of this group, cortical neurological symptoms were observed. In 37 patients in which the size of LAA was equal to that of LDA, abnormality of the major arteries was observed in only 7 percentages. These results indicated that the discrepancy mainly reflected the infarction due to irreversible ischemic change of perforate artery with the cortical low perfusion caused by the major artery disease. In some patients, the discrepancy was believed to show the remote effect caused by neurological pathway disturbance.


[67Ga scintigram and MRI in malignant bone tumors and malignant soft tissue tumors].

We have analyzed the characteristics of 67Ga scintigram and MRI in 11 malignant bone tumors and 11 malignant soft tissue tumors. Osteosarcoma showed a high accumulation in 67Ga scintigram and low signal intensity in T1 weighted image. T2 weighted image were not characteristic. Chondrosarcoma showed medium 67Ga accumulation and low signal in T1 weighted image and high signal in T2 weighted image. Ewing sarcoma showed low accumulation in 67Ga scan and medium intensity in MRI. Malignant soft tissue tumors showed rather low 67Ga accumulation compared with malignant bone tumors. Malignant fibrous histiocytoma showed medium accumulation of 67Ga, low signal in T1 weighted image and high signal in T2 weighted image. Liposarcoma showed low 67Ga accumulation and medium signal in T1 weighted image and high signal in T2 weighted image. To summarize these characteristics, three dimensional display is demonstrated.


[Analysis of stereoisomers involved products of synthesized 18F-2-deoxy-2-fluoro-D-glucose by 1H-NMR spectroscopy].

18F-2-fluoro-2-deoxy-D-mannose (FDM) is eventually involved in side products of 18F-2-fluoro-D-glucose (FDG) synthesized by the acetylhypofluorite method. We attempted the measurement of existence ratio of FDM and FDG, FDM alpha and FDM beta, FDG alpha and FDG beta by 400 MHz 1H-NMR spectroscopy. The ratio of FDM to FDG were 4.0%. The amounts of FDG beta were much larger than those of FDG alpha. The difference between the amounts of FDM alpha and FDM beta were not significant. 1H-NMR spectroscopy could be utilized in quantitative analysis of products and byproducts in cyclotron chemicals. The FDM in FDG synthesized in our cyclotron system was not considered to affect a lot of influence in PET study.


[81mKr scintigraphic evaluation of hemodynamics in gynecologic malignancies under condition of angiotensin II-induced hypertension].

Transcatheter arterial infusion chemotherapy is one of the most useful therapeutic procedures for gynecologic malignancies. Recently, several reports have been published about Angiotensin II-induced hypertension chemotherapy and the efficacy of the method, but there have been no reports to evaluate an application for gynecologic malignancies. We evaluate the usefulness of the method for gynecologic malignancies demonstrating the changes of hemodynamics of the tumor using 81mKr scintigraphy. Thirteen patients with pathologically confirmed gynecologic malignancies were evaluated by angiography and continuous infusion of 81mKr via the catheter with and without Angiotensin II. At first, continuous infusion of 81mKr was performed under the superselective catheterization of the uterine artery. The radioactivities in the ROI were counted. Then, withdrew the catheter from the uterine artery to the internal iliac artery, and again continuously infused 81mKr and counted the radioactivities in the same ROI. Finally, keeping the catheter in the internal iliac artery, Angiotensin II and 81mKr were infused simultaneously. And counted the radioactivities. The radioactivities were highest when the catheter tip was placed in uterine arteries and lowest when the catheter tip was placed in internal iliac arteries. But radioactivities in the ROIs were definitely increased when Angiotensin II was used, even if the catheter tip was keeping in the internal iliac arteries. The optimal catheter position of transcatheter arterial chemotherapy for gynecologic malignancies is at proximal uterine artery. Since Angiotensin II-induced hypertension may increase blood flow of tumors, it seems to have indication for post-operative cases, highly advanced cases and cases with difficulties to perform superselective catheterization.(ABSTRACT TRUNCATED AT 250 WORDS)


[The usefulness of the emergency hepatobiliary scintigraphy to rule out acute cholecystitis--43 patients report].

We studied emergency hepatobiliary scintigraphy in the 43 patients to rule out acute cholecystitis. After injection of 185-222 MBq (5-6 mCi) of 99mTc-EHIDA or 99mTc-HIDA, serial static scintigraphic images were obtained up to 7 hours in maximum. Of 43 patients in this study, 20 had a normal scan and finally in all of them cholecystitis was ruled out. Of the 43 patients, 14 had an abnormal scan (nonvisualized gall bladder). In 10 of them the diagnosis of acute cholecystitis was confirmed after emergency cholecystectomy. The other 9 patients of 43 had an incomplete scan mainly due to liver dysfunction. Four of them had acute cholecystitis in the cholecystectomy. These results indicate that acute cholecystitis can be excluded by the findings of gall bladder visualization in hepatobiliary scintigram. We concluded that emergency hepatobiliary scintigraphy is very useful to rule out acute cholecystitis.


[Phase I clinical study of 99mTc-ECD].

A phase I clinical study of 99mTc-L,L-ethyl cysteinate dimer (99mTc-ECD) was carried out in 3 normal volunteers. There was no significant change in vital signs and laboratory parameters attributing to the radiopharmaceutical. 99mTc-ECD was rapidly taken up by the brain, reaching the maximum peak activity within 1 min after the injection and remained relatively constant over several hours. The brain uptake of 99mTc-ECD at 5 min was 5.4 +/- 0.5% which decreased to 5.0 +/- 0.3% by 65 min. 99mTc-ECD cleared rapidly from other organs. The primary excretion route was through the kidneys. Cumulative 99mTc activity in the urine at 90 min and 24 hr were 60.2 +/- 7.3% and 88.5 +/- 10.3%, respectively. The critical organ was the bladder wall with an estimated radiation dose of 0.073 mGy/MBq, which was acceptable value. Clear SPECT images were obtained at 30, 90 and 150 min postinjection. In conclusion, 99mTc-ECD is a safe and promising radiopharmaceutical for the evaluation of regional cerebral blood flow.


[A case of unusually muscle localization of 99mTc-hydroxy methylene diphosphonate scintigraphy in a patient with acute rhabdomyolysis].

