Inactive Tissues Research Articles

Elevated plasma FXII is associated with disease activity in ANCA-associated vasculitis: A Retrospective Cross-Sectional Study in Western China

This study examined whether plasma FXII levels reflect disease activity in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Plasma FXII levels were detected by ELISA in 127 patients with AAV, and their associations with disease activity and plasma myeloperoxidase (MPO)-ANCA titre were examined. Immunofluorescent co-staining of FXII and neutrophils was performed on the renal tissues of patients with AAV. MPO expression in renal biopsy tissues was determined by immunohistochemical staining. The association between plasma FXII levels and histological activity was assessed in 82 patients who underwent kidney biopsy. Plasma FXII levels were considerably increased in patients with clinically active AAV compared to those in clinical remission and healthy individuals. Plasma FXII levels correlated positively with creatinine (r = 0.377), CRP (r = 0.222), urine red blood cell (r = 0.203), serum MPO-ANCA titer (r = 0.353), white blood cell (r = 0.194), percentage of glomeruli with crescents (P = 0.001), capillary breaks (P = 0.001), interstitial inflammation (P < 0.001) and fibrinoid necrosis (p < 0.001) on kidney biopsy. The plasma FXII optimal cut-off value for evaluating AAV activity was 24.5 μg/mL (sensitivity = 0.81, specificity = 0.82, P = 0.0001), which was superior to that achieved using conventional serologic biomarkers. Co-expression of FXII and neutrophils was higher, with increased MPO expression, in renal tissue with pathologically active AAV than that observed in pathologically inactive tissues. In conclusion, elevated plasma FXII levels reflect AAV clinical and histologic activity, and can serve as markers of active AAV.

Insights into natal origins of migratory Nearctic hover flies (Diptera: Syrphidae): new evidence from stable isotope (δ2H) assignment analyses

Hover flies (Diptera: Syrphidae) are an important group of insects that provide a multitude of key ecosystem services including pollination and biological control, yet many of their major life history traits are not understood. Some Palearctic hover fly species are known to migrate in response to changing seasonal conditions, yet this behavior is almost entirely unrecognized in Nearctic species. At least one species, Eupeodes americanus, is partially migratory during autumn while Allograpta obliqua may be non‐migratory, but it is unknown where these insects originate and how far they may travel. We examined natal origins of two Nearctic hover fly species, A. obliqua and E. americanus, using stable hydrogen isotope (δ2H) measurements of metabolically inactive tissues (wings and legs) to derive a hover fly δ2H isoscape. While A. obliqua was mostly of local origin, several E. americanus were sourced from northern latitudes in the Midwestern United States and Canada, representing travel distance of up to 3000 km likely using seasonally favorable air currents. This phenomenon is expected to have major ecological and economic ramifications, especially in the realm of plant pollination ecology and biological control.

LSTM-Based RNN Framework to Remove Motion Artifacts in Dynamic Multicontrast MR Images with Registration Model

Today, many people under the age of 10 are being examined for brain-related issues, including tumours, without displaying any symptoms. It is not unusual for children to develop brain-related concerns such as tumours and central nervous system disorders, which may affect 15% of the population. Medical experts believe that the irregular eating habits (junk food) and the consumption of pesticide-tainted fruits and vegetables are to blame. The human body is naturally resistant to harmful gears, but only up to a point. If it exceeds the limit, a cell manipulation process is automatically initiated that can remove dangerous inactive tissues from the cell membrane and later grows into tumour blockage in the human body. Thus, the adoption of an advanced computer-based diagnostic system is highly recommended in order to generate visually enhanced images for anomaly identification and infectious tissue segmentation. In most cases, an MR image is chosen since it is easier to distinguish between affected and nonaffected tissue. Conventional convolution neural network (CCNN) mapping and feature extraction are difficult because of the vast volume of data. In addition, it takes a lengthy time for the MRI scanning process to obtain diverse positions for anomaly identification. Aside from the discomfort, the patient may experience motion abnormalities. Recurrent neural network (RNN) classifies tumour regions into several isolated portions much faster and more accurately, so that it can be prevented. To remove motion artefacts from dynamic multicontrast MR images, a novel long short-term memory- (LSTM-) based RNN framework is introduced in this research. With this method, the MR image’s visual quality is improved over CCNN while simultaneously mapping a larger volume and extracting more quiet characteristics than CCNN can. DC-CNN, SMSR-CNN, FMSI-CNN, and DRCA-CNN results are compared. For both low and high signal-to-noise ratios, the suggested LSTM-based RNN framework has gained reasonable feature intelligibility (SNRs). In comparison to previous approaches, it requires less computing and has higher accuracy when it comes to detecting infected portions.

