Antiallergic effect of ardisiaquinone A, a potent 5-lipoxygenase inhibitor.

The antiallergic effects of ardisiaquinone A, a potent 5-lipoxygenase inhibitor, were examined. Pretreatment with ardisiaquinone A (0.1-10 microM) significantly inhibited compound 48/80-induced production of cysteinyl-leukotrienes (cys-LTs; LTC4, LTD4 and LTE4) in rat peritoneal mast cells, but not histamine release. The IC50 value was 5.56 microM. Pre-administration with ardisiaquinone A (0.1-1 mg/kg, s.c.) dose-dependently inhibited rat homologous passive cutaneous anaphylaxis (PCA) and the maximal inhibitory ratio was 22.3 +/- 3.9% at the dose of 1 mg/kg. Ardisiaquinone A (1-5 mg/kg, s.c.) dose-dependently prevented the allergen-induced increase of tracheal pressure in ovalbumin-sensitized guinea pigs, especially during the late phase. In conclusion, the findings of this study show that 5-lipoxygenase inhibitor ardisiaquinone A partially attenuates the allergen-induced increases of vascular permeability and tracheal pressure via the inhibition of cys-LTs production in mast cells.

The Bisurface total knee replacement: a unique design for flexion. Four-to-nine-year follow-up study.

BACKGROUND: The Bisurface knee prosthesis was designed in 1989 to improve knee flexion without affecting the durability of the prosthesis. The prosthesis has a unique ball-and-socket joint in the midposterior portion of the femoral and tibial components, which functions as a posterior stabilizing cam mechanism and causes femoral rollback. The femoral component was made of alumina ceramic. The purpose of this study was to review the clinical results of the first 223 arthroplasties performed with this prosthesis in order to assess whether this new implant had achieved its design objectives. METHODS: From December 1989 to May 1994, all patients who were scheduled for primary total knee arthroplasty were enrolled in a prospective study of the Bisurface knee. The patients were evaluated clinically according to The Hospital for Special Surgery knee-rating system and with a self-administered questionnaire, and they were evaluated radiographically according to the system of the Knee Society. Kaplan-Meier survivorship analysis was performed with revision of the knee or recommendation for revision as the end point. RESULTS: One hundred and sixty-six patients treated with a total of 223 consecutive primary total knee arthroplasties were enrolled in the study, and 182 knees were followed for 3.9 to 9.0 years (mean, 5.8 years). Preoperatively, the mean Hospital for Special Surgery knee score was 44.5 points. At the time of latest follow-up, the mean knee score was 86.3 points. The mean preoperative and postoperative ranges of flexion were 119 and 124 degrees, respectively. The patients, even those with a good preoperative range of motion, rarely lost deep flexion of the knee after the procedure. A revision operation was performed in eight knees (because of infection in five, instability in two, and breakage of the peg of the patellar component in one). Two knees had recurrent medial-lateral subluxations of the femorotibial articulation, which were treated nonoperatively. No prosthesis had loosened aseptically and no alumina ceramic femoral component had broken by the time of latest follow-up. The rate of survival of the implant was 94 percent (95 percent confidence interval, 90 to 98 percent) at six years. According to the patient questionnaires, 20 percent of the knees sometimes felt loose in daily living activities, which prompted us to improve the intrinsic stability of the prosthesis by improving the congruity of the ball-and-socket joint. CONCLUSIONS: Total knee arthroplasty with the Bisurface prosthesis resulted in an excellent range of motion and a high level of satisfaction with the operation; the durability of the prosthesis is promising.

Effects of tannins and related polyphenols on superoxide-induced histamine release from rat peritoneal mast cells.

The effects of tannins and related polyphenols on KO2- and compound 48/80-induced histamine release from rat peritoneal mast cells were examined. Pretreatment with hydrolyzable tannins (1-100 microM) significantly inhibited KO2-induced histamine release. Dimeric ellagitannins, which have hexahydroxydiphenoyl (HHDP) and valoneoyl residues and/or a valoneoyl-related acyl unit in the molecule, showed more potent inhibitory effects than monomeric hydrolyzable tannins. The most effective inhibition was exhibited by agrimoniin and euphorbin C (IC50 0.68 and 0.80 microM), which have dehydrodigalloyl and euphorbinoyl groups, respectively, as well as the HHDP group. However, procyanidins, flavonoids and related polyphenols with small molecular weights, except for epigallocatechin gallate, exhibited negligible effects. Although clinically used antiallergic drugs, azelastine, astemizole, ketotifen and epinastine have been shown to prevent KO2-induced histamine release, their potencies were all less than those of ellagitannins. An inhibitory effect on compound 48/80-induced histamine release was also exhibited by higher molecular weight tannins. The inhibitory effect on histamine release caused by different stimulants suggested that ellagitannins act as cell membrane stabilizers as well as radical scavengers.

