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Biomedical subjects

T Kadota

Publications and source records attributed to T Kadota.

At least 91 records · Page 5Linked to original sources
PubMed1992

[Cefepime (BMY-28142 diHCl/L-arginine blend): one-month repeated dose subcutaneous toxicity study in rats].

In order to investigate the toxicity of cefepime (CFPM, BMY-28142 diHCl/L-arginine blend upon repeated subcutaneous dosing), the test article was administered to Crj:CD(SD) rats of both sexes at daily dose levels of 150 (low dose), 500 (intermediate dose) and 1,500 (high dose) mg/kg/day by subcutaneous route for 28 days. Two additional groups of rats were given either saline (negative control) or L-arginine (vehicle control). Doses were equally divided and administered twice each day with an interval of approximately 5 hours between the 2 doses of a same day. A half of rats in negative control and high dose groups were retained for examination during one-month recovery period. The results obtained are summarized as follows: 1. Upon general observations, it was found that drug-related changes were restricted to the injection sites. Depilation and scab-formation of the injection sites were noted in high dose rats of both sexes and intermediate dose females. No deaths occurred during the study. 2. Slightly depressed body weight gains were observed for high dose males during the latter part of the dosing period. 3. Slightly lower food consumptions were noted for intermediate and high dose males at Week 1. 4. Slightly higher water consumptions were generally detected for high dose rats during the dosing period. 5. Hematological examinations revealed that a slight decrease in the average value of relative lymphocyte counts and a slight increase in the average value of relative segmented neutrophil counts were evident for high dose males. These findings might be attributable to the inflammatory reactions at the injection sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

[Reproductive and developmental toxicity studies on cefepime dihydrochloride administered subcutaneously to rats during the premating, gestation and lactation periods].

Cefepime dihydrochloride (CFPM) was administered subcutaneously daily at doses of 0, 150, 500 and 1,000 mg/kg for 63 days prior to mating and during mating to male Crj: CD (SD) rats and for 14 days prior to mating and during mating, as well as periods of gestation and lactation to female SD rats. Saline and L-arginine hydrochloride (L-arginine) were used as control articles. Daily doses of test and control articles were equally divided and administered twice a day (b.i.d.). The results obtained are summarized as follows: 1. Soft stool was observed for both male and female F0 rats at CFPM 1,000 mg/kg at the first week of administration period. Further, depilation of injection sites was found in 7 males and 12 females at the same dose level. 2. Body weight gains were suppressed in male F0 rats from Day 28 to 63 of administration period at CFPM 1,000 mg/kg. Moreover, food consumption was reduced in F0 female rats during the first week of administration period at all dose levels of CFPM. 3. CFPM failed to affect the reproductive performance in both male and female F0 rats. 4. Kidney weights were increased in both male and female F0 rats and adrenal weights were augmented in male F0 rats at CFPM 1,000 mg/kg. On the other hand, cecal enlargement were observed for F0 dams treated with CFPM. However, these changes were not considered to be unique to this drug, because they have been described with most antibiotics in this species and appears to be results of modifications in gut flora. 5. Prenatal developments in F1 fetuses were not affected by CFPM. 6. CFPM failed to affect delivery status of F0 dams or survival and lactation indices in F1 pups. 7. CFPM did not affect postnatal differentiations, developmental behaviors, learning ability and memory, spontaneous motor activity or emotionality in F1 rats. 8. Body weight gains and food consumption in both male and female F1 rats were not affected by CFPM. 9. CFPM did not alter the organ weights in both male and female F1 rats. 10. There were no significant differences between drug treated animals and controls regarding the reproductive performance and delivery status of F1 rats. 11. Influences on survival indices, body weights and organ weights were not apparently observed for F2 pups even at CFPM 1,000 mg/kg. Based on the reproductive and developmental indices, the no-effect dose level of CFPM under the present experimental condition was estimated to be 1,000 mg/kg/day against dams (F0) and their offspring (F1).

Animals↗
PubMed1991

Portal-systemic encephalopathy: presence of basal ganglia lesions with high signal intensity on MR images.

