Effectiveness of 980-mm Diode and 1064-nm Extra-Long-Pulse Neodymium-Doped Yttrium Aluminum Garnet Lasers in Implant Disinfection

Objective: To evaluate the potential of 980-nm gallium aluminum arsenide (GaAlAs) and 1064-nm neodymium-doped yttrium aluminum garnet (Nd:YAG) lasers to reduce bacteria after irradiation of implant surfaces contaminated with Enterococcus faecalis and Porphyromonas gingivalis and on irradiated implant surface morphology. Background: Despite the frequency of implant success, some implant loss is related to peri-implantitis because of difficulty in eliminating the biofilm. Methods: Implants (3.75 x 13 mm) with machined surfaces, surfaces sand blasted with titanium oxide (TiO(2)), and sand-blasted and acid-etched surfaces were exposed to P. gingivalis and E. faecalis cultures and irradiated with 980-nm GaAlAs or 1064-nm Nd: YAG lasers. After laser treatments, the number of remaining colony-forming units and implant surface morphology were analyzed using scanning electron microscopy (SEM). Results: The Nd: YAG laser was able to promote a total contamination reduction on all implants irradiated. The results with the GaAlAs laser showed 100% bacteria reduction on the implants irradiated with 3 W. Irradiation with 2.5 W and 3 W achieved 100% of bacteria reduction on P. gingivalis-contaminated implants. Decontamination was not complete for the sand-blasted TiO(2) (78.6%) and acid-etched surfaces (49.4%) contaminated with E. faecalis and irradiated with 2.5 W. SEM showed no implant surface changes. Conclusion: The wavelengths used in this research provided bacteria reduction without damaging implant surfaces. New clinical research should be encouraged for the use of this technology in the treatment of peri-implantitis.

Gene Expression Noise in Spatial Patterning: hunchback Promoter Structure Affects Noise Amplitude and Distribution in Drosophila Segmentation

Positional information in developing embryos is specified by spatial gradients of transcriptional regulators. One of the classic systems for studying this is the activation of the hunchback (hb) gene in early fruit fly (Drosophila) segmentation by the maternally-derived gradient of the Bicoid (Bcd) protein. Gene regulation is subject to intrinsic noise which can produce variable expression. This variability must be constrained in the highly reproducible and coordinated events of development. We identify means by which noise is controlled during gene expression by characterizing the dependence of hb mRNA and protein output noise on hb promoter structure and transcriptional dynamics. We use a stochastic model of the hb promoter in which the number and strength of Bcd and Hb (self-regulatory) binding sites can be varied. Model parameters are fit to data from WT embryos, the self-regulation mutant hb(14F), and lacZ reporter constructs using different portions of the hb promoter. We have corroborated model noise predictions experimentally. The results indicate that WT (self-regulatory) Hb output noise is predominantly dependent on the transcription and translation dynamics of its own expression, rather than on Bcd fluctuations. The constructs and mutant, which lack self-regulation, indicate that the multiple Bcd binding sites in the hb promoter (and their strengths) also play a role in buffering noise. The model is robust to the variation in Bcd binding site number across a number of fly species. This study identifies particular ways in which promoter structure and regulatory dynamics reduce hb output noise. Insofar as many of these are common features of genes (e. g. multiple regulatory sites, cooperativity, self-feedback), the current results contribute to the general understanding of the reproducibility and determinacy of spatial patterning in early development.

Design and Characterization of a Biomimetic Piezoelectric Pump Inspired on Group Fish Swimming Effect

Flow pumps are important tools in several engineering areas, such as in the fields of bioengineering and thermal management solutions for electronic devices. Nowadays, many of the new flow pump principles are based on the use of piezoelectric actuators, which present some advantages such as miniaturization potential and lower noise generation. In previous work, authors presented a study of a novel pump configuration based on placing an oscillating bimorph piezoelectric actuator in water to generate flow. It was concluded that this oscillatory behavior (such as fish swimming) yields vortex interaction, generating flow rate due to the action and reaction principle. Thus, following this idea the objective of this work is to explore this oscillatory principle by studying the interaction among generated vortex from two bimorph piezoelectric actuators oscillating inside the same pump channel, which is similar to the interaction of vortex generated by frontal fish and posterior ones when they swim together in a group formation. It is shown that parallel-series configurations of bimorph piezoelectric actuators inside the same pump channel provide higher flow rates and pressure for liquid pumping than simple parallel-series arrangements of corresponding single piezoelectric pumps, respectively. The scope of this work includes structural simulations of bimorph piezoelectric actuators, fluid flow simulations, and prototype construction for result validation.

