Four Novel p.N385K,p.V36A,c.1033–1034insT and c.1417–1418delCT Mutations in the Sphingomyelin Phosphodiesterase 1 (SMPD1) Gene in Patients with Types A and B Niemann-Pick Disease (NPD)

Background: Types A and B Niemann-Pick disease (NPD) are autosomal-recessive lysosomal storage disorders caused by the deficient activity of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene. Methods: In order to determine the prevalence and distribution of SMPD1 gene mutations, the genomic DNA of 15 unrelated Iranian patients with types A and B NPD was examined using PCR, DNA sequencing and bioinformatics analysis. Results: Of 8 patients with the p.G508R mutation, 5 patients were homozygous, while the other 3 were heterozygous. One patient was heterozygous for both the p.N385K and p.G508R mutations. Another patient was heterozygous for both the p.A487V and p.G508R mutations. Two patients (one homozygous and one heterozygous) showed the p.V36A mutation. One patient was homozygous for the c.1033–1034insT mutation. One patient was homozygous for the c.573delT mutation, and 1 patient was homozygous for the c.1417–1418delCT mutation. Additionally, bioinformatics analysis indicated that two new p.V36A and p.N385K mutations decreased the acid sphingomyelinase (ASM) protein stability, which might be evidence to suggest the pathogenicity of these mutations. Conclusion: with detection of these new mutations, the genotypic spectrum of types A and B NPD is extended, facilitating the definition of disease-related mutations. However, more research is essential to confirm the pathogenic effect of these mutations.     

Fabrication,characterization, and thermal property evaluation of silver nanofluids

Silver nanoparticles were successfully prepared in two different solvents using a microwave heating technique, with various irradiation times. The silver nanoparticles were dispersed in polar liquids (distilled water and ethylene glycol) without any other reducing agent, in the presence of the stabilizer polyvinylpyrrolidone (PVP). The optical properties, thermal properties, and morphology of the synthesized silver particles were characterized using ultraviolet-visible spectroscopy, photopyroelectric technique, and transmission electron microscopy. It was found that for the both solvents, the effect of microwave irradiation was mainly on the particles distribution, rather than the size, which enabled to make stable and homogeneous silver nanofluids. The individual spherical nanostructure of self-assembled nanoparticles has been formed during microwave irradiation. Ethylene glycol solution, due to its special properties, such as high dielectric loss, high molecular weight, and high boiling point, can serve as a good solvent for microwave heating and is found to be a more suitable medium than the distilled water. A photopyroelectric technique was carried out to measure thermal diffusivity of the samples. The precision and accuracy of this technique was established by comparing the measured thermal diffusivity of the distilled water and ethylene glycol with values reported in the literature. The thermal diffusivity ratio of the silver nanofluids increased up to 1.15 and 1.25 for distilled water and ethylene glycol, respectively.     

Role of hormonal and environmental factors on early incidence of breast cancer in Iran

Although the probability of having breast cancer increases with the age in general, this malignancy affects Iranian women at least one decade younger than their counterparts in other countries. However the underlying risk factors for the discrepancy have not been identified. The aryl hydrocarbon receptor (AhR) mediates the effects of many environmental endocrine disruptors and contributes to the loss of normal ovarian function in polluted environments. This study was aimed to compare the interactions between AhR and other fundamental genes (p53, K-Ras, ER, PgR) in a clinical setting. To conduct the immunohistochemical studies using appropriate monoclonal antibodies, 25 premenopausal invasive ductal carcinoma, 29 postmenopausal invasive ductal carcinoma and 30 breast fibroadenoma were selected retrospectively from 2004 to 2007 in the pathology department of Imam Khomeini hospital complex of Tehran University of Medical Sciences . Higher levels of AhR in epithelial cells of premenopausal patients and breast fibroadenoma emphasized the susceptibility of these cells to environmental-induced tumors. AhR overexpression contributed to ER-/PgR-immunophenotype in young/premenopausal patients but the same pattern was not observed in benign and postmenopausal malignant tumors. It seems that early incidence of breast cancer in Iran is the result of interactions between hormonal and environmental factors.     

