FGF-2-containing dalteparin/protamine nanoparticles (FGF-2&D/P NPs) ameliorate UV-induced skin photoaging in hairless mice.

UVB exposure penetrates deeply into the dermis to alter skin barrier function, which is a primary factor in skin photoaging. We previously reported that dalteparin and protamine nanoparticles (D/P NPs) are effective carriers of FGF-2. This study aimed to examine the ability of FGF-2-containing D/P NPs (FGF-2&D/P NPs) to ameliorate UVB-induced skin photoaging in hairless mice. Dorsal skin of HR-1 hairless mice were exposed to UVB irradiation 5 days/week for 8 weeks (UV (+): final total, 2700 mJ/cm2). Mice were divided into four groups: Non-UVB (UV (-)) + saline, UV (+) + saline, UV (+) + FGF-2&D/P NPs, UV (+) + FGF-2, and UV (+) + D/P NPs, and following UVB irradiation, FGF-2&D/P NPs, FGF-2, and D/P NPs were applied to the groups of mice just after each UVB irradiation. Each group was subjected to evaluation of skin changes (elasticity), and histological examination using hematoxylin & eosin and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. UVB irradiation of mice significantly induced a decline in elasticity and acanthosis, which was alleviated by application of FGF-2&D/P NPs. Furthermore, TUNEL-staining showed the proportions of apoptotic dermal fibroblast cells (DFCs) and epidermal keratinocyte cells (EKCs) in the UV (+) + FGF-2&D/P NPs group were significantly lower than those in the UV (+) + saline, UV (+) + FGF-2, and UV (+) + D/P NPs groups. Thus, FGF-2&D/P NPs may be effective in preventing skin photoaging accelerated by UVB irradiation such as declining elasticity, acanthosis, and apoptosis of DFCs and EKCs.

Improved Survival of Full-Thickness Skin Graft With Low-Molecular Weight Heparin-Protamine Micro/Nanoparticles Including Platelet-Rich Plasma.

BACKGROUND: Activated platelet-rich plasma secrets many growth factors (GFs), and low-molecular weight heparin-protamine micro/nanoparticles (LMWH-P M/NPs) significantly interact with, enhance, and stabilize the secreted GFs. OBJECTIVE: The purpose of this study was to evaluate the effects of LMWH-P M/NPs and GFs (from platelet-rich plasma) on full-thickness skin graft (FTSG). METHODS: A total of 96 inbred male rats were anesthetized and 4-cm full-thickness skin wound were created on dorsal skin of rats. LMWH-P M/NPs and GFs, LMWH-P M/NPs, GFs and saline (control) were then injected evenly into cutaneous muscles at the wound. The next day, the rats underwent FTSG. On the indicated days after FTSG, blood flow of FTSG site (wound bed and FTSG) was examined by 2-dimensional laser Doppler blood flowmeter. On 10 days, pictures of FTSG site were taken and FTSG survival rate was evaluated. Histologic analyses of skin samples were performed on 4, 7, and 10 days. RESULTS: Treatment of full-thickness skin wound with LMWH-P M/NPs and GFs effectively promoted survival rate of FTSG and blood flow of FTSG site compared with those treated with GFs, LMWH-P M/NPs, and control. LMWH-P M/NPs and GFs also promoted new vessel formation at FTSG site. CONCLUSIONS: The prior injection of LMWH-P M/NPs and GFs into wound bed increases FTSG survival rate, and promotes blood flow and angiogenesis at FTSG site.

Enhanced effect of fibroblast growth factor-2-containing dalteparin/protamine nanoparticles on hair growth.

