Advances in Mechanical Thrombectomy for Acute Ischemic Stroke Due to Large Vessel Occlusion.

Acute ischemic stroke (AIS) is a significant cause of global morbidity and mortality, with functional implications for quality of life and long-term disability. The limitations of intravenous thrombolytic therapy for the treatment of AIS, especially for emergent large vessel occlusion (ELVO), have paved the way for alternative therapies and the rapidly evolving landscape of endovascular therapy (EVT). Here, we summarize the major landmark trials that have advanced the field largely due to ongoing biomedical engineering device development that have translated into significantly improved clinical outcomes. Our review describes the clinical success of EVT, and current and future trends.

Effects of nine weeks L-Carnitine supplementation on exercise performance, anaerobic power, and exercise-induced oxidative stress in resistance-trained males.

PURPOSE: Studies of L-carnitine in healthy athletic populations have yielded equivocal results. Further scientific-based knowledge is needed to clarify the ability of L-carnitine to improve exercise capacity and expedite the recovery process by reducing oxidative stress. This study aimed to examine the 9-week effects of L-carnitine supplementation on exercise performance, anaerobic capacity, and exercise-induced oxidative stress markers in resistance-trained males. METHODS: In a double-blind, randomized, and placebo-controlled treatment, 23 men (age, 25±2y; weight, 81.2±8.31 kg; body fat, 17.1±5.9%) ingested either a placebo (2 g/d, n=11) or L-carnitine (2 g/d, n=12) for 9 weeks in conjunction with resistance training. Primary outcome measurements were analyzed at baseline and at weeks 3, 6, and 9. Participants underwent a similar resistance training (4 d/w, upper/lower body split) for a 9-week period. Two-way ANOVA with repeated measures was used for statistical analysis. RESULTS: There were significant increases in bench press lifting volume at wk-6 (146 kg, 95% CI 21.1, 272) and wk-9 (245 kg, 95% CI 127, 362) with L-carnitine. A similar trend was observed for leg press. In the L-carnitine group, at wk-9, there were significant increases in mean power (63.4 W, 95% CI 32.0, 94.8) and peak power (239 W, 95% CI 86.6, 392), reduction in post-exercise blood lactate levels (-1.60 mmol/L, 95% CI -2.44, -0.75) and beneficial changes in total antioxidant capacity (0.18 mmol/L, 95% CI 0.07, 0.28). CONCLUSION: L-carnitine supplementation enhances exercise performance while attenuating blood lactate and oxidative stress responses to resistance training.

Integrating health care for high-need medicaid beneficiaries with serious mental illness and chronic physical health conditions at managed care, provider, and consumer levels.

OBJECTIVE: Policies supporting value-based care and alternative payment models, notably in the Affordable Care Act and the Medicare Access & CHIP Reauthorization Act of 2015, offer hope to advance care integration for individuals with behavioral and chronic physical health conditions. The potential for integration to improve quality while managing costs for individuals with high needs, coupled with the remaining financial, operational, and policy challenges, underscores a need for continued discussion of integration programs' preliminary outcomes and lessons. The authors describe the early efforts of the HealthChoices HealthConnections pilot program for adult Medicaid beneficiaries with serious mental illness and co-occurring chronic conditions, which used a navigator model in 3 southeastern Pennsylvania counties. METHOD: The authors conducted a difference-in-differences analysis of emergency department (ED) visits, hospitalizations, and readmissions using Medicaid claims data and collected data about program implementation. RESULTS: ED visits decreased 4% among study group members (n = 4,788) while increasing almost 6% in the comparison group (n = 7,039) during the intervention period (p = .036); there were no statistically significant differences in hospitalizations or readmissions. This pilot demonstrated the promise of nurse navigators (care managers) to bridge gaps between the physical and mental health care systems, and the success of a private-public partnership developing a member profile to share behavioral and physical health information in the absence of an interoperable health information technology system. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: The implementation lessons can inform state Medicaid Health Home models as well as accountable care organizations considering incorporation of behavioral health care. (PsycINFO Database Record

Effects of ingesting a pre-workout dietary supplement with and without synephrine for 8 weeks on training adaptations in resistance-trained males.

