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H Shirota

Publications and source records attributed to H Shirota.

At least 37 records · Page 2Linked to original sources
PubMed1991

A novel inhibitor of IL-1 generation, E5090: in vivo inhibitory effect on the generation of IL-1-like factor and on granuloma formation in an air-pouch model.

The in vivo production of IL-1-like activity was investigated in the exudate of a rat air-pouch inflammatory model. An inflammatory reaction was induced by LPS injection into the air-pouch. IL-1 activity in the exudate reached the maximum level at 4 h and then rapidly decreased until 8 h after the injection of LPS. Orally administered E5090 and prednisolone dose-dependently inhibited the generation of IL-1 activity. Both compounds also suppressed chronic granuloma formation in parallel with the IL-1 inhibition. On the other hand, indomethacin had no effect on either IL-1 generation or granuloma formation in spite of the complete inhibition of PGE2 generation. These results suggest that E5090 inhibits the production of IL-1-like activity in the exudate and exhibits steroid-like antiinflammatory effects.

Acrylates↗
PubMed1990

Inhibitory effect of indomethacin farnesil, a novel antiinflammatory prodrug, on carrageenin-induced inflammation in rats.

Antiinflammatory effects of indomethacin farnesil (IMF), a novel prodrug of indomethacin, was examined after both oral and local administration. In the air pouch carrageenin-induced inflammation, an oral dose of IMF exerted dose dependent inhibitory effects on the accumulation of inflammatory exudate fluid and the migration of leukocytes into the exudate. Both the increased vascular permeability and the prostaglandin E2 levels in the exudate fluid were reduced by IMF. Significant levels of free indomethacin were detected in the pouch fluid. In spite of the inability of IMF to inhibit prostaglandin synthesis in a cell free cyclooxygenase system, IMF injected locally inhibited carrageenin paw edema, and the inhibitory effect was comparable to that of indomethacin itself. When injected locally into the paw together with carrageenin, 14C-IMF was effectively converted to its active metabolite, indomethacin. The indomethacin concentration in the paw tissue was comparable to that of indomethacin injected paws with the same molar dose of free indomethacin.

Animals↗
PubMed1990

[Behavior of drug resistant fecal coliforms and R plasmids in a wastewater treatment plant].

Fecal coliforms were isolated from the inlet, the primary sedimentation tank, the activated sludge digestion tank, the final settling tank, the outlet and the return activated sludge drain at the municipal wastewater plant in Ube City, and examined for drug resistance and presence of R plasmids. Drug concentrations employed to distinguish resistant isolates from sensitive isolates were 25 micrograms/ml for tetracycline, kanamycin, chloramphenicol and streptomycin, 50 micrograms/ml for ampicillin, nalidixic acid and rifampicin, and 200 micrograms/ml for sulfisoxazole, respectively. Of a total of 900 isolates, 45.7% were drug resistant and 51.1% of them carried R plasmids. The further along that wastewater had progressed through the treatment process the greater the tendency was for appearance of the multiresistant isolates. These isolates also were shown to simultaneously carry transferable R plasmids. Observed resistant patterns of R plasmids were mainly multiple and encoded to resistance to tetracycline, chloramphenicol, streptomycin and sulfisoxazole. It became clear that multiplication of R plasmids took place in the activated sludge digestion tank. This study show that drug resistance transfer mediated by these R plasmids may occur in actual wastewater treatment plants.

Drug Resistance, Microbial↗
PubMed1989

Inhibitory effects of E-5110 on interleukin-1 generation from human monocytes.

Effects of E-5110, a novel non-steroidal antiinflammatory drug, on interleukin-1 (IL-1) generation from human monocytes were studied in vitro. E-5110 reduced the amounts of extra- and intracellular IL-1 activity induced by lipopolysaccharide (LPS, 1 micrograms/ml) in a dose-dependent manner (1-10 microM). E-5110 also inhibited the IL-1 generation induced by antigen-antibody complexes, opsonized zymosan and silica particles. It was suggested that the inhibition of IL-1 generation by E-5110 was independent of the inhibitory effects on arachidonate cyclooxygenase and/or lipoxygenase because indomethacin, piroxicam, BW755C and AA861 had no effects on IL-1 generation. Hydrocortisone (IC50:0.084 microM), aurothioglucose (11.5 microM) and lobenzarit (75.0 microM), which are clinically effective antirheumatic drugs, also inhibited IL-1 generation, like E-5110 (1.21 microM). It is expected that E-5110 will be superior to classical non-steroidal antiinflammatory drugs in medical treatment of rheumatoid arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

Interleukin-1-like activity in the exudate of air-pouch inflammation in rats, and its participation in granuloma formation.