A 85-year-old man was admitted with a history of right upper arm pain following trauma. Laboratory studies included an initial CPK level of 5,385 IU/liter. Other laboratory values were GOT, 114 IU/L; LDH, 701 IU/L; myoglobin, 1,100 ng/ml; aldolase, 13.8 IU/L. The patient was presumed to have have rhabdomyolysis. A 99mTc-hydroxy methylene diphosphonate (99mTc-HMDP) scan revealed an increased uptake in the right shoulder area. 99mTc-HMDP scan is a sensitive indicator of local skeletal muscle injury in rhabdomyolysis.


[Clinical assessment of serum myosin light chain I in patients with dilated cardiomyopathy].

Serum cardiac myosin light chain I (LCI) levels were quantitated using a radioimmunoassay kit in patients suspected of dilated cardiomyopathy (DCM). In this study, 55 patients were evaluated between 1986 and 1991. They were composed of 40 males and 15 females, and their age was 27-75 years (51 +/- 11 years). The patients with renal dysfunction were excluded due to their serum creatinine levels (greater than 2.0 mg/dl). 1) After cardiac catheterization, endomyocardial biopsy and echocardiography, 44 patients were diagnosed as DCM, 2 as ischemic heart disease, 2 as chronic myocarditis, 1 as restrictive cardiomyopathy, 1 as dilated hypertrophic cardiomyopathy, 1 as cardiac amyloidosis, 2 as myopathy, 1 as polymyositis and 1 as hypothyroidism. 2) Only two patients with DCM had elevated LCI. Besides, two patients with myopathy or hypothyroidism had elevated LCI. 3) In the follow-up, one patient died suddenly 6 months later and another showed normal value of LCI four years later. 4) LCI elevation in DCM was not related to either the severity of heart failure or cardiac function and it showed no finding of 201Tl myocardial defect or elevated CPK. 5) The mechanism for elevated LCI in myopathy is related to a cross-reaction with myosin light chain in the skeletal muscle. In hypothyroidism, it may be related to decreased clearance of normal LCI concentration or increased myosin light chain from damaged skeletal muscle. In conclusion, it is evident that the measurement of LCI is not helpful in clinical assessment of patients with DCM, but may be useful in detection of secondary cardiomyopathy.


[Metabolism of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in blood--mainly in vitro].

Metabolism of 99mTc-ethyl cysteinate dimer (99mTc-ECD) in blood was studied mainly in vitro. When 99mTc-ECD was mixed with blood taken from 12 subjects, the octanol extraction ratio of ECD (y) decreased rapidly and the octanol extraction ratio-time profile well fitted a monoexponential curve (y = Ae-kt/1000, A, k: constant, t: time after mixing). The k value and hematocrit (Ht) were significantly correlated (k = 0.376Ht-3.27, r = 0.897, p less than 0.001), therefore, it was suggested that the majority of the enzyme which dissolves ECD exists in red blood cells. When ECD was mixed with blood, there were more hydrophilic products of ECD in plasma than those generated by the enzyme in plasma. In vivo input function of 99mTc-ECD was calculated by arterial blood sampling and octanol extraction. The duration of effective input was relatively short, which was attributed to rapid decrease of octanol extraction ratio in vivo.


[A new polar map to quantify reversible area by myocardial 201Tl single photon emission computed tomography and clinical application to patients before and after percutaneous transluminal coronary angioplasty].

In the studies of stress 201Tl single photon emission computed tomography, we have developed a computer method to discriminate reversible from irreversible defect, then quantify each area and display the area on the polar map. Initial percent uptake (%Ui) and delayed percent uptake (%Ud) were expressed as percent of the maximum uptake area and were defined as regional myocardial 201Tl uptake in initial and delayed image, respectively. The %Ud/%Ui ratio was defined as redistribution ratio (RD-ratio). The values of %Ui obtained from each pixel of short axis slices were plotted against the values of RD-ratio on XY co-ordinates. In this graphic display, normal area, ischemic viable area and non viable area were separated by the following four lines. A; The straight line (Y = 2.0-0.012X) indicating the relationship between %Ui and RD-ratio for the group with ischemic viable myocardium. B; The parallel line to A and shifted to -1.5 SD from A. C; The vertical line at 67.0% level (ischemic upper level). D; The vertical line at 27.6% level (viable lower level). Each area was discriminated by color display and calculated relative area values were displayed on the polar map. Criteria for discriminating each area were derived from the results of ischemic pre-transluminal coronary angioplasty (PTCA) lesions (n = 21) in which viability was confirmed by successful PTCA and previous results of 66 cases with single vessel disease and 16 cases of control group. This new computerized technique was applied for evaluation of another group with successful PTCA (n = 15).(ABSTRACT TRUNCATED AT 250 WORDS)


[Phase III trial of 99mTc-rhenium colloid for lymphoscintigraphy].

A multicenter study was carried out on 191 patients (196 examinations) with lymphatic system disorders to evaluate the efficacy and safety of 99mTc-rhenium Colloid, a tracer for lymphoscintigraphy (TCK-17). Local pain and swelling occurred at the site of injection in 79.6% and 5.1% of patients, respectively, and 2 patients experienced mild fever. The accuracy was calculated on the basis of the results obtained by other diagnostic methods. Lymphoscintigraphy using TCK-17 was sensitive diagnostic procedures, but low specificity. The efficacy was classified into five grades: "Excellent", "Good", "Moderate", "Equivocal", and "Poor". 67.3% of all examination were evaluated as "Excellent" or "Good". This study revealed TCK-17 was a useful radiopharmaceutical for lymphoscintigraphy because of its safety and effectiveness.


[Clinical usefulness of exercise/rest 99mTc-teboroxime SPECT imaging: results of a Japanese multi-center phase II study].

99mTc-Teboroxime [Chloro[tris(cyclohexyldioxime)methaneboronic acid] (99mTc)technetium], a perfusion agent for myocardial imaging, has a distinct advantage over 201Tl because of its very high myocardial extraction and is a 99mTc compound ideal for gamma camera imaging. This agent also demonstrates rapid myocardial washout, which allows completion of exercise and rest imaging studies in a short interval (to 1 hour). However, the rapid washout necessitates the completion of image acquisition very quickly after injection and therefore may require nonconventional SPECT imaging. In this Phase II study we evaluate the safety and efficacy of 99mTc-Teboroxime to detect coronary artery disease by exercise and rest SPECT imaging in 38 patients with prior myocardial infarction, 31 patients with angina pectoris, and 4 patients with non-coronary cardiac diseases. The 99mTc-Teboroxime dose used was 370-740 MBq in each study. The findings were compared with coronary angiography or 201Tl exercise and redistribution SPECT. No significant adverse reactions or laboratory abnormalities attributable to 99mTc-Teboroxime were observed. The quality of SPECT images was optimal in 62.5% of all patients. The relatively large population of suboptimal cases (37.5%) was attributed to the delay of the start and prolongation of the image acquisition time. In 85.7% of patients whose imaging was started within 5 minutes and completed within 11 minutes after injection, optimal quality was observed. Thus, 99mTc-Teboroxime SPECT requires the rapid completion of image acquisition after injection to achieve optimal image quality. Abnormalities of 99mTc-Teboroxime distribution were detected in 97.1% and 62.1% of patients with prior myocardial infarction or angina pectoris, respectively. The concordance with coronary angiography was 84.4% and 68.0%, and with 201Tl was 78.1% and 74.1%, respectively. Although standardization of the image protocol suitable for this agent is needed for the next study, these high correlations suggest the potential usefulness of 99mTc-Teboroxime SPECT imaging.


