Thermal Burn Injury Generates Bioactive Microvesicles: Evidence for a Novel Transport Mechanism for the Lipid Mediator Platelet-Activating Factor (PAF) That Involves Subcellular Particles and the PAF Receptor.

Thermal burn injuries are an important environmental stressor that can result in considerable morbidity and mortality. The exact mechanism by which an environmental stimulus to skin results in local and systemic effects is an area of active research. One potential mechanism to allow skin keratinocytes to disperse bioactive substances is via microvesicle particles, which are subcellular bodies released directly from cellular membranes. Our previous studies have indicated that thermal burn injury of the skin keratinocyte in vitro results in the production of the lipid mediator platelet-activating factor (PAF). The present studies demonstrate that thermal burn injury to keratinocytes in vitro and human skin explants ex vivo, and mice in vivo generate microvesicle particles. Use of pharmacologic and genetic tools indicates that the optimal release of microvesicles is dependent upon the PAF receptor. Of note, burn injury-stimulated microvesicle particles do not carry appreciable protein cytokines yet contain high levels of PAF. These studies describe a novel mechanism involving microvesicle particles by which a metabolically labile bioactive lipid can travel from cells in response to environmental stimuli.

Integrated on-site collection and detection of airborne microparticles for smartphone-based micro-climate quality control.

The rapid emergence of air-mediated diseases in a micro-climate demands on-site monitoring of airborne microparticles. The on-site detection of airborne microparticles becomes more challenging as the particles are highly localized and change dynamically over time. However, most existing monitoring systems rely on time-consuming sample collection and centralized off-site analysis. Here, we report a smartphone-based integrated microsystem for on-site collection and detection that enables real-time detection of indoor airborne microparticles with high sensitivity. The collection device, inspired by the Venturi effect, was designed to collect airborne microparticles without requiring an additional power supply. Our systematic analysis showed that the collection device was able to collect microparticles with consistent negative pressure, regardless of the particle concentration in the air sample. By incorporating a microfluidic-biochip based on inertial force to trap particles and an optoelectronic photodetector into a miniaturized device with a smartphone, we demonstrate real-time and sensitive detection of the collected airborne microparticles, such as Escherichia coli, Bacillus subtilis, Micrococcus luteus, and Staphylococcus with a particle-density dynamic range of 103-108 CFU mL-1. Because of its capabilities of minimal-power sample collection, high sensitivity, and rapid detection of airborne microparticles, this integrated platform can be readily adopted by the government and industrial sectors to monitor indoor air contamination and improve human healthcare.

Expression of Nur77 induced by an n-butylidenephthalide derivative promotes apoptosis and inhibits cell growth in oral squamous cell carcinoma.

In spite of numerous advances, the 5-year survival rate for head and neck squamous cell cancer has remained largely stagnant and few new anti-tumor drugs have been developed. PCH4, a derivative of n-butylidenephthalide, has been investigated for its anti-tumor effects on oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the anti-tumor mechanism of a potential target gene, Nur77, in OSCC cells, which can be induced by PCH4 treatment. Data show that PCH4 promoted Nur77 translocation from the nucleus to the cytoplasm and induced cell apoptosis in OSCC cells. When Nur77 translocation was blocked, the degree of tumor apoptosis caused by PCH4 was significantly inhibited (p < 0.05). Within the MAPK pathway, PCH4 only induced JNK phosphorylation. Furthermore, treatment with a JNK inhibitor significantly reduced PCH4-induced apoptosis (p < 0.05) and decreased PCH4-induced Nur77 expression (p < 0.05). In a xenograft animal model, administration of PCH4 also showed anti-tumor effects. We have demonstrated that OSCC cells are sensitive to PCH4 and that Nur77 protein translocation from the nucleus to the cytoplasm might be associated with the induction of apoptosis by PCH4. These results indicate that PCH4 may serve as a potential anti-tumor drug for OSCC therapy.

The Emerging Applications of Nanotechnology in Neuroimaging: A Comprehensive Review.

