bluuebunny/crossref_metadata_2025 huggingface dataset:
UPDATE ON THE TREATMENT OF CHRONIC KIDNEY DISEASE‐MINERAL AND BONE DISORDER
Authors: Bover Jordi , Farré Neus , Andrés Enric , Canal Cristina , Olaya María Teresa , Alonso Maite , Quílez Begoña , Ballarín José
Published: February 2009

Chronic kidney disease (CKD) is associated with increased morbidity and mortality. Mineral metabolism disturbances appear to contribute to the high mortality rate. A CKD‐mineral bone disorder (CKD‐MBD) has recently been defined as a systemic disorder manifested by one or a combination of abnormalities in bone biopsy, laboratory parameters and/or vascular or other soft‐tissue calcifications. New available treatments have contributed to move from the former treatment paradigm of renal osteodystrophy to CKD‐MBD management, beyond mere control of parathyroid hormone (PTH) and trying to improve cardiovascular or survival outcomes. Thus, the recommended multidisciplinary approach among nurses, dieticians and clinicians, helping not only through dietary assessment but also through education, behaviour control and by increasing the patient's personal motivation, may have additional important benefits. This article will review the current therapeutic approach with phosphate binders including the latest developments, vitamin D derivatives and selective vitamin D receptor activators as well as the new calcimimetics, all used in the treatment of this systemic disease.
PATHOGENESIS OF BONE AND MINERAL RELATED DISORDERS IN CHRONIC KIDNEY DISEASE: KEY ROLE OF HYPERPHOSPHATEMIA
Authors: Román‐García Pablo , Carrillo‐López Natalia , Cannata‐Andía Jorge B.
Published: February 2009

This paper reviews the pathogenesis of hyperphosphataemia and its role in the regulation of parathyroid hormone synthesis and parathyroid cell proliferation in chronic kidney disease. The association between hyperphosphaemia and vascular calcification, and the interventions that can be used to control plasma phosphate are also discussed.
THE USE OF PHOSPHATE BINDERS: DATA FROM CONTRIBUTORS TO THE EUROPEAN PRACTICE DATABASE
Authors: Elseviers Monique , De Vos Jean‐Yves
Published: February 2009

Data of the European Practice Database (EPD) were used to investigate the use of phosphate binders in the European HD population. A cross‐sectional observation among five participating countries of the cycle 2 study revealed that most patients used phosphate binders and many of them used more than one agent. Calcium‐based products were most frequently used (55% of HD patients) followed by sevelamer (37%). There was a wide variation between different countries in the kind of phosphates that were used. Renal dietitians advised regularly on therapy adjustment for calcium/phosphorus metabolism in one third of European centres and their involvement is increasing.
ORAL PHOSPHATE BINDERS FOR THE MANAGEMENT OF SERUM PHOSPHATE LEVELS IN DIALYSIS PATIENTS
Authors: Mohammed Ismail , Hutchison Alastair J.
Published: February 2009

Hyperphosphataemia is an inevitable consequence of end stage chronic kidney disease and is present in the majority of dialysis patients. Hyperphosphataemia is statistically associated with increased cardiovascular mortality among dialysis patients. Dietary restriction of phosphate and current dialysis modalities are not sufficiently effective to maintain serum phosphate levels within the recommended range so that the majority of dialysis patients require oral phosphate binders. However, benefits of achieving the recommended range have yet to be demonstrated prospectively.

Unfortunately, conventional phosphate binders are not reliably effective and are associated with a range of limitations and side effects. Aluminium containing agents are highly efficient but no longer widely used because of well‐established and proven toxicity. Calcium‐based salts are inexpensive, effective and most widely used but there is now concern about their association with hypercalcaemia and vascular calcification. Sevelamer hydrochloride and lanthanum carbonate are non‐aluminium, calcium‐free phosphate binders. They are effective and reasonably well tolerated, but still do not control phosphate levels in all patients.

Patient education programmes have been shown to be a useful and effective method of improving achievement of serum phosphate targets.
VASCULAR CALCIFICATION IN CHRONIC KIDNEY DISEASE: A CLINICAL REVIEW
Authors: Eddington Helen , Sinha Smeeta , Kalra Philip A.
Published: February 2009

Vascular calcification, which is associated with arterial stiffness, is now known to be an important predictor of cardiovascular and all‐cause mortality in patients with renal disease. This calcification starts developing in the early stages of chronic kidney disease (CKD) and is present in over 50% of patients at the time of dialysis commencement. Once calcification is present it continues to progress, though some medications have been shown to slow this progression. Vascular calcification and bone abnormalities are now both encompassed by the term of CKD—mineral bone disorder and are thought to be part of the same disease process in CKD.

