Effect of sodium dipropylacetate on conflict behavior in rats.
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Biomedical subjects
Publications and source records attributed to K Ohmori.
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A simple passive type sampling device has been developed for personal monitoring of ozone exposure in the workshop of welding. Atmospheric ozone is collected on a filter paper soaked in 1,2-di-(4-pyridyl)-ethylene. Pyridine-4-aldehyde is produced by the ozonolysis reaction. Analysis of the results showed the time-weighted (TWA) exposure concentration of ozone. The relationship showed a good linearity between the pyridine-4-aldehyde produced and the ozone concentration. Coefficient of variation of the data of measurement after exposure was less than 10%. and the range of the data was from 0.05 to above 1.42 ppm hr. Promising results have been obtained in the data of controlled exposures to nitrogen dioxide, and excellent stability for delayed analysis after sampling. According to these results, we believe that the simple sampling device can be used for the evaluation of personal exposure dose for ozone.
New antitumor anthracycline antibiotic, aclacinomycin A was given to dd-mice and Wistar rats for acute toxicity study. The LD50 values were 29 approximately 39 mg/kg (i.v., i.p. and s.c.) and 62 approximately 69 mg/kg (p.o.) in mice, and 18 approximately 28 mg/kg (i.v., i.p. and s.c.) and 58 approximately 59 mg/kg (p.o.) in rats, respectively, which were calculated by mortality rate during a 14 day observation period. Depression of spontaneous activity, anorexia, diarrhea and slight alopecia were observed. Autopsy findings in animals killed by drug included atrophy of the thymus and spleen, and hyperemia and hemorrhage in the stomach and intestines. But no remarkable change was found in animals which survived through the observation period. Mongrel dogs were given the drug intravenously at 3, 5, 7.5, 10 and 15 mg/kg, respectively. All dogs (3/3) in the three higher dose groups and 1/3 dog in 5 mg/kg dose group died within day 0 approximately 5. Others survived more than 27 days. Depression of spontaneous activity and anorexia were found from 30 minutes to 2 hours after administration, followed by vomiting and diarrhea. Increase of GOT, GPT and LDH and decrease of WBC count were detected in dogs which died. Hyperemia and hemorrhage of the lungs, stomach and intestine were found among the groups given higher doses, whereas no significant changes were recognized among the two lower dose groups.
Wistar rats, both male and female, were treated with aclacinomycin A at 4 dosage levels (0.375, 0.75, 1.5 and 3.0 mg/kg/day) by daily intraperitoneal injection for 30 days. Several rats died in the two higher dose groups (1.5 mg/kg/day: male 2/8 and 3.0 mg/kg: male 8/8, female 8/8. Piloerection, anorexia, depression of spontaneous activity, diarrhea and slight incontinence were observed in rats in 3.0 mg/kg/day dose group. Body weight gain decreased after day 3 in rats receiving 1.5 and 3.0 mg/kg/day. A significant decrease in the total WBC count and a slight decrease in RBC count were observed in animals of 1.5 mg/kg/day dose group which were survived for 30 days. Autopsy findings demonstrated atrophy of the thymus and spleen, and hyperemia and hemorrhage in the intestine. The atrophy of the thymus and decreased hematopoiesis in the bone marrow were histologically noted in the two highest dose groups. No cardiotoxicity was observed.
An anthracycline antitumor antibiotic, aclacinomycin A, was given to mice, rabbits or dogs intravenously to study the pharmacokinetics by photometric assay based on the absorption of anthracycline ring. The drug was rapidly eliminated from the blood in these animals. Drug levels were much higher in the blood cells than in the plasma. Tissue levels in dogs were 50 approximately 100 times higher than the blood levels, which showed the drug was rapidly transferred from the blood to tissues after administration. Higher levels were observed in the lungs, spleen and lymph nodes, where the drug was present as aclacinomycin A itself and the glycoside-type metabolites that were biologically active. The active form was also detected in the pancreas, heart, thymus, bone marrow and gastrointestinal tract. In the liver and kidneys, biologically inactive aglycone-type metabolites were observed. About 2 approximately 4% of the drug given to rabbits or dogs was recovered in the urine by 72 hours after administration, in which only 10% of the excreted drug was active form in rabbits but about 65% in dogs. The rest was inactive aglycone-type metabolites that were excreted almost in the conjugated form. Biliary excretion also contributed to the total clearance of the drug. Aclacinomycin A was absorbed even by oral administration in rabbits and dogs. Tissue distribution of the drug orally given to dogs was similar to that in intravenous administration, except that higher levels of active form were detected in the gastrointestinal tract and of inactive form in the liver.