Neuroimaging modalities such as computer tomography and magnetic resonance imaging have greatly improved in their ability to achieve higher spatial resolution of neurovascular and soft tissue neuroanatomy, allowing for increased accuracy in the diagnosis of neurological conditions. However, the use of conventional contrast agents that have short tissue retention time and associated renal toxicities, or expensive radioisotope tracers that are not widely available, continue to limit the sensitivity of these imaging modalities. Nanoparticles can potentially address these shortcomings by enhancing tissue retention and improving signal intensity in the brain and neural axis. In this review, we discuss the use of different types of nanotechnology to improve the detection, diagnosis, and treatment of a wide range of neurological diseases.

Neuroprotection effects of retained acupuncture in neurotoxin-induced Parkinson's disease mice.

The aim of this study was to investigate the role of retained acupuncture (RA) in neurotoxin-induced Parkinson's disease (PD) mice. Male C57BL/6 mice were injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce the PD model. The mice were divided into four groups, namely, (1) normal; (2) MPTP+retained acupuncture (RA); (3) MPTP+electroacupuncture (EA); (4) MPTP+sham acupuncture (SA). After mice being manipulated with/without acupuncture at acupoints (Daling, PC 7), groups 2-4 were injected with MPTP (15 mg/kg/d). The mice were evaluated for behavioral changes, in terms of time of landing, after acupuncture treatment. The animals were sacrificed and their brains assayed for dopamine and its metabolites and tyrosine hydroxylase (TH) expression by using HPLC and immunohistochemistry/Western blotting, respectively. [(123)I] IBZM-SPECT imaging between SA and RA groups were compared. The results showed that the time of landing of the three groups with treatment was significant longer than group 1 (normal) (4.33±0.15 s). Nonetheless, group 2 (RA) (7.13±0.20 s) had a shorter time of landing than group 4 (SA) (7.89±0.46 s). The number of TH (+) neurons and the expression of TH proteins were significantly higher in the RA group than in the SA/EA groups. RA also increased the uptake of [(123)I] IBZM into the triatum compared to the SA group. We conclude that RA possibly attenuates neuronal damage in MPTP-induced PD mice, which suggests RA may be useful as a complementary strategy when treating human PD.

Tempering of cocoa butter and chocolate using minor lipidic components.

Chocolate manufacture includes a complex tempering procedure to direct the crystallization of cocoa butter towards the formation of fat crystal networks with specific polymorphism, nano- and microstructure, melting behavior, surface gloss and mechanical properties. Here we investigate the effects of adding various minor non-triglyceride lipidic components to refined cocoa butter and chocolate on their physical properties. We discover that addition of saturated phosphatidylcholine and phosphatidylethanolamine to neutralized and bleached cocoa butter or molten and recrystallized commercial chocolate at 0.1% (w/w) levels, followed by rapid cooling to 20 °C in the absence of shear, accelerates crystallization, stabilizes the desirable Form V polymorph and induces the formation of chocolate with an optimal microstructure, surface gloss and mechanical strength. Final chocolate structure and properties are comparable to those of a commercial tempered chocolate. Minor lipidic component addition represents an effective way to engineer chocolate material properties at different length scales, thus simplifying the entire tempering process.

N-palmitoyl glycine, a novel endogenous lipid that acts as a modulator of calcium influx and nitric oxide production in sensory neurons.

