bluuebunny/crossref_metadata_2025 huggingface dataset:
Economic Catastrophe Bonds
Authors: Coval Joshua D , Jurek Jakub W , Stafford Erik
Published: June 2009

The central insight of asset pricing is that a security's value depends both on its distribution of payoffs across economic states and on state prices. In fixed income markets, many investors focus exclusively on estimates of expected payoffs, such as credit ratings, without considering the state of the economy in which default occurs. Such investors are likely to be attracted to securities whose payoffs resemble economic catastrophe bonds—bonds that default only under severe economic conditions. We show that many structured finance instruments can be characterized as economic catastrophe bonds, but offer far less compensation than alternatives with comparable payoff profiles. (JEL G11, G12)
Distributional and Efficiency Impacts of Increased US Gasoline Taxes
Authors: Bento Antonio M , Goulder Lawrence H , Jacobsen Mark R , von Haefen Roger H
Published: June 2009

We examine the impacts of increased US gasoline taxes in a model that links the markets for new, used, and scrapped vehicles and recognizes the considerable heterogeneity among households and cars. Household choice parameters derive from an estimation procedure that integrates individual choices for car ownership and miles traveled. We find that each cent-per-gallon increase in the price of gasoline reduces the equilibrium gasoline consumption by about 0.2 percent. Taking account of revenue recycling, the impact of a 25-cent gasoline tax increase on the average household is about $30 per year (2001 dollars). Distributional impacts depend importantly on how additional revenues from the tax increase are recycled. (JEL D12, H22, H25, L62, L71)
Trade, Tragedy, and the Commons
Authors: Copeland Brian R , Taylor M. Scott
Published: June 2009

We develop a theory of resource management where the degree to which countries escape the tragedy of the commons, and hence the de facto property rights regime, is endogenously determined. Three forces determine success or failure in resource management: the regulator's enforcement power, the extent of harvesting capacity, and the ability of the resource to generate competitive returns without being extinguished. The model can explain heterogeneity across countries and resources in the effectiveness of resource management, and it predicts that changes in prices, population, and technology can cause transitions to better or worse management regimes. (JEL P14, Q21, Q22, Q23, Q32)
The Young, the Old, and the Restless: Demographics and Business Cycle Volatility
Authors: Jaimovich Nir , Siu Henry E
Published: June 2009

We investigate the consequences of demographic change for business cycle analysis. We find that changes in the age composition of the labor force account for a significant fraction of the variation in cyclical volatility observed in the G7. Since World War II, these countries have experienced dramatic demographic changes, although details regarding timing and nature differ across countries. We exploit this variation to show that the workforce age composition has a large and significant effect on cyclical volatility. We relate our results to the recent decline in US macroeconomic volatility, finding that demographic change accounts for approximately one-fifth to one-third of this moderation. (JEL E32, J11)
Observational Learning: Evidence from a Randomized Natural Field Experiment
Authors: Cai Hongbin , Chen Yuyu , Fang Hanming
Published: June 2009

We report results from a randomized natural field experiment conducted in a restaurant dining setting to distinguish the observational learning effect from the saliency effect. We find that, when customers are given ranking information of the five most popular dishes, the demand for those dishes increases by 13 to 20 percent. We do not find a significant saliency effect. We also find modest evidence that the observational learning effects are stronger among infrequent customers, and that dining satisfaction is increased when customers are presented with the information of the top five dishes, but not when presented with only names of some sample dishes. (JEL C93, D83)
Misselling through Agents
Authors: Inderst Roman , Ottaviani Marco
Published: June 2009

This paper analyzes the implications of the inherent conflict between two tasks performed by direct marketing agents: prospecting for customers and advising on the product's “suitability” for the specific needs of customers. When structuring salesforce compensation, firms trade off the expected losses from “misselling” unsuitable products with the agency costs of providing marketing incentives. We characterize how the equilibrium amount of misselling (and thus the scope of policy intervention) depends on features of the agency problem including: the internal organization of a firm's sales process, the transparency of its commission structure, and the steepness of its agents' sales incentives. (JEL M31, M37, M52)
Reference-Dependent Consumption Plans
Authors: Kőszegi Botond , Rabin Matthew
Published: June 2009

We develop a rational dynamic model in which people are loss averse over changes in beliefs about present and future consumption. Because changes in wealth are news about future consumption, preferences over money are reference-dependent. If news resonates more when about imminent consumption than when about future consumption, a decision maker might (to generate pleasant surprises) overconsume early relative to the optimal committed plan, increase immediate consumption following surprise wealth increases, and delay decreasing consumption following surprise losses. Since higher wealth mitigates the effect of bad news, people exhibit an unambiguous first-order precautionary-savings motive. (JEL D14, D81, D83, D91)
Cooperation among Strangers under the Shadow of the Future
Authors: Camera Gabriele , Casari Marco
Published: June 2009

We study the emergence of norms of cooperation in experimental economies populated by strangers interacting indefinitely. Can these economies achieve full efficiency even without formal enforcement institutions? Which institutions for monitoring and enforcement facilitate cooperation? Finally, what classes of strategies do subjects employ? We find that, first, cooperation can be sustained even in anonymous settings; second, some type of monitoring and punishment institutions significantly promote cooperation; and, third, subjects mostly employ strategies that are selective in punishment. (JEL C71, C73, D12, Z13)
Route Design for Delivery of Voting Machines in Hamilton County, Ohio
Authors: Fry Michael J. , Ohlmann Jeffrey W.
Published: June 2009

