Copper salt-catalyzed homo-coupling reaction of potassium alkynyltrifluoroborates: a simple and efficient synthesis of symmetrical 1,3-diynes

The copper-catalyzed dimerization of alkynyltrifluoroborates proceeds readily with good yields. The homo-coupling reaction can be effected in DMSO, in the open air, using Cu(OAc)(2) as catalyst in the absence of any other additives. A variety of functional groups are tolerated. (C) 2008 Elsevier Ltd. All rights reserved.

Stability and in vitro penetration study of rutin incorporated in a cosmetic emulsion through an alternative model biomembrane

Rutin is employed as antioxidant and to prevent the capillary fragility and, when incorporated in cosmetic emulsions, it must target the action site. In vitro cutaneous penetration studies through human skin is the ideal situation, however, there are difficulties to obtain and to maintain this tissue viability. Among the membrane models, shed snake skin presents itself as pure stratum corneum, providing barrier function similar to human and it is obtained without the animal sacrifice. The objectives of this research were the development and stability evaluation of a cosmetic emulsion containing rutin and propylene glycol (penetration enhancer) and the evaluation or rutin in vitro cutaneous penetration and retention from the emulsion, employing an alternative model biomembrane. Emulsion was developed with rutin and propylene glycol, both at 5.0% w/w. Active substance presented on the formulation was quantified by a validated spectrophotometric method at 361.0 nm. Rutin Rutin cutaneous penetration and retention was performed in vertical diffusion cells with shed snake skin of Crotalus durissus, as alternative model biomembrane, and distilled water and ethanol 99.5% (1:1), as receptor fluid. The experiment was conducted for six hours, at 37.0 +/- 0.5 degrees C with constant stirring of 300 rpm. Spectrophotometry at 410.0 nm, previously validated, determined the active substance after cutaneous penetration/ retention. Emulsion did not promote rutin cutaneous penetration through C. durissus skin, retaining 0.931 +/- 0.0391 mu g rutin/mg shed snake skin. The referred formulation was chemically stable for 30 days after stored at 25.0 +/- 2.0 degrees C, 5.0 +/- 0.5 degrees C and 45.0 +/- 0.5 degrees C. In conclusion, it has not been verified the active cutaneous penetration through the model biomembrane, but only its retention on the Crotalus durissus stratum corneum, condition considered stable for 30 days.

Optimization of preservative system in ophthalmic suspension with dexamethasone and polymyxin B

A simplex-lattice statistical project was employed to study an optimization method for a preservative system in an ophthalmic suspension of dexametasone and polymyxin B. The assay matrix generated 17 formulas which were differentiated by the preservatives and EDTA (disodium ethylene diamine-tetraacetate), being the independent variable: X-1 = chlorhexidine digluconate (0.010 % w/v); X-2 = phenylethanol (0.500 % w/v); X-3 = EDTA (0.100 % w/v). The dependent variable was the Dvalue obtained from the microbial challenge of the formulas and calculated when the microbial killing process was modeled by an exponential function. The analysis of the dependent variable, performed using the software Design Expert/W, originated cubic equations with terms derived from stepwise adjustment method for the challenging microorganisms: Pseudomonas aeruginosa, Burkholderia cepacia, Staphylococcus aureus, Candida albicans and Aspergillus niger. Besides the mathematical expressions, the response surfaces and the contour graphics were obtained for each assay. The contour graphs obtained were overlaid in order to permit the identification of a region containing the most adequate formulas (graphic strategy), having as representatives: X-1 = 0.10 ( 0.001 % w/v); X-2 = 0.80 (0.400 % w/v); X-3 = 0.10 (0.010 % w/v). Additionally, in order to minimize responses (Dvalue), a numerical strategy corresponding to the use of the desirability function was used, which resulted in the following independent variables combinations: X-1 = 0.25 (0.0025 % w/v); X-2 = 0.75 (0.375 % w/v); X-3 = 0. These formulas, derived from the two strategies (graphic and numerical), were submitted to microbial challenge, and the experimental Dvalue obtained was compared to the theoretical Dvalue calculated from the cubic equation. Both Dvalues were similar to all the assays except that related to Staphylococcus aureus. This microorganism, as well as Pseudomonas aeruginosa, presented intense susceptibility to the formulas independently from the preservative and EDTA concentrations. Both formulas derived from graphic and numerical strategies attained the recommended criteria adopted by the official method. It was concluded that the model proposed allowed the optimization of the formulas in their preservation aspect.

