bluuebunny/crossref_metadata_2025 huggingface dataset:
Redistributive Taxation and Public Education
Authors: KRAUSE ALAN
Published: December 2006

This paper examines the relative effectiveness of publicly provided ‘white collar’ professional (university) education versus ‘blue collar’ vocational training in achieving the government's redistributive goals. Although professional education directly benefits high‐skill high‐income workers and vocational training directly benefits low‐skill low‐income workers, we show that either provision of more professional education or less vocational training than in the first‐best allocation is optimal along the second‐best Paretian frontier since this facilitates incentive compatibility in labor supply decisions. Accordingly, the observation that public higher education expenditures in most countries favor universities is not necessarily inconsistent with an optimal redistributive program.
Business Cycles, Heuristic Expectation Formation, and Contracyclical Policies
Authors: WESTERHOFF FRANK H.
Published: December 2006

We develop a simple Keynesian‐type business cycle model in which agents use simple heuristics to predict national income. To be precise, the agents either form (destabilizing) extrapolative expectations or (stabilizing) regressive expectations, a decision which depends on the rules forecasting performance in the recent past. As it turns out, an unending evolutionary competition between the rules may generate endogenous complex business cycles. We also explore the effectiveness of some common governmental intervention strategies. Our model suggests that policy makers may be able to stabilize output fluctuations, yet due to system immanent nonlinearities this may prove to be quite difficult.
Bureaucracy, Tax System, and Economic Performance
Authors: OTT INGRID
Published: December 2006

This paper investigates the consequences for government size, growth and welfare if a selfish bureaucracy provides a congested input. Alternative exogenous tax systems are introduced and numerical analyses are carried out. The welfare optimum is only met under very specific assumptions: proportional congestion, a tax system only consisting of distortionary taxes and a bureaucracy that maximizes the budget's growth rate. Otherwise the relative size of the public sector becomes suboptimally large thus inducing welfare losses. From a welfare economic point of view bureaucratic selfishness is worse than a suboptimal taxing regime that does not (completely) internalize the congestion externalities.
Functional biology of plant phosphate uptake at root and mycorrhiza interfaces
Authors: Bucher Marcel
Published: December 2006

Phosphorus (P) is an essential plant nutrient and one of the most limiting in natural habitats as well as in agricultural production world‐wide. The control of P acquisition efficiency and its subsequent uptake and translocation in vascular plants is complex. The physiological role of key cellular structures in plant P uptake and underlying molecular mechanisms are discussed in this review, with emphasis on phosphate transport across the cellular membrane at the root and arbuscular–mycorrhizal (AM) interfaces. The tools of molecular genetics have facilitated novel approaches and provided one of the major driving forces in the investigation of the basic transport mechanisms underlying plant P nutrition. Genetic engineering holds the potential to modify the system in a targeted way at the root–soil or AM symbiotic interface. Such approaches should assist in the breeding of crop plants that exhibit improved P acquisition efficiency and thus require lower inputs of P fertilizer for optimal growth. Whether engineering of P transport systems can contribute to enhanced P uptake will be discussed.

Contents

Summary
11

I.
Introduction
11

II.
Phosphate uptake and its regulation
14

III.
Phosphate uptake assisted by the arbuscular—mycorrhizal symbiosis
18

IV.
Agricultural potential
21

V.
Conclusions and perspectives
21

Acknowledgements
22

References
22
CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: The Epidemiology and Outcome of Acute Renal Failure and the Impact on Chronic Kidney Disease
Authors: Block Clay A. , Schoolwerth Anton C.
Published: December 2006

Acute renal failure (ARF) is a common condition, especially among the critically ill, and confers a high mortality. Recent publications have highlighted changes in the epidemiology and improvement in mortality that was long thought to be static despite improvements in clinical care. The incidence of ARF is increasing. Efforts, such as the Acute Dialysis Quality Initiative, are being undertaken to establish a consensus definition of ARF, and to distinguish between varying degrees of acute kidney injury. Data are emerging to allow comparison of the epidemiology of ARF across institutions internationally. There is ongoing recognition of the important interaction between ARF and chronic kidney disease. Two brief case reports are offered to help frame the context and clinical impact of this disorder, followed by a review of some of the recent literature that addresses these points.
CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: Low‐dose Dopamine in the Intensive Care Unit
Authors: Karthik Swaminathan , Lisbon Alan
Published: December 2006

For much of the last four decades, low‐dose dopamine has been considered the drug of choice to treat and prevent renal failure in the intensive care unit (ICU). The multifactorial etiology of renal failure in the ICU and the presence of coexisting multisystem organ dysfunction make the design and execution of clinical trials to study this problem difficult. However, in the last decade, several meta‐analyses and one large randomized trial have all shown a lack of benefit of low‐dose dopamine in improving renal function. There are multiple reasons for this lack of efficacy. While dopamine does cause a diuretic effect, it does very little to improve mortality, creatinine clearance, or the incidence of dialysis. Evidence is also growing of its adverse effects on the immune, endocrine, and respiratory systems. It may also potentially increase mortality in sepsis. It is the opinion of the authors that the practice of using low‐dose dopamine should be abandoned. Other drugs and treatment modalities need to be explored to address the serious issue of renal failure in the ICU.
CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: Perioperative Fluid Management: Current Consensus and Controversies
Authors: Yeager Mark P. , Spence Brian C.
Published: December 2006