BACKGROUND: The purpose of this study was to examine whether ingesting a pre-workout dietary supplement (PWS) with and without synephrine (S) during training affects training responses in resistance-trained males. METHODS: Resistance-trained males (N = 80) were randomly assigned to supplement their diet in a double-blind manner with either a flavored placebo (PLA); a PWS containing beta-alanine (3 g), creatine nitrate as a salt (2 g), arginine alpha-ketoglutarate (2 g), N-Acetyl-L-Tyrosine (300 mg), caffeine (284 mg), Mucuna pruiriens extract standardized for 15% L-Dopa (15 mg), Vitamin C as Ascorbic Acid (500 mg), niacin (60 mg), folate as folic acid (50 mg), and Vitamin B12 as Methylcobalamin (70 mg); or, the PWS supplement with Citrus aurantium extract containing 20 mg of synephrine (PWS + S) once per day for 8-weeks during training. Participants donated a fasting blood sample and had body composition (DXA), resting heart rate and blood pressure, cognitive function (Stroop Test), readiness to perform, bench and leg press 1 RM, and Wingate anaerobic capacity assessments determined a 0, 4, and 8-weeks of standardized training. Data were analyzed by MANOVA with repeated measures. Performance and cognitive function data were analyzed using baseline values as covariates as well as mean changes from baseline with 95% confidence intervals (CI). Blood chemistry data were also analyzed using Chi-square analysis. RESULTS: Although significant time effects were seen, no statistically significant overall MANOVA Wilks' Lambda interactions were observed among groups for body composition, resting heart and blood pressure, readiness to perform questions, 1RM strength, anaerobic sprint capacity, or blood chemistry panels. MANOVA univariate analysis and analysis of changes from baseline with 95% CI revealed some evidence that cognitive function and 1RM strength were increased to a greater degree in the PWS and/or PWS + S groups after 4- and/or 8-weeks compared to PLA responses. However, there was no evidence that PWS + S promoted greater overall training adaptations compared to the PWS group. Dietary supplementation of PWS and PWS + S did not increase the incidence of reported side effects or significantly affect the number of blood values above clinical norms compared to PLA. CONCLUSION: Results provide some evidence that 4-weeks of PWS and/or PWS + S supplementation can improve some indices of cognitive function and exercise performance during resistance-training without significant side effects in apparently health males. However, these effects were similar to PLA responses after 8-weeks of supplementation and inclusion of synephrine did not promote additive benefits. TRIAL REGISTRATION: This trial (NCT02999581) was retrospectively registered on December 16th 2016.

Effects of acute ingestion of a pre-workout dietary supplement with and without p-synephrine on resting energy expenditure, cognitive function and exercise performance.

BACKGROUND: The purpose of this study was to examine the effects of acute ingestion of a pre-workout dietary supplement (PWS) with and without p-synephrine (S) on perceptions of readiness to perform, cognitive function, exercise performance, and markers of safety. METHODS: In a randomized, double-blind, and counterbalanced manner; 25 healthy and recreationally active male and female participants ingested a flavored maltodextrin placebo (PLA), a PWS containing beta-alanine (3 g), creatine nitrate as a salt (2 g), arginine alpha-ketoglutarate (2 g), N-Acetyl-L-Tyrosine (300 mg), caffeine (284 mg), Mucuna pruiriens extract standardized for 15% L-Dopa (15 mg), Vitamin C as Ascorbic Acid (500 mg), niacin (60 mg), folate as folic acid (50 mg), and Vitamin B12 as Methylcobalamin (70 mg) with 2 g of maltodextrin and flavoring; or, the PWS with Citrus aurantium (PWS + S) extract standardized for 30% p-synephrine (20 mg). Participants had heart rate (HR), blood pressure, resting energy expenditure (REE), 12-lead electrocardiograms (ECG), perceptions about readiness to perform, cognitive function (Stroop Color-Word test), bench and leg press performance (2 sets of 10 repetitions at 70% of 1RM and 1 set to failure), and Wingate anaerobic capacity (WAC) sprint performance determined as well as donated blood samples prior to and/or following exercise/supplementation. Data were analyzed by MANOVA with repeated measures as well as mean changes from baseline with 95% confidence intervals (CI). RESULTS: No clinically significant differences were observed among treatments in HR, blood pressure, ECG, or general clinical blood panels. There was evidence that PWS and PWS + S ingestion promoted greater changes in REE responses. Participants reported higher perception of optimism about performance and vigor and energy with PWS and PWS + S ingestion and there was evidence that PWS and PWS + S improved changes in cognitive function scores from baseline to a greater degree than PLA after 1 or 2 h. However, the scores in the PWS + S treatment did not exceed PLA or PWS responses at any data point. No statistically significant differences were observed among treatments in total bench press lifting volume, leg press lifting volume or WAC sprint performance. CONCLUSIONS: Within the confines of this study, ingestion of PWS and/or PWS + S prior to exercise appears to be well-tolerated when consumed by young, healthy individuals. The primary effects appear to be to increase REE responses and improve perceptions about readiness to perform and cognitive function with limited to no effects on muscular endurance and WAC. The addition of 20 mg of p-synephrine to the PWS provided limited to no additive benefits. TRIAL REGISTRATION: This trial (NCT02952014) was retrospectively registered on September 13th 2016.

