Presence of the brown fat-specific mitochondrial uncoupling protein and iodothyronine 5'-deiodinase activity in subcutaneous adipose tissue of neonatal lambs

AbstractSubcutaneous adipose tissue of neonatal lambs has been examined for the presence of markers diagnostic of thermogenic brown fat. Uncoupling protein, uncoupling protein mRNA, and iodothyronine 5'-deiodinase activity were each detected in subcutaneous adipose tissue, as well as in the major internal fat depot (perirenal), of newborn lambs. These brown fat markers were not present, however, in adipose tissue of adult sheep. It is concluded that subcutaneous fat in newborn lambs is functionally ‘brown’, and similar to the internal fat; subcutaneous and internal adipose tissues follow a similar developmental path - from ‘brown’ to ‘white’

Uterine miR-877-3p and let-7a-5p are increased during simulated menstruation in a mouse model

Heavy periods are common and debilitating, but we do not fully understand how they are caused. Increased understanding of menstrual bleeding could result in new treatments for problematic periods. Low oxygen levels are present in the womb lining during a period. These low oxygen levels help trigger the repair process required to stop menstrual bleeding. MicroRNAs (miRNAs) are small molecules that can affect cell function, and some are regulated by oxygen levels. We examined whether such miRNAs were present in the womb lining during a period. To overcome the variability present in humans, we studied the womb of mice given hormones to mimic the human menstrual cycle. We revealed that two miRNAs known to be regulated by oxygen levels were increased in the womb during menstruation. These miRNAs may help regulate menstrual blood loss and merit further study as a potential target for future treatments for heavy periods

Estrogen biosynthesis in human H295 adrenocortical carcinoma cells

Adrenocortical carcinoma is an uncommon malignancy and feminizing symptoms secondary to adrenal estrogen-secretion are extremely rare. The direct secretion of estradiol by adrenocortical tumors requires, in addition to the expression of aromatase (CYP19), the expression of one or more of the reductive 17β-hydroxysteroid dehydrogenases. The expression of CYP19 transcripts and protein were markedly induced in the H295 adrenocortical carcinoma cell line after treatment with either forskolin or vasoactive intestinal peptide (VIP). Western immunoblotting demonstrated a marked induction of the CYP19 protein of characteristic size after only a short (6 h) treatment period with VIP or forskolin. The CYP19 mRNA transcripts were derived from both promoters PII (Ic) and I.3 (Id) after treatment with both agents. The reductive type 5 17β-hydroxysteroid dehydrogenase (AKR1C3) was also constitutively expressed in the H295 cells but neither its mRNA transcript nor protein levels were altered after forskolin or VIP treatment. Western immunoblotting of an estrogen-secreting adrenal carcinoma revealed notable levels of both aromatase and AKR1C3 expression while an aldosterone-producing adrenal adenoma lacked aromatase expression and showed a reduced level of AKR1C3 expression. Immunohistochemistry of the carcinoma-bearing adrenal revealed localization of AKR1C3 not only in the tumor but also principally in the zona reticularis of the normal adrenal tissue. Adrenal aromatase and AKR1C3 expression therefore appear to be features of adrenocortical malignancies that are associated with biosynthesis of active estrogen

Parliament and the Auditor General: The accountability gap and what can be done about it?

Dr Nicol is consulting as the senior researcher on this project. Also participating in the Checks and Balances Project are staff members of the Institute for African Alternatives (IFAA), Bruce Kadalie, who is responsible for IFAA’s events and research, and Moira Levy, production manager of New Agenda

Investigating the effects of Liquorice consumption on Salivary Steroid hormones profile and blood pressure in healthy volunteers

Glycyrrhetinic acid (GA) has diverse in vitro effects as an inhibitor of 11beta hydroxysteroid dehydrogenase (11HSD), 5alpha reductase and hormone receptor binding. However, in vivo GA studies have focussed on the hypertensive effects associated with the syndrome of apparent mineralocorticoid excess (SAME) in which 11HSD inhibition allows glucocorticoid hormones to bind inappropriately to MR and subsequent decreased aldosterone synthesis. Here we consider whether GA's other in vitro effects are reflected in altered steroid hormone profiles in vivo. The effect of liquorice (containing GA) has been assessed by measuring steroid hormone levels in healthy individuals. Ten men and 10 women (18-30 years) were given 100 g liquorice sweets (3% liquorice extract) or non-liquorice containing confectionary for 7 days in a crossover study. Saliva was collected 30 min after waking, at 1100-1300 h and at 1800-2100 h for cortisol, cortisone, aldosterone (Aldo), deoxycorticosterone (DOC), DHEA and testosterone measurements by in-house, sensitive and specific ELISA methods. Systolic blood pressure measured at the end of the two periods of treatment showed non-significant increases (P=0.127) in response to liquorice consumption. Cortisol was significantly higher (P=0.003) and cortisone and aldo were reduced by liquorice (P<0.001) consistent with the SAME. DHEA, testosterone and DOC were increased (P<0.001) possibly because of reduced hepatic clearance. However, these steroids are not 11HSD type 2 substrates indicating liquorice might also have inhibited hepatic 5alpha reductase. Recent studies also implicate the bi-directional 11HSD type1 enzyme in DHEA metabolism. GA is equipotent as an inhibitor of 11HSD type 1 and type 2 oxidase activity. 7-Hydroxy-DHEA, a major metabolite of DHEA is inter-converted with 7-keto-DHEA by 11HSD type 1 and could, therefore, secondarily interfere with DHEA metabolism. We conclude that in addition to cortisol, other biologically active steroid hormones are affected by liquorice. Increased salivary levels of DHEA and testosterone suggest that liquorice modulates their bioavailability.sch_diepub792pu