The Help America Vote Act that Congress passed in 2002 required election boards to update their punch card voting systems with new voting technologies by 2006. This change greatly increases the operational and logistical complexities of administering elections in many areas. Because of security concerns and the large physical size of some types of new voting machines, they must be delivered to each polling location during a specified day and time window. Therefore, to generate feasible, cost-effective delivery routes, election boards must solve a difficult vehicle-routing problem. Routes designed by our solution methods have been successfully implemented in Hamilton County, Ohio, to deliver voting machines to polling locations for multiple elections since May 2006. We describe our solution methods and analyze the sensitivity of route costs to time-window and delivery-day constraints. Our sensitivity analysis identified cost-savings strategies that the Hamilton County Board of Elections used to negotiate a new scheduling protocol with poll workers; this protocol reflects a compromise between accommodating poll workers' schedules and reducing the cost of delivering the voting machines. The Board of Elections successfully implemented this new method of specifying delivery time windows, which allowed greater routing flexibility, for the November 2006 midterm election.
Towards a Single European Sky
Authors: Grushka-Cockayne Yael , De Reyck Bert
Published: June 2009

We describe an integrated decision-making framework and model that we developed to aid EUROCONTROL, the European air traffic management organization, in its vital role of constructing a single unified European sky. Combining multicriteria decision analysis with large-scale optimization methods, such as integer programming and column generation using branch and price, our model facilitates the process by which the numerous European aviation stakeholders evaluate and select technological enhancements to the European air traffic management system. We consider multiple objectives and potential disagreements by stakeholders regarding the impact of proposed system enhancements and allow for different priorities for each key performance area. In an earlier paper, we described the mathematical programming model in detail. In this paper, we elaborate on the broader decision framework and supporting methodologies to help EUROCONTROL in its facilitation role. Using our model and decision framework, EUROCONTROL is currently selecting a set of enhancements to the European aviation system upon which all stakeholders have agreed.
Managing Inventory in Supply Chains with Nonstationary Demand
Authors: Neale John J. , Willems Sean P.
Published: June 2009

Many companies experience nonstationary demand because of short product life cycles, seasonality, customer buying patterns, or other factors. We present a practical model for managing inventory in a supply chain facing stochastic, nonstationary demand. Our model is based on the guaranteed service modeling framework. We first describe how inventory levels should adapt to changes in demand at a single stage. We then show how nonstationary demand propagates in a supply chain, allowing us to link stages and apply a multiechelon optimization algorithm designed originally for stationary demand. We describe two successful applications of this model. The first is a tactical implementation to support monthly safety stock planning at Microsoft. The second is a strategic project to evaluate the benefits of using an inventory pool at Case New Holland.
Setting Prices on Priceline
Authors: Anderson Chris K.
Published: June 2009

Priceline is best known for its name-your-own-price format, in which consumers bid for services but not for service providers. Because Priceline serves as an opaque selling mechanism, it attracts price-conscious consumers. Sellers also benefit because they can price into multiple market segments without worrying that they are diluting revenue they might receive from customers who are willing to use conventional selling channels and pay more. A firm that releases its inventory to Priceline must manage the trade-off of pricing its inventory too low (and forgoing revenue) versus pricing it too high and forgoing a sale. In this paper, we outline the mechanism that Priceline uses to determine if customer bids are successful and, given this mechanism, establishes optimal prices and inventory allocations for Kimpton Hotels.
Organizational Linkages for Surviving Technological Change: Complementary Assets, Middle Management, and Ambidexterity
Authors: Taylor Alva , Helfat Constance E.
Published: June 2009

Technological innovation sometimes requires industry incumbents to shift to a completely new core technology. To successfully navigate a technological transition, firms often face the ambidextrous challenge of “exploiting” existing complementary assets to support the new “exploratory” core technology. We argue that an industry incumbent attempting to make a transition to a new technology requires linkages between organizational units responsible for developing the new technology and units in charge of complementary assets needed to commercialize the innovation. These linkages are critical but overlooked elements of organizational ambidexterity. This paper develops a conceptual framework in which the ability to build and leverage organizational linkages involving the new technology and its complementary assets is essential for a successful technological transition. The framework also highlights the importance of middle management in creating and maintaining these linkages, which are critical to dynamic capabilities in technological transitions. We identify four critical influences—economic, structural, social, and cognitive—on managerial linking activity that enable firms to transition to a new technology while utilizing valuable preexisting capabilities. The technological transitions of IBM and NCR illustrate the importance of organizational linkages and managerial linking activity.
Young and No Money? Never Mind: The Material Impact of Social Resources on New Venture Growth
Authors: Khaire Mukti
Published: June 2009