Rubi Fructus (Rubus coreanus) activates the expression of thermogenic genes in vivo and in vitro.

OBJECTIVE: To investigate the anti-obesity effect of Rubi Fructus (RF) extract using brown adipose tissue (BAT) and primary brown preadipocytes in vivo and in vitro. METHODS: Male C57BL/6 J mice (n=5 per group) were fed a high-fat diet (HFD) for 10 weeks with or without RF. Brown preadipocytes from the interscapular BAT of mice (age, post-natal days 1-3) were cultured with differentiation media (DM) including isobutylmethylxanthine, dexamethasone, T3, indomethacin and insulin with or without RF. RESULTS: In HFD-induced obese C57BL/6 J mice, long-term RF treatment significantly reduced weight gain as well as the weights of the white adipose tissue, liver and spleen. Serum levels of total cholesterol and low-density lipoprotein cholesterol were also reduced in the HFD group which received RF treatment. Furthermore, RF induced thermogenic-, adipogenic- and mitochondria-related gene expressions in BAT. In primary brown adipocytes, RF effectively stimulated the expressions of thermogenic- and mitochondria-related genes. In addition, to examine whether LIPIN1, a regulator of adipocyte differentiation, is regulated by RF, Lipin1 small interfering RNA (siRNA) and RF were pretreated in primary brown adipocytes. Pretreatment with Lipin1 siRNA and RF downregulated the DM-induced expression levels of thermogenic- and mitochondria-related genes. Moreover, RF markedly upregulated AMP-activated protein kinase. Our study shows that RF is capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes. CONCLUSIONS: This study demonstrates that RF prevents the development of obesity in mice fed with a HFD and that it is also capable of stimulating the differentiation of brown adipocytes through the modulation of thermogenic genes, which suggests that RF has potential as a therapeutic application for the treatment or prevention of obesity.

Effect of DA-9701, a novel prokinetic agent, on stress-induced delayed gastric emptying and hormonal changes in rats.

BACKGROUND: DA-9701 is a novel prokinetic agent formulated with Pharbitis Semen and Corydalis Tuber. This study aimed to evaluate the effect of DA-9701 on stress-induced delay in gastric emptying and changes in plasma adrenocorticotropic hormone and ghrelin levels in rats. METHODS: Changes in gastric emptying in response to different durations of stress were evaluated. Gastric emptying was compared between the following groups: (i) nonstressed vehicle- or DA-9701-treated group, (ii) nonstressed vehicle- or mosapride-treated group, (iii) 2-h stressed vehicle- or DA-9701-treated group, and (iv) 2-h stressed vehicle- or mosapride-treated group. Water immersion restraint stress was used as the stressor. DA-9701 or mosapride at 3 mg kg(-1) was administered to the rats after subjecting them to 2-h stress, and then gastric emptying was measured using the phenol red method. KEY RESULTS: Gastric emptying was significantly delayed in the 2-h stressed group compared with the nonstressed group. Mosapride administration resulted in significant recovery from the stress-induced delay in gastric emptying. Gastric emptying in the rats that underwent 2-h stress followed by DA-9701 administration was not significantly different from that in the nonstressed group. The plasma adrenocorticotropic hormone and active ghrelin levels in the 2-h stressed group were significantly higher than those in the nonstressed group. These increases were significantly inhibited by DA-9701. CONCLUSIONS & INFERENCES: The administration of DA-9701 improved delayed gastric emptying and inhibited the hormonal changes induced by stress, suggesting that DA-9701 can be used as a gastroprokinetic agent for the treatment of delayed gastric emptying, particularly that associated with stress.

