Search PubMed⌕ Search

Biomedical subjects

T Sakaguchi

Publications and source records attributed to T Sakaguchi.

At least 271 records · Page 15Linked to original sources
PubMed1988

Effects of pentobarbital and cyproheptadine on brain ischemia induced by bilateral occlusions of carotid arteries and vertebral arteries of second cervical vertebra in rats.

The bilateral hemispheric ischemia in rats was induced by the occlusion of bilateral common carotid arteries after permanent electrocauterization of bilateral vertebral arteries at the level of the second cervical vertebra. In ischemic rats, (a) electroencephalograms became flat immediately after occlusion of carotid arteries, and (b) mortalities reached maximum levels at day 3 after recirculation. These results suggested that a constant level of cerebral ischemia was produced in this rat model. Pentobarbital markedly inhibited the mortality in these ischemic rats, whereas cyproheptadine did not.

Animals↗
PubMed1988

[Acute toxicity study of cefodizime sodium].

Acute toxicity of cefodizime sodium (THR-221) was examined in mice of both sexes, rats of both sexes (including 5-day-old young), and male dogs. The LD50 values of THR-221 (mg/kg) were as follows: (1) mice: intravenous, 7200 for males and 5000 for females; intraperitoneal, 10500 for males and 11000 for females; subcutaneous, 17500 for males and 16500 for females; and oral, 28000 for males and 29000 for females. (2) rats (adult): intravenous, 7000 for males and 8200 for females; intraperitoneal, 9500 for males and 8800 for females; subcutaneous, 17000 for males and 15500 for females; oral, more than 20000 for both sexes; and intramuscular, more than 3200 for both sexes. (3) 5-day-old rats: subcutaneous, 5278 for males and 5314 for females. (4) male dogs: intravenous, more than 5000. Major changes in general conditions observed in mice and rats were decreased spontaneous activity, lying prone, respiratory changes, staggering gait, clonic or clonic-tonic convulsions, and cyanosis, and in the animals dosed orally, diarrhea or salivation was also noted. The changes in 5-day-old rats were respiratory changes, agony, loss of reflex to an external stimulus, and congestion at the injection site, and those in dogs were vomiting, dryness of the nose, and soft or mucous stools. Autopsies on the mice and rats which died revealed hemorrhage on the brain surface. In addition, the following were seen: intraperitoneal retention of fluid and dark red spots on the abdominal wall (i.p.), subcutaneous retention of fluid or jellylike material and hemorrhage at the injection site (s.c.), and retention of fluid and dark red spots on the mucosa in the digestive tract (mice p.o.). In 5-day-old rats which died, the subcutaneous tissue at the injection site showed hemorrhage macroscopically and inflammatory changes microscopically. Hematological and blood chemical tests performed in dogs showed an increase in white blood cells and changes suggesting anemia, increases in GOT, LDH and ALP activities, and slight changes in urea nitrogen and inorganic phosphorus. In one animal given a low dose of 2500 mg/kg, an increase in GPT activity was also seen. However, these changes were all transient. Microscopic findings in dogs were slight inflammatory changes in the subcutaneous tissue around the injection site.

Administration, Oral↗
PubMed1988

[One-month subacute intravenous toxicity study of cefodizime sodium in rats].

One-month subacute intravenous toxicity study of cefodizime sodium (THR-221) in rats was carried out with dose levels of 2000, 1000 and 500 mg/kg/day. Sixteen males and 16 females were used per group (including the control group). THR-221 caused neither death nor change in general conditions at any dose level throughout the study, except that decreased spontaneous activity appeared only transiently in a part of the animals given 2000 mg/kg/day. Increases in water intake were observed in all compound groups, and transient decreases in food consumption were seen at an early stage of the administration period. However, the compound did not affect the body weight at any dose level. In urinalysis, the urine sediments in all THR-221 groups contained an increased number of epithelial cells as compared with the controls. At autopsy, dilation of the cecum was observed in all THR-221 groups, and in a part of the rats with this change, red spots or reddening of the serous membrane of the organ also appeared. Light microscopy revealed brown granules in the epithelium of renal tubules in all compound groups (with dose-dependent incidences) and congestion or hemorrhage in the cecum in some compound-treated animals. Electron microscopy on the kidney showed small bodies (considered to be lysosomes) in the tubular epithelium in all compound groups. No other changes related to THR-221 were observed. From the present results that no marked toxic signs were seen at any dose level, the toxicologically non-effective dose of THR-221 for rats of both sexes is considered to be more than 2000 mg/kg/day.

