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Search Results: 1 - 10 of 28 matches for " Malisa Sarntinoranont "
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Effect of Needle Insertion Speed on Tissue Injury, Stress, and Backflow Distribution for Convection-Enhanced Delivery in the Rat Brain
Fernando Casanova, Paul R. Carney, Malisa Sarntinoranont
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0094919
Abstract: Flow back along a needle track (backflow) can be a problem during direct infusion, e.g. convection-enhanced delivery (CED), of drugs into soft tissues such as brain. In this study, the effect of needle insertion speed on local tissue injury and backflow was evaluated in vivo in the rat brain. Needles were introduced at three insertion speeds (0.2, 2, and 10 mm/s) followed by CED of Evans blue albumin (EBA) tracer. Holes left in tissue slices were used to reconstruct penetration damage. These measurements were also input into a hyperelastic model to estimate radial stress at the needle-tissue interface (pre-stress) before infusion. Fast insertion speeds were found to produce more tissue bleeding and disruption; average hole area at 10 mm/s was 1.87-fold the area at 0.2 mm/s. Hole measurements also differed at two fixation time points after needle retraction, 10 and 25 min, indicating that pre-stresses are influenced by time-dependent tissue swelling. Calculated pre-stresses were compressive (0 to 485 Pa) and varied along the length of the needle with smaller average values within white matter (116 Pa) than gray matter (301 Pa) regions. Average pre-stress at 0.2 mm/s (351.7 Pa) was calculated to be 1.46-fold the value at 10 mm/s. For CED backflow experiments (0.5, 1, and 2 μL/min), measured EBA backflow increased as much as 2.46-fold between 10 and 0.2 mm/s insertion speeds. Thus, insertion rate-dependent damage and changes in pre-stress were found to directly contribute to the extent of backflow, with slower insertion resulting in less damage and improved targeting.
Influence of Neuropathology on Convection-Enhanced Delivery in the Rat Hippocampus
Svetlana Kantorovich, Garrett W. Astary, Michael A. King, Thomas H. Mareci, Malisa Sarntinoranont, Paul R. Carney
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080606
Abstract: Local drug delivery techniques, such as convention-enhanced delivery (CED), are promising novel strategies for delivering therapeutic agents otherwise limited by systemic toxicity and blood-brain-barrier restrictions. CED uses positive pressure to deliver infusate homogeneously into interstitial space, but its distribution is dependent upon appropriate tissue targeting and underlying neuroarchitecture. To investigate effects of local tissue pathology and associated edema on infusate distribution, CED was applied to the hippocampi of rats that underwent electrically-induced, self-sustaining status epilepticus (SE), a prolonged seizure. Infusion occurred 24 hours post-SE, using a macromolecular tracer, the magnetic resonance (MR) contrast agent gadolinium chelated with diethylene triamine penta-acetic acid and covalently attached to albumin (Gd-albumin). High-resolution T1- and T2-relaxation-weighted MR images were acquired at 11.1 Tesla in vivo prior to infusion to generate baseline contrast enhancement images and visualize morphological changes, respectively. T1-weighted imaging was repeated post-infusion to visualize final contrast-agent distribution profiles. Histological analysis was performed following imaging to characterize injury. Infusions of Gd-albumin into injured hippocampi resulted in larger distribution volumes that correlated with increased injury severity, as measured by hyperintense regions seen in T2-weighted images and corresponding histological assessments of neuronal degeneration, myelin degradation, astrocytosis, and microglial activation. Edematous regions included the CA3 hippocampal subfield, ventral subiculum, piriform and entorhinal cortex, amygdalar nuclei, middle and laterodorsal/lateroposterior thalamic nuclei. This study demonstrates MR-visualized injury processes are reflective of cellular alterations that influence local distribution volume, and provides a quantitative basis for the planning of local therapeutic delivery strategies in pathological brain regions.
MRI-Based Computational Model of Heterogeneous Tracer Transport following Local Infusion into a Mouse Hind Limb Tumor
Kulam Najmudeen Magdoom, Gregory L. Pishko, Lori Rice, Chris Pampo, Dietmar W. Siemann, Malisa Sarntinoranont
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0089594
Abstract: Systemic drug delivery to solid tumors involving macromolecular therapeutic agents is challenging for many reasons. Amongst them is their chaotic microvasculature which often leads to inadequate and uneven uptake of the drug. Localized drug delivery can circumvent such obstacles and convection-enhanced delivery (CED) - controlled infusion of the drug directly into the tissue - has emerged as a promising delivery method for distributing macromolecules over larger tissue volumes. In this study, a three-dimensional MR image-based computational porous media transport model accounting for realistic anatomical geometry and tumor leakiness was developed for predicting the interstitial flow field and distribution of albumin tracer following CED into the hind-limb tumor (KHT sarcoma) in a mouse. Sensitivity of the model to changes in infusion flow rate, catheter placement and tissue hydraulic conductivity were investigated. The model predictions suggest that 1) tracer distribution is asymmetric due to heterogeneous porosity; 2) tracer distribution volume varies linearly with infusion volume within the whole leg, and exponentially within the tumor reaching a maximum steady-state value; 3) infusion at the center of the tumor with high flow rates leads to maximum tracer coverage in the tumor with minimal leakage outside; and 4) increasing the tissue hydraulic conductivity lowers the tumor interstitial fluid pressure and decreases the tracer distribution volume within the whole leg and tumor. The model thus predicts that the interstitial fluid flow and drug transport is sensitive to porosity and changes in extracellular space. This image-based model thus serves as a potential tool for exploring the effects of transport heterogeneity in tumors.