Although growth is a desirable outcome for new ventures due to the many advantages of large size, most new firms fail to grow, largely because of their limited resources and adaptability. This paper addresses the question of how new ventures grow despite their limited financial resources. I explore the effect of two specific nonfinancial, social resources—legitimacy and status—on new venture growth. I propose that new firms can acquire legitimacy by mimicking the structures and ceremonial activities of established firms in their industry, and can acquire status by affiliating with high-status entities. Using a unique panel data set on a cohort of advertising agencies founded in New York and Chicago between 1977 and 1985, I show that legitimacy and status have favorable impacts on new firms' growth in revenues and number of employees. The paper makes important contributions to social embeddedness and institutional research by examining the strategic implications of firm-level social resources, and to the literature on entrepreneurship in general and new venture growth in particular.
Experiencing Rare and Unusual Events Richly: The Role of Middle Managers in Animating and Guiding Organizational Interpretation
Authors: Beck Tammy E. , Plowman Donde Ashmos
Published: June 2009

Organizations have difficulty learning from rare and unusual events because of their inability to interpret these events. Because organizations develop habitual ways of interpreting events—often top down—they can easily miss the novelty of rare and unusual events, which prevents them from experiencing events “richly.” We propose a multilevel, multistaged model of organizational interpretation that highlights the important, but generally unacknowledged, role middle managers can play in helping organizations experience rare and unusual events richly. Our model accounts for the effect of cognitive biases and hierarchical context on organizational interpretation. Because of their proximity to the interpretations of both strategic and front-line managers, middle managers can encourage divergence in interpretations of managers across hierarchical levels during early stages of the interpretation process and can blend and synthesize the divergent interpretations of managers during later stages. In this way middle managers contribute to a dynamic process of organizational interpretation in which multiple filters from throughout the organization help frame and enrich interpretations of rare and unusual events, which enables organizational learning.
Significance Evaluation of Material and Additive Factors Influencing Moisture Susceptibility of Asphalt Mixtures
Authors: Zeng Menglan , Wu Chaofan , Huang Kaiyu
Published: June 2009

Many factors have been identified to have influences on the moisture susceptibility of asphalt mixtures. This research study attempts to evaluate such factors as binder type, aggregate type, mixture type, additive usage, additive type, additive application approach, and additive organic nature. Tensile strength ratio (TSR) was tested on twelve asphalt mixtures of three types, with two binders and three aggregates, and with improving measures as three antistripping additives and two application approaches. Multiple variable statistical analyses were employed on the TSR data in assessing the significance of the factor. Test results and data analyses indicate that the extent of the influence varies considerably from one factor to another. The styrene-butadiene-styrene modified binder is superior to neat petroleum binder for producing asphalt mixtures subject to damp conditions. Granite, basalt, and limestone aggregates make asphalt mixtures that are least, in-between, and most resistant to moisture damage, respectively. Compared with dense graded asphalt concrete (AC) and stone matrix asphalt (SMA) mixtures, porous asphalt macadam (AM) mixtures are more prone to stripping. The usage of inorganic hydrated lime and Portland cement, and organic amine antistripping agent can substantially improve the moisture susceptibility of asphalt mixtures; the wet approach for applying the inorganic additives can result in better effects than the dry approach. Different additives show little difference in improving effects with mixed trends and the inorganic and organic additives are similar in performance with variations that are immaterial.
Preliminary Study on Asphalt Emulsion Used in Cement Asphalt Mortar
Authors: Fazhou Wang , Yunhua Zhang , Yunpeng Liu , Tao Gao , Jinzhong Zou , Liang Chen
Published: June 2009

Asphalt emulsion is an important component in the preparation of cement asphalt mortar. In the work reported here, different emulsifiers and basic asphalts were used to manufacture emulsions and their properties were investigated. Results indicate that a diamine-based emulsifier renders asphalt emulsion that exhibits better compatibility with cement; lower density and higher ductility basic asphalt; and that styrene-butadiene-styrene modifiers are more appropriate in the manufacturing of emulsion.
The Damage Analysis of Asphalt Pavement Under Repeated Loads
Authors: Jingsong Shan , Xiaoming Huang
Published: June 2009

Generally, the process of pavement deterioration occurs before the macrocrack appearing in asphalt pavement structure. It is always useful to understand the causes of pavement cracking and present preventive measures. In this paper, damage regularity of asphalt pavement under the condition of repeated loading is studied in terms of dynamic damage finite element method. The software ABAQUS was used for calculation and subroutine of damage was obtained by using the interface of the vectorized user material routine. The relationships between the times of loading and the damage degree, maximum tension stress of element and maximum tension strain of element are analyzed and discussed.
Optimal Bitumen-Aggregate Ratio Selection Method of Hot Mix Asphalt Based on Closest Compaction Condition
Authors: Wang Xu-dong , Zhang Lei
Published: June 2009

An optimal bitumen-aggregate ratio selection method for hot mix asphalt, based on aggregate closest compact condition, was introduced. According to research, high correlation within dry density, voids in mineral aggregate (VMA) and voids in coarse aggregate (VCA) versus bitumen-aggregate ratio was discovered. Dry density increases with increase of bitumen-aggregate ratio until it reaches a peak, and then decreases. VMA and VCA have the inverse trend. The advantage of the unique extreme point rule of the conic is the relationship of bitumen-aggregate ratio versus dry density and that the VMA and VCA can be indicated by conic regression analysis, and the corresponding bitumen-aggregate ratio can be achieved as well. In this paper, the new design method was adopted for hot mix asphalt in various gradations and the differences from the previous design method were also illustrated. The inaccurate bitumen-aggregate ratio due to previous design criterion can be avoided through setting the closest compact condition. This can also be recommended as the design criterion.
Metabolic effects of pulsatile insulin infusion in the elderly
Authors: Paolisso Giuseppe , Salvatore Teresa , Sgambato Saverio , Torella Roberto , Varricchio Michele , D'Onofrio Felice
Published: June 2009

