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Biomedical subjects

H Hayasaka

Publications and source records attributed to H Hayasaka.

At least 55 records · Page 3Linked to original sources
PubMed1985

[Preventive effect of fosfomycin on the renal toxicity of cisplatin].

Cisplatin caused toxic effects in adult male rats, such as renal disturbance, decrease of platelet and WBC, increase of RBC, elevation of GPT and GOT activity, decrease of plasma protein and albumin, loss of body weight gain and lethal effect when treated intravenously with 1 mg/kg/day of cisplatin for 12 days. Fosfomycin (FOM) exerted preventive effects on the renal disturbance, the changes in blood cells and plasma protein and the lethal effect induced by cisplatin when treated with a combination of FOM and cisplatin. However, FOM did not prevent the cisplatin-induced effects on GPT and GOT activity and body weight gain. These results suggest that FOM prevents the cisplatin-induced disturbance of renal and hematopoietic function but does not the cisplatin-induced hepatic disturbance.

Alanine Transaminase↗
PubMed1985

[Studies of plasma gastrointestinal glucagon after LD100 E. coli infusion].

We postulate that high plasma concentrations of gastrointestinal-derived glucagon may be used to identify severe sepsis and correlate with the effect of therapy. Eighteen adult dogs were separated into three groups: Group I-LD100 E. coli alone, group II-LD100 E. coli + tobramycin (TOB) and group III-LD100 E. coli + TOB + methylprednisolone sodium succinate (MPSS). E. coli was infused intravenously for one hour. Each animal was monitored for six hours and observed for a 7-day recovery period. Percent survival (greater than 7 days): I = 0%, II = 17% and III = 83%. Concentrations of gastrointestinal glucagon were 3417 pg/ml in group I, 5167 pg/ml in group II and 1081 pg/ml in group III at six hours after E. coli infusion. In group III these concentration returned to control values by 7 days after E. coli infusion. Increases in gastrointestinal glucagon were more readily induced by E. coli infusion than those of pancreatic glucagon. Gastrointestinal glucagon concentrations were related to the severity of E. coli induced shock and the beneficial effects of MPSS/TOB therapy. Therefore, plasma gastrointestinal glucagon concentrations may be useful in recognizing the presence of severe sepsis and directly related to the beneficial effects of therapy.

Animals↗
PubMed1985

[Alanine metabolism in the skeletal muscle and plasma in endotoxemia].

Utilizing a 24 hour fasting rabbit (N = 30), we measured free amino acids in the femoral artery and vein and the quadriceps femoris muscle. The endotoxin E. coli 026, 3.0mg/kg (LD100) was injected and free amino acid plasma levels were monitored for 6 hours. Changes in free amino acid plasma levels were variable and marked after endotoxin injection. By 360 min. after endotoxin injection: (a) the rate of increase in free amino acid levels in the femoral artery was 366 mumole/l of alanine, 162 mumole/l of glycine and 85 mumole/l of proline; (b) the rate of increase in free amino acid of the quadriceps femoris muscle was 1376 nmole/g of alanine, 156 nmole/g of glycine and 109 nmole/g of serine; and (c) the femoral arteriovenous difference was -225 nmole/l of alanine, -118 nmole/l of glycine and -77nmole/l of proline. Within 10 min. after endotoxin injection, alanine concentration was higher in the femoral vein. This change in concentration became significant by 60 min. The results show the following: Skeletal muscle appears to be an important source of amino acids for amino acid metabolism during endotoxemia, especially plasma alanine which is closely connected with alanine levels in skeletal muscle.

Alanine↗
PubMed1984

Discriminative structural analysis using pattern recognition techniques in the structure-taste problem of perillartines.

Pattern recognition techniques have been applied to the study of structure-taste correlations for perillartine derivatives. The structure of each compound was described by hydrophobicity (log P), logarithm of water solubility (log S), and topological descriptors relating to some positions which were assigned by superposing each compound on a "template" structure. The fragment molecular connectivities were calculated as the topological descriptors. The discriminant functions between the sweet and bitter taste classes were computed by the use of the simplex optimization technique, which correctly recognized most of the compounds under investigation. It was found that the hydrophobicity and one or two topological descriptors concerned with a specific part of the molecules contributed significantly to the discrimination. The discriminant function obtained correctly classified seven of nine compounds (which were not involved in the data set for developing the function) into the taste class to which they belonged.