The in vivo production of lymphocyte activating factor (LAF) activity was investigated in the exudate of the rat air-pouch inflammation model. An inflammatory reaction was induced by lipopolysaccharide (LPS) injection into the air-pouch, and the time course of LAF activity in the exudate was investigated. LAF activity in the exudate reached a peak by 6 h, and rapidly decreased at 10 to 48 h after the LPS injection. Dexamethasone revealed strong inhibitory action on LAF activity and granuloma formation. On the other hand, indomethacin could not inhibit either of the phenomena. In conclusion, LAF (IL-1) is rapidly produced after the onset of inflammation and may participate in the subsequent granuloma formation.

Animals↗
PubMed1988

Plasma and bone osteocalcin levels in rats with type II collagen-induced arthritis.

Osteocalcin levels in plasma and bone were measured by enzyme immunoassay in rats with arthritis induced by immunization with type II collagen and in untreated control rats. Compared with levels in control rats, the plasma levels of osteocalcin in arthritic rats were markedly decreased 1-3 weeks after immunization; during weeks 8-14, these levels were significantly increased. The osteocalcin content of tarsal bones changed in parallel with the plasma levels. These data suggest that osteocalcin levels in the plasma of arthritic rats reflect alterations in bone formation activity.

Animals↗
PubMed1988

Application of adjuvant-induced local hyperthermia for evaluation of anti-inflammatory drugs.

A recently established method for determining the surface temperature of adjuvant-inflamed rat's paw was used to examine the anti-inflammatory potencies of various nonsteroidal and steroidal anti-inflammatory drugs, which are currently in clinical use. The results were compared with those obtained by the carrageenin paw edema method and with the inhibitory potencies on prostaglandin E2 generation. The clinically effective single doses of the drugs were better correlated with the effective doses on local hyperthermia than with those on carrageenin paw edema, or with the inhibitory activities of the drugs on prostaglandin E2 generation from cultured rat synovial cells. Although care should be taken to avoid false-positive anti-inflammatory effects arising from vasoconstrictor activity or toxicity, determination of lowering effects on local hyperthermia in this inflammatory model may be useful for the evaluation of anti-inflammatory compounds.

Animals↗
PubMed1987

Pharmacological properties of N-methoxy-3-(3,5-ditert-butyl-4-hydroxybenzylidene)-2-pyrrolidone (E-5110), a novel nonsteroidal antiinflammatory agent.

The antiinflammatory activity of a novel pyrrolidone derivative E-5110 was investigated using anti-inflammatory, analgesic and antipyretic animal models in comparison to indomethacin (IND) and piroxicam (PIR). The acute antiinflammatory activity of E-5110 on carrageenin paw edema was similar to IND, and half of PIR. E-5110 inhibited the pleural exudate volume and leucocyte infiltration in a reversed passive Arthus reaction more potent than IND. The chronic inflammatory responses in the established adjuvant- and type II collagen-induced arthritis were suppressed by E-5110 similar to IND and PIR. The analgesic potency of E-5110 was similar to IND and PIR, but the antipyretic activity of E-5110 was more potent than that of IND, and slightly more potent than that of PIR. The ulcerogenic effect of E-5110 on rat gastric mucosa was less than that of the reference drugs.

Animals↗
PubMed1987

In vitro effect of N-methoxy-3-(3,5-ditert-butyl-4-hydroxybenzylidene)-2-pyrrolidon e (E-5110), a novel nonsteroidal antiinflammatory agent, on generation of some inflammatory mediators.

Cultured rat synovial cells generate PGE2 upon stimulation with a factor derived from rate polymorphonuclear cells (Prostaglandins 27, 697, 1984). E-5110 inhibited PGE2 generation by the synovial cells. The IC50 values (microM) for inhibition of PGE2 generation were 0.026 for E-5110, 0.008 for indomethacin, 0.112 for piroxicam, 0.003 for R-830, 0.667 for BW-755C and 2.05 for benoxaprofen. Calcium ionophore A-23187-stimulated LTB4 generation by human neutrophils was inhibited by E-5110 with an IC50 value of 0.20 microM, which was similar to NDGA. The inhibition of LTB4 by E-5110 was more potent than that of R-830, BW-755C or benoxaprofen. E-5110 also inhibited superoxide generation by human neutrophils stimulated with opsonized zymosan, f-Met-Leu-Phe and phorbol myristate acetate. These results indicate that E-5110 is a potent dual inhibitor that suppresses superoxide generation.