The scientific knowledge base that supports clinical decisions about perioperative fluid management continues to evolve. However, despite these advancements in the understanding of the physiology of fluid replacement, the definition of ‘‘optimal’’ perioperative fluid management remains a matter of clinical judgment. With an appreciation of the many factors, both sensible and insensible, that contribute to changes in blood and extracellular fluid volume during surgery, clinicians have tried to create reproducible and generally applicable formulas for replacement of fluid during surgery. These formulas have been challenged recently by the introduction of new tools for monitoring cardiopulmonary function, by the implementation of monitor‐guided protocols for fluid management, and, more recently, by clinical data suggesting that fluid restriction may improve surgical outcomes in some clinical settings. The relative ease of pre‐identified fluid replacement protocols is being slowly replaced by data‐guided interventions that take into account a variety of factors. Clinicians are therefore required to tailor their fluid replacement strategies based on preoperative patient characteristics, the type of surgery and even the type of anesthetic that is utilized. Some of the benefits of this new approach range from relatively ‘‘minor’’ outcomes such as diminished nausea after surgery to preventing postoperative complications such as wound breakdown and cardiopulmonary failure.
CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: The Pulmonary Artery Catheter in Critical Care
Authors: McGee William T. , Mailloux Patrick , Jodka Paul , Thomas Joss
Published: December 2006

Pulmonary artery catheterization has been a routine part of care for critically ill patients over the past 25 years. Primary hemodynamic data regarding cardiac output and pulmonary pressures can be utilized to make diagnoses and guide therapy. Tissue oxygen delivery and utilization allow inferences about the efficiency of the cardiopulmonary system and the impact of disease and medical therapies on tissue metabolism. Goals of high level invasive monitoring of cardiopulmonary function with pulmonary artery catheterization are organ salvage and minimizing complications associated with critical illness. Optimizing renal perfusion and minimizing pulmonary congestion with precise volume titration are common reasons for performing pulmonary artery catheterization in the intensive care unit. Despite being reassuring to clinicians that hemodynamic therapy is optimal, multiple data from well conducted clinical studies have not demonstrated outcome benefits to patients related to pulmonary artery catheterization. Less invasive techniques to obtain data regarding hemodynamic function are now entering the clinical arena and are being actively investigated.
CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: Electrolyte Disturbances in the Intensive Care Unit
Authors: Sedlacek Martin , Schoolwerth Anton C. , Remillard Brian D.
Published: December 2006

The development of many electrolyte disturbances in the ICU can be prevented by attention to the use of intravenous fluids and nutrition. Hyponatremia is a relative contraindication to the use of hypotonic intravenous fluids and hypernatremia calls for the administration of water. Formulae have been devised to guide the therapy of severe hyponatremia and hypernatremia. All formulae regard the patient as a closed system, and none takes into account ongoing fluid losses that are highly variable between patients. Thus, therapy of severe hyponatremia and hypernatremia must be closely monitored with serial electrolyte measurements. The significance of hypocalcemia in the critically ill is controversial. Hypokalemia, hypophosphatemia, and hypomagnesemia should be corrected.
CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: Current Diagnosis and Management of Hypertensive Emergency
Authors: Haas Andrew R. , Marik Paul E.
Published: December 2006

The appropriate and timely evaluation and treatment of patients with severely elevated blood pressure is essential to avoid serious adverse outcomes. Most importantly, the distinction between a hypertensive emergency (crisis) and urgency needs to be made. A sudden elevation in systolic (SBP) and/or diastolic blood pressure (DBP) that is associated with acute end organ damage (cardiovascular, cerebrovascular, or renal) is defined as a hypertensive crisis or emergency. In contrast, acute elevation in SBP and/or DBP not associated with evidence of end organ damage is defined as hypertensive urgency. In patients with a hypertensive emergency, blood pressure control should be attained as expeditiously as possible with parenteral medications to prevent ongoing and potentially permanent end organ damage. In contrast, with hypertensive urgency, blood pressure control can be achieved with the use of oral medications within 24–48 hours. This paper reviews the management of hypertensive emergencies.
CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: Anemia and Red Blood Cell Transfusion in the Critically Ill
Authors: Corwin Howard L.
Published: December 2006

Critically ill patients are anemic early in their intensive care unit (ICU) course. As a consequence of this anemia they receive a large number of red blood cell (RBC) transfusions. There is little evidence that “routine” transfusion of stored allogeneic RBCs is beneficial to critically ill patients and may in fact be associated with worse clinical outcomes. It is clear that most critically ill patients can tolerate hemoglobin levels as low as 7 g/dl and therefore a more conservative approach to RBC transfusion is warranted. Strategies to minimize loss of blood and increase the production of RBCs are also important in the management of all critically ill patients.
CRITICAL CARE ISSUES FOR THE NEPHROLOGIST: Mechanical Ventilation in the Management of Acute Respiratory Distress Syndrome
Authors: Delong Peter , Murray James A. , Cook Christopher K.
Published: December 2006