Animals↗
PubMed1988

[Effect of cefodizime sodium on the kidney function in male rabbits--single and 7-day repeated intravenous administration].

Renal effects of cefodizime sodium (THR-221) administered by the intravenous route singly and for 7 consecutive days to male rabbits, were compared with those of cefazolin sodium (CEZ) and cephalothin sodium (CET). Four animals were used in each group including control groups. In the single-dose study, THR-221 (600 and 1800 mg/kg) and CET (1800 mg/kg) caused no nephrotoxic effects. In the CEZ groups (600 and 1800 mg/kg), findings indicative of the decreased renal function were obtained: serum urea nitrogen and creatinine levels increased over the control values, and phenolsulfonphthalein (PSP) retention test showed a delay in PSP excretion from the blood. In addition, the white surface of the kidney was macroscopically observed, and microscopic examination revealed renal proximal tubular changes such as necrosis, hyaline cast and calcification, suggesting renal disorders. The repeated-dose study also showed similar results to those described above. Administration of THR-221 (200 and 600 mg/kg/day) and CET (600 mg/kg/day) caused no effects on the kidney. In the CEZ groups (200 and 600 mg/kg/day), serum chemical and PSP test results suggested the decreased renal function, and macroscopic and microscopic findings included organic changes in the kidney. These results suggest that under the conditions tested THR-221 dose not elicit signs of nephrotoxicity in contrast to CEZ, and behaves almost equally to CET.

Animals↗
PubMed1988

[Six-month chronic subcutaneous toxicity study of cefodizime sodium in rats].

Six-month chronic subcutaneous toxicity study of cefodizime sodium (THR-221) in rats was carried out with dose levels of 3000, 1000, 300 and 100 mg/kg/day. The systemic change observed was slightly decreased spontaneous activity, which appeared only in a very few animals. At the injection site of the animals at 1000 and 3000 mg/kg/day, various cutaneous changes (subcutaneous retention of fluid, incrustation, loss of hair and perforation) were observed. The body weight gains of the males at 1000 and 3000 mg/kg/day were depressed from 1 month of administration onward, but the food consumption was not affected in any group. The water intakes at 1000 and 3000 mg/kg/day were increased. Hematological findings were signs of anemia, a slight decrease in red blood cell count or increases in platelet and/or reticulocyte counts in all THR-221 groups. At 3000 mg/kg/day, increases in white blood cell and neutrophil counts and a decrease in lymphocyte count were also observed. Plasma chemistry revealed decreases in total protein amount and, albumin (A) or globulin (G) amounts, and a decrease or increase in A/G ratio in all compound groups. Autopsy revealed dilation of the cecum and hematoma, dark red spots and yellowish brown spots in the subcutaneous tissue at the injection site in all THR-221 groups. Hypertrophy of the spleen was also noted at 300-3000 mg/kg/day. Changes in organ weights were a decrease in liver weight in all compound groups and an increase in spleen weight at 3000 mg/kg/day. Microscopically, the following were observed: brown granules or hyaline droplets in the epithelium of renal tubules; hemorrhage and inflammatory changes in the subcutaneous tissue at the injection site; and an increased number of lymphocytes or granulocytes in the spleen and bone marrow. Urinalysis and ocular and auditory tests showed no changes related to THR-221. From the present results, the toxicologically non-effective doses of THR-221 are considered to be 300 mg/kg/day for male rats and more than 1000 mg/kg/day for female rats.

Anemia↗
PubMed1988

[Malfunction of gene expression as a possible cause of delayed neuronal death].

