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In the present study, acute onset of severe lupus nephritis was successfully treated in mice using a new, benzamide-linked, small molecule that targets immune modulation and the NLRP3 inflammasome. Specifically, 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione (Cf-02) (a) reduced serum levels of IgG anti-dsDNA, IL-1β, IL-6, and TNF-α, (b) inhibited activation of dendritic cells and differentially regulated T cell functions, and (c) suppressed the NF-κB/NLRP3 inflammasome axis, targeting priming and activating signals of the inflammasome. Moreover, treatment with Cf-02 significantly inhibited secretion of IL-1β in lipopolysaccharide-stimulated macrophages, but this effect was abolished by autophagy induction. These results recommend Cf-02 as a promising drug candidate for the serious renal conditions associated with systemic lupus erythematosus. Future investigations should examine whether Cf-02 may also be therapeutic in other types of chronic kidney disease involving NLRP3 inflammasome-driven signaling.

Men with diabetic erectile dysfunction (ED) respond poorly to the currently available oral phosphodiesterase-5 inhibitors. Therefore, functional therapies for diabetic ED are needed. Stromal vascular fraction (SVF) and the adenovirus-mediated cartilage oligomeric matrix angiopoietin-1 (Ad-COMP-Ang1) gene are known to play critical roles in penile erection. We previously reported that SVF and Ad-COMP-Ang1 have only a short-term effect in restoring erectile function. Further improvements to ED therapy are needed for long-lasting effects. In the present study, we aimed to test if the combination of SVF and Ad-COMP-Ang1 could extend the erection effect in diabetic ED. We found that the combination therapy showed a long-term effect in restoring erectile function through enhanced penile endothelial and neural cell regeneration. Combination therapy with SVF and Ad-COMP-Ang1 notably restored cavernous endothelial cell numbers, pericyte numbers, endothelial cell-cell junctions, decreased cavernous endothelial cell permeability, and promoted neural regeneration for at least 4 weeks in diabetic mice. In summary, this is an initial description of the long-term effect of combination therapy with SVF and Ad-COMP-Ang1 in restoring erectile function through a dual effect on endothelial and neural cell regeneration. Such combination therapy may have therapeutic potential for the treatment of diabetic ED.

Transversus abdominis plane (TAP) block reduces opiate requirements and pain scores in abdominal surgery, but the effect has not been evaluated in hernia surgery. The aim of this study was to evaluate the efficacy of TAP block in hernia surgery.A meta-analysis of randomized clinical trials (RCTs) evaluating the effect of TAP block in adults undergoing hernia surgery was performed. The primary outcomes were morphine requirements 24 hours after surgery and the number of rescue analgesia patients. Secondary outcomes were pain scores on rest and on movement at 24 hours after surgery, postoperative nausea and vomiting and general postoperative complications.The search strategy yielded 231 articles after duplicates have been removed, and finally 8 RCTs with a total of 791 patients were included. In patients who received a TAP block, the cumulative morphine utilization was significantly reduced at 24 hours (weighted mean difference [WMD] -11.40 mg, -22.41 to -0.39; P=0.04). The number of patients needing a rescue analgesia (relative risk: 0.35, 0.22 to 0.55; P0.001), the pain scores on rest 24 hours after surgery (WMD: -0.29, -0.55 to -0.04; P=0.02) and the pain scores on movement or coughing 24 hours after surgery (WMD: -0.70, -1.33 to -0.06; P=0.03) were all lower in patients who received a TAP block. There was also significant reduction in the postoperative nausea and vomiting, and the general postoperative complications in TAP block group.Within a heterogeneous group of RCTs, TAP block reduces postoperative morphine requirements and the severity of pain after hernia surgery.

In this study, two kojic acid-methimazole (2-mercapto-1-methylimidazole, MMI, 1) derivatives, 5-hydroxy-2-{[(1-methyl-1H-imidazol-2-yl)thio]methyl}-4H-pyran-4-one (compound 4) and 5-methoxy-2-{[(1-methyl-1H-imidazol-2-yl)thio]methyl}-4H-pyran-4-one (compound 5), were synthesized to examine their inhibitory kinetics on mushroom tyrosinase. Compound 4 exhibited a potent inhibitory effect on monophenolase activity in a dose-dependent manner, with an IC50 value of 0.03 mM. On diphenolase activity, compound 4 exhibited a less inhibitory effect (IC50 = 1.29 mM) but was stronger than kojic acid (IC50 = 1.80 mM). Kinetic analysis indicated that compound 4 was both as a noncompetitive monophenolase and diphenolase inhibitor. By contrast, compound 5 exhibited no inhibitory effects on mushroom tyrosinase activity. The IC50 value of compound 4 for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was 4.09 mM, being much higher than the IC50 of compound 4 for inhibiting the tyrosinase activity. The results indicated that the antioxidant activity of compound 4 may be partly related to the potent inhibitory effect on mushroom tyrosinase. Compound 4 also exerted a potent inhibitory effect on intracellular melanin formation in B16/F10 murine melanoma cells, and caused no cytotoxicity. Furthermore, compound 4 induced no adverse effects on the Hen's egg test-chorioallantoic membrane (HET-CAM).

