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Biomedical subjects

S Higuchi

Publications and source records attributed to S Higuchi.

At least 505 records · Page 28Linked to original sources

[Antiedema effects of basic nonsteroidal anti-inflammatory drugs that are not inhibitors of prostaglandin biosynthesis].

Antiedema effects of basic nonsteroidal anti-inflammatory drugs that don't inhibit prostaglandin biosynthesis were investigated with carrageenin-induced hind paw edema in rats. Locally administered mepirizole, tiaramide.HCl and aminopyrine, the basic nonsteroidal anti-inflammatory drugs, didn't show any suppression against the edema formation. In the case of indomethacin, phenylbutazone and ketoprofen, inhibitors of prostaglandin biosynthesis, they inhibited the edema formation. Inhibitory effects of orally and subcutaneously administered basic nonsteroidal anti-inflammatory drugs such as tiaramide.HCl and benzydamine on the edema formation were more potent in fasted rats than in nonfasted rats. In the case of acidic nonsteroidal anti-inflammatory drugs such as indomethacin and ibuprofen, their inhibitory activities were almost the same in both the fasted rats and nonfasted rats. These results suggest that the site of action of the basic nonsteroidal anti-inflammatory drugs such as tiaramide.HCl and mepirizole is not the inflamed site, and certain systemic effects may contribute to the anti-edema effects.

Animals↗

[The modes of anti-inflammatory and analgesic actions of aspirin and salicylic acid].

The modes of anti-inflammatory and analgesic actions of aspirin and salicylic acid were investigated using some experimental animal models. Anti-inflammatory potencies of aspirin were almost equal to those of sodium salicylate in the carrageenin hind paw edema, the cotton pellet granuloma and the adjuvant arthritis tests in rats. On the other hand, in the ultra-violet ray erythema and the arachidonic acid erythema tests in guinea pigs, aspirin was more potent than sodium salicylate. Aspirin and sodium salicylate exhibited almost the same inhibitions of the rat hind paw edema induced by a mixture of carrageenin and prostaglandin E1. These results suggest that inhibition of cyclo-oxygenase by aspirin does not play any important roles for the prevention of the vascular permeability increment and the granulation in the inflamed tissue. Aspirin may exert its antiinflammatory activity mainly as salicylic acid which is not an inhibitor of prostaglandins biosynthesis in vitro. Aspirin showed about 5 times more potent analgesic action than sodium salicylate in the lameness test using adjuvant arthritic rats. Analgesic potency of aspirin was decreased to the level of sodium salicylate by injection of prostaglandin E2 into the inflamed rat paw in the adjuvant-induced lameness test. On the other hand, analgesic potency of sodium salicylate was not decreased by the same treatment. It is concluded that aspirin has two analgesic effects on the inflammatory pain, one is inhibition of prostaglandins biosynthesis by acetylation of cyclo-oxygenase and the other is an action due to salicylic acid, but the action of salicylic acid was not totally explained by the inhibition of prostaglandins synthetase.

Animals↗

[The modes of anti-inflammatory and analgesic actions of 2-[4-(3-methyl-2-butenyl) phenyl] propionic acid (TA-60) and 2-[4-(2,2-dichlorovinyl) phenyl] propionic acid (TA-668) and effect of TA-60 on the gastrointestinal tract].

TA-668 and TA-60, potent anti-inflammatory compounds, showed no inhibition against the dextran-, the serotonin- and the carrageenin + prostaglandin E2 (PGE2)-induced hind paw edemas in rats and neither did typical acidic non-steroidal anti-inflammatory drugs (ANSAIDs) such as indomethacin. On the other hand, salicylic acid, mepirizole and tiaramide X HCl inhibited the hind paw edema induced by carrageenin + PGE2 in rats. TA-668 and TA-60 as well as other ANSAIDs inhibited the arachidonic acid (AA)-induced erythema, but did not inhibit the PGE2-induced erythema. Mepirizole and tiaramide X HCl showed no inhibition against both the AA- and the PGE2-induced erythemas. TA-668 and TA-60 showed analgesic activities in the adjuvant-induced hind paw edematous rats. The analgesic activities of these compounds disappeared when PGE2 was injected into the inflamed paw as well as indomethacin and ibuprofen. It is concluded that anti-inflammatory and analgesic activities of both TA-668 and TA-60 were based on the inhibition of cyclo-oxygenase. TA-60 showed a protective effect against gastric necrosis induced by necrotizing agents such as HCl, NaOH or NaOH + EtOH. TA-60 showed about a 4 times less potent activity than ibuprofen in delay of occurring time of castor oil-induced diarrhea in rats. These results suggest that the slight ulcerating effect of TA-60 on the gastrointestinal tract might be attributed to its gastric protective effect and slight decreasing effect on the gastrointestinal level of PGE2.