Sixteen patients with cirrhosis of the liver underwent cranial magnetic resonance (MR) imaging and transarterial portography to evaluate the relationship between basal ganglia lesions and portal-systemic collateral vessels. No neuropsychiatric disturbance was observed in any of the patients at the time of the MR examination, but four patients with portal-systemic encephalopathy were included in the study. Basal ganglia lesions, characterized by increased signal intensity on T1-weighted MR images, were observed in nine of the 16 patients, including the four with portal-systemic encephalopathy. These nine patients had large portal-systemic collateral vessels that were more than 10 mm in diameter. These collateral vessels were receiving blood from the superior mesenteric vein (SMV) in all nine patients. The lesions involved the globus pallidus and portions of internal capsules in a bilateral and symmetric fashion and did not exhibit mass effect. The authors conclude that there may be a significant relationship between high-intensity basal ganglia lesions and large portal-systemic collateral vessels receiving blood from the SMV.

Aged↗
PubMed1991

Immunocytochemical localization of synaptophysin on the smooth-surfaced tubular membranes present in nerve terminal and preterminal areas in the rat cerebellar cortex.

The distribution of synaptophysin, a major protein of the synaptic vesicle membrane, was immunocytochemically examined in the rat cerebellar cortex. A monoclonal antibody against synaptophysin recognized the epitope to be present in the presynaptic membranous structures including synaptic vesicles, presynaptic membrane, coated vesicles, and vacuoles of endocytotic origin. In the nerve terminal as well as preterminal areas, the antibody labeled the smooth-surfaced tubular membranes which were located in the relatively interior parts of these areas and consistent in size and appearance with the short tubules comprising the thinner parts of the axonal reticulum. However, the antibody did not stain the short tubular membranes, though similar in appearance to the above, which existed right below the axolemma in the preterminal and nerve terminal areas. The results are discussed with special reference to the precursor membrane compartments of synaptic vesicles.

Animals↗
PubMed1991

[Clinico-experimental analysis of backgrounds of the severe surgical infections].

The purpose of this study was to analyse the clinical course of 410 patients of severe surgical infections (primary 251, postoperative 159) during recent 5 years and to evaluate the important background factors which make these patients serious. As a result, the following patients such as, (1) who have refractory primary infections, for example malignant lymphoma, severe pancreatitis etc. (2) whose infectious foci were uncontrolled. (3) who had finally complicated a septic MOF or DIC, seemed to be especially critical even though recent advanced surgical therapy. To improve these severe conditions, we believe to need a renewed approach like so called "multi-disciplinary therapy", additionally with both conventional antibiotics administration and drainage for infectious foci. Several methods such as, (1) rational nutrition management using indirect calorimetry. (2) plasma exchange for removing toxic substances such as bacterial toxins, chemical mediators etc, from circulating blood. (3) pharmacological block of these toxic substances, were shown. In terms of the harmful chemical mediators, we supposed that both PAF (platelet activating factor) and oxygen free radical were extremely important in septic conditions from previous clinico-experimental studies. Therefore the effects of those pharmacological blockers such as PAF antagonists, SOD, protease inhibitor in experimental endotoxin shock were discussed in detail.

Animals↗
PubMed1990

[Acute toxicity study of buspirone hydrochloride in mice, rats and dogs].

Buspirone hydrochloride (abbr. to BH), an anxiolytic drug, was examined for its intravenous, subcutaneous or oral acute toxicity using Crj: CD-1 (ICR) mice, Crj: CD (Sprague-Dawley) rats and beagle dogs of both sexes. The results obtained were summarized as follows: 1. Drug-related toxic signs included decreased activity and convulsions accompanied with salivation and opisthotonus in mice and rats treated with BH regardless of administration routes, and tremors and clonic convulsions accompanied with salivation in dogs treated with BH orally. 2. Pathological examinations revealed distention of the stomach in dead rats treated with BH orally, and hypersecretion of gastric juice and alterations (viz. edema, necrosis and petechia) on the superficial mucous membrane in the gastropyloric region in dead dogs treated with BH orally. 3. The cause of death was considered to be due to respiratory insufficiency in every species of animals examined. 4. LD50 values (mg/kg) were as follows: [table: see text] 5. No sex differences were observed in every species of animals regardless of administration routes on the basis of toxicological parameters examined.