Acetylcholine (Ach) is the key anti-inflammatory transmitter in the cholinergic anti-inflammatory pathway. In this study, critically ill patients treated with early enteral nutrition (EEN) were observed to explore whether EEN affected Ach levels and inflammation.One hundred thirteen patients were included in this prospective observational study. All patients were provided the early enteral nutrition protocol 24-48 h after admission to the intensive care unit (ICU). Blood samples were collected, and the plasma levels of Ach, cholecystokinin (CCK), and inflammatory markers (tumour necrosis factor alpha (TNF-α), interleukin 1beta (IL1-β), and IL6) were measured on Days 0, 1, 3, 5, and 7. Nutritional intervention data were recorded within one week, including the number of patients receiving nutrition, the number of days nutrition was provided, the caloric intake and protein intake, feeding intolerance and prokinetic drug administration. Other collected data included the sequential organ failure assessment score (SOFA score), the Acute Physiology and Chronic Health Evaluation (APACHE) II score, the use of mechanical ventilation (the number of patients and the duration), use of vasoactive drugs and the number of renal replacement treatments (RRT) received by each patient during their ICU stay. The primary outcome was 28-day mortality. Additionally, we analysed the correlation between plasma Ach levels and inflammation, as well as the correlation between plasma Ach and CCK levels. Moreover, a multivariate regression analysis was performed to examine the independent effects of different variables on 28-day mortality and Ach levels.The overall 28-day mortality was 28.3% (32/113). Eighty-two patients tolerated enteral nutrition. Compared with Day 0 15.6 (2.8) nmol/l, the plasma Ach level was significantly increased on Day 3 18.6 (6.7) nmol/l, Day 5 19.3 (6.2) nmol/l and Day 7 19.7 (4.3) nmol/l (p .001). Compared with Day 0176.2 (50.4) pg/ml, the plasma TNF-α level was significantly decreased on Day 3144.0 (77.4) pg/ml, Day 5127.3 (51.8) pg/ml and Day 7111.4 (42.5) pg/ml (p .05). Compared with Day 0, the plasma IL1-β level was significantly decreased on Day 7 (p .05). The plasma IL6 level was significantly decreased on Day 5 and Day 7 (p .05) compared with Day 0. Compared with Day 0, the plasma CCK level was significantly increased on Day 3, 5 and 7 (p .001). The correlation analysis revealed negative correlations between Ach levels and inflammation (p .001), and a positive correlation between CCK and Ach levels (r = 0.775, p .001). A comparison of patients who did or did not tolerate EEN revealed significant differences in the plasma levels of Ach, TNF-α, IL6 and CCK (p .05). Significant differences in plasma levels of Ach, TNF-α, IL1-β, IL6 and CCK were observed between 28-day survivors and non-survivors (p .05). The multivariate logistic regression analysis identified vasopressor support, RRT, the administration of EEN, SOFA score, APACHE II score at ICU admission and plasma Ach levels as independent determinants of 28-day mortality. Additionally, the multivariate linear regression analysis identified EEN, plasma lactate, mechanical ventilation, the SOFA score and plasma CCK levels as independent determinants of plasma Ach levels.The administration of EEN to critically ill patients contributed to the increased plasma Ach levels and decreased inflammatory markers. The effect of EEN on Ach levels is partially attributed to the increase in CCK levels. Elevated plasma Ach levels indicate a better prognosis. Clinical trials identifier: NCT03612206.