Investigating the spatial resolution of EMG and MMG based on a systemic multi-scale model

While electromyography (EMG) and magnetomyography (MMG) are both methods to measure the electrical activity of skeletal muscles, no systematic comparison between both signals exists. Within this work, we propose a novel in silico model for EMG and MMG and test the hypothesis that MMG surpasses EMG in terms of spatial selectivity, i.e. the ability to distinguish spatially shifted sources. The results show that MMG provides a slightly better spatial selectivity than EMG when recorded directly on the muscle surface. However, there is a remarkable difference in spatial selectivity for non-invasive surface measurements. The spatial selectivity of the MMG components aligned with the muscle fibres and normal to the body surface outperforms the spatial selectivity of surface EMG. Particularly, for the MMG’s normal-to-the-surface component the influence of subcutaneous fat is minimal. Further, for the first time, we analyse the contribution of different structural components, i.e. muscle fibres from different motor units and the extracellular space, to the measurable biomagnetic field. Notably, the simulations show that for the normal-to-the-surface MMG component, the contribution from volume currents in the extracellular space and in surrounding inactive tissues, is negligible. Further, our model predicts a surprisingly high contribution of the passive muscle fibres to the observable magnetic field.

A deep learning pipeline to simulate fluorodeoxyglucose (FDG) uptake in head and neck cancers using non-contrast CT images without the administration of radioactive tracer

ObjectivesPositron emission tomography (PET) imaging is a costly tracer-based imaging modality used to visualise abnormal metabolic activity for the management of malignancies. The objective of this study is to demonstrate that non-contrast CTs alone can be used to differentiate regions with different Fluorodeoxyglucose (FDG) uptake and simulate PET images to guide clinical management.MethodsPaired FDG-PET and CT images (n = 298 patients) with diagnosed head and neck squamous cell carcinoma (HNSCC) were obtained from The cancer imaging archive. Random forest (RF) classification of CT-derived radiomic features was used to differentiate metabolically active (tumour) and inactive tissues (ex. thyroid tissue). Subsequently, a deep learning generative adversarial network (GAN) was trained for this CT to PET transformation task without tracer injection. The simulated PET images were evaluated for technical accuracy (PERCIST v.1 criteria) and their ability to predict clinical outcome [(1) locoregional recurrence, (2) distant metastasis and (3) patient survival].ResultsFrom 298 patients, 683 hot spots of elevated FDG uptake (elevated SUV, 6.03 ± 1.71) were identified. RF models of intensity-based CT-derived radiomic features were able to differentiate regions of negligible, low and elevated FDG uptake within and surrounding the tumour. Using the GAN-simulated PET image alone, we were able to predict clinical outcome to the same accuracy as that achieved using FDG-PET images.ConclusionThis pipeline demonstrates a deep learning methodology to simulate PET images from CT images in HNSCC without the use of radioactive tracer. The same pipeline can be applied to other pathologies that require PET imaging.

Dielectric Properties of Human Active Liver, Kidney and Spleen Compared to Those of Respective Inactive Tissues, Porcine Tissues and the Data Provided by a Database in the Frequency Range of 10 Hz to 100 MHz.

The purpose of this work is to study whether the active state and species of biological tissues can influence changes in their dielectric properties. In this paper, the dielectric properties of liver, kidney and spleen tissues from human active, human inactive and animal tissues are measured in the frequency range of 10 Hz to 100 MHz. The four- and two-electrode methods are used to measure dielectric properties at different frequencies. Statistical analysis and the pattern recognition method are used to compare the dielectric properties of human active tissues, human inactive tissues, animal tissues and data provided by the IFAC database. The results show that the dielectric properties of human active tissues are significantly different from those of human inactive tissues and animal tissues, resulting in a great difference between the dielectric properties provided by the IFAC database and those of human active tissues. The dielectric properties of human active tissues can be identified by the pattern recognition method based on principal component analysis, which further proves that the dielectric properties of human active tissues cannot be replaced. The dielectric properties of biological tissues are closely related to the activity and species of tissues. The dielectric properties of human active tissues cannot be replaced by those of human cadaver tissues or animal tissues. The significance of this study is suggesting that the IFAC database should be updated with the dielectric properties of human active tissues to provide accurate data for bioelectromagnetics research.