Vascular calcification and arterial stiffness have been extensively researched in the renal population and many factors are known to be associated with their presence and progression. This calcification is an important factor to be considered in the management of the renal patient but there are different methods available for its measurement. These details will be discussed further in this review along with evidence available for management of this important complication of renal disease.
SOFT BONES AND HARD ARTERIES—CAN WE REVERSE THE TREND IN CKD?
Authors: Tomlinson James , Cunningham John
Published: February 2009

Chronic kidney disease‐bone and mineral disorder (CKD‐MBD) signifies the complex pathophysiological interactions between calcium, phosphorus and regulatory hormones which are associated, sometimes causally, with impaired bone mineralisation and increased fracture risk in patients with CKD. It also signifies a predisposition to vascular calcification (VC), the emergence of which as a likely side effect of some of the current therapies poses a difficult problem for physicians aiming to treat patients with CKD. This complex disorder has seen several important advances in relation to understanding of the pathophysiology and, it is hoped, refinement of therapeutic approaches.
ANAEMIA AND MINERAL BONE DISORDER IN CHRONIC KIDNEY DISEASE: A REVIEW OF THE CURRENT LITERATURE AND IMPLICATIONS FOR CLINICAL NURSING PRACTICE
Authors: Limrick Claire , McNichols‐Thomas Coral
Published: February 2009

Secondary hyperparathyroidism (SHPT) is one of the factors reported to have a negative impact on anaemia of chronic kidney disease (ACKD) and its treatment. SHPT is one of the abnormalities resulting from altered bone mineral metabolism. Five possible mechanisms have been proposed as to how SHPT impacts on anaemia in this paper. Each of these mechanisms will be considered and the treatment options reviewed including the implications for erythropoietic stimulating agents (ESA) prescribing. Anaemia and SHPT are both strongly predictive of complications and death from cardiovascular events in patients with chronic kidney disease (CKD). Nursing care of this group of patients should, therefore, be holistic in order to ensure optimum management. Ways in which we can practice to enhance quality of life and outcomes in this patient population will be discussed.
EARLY INITIATION OF PHOSPHATE LOWERING DIETARY THERAPY IN NON‐DIALYSIS CHRONIC KIDNEY DISEASE: A CRITICAL REVIEW
Authors: Sigrist M.K. , Chiarelli G. , Lim L. , Levin A.
Published: February 2009

Dietary management of hyperphosphatemia and hyperparathyroidism have long been important elements in the clinical management of CKD stage 4 and 5 for the prevention of mineral bone disease. The rationale for phosphate lowering has been further justified, given the accumulating data to support the association of phosphate with vascular damage, in this population who are at high risk of cardiovascular (CV) death. Phosphate is a novel CV risk factor in both CKD and in the general population, and a growing body of literature suggests that high normal serum phosphate may be a risk factor for progression of CKD. Few studies have examined hard outcomes after phosphate lowering. Nonetheless, given the balance of data both in cell, animal and human studies, the use of phosphate lowering strategies at earlier stages of CKD, perhaps even prior to serum phosphate level rising, may well be justified.

This review will discuss the complications associated with higher serum phosphate, the potential benefits of early phosphate intervention, practical considerations of low phosphate diets and novel strategies for evaluating these strategies in clinical practice.
VASCULAR CALCIFICATION: LESSONS FROM SCIENTIFIC MODELS
Authors: Sinha Smeeta , Eddington Helen , Kalra Philip A.
Published: February 2009

Patients with chronic kidney disease have increased cardiovascular mortality from a combination of increased atherosclerotic disease, left ventricular hypertrophy and increased prevalence of vascular calcification (VC). Previously VC was thought to be a passive process which involved the deposition of calcium and phosphate into the vessel wall. However, recent studies have shown that VC is a highly regulated, cell‐mediated process similar to bone formation, in that it is associated with expression of bone‐related proteins, such as type I collagen and alkaline phosphatase.

Animal and in vitro models of VC have shown that a multitude of factors including phosphate, matrix gla protein (MGP) and fetuin are involved in regulating VC. Certain factors induce calcification whereas others inhibit the process. Despite these insights, it is still not fully known how VC is regulated and a treatment for VC remains elusive. Ongoing research will hopefully elucidate these mechanisms and thereby produce targets for future therapeutic intervention. This review will highlight some of the scientific models of VC and how they have increased the understanding of this complex process.
CHRONIC KIDNEY DISEASE—MINERAL AND BONE DISORDER (CKD‐MBD): A NEW TERM FOR A COMPLEX APPROACH
Authors: Švára František
Published: February 2009

The global widespread of the chronic kidney disease (CKD) is a worldwide health problem. Its increasing incidence and prevalence and adverse outcomes (including decreased quality of life, increased morbidity and mortality) represents a huge challenge for all recent health are systems. Reflecting this situation, the new, global initiative (KDIGO) was established to enhance communication and clinical decision‐making, promote the use of evidence based medicine and facilitate clinical research. The new definition, evaluation and classification of “renal osteodystrophy”; has been one of the first outcome of this initiative, suggesting the topic of chronic kidney disease—mineral and bone disorder (CKD‐MBD) to be a hot problem of recent nephrology. The new terminology is consistent with a recent view on this topic and describes CKD‐MBD as a complex syndrome, including abnormal mineral and PTH metabolism, altered bone structure as far as extra‐skeletal calcifications.
THE EFFICACY OF A SINGLE DOSE OF INTRAVENOUS FERRIC CARBOXYMALTOSE (FERINJECT®) ON ANAEMIA IN A PRE‐DIALYSIS POPULATION OF CHRONIC KIDNEY DISEASE PATIENTS
Authors: Tagboto Senyo , Cropper Liz , Turner June , Pugh‐Clarke Karen
Published: February 2009