Background Acute gastrointestinal injury is associated with significantly increased mortality in critically ill patients. However, markers for measuring acute gastrointestinal injury are neither sensitive nor specific. Objective To determine whether enzymes in digestive fluid are predictive of the severity of acute gastrointestinal injury. Methods A prospective observational study was conducted between June 2015 and December 2015 in a surgical intensive care unit. Enrolled patients were classified by acute gastrointestinal injury grade according to the 2012 European Society of Intensive Care Medicine system. Digestive fluid was collected through nasointestinal tubes and analyzed 24 hours after the diagnosis of acute gastrointestinal injury. Intestinal markers of injury (pH, interleukin 6, interleukin 10, tumor necrosis factor α, and secretory immunoglobulin A) were measured in digestive fluid. Results Of the 76 patients included, acute gastrointestinal injury was grade I in 41, grade II in 20, grade III in 8, and grade IV in 7. Secretory immunoglobulin A was an independent predictor of grade III acute gastrointestinal injury. When data from patients with grades I and II injury and patients with grades III and IV injury were grouped together, analysis revealed that pH, interleukin 10, and secretory immunoglobulin A were independent predictors of acute gastrointestinal failure. Conclusions Secretory immunoglobulin A was predictive of grade III acute gastrointestinal injury. Digestive fluid markers of injury (pH, interleukin 10, and secretory immunoglobulin A) were predictors of acute gastrointestinal failure. Further study is required to determine if other markers are specific or sensitive for acute gastrointestinal injury.

Triptolide, a traditional Chinese medicine, obtained from Tripterygium wilfordii Hook F, has anti-inflammatory, antiproliferative, and proapoptotic properties. We investigated the potential efficacy of triptolide on murine leukemia by measuring the triptolide-induced cytotoxicity in murine leukemia WEHI-3 cells in vitro. Results indicated that triptolide induced cell morphological changes and induced cytotoxic effects through G0/G1 phase arrest, induction of apoptosis. Flow cytometric assays showed that triptolide increased the production of reactive oxygen species, Ca2+ release and mitochondrial membrane potential (ΔΨm ), and activations of caspase-8, -9, and -3. Triptolide increased protein levels of Fas, Fas-L, Bax, cytochrome c, caspase-9, Endo G, Apaf-1, PARP, caspase-3 but reduced levels of AIF, ATF6α, ATF6β, and GRP78 in WEHI-3 cells. Triptolide stimulated autophagy based on an increase in acidic vacuoles, monodansylcadaverine staining for LC-3 expression and increased protein levels of ATG 5, ATG 7, and ATG 12. The in vitro data suggest that the cytotoxic effects of triptolide may involve cross-talk between cross-interaction of apoptosis and autophagy. Normal BALB/c mice were i.p. injected with WEHI-3 cells to generate leukemia and were oral treatment with triptolide at 0, 0.02, and 0.2 mg/kg for 3 weeks then animals were weighted and blood, liver, spleen samples were collected. Results indicated that triptolide did not significantly affect the weights of animal body, spleen and liver of leukemia mice, however, triptolide significant increased the cell populations of T cells (CD3), B cells (CD19), monocytes (CD11b), and macrophage (Mac-3). Furthermore, triptolide increased the phagocytosis of macrophage from peripheral blood mononuclear cells (PBMC) but not effects from peritoneum. Triptolide promoted T and B cell proliferation at 0.02 and 0.2 mg/kg treatment when cells were pretreated with Con A and LPS stimulation, respectively; however, triptolide did not significant affect NK cell activities in vivo. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 550-568, 2017.

This study investigated the polyphenol content, antioxidant activity, and inhibition ability of mushroom tyrosinase and melanogenesis of Dendrobium tosaense (DT) extract. Ground DT was extracted using deionized water (W) or 50% ethanol (50E) at room temperature (RT) or 50 &deg, C (50T) for 20 min. The 50T + 50E extract exhibited the highest total phenol content 47.0 &plusmn, 4.0 mg gallic acid equivalent/g DT extract, the highest level of 2,2&prime, azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) free-radical scavenging 66.0 &plusmn, 3.0 mg Trolox equivalent/g DT extract, and the highest reducing power 12.00 &plusmn, 0.50 mg vitamin C equivalent/g DT extract. The RT + W extract had the highest total flavonoid content 110.0 &plusmn, 3.0 mg quercetin equivalent/g DT extract. The RT + 50E extract had the lowest half maximal inhibitory concentration 1.30 &plusmn, 0.00 mg/mL for 2,2-diphenyl-1-picrylhydrazyl free-radical scavenging, and the lowest half maximal inhibitory concentration 6.40 &plusmn, 0.30 mg/mL for mushroom tyrosinase inhibition activity. DT extracts, especially RT + W and 50T + W, exhibited potent inhibitory effects on melanogenesis of B16/F10 cells. These results demonstrated the application potential of DT extract for skincare.

