Mechanisms of aminoglycoside ototoxicity and targets of hair cell protection.

Aminoglycosides are commonly prescribed antibiotics with deleterious side effects to the inner ear. Due to their popular application as a result of their potent antimicrobial activities, many efforts have been undertaken to prevent aminoglycoside ototoxicity. Over the years, understanding of the antimicrobial as well as ototoxic mechanisms of aminoglycosides has increased. These mechanisms are reviewed in regard to established and potential future targets of hair cell protection.

Spatial Distribution of Stem Cell-Like Keratinocytes in Dissected Compound Hair Follicles of the Dog

Hair cycle disturbances are common in dogs and comparable to some alopecic disorders in humans. A normal hair cycle is maintained by follicular stem cells which are predominately found in an area known as the bulge. Due to similar morphological characteristics of the bulge area in humans and dogs, the shared particularity of compound hair follicles as well as similarities in follicular biomarker expression, the dog is a promising model to study human hair cycle and stem cell disorders. To gain insight into the spatial distribution of follicular keratinocytes with stem cell potential in canine compound follicles, we microdissected hair follicles in anagen and telogen from skin samples of freshly euthanized dogs. The keratinocytes isolated from different locations were investigated for their colony forming efficiency, growth and differentiation potential as well as clonal growth. Our results indicate that i) compound and single hair follicles exhibit a comparable spatial distribution pattern with respect to cells with high growth potential and stem cell-like characteristics, ii) the lower isthmus (comprising the bulge) harbors most cells with high growth potential in both, the anagen and the telogen hair cycle stage, iii) unlike in other species, colonies with highest growth potential are rather small with an irregular perimeter and iv) the keratinocytes derived from the bulbar region exhibit characteristics of actively dividing transit amplifying cells. Our results now provide the basis to conduct comparative studies of normal dogs and those with hair cycle disorders with the possibility to extend relevant findings to human patients.

(Table 1) Cortisol concentration in hair of East Greenland polar bears (Ursus maritimus)

To demonstrate the ability to assess long-term hypothalamic-pituitary-adrenocortical (HPA) axis activity in polar bears (Ursus maritimus), a pilot study was conducted in which cortisol concentration was analyzed in hair from 7 female (3-19 years) and 10 male (6-19 years) East Greenland polar bears sampled in 1994-2006. The hair was chosen as matrix as it is non-invasive, seasonally harmonized, and has been validated as an index of long-term changes in cortisol levels. The samples were categorized according to contamination: eight were clean (2 females, 6 males), 5 had been contaminated with bear blood (2 F, 3 M), and 4 with bear fat (3 F, 1 M). There was no significant difference in cortisol concentration between the three categories after external contamination was removed. However, contaminated hair samples should be cleaned before cortisol determination. Average hair cortisol concentration was 8.90 pg/mg (range: 5.5 to 16.4 pg/mg). There was no significant correlation between cortisol concentration and age (p = 0.81) or sampling year (p = 0.11). However, females had higher mean cortisol concentration than males (females mean: 11.0 pg/mg, males: 7.3 pg/mg; p = 0.01). The study showed that polar bear hair contains measurable amounts of cortisol and that cortisol in hair may be used in studies of long-term stress in polar bears.

(Table 1) Concentration of pollutants in hair of East Greenland polar bears (Ursus maritimus)

Hair sampled from 96 East Greenland polar bears (Ursus maritimus) over the periods 1892-1927 and 1988-2009 was analyzed for cortisol as a proxy to investigate temporal patterns of environmental stress. Cortisol concentration was independent of sex and age, and was found at significantly higher (p<0.001) concentrations in historical hair samples (1892-1927; n = 8) relative to recent ones (1988-2009; n = 88). In addition, there was a linear time trend in cortisol concentration of the recent samples (p< 0.01), with an annual decrease of 2.7%. The recent hair samples were also analyzed for major bioaccumulative, persistent organic pollutants (POPs). There were no obvious POP related time trends or correlations between hair cortisol and hair POP concentrations. Thus, polar bear hair appears to be a relatively poor indicator of the animal's general POP load in adipose tissue. However, further investigations are warranted to explore the reasons for the temporal decrease found in the bears' hair cortisol levels.

