Ian Smith

Arginine Vasopressin Is a Much More Potent Stimulus to ACTH Release from Ovine Anterior Pituitary Cells than Ovine Corticotropin-Releasing Factor

Cultured rat and ovine anterior pituitary cells were treated with a range of doses (0.01-1,000 nM) of arginine vasopressin (AVP) and ovine corticotropin-releasing factor (CRF), alone or in combination, and medium and cell content of immunoreactive (ir-)ACTH determined. In rat cells, a dose-response curve to CRF was obtained, with a threshold dose of 0.1 nM; AVP was much less effective alone, but augmented CRF responses when administered with CRF. In ovine pituitary cells AVP markedly stimulated ACTH release in a dose-dependent fashion, and with a threshold of 0.1 nM; in contrast, CRF increased ACTH release over basal only at doses greater than 100 nM. In combination, subthreshold doses of AVP potentiated rat pituitary cell responses to CRF; addition of 1 nM of AVP to varying doses of CRF was more effective in terms of ACTH release than addition of 1 nM of CRF to increasing doses of AVP. In contrast, in ovine cells the addition of 1 nM CRF to increasing doses of AVP elicited a larger ACTH response than the addition of 1 nM AVP to increasing doses of CRF. Dexamethasone pretreatment (5 nM) for 48 h significantly decreased CRF potentiation of AVP-stimulated ACTH release in ovine cells. These studies confirm that CRF is a more potent stimulus of ACTH release than AVP in the rat, and establish that in contrast AVP is a much more potent stimulus of ACTH secretion than CRF in isolated ovine pituitary cells.

A portable system for collecting anatomical joint angles during stair ascent: a comparison with an optical tracking device

BackgroundAssessments of stair climbing in real-life situations using an optical tracking system are lacking, as it is difficult to adapt the system for use in and around full flights of stairs. Alternatively, a portable system that consists of inertial measurement units (IMUs) can be used to collect anatomical joint angles during stair ascent. The purpose of this study was to compare the anatomical joint angles obtained by IMUs to those calculated from position data of an optical tracking device.MethodsAnatomical joint angles of the thigh, knee and ankle, obtained using IMUs and an optical tracking device, were compared for fourteen healthy subjects. Joint kinematics obtained with the two measurement devices were evaluated by calculating the root mean square error (RMSE) and by calculating a two-tailed Pearson product-moment correlation coefficient (r) between the two signals.ResultsStrong mean correlations (range 0.93 to 0.99) were found for the angles between the two measurement devices, as well as an average root mean square error (RMSE) of 4 degrees over all the joint angles, showing that the IMUs are a satisfactory system for measuring anatomical joint angles.ConclusionThese highly portable body-worn inertial sensors can be used by clinicians and researchers alike, to accurately collect data during stair climbing in complex real-life situations.

Many peptides that are present in the external zone of the median eminence are not secreted into the hypophysial portal blood of sheep

Apart from the well recognized factors that are produced by the hypothalamus and secreted into hypophysial portal blood to regulate pituitary function, there is a range of neuropeptides that are present in the median eminence and could be secreted to serve a modulatory function. In this study we have collected hypophysial portal blood and jugular venous blood from sheep in an attempt to identify which of these putative modulatory peptides might be secreted from the median eminence. We have measured neuropeptide Y (NPY), substance P (SP), galanin (GAL), neurokinin A (NKA), peptide histidine isoleucine (PHI), vasoactive intestinal peptide (VIP), neurotensin (NT) and cholecystokinin (CCK). We also examined the sheep median eminence using immunohistochemistry for NPY, SP and GAL and determined degradation profiles of NPY, SP, GAL and NKA in portal and jugular plasma. In no instance did we find that levels of the above peptides were consistently higher in portal blood than in peripheral blood. In some cases levels of peptide were lower in portal plasma e.g. for NPY (6/10 sheep). In one experimental series SP levels in portal plasma were significantly (p < 0.05) lower than levels in jugular plasma but this was not found in another experimental series. Galanin levels were significantly (p < 0.01) lower in portal plasma compared to levels in jugular plasma. We conducted in vitro studies to determine whether or not the above peptides are selectively degraded in portal blood but were unable to show any differences between the rates of degradation in portal and jugular plasma. Immunohistochemistry revealed projections into the external zone of the median eminence for NPY, GAL and SP. This study shows that none of the above peptides are secreted into the hypophysial portal blood of sheep. For some peptides e.g. GAL, enzymes from the endothelial cells of the portal vessels may enhance degradation. Projections into the external zone of the median eminence of neuronal systems containing these peptides may serve to modulate the secretion of the well recognized release and inhibiting factors by acting on the neurosecretory terminals.