To clarify a possible cause of delayed neuronal death, synthesis of protein and ribonucleic acid (RNA) following transient forebrain ischemia was evaluated autoradiographically. Mongolian gerbils were subjected to transient forebrain ischemia for 5 minutes by occluding bilateral common carotid arteries. They were used for autoradiographic study at 1, 2, and 5 days after ischemia. Tracer dose of 14C-valine or 14C-uridine was injected intravenously, and animals were sacrificed 45 minutes thereafter. Brains were frozen and thin sliced for macroautoradiography. After the first autoradiogram was obtained, tissue sections were incubated in cold 5% trichloroacetic acid for 1 hour, dried and again used for autoradiogram. With this preparation we could differentiate the tracer incorporated into protein or RNA fraction from the total tissue radioactivity. In the different set of animals, microautoradiograms of 3H-valine and 3H-uridine was obtained to detect subcellular distribution of synthesized protein or RNA. At 1 day after ischemia, protein synthesis in the CA 1 region of the hippocampus was reduced by 57% of the sham control, but RNA synthesis was not reduced quantitatively. Microautoradiogram of 3H-uridine however, indicated that silver grains in the cytoplasms of the CA 1 pyramidal cells were much reduced as compared to sham controls, though the amount of silver grains in the nucleus was the same as sham controls. Therefore, synthesized RNA in the nucleus was not transported to the cytoplasm. At 2 days after ischemia, protein and RNA synthesis was preserved to the same level as sham controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Sympathetic activity and food intake of rats with ventromedial hypothalamic lesions.

Following ventromedial hypothalamic lesions, food intake increased from 60 to slightly more than 77 kcal/day during the first 6 days. Body weight increased and sympathetic activity, as measured by the electrical firing rate of efferent nerves to interscapular brown adipose tissue, decreased significantly. During a 6-day period of intragastric overfeeding in which animals with hypothalamic lesions received 60 kcal for the first day and 80 kcal for the remaining 5 days, the VMH-lesioned animals gained significantly more weight than the intact, sham-lesioned controls. This difference in weight gain was paralleled by the increased weight of liver and white adipose tissue. The lesioned animals showed a highly significant reduction in sympathetic activity compared to the normal or slightly increased values observed in the sham-lesioned animals. These studies are consistent with the hypothesis that food-induced increases in sympathetic activity are modulated by the ventromedial hypothalamus.

Animals↗
PubMed1988

[In vitro synergy between cefotaxime and its main metabolite, desacetylcefotaxime].

In vitro synergistic interaction between cefotaxime (CTX) and its main metabolite, desacetyl-cefotaxime (DCTX), against 7 species of clinical isolates (23-27 strains per species) was examined. Complete or partial synergy was noted with a 1:1 combination of CTX and DCTX against 22-78% of the Bacteroides fragilis, Staphylococcus aureus, Citrobacter freundii, Pseudomonas cepacia and Enterobacter cloacae isolates examined. Antagonistic effects of the drugs appeared against 11% of Proteus vulgaris and 4% of Serratia marcescens. When combined at various ratios by the checkerboard method and tested against B. fragilis, CTX and DCTX were found to act synergistically, and no antagonism occurred. The combined use of CTX and DCTX exhibited strong bactericidal activity against B. fragilis and inhibited bacterial regrowth. An experiment with concentrations of CTX and DCTX simulating human serum levels after intravenous administration also showed that the coexistence of DCTX augmented bactericidal activity of CTX against B. fragilis and brought inhibitory effects on bacterial regrowth. It is presumed from the present results that clinically applied CTX would have more potent effects than expected from in vitro sensitivity test data.

Bacteria↗
PubMed1988

[Two cases of strangulated urethral prolapse].

This is a report of two cases of strangulated urethral prolapse we recently experienced. One patient, a 70-year-old woman, was admitted to our hospital because of dysuria, painful urination, genital mass (phi 3.0 cm) and bleeding. The other patient, 54 years old, visited our department complaining of pain on urination, and genital mass (phi 2.0 cm) and bleeding. Surgical excision was performed for these prolapsed urethra, and in pathological findings, vascular dilation, blood congestion and partial thromboformation were recognized. Their postoperative course was uneventful without recurrence or abnormal urination. Urethral prolapse is defined as the circular eversion of the urethral mucosa through the external meatus. This condition is a relatively uncommon lesion in the literature, but is a common clinical entity in postmenopausal women and prepubertal girls. Most of the urethral prolapses are small and asymptomatic, but if the prolapsed urethra is large, the mass becomes strangulated, and urinary symptoms, pain and bleeding are present. For the treatment of the urethral prolapse, surgical excision has been widely practiced and is successful.