Antitumor effect of novel small chemical inhibitors of Snail-p53 binding in K-Ras-mutated cancer cells.

p53 is frequently mutated by genetic alternation or suppressed by various kinds of cellular signaling pathways in human cancers. Recently, we have revealed that p53 is suppressed and eliminated from cells by direct binding with oncogenic K-Ras-induced Snail. On the basis of the fact, we generated specific inhibitors against p53-Snail binding (GN25 and GN29). These chemicals can induce p53 expression and functions in K-Ras-mutated cells. However, it does not show cytotoxic effect on normal cells or K-Ras-wild-type cells. Moreover, GN25 can selectively activate wild-type p53 in p53(WT/MT) cancer cells. But single allelic mt p53 containing cell line, Panc-1, does not respond to our chemical. In vivo xenograft test also supports the antitumor effect of GN25 in K-Ras-mutated cell lines. These results suggest that our compounds are strong candidate for anticancer drug against K-Ras-initiated human cancers including pancreatic and lung cancers.

Inactivation of Enterobacter sakazakii by water-soluble muscadine seed extracts.

Hot and cold water-soluble muscadine (Vitis rotundifolia) seed extracts and their polar and polyphenol fractions from two Muscadine cultivars ('Ison', purple and 'Carlos', bronze) were investigated for their inhibition of Enterobacter sakazakii. The heat treatment on each seed extract not only increased total phenolics and tannic acid but also enhanced antimicrobial activity against two strains of E. sakazakii. Within 1 h, all seed extracts reduced an initial population (approximately 6 log CFU/mL) of E. sakazakii to a non-detectable level (minimum detection limit, 10 CFU/mL). Regardless of extraction method and cultivar, only the polar fractions which contained malic, tartaric and tannic acids showed antimicrobial activity against two strains of E. sakazakii. The polyphenol fractions which contained gallic acid, catechin, epicatechin, ellagic acid and pigments showed slight inhibition against E. sakazakii. Results showed that water-soluble muscadine seed extracts (pH 3.3-3.78) contained strong antimicrobial inhibitors against E. sakazakii while acidified peptone water (pH 3.3) did not show any antimicrobial activity.

Generation and spectral manipulation of coherent terahertz radiation with two-stage optical rectification.

We propose and experimentally demonstrate the generation of single-cycle terahertz radiation with two-stage optical rectification in GaSe crystals. By adjusting the time delay between the pump pulses employed to excite the two stages, the terahertz radiation from the second GaSe crystal can constructively superpose with the terahertz field injected from the first stage. The high mutual coherence between the two terahertz radiation fields is ensured with the coherent optical rectification process and can be further used to synthesize a desired spectral profile of coherent THz radiation. The technique is also potentially useful for generating high-power single-cycle terahertz pulses, usually limited by the pulse walk-off effect of the nonlinear optical crystal used.

Antimicrobial effect of water-soluble muscadine seed extracts on Escherichia coli O157:H7.