A biomimetic piezoelectric pump: Computational and experimental characterization

Flow pumps have been developed for classical applications in Engineering, and are important instruments in areas such as Biology and Medicine. Among applications for this kind of device we notice blood pump and chemical reagents dosage in Bioengineering. Furthermore, they have recently emerged as a viable thermal management solution for cooling applications in small-scale electronic devices. This work presents the performance study of a novel principle of a piezoelectric flow pump which is based oil the use of a bimorph piezoelectric actuator inserted in fluid (water). Piezoelectric actuators have some advantages over classical devices, such as lower noise generation and ease of miniaturization. The main objective is the characterization of this piezoelectric pump principle through computational simulations (using finite element software), and experimental tests through a manufactured prototype. Computational data, Such as flow rate and pressure curves, have also been compared with experimental results for validation purposes. (C) 2009 Elsevier B.V. All rights reserved.

Thermal properties of amphiphilic biodegradable triblock copolymer of l,l-lactide and ethylene glycol

Samples of poly(l,l-lactide)-block-poly(ethylene glycol)-block-poly(l,l-lactide) (PLLA-PEG-PLLA) were synthesized from l,l-lactide polymerization using stannous 2-ethylhexanoate, Sn(Oct)(2) as initiator and di-hydroxy-terminated poly(ethylene glycol) (PEG) (M (n) = 4000 g mol(-1)) as co-initiator. The chemical linkage between the PEG segment and the PLA segments was characterized by Fourier transform infrared spectroscopy (FTIR). Thermogravimetry analysis (TG) revealed the copolymers composition and was capable to show the deleterious effect of an excess of Sn(Oct)(2) in the polymer thermal stability, while Differential Scanning Calorimetry (DSC) allowed the observation of the miscibility between the PLLA and PEG segments in the different copolymers.

Influence of gamma radiation onto polymeric matrix with papain

Papain is a proteolytic enzyme that has been widely used as debridement agent for scars and wound healing treatment. However, papain presents low stability, which limits its use to extemporaneous or short shelf-life formulations. The purpose of this study was to entrap papain into a polymeric matrix in order to obtain a drug delivery system that could be used as medical device. Since these systems must be sterile, gamma radiation is an interesting option and presents advantages in relation to conventional agents: no radioactive residues are formed: the product can be sterilized inside the final packaging and has an excellent reliability. The normative reference for the establishment of the sterilizing dose determines 25 kGy as the inactivation dose for viable microorganisms. A silicone dispersion was selected to prepare membranes containing 2% (w/w) papain. Irradiated and non-irradiated membranes were simultaneously assessed in order to verify whether gamma radiation interferes with the drug-releasing profile. Results showed that irradiation does not affect significantly papain release and its activity. Therefore papain shows radioresistance in the irradiation conditions applied. In conclusion, gamma radiation can be easily used as sterilizing agent without affecting the papain release profile and its activity onto the biocompatible device is studied. (C) 2009 Elsevier Ltd. All rights reserved.

Development and Characterization of L-Alanyl-L-Glutamine Containing Pellets employing Extrusion-Spheronization Method and Drying Process in Fluidized Bad Equipment.

Development and Characterization of L-Alanyl-L-Glutamine Containing Pellets employing Extrusion-Spheronization Method and Drying Process in Fluidized Bad Equipment"". In this work, five formulations of L-alanyl-L-glutamine (glutamine dipeptide) containing pellets with different drug concentration were developed and evaluated: F1 (9.07%); F2 (17.70%); F3 (27.98%); F4 (37.74%) e F5 (47.53%). Pellets were prepared by extrusion-spheronization method and, further, dried in fluidized bad equipment. The following assays were carried out with the batches obtained: granulometry, friability, true density and morphologic analysis. Between the five formulations evaluated, pellets obtained from F3 present best yield (75.80%), most uniform particle size distribution (89.67% of pellets with size in the range of 0.80 to 1.18), most high true density (2.1634 g/ml) and best aspect (1.0795 +/- 0.0410). Due to these features, pellets obtained from F3 were considered adequate to further polymeric coating process in order to produce a multiparticulate system to prolong L-alanyl-L-glutamine release.

