The blood-brain barrier (BBB) is located at the level of the cerebral microcapillaries, and functions to maintain environmental homeostasis by allowing the neurons access to the required nutrients and enabling the exchange of metabolic waste. BBB dysfunction has been observed in a number of pathophysiologic statres including peripheral inflammatory pain (Huber et al., 2001b). Using the lamda-carrageenan inflammatory pain (CIP) model, we observed alterations in the tight junction (TJ) proteins paralleled by an increase in BBB permeability to [14C] sucrose. The mechanisms by which these perturbations occurred remain to be elucidated. In the current study, we investigate the central mechanism for the BBB perturbations under CIP. It is our hypothesis that the modulations of the BBB under CIP, are mediated via a central signaling pathway. First, to investigate the involvement of neuronal input from pain activity on alterations in BBB, we developed a method for inhibiting the nociceptive input from the paw. Using a perineural injection of 0.75% bupivacaine into the right hind leg prior to CIP, we were able inhibit development thermal hyperalgesia induced by CIP, as tested by infrared heat stimulus, without effecting edema formation 1 h post CIP. Upon inhibition of nociception under CIP, there was an attenuation of both the changes in permeability and the changes in tight junction protein expression, with both returning to control levels. Next, we investigated intercellular adhesion molecule-1 (ICAM-1), a key signaling protein at the BBB, which in the presence of proinflammatory mediators, increases in expression leading to the activation of signaling pathways as well as morphological changes. We found a region specific increase in ICAM-1 mRNA and protein expression following CIP which directly correlated with increased expression of activated microglia. Finally, we investigated the influence activated microglia had on BBB permeability. Using an 0.150 mg intrathecal bolus injection of minocycline, a potent inhibitor of microglia activation (Klein and Cunha, 1995), we were able to inhibit the increased expression of activated microglia, and saw an attenuation of permeability to control levels. These findings suggest CIP induced BBB disruption is localized and has a central-mediated component independent of peripheral influence.

The current study has evaluated shoreline dynamics and environmental change at St. Catherines Island, Georgia, with attention to the two major controls of barrier island formation and modification processes. These major controls include the increase in accommodation space, or the rate of sea level rise for the Georgia Bight which has remained constant in 20th and 21st century tide gauge data and dynamically changing rates of sediment supply based on anthropogenic modifications to land cover (Trimble, 1974) that are reflected in sediment transport (McCarney-Castle et al., 2010). Vibracoring and radiocarbon data provided valuable insights into the stratigraphy and development of St. Catherines Island. A stratigraphic model has been developed for the sediments associated with the Late Holocene accretional terrains where multiple small scale fluctuations in sea level have resulted in the formation of a sedimentary veneer punctuated with transgressive surfaces and regressive sequences. A working model for an interpolated Late Holocene sea level curve has been constructed using direct evidence from vibracore data as constraining points and indirect evidence from other regional sea level studies to provide additional structure. The relationship between the timing of the regressions versus periods of beach ridge formation and implications from the current shoreline dynamics study regarding the role of sediment supply complement each other. The ages of beach ridge formation strongly correlate to periods that are associated with regressions in sea level based on the sedimentary record and an evaluation of Late Holocene sea level conditions. The evaluation of anthropogenic modifications to the rate of sediment supply performed under the current study indicates that in spite of significant changes in sediment flux rates of +300% (pre-dam era) and -20% (post-dam era), shoreline retreat was continuous during the study period with an acceleration noted in the rates of shoreline retreat associated with spit and berm landforms during the post-dam or modern era. The two associations indicate strongly that the rate of sediment supply plays a secondary role to the major control of the rate of sea level rise in the formation and modification processes at St. Catherines Island.