Anti-tumour effects of localized hyperthermia on an experimental bone tumour using an intramedullary nail.

A new localized hyperthermia system for an experimental bone tumour in the rabbit tibia was developed. This system was composed of an induction coil, generator and a Kirschner wire, which was inserted into the medullary canal of the tibia as a heat-generating ferromagnetic implant. The metastatic bone tumour model was created by implantation of VX2 carcinoma in the medullary canal of the tibia diaphysis. The days after VX2 implantation, hyperthermia was induced for 50 min. Three weeks after the treatment, rabbits were sacrificed for histological and radiological evaluation. According to the semi-quantitative scoring system, anti-tumour effects of the single dose of hyperthermia was noted radiologically (p < 0.01) and histologically (p < 0.05) where the temperature was at a sufficient level to cause hyperthermia (> 42.5 degrees C). This new heating method, which is relatively simple and clinically applicable, appears to be promising for the treatment of metastatic tumours of the long bone.

Cloning of a mouse smoothened cDNA and expression patterns of hedgehog signalling molecules during chondrogenesis and cartilage differentiation in clonal mouse EC cells, ATDC5.

Hedgehog (hh) family proteins appear to use the conserved targets in their signalling pathway including Patched (Ptc), Smoothened (Smo), and Gli. Although Indian hedgehog (Ihh) plays an important role in endochondral bone formation, the involvement of hh signalling molecules in skeletogenesis is unknown. We cloned a mouse (m) Smo cDNA and studied the expression patterns of Ihh, Ptc, Smo, and Gli mRNAs in mouse chondrogenic EC cells, ATDC5. The deduced amino acid sequence of mSmo consisted of 793 amino acids and was 98 and 93% homologous to the rat (r) Smo and human (h) Smo, respectively. In ATDC5 cells, the expression of Ihh mRNA paralleled that of type X collagen mRNA. Smo, Ptc, and Gli mRNAs were constitutively expressed throughout chondrogenesis and the subsequent cartilage differentiation processes except for the transient decrease in Ptc mRNA at the cellular condensation stage. Our data suggest that hh signalling molecules may be involved in chondrogenesis and cartilage differentiation in ATDC5 cells.

Anti-allergic effect of tea-leaf saponin (TLS) from tea leaves (Camellia sinensis var. sinensis).

We investigated the anti-allergic effect of tea-leaf saponin (TLS), which was a mixture of saponins separated from the leaves of Camellia sinensis var. sinensis, in guinea pigs and rats. TLS (20-100 mg/kg) dose-dependently inhibited experimentally-induced asthma, and ID50 was 61.7 mg/kg. TLS (20-100 mg/kg) dose-dependently inhibited a 48 h homologous PCA (passive cutaneous anaphylaxis) reaction, and the inhibitory effect was similar to that of tranilast. TLS (1-100 microg/ml) also inhibited the release of antigen-induced leukotriene (LT) C4 from sensitized guinea pig lung samples in a dose-dependent fashion, but did not prevent histamine release. TLS (0.01-0.5 microg/ml) inhibited histamine release from rat peritoneal mast cells induced by compound 48/80. At higher concentrations, TLS elicited histamine release. These findings suggest that TLS may be a useful protective agent against clinical allergy, and that the inhibitory effects of TLS on mediator release are in some way related to its inhibitory effect on experimentally-induced asthma and PCA reaction.

Anti-allergic constituents in the culture medium of Ganoderma lucidum. (I). Inhibitory effect of oleic acid on histamine release.

The chloroform extract from Ganoderma lucidum broth markedly inhibited histamine release from rat peritoneal mast cells. From the active fractions, palmitic acid, stearic acid, oleic acid and linoleic acid were isolated. Oleic acid dose-dependently inhibited the histamine release and 45Ca uptake into mast cells induced by compound 48/80 and A-23187 at concentrations of 5 to 50 microM and 0.5 to 5 microM, respectively. Saturated fatty acids, however, had only a weak inhibitory effect on histamine release. Although linoleic acid and linolenic acid effectively prevented this release, these two compounds caused marked release at concentrations higher than 10 microM and 20 microM, respectively. Oleic acid induces membrane-stabilization in model membrane systems. It was concluded that one of the effective constituents obtainable from the chloroform extract of G. lucidum-cultured broth is oleic acid.

Anti-allergic constituents in the culture medium of Ganoderma lucidum. (II). The inhibitory effect of cyclooctasulfur on histamine release.

