Folic Acid Functionalized Nanoparticles for Enhanced Oral Drug Delivery

The oral absorption of drugs that have poor bioavailability can be enhanced by encapsulation in polymeric nanoparticles. Transcellular transport of nanoparticle-encapsulated drug, possibly through transcytosis, is likely the major mechanism through which nanoparticles improve drug absorption. We hypothesized that the cellular uptake and transport of nanoparticles can be further increased by targeting the folate receptors expressed on the intestinal epithelial cells. The objective of this research was to study the effect of folic acid functionalization on transcellular transport of nanoparticle-encapsulated paclitaxel, a chemotherapeutic with poor oral bioavailability. Surface-functionalized poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles loaded with paclitaxel were prepared by the interfacial activity assisted surface functionalization technique. Transport of paclitaxel-loaded nanoparticles was investigated using Caco-2 cell monolayers as an in vitro model. Caco-2 cells were found to express folate receptor and the drug efflux protein, p-glycoprotein, to high levels. Encapsulation of paclitaxel in PLGA nanoparticles resulted in a 5-fold increase in apparent permeability (P(app)) across Caco-2 cells. Functionalization of nanoparticles with folic acid further increased the transport (8-fold higher transport compared to free paclitaxel). Confocal microscopic studies showed that folic acid-functionalized nanoparticles were internalized by the cells and that nanoparticles did not have any gross effects on tight junction integrity. In conclusion, our studies indicate that folic acid functionalized nanoparticles have the potential to enhance the oral absorption of drugs with poor oral bioavailability

Can oral infection be a risk factor for Alzheimer’s disease?

Alzheimer’s disease (AD) is a scourge of longevity that will drain enormous resources from public health budgets in the future. Currently, there is no diagnostic biomarker and/or treatment for this most common form of dementia in humans. AD can be of early familial-onset or sporadic with a late-onset. Apart from the two main hallmarks, amyloid-beta and neurofibrillary tangles, inflammation is a characteristic feature of AD neuropathology. Inflammation may be caused by a local central nervous system insult and/or by peripheral infections. Numerous microorganisms are suspected in AD brains ranging from bacteria (mainly oral and non-oral Treponema species), viruses (Herpes simplex type I) and yeasts (Candida species). A causal relationship between periodontal pathogens/non-oral Treponema species of bacteria has been proposed via the amyloid-beta and inflammatory links. Periodontitis constitutes a peripheral oral infection that can provide the brain with intact bacteria and virulence factors and inflammatory mediators due to daily, transient bacteraemias. If and when genetic risk factors meet environmental risk factors in the brain, disease is expressed, in which neurocognition may be impacted, leading to the development of dementia. To achieve the goal of finding a diagnostic biomarker and possible prophylactic treatment for AD, there is an initial need to solve the etiological puzzle contributing to its pathogenesis. This review therefore addresses oral infection as the plausible aetiology of late onset AD (LOAD)

Chlamydia pneumoniae: An Etiologic Agent for Late-Onset Dementia

The disease known as late-onset Alzheimer\u27s disease is a neurodegenerative condition recognized as the single most common form of senile dementia. The condition is sporadic and has been attributed to neuronal damage and loss, both of which have been linked to the accumulation of protein deposits in the brain. Significant progress has been made over the past two decades regarding our overall understanding of the apparently pathogenic entities that arise in the affected brain, both for early-onset disease, which constitutes approximately 5% of all cases, as well as late-onset disease, which constitutes the remainder of cases. Observable neuropathology includes: neurofibrillary tangles, neuropil threads, neuritic senile plaques and often deposits of amyloid around the cerebrovasculature. Although many studies have provided a relatively detailed knowledge of these putatively pathogenic entities, understanding of the events that initiate and support the biological processes generating them and the subsequent observable neuropathology and neurodegeneration remain limited. This is especially true in the case of late-onset disease. Although early-onset Alzheimer\u27s disease has been shown conclusively to have genetic roots, the detailed etiologic initiation of late-onset disease without such genetic origins has remained elusive. Over the last 15 years, current and ongoing work has implicated infection in the etiology and pathogenesis of late-onset dementia. Infectious agents reported to be associated with disease initiation are various, including several viruses and pathogenic bacterial species. We have reported extensively regarding an association between late-onset disease and infection with the intracellular bacterial pathoge