Administration, Oral↗
PubMed1990

[Reproductive and developmental toxicity studies of buspirone hydrochloride (I)--Oral administration to rats during the period of fetal organogenesis].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at the same dose level. 2. Liver weights were increased in F0 dams at term at buspirone 12 mg/kg and higher. Besides, brain, pituitary, adrenal and ovarian weights were increased in F0 dams at term at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the inhibition of fetal growth followed by the lowered values in fetal weights, crown-rump distances and tail lengths. Furthermore, the elevated incidence of skeletal abnormalities such as nodular and wavy ribs and unossified 5th and 6th sternum , as well as retarded ossification of cervical vertebrae, forelimbs and hindlimbs were also noted in this dose level. Also, the retarded ossification was observed at 12 mg/kg. 4. Buspirone failed to affect the parturition of F0 dams. 5. Buspirone did not function the viability of newborns (F1), and postnatal differentiations, learning ability, motility, motor activity or emotional development in F1 animals. 6. Body weight gains were depressed in female F1 rats from 4 to 9 weeks of age and food consumption was decreased in male F1 rats from 6 to 8 weeks of age at buspirone 75 mg/kg. 7. Buspirone 75 mg/kg produced suppressions of brain weights at 10 weeks of age in male and female F1 rats and lung weights at weaning in male F1 rats. Spleen weights were increased in female F1 rats at 10 weeks of age at the same dose level. However, buspirone failed to affect their reproductive ability. 8. F2 neonates derived from F1 rats whose dams had ever received buspirone during the period of fetal organogenesis showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗
PubMed1990

[Reproductive and developmental toxicity studies of buspirone hydrochloride (II)--Oral administration to rats during perinatal and lactation periods].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 17 of gestation through day 20 of postpartum at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at buspirone 12 mg/kg and higher. 2. Brain and adrenal weights were increased in F0 dams at buspirone 12 mg/kg and higher. Besides, lung and pituitary weights were augmented in F0 dams at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the increased number of stillbirths in F1 neonates. 4. Buspirone 75 mg/kg lowered the viability of newborns (F1) on postnatal day 3 and prolonged the days required for pinnae detachment, presence of abdominal hair and eye opening in offspring (F1), but failed to function their learning ability, motility, motor activity or emotional development. 5. Body weight gains were depressed in both male and female F1 rats at buspirone 12 mg/kg and higher. Food consumption was also decreased in both sexes at the same dose levels. 6. Heart weights were decreased in female F1 rats after mating at buspirone 12 mg/kg and higher. Further, buspirone 75 mg/kg brought a suppression of brain weights at 10 weeks of age in male and female F1 rats, but failed to affect their reproductive ability. 7. F2 neonates derived from F1 rats whose dams had ever received buspirone during the perinatal and lactation periods showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗
PubMed1990

Proximal gastric vagotomy with carbon dioxide laser: experimental studies in animals.

Proximal gastric vagotomy has been widely used as a surgical treatment for peptic ulcer disease. However, it is technically complex and time-consuming. Moreover, it may cause circulatory problems in the gastric mucosa. We have reported a new method of blood flow-preserving vagotomy with a carbon dioxide laser (CO2 laser vagotomy) developed in our laboratory. To assess its efficacy, we used cysteamine-induced ulcer and measured gastric mucosal blood flow in rats. The incidence of cysteamine-induced ulcer formation was reduced significantly in the group that underwent CO2 laser vagotomy compared with a group treated with proximal gastric vagotomy. Gastric mucosal blood flow was significantly better in the CO2 laser vagotomy group. Long-term follow-up of acid reduction was evaluated in dogs by the pentagastrin-stimulation test. Acid reduction in dogs was satisfactory during the 12 months of this study. CO2 laser vagotomy is a new, easy, time-saving, and circulatory-preserving technique for peptic ulcer disease.

Animals↗
PubMed1990

[CT and MR imaging in the evaluation and staging of lung cancer].

Cancer of the lung is one of the most frustrating yet important challenges facing medicine today. Despite screening programs and education of the public concerning the established link of lung cancer and cigarette smoking, the overall incidence of lung cancer continues to rise. Improved imaging has led to more accurate staging. Expanded treatment has yielded improving survivals of certain specific tumors. Accurate diagnosis and staging of lung cancer is important in detecting therapy and prognosis. Computed tomography (CT) has been established as an important component of the staging process. More recently, applications of magnetic resonance imaging (MRI) are ideally suited to evaluate tumor extent and nodal disease. We reviewed the uses and limitation of CT and MRI. Compared with CT, the relatively low signal in the lung limits the detection of pulmonary nodules and other lung parenchymal diseases, and noise due to motion has been a frequent and significant problem in thoracic MRI. Because of its superior spatial resolution and ability to detect calcification, CT is better than MRI for the detection and evaluation of lung nodules and mediastinal adenopathy when assessing lung cancer. For the detection of mediastinal invasion or lymph node metastases, CT and MRI generally provide similar information. However, volume averaging problems, which may occur on trasaxial CT, can be avoided or clarified using MRI, and nodes can sometimes be more clearly distinguished from vessels using this technique. In the diagnosis of hilar masses or lymphadenopathy, CT and MR provide similar information in the majority of cases, but occasionally MR may more clearly indicate the presence or absence of a mass. Because of superb vascular imaging capability (without the need for exogenous contrast agents), exquisite soft tissue contrast, the ability to image the chest directly in multiple planes, and the potential to characterize certain tissues, MRI appears to be superior to CT in defining the extent of chest-wall invasion. In general, CT is superior to MRI as an all-around tool for imaging the wide range of thoracic abnormalities that can be present in patients with lung cancer. Limited availability, and longer examination time of MRI compared with CT has restricted the use of thoracic MRI. If MRI is used selectively as a secondary imaging study to answer specific questions raised or unanswered by CT, its value can be optimized.

