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T Koeda

Publications and source records attributed to T Koeda.

At least 163 records · Page 9Linked to original sources

[Toxicological studies on dibekacin for intravenous injection use. I. Subacute toxicity in rats and rabbits (author's transl)].

Dibekacin sulfate (DKB) dissolved in physiological saline J.P. was administered to rats intraperitoneally and rabbits intravenously for subacute 35-day toxicity test. The results were as follows: I. Wistar-strain rats (1) All the animals of both male and female died in the group with 500 mg/kg. (2) In general conditions stretching physical positions, decrease in spontaneous movements, decrease in respiration rates, unsteady steps of walking and muscular relaxation developed in the groups of high doses of either sex. The effects through the administration of this drug were also noted on the progress of body weights and food intakes in the groups of high doses. (3) In the hematological and histopathological studies, degenerative and reparative changes of tubular epithelia were evidently noted in the groups which were administered more than 100 mg/kg of DKB in both male and female. No pathological findings were noted in administration groups less than 20 mg/kg. (4) Microscopically, slight inflammatory changes were noted in the bladder of the male groups of high doses and the direct stimulative effects on the peritoneum due to intraperitoneal administration were noted but slightly in the serous membrane of the liver, spleen and the gastrointestinal tracts. (5) Judging from the above-mentioned results, "the maximal non toxic dose" through the intraperitoneal administration to rats of this drug was assumed 20 mg/kg in either sex. II. Albino rabbits (1) Neither remarkable change in the general conditions nor death was noted in each administration group. (2) The increase in the mean body weight in each group was almost similar to the control value. They consumed the amounts of food given. (3) The specific abnormal finding was not noted in the hematology and biochemical tests of serum or urine. (4) Since no change was noted on ERG in each rabbits, we estimate there is no effect to the visual organs. (5) In histopathological study, several changes revealed in some organs through the macroscopic findings, organ weights and microscopic findings but they were no more the serious changes attributable to administration. (6) We estimate "the maximal non effective dose" in this test was 10 mg/kg.

Animals↗

[Toxicological studies on dibekacin for intravenous injection use. II. Chronic toxicity in rats (author's transl)].

The toxic effects of dibekacin sulfate (DKB) in male and female rats were examined in chronic toxicity test (intraperitoneal injection), and the following results were obtained. 1) No death was noted in both male and female. 2) In general conditions, the excretion of soft or diarrheal stool was noted in groups of more than 20 mg/kg of either sex. The mean body weight was less than the control during a certain period in the male group of 40 mg/kg and in the female group of 20 mg/kg. But, in the food intakes, no particular change was noted in each group of either sex. 3) In the auricle reflex, no abnormality was noted in each group of either sex. 4) In the hematological test, the findings such as an increase of BUN, anemia, etc. were noted in the groups more than 10 mg/kg of male and more than 20 mg/kg of female. 5) In the histopathological study, evident degenerative changes of renal tubular epithelia were noted in the groups which were administered more than 20 mg/kg of DKB in both male and female, but no evident pathological findings due to the renal failure were noted in the groups of less than 10 mg/kg. Several slight changes of the thyroid gland noted in a few rats of DKB administration group of both male and female seemed to be artifact, and inflammatory changes owing to intraperitoneal injection were occasionally noted in the peritoneum of DKB injected animals. 6) Considering the above results, "the maximal non effective dose" was estimated to be 10 mg/kg in both male and female.

Animals↗

[Effect of fosfomycin-calcium on reproductive performance of rats. II. Fertility test (author's transl)].

Fosfomycin calcium (FOM-Ca) was orally administered to Wistar rats for 60 consecutive days in males and 14 consecutive days in females in varying doses of 140 mg/kg, 700 mg/kg and 1,400 mg/kg, and then the animals were subjected to mating. It was further administered to pregnant female rats for another week to investigate its effects upon the embryos and fetus. The following results were obtained. 1) In parent animals, soft stools were noted in both sexes of the groups with higher doses, but otherwise there was no remarkable abnormality noted. 2) No increase was seen in the rates of development of dead embryos or externally abnormal fetus. 3) Skeletal abnormality was seen only slightly in the animals of the group with 700 mg/kg, but otherwise all the other groups were similar to the control group, showing that there would be no adverse effects by the tested drug upon the fetal skeletal structure. 4) On the ground of the above-mentioned test results, it was claimed that FOM-Ca exerts adverse effects upon the fetus of rats even in the dose of 700 mg/kg and that the safe dose to fetus of rats would be 140 mg/kg. It was also judged that it has no teratogenicity through administration before or at the initial stage of gestation.