Development and In Vitro Evaluation of Propranolol Hydrochloride Controlled Release Tablets Using HPMC as Matrix Former

The purpose of this paper was to produce controlled-release matrices with 120 mg of propranolol hydrochloride (PHCl) employing hydroxypropyl methylcellulose (HPMC, Methocel (R) K100) as the gel forming barrier. Although this class of polymers has been commonly used for direct compression, with the intent of use reduced polymer concentrations to achieve controlled drug release, in this study tablets were produced by the wet granulation process. HPMC percentages ranged from 15-34 % and both soluble and non soluble diluents were tested in the 10 proposed tablet compositions. Dissolution testing of matrices was performed over a 12 h period in 1.2 pH medium (the first 2 h) and in pH 6.8 (10 h). Dissolution kinetic analysis was performed by applying Zero-order, First-order and Higuchi models with the aim of elucidating the drug release mechanism. All physical-chemical characteristics such as average weight, friability, hardness, diameter, height, and drug content were in accordance to the pharmacopeial specifications. Taking into account that PHCl is a very soluble drug, low concentrations (15 %) of HPMC were sufficient to reduce the drug release and to promote controlled release of PHCl, presenting good dissolution efficiencies, between 50 % and 63 %. The Higuchi model has presented the best fit to the 15 % HPMC formulations, indicating that the main release mechanism was diffusion. It could be concluded that the application of the wet granulation method reduced matrices erosion and promoted controlled release of the drug at low HPMC percentages.

Influence of Pluronic (R) F68 on Ceftazidime Biological Activity in Parenteral Solutions

beta-Lactam antimicrobials are known to have a low concentration/therapeutic response. However, extending the period in which beta-lactam are free in the plasma does directly influence therapeutic outcomes. The objective of this study was to evaluate the influence of Pluronic (R) F68 on the antimicrobial activity of ceftazidime when admixed with aminophylline in parenteral solutions by the evaluation of its minimal inhibitory concentration (MIC) within 24 h. Ceftazidime, aminophylline, and Pluronics (R) F68 were evaluated using the MIC method against Escherichia coli and Pseudomonas aeruginosa, with these compounds individually and associated in the same parenteral solutions. When Pluronics (R) F68 was admixtured with ceftazidime alone or with ceftazidime and aminophylline, it was possible to observe lower MIC values not only at 24 h but also at 0 h for both microorganisms. This indicates that Pluronics (R) F68 may be able to enhance ceftazidime antimicrobial activity in the presence or absence of aminophylline. This fact suggests that Pluronics (R) F68 can be applied to allow the administration of ceftazidime under continuous infusion in parenteral solutions, beneficiating hospital pharmacotherapy. It may also be possible to reduce ceftazidime doses in formulations achieving the same therapeutic results. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:715-720, 2011

Preparation and characterization of ethanol-treated silk fibroin dense membranes for biomaterials application using waste silk fibers as raw material

The possibility of producing valued devices from low cost natural resources is a subject of broad interest. The present study explores the preparation and characterization of silk fibroin dense membranes using waste silk fibers from textile processing. Morphology, crystallinity, thermal resistance and cytotoxicity of membranes as well as the changes on the secondary structure of silk fibroin were analyzed after undergoing treatment with ethanol. Membranes presented amorphous patterns as determined via X-ray diffraction. The secondary structure of silk fibroin on dense membranes was either random coil (silk I) or p-sheet (silk II), before and after ethanol treatment, respectively. The sterilized membranes presented no cytotoxicity to endothelial cells during in vitro assays. This fact stresses the material potential to be used in the fabrication of biomaterials, as coatings of cardiovascular devices and as membranes for wound dressing or drug delivery systems. (C) 2010 Elsevier Ltd. All rights reserved.

Biochemical and biophysical characterization of lysozyme modified by PEGylation

PEGylation is a strategy that has been used to improve the biochemical properties of proteins and their physical and thermal stabilities. In this study, hen egg-white lysozyme (EC 3.2.1.17; LZ) was modified with methoxypolyethylene glycol-p-nitrophenyl carbonate (mPEG-pNP, MW 5000). This PEGylation of LZ produced conjugates that retained full enzyme activity with glycol chitosan, independent of degree of enzyme modification; its biological activity with the substrate Micrococcus lysodeikticus was altered according to its degree of modification. The conjugate obtained with a low degree of mPEG-pNP/NH(2) modification was studied by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF), demonstrating a spectral peak at m/z 19,988 Da with 77% of its original enzymatic activity. Spectroscopic studies of Fourier transform infrared (FIR) and circular dichroism (CD) did not show any relevant differences in protein structure between the native and conjugate LZ. Studies of the effects of pH and temperature on PEGylated LZ indicated that the conjugate was active over a broad pH range, stable at 50 degrees C, and demonstrated resistance to proteolytic degradation. (C) 2010 Elsevier B.V. All rights reserved.

