bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of in vivo oestrogen pretreatment on the contractile response of rat isolated detrusor muscle
Authors: Elliott Ruth A. , Castleden C.M. , Miodrag A.
Published: July 2012

The effect of oestradiol pretreatment was investigated on the response of rat isolated detrusor muscle to cholinergic, electrical and 5‐hydroxytryptamine (5‐HT) stimulation with and without diethystilboestrol (DES) (2 μm) in the organ bath.

Virgin female Wistar rats were injected subcutaneously for 8 days with oestradiol benzoate 150 μg kg−1. Control rats received no injections or injection only with the vehicle, ethyl oleate.

Detrusor muscle from treated rats showed a decreased sensitivity to acetylcholine (ACh) and carbachol‐induced contractile responses. The dose‐response curves to these agonists showed a 44% reduction in maximum contractile response for ACh (P < 0.001), and a 38% reduction in maximum contractile response for carbachol (P < 0.05). The addition of 2 μm DES to the bathing medium further significantly reduced the maximum contractile response by 56 and 57% of control respectively.

Electrically stimulated detrusor muscle from treated rats showed a significant 49% reduction in the maximum contractile response (P < 0.001). The addition of 2 μm DES to the bathing medium further significantly reduced the maximum contractile response by 66% of control. The tetrodotoxin resistant responses were smaller in pretreated rats, suggesting a reduced sensitivity of the smooth muscle to direct electrical stimulation.

The response to 5‐HT stimulation by detrusor muscle samples from oestradiol‐treated rats showed a non‐significant reduction in maximum contractile response, but the addition of 2 μm DES to the bath chamber resulted in a 67% reduction in the response (P < 0.001).

Oestradiol pretreatment did not affect the potassium dose‐response curve.

Oestradiol pretreatment reduced the rat detrusor muscle sensitivity to the blocking effect of atropine on the response to electrical field stimulation. Pretreatment also reduced the potentiating effect of physostigmine on the same response.

These results suggest that oestradiol pretreatment had a modulating effect on cholinergic responses. The addition of oestrogen to the tissue environment enhances this inhibitory effect.
Effects of neuropeptide Y and agonists selective for neuropeptide Y receptor sub‐types on arterioles of the guinea‐pig small intestine and the rat brain
Authors: Xia J. , Neild T.O. , Kotecha N.
Published: July 2012

The actions of neuropeptide Y (NPY) and agonists selective for NPY receptor subtypes were examined on arterioles from the guinea‐pig small intestine and the rat pia in order to characterize the receptors mediating the vasoconstrictor and potentiating effects of NPY.

A method was developed for measuring the potentiating effects of NPY in situations where it was not possible to obtain a full concentration‐response relationship for the vasoconstrictor. NPY, 50 nm, had a greater potentiating effect on the guinea‐pig intestinal arterioles than those from the rat pia.

NPY and the Y1‐selective agonist, NPY[Leu31,Pro34], potentiated the constrictor responses to U46619 in both arterioles and responses to noradrenaline in the guinea‐pig arterioles. There was marked desensitization of the potentiating effect, and cross‐desensitization between NPY and NPY[Leu31,Pro34]. Both NPY and NPY[Leu31,Pro34] caused constriction of the rat pial arterioles but not of those from the guinea‐pig intestine.

The Y2‐selective agonist PYY(13–36) caused no potentiation or vasoconstriction and did not affect the potentiation by NPY or NPY[Leu31,Pro34].

The potentiating and vasoconstrictor effects of NPY on these arterioles were mediated by Y1 receptors.
A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder
Authors: Hall Judith M. , Flowers Joanna M. , Morton Ian K.M.
Published: July 2012

We have estimated potencies of tachykinin receptor agonist and antagonist analogues in order to determine the recognition characteristics of tachykinin receptors mediating phasic contractile responses of the rat isolated urinary bladder in vitro.

The NK1‐selective synthetic agonists, substance P methyl ester and GR73632, the synthetic NK2‐selective agonists [β‐Ala8]‐NKA(4–10) and GR64349, and the mammalian tachykinins, neurokinin A and neurokinin B, were assayed relative to substance P and were found to be approximately equipotent. The NK3‐selective agonist, senktide, was inactive (10 μm).

Potencies of all these agonists were not significantly different (P > 0.05) when experiments were carried out in the presence of the neutral endopeptidase inhibitor, phosphoramidon, and the kininase II inhibitor, enalaprilat (both 1 μm).

The NK1‐selective antagonist, GR82334, inhibited responses to substance P methyl ester in a competitive manner in the rat urinary bladder and the rat ileum, and also in the guinea‐pig ileum. Markedly different pKB estimates were obtained in the rat bladder (6.38) and rat ileum (6.56) compared to the guinea‐pig ileum (7.42). GR82334 (3 μm) was inactive against responses of the rat bladder to [β‐Ala8]‐NKA(4–10).

The NK1‐selective antagonist (±)‐CP‐96,345 also inhibited responses of the rat bladder and guinea‐pig ileum to substance P methyl ester; however, in the rat bladder at 1 μm, this antagonist reversibly inhibited responses both to the NK2‐selective agonist [β‐Ala8]‐NKA(4–10) and to the muscarinic agonist carbachol (P ≤ 0.01), thus showing evidence of some non‐selective depressant actions.

The NK2‐selective antagonists, MEN10207 and L‐659,874, competitively inhibited responses of the rat bladder to the NK2‐selective agonist [β‐Ala8]‐NKA(4–10) giving pKB estimates of 5.75 and 6.68, respectively. Both antagonists (10 μm) were inactive against responses to the NK1‐selective agonist substance P methyl ester.

