Glucose-induced down regulation of thiamine transporters in the kidney proximal tubular epithelium produces thiamine insufficiency in diabetes

Increased renal clearance of thiamine (vitamin B1) occurs in experimental and clinical diabetes producing thiamine insufficiency mediated by impaired tubular re-uptake and linked to the development of diabetic nephropathy. We studied the mechanism of impaired renal re-uptake of thiamine in diabetes. Expression of thiamine transporter proteins THTR-1 and THTR-2 in normal human kidney sections examined by immunohistochemistry showed intense polarised staining of the apical, luminal membranes in proximal tubules for THTR-1 and THTR-2 of the cortex and uniform, diffuse staining throughout cells of the collecting duct for THTR-1 and THTR-2 of the medulla. Human primary proximal tubule epithelial cells were incubated with low and high glucose concentration, 5 and 26 mmol/l, respectively. In high glucose concentration there was decreased expression of THTR-1 and THTR-2 (transporter mRNA: −76% and −53% respectively, p<0.001; transporter protein −77% and −83% respectively, p<0.05), concomitant with decreased expression of transcription factor specificity protein-1. High glucose concentration also produced a 37% decrease in apical to basolateral transport of thiamine transport across cell monolayers. Intensification of glycemic control corrected increased fractional excretion of thiamine in experimental diabetes. We conclude that glucose-induced decreased expression of thiamine transporters in the tubular epithelium may mediate renal mishandling of thiamine in diabetes. This is a novel mechanism of thiamine insufficiency linked to diabetic nephropathy

Vitamin D Induction of the Human Antimicrobial Peptide Cathelicidin in the Urinary Bladder

The urinary tract is frequently being exposed to potential pathogens and rapid defence mechanisms are therefore needed. Cathelicidin, a human antimicrobial peptide is expressed and secreted by bladder epithelial cells and protects the urinary tract from infection. Here we show that vitamin D can induce cathelicidin in the urinary bladder. We analyzed bladder tissue from postmenopausal women for expression of cathelicidin, before and after a three-month period of supplementation with 25-hydroxyvitamin D3 (25D3). Cell culture experiments were performed to elucidate the mechanisms for cathelicidin induction. We observed that, vitamin D per se did not up-regulate cathelicidin in serum or in bladder tissue of the women in this study. However, when the bladder biopsies were infected with uropathogenic E. coli (UPEC), a significant increase in cathelicidin expression was observed after 25D3 supplementation. This observation was confirmed in human bladder cell lines, even though here, cathelicidin induction occurred irrespectively of infection. Vitamin D treated bladder cells exerted an increased antibacterial effect against UPEC and colocalization to cathelicidin indicated the relevance of this peptide. In the light of the rapidly growing problem of resistance to common urinary tract antibiotics, we suggest that vitamin D may be a potential complement in the prevention of UTI

Plant defences mediate interactions between herbivory and the direct foliar uptake of atmospheric reactive nitrogen

Reactive nitrogen from human sources (e.g., nitrogen dioxide, NO2) is taken up by plant roots following deposition to soils, but can also be assimilated by leaves directly from the atmosphere. Leaf uptake should alter plant metabolism and overall nitrogen balance and indirectly influence plant consumers; however, these consequences remain poorly understood. Here we show that direct foliar assimilation of NO2 increases levels of nitrogen-based defensive metabolites in leaves and reduces herbivore consumption and growth. These results suggest that atmospheric reactive nitrogen could have cascading negative effects on communities of herbivorous insects. We further show that herbivory induces a decrease in foliar uptake, indicating that consumers could limit the ability of vegetation to act as a sink for nitrogen pollutants (e.g., smog from mobile emissions). Our study suggests that the interactions of foliar uptake, plant defence and herbivory could have significant implications for understanding the environmental consequences of reactive nitrogen

The Heroic and the Villainous: a qualitative study characterising the role models that shaped senior doctors’ professional identity

The successful development and sustaining of professional identity is critical to being a successful doctor. This study explores the enduring impact of significant early role models on the professional identity formation of senior doctors.Personal Interview Narratives were derived from the stories told by twelve senior doctors as they recalled accounts of people and events from the past that shaped their notions of being a doctor. Narrative inquiry methodology was used to explore and analyse video recording and transcript data from interviews.Role models were frequently characterised as heroic, or villainous depending on whether they were perceived as good or bad influences respectively. The degree of sophistication in participants' characterisations appeared to correspond with the stage of life of the participant at the time of the encounter. Heroes were characterised as attractive, altruistic, caring and clever, often in exaggerated terms. Conversely, villains were typically characterised as direct or covert bullies. Everyday events were surprisingly powerful, emotionally charged and persisted in participants' memories much longer than expected. In particular, unresolved emotions dating from encounters where bullying behaviour had been witnessed or experienced were still apparent decades after the event.The characterisation of role models is an important part of the professional identity and socialisation of senior doctors. The enduring impact of what role models say and do means that all doctors, need to consistently reflect on how their own behaviour impacts the development of appropriate professional behaviours in both students and training doctors. This is especially important where problematic behaviours occur as, if not dealt with, they have the potential for long-lasting undesirable effects. The importance of small acts of caring in building a nurturing and supportive learning atmosphere at all stages of medical education cannot be underestimated