The general pharmacology of aclacinomycin A, a new antitumor antibiotic, was studied in mice, rats, guinea-pigs, frogs, rabbits and dogs. The LD50 values of aclacinomycin A were 32.5 mg/kg (i.v.), 30.1 mg/kg (i.p.), 33.9 mg/kg (s.c.) and 69.7 mg/kg (p.o.), respectively in male mice, and 28.8 mg/kg (i.v.), 21.1 mg/kg (i.p.), 26.4 mg/kg (s.c.) and 58.6 mg/kg (p.o.), respectively in male rats. Aclacinomycin A had no effect on the central nervous system except potenciation of the pentobarbital sodium-induced anesthesia in mice. The contraction of isolated heart was stimulated in frogs while slightly inhibited in rabbits at higher concentration. Transient increases in the heart rate and the blood flow of peripheral vasculature were observed but the blood pressure was slightly lowered with respiratory excitation in anesthetized rabbits and dogs. The ECG (II-lead) demonstrated slight depression of R wave amplitude and slight sinus arrhythmia in dogs. Aclacinomycin A inhibited the contraction of isolated smooth muscle and antagonized some spasmogens. It inhibited the spontaneous movement of isolated rabbit ileum and rat uterus at higher concentration, and antagonized acetylcholine, histamine, serotonin and barium chloride in the contraction of isolated guinea-pig ileum. The antagonism was competitive to oxytocin and noncompetitive to acetylcholine in rat uterus, and noncompetitive to noradrenaline in rat deferent duct. The drug showed no apparent effect on the gastrointestinal propulsion in mice and on mucous membrane of the stomach in rats. However, it depressed gastric acid secretion in rats while slightly increased bile secretion in guinea-pigs. Urine volume and urinary excretion of electrolytes (Na+, K+) decreased in rats. Vascular permeability was slightly inhibited by the drug in rabbits and mice. No hemolytic effect was shown. Aclacinomycin A showed no antigenicity in anaphylactic reaction and SCHULTZ-DALE reaction in guinea-pigs.
Male and female Wistar rats were treated with aclacinomycin A, a new anthracycline antitumor antibiotic, at 5 dosage levels (0.08, 0.15, 0.3, 0.6 and 1.2 mg/kg/day) by daily intraperitoneal injections for 180 days for a chronic toxicity study. Recovery was also examined for 30 days after completion of the administration. Mortality was as follows: Male 5/24, female 3/24 in 0.6 mg/kg/day dose group and male 19/24, female 8/24 in 1.2 mg/kg/day dose group. Anorexia, depression of spontaneous activity and unformed feces were observed in rats in 0.6 and 1.2 mg/kg/day dose groups after day 90. Body weight gain decreased during the period. No significant change was found in rats receiving the drug at 0.3 and less mg/kg/day all through the observation period. Remarkable decreases in WBC count were noted in rats in the two highest dose groups on day 90. Autopsy findings included atrophy of the thymus and hyperemia and hemorrhage in the gastrointestinal tract and mesenteric lymph node in the animals treated at 0.6 and 1.2 mg/kg/day in the examination on day 90. Histologically, atrophy of the thymus and hyperplasia of the spleen were observed in the higher dose groups on day 90. But no remarkable abnormalities were found in histological examination on day 180. The changes in general symptom and decrease in body weight gain, which were observed during the dosing period in rats in 0.6 mg/kg/day dose group, recovered within 30 days after the drug administration was discontinued but no complete recovery of the WBC count decrease was observed.
Japan White rabbits were treated with aclacinomycin A, a new anthracycline antitumor antibiotic, at a dose of 6.25 or 25.0 mg/kg by single intravenous, or 12.5 or 50.0 mg/kg by single oral administration, respectively. Beagle dogs were treated at a dose of 3.0 or 6.0 mg/kg by single intravenous injection. In rabbits in higher dose groups, RBC and WBC counts as well as lymphocyte ratio in peripheral blood decreased on day 1. Nucleated cell counts and erythroid elements in bone marrow decreased to raise M/E ratio (Myeloid/Erythroid ratio) on day 3. In a dog given at 6.0 mg/kg, WBC and platelet counts, lymphocyte and neutrocyte per cents in peripheral blood and also nucleated cells, particularly erythroid elements in bone marrow remarkably decreased on day 3 accompanied with an increase in M/E ratio. These changes were almost completely recovered by day 14 in both animals. No abnormalities were found in lower dose groups. Male Wistar rats, treated with the drug at a dose of 1.5 mg/kg by daily intraperitoneal injection for 30 days, showed slight decreases in peripheral WBC and RBC counts and M/E ratio in bone marrow. No change was observed in rats treated at 0.75 mg/kg and less for 30 days.