These results support the proposal of a mixed population of NK1 and NK2 receptors mediating contraction of the rat isolated urinary bladder. The NK2 receptor is characterized by a relatively low affinity for the NK2‐selective antagonist MEN10207 but a high affinity for L‐659,874. The NK1‐mediated responses are inhibited by (±)‐CP‐96,345: this compound however, has non‐specific depressant effects in the rat bladder at high concentration (1 μm). In contrast, the NK1‐receptor peptide antagonist GR82334, did not have non‐specific depressant effects and competitively inhibited NK1 responses in the rat bladder and rat ileum with an affinity significantly lower than at the NK1‐receptors in the guinea‐pig ileum.
Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888
Authors: Fujii Takashi , Murai Masako , Morimoto Hiroshi , Maeda Yasue , Yamaoka Makiko , Hagiwara Daijiro , Miyake Hiroshi , Ikari Norihiro , Matsuo Masaaki
Published: July 2012

In our search for compounds that inhibit the binding of [3H]‐substance P (SP) to guinea‐pig lung membranes, the dipeptide SP antagonist, FK888, was developed by chemical modification of the parent compound, (d‐Pro4, d‐Trp7,9,10, Phe11)SP4– 11.

In a [3H]‐SP binding assay using guinea‐pig lung membranes and rat brain cortical synaptic membranes, FK888 displaced [3H]‐SP binding with a Ki value of 0.69 ± 0.13 nm and 0.45 ± 0.17 μm, respectively, in a competitive manner.

FK888 inhibited the contraction of guinea‐pig isolated ileum induced by SP in the presence of atropine and indomethacin (a NK1 receptor bioassay) with a pA2 value of 9.29 (8.60–9.98).

FK888 inhibited contractions of rat vas deferens by NKA (a NK2 receptor bioassay) and of rat portal vein by NKB (a NK3 receptor bioassay) at concentrations at least 10,000 times greater than that required to inhibit contractions of guinea‐pig ileum.

FK888 also inhibited SP‐induced airway oedema in guinea‐pig after both intravenous and oral administration.

These data demonstrate that FK888 is a potent and selective NK1 antagonist which is active both in vitro and in vivo.
Membrane potential and current responses to neurotensin in the longitudinal muscle of the rectum of the fowl
Authors: Komori Seiichi , Matsuoka Takaaki , Kwon Seong‐Chun , Takewaki Tadashi , Ohashi Hidenori
Published: July 2012

The effects of neurotensin (NT) on membrane potential and membrane current of the longitudinal smooth muscle of chicken rectum were investigated by intracellular recording and whole‐cell voltage clamp.

NT (3 nm−1.2 μm), when applied via the bathing medium, produced a concentration‐dependent membrane depolarization with an EC50 of 18 ± 2 nm (n = 7) which was accompanied by an increase in the membrane conductance. The effect was biphasic: an initial, rapid depolarization reached a peak within 2–3 min and then declined to a lower but still elevated level which was sustained until washout.

Excitatory junction potentials (e.j.ps), which were non‐adrenergic non‐cholinergic (NANC) in nature, were decreased in amplitude and total duration in the presence of NT (0.6 μm). The depression of the e.j.p. was due mainly to the reduction of the membrane resistance.

When NT was applied locally by means of pressure ejection from a micropipette containing NT, some cells responded with a membrane depolarization and some failed to respond, whereas e.j.ps could invariably be elicited from all of them.

In single muscle cells enzymatically isolated from the muscle and dialyzed under voltage clamp at — 50 mV with a CsCl‐rich solution, NT (5 or 10 μm) produced an inward current. NT‐induced inward currents were obtained with inclusion of 10 mm EGTA in the pipette solution and their reversal potential was around 0 mV. In cells dialyzed under voltage clamp at 0 mV with a KCl‐rich solution, NT (5 μm) produced a brief outward current followed by abolition of spontaneous transient outward currents.

The present results suggest that the membrane depolarization, which may arise from activation of non‐selective cation channels, and release of calcium from internal stores produced by neurotensin are responsible for its contractile activity in the longitudinal smooth muscle of chicken rectum. Further, the depolarizing effect may provide support for the involvement of NT in the NANC transmission in this preparation.
Antagonism of kinin effects on epithelia by Hoe 140: apparently competitive and non‐competitive interactions
Authors: Cuthbert A.W. , MacVinish L.J. , Pickles R.J.
Published: July 2012

Hoe‐140, a potent kinin receptor antagonist, was investigated for its ability to inhibit the effects of lysylbradykinin (kallidin) on a cultured colonic epithelium, HCA‐7 Colony 29, derived from a human adenocarcinoma.

Measurements of electrogenic chloride secretion (as short circuit current), and of intracellular Ca2+ (from Fura‐2 fluorescence) were used to assess the action of lysylbradykinin in the absence and presence of Hoe 140.

From short circuit current data, Hoe 140 appeared to be a competitive antagonist with a Ki value of 5 nm. However, with measurements of intracellular Ca2+ Hoe 140 was apparently a non‐competitive antagonist with a Ki of between 4–6 nm.

Because of the unexpected finding of non‐competitive antagonism, measurements were made with a second antagonist pair, histamine and mepyramine. Mepyramine behaved as a competitive antagonist against responses to histamine with a Ki value of ≅5 nm when short circuit current measurements were evaluated. However, when intracellular Ca2+ concentration was used as a measure mepyramine, 30 nm, produced a near parallel shift in the response curve, but at 100 nm the maximal response was depressed.