Altitudinal variation of trace elements deposition in forest ecosystems along the NW side of Mt. Amiata (central Italy): Evidence from topsoil, mosses and epiphytic lichens

Mt. Amiata (1738 m) is a volcanic peak in central Italy, completely covered with native oak, chestnut and beech forests. In this Natura 2000 site of Community Importance overlying a large shallow aquifer, climate change and the long-range transport of nutrients and contaminants might have negative impacts on relict plants populations and spring water chemistry. To evaluate the atmospheric deposition of trace elements in Mt. Amiata forest ecosystems, we analyzed the elemental composition of topsoils, epiphytic lichens (Parmelia species) and epigeic moss (Hypnum cupressiforme) between 120 and 1730 m a.s.l. along the NW side of the mountain, which is scarcely affected by natural and anthropogenic sources of metals. The elemental composition of the topsoil is mainly influenced by the different lithologies of the study area (calcareous up to an elevation of 700 m, volcanic up to the summit) and only Pb concentrations increased significantly with the altitude. The total element concentrations in cryptogams, particularly net of the possible contribution from soil particles, showed an enhanced accumulation of Pb, Cd, Hg and Zn in samples collected at altitudes above 1300 m, where beech forest are frequently shrouded in clouds and fog and receive more snow and rain than the lower chestnut and oak woods. Interestingly, the older and metabolically inactive tissues at the base of moss shoots, which are usually overlooked in biomonitoring surveys, appeared to behave as long-term accumulators of Pb. The possible mechanisms involved in the increased bioaccumulation of Mn in cryptogams inhabiting chestnut woods are discussed.

Evaluation Of Functional Sympatholysis Occurring Within Contracting Skeletal Muscle Microvasculature In Humans

The ability of contracting skeletal muscle to blunt sympathetic vasoconstriction, termed functional sympatholysis, is thought to contribute to supplying adequate blood to the exercising muscle despite increased sympathetic tone. However, previous studies in humans primarily investigated vascular responses of exercising limb as a whole that reflects not only responses of contracting skeletal muscles but also responses of inactive tissues such as skin, adipose and bones. PURPOSE: We aimed to more directly investigate the functional sympatholysis occurring within exercising skeletal muscle in humans. METHODS: In 26 healthy male volunteers, we examined the effects of acute sympathoexcitation by 90-s forehead cooling at rest and during dynamic handgrip exercise at 10% and 30% of maximum voluntary contraction (10%Ex and 30%Ex), respectively. The handgrip exercises were continued 3 min and forehead cooling was applied at latter half of the exercise period. The subjects also performed handgrip exercises without forehead cooling as control conditions. We employed near-infrared diffuse correlation spectroscopy, an emerging optical technique for noninvasive measurement of deep tissue hemodynamics, to continuously measure the microcirculatory blood flow index (BFI) within the flexor digitorum superficialis muscle, the muscle primarily responsible for handgrip. RESULTS: The acute sympathoexcitation induced significant decrease in vascular conductance (BFI / mean arterial pressure) at rest (baseline vs. forehead cooling: 1.00 ± 0 vs. 0.75 ± 0.03 AU, p < 0.05) and during 10%Ex (control vs. forehead cooling: 1.66 ± 0.08 vs. 1.32 ± 0.10 AU, p < 0.05), but not during 30%Ex (control vs. forehead cooling: 4.00 ± 0.56 vs. 3.66 ± 0.50 AU, p > 0.05). In addition, the percentage reduction in vascular conductance by forehead cooling was significantly decreased during 30%Ex compared to rest (-25.2 ± 2.5 vs. -4.9 ± 5.1 %, p < 0.05). CONCLUSIONS: Our study demonstrated the functional sympatholysis occurring within the contracting skeletal muscle microvasculature in humans. Furthermore, our results revealed the clear intensity-dependent response such that mild exercise hardly interferes with sympathetic vasoconstriction, whereas moderate exercise substantially attenuates it.