A Preclinical Assessment of Neural Stem Cells as Delivery Vehicles for Anti-Amyloid Therapeutics
eMalick G. Njie, Svetlana Kantorovich, Garrett W. Astary, Cameron Green, Tong Zheng, Susan L. Semple-Rowland, Dennis A. Steindler, Malisa Sarntinoranont, Wolfgang J. Streit, David R. Borchelt
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034097
Abstract: Transplantation of neural stems cells (NSCs) could be a useful means to deliver biologic therapeutics for late-stage Alzheimer's disease (AD). In this study, we conducted a small preclinical investigation of whether NSCs could be modified to express metalloproteinase 9 (MMP9), a secreted protease reported to degrade aggregated Aβ peptides that are the major constituents of the senile plaques. Our findings illuminated three issues with using NSCs as delivery vehicles for this particular application. First, transplanted NSCs generally failed to migrate to amyloid plaques, instead tending to colonize white matter tracts. Second, the final destination of these cells was highly influenced by how they were delivered. We found that our injection methods led to cells largely distributing to white matter tracts, which are anisotropic conduits for fluids that facilitate rapid distribution within the CNS. Third, with regard to MMP9 as a therapeutic to remove senile plaques, we observed high concentrations of endogenous metalloproteinases around amyloid plaques in the mouse models used for these preclinical tests with no evidence that the NSC-delivered enzymes elevated these activities or had any impact. Interestingly, MMP9-expressing NSCs formed substantially larger grafts. Overall, we observed long-term survival of NSCs in the brains of mice with high amyloid burden. Therefore, we conclude that such cells may have potential in therapeutic applications in AD but improved targeting of these cells to disease-specific lesions may be required to enhance efficacy.
Petrography and mineral chemistry of the pelitic and semi-pelitic gneisses of the merelani tanzanite mining area, northeastern Tanzania
EP Malisa
Tanzania Journal of Science , 2005,
Abstract: Sillimanite/kyanite + K-feldspar + quartz ± garnet + biotite ± Fe-Ti oxide-bearing rocks occur associated with calc-silicate rocks in the Merelani tanzanite mining area north-eastern Tanzania. The whole rock chemistry shows varying rock oxidation ratios, which are reflected in the mineralogical assemblages. Almandine garnet is oxidized to mixtures of hematite, quartz, and hydrous aluminosilicates in oxidized rocks and is absent in highly oxidized rocks. In the latter, ilmenite is oxidized into mixtures of rutile and hematite. Such relatively high temperature alteration/oxidation effects could have occurred with the influx of water. Absence of staurolite in these aluminium-rich rocks is indicative of high fugacity of oxygen during metamorphism. These rocks were regionally metamorphosed to the high-grade granulite facies with estimated formation temperatures and pressures of 596 – 726o C and 7.7 – 9.1 kbars and later, underwent retrograde metamorphism to the amphibolite facies. Tanzania Journal of Science Vol. 31 (2) 2005: pp. 81-92
Petrology and lithogeochemistry of the mineralized tanzanite-grossular bearings rocks in the Merelani-Lelatema area, northeastern Tanzania
EP Malisa
Tanzania Journal of Science , 2003,
Abstract: The Merelani-Lelatema area, which is occupied by late Proterozoic metasedimentary rocks, lies along the Lelatema fault zone. The rocks are mainly pelitic and semi-pelitic gneisses, psammitic gneisses, hydrothermally altered rocks, crystalline dolostones, pegmatites and quartz veins. The occurrence of gem-quality tanzanite and grossular has been found to occur mainly in boudinaged pegmatitic veins and hydrothermal fracture fillings. These fracture fillings occur in brecciated and hydrothermally altered graphite-bearing gneiss in a mineral association containing glass-clear quartz, diopside, zoisite, graphite and calcite. The psammitic gneisses are more siliceous and enriched in feldspars. They are grouped into graphite-kyanite gneiss with thin interlayers of quartz-feldspar fels. The pelitic and semi-pelitic gneisses are aluminium-rich and thus have been grouped into garnet-biotite-sillimanite and/or kyanite graphite gneisses. The hydrothermally altered rocks are strongly deformed and contain varying amounts of clay minerals, which characteristically show distinct banded layers due to alterations of minerals. The rocks have been folded and the fold structures have undergone three deformation episodes (D1, D2 and D3) D1 and D2 were accompanied by high-grade metamorphism whereas D3 was associated with retrograde metamorphism and the formation of retrograde shear zones. Evidence from metamorphosed graded bedding confirms the existence of the antiform and also shows that the macroscopic F2 folds are superimposed on a previously inverted stratigraphic succession. This inversion is the consequence of D1 deformation. The polyphase nature of these rocks with which pegmatites and quartz veins occur is