N-arachidonoyl glycine is an endogenous arachidonoyl amide that activates the orphan G protein-coupled receptor (GPCR) GPR18 in a pertussis toxin (PTX)-sensitive manner and produces antinociceptive and antiinflammatory effects. It is produced by direct conjugation of arachidonic acid to glycine and by oxidative metabolism of the endocannabinoid anandamide. Based on the presence of enzymes that conjugate fatty acids with glycine and the high abundance of palmitic acid in the brain, we hypothesized the endogenous formation of the saturated N-acyl amide N-palmitoyl glycine (PalGly). PalGly was partially purified from rat lipid extracts and identified using nano-high-performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry. Here, we show that PalGly is produced after cellular stimulation and that it occurs in high levels in rat skin and spinal cord. PalGly was up-regulated in fatty acid amide hydrolase knockout mice, suggesting a pathway for enzymatic regulation. PalGly potently inhibited heat-evoked firing of nociceptive neurons in rat dorsal horn. In addition, PalGly induced transient calcium influx in native adult dorsal root ganglion (DRG) cells and a DRG-like cell line (F-11). The effect of PalGly on the latter cells was characterized by strict structural requirements, PTX sensitivity, and dependence on the presence of extracellular calcium. PalGly-induced calcium influx was blocked by the nonselective calcium channel blockers ruthenium red, 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole (SK&F96365), and La3+. Furthermore, PalGly contributed to the production of NO through calcium-sensitive nitric-oxide synthase enzymes present in F-11 cells and was inhibited by the nitric-oxide synthase inhibitor 7-nitroindazole.

Habitual cocaine use is associated with high defibrillation threshold during ICD implantation.

BACKGROUND: Habitual cocaine use can lead to dilated cardiomyopathy (DCM) and sudden cardiac death. Based on prior clinical observations, we hypothesized that prior habitual cocaine use is a strong predictor of high defibrillation threshold (DFT) during implantable cardioverter-defibrillator (ICD) implant. METHODS: We reviewed the medical records of 130 consecutive patients undergoing initial ICD implantation or revision at Parkland Hospital and the Dallas VA Hospital, Dallas, TX, from January 2002 to November 2005. Patient characteristics and DFT data were collected retrospectively. RESULTS: The study group includes 11 patients (8.46%) who were identified as having a history of prior habitual cocaine use as demonstrated by history and urine toxicology; the rest (119 patients) form the control group. Cocaine-using patients tended to be younger (48.2 +/- 10 vs 60.1 +/- 12.3 years; P = 0.0026), were less likely to have coronary disease (36.3% vs 72.2%; P = 0.032), and had less comorbidity. The average DFT was 27.9 +/- 7.8 J for all cocaine-using patients and 14.5 +/- 4.1 J for noncocaine-using patients (P = 0.00018). In the cocaine-using group, three out of 11 patients required a subcutaneous array compared to none in the control group. CONCLUSIONS: Our results suggest that patients with a history of habitual cocaine use may be at increased risk to have a high DFT during ICD implantation. This is the first study to demonstrate such association. ICD implantation in patients with this history should be planned with these findings in mind, as larger output generators or subcutaneous arrays might be required.

Targeted lipidomics: fatty acid amides and pain modulation.

Mass spectrometric approaches to the identification and quantification of lipid signalling molecules are reviewed. Fatty acid amides are an important new class of lipid signalling molecules which include oleamide, the endocannabinoid anandamide, the endovanilloid/endocannabinoid N-arachidonoyldopamine (NADA) and the endovanilloid N-oleoyldopamine (OLDA) among many others. This diverse group of endogenous compounds comprises combinations of acyl backbones coupled by an amide bond to any of a variety of different small polar molecules such as ethanolamine, various amino acids, and catecholamines. Many fatty acid amides appear to play a role in pain and inflammation. Targeted lipidomics of fatty acid amides aims to identify new members of this diverse class of compounds, of which only a few representative molecules have been characterized to date. This effort has been made feasible by advances in chromatography and mass spectrometry, which permits: (1) identification of compounds present in complex mixtures, (2) astronomical increases in sensitivity due to miniaturization of HPLC components, and (3) novel scanning modes that permit the identification of compounds exhibiting similar structural components. Insofar as lipid signalling molecules such as prostanoids, leukotrienes and endocannabinoids operate via G-protein coupled receptors (GPCR), it appears likely that many of the numerous lipids awaiting identification may serve as ligands for any of the greater than 150 orphan GPCRs.

Rapid-rate nonsustained ventricular tachycardia found on implantable cardioverter-defibrillator interrogation: relationship to outcomes in the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial).

