Development and in vitro evaluation of lipid nanoparticle-based dressings for topical treatment of chronic wounds.

This research addresses the development and in vitro evaluation of lipid nanoparticle (NP)-based dressings to optimize the delivery of human recombinant epidermal growth factor (rhEGF) for the topical treatment of chronic wounds. The systems investigated were rhEGF-loaded solid lipid nanoparticles (rhEGF-SLN) and rhEGF-loaded nanostructured lipid carriers (rhEGF-NLC) formulated in wound dressings comprising either semi-solid hydrogels or fibrin-based solid scaffolds. Following detailed characterisation of the NP, in vitro diffusion cell experiments (coupled with dermatopharmacokinetic measurements), together with confocal microscopic imaging, conducted on both intact skin samples, and those from which the barrier (the stratum corneum) had been removed, revealed that (a) the particles remained essentially superficially located for at least up to 48h post-application, (b) rhEGF released on the surface of intact skin was unable to penetrate to the deeper, viable layers, and (c) sustained release of growth factor from the NP "drug reservoirs" into barrier-compromised skin was observed. There were no significant differences between the in vitro performance of rhEGF-SLN and rhEGF-NLC, irrespective of the formulation employed. It is concluded that, because of their potentially longer-term stability, the fibrin-based scaffolds may be the most suitable approach to formulate rhEGF-loaded lipid nanoparticles.

Strain dynamics of ultrathin VO2 film grown on TiO2 (001) and the associated phase transition modulation.

Tuning the metal insulator transition (MIT) behavior of VO2 film through the interfacial strain is effective for practical applications. However, the mechanism for strain-modulated MIT is still under debate. Here we directly record the strain dynamics of ultrathin VO2 film on TiO2 substrate and reveal the intrinsic modulation process by means of synchrotron radiation and first-principles calculations. It is observed that the MIT process of the obtained VO2 films can be modulated continuously via the interfacial strain. The relationship between the phase transition temperature and the strain evolution is established from the initial film growth. From the interfacial strain dynamics and theoretical calculations, we claim that the electronic orbital occupancy is strongly affected by the interfacial strain, which changes also the electron-electron correlation and controls the phase transition temperature. These findings open the possibility of an active tuning of phase transition for the thin VO2 film through the interfacial lattice engineering.

Nonadverse effects on allergenicity of isopentenyltransferase-transformed broccoli.

BACKGROUND: Genetically modified organisms (GMOs) provide modern agriculture with improvements in efficiency and the benefits of enhanced food production; however, the potential impact of GMOs on human health has not yet been clarified. OBJECTIVE: To investigate the allergenicity of isopentenyltransferase (ipt)-transformed broccoli compared with non-GM broccoli. METHODS: Sera from allergic individuals were used to identify the allergenicity of GM and non-GM broccoli. Immunoglobulin (Ig) binding of different lines of GM and non-GM broccoli was identified using immunoblotting, enzyme-linked immunosorbent assay, and the histamin release assay. RESULTS: Positive reactions to broccoli (Brassica Oleracea) were observed in 7.02% of individuals. Specific IgE to broccoli and total IgE fro allergic individuals were well correlated. The different tests performed showed no significant differences in the allergenicity of conventionally raised and GM broccoli, indicating the absence of unexpected effects on allergenicity in ipt-transformed plants. Using Western blot analysis we detected heterogeneous IgE-reactive allergenic components in broccoli-allergic sera, but no significant differences between GM an non-GM broccoli were observed in serum from the same patients. CONCLUSIONS: Our study demonstrates that there are no differences between GM (ipt-transformed) broccoli and non-GM broccoli, as determined by specific IgE in sera from broccoli-allergic patients. This indicates that there were no unexpected effects on allergenicity in this GM broccoli.

Pressure-induced amorphous-to-amorphous configuration change in Ca-Al metallic glasses.

Pressure-induced amorphous-to-amorphous configuration changes in Ca-Al metallic glasses (MGs) were studied by performing in-situ room-temperature high-pressure x-ray diffraction up to about 40 GPa. Changes in compressibility at about 18 GPa, 15.5 GPa and 7.5 GPa during compression are detected in Ca(80)Al(20), Ca(72.7)Al(27.3), and Ca(66.4)Al(33.6) MGs, respectively, whereas no clear change has been detected in the Ca(50)Al(50) MG. The transfer of s electrons into d orbitals under pressure, reported for the pressure-induced phase transformations in pure polycrystalline Ca, is suggested to explain the observation of an amorphous-to-amorphous configuration change in this Ca-Al MG system. Results presented here show that the pressure induced amorphous-to-amorphous configuration is not limited to f electron-containing MGs.

