Functionalized carbon nanomaterials: exploring the interactions with Caco-2 cells for potential oral drug delivery

Although carbon nanomaterials (CNMs) have been increasingly studied for their biomedical applications, there is limited research on these novel materials for oral drug delivery. As such, this study aimed to explore the potential of CNMs in oral drug delivery, and the objectives were to evaluate CNM cytotoxicity and their abilities to modulate paracellular transport and the P-glycoprotein (P-gp) efflux pump. Three types of functionalized CNMs were studied, including polyhydroxy small-gap fullerenes (OH-fullerenes), carboxylic acid functionalized single-walled carbon nanotubes (f SWCNT-COOH) and poly(ethylene glycol) functionalized single-walled carbon nanotubes (f SWCNT-PEG), using the well-established Caco-2 cell monolayer to represent the intestinal epithelium. All three CNMs had minimum cytotoxicity on Caco-2 cells, as demonstrated through lactose dehydrogenase release and 3-(4,5-dimethyliazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Of the three CNMs, f SWCNT-COOH significantly reduced transepithelial electrical resistance and enhanced transport of Lucifer Yellow across the Caco-2 monolayer. Confocal fluorescence microscopy showed that f SWCNT-COOH treated cells had the highest perturbation in the distribution of ZO-1, a protein marker of tight junction, suggesting that f SWCNT-COOH could enhance paracellular permeability via disruption of tight junctions. This modulating effect of f SWCNT-COOH can be reversed over time. Furthermore, cellular accumulation of the P-gp substrate, rhodamine-123, was significantly increased in cells treated with f SWCNT-COOH, suggestive of P-gp inhibition. Of note, f SWCNT-PEG could increase rhodamine-123 accumulation without modifying the tight junction. Collectively, these results suggest that the functionalized CNMs could be useful as modulators for oral drug delivery, and the differential effects on the intestinal epithelium imparted by different types of CNMs would create unique opportunities for drug-specific oral delivery applications

Perorally active nanomicellar formulation of quercetin in the treatment of lung cancer

10.2147/IJN.S26538International Journal of Nanomedicine7651-66

Demonstration of a Longitudinal Action Medical Mission (LAMM) Model to Teach Point-of-Care Ultrasound in Resource-Limited Settings

BACKGROUND: Short-term medical missions prevail as the most common form of international medical volunteerism, but they are ill-suited for medical education and training local providers in resource-limited settings. OBJECTIVE: The purpose of this study is to evaluate the effectiveness of a longitudinal educational program in training clinicians how to perform point-of-care ultrasound (POCUS) in resource-limited clinics. DESIGN: A retrospective study of such a four-month POCUS training program was conducted with clinicians from a rural hospital in Haiti. The model included one-on-one, in-person POCUS teaching sessions by volunteer instructors from the United States and Europe. The Haitian trainees were assessed at the start of the program and at its conclusion by a direct objective structured clinical examination (OSCE), administered by the visiting instructors, with similar pre- and post- program ultrasound competency assessments. RESULTS: Post-intervention, a significant improvement was observed (p < 0.0001), and each trainee showed significant overall improvement in POCUS competency independent of the initial competency pre-training (p < 0.005). There was a statistically significant improvement in POCUS application for five of the six medically relevant assessment categories tested. CONCLUSION: Our results provide a proof-of-concept for the longitudinal education-centered healthcare delivery framework in a resource-limited setting. Our longitudinal model provides local healthcare providers the skills to detect and diagnose significant pathologies, thereby reducing avoidable morbidity and mortality at little or no addition cost or risk to the patient. Furthermore, training local physicians obviates the need for frequent volunteering trips, saving costs in healthcare training and delivery

Efficacy and Mechanism of Panax Ginseng in Experimental Stroke

Stroke is one of the leading causes of death and long-term disability worldwide. However, effective therapeutic approaches are still limited. The disruption of blood supply triggers complicated temporal and spatial events involving hemodynamic, biochemical, and neurophysiologic changes, eventually leading to pathological disturbance and diverse clinical symptoms. Ginseng (Panax ginseng), a popular herb distributed in East Asia, has been extensively used as medicinal and nutritional supplements for a variety of disorders worldwide. In recent years, ginseng has displayed attractive beneficial effects in distinct neurological disorders including stroke, involving multiple protective mechanisms. In this article, we reviewed the literature on ginseng studies in the experimental stroke field, particularly focusing on the in vivo evidence on the preventive or therapeutic efficacy and mechanisms of ginseng and ginsenosides in various stroke models of mice and rats. We also summarized the efficacy and underlying mechanisms of ginseng and ginsenosides on short- and long-term stroke outcomes

Application of Static Modeling in the Prediction of In Vivo Drug-Drug Interactions between Rivaroxaban and Antiarrhythmic Agents Based on In Vitro Inhibition Studies