Alcohol-related brain damage: report from a Medical Council on Alcohol Symposium, June 2010

### Alcohol-Related Brain Damage: Challenges and OpportunitiesnnColin DrummondnnNational Addiction Centre, Institute of Psychiatry, Kings College London, UKnnAlcohol is a toxic and dependence-producing substance that can damage most organs in the body, and is implicated in more than 60 different diseases (Oforei-Adjei et al. , 2007). Alcohol is now the third leading cause of ill health in Europe (Rehm et al. , 2009). In the UK, alcohol-related morbidity and mortality have been increasing over the last 30 years, and alcohol-related hospital admissions now exceed 1 million per annum in England (North West Public Health Observatory, 2011).nnThe brain is particularly sensitive to the toxic effects of alcohol either directly, particularly in the foetus and young people, or in the context of malnutrition and thiamine deficiency leading to Wernicke–Korsakoff syndrome; or following repeated episodes of alcohol withdrawal. The precise mechanisms of alcohol-related brain damage (ARBD) remain to be fully understood and several papers in this series describe the limits of knowledge. However, enough is already known to make a significant impact on the prevalence of ARBD through relatively inexpensive preventive strategies. Yet, such preventive strategies are poorly implemented in the UK. Why is this the case?nnFirst, there has been a lack of training and clear guidance to clinicians on preventing and managing alcohol problems, including ARBD. This has resulted in low levels of identification and intervention of patients at risk of alcohol-related complications in medical and psychiatric care (Barnaby et al. , 2003; Cheeta et al. , 2008). The recently published suite of NICE guidance on alcohol-use disorders aims to improve detection, prevention and management (NICE, 2010a, b, 2011). However, effective implementation will require a significant investment in staff training to raise awareness, knowledge and skills.nnSecondly, there is the issue of stigma. Patients who misuse alcohol face stigma and opprobrium, …

HAEMORPHIN PEPTIDES MAY BE ENDOGENOUS LIGANDS FOR BRAIN ANGIOTENSIN AT4 RECEPTORS

1. Angiotensin IV (AngIV), the (3–8) fragment of AngII, was previously believed to be an inactive metabolite. However, specific binding sites, termed AT4 receptors, have been identified in the brain and peripheral organs and the peptide has been reported to enhance memory recall in passive avoidance studies and to dilate pial and renal cortical vessels.

Procedural differences directly affect timed up and go times.

1. Lee DC, Chu J, Satz W et al. Low plasma thiamine levels in elder patients admitted through the emergency department. Acad Emerg Med 2000;7:1156– 1159. 2. Iber FL, Blass J, Brin M et al. Thiamin in the elderly-relation to alcoholism and to neurological degenerative disease. Am J Clin Nutr 1982;6:1067–1082. 3. Nichols HK, Basu TK. Thiamin status of the elderly: Dietary intake and thiamin pyrophosphate response. J Am Coll Nutr 1994;13:57–61. 4. Hanninen SA, Darling PB, Sole MJ et al. The prevalence of thiamin deficiency in hospitalized patients with congestive heart failure. J Am Coll Cardiol 2006;47:354–361.

Amino acid efflux in the isolated perfused rat pancreas: trans‐stimulation by extracellular amino acids.