Animals↗
PubMed1987

Synthesis and antiinflammatory activities of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-ones.

A series of 3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-ones was synthesized and evaluated as candidate antiinflammatory/analgesic agents as well as dual inhibitors of prostaglandin and leukotriene synthesis. Some compounds that showed dual inhibitory activity were found to possess equipotent antiinflammatory activities to indomethacin, with reduced ulcerogenic effects. One of the compounds, N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-o ne, was found to have a wider safety margin than indomethacin or piroxicam, and was selected for detailed evaluation as a candidate drug for clinical application.

Animals↗
PubMed1987

Effect of the novel non-steroidal antiinflammatory agent N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-one on in vitro generation of some inflammatory mediators.

A newly synthesized compound, the non-steroidal antiinflammatory agent N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-o ne (E-5110) was investigated. E-5110 inhibited prostaglandin E2 (PGE2) generation by cultured rat synovial cells upon stimulation with interleukin-1-like factor of rat polymorphonuclear leucocytes (PMN). The IC50 values (mumol/l) for PGE2 generation were 0.026 for E-5110, 0.008 for indometacin, 0.112 for piroxicam and 0.667 for the compound B (3-amino-1-(M-trifluoromethyl-phenyl-2-pyrazoline). Calcium ionophore A23187-stimulated leukotriene B4 generation by human PMN was inhibited by E-5110 with an IC50 value of 0.20 mumol/l; E-5110 was as inhibitory as nordihydroguaiaretic acid and was more potent than the compound B (IC50 of 2.58 mumol/l). E-5110 suppressed superoxide generation by human PMN stimulated with opsonized zymosan, f-Met-Leu-Phe and phorbol myristate acetate. E-5110 also inhibited the generation of leucocytic pyrogen and leucocyte factor(s) which stimulated collagenase production by cultured synovial cells.

Animals↗
PubMed1987

Pharmacological properties of the novel non-steroidal antiinflammatory agent N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2 -one.

The antiinflammatory activity of the novel pyrrolidin-2-one derivative N-methoxy-3-(3,5-di-tert-butyl-4-hydroxybenzylidene)pyrrolidin-2-o ne (E-5110) was investigated and compared with those of indomethacin and piroxicam in various antiinflammatory, analgesic and antipyretic animal models. The acute antiinflammatory activity of E-5110 on the carrageenin paw edema was similar to that of indomethacin, and half that of piroxicam. The chronic inflammatory responses in established adjuvant- and type II collagen-induced arthritis, which are widely used models of rheumatoid arthritis, were suppressed as effectively by E-5110 as by indomethacin and piroxicam. E-5110 decreased the pleural exudate volume and inhibited leucocyte infiltration in a reversed passive Arthus reaction more potently than indomethacin, suggesting that mediators other than prostaglandin E2 may play an important role in this inflammatory process. The analgesic potency of E-5110 against inflammatory pain was similar to that of indomethacin or piroxicam, but the antipyretic activity of E-5110 was more potent than that of the reference drugs. The ulcerogenic effect of E-5110 on rat gastric mucosa was less than those of indomethacin and piroxicam. In conclusion, E-5110 is a very potent antiinflammatory compound acting against various types of inflammation, and has a favorable therapeutic index.

Animals↗
PubMed1984

Stimulation of prostaglandin synthesis in cultured rat synovial cells by a factor derived from polymorphonuclear leukocytes.

Stimulation of synovial cell prostaglandin production by a factor obtained from casein-induced peritoneal polymorphonuclear (PMN) cells has been investigated. Both the extract and short time cultured medium of rat peritoneal PMN cells stimulate prostaglandin (PG)E2 production as well as collagenase production in the culture of rat synovial cells. PGE2 production by the cells in the presence of the PMN factor is much faster (5 to 24 hr) than collagenase production (24 hr or later, Biomedical Res. 3, 506-516, 1982). This stimulating factor is confirmed to be derived from PMN cells, based on the purification of the cells from peritoneal exudate cells by the Ficoll-Urographin method. Elution profile of the factor on gel filtration has indicated that both PGE2 and collagenase productions by synovial cells are stimulated by the same effluent fractions corresponding to molecular weights of 15,000 - 20,000 daltons and 30,000 - 40,000 daltons. These results suggest that PMN cells are involved in PG production as well as collagenase production in the inflamed tissue by stimulating connective tissue cells such as synovial cells.

Animals↗
PubMed1984

Determination of inflamed paw surface temperature in rats.

