Comparative toxicity of 24 manufactured nanoparticles in human alveolar epithelial and macrophage cell lines

Background  

A critical issue with nanomaterials is the clear understanding of their potential toxicity. We evaluated the toxic effect of 24 nanoparticles of similar equivalent spherical diameter and various elemental compositions on 2 human pulmonary cell lines: A549 and THP-1. A secondary aim was to elaborate a generic experimental set-up that would allow the rapid screening of cytotoxic effect of nanoparticles. We therefore compared 2 cytotoxicity assays (MTT and Neutral Red) and analyzed 2 time points (3 and 24 hours) for each cell type and nanoparticle. When possible, TC50 (Toxic Concentration 50 i.e. nanoparticle concentration inducing 50% cell mortality) was calculated.     

Switching from water to ionic liquids for the production of methylchloride: Catalysis and reactor issues

The synthesis of methyl chloride from methanol and hydrogen chloride catalysed by zinc chloride was investigated in water and in two room temperature ionic liquids in a CSTR reactor. Both Aliquat336 and BMICl drive to similar rate of reactions as the traditional process albeit at lower temperatures. More importantly, the formation of the side product Me₂O is decreased in ionic liquids. From the reactor point of view and on the basis of kinetics and simulations, a new process involving plug flow behaviour using ionic liquids is proposed which would lead to process intensification, i.e. (50×) productivity increase.     

Enteral nutrition in adult Crohn's disease: present status and perspectives

Enteral nutrition has long been a therapeutic alternative often used in adult Crohn's disease patients to obtain remission or clinical response, especially in those not responding to conventional therapy such as corticosteroids. However, the increasing use of immunosuppressors (6-mercaptopurine and azathioprine, methotrexate, etc.), and the advent of biotherapies (especially anti-tumor necrosis factor-alpha (TNF-alpha) antibodies), decreased its use in adult Crohn's disease. Nevertheless, enteral nutrition remains of interest in patients presenting concomitant malnutrition (in particular in nonobstructed patients needing surgery), or in those intolerant or who failed to other therapeutics. In addition, recent studies provide data indicating its potential interest in maintenance therapy in selected patients groups. Finally, future research (in particular in the field of immuno- or pharmaconutrition) could lead to enteral formula's improvement, with better tolerance and acceptability, as well as increased efficacy.     

Evaluation of thermal and moisture management properties on knitted fabrics and comparison with a physiological model in warm conditions

This study reports on an experimental investigation of physical properties on the textile thermal comfort. Textile properties, such as thickness, relative porosity, air permeability, moisture regain, thermal conductivity, drying time and water-vapour transmission rate have been considered and correlated to the thermal and vapour resistance, permeability index, thermal effusivity and moisture management capability in order to determine the overall comfort performance of underwear fabrics. The results suggested that the fibre type, together with moisture regain and knitted structure characteristics appeared to affect some comfort-related properties of the fabrics. Additionally, thermal sensations, temperature and skin wetness predicted by Caseto^® software for three distinct activity levels were investigated. Results show that the data obtained from this model in transient state are correlated to the thermal conductivity for the temperature and to Ret, moisture regain and drying time for the skin wetness. This provides potential information to determine the end uses of these fabrics according to the selected activity level.     

Respiratory disease among workers exposed to man-made mineral fibers

Fibrous glass and mineral wool workers exposed to airborne man-made mineral fibers prior to 1964 were identified and followed for deaths caused by respiratory disease. Fiber exposure levels were estimated for each worker. Average fiber concentrations were very low in relation to a National Institute of Occupational Safety and Health recommendation that exposure to man-made mineral fibers less than 3.5 microns in diameter be limited to 3 fibers per cubic centimeter of air. Fibrous glass workers were exposed to about one hundredth and mineral wool workers to about one tenth of that amount. Respiratory cancer death rates were not excessive for the fibrous glass workers, but they were significantly elevated for the mineral wool workers. When respiratory cancer deaths were compared with fiber exposure levels, however, there was in no instance a strong positive correlation. There was a significant excess in nonmalignant respiratory disease deaths (excluding influenza and pneumonia) for fibrous glass workers and for the total cohort. When these nonmalignant respiratory disease deaths were compared with fiber exposure levels, however, there was in no instance a strong positive association. A special study was made of workers exposed to small diameter fibers. Respiratory cancer deaths were not in excess; however, there was an excess in nonmalignant respiratory disease deaths. This study provided no consistent evidence of a respiratory disease hazard related to exposure to man-made mineral fibers among the workers who produce these fibers. Results must be interpreted in relation to the relatively low exposure levels for these workers.     