Ecophysiology of nickel hyperaccumulating plants from South Africa - from ultramafic soil and mycorrhiza to plants and insects.

An overview of 30 years of studies related to South African nickel hyperaccumulators is presented. Only five species have so far been identified as Ni hyperaccumulator plants among very rich and diversified South African flora. All of them occur on soils derived from ultramafic (serpentine) rocks and belong to the family Asteraceae: Berkheya coddii Roessler, Berkheya zeyheri subsp. rehmannii var. rogersiana, Berkheya nivea, Senecio coronatus, Senecio anomalochrous. Several techniques and methods were used to investigate ecophysiological aspects of the Ni hyperaccumulation phenomenon, from basic field and laboratory studies, to advanced instrumental methods. Analysis of elemental distribution in plant parts showed that in most cases the hyperaccumulated metal was stored in physiologically inactive tissues such as the foliar epidermis. However, an exception is Berkheya coddii, which has a distinctly different pattern of Ni distribution in leaves, with the highest concentration in the mesophyll. Such a distribution suggests that different physiological mechanisms are involved in the Ni transport, storage location and detoxification, compared to other hyperaccumulator species. Berkheya coddii is a plant with high potential for phytoremediation and phytomining due to its large biomass and potentially high Ni yield, that can reach 7.6% of Ni in dry mass of leaves. Senecio coronatus is the only known hyperaccumulator with two genotypes, hyperaccumulating and non-hyperaccumulating, growing on Ni-enriched/metalliferous soil. Detailed ultrastructural studies were undertaken to characterize specialized groups of cells in the root cortex of Ni-hyperaccumulating genotype, that are not known from any other hyperaccumulator. The occurrence of arbuscular mycorrhiza (AM) in Ni-hyperaccumulating plants was found for the first time in South African hyperaccumulator plants, and this type of symbiosis has been proved obligatory in all of them. There is a significant influence of mycorrhiza on the concentration and distribution of several elements. Three highly specialized herbivore insects feeding only on Ni hyperaccumulator plants were identified: Chrysolina clathrata (formerly Chrysolina pardalina), Epilachna nylanderi and Stenoscepa sp. The Ni-elimination strategies of these specialised insects have been established. Microbiological studies have revealed several genera of fungi and bacteria isolated from B. coddii leaves as well as presence of specialised, Ni-resistant yeasts in the C. clathrata gut. Understanding ecophysiological response to harsh environment broadens our knowledge and can have practical applications in cleaning polluted environments through phytomining/agromining. Finally, conservation aspects are also discussed and lines for future research are proposed.

Phytoextraction of heavy metals from contaminated soil, water and atmosphere using ornamental plants: mechanisms and efficiency improvement strategies.

Accumulation of heavy metals (HMs) in soil, water and air is one of the major environmental concerns worldwide, which mainly occurs due to anthropogenic activities such as industrialization, urbanization, and mining. Conventional remediation strategies involving physical or chemical techniques are not cost-effective and/or eco-friendly, reinforcing the necessity for development of novel approaches. Phytoextraction has attracted considerable attention over the past decades and generally refers to use of plants for cleaning up environmental pollutants such as HMs. Compared to other plant types such as edible crops and medicinal plants, ornamental plants (OPs) seem to be a more viable option as they offer several advantages including cleaning up the HMs pollution, beautification of the environment, by-product generation and related economic benefits, and not generally being involved in the food/feed chain or other direct human applications. Phytoextraction ability of OPs involve diverse detoxification pathways such as enzymatic and non-enzymatic (secondary metabolites) antioxidative responses, distribution and deposition of HMs in the cell walls, vacuoles and metabolically inactive tissues, and chelation of HMs by a ligand such as phytochelatins followed by the sequestration of the metal-ligand complex into the vacuoles. The phytoextraction efficiency of OPs can be improved through chemical, microbial, soil amending, and genetic approaches, which primarily target bioavailability, uptake, and sequestration of HMs. In this review, we explore the phytoextraction potential of OPs for remediation of HMs-polluted environments, underpinning mechanisms, efficiency improvement strategies, and highlight the potential future research directions.