The present study investigated the metabolic effects of pulsatile insulin delivery at a pulse rate of 2+ 11 and 2+18 min in 7 healthy, elderly subjects (71.4±2.1 years), submitted to 260 min controlled iv glucose infusion via the Biostator. The endogenous secretion of pancreatic hormones was inhibited by somatostatin (3 μg/min) and glucagon was replaced (67 ng/min) to basal levels. The same total insulin dose was delivered on both occasions. Insulin infusion rate was 1.3 and 2.0 mIU · kg−1 · min−1 during switching on/off of 2+11 and 2+18 min, respectively. Blood glucose levels and glucose infusion rate were monitored continuously by the Biostator; [D-3-3H]glucose infusion allowed determination of glucose turnover. During the last 60 min of the experiment, pulsatile insulin at a pulse rate of 2+11 vs 2+18 min produced a stronger inhibition of endogenous glucose production, whereas glucose disappearance rate and glucose metabolic clearance rate were similarly affected. Plasma triglycerides, apolipoprotein B, and free fatty acids levels were also more suppressed during insulin delivery at pulse rate of 2+11 than at 2+18 min.
Androgen receptor levels in patients with isolated hypospadias
Authors: Terakawa Tomoyoshi , Shima Hiroki , Yabumoto Hidenori , Koyama Koji , Ikoma Fumihiko
Published: June 2009

The binding of [3H]dihydrotestosterone (17β-hydroxy-5α-androstan-3-one) to the androgen receptor was studied in 26 prepubertal boys with isolated hypospadias (no associated anomaly) using fibroblasts cultured from surgical specimens of hypospadiac penile skin and/or chordal tissue. Maximal binding capacities of androgen receptor for [3H] dihydrotestosterone in 10 patients with mild degree (2 glandular+8 penile), 6 with severe degree (4 penoscrotal + 2 scrotal), chordal tissues of hypospadias (N=10), and controls (10 endocrinologically normal boys) were, respectively, 11750±2410, 10720±2680, 16100±7570, and 11570±3830 (mean ± sd) sites per cell. Dissociation constants in these subjects were 1.09±0.29,0.93±0.22,1.20±0.31, and 1.22±0.41 × 10−10 mol/l respectively. There were no significant differences as to both maximal binding capacity and dissociation constant of androgen receptor among any groups. Abnormal receptor thermolability was not found in 5 patients with severe degree of hypospadias either. It is, therefore, concluded that prepubertal boys with isolated hypospadias have primarily normal androgen receptor activity.
Effect of prolonged overnight fasting on energy metabolism in non-insulin-dependent diabetic and non-diabetic subjects
Authors: Groop Leif C. , Bonadonna Riccardo , DelPrato Stefano , Ratheiser Klaus , DeFronzo Ralph A.
Published: June 2009

The effect on energy metabolism of a 6-h prolongation of the conventional 12-h overnight fast was examined in 9 healthy subjects and in 7 patients with non-insulin-dependent diabetes mellitus. Plasma glucose concentration decreased by 7 and 23%, in control and diabetic subjects, respectively. In control subjects, the fall in plasma glucose was associated with a slight but significant fall in plasma insulin and a rise in plasma free fatty acid concentrations. During this same period, the rates of plasma free fatty acid oxidation, measured by infusion of [14C]palmitate, and net lipid oxidation, measured by indirect calorimetry, increased in normal subjects by 55 and 76%, respectively; the rate of glucose oxidation measured by indirect calorimetry decreased by 37%. In the diabetic patients, the free fatty acid oxidation rate was enhanced already after 12 h of fasting compared with controls (2.06 vs 1.30 μmol · kg−1 · min−1; p<0.05) and did not change significantly during the 6-h observation period. After 18 h of fasting, the rate of plasma free fatty acid oxidation was similar in control and diabetic subjects. The data thus emphasize the need for strict standardization of the overnight fasting period for metabolic studies, and demonstrate the difficulties in comparing basal rates of substrate oxidation between healthy and diabetic subjects.
Kallidin-induced stimulation of inositol phosphate production and prolactin release in rat anterior pituitary cells
Authors: Jones T. Hugh , Brown Barry L. , Dobson Pauline R. M.
Published: June 2009

The effect of the kinin, kallidin (lysyl-brady-kinin) on phosphoinositide metabolism and prolactin secretion was examined in male rat anterior pituitary cells in primary culture. Kallidin was found to stimulate both total inositol phosphate production and prolactin release. The stimulation of inositol phosphate was biphasic in nature, similar to that previously reported for bradykinin, although kallidin was approximately 10-fold more potent. Kallidin also stimulated prolactin secretion provoking a maximal stimulation of 193.0±11.1 (sem)% at 1 μmol/l. These findings suggest that kallidin-induced prolactin secretion may be mediated intracellularly by activation of phosphoinositide metabolism. The B2 receptor antagonists had no significant inhibitory effects on kallidin-stimulated phosphoinositide metabolism or prolactin release. The B1 agonist des-Arg9-bradykinin has previously been shown to have no effect on either parameter. As the effects of kinins on anterior pituitary cells do not appear to be mediated by either of the known kinin receptors, they may, therefore, act via a hitherto unrecognised kinin receptor.
Circulating forms and biological activity of intact and truncated insulin-like growth factor I in adult and neonatal rats
Authors: Drakenberg Katarina , Östenson Claes-Göran , Sara Vicki
Published: June 2009