W/O/W multiple emulsions obtained by one-step emulsification method and evaluation of the involved variables

The effects of some composition variables on the development of multiple emulsions by one-step method were evaluated and their morphology characterized. The formulations that remained stable during the period of the test were submitted to centrifugation and thermal stress tests. The stability and the morphology of multiple droplets were affected not only by the type and concentration of the surfactants employed, but also by the water/oil ratios used. The results suggest that the formation of multiple droplets could involve a combination of transitional and catastrophic phase inversions. The results provide improved knowledge about the one-step emulsification method, a simplified process to prepare multiple emulsions when compared to the two-steps method.

O/W Nanoemulsion After 15 Years of Preparation: A Suitable Vehicle for Pharmaceutical and Cosmetic Applications

The application of nanoemulsions is due to have good stability, uniform spreading and enhance active penetration upon skin. Nanometer emulsions can be obtained by low-energy emulsification method. The required hydrophilic and lipophilic balance indicates the better balance of emulsifier for optimum system emulsification. Emulsion stability is evidently controlled for the properties of the adsorbed layer formed in the surface of its globules, know as potential zeta. The aim of this work was to evaluate the oil/water nanoemulsion of formulation obtained after 15 years of preparation. The results suggested that the nanoemulsion have performed stability for many years.

Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity

This study described the formulation and characterisation of the viscoelastic, mechanical and mucoadhesive properties of thermoresponsive, binary polymeric systems composed of poloxamer (P407) and poly(acrylic acid, C974P) that were designed for use as a drug delivery platform within the oral cavity. Monopolymeric and binary polymeric formulations were prepared containing 10, 15 and 20% (w/w) poloxamer (407) and 0.10-0.25% (w/w) poly(acrylic acid, 934P). The flow theological and viscoelastic properties of the formulations were determined using controlled stress and oscillatory rheometry, respectively, the latter as a function of temperature. The mechanical and mucoadhesive properties (namely the force required to break the bond between the formulation and a pre-hydrated mucin disc) were determined using compression and tensile analysis, respectively. Binary systems composed of 10% (w/w) P407 and C934P were elastoviscous, were easily deformed under stress and did not exhibit mucoadhesion. Formulations containing 15 or 20% (w/w) Pluronic P407 and C934P exhibited a sol-gel temperature T(sol/gel), were viscoelastic and offered high elasticity and resistance to deformation at 37 degrees C. Conversely these formulations were elastoviscous and easily deformed at temperatures below the sol-gel transition temperature. The sol-gel transition temperatures of systems containing 15% (w/w) P407 were unaffected by the presence of C934P; however, increasing the concentration of C934P decreased the T(sol/gel) in formulations containing 20%(w/w) P407. Rheological synergy between P407 and C934P at 37 degrees C was observed and was accredited to secondary interactions between these polymers, in addition to hydrophobic interactions between P407 micelles. Importantly, formulations composed of 20% (w/w) P407 and C934P exhibited pronounced mucoadhesive properties. The ease of administration (below the T(sol/gel)) in conjunction with the viscoelastic (notably high elasticity) and mucoadhesive properties (at body temperature) render the formulations composed of 20% (w/w) P407 and C934P as potentially useful platforms for mucoadhesive, controlled topical drug delivery within the oral cavity. (c) 2009 Published by Elsevier B.V.

Differential roles of galectin-1 and galectin-3 in regulating leukocyte viability and cytokine secretion

Galectin-1 (Gal-1) and galectin-3 (Gal-3) exhibit profound but unique immunomodulatory activities in animals but their molecular mechanisms are incompletely understood. Early studies suggested that Gal-1 inhibits leukocyte function by inducing apoptotic cell death and removal, but recent studies show that some galectins induce exposure of the common death signal phosphatidylserine (PS) independently of apoptosis. In tfhis study, we report that Gal-3, but not Gal-1, induces both PS exposure and apoptosis in primary activated human T cells, whereas both Gal-1 and Gal-3 induce PS exposure in neutrophils in the absence of cell death. Gal-1 and Gal-3 bind differently to the surfaces of T cells and only Gal-3 mobilizes intracellular Ca(2+) in these cells, although Gal-1 and Gal-3 bind their respective T cell ligands with similar affinities. Although Gal-1 does not alter T cell viability, it induces IL-10 production and attenuates IFN-gamma production in activated T cells, suggesting a mechanism for Gal-1-mediated immunosuppression in vivo. These studies demonstrate that Gal-1 and Gal-3 induce differential responses in T cells and neutrophils, and identify the first factor, Gal-3, capable of inducing PS exposure with or without accompanying apoptosis in different leukocytes, thus providing a possible mechanism for galectin-mediated immunomodulation in vivo.