The reasons why the apparent type of antagonism depends upon the method of measurement is discussed, bearing in mind that the increase in intracellular Ca2+ is a signal which precedes the increase in short circuit current.
Angiotensin converting enzyme binding sites in human heart and lung: comparison with rat tissues
Authors: Vago T. , Bevilacqua M. , Conci F. , Baldi G. , Ongini E. , Chebat E. , Monopoli A. , Norbiato G.
Published: July 2012

Angiotensin converting enzyme (ACE), a dipeptidyl carboxypeptidase which catalyzes the final activation step in the formation of angiotensin II, was identified by radioligand studies in rat heart and lung. In this work we identified ACE binding sites in human left ventricle and lung by radioligand binding using the ACE inhibitor [3H]‐ramiprilat, and compared its binding characteristics in human and rat tissues.

Binding of [3H]‐ramiprilat in all tissues tested was saturable, temperature and zinc‐dependent, and inhibited by EDTA. In human left ventricle homogenate we found a density of binding sites of 121 ± 15 fmol mg−1 protein (n = 4) with an affinity (Kd) of 850 ± 55 pm, whereas in rat left ventricle the same values were 23 ±4 fmol mg−1 protein and 315 ± 30 pm, (n = 4), respectively.

[3H]‐ramiprilat binding to rat (n = 4) and human lung (n = 4) showed a binding site density of 2132 ± 155 and 1085 ± 51 fmol mg−1 protein respectively with an affinity of 639 ± 54 and 325 ± 22 pm. The lung: heart ratio of ACE binding site density was about 9:1 in man and 100:1 in rat.

The binding affinities of 13 ACE inhibitors were evaluated on human heart and lung: the drugs tested showed a wide range of affinities for the ACE binding sites in both tissues, and the affinity for lung was significantly greater than for heart for most of the drugs.

The greater potency of some ACE inhibitors in displacing [3H]‐ramiprilat in human lung compared with the heart indicates differences between ACE binding sites in these tissues and suggests the possibility of a selective organ‐targeted therapeutic approach.
Endotoxin impairs the response of rabbit mesenteric artery to electrical stimulation via a prejunctional mechanism
Authors: Tomikawa Shigeji , Okabe Eiichiro
Published: July 2012

The effect of E. coli lipopolysaccharide (LPS) on sympathetic neuro‐effector transmission was studied in the rabbit mesenteric artery. The experiments were performed on artery rings isolated 5 or 20 h after intravenous treatment with LPS or saline as well as on artery rings isolated from non‐treated rabbits (for assessment of the effect of in vitro preincubation with LPS). In most experiments, neural elements in the arteries were stimulated electrically (10 V, 2 ms, 1–32 Hz).

Preincubation with LPS (10 μg ml−1) for 5 or 20 h had no effect on the contraction responses of endothelium‐intact artery rings to electrical stimulation. In contrast, in vivo intravenous pretreatment with LPS (10 μg) led to an inhibition of the contraction; LPS elicited this effect when injected 20 h, but not 5 h, before the experiment. The effect of LPS was eliminated in artery rings isolated from animals receiving an inhibitor of protein synthesis (actinomycin D or cycloheximide) before treatment with LPS. LPS (injected 20 h before the experiment) had no effect on the concentration‐response curves for exogenous noradrenaline and tyramine in endothelium‐intact artery rings.

The inhibition of electrically induced contractions produced by LPS treatment in endothelium‐intact artery rings was attenuated by atropine and yohimbine, but not by phentolamine. Yohimbine plus atropine restored the depressed contraction to the normal level. Clonidine and acetylcholine mimicked the effect of LPS in endothelium‐intact artery rings isolated from saline‐treated animals.

When steady‐state contractions were induced by 5 min of stimulation at 16 Hz, acetylcholine or clonidine reduced the contraction in endothelium‐denuded artery rings from both saline‐treated rabbits and animals receiving LPS 20 h before the experiment. The reduction produced by acetylcholine or clonidine of the contraction in artery rings from LPS‐treated rabbits was significantly greater than in artery rings from saline‐treated animals.

These results suggest that treatment of rabbits with LPS inhibits noradrenaline release from sympathetic nerve endings via increased sensitivity of both prejunctional inhibitory muscarinic receptors and α2‐adrenoceptors in mesenteric arteries. They also suggest that the effect of LPS is independent of endothelial cells but linked to protein synthesis.
Nitric oxide synthase in ferret brain: localization and characterization
Authors: Matsumoto Takahiro , Mitchell Jane A. , Schmidt Harald H.H.W. , Kohlhaas Kathy L. , Warner Timothy D. , Förstermann Ulrich , Murad Ferid
Published: July 2012

In the present study, we have investigated the distribution of nitric oxide synthase in the ferret brain. Nitric oxide snythase was determined biochemically and immunochemically.

In the rat brain, the highest nitric oxide snythase activity has been detected in the cerebellum. However, in the ferret brain, the highest activity was found in the striatum and the lowest in the cerebellum and cerebral cortex. The enzymatic activity was localized predominantly in the cytosolic fractions, it was dependent on NADPH and Ca2+, and inhibited by NG‐nitro‐l‐arginine or NG‐methyl‐l‐arginine.

Western blot analysis revealed that all regions of the ferret brain contained a 160 kD protein crossreacting with an antibody to nitric oxide synthase purified from the rat cerebellum, and the levels of relative intensity of staining by the antibody correlated with the distribution of nitric oxide synthase activity.