Aclacinomycin A, a new anthracycline antitumor antibiotic, was given to rabbits by single instillation or single intracutaneous injection and to guinea pigs by single subcutaneous or intramuscular injection to examine the irritative effect. Slight dilatation of blood vessel and swelling in the conjunctiva and nictitating membrane were observed in the eyes of rabbits given 1% solution. Edema in the bulbar conjunctiva, iris and cornea was histologically noted. Washing of the eyes after drug instillation prevented these damages. Subcutaneous and intracutaneous injections of 1% solution (0.2 ml) gave hyperemia, swelling and necrosis at injection site. Cellular infiltration, fibrosis and necrosis were histologically detected. Intramuscular injection of 1% solution (0.2 ml) also provided induration and swelling at injection site. Histologically cellular infiltration and necrosis were observed. These irritative effects were much slighter in administration of 0.1% solution. No change was observed with 0.01% solution.
Cell surface antigens on neoplastic lymphoid cells of T cell lineage were analyzed with a fluorescence-activated cell sorter (FACS-II) by utilizing rabbit antisera raised against human brain tissue (anti-Br) and fetal thymocytes (anti-Ty). Both before and after extensive absorption with normal peripheral blood lymphocytes (PBL), the anti-Br antiserum was capable of staining neoplastic lymphoid cells from patients with Sézary syndrome, mycosis fungoides, thymoma, and chronic lymphocytic leukemia. The absorption of anti-Ty with normal PBL, however, resulted in loss of the ability to stain normal bone marrow cells and preabsorbed with normal PBL was found to stain normal bone marrow cells and neoplastic myeloid cells but not fetal thymocytes. It is suggested that the absorbed anti-Br is capable of detecting differentiation antigens present on immature hematopoietic cells in the bone marrow, which would be anomalously expressed on neoplastic lymphoid cells to T cell lineage.
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A successful replantation of a finger on an infant aged twelve months and fifteen days by microsurgical repair is reported.
A new approach to total rhinoplasty, using a free dorsalis pedis flap containing part of the second metatarsal bone, is reported.
Two T lymphocyte-specific antisera, i.e. naturally-occurring auto-antibody to T cells of systemic lupus erythematosus patients (natural T cell toxic autoantibody) and heterologous antiserum against human brain tissue (antibrain-associated T-cell antigen), were used to detect cell surface antigens of human peripheral T lymphocytes. Nylon column-purified T cells from normal aged individuals and patients with Werner's syndrome (a premature aging syndrome) were reacted with these auto- and heterologous antibodies followed by staining with appropriate fluorescence reagents. The cells were subjected to the automated analysis with fluorescence-activated cell sorter. Fluorescence profiles to T cells of both aged individuals of over 90 yr and Werner's syndrome showed a very similar pattern, with a drastic decrease in the population that had high fluorescence intensity stained with either antiserum accompanied by the relative increase in the cell population that had low fluorescence intensity. Natural T cell toxic autoantibody comparable to that detected in systemic lupus erythematosus patients was found in the serum of six out of seven patients with Werner's syndrome, whereas normal aged individuals produced no such an autoantibody. The results suggest that Werner's syndrome has a change in the lymphocyte population very similar to old individuals, and that such a change is caused by the production of autoantibodies reactive to T lymphocytes.
Effects of stimulation of the locus coeruleus (LC) on evoked potential in the medial amygdala elicited by stimulation of the olfactory bulb (OB-AME potentials) were studied in the gallamine-immobilized rats. The amplitude of the OB-AME potential was inhibited 27.5% by the conditioning stimulation of LC delivered 30 msec before the test stimulation. The inhibitory effect of LC was reduced by propranolol 5 mg/kg i.p., but not by phentolamine 10 mg/kg i.p.. This effect was also reduced by tetrabenazine 10 mg/kg i.p.. Methamphetamine 5 mg/kg i.p. produced considerable potentiation of the LC inhibitory effect and a reduction of the OB-AME potential itself. These results suggest that the LC plays an inhibitory role in the electrical activity of the medial amygdala.