Facilitatory and inhibitory processes in the thalamic ventrobasal nucleus of the rat.

Experiments were carried out on anesthetized rats to clarify the actions of the corticothalamic input on the thalamic ventrobasal neuron (VB). The field potentials and the unit activities were evoked in the VB by the electrical stimulation of the contralateral (cSCx) and ipsilateral somatosensory cortex (SCx), the thalamic radiation (TR), and the medial lemniscus (ML). The corticothalamic axons could be activated from cSCx via the ipsilateral SCx, with the result of a clear excitation followed by the inhibition of VB neurons. These VB responses were also evoked from SCx, TR, or even ML with other responses. Paired stimulation of these sites revealed that the corticothalamic input exerted facilitation on the succeeding corticothalamic input for 690 +/- 74.2 ms (n = 5). It was confirmed that these corticothalamic actions were abolished by the lesion of SCx. In contrast to the corticothalamic-induced VB responses, the VB responses to ML input received powerful inhibitory effects from ML or SCx for 1,150 +/- 35.4 ms (n = 5). It is concluded that the corticothalamic input can excite the VB neuron in a mechanism that differs from that of ML input.


Reappraisal of the corticothalamic and thalamocortical interactions that contribute to the augmenting response in the rat.

In urethane-anesthetized rats, low frequency electrical stimulation of the thalamic radiation (TR) evoked an augmenting response in the somatosensory cortex (SCx) which was followed by rhythmic slow waves. The augmenting response mainly consists of the incremental secondary response (II-response). Simultaneously, augmentation also occurs in the ventrobasal nucleus of thalamus (VB) on the late component responses, C- and D-waves, to TR stimulation. The latencies of these augmented responses were shorter for the C-wave and the accompanying unit discharges in the VB relay neurons than for the D-wave and the II-response. We hypothesized that the thalamo-cortico-thalamic reverberating circuit was crucial in generating the augmenting response in the SCx. To test this hypothesis, an attempt was made to block temporarily the corticothalamic glutamatergic transmission by means of microinjections of kynurenate (KYN), an antagonist of glutamate, into the VB with a dose of more than 2 mM. This local procedure blocked all of the augmenting phenomena completely with a full recovery after the duration that depended on the dose of KYN. Besides, in the stage of complete blocking of the II-response to the test TR stimuli, the augmentation was able to be restored by adding a short train of high frequency TR stimuli that mimicked a burst discharge of VB relay neurons. These results in support of the hypothesis would reappraise the functional significance of the reverberating circuit in augmentation that has recently been controversial.


Effects of blood gas, pH, lactate, potassium on the oxygen uptake time courses during constant-load bicycle exercise.

Changes in the time courses of VO2 during constant-load exercise were examined in connection with other cardiorespiratory and blood chemical parameters. Eleven healthy male subjects performed a ramp exercise and three to six constant-load exercises at varying degrees of load using an electro-braked bicycle ergometer. Heart rate, ventilation, and gas exchange were measured during both types of exercise, and chemical parameters of the subject's blood (blood gas, pH, lactate, and electrolytes) were determined during two intensities of constant-load exercise. The time courses of cardiorespiratory and blood chemical data 3 min after the onset of constant-load exercise were fitted by linear regressions to see whether these parameters had reached the steady state or not. Heart rate increased significantly at a lower intensity of constant-load exercise than VE, VO2, and VCO2. While the increase in VCO2 was slower than that of VO2, a definite difference in time courses was not found between VE and VO2. The time courses of changes in blood gas, pH, bicarbonate, and lactate were not correlated with those of VO2. However, changes in blood potassium concentration were closely correlated with those of VO2 in terms of time courses and magnitude. This suggests the possibility that blood potassium may play an important role in the control of VO2 time course during constant-load exercise.


Responses of muscle sympathetic nerve activity and cardiac output to the cold pressor test.

We measured muscle sympathetic nerve activity (MSA) to clarify the mechanisms of the blood pressure rise during cold pressor test (CPT), simultaneously with impedance cardiography and blood pressure wave measurement in 10 healthy subjects. MSA remained unchanged during the initial period of 0-30s of the CPT and increased remarkably during the later period of 30-90s of the CPT, while cardiac output exhibited a slight increase during the initial period but not during the later period. Mean blood pressure increased significantly throughout the entire period of CPT and reached the maximal level during 90-120s of the CPT. The mean blood pressure and total peripheral resistance during the CPT showed a linear correlation with MSA. In conclusion, an increase of cardiac output elevates blood pressure at the initial period of the CPT with little increase in MSA, while an increase of MSA plays an essential role to elevate the blood pressure at the later period of the CPT.


ANP decreases arterial oxygen partial pressure by increasing shunt flow in pulmonary circulation.

This study was designed to clarify the decreased arterial oxygen partial pressure (PaO2) mechanism induced by atrial natriuretic peptide (ANP) infusion. In order to examine the effects of ANP on gas exchange across the normal lungs, ANP was infused to eight anesthetized dogs, ventilated with mixed gases of oxygen and nitrogen. PaO2 and venous oxygen partial pressure (PvO2), ventilation-perfusion ratio (VA/Q), shunt-total blood flow ratio (QS/QT) were measured before and during ANP infusion under ventilation with 10, 20, 30% oxygen. In this study ANP decreased PaO2 from 89.0 +/- 4.2 to 85.4 +/- 5.4 mmHg during 20% oxygen ventilation, and from 138.1 +/- 3.6 to 132.5 +/- 4.1 mmHg during 30% oxygen ventilation. ANP increased VA/Q and QS/QT. We conclude that the decrease in PaO2 caused by ANP infusion was mainly due to the increased venous admixture.


