Small bowel perforation due to ingested frog bone: a case report.

Perforation of the gastrointestinal tract by ingested foreign body is an uncommon surgical emergency, most typically associated with the consumption of fish and chicken bones. We present an unusual case of a gentleman presenting emergently with an acute abdomen following ingestion of a meal containing frog meat. Emergent computed tomography (CT) revealed findings suggestive of jejunal perforation due to a foreign body. At laparotomy, a mid-jejunal site of perforation was noted due to a protruding piece of fractured frog bone. Washout and primary repair of the small bowel enterotomy were performed, and the patient made an excellent post-operative recovery.

Prevention of 1-palmitoyl lysophosphatidylcholine-induced inflammation by polyunsaturated acyl lysophosphatidylcholine.

OBJECTIVE: The aim of this study was to examine the inflammation induced by saturated acyl lysophosphatidylcholine (LPC) in vivo and to investigate whether it could be attenuated by the action of polyunsaturated acyl lysophosphatidylcholines (LPCs), which are known as anti-inflammatory lipid mediators. METHODS: First, saturated acyl LPC was administered intraperitoneally (i.p.) to mice and the inflammatory profile was extensively characterized. Subsequently, the preventive effect of polyunsaturated acyl LPCs, i.p. administered 30 min after saturated acyl LPC, was evaluated by measuring indices of inflammation such as leukocyte migration, plasma leakage, and eicosanoid or cytokine formation by light microscopy, Evans blue dye as indicator, and enzyme-linked immunosorbent assay, respectively. RESULTS: Saturated acyl LPCs as LPC16:0 (100 mg/kg, i.p.) proved to be an effective inflammation inducer which causes a significant increase in plasma leakage, leukocyte migration into peritoneum and elevation of pro-inflammatory mediators. Interestingly, LPC20:4 and LPC22:6 (50 and 150 µg/kg) significantly nullified LPC16:0-induced inflammation. The anti-inflammatory effects of LPC20:4 and LPC22:6 were related to down-regulation of leukocyte extravasation, plasma leakage, and formation of pro-inflammatory mediators (IL-5, IL-6, NO, 12-HETE and PGE(2)) stimulated by LPC16:0, and up-regulation of anti-inflammatory mediators (IL-4 and IL-10). CONCLUSION: These results indicated that the pro-inflammatory activity of saturated acyl LPCs could be antagonized by the actions of polyunsaturated acyl LPCs, anti-inflammatory lipid mediators.

2-Polyunsaturated acyl lysophosphatidylethanolamine attenuates inflammatory response in zymosan A-induced peritonitis in mice.

In the present study, the anti-inflammatory action of lysophosphatidylethanolamine (lysoPtdEtn), orally administered, in zymosan A-induced peritonitis was examined. Oral administration of 2-DHA-lysoPtdEtn (ED(50), ~111 µg/kg) or 2-ARA-lysoPtdEtn (ED(50), 221 µg/kg) was found to inhibit the plasma leakage in mice treated with zymosan A. In support of this, 2-polyunsaturated acyl-lysoPtdEtn diminished the formation of LTC(4), a lipid mediator responsible for vascular permeability. Next, 2-DHA-lysoPtdEtn (ED(50), 110 µg/kg) or 2-ARA-lysoPtdEtn (ED(50), 123 µg/kg) effectively inhibited the leukocyte extravasation into the peritoneum. Consistent with this, each polyunsaturated-lysoPtdEtn diminished the formation of LTB(4) and 12-HETE, potent chemotactic factors. Additionally, the level of pro-inflammatory mediator (IL-1 ß, IL-6, TNF-α or NO) was lowered remarkably in contrast to the augmentation of anti-inflammatory interleukin IL-10. Furthermore, 2-(15-HETE)-lysoPtdEtn and 2-(17-HDHE)-lysoPtdEtn, 15-lipoxygenation product of 2-ARA-lysoPtdEtn and 2-DHA-lysoPtdEtn, respectively, were more potent than corresponding lysoPtdEtn, suggesting the action of 2-acyl-lysoPtdEtn might be expressed through 15-lipoxygenation. In support of this, the formation of 15-HETE and LXA(4) was upgraded in accordance with an increasing dose of 2-ARA-lysoPtdEtn. Separately, anti-inflammatory actions, 2-polyunsaturated acyl-lysoPtdEtns also drastically diminished leukocyte infiltration in a later phase of zymosan A-induced peritonitis, indicating that these lipids also possess pro-resolving activity. Taken together, it is suggested that polyunsaturated lysoPtdEtns and their lipoxygenation derivatives, could be classified as potent anti-inflammatory lipids.

Mechanisms for anti-inflammatory effects of 1-[15(S)-hydroxyeicosapentaenoyl] lysophosphatidylcholine, administered intraperitoneally, in zymosan A-induced peritonitis.

