Influence of non-steroidal anti-inflammatory drugs on antiplatelet effect of aspirin.

WHAT IS KNOWN AND OBJECTIVE: It has been reported that ibuprofen interferes with the antiplatelet effect of low-dose aspirin. This interaction is ascribed to steric hindrance at the active site of cyclooxygenase-1 by ibuprofen, when aspirin is administered after ibuprofen. However, whether other non-steroidal anti-inflammatory drugs (NSAIDs) interact with aspirin similarly is not well defined. The aim of this study was to assess the influence of nine NSAIDs on the antiplatelet effect of aspirin. METHODS: We investigated the antiplatelet effect of NSAIDs using steady-state plasma concentration reported after usual doses. We studied the in vitro antiplatelet effect of NSAID alone, aspirin alone, aspirin before NSAID addition and aspirin after NSAID addition to platelet-rich plasma. The rates of platelet aggregation induced by collagen were determined. The final concentration of aspirin used was the 50% effective concentration (EC(50)) previously estimated in vitro. RESULTS AND DISCUSSION: Ibuprofen and mefenamic acid interfere with the antiplatelet effect of aspirin when added before the latter. The rate of platelet aggregation was reduced by 48·1% and 22·7%, respectively. The other NSAIDs tested did not significantly affect the aspirin antiplatelet effect when exposure was prior to aspirin. None of the nine NSAIDs altered the aspirin effect if administration followed that of aspirin. WHAT IS NEW AND CONCLUSION: Naproxen and flurbiprofen have significant antiplatelet effects at plasma concentrations seen with usual doses. Our in vitro model suggests that the antiplatelet effect of aspirin is significantly diminished when taken after, but not before, ibuprofen or mefenamic acid. None of the other NSAIDs tested had any effect irrespective of the timing of dosing.

[MRI finding of CNS cryptococcosis in an HIV-positive patient].

We report an HIV-positive patient with CNS cryptococcosis, diagnosis of which was based on detection of Cryptococcus neoformans by Indian ink staining and culture of CSF. MRI displayed dilated Virchow-Robin space in bilateral basal ganglia which were hypointense on T1-weighted images, hyperintense on T2-weighted images, and enhanced by gadolinium administration. In addition cryptococcoma in the cerebellum was observed by MRI. This finding may suggest a progression from cryptococcal meningitis to intraparenchymal invasion, accompanied with breakdown of the blood brain barrier.

Impaired vitamin A-mediated mucosal IgA response in IL-5 receptor-knockout mice.

To clarify actions of vitamin A on mucosal immunity associated with interleukin-5 (IL-5), we examined effects of vitamin A on mucosal IgA level in IL-5 receptor alpha-chain-knockout (IL-5Ralpha(-/-)) mice. Daily supplementation of retinyl acetate (1 mg/mouse) increased Th2 cytokine levels and a number of their positive cells in the small intestinal mucosa of IL-5Ralpha(-/-) mice, as observed in wild-type or IL-5Ralpha(+/-) mice. Wild-type and heterozygous mice increased the IgA level and a number of IgA-containing cells in the mucosa in response to the vitamin A treatment, but not in IL-5Ralpha(-/-) mice. Retinyl acetate increased anti-cholera toxin (CT) IgA level in the mucosa of wild-type mice, improving their survival rate after an exposure to 0.4 mg of CT. However, retinyl acetate failed to induce resistance to CT toxicity in IL-5Ralpha(-/-) mice. Our results suggest that IL-5 may play an important role in an action of vitamin A on mucosal IgA system.

Interleukin-1beta enhances retinoic acid-mediated expression of bone-type alkaline phosphatase in rat IEC-6 cells.