Animals↗

Interactions of 2-methyladenines and poly(m2A) with poly(br5U).

Mixing curve experiments and melting curve analyses have shown that poly(m2A) forms complexes with poly(br5U) with stoichiometries of either 1:1 or 1:2 in high ionic strengths. CD spectra of poly(m2A).poly(br5U) and poly(m2A).2 poly(br5U) both resemble quite well to those of poly(A). poly(br5U) and poly(A).2poly(br5U), respectively. This suggests that the corresponding complexes are closely related in the structural details. Significant similarities of the CD spectra were observed for poly(m2A).2poly(br5U) and complexes between 2,9-dimethyladenine or 2-methyladenosine and poly(br5U) in the presence of spermine, indicating also the 1:2 stoichiometry. Thus, a methyl group at the position 2 of adenine ring is not necessarily hindering a formation of the Watson-Crick type base pairings.

Adenine↗

Immunologic studies of peripheral blood in a child with hypogammaglobulinemia. Suggested mechanism for the development of malignant B-cell lymphoma.

A case of a 7-year-old boy with common variable hypogammaglobulinemia who developed B-cell-type non-Hodgkin's lymphoma is reported. Immunologic studies of his peripheral blood before the development of lymphoma revealed: (1) although peripheral T-cell and B-cell counts were normal, serum IgG and IgA levels were remarkably reduced; (2) DNA synthesis in response to phytohemagglutinin-P (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) stimulation were decreased; (3) DNA synthesis in response to EBV was enhanced; (4) in vitro IgG production with the patient's peripheral blood lymphocytes was significantly depressed; and (5) helper and suppressor activities of the patient's T-cells did not differ from that of normal controls. Six months after the investigation systemic involvement of malignant lymphoma appeared. The lymphoma was diagnosed as a lymphoblastic diffuse one. Lymph node cell marker analysis revealed that the lymphoblasts had surface mu and kappa chain, cytoplasmic IgM, and HLA-DR antigen. Blastogenesis of B-cell series may be suppressed by a feedback mechanism with the B-cells and antibody. In the current case, impairment of such a mechanism with defect of immunoglobulin production might finally induce malignant B-lymphoid proliferation.

Agammaglobulinemia↗

[Anti-inflammatory activity of a non-steroidal anti-inflammatory agent, oxaprozin, in experimental models].

Anti-inflammatory activity and mode of action of oxaprozin, a new non-steroidal anti-inflammatory agent, were investigated in experimental animal models and in vitro tests. Anti-inflammatory potency of oxaprozin was almost equal to that of aspirin in acetic acid vascular permeability, carrageenin hind paw edema, cotton pellet granuloma and adjuvant arthritis tests in rats. On the other hand, in mice, oxaprozin was more potent than aspirin, ibuprofen and phenylbutazone, and it was as potent as sulindac and fenbufen in acetic acid vascular permeability and carrageenin hind paw edema tests. In adrenalectomized rats, the anti-edema activity of oxaprozin in the carrageenin hind paw edema test was the same as that in intact rats. Oxaprozin inhibited erythema formation induced by ultra-violet rays in guinea pigs. The inhibitory potency of oxaprozin against prostaglandin E2 biosynthesis in vitro was equal to that of ibuprofen. Oxaprozin showed a concentration-dependent inhibition of heat-induced denaturation of bovine serum albumin and lysis of rabbit erythrocytes in vitro. However, oxaprozin did not inhibit rat hind paw edemas induced by dextran, formalin and serotonin. It was suggested from these results that the mode of action of oxaprozin is similar to those of other acidic non-steroidal anti-inflammatory drugs. Ulcerogenicity of oxaprozin was weaker than those of phenylbutazone and aspirin in rats. Species differences in the metabolic rate of oxaprozin were shown. The blood concentration of oxaprozin in rats is extremely low because the metabolic rate of oxaprozin is rapid in rats. Therefore, in rats, oxaprozin exhibited a weak anti-inflammatory effect. However, in mice, oxaprozin had a low metabolic rate, and the effect of oxaprozin was as potent as sulindac and fenbufen. The elimination half-life of oxaprozin is extended, 49 to 69 hr, in humans. It was suggested from these findings that oxaprozin is a potent and long acting anti-inflammatory drug in clinical use.