Anaemia due to chronic kidney disease (CKD) is common and may be managed with erythropoiesis stimulating agents and/or iron preparations. Iron preparations may be administered orally, intravenously or by intramuscular injection. Oral preparations pose a significant tablet burden on patients who are often taking multiple medications and may have undesirable gastrointestinal side effects. The existing intravenous preparation Venofer® requires multiple doses of drug (typically 100–200 mg) at multiple clinic visits. The preparation Cosmofer® may be given as a single dose, but this requires four to six hours to administer. For these reasons, their use in pre‐dialysis patients remains limited in practice. The new intravenous iron preparation Ferric Carboxymaltose (Ferinject®) may be given as a single dose of up to 1000 mg (but not exceeding 15 mg/kg/week) as an infusion over 6–15 minutes. This offers a significant advance in the management of these patients. We describe our initial experience with using this drug in a non‐dialysis patient population with chronic kidney disease.
COMPARISON OF NEPHROLOGY NURSING INTERVENTIONS ACROSS FIVE EUROPEAN COUNTRIES
Authors: Zampieron Alessandra , Ormandy Paula , Elseviers Monique , De Vos Jean Yves , Kafkia Theodora
Published: February 2009

Comparing nursing interventions between different countries is helpful towards developing a common nursing culture within Europe. The aim of the study was to compare the frequency of 14 specific nursing interventions indicators across five European countries (Belgium, Scotland, Czech Republic, Greece and the North of England). Data were collected as an integral part of the European Practice Database Project across two cycles (2005 and 2006) involving 172 renal centres. Using Pearson's chi‐square and descriptive statistics the frequency of 11 out of the 14 nurse intervention indicators was found to vary significantly across the five countries. Indeed specific nurse interventions such as delegation, telephone consultations and laboratory data interpretation potentially identify where nurse activity is changing in response to pressures such as advancing nurse roles, staff shortages and increased patient demand.
A PROGRAMME TO ENCOURAGE PARTICIPATION OF HAEMODIALYSIS PATIENTS IN AN EXERCISE REGIMEN
Authors: Tobita Itoko , Suzuki Sumie , Kobayashi Tamami , Shimizu Yasuko , Umeshita Koji
Published: February 2009

Recent research has reinforced the idea that haemodialysis (HD) patients should exercise to maintain their physical functioning and improve their quality of life. Some effective exercise programmes are available for HD patients. However, these programmes are not always completed by the patients who enrol in them, and therefore, these patients do not maintain long‐term physical activity. In this study, a support programme based on the concepts of self‐monitoring, verbal reinforcement and motivation was developed to encourage continued participation of HD patients in an exercise regimen. Intervention group participants were provided a support programme in addition to the exercise programme, whereas nonintervention group participants were only provided the exercise programme. The two groups were compared for 12 weeks. The intervention group participants showed a significantly higher rate of continuation of independent exercise than the nonintervention group participants.
Hypothalamic‐Pituitary‐Adrenal Axis Assessment in Healthy Term Neonatal Foals Utilizing a Paired Low Dose/High Dose ACTH Stimulation Test
Authors: Hart K.A. , Heusner G.L. , Norton N.A. , Barton M.H.
Published: February 2009

Background:Hypothalamic‐pituitary‐adrenal (HPA) axis function is dynamic in the neonatal foal. The paired low dose/high dose cosyntropin (ACTH) stimulation test allows comprehensive HPA axis assessment, but has not been evaluated in neonatal foals.

Hypothesis:Foal age will significantly affect cortisol responses to a paired 10 and 100 μg dose cosyntropin stimulation test in healthy neonatal foals.

Animals:Twenty healthy neonatal foals.

Methods:HPA axis function was assessed in 12 foals at birth and at 12–24, 36–48 hours, and 5–7 days of age. At each age, basal cortisol and ACTH concentrations were measured and cortisol responses to 10 and 100 μg cosyntropin were assessed with a paired ACTH stimulation test protocol. Eight additional 36–48‐hour‐old foals received saline instead of 10 μg cosyntropin in the same‐paired ACTH stimulation test design.

Results:At birth, foals had significantly higher basal cortisol and ACTH concentrations and higher basal ACTH : cortisol ratios compared with foals in all other age groups. A significant cortisol response to both the 10 and 100 μg doses of cosyntropin was observed in all foals. The magnitude of the cortisol response to both doses of cosyntropin was significantly different across age groups, with the most marked responses in younger foals. There was no effect of the paired ACTH stimulation test design itself on cortisol responses.

Conclusions and Clinical Importance:A paired 10 and 100 μg cosyntropin stimulation test can be used to evaluate HPA axis function in neonatal foals. Consideration of foal age is important in interpretation of HPA axis assessment.
Exogenous Insulin Treatment after Hypofractionated Radiotherapy in Cats with Diabetes Mellitus and Acromegaly
Authors: Dunning M.D. , Lowrie C.S. , Bexfield N.H. , Dobson J.M. , Herrtage M.E.
Published: February 2009

Background:The optimal treatment for feline acromegaly has yet to be established. Surgical and medical therapies are minimally effective although radiotherapy might have greater efficacy. The purpose of this study was to review the response and outcome of cats with acromegaly and insulin‐resistant diabetes mellitus (DM) to radiotherapy.

Hypotheses:That radiotherapy improves glycemic control in cats with acromegaly and that improved glycemic control is due to remission of clinical acromegaly; demonstrated by a fall in serum insulin‐like growth factor‐1 (IGF‐1) concentrations.

