Dynamic adverse selection and debt

This paper argues that the strategic use of debt favours the revelationof information in dynamic adverse selection problems. Our argument is basedon the idea that debt is a credible commitment to end long term relationships.Consequently, debt encourages a privately informed party to disclose itsinformation at early stages of a relationship. We illustrate our pointwith the financing decision of a monopolist selling a good to a buyerwhose valuation is private information. A high level of (renegotiable)debt, by increasing the scope for liquidation, may induce the highvaluation buyer to buy early at a high price and thus increase themonopolist's expected payoff. By affecting the buyer's strategy, it mayreduce the probability of excessive liquidation. We investigate theconsequences of good durability and we examine the way debt mayalleviate the ratchet effect.

Effects of mineralocorticoid and K+ concentration on K+ secretion and ROMK channel expression in a mouse cortical collecting duct cell line.

The cortical collecting duct (CCD) plays a key role in regulated K(+) secretion, which is mediated mainly through renal outer medullary K(+) (ROMK) channels located in the apical membrane. However, the mechanisms of the regulation of urinary K(+) excretion with regard to K(+) balance are not well known. We took advantage of a recently established mouse CCD cell line (mCCD(cl1)) to investigate the regulation of K(+) secretion by mineralocorticoid and K(+) concentration. We show that this cell line expresses ROMK mRNA and a barium-sensitive K(+) conductance in its apical membrane. As this conductance is sensitive to tertiapin-Q, with an apparent affinity of 6 nM, and to intracellular acidification, it is probably mediated by ROMK. Overnight exposure to 100 nM aldosterone did not significantly change the K(+) conductance, while it increased the amiloride-sensitive Na(+) transport. Overnight exposure to a high K(+) (7 mM) concentration produced a small but significant increase in the apical membrane barium-sensitive K(+) conductance. The mRNA levels of all ROMK isoforms measured by qRT-PCR were not changed by altering the basolateral K(+) concentration but were decreased by 15-45% upon treatment with aldosterone (0.3 or 300 nM for 1 and 3 h). The paradoxical response of ROMK expression to aldosterone could possibly work as a preventative mechanism to avoid excessive K(+) loss which would otherwise result from the increased electrogenic Na(+) transport and associated depolarization of the apical membrane in the CCD. In conclusion, mCCD(cl1) cells demonstrate a significant K(+) secretion, probably mediated by ROMK, which is not stimulated by aldosterone but increased by overnight exposure to a high K(+) concentration.

Effects of prolonged administration of the angiotensin converting enzyme inhibitor CGS 16617 in normotensive volunteers.

A new, orally active angiotensin converting enzyme (ACE) inhibitor, CGS 16617, has been evaluated in normotensive subjects during acute and prolonged administration. Single ascending doses of CGS 16617 20 to 100 mg were given to 9 normotensive volunteers at one week intervals and the changes in blood pressure, plasma ACE and renin activity were examined up to 72 h after drug intake. Also, CGS 16617 50 mg/day or placebo were given for 30 days to 8 and 6 normotensive subjects, respectively, maintained on an unrestricted salt diet. Blood pressure was measured daily in the office and ambulatory blood pressure profiles were also obtained before, during and after therapy, using the Remler M 2000 blood pressure recording system. CGS 16617 was an effective and long lasting ACE inhibitor. It did not induce a consistent change in blood pressure, but, the individual responses were very variable and several subjects experienced a clear decrease in the average of the blood pressures recorded during the daytime.

Adult sex ratio effects on male survivorship of Drosophila melanogaster Meigen (Diptera, Drosophilidae)

The behavioral biology has a central role in evolutionary biology mainly because the antagonistic relations that occur in the sexual reproduction. One involves the effect of reproduction on the future life expectation. In this scenario, changes in male operational sex ratio could lead to an increase in mortality due to costs associated with excessive courtship and mating displays. Thus, this work experimentally altered the male sex ratio of Drosophila melanogaster Meigen, 1830, to determine its impact on mortality. The results indicated that mortality increases as the sex ratio changes, including modifications in the survivorship curve type and in the curve concavity, measured by entropy.