The occurrence of acute respiratory distress syndrome (ARDS), is now common in intensive care units throughout the world. The diagnosis of ARDS is based on a definition that includes bilateral pulmonary infiltrates on chest radiographs, impaired oxygenation, and the absence of clinical evidence of elevated left atrial pressure. ARDS is the clinical result of a group of diverse processes, which range from physical or chemical injury, to extensive activation of innate inflammatory response. All these processes damage the integrity of the alveolar‐capillary barrier causing increased alveolar‐capillary permeability and an influx of protein‐rich fluid into the alveolar space. This alveolar flooding results in hypoxemia, inactivated surfactant, intrapulmonary shunt, and impaired alveolar ventilation. The treatment of acute respiratory distress syndrome is largely supportive in nature, keeping patients alive while allowing their lungs to heal, and minimizing further pulmonary insult. In 1994 the National Heart, Lung, and Blood Institute (NHLBI) established the ARDS Network for the conduct of clinical trials. This is a network, supported by the National Institutes of Health, that provided the infrastructure for well‐designed, multicenter, randomized trials of therapies for ARDS. The first study from this group in 2001 produced landmark data demonstrating mortality improvements in ARDS with particular mechanical ventilation strategies. Specifically, low tidal volume mechanical ventilation was demonstrated to reduce mortality by 22%. Other strategies such as high positive end expiratory pressure and prone positioning have not been shown to reduce mortality. Clinicians who are involved in the care of patients with ARDS should have a basic understanding of mechanical ventilation and the evidence guiding the mechanical ventilation strategies of these patients. Until further evidence is published, providers should adopt the use of a volume and pressure limited approach to mechanical ventilation.
The Classification of Procedure‐Related Complications—A Fresh Approach
Authors: Beathard Gerald A. , Urbanes Aris , Litchfield Terry
Published: December 2006

As with any type of medical procedure, endovascular procedures result in procedure‐related complications (PRCs). A PRC system as part of an outcome‐based practice monitoring strategy is essential. Such a program should have several features. It should be realistic, it should be standardized, it should have credibility, it must allow for comparisons with other physicians who are performing the same procedure, and it should be easily accomplished. Currently the only system in popular use is the system designed by the Society of Interventional Radiology (SIR). Definitions within this system are excessively broad and somewhat difficult to apply. This leads to inconsistencies. SIR indicates that their system is intended for use in publications of clinical research and may not be appropriate for use in routine clinical practice. There is a need for a system specifically aimed at and designed for day to day use by the practicing interventionalist whose work is not necessarily directed toward publication. We have described a system from the clinical applications viewpoint.
Vascular Access Outcomes and Medication Use: A USRDS Study
Authors: Yevzlin Alexander S. , Conley Emily L. , Sanchez Robert J. , Young Henry N. , Becker Bryan N.
Published: December 2006

Several medications have been proposed to improve hemodialysis (HD) vascular access outcomes based on potentially favorable anticoagulant, antiplatelet, or pleiotropic properties. The purpose of this study was to evaluate the relationship between medication use and vascular access patency in a group of HD patients. We conducted a historical cohort study of the US Renal Data System Dialysis Mortality and Morbidity Wave II study to identify patients with an arteriovenous fistula (AVF), polytetrafluoroethylene (PTFE) graft, or a permanent catheter for vascular access. Cox regression analysis, adjusted for age, gender, race, history of coronary artery disease, peripheral vascular disease, or coronary artery bypass graft, was used to model the hazard ratio (HR) of permanent vascular access failure. Of the 2001 HD patients in the Wave II study, 901 (45%) were included in the analysis. PTFE graft patency was greater for males (HR, 0.73; 95% CI 0.53–1.00, p = 0.05) and for older individuals (HR, 0.99; 95% CI 0.98–1.00, p = 0.02). Treatment with antiplatelet medications, ticlopidine and dipyridamole (HR, 3.54; 95% CI 1.07–11.76; p = 0.04), or aspirin (HR, 2.49; 95% CI 1.31–4.73; p = 0.005) was associated with significantly worse AVF patency. Antiplatelet agents had a significant negative association with access patency in this cohort. In contrast to other published data, it was difficult to identify any beneficial effect of specific medications on access patency.
ASDM Clinical Case Focus: Persistent Left Superior Vena Cava: Diagnosis and Implications for the Interventional Nephrologist
Authors: Wasse Haimanot
Published: December 2006

Awareness and recognition of anatomic anomalies of the great vessels of the neck and chest are important for the interventional nephrologist, as central venous catheter placement is a common procedure. A persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly (0.3–0.5% of the population), and can present difficulty during internal jugular or subclavian vein catheter insertion, as well as pose a diagnostic dilemma. In this report, two cases of PLSVC are described, and the clinical significance and diagnosis of PLSVC are reviewed.
Overutilization of Central Venous Catheters in Incident Hemodialysis Patients: Reasons and Potential Resolution Strategies
Authors: Lenz Oliver , Sadhu Sanghamitra , Fornoni Alessia , Asif Arif
Published: December 2006