Differential expression of immunomodulatory galectin-1 in peripheral leukocytes and adult tissues and its cytosolic organization in striated muscle

Galectin-1 (Gal-1) is important in immune function and muscle regeneration, but its expression and localization in adult tissues and primary leukocytes remain unclear. To address this, we generated a specific monoclonal antibody against Gal-1, termed alpha hGal-1, and defined a sequential peptide epitope that it recognizes, which is preserved in human and porcine Gal-1, but not in murine Gal-1. Using alpha hGal-1, we found that Gal-1 is expressed in a wide range of porcine tissues, including striated muscle, liver, lung, brain, kidney, spleen, and intestine. In most types of cells, Gal-1 exhibits diffuse cytosolic expression, but in cells within the splenic red pulp, Gal-1 showed both cytosolic and nuclear localization. Gal-1 was also expressed in arterial walls and exhibited prominent cytosolic and nuclear staining in cultured human endothelial cells. However, human peripheral leukocytes and promyelocytic HL60 cells lack detectable Gal-1 and also showed very low levels of Gal-1 mRNA. In striking contrast, Gal-1 exhibited an organized cytosolic staining pattern within striated muscle tissue of cardiac and skeletal muscle and colocalized with sarcomeric actin on I bands. These results provide insights into previously defined roles for Gal-1 in inflammation, immune regulation and muscle biology.

Central Cardiovascular Anatomy and Function in Crocodilia

Abstract: Among the vertebrates, crocodilians have the most complex anatomy of the heart and outflow channels. Their cardiovascular anatomy may also be the most func­tionally sophisticated, combining as it does the best features of both reptilian and mammalian (and avian) systems. The puzzlingly complex "plumbing" of crocodilians has fascinated ana­tomists and physiologists for a very long time, the first paper being that by Panizza (1833). Gradually, with the application of successive techniques of investigation as they became available, its functional significance has become reasonably clear, and the complexity is now revealed as a cardiovascular system of considerable elegance. In this paper I will review the main anatomical features of the heart and outflow channels, discuss what is known about the way they work, and speculate about the probable functional significance.

Measurement Function Design for Visual Tracking Applications

Extracting human postural information from video sequences has proved a difficult research question. The most successful approaches to date have been based on particle filtering, whereby the underlying probability distribution is approximated by a set of particles. The shape of the underlying observational probability distribution plays a significant role in determining the success, both accuracy and efficiency, of any visual tracker. In this paper we compare approaches used by other authors and present a cost path approach which is commonly used in image segmentation problems, however is currently not widely used in tracking applications.

Kidney and cloaca function in the estuarine crocodile (Crocodylus porosus) at different salinities: Evidence for solute-linked water uptake

Kidney function and the role of the cloacal complex in osmoregulation was investigated in estuarine crocodile (Crocodylus porosus) exposed to three environmental salinities: hypo-, iso- and hyperosmotic to the plasma. Plasma homeostasis was maintained over the range of salinities. Antidiuresis occurred with increased salinity. Although urine from the kidneys retained an osmotic pressure between 77% and 82% of the plasma, over 93% and 98% of plasma chloride filtered at the glomeruli was reabsorbed during passage through the kidneys under hypo and hyperosmotic conditions, respectively, and only 64% in iso-osmotic water. The kidneys were the primary site of sodium reabsorption under hypo-and hyperosmotic conditions. Secondary processing of urine during storage in the cloaca varied with salinity. During post renal storage of urine, the difference in urine osmotic pressure increased from -26.1 +/- 15.5 to 35.66 +/- 9.29 mOsM with increased salinity, and potassium concentration of urine increased over 3-fold in C. porosus from freshwater. The almost complete reabsorption of both sodium and chloride under hyperosmotic conditions indicates the necessity for secretory activity by the lingual salt glands. The osmoregulatory response of the kidneys and cloacal complex to environmental salinity is both plastic and complementary. (C) 1998 Elsevier Science Inc.

Muscle metabolites and performance during high-intensity, intermittent exercise

Six men were studied during four 30-s all-out exercise bouts on an air-braked cycle ergometer. The first three exercise bouts were separated by 4 min of passive recovery; after the third bout, subjects rested for 4 min, exercised for 30 min at 30-35% peak O-2 consumption, and rested for a further 60 min before completing the fourth exercise bout. Peak power and total work were reduced (P < 0.05) during bout 3 [765 +/- 60 (SE) W; 15.8 +/- 1.0 kJ] compared with bout 1 (1,168 +/- 55 mT, 23.8 +/- 1.2 kJ), but no difference in exercise performance was observed between bouts 1 and 4 (1,094 +/- 64 W, 23.2 +/- 1.4 kJ). Before bout 3, muscle ATP, creatine phosphate (CP), glycogen, pH, and sarcoplasmic reticulum (SR) Ca2+ uptake were reduced, while muscle lactate and inosine 5'-monophosphate were increased. Muscle ATP and glycogen before bout 4 remained lower than values before bout I (P < 0.05), but there were no differences in muscle inosine 5'-monophosphate, lactate, pH, and SR Ca2+ uptake. Muscle CP levels before bout 4 had increased above resting levels. Consistent with the decline in muscle ATP were increases in hypoxanthine and inosine before bouts 3 and 4. The decline in exercise performance does not appear to be related to a reduction in muscle glycogen. Instead, it may be caused by reduced CP availability, increased H+ concentration, impairment in SR function, or some other fatigue-inducing agent.