Cyclohexenes↗
PubMed1984

Effects of anti-shock agents on the re-opened superior mesenteric artery flow.

We investigated intestinal blood circulation after re-opening of a fixed-time occlusion of the superior mesenteric artery (SMA) in rabbits. The SMA root was occluded for 60 minutes, after which blood pressure and SMA flow were monitored for one hundred minutes under the administration with fluid infusion of three anti-shock agents; dopamine, phenoxybenzamine and dexamethasone. The intestinal wall tissue circulation in parallel with SMA flow was also studied. Blood pressure and SMA flow decreased after release of the SMA occlusion (SMAO), as compared those during pre-occlusive time in the control group. Fluid infusion alone did not improve blood pressure and SMA flow. Pre-administration of dexamethasone with fluid infusion improved blood pressure, SMA flow and the survival rate. Phenoxybenzamine with fluid infusion improved SMA flow, despite the low blood pressure. Circulatory damage to the intestinal wall was more extensive than that to SMA flow. These findings suggest that the severity and mortality of SMAO shock was not caused by plasma loss but rather by toxic metabolites and endotoxin from the ischemic intestine.

Animals↗
PubMed1984

[Hepatic glycolytic intermediates and glucoregulatory enzymes in septic shock due to peritonitis: experimental study in rats].

The hypoglycemia in septic shock due to peritonitis indicates deranged carbohydrate metabolism. To determine if this metabolic failure could be attributed to changes of glucoregulatory enzymes and glycolytic intermediates, activities and changes of these substances in septic shock have been studied in rats. Liver tissue was sampled 5 hours after induction of peritonitis by cecal incision in fasted male rats. Hepatic glycolytic intermediates were assayed by UV-spectrophotometry. Peritonitis caused 33% decrease in glucose-6-phosphate (G6P), a 2.5 fold increase in fructose-1,6-diphosphate (FDP) and a 3.5 fold increase in lactate. Phosphoenolpyruvate (PEP) levels did not show a significant increase in peritonitis. We investigated activities of glucose-6-phosphatase (G6Pase), fructose-1,6-diphosphatase (FDPase), phosphofructokinase ( PFKase ) and pyruvate kinase ( PKase ) in mitochondria-free supernatants from rat liver homogenates. Tissue was sampled 5 hours after induction of peritonitis by cecal incision. Assays were conducted at optimal substrate levels at pH 7.4; NADH charges produced by coupled reactions were determined by UV-spectrophotometry. A significant increase of PFKase and PKase specific activity was observed. These changes were consistent with stimulated glycolysis. For gluconeogenesis to achieve maximum efficiency it would be necessary to inhibit PFKase and PKase completely.

Animals↗
PubMed1984

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miokamycin). Part II-2. Subacute toxicity in rabbits.

Miokamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic isolated from a culture broth of Streptomyces mycarofaciens. The objective of this study was to examine toxicological effects in male and female rabbits after repeated oral administration of MOM, non-crystalline solid, for 5 weeks at daily dosages of 400, 800, 1,600 and 3,200 mg/kg. In conclusion, the maximum non-toxic dosage level of MOM, non-crystalline solid, is presumed to be 400 mg/kg in male and female rabbits with p.o. administered once daily for 5 weeks.

Administration, Oral↗
PubMed1984

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-3. Toxicity of metabolites of miocamycin: subacute toxicity of Mb1 in rats.

Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. In the previous study, LD0 values of Mb1 were estimated more than 5,000 mg/kg in male and female rats as Mb1 did not exhibited any lethal toxicity even at the maximum physically applicable dose of 5,000 mg/kg. The object of this study was to examine subacute toxicity in male and female rats after repeated p.o. administration of Mb1 for 5 weeks at a daily dosage of 125, 250, 500 and 1,000 mg/kg. It is concluded that no manifest toxicity was observed in this subacute toxicity study on Mb1 in rats.

Animals↗
PubMed1984

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-6. Toxicity of metabolites of miocamycin: subacute toxicity of Mb2 in rats.

Miocamycin (MOM) is a derivative of midecamycin, a macrolide antibiotic and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. At previous study, the acute and subacute toxicity of Mb1 and acute toxicity of Mb2 were performed that those metabolites did not exhibit any lethal toxicity even at the maximum physically applicable dose. The object of this study was to examine subacute toxicity in male and female rats after repeated p.o. administration of Mb2 for 5 weeks at a daily dosage of 125, 250, 500 and 1,000 mg/kg. It is, therefore, concluded that Mb2 exerted no toxic effects in this subacute toxicity.