Excitatory and inhibitory controls of the masseter and temporal muscles elicited from teeth in the rat.

The periodontal mechanism that controls the jaw reflexes was examined in lightly anesthetized rats. Motor-unit activity in the masseter and temporal muscles was recorded electromyographically and pressure stimulation was applied to either an upper incisor or an upper molar. Reflex effects of dental stimulation varied depending on the level of ongoing activity (background activity, BGA) in each motor unit. Incisal or molar stimulation elicited excitatory reflexes in both the masseter and temporal motor units at a low BGA, but inhibitory reflexes in both types of motor unit at a higher BGA. In contrast to these synergistic reflex actions, the reciprocal reflex actions of the two motor units that belonged to the respective muscles occurred when the BGA was intermediate. The results suggest that different patterns of periodontal jaw reflexes may be elicited, depending on the different levels of BGAs. Furthermore, the present reflexes were modified with the site of a stimulated tooth within the dentition. Incisal stimulation produced greater excitation in the masseter motor unit than in the temporal one, and the opposite type of response occurred during molar stimulation. Moreover, smaller-amplitude motor units with a low reflex threshold and larger-amplitude motor units with a higher reflex threshold tended to exhibit excitatory and inhibitory reflexes, respectively.


Effect of immobilization stress on in vitro and in vivo thermogenesis of brown adipose tissue.

Repetitive intermittent stress such as immobilization has been shown to induce an improved cold tolerance through an enhanced capacity of nonshivering thermogenesis (NST), causing positive cross adaptation between nonthermal stress and cold. In the present study, effect of 3-h-daily immobilization stress for 4-5 weeks was investigated on in vitro and in vivo thermogenesis of interscapular brown adipose tissue (BAT). In vitro thermogenesis was measured in the minced tissue blocks incubated in Krebs-Ringer phosphate buffer with glucose and albumin at 37 degrees C, using a Clark-type oxygen electrode. The stressed rats showed less body weight gain during the experiment. The BAT weight, its protein and DNA contents were significantly greater in the stressed rats. Basal, noradrenaline- and glucagon-stimulated oxygen consumptions were significantly greater in the stressed rats. In vivo thermogenesis was assessed by the changes of temperatures in colon (Tcol), BAT (TBAT), and tail skin (Tsk) induced by noradrenaline or glucagon infusion in the anesthetized rats. Noradrenaline and glucagon increased the TBAT and the extent of increase was greater in the stressed rats. These results indicate that cross adaptation between nonthermal stress and cold may be mediated through an enhanced thermogenic activity of BAT.


Effects of selective vagal stimulation on the gallbladder and sphincter of Oddi and peripheral vagal routes mediating bile evacuative responses induced by hypothalamic stimulation.

Peripheral routes of the vagus nerves to the biliary system were studied in anesthetized dogs using various selective vagal stimulation. Efferent stimulation of the gastric, hepatic, or celiac vagal branch as well as the cervical or thoracic vagal trunk induced gallbladder and Oddi's sphincter contractions, but those induced by hepatic vagal stimulation were rather small. The contraction responses in the gallbladder and sphincter of Oddi induced by thoracic vagal stimulation were greatly reduced after an external ligation around the pyloric sphincter. After administration of sympathetic blockers and atropine, vagally-induced gallbladder contractions were completely abolished and slight relaxation was seen in some animals. On the other hand, relaxation or transient relaxation followed by enhanced contractions was elicited in the sphincter of Oddi by vagal stimulation after atropine and sympathetic blockers. The relaxation response in the gallbladder after atropine and sympathetic blockers was abolished and that in the sphincter of Oddi was greatly reduced after the ligation around the pyloric sphincter. Stimulation of a ventral part of the anterior hypothalamic area induced gallbladder contraction and simultaneous relaxation of the sphincter of Oddi. These responses were completely abolished by the ligation around the pyloric sphincter in six dogs, while a slight relaxation response in the sphincter of Oddi remained in two dogs. These results suggest that the vagal fibers passing across the pyloric sphincter region are important for regulation of canine biliary motility and that extragastric vagal routes play a minor role in the nervous control of canine bile evacuation.


Nitroarginine-sensitive and -insensitive components of the endothelium-dependent relaxation in the guinea-pig carotid artery.

In the guinea-pig carotid arteries, nitroarginine elevated the resting tension (greater than 3 x 10(-6) M) and enhanced the noradrenaline (NA)- and high-potassium (high-K, 29.6 mM) induced contractions (greater than 10(-7) M), in a concentration-dependent manner, with no significant change in the resting membrane potential and depolarizations elicited by NA or high-K. ACh (10(-6) M) relaxed the muscles precontracted with NA or high-K by 96 or 46% of the contraction, respectively. In the presence of nitroarginine (10(-5) M) for 1-3 h, the ACh-induced relaxation was reduced to 40 or 0% of the NA- or high-K-contractions, respectively. In tissues contracted with NA and exposed to nitroarginine, the ACh-induced relaxation changed from a sustained to a transient form. ACh relaxed the muscles to a similar extent, at any given level of tension, as elevated by different concentrations of NA to 1-3 times the level produced by 10(-6) M NA, either in the presence or absence of nitroarginine. ACh (greater than 10(-8) M) produced a transient hyperpolarization of the membrane, in an endothelium-dependent manner, and the responses were blocked by atropine (10(-6) M) or high-K solution, but not by NA or nitroarginine. We propose that 1) endothelium-derived hyperpolarizing factor (EDHF) is produced by pathways independent of the biosynthesis of endothelium-derived relaxing factor (EDRF), 2) the sustained release of EDRF maintains the muscle tone at a low level, and 3) the endothelium-dependent relaxation is produced by both EDRF and EDHF, and they elicit sustained and transient relaxations, respectively.


Effects of brain natriuretic peptide and C-type natriuretic peptide infusion on urine flow and jejunal absorption in anesthetized dogs.

Effects of brain natriuretic peptide (BNP) or C-type natriuretic peptide (CNP) on urinary excretion and jejunal absorption of fluid and electrolytes were examined in anesthetized dogs. Intravenous infusion of BNP increased urinary fluid and electrolyte excretion and decreased jejunal fluid and electrolyte absorption. CNP had a similar effect on jejunal absorption as BNP. However, CNP had no significant effect on renal fluid or electrolyte excretion. These results indicate that: 1) BNP is a powerful natriuretic peptide comparable to ANP and; 2) CNP may also contribute to the regulation of body fluid homeostasis by way of inhibiting net jejunal fluid and electrolyte absorption.