In this study, we synthesized 4 methimazole (2-mercapto-1-methylimidazole, MMI) derivatives. The kinetics of inhibition on mushroom tyrosinase by methimazole and its derivatives were investigated. The results indicated that tert-butyl 3-methyl-2-sulfanylidene-2,3-dihydro-1H-imidazole-1-carboxylate (compound 3; 3), 2-mercaptoimidazole (MI; compound 1; 1) and MMI (compound 2; 2) significantly inhibited tyrosinase activity in a dose-dependent manner, exhibiting an IC50 value of 1.50 mM, 4.11 mM, and 1.43 mM. However, compound 4 (4), compound 5 (5), and compound 6 (6) exerted no inhibitory effect on mushroom tyrosinase activity. Kinetic analysis indicated that 3 was a noncompetitive tyrosinase inhibitor, whereas both 1 and 2 were exhibited as mixed-type tyrosinase inhibitors. Furthermore, 3 exerted a potent inhibitory effect on intracellular melanin formation in the B16/F10 murine melanoma cells and did not cause cytotoxicity, as 1 and 2 did.

This study was aimed at investigating the antioxidant, whitening, and moisture-retention properties of Lactobacillus rhamnosus spent culture supernatant (Lr-SCS) in cosmetic applications. Results reveal that Lr-SCS effectively and gradually scavenges 1,1-diphenyl-2-picrylhydrazyl as well as 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cations, and increases reducing power in a dose-dependent manner. Additionally, Lr-SCS can also suppress tyrosinase activity in vitro and effectively promote moisture retention. Heat treatment at 100 °C for 30 min does not influence the functions of Lr-SCS. We conclude that Lr-SCS can be used effectively in skin care cosmetics.

Summary Traditionally, tea is steeped in boiled water in Taiwan. In this study, Bi Luo Chun (250 μg mL−1) steeped at 4, 22, 30, 40 and 50 °C reached the saturation of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging capacity at the time of 15, 8, 2, 0.17 (10 s) and 0.17 min (10 s), respectively. The result indicated that tea steeped in cold water (under 22 °C) still can reach a saturation of antioxidant capacity in 15 min. However, the initial scavenging rate (% min−1) was quick and decreased with time at all steeping temperatures (r: −0.98 to −1.00). Total phenols and the DPPH scavenging capacity of Bi Luo Chun showed excellent correlation with time. However, the plot of DPPH scavenging capacity vs. total phenols was not always correlated. The result indicated that polyphenol infusion at different times may have a different DPPH scavenging capacity.

The biological effects of specific wavelengths, so-called “far-infrared radiation” produced from ceramic material (cFIR), on whole organisms are not yet well understood. In this study, we investigated the biological effects of cFIR on murine melanoma cells (B16-F10) at body temperature. cFIR irradiation treatment for 48 h resulted in an 11.8% decrease in the proliferation of melanoma cells relative to the control. Meanwhile, incubation of cells with cFIR for 48 h significantly resulted in 56.9% and 15.7% decreases in the intracellular heat shock protein (HSP)70 and intracellular nitric oxide (iNO) contents, respectively. Furthermore, cFIR treatment induced 6.4% and 12.3% increases in intracellular reactive oxygen species stained by 5-(and 6)-carboxyl-2′,7′-dichlorodihydrofluorescein diacetate and dihydrorhodamine 123, respectively. Since malignant melanomas are known to have high HSP70 expression and iNO activity, the suppressive effects of cFIR on HSP70 and NO may warrant future interest in antitumor applications.

This study reports the preparation of four varieties of water extract from sweet potato leaves from Taiwan, including TNG10, TNG57, TNG66 and YSP, and evaluates their antioxidative activity. The EC50 values (scavenging DPPH radicals) of TNG10, TNG57, TNG66 and YSP were 0.27 ± 0.01, 0.19 ± 0.01, 0.41 ± 0.02, and 0.31 ± 0.02 mg/ml, respectively, on a freeze-dry weight basis. The total phenolic contents of these water extracts were in the order: TNG57 > TNG10 > TNG66 > YSP. The TNG10 and TNG57 extracts exhibited better reducing power and scavenging effects of superoxide radicals than did TNG66 and YSP. At a concentration of 1 mg/ml, TNG10 and TNG57 significantly protected HaCaT cells from H2O2-induced cytotoxicity. The water extracts of YSP had more flavonoids than had those of TNG66 which may have contributed to their higher activity in many antioxidative assays. These results suggest that the water extracts of all four varieties of sweet potato leaves, and especially TNG10 and TNG57, display potent antioxidative effects.

