Studies on urinary glycosaminoglycans and hydroxyproline from patients with myotonic dystrophy.
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Biomedical subjects
Publications and source records attributed to K Tsurumi.
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A simple method for the preparation of 3'-sialyllactose from normal human urine is described. The method for the collection of sialooligosaccharides is based on adsorption on charcoal followed by elution with a mixture of ethanol, pyridine, and water. The sialooligosaccharide mixture is then fractionated by means of gel filtration on Sephadex G-25 and the low molecular weight fraction is further fractionated on Dowex 1 (eluted with pyridinium acetate) to give five fractions. The last fraction contains almost pure 3'-sialyllactose.
It has been already reported that ketoprofen (KP) has a potent anti-inflammatory action comparable to indomethacin, but with oral administration, gastric mucous membrane disturbances occur. In the present work, we administered the Na salt of KP (KP-Na) subcutaneously and found that the anti-inflammatory action was more potent in subacute and chronic inflammations than in the acute one. As an acidic compound, KP-Na had a relatively potent analgesic-antipyretic action and a medical efficacy comparable to the usual non-steroidal anti-inflammatory drugs given orally. The efficacy in case of subcutaneous administration was 2 to 3 times stronger over both acute and chronic inflammations than in case of oral administration. On the other hand, the gastric mucous membrane disturbance was decreased to about 1/3 in case of subcutaneous administration, thus the gastric disturbance could be abated and the medical efficacy can be increased when KP-Na is given subcutaneously. As KP-Na was less irritative at the injection site, the compound could be used clinically for a subcutaneous administration.
TAI-284, a new non-steroidal acidic analgesic and anti-inflammatory agent was investigated and the interactions with biopolymers were compared with those of indomethacin (IMC) and ibuprofen (IP). TAI-284 inhibited the heat denaturation of bovine serum albumin at pH 5.3, similar to that seen with IMC and weaker than that seen with phenylbutazone. TAI-284 prevented the rat erythrocyte from heat-induced hemolysis and was twice as potent as IMC. TAI-284 produced alterations in platelet function as characterized by loss of secondary aggregation in response to ADP and inhibition of aggregation by collagen. Both these effects were one fifth as potent as those seen with IMC. In rats, platelet aggregation induced by collagen and secondary ADP aggregation was reduced in a dose-dependent manner by a single oral administration of TAI-284. The inhibitory activity was approximately one fourth that of IMC or twice that of IP in the former and in the latter one fifth that of IMC or similar as that of IP. These results suggest that the essential feature of TAI-284 is its potent membrane stabilizing action which is considered to be an necessary mechanism in the action of anti-inflammatory drugs. It is considered that TAI-284 may be less active than IMC in inhibiting prostaglandin biosynthesis in platelets.
A method of making the multiple regional renograms and simple functional images are described. Thirty-six EDTA (or DTPA) images has been transferred from a gamma camera to a small computer with the magnetic tape. Thirteen regional renograms from a kidney have been made by using the single pixel ROIs from these images, a continuous 13 pixels horizontal and/or vertical of the matrix are selected, in distinction from right and left kidney. Two functional images have been made by the multi-frame images as a peak arrival time and it's peak counts. Small change of the radioisotopic transportation in the kidney could be observed by the method, and change of the urodynamics could be extracted by two functional images. It will be actualize quantitative diagnosis to the renal function disorders.
Anti-inflammatory activity and the mode of action of TAI-284 were investigated in animal models and compared with the activities of indomethacin. TAI-28 inhibited the increased vascular permeability in rats and mice which is the primary stage of inflammatory process, but the activity was less than that of indomethacin. The compound was as active as indomethacin in inhibiting acute rat paw edema induced by carrageenin and fracture. Furthermore, in the inhibitory effects on ultraviolet erythema in guinea pigs, durable paw edema induced by mustard and wound healing in rats, TAI-284 showed the same or more potent activity than indomethacin. Therefore, TAI-284 proved to have the same anti-inflammatory activity as indomethacin. TAI-284 protected rabbits from sudden death caused by intravenous injection of arachidonic acid, but the activity was about one twentieth less than that of indomethacin. The anti-inflammatory action of TAI-284 was derived from the mode of action of non-steroidal anti-inflammatory drugs, judging from the effects on ultraviolet erythema and death by arachidonic acid. On the other hand, the compound was more potent on secondary or thema and death by arachidonic acid. On the other hand, the compound was more potent on secondary or late stage than on primary stage of inflammation, and to some extent showed the mode of action seen with steroid antiinflammatory drugs. TAI-284 displayed marked inhibitory activity on nystatin induced paw edema in rats. It is suggested that the antinflammatory action of TAI-284 may be due to the lysosomal stabilizing effect.