shown by rotation of boudins, presence of overturned tight isoclinal folds resembling F1, presence of F2 folds and refolded folds shown by quartz veins. Features like boudins shown by quartz veins and pegmatites at the limbs and along the axial planes of F1 folds with S1 development in the host rocks and disruption of limbs of tight folds resembling F1, shown by these veins also point to significant amount of flattening during F1 folding phase and longitudinal stretching of the late stage of their development. Slippage in the later stages of deformation phase (D1) is also distinct in displaced veins. Lithogeochemical studies reveal that the gneissses originated from miogeosynclinal sediments composed of sand; organic matter rich in V, U and fine Al-rich materials. These underwent advanced weathering, deposited in a lake and during metamorphism and after the Pan-African tectonothermal event, the silicates were altered, trace elements released and migrated with hydrothermal solutions rich in Ca, Mg, CO2 and SO3. Finally these elements together with V, U, Sr, Zn and heavy REE elements were deposited in the hydrothermal zone. Emplacement of gemstones (tanzanite and green grossular) in the area is structurally controlled along the Lelatema fault system. Tanz. J. S
Trace elements characterization of the hydrothermally deposited tanzanite and green grossular in the Merelani – Lelatema shear zone, northeastern Tanzania
EPJ Malisa
Tanzania Journal of Science , 2003,
Abstract: Geochemical investigations of trace element contents of different rock samples were determined in the late Proterozoic metamorphic sequences of the Mozambique Belt along the Merelani–Lelatema shear zone, northeastern Tanzania. The area is composed of the following rock types: pelitic and semi-pelitic gneisses, psammitic, hydrothermally altered including carbonate-rich, carbonate-gypsum-rich, and iron-rich rocks, pegmatite dykes and crystalline limestones. Trace element characteristics of the principal rock units in and outside the shear zone have been compiled and studied. With the exception of higher barium contents in pelites, trace element contents in the psammitic and pelitic gneisses show some similarities while in the hydrothermally altered rocks where gemstones (tanzanite and green grossular) are localized reveal that the following trace elements: Ba, Cu, Mo, Ni, Rb, Sr, U, V and Zn have been enriched, while As, Ag, Co, Cr, Cs, Pb, Th and Zr were relatively depleted compared to the other rock types. Calculated CI/ Br ratios are at maximum of 900, which are the same as found in waters of deep drill holes and in salt waters associated with oil deposits. Calculated Co/Ni ratios are low, less than unity in most rocks except the psammitic gneisses and carbonate-rich rocks whose values are approximately 3.4 and 6.5 respectively. The low Co and Ni values in these rocks may be a result of low aco2+ and ani2+ in the hydrothermal fluids and / or lower temperature of crystallization. The high V contents result in an unusual degree of V substitution in a number of silicate and oxide phases. The high levels of V in the metasediments, together with that of Ni and Sr, is reflected in their enhanced concentration in the hydrothermally altered zone indicating that they may have been partly re-distributed by the hydrothermal fluids. Vanadium contents in the hydrothermally altered rocks are strongly enriched especially in the calcium-magnesium-aluminium-rich rocks but low in carbonate-sulphate-rich rocks. It is most likely that at the stage when tanzanite and green grossular were crystallized Al, Ca, Mg, Si, and V were migrating together and were incorporated into the minerals precipitated. Vanadium (V3+) substitutes for iron (Fe3+) and aluminium (Al3+) diadochically in the crystal lattices of silicates mainly zoisite and green grossular. The data suggest that the gemstone deposits are the result of a sequence of long-continued and overlapping geological processes culminating in intense shearing, considerable mobilization of trace elements and syn-tectonic hydrothermal intrusion.The Proterozoic metasedimentary rocks of the shear zone, as well as those enclosing it, served as the source of trace elements, while diffusion of the trace element constituents and their precipitation in physico-chemically favorable traps, formed in response to folding and shearing, resulted in the gemstone deposition. Tanz. J. Sci. Vol.29(1) 2003: 45-60
Artemisinin combination therapies price disparity between government and private health sectors and its implication on antimalarial drug consumption pattern in Morogoro Urban District, Tanzania
Allen Malisa, Deodatus Kiriba
BMC Research Notes , 2012, DOI: 10.1186/1756-0500-5-165