The surface temperature of a rat's paw is greatly affected by heat transfer because of its contacts with the body, as well as several environmental conditions. To establish a methodology for determining the surface temperature of the inflamed rat's paw, we devised an individual cage with a pair of rolling rods. The rods were set to protect contacts of paws with the body and were devised to roll easily when rats put their feet on the rods. When a rat was transferred to the individual cage with rolling rods from a group cage, the surface temperature of a normal or inflamed paw fell gradually and reached equilibrium within 10 minutes. The application of the rolling rods markedly narrowed the range of fluctuation of paw surface temperatures at the equilibrium, and increased the temperature difference between inflamed and noninflamed paws. We compared local hyperthermia and swelling of inflamed paws, and tested the effects of indomethacin. The results suggest that the local hyperthermia is a useful index of inflammation and a sensitive parameter for the pharmacological evaluation of antiinflammatory drugs.

Animals↗
PubMed1982

Comparison of Tl-201 chloride and Ga-67 citrate scintigraphy in the diagnosis of thyroid tumor: concise communication.

Twenty-five patients with thyroid tumors were scintigraphed with both Tl-201 chloride and Ga-67 citrate. All cases showed a focal area of decreased activity with I-131 or pertechnetate (Tc-99m), and each had a histological diagnosis after surgery or excisional biopsy. From the data we conclude the following: (1) Tumors giving a positive scan with Tl-201 chloride but negative results using Ga-67 citrate prove to be differentiated carcinoma or poorly differentiated adenoma. (2) All tumors that are positive with Ga-67 are highly malignant types, and if these tumors are negative by Tl-201, undifferentiated carcinoma is suggested. (3) Ga-67 citrate scintigraphy is a useful procedure in locating distant metastases, in determining the area to be irradiated, and in judging the effect of therapy on undifferentiated carcinoma.

Adenocarcinoma↗
PubMed1982

[Comparison of 201T1-chloride and 67Ga-citrate in thyroid tumor scintigraphy].

Twenty-five patients with thyroid tumors were examined by 201T1-chloride and 67Ga-citrate scintigraphy heterochronously in our department. All cases showed the cold nodule with 131I or 99mTc-pertechnetate thyroid scintigraphy and each one was given a histological diagnosis after surgery or excisional biopsy. In 15 cases of thyroid carcinoma, 12 (80%) were positive by 201T1-chloride; 4 (26.7%) were positive by 67Ga-citrate. In examining each histological type, 8 of 9 cases of papillary carcinoma (88.9%) were positive by 201T1-chloride. In 1 negative case the tumor was almost completely encysted; however, they were all negative by 67Ga-citrate. In 2 patients with follicular carcinoma, both of them revealed a positive figure by 201T1-chloride, and one of these with oxyphilic cell carcinoma showed a positive figure by 67Ga-citrate. In 1 case of medullary carcinoma there was slight accumulation with 201T1-chloride, but there was no accumulation with 67Ga-citrate. In 3 cases of undifferentiated carcinoma, 2 patients with small carcinoma showed a negative figure by 201T1-chloride. However, they all showed a positive figure using 67Ga-citrate and this medium also disclosed distant metastases of undifferentiated carcinoma. In 10 patients with thyroid adenoma, 3 (30%) showed a positive figure by 201T1-chloride. Histologically, these were all tubular adenoma, but in all cases of thyroid adenoma 67Ga-citrate revealed a negative figure. From the above mentioned results, the following conclusion were reached. Tumors showing a positive figure by 201T1-chloride that elicited negative results using 67Ga-citrate proved to be differentiated carcinoma or low differentiated types of adenoma. Surgery is indicated in these cases. All of the tumors revealing a positive figure by 67Ga-citrate were highly malignant types. If these tumors showed a negative figure when 201T1-chloride was used, undifferentiated carcinoma was suggested. In undifferentiated carcinoma, 67Ga-citrate scintigraphy is a useful procedure in locating distant metastases, in determining the area to be irradiated, and in judging the effect of therapy.

Adenocarcinoma↗
PubMed1981

Diagnostic usefulness of 201Tl-chloride scintigraphy for preoperative localization of parathyroid tumors.

201Tl-chloride scintigraphy was performed in 10 patients with hyperparathyroidism to assess the localization of abnormal parathyroid glands. This approach proved to be useful in 8 of 10 patients. In particular, an intramediastinal ectopic gland was clearly demonstrated in one patient. Several disadvantages were noted, however, 201Tl-chloride scintigraphy could be the first choice for preoperative localization of abnormal parathyroid glands. If a negative image is obtained, further examinations such as arteriography or parathyroid hormone assay be selective venous blood sampling should be done.

Adult↗