Defunct brain stem cardiovascular regulation underlies cardiovascular collapse associated with methamphetamine intoxication

<p>Abstract</p> <p>Background</p> <p>Intoxication from the psychostimulant methamphetamine (METH) because of cardiovascular collapse is a common cause of death within the abuse population. For obvious reasons, the heart has been taken as the primary target for this METH-induced toxicity. The demonstration that failure of brain stem cardiovascular regulation, rather than the heart, holds the key to cardiovascular collapse induced by the pesticide mevinphos implicates another potential underlying mechanism. The present study evaluated the hypothesis that METH effects acute cardiovascular depression by dampening the functional integrity of baroreflex via an action on brain stem nuclei that are associated with this homeostatic mechanism.</p> <p>Methods</p> <p>The distribution of METH in brain and heart on intravenous administration in male Sprague-Dawley rats, and the resultant changes in arterial pressure (AP), heart rate (HR) and indices for baroreflex-mediated sympathetic vasomotor tone and cardiac responses were evaluated, alongside survival rate and time.</p> <p>Results</p> <p>Intravenous administration of METH (12 or 24 mg/kg) resulted in a time-dependent and dose-dependent distribution of the psychostimulant in brain and heart. <b/>The distribution of METH to neural substrates associated with brain stem cardiovascular regulation was significantly larger than brain targets for its neurological and psychological effects; the concentration of METH in cardiac tissues was the lowest among all tissues studied. In animals that succumbed to METH, the baroreflex-mediated sympathetic vasomotor tone and cardiac response were defunct, concomitant with cessation of AP and HR. On the other hand, although depressed, those two indices in animals that survived were maintained, alongside sustainable AP and HR. Linear regression analysis further revealed that the degree of dampening of brain stem cardiovascular regulation was positively and significantly correlated with the concentration of METH in key neural substrate involved in this homeostatic mechanism.</p> <p>Conclusions</p> <p>We conclude that on intravenous administration, METH exhibits a preferential distribution to brain stem nuclei that are associated with cardiovascular regulation. We further found that the concentration of METH in those brain stem sites dictates the extent that baroreflex-mediated sympathetic vasomotor tone and cardiac responses are compromised, which in turn determines survival or fatality because of cardiovascular collapse.</p

The interaction of marine fouling organisms with topography of varied scale and geometry: a review

Many studies have examined the effects of surface topography on the settlement behaviour of marine organisms and this article reviews these investigations with more emphasis on the effects of topography scale. It has been observed that macro topographies (1-100 mm) are generally favoured by marine fouling taxa and are unsuitable for antifouling applications. This is because macro topographies are usually large enough to fit fouling organisms and provide refuge from dangers in the marine environment. Micro topographies had only limited success at reducing fouling from a wide range of marine taxa. The antifouling performance of micro topographies (1 to ≤1000 μm) is dependent on the properties of topography features in terms of symmetry, isotropy, width, length, height/depth, separation distance and average roughness. In terms of the antifouling performance of micro topography, topography geometry may only be of secondary importance in comparison to the size of features itself. It is also noted that hydrodynamic stresses also contribute to the settlement trends of foulers on textured surfaces. Future studies on antifouling topographies should be directed to hierarchical topographies because the mixed topography scales might potentially reduce fouling by both micro and macro organisms. Patterned nano-topographies (1- ≤1000 nm) should also be explored because the antifouling mechanisms of these topographies are not yet clear

Color changes upon cooling of Lepidoptera scales containing photonic nanoarchitectures, and a method for identifying the changes

The effects produced by the condensation of water vapor from the environment in the various intricate nanoarchitectures occurring in the wing scales of several Lepidoptera species were investigated by controlled cooling (from 23° C, room temperature to -5 to -10° C) combined with in situ measurements of changes in the reflectance spectra. It was determined that all photonic nanoarchitectures giving a reflectance maximum in the visible range and having an open nanostructure exhibited alteration of the position of the reflectance maximum associated with the photonic nanoarchitectures. The photonic nanoarchitectures with a closed structure exhibited little to no alteration in color. Similarly, control specimens colored by pigments did not exhibit a color change under the same conditions. Hence, this method can be used to identify species with open photonic nanoarchitectures in their scales. For certain species, an almost complete disappearance of the reflectance maximum was found. All specimens recovered their original colors following warming and drying. Cooling experiments using thin copper wires demonstrated that color alterations could be limited to a width of a millimeter or less. Dried museum specimens did not exhibit color changes when cooled in the absence of a heat sink due to the low heat capacity of the wings

Effect of dietary omega-3 fatty acids on castrate-resistant prostate cancer and tumor-associated macrophages.

