Nutritional status and the gonadotrophic response to a polar expedition.

Polar expeditions have been associated with changes in the hypothalamic-pituitary-testicular axis consistent with central hypogonadism (i.e., decreased testosterone, luteinising hormone (LH), and follicle stimulating hormone (FSH)). These changes are typically associated with body mass loss. Our aim was to evaluate whether maintenance of body mass during a polar expedition could mitigate against the development of central hypogonadism. Male participants (n = 22) from a 42-day expedition (British Services Antarctic Expedition 2012) volunteered to take part in the study. Body mass, body composition, and strength data were recorded pre- and postexpedition in addition to assessment of serum testosterone, LH, FSH, thyroid hormones, insulin-like growth factor 1 (IGF-1), and trace elements. Energy provision and energy expenditure were assessed at mid- and end-expedition. Daily energy provision was 6335 ± 149 kcal·day(-1). Estimated energy expenditure midexpedition was 5783 ± 1690 kcal·day(-1). Body mass and percentage body fat did not change between pre- and postexpedition. Total testosterone (nmol·L(-1)) (14.0 ± 4.9 vs. 17.3 ± 4.0, p = 0.006), calculated free testosterone (pmol·L(-1)) (288 ± 82 vs. 350 ± 70, p = 0.003), and sex hormone binding globulin (nmol·L(-1)) (33 ± 12 vs. 36 ± 11, p = 0.023) concentrations increased. LH and FSH remained unchanged. Thyroid stimulating hormone (TSH; IU·L(-1)) (2.1 ± 0.8 vs. 4.1 ± 2.1, p < 0.001) and free triiodothyronine (FT3; IU·L(-1)) (5.4 ± 0.4 vs. 6.1 ± 0.8, p < 0.001) increased while free thyroxine, IGF-1, and trace elements remained unchanged. Hand-grip strength was reduced postexpedition but static lift strength was maintained. Maintenance of body mass and nutritional status appeared to negate the central hypogonadism previously reported from polar expeditions. The elevated TSH and free FT3 were consistent with a previously reported "polar T3 syndrome"

Characterisation and In Vitro Antimicrobial Activity of Biosynthetic Silver-loaded Bacterial Cellulose Hydrogels

Wounds that remain in the inflammatory phase for a prolonged period of time are likely to be colonised and infected by a range of commensal and pathogenic microorganisms. Treatment associated with these types of wounds mainly focuses on controlling infection and providing an optimum environment capable of facilitating re-epithelialisation, thus promoting wound healing. Hydrogels have attracted vast interest as moist wound-responsive dressing materials. In the current study, biosynthetic bacterial cellulose hydrogels synthesised by Gluconacetobacter xylinus and subsequently loaded with silver were characterised and investigated for their antimicrobial activity against two representative wound infecting pathogens, namely S. aureus and P. aeruginosa. Silver nitrate and silver zeolite provided the source of silver and loading parameters were optimised based on experimental findings. The results indicate that both AgNO3 and AgZ loaded biosynthetic hydrogels possess antimicrobial activity (p < .05) against both S. aureus and P. aeruginosa and may therefore be suitable for wound management applications

Liposome encapsulated Disulfiram inhibits NFκB pathway and targets breast cancer stem cells in vitro and in vivo

Breast cancer stem cells (BCSCs) are pan-resistant to different anticancer agents and responsible for cancer relapse. Disulfiram (DS), an antialcoholism drug, targets CSCs and reverses pan-chemoresistance. The anticancer application of DS is limited by its very short half-life in the bloodstream. This prompted us to develop a liposomeencapsulated DS (Lipo-DS) and examine its anticancer effect and mechanisms in vitro and in vivo. The relationship between hypoxia and CSCs was examined by in vitro comparison of BC cells cultured in spheroid and hypoxic conditions. To determine the importance of NFκB activation in bridging hypoxia and CSC-related pan-resistance, the CSC characters and drug sensitivity in BC cell lines were observed in NFκB p65 transfected cell lines. The effect of Lipo-DS on the NFκB pathway, CSCs and chemosensitivity was investigated in vitro and in vivo. The spheroid cultured BC cells manifested CSC characteristics and pan-resistance to anticancer drugs. This was related to the hypoxic condition in the spheres. Hypoxia induced activation of NFκB and chemoresistance. Transfection of BC cells with NFκB p65 also induced CSC characters and pan-resistance. Lipo-DS blocked NFκB activation and specifically targeted CSCs in vitro. Lipo-DS also targeted the CSC population in vivo and showed very strong anticancer efficacy. Mice tolerated the treatment very well and no significant in vivo nonspecific toxicity was observed. Hypoxia induced NFκB activation is responsible for stemness and chemoresistance in BCSCs. Lipo-DS targets NFκB pathway and CSCs. Further study may translate DS into cancer therapeutics

