Combined effect of oleic acid and polyethylene glycol 200 on buccal permeation of [D-ala2, D-leu5]enkephalin from a cubic phase of glyceryl monooleate.
The combined use of the lipophilic permeation enhancer, oleic acid together with polyethylene glycol 200 (PEG 200) as a co-enhancer and incorporated into the cubic liquid crystalline phase of glyceryl monooleate was investigated in the ex vivo buccal permeation of [D-Ala2, D-Leu5]enkephalin (DADLE) through porcine buccal mucosa mounted in a Franz cell. The addition of oleic acid (1%) and PEG 200 (1-10%) did not change the intact appearance of the cubic phase. PEG 200 increased the aqueous solubility of oleic acid incorporated into the cubic phase and hence promoted the transport of oleic acid into the porcine buccal mucosa. The solubilising effect of PEG 200 on oleic acid incorporated into the cubic phase was dependent on the PEG 200 concentration but was non-linear. The buccal permeation flux of DADLE significantly increased when 5% (P<0.01) or 10% (P<0.001) of PEG 200 was co-administered with 1% oleic acid compared with the cubic phase containing 1% oleic acid alone. The present results suggest that PEG 200 enhances the action of the lipophilic permeation enhancer oleic acid and that the combination of oleic acid and PEG 200 as a co-enhancer can be a useful tool to improve the membrane permeability in the buccal delivery of peptide drugs using a cubic liquid crystalline phase of glyceryl monooleate and water.

title: Hydrotropic Solubilization of Paclitaxel: Analysis of Chemical Structures for Hydrotropic Property
abstract: AbstractPurpose. To identify hydrotropic agents that can increase aqueous paclitaxel (PTX) solubility and to study the chemical structures necessary for hydrotropic properties so that polymeric hydrotropic agents can be synthesized.
Methods. More than 60 candidate hydrotropic agents (or hydro- tropes) were tested for their ability to increase the aqueous PTX solubility. A number of nicotinamide analogues were synthesized based on the observation that nicotinamide showed a favorable hydrotropic property. The identified hydrotropes for PTX were used to examine the structure-activity relationship. N,N-Diethylnicotinamide (NNDENA) was found to be the most effective hydrotropic agent for PTX. The aqueous PTX solubility was 39 mg/ml and 512 mg/ml at NNDENA concentrations of 3.5 M and 5.95 M, respectively. These values are 5-6 orders of magnitude greater than the intrinsic solubility of 0.30 ± 0.02 μg/ml. N-Picolylnicotinamide, N-allylnicotinamide, and sodium salicylate were also excellent hydrotropes for PTX. Solubility data showed that an effective hydrotropic agent should be highly water soluble while maintaining a hydrophobic segment.
 The present study identified several hydrotropic agents effective for increasing aqueous solubility of PTX and analyzed the structural requirements for this hydrotropic property. This information can be used to find other hydrotropic compounds and to synthesize polymeric hydrotropes that are effective for PTX and other poorly water-soluble drugs.

title: Enhancedex vivo buccal transport of propranolol: Evaluation of phospholipids as permeation enhancers
abstract: The aim of the present study was to evaluate the effects of two phospholipid permeation enhancers, lysophosphatidylcholine (LPC) and didecanoylphosphatidylcholine (DDPC), along with a fusidic acid derivative, sodium taurodihydrofusidate (STDHF) and ethanol (EtOH) on the buccal transport of propranolol hydrochloride (PPL) using anex vivo buccal diffusion model. The permeation rate of [3H]PPL as measured by steady-state fluxes increased with increasing EtOH concentration. A significant flux enhancement (P<0.05) was achieved by EtOH at 20 and 30 %v/v concentrations. At a 0.5 %w/v permeation enhancer concentration, the buccal permeation of [3H]PPL was significantly enhanced by all the enhancers studied (i.e., LPC, DDPC and STDHF) compared to the control (phosphate-buffered saline pH 7.4, PBS). LPC and DDPC displayed a greater degree of permeation enhancement compared with STDHF and EtOH-PBS mixtures with an enhancement ratio of 3.2 and 2.9 for LPC and DDPC, respectively compared with 2.0 and 1.5 for STDHF and EtOH:PBS 30:70 %v/v mixture, respectively. There was no significant difference between LPC and DDPC for the flux values and apparent permeability coefficients of [3H]PPL. These results suggest that phospholipids are suitable as permeation enhancers for the buccal delivery of drugs.