BackgroundM2-like macrophages are associated with the pathogenesis of castrate-resistant prostate cancer (CRPC). We sought to determine if dietary omega-3 fatty acids (ω-3 FAs) delay the development and progression of CRPC and inhibit tumor-associated M2-like macrophages.MethodsMycCap cells were grown subcutaneously in immunocompetent FVB mice. Mice were castrated when tumors reached 300 mm2. To study effects of dietary ω-3 FAs on development of CRPC, ω-3 or ω-6 diets were started 2 days after castration and mice sacrificed after early regrowth of tumors. To study ω-3 FA effects on progression of CRPC, tumors were allowed to regrow after castration before starting the diets. M2 (CD206+) macrophages were isolated from allografts to examine ω-3 FA effects on macrophage function. Omega-3 fatty acid effects on androgen-deprived RAW264.7 M2 macrophages were studied by RT-qPCR and a migration/ invasion assay.ResultsThe ω-3 diet combined with castration lead to greater MycCap tumor regression (tumor volume reduction: 182.2 ± 33.6 mm3) than the ω-6 diet (tumor volume reduction: 148.3 ± 35.2; p = 0.003) and significantly delayed the time to CRPC (p = 0.006). Likewise, the ω-3 diet significantly delayed progression of established castrate-resistant MycCaP tumors (p = 0.003). The ω-3 diet (as compared to the ω-6 diet) significantly reduced tumor-associated M2-like macrophage expression of CSF-1R in the CRPC development model, and matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the CRPC progression model. Migration of androgen-depleted RAW264.7 M2 macrophages towards MycCaP cells was reversed by addition of docosahexaenoic acid (ω-3).ConclusionsDietary omega-3 FAs (as compared to omega-6 FAs) decreased the development and progression of CRPC in an immunocompetent mouse model, and had inhibitory effects on M2-like macrophage function. Clinical trials are warranted evaluating if a fish oil-based diet can delay the time to castration resistance in men on androgen deprivation therapy, whereas further preclinical studies are warranted evaluating fish oil for more advanced CRPC

Polybrominated Diphenyl Ether (PBDE) Flame Retardants and Thyroid Hormone during Pregnancy

BACKGROUND: Human exposure to polybrominated diphenyl ether (PBDE) flame retardants has increased exponentially over the last three decades. Animal and human studies suggest that PBDEs may disrupt thyroid function. Although thyroid hormone (TH) of maternal origin plays an essential role in normal fetal brain development, there is a paucity of human data regarding associations between exposure to PBDEs and maternal TH levels during pregnancy. OBJECTIVES: Our goal was to determine whether PBDE serum concentrations are associated with TH levels in pregnant women. METHODS: We measured the concentration of 10 PBDE congeners, free thyroxine (T4), total T4, and thyroid-stimulating hormone (TSH) in 270 pregnant women around the 27th week of gestation. RESULTS: Serum concentrations of individual PBDE congeners with detection frequencies > 50% (BDEs 28, 47, 99, 100, and 153) and their sum (ΣPBDEs) were inversely associated with TSH levels. Decreases in TSH ranged between 10.9% [95% confidence interval (CI), -20.6 to 0.0] and 18.7% (95% CI, -29.2 to -4.5) for every 10-fold increase in the concentration of individual congeners. Odds of subclinical hyperthyroidism (low TSH but normal T4) were also significantly elevated in participants in the highest quartile of ΣPBDEs and BDEs 100 and 153 relative to those in the first quartile. Associations between PBDEs and free and total T4 were not statistically significant. Results were not substantially altered after the removal of outliers and were independent of the method used to adjust for blood lipid levels and to express ΣPBDEs. CONCLUSIONS: Results suggest that exposure to PBDEs is associated with lower TSH during pregnancy. Findings may have implications for maternal health and fetal development

Sebomic identification of sex- and ethnicity-specific variations in residual skin surface components (RSSC) for bio-monitoring or forensic applications

