Development and characterization of Fluconazole Solid lipid nanoparticles

Solid Lipid Nanoparticles are first-generation colloidal carriers based on lipids, with their sizes ranging from 40-1000 nm. They are composed of biocompatible lipids, which are dispersed in an aqueous medium containing surfactant to form a lipid core. The active pharmaceutical ingredient is dispersed uniformly in the lipid matrix of the formulation. Water, along with lipids, is one of the major constituents in the preparation of solid lipid nanoparticles. Various active ingredients have adverse effects when taken by oral route and hence can be formulated as alternative drug delivery methods for the reduction of side effects. The objective of the present study was to develop and characterize solid lipid nanoparticles suitable for incorporating an anti-fungal drug, Fluconazole in solid lipid nanoparticles for formulation stability and reducing adverse effects associated with the oral administration of the drug.Fluconazole (FLZ) was selected as a model drug for preparing solid lipid nanoparticles consisting of Stearic acid and Precirol ATO 5 as the lipids, Tween 80 as the surfactant, and Polyvinyl alcohol as the stabilizer. Hot homogenization and probe sonication techniques were used for the development of the fluconazole solid lipid nanoparticle formulation. Developed SLNs were characterized for the following: Particle size, polydispersity index, zeta potential, entrapment efficiency, and in-vitro drug release. The in-vitro release of the best formulation also showed promising results with 92.13% release in 24 hrs., with initial burst release followed by a sustained release. The particle size, PDI, and zeta potential of the prepared formulations were found to be in the range of 336.4 to 401.5 nm, 0.216 to 0.312, and -21.8 to -28.9 mV respectively

Studies on Biological Evaluation of Novel Heterocyclic Compounds

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Feasibility and Operational Limits for a 236 GHz Hollow-Cavity Gyrotron for DEMO

The DEMOnstration fusion power plant (DEMO) will be the first fusion reactor, which is intended to generate net electrical power. For successful operation of DEMO, high-power gyrotrons with operating frequencies up to 240 GHz are required for plasma heating and stabilization. In this work, a systematic feasibility study and tolerance analysis are performed for the conventional-type hollow-cavity DEMO gyrotrons. The various approaches are also suggested to identify its operational limits

Ranking Significant Discrepancies in Clinical Reports

Medical errors are a major public health concern and a leading cause of death worldwide. Many healthcare centers and hospitals use reporting systems where medical practitioners write a preliminary medical report and the report is later reviewed, revised, and finalized by a more experienced physician. The revisions range from stylistic to corrections of critical errors or misinterpretations of the case. Due to the large quantity of reports written daily, it is often difficult to manually and thoroughly review all the finalized reports to find such errors and learn from them. To address this challenge, we propose a novel ranking approach, consisting of textual and ontological overlaps between the preliminary and final versions of reports. The approach learns to rank the reports based on the degree of discrepancy between the versions. This allows medical practitioners to easily identify and learn from the reports in which their interpretation most substantially differed from that of the attending physician (who finalized the report). This is a crucial step towards uncovering potential errors and helping medical practitioners to learn from such errors, thus improving patient-care in the long run. We evaluate our model on a dataset of radiology reports and show that our approach outperforms both previously-proposed approaches and more recent language models by 4.5% to 15.4%.Comment: ECIR 2020 (short

Morphometry of the hippocampal microvasculature in post-stroke and age-related dementias

BACKGROUND: Optimal vascular function is vital for prevention of dementia. We hypothesized that elderly post-stroke survivors who preserve cognitive function show unperturbed cerebral microvasculature compared with those who develop dementia. METHODS: Using stereological spherical probe software, we compared the length density (Lv, cumulative vessel length per unit tissue volume) of hippocampal microvessels in post mortem brain tissue from post-stroke survivors, Alzheimer's disease (AD), vascular dementia (VaD) and normal ageing control subjects. We also assessed microvessel diameters in the same subjects. Microvessels were identified by markers of endothelial cells (glucose transporter 1; GLUT1), basement membrane (collagen IV; COL4) and smooth muscle cell α-actin (SMA). RESULTS: We found increased Lv of both GLUT1 and COL4 immunostained microvessels (P < 0.05) in the hippocampal CA1 region of post-stroke demented (PSD) and AD cases compared with post-stroke nondemented (PSND), control and VaD subjects. However, no changes were apparent in the CA2 region. We also noted significant increase in Lv in the entorhinal cortex of AD compared with PSND and PSD subjects. The mean diameter of microvessels was decreased in PSD, compared with PSND, as well as in AD and VaD compared with controls. Cumulative frequency analysis showed PSND subjects to have significantly greater proportion of microvessels with diameters, ranging from 7 to 12 μm. CONCLUSIONS: An increase in microvascular Lv in AD and PSD suggests either an increase in angiogenesis or the formation of newer microvessel loops in response to cerebral hypoperfusion. The decreased vessel diameters found in AD and VaD suggests increased vasoconstriction in dementia