Synthesis,characterization and in-vitro behavior of natural chitosan-hydroxyapatite-diopside nanocomposite scaffold for bone tissue engineering

Composite materials based on a combination of biodegradable polymers and bioactive ceramics, including chitosan and hydroxyapatite are discussed as suitable materials for scaffold fabrication. Diopside is a member of bioactive silicates; it is a good choice for hard tissue engineering because of its biocompatibility with host tissue and high mechanical strength. Chitosan and hydroxyapatite were extracted from shrimp shell and bovine bone, respectively and diopside nanoparticles were prepared by the sol-gel method. The present study reports on a chitosan composite which was reinforced by hydroxyapatite and diopside; the scaffolds were fabricated by the freeze-drying method. The so-produced chitosan-hydroxyapatite-diopside (CS-HA-DP) scaffolds were further cross-linked using tripolyphosphate (TPP) to achieve enhanced mechanical strength. The ratios of the ceramic components in composites were 5-58-37, 10-55-35, and 15-52-33 (diopside-hydroxyapatite-chitosan, w/w %). The physicochemical properties of scaffolds were investigated using Fourier-transform infrared spectrometry (FT-IR), X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) techniques. The effect of scaffolds composition on bioactivity and biodegradability were studied well. To investigate mechanical properties of samples, compression test was done. Results showed that the composite scaffold with 5% DP has the highest mechanical strength. The porosity of composites dropped from 92% to 76% by increasing the amount of DP. Cytocompatibility of the scaffolds was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, alkaline phosphatase (ALP) activity, and cell attachment studies using human osteoblast cells. Results demonstrated no sign of toxicity and cells were found to be attached to the pore walls within the scaffolds; moreover, results illustrated that the developed composite scaffolds could be a potential candidate for tissue engineering.     

A multiple emulsion method for loading 5‐fluorouracil into a magnetite‐loaded nanocapsule: a physicochemical investigation

The preparation of 5‐fluorouracil (5‐FU) loaded poly(lactic‐co‐glycolic acid) (PLGA) biodegradable nanocapsules containing magnetite nanoparticles was studied through the modified multiple emulsion solvent evaporation method for magnetically controlled delivery of anticancer drugs. The morphology and size distribution of the prepared magnetite/PLGA nanocapsules were investigated by transmission and scanning electron microscopy. The micrographs showed that the magnetic nanocapsules were almost spherical in shape and their mean diameter was in the nanometer range with a narrow size distribution. Fourier transform infrared and ultraviolet–visible spectroscopy confirmed incorporation of 5‐FU molecules into the PLGA matrix. The magnetite content was assessed by thermogravimetric and magnetometry analysis and the results showed a magnetite content of 35 wt% with high magnetic responsivity. Magnetometry measurements showed superparamagnetic properties of the magnetic nanocapsules with a saturation magnetization of 13.7 emu g^?1. Such biodegradable magnetic nanocapsules could be considered as an appropriate choice for drug targeting. Furthermore, the influence of some important processing parameters such as PLGA concentration, initial loading of 5‐FU and poly(vinyl alcohol) concentration on drug content, encapsulation efficiency and in vitro drug release kinetics was investigated and optimized. The drug content and encapsulation efficiency of the magnetic nanocapsules were 4–7 wt% and 60%–80%, respectively, and the nanocapsules demonstrated controlled release of 5‐FU at 37 °C in a buffer solution. All samples exhibited a burst release at the initial stage and this burst release showed its close dependence on the formulation parameters. Copyright © 2012 Society of Chemical Industry     

Heat Transfer Enhancement in Shell-and-Tube Heat Exchangers Using Porous Media

A numerical simulation has been carried out to investigate the heat transfer enhancement in a shell-and-tube heat exchanger using a porous medium inside its shell and tubes, separately. A three-dimensional geometry with k-? turbulent model is used to predict the heat transfer and pressure drop characteristics of the flow. The effects of porosity and dimensions of these media on the heat exchanger's thermal performance and pressure drop are analyzed. Inside the shell, the entire tube bundle is wrapped by the porous medium, whereas inside the tubes the porous media are located in two different ways: (1) at the center of the tubes, and (2) attached to the inner wall of the tubes. The results showed that this method can improve the heat transfer at the expense of higher pressure drop. Evaluating the method showed that using porous media inside the shell, with particular dimension and porosity can increase the heat transfer rate better than pressure drop. Using this method inside the tubes leads to two diverse results: In the first configuration, pressure loss prevails over the heat transfer augmentation and it causes energy loss, whereas in the second configuration a great performance enhancement is observed.     