Neglected risks, financial innovation and financial fragility

We present a standard model of financial innovation, in which intermediaries engineer securities with cash flows that investors seek, but modify two assumptions. First, investors (and possibly intermediaries) neglect certain unlikely risks. Second, investors demand securities with safe cash flows. Financial intermediaries cater to these preferences and beliefs by engineering securities perceived to be safe but exposed to neglected risks. Because the risks are neglected, security issuance is excessive. As investors eventually recognize these risks, they fly back to safety of traditional securities and markets become fragile, even without leverage, precisely because the volume of new claims is excessive.

Identification and Characterization of Natural Anti-Breast Cancer Compound: Costunolide

Breast cancer is the most common cancer among women, 23% (1.3 million) of the total of new cases and the second leading cause of cancer death in women exceeded only by lung cancer. Natural medicines have been proven to be a central source of narrative agents with a pharmaceutical potential. Costunolide is sesquiterpene lactones consisting of diverse plant chemicals that exhibit anti cancer action through cytotoxic effects on various cancer cells. The objectives of present study were to explore the effects of natural compounds on the proliferation of MCF-7 cells and to determine the role of ROS in natural compounds-induced apoptosis in breast cancer cells with a therapeutic potential. Results showed that costunolide screened, possess potent anticancer properties against breast cancer MCF-7 cells, Costunolide was observed as strong anti-proliferative agent with IC50 = 50µM. The anti-proliferative effect of costunolide on MCF cells was confirmed by live/dead assay using fluorescent probes calcein AV/PI. The results demonstrated that treatment of cells with costunolide decreased the viability of MCF-7 cells in a dose-dependent manner. To determine the costunolide-induced apoptosis, flow cytometric analysis was carried out. The results showed that costunolide induced apoptosis in a dose-dependent manner in breast cancer MCF-7cells. ROS are well known mediators of intracellular signaling of cascades. The excessive generation of ROS can induce oxidative stress, loss of cell functioning, and apoptosis. In the present study, we assumed that costunolide might arouse ROS level, which could be involved in induction of apoptosis. Therefore, the intracellular ROS level was measured using the ROS-detecting fluorescence dye 2, 7-dichlorofluorescein diacetate (DCF-DA). Interestingly these effects were significantly abrogated when the cells were pretreated with N-acetyl- cysteine (NAC), a specific ROS inhibitor. Costunolide induces apoptosis through extrinsic pathway in MCF-7 breast cancer cells, In order to examine whether costunolide suppresses cell growth inducing apoptotic cell death, we analyzed DNA contents and apoptosis-related proteins expression level by flow cytometry and western blot, respectively in MCF-7 breast cancer cells we investigated whether costunolide activates extrinsic apoptotic pathway. We examined the expression levels of death receptor signaling-related proteins, caspase-3, and PARP. The results showed that procaspase-3 was cleaved to yield 17 and 20kDa fragments and activation of PARP in treated cells with 25 and 50μM of costunolide. Costunolide induce apoptosis through intrinsic mitochondria pathway in MCF-7 breast cancer Cells. We examined the expression levels of mitochondrial apoptotic pathway related proteins such as anti-apoptotic protein, B-cell lymphoma protein-2 (Bcl2), and pro-apoptotic protein Bax. Costunolide involved in the down regulation of Bcl-2 and up regulation of Bax. These results suggest that costunolide may have beneficial effects for the reduction of breast cancer growth, and new therapeutic strategy for the treatment of human cancers.

Ambulatory blood pressure monitoring: a mean to stratify cardiovascular risk.

OBJECTIVE: Current hypertension guidelines stress the importance to assess total cardiovascular risk but do not describe precisely how to use ambulatory blood pressures in the cardiovascular risk stratification. METHOD: We calculated here global cardiovascular risk according to 2003 European Society of Hypertension/European Society of Cardiology guidelines in 127 patients in whom daytime ambulatory blood pressures were recorded and carotid/femoral ultrasonography performed. RESULTS: The presence of ambulatory blood pressures >or =135/85 mmHg shifted cardiovascular risk to higher categories, as did the presence of hypercholesterolemia and, even more so, the presence of atherosclerotic plaques. CONCLUSION: Further studies are, however, needed to define the position of ambulatory blood pressures in the assessment of cardiovascular risk.