The reproducibility and sensitivity of sural nerve morphometry in the assessment of diabetic peripheral polyneuropathy

The nerve fibre loss, atrophy and injury of diabetic peripheral polyneuropathy and their responses to metabolic intervention have been studied by morphometric analysis of sural nerve biopsies. The magnitudes and sources of intra- and inter-individual variation in these morphometric measures have not been investigated previously in a systematic manner. Morphometric parameters of nerve fibre damage were measured in four separate fascicles from bilateral sural nerve specimens obtained post-mortem from 13 diabetic and 13 non-diabetic subjects. Intra- and inter-individual coefficients of variation were computed and compared to the magnitude of the differences between normal and diabetic subjects. Several morphometric variables emerged as highly sensitive and reproducible measures of nerve fibre damage suitable for clinical studies of diabetic peripheral polyneuropathy. These observations provide a rational basis for the design of future clinical trials employing morphometric end-points.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46025/1/125_2004_Article_BF00400485.pd

Copeptin reflects physiological strain during thermal stress.

PURPOSE: To prevent heat-related illnesses, guidelines recommend limiting core body temperature (T c) ≤ 38 °C during thermal stress. Copeptin, a surrogate for arginine vasopressin secretion, could provide useful information about fluid balance, thermal strain and health risks. It was hypothesised that plasma copeptin would rise with dehydration from occupational heat stress, concurrent with sympathoadrenal activation and reduced glomerular filtration, and that these changes would reflect T c responses. METHODS: Volunteers (n = 15) were recruited from a British Army unit deployed to East Africa. During a simulated combat assault (3.5 h, final ambient temperature 27 °C), T c was recorded by radiotelemetry to differentiate volunteers with maximum T c > 38 °C versus ≤ 38 °C. Blood was sampled beforehand and afterwards, for measurement of copeptin, cortisol, free normetanephrine, osmolality and creatinine. RESULTS: There was a significant (P  38 °C (n = 8) vs ≤ 38 °C (n = 7) there were significantly greater elevations in copeptin (10.4 vs. 2.4 pmol L(-1)) and creatinine (10 vs. 2 μmol L(-1)), but no differences in cortisol, free normetanephrine or osmolality. CONCLUSIONS: Changes in copeptin reflected T c response more closely than sympathoadrenal markers or osmolality. Dynamic relationships with tonicity and kidney function may help to explain this finding. As a surrogate for integrated physiological strain during work in a field environment, copeptin assay could inform future measures to prevent heat-related illnesses

Growth cone guidance and neuron morphology on micropatterned laminin surfaces

Neurite growth cones detect and respond to guidance cues in their local environment that determine stereotyped pathways during development and regeneration. Micropatterns of laminin (which was found to adsorb preferentially to photolithographically defined hydrophobic areas of micropatterns) were here used to model adhesive pathways that might influence neurite extension. The responses of growth cones were determined by the degree of guidance of neurite extension and also by examining growth cone morphology. These parameters were found to be strongly dependent on the geometry of the patterned laminin, and on neuron type. Decreasing the spacing of multiple parallel tracks of laminin alternating with non-adhesive tracks, resulted in decreased guidance of chick embryo brain neurons. Single isolated 2 microns tracks strongly guided neurite extension whereas 2 microns tracks forming a 4 microns period multiple parallel pattern did not. Growth cones appear to be capable of bridging the narrow non-adhesive tracks, rendering them insensitive to the smaller period multiple parallel adhesive patterns. These observations suggest that growth cones would be unresponsive to the multiple adhesive cues such as would be presented by oriented extracellular matrix or certain axon fascicle structures, but could be guided by isolated adhesive tracks. Growth cone morphology became progressively simpler on progressively narrower single tracks. On narrow period multiple parallel tracks (which did not guide neurite extension) growth cones spanned a number of adhesive/non-adhesive tracks, and their morphology suggests that lamellipodial advance may be independent of the substratum by using filopodia as a scaffold. In addition to acting as guidance cues, laminin micropatterns also appeared to influence the production of primary neurites and their subsequent branching. On planar substrata, dorsal root ganglion neurons were multipolar, with highly branched neurite outgrowth whereas, on 25 microns tracks, neurite branching was reduced or absent, and neuron morphology was typically bipolar. These observations indicate the precision with which growth cone advance may be controlled by substrata and suggest a role for patterned adhesiveness in neuronal morphological differentiation, but also highlight some of the limitations of growth cone sensitivity to substratum cues