Liver angiosarcoma, a rare liver malignancy, presented with intraabdominal bleeding due to rupture--a case report.

Liver angiosarcoma is a rare disease, however it still ranks as the third of most common primary liver maligancies. The prognosis of liver angiosarcoma is very poor with almost all patients with this kind of disease die within 2 years after diagnosis. No specific symptoms and signs are closely associated with this disease. Here, we report a case presenting shock status at first due to rupture of liver angiosarcoma- induced internal bleeding. After emergent transarterial embolization (TAE), she received partial hepatectomy two weeks later. 4 months after operation, she is still with a good performance status without obvious recurrence or metastasis identified.

Effects of Castration Age on the Growth Performance of Nubian Crossbred Male Goats.

To determine the optimal timing for performing castration on goats, eighteen male Nubian crossbred goats were randomly assigned to two groups and castrated at 3 months and 6 months of age, respectively. Daily dry matter intake, biweekly body weights, and ultrasonic measurements of longissimus dorsi muscle growth were recorded. Results indicated that there was no significant difference between the two groups in terms of the blood parameter analysis (except testosterone, 0.36 ± 0.26 vs. 3.61 ± 0.27 ng/mL at 25 weeks old), economic analysis, and growth performance, including final body weight, total weight gain, average daily gain, total dry-matter intake, and feed conversion ratio (p > 0.05). However, the longissimus dorsi muscle depth of goats castrated at 6 months of age was significantly higher than that of goats castrated at 3 months of age. In conclusion, castration timing does not have a significant effect on the growth performance of goats; therefore, castrating goats at 3 months of age may be the best practice considering animal welfare and possible risks associated with late castration.

Point-of-care N-terminal pro B-type natriuretic peptide assay to screen apparently healthy cats for cardiac disease in general practice.

BACKGROUND: Point-of-care (POC) N-terminal pro B-type natriuretic peptide (NT-proBNP) ELISA test has been evaluated for screening cats for cardiac disease in the referral veterinary setting but less is known about its use in general practice (GP). OBJECTIVES: To evaluate the diagnostic utility of a POC NT-proBNP ELISA in cats seen in GPs. ANIMALS: Two hundred and seventeen apparently healthy cats from 21 GPs. METHODS: This was a prospective, cross-sectional study. Cardiac auscultation and POC NT-proBNP ELISA were done by veterinarians at their GPs. After enrollment at GPs, cats were sent to a cardiology referral hospital for cardiac auscultation and echocardiographic diagnosis. Results were interpreted based on whether cats had normal or abnormal echocardiographic findings. RESULTS: Point-of-care NT-proBNP ELISA results differentiated cats in the abnormal group from those in the normal group with a sensitivity of 43%, specificity of 96%. In cats with a heart murmur at GPs, POC NT-proBNP ELISA results differentiated cats in the abnormal group from those in the normal group with a sensitivity of 71% and a specificity of 92%. CONCLUSION AND CLINICAL IMPORTANCE: In apparently healthy cats in GPs, positive POC NT-proBNP results are associated with heart disease, warranting an echocardiogram, but negative results do not reliably exclude heart disease. These results suggest POC NT-proBNP is not an effective screening test for apparently healthy cats in GPs, although its performance is improved if it is used only in cats that have a heart murmur.

Dimemorfan protects rats against ischemic stroke through activation of sigma-1 receptor-mediated mechanisms by decreasing glutamate accumulation.

Dimemorfan, an antitussive and a sigma-1 (sigma(1)) receptor agonist, has been reported to display neuroprotective properties. We set up an animal model of ischemic stroke injury by inducing cerebral ischemia (for 1 h) followed by reperfusion (for 24 h) (CI/R) in rats to examine the protective effects and action mechanisms of dimemorfan against stroke-induced damage. Treatment with dimemorfan (1.0 microg/kg and 10 microg/kg, i.v.) either 15 min before ischemia or at the time of reperfusion, like the putative sigma(1) receptor agonist, PRE084 (10 microg/kg, i.v.), ameliorated the size of the infarct zone by 67-72% or 51-52%, respectively, which was reversed by pre-treatment with the selective sigma(1) receptor antagonist, BD1047 (20 microg/kg, i.v.). Major pathological mechanisms leading to CI/R injury including excitotoxicity, oxidative/nitrosative stress, inflammation, and apoptosis are all downstream events initiated by excessive accumulation of extracellular glutamate. Dimemorfan treatment (10 microg/kg, i.v., at the time of reperfusion) inhibited the expressions of monocyte chemoattractant protein-1 and interleukin-1beta, which occurred in parallel with decreases in neutrophil infiltration, activation of inflammation-related signals (p38 mitogen-activated protein kinase, nuclear factor-kappaB, and signal transducer and activator of transcription-1), expression of neuronal and inducible nitric oxide synthase, oxidative/nitrosative tissue damage (lipid peroxidation, protein nitrosylation, and 8-hydroxy-guanine formation), and apoptosis in the ipsilateral cortex after CI/R injury. Dimemorfan treatment at the time of reperfusion, although did not prevent an early rise of glutamate level, significantly prevented subsequent glutamate accumulation after reperfusion. This inhibitory effect was lasted for more than 4 h and was reversed by pre-treatment with BD1047. These results suggest that dimemorfan activates the sigma(1) receptor to reduce glutamate accumulation and then suppresses initiation of inflammation-related events and signals as well as induction of oxidative and nitrosative stresses, leading to reductions in tissue damage and cell death. In conclusion, our results demonstrate for the first time that dimemorfan exhibits protective effects against ischemic stroke in CI/R rats probably through modulation of sigma(1) receptor-dependent signals to prevent subsequent glutamate accumulation and its downstream pathologic events.