Liquid Chromatography- Tandem Mass Spectrometry (LC-MS-MS) as a detection method for Cocaine as a Perfomance Enhancing Drug

Presenters: Isha Kalaria, Shrishti Dubeyhttps://egrove.olemiss.edu/pharm_annual_posters_2021/1011/thumbnail.jp

Alpha-Synuclein Post-translational Modifications: Implications for Pathogenesis of Lewy Body Disorders

\ua9 Copyright \ua9 2021 Manzanza, Sedlackova and Kalaria. Lewy Body Disorders (LBDs) lie within the spectrum of age-related neurodegenerative diseases now frequently categorized as the synucleinopathies. LBDs are considered to be among the second most common form of neurodegenerative dementias after Alzheimer\u27s disease. They are progressive conditions with variable clinical symptoms embodied within specific cognitive and behavioral disorders. There are currently no effective treatments for LBDs. LBDs are histopathologically characterized by the presence of abnormal neuronal inclusions commonly known as Lewy Bodies (LBs) and extracellular Lewy Neurites (LNs). The inclusions predominantly comprise aggregates of alpha-synuclein (aSyn). It has been proposed that post-translational modifications (PTMs) such as aSyn phosphorylation, ubiquitination SUMOylation, Nitration, o-GlcNacylation, and Truncation play important roles in the formation of toxic forms of the protein, which consequently facilitates the formation of these inclusions. This review focuses on the role of different PTMs in aSyn in the pathogenesis of LBDs. We highlight how these PTMs interact with aSyn to promote misfolding and aggregation and interplay with cell membranes leading to the potential functional and pathogenic consequences detected so far, and their involvement in the development of LBDs

Stroke injury, cognitive impairment and vascular dementia

AbstractThe global burden of ischaemic strokes is almost 4-fold greater than haemorrhagic strokes. Current evidence suggests that 25–30% of ischaemic stroke survivors develop immediate or delayed vascular cognitive impairment (VCI) or vascular dementia (VaD). Dementia after stroke injury may encompass all types of cognitive disorders. States of cognitive dysfunction before the index stroke are described under the umbrella of pre-stroke dementia, which may entail vascular changes as well as insidious neurodegenerative processes. Risk factors for cognitive impairment and dementia after stroke are multifactorial including older age, family history, genetic variants, low educational status, vascular comorbidities, prior transient ischaemic attack or recurrent stroke and depressive illness. Neuroimaging determinants of dementia after stroke comprise silent brain infarcts, white matter changes, lacunar infarcts and medial temporal lobe atrophy. Until recently, the neuropathology of dementia after stroke was poorly defined. Most of post-stroke dementia is consistent with VaD involving multiple substrates. Microinfarction, microvascular changes related to blood–brain barrier damage, focal neuronal atrophy and low burden of co-existing neurodegenerative pathology appear key substrates of dementia after stroke injury. The elucidation of mechanisms of dementia after stroke injury will enable establishment of effective strategy for symptomatic relief and prevention. Controlling vascular disease risk factors is essential to reduce the burden of cognitive dysfunction after stroke. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock

Current perspectives on prevention of vascular cognitive impairment and promotion of vascular brain health

\ua9 2023 The Author(s). Published by Informa UK Limited, trading as Taylor &amp; Francis Group. Introduction: The true global burden of vascular cognitive impairment (VCI) is unknown. Reducing risk factors for stroke and cardiovascular disease would inevitably curtail VCI. Areas Covered: The authors review current diagnosis, epidemiology, and risk factors for VCI. VCI increases in older age and by inheritance of known genetic traits. They emphasize modifiable risk factors identified by the 2020 Lancet Dementia Commission. The most profound risks for VCI also include lower education, cardiometabolic factors, and compromised cognitive reserve. Finally, they discuss pharmacological and non-pharmacological interventions. Expert Opinion: By virtue of the high frequencies of stroke and cardiovascular disease the global prevalence of VCI is expectedly higher than prevalent neurodegenerative disorders causing dementia. Since ~ 90% of the global burden of stroke can be attributed to modifiable risk factors, a formidable opportunity arises to reduce the burden of not only stroke but VCI outcomes including progression from mild to the major in form of vascular dementia. Strict control of vascular risk factors and secondary prevention of cerebrovascular disease via pharmacological interventions will impact on burden of VCI. Non-pharmacological measures by adopting healthy diets and encouraging physical and cognitive activities and urging multidomain approaches are important for prevention of VCI and preservation of vascular brain health