Aged↗
PubMed1987

Lateral hypothalamic lesions and activity of the sympathetic nervous system.

The firing rate of efferent sympathetic nerves to brown adipose tissue was measured on 18 h or 18 d following lateral hypothalamic lesions (LH). Eighteen hours following acute lateral hypothalamic lesions, sympathetic firing rate was significantly increased. Following chronic LH lesions there was a decrease in food intake and a fall in body weight which had stabilized by four days. Eleven days after surgery a group of control animals were food restricted and subsequently pair fed twice daily to maintain a body weight comparable to that of the LH lesioned animals. Food intake was lower in the pair-gained animals on all but one day of the experiment. When studied 18 days following LH lesions, sympathetic firing rates were significantly higher than in either the ad lib or pair-fed controls. Sympathetic firing rate in pair fed rats, on the other hand, was significantly lower than in the sham lesioned rats. These data are consistent with the hypothesis that the LH lesion removes an inhibitory control over sympathetic firing rate both acutely and in chronically lesioned animals and that this increased sympathetic firing rate may play an important role in the maintenance of a lower body weight.

Adipose Tissue, Brown↗
PubMed1987

Inhibition of gastric acid secretion evoked by activation of the hypothalamic paraventricular nucleus.

Electrical stimulation of the paraventricular nucleus depressed the gastric acid output of adrenalectomized male rats of which gastric acid output had been induced by insulin hypoglycemia. Electrical stimulation of the pituitary stalk produced a similar secretory response, but the response was abolished by bilateral lesion of the paraventricular nucleus. These findings allow us to speculate that the paraventricular nucleus is capable of modulating gastric acid secretion, and suggest that the nucleus has a neural connection between the neurohypophysis and the system relevant to gastric acid secretion.

Adrenalectomy↗
PubMed1987

Some in vivo electrophysiological properties of locus coeruleus neurones in fetal rats.

The electrical activity of locus coeruleus (LC) neurones was recorded extracellularly in fetal rats still in contact with their dams by an intact umbilical cord. Pregnant rats, at gestation days 18 to 22, were anesthetized with urethane. The head of a fetal rat was exposed from the uterus and fixed to a conventional stereotaxic apparatus by means of a simple device. The location of the LC in the fetal rats was determined by the appearance of field responses evoked by stimulation of the dorsal noradrenergic bundle. Antidromic spikes of single LC neurones were evoked superimposed upon the field responses. The mean conduction velocity of LC axons was calculated to be 0.25 m/s. Some fetal LC units were activated antidromically by stimulation of the frontal cortex (FC) with latencies ranging from 21 to 67 ms, values nearly the same as those obtained in neonates and adults. Although the majority of fetal LC neurones recorded were not spontaneously active, a small number of them revealed epochs of sporadic firing, which appeared to occur synchronously in many or all of the LC neurones. Sensory stimuli (e.g., air puffs to the skin) were effective in activating LC neurones. These results indicate that LC neurones have already developed projections to the FC, and are functionally active in prenatal periods.

Animals↗
PubMed1987

D-glucose anomers in the nucleus of the tractus solitarius can reduce gastric acid secretion of rats.

The infusion of alpha-, beta-, or equilibrated (alpha:36%, beta:64%) D-glucose solution in or in the vicinity of the nucleus of the tractus solitarius decreased gastric acid output caused by insulin in rats with bilateral adrenalectomy. This effect was not reproduced after vagotomy at the cervical level. Of the three forms of D-glucose solution, the effect of beta-D-glucose was greatest. The infusion of equitonic NaCl, however, produced no change in the acid output. These results suggest that blood beta-D-glucose may predominantly activate a brain mechanism which through the vagus nerve modulates gastric acid secretion at the medullary level.

Animals↗
PubMed1987

Changes in water intake following pharyngolaryngeal deafferentation in the rat.

The role of afferent information arising from the pharyngolaryngeal region in the regulation of water intake was evaluated in rats. The animals received picric application to the mucosa of either the pharyngolaryngeal or the hard palate region. Water intake of the pharyngolaryngeal treated animals was reduced significantly, while no reduction in water intake was shown in the control and hard palate treated animals.

Animals↗