Even after adjusting for comorbidities, the outcomes in hemodialysis (HD) patients using a central venous catheter (CVC) as dialysis access are worse than in those with a permanent vascular access. In spite of this, nationwide data suggest that only about 25% of incident HD patients initiate dialysis with an arteriovenous fistula. We conducted a retrospective study to identify reasons and resolution strategies for CVC use in patients who initiated HD at an academic medical center with a well‐established chronic kidney disease (CKD) clinic and a dedicated vascular surgeon. Estimated glomerular filtration rate (eGFR) loss over time to record progression of patients to HD was also examined. The charts of 170 consecutive patients were reviewed. Ninety‐two percent were found to initiate HD using a CVC. Three factors explained 93% of all CVC in our cohort: absence of adequate predialysis care (45%), acute illness with failure to recover from an episode of acute renal failure (31%), and patient's failure to adhere to scheduled clinic or surgical appointments (17%). In addition, analyses of eGFR suggest that the velocity of GFR loss rather than a defined degree of renal function might be a better trigger for vascular access referral. We conclude that early referral, a close follow up of CKD patients who initiate dialysis due to acute illness, and patient education may have a positive impact to counteract overutilization of CVCs for dialysis. The rate in eGFR decline might also be used to calculate the referral time adequate for fistula creation.
Acute intermittent hypoxia increases both phrenic and sympathetic nerve activities in the rat
Authors: Dick Thomas E. , Hsieh Yee‐Hsee , Wang Ning , Prabhakar Nanduri
Published: December 2006

The respiratory system expresses multiple forms of plasticity, defined as alterations in the breathing pattern that persist or develop after a stimulus. Stimulation of breathing with intermittent hypoxia (IH) elicits long‐term facilitation (LTF), a type of plasticity in which respiratory motor activity progressively increases in anaesthetized animals, even after the stimuli have ceased and blood gases have normalized. It is unknown whether the sympathetic nervous system similarly expresses IH‐induced plasticity, but we predicted that IH would evoke LTF in sympathetic nerve activity (SNA) because respiratory and sympathetic control systems are coupled. To test this idea, we recorded splanchnic (sSNA) and phrenic nerve activities (PNA) in equithesin‐anaesthetized rats. Animals were exposed to 10 45 s episodes of 8% O2–92% N2, separated by 5 min intervals of 100% O2, and recordings were continued for 60 min following the last hypoxic exposure. Cycle‐triggered averages of integrated PNA and sSNA from periods preceding, and 5 and 60 min following the hypoxic stimuli were compared. Intermittent hypoxia significantly increased both sSNA and PNA. Treatment with methysergide (3 mg kg−1, i.v.) 20 min before the intermittent hypoxic exposures prevented the increases in integrated PNA and sSNA 60 min after IH, indicating a role of serotonergic pathways in this form of plasticity. No increases in PNA and sSNA occurred at comparable times (60 and 120 min) in rats not exposed to hypoxia. The increased sSNA was not simply tonic, but was correlated with respiratory bursts, and occurred predominantly during the first half of expiration. These findings support the hypothesis that sympathorespiratory coupling may underlie the sustained increase in SNA associated with the IH that occurs during sleep apnoea.
High‐frequency oscillations in phrenic activity during pontile and medullary respiratory rhythms in rats
Authors: St‐John Walter M. , Leiter J. C.
Published: December 2006

High‐frequency oscillations may be signatures of the basic mechanisms underlying the neurogenesis of various patterns of automatic ventilatory activity. These high‐frequency oscillations in phrenic activity differ greatly in eupnoea and gasping, implying different mechanisms of neurogenesis. In a decerebrate, in situ preparation of the rat, the peak frequency of high‐frequency oscillations fell in apneusis following removal of the rostral pons. Following removal of all pons, phrenic discharge had a mixed pattern of gasps and multiple bursts; some of the latter were incrementing, as in eupnoea. Regardless of pattern, peak frequencies were significantly below those which were found during eupnoea, apneusis or gasping of the decerebrate preparation. Results do not support the concept that ‘non‐gasping’ rhythmic patterns that can be recorded following a removal of pons are generated by the same mechanisms as those generating eupnoea. Indeed, both pons and medulla appear essential for all aspects of eupnoea to be expressed.
Modelling the glucocorticoid receptor and producing therapeutic agents with anti‐inflammatory effects but reduced side‐effects
Authors: McMaster Andrew , Ray David William
Published: December 2006

Glucocorticoid hormones exert a wide spectrum of metabolic and immunological effects. They are synthesized from a cholesterol precursor and are structurally related to the other steroid hormones, progesterone, aldosterone and oestrogen. They act through the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily. The GR is an intracellular receptor; the hydrophobic ligand accesses its receptor by diffusion across the plasma membrane. The ligand‐activated GR translocates to the nucleus to regulate expression of its target genes. The GR, in common with the rest of the receptor family, can be functionally divided into an N‐terminal transcription activation domain, a central DNA binding domain and a C‐terminal ligand binding domain, which also includes a second transactivation domain. Although synthetic glucocorticoids are the most potent anti‐inflammatory agents known, their use is limited owing to the range and severity of their side‐effects. The structure of the ligand binding domain of the glucocorticoid receptor has now been solved, and a series of studies has shown that even subtle changes to the ligand structure alter the final conformation of the ligand–receptor complex, with consequences for further protein recruitment and for the function of the receptor. This, coupled with the successful development of selective oestrogen receptor agonists, has led to concerted efforts to find selective GR ligands, with preserved beneficial anti‐inflammatory activity, but reduced side‐effect profile. Current efforts have identified several useful tool compounds, and further molecules are in development in several pharmaceutical companies.
Ultrastructural changes and sarcoplasmic reticulum Ca2+ regulation in red vastus muscle following eccentric exercise in the rat
Authors: Chen Wan , Ruell Patricia A. , Ghoddusi Majid , Kee Anthony , Hardeman Edna C. , Hoffman Kylie M. , Thompson Martin W.
Published: December 2006