Animals:Fourteen cats with naturally occurring acromegaly.

Methods:Retrospective case review; records of all cats treated for acromegaly with radiotherapy were reviewed from 1997 to 2008. Cats were selected on the basis of compatible clinical signs, laboratory features, and diagnostic imaging findings. Fourteen cats received radiotherapy, delivered in 10 fractions, 3 times a week to a total dose of 3,700 cGy.

Results:Thirteen of 14 cats had improved diabetic control after radiotherapy. These improvements were sustained for up to 60 months. DM progressed in 2 cats and 1 did not respond. Seven cats responded before the final treatment. Ten cats were euthanized, 1 as a consequence of radiotherapy. In 8 cats in which IGF‐1 was measured after treatment, changes in its concentration did not reflect the clinical improvement in glycemic control.

Conclusions and Clinical Importance:Radiotherapy represents an effective treatment for cats with insulin‐resistant DM resulting from acromegaly. IGF‐1 concentration after treatment does not provide a suitable method by which remission from either acromegaly or insulin‐resistant DM may be assessed.
Effect of Parenteral Selenium Administration to Sheep on Prevalence and Recovery from Footrot
Authors: Hall J.A. , Bailey D.P. , Thonstad K.N. , Van Saun R.J.
Published: February 2009

Background:Insufficient intake of selenium (Se) is common in many regions, and can contribute to increased susceptibility to and prolonged recovery from infectious diseases.

Objective:To determine the effect of Se administration in decreasing the severity and prevalence of footrot in sheep.

Animals:Thirty‐eight footrot‐affected and 19 nonaffected sheep from a commercial flock of known high incidence of footrot.

Methods:Placebo‐controlled, prospective, 15‐month clinical trial. Footrot‐affected sheep were randomly assigned into 2 groups (n = 19) and injected with either 5 mg Se (footrot [FR]‐Se) or saline (FR‐Sal) at 1‐month intervals for the duration of the study. Unaffected sheep (controls) received no treatment. Sheep feet were examined, trimmed, and scored for footrot with a scale of 0 (no footrot) to 4 (extensive) at 0, 3, 6, 9, and 15 months. Sheep were also bled at time 0 and then at 3, 6, and 15 months to assess whole blood Se concentrations.

Results:At time 0, control sheep (255 ± 11 ng/mL) had higher (P< .05) whole blood Se concentrations compared with FR‐Se (205 ± 12 ng/mL) and FR‐Sal (211 ± 14 ng/mL) sheep. By 6 months, FR‐Se sheep (317 ± 9 ng/mL) had whole blood Se concentrations greater (P< .05) than both control (281 ± 14 ng/mL) and FR‐Sal (277 ± 16 ng/mL) sheep. FR‐Se ewes showed a faster decline in highest lesion score at 3 (P= .012) and 6 (P= .0036) months, and a greater decrease in the number of feet with foot score >0 at 6 (P= .020) months compared with FR‐Sal ewes. Sheep with blood Se concentrations <300 ng/mL were at 3.5 times greater risk (1.1–12.1 confidence interval, odds ratio) for FR, although this relationship was only significant (P= .04) at 6 months of the study.

Conclusions and Clinical Importance:In sheep with footrot, improved Se status in conjunction with routine control practices result in more rapid improvement of foot lesions.
Incidence of Transfusion Reactions and Retention of Procoagulant and Anticoagulant Factor Activities in Equine Plasma
Authors: Wilson E.M. , Holcombe S.J. , Lamar A. , Hauptman J.G. , Brooks M.B.
Published: February 2009

Background:The extent of preservation of clotting factors and incidence of transfusion reactions to noncommercial equine plasma is not documented.

Hypothesis:Equine frozen plasma would retain its coagulation factor activity within the reference range and the incidence of transfusion reactions would be low.

Animals:Ten plasma donor horses. Fifty clinically ill hospitalized horses receiving plasma were reviewed to determine the incidence of reactions.

Methods:In vitro study and retrospective case review. Plasma was prepared by gravity sedimentation from whole blood refrigerated for 48 hours. The activities of factors VII through XII, antithrombin (AT), and Protein C were measured. Factor activities were compared for plasma samples obtained before blood collection (S0), after 48 hours of gravity sedimentation at 5 °C and after plasma separation (S1), and after 90 days of storage at −20 °C (S90). The medical records of 50 consecutive clinically ill horses receiving frozen plasma were reviewed to determine the incidence of transfusion reactions.

Results:The combined effect of plasma harvest, gravity sedimentation, decantation, and freezing caused significant reductions in factors IX, (43%P= .0013), X, (33%P= .0001), XI, (48%P= .0008), AT, (10%P= .02), and Protein C (26%P= .0001). Activities for all factors analyzed, except factor X, remained within the reference ranges. Transfusion reactions were recorded for 5/50 horses.