Optical properties of metallic films for vertical-cavity optoelectronic devices

We present models for the optical functions of 11 metals used as mirrors and contacts in optoelectronic and optical devices: noble metals (Ag, Au, Cu), aluminum, beryllium, and transition metals (Cr, Ni, Pd, Pt, Ti, W). We used two simple phenomenological models, the Lorentz-Drude (LD) and the Brendel-Bormann (BB), to interpret both the free-electron and the interband parts of the dielectric response of metals in a wide spectral range from 0.1 to 6 eV. Our results show that the BE model was needed to describe appropriately the interband absorption in noble metals, while for Al, Be, and the transition metals both models exhibit good agreement with the experimental data. A comparison with measurements on surface normal structures confirmed that the reflectance and the phase change on reflection from semiconductor-metal interfaces (including the case of metallic multilayers) can be accurately described by use of the proposed models for the optical functions of metallic films and the matrix method for multilayer calculations. (C) 1998 Optical Society of America.

Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta 1 subunit gene SCN1B

Febrile seizures affect approximately 3% of all children under six years of age and are by far the most common seizure disorder(1). A small proportion of children with febrile seizures later develop ongoing epilepsy with afebrile seizures(2). Segregation analysis suggests the majority of cases have complex inheritance(3) but rare families show apparent autosomal dominant: inheritance. Two putative loci have been mapped (FEB1 and FEB2), but specific genes have not yet been identified(4,5). We recently described a clinical subset, termed generalized epilepsy with febrile seizures plus (GEFS(+)), in which many family members have seizures with fever that may persist beyond six years of age or be associated with afebrile generalized seizures(6). We now report linkage, in another large GEFS(+) family, to chromosome region 19q13.1 and identification of a mutation in the voltage-gated sodium (Na+)-channel beta 1 subunit gene (SCN1B). The mutation changes a conserved cysteine residue disrupting a putative disulfide bridge which normally maintains an extracellular immunoglobulin-like fold. Go-expression of the mutant pr subunit with a brain Na+-channel alpha subunit in Xenopus laevis oocytes demonstrates that the mutation interferes with the ability of the subunit to modulate channel-gating kinetics consistent with a loss-of-function allele. This observation develops the theme that idiopathic epilepsies are a family of channelopathies and raises the possibility of involvement of other Na+-channel subunit genes in febrile seizures and generalized epilepsies with complex inheritance patterns.

Solution structure of amyloid beta-peptide(1-40) in a water-micelle environment. Is the membrane-spanning domain where we think it is?

The three-dimensional solution structure of the 40 residue amyloid beta-peptide, A beta(1-40), has been determined using NMR spectroscopy at pH 5.1, in aqueous sodium dodecyl sulfate (SDS) micelles, In this environment, which simulates to some extent a water-membrane medium, the peptide is unstructured between residues 1 and 14 which are mainly polar and likely solvated by water. However, the rest of the protein adopts an alpha-helical conformation between residues 15 and 36 with a kink or hinge at 25-27. This largely hydrophobic region is likely solvated by SDS. Based on the derived structures, evidence is provided in support of a possible new location for the transmembrane domain of A beta within the amyloid precursor protein (APP). Studies between pH 4.2 and 7.9 reveal a pH-dependent helix-coil conformational switch. At the lower pH values, where the carboxylate residues are protonated, the helix is uncharged, intact, and lipid-soluble. As the pH increases above 6.0, part of the helical region (15-24) becomes less structured, particularly near residues E22 and D23 where deprotonation appears to facilitate unwinding of the helix. This pH-dependent unfolding to a random coil conformation precedes any tendency of this peptide to aggregate to a beta-sheet as the pH increases. The structural biology described herein for A beta(1-40) suggests that (i) the C-terminal two-thirds of the peptide is an alpha-helix in membrane-like environments, (ii) deprotonation of two acidic amino acids in the helix promotes a helix-coil conformational transition that precedes aggregation, (iii) a mobile hinge exists in the helical region of A beta(1-40) and this may be relevant to its membrane-inserting properties and conformational rearrangements, and (iv) the location of the transmembrane domain of amyloid precursor proteins may be different from that accepted in the Literature. These results may provide new insight to the structural properties of amyloid beta-peptides of relevance to Alzheimer's disease.