This study examined the effects of a bout of low‐intensity, prolonged downhill exercise on sarcoplasmic reticulum (SR) Ca2+‐ATPase activity, Ca2+ uptake and release in rat red vastus muscle. Ionophore stimulation was determined to assess vesicle integrity by measuring the ratio of Ca2+‐ATPase activities in the presence and absence of A23187. Observations of the muscle ultrastructure were made to evaluate muscle damage at the level of the myofibrils and SR. Adult male Sprague–Dawley rats (weight, 395 ± 5.9 g) were either assigned as non‐exercise controls or subjected to 90 min of downhill treadmill exercise (–16 deg; 15 m min−1), and then killed immediately, 4, 24, 48, 72 or 144 h after exercise (n= 7). Calcium uptake was significantly lower (P < 0.05) compared with control values (19.25 ± 1.38 nmol min−1 (mg protein)−1), by 29 and 36% immediately and 4 h postexercise, respectively, and remained depressed (P < 0.05) 24 h postexercise. Calcium release was also significantly lower (P < 0.05) compared with control values (31.06 ± 2.36 nmol min−1 (mg protein)−1), by 37 and 39% immediately and 4 h postexercise, respectively, and remained depressed (P < 0.05) 24 h postexercise. Ca2+‐ATPase activity measured with ionophore was 31% lower (P < 0.05) 4 h postexercise, and remained lower (P < 0.05) 24 h postexercise. The ratio of Ca2+‐ATPase activities in the presence and absence of A23187 was not significantly changed after exercise, indicating that membrane integrity was not altered by the exercise. Focal dilatations of the SR were observed immediately and 4 h following exercise, implying that SR may be susceptible to damage in the localized regions of overstretched sarcomeres. The results demonstrate that a bout of low‐intensity, prolonged downhill exercise results in a long‐lasting depression of SR function that is not fully restored after 2 days of recovery, which may underlie some functional impairments induced by eccentric exercise.
Lack of involvement of the autonomic nervous system in early ventilatory and pulmonary vascular acclimatization to hypoxia in humans
Authors: Liu Chun , Smith Thomas G. , Balanos George M. , Brooks Jerome , Crosby Alexi , Herigstad Mari , Dorrington Keith L. , Robbins Peter A.
Published: December 2006

The activity within the autonomic nervous system may be altered following sustained exposure to hypoxia, and it is possible that this increase in activity underlies the early acclimatization of both ventilation and the pulmonary vasculature to hypoxia. To test this hypothesis, seven individuals were infused with the ganglionic blocker trimetaphan before and after an 8 h exposure to hypoxia. The short half‐life of trimetaphan should ensure that the initial infusion does not affect acclimatization to the 8 h hypoxia exposure, and the use of a ganglion blocking agent should inhibit activity within all branches of the autonomic nervous system. During the infusions of trimetaphan, measurements of ventilation and echocardiographic assessments of pulmonary vascular tone (ΔPmax) were made during euoxia and during a short period of isocapnic hypoxia. Subjects were also studied on two control days, when a saline infusion was substituted for trimetaphan. Trimetaphan had no effect on either euoxic ventilation or the sensitivity of ventilation to acute hypoxia. Trimetaphan significantly reduced ΔPmax in euoxia (P < 0.05), but had no significant effect on the sensitivity of ΔPmax to acute hypoxia once changes in cardiac output had been controlled for. The 8 h period of hypoxia elevated euoxic ventilation (P < 0.001) and ΔPmax (P < 0.001) and increased their sensitivities to acute hypoxia (P < 0.001 for both), indicating that significant acclimatization had occurred. Trimetaphan had no effect on the acclimatization response of any of these variables. We conclude that altered autonomic activity following 8 h of hypoxia does not underlie the acclimatization observed in ventilation or pulmonary vascular tone.
TRPpathies
Authors: Kiselyov Kirill , Soyombo Abigail , Muallem Shmuel
Published: December 2006

Many human diseases are caused by mutations in ion channels. Dissecting the pathogenesis of these ‘channelopathies’ has yielded important insights into the regulation of vital biological processes by ions and has become a productive tool of modern ion channel biology. One of the best examples of a synergism between the clinical and basic science aspects of a modern biological topic is cystic fibrosis. Not only did the identification of the ion channel mutated in cystic fibrosis pinpoint the root cause of this disease, but it also has significantly advanced our understanding of basic biological processes as diverse as protein folding and epithelial fluid and electrolyte secretion. The list of confirmed ‘channelopathies’ is growing and several members of the TRP family of ion channels have been implicated in human diseases such as mucolipidosis type IV (MLIV), autosomal dominant polycystic kidney disease (ADPKD), familial focal segmental glomerulosclerosis (FSG), hypomagnesemia with secondary hypocalcaemia (HSH), and several forms of cancer. Analysing pathogenesis of the diseases linked to TRP dysregulation provides an exciting means of identifying novel functions of TRP channels.
Role of myosin heavy chain composition in the stretch activation response of rat myocardium
Authors: Stelzer Julian E. , Brickson Stacey L. , Locher Matthew R. , Moss Richard L.
Published: December 2006