Batch purification of high-purity lysozyme from egg white and characterization of the enzyme modified by PEGylation

PEGylation is one of the most promising and extensively studied strategies for improving the pharmacological properties of proteins as well as their physical and thermal stability. Purified lysozyme obtained from hen egg white by batch mode was modified by PEGylation with methoxypolyethyleneglycol succinimidyl succinato (mPEG-SS, MW 5000). The conjugates produced retained full enzyme activity with the substrate glycol chitosan, independent of degree of enzyme modification, although lysozyme activity with the substrate Micrococcus lysodeikticus was altered according to the degree of modification. The conjugate with a low degree of modification by mPEG-SS retained 67% of its enzyme activity with the M. lysodeikticus substrate. The mPEG-SS was also shown to be a highly reactive polymer. The effects of pH and temperature on PEGylated lysozymes indicated that the conjugate was active over a wide pH range and was stable up to 50 degrees C. This conjugate also showed resistance to proteolytic degradation, remained stable in human serum, and displayed greater antimicrobial activity than native lysozyme against Gram-negative bacteria.

A convergent approach for the generation of dendrimers containing the [Ru3O(CH3COO)(6)] electroactive core

We report on a convergent approach for the generation of dendrimers containing the [Ru3O(aC)(6)] electroactive core, of great interest as multielectron transfer catalysts. The proposed strategy is based on the generation of the trimeric complex [(Ru3O(ac)(6)(4-pic)(2)(pz))2-mu(2)-Ru3O(ac)(6)(CH3OH)](3+) (ac = acetate, 4-pic = 4-methylpyridine, pz = pyrazine). In this complex, the labile CH3OH ligand can be displaced by the bridging pyrazine ligand of [Ru3O(ac)(6)(pz)3](0), leading to the self-assembly of the [{[Ru3O(ac)(6)(4-pic)(2)(pz)](2)-mu(2)-Ru3O(ac)(6)(pz)}(3)- mu(3)-Ru3O(ac)(6)](n+) dendrimer containing 30 ruthenium atoms. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008).

Photocytotoxic activity of a nitrosyl phthalocyanine ruthenium complex - A system capable of producing nitric oxide and singlet oxygen

The synthesis, structural aspects, pharmacological assays, and in vitro photoinduced cytotoxic properties of [Ru(NO)(ONO)(pc)] (pc = phthalocyanine) are described. Its biological effect on the B16F10 cell line was studied in the presence and absence of visible light irradiation. At comparable irradiation levels, [Ru(NO) (ONO)(pc)] was more effective than [Ru(pc)] at inhibiting cell growth, suggesting that occurrence of nitric oxide release following singlet oxygen production upon light irradiation may be an important mechanism by which the nitrosyl ruthenium complex exhibits enhanced biological activity in cells. Following visible light activation, the [Ru(NO)(ONO)(pc)] complex displayed increased potency in B16F10 cells upon modifications to the photoinduced dose; indeed, enhanced potency was detected when the nitrosyl ruthenium complex was encapsulated in a drug delivery system. The liposome containing the [Ru(NO)(ONO)(pc)] complex was over 25% more active than the corresponding ruthenium complex in phosphate buffer solution. The activity of the complex was directly proportional to the ruthenium amount present inside the cell, as determined by inductively coupled plasma mass spectroscopy. Flow cytometry analysis revealed that the photocytotoxic activity was mainly due to apoptosis. Furthermore, the vasorelaxation induced by [Ru(NO)(ONO)(pc)], proposed as NO carrier, was studied in rat isolated aorta. The observed vasodilation was concentration-dependent. Taken together, the present findings demonstrate that the [Ru(NO)(ONO)(pc)] complex induces vascular relaxation and could be a potent anti-tumor agent. Nitric oxide release following singlet oxygen production upon visible light irradiation on a nitrosyl ruthenium complex produces two radicals and may elicit phototoxic responses that may find useful applications in photodynamic therapy. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.

Preparation and characterization of D, L-PLA loaded 17-beta-Estradiol valerate by emulsion/evaporation methods

PLA microparticles containing 17-beta-estradiol valerate were prepared by an emulsion/evaporation method in order to sustain drug release. This system was characterized concerning particle size, particle morphology and the influence of formulation and processing parameters on drug encapsulation and in vitro drug release. The biodegradation of the microparticles was observed by tissue histological analysis. Scanning electron microscopy and particle size analysis showed that the microparticles were spherical, presenting non-aggregated homogeneous surface and had diameters in the range of 718-880 nm (inert microparticles) and 3-4 mu m (drug loaded microparticles). The encapsulation efficiency was similar to 80%. Hormone released from microparticles was sustained. An in vivo degradation experiment confirmed that microparticles are biodegradable. The preparation method was shown to be suitable, since the morphological characteristics and efficiency yield were satisfactory. Thus, the method of developed microparticles seems to be a promising system for sustained release of 17-beta-estradiol.