For centuries, Ganoderma lucidum has been used in Oriental medicine for the treatment of chronic bronchitis. Sequential fractions of the culture medium of this plant revealed that one of the active constituents was cyclooctasulfur. The latter effectively inhibited histamine release from rat peritoneal mast cells and impeded 45Ca uptake into these cells without affecting the cyclic AMP content. SDS-PAGE analysis indicated that cyclooctasulfur induced some changes in protein bands obtained from the membrane fraction of mast cells, suggesting that this compound interacts with membrane proteins so as to inhibit 45Ca uptake, and that this may be the main cause of histamine release inhibition.

Isolation of complementary DNA clones for genes exhibiting reduced expression after treatment of mouse teratocarcinoma stem cells with a tumor-promoting phorbol ester.

For the study of the effects of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) on early mammalian cell differentiation, a complementary DNA (cDNA) library was constructed on the poly(A)+RNAs extracted from undifferentiated F9 cells derived from a 129/Sv mouse teratocarcinoma OTT6050, and screening was done for the cNDA sequences corresponding to the mRNAs, the levels of which decreased significantly in the F9 cells after the TPA treatment. From about 80,000 clones screened, 3 different cDNA clones, pFT27, pFT43, and pFT60, were isolated and characterized. Levels of the RNAs hybridizable to these clones were decreased by fourfold to more than fiftyfold within 1-10 hours in the presence of TPA. Northern blotting experiments identified transcripts corresponding to these clones: pFT27 hybridized to 3.0 kb RNA, pFT43 hybridized to 1.5 kb RNA, and pFT60 hybridized to 1.0 kb RNA. The levels of these 3 transcripts were also decreased after treatment of the undifferentiated F9 cells with retinoic acid (RA) and dibutyryl cyclic AMP (cAMP). The TPA-induced as well as the RA- and cAMP-induced decreases in the RNAs hybridizable to pFT27 were regulated at the transcriptional level, whereas similar decreases in the RNAs hybridizable to pFT43 and pFT60 were regulated at the post-transcriptional level. These findings show that TPA treatment shares common effects with RA and cAMP on the undifferentiated F9 cells.

Solitary ulcer of the rectum: report of a case and review of the literature.

A 13-year-old girl with Prader-Willi syndrome was admitted to our hospital with an 18-month history of anal bleeding and mucus discharge on defecation. Physical examination revealed obesity, hypogonadism, hypotonia and hypomentia. On digital examination, a nodular mass was palpated on the right wall of the ampulla recti, which was suspected to be carcinoma on a barium enema study. Proctoscopic examination revealed a large, irregular ulceration with white slough at the base, surrounded by the nodular and lumpy mucosa. The lesion was excised by the abdomino-anal pull-through method. The resected specimen showed a lesion of large, shallow, irregular ulcer, 5.0 x 2.2 cm in size. Microscopic examination revealed obliterated lamina propria by fibroblasts and muscle fibers derived from the muscularis mucosae, and misplaced cystic dilated glands in the submucosa at the margin of the ulcer. The gross and microscopic appearances are identical to those of "solitary ulcer of the rectum" described by Madigan and others, and similar to those of "colitis cystica profunda" described by Goodall and others. According to these findings, this lesion was diagnosed as solitary ulcer of the rectum. In the present report, the relationship between solitary ulcer of the rectum and colitis cystica profunda was discussed.

Effects of diphenhydramine, naphazoline and m-amino-alpha(1-aminoethyl)benzyl alcohol dihydrochloride on the nasal mucosa determined by impedance method: a simple method for evaluation of nasal decongestant.

A simple, new method was devised for evaluating nasal decongestants. In anesthetized dogs, two needle electrodes were inserted bilaterally into the superficial mucosa of the nasal wings. An impedance plethysmorgraphy provided with a DC output was used to measure impedance between the two electrodes. When 1% histamine solution was sprayed into a nostril focusing on the inside mucosa of a nasal wing, impedance decreased markedly and thereafter recovered to a control level within 1-1.5 h. Comparable responses were obtained when the same solution was sprayed into the opposite nostril. The drugs to be tested were administered intravenously or topically between these two histamine application. Intravenous administrations of diphenhydramine (0.5 mg/kg) and m-amino-alpha)1-aminoethyl) benzyl alcohol dihydrochloride (0.1 mg/kg) inhibited the histamine effect completely. Pretreatment with naphazoline administered topically also inhibited impedance changes cause by histamine application. Local appliations of acetycholine (10%) and bradykinin (0.1%) did not change nasal impedance significantly in any instances.