Insulin and insulin-like growth factor-I responsiveness and signalling mechanisms in C2C12 satellite cells: effect of differentiation and fusion

AbstractIn proliferating C2C12 myoblasts, serum and physiological concentrations of insulin and IGF-I stimulated protein synthesis and RNA accretion. After fusion, the multinucleated myotubes remained responsive to serum but not to insulin or IGF-I, even though both insulin and type-1 IGF receptor mRNAs increased in abundance. Protein synthetic responses to insulin and IGF-I in myoblasts were not inhibited by dexamethasone, ibuprofen or Ro-31-8220, thus phospholipase A2, cyclo-oxygenase and protein kinase C did not appear to be involved in the signalling mechanisms. Neither apparently were polyphosphoinositide-specific phospholipase C or phospholipase D since neither hormone increased inositol phosphate, phosphatidic acid, choline or phosphatidylbutanol production. Only the phosphatidylinositol-3-kinase inhibitor, wortmannin, and the 70 kDa S6-kinase inhibitor, rapamycin, wholly or partially blocked the effects of insulin and IGF-I on protein synthesis. 2-deoxyglucose uptake remained responsive to insulin and IGF-I after fusion and was also inhibited by wortmannin. The results suggest that the loss of responsiveness after fusion is not due to loss of receptors, but to the uncoupling of a post-receptor pathway, occurring after the divergence of the glucose transport and protein synthesis signalling systems, and that, if wortmannin acts at a single site, this is prior to that point of divergence

Readiness to enter the workforce: perceptions of health professions students at a regional Australian university

Background: Perceived readiness for practice can help mitigate the stress and uncertainty associated with transitioning from university into the workforce. This study aimed to identify factors influencing the readiness for clinical practice among final-year medical, dental, and pharmacy students at an Australian regional university. Methods: The study utilised a sequential explanatory mixed-methods approach with surveys administered for the quantitative phase and interviews/focus groups for the qualitative phase. Descriptive statistics and inductive thematic analysis were utilised for the quantitative and qualitative data, respectively. Triangulation of findings from both phases facilitated in-depth understanding of the factors that influenced participants’ self-perceived readiness for clinical practice. Results: From the three disciplines, 132 students completed the survey and 14 participated in the focus groups and interviews. Students felt most prepared in their patient-centred capabilities, core skills, and advanced consultation skills, and least prepared in their system-related capabilities and clinical care skills. Themes identified as essential enablers and confidence builders in relation to workforce readiness in all three disciplines were: gained knowledge and skills, value of clinical placement experiences, support from peers, family and staff. However, students felt their work-readiness was impaired by heavy academic workloads and poor knowledge of health care systems, which affected skills development. Participants suggested additional support in health care system and clinical governance, mental healthcare, and induction to placement sites to further improve their work readiness. Conclusions: The findings of this study suggest that improving work-readiness of healthcare students requires alignment of learning needs to real-world practice opportunities, ensuring support systems are appropriate, and early familiarisation with the healthcare system

Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

“The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

Arylstibonic acids are potent and isoform-selective inhibitors of Cdc25a and Cdc25b phosphatases

Arylstibonates structurally resemble phosphotyrosine side chains in proteins and here we addressed the ability of such compounds to act as inhibitors of a panel of mammalian tyrosine and dual-specificity phosphatases. Two arylstibonates both possessing a carboxylate side chain were identified as potent inhibitors of the protein tyrosine phosphatase PTP-β. In addition, they inhibited the dual-specificity, cell cycle regulatory phosphatases Cdc25a and Cdc25b with sub-micromolar potency. However, the Cdc25c phosphatase was not affected demonstrating that arylstibonates may be viable leads from which to develop isoform specific Cdc25 inhibitors

Weight management

Kelly is a mother of two young children and you, the pharmacist, know her well. Today she comes in to ask for your advice. She explains that she has put on 20 kg over the last two years, and she is concerned that her weight will continue to increase if she doesn't make some changes

Nocturnal enuresis

Although nocturnal enuresis (or 'bedwetting') is common in young children, it is regarded in the majority of cases as part of the normal process of developing continence. It can, however, have a significant psychological impact on a young child, both emotionally and socially, and may be associated with feelings of helplessness, guilt, shame and loss of self esteem. Parents or carers may feel angry and frustrated as they do not know how to help their child and will often turn to a health professional for advice

Design, development and delivery of a pharmacist tutor training program at James Cook University