Cytokine regulation of adult human osteoblast-like cell prostaglandin biosynthesis

Prostaglandin (PG) biosynthesis by cytokine stimulated normal adult human osteoblast-like (hOB) cells was evaluated by thin layer chromatography, high performance liquid chromatography, and specific immunoassays. PGE2 was the predominant PG formed under all incubation conditions tested. Control samples produced measurable amounts of PGE2, and the measured level of this metabolite increased by 22-fold (from 7 to 152 ng/ml) following a 20 h treatment with the combination of TGF beta and tumor necrosis factor-alpha(TNF). The production of 6-keto-PGF1 alpha (the stable metabolite of prostacyclin) and of PGF2 alpha were each increased by about five-fold (from about 0.5 to 2.5 ng/ml) in samples treated with the cytokines. Thus, TGF beta and TNF exerted a regulation of hOB cell PG biosynthesis that was principally directed towards an increased PGE2 biosynthesis, with lesser effects on the production of other PG metabolites. COX-2 mRNA levels were increased within 2 h of cytokine stimulation, reached a maximum at 6-12 h, and levels had appreciably diminished by 24 h after treatment. Both TGF beta and TNF could independently increase COX-2 mRNA levels and PG biosynthesis. However, the increased production of PGE2 resulting from TNF stimulation was blocked by the addition of an interleukin-1 beta (IL-1 beta) neutralizing antibody, suggesting that TNF regulation of hOB cell PG synthesis was secondary to its capacity to increase hOB cell IL-1 beta production. TGF beta regulation of PG production was not affected by the addition of the neutralizing antibody. These studies support the proposition that PGs can be important autocrine/paracrine mediators of bone biology, whose production by hOB cells is responsively regulated by osteotropic cytokines.     

Further genetic analysis of the C-terminal external loop region in Escherichia coli maltoporin

LamB specifically facilitates the diffusion of maltose and maltodextrins through the bacterial outer membrane, and acts as a general (i.e. non-specific) porin for small hydrophilic molecules (< 600 daltons). We reported previously that deletion of the last predicted external domain near the C-terminus of the Eschirichia coli LamB protein (residues 376 to 405), affected in vivo the binding and transport of maltodextrins (specific pore functions), and also increased bacterial sensitivity to large antibiotics. The residues covered by this deletion correspond almost exactly to the major cell surface loop of LamB on the structural model based on X-ray crystallography (loop L9, residues 375 to 405). The L9 loop comprises a large central portion, which varies in size and sequence between the LamB proteins from different species. This variable region is flanked by two highly charged and conserved portions, which overlap with the adjacent beta strands. To identify subregions in L9 that influence the pore properties of LamB, we constructed and analysed nine mutants in loop L9 and its flanking sequences. Deletion of the 23-amino-acids central variable portion of the loop (residues 379 to 401), and deletion of the downstream conserved region (residues 402 to 409), only moderately affected specific maltoporin function. In contrast, deletion of the conserved region (residues 372 to 378) upstream of the variable portion strongly decreased specific maltoporin function and also increased sensitivity to large antibiotics, accounting for most, if not all, of the effects of the complete deletion of L9.     

Demonstration of an Na+/H+ exchanger in mouse keratinocytes measured by the novel pH-sensitive fluorochrome SNARF-calcein

In many cell types cytoplasmic alkalization is an early marker for cell activation. An amiloride-sensitive Na+/H+ exchanger is an important regulator of this process. However, in keratinocytes the existence of a Na+/H+ exchanger nor a proliferation-associated increase in intracellular pH (pHi) has been demonstrated. The aim of this study was to investigate whether or not keratinocytes, derived from the BALB/MK cell line, contain a Na+/H+ exchanger and whether cytoplasmic alkalization is proliferation-associated in these cells. This mouse keratinocyte cell line can easily be switched between a proliferative and a quiescent state under defined culture conditions. The novel pH-sensitive dye seminaphthorhodafluor (SNARF)-calcein proved to be very suitable for flow cytometric pHi measurements in BALB/MK cells. Initial measurements of the pHi using a cocktail of the established fluorochromes 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF) and SNARF-1 failed because of the differential uptake and binding kinetics of these pH-sensitive dyes. Using SNARF-calcein we were able to show proliferation to be associated with increased pHi. However, culture conditions were critical for these measurements. Our data indicate that the Na+/H+ exchanger is involved in this process, since acid load and pHi-recovery experiments showed the alkalization to be amiloride-sensitive.     

Comparison of red-green, blue-yellow and achromatic losses in glaucoma

Achromatic losses in glaucoma would be expected to be greater than, or equal to, red-green chromatic losses if the following assumptions are made: (1) the function of the remaining axons is either unchanged or non-selectively reduced; (2) red-green chromatic information is signaled by the midget ganglion cell system; and (3) the function of the magnocellular system is reduced at least as much as that of the midget ganglion cells. This prediction was tested by measuring red-green (along with blue-yellow) mixture thresholds for 1 deg, 0.2 sec test spots presented on a color monitor on a white background of 50 cd/m2. Ellipses were fitted to plots of green contrast as a function of red contrast (or yellow as a function of blue), and major and minor axes of these ellipses were taken as measures of chromatic and achromatic thresholds, respectively. The study population consisted of 29 eyes in 29 patients with early glaucoma; control data were derived from a data bank of 83 normal eyes. Red-green losses were significantly (P < 0.05) greater than achromatic losses in 6 out of the 11 eyes which showed significant losses of either chromatic or achromatic sensitivity (or both). It is concluded that, for these eyes, at least one of the above three assumptions is incorrect.