Animals↗

[Effects of anti-inflammatory drugs on the lame walking reaction in adjuvant-induced edematous rats].

Acute inflammatory paw edema of rats was formed by the injection of 0.5% Mycobacterium tuberculosis-liquid parraffin suspension into the hind paw, and then the pain threshold of the inflamed paw decreased. At that time, the rats showed a three-legged gait, namely, the lame walking reaction. The reaction was inhibited by acidic nonsteroidal anti-inflammatory drugs, e.g., indomethacin, ibuprofen and aspirin, inhibitors of prostaglandins biosynthesis, at a lower dose level than those in the Randall-Selitto test using yeast edematous rats and in the flection tests using adjuvant arthritic or silver nitrate arthritic rats. On the other hand, basic nonsteroidal anti-inflammatory drugs, e.g., tiaramide HC1, mepirizole and perisoxal citrate, not inhibitors of prostaglandins biosynthesis, were less potent than the acidic nonsteroidal anti-inflammatory drugs in the inhibition of the lame walking reaction. When prostaglandin E2 was injected into the inflamed paw, the inhibitory effects of acidic non-steroidal anti-inflammatory drugs on the reaction disappeared, but those of the basic nonsteroidal anti-inflammatory drugs didn't disappear. Bradykinin had no influence on the effects of both acidic and basic nonsteroidal anti-inflammatory drugs in the inhibition of the reaction. Analgesic evaluation with the lame walking reaction is more sensitive than with the Randall-Selitto or the flection methods. Morphine, pentazocine and acetaminophen inhibited the reaction, and these effects didn't disappear by the injection of prostaglandin E2 into the inflamed paw. These results suggest that prostaglandins play important roles in inflammatory pain, and the lameness test can serve as a new method for evaluating analgesics such as anti-inflammatory drugs and for investigating the mechanism of inflammatory pain.

Analgesics↗

NMR analyses on the molecular mechanism of the conformational rigidity of 2-thioribothymidine, a modified nucleoside in extreme thermophile tRNAs.

1H-NMR analyses have been made on the conformations of 2-thioribothymidine (s2T), 2-thiodeoxyribothymidine (s2dT), as well as ribothymidine (T) and deoxyribothymidine (dT). s2T and s2dT exclusively take the anti form rather than the syn form. The C3'-endo-gg form of the sugar moiety is remarkably stabilized on modification of T to s2T, but not on modification of dT to s2dT. The steric effects of the 2-thiocarbonyl group and the 2'-hydroxyl group cause the rigidity of the C3'-endo-gg form of s2T. Such rigidity of s2T probably contributes to the thermostability of 2-thiopyrimidine polyribonucleotides and extreme thermophile tRNAs.

Eubacterium↗

Raman diagnosis of nucleic acid structure: sugar-puckering and glycosidic conformation in the guanosine moiety.

Observations of Raman spectra of various nucleic acids indicate that the guanine ring breathing frequency is sensitive to the internal rotation angle around the glycosidic bond and to the conformation of the five-membered ring of the ribose residue that is directly connected with the guanine residue in question. It is found that 682 cm-1 for C2'-endo-anti, at 665 cm-1 for C3'-endo-anti, and at 625 cm-1 for C3'-endo-syn. A DNA octamer d(GpGpApApTpTpCpC) shows, in its aqueous solution, a broad Raman band at 680 cm-1 with a tail at 670 cm-1. This fact suggests that the guanosine residues in this oligomer take primarily C2'-endo-anti conformation but an appreciable amount of fluctuation of the ribose ring structure towards C3'-endo is involved.

Base Sequence↗