Abstract A45: Proteins involved in the Calreticulin translocation pathway are altered in human ovarian cancer samples.

Abstract Ovarian cancer is the seventh most common cancer among women worldwide, with more than 200,000 new cases every year. The 5-year survival rate of advanced ovarian cancer ranges from 11 to 28 per cent. Thus, a better understanding of its pathogenesis at a molecular level is necessary to develop more effective therapies. Calreticulin (CRT) is a Ca+2 binding chaperone localized mainly in the endoplasmic reticulum (ER). However, it has been found in other cellular compartments, including the cytosol, nucleus, the plasma membrane and the extracellular space. At the cell surface, CRT acts as an “eat-me” signal, allowing the recognition of a cancer cell by the immune system and inducing an anti-cancer immune response. CRT translocation from the ER to the plasma membrane can be induced by several cytotoxic anti-cancer drugs; however, the exact mechanism is not completely understood. It involves the activation of an ER stress response, particularly the activation of PERK and eIF2αproteins. Once on the cell membrane, CRT would be able to interact with CD91. In previous work, we found that CRT levels increase in ovarian cancer samples compared to non-cancerous tumors and normal tissue. By immunohistochemistry, we detected CRT on the periphery of normal inactive cells, while it had a mainly perinuclear distribution on cancer cells, consistent with ER localization. We have also found that Nerve Growth Factor (NGF) is involved in ovarian cancer pathogenesis and it increases CRT protein levels in a human ovarian cancer cell line (A2780). The aim of this work was to evaluate the levels of proteins associated with CRT translocation, including eIF2α, PERK and CD91 in human ovarian samples and to evaluate CRT subcellular localization in A2780 cells treated with NGF, thapsigargin (ER inductor) and mitoxantrone (cytotoxic drug) for 2 and 4 hours. Human ovarian samples (six normal inactive ovarian tissues, twelve ovarian tumors and sixteen epithelial ovarian cancer samples) were obtained after written consent by patients from the Clinical Hospital University of Chile and with approval of its Ethics Committee. In ovarian tissues, levels of eIF2α, PERK and CD91 were evaluated by western blot and the localization of CD91 was evaluated by immunohistochemistry. CRT localization in treated A2780 cells was determined by confocal immunofluorescence microscopy. We found increased levels of phosphorylated eIF2α and phosphorylated PERK (active forms) relative to total protein, in ovarian cancer samples compared to tumors (p&amp;lt;0.05) and to normal inactive tissues (p &amp;lt;0.05). We also found the presence of CD91 on both normal and pathologic ovarian samples by western-blot and immunohistochemistry. Interestingly, NGF didn't induce changes of eIF2α and PERK. Also, CRT kept a mainly peri-nuclear distribution with NGF treatment, while it changed with thapsigargin and mitoxantrone treatments, acquiring a distribution near the plasma membrane and in the cytoplasm. Several studies have shown that the ER stress response is elevated in several types of cancer. In this work, we found that this is also the case in epithelial ovarian cancer. These results suggest that ovarian cancer tissues have the machinery necessary to induce CRT translocation, including the presence of CD91, making it an attractive target for future immunotherapy developments. However, despite the activation of at least part of the pathway, CRT seems to remain on the endoplasmic reticulum in cancer cells. This could be indicating the presence of a mechanism that inhibits its mobilization, possibly involving NGF. Grants: FONDECYT 1110372, CONICYT-FONDAP 15130011 and CONICYT Scholarship 21120252 Citation Format: Carolina Vera, Paula García, Alberto Selman, Fernando Gabler, Margarita Vega, Arturo Ferreira, Carmen Romero. Proteins involved in the Calreticulin translocation pathway are altered in human ovarian cancer samples. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A45.