Peristaltic movement evoked in intestinal tube devoid of mucosa and submucosa.

Computerized analysis of video-recorded peristalsis was made in a preparation of guinea-pig ileum tube from which both mucosa and submucosa were mechanically scraped off. Threshold value for provoking peristalsis was higher, conduction velocity of peristalsis was slower, and peristaltic force was weaker in comparison with the ileum tube from which only mucosa was scraped off and with the normal ileum tube. A histological control of the preparation proved that there was no nerve cell body of submucous plexus on the surface of separated circular muscle. It was concluded that peristalsis, though impaired, could be provoked by way of activation of the reflex arch consisted by neural circuit of myenteric neurons which should be produced by excitation of stretch receptors in the muscularis externa.


Pulmonary C-fibers do not play a role in ammonia-induced brief tachypnea in the rabbit.

To determine the role of pulmonary C-fibers in evoking a brief tachypnea induced by ammonia vapor, we examined the responses of diaphragm electromyogram (DIAP EMG) to ammonia inhalation before and after procaine treatment to the contralateral vagus nerve in urethane-anesthetized, spontaneously breathing rabbits with unilateral vagotomy. Procaine treatment that blocked the conduction of vagal afferent C wave did not significantly alter the response of brief tachypnea to ammonia. Furthermore, the stimulation of pulmonary C-fibers by ammonia inhalation did not coincide with the induction of brief tachypnea. In addition, we also examined the responses of rapidly adapting receptors (RARs) and slowly adapting receptors (SARs) to ammonia inhalation in rabbits, particularly in which inhalation of this chemical gas produced a brief tachypnea. The burst activity of RARs evoked by ammonia inhalation coincided with the phase of rapid shallow breathing for a few breaths. The discharge rates of SARs during both inspiration and expiration increased when ammonia inhalation caused a brief tachypnea. From these results, it can be suggested that the ammonia-induced brief tachypnea is probably mediated by transient stimulation of both SAR and RAR activities but does not occur as a result of the pulmonary C-fiber stimulation.


Acid-induced two-step depolarization in the peritubular membrane of bullfrog kidney proximal tubules.

Using ion-selective microelectrode technique, we investigated acid-induced changes of peritubular membrane potential (EM) and intracellular activity of Na+ and H+ ((Na)i and pHi) in the proximal tubule of perfused bullfrog kidney in vivo. When peritubular pH was reduced at constant PCO2, EM was depolarized in two steps: i.e., an initial sharp fall followed by an additional deeper fall. This was termed as the acid-induced two-step depolarization. During this change, pHi was decreased gradually from 7.4 to 6.9 in response to 1/10 HCO3- reduction (pH from 7.7 to 6.7), whereas (Na)i was increased after a transient decrease. This result supports the peritubular rheogenic HCO3- exit coupled to Na+ movement during the initial depolarization period. Complete removal of peritubular HCO3- at constant pH produced a less marked initial depolarization with a transient rise of pHi, followed by a partial repolarization without appreciable change in (Na)i. Peritubular SITS administration inhibited these depolarization responses to the acid perfusion. The above findings suggest that 1) the initial part of the two-step EM depolarization produced by low HCO3- or HCO(3-)-free perfusion resulted mainly from the peritubular rheogenic exist of HCO3-, 2) the magnitude of initial depolarization would also be affected by pHi, and 3) the subsequent delayed changes of EM were mainly determined by the pHi-sensitive K+ conductance of the peritubular membrane.


Forced vital capacity in Malaysian females.

Spirometry was performed on 614 female subjects ranging in age from 13 to 69 years and comprising all the main races in Malaysia. They were divided into six age categories. Mean forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were 2.51 +/- 0.02 and 2.31 +/- 0.02l, respectively. Both FVC and FEV1 correlated negatively with age. Regression analysis revealed an age-related decline in FVC of 220 ml per decade of life. Multiple stepwise regression of the data for the prediction of an individual's FVC above the age of 20 years gave an equation: FVC(l) = 0.0312 (height)-0.022 (age)-1.64. Predicted FVC values derived from equations based on other populations were considerably higher than the observed mean in this study. Our study, therefore, reemphasizes the need to be cautious when applying formulae derived from one population to another. Grossly erroneous conclusions may be reached unless predicted equations for lung-function tests for a given population group are derived from studies based on the same population group.


Ca(2+)-activated K+ channel is present in guinea-pig but lacking in rat hepatocytes.

The mechanisms of norepinephrine-induced membrane responses in isolated hepatocytes from guinea-pigs and rats were compared using the suction-pipette, patch-clamp method, and intracellular Ca2+ concentration ([Ca2+]i) was measured using the Ca2+ fluorescent dye, Quin 2. The resting membrane potentials of isolated guinea-pig hepatocytes were -50 +/- 1 mV (mean +/- SD; n = 38), which is similar to that previously reported in rat hepatocytes by Sawanobori et al. (J Cell Physiol 139: 580-585, 1989). In guinea-pig hepatocytes, norepinephrine (6 microM) caused a membrane hyperpolarization, and norepinephrine (6 microM) or Ca(2+)-ionophore (A23187) (0.4 microM) caused a corresponding outward current. The sensitive current produced by norepinephrine and Ca(2+)-ionophore reversed its polarity at -74 +/- 9 mV (n = 7). The single channel recorded by cell-attached patch and inside-out patch had mean conductance of around 20 + 1 pS and was activated by 1 microM [Ca2+]i. On the other hand, neither norepinephrine (6-20 microM) nor Ca(2+)-ionophore (A 23187) (0.4 microM) caused any change in membrane potential and current in rat hepatocytes, whereas norepinephrine increased [Ca2+]i both in rat and guinea-pig hepatocytes to a similar degree. In the single-channel recording, we recorded single channels that had a mean conductance of 109.8 +/- 17.7 pS different from around 20 pS in guinea-pig. In inside-out patches, increased Ca2+ concentration from 10(-6) to 10(-3) M at the intracellular face of the membrane did not modify the single channel of rat hepatocytes. These results indicate that increased [Ca2+]i activates this channel in guinea-pigs, but that the channel activated by increased [Ca2+]i is lacking in rat hepatocytes membrane. Therefore, different mechanism operates in different species of liver cells to keep the constant state.


Transient increase in deformability of stressed red blood cells and role of plasma proteins.