ABSTRACT Rivaroxaban, a direct Factor Xa inhibitor, is indicated for stroke prevention in nonvalvular atrial fibrillation (AF). Studies have revealed that the clearance of rivaroxaban is largely attributed to CYP3A4, CYP2J2 metabolism, and P-glycoprotein (P-gp) efflux pathways. Amiodarone and dronedarone are antiarrhythmic agents employed in AF management. Amiodarone, dronedarone, and their major metabolites, N-desethylamiodarone (NDEA) and N-desbutyldronedarone (NDBD), demonstrate inhibitory effects on CYP3A4 and CYP2J2 with U.S. Food and Drug Administration-recommended probe substrates. In addition, both amiodarone and dronedarone are known P-gp inhibitors. Hence, the concomitant administration of these antiarrhythmic agents has the potential to augment the systemic exposure of rivaroxaban through simultaneous impairment of its clearance pathways. Currently, however, clinical data on the extent of these postulated drug-drug interactions are lacking. In this study, in vitro inhibition assays using rivaroxaban as the probe substrate demonstrated that both dronedarone and NDBD produced reversible inhibition as well as irreversible mechanism-based inactivation of CYP3A4-and CYP2J2-mediated metabolism of rivaroxaban. However, amiodarone and NDEA were observed to cause reversible inhibition as well as mechanism-based inactivation of CYP3A4 but not CYP2J2. In addition, amiodarone, NDEA, and dronedarone, but not NDBD, were determined to inhibit P-gpmediated rivaroxaban transport. The in vitro inhibition parameters were fitted into a mechanistic static model, which predicted a 37% and 31% increase in rivaroxaban exposure due to the inhibition of hepatic and gut metabolism by amiodarone and dronedarone, respectively. A separate model quantifying the inhibition of P-gpmediated efflux by amiodarone or dronedarone projected a 9% increase in rivaroxaban exposure

Precise measurement of the W-boson mass with the CDF II detector

We have measured the W-boson mass MW using data corresponding to 2.2/fb of integrated luminosity collected in proton-antiproton collisions at 1.96 TeV with the CDF II detector at the Fermilab Tevatron collider. Samples consisting of 470126 W->enu candidates and 624708 W->munu candidates yield the measurement MW = 80387 +- 12 (stat) +- 15 (syst) = 80387 +- 19 MeV. This is the most precise measurement of the W-boson mass to date and significantly exceeds the precision of all previous measurements combined

X-ray emission from the Sombrero galaxy: discrete sources

We present a study of discrete X-ray sources in and around the bulge-dominated, massive Sa galaxy, Sombrero (M104), based on new and archival Chandra observations with a total exposure of ~200 ks. With a detection limit of L_X = 1E37 erg/s and a field of view covering a galactocentric radius of ~30 kpc (11.5 arcminute), 383 sources are detected. Cross-correlation with Spitler et al.'s catalogue of Sombrero globular clusters (GCs) identified from HST/ACS observations reveals 41 X-rays sources in GCs, presumably low-mass X-ray binaries (LMXBs). We quantify the differential luminosity functions (LFs) for both the detected GC and field LMXBs, whose power-low indices (~1.1 for the GC-LF and ~1.6 for field-LF) are consistent with previous studies for elliptical galaxies. With precise sky positions of the GCs without a detected X-ray source, we further quantify, through a fluctuation analysis, the GC LF at fainter luminosities down to 1E35 erg/s. The derived index rules out a faint-end slope flatter than 1.1 at a 2 sigma significance, contrary to recent findings in several elliptical galaxies and the bulge of M31. On the other hand, the 2-6 keV unresolved emission places a tight constraint on the field LF, implying a flattened index of ~1.0 below 1E37 erg/s. We also detect 101 sources in the halo of Sombrero. The presence of these sources cannot be interpreted as galactic LMXBs whose spatial distribution empirically follows the starlight. Their number is also higher than the expected number of cosmic AGNs (52+/-11 [1 sigma]) whose surface density is constrained by deep X-ray surveys. We suggest that either the cosmic X-ray background is unusually high in the direction of Sombrero, or a distinct population of X-ray sources is present in the halo of Sombrero.Comment: 11 figures, 5 tables, ApJ in pres

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO

Performance of CMS muon reconstruction in pp collision events at sqrt(s) = 7 TeV

The performance of muon reconstruction, identification, and triggering in CMS has been studied using 40 inverse picobarns of data collected in pp collisions at sqrt(s) = 7 TeV at the LHC in 2010. A few benchmark sets of selection criteria covering a wide range of physics analysis needs have been examined. For all considered selections, the efficiency to reconstruct and identify a muon with a transverse momentum pT larger than a few GeV is above 95% over the whole region of pseudorapidity covered by the CMS muon system, abs(eta) < 2.4, while the probability to misidentify a hadron as a muon is well below 1%. The efficiency to trigger on single muons with pT above a few GeV is higher than 90% over the full eta range, and typically substantially better. The overall momentum scale is measured to a precision of 0.2% with muons from Z decays. The transverse momentum resolution varies from 1% to 6% depending on pseudorapidity for muons with pT below 100 GeV and, using cosmic rays, it is shown to be better than 10% in the central region up to pT = 1 TeV. Observed distributions of all quantities are well reproduced by the Monte Carlo simulation.Comment: Replaced with published version. Added journal reference and DO