Carbon and nitrogen discrimination factors of wolves and accuracy of diet inferences using stable isotope analysis

Dietary inferences using stable isotope analysis rely on comparing stable carbon and nitrogen isotope content of consumer to prey tissues by modeling discrimination between these tissues. Diet–tissue discrimination factors applied in these models for wild populations must be obtained from controlled feeding studies where consumer diets are known. Species-specific discrimination factors are lacking for wolves (Canis lupus), and most researchers assessing the diet of free-ranging wolves have used discrimination factors derived from red foxes (Vulpes vulpes) fed a commercial pellet diet. We calculated diet–tissue discrimination factors for various tissues from captive wolves fed a controlled diet of horse (Equus caballus) meat and also assessed the feasibility of seasonal delineation of diet through the partitioning of metabolically inactive tissues such as guard hairs and whiskers. Stable carbon isotopic discrimination in wolves was highest in whiskers (4.31‰), followed by guard hair (4.25‰), and lowest in serum (2.21‰) and red blood cells (2.16‰). Stable nitrogen isotopic discrimination was highest in serum (4.54‰), guard hair (3.09‰), and whiskers (3.05‰), and lowest in red blood cells (2.99‰). Using these values, we demonstrated the sensitivity of estimated wolf diet proportions to choice of discrimination factors. We also documented a decrease in growth rate of hair and whiskers from summer through autumn, which cautions estimating temporally explicit diet of mammals based on stable isotope analysis of discrete sections of hair and whiskers. We conclude that species-specific discrimination estimates should be used in dietary assessments based on stable isotope analyses to limit inaccuracies in diet interpretation of wild populations. © 2015 The Wildlife Society.

Reply to “Letter to the editor: ‘Deconstructing the dogma of sympathetic restraint and its role in the cardiovascular response to exercise’”

: We thank Dr. Tschakovsky (3) for his interest andenthusiasm regarding our recent study (1) dealing with sym-pathetic control of blood flow in different tissues of the leg inhumans at rest and during exercise. Dr. Tschakovsky impor-tantly emphasises that exercise-evoked vasodilation cannotdirectly spread from the active quadriceps muscle group to theinactive hamstring muscles. This was not what we literallymeant, and although according to our understanding ascendingvasodilatation and its spread to inactive tissues could be con-tributing to some marginal extent, his concern in this regardwas apparently mainly raised from our integration of ourfindings with those of Moore and colleagues (2), togethersuggesting that -adrenergic-mediated sympathetic constraintis important for optimization of blood flow and oxygen extrac-tion to the most metabolically active tissues of the limb. Wealso fully agree with Dr. Tschakovsky that investigating bloodflow in active versus inactive muscle groups is not the samething as investigating blood flow around active versus inactivemuscle fibers within an exercising muscle. We tried to empha-sise this notion already in the introduction of our paper (1).Regarding the findings from -adrenergic blockade duringexercise, we indeed could not document any change in bloodflow in the exercising muscle. Increased blood flow occurred ininactive muscles and other tissues, indeed very much challeng-ing the common belief that there is sympathetic constraint inthe vasculature of active muscles during exercise, as pointedout by Dr. Tschakovsky (3). Moreover, to the best of ourknowledge, previous research in this area has relied on ratherindirect assessments and estimations. Our study is one of thefirst to directly and quantitatively address this topic in humans.However, as also discussed in the original report (1), we madeour observations during fairly low-intensity exercise, whenalso an only fairly small mass of active muscle was exercising.Thus, even if methodologically quite challenging, it still re-mains to be tested whether the findings are similar at higherexercise intensities and particularly when performing wholebody exercise. In those conditions, it might well be that somesympathetic restraint is needed also in active muscle vascula-ture. At this moment, there is little human experimental evi-dence to support this idea, despite some indirect estimations. Inall, we think that the insightful comments of Dr. Tschakovskywill help vascular and exercise physiologists to better under-stand sympathetic regulation of cardiovascular function duringexercise in humans.

Role of vascular dysfunction in prostate tumor perfusion during exercise

During exercise, blood flow to inactive tissues is reduced through changes in vascular tone elicited largely by the autonomic nervous system. However, in tumors the reduced innervation of feed arteries and possibly blunted adrenergic vasoconstriction may lead to an increased tumor perfusion during exercise. We used control (CON; n=16) and prostate tumor bearing (TB; n=14) Copenhagen rats to test the hypothesis that α‐adrenergic (via norepinephrine; NE) and myogenic vasoconstrictor responses are diminished in the prostatic tumor feed arteries (PTA), resulting in an increased tumor perfusion during exercise. Dunning R‐3327 MatLyLu tumor cells (104) were injected into the ventral prostates of rats. PTA and prostate arteries (CON) were studied in vitro and exposed to cumulative additions of NE (10−9to 10−4M) and increases in intraluminal pressure (myogenic response; 0 to 135 cmH2O). In vivo quantification of perfused tumor vessels during rest and acute exercise (treadmill; 5 min) was determined using Hoechst‐33342 staining. Both α‐adrenergic (7 ± 6% vs. 88 ± 2%, p&lt;0.05) and myogenic vasoconstriction were blunted in PTA versus CON, while the number of PTA perfused increased ~113% with exercise. These data suggest that dysfunction in the PTA results in an inability to augment vascular resistance during exercise, resulting in an enhanced tumor perfusion.Supp.: NIH (AG‐31317) &amp; Florida Biomed. Res. Prog. (1BN‐02).