In the context of possible fatigue and eventual destruction of red blood cells (RBCs) in the circulation, changes in deformability (filterability) were studied in RBCs which had just undergone deformation. Fresh human RBCs suspended in media of varying protein concentrations were stressed by causing them to pass through a 5-microns Nuclepore filter. Resultant changes in their deformability were assessed from their mean pore passage time in a subsequent filter passage. Contrary to the expectation, that deformability would be reduced, shortened passage times were observed for those stressed RBCs. The changes were, however, transient and, like the initial passage times, were an increasing function of the protein concentration in the suspending fluid. These results appeared to be consistently explicable by assuming release due to stresses and readsorption in time for plasma protein molecules normally adsorbed on cell surfaces. An analysis, furthermore, yielded acceptable estimates for magnitude of the cell-plasma protein interaction, number of protein molecules normally adsorbed on a cell, and also cell membrane viscosity and its apparent change due to the protein adsorption.


Frequency thresholds of rat cochlear nerve fibers.

Activities of single cochlear nerve fibers of Wistar rats were recorded extracellularly. Best frequencies (BF) distributed from 0.50 to 62.6 kHz. The audiogram was made as the minimum boundary of the BF threshold distribution. The range of audible frequency was 0.54-63 kHz at 60 dB SPL and 0.15-67 kHz at 100 dB SPL. The lowest trough of the audiogram was 5 dB SPL at 41.2 kHz. There was the second trough of 10 dB SPL at 7.01 kHz leaving a notch between the two troughs. The shapes of the frequency-threshold curves (FTCs) of fibers were evaluated quantitatively and typical FTCs were shown as a function of BF.


Muscle activity during forelimb stepping in decerebrate cats.

In decerebrate cats with the lower thoracic cord transected, electromyographic activities were analyzed in up to 41 forelimb muscles, almost all muscles involved in forelimb stepping (intrinsic hand muscles were not included). From the active period in the step cycle, muscles were classified into three groups: extensors, of which activity is like that of elbow extensors; flexors, activity like that of elbow flexors; others, including dorsiflexors of the wrist, pronators, and supinator. The results were well consistent with those from conscious animals as well as efferent pattern of fictive locomotion in elbow and distal muscles. Nevertheless, in some proximal muscles discrepancies were noted, suggesting their changeability depending on environmental conditions. Recording from almost all muscles allowed to estimate rhythmic change of the overall output of the forelimb central pattern generator.


Activity of cervical neurons during forelimb fictive locomotion in decerebrate cats.

Unit activities were recorded from cervical neurons during forelimb fictive locomotion. Rhythmic activities were evaluated by onset and termination. Rhythmically-active neurons were classified into 4 major groups: (1) <f> neurons, the active periods covered the whole flexor phase; (2) f+e neurons, the active periods commenced prior to and terminated in the extensor phase; (3) e neurons, the active periods appeared within the extensor phase; (4) e+f neurons, the active periods commenced prior to and terminated in the flexor phase. In addition, a few neurons that were not classified were observed. Neuronal behaviors seemed to suggest that <f> and e+f were grouped "flexor-like," while e and f+e were grouped as "extensor-like." "Flexor-like" neurons were likely distributed in the dorsal (lamina V-VI) and rostral (C5-C6) region, whereas "extensor-like" neurons distributed mainly in the ventral (lamina VI-VII) and caudal (C7-T1) region. Some neurons showed rhythmic activities prior to appearance of fictive locomotion (prelude rhythm). The structure of the central pattern generator was discussed.


Hypothalamic corticotropin-releasing hormone (CRH) secretion into hypophysial portal blood is regulated by cutaneous sensory stimulation in anesthetized rats.

The effects of noxious and non-noxious mechanical stimulation of various segmental skin areas (face, forelimb and forepaw, abdomen, hindlimb and hindpaw) on the secretion of immunoreactive corticotropin-releasing hormone (iCRH) from the hypothalamus into hypophysial portal blood was examined in artificially ventilated rats under halothane anesthesia. Secretion of iCRH was calculated from the iCRH concentration in hypophysial portal plasma and the plasma flow rate. Noxious mechanical stimulation of the skin was delivered by pinching using surgical clamps, while non-noxious mechanical stimulation was provided by brushing with tooth brushes. Pinching of the bilateral forepaws or hindpaws and brushing of the bilateral hindlimbs for 20 min increased hypothalamic iCRH secretion. In contrast, pinching of the face or abdomen and brushing of the face, forelimbs, or abdomen for 20 min did not significantly influence it. These results indicate that cutaneous mechanical sensory stimulation contributes to the reflex regulation of CRH secretion from the hypothalamus into hypophysial portal blood, and also that this effect is highly dependent on the site of stimulation.


Intracellular and extracellular chloride ions in the horizontal cells of the stingray retina.

Intracellular and extracellular concentrations of chloride ([Cl-]i, [Cl-]o) ions in the horizontal cells of the stingray retina were studied by means of ion-selective microelectrodes. The electrodes used were of the double-barreled type and Corning's #477315 resin was used as the exchanger. The average [Cl-]o and [Cl-]i in the L-type cells were 320 and 130 mM, respectively (n = 37), and the equilibrium potential (ECl) was calculated as -23.3 mV. In some cases, dark membrane potentials were more positive than the ECl. With white light stimulus, the membrane hyperpolarized to a more negative level than ECl. Based on the experiments described above, the hypothesis that the hyperpolarizing response of horizontal cells is due to the permeability change of the membrane to chloride ion was excluded in the stingray retina.


Effects of KB-2796, a new diphenylpiperazine calcium antagonist, on renal hemodynamics and urine formation in anesthetized dogs.

The effects of KB-2796, a new calcium antagonist with a diphenylpiperazine moiety, on renal hemodynamics and urine formation were investigated in anesthetized dogs. Intravenous infusion of KB-2796 (10, 30, and 100 micrograms/kg/min) decreased mean blood pressure (MBP) and renal vascular resistance (RVR) in a dose-dependent manner, but did not change renal blood flow (RBF). At the highest dose, glomerular filtration rate (GFR) and urine flow (UF) tended to decrease. Nicardipine (0.1, 0.3, and 1 microgram/kg/min) also dose-dependently decreased MBP, RVR, GFR, and UF. When KB-2796 was infused into the renal artery at lower doses of 3 and 10 micrograms/kg/min, UF and urinary excretion of electrolytes increased without a significant change in RBF and GFR. Intrarenal infusion of KB-2796 at 30 micrograms/kg/min and nicardipine at 0.3 microgram/kg/min produced a significant increase in GFR, RBF, UF, urinary excretion of electrolytes, and renin secretion rate. These results suggest that KB-2796 administered intrarenally exerts a diuretic action via tubular effects and the alteration of renal hemodynamics. However, its diuretic action might be masked by diminished urine formation via a reflex activation of the sympathetic nerves and/or via a reduction of renal perfusion pressure when it is administered systemically.