1. Epithelial uptake and efflux of the non‐metabolized system A analogue 2‐methylaminoisobutyric acid (MeAIB) and L‐serine were studied in the isolated perfused rat pancreas using a dual tracer loading and wash‐out technique. Uptakes of 2‐[14C]MeAIB and L‐[3H]serine were measured relative to D‐[3H or 14C]mannitol (extracellular tracer) during a 20 min cell loading period. Maximal uptake for MeAIB (34 +/‐ 2%, n = 6) occurred within 2‐3 min and decreased to 14 +/‐ 2% after 20 min tracer loading. Uptake for L‐serine reached a maximum (62 +/‐ 4%, n = 7) within 1 min and decreased to 19 +/‐ 2% after 20 min tracer loading. 2. When tracer wash‐out was monitored during subsequent perfusion of the preloaded pancreas with an isotope‐free solution, D‐mannitol predominantly cleared from a fast exchanging compartment (0.54 +/‐ 0.05 ml g‐1, n = 9) with a time constant (Tfast) of 0.68 +/‐ 0.04 min. Although MeAIB and L‐serine exhibited similar fast phases of wash‐out, a much larger efflux occurred from a slowly exchanging pool with respective time constants (Tslow) of 15.47 +/‐ 0.45 min (n = 6) and 5.98 +/‐ 0.46 min (n = 7). 3. A rapid vascular challenge of the pancreas with 100 mM‐L‐serine transiently accelerated cellular efflux of 2‐[14C]MeAIB and L‐[3H]serine without affecting wash‐out of D‐[14C]mannitol. Tracer efflux following cell loading with 2‐[14C]MeAIB or L‐[3H]serine was not stimulated by a challenge with 100 mM‐MeAIB. 4. The time course of amino acid evoked 2‐[14C]MeAIB and L‐[3H]serine efflux paralleled the extracellular dilution profile of a vascular stimulus, suggesting that the acceleration of efflux was due to trans‐stimulation. 5. Trans‐stimulation of 2‐[14C]MeAIB and L‐[3H]serine efflux by a further twenty‐two naturally occurring and three synthetic amino acids was then examined. L‐Proline, N‐methyl‐DL‐alanine, L‐lysine and D‐lysine selectively stimulated MeAIB efflux. Efflux of both tracer amino acids was accelerated by aminoisobutyric acid (AIB), L‐serine, L‐alanine, L‐cysteine, L‐threonine, glycine, branched‐chain and large neutral amino acids, but affected negligibly by D‐alanine, beta‐alanine, MeAIB, L‐arginine, L‐aspartate, L‐glutamate, taurine or D‐mannitol. 6. In summary, we have characterized amino acid exchange mechanisms in the isolated pancreas and conclude that efflux of intracellular amino acids from pancreatic acinar cells may be mediated by at least two transporters with differing specificity for extracellular amino acids.(ABSTRACT TRUNCATED AT 400 WORDS)

Using a body sensor network to measure the effect of fatigue on stair climbing performance

In terms of self-rated health, the most important activities of daily living are those involving mobility. Of these activities stair climbing is regarded as the most strenuous. A loss of stair climbing ability with age is normally associated with a loss of muscle strength and power, while other factors that influence muscle function, such as fatigue, are often not taken into account. So far no research has been published on how long-lasting fatigue affects activities of daily living, despite the fact that it has been repeatedly proven, in laboratory settings, to influence muscle force production over long periods of time. Technological advances in body sensor networks (BSNs) now provide a method to measure performance during complex real-life situations. In this study the use of a BSN was explored to investigate the effects of long-lasting fatigue on stair climbing performance in 20 healthy adults. Stair climbing performance was measured before and after a fatiguing protocol using a BSN. Performance was defined by temporal and spatial parameters. Long-lasting fatigue was successfully induced in all participants using an exercise protocol. The BSN showed that post-exercise fatigue did not influence stair climbing times (p > 0.2) and no meaningful changes in joint angles were found. No effect on overall stair climbing performance was found, despite a clear presence of long-lasting fatigue. This study shows that physiological paradigms can be further explored using BSNs. Ecological validity of lab-based measurements can be increased by combining them with BSNs.

A novel method for determining ground-referenced contacts during stair ascent: Comparing relative hip position to quiet standing hip height

Stair climbing can be measured using body-fixed sensors, whereby the origin and axes of the coordinate system are fixed with respect to the geometry of a body segment. These sensors can be part of a portable system, which provides the possibility to collect data in complex real-life environments. However due to the fact that the sensors are body-fixed, difficulties in determining the ground-based parameters of stair ascent can occur. The purpose of this study is to present a new approach for determining initial contacts based on a multi-chain biomechanical model combined with a new analysis method, in which relative hip height is compared to hip height during normal standing. Initial contacts obtained from the proposed method were compared to those obtained using an optical tracking device. An average absolute timing difference ranging from 0.04 (SD + or - 0.03) to 0.06 (+ or - 0.03) s and a root mean square error ranging from 0.05 to 0.07 s were found between the two techniques. This shows that the new approach presented in this study can be used to accurately determine initial contacts during stair ascent using portable equipment.