PURPOSE: Although treatments for alopecia are in high demand, not all treatments are safe and reliable. Dalteparin/protamine nanoparticles (D/P NPs) can effectively carry growth factors (GFs) such as fibroblast GF (FGF)-2. The purpose of this study was to identify the effects of FGF-2-containing D/P NPs (FGF-2&D/P NPs) on hair growth. PATIENTS AND METHODS: In this study, the participants were 12 volunteers with thin hair. One milliliter of FGF-2 (100 ng/mL) and D/P NPs (56 µg/mL) was applied and massaged on the skin of the scalp by the participants twice a day. They were evaluated for 6 months. Participants were photographed using a digital camera for general observation and a hair diagnosis system for measuring hair diameter. RESULTS: The mean diameter of the hairs was significantly higher following the application of FGF-2&D/P NPs for 6 months. Objective improvements in thin hair were observed in two cases. Nine participants experienced greater bounce and hair resilience. CONCLUSION: The transdermal application of FGF-2&D/P NPs to the scalp can be used as a new treatment for alopecia.

Improved angiogenesis and healing in crush syndrome by fibroblast growth factor-2-containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles.

BACKGROUND: We produced fibroblast growth factor (FGF)-2-containing low-molecular-weight heparin (Fragmin)/protamine nanoparticles (FGF-2 + F/P NPs). The purpose of this study was to evaluate the effectiveness of the local administration of FGF-2 + F/P NPs on repairing crush syndrome (CS)-injured lesions after compression release using a nonlethal and reproducible CS injury rat model. MATERIALS AND METHODS: The hind limbs of the anesthetized rats were compressed for 6 h using 3.6 kg blocks, as previously described. The effects of administering FGF-2 + F/P NPs (group A), F/P NPs alone (group B), FGF-2 alone (group C), and saline (control; group D) were examined. Motor function, surface blood flow in the hind limbs, and the wet/dry weight ratio in the tibialis anterior muscle were examined for 1-28 d after the compression release. Histologic analyses were also performed. RESULTS: At the middle and late stages (3-28 d after the compression release), group A had higher scores in the motor function, improved blood flow, increased number of blood vessels, and faster recovered muscle tissue, compared with the other groups. There was no significant difference in enhanced edema in the tibialis anterior muscle among all groups. CONCLUSIONS: The local administration of FGF-2 + F/P NPs to a CS-injured lesion was effective in repairing damaged muscle tissue after compression release.

Enhanced healing of mitomycin C-treated healing-impaired wounds in rats with PRP-containing fragmin/protamine microparticles (PRP&F/P MPs).

PURPOSE: The purpose of this study was to evaluate the accelerating effects of platelet-rich plasma-containing (PRP&) fragmin/protamine microparticles (F/P MPs) for repairing mitomycin C-treated healing-impaired wounds. Staining with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling (TUNEL-staining) showed that apoptosis of dermal fibroblast cells (DFCs) and epidermal keratinocyte cells (EKCs) were significantly induced in the skin of the mitomycin C-treated rats. METHOD: Full-thickness skin defects were made on the back of rats and mitomycin C was applied on the wounds to prepare a healing-impaired wound. After washing out the mitomycin C, saline (control), F/P MPs alone, PRP alone, and PRP&F/P MPs were injected around the wounds. The rats were later euthanised and histological sections of the wounds were then prepared at indicated time periods after the treatment. RESULTS AND CONCLUSION: These results indicated the numbers of large, medium, and small capillary lumens 7 days after injection of PRP&F/P MPs were significantly higher than those after injection of PRP or F/P MPs alone. Furthermore, epithelium and granulation tissue formations were significantly stimulated in the healing-impaired wounds treated with PRP&F/P MPs 3, 7 and 14 days after injection of PRP&F/P MPs.

Large Parosteal Lipoma without Periosteal Changes.