Non-antimicrobial actions of oleandomycin (triacetyloleandomycin and oleandomycin phosphate) were studied in patients with bronchial asthma. Twenty-one cases of the disease without associating infections entered the study, and they were given 750mg of oleandomycin or triacetryloleandomycin in three divided doses daily for two weeks. Clinical manifestations and laboratory findings were compared to assess the effectiveness of the antibiotic therapy between the three 2-week periods before, during and after the therapy. Improvements in clinical manifestations were attained in 11 of 21 cases (52.3%), and last after discontinuance of the therapy in 8(38.1%). The blood level of 11-OHCS as determined by the Demoorr's fluorescence method increased by greater than 20% at the end of thearpy in 7 of 18 cases (38.9%). In 5 of the 7 cases favorable responses were seen clinically to the oleandomycin therapy. The serum IgE level determined by the radioimmunosorbent test was compared before and after the therapy to reveal that oleandomycin caused decrease of IgE in 10 and increase in 9 of 20 cases examined. The oleandomycin therapy resulted increases by greater than 20% of the vital capacity and FEV 1.0 in 2 and 3, respectively, of 15 cases. Jaundice in association with elevations of the GOT, GPT and alkaline phosphatase developed in one patient, and generalized skin eruption in another. Both of these cases were given triacetyloleandomycin.
PZ-177 was found to have potent analgesic, anti-inflammatory and mild central depressive actions. In the present work, the general pharmacological actions of PZ-177 were tested in order to investigate other significant actions and to determine the side effects. PZ-177 showed no significant pharmacological activities on the respiratory and cardiovascular system, on the renal function, on the autonomic nervous system, on the sugar level and coagulation in blood and on local irritation. Volume and acidity of gastric juice were decreased and turn over was not inhibited in the connective tissure. Thus PZ-177 was considered to have no ulcerogenic action on the gastric mucosa. The compound relaxed the tonus of isolated small intestine, tracheal muscles and uterus and stopped spontaneous movement. Moreover the contraction of those smooth muscles by such spasmogens as acetylcholine, histamine serotonin, BaCl2 and oxytocin was inhibited by PZ-177 and the activity was almost the same with each spasmogen. It was found therefore to have spasmolytic activity and no specific antagonistic action on the chemical mediators. PZ-177 showed also wear relaxant activity on the skeletal muscle. Those actions on the muscles may have a curative effect on inflammation in bronchotracheal and gastrointestinal tracts or on pain with contraction of skeletal muscle. From the above results, it may be considered that PZ-177 is a relatively safe and useful analgesic and anti-inflammatory compound.
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In a previous paper, we reported that PZ-177 had potent anti-inflammatory and analgesic activities. In the present work, acute toxicity and action of PZ-177 on the central nervous system were tested in comparison with PZ-222, one of metabolites of PZ-177, and mepirizole. Acute toxicity of PZ-177 was slightly less than that of aminopyrine and the same as that of mepirizole in mice and rats. PZ-177 produced from sedation to loss of righting reflex with the increase of dose. At a low dose with which the righting reflex was hot lost, PZ-177 decreased spontaneous locomotion of mice in the Animex test, produced muscle relaxation in rotarod and inclined screen tests, produced sleeping-pattern in electroencephalogram of rabbit, potentiated hypnosis of barbiturates and exerted an anti-convulsive effect in mice. In these depressive effects on the central nervous system, PZ-222 was very much lower and mepirizole slightly lower than PZ-177. It would thus appear that PZ-177 has more potent analgesic, antipyretic and anti-tussive actions than do PZ-222 and mepirizole.
From the screening of a number of new pyrazole derivatives, the title compound, PZ-177, was selected as the most significant derivative for analgestic and anti-edematous actions, in this paper, we report the anti-edematous activity of PZ-177 as assessed by detailed analysis. PZ-177 showed a markedly inhibitory effect against rat paw edema induced by various phlogists (carragenin, dextran, egg albumin, serotonin, formalin and bradykinin). It also inhibited edema induced by anti-rat rabbit serum. The activity of PZ-177 was more potent than that of mepirizole and the same as that of phenylbutazone. Though this agent has a central depressive effect, it is considered that the action has actually little influence on anti-edematous effect, as carrageenin-induced edema was inhibited in spinal rats. On the other hand, the anti-edematous effect of PZ-177 was reduced significantly in adrenalectomized rats. It is therefore suggested that the potent anti-edematous action of PZ-177 is exerted partially by a direct action at the inflamed site and mediated partially by stimulation of the hypophysis-adrenal system.
We have reported that PZ-177 was found to have potent inhibitory activity on acute inflammatory edema. In this paper, the anti-inflammatory, analgesic and antipyretic properties of PZ-177 were assessed by a battery of standard tests. PZ-177 inhibited the increased vascular permeability induced by histamine, xylene and acetic acid. The activity was the same as the anti-edematous one and was more potent than that of mepirizole. PZ-177 did not inhibit ultraviolet erythema in guinea pigs, proliferation of granulation tissue in cotton pellet and granuloma pouch tests of rats and adjuvant arthritis in rats. Wound healing was not prolonged and the agent was weak in ulcerogenic action. PZ-177 did not affect heat denaturation of bovine serum albumin at pH 5.3, but inhibited hyperthermic hemolysis at pH 7.4 and exerted a stabilizing effect on biological membranes. This is considered to be one of the mechanisms of action. When analgesic action was tested by the writhing and Haffner's methods in mice, the compound revealed a more potent activity than did mepirizole and aminopyrine. Utilizing the Randall-Selitto's analgesic method in rats, a significant rise in pain threshold was obtained only at the inflamed foot. The antipyretic action was less than aminopyrine in febrile rabbits. From the above results, PZ-177 may be classified as a potent analgesic and anti-inflammatory agent but has no effect on proliferation of granulation tissue and chronic inflammatory disease.
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