OBJECTIVES: The aim of this study was to examine rapid-rate nonsustained ventricular tachycardia (RR-NSVT) during routine implantable cardioverter-defibrillator (ICD) evaluation in patients with heart failure and its relationship to outcomes. BACKGROUND: The clinical implications of RR-NSVT identified during routine ICD interrogation are unclear. In this study, the occurrence of RR-NSVT and its association with ICD shocks and mortality in SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) were examined. METHODS: The 811 patients who received ICDs in SCD-HeFT constituted the study population. The occurrence of RR-NSVT and its association with ICD shocks and mortality in SCD-HeFT were examined. RESULTS: RR-NSVT was documented on ICD interrogation in 186 of 811 patients (22.9%). The mean duration of RR-NSVT was 26.4 ± 9.1 beats (7.5 ± 2.6 s), with a mean cycle length of 259 ± 32 ms. Polymorphic RR-NSVT accounted for 56% of episodes. Compared with patients without RR-NSVT, those with RR-NSVT were less likely to be taking beta-blockers, statins, or aspirin at enrollment. After adjusting for other known predictors of mortality in SCD-HeFT, RR-NSVT was independently associated with appropriate ICD shocks (hazard ratio: 4.25; 95% confidence interval: 2.94 to 6.14; p < 0.0001), with all-cause mortality (hazard ratio: 2.40; 95% confidence interval: 1.62 to 3.54; p < 0.0001), and with a composite of all-cause mortality and appropriate ICD shocks (hazard ratio: 3.03; 95% confidence interval: 2.21 to 4.15; p < 0.0001). CONCLUSIONS: RR-NSVT identified on routine ICD interrogation should be considered an important clinical event. RR-NSVT during ICD interrogation is associated with appropriate ICD shocks and all-cause mortality. The clinical evaluation of patients with RR-NSVT should include intensification of medical therapy, particularly beta-blockers, or other appropriate clinical interventions. (Sudden Cardiac Death in Heart Failure Trial [SCD-HeFT]; NCT00000609).

Cross-cultural effect on suboptimal effort detection: an example of the Digit Span subtest of the WAIS-III in Taiwan.

Suppressed Digit Span performance has been proposed as an embedded indicator for suboptimal effort detection in neuropsychological evaluations in Western societies, particularly in the USA. However, its effectiveness in Chinese countries remains unexplored. The purposes of this study were first to explore normative Digit Span performance patterns between the Taiwan and American standardization samples, then to examine performances of patients with traumatic brain injury and with psychiatric diseases on the embedded measures (the Digit Span Scaled Score, Vocabulary minus Digit Span difference score, Reliable Digit Span, and the longest string of digits forward and backward) through retrospective data analysis. The normative Digit Span performance differs between the two cultural populations. Although litigating and nonlitigating participants perform differently on these measures, further prospective studies are needed to explore this issue with comprehensive external corroborating validity data.

Image segmentation and activity estimation for microPET 11C-raclopride images using an expectation-maximum algorithm with a mixture of Poisson distributions.

The objective of this study was to use a mixture of Poisson (MOP) model expectation maximum (EM) algorithm for segmenting microPET images. Simulated rat phantoms with partial volume effect and different noise levels were generated to evaluate the performance of the method. The partial volume correction was performed using an EM deblurring method before the segmentation. The EM-MOP outperforms the EM-MOP in terms of the estimated spatial accuracy, quantitative accuracy, robustness and computing efficiency. To conclude, the proposed EM-MOP method is a reliable and accurate approach for estimating uptake levels and spatial distributions across target tissues in microPET (11)C-raclopride imaging studies.

The biosynthesis of N-arachidonoyl dopamine (NADA), a putative endocannabinoid and endovanilloid, via conjugation of arachidonic acid with dopamine.