We previously showed that vitamin A upregulated the expression of bone-type alkaline phosphatase (ALP) in fetal rat small intestine and rat intestinal IEC-6 cells. In this study, we examined interactions between retinoic acid (RA) and several growth factors/cytokines on the isozyme expression in IEC-6 cells. Epidermal growth factor and interleukins (ILs)-2, -4, -5, and -6 completely blocked the RA-mediated increase in ALP activity. In contrast, IL-1beta markedly increased the activity, protein, and mRNA of the bone-type ALP only when RA was present. IL-1beta and/or RA did not change the type 1 IL-1 receptor transcript level, whereas IL-1beta enhanced the RA-induced expressions of retinoic acid receptor-beta (RAR-beta) and retinoid X receptor-beta (RXR-beta) mRNAs and RA-mediated RXR response element binding. The synergism of IL-1beta and RA on ALP activity was completely blocked by protein kinase C (PKC) inhibitors. Our results suggest that IL-1beta may modify the ALP isozyme expression in small intestinal epithelial cells by stimulating PKC-dependent, RAR-beta- and/or RXR-beta-mediated signaling pathways.

Chronological changes in cerebral air embolism that occurred during continuous drainage of infected lung bullae.

We present a 43-year-old man with cerebral air embolism that occurred during continuous drainage of infected lung bullae. This complication is extremely rare, and may have been caused by the passage of air into the pulmonary venous circulation through a bronchovenous fistula and/or damaged pulmonary vessels. Air densities were demonstrated along the right frontal gyri on a CT performed 1 h after the onset of embolism, then moved to the deep cortex after 2.5 h. Three days later, a cortical infarct accompanied with extensive white matter edema in the right frontal lobe was confirmed by MRI. These CT and MRI findings may indicate the passage of intravascular air from the superficial to the deep cortex and subsequent cerebral infarction.

Vitamin A up-regulates expression of bone-type alkaline phosphatase in rat small intestinal crypt cell line and fetal rat small intestine.

Vitamin A is a potent inducer for liver/bone/kidney alkaline phosphatase (L/B/K ALP) in a variety of tissues. However, the evidence for induction of L/B/K ALP by vitamin A in small intestine is limited. In this study, we investigated the influence of vitamin A on L/B/K ALP expression in rat small intestinal crypt IEC-6 cells and fetal rat small intestine. Treatment of IEC-6 cells with all-trans retinoic acid (RA) increased the levels of activity, protein and mRNA of L/B/K ALP, whereas enterocyte-specific proteins, including intestinal ALP, sucrase-isomaltase and glucose transporter-2, were not induced. The reverse transcription-polymerase chain reaction technique revealed that this L/B/K ALP transcript had the bone-type but not the liver-type leader exon. IEC-6 cells constitutively expressed mRNAs of all subtypes of retinoic acid receptor (RAR) and retinoid X receptor (RXR) at varied concentrations. Among these receptor mRNAs, RARbeta mRNA quickly responded to RA treatment, and the level was doubled within 4 h. Gel mobility shift assay showed that RA induced an RXRE-binding activity in IEC-6 cells. The L/B/K ALP transcript, expressed in fetal rat small intestine, also contained the bone-type leader exon. Intragastric administration of 10 mg retinyl acetate to pregnant rats from gestational d 7 to 15 increased the levels of this transcript and enzyme in 15-d fetal rat small intestine. Our results suggest that vitamin A may be an important regulator for L/B/K ALP expression in fetal rat small intestine as well as in IEC-6 cells.

Induction of heme oxygenase protein protects neurons in cortex and striatum, but not in hippocampus, against transient forebrain ischemia.