Paediatric case mix in a rural clinical school is relevant to future practice

Abstract Background Exposure to a representative case mix is essential for clinical learning, with logbooks established as a way of demonstrating patient contacts. Few studies have reported the paediatric case mix available to geographically distributed students within the same medical school. Given international interest in expanding medical teaching locations to rural contexts, equitable case exposure in rural relative to urban settings is topical. The Rural Clinical School of Western Australia locates students up to 3500 km from the urban university for an academic year. There is particular need to examine paediatric case mix as a study reported Australian graduates felt unprepared for paediatric rotations. We asked: Does a rural clinical school provide a paediatric case mix relevant to future practice? How does the paediatric case mix as logged by rural students compare with that by urban students? Methods The 3745 logs of 76 urban and 76 rural consenting medical students were categorised by presenting symptoms and compared to the Australian Institute of Health and Welfare (AIHW) database Major Diagnostic Categories (MDCs). Results Rural and urban students logged core paediatric cases, in similar order, despite the striking difference in geographic locations. The pattern of overall presenting problems closely corresponded to Australian paediatric hospital admissions. Rural students logged 91% of cases in secondary healthcare settings; urban students logged 90% of cases in tertiary settings. The top four presenting problems were ENT/respiratory, gastrointestinal/urogenital, neurodevelopmental and musculoskeletal; these made up 60% of all cases. Rural and urban students logged similar proportions of infants, children and adolescents, with a variety of case morbidity. Conclusions Rural clinical school students logged a mix of core paediatric cases relevant to illnesses of Australian children admitted to public hospitals, with similar order and pattern by age group to urban students, despite major differences in clinical settings. Logged cases met the curriculum learning outcomes of graduates. Minor variations were readily addressed via recommendations about logging. This paper provides evidence of the legitimacy of student logs as useful tools in affirming appropriate paediatric case mix. It validates the rural clinical school context as appropriate for medical students to prepare for future clinical paediatric practice

Feedback learning opportunities from medical student logs of paediatric patients

Abstract Background Feedback can alter medical student logging practices, although most learners feel feedback is inadequate. A varied case mix in rural and urban contexts offers diverse clinical encounters. Logs are an indicator of these clinical experiences, and contain opportunities for feedback, which can greatly influence learning: we labelled these ‘feedback learning opportunities’ (FLOs). We asked:How often do FLOs occur?What are the case complexities of rural compared to urban paediatric logs?Do more complex cases result in more FLOs? Methods In Western Australia, 25% of medical students are dispersed in a Rural Clinical School (RCSWA) up to 2175 miles (3500 km) from the city. Urban students logged 20 written cases; rural students logged a minimum of 25 paediatric cases electronically. These were reviewed to identify FLOs, using a coding convention. FLO categories provided a structure for feedback: medical, professionalism, insufficient, clinical reasoning, student wellbeing, quality and safety, and sociocultural. Each log was assigned an overall primary, secondary or tertiary case complexity. Results There were 76 consenting students in each urban and rural group, providing 3034 logs for analysis after exclusions. FLOs occurred in more than half the logs, with significantly more rural (OR 1.35 95% CI 1.17, 1.56; p < 0.0001). Major FLOs occurred in over a third of logs, but with no significant difference between rural and urban (OR 1.10 95% CI 0.94, 1.28; p = 0.24). Medical FLOs were the most common, accounting for 64.0% of rural and 75.2% of urban FLOs (OR 1.71 95% CI 1.37, 2.12; p < 0.0001). Students logged cases with a variety of complexities. Most cases logged by urban students in a tertiary healthcare setting were of primary and secondary complexity. Major medical FLOs increased with increasing patient complexity, occurring in 32.1% of tertiary complexity cases logged by urban students (p < 0.001). Conclusions Case logs are a valuable resource for medical educators to enhance students’ learning by providing meaningful feedback. FLOs occurred often, particularly in paediatric cases with multiple medical problems. This study strengthens recommendations for regular review and timely feedback on student logs. We recommend the FLOs categories as a framework for medical educators to identify FLOs