Interleukin-12p40 overexpression promotes interleukin-12p70 and interleukin-23 formation but does not affect bacille Calmette-Guérin and Mycobacterium tuberculosis clearance.

Interleukin (IL)-12p40, a subunit of IL-12p70 and IL-23, has previously been shown to inhibit IL-12p70 activity and interferon-gamma (IFN-gamma) production. However, recent evidence has suggested that the role of IL-12p40 is more complex. To study the contribution of IL-12p40 to immune responses against mycobacterial infections, we have used transgenic (tg) mice overexpressing IL-12p40 under the control of a major histocompatibility complex-II promoter. The IL-12p40 transgene was expressed during steady state at concentrations of 129 +/- 25 ng/ml of serum and 75 +/- 13 ng per spleen, while endogenous IL-12p40 was hardly detectable in control littermates. Bacille Calmette-Guérin (BCG) infection strongly induced the expression of IL-12p40 transgene in infected organs, and IL-12p40 monomeric and dimeric forms were identified in spleen of IL-12p40 tg mice. Excessive production of IL-12p40 resulted in a 14-fold increase in IL-12p70 serum levels in tg mice versus non-transgenic mice. IL-23 was also strongly elevated in the serum and spleens of IL-12p40 tg mice through BCG infection. While IFN-gamma and tumour necrosis factor protein levels were similar in IL-12p40 tg and non-transgenic mice, Th2 type immune responses were reduced in IL-12p40 tg mice. The number of BCG granulomas and macrophage expressing inducible nitric oxide synthase were similar in IL-12p40 tg and non-transgenic mice. IL-12p40 tg mice were as resistant as non-transgenic mice to BCG and Mycobacterium tuberculosis infections as they could efficiently control bacillary growth. These data show that high amounts of IL-12p40 promotes IL-12p70 and IL-23 formation, but that does not affect T helper 1 type immune responses and granuloma function, thus leading to normal mycobacterial clearance in infected organs.

Allergo-immunologie. 1. Nouveautés dans le traitement des crises aiguës d'angioedème héréditaire [Allergy-immunology. New therapies for acute attacks in hereditary angioedema].

Hereditary angioedema is a disease which develops as a result of a deficiency or dysfonction of C1-inhibitor, a key regulator of the complement, coagulation and contact cascades, resulting among others in excessive release of bradykinin. This disease mortality rate is high in absence of immediate and effective treatment, in particular in presence of acute attacks of the upper respiratory tract (laryngeal edema). Until now only administration of a purified C1-inhibitor extract was effective against these symptoms. This paper aims to synthesise essentials knowledge concerning news drugs, in particular icatibant, a selective bradykinin B2- receptor antagonist whose use should be widened to the treatment of angioedema with ACE-inhibitors intolerance.

International capital flows and credit market imperfections: A tale of two frictions

The financial crisis of 2007-08 has underscored the importance of adverse selection in financialmarkets. This friction has been mostly neglected by macroeconomic models of financialimperfections, however, which have focused almost exclusively on the effects of limited pledgeability.In this paper, we fill this gap by developing a standard growth model with adverseselection. Our main results are that, by fostering unproductive investment, adverse selection:(i) leads to an increase in the economy s equilibrium interest rate, and; (ii) it generates a negativewedge between the marginal return to investment and the equilibrium interest rate. Underfinancial integration, we show how this translates into excessive capital inflows and endogenouscycles. We also extend our model to the more general case in which adverse selection and limitedpledgeability coexist. We conclude that both frictions complement one another and show thatlimited pledgeability exacerbates the effects of adverse selection.

The elusive costs and the immaterial gains of fiscal contraints

We study whether and how fiscal restrictions alter the business cycle features macrovariables for a sample of 48 US states. We also examine the 'typical' transmission properties of fiscal disturbances and the implied fiscal rules of states with different fiscal restrictions. Fiscal constraints are characterized with a number of indicators. There are similarities in second moments of macrovariables and in the transmission properties of fiscal shocks across states with different fiscal constraints. The cyclical response of expenditure differs in size and sometimes in sign, but heterogeneity within groups makes point estimates statistically insignificant. Creative budget accounting isresponsible for the pattern. Implications for the design of fiscal rules and thereform of the Stability and Growth Pact are discussed.