To clarify whether heme oxygenase-1 (HO-1) protein plays a protective role against cerebral ischemia, we investigated the effects of an HO inhibitor (tin mesoporphyrin IX [SnMP] three doses of 30 micromol/kg, intraperitoneally) and an HO inducer (hemin, three doses of 30 micromol/kg, intraperitoneally) on the pathologic outcome and on the immunohistochemical reaction for HO-1 after 20-minute transient forebrain ischemia followed by 3-day reperfusion in rats. Hemin significantly increased viable neurons in the cortex (compared to the SnMP-treated group, P < .05) and striatum (compared to the saline-treated group at P < .01 and SnMP-treated group at P < .05), and intense HO-1 immunoreactivity was observed in cortex and striatum, whereas the administration of SnMP tended to decrease viable neurons in the parietal cortex. In contrast, neither hemin nor SnMP affected the pathologic outcome in the CA1 and CA3 hippocampi, in which HO-1 immunoreactivity was weak. These results suggest that induction of HO-1 protein may contribute to cellular defense against ischemic damage in brain regions where potential ability to synthesize HO-1 is retained in ischemia.

[An adult case of purulent meningitis secondary to retropharyngeal and deep neck abscess after treatment of odontogenic infection].

Retropharyngeal and deep neck abscess, which may follow odontogenic infection, is uncommon in adults, but can be fatal. Furthermore, bacterial meningitis secondary to this disorder is extremely rare. A 67-year-old man was brought to our hospital because he had developed neck pain, trismus, and disturbance of consciousness over several days. A few days prior to the appearance of neck pain, he had the periodontitis treated. Based on CSF, cervical X-ray and CT findings, he was diagnosed as having bacterial meningitis secondary to deep neck abscess. Culture of the CSF yielded gram-positive cocci, later identified as Gemella species, that is a rare organism for bacterial meningitis. Although the administration of antibiotics and drainage of the abscess resulted in gradual improvement of the infectious process, neurologically he remained with apallic syndrome. We would like to stress the importance of odontogenic and pharyngolaryngogenic sources as potential foci of purulent meningitis.

Inhibitory effects of dehydrocorydaline isolated from Corydalis Tuber against type I-IV allergic models.

An alkaloidal component, dehydrocorydaline (DHC) isolated from Corydalis Tuber (tuber of Corydalis turtschaninovii forma yanhusuo), has been screened for activity against types I-IV allergic reactions. In a type I allergic models, DHC at a dose of 0.5 mmol/kg, p.o. inhibited 48 h homologous passive cutaneous anaphylaxis (PCA) in rats, which is related to IgE. DHC also exhibited an inhibitory effect on antigen-induced histamine release from peritoneal mast cells. In a type II allergic model, DHC did not inhibit reversed cutaneous anaphylaxis (RCA) in rats. In a type III allergic model, DHC showed weak inhibition on direct passive arthus reaction (DPAR) in rats. Furthermore, in a type IV allergic model, DHC had inhibitory effects on the induction phase and effector phase in picryl chloride-induced contact dermatitis (PC-CD). These results indicated that DHC not only inhibits antibody-mediated allergic reactions but also influences cell-mediated allergia reactions, and the inhibitory effect of Corydalis Tuber on allergic reactions may be partially attributed to DHC.

Inhibitory effects of methanolic extract from corydalis tuber against types I-IV allergic models.

Methanolic extract (CM-ext) from tubers of Corydalis turtschaninovii forma yanhusuo has been screened for activity in experimental models of types I-IV allergy. In type I allergic models, CM-ext at doses of 200, 500 mg/kg, p.o. inhibited 48-h homologous passive cutaneous anaphylaxis (PCA) in rats which is related to IgE, and 4-h heterologous PCA in guinea pigs which is related to IgG. The inhibition of CM-ext on 48-h PCA was also recognized in adrenalectomized rats. CM-ext exhibited the inhibitory effect on formation of IgE antibody in BALB/c mice. In type II allergic model, it was found that CM-ext inhibits reversed cutaneous anaphylaxis (RCA). In type III allergic model, CM-ext showed the inhibitory effect on direct passive arthus reaction (DPAR) in rats. Furthermore, in type IV allergic model, CM-ext had the inhibitory effects on induction phase and effector phase in picryl chloride-induced contact dermatitis (PC-CD). It also showed therapeutic action on PC-CD. These results indicated that CM-ext not only inhibits antibody-mediated allergic reactions but also influences cell-mediated allergic reactions and should be recognized as a potent material for allergic reactions, although the mechanisms and active principles of CM-ext have not yet been completely determined.