A variant of IGF-I with a truncated aminoterminal region has been isolated and shown to display increased biological activity in vitro, but weak affinity of binding to the IGF binding proteins compared with intact IGF-I. In the present study, the circulating molecular forms and biological activity of intact and truncated IGF-I were compared after in vivo administration. Adult and 10-day-old rats were given 125I-truncated or 125I-intact IGF-I iv. In both adult and 10-day-old rats 125I-truncated IGF-I showed weaker affinity of binding to the IGF binding proteins and greater degradation than 125I-intact IGF-I. Serum half-life was 2 h for 125I-truncated IGF-I and 3 h for 125I-intact IGF-I in adult rats. The half-life in 10-day-old rats was 20.5 min for 125I-truncated IGF-I and 27 min for 125I-intact IGF-I. The uptake of 125I-truncated IGF-I into the kidney, liver and brain of 10-day-old rats was significantly higher than for 125I-intact IGF-I 15 min after iv administration. The insulin-like effects of the IGF-I peptides were examined in vitro and in vivo. Truncated IGF-I stimulated [3-3H]glucose incorporation into free fatty acids in adipocytes in vitro to a greater extent than did intact IGF-I. In vivo administration of both intact and truncated IGF-I to adult rats significantly decreased serum glucose levels and significantly increased the incorporation of [U-14C]glucose into glycogen. Thus, the present results demonstrated that truncated IGF-I displays reduced binding to the IGF binding proteins in vivo compared with intact IGF-I.
Triiodothyronine affects the electrical properties of GH3 cells
Authors: du Pont John S.
Published: June 2009

Electrophysiological experiments show that T3 has a direct effect on the cell membrane of GH3 cells, a transformed line from the rat pituitary. Slope conductance versus membrane potential, resting membrane resistance, potential, capacity and action potentials were measured in this study. Using a current clamp technique, the effects of tetrodotoxin, tetraethylammonium, apamin, and nifedipine were measured and compared with those directly evoked by T3. T3 increased the slope conductance: 1. at around −60 mV, as did tetrodotoxin (Na+ channel blocker); 2. at about −40 mV, as did nifedipine (Ca2+ channel blocker), but decreased this conductance strongly between −20 and −30 mV, as did both nifedipine and apamin (Ca2+-sensitive K+ channel blocker). Action potentials were inhibited by T3 and by nifedipine. Action potentials in these cells are primarily related to Ca2+ ions. It seems that T3 inhibits the Ca2+ current and, as a consequence, the Ca2+-sensitive K+ current.
Gender-related differences of serum thyroxine-binding proteins in the rat
Authors: Emerson Charles H. , Cohen Joseph H. , Young Ruth A. , Alex Sharon , Fang Shih-Lieh
Published: June 2009

Because little information is available, studies were performed to determine the relationship between gender and sex steroid status on serum T4 binding proteins in the rat. The binding capacity of serum thyroxinebinding globulin was greater in female rats than in male rats (27 ± 1.3 vs 18.0 ± 1.3 nmol/l, p<0.01) and in fasted female rats than in fasted male rats (64.4 ± 2.6 vs 30.8 ± 2.7 nmol/l, p<0.01). The binding capacity of serum transthyretin was lower in female rats than in male rats (2.1 ± 0.1 vs 3.1 ± 0.1 μmol/l, p < 0.01). Neither ovariectomy or orchidectomy affected the binding capacity of serum thyroxine-binding globulin and it was not increased in ovariectomized rats treated with estrogen. Orchidectomy did not cause a decrease in the binding capacity of serum transthyretin and testosterone administration did not increase it. In contrast, ovariectomy caused an increase in the binding capacity of serum transthyretin (Intact = 2.2 ± 0.1 vs ovariectomized = 2.8 ± 0.1 μmol/l, p <0.01) and estrogen administration caused a decrease (ovariectomized = 2.8 ± 0.1 vs ovariectomized + E2 = 1.9 ± 0.1 μmol/l, p <0.05). The results indicate that the binding capacity of serum thyroxine-binding globulin is higher in female rats than in male rats but this difference is not due to differences in the secretion of gonadal hormones. The binding capacity of transthyretin is lower in female rats than in male rats. This is probably due to the higher circulating levels of estrogen in the female compared to the male.
Thyroid status regulates particulate but not soluble TRH-degrading pyroglutamate aminopeptidase activity in the rat liver
Authors: Scharfmann Raphaël , Ebiou Jean-Claude , Morgat Jean-Louis , Aratan-Spire Sonia
Published: June 2009