Ultrasound-facilitated formalin fixation of biological specimens.

In a previous study, we showed that ultrasound can dramatically reduce the time required for tissue fixation in formalin. It generally is believed that ultrasound increases the speed of tissue fixation in two possible ways: 1) increasing the speed of penetration of fixative molecules into tissue samples and 2) increasing the speed of cross-linking reactions. We addressed here the second possible way by using protein solutions and cultured cells, which minimized the effects of the penetration factor. Proteins or cultured cells in solution were fixed with formalin with or without ultrasound irradiation. Fixed proteins and cell lysates then were separated by SDS-poly acrylamide gel electrophoresis and subjected to Western blotting to examine cross-linking formation in certain proteins. Unexpectedly, irradiation with ultrasound did not produce an observable difference in the rate of cross-linking in protein solutions. In similar experiments using cultured cells, however, we observed a significant reduction in recovery of certain proteins from cells fixed by formalin under the influence of ultrasound, which indicated that the ultrasound fixation procedure accelerated cross-linking formation within cells. Studies on protein and cell fixation without ultrasound showed that cross-linking formation was closely related to incubation temperature, which indicates that the heating function, which is inherently associated with ultrasound is another major factor in the ability of ultrasound to accelerate cross-linking.

Potassium doping effect on the lattice softening and electronic structure of Ba(1-x)K(x)Fe(2)As(2) probed by X-ray absorption spectroscopy.

Ba(1-x)K(x)Fe(2)As(2) superconducting samples (x = 0, 0.2, 0.4, 0.5) were synthesized by the solid-state reaction method. In this contribution the doping effect of potassium on the lattice dynamics in this newly discovered Ba(1-x)K(x)Fe(2)As(2) superconductor has been investigated by extended X-ray absorption fine-structure spectroscopy. The analysis shows that with potassium doping an increased disorder in the iron layers is mainly related to the softening of the Fe-Fe bond. Information about the electronic structure of these materials has also been obtained by looking at the X-ray absorption near-edge structure spectra that point out the presence of holes in the Fe-3d/As-4p hybridized orbital of the BaFe(2)As(2)-based system.

Local structural disorder in REFeAsO oxypnictides by RE L(3) edge XANES.

The REFeAsO (RE = La, Pr, Nd and Sm) system has been studied by RE L(3) x-ray absorption near edge structure (XANES) spectroscopy to explore the contribution of the REO spacers between the electronically active FeAs slabs in these materials. The XANES spectra have been simulated by full multiple scattering calculations to describe the different experimental features and their evolution with the RE size. The near edge feature just above the L(3) white line is found to be sensitive to the ordering/disordering of oxygen atoms in the REO layers. In addition, shape resonance peaks due to As and O scattering change systematically, indicating local structural changes in the FeAs slabs and the REO spacers due to RE size. The results suggest that interlayer coupling and oxygen order/disorder in the REO spacers may have an important role in the superconductivity and itinerant magnetism of the oxypnictides.

A large iron isotope effect in SmFeAsO(1 - x)F(x) and Ba(1 - x)K(x)Fe(2)As(2).

The recent discovery of superconductivity in oxypnictides with a critical transition temperature (T(C)) higher than the McMillan limit of 39 K (the theoretical maximum predicted by Bardeen-Cooper-Schrieffer theory) has generated great excitement. Theoretical calculations indicate that the electron-phonon interaction is not strong enough to give rise to such high transition temperatures, but strong ferromagnetic/antiferromagnetic fluctuations have been proposed to be responsible. Superconductivity and magnetism in pnictide superconductors, however, show a strong sensitivity to the crystal lattice, suggesting the possibility of unconventional electron-phonon coupling. Here we report the effect of oxygen and iron isotope substitution on T(C) and the spin-density wave (SDW) transition temperature (T(SDW)) in the SmFeAsO(1 - x)F(x) and Ba(1 - x)K(x)Fe(2)As(2) systems. The oxygen isotope effect on T(C) and T(SDW) is very small, while the iron isotope exponent alpha(C) = -dlnT(C)/dlnM is about 0.35 (0.5 corresponds to the full isotope effect). Surprisingly, the iron isotope exchange shows the same effect on T(SDW) as T(C). This indicates that electron-phonon interaction plays some role in the superconducting mechanism, but a simple electron-phonon coupling mechanism seems unlikely because a strong magnon-phonon coupling is included.