These results indicate that the ferret brain contains a nitric oxide snythase similar to the rat brain, but the distribution of enzymatic activity in the ferret brain differs markedly from the rat brain.
Endothelin ETA and ETB receptors mediate vascular smooth muscle contraction
Authors: Sumner Michael J. , Cannon Toby R. , Mundin Jason W. , White David G. , Watts Ian S.
Published: July 2012

We have investigated the receptors mediating endothelin‐induced contraction of rabbit isolated jugular vein (RJV) and rat isolated thoracic aorta (RTA).

Endothelin‐1 (ET‐1) and endothelin‐3 (ET‐3) contracted RJV preparations with similar potency (EC50 values ∼ 1 nm), whereas, ET‐1 (EC50:4.5 nm) was ∼ 80 fold more potent than ET‐3 in contracting RTA. In addition, the ETB receptor‐selective agonist [Ala1,3,11,15]ET‐l contracted RJV (EC50:2.1 nm) but not RTA.

The ETA receptor antagonist, BQ123, competitively antagonized (pA2 6.93) the contraction of RTA produced by ET‐1, but had no effect (at 10 μm) on the contractile effects of either ET‐1, ET‐3 or [Ala1,3,11,15]ET‐1 in RJV.

These data suggest that both ETA and ETB receptors can mediate vascular smooth muscle contraction.
Protection against the effects of anticholinesterases on the latencies of action potentials in mouse skeletal muscles
Authors: Kelly S.S. , Ferry C.B. , Bamforth J.P. , Das S.K.
Published: July 2012

Adult male albino mice were injected subcutaneously with an organophosphorous anticholinesterase to initiate excessive variability in the latency of indirectly elicited muscle action potentials (jitter) when assessed 5 days later.

Pretreatment of the mice with a single dose of pyridostigmine prevented the development of jitter after subsequent dosing with an organophosphate.

Treatment with one dose of pralidoxime (2PAM) prevented the development of jitter if given less than 1 h after treatment with ecothiopate, a reactivatable inhibitor of cholinesterase. Similar treatment with 2PAM after a non‐reactivatable inhibitor did not prevent the development of jitter. The repeated administration of 2PAM over 12 h did ameliorate jitter.

Pretreatment of mice orally with α‐tocopherol and N‐acetylcysteine, known to prevent ecothiopateinduced myopathy, did not prevent the development of jitter after ecothiopate.

It is concluded that the development of jitter was a consequence of the inhibition of acetylcholinesterase, and although jitter did not develop acutely, the potential for the full development of jitter was achieved about 1 h after intoxication with ecothiopate. The development of jitter did not involve the generation of free radicals. Reduction of the early effects of intoxication with anticholinesterases by pyridostigmine or 2PAM prevented the development of jitter.
Ornithine and histidine decarboxylase activities in mice sensitized to endotoxin, interleukin‐1 or tumour necrosis factor by d‐galactosamine
Authors: Endo Yasuo , Kikuchi Takashi , Nakamura Masanori
Published: July 2012

An injection of d‐galactosamine (GalN) into mice together with a lipopolysaccharide (LPS or endotoxin), interleukin‐1 (IL‐1) or tumour necrosis factor (TNF), sensitized the mice and induced fulminant hepatitis with severe congestion resulting in rapid death. Since LPS and these cytokines induce ornithine decarboxylase (ODC) and histidine decarboxylase (HDC) in the liver and spleen of mice, the effects of GalN on the induction of ODC and HDC in these organs were examined.

The induction of ODC by LPS, IL‐1 or TNF was suppressed by GalN in the liver, and this suppression preceded the hepatic congestion. There was good agreement between the degree of hepatic congestion and the suppression of ODC induction by various amounts of GalN. The induction of ODC in the spleen was suppressed only at the highest dose of GalN examined.

GalN is known to deplete uridine 5′‐triphosphate (UTP), resulting in the suppression of RNA and protein synthesis. An injection of uridine, the precursor of UTP, diminished the GalN‐induced suppression of ODC induction by LPS and prevented the hepatic congestion and death.

LPS‐pretreatment before injection of LPS plus GalN prevented the suppression of ODC activity and prevented the hepatic congestion and death.

An injection of putrescine, the product of ODC, prolonged survival time and delayed the development of hepatic congestion. However, injection of an ODC inhibitor into the mice given LPS did not produce hepatic congestion.

The induction of HDC in the liver by LPS, IL‐1 or TNF was not suppressed by GalN and, at high doses, the response to LPS was enhanced. An inhibitor of HDC neither prevented the hepatic congestion nor enhanced the protective effect of putrescine.

Although GalN in combination with IL‐1α induced a markedly higher HDC activity than was observed when it was combined with TNFα, and suppressed the induction of ODC, the former combination at the doses used did not produce hepatic congestion or death. However, the sensitization to TNFα by GalN was markedly potentiated by IL‐1α.

These results suggest that suppression of the induction of ODC by GalN may be one cause of the sensitization to LPS, IL‐1 or TNF, and that the induction of HDC, i.e. histamine formation, may not be involved in this sensitization.

These results are consistent with the hypothesis that both IL‐1 and TNF are involved in the sensitization to LPS.
Regulation of apoptosis in HL‐1 cardiomyocytes by phosphorylation of the receptor tyrosine kinase EphA2 and protection by lithocholic acid
Authors: Jehle J , Staudacher I , Wiedmann F , Schweizer PA , Becker R , Katus HA , Thomas D
Published: July 2012

Background and Purpose

Heart failure and atrial fibrillation are associated with apoptosis of cardiomyocytes, suggesting common abnormalities in pro‐apoptotic cardiac molecules. Activation of the receptor tyrosine kinase EphA2 causes apoptosis in vitro, and dysregulation of EphA2‐dependent signalling is implicated in LEOPARD and Noonan syndromes associated with cardiomyopathy. Molecular pathways and regulation of EphA2 signalling in the heart are poorly understood. Here we elucidated the pathways of EphA2‐dependent apoptosis and evaluated a therapeutic strategy to prevent EphA2 activation and cardiac cell death.

Experimental Approach

EphA2 signalling was studied in an established model of doxazosin‐induced apoptosis in HL‐1 cells. Apoptosis was measured with TUNEL assays and as cell viability using a formazan method. Western blotting and siRNA for EphA2 were also used.

Key Results

Apoptosis induced by doxazosin (EC50 = 17.3 μM) was associated with EphA2 activation through enhanced phosphorylation (2.2‐fold). Activation of pro‐apoptotic downstream factors, phospho‐SHP‐2 (3.9‐fold), phospho‐p38 MAPK (2.3‐fold) and GADD153 (1.6‐fold) resulted in cleavage of caspase 3. Furthermore, two anti‐apoptotic enzymes were suppressed (focal adhesion kinase, by 41%; phospho‐Akt, by 78%). Inactivation of EphA2 with appropriate siRNA mimicked pro‐apoptotic effects of doxazosin. Finally, administration of lithocholic acid (LCA) protected against apoptosis by increasing EphA2 protein levels and decreasing EphA2 phosphorylation.

Conclusions and Implications

EphA2 phosphorylation and activation of SHP‐2 are critical steps in apoptosis. Reduction of EphA2 phosphorylation by LCA may represent a novel approach for future anti‐apoptotic treatment of heart failure and atrial fibrillation.
Substance Use Patterns among High‐Risk American Indians/Alaska Natives in Los Angeles County
Authors: Dickerson Daniel L. , Fisher Dennis G. , Reynolds Grace L. , Baig Safia , Napper Lucy E. , Anglin M. Douglas
Published: July 2012

Background:
Substance abuse among American Indians/Alaska Natives (AI/ANs) is a significant and long‐standing health problem in the U.S. Two‐thirds of American AIs/ANs reside in the urban setting. However, studies analyzing substance use characteristics among urban AI/ANs are very limited.
  Methods:Substance use patterns among a sample of AI/ANs (n = 77) and other ethnic/racial groups in Los Angeles County at high risk of substance abuse were analyzed utilizing three datasets from programs targeting individuals at high risk for substance abuse and risky sexual behaviors.  Results:Compared to all other ethnic/racial groups, AI/ANs demonstrated significantly younger age of onset of alcohol, marijuana, methamphetamine, and “other” drug use, higher correlations of age of first use of amphetamine with a measure of the drug's reinforcement, and higher mean number of illicit drug injections in the 30 days before being interviewed.  Conclusions:Results from this study highlight a critical need for furthering our understanding of substance abuse problems among urban AI/ANs.(Am J Addict 2012;00:1–8)
Relations between Conspecific Density and Effects of Ultraviolet‐B Radiation on Tadpole Size in the Striped Marsh Frog
Authors: Mitchell Toby , Alton Lesley A. , White Craig R. , Franklin Craig E.
Published: July 2012

Global increases in ultraviolet‐B radiation (UVBR) associated with stratospheric ozone depletion are potentially contributing to the decline of numerous amphibian species around the world. Exposure to UVBR alone reduces survival and induces a range of sublethal effects in embryonic and larval amphibians. When additional environmental stressors are present, UVBR can have compounding negative effects. Thus, examination of the effects of UVBR in the absence of other stressors may substantially underestimate its potential to affect amphibians in natural habitats. We examined the independent and interactive effects of increased UVBR and high conspecific density would have embryonic and larval striped marsh frogs (Limnodynastes peronii). We exposed individuals to a factorial combination of low and high UVBR levels and low, medium, and high densities of striped marsh frog tadpoles. The response variables were time to hatching, hatching success, posthatch survival, burst‐swimming performance of tadpoles (maximum instantaneous swim speed following an escape response), and size and morphology of tadpoles. Consistent with results of previous studies, we found that exposure to UVBR alone increased the time to hatching of embryos and reduced the burst‐swimming performance and size of tadpoles. Similarly, increasing conspecific density increased the time to hatching of embryos and reduced the size of tadpoles, but had no effect on burst‐swimming performance. The negative effect of UVBR on tadpole size was not apparent at high densities of tadpoles. This result suggests that tadpoles living at higher densities may invest relatively less energy in growth and thus have more energy to repair UVBR‐induced damage. Lower densities of conspecifics increased the negative effects of UVBR on developing amphibians. Thus, low‐density populations, which may include declining populations, may be particularly susceptible to the detrimental effects of increased UVBR and thus may be driven toward extinction faster than might be expected on the basis of results from single‐factor studies.

Relaciones entre la Densidad Conespecífica y los Efectos de la Radiación Ultravioleta‐B sobre el Tamaño de Renacuajos de Limnodynastes peronei
Tectonic interpretation of metamorphic tectonites: integrating compositional mapping, microstructural analysis and in situ monazite dating
Authors: WILLIAMS M. L. , JERCINOVIC M. J.
Published: July 2012

Interpreting tectonic histories from metamorphic tectonites requires an understanding of the linkages and feedbacks between deformation and metamorphism. Relationships between deformation and metamorphism can be divided into two broad groups: active and passive. Active relationships involve direct interactions whereby deformation directly influences metamorphic reactions or metamorphism directly affects the rate or style of deformation. One of the most important ‘active’ relationships is the role that deformation plays in helping to remove unstable reactant phases and to promote the growth of stable product phases. Passive relationships are correlations or linkages that allow the deformation history to be integrated with the metamorphic history. Compositional mapping of major and accessory phases and especially maps of larger thin section domains are particularly valuable for evaluating strain partitioning, scales of equilibrium, relationships between metamorphic textures and deformational fabrics, and in particular, for interpreting geochronological data. Petrological pseudosections are an increasingly utilized tool for interpreting microtextures and for linking deformation, metamorphism, and large‐scale tectonics. In situ geochronology and petrological analysis of chronometer phases (i.e. monazite, xenotime, titanite, allanite, etc.) are a critical part of tectonic analysis of metamorphic rocks. The electron microprobe plays an essential role in characterizing chronometer phases and placing them into the context of silicate fabrics and textures.
Effects of Macroalgal Chemical Extracts on Spore Behavior of the Antarctic Epiphyte Elachista antarctica Phaeophyceae
Authors: Bucolo Philip , Amsler Charles D. , McClintock James B. , Baker Bill J.
Published: July 2012

Most macroalgal species along the Western Antarctic Peninsula (WAP) are defended against predation, many using chemical defenses. These subtidal communities are also mostly devoid of free living filamentous algae. However, one endo/epiphyte, Elachista antarctica, is found growing exclusively out of the palatable rhodophyte Palmaria decipiens. To understand this unusual and exclusive epiphytization, we tested whether macroalgal secondary metabolites such as those responsible for deterring sympatric grazers, affect the behaviors of the epiphyte's spores. Settlement, germination, and swimming behaviors of the epiphyte's motile spores were quantified in the presence of fractionated lipophilic and hydrophilic extracts of host P. decipiens and other rhodophytes from the shallow subtidal. Host P. decipiens was the only alga tested that did not inhibit spore settlement or germination. We also examined whether extracts from these chemically rich algae affect spore swimming behaviors and found spores to be chemotactically attracted to seawater soluble extract fractions of host P. decipiens. These results indicate that chemosensory behaviors of the epiphyte's spores to metabolites associated with these chemically defended macrophytes can explain this exclusive epiphyte–host interaction.
Children with Heavy Prenatal Alcohol Exposure Experience Reduced Control of Isotonic Force
Authors: Nguyen Tanya T. , Levy Susan S. , Riley Edward P. , Thomas Jennifer D. , Simmons Roger W.
Published: July 2012

Background

Heavy prenatal alcohol exposure can result in diverse and extensive damage to the central nervous system, including the cerebellum, basal ganglia, and cerebral cortex. Given that these brain regions are involved in the generation and maintenance of motor force, we predicted that prenatal alcohol exposure would adversely affect this parameter of motor control. We previously reported that children with gestational alcohol exposure experience significant deficits in regulating isometric (i.e., constant) force. The purpose of this study was to determine whether these children exhibit similar deficits when producing isotonic (i.e., graded) force.

Methods

Children with heavy prenatal alcohol exposure and typically developing children completed a series of isotonic force contractions by exerting force on a load cell to match a criterion target force displayed on a computer monitor. Two levels of target force (5 or 20% of maximum voluntary force) were investigated in combination with varying levels of visual feedback.

Results

Compared with control children, children with heavy prenatal alcohol exposure generated isotonic force signals that were less accurate, more variable, and less complex in the time domain. Specifically, interactions were found between group and visual feedback for response accuracy and signal complexity, suggesting that these children have greater difficulty altering their motor output when visual feedback is low.

Conclusions

These data suggest that prenatal alcohol exposure produces deficits in regulating isotonic force, which presumably result from alcohol‐related damage to developing brain regions involved in motor control. These children will most likely experience difficulty performing basic motor skills and daily functional skills that require coordination of finely graded force. Therapeutic strategies designed to increase feedback and, consequently, facilitate visual‐motor integration could improve isotonic force production in these children.
Use of AUDIT‐Based Measures to Identify Unhealthy Alcohol Use and Alcohol Dependence in Primary Care: A Validation Study
Authors: Johnson J. Aaron , Lee Anna , Vinson Daniel , Seale J. Paul
Published: July 2012

Background

As programs for screening, brief intervention, and referral to treatment (SBIRT) for unhealthy alcohol use disseminate, evidence‐based approaches for identifying patients with unhealthy alcohol use and alcohol dependence (AD) are needed. While the National Institute on Alcohol Abuse and Alcoholism Clinician Guide suggests use of a single alcohol screening question (SASQ) for screening and Diagnostic and Statistical Manual checklists for assessment, many SBIRT programs use alcohol use disorders identification test (AUDIT) “zones” for screening and assessment. Validation data for these zones are limited. This study used primary care data from a bi‐ethnic southern U.S. population to examine the ability of the AUDIT zones and other AUDIT‐based approaches to identify unhealthy alcohol use and dependence.

Methods

Existing data were analyzed from interviews with 625 female and male adult drinkers presenting to 5 southeastern primary care practices. Timeline follow‐back was used to identify at‐risk drinking, and diagnostic interview schedule was used to identify alcohol abuse and dependence. Validity measures compared performance of AUDIT, AUDIT‐C, and AUDIT dependence domains scores, with and without a 30‐day binge drinking measure, for detecting unhealthy alcohol use and dependence.

Results

Optimal AUDIT scores for detecting unhealthy alcohol use were lower than current commonly used cutoffs (5 for men, 3 for women). Improved performance was obtained by combining AUDIT cutoffs of 6 for men and 4 for women with a 30‐day binge drinking measure. AUDIT scores of 15 for men and 13 for women detected AD with 100% specificity but low sensitivity (20 and 18%, respectively). AUDIT dependence subscale scores of 2 or more showed similar specificity (99%) and slightly higher sensitivity (31% for men, 24% for women).

Conclusions

Combining lower AUDIT cutoff scores and binge drinking measures may increase the detection of unhealthy alcohol use in primary care. Use of lower cutoff scores and dependence subscale scores may increase diagnosis of AD; however, better measures for detecting dependence are needed.
Antisocial Symptoms Decrease to Normal Levels in Long‐Term Abstinence
Authors: Fein George , Fein David
Published: July 2012

Background

We have previously shown highly elevated antisocial symptoms and measures of social deviance proneness and antisocial disposition in long‐term abstinent alcohol dependence versus non‐substance‐abusing controls (NSAC). Current antisocial symptoms were reduced to subdiagnostic levels in long‐term abstinence; however, the number of current symptoms was not measured beyond its being subdiagnostic.

Methods

Here we measured social deviance proneness, antisocial disposition, and both lifetime and current antisocial symptoms in short‐term and long‐term abstinent substance‐dependent and NSAC samples.

Results

Lifetime antisocial symptoms (and diagnoses) and social deviance proneness and antisocial disposition were highly elevated in both short‐ and long‐term abstinence, replicating earlier findings. Current antisocial symptoms were dramatically reduced in long‐term versus short‐term abstinent samples, close to levels in controls. In contrast, social deviance proneness and antisocial disposition remain highly elevated in long‐term abstinence.

Conclusions

These findings suggest that antisocial behavior is reduced in extended abstinence, despite continued elevated social deviance proneness an antisocial disposition. This suggests a top‐down model in extended abstinence, whereby executive control inhibits deviance‐prone tendencies.
Ethanol‐Induced Htr3a Promoter Methylation Changes in Mouse Blood and Brain
Authors: Barker Jacqueline M. , Zhang Yuqi , Wang Fan , Taylor Jane R. , Zhang Huiping
Published: July 2012

Background

Abnormal DNA methylation has been observed in promoter regions of a number of genes in human alcoholics. It is unclear whether DNA methylation changes in alcoholics result directly from alcohol consumption or predated the occurrence of alcohol abuse or dependence and whether altered DNA methylation influences gene expression.

Methods

We investigated ethanol (EtOH)‐induced DNA methylation changes in mouse serotonin receptor 3a gene (Htr3a). A 5‐day drinking‐in‐the‐dark paradigm was applied to 28 male outbred CD‐1 mice (15 EtOH‐drinking and 13 water‐drinking). The Sequenom MassARRAY approach was used to quantify methylation levels of 8 CpGs around Htr3a transcription start site in trunk blood and 9 brain regions (dorsomedial prefrontal cortex [DMPFC], ventromedial prefrontal cortex, ventral tegmental area, dorsolateral striatum, dorsomedial striatum [DMSTR], ventral striatum, amygdala, hippocampus [HIPPO], and cerebellum). DNA methylation differences between the 2 groups of mice (EtOH‐ and water‐drinking) were analyzed using multivariate analysis of covariance with consideration of EtOH consumption amount. Expression levels of Htr3a in the DMSTR were measured by real‐time PCR in 14 EtOH‐drinking and 14 water‐drinking male CD‐1 mice.

Results

EtOH drinking increased methylation levels of specific Htr3a promoter CpGs in mouse blood (CpG−27: p = 0.028; CpG+54: p = 0.044) and HIPPO (CpG+151: p = 0.012) but reduced methylation levels of specific Htr3a promoter CpGs in mouse DMSTR (CpG−96: p = 0.020; CpG−27: p = 0.035) and DMPFC (CpG+138: p = 0.011; CpG+151: p = 0.040). Nevertheless, methylation levels of Htr3a promoter CpGs in 6 other brain regions were not significantly altered by EtOH consumption. Additionally, the expression level of Htr3a in the DMSTR was 1.43‐fold higher in alcohol‐drinking mice than in water‐drinking mice (p = 0.044).

Conclusions

Our findings indicate that alcohol consumption may induce tissue‐specific DNA methylation changes and further suggest that Htr3a promoter methylation levels may be reversely correlated with Htr3a expression levels in specific brain regions such as DMSTR.
Individual Differences in Voluntary Ethanol Consumption Lead to Differential Activation of the Central Amygdala in Rats: Relationship to the Anxiolytic and Stimulant Effects of Low Dose Ethanol
Authors: Sharko Amanda C. , Kaigler Kris F. , Fadel Jim R. , Wilson Marlene A.
Published: July 2012

Background

Although alcohol use disorders and anxiety disorders are highly comorbid, the relationship between these 2 disorders is not fully understood. Previous work from our laboratory shows that anxiety‐like behavior is highly variable in outbred Long‐Evans rats and is related to the level of voluntary ethanol (EtOH) consumption, suggesting that basal anxiety state influences EtOH intake. To further examine the relationship between the acquisition of EtOH consumption and anxiety phenotype, Long‐Evans rats were assessed for anxiety‐like behavior and neuronal activation following voluntary EtOH consumption in a limited access drinking paradigm.

Methods

Rats were allowed to self‐administer EtOH (6% v/v) for 4 days using a limited access drinking in the dark paradigm and divided into high‐ and low‐drinking groups based on a median split of average daily EtOH intake. Immediately following the fourth drinking session, animals were tested on the elevated plus maze and evaluated for anxiety‐like behaviors. Fos immunoreactivity was assessed in the central and basolateral amygdala, as well as the bed nucleus of the stria terminalis.

Results

High EtOH drinkers spent significantly more time on the open arms of the plus maze than low EtOH drinkers. High EtOH drinkers also had increased locomotor activity as compared to both low EtOH drinkers and water drinkers. Fos immunoreactivity was positively correlated with EtOH consumption in all brain regions examined, although Fos‐positive cell counts were only significantly different between high and low EtOH drinkers in the central amygdala (CeA).

Conclusions

Our findings demonstrate that outbred rats will voluntarily consume behaviorally effective doses of EtOH in a short‐term access model and EtOH consumption is positively correlated with increased neuronal activation in the CeA.
A Meta‐Analysis on the Impact of Alcohol Dependence on Short‐Term Resting‐State Heart Rate Variability: Implications for Cardiovascular Risk
Authors: Quintana Daniel S. , McGregor Iain S. , Guastella Adam J. , Malhi Gin S. , Kemp Andrew H.
Published: July 2012

Background

Alcohol dependence is associated with an increased likelihood of cardiac events. Reductions in heart rate variability (HRV) may be one mechanism linking dependence with these events. HRV may also be related to poor social functioning and the lack of impulse control commonly observed in alcohol‐dependent individuals. However, prior studies on the impact of alcohol dependence on HRV have reported contradictory findings highlighting the need for a meta‐analysis.

Methods

Studies comparing short‐term HRV in alcohol‐dependent populations and healthy controls who were nondependent were considered for meta‐analysis. Only studies reporting findings from participants without cardiovascular disease were included in the analysis.

Results

Meta‐analyses were based on 6 articles that fulfilled inclusion criteria, comprising a total of 177 alcohol‐dependent participants and 216 nondependent participants. Alcohol‐dependent participants displayed reduced HRV (Hedges' g = −0.6, p > 0.001) in comparison with nondependent participants. No differences were observed between the summary effect sizes obtained from different HRV domains (Q = 1.19, p = 0.55).

Conclusions

Alcohol dependence is associated with reduced HRV, an effect associated with a medium effect size. Findings highlight the importance of monitoring alcohol‐dependent patients for cardiac disease and emphasize the need for cardiovascular risk reduction strategies in these patients.
On the Welfare Gains of Price Dispersion
Authors: DUTU RICHARD , JULIEN BENOIT , KING IAN
Published: July 2012

Can price dispersion be associated with higher levels of welfare? To answer we compare two economies that differ only in the way prices are formed. In the first, sellers post a unique price–quantity pair, with no price dispersion. In the second, sellers post a quantity only and let prices be determined ex post by realized demand, resulting in price dispersion. We show that while agents trade lower quantities when prices are dispersed (an intensive margin effect), they also trade more often (an extensive margin effect). At low inflation, the extensive margin dominates making agents better off with price dispersion.
The Friedman Rule in a Model with Endogenous Growth and Cash‐in‐Advance Constraint
Authors: GAHVARI FIROUZ
Published: July 2012

This paper introduces money into an overlapping‐generations model with endogenous growth. The main message of the paper is that as long as the modified golden rule is attained, the Friedman rule is optimal. The result holds regardless of the ability of the government to internalize the externality and control the level of human capital. Other results include: (i) violation of the Friedman rule for a different second‐best environment wherein human capital accumulation is controlled but not physical capital accumulation and (ii) existence of a negative relationship between money growth rate and the economy’s endogenous growth rate.
The Advantage of Flexible Targeting Rules
Authors: FERRERO ANDREA
Published: July 2012

This paper investigates the consequences of debt stabilization for inflation targeting. If the fiscal authority holds constant the real value of debt at maturity under strict inflation targeting, the equilibrium dynamics are indeterminate for a wide range of parameters and steady‐state fiscal stances. “Flexible” targeting rules that include a concern for stabilization of the output gap can restore determinacy of the equilibrium. Flexible inflation targeting appears to be more robust than flexible debt targeting to alternative parameterizations. The fiscal authority can prevent indeterminacy under strict targeting rules by committing to hold constant debt net of interest rate spending.
Illiquidity in the Interbank Payment System Following Wide‐Scale Disruptions
Authors: BECH MORTEN L. , GARRATT RODNEY J.
Published: July 2012

We show how the interbank payment system can become illiquid following wide‐scale disruptions. Two forces are at play in such disruptions—operational problems and changes in participants’ behavior. If the disruption is large enough, hits a key geographic area, or hits a “too‐big‐to‐fail” participant, then the smooth processing of payments can break down, and central bank intervention might be required to reestablish the socially efficient equilibrium. The paper provides a theoretical framework to analyze the effects of events such as the September 11 attack. In addition, the model can be reinterpreted to analyze shocks to fundamentals that affect the parameters of the intraday liquidity management game. We demonstrate this by showing how processing behavior changed in response to heightened credit risk at the time of the Lehman Brothers failure.
New Executives from Inside or Outside? The Effect of Executive Replacement on Organizational Change
Authors: Villadsen Anders R.
Published: July 2012

This article investigates how executive succession influences the comprehensiveness of structural changes pursued by public organizations. Executive successions are important events for organizations that provide salient opportunities for introducing organizational change, yet little research has analyzed this relationship. The author argues that the less familiarity a new executive has with the organization and the field in which it works, the more likely it is that comprehensive organizational change will take place. Empirical results from quantitative analyses of executive succession events in Danish municipalities from 1984 to 2000 confirm this. Interestingly, the degree to which new practices are legitimized moderates the findings. Inside successors are more likely to conduct comprehensive structural changes after new practices receive normative and regulatory legitimacy. The article contributes to the literature on executive succession by highlighting how it is an antecedent to different types of organizational change. Contributions to practitioner and public management research are discussed.