Stimulation by capsaicin of gastric alkaline secretion in anesthetized rats.

Effects of mucosal application of capsaicin on alkaline secretion were examined in the stomachs of anesthetized rats and compared with those in the duodenum. The stomach (acid secretion was inhibited by omeprazole given i.p.) or the duodenum was perfused with saline (pH 4.5); both the pH of the perfusate and transmucosal potential difference (PD) were continuously monitored; and the HCO3- output was determined by the pH change. Under these conditions, the mucosal application of capsaicin (0.3-6 mg/ml for 30 min) caused significantly increased pH and HCO3- output in a concentration-related manner in both tissues, while PD increased in the duodenum and decreased in the stomach. The HCO3- stimulatory action of capsaicin was markedly attenuated by sensory deafferentation, significantly mitigated by prior administration of indomethacin, and exhibited a marked tachyphylaxis after the repeated exposure at a high concentration (6 mg/ml). None of these treatments had any effect on the pH, PD and HCO3- responses induced by prostaglandin E2 (300 micrograms/kg, i.v.) in these tissues. These results indicate that mucosal application of capsaicin increased the gastroduodenal HCO3- output by stimulation of capsaicin-sensitive sensory neurons. This action may be in part mediated by endogenous prostaglandins.


Studies on the antinephritic effect of plant components (4): Reduction of protein excretion by berberine and coptisine in rats with original-type anti-GBM nephritis.

The present study was conducted to investigate the antinephritic effects of berberine and coptisine, which are contained in Coptidis rhizoma, on original-type anti-GBM nephritis in rats. Berberine and coptisine at the doses of 0.5, 1.0 and 5.0 mg/kg/day, i.p. were effective in inhibiting urinary protein excretion, elevation of serum cholesterol and creatinine contents as well as glomerular histopathological changes. In addition, berberine at 20 mg/kg/day, p.o. also inhibited urinary protein excretion throughout the experimental periods. Berberine and coptisine inhibited platelet aggregation in both in vitro and in vivo assays, and berberine inhibited the decline of renal blood flow. Although berberine inhibited an increase in thromboxane B2 formation, it increased the formation of 6-keto-prostaglandin F1 alpha in platelets and isolated glomeruli. These results indicate that the antinephritic effects of berberine and coptisine may be partly due to antiplatelet action and improved renal hemodynamics via changing prostanoid synthesis.


Effects of semotiadil (SD-3211), a benzothiazine calcium antagonist, on blood pressure and atrioventricular conductivity in anesthetized dogs.

We investigated the effects of semotiadil (SD-3211), a novel calcium antagonist, on blood pressure and the atrioventricular (AV) conduction time and functional refractory period (FRP) of the AV conduction system (AV conductivity) in anesthetized open-chest dogs. The heart was electrically stimulated at a constant rate. In dogs with an intact nerve supply to the heart, i.v.-injections of semotiadil (0.03 to 0.3 mg/kg) produced a fall of blood pressure in a dose-dependent manner. AV conduction time and FRP were prolonged by rather higher doses (0.3 mg/kg), and second-degree AV block occurred only with the highest dose (1 mg/kg). In dogs with the nerve supply to the heart interrupted, the vasodepressor effects and suppressant effects of semotiadil on AV conductivity were slightly enhanced. The suppressant effects on AV conductivity became marked as pacing rates were increased. These results suggest that semotiadil at appropriate doses produces a vasodepressor effect without affecting AV conductivity even in the heart deprived of nervous control, e.g., the heart with beta-adrenoceptors blocked. The frequency-dependent suppressant effect on FRP of semotiadil is also noteworthy in the treatment of reentrant supraventricular tachycardia that involves the AV node.


Inhibitory action of dilazep on histamine-stimulated cytosolic Ca2+ increase in cultured human endothelial cells.

Using a fluorescent Ca(2+)-sensitive dye, fura-2, and photometric fluorescence microscopy, we measured changes in cytosolic Ca2+ concentration ([Ca2+]i) in cultured human endothelial cells and studied the effect of dilazep on [Ca2+]i elevation induced by histamine. Histamine (1 microM) caused a rapid transient peak in the average [Ca2+]i of a group of cells (approximately 10(2) cells), followed by a decrease to a sustained elevation. Dilazep as well as diltiazem (1.0 to 100 microM) concentration-dependently inhibited the latter sustained elevation, which was eliminated by removal of extracellular Ca2+, while the initial transient response was not changed by dilazep at concentrations up to 100 microM. The IC50 values of dilazep and diltiazem were 16 and 58 microM, respectively. The patterns of the [Ca2+]i elevation responses to histamine were variable among individual cells. Some single cells showed a transient peak and a sustained elevation as observed in a group of cells. Some single cells caused a repetitive spikelike elevation of [Ca2+]i. Dilazep lowered the sustained elevation to the resting level and in some single cells, changed the sustained elevation to the spikelike elevation. The frequency of the spikelike [Ca2+]i elevation was also decreased by dilazep. Decrease in extracellular [Ca2+] showed the same pattern of inhibitory actions as dilazep did. These results indicate that dilazep inhibits the extracellular Ca2+ influx in endothelial cells.


Myocardial Na+ during ischemia and accumulation of Ca2+ after reperfusion: a study with monensin and dichlorobenzamil.

The intracellular cation contents were determined in isolated perfused rat heart using cobaltic EDTA as a marker of the extracellular space. In hearts in which Na+ accumulation was induced with monensin, a Na+ ionophore, during 20 min-ischemia which otherwise did not result in accumulation of Na+, the levels of Na+ and Ca2+ were significantly higher after reperfusion with a significant decrease in K+. While the recovery of the cardiac mechanical function (CMF) was complete after reperfusion in control hearts, the recovery was incomplete in monensin-hearts. Dichlorobenzamil (DCB), the most specific inhibitor of Na(+)-Ca2+ exchanger, infused for 10 min before induction of ischemia in a dose of 10(-5) M, which produced a definite suppression of CMF (over 80%), inhibited the accumulation of Ca2+ and Na+ and the loss of K+ and ATP after 40 min-ischemia and reperfusion. The same dose of DCB given for 3 min before induction of ischemia and after reperfusion, which produced a less than 20% inhibition of CMF, failed to prevent the Ca2+ accumulation after 40 min-ischemia and reperfusion. These findings are at variance with the idea that the accumulation of Na+ during ischemia and the consequent augmented operation of Na(+)-Ca2+ exchange is responsible for accumulation of Ca2+ after reperfusion.