Correlation between local vibrations and metal mass in AlB2-type transition-metal diborides.

Lattice vibrations have been investigated in TiB2, ZrB2 and HfB2 by temperature-dependent extended X-ray absorption fine structure (EXAFS) experiments. Data clearly show that the EXAFS oscillations are characterized by an anomalous behavior of the Debye-Waller factor of the transition-metal-boron pair, which is suggested to be associated with a superposition of an optical mode corresponding to phonon vibrations induced by the B sublattice and an acoustic mode corresponding to the transition-metal (TM) sublattice. Data can be interpreted as a decoupling of the metal and boron vibrations observed in these transition-metal diborides (TMB2), a mechanism that may be responsible for the significant reduction of the superconducting transition temperature observed in these systems with respect to the parent MgB2 compound. The vibrational behavior of TM-TM bonds has also been investigated to study the occurrence of anisotropy and anomalies in the lattice vibrational behavior of TM-TM bonds.

Lattice vibrational property in the transition-metal diboride ZrB2.

Lattice vibrational property has been determined in ZrB(2) system using the temperature-dependent extended X-ray-absorption fine-structure (EXAFS) technique from room temperature to 28K. The smooth behavior of Debye-Waller factor curve with temperature is slightly abnormal for the first pair Zr-B. In order to reproduce this curve, an improved Einstein mode with two Einstein frequencies has been used. The quantitative analysis of temperature-dependent Debye-Waller factor of Zr-B pair shows one Einstein frequency is very high and the other is small. These frequencies correspond to the vibration of boron layer atoms and transition-metal layer atoms, respectively. Based on the Einstein mode with one frequency, the vibrational frequency for Zr-Zr pair has been also obtained. Zirconium diboride has two types of Zr-Zr interaction. One is in-plane and the other is out-of-plane along the high symmetry axis. Our analysis shows there is a little difference between in-plane Zr-Zr vibration and out-of-plane one. And the smaller Einstein vibrational frequency for the Zr-B shell is just between the two ones of the Zr-Zr shells. Our results show that the lattice vibrational behavior in ZrB(2) presents obvious particularity and anisotropy.

Type 2 diabetes susceptibility genes on chromosome 1q21-24.

Type 2 diabetes (T2D) has been linked to chromosome 1q21-24 in multiple samples, including a Utah family sample. Variants in 13 of the numerous candidate genes in the 1q region were tested for association with T2D in a Utah case-control sample. The most promising, 19 variants in 6 candidates, were genotyped on the Utah family sample. Herein, we tested the 19 variants individually and in pairs for an effect on T2D risk in family members using a logistic regression model that accounted for gender, age, and BMI and attributed residual genetic effects to a polygenic component. Seven variants increased risk significantly through 5 pairs of interactions. The significant variant pairs were apolipoprotein A-II (APOA2) rs6413453 interacting with calsequestrin 1 (CASQ1) rs617698, dual specificity phosphatase 12 (DUSP12) rs1503814, and retinoid X receptor gamma (RXRG) rs10918169, a poly-T insertion-deletion polymorphism in liver pyruvate kinase (PKLR) interacting with APOA2 rs12143180, and DUSP12 rs1027702 interacting with RXRG rs10918169. Genotypes of these 5 variant pairs accounted for 25.8% of the genetic variance in T2D in these pedigrees.

Transcription factor 7-like 2 polymorphisms and type 2 diabetes, glucose homeostasis traits and gene expression in US participants of European and African descent.