Transverse Dynamics and Energy Tuning of Fast Electrons Generated in Sub-Relativistic Intensity Laser Pulse Interaction with Plasmas

The regimes of quasi-mono-energetic electron beam generation were experimentally studied in the sub-relativistic intensity laser plasma interaction. The observed electron acceleration regime is unfolded with two-dimensional-particle-in-cell simulations of laser-wakefield generation in the self-modulation regime.Comment: 10 pages, 5 figure

On the re-acceleration of bunched beams

We examine the re-acceleration of a bunched beam through a linear induction accelerator (LIA) cavity, with attention to the energy lost through coupling to the TM modes of the structure. We find that the energy lost at 1 kA peak current is a small fraction of the boost which the LIA is designed to impart. We discuss implications for a Relativistic Klystron or Free Electron Laser (FEL) version of the Two-Beam Accelerator (TBA). 18 refs., 5 figs., 1 tab

Observation of Parity Nonconservation in Moller Scattering

We report a measurement of the parity-violating asymmetry in fixed target electron-electron (Moller) scattering: A_PV = -175 +/- 30 (stat.) +/- 20 (syst.) parts per billion. This first direct observation of parity nonconservation in Moller scattering leads to a measurement of the electron's weak charge at low energy Q^e_W = -0.053 +/- 0.011. This is consistent with the Standard Model expectation at the current level of precision: sin^2\theta_W(M_Z)_MSbar = 0.2293 +/- 0.0024 (stat.) +/- 0.0016 (syst.) +/- 0.0006 (theory).Comment: Version 3 is the same as version 2. These versions contain minor text changes from referee comments and a change in the extracted value of Q^e_W and sin^2\theta_W due to a change in the theoretical calculation of the bremsstrahulung correction (ref. 16

Role of Secreted Conjunctival Mucosal Cytokine and Chemokine Proteins in Different Stages of Trachomatous Disease

Trachoma, a disease of antiquity dating back to the 16th century B.C.E., predominates among developing countries, where it remains the primary cause of preventable blindness worldwide. In trachoma, recurrent Chlamydia trachomatis bacterial infections during childhood are thought to result in inflammation and subsequent conjunctival scarring that can progress to trichiasis (TT; chronic trachoma; inversion of ≥1 eyelash that touches the globe of the eye). The trachomatous follicular grade (TF; active disease) is a self-limiting disease, suggesting the coexistence of protective inflammatory proteins. The trachomatous inflammatory grade (TI; active disease) is more likely to progress to trachomatous scarring (TS; chronic trachoma). To date, there are only a handful of studies that have examined the immune response in trachoma, and these were primarily based on gene expression. Characterizing quantified conjunctival mucosal immune differences for secreted proteins among individuals with no, active, and chronic trachoma may identify protein biomarkers associated with protection versus disease, which would greatly aid our understanding of the immunopathogenesis of trachoma. In this study, we characterized 25 cytokine and chemokine proteins for all trachoma grades. We identified eight cytokines and chemokines as risk factors for chronic trachoma and four as protective. Together, these findings further characterize the immunopathologic responses involved during trachoma, which will likely aid in the design of a vaccine and immunomodulating therapeutics for trachoma

Measurements of Radiation Near An Atomic Spectral Line From the Interaction of a 30-GeV Electron Beam And a Long Plasma

Emissions produced or initiated by a 30 GeV electron beam propagating through a {approx}1 m long heat pipe oven containing neutral and partially ionized vapor have been measured near atomic spectral lines in a beam-plasma wakefield experiment. The Cerenkov spatial profile has been studied as a function of oven temperature and pressure, observation wavelength, and ionizing laser intensity and delay. The Cerenkov peak angle is affected by the creation of plasma; estimates of plasma and neutral density have been extracted. Increases in visible background radiation consistent with increased plasma recombination emissions due to dissipation of wakefields were simultaneously measured