Fabrication of a bimetallic Cu/Pt particle-modified carbon nanotube paste electrode and its use for the electrocatalytic oxidation of methanol

In this work, carbon nanotube paste electrode (CNTPE) was used as a substrate for deposition of bimetallic Cu/Pt particles. At first, a Cu film was prepared by electrochemical reduction of Cu ions onto the CNTPE in 0.1 M H₂SO₄ solution. Cu/Pt catalysts were prepared by partial galvanic replacement of Cu with Pt by simply immersion of the Cu-coated CNTPE in 2.0 mM H₂PtCl₆ solution. The nature and surface morphology of the bare CNTPE and fabricated Cu/Pt species were characterized by scanning electron microscopy and energy dispersive X-ray spectrometry. The Cu/Pt-modified CNTPE exhibits remarkable electrocatalytic activity towards methanol oxidation. It has been shown that carbon nanotubes improve the electrocatalytic activity of the catalysts towards oxidation. Then, the influence of various parameters such as Cu source concentration, electrodeposition time, replacement time, and methanol concentration on its oxidation as well as long-term stability of the modified electrode have been investigated by electrochemical methods.     

Growth of InAs/InP core-shell nanowires with various pure crystal structures

We have studied the epitaxial growth of an InP shell on various pure InAs core nanowire crystal structures by metal-organic vapor phase epitaxy. The InP shell is grown on wurtzite (WZ), zinc-blende (ZB), and {111}- and {110}-type faceted ZB twin-plane superlattice (TSL) structures by tuning the InP shell growth parameters and controlling the shell thickness. The growth results, particularly on the WZ nanowires, show that homogeneous InP shell growth is promoted at relatively high temperatures (～500?°C), but that the InAs nanowires decompose under the applied conditions. In order to protect the InAs core nanowires from decomposition, a short protective InP segment is first grown axially at lower temperatures (420-460?°C), before commencing the radial growth at a higher temperature. Further studies revealed that the InP radial growth rate is significantly higher on the ZB and TSL nanowires compared to WZ counterparts, and shows a strong anisotropy in polar directions. As a result, thin shells were obtained during low temperature InP growth on ZB structures, while a higher temperature was used to obtain uniform thick shells. In addition, a schematic growth model is suggested to explain the basic processes occurring during the shell growth on the TSL crystal structures.     

Self-assembled nanomicelles using PLGA–PEG amphiphilic block copolymer for insulin delivery: a physicochemical investigation and determination of CMC values

Self-assembled nanomicelles can be used as synthetic biomaterials and colloidal carriers for poorly water-soluble drug delivery systems. Some of these micellar systems have been introduced in clinical trials and showed hopeful results relating to their therapeutic index in patients. Biodegradable nanomicelle was prepared from self-assembling amphiphilic block copolymer composed of poly(dl-lactic-co-glycolic acid) (PLGA) as a core and polyethylene glycol (PEG) as a corona. The PLGA–PEG block copolymer was first synthesized and characterized by FTIR, ¹H NMR, GPC and inherent viscosity measurements. The nanomicelle formed by PLGA–PEG block copolymer in the aqueous solution was characterized by dynamic light scattering, zeta potential, scanning electron microscopy (SEM) and fluorescence excitation and emission spectra of pyrene probe. The critical micelle concentration of obtained nanomicelle was about 0.006 mg/mL, with the size of about 160 nm and the zeta potential of −29 mV. Insulin-loaded PLGA–PEG nanomicelles were prepared by modified dialysis method and the physicochemical parameters of the micelles such as drug content, entrapment efficiency and in vitro drug release were characterized. The results showed that insulin was entrapped into PLGA–PEG nanomicelles with drug loading of 3.9 wt% and entrapment efficiency of 55 wt%. The nanomicelles containing insulin exhibited a controlled release profile. These observations suggested that the PLGA–PEG block copolymers nanomicelles have been prepared by a new synthetic route are potent nanocarrier for poorly water-soluble drugs as insulin.