Abstract: To quantify the effect of price disparity between the government and private health systems, this study have audited 92 government and private Drug Selling Units (DSUs) in Morogoro urban district in Tanzania to determine the levels, trend and consumption pattern of antimalarial drugs in the two health systems. A combination of observation, interviews and questionnaire administered to the service providers of the randomly selected DSUs were used to collect data.ALU was the most selling antimalarial drug in the government health system at a subsidized price of 300 TShs (0.18 US$). By contrast, ALU that was available in the private sector (coartem) was being sold at a price of about 10,000 TShs (5.9 US$), the price that was by far unaffordable, prompting people to resort to cheap but failed drugs. As a result, metakelfin (the phased out drug) was the most selling drug in the private health system at a price ranging from 500 to 2,000 TShs (0.29–1.18 US$).In order for the prompt diagnosis and treatment with effective drugs intervention to have big impact on malaria in mostly low socioeconomic malaria-endemic areas of Africa, inequities in affordability and access to effective treatment must be eliminated. For this to be ensued, subsidized drugs should be made available in both government and private health sectors to promote a universal access to effective safe and affordable life saving antimalarial drugs.Prompt treatment with effective antimalarial drugs is among major strategies for control of the life-threatening malaria disease. However, the success of this strategy faces daunting challenges of spread of drug resistance and impediment of access to effective treatment for malaria [1]. Development assistance has been routed largely through government channels, whereas affected individuals seek treatment mostly through the private sector and the new artemisinin-based combination treatments (ACTs), recommended by WHO for uncomplicated falciparum malaria, are too expensi
Environmental risks for gemstone miners with reference to Merelani tanzanite mining area, Northeastern Tanzania
EP Malisa, CP Kinabo
Tanzania Journal of Science , 2005,
Abstract: Artisanal and small-scale gemstone miners are the workers with the highest health risk exposure in Tanzania. Gemstone mining at Merelani tanzanite mines which has gone to depths of 100 m or more in narrow straight and inclined shafts, underground artisanal miners work under a very harsh environment. Tanzanite deposits are located within sheared zones, lying along a deep-seated Lelatema fault zones. Rocks along these zones which are mainly graphitic and or/gypsum-bearing gneisses surrounded by limestone are soft, fractured and strongly weathered. Poor mining techniques, lack of geological background, chronic shortage of capital, and the lack of awareness on environmental pollution in the shafts have led to health and safety problems. In deep mines such as Merelani tanzanite mine, where the rocks are graphitic (C-rich), existence of poisonous gases is common. Dust exposure during drilling, blasting and shovelling indicates high average levels of overall respirable dust 15.5 mg/m3 whereby respirable quartz and graphite are 2.4 mg/m3 and 1.5mg/m3, respectively. The total amount of dust is 28.4 mg/m3. Supply of air (oxygen) to such depths by using small compressors is unreliable and inadequate, since they sometimes fail or deliberately are switched off. Further, lack of adequate ventilation for eliminating the toxic gases after blasting results in particles hazardous to the miners. Exposure to dust mixed with graphite; quartz and micas particles are harmful and may cause lung cancers or development of chronic silicosis. The workers and mine owners are supposed to adhere to mining rules, regulations and code of practice. Mines must be properly ventilated and back filling is necessary in mined out pits. Most of artisanal gemstone mining in Tanzania is sub-standard which results in fatal accidents. It is recommended that proper mining methods should be adhered to following the code of practice issued by the Ministry of Energy and Minerals. Tanzania Journal of Science Vol. 31 (1) 2005: pp. 1-12
Multiple Redundancy Constants with Trickle
Titouan Coladon,Malisa Vucinic,Bernard Tourancheau
Computer Science , 2015,
Abstract: Wireless sensor network protocols very often use the Trickle algorithm to govern information dissemination. For example, the widely used IPv6 Routing Protocol for Low-Power and Lossy Networks (RPL) uses Trickle to emit control packets. We derive an analytical model of Trickle to take into account multiple redundancy constants and the common lack of synchronization among nodes. Moreover, we demonstrate message count unfairness when Trickle uses a unique global redundancy constant because nodes with less neighbors transmit more often. Consequently, we propose a heuristic algorithm that calculates a redundancy constant for each node as a function of its number of neighbors. Our calculated redundancy constants reduce unfairness among nodes by distributing more equally the number of transmitted messages in the network. Our analytical model is validated by emulations of constrained devices running the Contiki Operating System and its IPv6 networking stack. Furthermore, results very well corroborate the heuristic algorithm improvements.
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