bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of substituted furyltetrazolyl acetates by means of 13C NMR spectrometry
Authors: Světlík Jan , Goljer Igor , Janda Ľubomír
Published: February 2011

13C NMR data of a series of 5-[5-(substituted phenyl)-2-furyl]-1- and -2-tetrazolyl acetates are presented. Examination of diagnostic resonances emphasizing particularly those arising from the tetrazole ring system enabled both isomers to be easily distinguished. The chemical shift increment for 5-(2-furyl)-1- and -2-tetrazolyl acetate unit has been deduced.
Configuration of sodium salt and preparation of sulphonates and carboxylates of (E)- and (Z)-3-(hydroxymethylene)dihydro-2(3H)-furanone
Authors: Jonas Jaroslav
Published: February 2011

The sodium salt of 3-(hydroxymethylene)dihydro-2(3H)-furanone (I) can be obtained in solid state in the form of (Z)-isomer, or their mixture, whereas in solutions it only exists in the form of (E)-isomer. Reactions of these sodium salts with sulphonyl or acyl chlorides or sulphonic acid anhydrides give the respective (E)- and (Z)-sulphonates or carboxylates of 3-(hydroxymethylene)dihydro-2(3H)-furanone in high yields and purity. Configuration of the sodium salt isomers has been confirmed by their IR and 12C NMR spectra in solid state, that of the isomeric sulphonates and carboxylates has been confirmed by their 1H and 13C NMR spectra in solution.
Density estimation of ternary aqueous solutions
Authors: Söhnel Otakar , Novotný Petr , Šolc Zdeněk
Published: February 2011

Relations are presented for estimating the density of ternary aqueous solution on the basis of known densities of binary solutions of both components of the ternary solution. Accuracy of the estimation is tested using both the diluted and concentrated ternary solutions at temperatures of 15 - 100 °C.
Synthesis and properties of carba-6-analogues of oxytocin containing a deaminopenicillamine residue in position 1
Authors: Lebl Michal , Barth Tomislav , Servítová Linda , Slaninová Jiřina , Hrbas Pavel
Published: February 2011

A study was made of the influence of the so-called carba substitution of the disulphide bridge on the properties of inhibitors obtained by the introduction of deaminopenicillamine into position 1 of the oxytocin molecule. Two analogues - [dPen1]carba-6-oxytocin (Ia) and [dPen1, Tyr(Me)2]carba-6-oxytocin (Ib) were prepared and their biological activities were assayed. Compound Ia is a strong agonist in the uterotonic assay in vivo (280 I.U./mg) and a weak antagonistin the pressor assay. Compound Ib inhibited the utertonic activity of oxytocin in vitro (pA2 = 8.43) and in vivo (pA2 = 7.13) as well as the pressor action of lysine vasopressin (pA2 = 7.43).
Probable mechanism of the effect of thermal history of solution on the metastable zone width
Authors: Nývlt Jaroslav
Published: February 2011

The metastable zone width of an aqueous solution of FeSO4 has been measured as a function of the temperature of solution overheating. For the solution overheated to a temperature lower than that of hydrate transformation, the data fit to a continuous, smooth curve, while points obtained in overheating the solution above the hydrate transformation temperature lie distinctly above the extension of the curve. Of hypotheses advanced in the literature to explain the thermal history of solution, only that based on redistribution of subcritical cluster sizes of crystallizing substance seems compatible with the observation.
The effect of a sorbent dilution with inert material on isothermal dynamic adsorption
Authors: Kočiřík Milan , Zikánová Arlette , Drahorádová Eva
Published: February 2011

The derived expression show the dependence of the efficiency of a sorption layer on dilution of this layer with inert material. The presence of the inert material in the space between granules has effect on the term of axial dispersion, while the same material inside the granules affects both the term of axial dispersion and the internal diffusion. The inert material presence can change in the isothermal sorption processes a relative importance of the individual rate steps. The derived expressions can be applied for testing the rate mechanism and their dependence on the dilution extent.
Study of the effect of aggregation on the structure of syndiotactic poly(methyl methacrylate) by infrared spectra of its deuterated analogues
Authors: Dybal Jiří , Schneider Bohdan , Mihailov Marian
Published: February 2011

The temperature trends of the infrared spectra of the films of some specifically deuterated analogues of syndiotactic poly(methyl methacrylate) were measured and vibrational bands sensitive to the conformational structure of the carbon backbone and to the orientation of ester groups with respect to the main chain were determined. Analysis of the spectra has confirmed that aggregated syndiotactic poly(methyl methacrylate) contains a higher population of diads in the extended chain conformation in long syndiotactic sequences as compared to the nonaggregated polymer, and has shown that in the aggregate, ordering of ester groups also takes place.
Effect of the structure of alkyllithium on the polymerization kinetics of isoprene
Authors: Bajpai U. D. N. , Kašpar Miroslav , Trekoval Jiří
Published: February 2011

The kinetics of polymerization of isoprene in benzene initiated with ethyl-, propyl-, butyl-, hexyl-, octyl-, 2-butyl-, 3-hexyl-, 2-octyl-, and 6-methylheptyllithium was investigated. With the exception of ethyllithium , a distinct initial induction period decreasing steeply with increasing concentration of the initiator was observed for all n-alkyllithium initiators. No induction period was observed with the other initiators. The reaction orders decreased at the highest concentrations for most of the initiators, sometimes even to negative values. In the case of ethyl-, 2-butyl- and octyl-lithium this phenomenon has not been observed in the range investigated.
The aposteriori uncertainty of qualitative and identification analyses
Authors: Eckschlager Karel , Král Milan
Published: February 2011

It is shown that the uncertainty remaining after a qualitative, identification, chemical or instrumental analysis depends on the structure of the reagent and of the reacting component, on the physico-chemical properties of the arising substance and, in the case of an instrumental proof, also on the properties of the device used.
Selectivity coefficients of some simple and complex inorganic ions for Spheron DEAE
Authors: Vláčil František , Koňák Karel
Published: February 2011

The selectivity coefficients of the nitrate and chloride ions and of anionic chloro complexes of Au(III), Rh(III), Pd(II), and Pt(IV) for ion exchange on Spheron DEAE in the chloride form are determined by the dynamic method. the complex anion species formed are identified and the ion exchange nature of the sorption of precious metals on this sorbent is confirmed based on the elution order of the precious metals as determined previously by the column chromatography on Spheron DEAE using hydrochloric acid as the mobile phase. The effect of the presence of perchlorate in the mobile phase during the liquid chromatography of precious metals and during the chromatographic determination of nitrate traces is explained.
Photochemical oxidation of ethylbenzene and other hydrocarbons in the presence of cobalt(III) 2,4-pentanedionate
Authors: Žilková Naděžda , Shulpin Georgiy B. , Lederer Pavel
Published: February 2011

The photochemical oxidation of ethylbenzene in the presence of cobalt(III) 2,4-pentanedionate has been investigated. On the basis of results for the kinetics of chemical transformation of catalyst in the course of this reaction, a hypothesis is advanced concerning photoinitiating effect of cobalt(III) 2,4-pentanedionate on ethylbenzene oxidation.
Preparation of 3- and 3,5-substituted 1,2,4-triazoles
Authors: Vaněk Tomáš , Velková Vlasta , Gut Jiří
Published: February 2011

Ethyl 1,2,4-triazole-3-carboxylate (V), its 5-methyl and 5-phenyl derivatives (V and VI, respectively), 3-methyl-1,2,4-triazole (VIII), 3-phenyl-1,2,4-triazole(IX), 3,5-dimethy-1,2,4-triazole(X), 3,5-diphenyl-1,2,4-triazole (XI) and 3-phenyl-5-methyl-1,2,4-triazole (XII) were prepared in 40 - 70% yields by thermal cyclization of acylamidrazones III.
Reduction and spin transition of some macrocyclic Fe(III) complexes
Authors: Wagnerová Dana M. , Stopka Pavel , Lassmann Günter , Ebert Bernd
Published: February 2011

The ESR and absorption spectroscopies were used to study the reduction of Fe(III) tetrasulphophthalocyanine (FeTSP) and Fe(III) chloro-deuteroporphyrin (FeCDP) by ascorbic acisd and cysteine. Only the monomeric form of Fe(III)TSP gives an ESR spectrum, while the dimer is ESR quiet. The complex is low-spin, and is rapidly reduced by both substrates to Fe(II)TSP. The spin states of the complexes are correlated with their catalytic activity in the oxidation of the substrates by dioxygen.
Structure of polyelectrolyte solutions, SAXS study of poly(aspartic acid)
Authors: Pleštil Josef , Hlavatá Drahomíra , Ostanevich Yurii Miaczeslavovich , Saudek Vladimír
Published: February 2011

The position of the maximum on small-angle scattering curves of solutions of poly(aspartic acid) neutralized with NaOH is proportional to the third root of concentration. The course of the interference function and the characteristic interchain distance were determined. The data may be interpreted using a model of ordered chains and assuming that the chain length per one monomer unit is smaller than would correspond to the all trans-conformation.
Acylation of 2-phenoxyethyl esters of 2-methyl- and 3-phenyl-2-propenoic acids
Authors: Lukáč Ivan , Zvara Ivan , Hrdlovič Pavol
Published: February 2011

1-(2-Methyl-2-propenoyloxy)-2-(4-acylphenoxy)ethanes II - V and 1-(3-phenyl-2-propenoyloxy)-2-[4-(3-chloropropanoyl)phenoxy]ethane (VI) were prepared by the Friedel-Crafts acylation, in the presence of anhydrons aluminium chloride, of 2-phenoxyethyl esters of 2-methyl- and 3-phenyl-2-propenoic acids with the corresponding acyl chlorides.
Potential antiparkinsonic agents: Synthesis and pharmacology of some 4-fluoro-4'-halogen'benzhydryl 2-(N,N-disubstituted amino)ethyl ethers
Authors: Vejdělek Zdeněk , Metyš Jan , Holubek Jiří , Svátek Emil , Protiva Miroslav
Published: February 2011

Reactions of 4,4'-dihalogenated benzhydrols and 1,1-diphenylethanols Xab and XIab with sodium hydride and 2-dimethylaminoethyl chloride and 2-pyrrolidinoethyl chloride afforded the ethers Vab-VIIIab. 2-Bromoethyl ethers IXab, obtained from the benzhydrols Xab and 2-bromoethanol by treatment with sulfuric acid, were subjected to substitution reactions with 4-phenylpiperidin-4-ol, 4-(2-tolyl)piperidin-4-ol (XVI), 4-(4-fluorophenyl)piperidin-4-ol and 4-(2-oxobenzimidazolin-1-yl)piperidine (XVII) and gave the amino ethers XIIab-XIVab and XIXab. The products were evaluated as potential antiparkinsonic agents and compared with flunamine (III). The ethers Va, Vb and VIa disclosed anticataleptic activity of a similar degree like that of flunamine (III).
Polysaccharides from the roots ofAlthaea officinalis L.: Structural features of D-glucans
Authors: Capek Peter , Toman Rudolf , Rosík Jozef , Kardošová Alžbeta , Janeček František
Published: February 2011

From the roots of the medicinal plant Althaea officinalis L., three D-glucans were isolated by gel chromatography which differed in molecular weights. The results of methylation analyses and 13C NMR measurements indicated predominantly linear character of the polysaccharide chains composed of α-D-glucopyranose units linked by 1 → 6 glycosidic bonds almost exclusively. The polymers had essentially the same structural features as D-glucan isolated from the leaves of this plant.
Amperometric assay of activity and pH-optimum of N2O reductase of Paracoccus denitrificans
Authors: Kučera Igor , Boublíková Pavla , Dadák Vladimír
Published: February 2011

The paper reports on a novel experimental procedure of amperometric assay of the activity of N2O reductase from the bacteria Paracoccus denitrificans by a Clark-type element. A suspension of baker's yeast is used to ensure the necessary anaerobic conditions and the reaction itself is triggered by the addition of P. denitrificans cells to the medium. The physiological pH-optimum of the N2O reductase of intact cells as determined by this assay is 8.0.
Theoretical study of the electron structure and properties of dithiocarbamates and their complexes with transition metals
Authors: Miertuš Stanislav , Frecer Vladimír
Published: February 2011

The semiempirical CNDO/2 method was used to calculate the electron structure of derivatives of dithiocarbamates, R2N-CS2, as anions and radicals. We studied changes in the oxidation-reduction and bonding properties by changes of R = H, CH2, C2H5, C3H5. Calculations were also carried out on model complexes of R2N-CS2 with metals Cu, Mn, Fe, Co, Ni. Differences in the electron structure of these complexes with various numbers of ligands, various states of oxidation and varying spin multiplicity of the central atoms were evaluated.
The gas side mass transfer coefficient in the turbulent flow in a packing with a significant dependence of the interfacial area on the density of irrigation
Authors: Červenka Jan , Kolář Václav
Published: February 2011

A theoretically derived relationship has been applied for the gas-side mass transfer coefficient to experimental values of kG. The experimental data have been obtained under the two-phase flow of gas and liquid in a plane vertical packing manufactured of the expanded metal sheet. This packing exhibits a significant dependence of the extent of interfacial area, and hence the geometry of the channel available for gas flow, on the density of irrigation.
Effect of sodium and potassium chloride on dehydration of karnallite
Authors: Poilov Vladimir Z. , Ederová Jana , Golovchenko Larisa V. , Blažek Antonín
Published: February 2011

Article in Russian
Contribution to the study of the kinetics of redox reactions proceeding via electrode processes. Theory of the method
Authors: Tockstein Antonín , Macenauer Jaroslav
Published: February 2011

A system of differential kinetic equations is derived for the redox reaction n2 Ox1 + n1 Red2 ⇌ n1 Ox2 + n2 Red1, proceeding only through electrode processes. Its numerical solution is compared with a simplified analytical solution which leads to linearization of the relations between measurable quantities and thus verification of the kinetic model used on real redox reactions.
The reaction of 1-phenylmethyl-4N-acetylimino-1H-1,2,4-triazolium betain with butynedioic acid dimethyl ester
Authors: Zálupský Peter , Bírošová Mária , Fišera Lubor
Published: February 2011

The reaction between 1-phenylmethyl-4N-acetylimino-1H-1,2,4-triazolium betain(I) and dimethyl butynedioate is decribed. By performing the reaction at ration 1:1 the enamide III is formed. With a fivefold excess of the dipolarophile, except III, also pyrrolo[1,2-d]-triazole XII and pyridine derivative XV were obtained.
Transarterial embolization with ONYX for treatment of intracranial non-cavernous dural arteriovenous fistula with or without cortical venous reflux
Authors: De Keukeleire Katrien , Vanlangenhove Peter , Kalala Okito Jean-Pierre , Hallaert Giorgio , Van Roost Dirk , Defreyne Luc
Published: February 2011

Background and purpose

To report our experience with transarterial ONYX embolization of intracranial non-cavernous dural arteriovenous fistulas (DAVFs) with or without cortical venous reflux.

Materials and methods

Retrospective analysis of transarterial ONYX embolization in 20 patients with 21 DAVFs, presenting with intracranial hemorrhage (n=7), pulsatile bruit (n=7), vertigo (n=3), non-pulsatile bruit (n=1), headache (n=1) and epilepsy (n=1). Risk grading of DAVFs was Borden type I (n=6), type II (n=4) and type III (n=11).

Results

18 of 21 (85.7%) DAVFs were angiographically occluded immediately after embolization, with ONYX embolization only, in either one (n=12) or two sessions (n=2); with a combination of ONYX and glue or transvenous coiling in a single session (n=2) or in two sessions (n=1); or after previous transvenous coiling/glue embolization (n=1). At the 6 (4–14) month control digital subtraction angiography (DSA), available in 14 of 18 occluded DAVFs, one patient showed a small residual fistula (17/21 or 81% occluded). Mid-term DSA was not available because of early death (n=2) or patients were awaiting the examination (n=2). In three cases, treatment was incomplete. Of six Borden type I DAVFs, four were cured and two partially occluded with resolution of symptoms. In two DAVFs, neurosurgical access to the feeding artery allowed distal microcatheterization and successful embolization.

Conclusion

Transarterial ONYX embolization offers an effective and safe treatment for all non-cavernous DAVFs, whether with or without cortical venous reflux.
Trends in mortality from appendicitis and from gallstone disease in English populations, 1979–2006: study of multiple-cause coding of deaths
Authors: Goldacre Michael J , Duncan Marie E , Griffith Myfanwy , Davidson Matt
Published: February 2011

Objective

To report on trends in mortality from appendicitis and from gallstone disease.

Design and setting

Analysis of data from death certificates including all certified causes of death, termed ‘mentions’, not just the underlying cause, using data from Oxford (‘mentions’ available from 1979 to 2006) and all England (‘mentions’ available from 1995 to 2006).

Outcome measures

Mortality rates across all years studied, and in periods defined by changes to national rules in selecting the underlying cause of death.

Results

In the Oxford region, mortality rates for appendicitis based on underlying cause fluctuated between periods defined by coding rule changes. Those based on mentions were more stable: they were 3.3 per million population in 1979–83 and 3.5 in 2001–6. Nationally, mentions-based rates fell from 3.4 per million in 1995–2000 to 3.1 in 2001–2006, a small but statistically significant decline. For gallstone disease in Oxford, rates fell in the early years but then levelled off. Mortality rates for gallstones in England actually rose slightly between 1995–2000 (15.0 deaths per million) and 2001–6 (15.6 per million). The majority of deaths from appendicitis and gallstone disease were in the elderly.

Conclusions

Appendicitis and gallstones are considered to be avoidable causes of death. Mortality rates for each cause have not shown any substantial falls in the recent periods covered by this study. It is possible that deaths were not, in fact, avoidable, but audits into the circumstances of deaths from these diseases may be warranted. Mortality data based on underlying cause alone substantially underestimate deaths from these two conditions.
Using the ISBAR handover tool in junior medical officer handover: a study in an Australian tertiary hospital
Authors: Thompson James E , Collett Luke W , Langbart Marc J , Purcell Natalie J , Boyd Stephanie M , Yuminaga Yuigi , Ossolinski Gemma , Susanto Clarissa , McCormack Ann
Published: February 2011

Background

Despite being essential to patient care, current clinical handover practices are inconsistent and error prone. Efforts to improve handover have attracted attention recently, with the ISBAR tool increasingly utilised as a format for structured handover communication. However, ISBAR has not been validated in a junior medical officer setting.

Objective

To assess the effect of the ISBAR handover tool on junior medical officer (JMO) handover communication in an Australian hospital.

Methods

JMOs who participated in after-hours handover during an 11 week clinical term from June to August 2009 were recruited. After-hours handover was audiotaped, and JMOs completed a survey to assess current handover perception and practice. JMOs then participated in a 1 h education session on handover and use of the ISBAR handover tool, and were encouraged to handover using this method. Following the education session, participants were surveyed to measure perceived changes in handover with use of ISBAR, and handover was again audiotaped to assess differences in information transfer and duration.

Results

Following the introduction of ISBAR, 25/36 (71%) of JMOs felt there was an overall improvement in handover communication. Specifically, they perceived improvement in the structure and consistency of handover, they felt more confident receiving handover, and they believed patient care and safety were improved. Audio-tape data demonstrated increased transfer of key clinical information during handover with no significant effect on handover duration.

Conclusions

Use of the ISBAR tool improves JMO perception of handover communication in a time neutral fashion. Consideration should be given to the introduction of ISBAR in all JMO handover settings.
International disease monitoring, October to December, 2010
Authors: Roberts H. , Lopez M. , Hartley M.
Published: February 2011

African swine fever in the Caucasus and Leningrad regions of Russia

Equine infectious anaemia in several EU member states

Foot‐and‐mouth disease in Bulgaria – the first in an EU member state since 2007

Highly pathogenic avian influenza H5N1 in the Far East

West Nile virus in southern Europe

These are among matters discussed in the international disease monitoring report for October to December 2010, prepared by Defra's Food and Farming Group, Veterinary Science Team
Ecological Physiology of Diet and Digestive Systems
Authors: Karasov William H. , Martínez del Rio Carlos , Caviedes-Vidal Enrique
Published: February 2011

The morphological and functional design of gastrointestinal tracts of many vertebrates and invertebrates can be explained largely by the interaction between diet chemical constituents and principles of economic design, both of which are embodied in chemical reactor models of gut function. Natural selection seems to have led to the expression of digestive features that approximately match digestive capacities with dietary loads while exhibiting relatively modest excess. Mechanisms explaining differences in hydrolase activity between populations and species include gene copy number variations and single-nucleotide polymorphisms. In many animals, both transcriptional adjustment and posttranscriptional adjustment mediate phenotypic flexibility in the expression of intestinal hydrolases and transporters in response to dietary signals. Digestive performance of animals depends also on their gastrointestinal microbiome. The microbiome seems to be characterized by large beta diversity among hosts and by a common core metagenome and seems to differ flexibly among animals with different diets.
Endocrine Disruptors: From Endocrine to Metabolic Disruption
Authors: Casals-Casas Cristina , Desvergne Béatrice
Published: February 2011

Synthetic chemicals currently used in a variety of industrial and agricultural applications are leading to widespread contamination of the environment. Even though the intended uses of pesticides, plasticizers, antimicrobials, and flame retardants are beneficial, effects on human health are a global concern. These so-called endocrine-disrupting chemicals (EDCs) can disrupt hormonal balance and result in developmental and reproductive abnormalities. New in vitro, in vivo, and epidemiological studies link human EDC exposure with obesity, metabolic syndrome, and type 2 diabetes. Here we review the main chemical compounds that may contribute to metabolic disruption. We then present their demonstrated or suggested mechanisms of action with respect to nuclear receptor signaling. Finally, we discuss the difficulties of fairly assessing the risks linked to EDC exposure, including developmental exposure, problems of high- and low-dose exposure, and the complexity of current chemical environments.
The Lung: The Natural Boundary Between Nature and Nurture
Authors: Seibold Max A. , Schwartz David A.
Published: February 2011

Common lung diseases such as asthma, COPD, and pulmonary fibrosis cause significant morbidity and mortality in the U.S. and worldwide. Research investigating the mechanisms of disease etiology has clearly indicated that genetic attributes and environmental exposures each play important roles in the development of these diseases. Emerging evidence underscores the importance of the interplay between genetic predisposition and environmental factors in fully understanding the development of lung disease. Herein we discuss recent advances in knowledge and technology surrounding the role of genetics, the environment, and gene-environment interactions in these common lung diseases.
Mechanisms Underlying Rapid Aldosterone Effects in the Kidney
Authors: Thomas Warren , Harvey Brian J.
Published: February 2011

The steroid hormone aldosterone is a key regulator of electrolyte transport in the kidney and contributes to both homeostatic whole-body electrolyte balance and the development of renal and cardiovascular pathologies. Aldosterone exerts its action principally through the mineralocorticoid receptor (MR), which acts as a ligand-dependent transcription factor in target tissues. Aldosterone also stimulates the activation of protein kinases and secondary messenger signaling cascades that act independently on specific molecular targets in the cell membrane and also modulate the transcriptional action of aldosterone through MR. This review describes current knowledge regarding the mechanisms and targets of rapid aldosterone action in the nephron and how aldosterone integrates these responses into the regulation of renal physiology.
Epithelial-Mesenchymal Interactions in Pulmonary Fibrosis
Authors: Chapman Harold A.
Published: February 2011

Lung epithelial cells have emerged as a frequent target of injury, a driver of normal repair, and a key element in the pathobiology of fibrotic lung diseases. An important aspect of epithelial cells is their capacity to respond to microenvironmental cues by undergoing epithelial-mesenchymal transition (EMT). EMT is not simply widespread conversion of epithelial cells to fibroblasts but a graded response whereby epithelial cells reversibly acquire mesenchymal features and enhanced capacity for mesenchymal cross-talk. Recent studies elucidate distinct integrin-sensing systems that coordinate activity of TGFβ1, a critical signaling element regulating EMT, with the presence of proinflammatory signals and cell injury. Repeated injury superimposes persistent inflammation and hypoxia onto these highly regulated repair pathways, potentially overwhelming orderly repair and creating sustained fibrogenesis. Understanding specific signaling mechanisms driving the mesenchymal response to TGFβ1 may reveal therapeutics to attenuate fibrogenesis yet preserve the important homeostatic functions of TGFβ1.
Myocardial Remodeling: Cellular and Extracellular Events and Targets
Authors: Dixon Jennifer A. , Spinale Francis G.
Published: February 2011

The focus of this review is on translational studies utilizing large-animal models and clinical studies that provide fundamental insight into cellular and extracellular pathways contributing to post–myocardial infarction (MI) left ventricle (LV) remodeling. Specifically, both large-animal and clinical studies have examined the potential role of endogenous and exogenous stem cells to alter the course of LV remodeling. Interestingly, there have been alterations in LV remodeling with stem cell treatment despite a lack of long-term cell engraftment. The translation of the full potential of stem cell treatments to clinical studies has yet to be realized. The modulation of proteolytic pathways that contribute to the post-MI remodeling process has also been examined. On the basis of recent large-animal studies, there appears to be a relationship between stem cell treatment post-MI and the modification of proteolytic pathways, generating the hypothesis that stem cells leave an echo effect that moderates LV remodeling.
Niemann-Pick C1-Like 1 (NPC1L1) Protein in Intestinal and Hepatic Cholesterol Transport
Authors: Jia Lin , Betters Jenna L. , Yu Liqing
Published: February 2011

Increased blood cholesterol is an independent risk factor for atherosclerotic cardiovascular disease. Cholesterol homeostasis in the body is controlled mainly by endogenous synthesis, intestinal absorption, and hepatic excretion. Niemann-Pick C1-Like 1 (NPC1L1) is a polytopic transmembrane protein localized at the apical membrane of enterocytes and the canalicular membrane of hepatocytes. It functions as a sterol transporter to mediate intestinal cholesterol absorption and counterbalances hepatobiliary cholesterol excretion. NPC1L1 is the molecular target of ezetimibe, a potent cholesterol absorption inhibitor that is widely used in treating hypercholesterolemia. Recent findings suggest that NPC1L1 deficiency or ezetimibe treatment also prevents diet-induced hepatic steatosis and obesity in addition to reducing blood cholesterol. Future studies should focus on molecular mechanisms underlying NPC1L1-dependent cholesterol transport and elucidation of how a cholesterol transporter modulates the pathogenesis of metabolic diseases.
Renin Release: Sites, Mechanisms, and Control
Authors: Kurtz Armin
Published: February 2011

In the adult organism, systemically circulating renin almost exclusively originates from the juxtaglomerular cells in the afferent arterioles of the kidneys. These cells share similarities with pericytes and myofibro-blasts. They store renin in a vesicular network and granules and release it in a regulated fashion. The release mode of renin is not understood; in particular, the involvement of SNARE proteins is unknown. Renin release is acutely increased via the cAMP signaling pathway, which is triggered mainly by catecholamines and other Gs-coupled agonists, and is inhibited by calcium-related pathways that are commonly activated by vasoconstrictors. Renin release from juxtaglomerular cells is directly modulated in an inverse fashion by the blood pressure inside the afferent arterioles and by the chloride content in the tubule fluid at the macula densa segment of the distal tubule. Renin release is stimulated by nitric oxide and by prostanoids released by neighboring endothelial and macula densa cells. Steady-state renin concentrations in the plasma are determined essentially by the number of renin-producing cells in the afferent arterioles, which changes in parallel with challenges to the renin-angiotensin-aldosterone system.
Regulation of Electroneutral NaCl Absorption by the Small Intestine
Authors: Kato Akira , Romero Michael F.
Published: February 2011

Na+ and Cl− movement across the intestinal epithelium occurs by several interconnected mechanisms: (a) nutrient-coupled Na+ absorption, (b) electroneutral NaCl absorption, (c) electrogenic Cl− secretion by CFTR, and (d) electrogenic Na+ absorption by ENaC. All these transport modes require a favorable electrochemical gradient maintained by the basolateral Na+/K+-ATPase, a Cl− channel, and K+ channels. Electroneutral NaCl absorption is observed from the small intestine to the distal colon. This transport is mediated by apical Na+/H+ (NHE2/3) and Cl−/HCO3− (Slc26a3/a6 and others) exchangers that provide the major route of NaCl absorption. Electroneutral NaCl absorption and Cl− secretion by CFTR are oppositely regulated by the autonomic nerve system, the immune system, and the endocrine system via PKAα, PKCα, cGKII, and/or SGK1. This integrated regulation requires the formation of macromolecular complexes, which are mediated by the NHERF family of scaffold proteins and involve internalization of NHE3. Through use of knockout mice and human mutations, a more detailed understanding of the integrated as well as subtle regulation of electroneutral NaCl absorption by the mammalian intestine has emerged.
Terminal Differentiation in Epithelia: The Role of Integrins in Hensin Polymerization
Authors: Al-Awqati Qais
Published: February 2011

Epithelia, the most abundant cell type, differentiate to protoepithelia from stem cells by developing apical and basolateral membrane domains and form sheets of cells connected by junctions. Following this differentiation step, the cells undergo a second step (terminal differentiation), during which they acquire a mature phenotype, which unlike the protoepithelial one is tissue and organ specific. An extracellular matrix (ECM) protein termed hensin (DMBT1) mediates this differentiation step in the kidney intercalated cells. Although hensin is secreted as a soluble monomer, it requires polymerization and deposition in the ECM to become active. The polymerization step is mediated by the activation of inside-out signaling by integrins and by the secretion of two proteins: cypA (a cis-trans prolyl isomerase) and galectin 3.
Venous Valvular Stasis–Associated Hypoxia and Thrombosis: What Is the Link?
Authors: Bovill Edwin G. , van der Vliet Albert
Published: February 2011

This review focuses on the role of the venous valves in the genesis of thrombus formation in venous thromboembolic disease (VTE). Clinical VTE and the evidence for the valvular origin of venous thrombosis are reviewed. Virchow's triad is then used as a framework for discussion to approach the question posed regarding the link between venous valvular stasis–associated hypoxia and thrombosis. Thus, the effects of blood flow stasis, hypercoagulability of blood, and the characteristics of the vessel wall within the venous valvular sinus are assessed in turn.
Zebrafish in Endocrine Systems: Recent Advances and Implications for Human Disease
Authors: Löhr Heiko , Hammerschmidt Matthias
Published: February 2011

Since its introduction as a genetic vertebrate model system approximately 30 years ago, the focus of zebrafish research has increasingly shifted to questions that are also relevant for human development and disease. Here, we review the potential of the zebrafish as a model for human endocrine systems. A recent review compared the functions of the different endocrine systems and glands in zebrafish with those in other vertebrates, including humans, coming to the conclusion that major aspects are conserved. Here, we present an updated overview of this rapidly growing field of zebrafish research, focusing on the hypothalamo-pituitary axis, which links the central nervous system with the endocrine systems, and on major processes that are under (neuro)endocrine control and are the subject of intensive current research in other endocrine model organisms, such as feeding circuits and energy homeostasis, sleep, stress, reproduction, osmoregulation, and calcium homeostasis. Finally, we summarize the strengths and weaknesses of zebrafish as a model for studying endocrine systems.
Role of Tissue Factor in Venous Thrombosis
Authors: Manly David A. , Boles Jeremiah , Mackman Nigel
Published: February 2011

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality worldwide. However, the mechanisms by which clots are formed in the deep veins have not been determined. Tissue factor (TF) is the primary initiator of the coagulation cascade and is essential for hemostasis. Under pathological conditions, TF is released into the circulation on small-membrane vesicles termed microparticles (MPs). Recent studies suggest that elevated levels of MP TF may trigger thrombosis. This review provides an overview of the role of TF in VTE.
Mesenchymal Cells of the Intestinal Lamina Propria
Authors: Powell D.W. , Pinchuk I.V. , Saada J.I. , Chen Xin , Mifflin R.C.
Published: February 2011

The mesenchymal elements of the intestinal lamina propria reviewed here are the myofibroblasts, fibroblasts, mural cells (pericytes) of the vasculature, bone marrow–derived stromal stem cells, smooth muscle of the muscularis mucosae, and smooth muscle surrounding the lymphatic lacteals. These cells share similar marker molecules, origins, and coordinated biological functions previously ascribed solely to subepithelial myofibroblasts. We review the functional anatomy of intestinal mesenchymal cells and describe what is known about their origin in the embryo and their replacement in adults. As part of their putative role in intestinal mucosal morphogenesis, we consider the intestinal stem cell niche. Lastly, we review emerging information about myofibroblasts as nonprofessional immune cells that may be important as an alarm system for the gut and as a participant in peripheral immune tolerance.
Protein hydrolysate-induced cholecystokinin secretion from enteroendocrine cells is indirectly mediated by the intestinal oligopeptide transporter PepT1
Authors: Liou Alice P. , Chavez Diana I. , Espero Elvis , Hao Shuzhen , Wank Stephen A. , Raybould Helen E.
Published: February 2011

Dietary protein is a major stimulant for cholecystokinin (CCK) secretion by the intestinal I cell, however, the mechanism by which protein is detected is unknown. Indirect functional evidence suggests that PepT1 may play a role in CCK-mediated changes in gastric motor function. However, it is unclear whether this oligopeptide transporter directly or indirectly activates the I cell. Using both the CCK-expressing enteroendocrine STC-1 cell and acutely isolated native I cells from CCK-enhanced green fluorescent protein (eGFP) mice, we aimed to determine whether PepT1 directly activates the enteroendocrine cell to elicit CCK secretion in response to oligopeptides. Both STC-1 cells and isolated CCK-eGFP cells expressed PepT1 transcripts. STC-1 cells were activated, as measured by ERK1/2phosphorylation, by both peptone and the PepT1 substrate Cefaclor; however, the PepT1 inhibitor 4-aminomethyl benzoic acid (AMBA) had no effect on STC-1 cell activity. The PepT1-transportable substrate glycyl-sarcosine dose-dependently decreased gastric motility in anesthetized rats but had no affect on activation of STC-1 cells or on CCK secretion by CCK-eGFP cells. CCK secretion was significantly increased in response to peptone but not to Cefaclor, cephalexin, or Phe-Ala in CCK-eGFP cells. Taken together, the data suggest that PepT1 does not directly mediate CCK secretion in response to PepT1 specific substrates. PepT1, instead, may have an indirect role in protein sensing in the intestine.
Preemptive conditioning of the swine heart by H11 kinase/Hsp22 provides cardiac protection through inducible nitric oxide synthase
Authors: Chen Li , Lizano Paulo , Zhao Xin , Sui Xiangzhen , Dhar Sunil K. , Shen You-Tang , Vatner Dorothy E. , Vatner Stephen F. , Depre Christophe
Published: February 2011

The second window of ischemic preconditioning (SWOP) provides maximal protection against ischemia through regulation of the inducible nitric oxide synthase (iNOS), yet its application is limited by the inconvenience of the preliminary ischemic stimulus required for prophylaxis. Overexpression of H11 kinase/Hsp22 (Hsp22) in a transgenic mouse model provides cardioprotection against ischemia that is equivalent to that conferred by SWOP. We hypothesized that short-term, prophylactic overexpression of Hsp22 would offer an alternative to SWOP in reducing ischemic damage through a nitric oxide (NO)-dependent mechanism. Adeno-mediated overexpression of Hsp22 was achieved in the area at risk of the left circumflex (Cx) coronary artery in chronically instrumented swine and compared with LacZ controls ( n = 5/group). Hsp22-injected myocardium showed an average fourfold increase in Hsp22 protein expression compared with controls and a doubling in iNOS expression (both P < 0.05). Four days after ischemia-reperfusion, regional wall thickening was reduced by 58 ± 2% in the Hsp22 group vs. 82 ± 7% in the LacZ group, and Hsp22 reduced infarct size by 40% (both P < 0.05 vs. LacZ). Treatment with the NOS inhibitor NG-nitro-l-arginine (l-NNA) before ischemia suppressed the protection induced by Hsp22. In isolated cardiomyocytes, Hsp22 increased iNOS expression through the transcription factors NF-κB and STAT, the same effectors activated by SWOP, and reduced by 60% H2O2-mediated apoptosis, which was also abolished by NOS inhibitors. Therefore, short-term, prophylactic conditioning by Hsp22 provides NO-dependent cardioprotection that reproduces the signaling of SWOP, placing Hsp22 as a potential alternative for preemptive treatment of myocardial ischemia.
Exercise protects against doxorubicin-induced oxidative stress and proteolysis in skeletal muscle
Authors: Smuder Ashley J. , Kavazis Andreas N. , Min Kisuk , Powers Scott K.
Published: February 2011

Doxorubicin (Dox) is a potent antitumor agent used in cancer treatment. Unfortunately, Dox is myotoxic and results in significant reductions in skeletal muscle mass and function. Complete knowledge of the mechanism(s) by which Dox induces toxicity in skeletal muscle is incomplete, but it is established that Dox-induced toxicity is associated with increased generation of reactive oxygen species and oxidative damage within muscle fibers. Since muscular exercise promotes the expression of numerous cytoprotective proteins (e.g., antioxidant enzymes, heat shock protein 72), we hypothesized that muscular exercise will attenuate Dox-induced damage in exercise-trained muscle fibers. To test this postulate, Sprague-Dawley rats were randomly assigned to the following groups: sedentary, exercise, sedentary with Dox, or exercise with Dox. Our results show increased oxidative stress and activation of cellular proteases (calpain and caspase-3) in skeletal muscle of animals treated with Dox. Importantly, our findings reveal that exercise can prevent the Dox-induced oxidative damage and protease activation in the trained muscle. This exercise-induced protection against Dox-induced toxicity may be due, at least in part, to an exercise-induced increase in muscle levels of antioxidant enzymes and heat shock protein 72. Together, these novel results demonstrate that muscular exercise is a useful countermeasure that can protect skeletal muscle against Dox treatment-induced oxidative stress and protease activation in skeletal muscles.
Application of carbon monoxide diffusing capacity in the mouse lung
Authors: Fallica Jon , Das Sandhya , Horton Maureen , Mitzner Wayne
Published: February 2011

In the past decade the mouse has become the primary animal model of a variety of lung diseases. To assess various mechanisms underlying such pathologies, it is essential to make functional measurements that can reflect the developing pathology. In this regard, the diffusing capacity for carbon monoxide is a variable that directly reflects structural changes in the lung. Although measurement of single-breath diffusing capacity of the lung for carbon monoxide (DlCO) has also been previously reported in mice by a number of investigators, a number of technical issues have precluded routine and widespread use of this metric in mouse models. In the present report, we describe a means to quickly and simply measure a dimensionless variable closely related to the DlCO in mice, termed a diffusion factor for carbon monoxide (DFCO). The DFCO procedure involves a 9-s lung inflation with tracer gases in an anesthetized mouse, followed by a 1-min gas analysis time. We have tested the approach with two common models of lung pathology, elastase-induced emphysema and bleomycin-induced fibrosis. Results show a significant 15% reduction in DFCO in emphysema, and a 41% reduction in the fibrosis model. Repeat measurements within a mouse were found to be highly reproducible. This pulmonary function test can thus be used to detect structural changes with these pathological models. The method can also be used to measure changes in pulmonary blood volume, since the uptake of CO is highly dependent on this variable in addition to the gas exchange surface area.
The Androgen Receptor Induces Integrin α6β1 to Promote Prostate Tumor Cell Survival via NF-κB and Bcl-xL Independently of PI3K Signaling
Authors: Lamb Laura E. , Zarif Jelani C. , Miranti Cindy K.
Published: February 2011

Recent studies indicate that androgen receptor (AR) signaling is critical for prostate cancer cell survival, even in castration-resistant disease wherein AR continues to function independently of exogenous androgens. Integrin-mediated adhesion to the extracellular matrix is also important for prostate cell survival. AR-positive prostate cancer cells express primarily integrin α6β1 and adhere to a laminin-rich matrix. In this study, we show that active nuclear-localized AR protects prostate cancer cells from death induced by phosphoinositide 3-kinase (PI3K) inhibition when cells adhere to laminin. Resistance to PI3K inhibition is mediated directly by an AR-dependent increase in integrin α6β1 mRNA transcription and protein expression. Subsequent signaling by integrin α6β1 in AR-expressing cells increased NF-κB activation and Bcl-xL expression. Blocking AR, integrin α6, NF-κB, or Bcl-xL concurrent with inhibition of PI3K was sufficient and necessary to trigger death of laminin-adherent AR-expressing cells. Taken together, these results define a novel integrin-dependent survival pathway in prostate cancer cells that is regulated by AR, independent of and parallel to the PI3K pathway. Our findings suggest that combined targeting of both the AR/α6β1 and PI3K pathways may effectively trigger prostate cancer cell death, enhancing the potential therapeutic value of PI3K inhibitors being evaluated in this setting. Cancer Res; 71(7); 2739–49. ©2011 AACR.
STAT3 Expression, Molecular Features, Inflammation Patterns, and Prognosis in a Database of 724 Colorectal Cancers
Authors: Morikawa Teppei , Baba Yoshifumi , Yamauchi Mai , Kuchiba Aya , Nosho Katsuhiko , Shima Kaori , Tanaka Noriko , Huttenhower Curtis , Frank David A. , Fuchs Charles S. , Ogino Shuji
Published: February 2011

Purpose: STAT3 is a transcription factor that is constitutively activated in some cancers. It seems to play crucial roles in cell proliferation and survival, angiogenesis, tumor-promoting inflammation, and suppression of antitumor host immune response in the tumor microenvironment. Although the STAT3 signaling pathway is a potential drug target, clinical, pathologic, molecular, or prognostic features of STAT3-activated colorectal cancer remain uncertain.

Experimental Design: Utilizing a database of 724 colon and rectal cancer cases, we evaluated phosphorylated STAT3 (p-STAT3) expression by immunohistochemistry. The Cox proportional hazards model was used to compute mortality HR, adjusting for clinical, pathologic, and molecular features, including microsatellite instability (MSI), the CpG island methylator phenotype (CIMP), LINE-1 methylation, 18q LOH, TP53 (p53), CTNNB1 (β-catenin), JC virus T-antigen, and KRAS, BRAF, and PIK3CA mutations.

Results: Among the 724 tumors, 131 (18%) showed high-level p-STAT3 expression (p-STAT3-high), 244 (34%) showed low-level expression (p-STAT3-low), and the remaining 349 (48%) were negative for p-STAT3. p-STAT3 overexpression was associated with significantly higher colorectal cancer–specific mortality [log-rank P = 0.0020; univariate HR (p-STAT3-high vs. p-STAT3-negative): 1.85, 95% CI: 1.30–2.63, Ptrend = 0.0005; multivariate HR: 1.61, 95% CI: 1.11–2.34, Ptrend = 0.015]. p-STAT3 expression was positively associated with peritumoral lymphocytic reaction (multivariate OR: 3.23; 95% CI: 1.89–5.53, P < 0.0001). p-STAT3 expression was not associated with MSI, CIMP, or LINE-1 hypomethylation.

Conclusions: STAT3 activation in colorectal cancer is associated with adverse clinical outcome, supporting its potential roles as a prognostic biomarker and a chemoprevention and/or therapeutic target. Clin Cancer Res; 17(6); 1452–62. ©2011 AACR.
Expanding the Acculturation Gap-Distress Model: An Integrative Review of Research
Authors: Telzer Eva H.
Published: February 2011

The acculturation gap-distress model purports that immigrant children acculturate to their new culture at a quicker pace than their parents, leading to family conflict and youth maladjustment. This article reviews literature on the acculturation gap-distress model, showing that acculturation gaps function in unique ways depending on many social and contextual variables. In contrast to the original model, which only discusses 1 type of acculturation gap, there are at least 4 types of acculturation gaps: (1) the child is more acculturated than the parent in the host culture, (2) the child is less acculturated than the parent in the host culture, (3) the child is more acculturated than the parent in the native culture, and (4) the child is less acculturated than the parent in the native culture. A review of research indicates that each of these types of gaps function in unique ways.