A Novel High-Throughput Assay for Islet Respiration Reveals Uncoupling of Rodent and Human Islets

The pancreatic beta cell is unique in its response to nutrient by increased fuel oxidation. Recent studies have demonstrated that oxygen consumption rate (OCR) may be a valuable predictor of islet quality and long term nutrient responsiveness. To date, high-throughput and user-friendly assays for islet respiration are lacking. The aim of this study was to develop such an assay and to examine bioenergetic efficiency of rodent and human islets.The XF24 respirometer platform was adapted to islets by the development of a 24-well plate specifically designed to confine islets. The islet plate generated data with low inter-well variability and enabled stable measurement of oxygen consumption for hours. The F1F0 ATP synthase blocker oligomycin was used to assess uncoupling while rotenone together with myxothiazol/antimycin was used to measure the level of non-mitochondrial respiration. The use of oligomycin in islets was validated by reversing its effect in the presence of the uncoupler FCCP. Respiratory leak averaged to 59% and 49% of basal OCR in islets from C57Bl6/J and FVB/N mice, respectively. In comparison, respiratory leak of INS-1 cells and C2C12 myotubes was measured to 38% and 23% respectively. Islets from a cohort of human donors showed a respiratory leak of 38%, significantly lower than mouse islets.The assay for islet respiration presented here provides a novel tool that can be used to study islet mitochondrial function in a relatively high-throughput manner. The data obtained in this study shows that rodent islets are less bioenergetically efficient than human islets as well as INS1 cells

α7-Nicotinic Acetylcholine Receptor: Role in Early Odor Learning Preference in Mice

Recently, we have shown that mice with decreased expression of α7-nicotinic acetylcholine receptors (α7) in the olfactory bulb were associated with a deficit in odor discrimination compared to wild-type mice. However, it is unknown if mice with decreased α7-receptor expression also show a deficit in early odor learning preference (ELP), an enhanced behavioral response to odors with attractive value observed in rats. In this study, we modified ELP methods performed in rats and implemented similar conditions in mice. From post-natal days 5–18, wild-type mice were stroked simultaneously with an odor presentation (conditioned odor) for 90 s daily. Control mice were only stroked, exposed to odor, or neither. On the day of testing (P21), mice that were stroked in concert with a conditioned odor significantly investigated the conditioned odor compared to a novel odor, as observed similarly in rats. However, mice with a decrease in α7-receptor expression that were stroked during a conditioned odor did not show a behavioral response to that odorant. These results suggest that decreased α7-receptor expression has a role in associative learning, olfactory preference, and/or sensory processing deficits

Convergence of Cells from the Progenitor Fraction of Adult Olfactory Bulb Tissue to Remyelinating Glia in Demyelinating Spinal Cord Lesions

Progenitor cells isolated from adult brain tissue are important tools for experimental studies of remyelination. Cells harvested from neurogenic regions in the adult brain such as the subependymal zone have demonstrated remyelination potential. Multipotent cells from the progenitor fraction have been isolated from the adult olfactory bulb (OB) but their potential to remyelinate has not been studied. cell bodies adjacent to and surrounding peripheral-type myelin rings.We report that neural cells from the progenitor fraction of the adult rat OB grown in monolayers can be expanded for several passages in culture and that upon transplantation into a demyelinated spinal cord lesion provide extensive remyelination without ectopic neuronal differentiation

Medicines use reviews: a potential resource or lost opportunity for general practice?

Background: Patient non-adherence to medicines represents a significant waste of health resource and lost opportunity for health gain. Medicine management services are a key health policy strategy to encourage patients to take medicines as they are prescribed. One such service is the English Medicines Use Review (MUR) which is an NHS-funded community pharmacy service involving a patient-pharmacist consultation aiming to improve patients’ knowledge of medicines and their use. To date the evidence for MURs to improve patient health outcomes is equivocal and GPs are reported to be sceptical about the value of the service. This paper presents the patient’s perspective of the MUR service and focuses on the importance of GP-pharmacist collaboration for patient care. Suggestions on how MURs may have value to GPs through the delivery of increased patient benefit are discussed. Method: A qualitative study involving ten weeks of ethnographic observations in two English community pharmacies. Observations were made of all pharmacy activities including patient-pharmacist MUR consultations. Subsequent interviews with these patients were conducted to explore their experience of the service. Interviews with the pharmacy staff were conducted after the period of observations. A thematic approach was used to analyse the data. Results: Fifty-four patients agreed to have their MUR observed of which thirty-four were interviewed. Seventeen pharmacy staff were also interviewed. Patients reported positive views about MURs. However, there was little evidence suggesting that pharmacists and GPs were working collaboratively or communicating outcomes resulting from MURs. MURs were conducted in isolation from other aspects of patient care. Patients considered GPs to have authority over medicines making a few wary that MURs had the potential to cause tensions between these professionals and possibly adversely affect their own relationship with their doctor. Conclusions: This study reveals the potential for effective GP-pharmacist collaboration to improve the capacity of the MUR service to support patient medicine taking. Closer collaboration between GPs and pharmacists could potentially improve patients’ use of medicines and associated health care outcomes. The current lack of such collaboration constitutes a missed opportunity for pharmacists and GPs to work together with patients to improve effective prescribing and optimise patient use of medicines