Animals↗

[Effect of fosfomycin-calcium on reproductive performance of rats. III. Peri- and post-natal examination (author's transl)].

The peri- and post-natal examination of fosfomycin-Ca (FOM-Ca) was undertaken in Wistar strain rats. Rats were treated orally at dose levels of 140, 1,400 and 2,800 mg/kg/day from the 14th day of gestation to 21st day after delivery. One-third of pregnant rats in each group were sacrificed on 20th day of gestation and then their fetuses were examined for external, visceral and skeletal observation. The remaining mothers were allowed to deliver naturally, and then their offsprings were examined for postnatal development. No effect of FOM-Ca treatment to rat mothers was found except soft stool was seen in 1,400 and 2,800 mg/kg groups. No effect of FOM-Ca on rat fetuses and newborns was found except fetal body weight and survival rate decreased and skeletal variation increased in maximum dose. Consequently, it can be concluded that FOM-Ca has no effect on rat mothers, fetuses, and newborns treated during peri- and post-natal period.

Abnormalities, Drug-Induced↗

Evaluation of the mutagenicity of aminoglycoside antibiotics in Salmonella typhimurium and Saccharomyces cerevisiae.

The mutagenicity of aminoglycoside antibiotics (KM, AKM, DKB, RSM, AMK, GM, TOB) has been studied in cells of the bacteria Salmonella typhimurium and in the yeast Saccharomyces cerevisiae. The bacterial strains (Ames') monitor reverse mutation (point mutation) and the yeast strain D5 monitors mitotic crossing-over, mitotic gene conversion and point mutation. None of these antibiotics demonstrated any mutagenic activities in either the bacteria or the yeast.

Aminoglycosides↗

[Toxicological studies on fosfomycin-Na salt. I. Acute toxicity in mice and rats (author's transl)].

The acute toxicity of sodium fosfomycin (FOM-Na), a new antibiotic in ICR mice and Wistar rats has been investigated. The LD50 values in mice were: 1,230 (male), 1,225 (female) mg/kg by i.v.; 2,175 (m), 2,467 (f) mg/kg by i.p.; 2,625 (m), 2,662 (f) mg/kg by i.m.; 5,100 (m), 6,150 (f) mg/kg by s.c. and 8,020 (m), 7,300 (f) mg/kg by p.o. The LD50 values in rats were: 1,650 (m), 1,560 (f) mg/kg by i.v.; 2,060 (m), 2,000 (f) mg/kg by i.p.; 2,630 (m), 2,460 (f) mg/kg by i.m.; 5,100 (m), 4,320 (f) mg/kg by s.c. and 4,700 (m), 4,550 (f) mg/kg by p.o. Animals dosed only i.v. died within 2 minutes. Signs of toxicity in mice or rats given FOM-Na were similar and included motor activity depression, reduced respiration and occasionally tremors. Surviving mice or rats given FOM-Na developed no pathological changes of the drug specificity.

Administration, Oral↗

[Toxicological studies on fosfomycin-Na salt. II. Subacute toxicity in rats and rabbits (author's transl)].