AIMS/HYPOTHESIS: We sought to determine: (1) the role of previously described transcription factor 7-like 2 (TCF7L2) variants in type 2 diabetes in African American individuals and in participants of European ancestry; (2) the physiological impact of these variants on glucose homeostasis; and (3) whether the non-coding variants altered TCF7L2 expression in adipocytes and transformed lymphocytes. METHODS: Association studies were conducted by genotyping 932 Europid and African American diabetic and control participants. Family studies were conducted in 673 members of 68 Europid families ascertained for at least two diabetic siblings. Metabolic studies were conducted in 585 non-diabetic individuals who had undergone frequently sampled intravenous glucose tolerance tests to determine insulin sensitivity and insulin secretion. Gene expression studies were conducted in 74 adipose samples and 64 muscle samples from non-diabetic individuals with known genotypes and also in 55 lymphoblastoid cell lines. RESULTS: TCF7L2 variants were associated with type 2 diabetes in a Europid case-control population and in families, but not in African Americans. Risk alleles increased the 60 min post-challenge glucose value in Europid families and reduced insulin sensitivity by 45% in Europids, but did not alter insulin secretion. TCF7L2 expression was not altered by genotype and did not correlate with insulin sensitivity or BMI. CONCLUSIONS/INTERPRETATION: We confirmed TCF7L2 as a risk factor in a population of European descent, where it reduced glucose tolerance and insulin sensitivity, but not insulin secretion. We found no role in African Americans and could not explain the association by altered adipocyte or muscle gene expression.

c-Kit (CD117) reactivity in extramedullary myeloid tumor/granulocytic sarcoma.

CONTEXT: c-kit, a proto-oncogene, encodes the transmembrane tyrosine kinase receptor CD117 and is detected by flow cytometry in the majority of cases of acute myeloid leukemia. The prognostic significance of the presence of c-Kit in acute myeloid leukemia is debated. Recently, c-kit inhibitors have been studied as possible therapies against hematopoietic malignancies; therefore, c-Kit detection may have important implications for treatment. OBJECTIVES: In this study, we investigated the expression of c-Kit in granulocytic sarcoma (GS) using paraffin-embedded tissue. DESIGN: Routinely formalin-fixed, paraffin-embedded tissues from 30 cases of GS were studied using immunohistochemistry. c-Kit (C-19) (a polyclonal antibody against carboxy terminal domain of c-Kit p145 or CD117) reactivity was compared with myeloperoxidase and lysozyme. The immunohistochemical panel also included CD34, CD68, CD43, Bcl-2, CD45RB, CD20, CD3, CD10, terminal deoxynucleotidyl transferase (TdT), and CD79a. RESULTS: The morphologic patterns included well-differentiated (5 cases), poorly differentiated (19 cases), and blastic forms (6 cases). Clinical data were obtained from 28 of 30 patients. Granulocytic sarcoma presented in lymph nodes in 10 cases, whereas in 20 cases it presented in extranodal sites. c-Kit reactivity was found in 87% (26/30) of the GS cases. There was no significant difference in c-Kit positivity between the nodal (90%, 9/10) and extranodal (85%, 17/20) neoplasms. c-Kit expression was not associated with the degree of the myeloid maturation. Two of 13 lymphoblastic lymphoma control cases and 1 of 28 of the large B-cell lymphomas were weakly immunoreactive with c-Kit. CONCLUSIONS: c-Kit reactivity can be demonstrated in a high percentage of GS cases; its presence may be useful not only in diagnosis, but also in the treatment of GS with new modalities.

Peritoneal dialysis in diabetic patients.

Diabetic nephropathy is the leading cause of end-stage renal disease worldwide. Although death rates of diabetic patients on hemodialysis and peritoneal dialysis (PD) have decreased substantially, they remain higher than rates in nondiabetics on both modalities. PD offers equal or better survival than hemodialysis for younger diabetic patients during early years of dialysis. PD technique survival does not appear different between diabetic and nondiabetic patients but is inferior to hemodialysis technique survival. PD may accelerate changes in peritoneal membrane structure and function in diabetics. Peritonitis and conventional PD solutions containing high glucose and glucose degradation products are implicated in PD technique failure. Increased peritoneal expression of vascular endothelial growth factor and transforming growth factor-beta1 and excessive accumulation of advanced glycosylation end products may be involved in the progressive increase in membrane permeability, loss of ultrafiltration, and peritoneal fibrosis. Nonglucose PD solutions or solutions containing low glucose degradation products may prevent or delay alterations in peritoneal membrane structure and function in diabetic as well as nondiabetic patients during long-term PD.

Neurologic injury after endovascular stent-graft and bilateral internal iliac artery embolization for infrarenal abdominal aortic aneurysm.

The authors report a rare neurologic complication after the implantation of a bifurcated stent-graft for abdominal aortic aneurysm. The stent-graft was extended to both external iliac arteries after embolization of both internal iliac arteries. The patient subsequently had weakness and numbness of both lower limbs with bowel and bladder incontinence. He probably had ischemic injury to the nerve roots or the lumbosacral plexus, which was related to extensive occlusion of their supplying arteries. The mechanism of spinal cord and neurologic ischemia after aortic stent-graft implantation is discussed.