Conclusions and Clinical Relevance:Clotting factors, AT, and Protein C were well preserved. The incidence of reactions to frozen plasma was 10%.
Effect of intracellular lipid droplets on cytosolic Ca2+ and cell death during ischaemia–reperfusion injury in cardiomyocytes
Authors: Barba Ignasi , Chavarria Laia , Ruiz‐Meana Marisol , Mirabet Maribel , Agulló Esperanza , Garcia‐Dorado David
Published: February 2009

Lipid droplets (LD) consist of accumulations of triacylglycerols and have been proposed to be markers of ischaemic but viable tissue. Previous studies have described the presence of LD in myocardium surviving an acute coronary occlusion. We investigated whether LD may be protective against cell death secondary to ischaemia–reperfusion injury. The addition of oleate–bovine serum albumin complex to freshly isolated adult rat cardiomyocytes or to HL‐1 cells resulted in the accumulation of intracellular LD detectable by fluorescence microscopy, flow cytometry and 1H‐nuclear magnetic resonance spectroscopy. Simulated ischaemia–reperfusion of HL‐1 cells (respiratory inhibition at pH 6.4 followed by 30 min of reperfusion) resulted in significant cell death (29.7 ± 2.6% of total lactate dehydrogenase release). However, cell death was significantly attenuated in cells containing LD (40% reduction in LDH release compared with control cells, P= 0.02). The magnitude of LD accumulation was inversely correlated (r2= 0.68, P= 0.0003) with cell death. The protection associated with intracellular LD was not a direct effect of the fatty acids used to induce their formation, because oleate added 30 min before ischaemia, during ischaemia or during reperfusion did not form LD and did not protect against cell death. Increasing the concentration of free oleate during reperfusion progressively decreased the protection afforded by LD. HL‐1 cells labelled with fluo‐4, a Ca2+‐sensitive fluorochrome, fluorescence within LD areas increased more throughout simulated ischaemia and reperfusion than in the cytosolic LD‐free areas of the same cells. As a consequence, cells with LD showed less cytosolic Ca2+ overload than control cells. These results suggest that LD exert a protective effect during ischaemia–reperfusion by sequestering free fatty acids and Ca2+.
Rapamycin administration in humans blocks the contraction‐induced increase in skeletal muscle protein synthesis
Authors: Drummond Micah J. , Fry Christopher S. , Glynn Erin L. , Dreyer Hans C. , Dhanani Shaheen , Timmerman Kyle L. , Volpi Elena , Rasmussen Blake B.
Published: February 2009

Muscle protein synthesis and mTORC1 signalling are concurrently stimulated following muscle contraction in humans. In an effort to determine whether mTORC1 signalling is essential for regulating muscle protein synthesis in humans, we treated subjects with a potent mTORC1 inhibitor (rapamycin) prior to performing a series of high‐intensity muscle contractions. Here we show that rapamycin treatment blocks the early (1–2 h) acute contraction‐induced increase (∼40%) in human muscle protein synthesis. In addition, several downstream components of the mTORC1 signalling pathway were also blunted or blocked by rapamycin. For instance, S6K1 phosphorylation (Thr421/Ser424) was increased post‐exercise 6‐fold in the control group while being unchanged with rapamycin treatment. Furthermore, eEF2 phosphorylation (Thr56) was reduced by ∼25% post‐exercise in the control group but phosphorylation following rapamycin treatment was unaltered, indicating that translation elongation was inhibited. Rapamycin administration prior to exercise also reduced the ability of raptor to associate with mTORC1 during post‐exercise recovery. Surprisingly, rapamycin treatment prior to resistance exercise completely blocked the contraction‐induced increase in the phosphorylation of ERK1/2 (Thr202/Tyr204) and blunted the increase in MNK1 (Thr197/202) phosphorylation. However, the phosphorylation of a known target of MNK1, eIF4E (Ser208), was similar in both groups (P > 0.05) which is consistent with the notion that rapamycin does not directly inhibit MAPK signalling. We conclude that mTORC1 signalling is, in part, playing a key role in regulating the contraction‐induced stimulation of muscle protein synthesis in humans, while dual activation of mTORC1 and ERK1/2 stimulation may be required for full stimulation of human skeletal muscle protein synthesis.
Properties of distinct ventral tegmental area synapses activated via pedunculopontine or ventral tegmental area stimulationin vitro
Authors: Good Cameron H. , Lupica Carl R.
Published: February 2009

Anatomical studies indicate that synaptic inputs from many cortical and subcortical structures converge on neurons of the ventral tegmental area (VTA). Althoughin vitroelectrophysiological studies have examined synaptic inputs to dopamine (DA) and non‐DA neurons in the VTA, they have largely relied upon local electrical stimulation to activate these synapses. This provides little information regarding the distinct properties of synapses originating from different brain areas. Using whole‐cell recordings in parasagittal rat brain slices that preserved subcortical axons from the pedunculopontine nucleus (PPN) to the VTA, we compared these synapses with those activated by intra‐VTA stimulation. PPN‐evoked currents demonstrated longer latencies than intra‐VTA‐evoked currents, and both VTA and PPN responses were mediated by GABAAand AMPA receptors. However, unlike VTA‐evoked currents, PPN currents were exclusively mediated by glutamate in 25–40% of the VTA neurons. Consistent with a cholinergic projection from the PPN to the VTA, nicotinic acetylcholine receptors (nAChR) were activated by endogenous acetylcholine released during PPN, but not VTA, stimulation. This was seen as a reduction of PPN‐evoked, and not VTA‐evoked, synaptic currents by the α7‐nAChR antagonist methyllycaconitine (MLA) and the agonist nicotine. The β2‐nAChR subunit antagonist dihydro‐β‐erythroidine had no effect on VTA‐ or PPN‐evoked synaptic currents. The effects of MLA on PPN‐evoked currents were unchanged by the GABAAreceptor blocker picrotoxin, indicating that α7‐nAChRs presynaptically modulated glutamate and not GABA release. These differences in physiological and pharmacological properties demonstrate that ascending PPN and presumed descending inputs to VTA utilize distinct mechanisms to differentially modulate neuronal activity and encode cortical and subcortical information.
The hungry fetus? Role of leptin as a nutritional signal before birth
Authors: Forhead Alison J. , Fowden Abigail L.
Published: February 2009