Animals↗
PubMed1984

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-9. Toxicity of metabolites of miocamycin: subacute toxicity of Mb6 in rats.

Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. It is also known that LD50 values of Mb6 were 4,150 mg/kg in male mice and 4,000 mg/kg in female mice but LD0 values in male and female rats were estimated more than 5,000 mg/kg. The object of this study was to examine subacute toxicological effects in male and female rats after repeated oral administration of Mb6 for 5 weeks at a daily dosage of 125, 250, 500 and 1,000 mg/kg. It is concluded that no manifest toxicity was observed in this study with Mb6 in male and female rats after oral administration at dosage levels of 125, 250, 500 and 1,000 mg/kg for 5 weeks.

Animals↗
PubMed1984

Toxicological studies on a new macrolide antibiotic, midecamycin acetate (miocamycin). Part IV-12. Toxicity of metabolites of miocamycin: subacute toxicity of Mb12 in rats.

Miocamycin (MOM) is a derivative of midecamycin and is metabolized into 4 main metabolites of Mb1, Mb2, Mb6 and Mb12. In the previous study, LD0 values of Mb12 in male and female rats were estimated more than 5,000 mg/kg. The object of this study was to evaluate subacute toxicity in male and female rats after repeated oral administration of Mb12 for 5 weeks at a daily dosage of 125, 250, 500 and 1,000 mg/kg. It is concluded that no manifest toxic effects were caused by Mb12 even at the highest dosage level of 1,000 mg/kg/day for 5 weeks to male and female rats.

Animals↗
PubMed1984

[Toxicological studies of a new cephamycin, MT-141. II. Its subacute toxicity in rats].

In this subacute study, male and female rats were administered with 100, 200, 400, 800 and 1,600 mg/kg/day of MT-141 through an intramuscular (i.m.) route or with 50, 100, 200, 400 and 800 mg/kg/day through an intravenous (i.v.) route for 30 days. MT-141 did not cause lethal effect on male and female rats even at the high dosage of 1,600 mg/kg/day i.m. (approx. one-6th of LD50) and 800 mg/kg/day i.v. (approx. one-8th of LD50). Histopathological findings revealed that MT-141 induced slight local irritation at the sites of i.m. and i.v. injection. Only at a high dose of 1,600 mg/kg/day i.m., MT-141 reduced significantly the gain of body weight in male rats, which was closely related to the decrease of food intake. A slight decrease in serum Cr. and Glc. was observed in male rats at the doses more than 200 mg/kg/day i.m. and a slight decrease of liver weight at the doses more than 800 mg/kg/day i.m., while a slight increase of serum CPK, GOT, A1-P and LDH was perceived at the doses more than 800 mg/kg/day i.m. The distention of cecum was induced by the doses more than 400 mg/kg/day i.m. but histopathological findings revealed no abnormality in the cecum. These results suggest that MT-141 at the dosage level of 1,600 mg/kg/day i.m. causes nonspecific slight toxicity based on the disturbance of nourishment in male rats. In female rats given 100 to 1,600 mg/kg/day i.m., MT-141 at the high doses induced a slight increase of serum GOT, LDH and CPK and distention of the cecum. It is assumed from these results that MT-141 at the dosage level of 1,600 mg/kg/day causes nonspecific slight toxicity in female rats. In male rats given 50 to 800 mg/kg/day through an i.v. route, the level of serum Glc. and Cr. and the liver weight slightly decreased at the doses more than 200 mg/kg/day i.v. The cecum distended at the doses more than 100 mg/kg/day i.v. The dose of 800 mg/kg/day i.v. increased the activity of LDH and CPK in the serum. In female rats, MT-141 raised slightly the level of serum GOT, A1-P, LDH and CPK even at the doses more than 400 mg/kg/day i.v., reduced the liver weight at the dose of 800 mg/kg/day i.v. and distended the cecum at the all doses. These results suggest that MT-141 at the dosage level of 800 mg/kg/day i.v. induces nonspecific slight toxicity in male and female rats.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

[Toxicological studies of a new cephamycin, MT-141. III. Its chronic toxicity in rats].

