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1.  Curcuma longa Extract Associated with White Pepper Lessens High Fat Diet-Induced Inflammation in Subcutaneous Adipose Tissue 
PLoS ONE  2013;8(11):e81252.
Supra-nutritional doses of curcumin, derived from the spice Curcuma longa, have been proposed as a potential treatment of inflammation and metabolic disorders related to obesity. The aim of the present study was to test whether Curcuma longa extract rich in curcumin and associated with white pepper (Curcuma-P®), at doses compatible with human use, could modulate systemic inflammation in diet-induced obese mice. We questioned the potential relevance of changes in adiposity and gut microbiota in the effect of Curcuma-P® in obesity.
Methodology/Principal Findings
Mice were fed either a control diet (CT), a high fat (HF) diet or a HF diet containing Curcuma longa extract (0.1 % of curcumin in the HF diet) associated with white pepper (0.01 %) for four weeks. Curcumin has been usually combined with white pepper, which contain piperine, in order to improve its bioavailability. This combination did not significantly modify body weight gain, glycemia, insulinemia, serum lipids and intestinal inflammatory markers. Tetrahydrocurcumin, but not curcumin accumulated in the subcutaneous adipose tissue. Importantly, the co-supplementation in curcuma extract and white pepper decreased HF-induced pro-inflammatory cytokines expression in the subcutaneous adipose tissue, an effect independent of adiposity, immune cells recruitment, angiogenesis, or modulation of gut bacteria controlling inflammation.
These findings support that nutritional doses of Curcuma longa, associated with white pepper, is able to decrease inflammatory cytokines expression in the adipose tissue and this effect could be rather linked to a direct effect of bioactive metabolites reaching the adipose tissue, than from changes in the gut microbiota composition.
PMCID: PMC3834320  PMID: 24260564
2.  VEGF and FGF-2 delivery from spinal cord bridges to enhance angiogenesis following injury 
The host response to spinal cord injury can lead to an ischemic environment that can induce cell death and limits cell transplantation approaches to promote spinal cord regeneration. Spinal cord bridges that provide a localized and sustained release of VEGF and FGF-2 were investigated for their ability to promote angiogenesis and nerve growth within the injury. Bridges were fabricated by fusion of poly(lactide-co-glycolide) microspheres using a gas foaming/particulate leaching technique, and proteins were incorporated by encapsulation into the microspheres and/or mixing with the microspheres before foaming. Compared to the mixing method, encapsulation reduced the losses during leaching and had a slower protein release, while VEGF was released more rapidly than FGF-2. In vivo implantation of bridges loaded with VEGF enhanced the levels of VEGF within the injury at one week, and bridges releasing VEGF and FGF-2 increased the infiltration of endothelial cells and the formation of blood vessel at 6 weeks post implantation. Additionally, substantial neurofilament staining was observed within the bridge; however, no significant difference was observed between bridges with or without protein. Bridges releasing angiogenic factors may provide an approach to overcome an ischemic environment that limits regeneration and cell transplantation based approaches.
PMCID: PMC3190227  PMID: 21630429
Spinal cord injury; angiogenesis; spinal cord bridges; PLG; protein delivery
3.  Electron Paramagnetic Resonance Highlights That the Oxygen Effect Contributes to the Radiosensitizing Effect of Paclitaxel 
PLoS ONE  2012;7(7):e40772.
Paclitaxel (PTX) is a potent anti-cancer chemotherapeutic agent and is widely used in the treatments of solid tumors, particularly of the breast and ovaries. An effective and safe micellar formulation of PTX was used to administer higher doses of PTX than Taxol® (the current commercialized drug). We hypothesize that PTX-loaded micelles (M-PTX) may enhance tumor radiosensitivity by increasing the tumor oxygenation (pO2). Our goals were (i) to evaluate the contribution of the “oxygen effect” to the radiosensitizing effect of PTX; (ii) to demonstrate the therapeutic relevance of the combination of M-PTX and irradiation and (iii) to investigate the underlying mechanisms of the observed oxygen effect.
Methodology and Principal Findings
We used (PEG-p-(CL-co-TMC)) polymeric micelles to solubilize PTX. pO2 was measured on TLT tumor-bearing mice treated with M-PTX (80 mg/kg) using electron paramagnetic resonance (EPR) oximetry. The regrowth delay following 10 Gy irradiation 24 h after M-PTX treatment was measured. The tumor perfusion was assessed by the patent blue staining. The oxygen consumption rate and the apoptosis were evaluated by EPR oximetry and the TUNEL assay, respectively. EPR oximetry experiments showed that M-PTX dramatically increases the pO2 24 h post treatment. Regrowth delay assays demonstrated a synergy between M-PTX and irradiation. M-PTX increased the tumor blood flow while cells treated with M-PTX consumed less oxygen and presented more apoptosis.
M-PTX improved the tumor oxygenation which leads to synergy between this treatment and irradiation. This increased pO2 can be explained both by an increased blood flow and an inhibition of O2 consumption.
PMCID: PMC3395636  PMID: 22808261
4.  In Vivo Methods for the Assessment of Topical Drug Bioavailability 
Pharmaceutical Research  2007;25(1):87-103.
This paper reviews some current methods for the in vivo assessment of local cutaneous bioavailability in humans after topical drug application. After an introduction discussing the importance of local drug bioavailability assessment and the limitations of model-based predictions, the focus turns to the relevance of experimental studies. The available techniques are then reviewed in detail, with particular emphasis on the tape stripping and microdialysis methodologies. Other less developed techniques, including the skin biopsy, suction blister, follicle removal and confocal Raman spectroscopy techniques are also described.
PMCID: PMC2217624  PMID: 17985216
cutaneous bioavailability; cutaneous drug concentration; dermatopharmacokinetics; microdialysis; tape stripping

Results 1-4 (4)