Studies of anti-cataract drugs from natural sources. I. Effects of a methanolic extract and the alkaloidal components from Corydalis tuber on in vitro aldose reductase activity.

The inhibitory of Corydalis tuber (Corydalis turtschaninovii Besser forma yanhusuo Y. H. Chou et C. C. Hsu) was tested on crude rat lens aldose reductase, an enzyme involved in the complications of diabetes. The methanolic extract (CM-ext) inhibited aldose reductase, while the aqueous extract (CA-ext) was ineffective. Only dehydrocorydaline, of the seven alkaloidal components isolated from CM-ext, inhibited aldose reductase. It is suggested that the inhibitory effect of CM-ext on aldose reductase may be partially attributed to dehydrocorydaline.

Anti-inflammatory activities of methanolic extract and alkaloidal components from Corydalis tuber.

A methanolic extract (CM-ext) from Corydalis tuber (Corydalis turtschaninovii Besser forma yanhusuo Y. H. Chou et C. C. Hsu) has been screened for activity in experimental models of inflammation. CM-ext (200 or 500 mg/kg, p.o.) inhibited an increase in vascular permeability in mice induced by acetic acid, and reduced acute paw edema in rats induced by compound 48/80 or carrageenin. CM-ext suppressed the development of adjuvant-induced edema in arthritic rats. CM-ext and its alkaloidal components, dehydrocorydaline, d-glaucine and l-tetrahydrocoptisine inhibited compound 48/80-induced histamine release from peritoneal mast cells of rats. Since these substances from C. tuber were found to be effective in both the acute and chronic phases of inflammation, the crude drug C. tuber can be considered to exert anti-inflammatory activity.

Purification and Some Properties of an Erythrose Reductase from an Aureobasidium sp. Mutant.

An erythrose reductase was obtained from the cells of an Aureobasidium sp. mutant having high erythritol-producing activity. This enzyme was purified 600-fold over the cell-free extract by ammonium sulfate precipitation, ion exchange chromatography, affinity chromatography, and hydrophobic chromatography. It gave a single band on polyacrylamide gel electrophoresis, and had a molecular weight of 37,000 and an isoelectric point of 4.8. This enzyme had maximum reductive activity at 45°C and pH 6.5. The optimum pH of the oxidative reaction was 9.5. It was stable at pH 6.0-8.0 and below 40°C. The enzyme showed the maximum activity to D-erythrose. D-Glyceraldehyde was reduced at a rate 66% of that for D-erythrose. p-Nitrobenzaldehyde, L-erythrulose, dihydroxyacetone, and D-glucuronate were also reduced, although at slower rates. The oxidative activity was less than 0.1% of the reductive one.

Sympodiomycopsis: a new yeast-like anamorph genus with basidiomycetous nature from orchid nectar.

A description is provided for a new anamorph genus Sympodiomycopsis (Hyphomycetes), which is neither ballistosporogenous nor sterigmatosporogenous. The genus is typified by S. paphiopedili sp. nov. and accommodates one species which was isolated from nectar of Paphiopedilum primurinum in Japan. Phenotypically, the genus shows some similarity to Sympodiomyces because of the presence of a yeast morph with sympodial conidiogenous cell proliferation, but it is distinguished from that genus morphologically by a yeast morph with the enteroblastic-annellidic conidiogenesis and the conspicuous development of a hyphal morph with holoblastic-sympodial conidiogenous cells, and chemotaxonomically by the ubiquinone system Q-10 and 10% difference in the guanine plus cytosine (G + C) content of the nuclear DNA. Phylogenetically, the type of cell wall and septal pore ultrastructure, and the primary biochemical and chemotaxonomic characters of S. paphiopedili indicate a basidiomycetous affinity.