BACKGROUND AND PURPOSE: Lysophosphatidylcholines (lysoPCs) with polyunsaturated acyl chains are known to exert anti-inflammatory actions. 15-Lipoxygeanation is crucial for anti-inflammatory action of polyunsaturated acylated lysoPCs. Here, the anti-inflammatory actions of 1-(15-hydroxyeicosapentaenoyl)-lysoPC (15-HEPE-lysoPC) and its derivatives were examined in a mechanistic analysis. EXPERIMENTAL APPROACH: Anti-inflammatory actions of 15-HEPE-lysoPC in zymosan A-induced peritonitis of mice were examined by measuring plasma leakage and leucocyte infiltration, and determining levels of lipid mediators or cytokines. KEY RESULTS: When each lysoPC, administered i.v., was assessed for its ability to suppress zymosan A-induced plasma leakage, 15-HEPE-lysoPC was found to be more potent than 1-(15-hydroperoxyeicosapentaenoyl)-lysoPC or 1-eicosapentaenoyl-lysoPC. Separately, i.p. administration of 15-HEPE-lysoPC markedly inhibited plasma leakage, in contrast to 15-HEPE, which had only a small effect. 15-HEPE-lysoPC also decreased leucocyte infiltration. Moreover, it reduced the formation of LTC4 and LTB4, 5-lipoxygenation products, as well as the levels of pro-inflammatory cytokines. The time-course study indicated that 15-HEPE-lysoPC might participate in both the early inflammatory phase and resolution phase. Additionally, 15-HEPE-lysoPC administration caused a partial suppression of LTC4-induced plasma leakage and LTB4-induced leucocyte infiltration. In the metabolism study, peritoneal exudate was shown to contain lysoPC-hydrolysing activity, crucial for anti-inflammatory activity, and a system capable of generating lipoxin A from 15-hydroxy eicosanoid precursor. CONCLUSIONS AND IMPLICATIONS: 15-HEPE-lysoPC, a precursor for 15-HEPE in target cells, induced anti-inflammatory actions by inhibiting the formation of pro-inflammatory leukotrienes and cytokines, and by enhancing the formation of lipoxin A. 15-HEPE-lysoPC might be one of many potent anti-inflammatory lipids in vivo.

Oral administration of 2-docosahexaenoyl lysophosphatidylcholine displayed anti-inflammatory effects on zymosan A-induced peritonitis.

Lysophosphatidylcholines (lysoPCs) have been known to be bioactive lipid mediators, which take part in various biological and pathological processes. In the present study, we examined the anti-inflammatory actions of 2-docosahexaenoyl lysophosphatidylcholine (2-docosahexaenoyl-lysoPC) in vitro as well as in vivo systems. When RAW 264.7 cells were treated with 2-docoshexaenoyl-lysoPC, a concentration-dependent decrease of LPS-induced formation of nitric oxide (NO), tumor necrosis factor alpha (TNF-α), or IL-6 was observed. Additionally, oral administration of 2-docosahexaenoyl-lysoPC was found to inhibit zymosan A-induced plasma leakage dose-dependently in mice with ED(50) value of 50 µg/kg and E (max) value of about 65%. Moreover, mechanistic study revealed that the anti-inflammatory action of 2-docosahexaenoyl-lysoPC seemed to be related largely to LTC(4) inhibition, but not PGE(2) inhibition. Moreover, 2-(17-hydroperoxydocosahexaneoyl)-lysoPC, intravenously administrated, was more effective than 2-docosahexaenoyl-lysoPC in the inhibition of zymosan A-induced plasma leakage, suggesting that 2-(17-hydroperoxydocosahexaneoyl)-lysoPC, a product from oxygenation of 2-docosahexaenoyl-lysoPC by 15-lipoxygenase (LOX), may be an active metabolite, intimately responsible for anti-inflammatory actions, generated from 2-docosahexaenoyl-lysoPC. In a related study, 2-docosahexaenoyl-lysoPC was found to be more efficient than 1-docosahexaenoyl-lysoPC or docosahexaenoic acid (DHA) as substrate for 15-lipoxygenases such as soybean LOX-1, leukocyte 12/15-LOX, and human 15-LOX-2. Taken altogether, it is suggested that 2-docosahexaenoyl-lysoPC and its oxygenation products may exert anti-inflammatory action after oral administration.

Lysophosphatidylcholine containing docosahexaenoic acid at the sn-1 position is anti-inflammatory.