Water-soluble extracts were prepared from purple (cultivar Ison) and bronze (cultivar Carlos) muscadine seeds with or without heating. The Ison extracts had strong antimicrobial activity against a cocktail of three strains of Escherichia coli O157: H7. This extract had higher acidity (pH 3.39 to 3.43), total phenolics (2.21 to 3.49 mg/ml), tartaric acid (5.6 to 10.7 mg/ml), tannic acid (5.7 to 8.1 mg/ml), and gallic acid (0.33 to 0.59 mg/ml) than did the Carlos extracts. Heat treatment on both extracts increased antimicrobial activity, possibly because of increased acidity, tartaric acid, total phenolics, and individual phenolics. Heating of Ison extracts increased ellagic acid up to 83%. Up to 10.7 mg/ml tartaric acid alone was not as effective against E. coli O157:H7 as were water-soluble seed extracts. This finding suggests the involvement of other factors, such as tannic and gallic acids, in inactivation of this pathogen. Water-soluble muscadine seed extracts may be useful for incorporation into juice and other beverage products as natural preservatives.

Synthesis and evaluation of N-acyl-2-(5-fluorouracil-1-yl)-D,L-glycine as a colon-specific prodrug of 5-fluorouracil.

N-nicotinyl-2-(5-fluorouracil-1-yl)-D,L-glycine (NFG) and N-isonicotinyl-2-(5-fluorouracil-1-yl)-D,L-glycine (INFG) were synthesized as colon-specific prodrugs of 5-fluorouracil (5-FU). As N-aromatic acyl amides of glycine, they are expected to be stable in the upper intestine and delivered to the colon as an intact form if they are nonabsorbable. Microbial hydrolysis of amide bond in the colon will give 2-(5-fluorouracil)-D,L-glycine, which releases 5-FU by spontaneous decomposition. NFG and INFG were soluble in water and stable in pH 1.2 and 7.4 buffer solutions. The apparent partition coefficient of NFG or INFG in 1-octanol/pH 7.4 phosphate buffer solution at 37 degrees was 0.025 or 0.024, respectively. On incubation with cecal contents of rats, conversion of NFG or INFG proceeded only 9 or 5% in 8 h, respectively, producing 5-FU and a metabolite. The metabolite formation was inhibited in the presence of diazouracil, a dihydrouracil dehydrogenase inhibitor. The HPLC retention time of the metabolite from the incubation of 5-FU, NFG, or INFG with cecal contents was identical to dihydro-5-fluorouracil (dihydro-5FU). When N-nicotinyl-2-hydroxy-D,L-glycine methyl ester (NHGM) was incubated with the cecal contents, the extent of amide bond hydrolysis was 85% in 24 h. The result suggested that steric hindrance imposed by 5-FU at 2-position of glycine retarded the hydrolysis of the amide bond in NFG or INFG and suppressed the prodrug conversion.

Rutaecarpine, a quinazolinocarboline alkaloid, inhibits prostaglandin production in RAW264.7 macrophages.

In order to delineate the mechanism involved in the anti-inflammatory activity of rutaecarpine, its effects on the production of prostaglandin (PG) and therein involved enzymes were examined. Rutaecarpine reduced the production of PGE(2) in RAW264.7 cells treated with lipopolysaccharide (LPS) in a dose dependent manner when added to the culture media at the time of stimulation. However, the inhibition of total cellular cyclooxygenase (COX) activity under the same experimental condition was observed only at high concentrations of rutaecarpine. Rutaecarpine did not affected the levels of COX-2 mRNA and protein in macrophages stimulated with LPS. Calcium ionophore A23187 induced-PG production and [(3)H]-arachidonic acid release were significantly decreased by the pretreatment of rutaecarpine for 30 minutes. With the same treatment schedule, however, rutaecarpine failed to alter the activities of cellular COX-1 and COX-2. Collectively, our data suggest that anti-inflammatory effect of rutaecarpine is, at least in part, ascribed to the diminution of PG production through inhibition of arachidonic acid release albeit the nature of its effects on PLA(2) activity remains to be elaborated.

EGCG, a major component of green tea, inhibits tumour growth by inhibiting VEGF induction in human colon carcinoma cells.