Background: It has been known for thousands of years that humans have meridian lines. Objective: To understand the effects of induction of Qi by acupuncture in the meridians. Design, Setting, and Patients: The study was performed in 56 healthy volunteers who were randomly selected from the university population at Chia-Nan University of Pharmacy and Science, Taiwan. Blood flow at the acupoints of Lieque (LU 7) and Chize (LU 5) of the right hand, or a nonacupuncture point chosen freely near LU 5, was recorded. Intervention: Acupuncture stimulation of a human LU 7 point for about 15 seconds, until the De Qi sensation was achieved. Main Outcome Measure: Skin blood flow detected using a laser Doppler flowmeter. Results: When LU 7 was stimulated by acupuncture, the blood flow was increased after the De Qi sensation; as long as the participant was getting the emergence of a strong De Qi feeling or feeling a flow of numbness to reach LU 5, there was a visible peak of upward LU 5 blood flow. Conclusions:...

The purpose of this study was to explore whether passive watching of a stroke videotape in the Emergency Department waiting room could be an effective method for patient education. The setting was an urban, inner city teaching hospital. After providing informed consent, subjects were randomized into two arms: those watching a 12-min educational video on stroke developed by the American Stroke Association (video group) and those not undergoing an intervention (control group). Both groups were administered a 13-question quiz covering different stroke-related issues, but only the video group received this same test again after the completion of the educational program. Those enrolled were contacted after 1 month to determine knowledge retention via the same test. Immediately after watching the educational program, participants demonstrated improved knowledge of stroke-related questions, with an increase of test scores from 6.7 +/- 2.5 to 9.5 +/- 2.6 (p0.01). Even at the 1-month follow-up, the video group had significantly higher test scores than the control group. A stroke educational videotape improves the knowledge of this dangerous disease and may be a valuable and relatively low-cost tool for focused patient education in the Emergency Department waiting room.

The chemical composition and functional activities of cold-pressed and water distilled peel essential oils ofCitrus paradisi(C. paradisi) andCitrus grandis(L.) Osbeck (C. grandis) were investigated in present study. Yields of cold-pressed oils were much higher than those of distilled oils. Limonene was the primary ingredient of essential oils ofC. paradisi(cold 92.83%; distilled 96.06%) andC. grandis(cold 32.63%; distilled 55.74%). In addition,C. grandisoils obtained were rich in oxygenated or nitrogenated compounds which may be involved in reducing cardiovascular diseases or enhancing sleep effectiveness. The order of free radical scavenging activities of 4 citrus oils was distilledC. paradisioil > cold-pressedC. paradisioil > distilledC. grandisoil > cold-pressedC. grandisoil. Cold-pressedC. grandisoil exhibited the lowest activity in all antioxidative assays. The order of antimicrobial activities of 4 citrus oils was distilledC. grandisoil, cold-pressedC. paradisioil > distilledC. paradisioil > cold-pressedC. paradisioil. Surprisingly, distilledC. grandisoil exhibited better antimicrobial activities than distilledC. paradisioil, especially againstEscherichia coliandSalmonella entericasubsp. The results also indicated that the antimicrobial activities of essential oils may not relate to their antioxidative activities.

Dequalinium (DQ, an anticancer drug) is a potent neurotoxicant in the cultured developing cerebellar granule neurons (CGNs) with an IC(50) of 1.31. M after 24 hr incubation. By utilizing fluorometric technique, we found that DQ initially induced apoptosis and then necrosis associated with a marked decrease in ATP contents. The purinergic P(2) receptor antagonists (suramin, and reactive blue 2) prevented DQ-cytotoxicity, although glutamate ionotropic receptor antagonists (MK 801 and NBQX) could not. Furthermore, we quantitatively determined a reduction of mitochondrial membrane potential and an increase of free radical production induced by DQ. Suramin abolished these detrimental events of DQ. This suggests that neuronal death induced by DQ is mediated, at least in part, through a signaling pathway of free radical production-mitochondrial dysfunction. Further evidence supporting this contention is that CGN progressively became more sensitive to both DQ-induced cytotoxicity and reduced mitochondrial membrane potential. This implies that neuronal mitochondria are apparently one of the target sites for DQ and suramin and directly or indirectly induce neurotoxicity and neuroprotection respectively. The alteration in mitochondrial membrane potential during neuronal maturation may be one of the determinants accounting for the increased susceptibility to neurotoxicants such as DQ.

The goal of this study was to extract β-carotene from CYY95-26 sweet potatoes. Acetone was used as the solvent to successfully extract β-carotene. To achieve better extraction results, acetone concentration was required to be higher than 75%. Two extraction parameters, including acetone concentration and extraction time, were evaluated with the response surface methodology. The process was optimized, and optimal extraction conditions were determined to be 91.1% of acetone and 19.6 min extraction. Acetone concentration was a significant factor of the β-carotene extraction. The multiple extraction improved the extraction performance. After the third extraction, 278.1 mg/kg of β-carotene was extracted. The major carotene of CYY95-26 sweet potatoes was all-trans-β-carotene. CYY95-26 also contained small amount of 9-cis-β-carotene and 13-cis-β-carotene which were carotene isomers.