Investigating mineralocorticoid hypertension.

About 3% of our hypertensive patients have high blood pressure induced by corticosteroids. Muscle weakness, tiredness, polyuria and polydipsia may indicate hypokalaemia. Hypokalaemic hypertension in the presence of a low plasma renin activity is the typical finding of corticosteroid hypertension. The most frequent cause of corticosteroid hypertension is primary aldosteronism (Conn's syndrome) due to an adrenal adenoma or bilateral hyperplasia of the adrenal glands. The plasma concentration of aldosterone and the ratio between plasma aldosterone and renin concentrations are high, and the kaliuresis exceeds 30 mmol/24 h in the presence of hypokalaemia. Adrenal carcinomas are rare and very malignant. The localization of an adrenal tumour is made by computer tomography (CT-scan) or nuclear magnetic resonance imaging and by measurement of the aldosterone/cortisol concentrations in the adrenal venous blood. Adenomas are removed under laparoscopy, and adrenal hyperplasias are treated with spironolactone (50-400 mg daily) or amiloride (5-30 mg daily). In rare cases (<1%), excessive stimulation of the mineralocorticoid receptor is due to cortisol (apparent mineralocorticoid excess, Cushing's disease, liquorice, or hereditary deficiency of 11beta-hydroxysteroid dehydrogenase) or to a chimeric gene coding for 11beta-hydroxylase (CYP11B1/CYP11B2). In these rare cases, the synthesis of aldosterone is under the control of the adrenocorticotrophic hormone, so treatment with glucocorticoids (dexamethasone 0.25-1.0 mg daily) is therefore possible (glucocorticoid-remediable aldosteronism). Excessive deoxycorticosterone (DOC) causes the same symptoms and signs as hyperaldosteronism. Excessive DOC is found in patients with adrenal tumours that secrete DOC, in those with hereditary or acquired disorders with dysfunctioning glucocorticoid receptors, or in those with congenital hyperplasia of the adrenal glands (deficiency of 17alpha-hydroxylase or 11beta-hydroxylase). Liddle's syndrome is a constitutive hyperactivity of the transepithelial transport of sodium, which under normal conditions is controlled by the mineralocorticoid receptor. Plasma renin and aldosterone concentrations are suppressed and the plasma potassium concentration may be normal. In contrast, plasma aldosterone and renin concentrations are increased in patients with hypokalaemic hypertension which represents secondary aldosteronism. The increased aldosterone is the consequence of stimulated renin activity due to renal or renovascular or other disorders, antihypertensive drugs or other medications. In conclusion, a work-up for corticosteroid-induced hypertension is indicated in patients with hypokalaemic hypertension and in those with severe hypertension even in the absence of hypokalaemia, and in hypertensive patients with a family history of cardiovascular diseases.

High-intensity running and plantar-flexor fatigability and plantar-pressure distribution in adolescent runners.

CONTEXT: Fatigue-induced alterations in foot mechanics may lead to structural overload and injury. OBJECTIVES: To investigate how a high-intensity running exercise to exhaustion modifies ankle plantar-flexor and dorsiflexor strength and fatigability, as well as plantar-pressure distribution in adolescent runners. DESIGN: Controlled laboratory study. SETTING: Academy research laboratory. PATIENTS OR OTHER PARTICIPANTS: Eleven male adolescent distance runners (age = 16.9 ± 2.0 years, height = 170.6 ± 10.9 cm, mass = 54.6 ± 8.6 kg) were tested. INTERVENTION(S): All participants performed an exhausting run on a treadmill. An isokinetic plantar-flexor and dorsiflexor maximal-strength test and a fatigue test were performed before and after the exhausting run. Plantar-pressure distribution was assessed at the beginning and end of the exhausting run. MAIN OUTCOME MEASURE(S): We recorded plantar-flexor and dorsiflexor peak torques and calculated the fatigue index. Plantar-pressure measurements were recorded 1 minute after the start of the run and before exhaustion. Plantar variables (ie, mean area, contact time, mean pressure, relative load) were determined for 9 selected regions. RESULTS: Isokinetic peak torques were similar before and after the run in both muscle groups, whereas the fatigue index increased in plantar flexion (28.1%; P = .01) but not in dorsiflexion. For the whole foot, mean pressure decreased from 1 minute to the end (-3.4%; P = .003); however, mean area (9.5%; P = .005) and relative load (7.2%; P = .009) increased under the medial midfoot, and contact time increased under the central forefoot (8.3%; P = .01) and the lesser toes (8.9%; P = .008). CONCLUSIONS: Fatigue resistance in the plantar flexors declined after a high-intensity running bout performed by adolescent male distance runners. This phenomenon was associated with increased loading under the medial arch in the fatigued state but without any excessive pronation.