Adenocarcinoma↗
PubMed1990

[Single dose oral toxicity study of BMY-28100 in juvenile rats and dogs].

In order to investigate the single dose oral toxicity of BMY-28100 in juvenile animals, the drug was administered in single doses to 4-day-old and 14-day-old Crj: CD (SD) rats of both sexes at a dose of 2,000 mg/kg, and to 4-week-old beagle dogs of both sexes at doses of 500, 1,000 and 2,000 mg/kg by oral route. The results obtained are summarized as follows: 1. In rats, decreases of the body weight gain were observed for male and female rats treated with the drug on postnatal day 4 through 5 days and 3 days after dosing, respectively. There were no apparent drug-related toxic signs. No deaths occurred during the observation period. Enlargement of the cecum was found in a few rats of both sexes administered the drug on postnatal day 4 or 14. 2. In dogs, watery-mucous diarrhea observed at 2 to 3 hours after dosing in all dose groups was not dose-related. This finding lasted in some dogs till 4 days after dosing. An increased incidence of emesis was induced in all males at 2,000 mg/kg and all females of all dose groups except one female at 2,000 mg/kg. Body weights increased normally for all dogs, but one male at 1,000 mg/kg showed a transient decrease in food consumption. No drug-related histopathological changes were found. Based upon these results, BMY-28100 at 2,000 mg/kg induced no apparent toxic changes in the present experimental conditions. Therefore, the single dose oral toxicity of the drug in juvenile animals appeared to be very slight and generally similar to that in adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

[Four-week repeated dose oral toxicity study of BMY-28100 in juvenile rats].

In order to investigate the repeated dose oral toxicity of BMY-28100 in juvenile rats, the drug was administered orally to 4-day-old Crj: CD(SD) rats of both sexes at daily doses of 250, 750 and 1,500 mg/kg for 4 weeks. The results obtained are summarized as follows: 1. Soiling around the anus apparently correlated to soft stool or diarrhea was observed at 750 and 1,500 mg/kg and the incidence appeared to be dose-related. Three deaths including 1 death due to cannibalization occurred at 750 and 1,500 mg/kg, but they were considered to have been caused by misadministration. 2. Slightly depressed body weight gains were noted in the 750 and 1,500 mg/kg dose groups during early dosing period. 3. Slightly increased averages of food and water consumption observed predominantly in the 1,500 mg/kg dose group at later dosing period and the recovery period were considered as incidental and unrelated to the treatment. 4. Though average values of some blood chemical parameters were slightly suppressed or elevated compared with those of controls at the completion of the dosing and recovery periods, these differences appeared to be generally within normal ranges and to be irrelevant to the drug treatment. No definitive drug-related changes were detected in hematological examinations and urinalyses. 5. The average absolute and/or relative organ weights of the brain, thymus, lungs and liver from male rats in the 1,500 mg/kg dose group were lower than those of the corresponding organs from controls. However, these findings were not considered to be toxicologically significant because no corroborative changes were detected microscopically. 6. Macroscopic and microscopic examinations demonstrated dilatation of the cecum in a dose-related fashion. This phenomenon has been reported with other antibiotics and appears to be drug-related and reversible caused by an alteration of the gut flora. There were no other microscopic changes that were considered to be related to the administration of the drug. 7. Electron microscopic examination revealed no drug-related changes in the liver and kidneys from rats of the 1,500 mg/kg dose group. Based upon these results, the no-effect dose level of BMY-28100 was estimated to be 250 mg/kg/day for both male and female juvenile rats in the 4-week repeated dose oral toxicity study if the finding of cecum dilatation was not considered.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1990

An easy and safe modified method of endoscopic balloon dilation for postgastrectomy anastomotic stricture.