(Table 1) Concentration of organohalogenated compounds in clean and contaminated hair of polar bears (Ursus maritimus) from East Greenland

In this pilot study, we report on levels of persistent organohalogenated contaminants (OHCs) in hair of polar bears (Ursus maritimus) from East Greenland sampled between 1999 and 2001. To our knowledge, this is the first study on the validation of polar bear hair as a non-invasive matrix representative of concentrations and profiles in internal organs and blood plasma. Because of low sample weights (13-140 mg), only major bioaccumulative OHCs were detected above the limit of quantification: five polychlorinated biphenyl (PCB) congeners (CB 99, 138, 153, 170 and 180), one polybrominated diphenyl ether (PBDE) congener (BDE 47), oxychlordane, trans-nonachlor and ß-hexachlorocyclohexane. The PCB profile in hair was similar to that of internal tissues (i.e. adipose, liver, brain and blood), with CB 153 and 180 as the major congeners in all matrices. A gender difference was found for concentrations in hair relative to concentrations in internal tissues. Females (n = 6) were found to display negative correlations, while males (n = 5) showed positive correlations, although p-values were not found significant. These negative correlations in females may reflect seasonal OHC mobilisation from periphery adipose tissue due to, for example, lactation and fasting. The lack of significance in most correlations may be due to small sample sizes and seasonal variability of concentrations in soft tissues. Further research with larger sample weights and sizes is therefore necessary to draw more definitive conclusions on the usefulness of hair for biomonitoring OHCs in polar bears and other fur mammals.

Relationship between fibre orientation and tensile strength of natural collagen membranes for heart valve leaflets

Heart valve prostheses are used to replace native heart valves which that are damaged because of congenital diseases or due to ageing. Biological prostheses made of bovine pericardium are similar to native valves and do not require any anticoagulation treatment, but are less durable than mechanical prostheses and usually fail by tearing. Researches are oriented in improving the resistance and durability of biological heart valve prostheses in order to increase their life expectancy. To understand the mechanical behaviour of bovine pericardium and relate it to its microstructure (mainly collagen fibres concentration and orientation) uniaxial tensile tests have been performed on a model material made of collagen fibres. Small Angle Light Scattering (SALS) has been also used to characterize the microstructure without damaging the material. Results with the model material allowed us to obtain the orientation of the fibres, relating the microstructure to mechanical performance

Effect of sugar beet pulp fibre fractions on growth performance, fecal digestibility and digestive physiology in rabbits around weaning

The present study investigated the effect of the different fibre components of sugar beet pulp (SBP) on growth performance and some digestive traits. Four semi-synthetic diets were formulated with similar NDF (33% DM) and protein (16% DM) level. Control diet was formulated to contain the lowest level of soluble fibre (3% DM) and SBP diet the highest (9%). The soluble (pectins) and insoluble fractions of SBP were studied in other two diets (Pectin and InsSBP diets). A total of 136 weanling rabbits (25 d of age) was housed individually, randomly assigned to 4 experimental groups, and fed ad libitum with the experimental diets during 10 days after weaning. The type of diet did not affect growth rate and stomach pH. Animals fed with SBP diet showed higher DM and NDF digestibility (4 and 83%, respectively), gain:feed ratio (13%), cecal and total tract weight (13 and 9%) and ileal viscosity (148%) than rabbits fed the Control diet, but lower cecal pH (9%). Pectin diet increased ileal viscosity and decreased the weight of stomach content with respect to SBP diet. Rabbits fed InsSBP diet showed similar results to SBP diet but lower ileal viscosity and cecal pH than those fed Pectin diet. In conclusion, SBP and their soluble and insoluble fractions are well digested in young rabbits. However the soluble and insoluble fibre of SBP produce different effects in the gastrointestinal tract.

A robust numerical framework for the analysis of material failure of fibre reinforced soft tissue

In this work, robustness and stability of continuum damage models applied to material failure in soft tissues are addressed. In the implicit damage models equipped with softening, the presence of negative eigenvalues in the tangent elemental matrix degrades the condition number of the global matrix, leading to a reduction of the computational performance of the numerical model. Two strategies have been adapted from literature to improve the aforementioned computational performance degradation: the IMPL-EX integration scheme [Oliver,2006], which renders the elemental matrix contribution definite positive, and arclength-type continuation methods [Carrera,1994], which allow to capture the unstable softening branch in brittle ruptures. The IMPL-EX integration scheme has as a major drawback the need to use small time steps to keep numerical error below an acceptable value. A convergence study, limiting the maximum allowed increment of internal variables in the damage model, is presented. Finally, numerical simulation of failure problems with fibre reinforced materials illustrates the performance of the adopted methodology.