N-arachidonoyl dopamine (NADA) is an endogenous ligand that activates the cannabinoid type 1 receptor and the transient receptor potential vanilloid type 1 channel. Two potential biosynthetic pathways for NADA have been proposed, though no conclusive evidence exists for either. The first is the direct conjugation of arachidonic acid with dopamine and the other is via metabolism of a putative N-arachidonoyl tyrosine (NA-tyrosine). In the present study we investigated these biosynthetic mechanisms and report that NADA synthesis requires TH in dopaminergic terminals; however, NA-tyrosine, which we identify here as an endogenous lipid, is not an intermediate. We show that NADA biosynthesis primarily occurs through an enzyme-mediated conjugation of arachidonic acid with dopamine. While this conjugation likely involves a complex of enzymes, our data suggest a direct involvement of fatty acid amide hydrolase in NADA biosynthesis either as a rate-limiting enzyme that liberates arachidonic acid from AEA, or as a conjugation enzyme, or both.

Back to the future: the role of the autonomic nervous system in atrial fibrillation.

The purpose of this manuscript is to review the current literature regarding the role of the autonomic nervous system (ANS) in atrial fibrillation (AF). We will be reviewing its effect on initiation, maintenance, and termination of AF, with emphasis on the role of baroreflex gain (BRG) and autonomic reflexes in the maintenance of this arrhythmia. While it is generally accepted that the ANS plays an important role in AF, the extent of that role remains controversial. Much of the controversy could be explained by the time frame during which the autonomic measurements were made, the differences in patient population, and possibly the differential effect of the autonomic changes on the trigger versus the substrate. While vagal stimulation results in shortening of the atrial effective refractory period and increased dispersion of refractoriness, its effect on the "trigger" might be antiarrhythmic. During AF, cardiac filling pressure increases while arterial blood pressure decreases sending conflicting messages to the medulla. The acute effect is an increase in sympathetic activity to ensure adequate hemodynamic stability. On the other hand, the long-term effects might be impairment in the cardiopulmonary BRG and changes that accentuate the presence of AF. While radiofrequency ablation has provided us with a unique insight into the role of possible denervation in AF suppression, the exact mechanisms involved are far from being completely understood. Today, in an era where great technological advances have occurred, our need to understand the role of the ANS in AF is greater than ever.

[Semi-analysis algorithm to retrieve pigment concentrations in the red tide area of the East China Sea].

For the purpose of detecting and forecasting research of red tides to reduce the loss, a semi-analytic algorithm to retrieve chlorophyll-a concentrations was established in the area where red tides often brought out, according to the data collected during the red tides cruise in the East China Sea in April 2002. In the algorithm, empirical equations were made based on the coefficients from the in-situ data, including the optical properties of the research area. The in-situ data were used to validate the algorithm. The discrepancy of chlorophyll-a absorption coefficients and concentrations are mainly located in the region of 30%. The root mean deviation of the chlorophyll-a concentrations between the observed and the calculated is 0.24, the maximum relative deviation 40.93%, the mean relative deviation 18.83% and the correlation coefficient 0.83. The results show that the precision of the algorithm is high and the algorithm is fit for the research area.

Targeted lipidomics: discovery of new fatty acyl amides.

The discovery of endogenous fatty acyl amides such as N-arachidonoyl ethanolamide (anandamide), N-oleoyl ethanolamide (OEA), and N-arachidonoyl dopamine (NADA) as important signaling molecules in the central and peripheral nervous system has led us to pursue other unidentified signaling molecules. Until recently, technical challenges, particularly those associated with lipid purification and chemical analysis, have hindered the identification of low abundance signaling lipids. Improvements in chromatography and mass spectrometry (MS) such as miniaturization of high-performance liquid chromatography components, hybridization of multistage mass spectrometers and time-of-flight technology, the development of electrospray ionization (ESI) and of information-dependent acquisition, now permit rapid identification of novel, low abundance, signaling lipids.

Wearable sensors for reliable fall detection.

Unintentional falls are a common cause of severe injury in the elderly population. By introducing small, non-invasive sensor motes in conjunction with a wireless network, the Ivy Project aims to provide a path towards more independent living for the elderly. Using a small device worn on the waist and a network of fixed motes in the home environment, we can detect the occurrence of a fall and the location of the victim. Low-cost and low-power MEMS accelerometers are used to detect the fall while RF signal strength is used to locate the person.