Active cutaneous anaphylaxis (ACA) in the mouse ear.

Active cutaneous anaphylaxis (ACA) was studied in the ear of female BALB/c mice. Mice were immunized with ovalbumin in the presence of aluminium hydroxide gel or complete Freund's adjuvant (CFA). Two weeks after the immunization, ACA was elicited in the mouse ear by injecting 10 microliters of antigen solution intradermally into the ear lobe. ACA was assessed by the amount of extravasated dye, which was given intravenously just after the antigen injection. Antiallergic drugs (tranilast, ketotifen and azelastine), antihistamines (chlorpheniramine, diphenhydramine and mequitazine), beta-stimulants (isoproterenol and salbutamol), theophylline and glucocorticoids (hydrocortisone, prednisolone and dexamethasone) inhibited the reaction significantly. These drugs inhibited both ACA in mice immunized with alum-precipitated antigen and ACA in mice injected with CFA-emulsified antigen similarly. ACA in the mouse ear might be a useful tool for studying drugs for allergy.


Influence of DOCA treatment on administration-time-dependent changes in the effects of furosemide in saline-loaded rats.

We have previously found that the administration-time-dependent change in the effects of furosemide, a loop diuretic agent, is observed in normal rats. The present study was undertaken to examine whether an alteration in this phenomenon occurs in rats with DOCA-saline hypertension. Unilateral nephrectomized rats were divided into three groups. The first group (DOCA-saline) received a 50 mg DOCA tablet intraperitoneally and drank 1% NaCl solution. The other two groups were given sham operations. A 1% NaCl solution was given as drinking water to the second group (control-saline), while tap water was given to the third group (control-water). Furosemide (30 mg/kg) was given orally to each group at 12 a.m. or 12 p.m. Urine was collected for 8 hours after the agent, and urinary excretion of sodium and furosemide were determined. Urine volume and urinary excretion of sodium and furosemide following the agent were significantly greater at 12 a.m. than at 12 p.m. in the control-water and control-saline groups. However, the administration-time-dependent changes in these parameters disappeared in the DOCA-saline rats. These results suggest that the mode of the administration-time-dependent changes in the effects of furosemide is altered in the DOCA-saline hypertensive rats.


Vagal afferent fibers and peripheral 5-HT3 receptors mediate cisplatin-induced emesis in dogs.

The involvement of visceral afferent fibers and 5-HT3 receptors in the emesis induced by cisplatin was studied in beagle dogs. The emesis induced by cisplatin (3 mg/kg, i.v.) was inhibited by the intravenous administration of ICS205930 (2 x 0.01 or 2 x 0.1 mg/kg) and MDL72222 (2 x 0.5 mg/kg), 5-HT3 receptor antagonists, but not by the intravenous administration of metoclopramide (2 x 0.5 mg/kg), a dopamine D2 receptor antagonist. The cisplatin-induced emesis was also suppressed by the intravenous administration of para-chlorophenylalanine (300 mg/kg/day for 3 days), an inhibitor of 5-HT synthesis. On the other hand, the administration of ICS205930 into the IVth ventricle (2 x 0.01 mg/animal) had no effects on the cisplatin-induced emesis. The cisplatin-induced emesis was completely inhibited by abdominal vagotomy and splanchnicectomy, but not by splanchnicectomy alone. On the contrary, the emesis induced by apomorphine was suppressed by the intravenous (0.1 mg/kg) or intracerebroventricular (0.05 mg/animal) administration of metoclopramide, but not by visceral nerve section. These results strongly suggest that cisplatin evokes emesis mainly by acting on the vagal afferent terminals through the release of 5-HT and that peripheral 5-HT3 receptors are involved in this action.


Recombinant human tumor necrosis factor-beta entrapped in liposomes formed by a modification of the dehydration-rehydration method retains potent cytotoxic activity on L929 cells in vitro.

Recombinant human tumor necrosis factor-beta (rhTNF-beta) may be encapsulated with high efficiency in phosphatidylcholine and distearoylphosphatidylcholine liposomes, with entrapment values of 93.4% and 92.3%, respectively, by first entrapping the substance in multilamellar vesicles using a high solute-to-phospholipid ratio followed by freeze-drying and then rehydration. The entrapped cytokine retains potent cytotoxic activity on L929 cells in vitro, causing 100% cytotoxicity, equal to that of free rhTNF-beta at a concentration of about 5 x 10(-8) g/ml.


Effect of endothelin (ET)-1, ET-3 and ET-(16-21) on the isolated and perfused rat kidney from normotensive and spontaneously hypertensive rats.

We have investigated the effect of endothelin (ET)-1, ET-3 and ET-(16-21) on isolated and perfused rat kidney (IPK). ET-1 and ET-3 produced a similar dose-dependent increase in perfusion pressure of IPK, while ET-(16-21) was completely inactive. The ET-1 effects were greater in spontaneously hypertensive rats (SHR) as compared to normotensive rats (WKYR), whereas the ET-3 effects were greater in the SHR group only at the lowest doses. The pressure response of IPK induced by ET-1 was partially modified by prior application of the nitric oxide synthetase inhibitor L-nitroarginine in both WKYR and SHR.


MK-801 prevents the post-ischemic cerebral hypoperfusion, but not the dysfunction of the vagal baroreflex in dogs.

Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) antagonist, failed to protect the vagal component of reflex bradycardia from 5-min global cerebral ischemia in dogs under pentobarbital anesthesia. On the other hand, MK-801 completely prevented the development of the post-ischemic cerebral hypoperfusion without affecting the cerebral blood flow in sham-operated animals. The results suggest that NMDA receptors may participate in the development of the secondary disturbance of the cerebral circulation, but are not involved in the post-ischemic dysfunction of the baroreflex system.


Effect of ketotifen on acute gastric lesions and gastric secretion in rats.

Ketotifen, a histamine H1-receptor antagonist and mast cell stabilizer, significantly protected the rat gastric mucosa against lesions induced by necrotizing agents, histamine or compound 48/80. The agent significantly inhibited the basal gastric acid secretion, but had little or no effect on the histamine-stimulated secretion. The mucosal protective effect was observed even at a dose that had little or no effect on gastric acid secretion, suggesting that ketotifen exhibits so-called cytoprotective activity.