Catechins are key components of teas that have antiproliferative properties. We investigated the effects of green tea catechins on intracellular signalling and VEGF induction in vitro in serum-deprived HT29 human colon cancer cells and in vivo on the growth of HT29 cells in nude mice. In the in vitro studies, (-)-epigallocatechin gallate (EGCG), the most abundant catechin in green tea extract, inhibited Erk-1 and Erk-2 activation in a dose-dependent manner. However, other tea catechins such as (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), and (-)-epicatechin (EC) did not affect Erk-1 or 2 activation at a concentration of 30 microM. EGCG also inhibited the increase of VEGF expression and promoter activity induced by serum starvation. In the in vivo studies, athymic BALB/c nude mice were inoculated subcutaneously with HT29 cells and treated with daily intraperitoneal injections of EC (negative control) or EGCG at 1.5 mg day(-1)mouse(-1)starting 2 days after tumour cell inoculation. Treatment with EGCG inhibited tumour growth (58%), microvessel density (30%), and tumour cell proliferation (27%) and increased tumour cell apoptosis (1.9-fold) and endothelial cell apoptosis (3-fold) relative to the control condition (P< 0.05 for all comparisons). EGCG may exert at least part of its anticancer effect by inhibiting angiogenesis through blocking the induction of VEGF.

Effect of SKI 306X, a new herbal anti-arthritic agent, in patients with osteoarthritis of the knee: a double-blind placebo controlled study.

SKI 306X is a purified extract from a mixture of three oriental herbal medicines (Clematis mandshurica, Trichosanthes kirilowii and Prunella vulgaris) that have been widely used for the treatment of inflammatory diseases such as lymphadenitis and arthritis in far East Asia. A double-blind, controlled study was performed to evaluate the efficacy and safety of SKI 306X with placebo in 96 patients with classical osteoarthritis of the knee. Patients were randomized to four treatment groups: placebo, 200 mg, 400 mg and 600 mg of SKI 306X t.i.d.. Clinical efficacy and safety were evaluated for 4 weeks continuous treatment. SKI 306X demonstrated its clinical efficacy, as assessed by 100 mm visual analogue scale (VAS), Lequesne index and patients' and investigators opinion of the therapeutic effect compared with placebo (p<0.01). No significant adverse events were observed in patients treated with SKI 306X. This study demonstrated that SKI 306X, a new herbal anti-arthritic agent provided clinical efficacy in patients with osteoarthritis.

Inhibition of tumour invasion and angiogenesis by epigallocatechin gallate (EGCG), a major component of green tea.

Epidemiological studies have suggested that consumption of green tea may decrease cancer risk. In addition, abundant pre-clinical data from several laboratories have provided convincing evidence that polyphenols present in green tea afford protection against cancer in both in vivo and in vitro studies. Recently, epigallocatechin gallate (EGCG), a putative chemopreventive agent and a major component of green tea, was reported to inhibit tumour invasion and angiogenesis, processes that are essential for tumour growth and metastasis. Understanding the basic principles by which EGCG inhibits tumour invasion and angiogenesis may lead to the development of new therapeutic strategies, in addition to supporting the role of green tea as a cancer chemopreventive agent.

Effects of ion beam-assisted deposition of hydroxyapatite on the osseointegration of endosseous implants in rabbit tibiae.

The aim of this study was to evaluate the effects of coating implants with hydroxyapatite (HA) by an ion beam-assisted deposition (IBAD) method and to compare them with implants prepared with sand-blasted and machined surfaces. Examination of osteoblast cultures displayed no difference in the secretion of alkaline phosphatase (ALP) between the various surfaces, but the IBAD-HA specimen showed low ALP secretion (P < .05). Removal torque tests showed that implants coated with HA by the IBAD method had values similar to the implants with a sandblasted surface, but values for the machined-surface implants differed. Implants placed in a group of ovariectomized rabbits showed lower mechanical test values than implants placed in sham-operated rabbits (P < .05). Implants coated with HA by the IBAD method demonstrated the highest mean bone-to-metal contact ratio on all threads and on the 3 best consecutive threads, followed by the implants with a sandblasted surface and implants with a machined surface (P < .05). Hydroxyapatite-coated implants showed a slightly higher bone-to-implant contact ratio than sandblasted implants, but no statistically significant difference was seen between the 2 materials. The implants placed in ovariectomized rabbits showed lower amounts of bone-to-metal contact than the implants placed in sham-operated rabbits, but no statistically significant difference was seen between the 2 groups. Evaluation of bone volume on all threads and the 3 best consecutive threads showed no statistically significant difference among the different surface treatment groups, but lower bone volume was seen in the ovariectomized rabbits than in the sham-operated animals (P < .05).