Dendritic cells (DCs) form a key component of the immune response, as they are involved in the innate and adaptive immunity and in the process of tolerance. Under normal conditions, DCs are absent from the Central Nervous System (CNS), as the blood brain barrier (BBB) restricts their entry. However, DCs have recently been implicated in the pathogenesis of several CNS diseases. The molecular mechanisms that mediate DC trafficking across the BBB are poorly understood. The objectives of this study were to examine the role of endothelial cell adhesion molecules (eCAMs) and their ligands in the process of DC adhesion to the BBB endothelium, and to investigate the participation of DCs in human CNS diseases. To study DC adhesion, DCs were generated in vitro by culturing human blood monocytes in the presence of GM-CSF and IL- 4, and DC maturation was induced by adding inflammatory cytokines (TNF-α, IL-1β, IL-6) and PGE₂. Immature and mature DCs displayed differences in their expression of surface molecules, including eCAM ligands, by flow cytometry. Adhesion to the cerebral endothelium was investigated using an in vitro model of the BBB consisting of primary cultures of human brain microvessel endothelial cells (HBMEC). Immature or mature DCs were incubated with resting or TNF-α-activated HBMEC for up to one hour. Only a few DCs adhered to resting HBMEC, but adhesion was upregulated upon activating HBMEC (p<O.Ol). Moreover, immature DCs adhered to activated HBMEC to a greater extent compared to mature DCs (p<O.OOl). Blocking experiments indicated that the adhesion of both immature and mature DCs to HBMEC was dependent upon ICAM-1-CD18 or ICAM-2-CD18, ICAM-2-DC-SIGN, and PECAM-l PECAM-l interactions. In addition, VCAM-1-VLA-4 interactions mediated the adhesion of immature but not mature DCs to activated HBMEC. Using immunohistochemistry for DC markers, we also examined the presence of DCs in human inflammatory, infectious, and neurodegenerative diseases, stroke and tumours. The results indicate accumulation of DC SIGN—, fascin—, and MHC class Il—expressing DCs in the CNS under most pathological conditions. These findings provide further insight into the mechanisms of neuroinflammation, and highlight the role of DCs and the BBB endothelium in this process.

Concerning Strainers generation mechanism in Schottky barriers.

Darbo tikslas – ištirti pacientų požiūrius į onkologinio skausmo kontrolės kliūtis. Darbo uždaviniai. Ištirti sergančiųjų onkologinėmis ligomis pacientų: požiūrį į skausmą ir jo kontrolę bei požiūrio poveikį patiriamo skausmo intensyvumui; bendravimą su gydytoju skausmo kontrolės klausimais ir jo poveikį patiriamo skausmo intensyvumui; analgetikų vartojimo rekomendacijų laikymąsi ir kokį poveikį tai turi patiriamo skausmo intensyvumui; patiriamo analgetikų nepageidaujamo poveikio įtaką skausmo kontrolei; emocines būsenas ir jų poveikį patiriamo skausmo intensyvumui. Metodai. Tyrimas kiekybinis analitinis atliekant anoniminę apklausą. Tyrimo klausimyną sudaro 6 anketos ir demografinis klausimynas. 5 anketos kol kas nebuvo naudotos Lietuvoje: Trumpa Skausmo Intensyvumo skalė (angl. Brief Pain Inventory (BPI), Short form); Modifikuotas Barjerų klausimynas (angl. The Barriers Questionnaire-II); Modifikuota Paciento Dalyvavimo Gydyme klausimyno versija (angl. Modified Version of the Patients’ Perceived Involvement in Care Scale); Vaistų vartojimo rekomendacijų laikymosi vertinimo skalės variantas (angl. Medication Adherence Report (MAR)). Sensoriniams trukdžiams įvertinti sudarytas klausimas, kuriuo paciento prašoma atsakyti ar jis dėl šalutinio analgetikų poveikio kada nors buvo nustojęs vartoti analgetikus. Jei dėl šalutinio vaistų poveikio pacientas nustojo vartoti analgetikus, prašoma juos nurodyti. Anketos buvo adaptuojamos ir verčiamos iš anglų į lietuvių kalbą. HAD skalė... [toliau žr. visą tekstą] / Aim of the study – to evaluate patients attitudes towards barriers for control of oncologic pain. Objectives: to evaluate characteristics of oncologic patients: attitudes towards pain and its control, perception of pain intensity; communication with physician about pain control and pain intensity; adherence of analgesics use related with pain intensity; analgesics side effects impact on pain control; emotional conditions and influence on pain intensity. Methods. The study was quantitative analytical, including anonymous survey. The questionnaire comprised 6 subscales (all of them except HAD not used in Lithuania this far) and demographic set. Subscales included Brief Pain Inventory (BPI; short form), the Barriers Questionnaire-II, Modified Version of the Patients’ Perceived Involvement in Care Scale, Medication Adherence Report (MAR), and Hospital Anxiety and Depression Scale (HAD). For evaluation of sensoric disorders the questionnaire was constructed that consisted of questions concerning patient's refusal to get analgesic due to its side effects. The questionnaires were adapted and translated from English to Lithuanian. The survey was conducted during April 31, 2007 and February 1, 2008 at Pain Treatment division and Department of Family Medicine, Kaunas University Hospital. The permission for study was obtained from University Bioethics Center and head of Kaunas University Hospital. Inclusion criteria: patient with oncologic disease, treated on out-patient basis, having... [to full text]