title: Peptide Washout and Permeability from Glyceryl Monooleate Buccal Delivery Systems
abstract: Simultaneous evaluation of the permeation and washout of a peptide from the mucoadhesive liquid crystalline phases of glyceryl monooleate (GMO) has been investigated using a donor compartment flow-through diffusion cell. [d-Ala2, d-Leu5]enkephalin (DADLE) was incorporated into the cubic and lamellar liquid crystalline phases of GMO and applied to excised porcine buccal mucosa mounted in the donor compartment flow-through cell. Phosphate-buffered saline pH 7.4 (PBS) was pumped across the upper surface of the liquid crystalline phases to mimic salivary flow. The steady-state fluxes of DADLE and GMO from the cubic phase were significantly greater than that from the lamellar phase (P<0.01). There was no statistical difference between the amounts of DADLE and GMO washed out from the lamellar and cubic phases (P>0.05). The donor compartment flow-through diffusion cell was found to be a useful tool to evaluate the impact of salivary washout on mucoadhesive oral mucosal delivery systems.

title: Kinetic characterization of swelling of liquid crystalline phases of glyceryl monooleate
abstract: Research in this paper focuses on the kinetic evaluation of swelling of the liquid crystalline phases of glyceryl monooleate (GMO). Swelling of the lamellar and cubic liquid crystalline phases of GMO was studied using twoIn vitro methods, a total immersion method and a Franz cell method. The swelling of the lamellar phase and GMO having 0 %w/w initial water content was temperature dependent. The swelling ratio was greater at 20°C than 37°C. The water uptake increased dramatically with decreasing initial water content of the liquid crystalline phases. The swelling rates obtained using the Franz cell method with a moist nylon membrane to mimic buccal drug delivery situation were slower than the total immersion method. The swelling was studied by employing first-order and second-order swelling kinetics. The swelling of the liquid crystalline phases of GMO could be described by second-order swelling kinetics. The initial stage of the swelling (t < 4 h) followed the square root of time relationship, indicating that this model is also suitable for describing the water uptake by the liquid crystalline matrices. These results obtained from the current study demonstrate that the swelling strongly depends on temperature, the initial water content of the liquid crystalline phases and the methodology employed for measuring the swelling of GMO.

title: The effect of storage conditions on the permeability of porcine buccal mucosa
abstract: The impact of storage conditions on the permeability of porcine buccal mucosa to [3H]water and [14C]mannitol was assessed. The fresh porcine buccal tissue (fresh tissue) was obtained by utilizing pig heads within 24 hours of slaughter. The stored and frozen porcine buccal tissues (stored tissue and frozen tissue) were obtained after the storage of the tissue intact in the pig heads at 4 degrees C or -20 degrees C, respectively, for 24 h. The results demonstrated that the barrier properties of the porcine buccal mucosa were maintained with regard to [3H]water permeability when stored at 4 degrees C for 24 h. However, freezing the tissue resulted in tissue damage illustrated by a significant increase in [3H]water permeability. [14C]Mannitol does not appear to be a suitable model solute to assess the ex vivo permeability of porcine buccal mucosa due to its extremely low permeability.

title: Measurement issues across different cultures.
abstract: The purposes of this methodologic paper are to (1) describe theoretical background in conducting research across different cultures; (2) address measurement issues related to instrument administration; and (3) provide strategies to deal with measurement issues.



A thorough review of the literature was conducted. A theoretical background is provided, and examples of administering instrument in studies are described.



When applying an instrument to different cultures, both equivalence and bias need to be established. Three levels of equivalence, i.e., construct equivalence, measurement unit equivalence, and full score comparability, need to be explained to maintain the same concept being measured. In this paper, sources of bias in construct, method, and item are discussed. Issues related to instrument administration in a cross-cultural study are described.