Rat liver contains two topologically different TRH-degrading pyroglutamate aminopeptidases. The particulate pyroglutamate aminopeptidase, unlike the soluble one, was highly specific for TRH and shared many physico-chemical properties with serum thyroliberinase, which is controlled by thyroid hormones. Both enzymes convert pGlu His Pro NH2 into His Pro NH2; the latter may be cyclized to cyclo His Pro known to possess several biological activities and specific binding sites in liver. The aim of the present study was to determine the effects of thyroid status on the particulate and soluble enzymes activity and gain more insight into their biological role. The regulatory pathway for the particulate pyroglutamate aminopeptidase was found similar to that of serum thyroliberinase: their specific activities decrease in hypothyroid rats and increase in hyperthyroid rats, whereas that of soluble enzyme remains unchanged. We postulate that the particulate pyroglutamate aminopeptidase may be a determining factor in the concentrations of TRH and/or cyclo His Pro reaching liver cells and a possible source for serum thyroliberinase. Taken together, these data suggest that this "converting enzyme" acts as a physiological regulator.
Hepatic lipase activity after liver denervation in hypothyroid rats
Authors: Berg Anna-Lena , Hammarström Lars-Erik , Hansson Per , Holmin Torsten , Nilsson-Ehle Peter
Published: June 2009

Hepatic hilar denervation, hepatic vagotomy or sham operation were performed in hypothyroid rats. Activities of hepatic lipase were measured nine days after surgery. Sham operation in itself was associated with a decrease of hepatic lipase activity by about 40% compared with non-operated animals. Both hilar denervation and hepatic vagotomy were associated with increased hepatic lipase activity (40% and 35%, compared with sham-operated animals). Liver contents of norepinephrine were reduced by about 90% after hilar denervation, whereas hepatic vagotomy did not affect norepinephrine levels. No major changes in lipids and lipoproteins were noted.
T3 receptor occupancy and T3 levels in plasma and cytosol during rat brain development
Authors: Ferreiro Beatriz , Pastor Rosa , Bernal Juan
Published: June 2009

The concentration and occupancy of the thyroid hormone receptor have been measured in rat brain nuclear extracts at the end of the fetal period and during the postnatal period. Receptor occupancy attained maximal values at postnatal day 15 (52% of total receptor binding sites occupied by T3) and correlated with plasma and cytosol total and free T3. The values for these parameters showed greater differences throughout development than did receptor occupancy. From gestational day 21 to postnatal day 15, total T3 increased in plasma from 0.18 to 1 nmol/l and in cytosol from 1 to 7.5 pmol/l. Free T3 increased in plasma from 1.2 to 6 pmol/l and in cytosol from 8 to 59 pmol/l. Nuclear free T3, calculated on the basis of receptor occupancy, and Kd increased in parallel, from 39.8 to 107 pmol/l at the same ages. Values for nuclear free T3 were between 2 and 5 times those in cytosol and between 10 and 40 times those in plasma, suggesting the presence of a small free T3 gradient from plasma to the nucleus. All of the above changes take place during the critical period of oligodendrocyte differentiation and the start of myelin gene expression, suggesting that thyroid hormone influences these important events of brain maturation.
Development of adrenomedullary function in suckling rats: Effects of high doses of thyroxine and cortisol
Authors: Goya L. , Aláez C. , Pascual-Leone A. M.
Published: June 2009

The development of epinephrine, norephinephrine, and total catecholamine secretion in plasma and andrenal glands was studied in newborn rats at short intervals: at day 2, 4, 6, 8, 10, 12 and 23. The increase in the plasma level of epinephrine represents a maturation of the secretion of the adrenal medulla. The increase in plasma of epinephrine and norepinephrine and the content of catecholamines in the adrenal glands of both normal animals and those treated with either high doses of T4 or cortisol at birth suggest a slowing down of the normal development of epinephrine secretion. This was confirmed by inducing hypoglycemia in these three groups of animals by a 20-h fast or by insulin administration (0.1436 μmol/kg). We conclude that both high doses of T4 and cortisol administered at birth seem to retard the development of the autonomic nervous system similar to the effect on the central nervous system.
Cortisol release in pigs following peripheral and central administration of ovine and human corticotropin-releasing hormone
Authors: Parrott R. F.
Published: June 2009

Prepubertal pigs (N = 6) were surgically implanted with iv and intracerebroventricular catheters. The animals were given oCRH or hCRH peripherally (0, 20 or 50 μg) or centrally (0, 10 or 20 μg) and the effect on plasma cortisol measured. Peak cortisol concentrations were observed 20 min after iv, and 40 min after intracerebroventricular, administration. A larger cortisol response was observed when 20 μg oCRH was given by the central, compared to the peripheral, route and intracerebroventricular administration of both 10 and 20 μg oCRH caused excitation and vocalisation. By contrast, the effect of hCRH on cortisol secretion was small, regardless of the route of administration, and only one animal displayed a behavioural response when the highest dose was given centrally.
Localization of renin substrate in fetoplacental tissue
Authors: Metsärinne Kaj P. , Pekonen Fredrika , Fyhrquist Frej Y.
Published: June 2009

Specific polyclonal rabbit anti-human renin substrate-antibodies were used in order to study the distribution of renin substrate immunoreactivity in human fetal and placental tissue. Renin substrate was immunohistochemically detected in human decidua and placenta, as well as in 19 weeks old human fetal liver and kidney. The presence of renin substrate in fetoplacental tissue supports the concept of a locally functioning renin-angiotensin system.
The mechanism for the discrepancy between serum total and free thyroxine values induced by autoantibodies: Report on two patients with Graves' disease
Authors: Iitaka Makoto I , Fukasawa Nobuhiko , Hara Yoshihito , Yanagisawa Morifumi , Hase Kazumasa , Miura Shiro , Sakatsume Yoshiki , Ishii Jun
Published: June 2009