We investigated the relationship between [Ca2+]i, myosin light chain (LC20) phosphorylation and isometric force in guinea pig aortic strips during contractions activated by a thromboxane A2 analogue, (15S)-hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5Z, 13E-dienoic acid (U46619). Isometric force and [Ca2+]i were measured simultaneously using preloaded aequorin as the intracellular calcium indicator. LC20 phosphorylation levels were determined by two dimensional polyacrylamide gel electrophoresis in parallel preparations. Contractions induced by U46619 were accompanied by increases in [Ca2+]i and LC20 phosphorylation. The chelation of extracellular calcium with 2.5 mM EGTA significantly inhibited U46619-induced increases in [Ca2+]i, isometric force and LC20 phosphorylation. Steady-state force assumed a similar dependence on LC20 phosphorylation for contractions stimulated by potassium depolarization, alpha 1-adrenergic agonist phenylephrine and U46619 either in the presence or absence of extracellular calcium. On the contrary, the [Ca2+]i/force relation revealed that both U46619 and phenylephrine stimulated greater isometric force at lower [Ca2+]i than did KCl depolarization. The addition of a protein kinase C inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), decreases force without significantly affecting either [Ca2+]i or LC20 phosphorylation levels. These results suggest that in guinea pig aortic smooth muscle U46619 increases the calcium sensitivity of the contractile apparatus but does not change the LC20 phosphorylation/force relation in comparison to K+ depolarization. Protein kinase C is activated during U46619-stimulated contraction and might be involved in mechanisms other than LC20 phosphorylation.

Advances in stroke care will have the greatest effect on stroke outcome if care is delivered within a regional stroke system designed to improve both efficiency and effectiveness. The ultimate goal of stroke care is to minimize ongoing injury, emergently recanalize acute vascular occlusions, and begin secondary measures to maximize functional recovery. These efforts will provide stroke patients with the greatest opportunity for a return to previous quality of life and decrease the overall societal burden of stroke.

Study objective The Institute of Medicine Committee on the Future of Emergency Care in the United States Health System (2003) identified a need to enhance the research base for emergency care. As a result, a National Institutes of Health (NIH) Task Force on Research in Emergency Medicine was formed to enhance NIH support for emergency care research. Members of the NIH Task Force and academic leaders in emergency care participated in 3 Roundtable discussions to prioritize current opportunities for enhancing and conducting emergency care research. We identify key research questions essential to advancing the science of emergency care and discuss the barriers and strategies to advance research by exploring the collaboration between NIH and the emergency care community. Methods Experts from emergency medicine, neurology, psychiatry, and public health assembled to review critical areas in need of investigation, current gaps in knowledge, barriers, and opportunities. Neurologic emergencies included cerebral resuscitation, pain, stroke, syncope, traumatic brain injury, and pregnancy. Mental health topics included suicide, agitation and delirium, substances, posttraumatic stress, violence, and bereavement. Results Presentations and group discussion firmly established the need for translational research to bring basic science concepts into the clinical arena. A coordinated continuum of the health care system that ensures rapid identification and stabilization and extends through discharge is necessary to maximize overall patient outcomes. There is a paucity of well-designed, focused research on diagnostic testing, clinical decisionmaking, and treatments in the emergency setting. Barriers include the limited number of experienced researchers in emergency medicine, limited dedicated research funding, and difficulties of conducting research in chaotic emergency environments stressed by crowding and limited resources. Several themes emerged during the course of the roundtable discussion, including the need for development of (1) a research infrastructure for the rapid identification, consent, and tracking of research subjects that incorporates innovative informatics technologies, essential for future research; (2) diagnostic strategies and tools necessary to understand key populations and the process of medical decisionmaking, including the investigation of the pathobiology of symptoms and symptom-oriented therapies; (3) collaborative research networks to provide unique opportunities to form partnerships, leverage patient cohorts and clinical and financial resources, and share data; (4) formal research training programs integral for creating new knowledge and advancing the science and practice of emergency medicine; and (5) recognition that emergency care is part of an integrated system from emergency medical services dispatch to discharge. The NIH Roundtable "Opportunities to Advance Research on Neurological and Psychiatric Emergencies" created a framework to guide future emergency medicine–based research initiatives. Conclusion Emergency departments provide the portal of access to the health care system for most patients with acute neurologic and psychiatric illness. Emergency physicians and colleagues are primed to investigate neurologic and psychiatric emergencies that will directly improve the delivery of care and patient outcomes.