Levels of Metallic Elements and Their Potential Relationships to Cognitive Function among Elderly from Federal Land Development Authority (FELDA) Settlement in Selangor Malaysia

Exposure to toxic metals and excessive amount of trace elements is a risk factor of cognitive decline. Continuous monitoring of these elements by the use of metabolically inactive tissues such as fingernails may help in taking preventive measures to delay the cognitive decline process. In this study, the cognitive function of 54 elderlies (60-72years old) from FELDA Sungai Tengi, Selangor, was evaluated using the Malay version of Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). The levels of arsenic (As), cadmium (Cd), copper (Cu), manganese (Mn), lead (Pb), and zinc (Zn) in fingernail were detected using Inductively Coupled Plasma-Mass Spectrometry. Results showed that (92.6%) our population was cognitively impaired based on the MoCA with mean score of 18.07 ± 5.11. The mean level of elements in fingernails for As, Cd, Cu, Mn, Pb, and Zn were 16.68 ± 3.52, 4.26 ± 0.91, 4.81 ± 1.16, 1.00 ± 0.23, 1.83 ± 0.47, and 40.86 ± 10.81μg/g, respectively. Significant inverse correlations were observed between MoCA with age (r = -0.543, p < 0.01), Cu level (r = -0.330, p < 0.05), and Mn level (r = -0.496, p < 0.01). MMSE was correlated to age (r = -0.346, p < 0.05) only. In conclusion, besides aging, the progression of cognitive decline among the elderly FELDA population was associated with increased levels of copper and manganese.

PIXE and metal hyperaccumulation: from soil to plants and insects

AbstractThe status of micro‐PIXE applications in investigations of ecophysiological aspects of the hyperaccumulation phenomenon in plants is reviewed. Measurements of elemental concentrations and distribution in organs, tissues and cells of plants hyperaccumulating Ni, Co, As, Mn, Zn and Cd, show that in most cases hyperaccumulated metals are stored in physiologically inactive tissues. However, some exceptions indicate that different physiological mechanisms are involved in metal transport, storage locations and detoxification. The influence of mycorrhiza on elemental concentration and distribution in the roots of the Ni‐hyperaccumulator Berkheya coddii is also discussed. Several herbivorous insects have been found feeding exclusively on Ni‐hyperaccumulating plants. A summary of micro‐PIXE contribution to studies aimed at explanation of their ability to survive in such extreme conditions is given. Copyright © 2011 John Wiley &amp; Sons, Ltd.

NADH as an Endogenous Marker of Cardiac Tissue Injury at the Site of Radiofrequency Ablation

Atrial fibrillation (AF) remains the most commonly occurring cardiac arrhythmia; its incidence is associated with a lower quality of life including a higher rate of morbidity & mortality. Percutaneous left atrial catheter ablation for the purpose of eliminating AF has become a common treatment option and is currently being investigated for superiority over medical therapy in a large clinical trial. RFA produces lesions that can block the spread of electrical activity from the sites of abnormal activity including pulmonary veins. Today, there are limited means for real time monitoring of tissue injury during the RFA procedure. To address this need, we explored the fluorescence of endogenous NADH as a possible live marker of tissue injury during the ablation procedure. Studies were conducted in blood-free and blood-perfused isolated rat hearts. Epicardial RFA lesions were seen as areas of low NADH fluorescence which encompassed both irreversible and reversibly damaged tissue. Their size significantly exceeded TTC negative staining (TTC - Triphenyl Tetrazolium Chloride, a redox indicator used to differentiate between metabolically active and inactive tissues). Real-time monitoring of NADH fluorescence allowed visualization of gaps of viable tissue between the RFA lesions. Dual recordings of NADH and epicardial electrical activity linked these gaps to the occurrence of post-ablation reentries. We conclude that fluorescence of endogenous NADH can assist visualization of injured epicardial tissue near the tip of the RFA catheter lesions.