Mechanism for antiplatelet effect of onion: AA release inhibition, thromboxane A(2)synthase inhibition and TXA(2)/PGH(2)receptor blockade.

Antiplatelet actions of aqueous extract of onion were investigated in rat and human platelet. IC(50)values of onion extract for collagen-, thrombin-, arachidonic acid (AA)-induced aggregations and collagen-induced thromboxane A(2)(TXA(2)) formation were 0.17 +/- 0. 01, 0.23 + 0.03, 0.34 +/- 0.02 and 0.12 +/- 0.01 g/ml, respectively. [(3)H]-AA release induced by collagen (10 microg/ml) in rat platelet was decreased by onion compared to control (22.1 +/- 2.13 and 5.2 +/- 0.82% of total [(3)H]-AA incorporated, respectively). In fura-2 loaded platelets, the elevation of intracellular Ca(2+)concentration stimulated by collagen was inhibited by onion. Onion had no cytotoxic effect in platelet. Onion significantly inhibited TXA(2)synthase activity without influence on COX activity. Platelet aggregation induced by U46619, a stable TXA(2)mimetic, was inhibited by onion, indicating its antagonism for TXA(2)/PGH(2)receptor. These results suggest that the mechanism for antiplatelet effect of onion may, at least partly, involve AA release diminution, TXA(2)synthase inhibition and TXA(2)/PGH(2)receptor blockade.

Molecular cloning and expression of Cu/Zn-containing superoxide dismutase from Fasciola hepatica.

The cytosolic superoxide dismutase (SOD) of Fasciola hepatica, a causative agent of fascioliasis, was purified and characterized. The enzyme consists of two identical subunits, each with an apparent molecular mass of 17.5 kDa. An analysis of the enzyme's primary structure and inhibition studies revealed that the enzyme is a copper/zinc-containing SOD (Cu/Zn-SOD). The enzyme activity was relatively stable in a broad pH range, from pH 7.0 to 10.0, and the enzyme showed maximum activity at pH 7.5. This enzyme also displayed strong antigenicity against sera of bovine and human subjects with fascioliasis. The SOD gene fragment was amplified by PCR with degenerate oligonucleotide primers derived from amino acid sequences conserved in the Cu/Zn-SODs of other organisms. An F. hepatica cDNA library was screened with the SOD gene fragment as a probe. As a result, a complete gene encoding the Cu/Zn-SOD was identified, and its nucleotide sequence was determined. The gene had an open reading frame of 438 bp and 146 deduced amino acids. Comparison of the deduced amino acid sequence of the enzyme with previously reported Cu/Zn-SOD amino acid sequences revealed considerably high homologies. The coding region of the F. hepatica Cu/Zn-SOD was cloned and expressed in Escherichia coli. Staining of native polyacrylamide gel for SOD activity of the expressed protein revealed SOD activity that was inactivated by potassium cyanide and hydrogen peroxide but not by sodium azide. This means that the presence of the recombinant fusion protein is indicative of Cu/Zn-SOD. The expressed protein also reacted with sera of bovine and human subjects with fascioliasis, but it did not react with sera of uninfected bovine and human subjects.

Glutamate and aspartate impair memory retention and damage hypothalamic neurons in adult mice.

We examined the effects of systemic administration of monosodium glutamate (MSG) or aspartate (ASP) on the memory retention and neuronal damage in the brains of adult mice. Compared with the control mice, a single intraperitoneal injection of either 4.0 mg/g MSG or 0.5 mg/g ASP after acquisition trial significantly shortened the response latency in the passive avoidance test, accompanying by the transient weight loss. Histopathological analysis of the brains of these mice revealed that neurons in the arcuate nucleus of hypothalamus were damaged markedly by MSG (4.0 mg/g) or ASP (0.5 mg/g). Other brain areas including cerebral cortex and hippocampus did not show any pathological changes. These findings suggest that systemic administration of MSG or ASP could impair memory retention and damage hypothalamic neurons in adult mice.