The sera from two patients with Graves' disease gave abnormally high serum free T4 values as compared with the total T4 and other hormone values, suggesting the presence of autoantibodies to labelled T4 analogue used in the Amersham free T4 assay kit. The autoantibodies appeared to develop after the initiation of methimazole therapy and disappeared again after the cessation of methimazole. This binding activity to labelled T4 analogue was demonstrated to be in the immunoglobulin G with a k light chain isotype in both sera, and was displaced by unlabelled T4 in a dose-dependent manner. The binding of immunoglobulin G purified from these sera to labelled T4 or T4 analogue was found to be almost identical to that of the corresponding serum binding. Since the specific radioactivity of labelled T4 analogue used in the Amersham free T4 assay kit is about 10 times higher than that of the labelled T4 in the Amersham total T4 assay kit, serum free T4 determinations are much more vulnerable to thyroid hormone autoantibodies. Thus, in the presence of autoantibodies, a large discrepancy develops between free T4 and total T4 values.
Endocrine, metabolic and cardiovascular responses to adrenaline after abdominal surgery
Authors: Hilsted J. , Wilken-Jensen C. , Birch K. , Nielsen M. Damkjær , Holst J. J. , Kehlet H.
Published: June 2009

Adrenaline-induced changes in heart rate, blood pressure, plasma adrenaline and noradrenaline, cortisol, glucagon, insulin, cAMP, glucose, lactate, glycerol and β-hydroxybutyrate were studied preoperatively and 4 and 24 h after skin incision in 8 patients undergoing elective cholecystectomy. Late postoperative responses of blood glucose, plasma cAMP, lactate and glycerol to adrenaline infusion were reduced, whereas other responses were unaffected. Blood glucose appearance and disappearance rate as assessed by [3H]3-glucose infusion was unchanged pre- and postoperatively. The increase in glucose appearance rate following adrenaline was similar pre- and postoperatively. These findings suggest that several β-receptor-mediated responses to adrenaline are reduced after abdominal surgery.
Analysis of the gonadotropin surges in patients with premature ovarian failure undergoing steroid replacement cycles
Authors: Pellicer Antonio , Matallin Pilar , Valldecabres Maria C. , Miró Fernando , Remohi José
Published: June 2009

Ovarian steroids regulate pituitary gonadotropin secretion in normal cycles. This regulation has also been demonstrated in hypogonadal women receiving exogenous drugs, and has been suggested in women with premature ovarian failure receiving cycles of steroid replacement for oocyte donation. The purpose of this study was to analyse the gonadotropin surges in patients with premature ovarian failure using different experimental protocols. Those protocols were planned to induce the surges with different combinations of estradiol valerate and progesterone. According to the first protocol, a typical sequencial administration of estradiol valerate and progesterone was given as a control. Maximal estradiol levels were detected on day 12 of the artificial cycle. The negative feed-back of estradiol was evident, with a significant (p<0.05) reduction of FSH and LH from the initial values. The positive feed-back showed a moderate LH surge in 6 out of 8 patients. In addition, a mild FSH increase was detected in 4 women. Both surges occurred on day 15 and were coincident with a decreased estradiol valerate and increased progesterone intake. A second protocol was scheduled for 5 patients in order to identify a real LH surge. High-dose estradiol valerate administration was maintained and progesterone was not administered. The LH surge clearly appeared on day 15 in all subjects, but the peak value was again moderate. The third protocol was designed in order to demonstrate a real FSH surge in 4 patients. Progesterone administration was advanced by 5 days. This trial showed a mild FSH surge, which was advanced together with progesterone administration. These data demonstrate that women receiving artificial cycles for oocyte donation have an LH surge 3 days after maximal estradiol levels are achieved. No real FSH surge is demonstrable.
Thyroid hormones and thermogenesis: A microcalorimetric study of overall cell metabolism in lymphocytes from patients with different degrees of thyroid dysfunction
Authors: Valdemarsson Stig , Ikomi-Kumm Julie , Monti Mario
Published: June 2009

We used microcalorimetry to measure lymphocyte heat production rate in patients with clinical and laboratoy hyperthyroidism (serum TSH ↓, serum FT4 ↑, serum FT3 ↑ ), subclinical hyperthyroidism (serum TSH ↓, serum FT4 ↑, serum FT3=), and subclinical hypothyroidism (serum TSH ↑, serum FT4 ↓, serum FT3=) compared with healthy controls (N= 13). The lymphocyte heat production rate was significantly correlated to the free thyroxine level (r=0.53, p<0.01) and to the free triiodothyronine level (r=0.51, p<0.01) when calculated from pooled data for the three patients groups. The hyperthyroid patients (N = 8) had a significantly increased lymphocyte heat production rate, 3.43±0.25 pW/cell, as compared with 2.31±0.12 pW/cell in the control group (p<0.001). The groups with subclinical hyperthyroidism (N = 7) and subclinical hypothyroidism (N=9) had lymphocyte heat production rates of 2.14±0.11 and 2.56±0.15 pW/cell, respectively, not significantly different from that in the controls. Consistently, there was no significant difference between patients with subclinical hyperthyroidism (N=5) and controls (N=5) with regard to lymphocyte energy production as calculated from separately measured oxygen comsumption rates in vitro, 1.36±0.20 and 1.56±0.12 pW/cell, respectively. Thus microcalorimetry seems to be suitable for studying the influence of thyroid hormones on cellular metabolism. Subclinical thyroid dysfunction does not seem to alter the overall rate of lymphocyte metabolism.
Between-lot variability in chromatographic and biochemical properties of hMG
Authors: Stone Bronte A. , Quinn Patrick , Marrs Richard P.
Published: June 2009