An easy and safe modified method for endoscopic balloon dilation was performed 24 times for 16 patients who had undergone subtotal gastrectomy without any ensuing complications. The balloon dilator was simply attached to the ultraslender forward-viewing fiberscope just above the flexible portion. The balloon dilator can be easily placed into the stricture by advancing the fiberscope into the duodenum under direct vision. The present technique is particularly useful for the tortuous stricture of B-I anastomosis after a surgical procedure for carcinoma of the stomach, as opposed to using the conventional bougie or previous balloon techniques. This method may also be useful for other kinds of complicated stricture of the upper or lower part of the gastrointestinal tract.

Adult↗
PubMed1989

Substance P immunoreactivity in the vagal nerve of mice.

After horseradish peroxidase was applied to the main trunk of the mouse vagal nerve, anterogradely labeled cells in the vagal ganglia and fibers in the solitary complex, and retrogradely labeled cells in the dorsal motor nucleus and the ambiguous nucleus were observed. Most of the cells in the nodose ganglion were labeled, but only a few cells in the jugular ganglion were labeled. Heavily labeled nerve terminals and fibers were found in 3 areas in the solitary nucleus: i.e., the lateral half of the medial nucleus, the ventrolateral nucleus, and the commissural nucleus. There was only weak labeling in the dorsolateral nucleus, ventral nucleus, and intermediate nucleus. Substance P immunoreactive neurons in the vagal ganglia were found in the jugular ganglion and the dorsal part of the nodose ganglion, but not in the ventral part of the nodose ganglion. Substance P immunoreactivity in the solitary nucleus was moderate in the commissural nucleus and the intermediate nucleus, but was lacking or very weak in the lateral half of the medial nucleus, ventral nucleus, dorsolateral nucleus, and ventrolateral nucleus. We conclude that most substance P containing fibers in the main trunk of the vagal nerve project centrally to the commissural nucleus and peripherally to some of the thoracic viscera.

Animals↗
PubMed1989

Toxicological study of etoposide (VP-16) in rats with special emphasis on testicular alteration.

Etoposide (VP-16) was administered intravenously to rats for 3 months. Testicular alterations induced by etoposide (VP-16) at 0.5 and 1.5 mg/kg/d were thoroughly assessed with light and electron microscopy. Light microscopic analyses demonstrated disorganization and moderate depletion of germinal epithelium at 0.5 mg/kg/d, and complete germ cell depopulation at 1.5 mg/kg/d. Ultrastructural studies revealed degenerative changes in spermatogonia and early spermatocytes, appearance of large spermatids with multi-nuclei, and nuclear alterations and cytoplasmic vacuolation in Sertoli cells. Moreover, the basement membrane of the seminiferous tubule showed wavy lamellae and infolding to the seminiferous epithelium. Leydig cells manifested no significant ultrastructural changes. The small intestine and ovaries were not affected. The 2-month recovery period following cessation of treatment led to the recovery of these testicular alterations at the 0.5 mg/kg/d dose, but not at the 1.5 mg/kg/d dose. Judging from these results, etoposide (VP-16) induced damage primarily in spermatogenic cells, followed by Sertoli cells and the basement membrane in seminiferous tubules. Though reversible at intermediate doses, higher doses of VP-16 might produce irreversible testicular lesions.

Animals↗
PubMed1989

[The role of oxygen free radical and free radical scavenger in septic and hemorrhagic shock].

The roles of oxygen free radical (O2-), lipoperoxide (LPO) and free radical scavenger were clinically and experimentally studied in septic and hemorrhagic shock. The reduction of hepatic tissue blood flow (TBF) were equalized in two groups (40-55% of normal level) and rats were subdivided into 3 groups: untreated, normal saline (NS) continuous IV and superoxide dismutase: SOD + catalase (S/c) continuous IV as free radical scavenger. The change of TBF, destruction of mitochondrial structure and elevation of LPO were prevented by S/c in Et shock. No significant effect by S/c was observed in hemorrhagic shock. The neutrophil derived O2- was markedly elevated in Et shock animals as well as septic shock patients but no significant change was noted in hemorrhagic shock animals or non septic shock patient. SOD and catalase were effective for neutrophil derived O2- in septic shock whereas little beneficial effect was noted in hemorrhagic or non septic shock.

Animals↗