The speed and force of myocardial contraction during systolic ejection is largely dependent on the intrinsic contractile properties of cardiac myocytes. As the myosin heavy chain (MHC) isoform of cardiac muscle is an important determinant of the contractile properties of individual myocytes, we studied the effects of altered MHC isoform expression in rat myocardium on the mechanical properties of skinned ventricular preparations. Skinned myocardium from thyroidectomized rats expressing only the β MHC isoform displayed rates of force redevelopment that were about 2.5‐fold slower than in myocardium from hyperthyroid rats expressing only the α MHC isoform, but the amount of force generated at a given level of Ca2+ activation was not different. Because recent studies suggest that the stretch activation response in myocardium has an important role in systolic function, we also examined the effect of MHC isoform expression on the stretch activation response by applying a rapid stretch (1% of muscle length) to an otherwise isometrically contracting muscle fibre. Sudden stretch of myocardium resulted in a concomitant increase in force that quickly decayed to a minimum and was followed by a delayed redevelopment of force (i.e. stretch activation) to levels greater than prestretch force. β MHC expression dramatically slowed the overall rate of the stretch activation response compared to expression of α MHC isoform; specifically, the rate of force decay was ∼2‐fold slower and the rate of delayed force development was ∼2.5‐fold slower. In contrast, MHC isoform had no effect on the amplitude of the stretch activation response. Collectively, these data show that expression of β MHC in myocardium dramatically slows rates of cross‐bridge recruitment and detachment which would be expected to decrease power output and contribute to depressed systolic function in end‐stage heart failure.
The electrogenic Na+/HCO3− cotransport modulates resting membrane potential and action potential duration in cat ventricular myocytes
Authors: Villa‐Abrille María C. , Petroff Martín G. Vila , Aiello Ernesto A.
Published: December 2006

Perforated whole‐cell configuration of patch clamp was used to determine the contribution of the electrogenic Na+/HCO3− cotransport (NBC) on the shape of the action potential in cat ventricular myocytes. Switching from Hepes to HCO3− buffer at constant extracellular pH (pHo) hyperpolarized resting membrane potential (RMP) by 2.67 ± 0.42 mV (n= 9, P < 0.05). The duration of action potential measured at 50% of repolarization time (APD50) was 35.8 ± 6.8% shorter in the presence of HCO3− than in its absence (n= 9, P < 0.05). The anion blocker SITS prevented and reversed the HCO3−‐induced hyperpolarization and shortening of APD. In addition, no HCO3−‐induced hyperpolarization and APD shortening was observed in the absence of extracellular Na+. Quasi‐steady‐state currents were evoked by 8 s duration voltage‐clamped ramps ranging from −130 to +30 mV. A novel component of SITS‐sensitive current was observed in the presence of HCO3−. The HCO3−‐sensitive current reversed at −87 ± 5 mV (n= 7), a value close to the expected reversal potential of an electrogenic Na+/HCO3− cotransport with a HCO3−:Na+ stoichiometry ratio of 2: 1. The above results allow us to conclude that the cardiac electrogenic Na+/HCO3− cotransport has a relevant influence on RMP and APD of cat ventricular cells.
Removal of phosphorylation sites of γ subunit of phosphodiesterase 6 alters rod light response
Authors: Tsang S. H. , Woodruff M. L. , Janisch Kerstin M. , Cilluffo M. C. , Farber D. B. , Fain G. L.
Published: December 2006

The phosphodiesterase 6 γ (PDE6γ) inhibitory subunit of the rod PDE6 effector enzyme plays a central role in the turning on and off of the visual transduction cascade, since binding of PDE6γ to the transducin α subunit (Tα) initiates the hydrolysis of the second messenger cGMP, and PDE6γ in association with RGS9‐1 and the other GAP complex proteins (Gβ5, R9AP) accelerates the conversion of TαGTP to TαGDP, the rate‐limiting step in the decay of the rod light response. Several studies have shown that PDE6γ can be phosphorylated at two threonines, T22 and T35, and have proposed that phosphorylation plays some role in the physiology of the rod. We have examined this possibility by constructing mice in which T22 and/or T35 were replaced with alanines. Our results show that T35A rod responses rise and decay more slowly and are less sensitive to light than wild‐type (WT). T22A responses show no significant difference in initial time course with WT but decay more rapidly, especially at dimmer intensities. When the T22A mutation is added to T35A, double mutant rods no longer showed the prolonged decay of T35A rods but remained slower than WT in initial time course. Our experiments suggest that the polycationic domain of PDE6γ containing these two phosphorylation sites can influence the rate of PDE6 activation and deactivation and raise the possibility that phosphorylation or dephosphorylation of PDE6γ could modify the time course of transduction, thereby influencing the wave form of the light response.
Increased responsiveness of rat colonic splanchnic afferents to 5‐HT after inflammation and recovery
Authors: Coldwell Jonathan R. , Phillis Benjamin D. , Sutherland Kate , Howarth Gordon S. , Blackshaw L. Ashley
Published: December 2006