Anti-inflammatory effects and mechanisms of the ethanol extract of Evodia rutaecarpa and its bioactive components on neutrophils and microglial cells.

Evodia rutaecarpa is commonly used as an anti-inflammatory drug in traditional Chinese medicine. We previously identified four bioactive compounds (dehydroevodiamine (I), evodiamine (II), rutaecarpine (III), and synephrine (IV)) from the ethanol extract of E. rutaecarpa, but their effects and mechanism(s) of action remain unclear. To study the anti-inflammatory potential and the possible underlying mechanism(s), their effects on phorbol-12-myristate-13-acetate (PMA)- and N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced reactive oxygen species production in neutrophils was studied, as well as lipopolysaccharide (LPS)-induced nitric oxide (NO) production and inducible NO synthetase (iNOS) expression in microglial cells. The ethanol extract of E. rutaecarpa displayed potent antioxidative effects against both PMA- and fMLP-induced reactive oxygen species production in neutrophils (with IC50 values of around 2.7-3.3 microg/ml). Although less potent than the ethanol extract of E. rutaecarpa, compounds I-IV all concentration-dependently inhibited PMA- and fMLP-induced reactive oxygen species production, with compound IV consistently being the most potent agent among these active components. The antioxidative effects of the ethanol extract of E. rutaecarpa and these compounds were partially due to inhibition (10%-33%) of NADPH oxidase activity, a predominant reactive oxygen species-producing enzyme in neutrophils, and to a minor extent to their direct radical-scavenging properties. The ethanol extract of E. rutaecarpa also inhibited LPS-induced NO production (with an IC50 of around 0.8 microg/ml) and iNOS upregulation in microglial cells that was partially mimicked by compounds I, II, and III, but not compound IV. Our results suggest that the ethanol extract of E. rutaecarpa and its four bioactive components all exhibited anti-inflammatory activities which could be partially explained by their different potentials for inhibiting NADPH oxidase-dependent reactive oxygen species and/or iNOS-dependent NO production in activated inflammatory cells.

Treatment of massive retroperitoneal hemorrhage from adrenal metastasis of hepatoma.

Spontaneous rupture of metastatic adrenal tumor with massive retroperitoneal hemorrhage and shock is an uncommon clinical event. Herein, we report a case of hepatocellular carcinoma (HCC), where left hepatic lobectomy and right adrenalectomy for metastatic HCC were performed in April and August 2002, respectively. Subsequently, the patient presented to the emergency room with acute-onset severe left flank and back pain in March 2004, accompanied by a falling hemoglobin level. Computed tomography revealed a 7-cm left adrenal tumor mass with retroperitoneal hemorrhage. The ruptured adrenal tumor was further confirmed by selective angiography, which demonstrated that the bleeder was supplied by the left suprarenal artery. Transarterial embolization (TAE) to stop tumor bleeding was performed successfully. The patient then underwent tumor resection with left adrenalectomy 5 days after the embolization, with pathology subsequently revealing metastatic HCC. The recurrent intrahepatic HCC was controlled with TAE, and the patient underwent hormone replacement therapy with prednisolone 10 mg/day. Metastatic adrenal tumor bleeding should be suspected in hepatoma patients who suffer abrupt flank pain and shock. Hemodynamically unstable patients require supportive transfusions and urgent surgical exploration. Angiographic embolization, if deemed feasible, may be a valuable adjunct for achievement of hemostasis prior to definite surgery.

The inhibitory effect of phenylpropanoid glycosides and iridoid glucosides on free radical production and beta2 integrin expression in human leucocytes.