Mitochondrial uncoupling as a regulator of life-history trajectories in birds: an experimental study in the zebra finch.

Mitochondria have a fundamental role in the transduction of energy from food into ATP. The coupling between food oxidation and ATP production is never perfect, but may nevertheless be of evolutionary significance. The 'uncoupling to survive' hypothesis suggests that 'mild' mitochondrial uncoupling evolved as a protective mechanism against the excessive production of damaging reactive oxygen species (ROS). Because resource allocation and ROS production are thought to shape animal life histories, alternative life-history trajectories might be driven by individual variation in the degree of mitochondrial uncoupling. We tested this hypothesis in a small bird species, the zebra finch (Taeniopygia guttata), by treating adults with the artificial mitochondrial uncoupler 2,4-dinitrophenol (DNP) over a 32-month period. In agreement with our expectations, the uncoupling treatment increased metabolic rate. However, we found no evidence that treated birds enjoyed lower oxidative stress levels or greater survival rates, in contrast to previous results in other taxa. In vitro experiments revealed lower sensitivity of ROS production to DNP in mitochondria isolated from skeletal muscles of zebra finch than mouse. In addition, we found significant reductions in the number of eggs laid and in the inflammatory immune response in treated birds. Altogether, our data suggest that the 'uncoupling to survive' hypothesis may not be applicable for zebra finches, presumably because of lower effects of mitochondrial uncoupling on mitochondrial ROS production in birds than in mammals. Nevertheless, mitochondrial uncoupling appeared to be a potential life-history regulator of traits such as fecundity and immunity at adulthood, even with food supplied ad libitum.

Gene deletion of dopamine beta-hydroxylase and alpha1-adrenoceptors demonstrates involvement of catecholamines in vascular remodeling.

In vitro studies have shown that stimulation of alpha1-adrenoceptors (ARs) directly induces proliferation, hypertrophy, and migration of arterial smooth muscle cells and adventitial fibroblasts. In vivo studies confirmed these findings and showed that catecholamine trophic activity becomes excessive after experimental balloon injury and contributes to neointimal growth, adventitial thickening, and lumen loss. However, past studies have been limited by selectivity of pharmacological agents. The aim of this study, in which mice devoid of norepinephrine and epinephrine synthesis [dopamine beta-hydroxylase (DBH-/-)] or deficient in alpha1-AR subtypes expressed in murine carotid (alpha1B-AR-/- and alpha1D-AR-/-) were used, was to test the hypothesis that catecholamines contribute to wall hypertrophy after injury. At 3 wk after injury of wild-type mice, lumen area and carotid circumference increased significantly, and hypertrophy of media and adventitia was in excess of that needed to restore circumferential wall stress to normal. In DBH-/- and alpha1B-AR-/- mice, increases in lumen area, circumference, and hypertrophy of the media and adventitia were reduced by 50-91%, resulting in restoration of wall tension to nearly normal (DBH-/-) or normal (alpha1B-AR-/-). In contrast, in alpha1D-AR-/- mice, increases in lumen area, circumference, and wall hypertrophy were unaffected and wall thickening remained in excess of that required to return tension to normal. When examined 5 days after injury, proliferation and leukocyte infiltration were inhibited in DBH-/- mice. These studies suggest that the trophic effects of catecholamines are mediated primarily by alpha1B-ARs in mouse carotid and contribute to hypertrophic growth after vascular injury.