In adult animals, leptin is an adipose‐derived hormone that is important primarily in the regulation of energy balance during short‐ and long‐term changes in nutritional state. Expression of leptin and its receptors is widespread in fetal and placental tissues, although the role of leptin as a nutritional signal in utero is unclear. Before birth, leptin concentration correlates with several indices of fetal growth, and may be an endocrine marker of fetal size and energy stores in the control of metabolism and maturation of fetal tissues. In addition, leptin synthesis and plasma concentration can be modified by insulin, glucocorticoids, thyroid hormones and oxygen availability in utero, and therefore, leptin may be part of the hormonal response to changes in the intrauterine environment. Evidence is emerging to show that leptin has actions before birth that are tissue‐specific and may occur in critical periods of development. Some of these actions are involved in the growth and development of the fetus and others have long‐term consequences for the control of energy balance in adult life.
A Ca2+–calmodulin–eEF2K–eEF2 signalling cascade, but not AMPK, contributes to the suppression of skeletal muscle protein synthesis during contractions
Authors: Rose Adam J. , Alsted Thomas J. , Jensen Thomas E. , Kobberø J. Bjarke , Maarbjerg Stine J. , Jensen Jørgen , Richter Erik A.
Published: February 2009

Skeletal muscle protein synthesis rate decreases during contractions but the underlying regulatory mechanisms are poorly understood. It was hypothesized that there would be a coordinated regulation of eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E‐binding protein 1 (4EBP1) phosphorylation by signalling cascades downstream of rises in intracellular [Ca2+] and decreased energy charge via AMP‐activated protein kinase (AMPK) in contracting skeletal muscle. When fast‐twitch skeletal muscles were contracted ex vivo using different protocols, the suppression of protein synthesis correlated more closely with changes in eEF2 than 4EBP1 phosphorylation. Using a combination of Ca2+ release agents and ATPase inhibitors it was shown that the 60–70% suppression of fast‐twitch skeletal muscle protein synthesis during contraction was equally distributed between Ca2+ and energy turnover‐related mechanisms. Furthermore, eEF2 kinase (eEF2K) inhibition completely blunted increases in eEF2 phosphorylation and partially blunted (i.e. 30–40%) the suppression of protein synthesis during contractions. The 3‐ to 5‐fold increase in skeletal muscle eEF2 phosphorylation during contractions in situ was rapid and sustained and restricted to working muscle. The increase in eEF2 phosphorylation and eEF2K activation were downstream of Ca2+–calmodulin (CaM) but not other putative activating factors such as a fall in intracellular pH or phosphorylation by protein kinases. Furthermore, blunted protein synthesis and 4EBP1 dephosphorylation were unrelated to AMPK activity during contractions, which was exemplified by normal blunting of protein synthesis during contractions in muscles overexpressing kinase‐dead AMPK. In summary, in fast‐twitch skeletal muscle, the inhibition of eEF2 activity by phosphorylation downstream of Ca2+–CaM–eEF2K signalling partially contributes to the suppression of protein synthesis during exercise/contractions.
Experimental
Investigation of the Clocking Effect in a 1.5-Stage Axial Turbine—Part II: Unsteady Results
and Boundary Layer Behavior
Authors: König Sven , Stoffel Bernd , Taher
Schobeiri M.
Published: February 2009

Comprehensive experimental investigations were conducted to get deeper insight into the physics of stator clocking in turbomachines. Different measurement techniques were used to investigate the influence of varying clocking positions on the highly unsteady flow field in a 1.5-stage axial low-pressure (LP) turbine. A Reynolds number typical for LP turbines as well as a two-dimensional blade design were chosen. Stator 2 was developed as a high-lift profile with a separation bubble on the suction side. This paper presents the results that were obtained by means of unsteady x-wire measurements upstream and downstream of Stator 2 and surface mounted hot-film measurements on the Stator 2 suction side. It was found that for the case when the Stator 1 wakes impinge close to the leading edge of Stator 2 the interaction between the Stator 1 and the rotor vortical structures takes place in proximity of the Stator 2 boundary layer, which leads to a shift of the transition point in the upstream direction. The major loss parameter concerning the Stator 2 aerodynamic performance could be attributed to the strength of the periodic fluctuations within the Stator 2 suction side boundary layer. A phase shift in the quasiwall shear stress signal in the front region of the Stator 2 vane was observed for different clocking positions.
On the Response of a Strongly Diffusing Flow to Propagating Wakes
Authors: Gostelow J. P. , Thomas R. L. , Adebayo D. S.
Published: February 2009