Structure and expression of an amylopullulanase gene from Bacillus stearothermophilus TS-23.

An amylopullulanase gene (apuTS) from Bacillus stearothermophilus TS-23 was cloned and characterized. apuTS consisted of an open reading frame of 6054 bp encoding a protein of 2018 amino acids with a calculated M(r) of 223811. The deduced amino acid sequence revealed four highly conserved regions that are common among amylolytic enzymes. In the C-terminal region, a six-amino-acid sequence (Pro-Gly-Ser-Gly-Thr-Thr) is repeated nine times. It shared the highest degree of homology with the amylopullulanase of Bacillus sp. XAL601. The enzyme also had moderate homology with amylopullulanases from thermophilic anaerobic bacteria. Low levels of homology were observed between the ApuTS of B. stearothermophilus TS-23 and amylopullulanases of Pyrococcus abyssi Orsay, P. furiosus and Bacillus sp. KSM1378. When the intact coding region of apuTS was expressed in Escherichia coli under the control of the lac promoter, the product was degenerate, as revealed by amylase activity staining after SDS/PAGE. The largest active polypeptide had an M(r) of about 220000, while the smallest one had an M(r) of about 105000. Upstream of the apuTS gene, a gene orfX was fortuitously cloned. The putative OrfX protein was weakly related to the myosin heavy chain. It was predicted to contain a central, 179-residue-long, coiled-coil domain.

Splenic inflammatory myofibroblastic tumor (inflammatory pseudotumor): a clinicopathologic and immunophenotypic study of 12 cases.

CONTEXT: Inflammatory pseudotumor is an uncommon and enigmatic lesion. The spindle cells found in this tumor have features of myofibroblasts. Because of the indefinite relationship of these lesions with inflammatory fibrosarcoma and their indefinite biologic behavior, inflammatory pseudotumor is currently classified as inflammatory myofibroblastic tumor (IMT). To date, only case reports or small series have been published on these tumors, which are primary in the spleen. DESIGN: In this study, we describe the clinical, morphologic, and immunophenotypic findings of 12 cases of splenic IMT and examine their relationship to Epstein-Barr virus (EBV). RESULTS: The patients included 8 women and 3 men, ranging from 19 to 77 years of age (mean, 53 years; median, 60 years). Demographic data were unavailable for 1 patient. Patients generally presented with abdominal pain (n = 5) and fever (n = 4). Associated lesions included renal cell carcinoma (n = 2), colonic adenocarcinoma (n = 1), and cholecystitis (n = 1). All tumors were composed of a bland spindle cell proliferation in association with a variable mixed inflammatory component. There were 2 growth patterns, namely, a cellular spindle cell pattern and a hypocellular fibrous pattern. An immunohistochemical panel confirmed the myofibroblastic nature of the spindle cells. The spindle cells of 2 cases were immunoreactive for EBV latent membrane protein 1, whereas 6 of 10 cases were positive for EBV-encoded RNA using in situ hybridization. Follow-up was available for 8 patients; 6 were alive with no evidence of recurrence and 2 were dead of other causes. CONCLUSION: Splenic IMTs are uncommon lesions that can be distinguished from other conditions using a combination of clinical, histologic, and immunophenotypic findings. Epstein-Barr virus may play a role in the pathogenesis of splenic IMT, and there may be an association of splenic IMT with concomitant disease or malignancy. Most splenic IMTs have an excellent long-term prognosis.

Apoptosis, bcl-2 expression, and p53 expression in gastrointestinal stromal/smooth muscle tumors.

The authors investigated the relations between outcome and apoptosis, immunohistochemical demonstration of bcl-2 protein, and immunohistochemical staining for p53 protein in patients with gastrointestinal stromal/smooth muscle tumors (GIST). Patients whose tumors demonstrated cellular apoptosis using the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay had an improved survival over those whose tumors did not improve. In contrast, patients whose tumors demonstrated staining for bcl-2 protein had a decreased survival compared with those whose tumors did not demonstrate bcl-2. There was no relation between p53 immunoreactivity and survival. These results suggest that inhibition of apoptosis may be associated with malignant behavior in patients with gastrointestinal stromal/smooth muscle tumors.