This study examined the impact of reformed fishing and reef management practices in a community-based marine ornamental fishery in Tejakula sub-district, Bali, Indonesia, on the development of effective community-based natural resource management. With the absence of cyanide fishing for one decade, the coral reef condition has improved from 26% of area coverage to 53%. T-test result shows that there is no significant difference in individual fishing revenue and a considerable decrease in total fishery revenue. The fishers have benefited in resource conservation and a 73% decrease in fishing costs. The overall number of ornamental fishers has declined, due to social pressure, a smaller overall fishing space because of No Take Zones (NTZ), and fewer orders for ornamental fish.Environmental education for local community members is critical to maintain adherence to the reformed method of fishing. Clear definition of the NTZS policy should be acknowledged to avoid recurring conflict among stakeholders.

This research evaluated the use of geosynthetic clay liners (GCLs) as a potential barrier material to the migration of metals that are leached from mine waste. This thesis consists of two parts. In the first part, micro analytical methods including µXRD with synchrotron-generated µXRF elemental mapping and synchrotron-based µXRD (S-µXRD) were used to characterize the GCL bentonite and distinguish how mechanisms of metal attenuation could be identified. These analytical methods were of particular use for the clay material as they offer non-destructive, in situ investigation of various soil characteristics with microspatial resolution. The combination of the analytical methods allowed for identification of minerals such as gypsum and pyrite, not accessible by conventional methods. In particular, distinguishing accessory crystalline phases present in the “starting material” bentonite from those formed as a result of interaction with metal-bearing leachates is critical, as the development of metal-attenuating crystalline phases can have a significant long-term impact on metal mobility. In the second part of the thesis, the migration behaviour of metals (As, Al, Cd, Cu, Fe, Mn, Ni, Sr, and Zn) was investigated by means of diffusion tests and permeation experiments using four metal-containing waters: acidic rock drainage (ARD), lime-treated ARD, water from gold mine tailings, and landfill leachate with metal loading. Effective diffusion coefficients of the metals were calculated by modelling laboratory diffusion and sorption data. Water pre-hydrated GCLs were permeated with 15-21 pore volumes (PVs) of solution and their interaction with these solutions was examined in terms of both the hydraulic conductivity and the change in the geochemical characteristics of the permeant over time. The greatest increase in hydraulic conductivity occurred for the acidic rock drainage, where it increased from 1.6x10-11 m/s to 1.3x10-10 m/s following 21 PVs of permeation; still a very low value when compared to regulatory standards for clay barrier materials. Observed delayed breakthrough curves were indicative of the GCL’s strong attenuation capacity for a number of metals. An understanding of mechanisms of metal retention at both the micro and macro-scale levels will facilitate effective pollution prevention using GCLs. / Thesis (Ph.D, Civil Engineering) -- Queen's University, 2009-04-26 18:46:23.02