FOM-Na solution in distilled water for injection, J.P., with its pH adjusted to 7.0 +/- 0.2 with diluted hydrochloric acid, was administered to rats and rabbits for subacute toxicity test. The results revealed the following: 1. It was intraperitoneally administered to Wistar rats each weighing 100 +/- 10 g at their age of 5 weeks, and intravenously into auricular veins of male albino rabbits each weighing about 3 kg, for 35 successive days except Sundays through one administration per day. There was no death in rats of both sexes with the doses less than 1,000 mg/kg, while 3/10 males and 5/10 females died with the dose of 2,000 mg/kg. In terms of general conditions, both stretched physical position and vocalization were noted, which were presumed to be attributable to the stimuli of the administration. In the postmortem examination mutual adhesion of organs in the peritoneum was noted, while in the lightmicroscopic examinations histological proliferation and adhesion were found out in the hepatic capsules or serous membrane of the intestine etc., but no abnormalities were detected in the other organs. In the mean body weights, there were no significant differences between the control group and the groups of males with doses less than 500 mg/kg and females with doses less than 1,000 mg/kg whereas in the groups of males with doses more than 1,000 mg/kg and the females with a dose of 2,000 mg/kg, a trend of reduced weight gain was noted in comparison with the control group. The feed intake also was reduced as the dose was elevated. In terms of the male group hematology, the In. P increased with doses higher than 250 mg/kg, while BUN was reduced in the groups with a dose of 250 mg/kg and doses higher than 1,000 mg/kg, and Na was reduced in the groups with doses from 125 up to 500 mg/kg. In the female groups, the loss of Hgb and rise in the Cl were noted in the doses higher than 500 mg/kg while the loss of WBC was noted in almost all the treated groups. However, none of these changes was suggestive of specific abnormalities when compared with the photomicroscopic findings and our hematological background data. 2. There were no significant changes in the general conditions of any group of rabbits. Their mean body weights and their mean feed intakes proceeded almost similarly with those of the control group. In the hematological and histopathological tests also, no specific abnormal finding was experienced, which were deemed to be attributable to the administration of FOM-Na.

Animals↗

[Effect of fosmocyin-Na on reproductive performance of rats and rabbits. I. Teratogenicity test (author's transl)].

The teratogenicity study of fosfomycin-Na (FOM-Na) was undertaken in Wistar rats and New Zealand white rabbits. Rats were treated intraperitoneally at dose levels of 125, 250, 750 and 1,500 mg/kg/day from day 7 to day 17 of gestation, and rabbits were treated intravenously at dose levels of 80, 100, 200, 400 and 800 mg/kg/day from day 6 to day 18 of gestation. In the case of rats, two-thirds of pregnant mothers in each group was sacrificed on day 20 of gestation and then their fetuses were examined for external, visceral and skeletal observation. The remaining mothers were allowed to deliver naturally, and then their offsprings were examined for postnatal development. In the case of rabbits, all pregnant mothers were sacrificed on day 29 of gestation and their fetuses were examined. Body weight of rat mothers during gestation were decreased and 4 mothers were dead until day 20 of gestation in the maximum dose. In this dose, foetal toxicity was recognized too. However, external, visceral and skeletal anomalies related with FOM-Na treatment were not observed in all groups. No effect on development of offsprings was observed. No effect of treatment of FOM-Na to rabbits was found except foetal body weight was slightly decreased in the maximum dose.

Animals↗

[Effect of fosfomycin-Na on reproductive performance of rats. II. Fertility test (author's transl)].

The fertility study of fosfomycin-Na (FOM-Na) was undertaken in Wistar rats. FOM-Na was administered intraperitoneally at dose levels of 125, 250, 750 and 1,500 mg/kg/day. The male rats were continuously treated with FOM-Na from 63 days before mating and the females were treated from 14 days before mating. The males and females were treated through the mating period and then the pregnant rats were treated until 7 days of gestation. All pregnant rats were sacrificed on day 20 of gestation and then their fetuses were examined for external, visceral and skeletal observation. Mean body weight of males decreased and 6 males and 3 females died in the maximum dose. However, no significant differences were found between treated groups and the control with regard to fertility rate and pregnant rate. External, visceral and skeletal anomalies related with FOM-Na treatment were not observed. In this experiment, no effects of FOM-Na for reproductive performance in rats were observed.

Abnormalities, Drug-Induced↗

[Effect of fosfomycin-Na on reproductive performance of rats. III. Peri- and post-natal examination (author's transl)].