Parosteal lipoma is a rare tumor, accounting for approximately 0.3% of all lipomas. Bony lesions are often found in patients with this tumor (59.2%), making the differential diagnosis of malignant tumors important. Our case was a 64-year-old male patient who complained of a 25 × 15-cm mass on his right thigh that had grown rapidly over a 2-month period. On magnetic resonance imaging, a high-intensity lesion was observed on the surface of the femur beneath the vastus medialis muscle on T1 and T2 images, with low intensity on a T1 fat suppression image. No significant bony changes were detected. During total tumor resection, the tumor was found on the femur with tight continuity, with tiny areas of spiculation palpable on the bone surface. The exact tumor size was 18 × 13 × 6 cm. The pathological diagnosis was lipoma, the same result as in the former open biopsy. This case was the largest parosteal lipoma of the femur reported without periosteal changes. In cases of deep parosteal lipomas, the detection of rapidly progressive and growing pseudotumors with ossification or chondromatous changes implies malignancy. A preoperative biopsy is mandatory and must be followed by careful planning and preparation for handling in malignant cases. Plastic surgeons should therefore keep the diagnosis of parosteal lipoma in mind to provide appropriate (not too much or too little) surgical treatment.

Platelet-rich plasma-containing fragmin-protamine micro-nanoparticles promote epithelialization and angiogenesis in split-thickness skin graft donor sites.

BACKGROUND: Platelet-rich plasma (PRP) contains multiple growth factors, and fragmin-protamine micro-nanoparticles (F-P M-NPs) significantly enhance and stabilize growth factors. The purpose of this study was to evaluate the effects of PRP-containing F-P M-NPs (PRP&F-P M-NPs) on wound repair in split-thickness skin graft (STSG-) donor sites (DS). MATERIALS AND METHODS: A total of 56 inbred male rats were anesthetized and split-thickness skin graft donor site (STSG-DS) were created with a Padgett dermatome. PRP&F-P M-NPs, F-P M-NPs, PRP, and saline (control) were then intradermally injected evenly into the STSG-DSs. On 3, 4, 5, 7, and 10 d after creation of STSG-DS, skin sample sections were stained with hematoxylin and eosin to evaluate reepithelialization and angiogenesis. RESULTS: Treatment of STSG-DS with PRP&F-P M-NPs effectively promoted epithelialization and new vessel formation compared with those treated with PRP, F-P M-NPs, and control (saline). CONCLUSIONS: The intradermal injection of PRP&F-P M-NPs promotes epithelialization and angiogenesis in STSG-DS wounds.

Axial chirality control of tropos BIPHEP-Rh complexes by chiral dienes: synergy effect in catalytic asymmetric hydrogenation.

Diastereopure tropos Rh complexes bearing not only BIPHEP but also chiral dienes can be employed as highly enantioselective hydrogenation catalysts for an olefinic substrate.

MAP-based kinetic analysis for voxel-by-voxel compartment model estimation: detailed imaging of the cerebral glucose metabolism using FDG.

We propose a novel algorithm for voxel-by-voxel compartment model analysis based on a maximum a posteriori (MAP) algorithm. Voxel-by-voxel compartment model analysis can derive functional images of living tissues, but it suffers from high noise statistics in voxel-based PET data and extended calculation times. We initially set up a feature space of the target radiopharmaceutical composed of a measured plasma time activity curve and a set of compartment model parameters, and measured the noise distribution of the PET data. The dynamic PET data were projected onto the feature space, and then clustered using the Mahalanobis distance. Our method was validated using simulation studies, and compared with ROI-based ordinary kinetic analysis for FDG. The parametric images exhibited an acceptable linear relation with the simulations and the ROI-based results, and the calculation time took about 10 min. We therefore concluded that our proposed MAP-based algorithm is practical.

Supervised clustering approach to form functional images in positron emission tomography.

The aim of this study is to investigate the availability of supervised statistical clustering algorithm for image-based model analysis in positron emission tomography or nuclear medicine to form a functional image. Voxel-by-voxel model analysis can derive functional images, but bad statistic property in voxel-based PET data and huge number of voxels prevent to realize practical algorithm to form parametric images. In this study, supervised clustering is applied to categorized PET data. The shape of tTAC is projected in multidimensional feature space, and noise propagation is modeled as multivariate Gaussian in the space. Simulation study shows that the estimates by the proposed algorithm was identical to the true values. And a clinical image of has physiologically acceptable aspect. We can conclude that supervised clustering sachem has potential to realize practical algorithm for voxel-based model analysis in PET.