5‐Hydroxytryptamine (5‐HT) activates colonic splanchnic afferents, a mechanism by which it has been implicated in generating symptoms in postinfectious and postinflammatory states in humans. Here we compared mechanisms of colonic afferent activation by 5‐HT and mechanical stimuli in normal and inflamed rat colon, and after recovery from inflammation. Colonic inflammation was induced in rats by dextran sulphate sodium. Single‐fibre recordings of colonic lumbar splanchnic afferents revealed that 58% of endings responded to 5‐HT (10−4m) in controls, 88% in acute inflammation (P < 0.05) and 75% after 21 days recovery (P < 0.05 versus control). Maximal responses to 5‐HT were also larger, and the estimated EC50 was reduced from 3.2 × 10−6 to 8 × 10−7m in acute inflammation and recovered to 2 × 10−6m after recovery. Responsiveness to mechanical stimulation was unaffected. 5‐HT3 receptor antagonism with alosetron reduced responses to 5‐HT in controls but not during inflammation. Responses to the mast cell degranulator 48/80 mimicked those to 5‐HT in inflamed tissue but not in controls, and more 5‐HT‐containing mast cells were seen close to calcitonin gene‐related peptide‐containing fibres in inflamed serosa. We conclude that colonic serosal and mesenteric endings exhibit increased sensitivity to 5‐HT in inflammation, with both an increase in proportion of responders and an increase in sensitivity, which is maintained after healing of inflammation. This is associated with alterations in the roles of 5‐HT3 receptors and mast cells.
Acceleration of AMPA receptor kinetics underlies temperature‐dependent changes in synaptic strength at the rat calyx of Held
Authors: Postlethwaite M. , Hennig M. H. , Steinert J. R. , Graham B. P. , Forsythe I. D.
Published: December 2006

It is well established that synaptic transmission declines at temperatures below physiological, but many in vitro studies are conducted at lower temperatures. Recent evidence suggests that temperature‐dependent changes in presynaptic mechanisms remain in overall equilibrium and have little effect on transmitter release at low transmission frequencies. Our objective was to examine the postsynaptic effects of temperature. Whole‐cell patch‐clamp recordings from principal neurons in the medial nucleus of the trapezoid body showed that a rise from 25°C to 35°C increased miniature EPSC (mEPSC) amplitude from −33 ± 2.3 to −46 ± 5.7 pA (n= 6) and accelerated mEPSC kinetics. Evoked EPSC amplitude increased from −3.14 ± 0.59 to −4.15 ± 0.73 nA with the fast decay time constant accelerating from 0.75 ± 0.09 ms at 25°C to 0.56 ± 0.08 ms at 35°C. Direct application of glutamate produced currents which similarly increased in amplitude from −0.76 ± 0.10 nA at 25°C to −1.11 ± 0.19 nA 35°C. Kinetic modelling of fast AMPA receptors showed that a temperature‐dependent scaling of all reaction rate constants by a single multiplicative factor (Q10= 2.4) drives AMPA channels with multiple subconductances into the higher‐conducting states at higher temperature. Furthermore, Monte Carlo simulation and deconvolution analysis of transmission at the calyx of Held showed that this acceleration of the receptor kinetics explained the temperature dependence of both the mEPSC and evoked EPSC. We propose that acceleration in postsynaptic AMPA receptor kinetics, rather than altered presynaptic release, is the primary mechanism by which temperature changes alter synaptic responses at low frequencies.
Window Ca2+ current and its modulation by Ca2+ release in hypertrophied cardiac myocytes from dogs with chronic atrioventricular block
Authors: Antoons Gudrun , Volders Paul G. A. , Stankovicova Tania , Bito Virginie , Stengl Milan , Vos Marc A. , Sipido Karin R.
Published: December 2006

Torsades de pointes (TdP) ventricular tachycardia typically occurs in the setting of early afterdepolarizations; it contributes to arrhythmias and sudden death in congenital and acquired heart disease. Window L‐type Ca2+ current (ICaL) has a central role in the arrhythmogenesis and may be particularly important under β‐adrenergic stimulation. We studied the properties of ICaL in myocytes from the dog with chronic atrioventricular block (cAVB) that has cardiac hypertrophy and an increased susceptibility to TdP. Peak ICaL densities at baseline (K+‐ and Na+‐free solutions, 10 mmol l−1[EGTA]pip) in cAVB were comparable to control, but inactivation was shifted to the right, resulting in a larger window current area in cAVB. Under β‐adrenergic stimulation, the window current area was increased and shifted to the left, but less so in cAVB (maximum at −27 mV, versus−32 mV in control). ICaL during a step to −35 mV showed a transient reduction immediately after the peak. Test steps to 0 mV, simultaneous recording of [Ca2+]i and manipulation of sarcoplasmic reticulum (SR) Ca2+ release showed that this resulted from inhibition and fast recovery of ICaL with SR Ca2+ release. The extent of this dynamic modulation was larger in cAVB than in control (23 ± 2% of the initially available current, versus 13 ± 3%; P < 0.05). Early afterdepolarizations (EADs) in cAVB myocytes under β‐adrenergic stimulation typically occurred in the window current voltage range and after decline of [Ca2+]i. In conclusion, in cAVB, the larger window current, its rightward shift and enhanced dynamic modulation by SR Ca2+ release may contribute to an increased incidence of EADs in cAVB under β‐adrenergic stimulation.
Ageing reduces nitric‐oxide‐ and prostaglandin‐mediated vasodilatation in exercising humans
Authors: Schrage William G. , Eisenach John H. , Joyner Michael J.
Published: December 2006

