Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in a simulated osteochondral environment is hydrogel dependent

Hydrogels pose interesting features for cartilage regeneration strategies, such as the option for injectability and in situ gelation resulting in optimal filling of defects. We aimed to study different hydrogels for their capability to support chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs). hBMSCs were encapsulated in alginate, alginate with hyaluronic acid (alginate/HA), fibrin or thermoresponsive HA grafted with poly(N-isopropyl acrylamide) side-chains (HA-pNIPAM). Glycosaminoglycan production and cartilage-related gene expression were significantly higher in hBMSC-alginate and hBMSC-fibrin constructs than in the other constructs. Supplementation of alginate with HA was not beneficial. hBMSC-alginate, hBMSC-fibrin and hBMSC-HA-pNIPAM constructs were placed in simulated defects in osteochondral biopsies and cultured in vitro for 28 d. Biopsies containing hBMSC-alginate and hBMSC-fibrin were implanted subcutaneously in nude mice for 12 weeks. hBMSC-alginate constructs had significantly higher cartilage-related gene expression after 28 d of culture as well as significantly more safranin-O positive repair tissue after 12 weeks in vivo than hBMSC-fibrin constructs. Although initial experiments with hBMSC-hydrogel constructs suggested comparable results of hBMSC-alginate, hBMSC-fibrin and hBMSC-HA-pNIPAM constructs, culture in the osteochondral biopsy model in vitro as well as in vivo revealed differences, suggests that chondrogenesis of hBMSCs in an osteochondral environment is hydrogel-dependent

Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in a simulated osteochondral environment is hydrogel dependent

Hydrogels pose interesting features for cartilage regeneration strategies, such as the option for injectability and in situ gelation resulting in optimal filling of defects. We aimed to study different hydrogels for their capability to support chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBMSCs). hBMSCs were encapsulated in alginate, alginate with hyaluronic acid (alginate/HA), fibrin or thermoresponsive HA grafted with poly(N-isopropyl acrylamide) side-chains (HA-pNIPAM). Glycosaminoglycan production and cartilage-related gene expression were significantly higher in hBMSC-alginate and hBMSC-fibrin constructs than in the other constructs. Supplementation of alginate with HA was not beneficial. hBMSC-alginate, hBMSC-fibrin and hBMSC-HA-pNIPAM constructs were placed in simulated defects in osteochondral biopsies and cultured in vitro for 28 d. Biopsies containing hBMSC-alginate and hBMSC-fibrin were implanted subcutaneously in nude mice for 12 weeks. hBMSC-alginate constructs had significantly higher cartilage-related gene expression after 28 d of culture as well as significantly more safranin-O positive repair tissue after 12 weeks in vivo than hBMSC-fibrin constructs. Although initial experiments with hBMSC-hydrogel constructs suggested comparable results of hBMSC-alginate, hBMSC-fibrin and hBMSC-HA-pNIPAM constructs, culture in the osteochondral biopsy model in vitro as well as in vivo revealed differences, suggests that chondrogenesis of hBMSCs in an osteochondral environment is hydrogel-dependent

Farm characteristics and farmer perceptions associated with bovine tuberculosis incidents in areas of emerging endemic spread

PublishedJournal ArticleWhile much is known about the risk factors for bovine tuberculosis (bTB) in herds located in high incidence areas, the drivers of bTB spread in areas of emerging endemicity are less well established. Epidemiological analysis and intensive social research identified natural and social risk factors that may prevent or encourage the spread of disease. These were investigated using a case-control study design to survey farmers in areas defined as recently having become endemic for bTB (from or after 2006). Telephone surveys were conducted for 113 farms with a recent history of a bTB incident where their officially tuberculosis free status had been withdrawn (OTFW) (cases) and 224 controls with no history of a bTB incident, matched on location, production type and the rate of endemic bTB spread. Farmers were questioned about a range of farm management strategies, farm characteristics, herd health, wildlife and biosecurity measures with a focus on farmer attitudes and behaviours such as farmers' perception of endemicity and feelings of control, openness and social cohesion. Data generated in the telephone surveys was supplemented with existing herd-level data and analysed using conditional logistic regression. Overall, herd size (OR 1.07), purchasing an animal at a cattle market compared to purchasing outside of markets (OR 2.6), the number of contiguous bTB incidents (2.30) and the number of inconclusive reactors detected in the 2 years prior to the case incident (OR 1.95) significantly increased the odds of a bTB incident. Beef herds using a field parcel more than 3.2km away from the main farm and dairy herds reporting Johne's disease in the previous 12 months were 3.0 and 4.7 times more likely to have a recent history of a bTB incident, respectively. Beef herds reporting maize growing near, but not on, their farm were less likely to be case herds. Operating a closed farm in the two years prior to the case breakdown did not reduce the odds of a bTB incident. Farmers that had recently experienced a bTB incident were more likely to have implemented badger biosecurity in the previous year, but no more likely than control farms to have implemented cattle biosecurity. Case farmers felt significantly less likely to be influenced by government, vets or other farmers compared to those with no history of bTB. This suggests that alternative methods of engaging with farmers who have recently had a breakdown may need to be developed.This research was funded by Defra (project code SE3045). We would like to thank the farmers and vets that participated in the research; Alison Prosser (APHA) for data support; Rosie Sallis and Jemma Aston (APHA) for project management, and Sara Downs, Amie Adkin and Colin Birch (APHA) for additional support. Thanks to the SE3045 project board for their contribution to the project. Thanks to Nick Lewis, Will Barber, Erin Shrimpton, Phil Wilson, Jacquetta Whatt-Watts, Alice Hamilton-Webb and Bethany Ledingham who conducted telephone interviews and Rob Berry for database assistance. Many thanks to Professor Glyn Hewinson, APHA and Professor Dirk Pfeiffer, RVC for helpful comments on the manuscript