Rapid production of reactive oxygen species (ROS) and upregulation of beta2 integrin by leucocytes are two important inflammatory responses in human leucocytes. To evaluate whether three phenylpropanoid glycosides (acteoside, crenatoside, and rossicaside B) and two iridoid glucosides (boschnaloside and 8-epideoxyloganic acid) identified from two medicinal plants with similar indications (Orobanche caerulescens and Boschniakia rossica) exhibited anti-inflammatory activity, their effects on N-formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol-12-myristate-13-acetate (PMA)-activated peripheral human neutrophils (PMNs) and mononuclear cells were examined. Pretreatment with 1-50 microM phenylpropanoid glycoside concentration-dependently diminished PMA- and fMLP-induced ROS production with IC50 values of approximately 6.8-23.9 and 3.0-8.8 muM, respectively. Iridoid glucoside was less effective than phenylpropanoid glycoside with an IC50 value of approximately 8.9-28.4 microM in PMA-activated PMNs and 19.1-21.1 microM in fMLP-activated mononuclear cells. Phenylpropanoid glycosides also effectively inhibited NADPH oxidase (NOX) and displayed potent free radical-scavenging activity, but did not interfere with pan-protein kinase C (PKC) activity. Furthermore, all compounds, except rossicaside B, significantly inhibited PMA- and fMLP-induced Mac-1 (a beta2 integrin) upregulation at 50 microM but not that of fMLP-induced intracellular calcium mobilization. These drugs had no significant cytotoxicity as compared with the vehicle control. Our data suggested that inhibition of ROS production, possibly through modulation of NOX activity and/or the radical scavenging effect, and beta2 integrin expression in leucocytes indicated that these compounds had the potential to serve as anti-inflammatory agents during oxidative stress.

Prevention of macrophage adhesion molecule-1 (Mac-1)-dependent neutrophil firm adhesion by taxifolin through impairment of protein kinase-dependent NADPH oxidase activation and antagonism of G protein-mediated calcium influx.

Taxifolin has been reported to down-regulate the expression of intercellular adhesion molecule-1 (ICAM-1), a receptor-mediating firm adhesion with beta2 integrin (e.g., Mac-1) expressed on leukocytes. To evaluate whether taxifolin could modulate Mac-1-dependent firm adhesion by neutrophils, and the possible mechanism(s) underlying its anti-inflammatory action, its effects on N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol-12-myristate-13-acetate (PMA)-activated peripheral human neutrophils were studied. Pretreatment with taxifolin (1-100 microM) concentration-dependently diminished fMLP- or (PMA)-induced Mac-1-dependent firm adhesion and upexpression of surface Mac-1. Mobilisation of intracellular calcium and production of reactive oxygen species (ROS) signal the upexpression of Mac-1 and firm adhesion by neutrophils. Taxifolin impeded the calcium influx induced by fMLP (a receptor-mediated activator) or AlF(4)(-) (a G protein-mediated activator). Taxifolin also effectively inhibited the fMLP- or PMA-induced ROS production with 50% inhibitory concentration (IC(50)) less than 10microM, possibly through impairing the activation of NADPH oxidase, a major ROS-generating enzyme in neutrophils, by restricting the activation of p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase C (PKC). In conclusion, we propose that impairment of ROS production by NADPH oxidase through interfering with p38 MAPK- and/or PKC-dependent signals, and antagonism of G protein-mediated calcium influx may account for the inhibition of Mac-1-dependent neutrophil firm adhesion that confers taxifolin the anti-inflammatory activity.

Evaluation of the anti-inflammatory and cytotoxic effects of anthraquinones and anthracenes derivatives in human leucocytes.

A variety of anthracene- and anthraquinone-related derivatives, modified from three types of lead structures, including 9-acyloxy 1,5-dichloroanthracene (type I), 1,5-bisacyloxy-anthraquinones with O-linked substituents (type II) and 1,5-bisacyloxy-anthraquinones with S-linked substituents (type III), were synthesized and evaluated by an in-vitro bioassay for their anti-inflammatory and cytotoxic effects in human leucocytes. Among these derivatives, type I compounds displayed potent anti-inflammatory activity against phorbol-12-myristate-13-acetate (PMA)-induced superoxide anion production, a bio-marker of inflammatory mediator production by neutrophils, with 50% inhibition (IC50) concentrations (microM) for compounds 1f, 1g, 1h and 1m being 13.8 +/- 3.0, 6.3 +/- 4.1, 33.2 +/- 1.3 and 33.9 +/- 5.7, respectively. Type II and type III derivatives (i. e., 1,5-bisacyloxy anthraquinone-related compounds) and the reference compound, emodin, exhibited relatively minor (20-40%) inhibitory effect against superoxide production by neutrophils. Furthermore, none of these compounds showed a significant cytotoxic effect in human neutrophils. In conclusion, these results suggest that compounds modified from 9-acyloxy 1,5-dichloroanthracence (type I) are more powerful than the other two types as anti-inflammatory drugs. This is the first demonstration that derivatives modified from anthracenes or anthraquinones possess anti-inflammatory activity with no significant cytotoxicity in human neutrophils.