In older humans, infusions of endothelial agonists suggest endothelial dysfunction, due in part to less nitric oxide (NO)‐ and prostaglandin (PG)‐mediated vasodilatation, and a shift toward PG‐mediated vasoconstriction. Ageing can also be associated with lower exercise blood flow (exercise hyperaemia), but the vascular mechanisms mediating this remain unknown. Notably, in young adults, inhibition of NO and PGs during exercise decreases exercise hyperaemia by ∼20 and ∼12%, respectively. We tested our first hypothesis that in older humans inhibition of NO would decrease hyperaemia, but that inhibition of PGs would increase hyperaemia by blocking vasoconstrictor PGs. Fifteen older subjects (65 ± 3 years) performed dynamic forearm exercise for 20 min (20 contractions min−1). Forearm blood flow (FBF) was measured beat‐to‐beat with Doppler ultrasound, while saline or drugs were infused sequentially via brachial artery catheter in the exercising forearm. After achieving steady‐state exercise, l‐NAME (25 mg) was infused over 5 min to inhibit NO synthase. After a further 2 min of exercise (saline), ketorolac (6 mg) was infused over 5 min to inhibit PGs, followed by a futher 3 min of exercise with saline. Drug order was reversed in seven subjects. l‐NAME reduced steady‐state exercise hyperaemia by 12 ± 3% in older subjects (P < 0.01), whereas ketorolac had no net effect on blood flow (3 ± 6%, P > 0.4). The effects of l‐NAME and ketorolac were independent of drug order. By comparing these results with our previous results in young adults, we tested our second hypothesis that in older humans inhibition of NO or PGs would have less impact on exercise hyperaemia due to less vasodilatation from these signals. Our results suggest that, compared with young adults, in older humans the relative contribution of NO to exercise hyperaemia is reduced ∼45% (22 ± 4 versus 12 ± 3%), but the role of PG in mediating vasodilatation is lost in ageing human skeletal muscle. Lower exercise hyperaemia in older humans may be mediated in part by less NO‐ and PG‐mediated vasodilatation during exercise.
Spectropolarimetric Diagnostics of Thermonuclear Supernova Explosions
Authors: Wang Lifan , Baade Dietrich , Patat Ferdinando
Published: December 2006

Even at extragalactic distances, the shape of supernova ejecta can be effectively diagnosed by spectropolarimetry. We present results for 17 type Ia supernovae that allow a statistical study of the correlation among the geometric structures and other observable parameters of type Ia supernovae. These observations suggest that type Ia supernova ejecta typically consist of a smooth, central, iron-rich core and an outer layer with chemical asymmetries. The degree of this peripheral asphericity is correlated with the light-curve decline rate of type Ia supernovae. These results lend strong support to delayed-detonation models of type Ia supernovae.
Slow Earthquakes Coincident with Episodic Tremors and Slow Slip Events
Authors: Ito Yoshihiro , Obara Kazushige , Shiomi Katsuhiko , Sekine Shutaro , Hirose Hitoshi
Published: December 2006

We report on the very-low-frequency earthquakes occurring in the transition zone of the subducting plate interface along the Nankai subduction zone in southwest Japan. Seismic waves generated by very-low-frequency earthquakes with seismic moment magnitudes of 3.1 to 3.5 predominantly show a long period of about 20 seconds. The seismicity of very-low-frequency earthquakes accompanies and migrates with the activity of deep low-frequency tremors and slow slip events. The coincidence of these three phenomena improves the detection and characterization of slow earthquakes, which are thought to increase the stress on updip megathrust earthquake rupture zones.
Homoploid Hybrid Speciation in an Extreme Habitat
Authors: Gompert Zachariah , Fordyce James A. , Forister Matthew L. , Shapiro Arthur M. , Nice Chris C.
Published: December 2006

According to theory, homoploid hybrid speciation, which is hybrid speciation without a change in chromosome number, is facilitated by adaptation to a novel or extreme habitat. Using molecular and ecological data, we found that the alpine-adapted butterflies in the genus
Lycaeides
are the product of hybrid speciation. The alpine populations possess a mosaic genome derived from both
L. melissa
and
L. idas
and are differentiated from and younger than their putative parental species. As predicted, adaptive traits may allow for persistence in the environmentally extreme alpine habitat and reproductively isolate these populations from their parental species.
Hip arthroscopy: current concepts and review of literature
Authors: Shetty Vijay D , Villar Richard N
Published: December 2006

Diagnosis and treatment of intra-articular hip problems in young patients present a challenge to hip surgeons. Previous studies have shown that non-invasive investigations such as radiography, computed tomography and magnetic resonance imaging provide limited help. Non-operative treatment is likely to result in persistent symptoms, and surgical options for intra-articular hip problems involve open arthrotomy of the hip joint, which carries potential risks associated with joint dislocation. Arthroscopy of the hip joint, therefore, seems to be an attractive option. It was once thought that introduction of a straight arthroscope into the ball-and-socket hip joint was almost impossible. Hip arthroscopy has seen several advances since then, and the speed at which it developed in recent years directly corresponded to the rate at which the conditions affecting the hip joint were identified. Athletes and other young individuals with hip injuries are increasingly being diagnosed with an ever evolving series of conditions. Many of these conditions were previously unrecognised and thus left untreated, resulting in premature ends to the patients’ competitive careers. Hip arthroscopy, as with any procedure, is not without risks. The procedure is not widely available as it requires specialist equipment and takes a long time to learn. Complications are few, occurring in <5% of patients.