Lysophosphatidylcholine is known to be a lipid mediator in various cellular responses. In this study, we examined the anti-inflammatory actions of lysophosphatidylcholine containing docosahexaenoic acid esterified at the sn-1 position. First, in RAW 264.7 cells, DHA-lysoPtdCho suppressed the LPS-induced formation of NO concentration-dependently. However, ARA-lysoPtdCho showed a partial suppression, and LNA-lysoPtdCho had no significant effect. Additionally, DHA-lysoPtdCho also reduced the level of TNF-alpha or IL-6, but not PGE(2). In animal experiments, the i.v. administration of ARA-lysoPtdCho (150 or 500 mug/kg) prevented zymosan A-induced plasma leakage remarkably with a maximal efficacy (Emax) of 50%, in contrast to no effect with LNA-lysoPtdCho. Remarkably, DHA-lysoPtdCho suppressed zymosan A-induced plasma leakage with an ED(50) value of 46 mug/kg and an Emax value of around 95%. Additionally, mechanistic studies indicated that the anti-inflammatory action of DHA-lysoPtdCho was partially related to the reduced formation of LTC(4,) TNF-alpha, and IL-6. When the interval time between lysoPtdCho administration and zymosan A challenge was extended up to 2 h, such a suppressive action of DHA-lysoPtdCho was augmented, suggesting that a DHA-lysoPtdCho metabolite is important for anti-inflammatory action. In support of this, 17-HPDHA-lysoPtdCho showed a greater anti-inflammatory action than DHA-lysoPtdCho. Furthermore, a similar anti-inflammatory action was also observed with i.p. administration of DHA-lysoPtdCho or a 17(S)-hydroperoxy derivative. Additionally, oral administration of DHA-lysoPtdCho also expressed a significant anti-inflammatory action. Taken together, it is proposed that DHA-lysoPtdCho and its metabolites may be anti-inflammatory lipids in vivo systems.

Purification and characterization of lysophospholipase C from pig brain.

In present study, lysophospholipase C (lysoPLC) was purified from homogenate of pig brain. LysoPLC was purified from brain membranes by procedures employing acetic acid precipitation, 1-butanol solubilization and ammonium sulfate fractionation, and chromatographies. In SDS-PAGE, the purified enzyme protein was relatively homogeneous with molecular mass of around 65 kDa. The lysoPLC activity possesses an optimal pH of 8.5, and Km and Vm values of 120.3 microM, and 141.6 micromole/h/mg protein, respectively for 1-lauroyl lysophosphatidylcholine(LPC), and 72.4 microM and 89.8 micromole/h/mg protein for glycerophosphorylcholine (GPC). In thermal denaturation at 60 degrees C, the enzyme expressed the same inactivation pattern in the hydrolysis of 1-lauroyl LPC and GPC. In the structure activity relationship, catalytic efficacy (Vm/Km value) was the greatest for 1-docosahexaenoyl LPC, followed by 1-arachidonoyl LPC, GPC, 1-hexanoyl LPC, 1-lauroyl LPC, 1-linoleoyl LPC, 1-myristoyl LPC and 1-oleoyl LPC. Metal ion requirement indicates that Zn(2+) was crucial for lysoPLC activity. Noteworthy, in the inhibition by oxyanions, the enzyme was selectively and noncompetitively inhibited by tellurite ions with Ki value of 0.16 and 0.18 microM in hydrolyzing 1-lauroyl LPC and GPC, respectively. Taken together, it is suggested that lysoPLC, possessing broad substrate specificity, may be implicated in the supply of phosphocholine in brain tissue.

Anti-inflammatory action of arachidonoyl lysophosphatidylcholine or 15-hydroperoxy derivative in zymosan A-induced peritonitis.

Arachidonic acid, released from PLA(2) hydrolysis of phosphatidylcholine, is converted to pro-inflammatory or anti-inflammatory mediators. Although lysophosphatidylcholine (lysoPC), another product, is known to be pro-inflammatory, the role of polyunsaturated lysoPCs is not clear. Here, we examined the role of arachidonoyl-lysoPC and its lipoxygenation product in inflammation. First, when the effect of arachidonoyl-lysoPC, administrated i.v., on zymosan A-induced plasma leakage in mice was examined, arachidonoyl-lysoPC was found to prevent zymosan A-induced plasma leakage remarkably. As the interval time between lysoPC administration and zymosan A challenge was extended, the suppression of plasma leakage was augmented, suggesting that a metabolism of arachidonoyl-lysoPC may be implicated in anti-inflammatory action. Additionally, 4-methyl-2-(4-methylpiperazinyl)pyrimido[4,5-b] benzothiazine, an inhibitor of 15-lipoxygenase, was found to diminish the suppressive action of arachidonyl-lysoPC, indicating that 15-HPETE-lysoPC may be a metabolite responsible for anti-inflammatory action of arachidonoyl-lysoPC. In support of this, 15-HPETE-lysoPC (ED(50), 32 microg/kg) exhibited a greater anti-inflammatory action than arachidonoyl-lysoPC. Further, mechanistic analysis indicates that anti-inflammatory action of 15-HPETE-lysoPC was related largely to the formation of lipoxin, and to less extent to the inhibition of LTC biosynthesis, but not to PGE formation. Further, i.p. administration of arachidonoyl-lysoPC or 15-HPETE-lysoPC also exhibited a dose-dependent effect, although less efficient than i.v. injection. Additionally, the time-dependent suppression was more remarkable for 15-HPETE-lysoPC than arachidonoyl-lysoPC, suggestive of different mechanisms for anti-inflammatory action in peritoneum. Taken together, it is proposed that arachidonoyl-lysoPC and its oxidation product may belong to endogenous lipids displaying anti-inflammatory effects in vivo.