Further evidence on the similarities between transition and separation phenomena occurring in turbomachinery and wind tunnel flows is provided by measurements on a large scale flat plate under a strong adverse pressure gradient. The flat plate has a long laminar separation bubble and is subjected to a range of disturbances with triggering caused by injection of a transverse jet and subsequently by wakes generated by rods moving transversely upstream of the leading edge. Wakes were originally presented individually. Each individual wake provoked a vigorous turbulent patch, resulting in the instantaneous collapse of the separation bubble. This was followed by a very strong, and stable, calmed region. Following the lead given by the experiments of Gutmark and Blackwelder (1987, “On the Structure of Turbulent Spot in a Heated Laminar Boundary Layer,” Exp. Fluids, 5, pp. 207–229.) on triggered turbulent spots, wakes were then presented in pairs at different wake spacing intervals. In this way wake interaction effects could be investigated in more detail. As in the work on triggered turbulent spots the spacing between impinging wakes was systematically varied; it was found that for close wake spacings the calmed region acted to suppress the turbulence in the following turbulent patch. To investigate whether this phenomenon was a recurring one or whether the flow then reverted back to its unperturbed state, the experiments were repeated with three and four rods instead of two. This has the potential for making available a wide range of variables including direction and speed of rod rotation. It was found that the subsequent wakes were also suppressed by the calming effect. It may be anticipated that this repeating situation is present in a turbomachine, resulting in hidden benefits for blade count and efficiency. There may also conceivably be blade loading advantages while retaining favorable heat transfer conditions in high pressure turbines or stall margin in axial compressors. The inherent and prospective benefits of the calming effect therefore need to be understood thoroughly and new opportunities exploited where this is feasible.a
On the Coupling of Inverse Design and Optimization Techniques for the Multiobjective, Multipoint Design of Turbomachinery Blades
Authors: Bonaiuti Duccio , Zangeneh Mehrdad
Published: February 2009

Automatic optimization techniques have been used in recent years for the aerodynamic and mechanical design of turbomachine components. Despite the many advantages, their use is usually limited to simple applications in industrial practice, because of their high computational cost. In this paper, an optimization strategy is presented, which enables the three-dimensional multipoint, multiobjective aerodynamic optimization of turbomachinery blades in a time frame compatible with industrial standards. The design strategy is based on the coupling of three-dimensional inverse design, response surface method, multiobjective evolutionary algorithms, and computational fluid dynamics analyses. The blade parametrization is performed by means of a three-dimensional inverse design method, where aerodynamic parameters, such as the blade loading, are used to describe the blade shape. Such a parametrization allows for a direct control of the aerodynamic flow field and performance, leading to a major advantage in the optimization process. The design method was applied to the redesign of a centrifugal and of an axial compressor stage. The two examples confirmed the validity of the design strategy to perform the three-dimensional optimization of turbomachine components, accounting for both design and off-design performance, in a time-efficient manner. The coupling of response functions and inverse design parametrization also allowed for an easy sensitivity analysis of the impact of the design parameters on the performance ones, contributing to the development of design guidelines that can be exploited for similar design applications.
An Experimental Study of Combustor Exit Profile Shapes on Endwall Heat Transfer in High Pressure Turbine Vanes
Authors: Barringer M. D. , Thole K. A. , Polanka M. D.
Published: February 2009

The design and development of current and future gas turbine engines for aircraft propulsion have focused on operating the high pressure turbine at increasingly elevated temperatures and pressures. The drive toward thermal operating conditions near theoretical stoichiometric limits as well as increasingly stringent requirements on reducing harmful emissions both equate to the temperature profiles exiting combustors and entering turbines becoming less peaked than in the past. This drive has placed emphasis on determining how different types of inlet temperature and pressure profiles affect the first stage airfoil endwalls. The goal of the current study was to investigate how different radial profiles of temperature and pressure affect the heat transfer along the vane endwall in a high pressure turbine. Testing was performed in the Turbine Research Facility located at the Air Force Research Laboratory using an inlet profile generator. Results indicate that the convection heat transfer coefficients are influenced by both the inlet pressure profile shape and the location along the endwall. The heat transfer driving temperature for inlet profiles that are nonuniform in temperature is also discussed.
Synchronizing Separation Flow Control With Unsteady Wakes in a Low-Pressure Turbine Cascade
Authors: Bloxham M. , Reimann D. , Crapo K. , Pluim J. , Bons J. P.
Published: February 2009

Particle image velocimetry (PIV) measurements were made on a highly loaded low-pressure turbine blade in a linear cascade. The Pack B blade has a design Zweifel coefficient of 1.15 and a peak Cp at 63% axial chord on the suction surface. Data were taken at Rec=20K with 3% inlet freestream turbulence and a wake-passing flow coefficient of 0.8. Without unsteady wakes, a nonreattaching separation bubble exists on the suction surface of the blade beginning at 68% axial chord. The time-averaged separation zone is reduced in size by approximately 35% in the presence of unsteady wakes. Phase-locked hot-wire and PIV measurements were used to document the dynamics of this separation zone when subjected to synchronized, unsteady forcing from a spanwise row of vortex generator jets (VGJs) in addition to the unsteady wakes. The phase difference between VGJ actuation and the wake passing was optimized. Both steady state Cp and phase-locked velocity measurements confirm that the optimal combination of wakes and jets yields the smallest separation.
Reduced Rough-Surface Parametrization for Use With the Discrete-Element Model
Authors: McClain Stephen T. , Brown Jason M.
Published: February 2009