Blood flow in the brachial artery increases after intense cycling exercise

During cycling blood flow is redistributed from physically inactive tissues to working leg muscles. It is unknown how long this situation persists after very intense exercise or whether it differs between intense exhausting and non-exhausting exercise. It is also not known to what extent the redistribution differs between different types of non-active tissues. Therefore nine healthy young men cycled first for 2min at 328 W (non-exhausting exercise, mean). Blood velocity in thigh and arm (ultrasound-doppler), perfusion of forearm skin (non-acral skin) and finger tip (acral skin, with arterio-venous anastomoses) were measured for 30min after exercise (laser-doppler). To be able to study vascular resistance and central circulation, blood pressure (Finometer), heart rate (ECG), and stroke volume (ultrasound-doppler) were measured. Thereafter the subjects cycled at the same power to exhaustion (4min), and the measurements were repeated. After both exercises mean blood pressure was unchanged (≤ 80mm Hg) despite increased cardiac output (≥ + 30% vs. pre-exercise). Blood velocity in the brachial artery was higher during the whole recovery period than at rest (p≤0.02; no differences between exercises). Blood perfusion of non-acral skin was unchanged from pre-exercise level after 2min of non-exhausting exercise, but it was twice as high after 4min cycling to exhaustion as at rest (p=0.02). Blood perfusion of acral skin rose after both exercises and did not differ between exhausting and non-exhausting exercise. In conclusion, arm blood flow increases above the pre-exercise level in the recovery period after short-lasting, strenuous exercise.

Potential use of Oxygen as a Metabolic Biosensor in Combination with T2*-Weighted MRI to Define the Ischemic Penumbra

We describe a novel magnetic resonance imaging technique for detecting metabolism indirectly through changes in oxyhemoglobin:deoxyhemoglobin ratios and T2(*) signal change during 'oxygen challenge' (OC, 5 mins 100% O(2)). During OC, T2(*) increase reflects O(2) binding to deoxyhemoglobin, which is formed when metabolizing tissues take up oxygen. Here OC has been applied to identify tissue metabolism within the ischemic brain. Permanent middle cerebral artery occlusion was induced in rats. In series 1 scanning (n=5), diffusion-weighted imaging (DWI) was performed, followed by echo-planar T2(*) acquired during OC and perfusion-weighted imaging (PWI, arterial spin labeling). Oxygen challenge induced a T2(*) signal increase of 1.8%, 3.7%, and 0.24% in the contralateral cortex, ipsilateral cortex within the PWI/DWI mismatch zone, and ischemic core, respectively. T2(*) and apparent diffusion coefficient (ADC) map coregistration revealed that the T2(*) signal increase extended into the ADC lesion (3.4%). In series 2 (n=5), FLASH T2(*) and ADC maps coregistered with histology revealed a T2(*) signal increase of 4.9% in the histologically defined border zone (55% normal neuronal morphology, located within the ADC lesion boundary) compared with a 0.7% increase in the cortical ischemic core (92% neuronal ischemic cell change, core ADC lesion). Oxygen challenge has potential clinical utility and, by distinguishing metabolically active and inactive tissues within hypoperfused regions, could provide a more precise assessment of penumbra.

MODELING THE EFFECTS OF THE ELECTRODES POSITION ON THE SURFACE EMG CHARACTERISTICS

— The uterine electromyogram (EMG) or electrohysterogram (EHG) could be used to detect a potential risk of preterm delivery in woman by analyzing its frequency content. In this study, we explore the effects of electrodes position, in terms of inactive tissues depth below the recording site and distance of electrodes to the potentials source, on the spectral characteristics of recorded signals. To explore these effects on skeletal muscle EMG and EHG, we used two numerical models but also real EHG. We have been able to notice specific effects in each situation but also cumulative effects. On real EHG, we could see that the main effect concerns the attenuation of high frequencies. Thus, the standardization of the electrode position during recording is a factor of importance.