Antioxidant and lipoxygenase inhibitory activity of oligostilbenes from the leaf and stem of Vitis amurensis.

ETHNOPHARMACOLOGICAL RELEVANCE: The root and stem of Vitis amurensis (Vitaceae) have popularly used as traditional medicine for treatment of cancer and various pains in Korea and Japan. Recent studies, its root and stem possess anti-inflammatory, anti-tumor activities, and protective effects against beta-amyloid-induced oxidative stress. AIM OF THE STUDY: This study deals with the isolation, structural identification of the potent bioactive compounds from the leaf and stem, and their antioxidant capacity, as well as anti-inflammatory effect via lipoxygenase inhibitory assay. MATERIALS AND METHODS: All isolated compounds yielded after using column chromatography were identified base on the physico-chemical properties and 1D, 2D NMR spectra. The scavenge ability against DPPH and ABTS(+) radicals, and to inhibit lipid peroxidation, as well as lipoxygenase type I inhibitory activity of all isolates were performed using in vitro assays. RESULTS: Eleven resveratrol derivatives (1-11), including a new oligostilbene cis-amurensin B (9), whose structures were determined on the basis of extensively spectral analyses, were isolated from the leaf and stem of Vitis amurensis. The isolates (1-11) were examined for their antioxidant activities by evaluating scavenge ability against DPPH and ABTS(+) radicals, and to inhibit lipid peroxidation. Stilbenes 1 and 4, and oligostilbenes 5-10 displayed moderate anti-lipid peroxidation activities, but all the isolates exhibited strong ABTS(+) radical scavenging activity in the dose-dependent manner. In addition, the isolates showed stronger inhibitory capacity against soybean lipoxygenase type I than that of baicalein, a positive control. Of the isolates, r-2-viniferin (8) exhibited the strongest scavenging activity against ABTS(+) radical with TEAC value of 5.57, and the most potential inhibitory effect on soybean lipoxygenase with the IC(50) value of 6.39 microM. CONCLUSION: This is the first report on the potential antioxidant and LOX-1 inhibitory effects of oligostilbenes isolated from the leaf and stem of Vitis amurensis. In addition, chemical compositions isolated from the leaf and stem are almost similar to those isolated from the root of Vitis amurensis. Therefore, the results may explain, in part, the uses of the leaf and stem, as well as the root of Vitis amurensis in the Korean traditional medicine.

Oxidative inactivation of lactonase activity of purified human paraoxonase 1 (PON1).

Paraoxonase1 (PON1), one of HDL-associated antioxidant proteins, is known to lose its activity in vivo systems under oxidative stress. Here, we examined the effect of various oxidants on lactonase activity of PON1, and tried to protect the lactonase activity from oxidative inactivation. Among the oxidative systems tested, the ascorbate/Cu(2+) system was the most potent in inactivating the lactonase activity of purified PON1; in contrast to a limited role of Fe(2+), Cu(2+) (0.05-1.0 microM) remarkably enhanced the inactivation of PON1 in the presence of ascorbate (0.02-0.1 mM). Moreover, Cu(2+) alone inhibited the lactonase activity at concentrations as low as 1 microM. The ascorbate/Cu(2+)-mediated inactivation of PON1 lactonase activity was prevented by catalase, but not general hydroxyl radical scavengers, suggesting the implication of Cu(2+)-bound hydroxyl radicals in the oxidative inactivation. Compared to arylesterase activity, lactonase activity appears to be more sensitive to Cu(2+)-catalyzed oxidation. Separately, ascorbate/Cu(2+)-mediated inactivation of lactonase activity was prevented by oleic acid as well as phoshatidylcholine. Taken together, our data demonstrate that Cu(2+)-catalyzed oxidation may be a primary factor to cause the decrease of PON1 lactonase activity under oxidative stress and that lactonase activity of PON1 is most susceptible to ascorbate/Cu(2+) among PON1 activities. In addition, we have showed that radical-induced inactivation of lactonase activity is prevented by some lipids.