Background: The worldwide increase in demand for academic staff in higher education over recent years has resulted in the employment of increasing numbers of sessional staff. This trend towards casual or sessional employment of academic staff has been of benefit to universities, providing both cost savings as well as increased diversity and flexibility of student education. For health professional programs, the use of practicing health professionals on a sessional basis has been invaluable in ensuring that student education is both current and relevant to their chosen profession. In terms of teaching workload, it has been estimated that internationally, a half of all teaching in tertiary institutions is undertaken by sessional staff.\ud \ud Recent Australian statistics indicate that sessional staff are estimated to comprise approximately a quarter of the workforce in higher education institutions and are responsible for 50% of the teaching in universities. This high teaching load of sessional academics, in combination with a lack of attention being paid to their management and support, has potential implications for the quality of teaching and learning at universities. Sessional staff training and support programs have become well established in higher education institutions in both the United States of America (USA) and the United Kingdom (UK), and are now being developed in the majority of universities around Australia. It is recognized that while general university wide policies are required for the support and management of sessional staff, training programs should be tailored to suit both the requirements of the particular institution and the specific school or discipline. For this reason, programs may vary widely in terms of structure and content, both within and between institutions. At the James Cook University (JCU), a general university-wide sessional staff orientation and training program has been in place since 2005 and attendance at this program is a requirement of ongoing employment for all JCU sessional staff. For tutors in the Discipline of Pharmacy, while this introductory session provides a good induction to the university environment and the process of student education, it is not pharmacy specific and in addition it does not address the ongoing needs of sessional staff.\ud \ud Aim: The aim of this study was therefore to design, develop and evaluate a tutor training program specifically for pharmacist tutors in the Discipline of Pharmacy at James Cook University.\ud \ud Methodology: In order to inform the design of the training program, a needs analysis study was conducted, which involved the development of a tutor questionnaire, which was sent to 40 past, present and potential pharmacist tutors at JCU. The questionnaire was used to inform a series of three focus groups involving pharmacist tutors, pharmacy academic staff and pharmacy students. Data from the tutor questionnaire was evaluated using mixed methods, integrating qualitative and quantitative data collection and analysis, with the data from the focus groups being analyzed using qualitative thematic analysis.\ud \ud The pharmacist tutor training program was implemented for the 14 currently employed tutors in February 2013 and evaluated using two post training self-evaluation surveys. The first survey, distributed immediately after the face-to-face training session, assessed the usefulness and relevance of the training program. The second survey, distributed after one full semester of tutoring, obtained general information on perceived program benefits, problems experienced and potential future program topics. The second survey also required that respondents self-rate their competence levels at three stages in their development as tutors: prior to the program, immediately after the program and then again after one full semester. Competence ratings were obtained for a range of tutoring skills and attributes, including confidence, marking and assessment and teaching knowledge and skills. Data from the two post-training surveys was analyzed, again by the use of mixed methods combining both quantitative data analysis and qualitative thematic analysis.\ud \ud Results and discussion: The needs analysis study highlighted the importance of pharmacist tutor involvement in the practical areas of the pharmacy curriculum, which included clinical dispensing, extemporaneous dispensing and clinical counselling. The tutor's role in marking and assessment was identified as an area for concern. The most important perceived benefits of a training program were enhanced teaching consistency and student learning and increased tutor confidence. Four major content areas for a tutor training program were identified as the provision of effective student feedback, student assessment, teaching practical skills and teaching communication skills.\ud \ud The results of the first post-training feedback survey were overwhelmingly positive, with the majority of the 12 tutor respondents (83%) indicating that the content of the program was relevant and that the program had met their current needs. Tutors felt that the main benefits of the program were an increase in general confidence levels, the opportunity for interaction with other tutors and staff, a better understanding of their roles and expectations and the acknowledgement of tutors as an integral part of the pharmacy teaching team. Importantly, tutors found that the topic of 'Assessing student learning' was one of the most useful sections of the training program, with 92% of tutors rating this section as either very useful or mostly useful. This indicated that the program had appropriately addressed the problem area of assessment and marking. The findings of the second evaluation survey showed that tutor self-competence had improved in all suggested areas of competence between just prior to the program and after one full semester of tutoring, with the most significant improvement occurring in the area of marking and assessment. Initial competence prior to training was rated as average to good in most areas, while competence after one full semester of tutoring was rated as good to very good.\ud \ud Conclusions: This study clearly indicates that the JCU pharmacist tutor training program has been successfully designed, developed and delivered to meet the needs of pharmacist tutors, in addition to delivering other benefits, including an improvement in both tutor confidence and competence. This program has also contributed towards the integration of pharmacist tutors into the Discipline of Pharmacy teaching team, which in turn will play a role in supporting academic staff in delivering improved learning outcomes for pharmacy students in the program at JCU

Weight loss product usage and advice in community pharmacies in North Queensland

Introduction. Obesity is currently one of the greatest health challenges in Australia, particularly in North Queensland, where in 2011-12, 75% of people living in the Townsville Mackay Region were either overweight or obese.1 Community Pharmacies play a significant role in the management of obesity through the provision of weight management programs and products as well as by providing weight loss advice to consumers. However, there is limited information available regarding the weight loss products that are recommended by pharmacies, whether they are providing evidenced based advice and whether consumers are making appropriate weight loss product choices. Aims. To identify trends in weight loss product recommendations and advice provided by pharmacies to consumers, to ascertain consumer usage patterns and to investigate the reasons for consumer choices of weight loss products. Methods. This project involved the distribution of a questionnaire to North Queensland Pharmacies. Responding pharmacies were then asked to distribute a brief survey to their consumers on the purchase of a weight loss product. Results. 78 different products were listed among the top 10 weight loss products sold by the respondent pharmacies. Both the pharmacist and consumer surveys indicated that the most popular weight loss products were meal replacements, with complementary medicines also being used by a significant number of consumers. Consumers were found to be predominantly female between the age of 26 and 45 years. Information sources used by community pharmacies for the provision of weight loss advice showed potential for bias as they were mainly from company weight loss product or program resources. Discussion. There is a need for more evidence based weight management training resources for community pharmacies. There is also a need for increased consumer awareness of the available evidence or lack of evidence for many weight loss products. Meal replacement products are a popular choice of product with some evidence of short-term benefits, however further studies to determine the long term efficacy of these products may be warranted. Given the higher obesity levels of males compared to females,1 consideration should also be given to increasing the promotion of weight loss services to the male population