Ten lots of dissociated hMG were characterized by reverse-phase gradient high-performance liquid chromatography. Areas of 12 discrete peaks were directly related to dosages of hMG injected. The lots were further analysed for immunoactive-FSH (41.6-106.2 IU/ampule), immunoactive-LH (11.0-20.4 IU/ampule), bioactive-LH (2.7-17.1 IU/ampule) and bioactive-hMG (149-298 pg E2/mIU immunoactive-FSH/ml). Relationships between integrated areas of the HPLC peaks and biochemical properties of the hMG lots were analysed by stepwise multiple linear regression. Between-lot differences in immunoactive-LH and immunoactive-FSH were related to HPLC peak areas (p<0.05); differences in bioactive-LH were not. Areas of 8 peaks were related to differences in bioactive-hMG activity, facilitating close approximation of bioactive-hMG from the derived multi-linear model (p<0.001). Rapid characterization of hMG by HPLC is of relevance as recent reports have shown that ovarian responses and pregnancy outcomes of patients are related to the immunoactive and bioactive gonadotropin content of hMG preparations used to induce multiple folliculogenesis before oocyte aspiration, in vitro fertilization, and embryo replacement.
Pyridostigmine partially restores the GH responsiveness to GHRH in normal aging
Authors: Ghigo E. , Goffi S. , Arvat E. , Nicolosi M. , Procopio M. , Bellone J. , Imperiale E. , Mazza E. , Baracchi G. , Camanni F.
Published: June 2009

In 11 elderly normal subjects and in 17 young healthy subjects we studied the response of plasma growth hormone to GH-releasing hormone (GHRH(29), 1 μg/kg iv) alone and preceded by pyridostigmine ( 120 mg orally 60 min before GHRH), a cholinesterase inhibitor likely able to suppress somatostatin release. The GH response to pyridostigmine alone was also examined. Basal plasma GH levels were similar in elderly and young subjects. In the elderly, GHRH induced a GH rise (AUC, median and range: 207.5, 43.5-444.0 μg · 1−1 · h−1) which was lower (p = 0.006) than that observed in young subjects (548.0, 112.5-2313.5 μg · 1−1 · h−1). The pyridostigmine-induced GH rise in the elderly was similar to that in young subjects (300.5, 163.0-470.0 vs 265.0, 33.0-514.5 μg · 1−1 · h−1). Pyridostigmine potentiated the GH responsiveness to GHRH in both elderly (437.5, 152.0-1815.5 μg · 1−1 · h−1; p = 0.01 vs GHRH alone) and young subjects (2140.0, 681.5-4429.5 μg · 1−1 · h−1; p = 0.0001 vs GHRH alone). However, the GH response to pyridostigmine + GHRH was significantly lower (p = 0.0001) in elderly than in young subjects. In conclusion, the cholinergic enhancement by pyridostigmine is able to potentiate the blunted GH response to GHRH in elderly subjects, inducing a GH increase similar to that observed after GHRH alone in young adults. This finding suggests that an alteration of somatostatinergic tone could be involved in the reduced GH secretion in normal aging. However, a decreased GH response to combined administration of pyridostigmine and GHRH in elderly subjects suggests that other abnormalities may coexist, leading to the secretory hypoactivity of somatotropes.
Physical and psychological capabilities during substitution therapy with recombinant growth hormone in adults with growth hormone deficiency
Authors: Degerblad Marie , Almkvist Ove , Grunditz Roland , Hall Kerstin , Kaijser Lennart , Knutsson Evert , Ringertz Hans , Thorén Marja
Published: June 2009

In a double-blind cross-over study with recombinant methionyl growth hormone (GH) and placebo during 12 weeks, the effect of GH substitution therapy (0.5-0.6 IU · kg−1 · week−1) on physical performance, muscle strength, bone mineral density, and mood and cognitive functions was investigated in 6 GH-deficient adults. During GH substitution serum concentrations of insulin-like growth factor-I and procollagen-III peptide increased in all 6 patients, whereas concentrations of serum urea decreased. Five of the patients identified the GH period and reported improved well-being with increased mental alertness and vitality and improved physical capacity and muscle strength. There was, however, no change of the isokinetic muscle strength during GH substitution therapy, and the working capacity on the bicycle ergometer was just slightly improved in some patients. The bone mineral density was low and unchanged in all patients. Mood and cognitive functions did not change during GH therapy. A reversible fluid retention was observed in one patient during the GH period. In conclusion, short-term GH substitution therapy to GH-deficient adults induced a subjective improvement of general wellbeing. Longer treatment periods will be necessary to establish the effect on physical capacity, muscle strength, bone mineral density, and mood and cognitive functions.