Anti-inflammatory ergostanes from the basidiomata of Antrodia salmonea.

Three new anti-oxidative ergostanes, methyl antcinate L (1), antcin M (2), and methyl antcinate K (3), together with nine additional known compounds, 3-ketodehydrosulphurenic acid, sulphurenic acid, dehydrosulphurenic acid, 3beta,15alpha-dihydroxylanosta-7,9(11),24-trien-21-oic acid, zhankuic acid A, zhankuic acid B, zhankuic acid C, antcin C, and antcin K were isolated from the basidiomata of Antrodia salmonea, a newly identified species of Antrodia (Polyporaceae) in Taiwan. These three new compounds were identified as methyl 3alpha,7alpha,12alpha-trihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oate (1), 3alpha,12alpha-dihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oic acid (2), and methyl 3alpha,4beta,7beta-trihydroxy-4alpha-methylergosta-8,24(29)-dien-11-on-26-oate (3) by spectroscopic analysis. We studied their antioxidative potential on the production of reactive oxygen species and nitric oxide (NO) in neutrophils and microglial cells, respectively. Compounds 1-3 displayed potent antioxidative activity with IC50 values of around 2.0-8.8 microM that was partially due to inhibition (6-67%) of NADPH oxidase activity but not through direct radical-scavenging properties. Compounds 1-3 also inhibited NO production with IC50 values of around 1.7-16.5 microM and were more potent than a non-specific NOS inhibitor. We conclude that these three new compounds 1, 2, and 3 exhibit anti-inflammatory activities in activated inflammatory cells.

New lanostanes and naphthoquinones isolated from Antrodia salmonea and their antioxidative burst activity in human leukocytes.

Four new compounds were isolated from the basidiomata of the fungus Antrodia salmonea, a newly identified species of Antrodia (Aphyllophorales) in Taiwan. These new compounds are named as lanosta-8,24-diene-3beta,15alpha,21-triol (1), 24-methylenelanost-8-ene-3beta,15alpha,21-triol (2), 2,3-dimethoxy-5-(2',5'-dimethoxy-3',4'-methylenedioxyphenyl)-7-methyl-[1,4]-naphthoquinone (3), and 2,3-dimethoxy-6-(2',5'-dimethoxy-3',4'-methylenedioxyphenyl)-7-methyl-[1,4]-naphthoquinone (4), respectively. Their structures were elucidated by spectroscopic methods. An in vitro cellular functional assay was performed to evaluate their anti-oxidative burst activity in human leukocytes. They showed inhibitory effects against phorbol 12-myristate-13-acetate (PMA), a direct protein kinase C activator, induced oxidative burst in neutrophils (PMN) and mononuclear cells (MNC) with 50 % inhibitory concentration (IC(50)) ranging from 3.5 to 25.8 microM. The potency order of these compounds in PMA-activated leukocytes was as 1 > 3 > 4 > 2. They were relatively less effective in formyl-Met-Leu-Phe (fMLP), a G-protein coupled receptor agonist, induced oxidative burst, except for compounds 3 and 4 in fMLP-activated PMN. These results indicated that three (1, 3, and 4) of these four newly identified compounds displayed anti-oxidative effect in human leukocytes with different potency and might confer anti-inflammatory activity to these drugs.

Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation.

Infarction in adult rat brain was induced by middle cerebral arterial occlusion (MCAO) followed by reperfusion to examine whether taxifolin could reduce cerebral ischemic reperfusion (CI/R) injury. Taxifolin administration (0.1 and 1.0 microg/kg, i.v.) 60 min after MCAO ameliorated infarction (by 42%+/-7% and 62%+/-6%, respectively), which was accompanied by a dramatic reduction in malondialdehyde and nitrotyrosine adduct formation, two markers for oxidative tissue damage. Overproduction of reactive oxygen species (ROS) and nitric oxide (NO) via oxidative enzymes (e.g., COX-2 and iNOS) was responsible for this oxidative damage. Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration. ROS, generated by leukocytes and microglial cells, activated nuclear factor-kappa B (NF-kappaB) that in turn signaled up-regulation of inflammatory proteins. NF-kappaB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin. Production of both ROS and NO by leukocytes and microglial cells was significantly antagonized by taxifolin. These data suggest that amelioration of CI/R injury by taxifolin may be attributed to its anti-oxidative effect, which in turn modulates NF-kappaB activation that mediates CI/R injury.