Vascular endothelial cells (VECs) maintain vascular integrity by regulating the passage of solutes, macromolecules, and cells between the vascular and perivascular space and are critical in a wide number of physiological processes, such as the delivery of nutrients and oxygen to surrounding tissues, leukocyte trafficking, angiogenesis, and tissue repair. VEC permeability is regulated, at least in part, by VE-cadherin-based adherens junctions that coordinate inter-VEC contacts and communicate the strength of these interactions to the cell via the actin cytoskeleton. Although the ubiquitous second messenger, cyclic adenosine 3'€™, 5'€™-monophosphate (cAMP), has been shown to reduce VEC permeability, the molecular basis of this effect is currently unclear. Herein, we report that cAMP and its two effectors, cAMP-dependent protein kinase A-II (PKA-II) and exchange protein activated by cAMP-1 (EPAC1), improve barrier function and differentially coordinate this effect through both VE-cadherin and actin cytoskeletal structures. We have also identified cyclic nucleotide phosphodiesterase (PDE) 4 as the major PDE regulating VEC barrier function. Through the use of cAMP-elevating agents and RNAi-mediated knockdown of PKA-Cα, EPAC1 and PDE4D, we have identified a dominant role for EPAC1 in VEC permeability as well as recognized PDE4D as a potential adaptor protein VE-cadherin-based complexes. Our results are consistent with previous reports of a role for both PKA and EPAC1 in controlling VE-cadherin mediated barrier function and additionally provide novel insight into the differential roles that PKA, EPAC1 and PDE4D play in stabilizing VEC barrier function. / Thesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2009-09-18 16:09:59.12

No description available.

The blood-brain barrier (BBB) formed by the brain capillary endothelial cells provides a protective barrier between the systemic blood and the extracellular environment of the central nervous system. Since most fatty acids in the brain enter from the blood, we examined the mechanism of permeability of various fatty acids across primary human brain microvessel endothelial cells (HBMEC). Cardiolipin (CL), a major mitochondrial phospholipid involved in energy metabolism in mammalian mitochondria, and fatty acid transport protein-1 (FATP-1) may regulate the intracellular level of fatty acyl-Coenzyme A’s. Since fatty acids are required for oxidative phosphorylation via mitochondrial oxidation, we also examined the effect of altering FATP-1 levels on CL biosynthesis. The permeability of radiolabeled fatty acids was determined using confluent cells grown on Transwell® inserts following inhibition of various fatty acid transporters. The passage of [1-14C]oleate across confluent HBMEC monolayers was significantly enhanced when fatty acid free albumin was present in the basolateral media. Knockdown of FATP-1, FATP-4, fatty acid translocase/CD36, or fatty acid binding protein 5 significantly decreased permeability of a number of radiolabeled fatty acids across the HBMEC monolayer from either apical as well as basolateral sides. The findings indicate that transport of some fatty acids across HBMEC is, in part, a transcellular process mediated by fatty acid transport proteins. Next, HEK 293 cells were used as a model to determine the effect of altering FATP-1 levels on CL. HEK-293 mock- and FATP-1 siRNA-transfected cells or mock and FATP-1 expressing cells were incubated for 24 h with 0.1 mM oleate bound to albumin (1:1 molar ratio) then incubated for 24 h with 0.1 mM [1,3-3H]glycerol and radioactivity incorporated into CL determined. FATP-1 siRNA-transfected cells exhibited reduced FATP-1 mRNA and increased incorporation of [1,3-3H]glycerol into CL (2-fold, p<0.05) compared to controls indicating elevation in de novo CL biosynthesis. In contrast, expression of FATP-1 resulted a reduction in incorporation of [1,3-3H]glycerol into CL (65%, p<0.05) indicating reduced CL synthesis. In addition, in vitro cytidine-5’-diphosphate-1,2-diacyl-sn-glycerol synthetase (CDS) activity was reduced by exogenous addition of oleoyl-Coenzyme A. The data indicate that CL de novo biosynthesis may be regulated by FATP-1 through CDS-2 expression in HEK 293 cells.