Background: “Residual skin surface components” (RSSC) is the collective term used for the superficial layer of sebum, residue of sweat, small quantities of intercellular lipids and components of natural moisturising factor present on the skin surface. Potential applications of RSSC include use as a sampling matrix for identifying biomarkers of disease, environmental exposure monitoring, and forensics (retrospective identification of exposure to toxic chemicals). However, it is essential to first define the composition of “normal” RSSC. Therefore, the aim of the current study was to characterise RSSC to determine commonalities and differences in RSSC composition in relation to sex and ethnicity. Methods: Samples of RSSC were acquired from volunteers using a previously validated method and analysed by high-pressure liquid chromatography–atmospheric pressure chemical ionisation–mass spectrometry (HPLC-APCI-MS). The resulting data underwent sebomic analysis. Results: The composition and abundance of RSSC components varied according to sex and ethnicity. The normalised abundance of free fatty acids, wax esters, diglycerides and triglycerides was significantly higher in males than females. Ethnicity-specific differences were observed in free fatty acids and a diglyceride. Conclusions: The HPLC-APCI-MS method developed in this study was successfully used to analyse the normal composition of RSSC. Compositional differences in the RSSC can be attributed to sex and ethnicity and may reflect underlying factors such as diet, hormonal levels and enzyme expression.Peer reviewedFinal Published versio

Contribution to the understanding of tribological properties of graphite intercalation compounds with metal chloride

Intrinsic tribological properties of lamellar compounds are usually attributed to the presence of van der Waals gaps in their structure through which interlayer interactions are weak. The controlled variation of the distances and interactions between graphene layers by intercalation of electrophilic species in graphite is used in order to explore more deeply the friction reduction properties of low-dimensional compounds. Three graphite intercalation compounds with antimony pentachloride, iron trichloride and aluminium trichloride are studied. Their tribological properties are correlated to their structural parameters, and the interlayer interactions are deduced from ab initio bands structure calculations

Transmissibility of pandemic H1N1 and genetically related swine influenza viruses in ferrets

Poster presentationlink_to_OA_fulltextAnnual Scientific Meeting of the Institut Pasteur International Network, Hong Kong, 22–23 November 2010. In BMC Proceedings, 2011, v. 5, suppl. 1, p. 1

Hospital outpatient perceptions of the physical environment of waiting areas: the role of patient characteristics on atmospherics in one academic medical center

<p>Abstract</p> <p>Background</p> <p>This study examines hospital outpatient perceptions of the physical environment of the outpatient waiting areas in one medical center. The relationship of patient characteristics and their perceptions and needs for the outpatient waiting areas are also examined.</p> <p>Method</p> <p>The examined medical center consists of five main buildings which house seventeen primary waiting areas for the outpatient clinics of nine medical specialties: 1) Internal Medicine; 2) Surgery; 3) Ophthalmology; 4) Obstetrics-Gynecology and Pediatrics; 5) Chinese Medicine; 6) Otolaryngology; 7) Orthopedics; 8) Family Medicine; and 9) Dermatology. A 15-item structured questionnaire was developed to rate patient satisfaction covering the four dimensions of the physical environments of the outpatient waiting areas: 1) visual environment; 2) hearing environment; 3) body contact environment; and 4) cleanliness. The survey was conducted between November 28, 2005 and December 8, 2005. A total of 680 outpatients responded. Descriptive, univariate, and multiple regression analyses were applied in this study.</p> <p>Results</p> <p>All of the 15 items were ranked as relatively high with a range from 3.362 to 4.010, with a neutral score of 3. Using a principal component analysis' summated scores of four constructed dimensions of patient satisfaction with the physical environments (i.e. visual environment, hearing environment, body contact environment, and cleanliness), multiple regression analyses revealed that patient satisfaction with the physical environment of outpatient waiting areas was associated with gender, age, visiting frequency, and visiting time.</p> <p>Conclusion</p> <p>Patients' socio-demographics and context backgrounds demonstrated to have effects on their satisfaction with the physical environment of outpatient waiting areas. In addition to noticing the overall rankings for less satisfactory items, what should receive further attention is the consideration of the patients' personal characteristics when redesigning more comfortable and customized physical environments of waiting areas.</p

Numerical simulation of blood flow and pressure drop in the pulmonary arterial and venous circulation

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281–1299, 2012) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of ‘large’ arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the ‘smaller’ arteries and veins of radii ≥ 50 μ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung