50 research outputs found

    Neurological Manifestations of HIV

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    Neurological manifestations of human immunodeficiency virus (HIV) infection are common in certain regions of the world, notably Sub-Saharan Africa. The chapter highlights the neurotropism and neurovirulence of HIV underlying its direct neuropathology. The high frequency of neurological HIV disease is discussed in respect with the different viral clades. Sub-Saharan Africa is highlighted as bearing the brunt of the HIV pandemic. An approach to neurological HIV disease is given with a sensible classification system of manifestations and complications according to the level of immune suppression, primary HIV-related versus secondary opportunistic conditions, and other metabolic, drug induced, nutritional, or unrelated causes. Major manifestations of neuro-HIV are aseptic meningitis, HIV-associated neurocognitive disorders, HIV myelopathies and pediatric HIV-associated CNS disease; these are discussed in detail, and reference is made to the discrepancy of available data and literature between the so-called developed and developing countries. The role of antiretroviral treatment and its potential limitation in reaching the CNS compartment is stressed

    Trends in the Molecular Pathogenesis and Clinical Therapeutics of Common Neurodegenerative Disorders

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    The term neurodegenerative disorders, encompasses a variety of underlying conditions, sporadic and/or familial and are characterized by the persistent loss of neuronal subtypes. These disorders can disrupt molecular pathways, synapses, neuronal subpopulations and local circuits in specific brain regions, as well as higher-order neural networks. Abnormal network activities may result in a vicious cycle, further impairing the integrity and functions of neurons and synapses, for example, through aberrant excitation or inhibition. The most common neurodegenerative disorders are Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis and Huntington’s disease. The molecular features of these disorders have been extensively researched and various unique neurotherapeutic interventions have been developed. However, there is an enormous coercion to integrate the existing knowledge in order to intensify the reliability with which neurodegenerative disorders can be diagnosed and treated. The objective of this review article is therefore to assimilate these disorders’ in terms of their neuropathology, neurogenetics, etiology, trends in pharmacological treatment, clinical management, and the use of innovative neurotherapeutic interventions

    A Review on Composite Liposomal Technologies for Specialized Drug Delivery

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    The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications

    Diagnosis and Treatment of Neurological and Ischemic Disorders Employing Carbon Nanotube Technology

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    Extensive research on carbon nanotubes has been conducted due to their excellent physicochemical properties. Based on their outstanding physicochemical properties, carbon nanotubes have the potential to be employed as theranostic tools for neurological pathologies such as Alzheimer’s disease and Parkinson’s disease including ischemic stroke diagnosis and treatment. Stroke is currently regarded as the third root cause of death and the leading source of immobility around the globe. The development and improvement of efficient and effective procedures for central nervous system disease diagnosis and treatment is necessitated. The main aim of this review is to discuss the application of nanotechnology, specifically carbon nanotubes, to the diagnosis and treatment of neurological disorders with an emphasis on ischemic stroke. Areas covered include the conventional current diagnosis and treatment of neurological disorders, as well as a critical review of the application of carbon nanotubes in the diagnosis and treatment of ischemic stroke, covering areas such as functionalization of carbon nanotubes and carbon nanotube-based biosensors. A broad perspective on carbon nanotube stimuli-responsiveness, carbon nanotube toxicity, and commercially available carbon nanotubes is provided. Potential future studies employing carbon nanotubes have been discussed, evaluating their extent of advancement in the diagnosis and treatment of neurological and ischemic disorders

    Ex vivo and In vivo characterization of interpolymeric blend/nanoenabled gastroretentive levodopa delivery systems

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    One approach for delivery of narrow absorption window drugs is to formulate gastroretentive drug delivery systems. This study was undertaken to provide insight into in vivo performances of two gastroretentive systems (PXLNET and IPB matrices) in comparison to Madopar® HBS capsules. The pig model was used to assess gastric residence time and pharmacokinetic parameters using blood, cerebrospinal fluid (CSF), and urine samples. Histopathology and cytotoxicity testing were also undertaken. The pharmacokinetic parameters indicated that levodopa was liberated from the drug delivery systems, absorbed, widely distributed, metabolized, and excreted. were 372.37, 257.02, and 461.28 ng/mL and MRT were 15.36, 14.98, and 13.30 for Madopar HBS capsules, PXLNET, and IPB, respectively. In addition, X-ray imaging indicated that the gastroretentive systems have the potential to reside in the stomach for 7 hours. There was strong in vitro-in vivo correlation for all formulations with values of 0.906, 0.935, and 0.945 for Madopar HBS capsules, PXLNET, and IPB, respectively. Consequently, PXLNET and IPB matrices have pertinent potential as gastroretentive systems for narrow absorption window drugs (e.g., L-dopa) and, in this application specifically, enhanced the central nervous system and/or systemic bioavailability of such drugs.The National Research Foundation (NRF) of South Africahttps://www.hindawi.com/journals/pdam2017Paraclinical Science

    In Silico Theoretical Molecular Modeling for Alzheimer’s Disease: The Nicotine-Curcumin Paradigm in Neuroprotection and Neurotherapy

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    The aggregation of the amyloid-β-peptide (AβP) into well-ordered fibrils has been considered as the key pathological marker of Alzheimer‘s disease. Molecular attributes related to the specific binding interactions, covalently and non-covalently, of a library of compounds targeting of conformational scaffolds were computed employing static lattice atomistic simulations and array constructions. A combinatorial approach using isobolographic analysis was stochastically modeled employing Artificial Neural Networks and a Design of Experiments approach, namely an orthogonal Face-Centered Central Composite Design for small molecules, such as curcumin and glycosylated nornicotine exhibiting concentration-dependent behavior on modulating AβP aggregation and oligomerization. This work provides a mathematical and in silico approach that constitutes a new frontier in providing neuroscientists with a template for in vitro and in vivo experimentation. In future this could potentially allow neuroscientists to adopt this in silico approach for the development of novel therapeutic interventions in the neuroprotection and neurotherapy of Alzheimer‘s disease. In addition, the neuroprotective entities identified in this study may also be valuable in this regard
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