The peri- and post-natal study of fosfomycin-Na (FOM-Na) was undertaken in Wistar rats. FOM-Na was administered intraperitoneally at dose levels of 250, 750 and 1,500 mg/kg/day from day 14 of gestation to day 21 after delivery. It could be concluded that delivery rate in the 750 and 1,500 mg/kg groups decreased, but no influence of FOM-Na was found on postnatal development of offspring (F1) and neonate (F2) without maximum dose.

Animals↗

[General pharmacological studies on fosfomycin sodium (author's transl)].

The pharmacological effects of fosfomycin sodium, a new antibiotic agent, were studied on central nervous system, neuromuscular junction, isolated smooth muscles, blood coagulation, red blood cell resistance, body temperature, permeability of skin vessels and IgG and IgE antibody formation in laboratory animals. Fosfomycin sodium inhibited activities on the isolated smooth muscles, elevated body temperature, and increased permeability of skin vessels. Any of these actions, however, was noticeable only when it was administered in higher doses. Except for these above effects, fosfomycin sodium did not show any actions. Consequently, it can be concluded that fosfomycin sodium has no specific pharmacological actions.

Animals↗

[Effect of fosfomycin-calcium on reproductive performance of rat and rabbit: teratogenicity test (author's transl)].

The teratogenicity study of fosfomycin-Ca (FOM-Ca) was undertaken in Wistar strain rats and JW strain rabbits. Rats were treated orally at dose levels of 140,700 and 1,400 mg/kg/day from 7th to 17th day of gestation, and rabbits were treated orally at dose levels of 80, 140 and 420 mg/kg/day from 6th to 18th day of gestation. In the case of rats, two-thirds of pregnant mothers in each group were sacrificed on 20th day of gestation and then their fetuses were examined for external, visceral and skeletal observation. The remaining mothers were allowed to deliver naturally, and then their offsprings were examined for postnatal development. In the case of rabbits, all pregnant mothers were sacrificed on 29th day of gestation and their fetuses were examined. No effect of FOM-Ca treatment to rat and rabbit mothers was found except soft stool was seen with maximum dose in rats. Dead or resorbed rate of fetuses increased, external anomalies (short tail, abdominal hernia) were found and skeletal anomalies slight increased with maximum dose in rats. However, there was no significant difference from the control or background data. While, no effect of FOM-Ca treatment was observed in rabbits and rat offsprings. Consequently, it can be concluded that FOM-Ca has no teratogenicity effects on rats and rabbits.

Abnormalities, Drug-Induced↗

[Effects of fosfomycin sodium upon renal functions (author's transl)].

Effects of fosfomycin-sodium (FOM-Na) upon renal functions were studied with male rats. 1) After fasting for 24 hours, 25 ml/kg body weight of physiological saline were orally administered and respectively 160 and 320 mg/kg of FOM-Na were intraperitoneally administered immediately thereafter. The subsequent urinations amounts at 4 hours' interval were determined to see no effect of FOM-Na upon the urination amount. 2) After suspending water supply for 2 days, 1,000 mg/kg of FOM-Na were intraperitoneally administered once a day for successive 2 days. On the 3rd day, 50 ml/kg of dextran were intraperitoneally administered, and one hour thereafter, 1,000 mg/kg of FOM-Na were intramuscularly administered to hind leg. Blood samples were collected the following day (suspension of water was continued until blood sample collection) to determine the BUN and UA in serum. FOM-Na was found exerting on reinforcing effect upon renal dysfunctions caused by dextran.

Animals↗

Measurement of digital arterial blood pressure and its recording on usual electrocardiograph paper.

A simple method for measuring digital arterial pressure and its recording on usual EKG heat-writing paper was devised. The method enabled us to measure exactly the digital systolic as well as diastolic blood pressure without providing the calibrating scale of pressure, since the pressure scale is recorded on the paper automatically as pulse signals at the interval of 10mmHg. The pulse waves are also registered on the same paper by means of the finger plethysmograph. By use of a right-angled triangle transparent rule, we could estimate the value of digital systolic pressure at which the pulse wave began to appear when the cuff pressure for compressing the artery was gradually lowered. Estimated values of the digital arterial pressures were compared with those obtained by another method of Mendlowitz and his coworkers.

Adult↗