Emergency physicians are routinely confronted with problems associated with language barriers. It is important for emergency health care providers and the health system to strive for cultural competency when communicating with members of an increasingly diverse society. Possible solutions that can be implemented include appropriate staffing, use of new technology, and efforts to develop new kinds of ties to the community served. Linguistically specific solutions include professional interpretation, telephone interpretation, the use of multilingual staff members, the use of ad hoc interpreters, and, more recently, the use of mobile computer technology at the bedside. Each of these methods carries a specific set of advantages and disadvantages. Although professionally trained medical interpreters offer improved communication, improved patient satisfaction, and overall cost savings, they are often underutilized due to their perceived inefficiency and the inconclusive results of their effect on patient care outcomes. Ultimately, the best solution for each emergency department will vary depending on the population served and available resources. Access to the multiple interpretation options outlined above and solid support and commitment from hospital institutions are necessary to provide proper and culturally competent care for patients. Appropriate communications inclusive of interpreter services are essential for culturally and linguistically competent provider/health systems and overall improved patient care and satisfaction.

AIM: To detect multiple H pylori antibodies in serum samples of individuals who carryH pylori by protein array. METHODS: Recombinant H pylori antigens, urease B subunit (UreB), vacuolating toxin A (VacA) and cytotoxin associated gene A protein (CagA), were prepared and immobilized in matrixes on nitrocellulose membrane by robotics to bind the specific immunoglobulin G (IgG) antibodies in serum. Staphylococcus protein A (SPA) labeled by colloid gold was used to integrate the immuno-complex and gave red color signal. The scanner based on charge-coupled device (CCD) could collect the image signal and convert it into digital signal. RESULTS: When human IgG was printed on the membrane in increasing concentrations and incubated with immunogold, a linear dose response curve was obtained and the detection limit for IgG was about 0.025 ng. The cutoff values, which were defined as the mean grey level plus 3 times of standard deviation, were 27.183, 28.546 and 27.402, for anti-UreB IgG, anti-CagA IgG and anti-VacA IgG, respectively, as 400 human serum samples with negative H pylori antibodies were detected by the protein array. When 180 serum samples from patients in hospital were employed for detection of IgG against UreB, CagA and VacA, the sensitivity of the protein array was 93.4%, 95.4%, 96.0%, and the specificity was 94.8%, 94.4% and 97.5%, respectively, as compared with the results obtained by ELISA. The assay also showed high reproducibility, uniformity and stability, and the results were available within 30 min. CONCLUSION: The protein array is a very practical method for rapid detection of multiple antibodies in serum samples. It is especially useful for large scale epidemiological investigation of the infection of H pylori.

The aim of this study was to investigate the effects of a human urine preparation on the differentiation of tumor cells.The pheochromocytoma PC12 cells were used to examine the effects of a human urine preparation, CDA-2 on the induction of differentiation markers, neurofilaments, and compared with that induced by nerve growth factor (NGF). The MAPK/ERK kinase (MEK) inhibitor U0126 was used to examine the involvement of mitogen-activated protein kinase (MAPK) signaling pathway in this differentiation inducing effect.We find that CDA-2 could induce differentiation of pheochromocytoma PC12 cells, as evidenced by the markedly increased expression of neurofilaments to a level comparable to those induced by NGF. This phenomenon was accompanied by the phosphorylation of extracellular-signal-regulated kinase (ERK) and could be inhibited by the MEK inhibitor, U0126.Our results demonstrate the presence of active components in the human urine extract that can induce differentiation of PC12 cells and may involve the ERK signaling pathway. This may provide new insights for seeking novel differentiation agents and offer hope for cancer patients.

Lovastatin (an HMG-CoA reductase inhibitor) and troglitazone (a PPAR-gamma agonist) have been intensively studied prospectively for their application in cancer treatment. However, clinical trials of lovastatin or troglitazone in cancer treatment resulted in only limited responses. To improve their efficacy, lovastatin and troglitazone have, respectively, been tried to combine with other anticancer agents with varied outcomes. In our study, we found a dramatic synergism between lovastatin and troglitazone in anticancer at clinically achievable concentrations. This synergism was found in far majority of cell lines tested including DBTRG 05 MG (glioblastoma) and CL1-0 (lung). This amazing synergism was accompanied by synergistic modulation of E2F-1 and p27(Kip1), which were reported to mediate the anticancer activities of lovastatin and troglitazone, respectively, and other cell cycle regulating proteins such as CDK2, cyclin A and RB phosphorylation status. With this dramatic combination effect of lovastatin and troglitazone, a promising regimen of cancer therapy may be materialized in the future.

