Determination of the effect of lipophilicity on the in vitro permeability and tissue reservoir characteristics of topically applied solutes in human skin layers

In order to establish the relationship between solute lipophilicity and skin penetration (including flux and concentration behavior), we examined the in vitro penetration and membrane concentration of a series of homologous alcohols (C2-C10) applied topically in aqueous solutions to human epidermal, full-thickness, and dermal membranes. The partitioning/distribution of each alcohol between the donor solution, stratum corneum, viable epidermis, dermis, and receptor phase compartments was determined during the penetration process and separately to isolated samples of each tissue type. Maximum flux and permeability coefficients are compared for each membrane and estimates of alcohol diffusivity are made based on flux/concentration data and also the related tissue resistance (the reciprocal of permeability coefficient) for each membrane type. The permeability coefficient increased with increasing lipophilicity to alcohol C8 (octanol) with no further increase for C10 (decanol). Log vehicle:stratum corneum partition coefficients were related to logP , and the concentration of alcohols in each of the tissue layers appeared to increase with lipophilicity. No difference was measured in the diffusivity of smaller more polar alcohols in the three membranes; however, the larger more lipophilic solutes showed slower diffusivity values. The study showed that the dermis may be a much more lipophilic environment than originally believed and that distribution of smaller nonionized solutes into local tissues below a site of topical application may be estimated based on knowledge of their lipophilicity alone.

Part 2. Carcass composition and fatty acid profiles of adipose tissue of male goats: effects of genotype and liveweight at slaughter

The dissected carcass composition and fatty acid profiles of intermuscular fat from 110 male goat kids from six genotypes i.e. Boer x Angora (BA), Boer x Feral (BF), Boer x Saanen (BS), Feral x Feral (1717), Saanen x Angora (SA) and Saanen x Feral (SF) and two slaughter weight groups i.e. Capretto and Chevon (liveweight at slaughter 14-22 and 30-35 kg, respectively) were compared. Carcass tissue distribution for various genotypes was: muscle (63-66%), fat (10-13%) and bone (21-24%). Genotype significantly (P < 0.05) influenced the carcass composition; BA and FF carcasses had significantly higher muscle to bone ratio, while carcasses from BS kids were leaner compared to other genotypes. However, the two slaughter weight groups did not differ significantly (P > 0.05) in terms of carcass composition, when compared at the same carcass weight. In the present study, significant (P < 0.01) correlations were observed between percentage of muscle, fat and bone in most of the primal cuts and that in the carcass side. The main saturated fatty acids (SFAs) identified were palmitic (16:0) and stearic acid (18:0), while oleic acid (18: 1, omega9) was the main unsaturated fatty acid (UFA) in the intermuscular fat from goat kids. There were significant (P < 0.05) differences between genotypes in the proportions of individual fatty acids. Adipose tissue from BS kids had significantly higher UFAs (mainly oleic acid) and thus had a significantly lower melting point compared to other genotypes. There were significantly higher proportions of palmitic acid (35%) in the adipose tissue from Capretto kids compared to that from Chevon kids (22%). The concentration of UFAs increased in the adipose tissue from Capretto to Chevon carcasses. (C) 2003 Elsevier Science B.V. All rights reserved.

Transposition of first digital pad for reconstruction of a palmar antebrachial soft tissue defect in a cat

An 8-year-old female neutered Siamese cat was presented with a recent history of incomplete excision of an apocrine gland adenocarcinoma from the palmar aspect of the right antebrachium, just proximal to the carpal joint. There was no evidence of metastasis. Wide surgical excision of the previous surgery site was performed resulting in a soft tissue defect. Partial reconstruction was achieved using digital pad transposition of the first digit (dewclaw), forming a local axial pattern flap that was transposed into the adjacent defect. The remaining defect was closed by primary apposition. The skin flap healed successfully. Some breakdown of the skin closed by primary apposition necessitated open wound management. The cosmetic and functional result of the first digital pad transposition was considered excellent, rendering it a useful means to reconstruct soft tissue defects in the carpal region.

Intramolecular electron transfer in a bacterial sulfite dehydrogenase

Sulfite dehydrogenase (SDH) from Starkeya novella, a sulfite-oxidizing molybdenum-containing enzyme, has a novel tightly bound αβ-heterodimeric structure in which the Mo cofactor and the c-type heme are located on different subunits. Flash photolysis studies of intramolecular electron transfer (IET) in SDH show that the process is first-order, independent of solution viscosity, and not inhibited by sulfate, which strongly indicates that IET in SDH proceeds directly through the protein medium and does not involve substantial movement of the two subunits relative to each other. The IET results for SDH contrast with those for chicken and human sulfite oxidase (SO) in which the molybdenum domain is linked to a b-type heme domain through a flexible loop, and IET shows a remarkable dependence on sulfate concentration and viscosity that has been ascribed to interdomain docking. The results for SDH provide additional support for the interdomain docking hypothesis in animal SO and clearly demonstrate that dependence of IET on viscosity and sulfate is not an inherent property of all sulfite-oxidizing molybdenum enzymes.

Transdermal penetration of vasoconstrictors - Present understanding and assessment of the human epidermal flux and retention of free bases and ion-pairs

Purpose. As reductions in dermal clearance increase the residence time of solutes in the skin and underlying tissues we compared the topical penetration of potentially useful vasoconstrictors (VCs) through human epidermis as both free bases and ion-pairs with salicylic acid (SA). Methods. We determined the in vitro epidermal flux of ephedrine, naphazoline, oxymetazoline, phenylephrine, and xylometazoline applied as saturated solutions in propylene glycol: water (1: 1) and of ephedrine, naphazoline and tetrahydrozoline as 10% solutions of 1: 1 molar ratio ion-pairs with SA in liquid paraffin. Results. As free bases, ephedrine had the highest maximal flux, Jmax = 77.4 +/- 11.7 mug/cm(2)/h, being 4-fold higher than tetrahydrozoline and xylometazoline, 6-fold higher than phenylephrine, 10-fold higher than naphazoline and 100-fold higher than oxymetazoline. Stepwise regression of solute physicochemical properties identified melting point as the most significant predictor of flux. As ion-pairs with SA, ephedrine and naphazoline had similar fluxes (11.5 +/- 2.3 and 12.0 +/- 1.6 mug/cm(2)/h respectively), whereas tetrahydrozoline was approximately 3-fold slower. Corresponding fluxes of SA from the ion-pairs were 18.6 +/- 0.6, 7.8 +/- 0.8 and 1.1 +/- 0.1 respectively. Transdermal transport of VC's is discussed. Conclusions. Epidermal retention of VCs and SA did not correspond to their molar ratio on application and confirmed that following partitioning into the stratum corneum, ion-pairs separate and further penetration is governed by individual solute characteristics.

Usefulness of myocardial tissue Doppler echocardiography to evaluate left ventricular dyssynchrony before and after biventricular pacing in patients with idiopathic dilated cardiomyopathy

Tissue Doppler imaging allows assessment of left ventricular dyssynchrony and resynchronization after biventricular pacing.

Ventricular dysfunction in early diabetic heart disease: detection, mechanisms and significance

The detection of preclinical heart disease is a new direction in diabetes care. This comment describes the study by Vinereanu and co-workers in this issue of Clinical Science in which tissue Doppler echocardiography has been employed to demonstrate subtle systolic and diastolic dysfunction in Type 11 diabetic patients who had normal global systolic function and were free of coronary artery disease. The aetiology of early ventricular dysfunction in diabetes relates to complex intramyocardial and extramyocardial mechanisms. The initiating event may be due to insulin resistance, and involves abnormal myocardial substrate utilization and uncoupling of mitochondrial oxidative phosphorylation. Dysglycaemia plays an important role via the effects of oxidative stress, protein kinase C activation and advanced glycosylation end-products on inflammatory signalling, collagen metabolism and fibrosis. Extramyocardial mechanisms involve peripheral endothelial dysfunction, arterial stiffening and autonomic neuropathy. The clinical significance of the ventricular abnormalities described is unknown. Confirmation of their prognostic importance for cardiac disease in diabetes would justify routine screening for presymptomatic ventricular dysfunction, as well as clinical trials of novel agents for correcting causal mechanisms. These considerations could also have implications for patients with obesity and the metabolic syndrome.

Ichthyotoxicity of Chattonella marina (Raphidophyceae) to damselfish (Acanthochromis polycanthus): the synergistic role of reactive oxygen species and free fatty acids

This investigation aimed to elucidate the relative roles of putative brevetoxins, reactive oxygen species and free fatty acids as the toxic principle of the raphidophyte Chattonella marina, using damselfish as the bioassay. Our investigations on Australian C. marina demonstrated an absence or only very low concentrations of brevetoxin-like compounds by radio-receptor binding assay and liquid chromatography-mass spectroscopy techniques. Chattonella is unique in its ability to produce levels of reactive oxygen species 100 times higher than most other algal species. However, high levels of superoxide on their own were found not to cause fish mortalities. Lipid analysis revealed this raphidophyte to contain high concentrations of the polyunsaturated fatty acid eicosapentaenoic acid (EPA; 18-23% of fatty acids), which has demonstrated toxic properties to marine organisms. Using damselfish as a model organism, we demonstrated that the free fatty acid (FFA) form of EPA produced a mortality and fish behavioural response similar to fish exposed to C. marina cells. This effect was not apparent when fish were exposed to other lipid fractions including a triglyceride containing fish oil, docosahexaenoate-enriched ethyl ester, or pure brevetoxin standards. The presence of superoxide together with low concentrations of EPA accelerated fish mortality rate threefold. We conclude that the enhancement of ichthyotoxicity of EPA in the presence of superoxide can account for the high C. marina fish killing potential. (C) 2003 Elsevier B.V All rights reserved.

Generation of aldehyde-derived protein modifications in ethanol-exposed heart

Background: Although excessive ethanol consumption is known to lead to a variety of adverse effects in the heart, the molecular mechanisms of such effects have remained poorly defined. We hypothesized that posttranslational covalent binding of reactive molecular species to proteins occurs in the heart in response to acute ethanol exposure. Methods: The generation of protein adducts with several aldehydic species was examined by using monospecific antibodies against adducts with malondialdehyde (MDA), acetaldehyde (AA), MDA-AA hybrids, and hydroxyethyl radicals. Specimens of heart tissue were obtained from rats after intraperitoneal injections with alcohol (75 mmol/kg body weight) with or without pretreatment with cyanamide (0.05 mmol/kg body weight), an aldehyde dehydrogenase inhibitor. Results: The amounts of MDA and unreduced AA adducts were found to be significantly increased in the heart of the rats treated with ethanol, cyanamide, or both, whereas no other adducts were detected in statistically significant quantities. Immunohistochemical studies for characterization of adduct distribution revealed sarcolemmal adducts of both MDA and AA in the rats treated with ethanol and cyanamide in addition to intracellular adducts, which were also present in the group treated with ethanol alone. Conclusions: These findings support the role of enhanced lipid peroxidation and the generation of protein-aldehyde condensates in vivo as a result of excessive ethanol intake. These findings may have implications in the molecular mechanisms of cardiac dysfunction in alcoholics.

Rates of electronic energy transfer in conformationally flexible bichromophoric macrocyclic complexes: a combined experimental and molecular modeling study

Electronic energy transfer (EET) rate constants between a naphthalene donor and anthracene acceptor in [ZnL4a](ClO4)(2) and [ZnL4b](ClO4)(2) were determined by time-resolved fluorescence where L-4a and L-4b are the trans and cis isomers of 6-((anthracen-9-yl-methyl)amino)-6,13-dimethyl-13-((naphthalen-1-yl-methyl)amino)-1,4,8,11-tetraazacyclotetradecane, respectively. These isomers differ in the relative disposition of the appended chromophores with respect to the macrocyclic plane. The trans isomer has an energy transfer rate constant (k(EET)) of 8.7 x 10(8) s(-1), whereas that of the cis isomer is significantly faster (2.3 x 10(9) s(-1)). Molecular modeling was used to determine the likely distribution of conformations in CH3CN solution for these complexes in an attempt to identify any distance or orientation dependency that may account for the differing rate constants observed. The calculated conformational distributions together with analysis by H-1 NMR for the [ZnL4a](2+) trans complex in the common trans-III N-based isomer gave a calculated Forster rate constant close to that observed experimentally. For the [ZnL4b](2+) cis complex, the experimentally determined rate constant may be attributed to a combination of trans-Ill and trans-I N-based isomeric forms of the complex in solution.

A review of drainage and spontaneous rupture in free standing thin films with tangentially immobile interfaces

A review of spontaneous rupture in thin films with tangentially immobile interfaces is presented that emphasizes the theoretical developments of film drainage and corrugation growth through the linearization of lubrication theory in a cylindrical geometry. Spontaneous rupture occurs when corrugations from adjacent interfaces become unstable and grow to a critical thickness. A corrugated interface is composed of a number of waveforms and each waveform becomes unstable at a unique transition thickness. The onset of instability occurs at the maximum transition thickness, and it is shown that only upper and lower bounds of this thickness can be predicted from linear stability analysis. The upper bound is equivalent to the Freakel criterion and is obtained from the zeroth order approximation of the H-3 term in the evolution equation. This criterion is determined solely by the film radius, interfacial tension and Hamaker constant. The lower bound is obtained from the first order approximation of the H-3 term in the evolution equation and is dependent on the film thinning velocity A semi-empirical equation, referred to as the MTR equation, is obtained by combining the drainage theory of Manev et al. [J. Dispersion Sci. Technol., 18 (1997) 769] and the experimental measurements of Radoev et al. [J. Colloid Interface Sci. 95 (1983) 254] and is shown to provide accurate predictions of film thinning velocity near the critical thickness of rupture. The MTR equation permits the prediction of the lower bound of the maximum transition thickness based entirely on film radius, Plateau border radius, interfacial tension, temperature and Hamaker constant. The MTR equation extrapolates to Reynolds equation under conditions when the Plateau border pressure is small, which provides a lower bound for the maximum transition thickness that is equivalent to the criterion of Gumerman and Homsy [Chem. Eng. Commun. 2 (1975) 27]. The relative accuracy of either bound is thought to be dependent on the amplitude of the hydrodynamic corrugations, and a semiempirical correlation is also obtained that permits the amplitude to be calculated as a function of the upper and lower bound of the maximum transition thickness. The relationship between the evolving theoretical developments is demonstrated by three film thickness master curves, which reduce to simple analytical expressions under limiting conditions when the drainage pressure drop is controlled by either the Plateau border capillary pressure or the van der Waals disjoining pressure. The master curves simplify solution of the various theoretical predictions enormously over the entire range of the linear approximation. Finally, it is shown that when the Frenkel criterion is used to assess film stability, recent studies reach conclusions that are contrary to the relevance of spontaneous rupture as a cell-opening mechanism in foams. (C) 2003 Elsevier Science B.V. All rights reserved.

A kinetic study of the thermally initiated free radical reactions of styrene with octanedithiol as a model for the reactions of multifunctional thiols with divinylbenzene

The kinetics of chain reactions of octanedithiol with styrene, thermally initiated with TX29B50 (a 50:50 wt% solution of TX29 diperoxy initiator in a phthalate plasticizer), have been studied over a range of initiator concentrations, a range of mixture formulations and a range of temperatures. This system has been investigated as a model system for the reactions of polyfunctional thiols with divinyl benzene. The reactions have been shown to follow first-order kinetics for both the thiol and the ene species and to be characterized by a dependence on the initiator concentration to the power of one half. The kinetic rate parameters have been shown to adhere to Arrhenius behaviour. A kinetic model for the chain reactions for this system has been proposed. (C) 2003 Society of Chemical Industry.

Electrochemistry of P450cin: new insights into P450 electron transfer

Electrochemistry of bacterial cytochrome P450cin (CYP176A) reveals that, unusually, substrate binding does not affect the heme redox potential, although a marked pH dependence is consistent with a coupled single electron/single proton transfer reaction in the range 6 < pH < 10.

Boletim eletr??nico de bibliografias especializadas: pol??tica de transfer??ncia condicionada de renda

As pol??ticas de Transfer??ncia Condicionada de Renda (TCR) s??o consideradas a mais nova gera????o de pol??ticas sociais. O fato tem chamado a aten????o de profissionais do setor p??blico e de acad??micos de diferentes ??reas. Nos ??ltimos anos, diversas experi??ncias, sobretudo na Am??rica Latina, t??m-se destacado pelo impacto positivo sobre os indicadores sociais da popula????o, entre elas: o Programa Bolsa Fam??lia, no Brasil; o Programa de Desarrollo Humano Oportunidades, no M??xico; e o Sistema Chile Solid??rio, no Chile. O Programa Bolsa Fam??lia, criado em 2003, constitui a maior pol??tica p??blica de TCR da Am??rica Latina, tanto em or??amento quanto em cobertura. Atualmente, atende cerca de 13.800.000 fam??lias, em todos os munic??pios do Pa??s. O Programa tem servido de modelo para a difus??o desse tipo de pol??tica no mundo. O tema envolve v??rias dimens??es da ??rea social, por se tratar de uma pol??tica essencialmente intersetorial. O Bolsa Fam??lia vem se destacando nos debates da administra????o p??blica, devido ?? sua forte capacidade de melhoria das condi????es das fam??lias benefici??rias. Diante disso, a 5a edi????o do Boletim Eletr??nico de Bibliografias Especializadas apresenta uma reuni??o de publica????es do acervo da Biblioteca Graciliano Ramos que abordam os seguintes temas: transfer??ncia condicionada de renda, programas sociais, desigualdade social, combate da pobreza e pol??ticas p??blicas. O objetivo ?? divulgar obras que auxiliem servidores p??blicos na reflex??o e compreens??o desses assuntos