Researchers need to acknowledge various group differences in concept and/or language that include a specific set of symbols and norms. There is a need to question the philosophical and conceptual appropriateness of an assessment measure that has been conceptualized and operationalized in a different culture. Additionally, testing different response formats such as narrowing response range can be considered to reduce bias.

title: On the contribution of deoxy-hemoglobin to MRI gray–white matter phase contrast at high field
abstract: High field (> or =7 T) MRI studies based on signal phase have been used to improve visualization of the fine structure of the brain, most notably the major white matter fiber bundles, the gray-white matter subdivision, and the laminar cortical architecture. The observed contrast has been attributed in part to local variations in magnetic susceptibility arising from iron in storage proteins and tissue lipid. Another contribution could come from the paramagnetic blood constituent deoxy-hemoglobin, the tissue concentration of which may vary through local variations in vascular density. To investigate this possibility, we examined phase contrast between gray and white matter in rats after intravenous administration of a superparamagnetic contrast agent at various dosages. At the maximum dosage (3 mg Fe/kg), which resulted in an estimated paramagnetic susceptibility shift 4-8 times larger than deoxy-hemoglobin, we observed a negligible increase in phase contrast between gray and white matter. This result suggests that endogenous deoxy-hemoglobin has no significant contribution to phase contrast between gray and white matter.

title: Underlying venous pathology causing perimesencephalic subarachnoid hemorrhage.
abstract: Perimesencephalic subarachnoid hemorrhage (PSH) is a relatively benign clinical entity with a low risk of recurrent bleeding. The precise etiology of PSH has not yet been determined. We report here three cases of PSH with clinical and radiological features that support a venous system as a cause.



The first patient, a 72-year-old woman, had PSH and venous hemorrhagic infarct in the left thalamus on non-contrast CT. Subsequent cerebral angiography revealed widespread thrombosis in the cerebral venous system, a potential cause for reflux overflow hemorrhage. The second patient, a 55-year-old man with an established diagnosis of neuro-Behçet's disease, a well-known cause for cerebral venulitis, presented with PSH one year later. The third patient, a 39-year-old female, with incomplete Behçet's disease was admitted with PSH.



Current concepts on the anatomic origin and the possible pathophysiologic mechanism leading to PSH are discussed. The underlying pathological conditions in the venous system in our cases provide theoretical clues to the anatomic origin of PSH in general.

title: Effect of selenium fertilizer on free amino acid composition of broccoli (Brassica oleracea Cv. Majestic) determined by gas chromatography with flame ionization and mass selective detection.
abstract: Selenium-enriched broccoli florets, harvested from plants grown on soil fertilized with four levels of sodium selenate, were evaluated for their free amino acid composition using alkylchlorformate derivatization, solid-phase extraction, and GC-FID or GC-MS. The selenium-enriched florets contained 0.4 (control), 5.7 (treatment A), 98.6 (treatment B), and 879.2 (treatment C) microg/g Se (dry weight). Twenty-one free amino acids were identified in the control and all three treatments. The total free amino acid content of the broccoli florets ranged from 178 mmol/kg (dry weight), for the control, to 479 mmol/kg (dry weight), for treatment C. Broccoli from treatment C contained the highest level of Se, had the most total free amino acids, and had an extremely high level of glutamine (Gln) when compared to the control and the other two treatments. In general, the smallest addition of Se to the soil (treatment A) induced increased levels of all detectable amino acids when compared to the control, whereas increased additions of Se (treatments B and C) produced mixed responses. Florets from treatment A contained the highest essential amino acid content.

title: Estimation of anatomical locations using standard frame of reference in chest CT scans
abstract: We propose a method to establish the standard chest frame of reference (CFOR) using the rib cage in a lung CT scan. Such a reference frame is essential for referring to a certain location within a chest region and may facilitate the registration across multiple scans of a given subject as well as the comparative studies within a cohort of subjects. The robustness of the established CFOR was evaluated by estimating the anatomical locations within chest in the follow-up scan given the location in the first scan. Specifically, tracheal bifurcation point of airway tree and the center of pulmonary nodule were used as the anatomical points of interest. The CFOR was also used for exploring the spatial distribution of the anatomical location for a large number of individuals. The results show that on average the point of interest can be estimated accurately within 10.3 mm for the bifurcation point and within 12.5 mm for the pulmonary nodule’s center point. Further analyzing the spatial distribution of the CFOR coordinates across 86 subjects shows that we can localize the bifurcation point to the small subregion within the CFOR.