Nationally, only 2-3% of patients with acute ischemic stroke (AIS) currently receive tissue plasminogen activator (TPA). To better understand the reasons, we investigated the practice patterns, level of familiarity and acceptance of TPA for AIS among emergency physicians in New York City (NYC). Fifty-seven 911-receiving hospital emergency department directors were surveyed regarding TPA use. Of those responding, 37% had never used TPA to treat AIS. Lack of neurological support was reported by 33%. Departments with formal protocols were more likely to use TPA for AIS. In conclusion, there is considerable variation in the practice, knowledge, and attitudes regarding the use of TPA for AIS in NYC emergency departments. Improved educational efforts and institutional support may be necessary to ensure the appropriate use of TPA by emergency physicians.

Hepatitis C is a world-wide epidemic disease stemming from the hepatitis C virus (HCV). HCV is not only the pathogenic factor of hepatitis C but also plays an important role in the process of triggering and development of cirrhosis and liver cancer. There are two indicators for detecting HCV infection: one is HCV RNA which is the gene of the virus itself and the other is anti-HCV which is the antibody produced when the HCV antigen stimulates the body. The HCV antibody detection includes the detection of HCV IgG and HCV-IgM antibody. At present, EIA and the recombinant immunoblot assay (RIBA) are mainly used for detecting anti-HCV-IgG. By using the colloidal gold labeling technique to fix the structural and the non-structural domains of HCV recombinant antigen on the millipore membrane, a dot immunogold filtration assay for detecting anti-HCV-IgG was successfully established.

In this study, we demonstrated that an anticancer drug, dequalinium, a bisquaternary ammonium compound, is a potent neurotoxicant with IC 50 of 0.46 μM on the cultured cerebellar granule neurons. Its selective neurotoxicity revealed by 100-fold more toxic than the other two analogs, pancuronium and vecuronium. The mechanisms underlying dequalinium (DQ)-induced neurotoxicity were explored and found to be associated with decreased mitochondrial membrane potential, increased free radical production and ATP depletion. Suramin (a nonselective purinergic P 2 receptor antagonist and an anticancer drug) but not the glutamate receptor antagonists, MK-801, NBQX (1,2,3,4 tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium), and DNQX (6,7-dinitroquinoxaline-2,3-dione) significantly prevents the DQ-induced neurotoxicity. By means of microfluorometric image-processing technique using the fluorescent probes, fluorescein diacetate/propidium iodide and Hoechst 33258, respectively, we showed that 1 μM DQ for 24 h induced about 53.5% of apoptosis and 37.5% of necrosis. All of these effects of DQ can be completely prevented by suramin. From these results, we conclude that DQ-induced neurotoxicity was not mediated by glutamate receptor, but by increasing free radical productions and cell energy depletion. Suramin with its beneficial antagonistic effects on DQ-induced neurotoxicity may provide an effective approach for neurodegeneration.

In the title compound, C(13)H(21)N(3)O(4)S, the mean plane of the -N(H)-C(=O)-O- group of the carbamate unit forms a dihedral angle of 64.7 (2)° with the mean plane of the -C-C(=O)-O- group of the ester unit. In the crystal, mol-ecules are linked by N-H⋯O=C hydrogen bonds, forming chains along the c-axis direction.

(2004). THE EFFECT OF WEATHER AND AIR POLLUTION ON EMS CALLS FOR BREATHING-RELATED COMPLAINTS IN AN URBAN CITY. Prehospital Emergency Care: Vol. 8, No. 1, pp. 107-107.

The hepatitis A virus specific immunoglobulin M (IgM) antibody is a specific serological marker for early diagnosis of hepatitis A. At present, the methods used at home or abroad for detecting anti-HAV IgM are RIA, ELISA and SPHAI. The dot immunogold combination assay that has been developed since 1989 is a new technique with the property of simple and rapid immunological detection, by using the red colloidal gold particles to label the antibodies as indicator, and the millipore filtering membrane coated with antigen as the carrier. Affected by filtration and condensation, the antigen antibody reaction is enabled to go on rapidly. When the reaction is positive, red dots appear on the membrane. It takes about 2 min to 4 min for the whole reaction to be carried out. With the above technique, we have established the dot immunogold filtration assay (DIGFA) for rapid detection of anti-HAV IgM with comparatively satisfactory results.