The chronic toxicity of MT-141 was studied in male and female Wistar rats with 182-time intramuscular injections of 50, 100, 200, 400, 800 and 1,600 mg/kg/day and the following results were obtained. MT-141 at all dosage levels caused no lethal effect on rats. However, it induced local inflammatory changes at the site of injection, such as hemorrhage, infiltration of round cells and fibrosis particularly at high doses. MT-141 at a high dose of 1,600 mg/kg/day decreased the gain of body weights in male rats but not in female rats. MT-141 increased the water intake in male and female rats from 8th day till last day after treatments with the doses more than 800 mg/kg/day. This compound also softened the feces and distended the cecum. MT-141 at the highest dosage level of 1,600 mg/kg/day increased the weight of kidney in male and female rats. Electron-microscopic findings revealed dissociation of basal infolding and dilatation of endoplasmic reticulum in renal epithelial cells of rats treated with the doses more than 800 mg/kg/day. These results suggest that MT-141 may induce renal toxicity in rats at these doses. The administration of MT-141 changed some toxicological parameters in gross and histopathological examinations and analyses of blood, serum and urine. However, the changes were accidental, independent on the dose and within physiological variations. It is concluded from above-mentioned results that the maximal "no effective" dose of MT-141 is 400 mg/kg/day in male and female rats.

Animals↗
PubMed1984

[Toxicological studies on a new cephamycin, MT-141, IV. Its acute toxicity in beagle dogs].

The acute toxicity of MT-141 was studied in adult Beagle dogs with intravenous (i.v.) or intramuscular (i.m.) administration to obtain following results. MT-141 at the doses ranging from 2,500 to 7,500 mg/kg i.v. caused no effect on life, bodyweight, food intake, eyeground and ECG in male and female Beagle dogs. MT-141 produced an increase in water intake, urine volume, WBC and LAP and a decrease in Lymph., U-Na, U-K and OP, but any histopathological change was not caused in the organs and tissues. It is suggested that these changes in blood, serum and urine are due to mechanical and transient effects induced by infusing a large volume of hypertonic solution of MT-141 into cephalic vein. When 1,000 or 2,000 mg/kg of MT-141 was injected into the muscles of hind legs, the hind legs had difficulty in walking. It is very probable that this change was due to mechanical effects induced by injecting a hypertonic solution of MT-141 at a rate of 70--130 ml/dog. An injection of 1,000 or 2,000 mg/kg i.m. of MT-141 changed activity of GPT, GOT and CPK in the serum within the limit of physiological variations but did not caused any effect on the other toxicological parameters such as bodyweight, food intake, water intake, urine volume, eyeground examination, ECG and histopathological examination. It is concluded from the above-mentioned results that MT-141 at the dose of 2,500--7,500 mg/kg i.v. or 1,000--2,000 mg/kg i.m. has no significant toxicity in Beagle dogs.

Animals↗
PubMed1984

[Toxicological studies on a new cephamycin, MT-141. V. Its subacute toxicity in beagle dogs].

The 30-day subacute toxicity of MT-141 was studied in adult Beagle dogs with intravenous (i.v.) administrations of 100 to 1,200 mg/kg/day. The obtained results were as follows. MT-141 at the doses lower than 800 mg/kg/day i.v. had no toxicity in male and female Beagle dogs. An increase in water intake was closely related to that in urine excretion after i.v. treatments with 1,200 mg/kg/day of MT-141 in the males and females. MT-141 at the doses higher than 1,000 mg/kg/day i.v. of MT-141 caused slight local irritation at the site of injection in the males and females. In the females, the dose-dependent changes induced by treatments with the doses above 1,000 mg/kg/day i.v. of MT-141 were a significant decrease in the level of serum K and a significant increase in the activity of serum LAP. In the males, this compound produced significant dose-dependent changes in toxicological parameters such as a decrease in the activity of GOT at the doses higher than 1,000 mg/kg/day i.v., a descent in the levels of U-K, U-Cl and OP at the dose of 1,200 mg/kg/day i.v., an elevation in the level of serum alpha 1- and alpha 2-G, and an increase in the volume of excreted urine at the dose of 1,200 mg/kg/day i.v. It is concluded from the above-mentioned results that the maximal "no effective" dose of MT-141 is 800 mg/kg/day i.v. and the toxic dose of MT-141 is above 1,000 mg/kg/day i.v. in male and female Beagle dogs.

Animals↗