A mathematical model of volatile release in mouth from the dispersion of gelled emulsion particles.

This paper presents a mathematical model of in-mouth volatile release from gelled emulsion particles dispersed in a continuous aqueous phase. Data based on APCI MS-Breath analysis is presented to demonstrate the effect of particle size, oil content and oil-water partition coefficients. It is shown that in-mouth release of aroma from the dispersion of gelled emulsion particles follows a two-component kinetic equation with fast and slow components. Both the fast and slow rate constants depend on the particle size, oil content and oil water partition coefficient of the aroma. The relative amount of aroma contributing to the fast and slow components also depends on the size of the particles. In order to understand this unexpected behaviour, an analytical model was developed that considers the interplay between the mass transfer of flavour across the interface of the particles and that across the air-liquid interface. Analytical expressions for the two rate constants and the relative ratio of aroma contributing to the fast component have been derived. From this model, three regimes of in-mouth release of aroma from the dispersion of gelled emulsion particles were identified including, the emulsion regime, the transition regime and the gel particle regime. In the emulsion regime, changes in the size of gelled emulsion particles had negligible impact on the overall release. In the transition regime, the release was controlled by the interaction of flavour transfer from the particles with that across the air-water interface. In the gel particle regime, aroma release at long times was governed by the particles and that at short times was governed by the air-water interface, and the two processes were fully decoupled. A simple relationship was derived for the critical size above which the release of aroma from the dispersion of gelled emulsion particles is affected by the size of the particles.     

Wound matrix attachment regulates actin content and organization in cells of the granulation tissue

Actin cytoskeletal polymerization is associated with a pro-proliferative, pro-survival state. We hypothesized that the actin polymerization of wound cells is increased in the presence of wound matrix attachment and is decreased after disruption of this attachment. Musculocutaneous flap and wound splinting models were used to investigate the effect of wound matrix attachment on the actin cytoskeleton. Disruption of wound matrix attachment was accomplished by incision of the wound matrix/dermis interface (wound matrix release) and/or desplinting. Polymerized actin was assayed with phalloidin labeling of wound specimens 24 hours after disruption of attachment and a method to quantify the content and organization of polymerized actin in granulation tissue was used. Disruption of wound matrix attachment decreased the content of polymerized actin, the actin staining intensity, and the actin fiber organization in the granulation tissue of both the flap and splint models. Disruption of wound matrix attachment decreased actin polymerization and fiber organization in the granulation tissue. Our data support the concept that the state of wound matrix attachment regulates the actin cytoskeleton of wound cells.     

Effect of Graft Size, Angle, and Intergraft Distance on Dense Packing in Hair Transplant

BACKGROUND: The maximum number of hair grafts that can be safely implanted in 1 cm2 is still debatable. To our knowledge, no previous report has addressed this issue in three dimensions, taking into account the size, the angle of the graft, and the intergraft distance. OBJECTIVES: To study the effect of the size and angle of the graft and the intergraft distance on dense packing. METHODS: Using a mathematical formula (the maximum number of hair grafts in 1 cm2 = 33 * cosine), the volume of the recipient area and the volume of the hair graft are calculated, assuming that the surface area of the recipient area is 1 cm2, the diameter of the hair graft is 1 mm, and the intergraft distance is 1.5 mm laterally and 1 mm anteriorly and posteriorly. RESULTS: The maximum number of hair grafts that could be implanted in 1 cm2 at a 90 angle in relation to the skin surface is 33 grafts, at a 60 angle is 28 grafts, and at a 30 angle is 16 grafts. CONCLUSION: The maximum number of hair grafts that can be implanted in any given recipient area depends on the graft size, the angle or direction of these grafts, and the intergraft distance. Where more space is allowed between the grafts, and the more acute the angle, the fewer hair grafts that can be implanted.     

The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies.

To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy.