Comparison of fluconazole pharmacokinetics in serum, aqueous humor, vitreous humor, and cerebrospinal fluid following a single dose and at steady state

The objective of this study was to characterize the pharmacokinetic parameters and penetration of fluconazole following a single dose in the serum, aqueous humor, vitreous humor and cerebrospinal fluid (CSF) of non pigmented rabbits using serial sampling techniques and to determine if the pharmacokinetic parameters in the eye and CSF are similar. Twenty healthy male rabbits received intravenous fluconazole 20 mg/kg as a single dose or 20 mg/kg every 12 hours for 4 doses. Serum, aqueous humor, vitreous humor and CSF samples were taken 15 minutes after the initial intravenous injection and hourly thereafter for six hours. Fluconazole concentrations were determined by microbiological assay. Pharmacokinetic analyses were performed using a nonlinear least-square regression program. Fluconazole's penetration in all anatomical compartments was > 70% than in the serum. Similar elimination half-lives and time to reach maximum concentrations were noted in all compartments. While mean concentrations in each anatomical compartment were similar in animals receiving a single dose or among those at serum steady state, the mean concentrations achieved in the serum, aqueous and vitreous humors and CSF were between 1.82 and 2.17 times higher at serum steady state than following a single dose. At serum concentrations that are comparable to those in humans, the penetration of fluconazole into the noninflamed aqueous and vitreous humors and CSF were > or = 70%. The CSF and ocular pharmacokinetic parameters closely resembled each other, so that either could be used as a surrogate for the other.     

Effects of thyroid status on cold-adaptive thermogenesis in Brandt's vole, Microtus brandti

Hyper- and hypothyroidism were induced by subcutaneous injection of thyroxine and by oral administration of methimazol in Brandt's voles. The effects of the two treatments on metabolic thermogenesis at 25 degrees C and 4 degrees C were investigated. The level of resting metabolic rate was closely related to thyroid status: high in the hyperthyroid case and low in the hypothyroid case. However, no increase in resting metabolic rate occurred in either case during further cold acclimation. Hyperthyroidism resulted in an increased nonshivering thermogenesis, which was much enhanced by lower temperature, but hypothyroidism led to a suppressed nonshivering thermogenesis in the cold. The state-4 and state-3 respirations and the activities of cytochrome-c oxidase of liver mitochondria were elevated in hyperthyroid animals but attenuated in hypothyroid ones. However, these levels were scarcely changed after further cold acclimation. Both hyperthyroidism and cold acclimation induced the recruitment of brown adipose tissue, but brown adipose tissue was different biochemically in the two cases: in hyperthyroidism, the total protein was reduced, while fat content increased; in cold acclimation, the total and mitochondrial proteins were increased. However, in hypothyroid voles, the normal adaptive changes in brown adipose tissue were impaired in further cold acclimation. The activity of cytochromec oxidase in brown adipose tissue was increased by hyperthyroidism and enhanced in further cold. In contrast, its activity was inhibited in hypothyroid animals, though activated to some extent in cold. These results demonstrate that normal thyroid function is essential for the cold-induced increase of resting metabolic rate and nonshivering thermogenesis and that there is a synergism between thyroid hormone and cold acclimation in the regulation of nonshivering thermogenesis in Brandt's vole. In addition, the blunted response of brown adipocytes to the cold may be the cytological mechanism for the suppressed nonshivering thermogenesis found with hypothyroidism.     

The fundamentals of flame treatment for the surface activation of polyolefin polymers - A review

This paper aims to provide an exhaustive and comprehensive overview on flame treatment as a valuable technique for improving the surface properties of polymers, especially polyolefins. It starts with a brief historical excursus on the origin of flame treatment, and the second section deals with the major fundamentals of flame chemistry, with a special focus on the combustion process and mechanism of surface activation. The most important parameters influencing the extent of the oxidation reaction along with relevant practical notes are discussed in the third section. The concluding section outlines how the most significant features of flame treatment can be profitably used to improve the wettability and adhesion properties of polyolefin surfaces, especially from the perspective of developing novel composite solutions such as polyolefins/bio-based coating pairs intended for many different applications.     

Mechanical behavior of masonry materials at high temperatures

An experimental campaign is presented to determine the effects of high temperatures on the mechanical properties of several materials for masonry walls (blocks and mortars), testing a series of cylindrical specimens (diameter of 100 mm and height of 200 mm). After compression tests at 20 °C, an experimental procedure was designed for high‐temperature testing. The cylindrical samples were heated in a muffle furnace, then were inserted into a specific apparatus (called ‘thermos’) for maintaining the prescribed temperature, and finally were subjected to a mechanical compression test. The results obtained by applying this procedure show a common variation of the strength, reduction of modulus of elasticity, and corresponding increments of the ultimate strain with temperature enhancement. Specific diagrams and discussion on the results are performed for each material. Copyright © 2014 John Wiley & Sons, Ltd.     

Mass Transfer Model for the De-oxidation of Molten Copper

In this paper, we present a mass transfer model that predicts two different mechanisms that control copper de-oxidation: (1) the transport of the reducing gas from the gas bubbles towards the melt/bubble interface, and (2) the transport of dissolved oxygen from the melt towards the melt/bubble interface. The model accounts for gas fluid flow and other process parameters such as lance submergence and nozzle diameter. The model was validated with published data and predictions from our model are in good agreement with the values reported. The key parameters to determine are the mass transfer coefficients of the reducing gas and that of the dissolved oxygen in the melt.     

Regenerative Neurology and Regenerative Cardiology: Shared Hurdles and Achievements

From the first success in cultivation of cells in vitro, it became clear that developing cell and/or tissue specific cultures would open a myriad of new opportunities for medical research. Expertise in various in vitro models has been developing over decades, so nowadays we benefit from highly specific in vitro systems imitating every organ of the human body. Moreover, obtaining sufficient number of standardized cells allows for cell transplantation approach with the goal of improving the regeneration of injured/disease affected tissue. However, different cell types bring different needs and place various types of hurdles on the path of regenerative neurology and regenerative cardiology. In this review, written by European experts gathered in Cost European action dedicated to neurology and cardiology-Bioneca, we present the experience acquired by working on two rather different organs: the brain and the heart. When taken into account that diseases of these two organs, mostly ischemic in their nature (stroke and heart infarction), bring by far the largest burden of the medical systems around Europe, it is not surprising that in vitro models of nervous and heart muscle tissue were in the focus of biomedical research in the last decades. In this review we describe and discuss hurdles which still impair further progress of regenerative neurology and cardiology and we detect those ones which are common to both fields and some, which are field-specific. With the goal to elucidate strategies which might be shared between regenerative neurology and cardiology we discuss methodological solutions which can help each of the fields to accelerate their development.     

A new six parameter model to estimate the friction factor

A new explicit formula for estimating the friction factor using six parameters is proposed. The model was set up by considering the effect of residual stresses in the flow by two distinct contributions: the first is attributed to the flow velocity (Reynolds number) and the second to the duct roughness. Compared to other models, this new equation gives the best fit with Nikuradse's results. A new model to calculate the friction is proposed. The model is based on assuming the residual stresses due to the laminar to turbulent flow transition by two distinct contributions: the first is attributed to the flow velocity (Reynolds number) and the second to the duct roughness. Compared to other models, this new equation gives the best fit with respect of Nikuradse's results. The model does not consider the effect of pipe wall on the velocity distribution. © 2019 American Institute of Chemical Engineers AIChE J, 65: 1144–1148, 2019     

Defining the arachidonic acid binding site of human 15-lipoxygenase. Molecular modeling and mutagenesis

Mammalian lipoxygenases have been implicated in the pathogenesis of several inflammatory disorders and are, therefore, important targets for drug discovery. Both plant and mammalian lipoxygenases catalyze the dioxygenation of polyunsaturated fatty acids, which contain one or more 1,4-cis,cis-pentadiene units to yield hydroperoxide products. At the time this study was initiated, soybean lipoxygenase-1 was the only lipoxygenase for which an atomic resolution structure had been determined. No structure of lipoxygenase with substrate or inhibitor bound is currently available. A model of arachidonic acid docked into the proposed substrate binding site in the soybean structure is presented here. Analysis of this model suggested two residues, an aromatic residue and a positively charged residue, could be critical for substrate binding. Validation of this model is provided by site-directed mutagenesis of human 15-lipoxygenase, despite the low amino acid sequence identity between the soybean and mammalian enzymes. Both a positively charged amino acid residue (Arg402) and an aromatic amino acid residue (Phe414) are identified as critical for the binding of fatty acid substrates in human 15-lipoxygenase. Thus, binding determinants shown to be characteristic of non-enzymatic fatty acid-binding proteins are now implicated in the substrate binding pocket of lipoxygenases.