The discrete-element model for flows over rough surfaces was recently modified to predict drag and heat transfer for flow over randomly rough surfaces. However, the current form of the discrete-element model requires a blockage fraction and a roughness-element diameter distribution as a function of height to predict the drag and heat transfer of flow over a randomly rough surface. The requirement for a roughness-element diameter distribution at each height from the reference elevation has hindered the usefulness of the discrete-element model and inhibited its incorporation into a computational fluid dynamics (CFD) solver. To incorporate the discrete-element model into a CFD solver and to enable the discrete-element model to become a more useful engineering tool, the randomly rough surface characterization must be simplified. Methods for determining characteristic diameters for drag and heat transfer using complete three-dimensional surface measurements are presented. Drag and heat transfer predictions made using the model simplifications are compared to predictions made using the complete surface characterization and to experimental measurements for two randomly rough surfaces. Methods to use statistical surface information, as opposed to the complete three-dimensional surface measurements, to evaluate the characteristic dimensions of the roughness are also explored.
Effects of Large Scale High Freestream Turbulence and Exit Reynolds Number on Turbine Vane Heat Transfer in a Transonic Cascade
Authors: Nasir Shakeel , Carullo Jeffrey S. , Ng Wing-Fai , Thole Karen A. , Wu Hong , Zhang Luzeng J. , Moon Hee Koo
Published: February 2009

This paper experimentally and numerically investigates the effects of large scale high freestream turbulence intensity and exit Reynolds number on the surface heat transfer distribution of a turbine vane in a 2D linear cascade at realistic engine Mach numbers. A passive turbulence grid was used to generate a freestream turbulence level of 16% and integral length scale normalized by the vane pitch of 0.23 at the cascade inlet. The base line turbulence level and integral length scale normalized by the vane pitch at the cascade inlet were measured to be 2% and 0.05, respectively. Surface heat transfer measurements were made at the midspan of the vane using thin film gauges. Experiments were performed at exit Mach numbers of 0.55, 0.75, and 1.01, which represent flow conditions below, near, and above nominal conditions. The exit Mach numbers tested correspond to exit Reynolds numbers of 9×105, 1.05×106, and 1.5×106 based on a vane chord. The experimental results showed that the large scale high freestream turbulence augmented the heat transfer on both the pressure and suction sides of the vane as compared to the low freestream turbulence case and promoted a slightly earlier boundary layer transition on the suction surface for exit Mach 0.55 and 0.75. At nominal conditions, exit Mach 0.75, average heat transfer augmentations of 52% and 25% were observed on the pressure and suction sides of the vane, respectively. An increased Reynolds number was found to induce an earlier boundary layer transition on the vane suction surface and to increase heat transfer levels on the suction and pressure surfaces. On the suction side, the boundary layer transition length was also found to be affected by increase changes in Reynolds number. The experimental results also compared well with analytical correlations and computational fluid dynamics predictions.
TU‐C‐J‐6B‐08: A Variational Deformable Image Registration Method Capable of Handling Large Organ Deformation
Authors: Gao S , Dong L , Wang H , Zhang L , Mohan R
Published: February 2009

Purpose: The goal of this research is to develop an accurate and reliable deformable image registration algorithm capable of handling large organ deformations for mapping daily CT images to the reference planning CT. Method and Materials: We previously developed a diffusion‐based deformable image registration algorithm using Thirion's “demons” algorithm. However, this implementation did not work well when large deformations occurred. In this study, we proposed a variational approach for deformable image registration within a multigrid computational framework. The differences of the two images were measured and minimized, and a regularization term was introduced to rule out discontinuities and other irregular solutions. In our numerical implementation, the well‐studied multigrid method was used for solving the nonlinear Euler‐Lagrange partial differential equation (PDE). In this multigrid approach, the results from the previous deformation field were used to initialize the next stage of deformation. Different smoothing parameters were also used at different stages. The solution to these PDEs gave the displacement fields which can be used to transform the daily CT images into the planning CT or vice versa. To test this approach, we performed deformable image registration using CT images of prostate cancer patients collected with an in‐room CT‐on‐rails system under an IRB‐approved protocol. Results: Daily CT images were selected for cases with severely distorted rectum (due to the presence of large bowl gas) or large variations in bladder filling. The results indicated that the proposed approach was capable of deforming very large shape changes of soft tissue or organ structures. Compared to the “demons” algorithm, the resulting registration was pronounced better visually and quantitatively using both distance and correlation measures. Conclusion: Our deformable registration approach demonstrated the capability of handling large deformations. Further validation studies need to be done to test its robustness.
Transmission of IncN Plasmids Carrying
bla
CTX-M-1
between Commensal
Escherichia coli
in Pigs and Farm Workers
Authors: Moodley Arshnee , Guardabassi Luca
Published: February 2009

CTX-M-1-producing
Escherichia coli
were isolated from 56 pigs, three farm personnel, two manure samples, and two air samples from two Danish pig farms where an association between prophylactic ceftiofur use and the occurrence of cephalosporin resistance was previously demonstrated. Human, animal, and environmental strains displayed high genetic diversity but harbored indistinguishable or closely related IncN plasmids carrying
bla
CTX-M-1
, indicating that IncN plasmids mediating cephalosporin resistance were transmitted between pigs and farm workers across multiple
E. coli
lineages.