bluuebunny/crossref_metadata_2025 huggingface dataset:
The management of patients with hip fractures who are taking Clopidogrel
Authors: Sim Welkee , Gonski Peter N
Published: September 2009

Aim:  To assess the outcomes of patients with acute proximal hip fractures who were taking Clopidogrel.

Method:  A retrospective study of 135 patients with proximal hip fractures. Demographic data and clinical outcomes were collected via review of hospital medical records.

Results:  21 patients taking Clopidogrel on admission were compared with 114 patients not on Clopidogrel. The groups were similar in their baseline characteristics. Postoperative haemoglobin and wound haematoma, hospital length of stay and death rate were similar in both groups even when the patients on Clopidogrel were operated on within 2 days of fracture. Days to surgery were longer in the Clopidogrel group than the control group (3.5 vs 0.9).

Conclusions:  This study demonstrated that patients on Clopidogrel do not have a worse outcome than those who were not taking the medication. We feel that it is safe to perform surgery as soon as possible.
Mechanisms of obesity and related pathologies: Role of apolipoprotein E in the development of obesity
Authors: Kypreos Kyriakos E. , Karagiannides Iordanes , Fotiadou Elisavet H. , Karavia Eleni A. , Brinkmeier Maria S. , Giakoumi Smaragda M. , Tsompanidi Eirini M.
Published: September 2009

Apolipoprotein E is a polymorphic glycoprotein in humans with a molecular mass of 34.5 kDa. It is a component of chylomicron remnants, very low density lipoprotein, low density lipoprotein and high density lipoprotein, and is primarily responsible for maintaining plasma lipid homeostasis. In addition to these well‐documented functions, recent studies in experimental mouse models, as well as population studies, show that apolipoprotein E also plays an important role in the development of obesity and insulin resistance. It is widely accepted that disruption in homeostasis between food intake and energy expenditure, and the subsequent deposition of excess fatty acids into fat cells in the form of triglycerides, leads to the development of obesity. Despite the pivotal role of obesity and dyslipidemia in the development of the metabolic syndrome and heart disease, the functional interactions between adipose tissue and components of the lipoprotein transport system have not yet been investigated thoroughly. In this minireview, we focus on the current literature pertinent to the involvement of apolipoprotein E in the development of pathologies associated with the metabolic syndrome.
Mechanisms of obesity and related pathologies: Androgen deficiency and endothelial dysfunction may be the link between obesity and erectile dysfunction
Authors: Traish Abdulmaged M. , Feeley Robert J. , Guay Andre
Published: September 2009

Obesity is associated with a high prevalence of erectile dysfunction; however, the pathophysiological link between obesity and erectile dysfunction remains poorly understood. In this minireview, we have attempted to evaluate the existing literature pertaining to obesity and erectile dysfunction to determine whether a common pathophysiological link exists. Visceral obesity is associated with increased inflammatory responses, which contribute to endothelial dysfunction. Furthermore, obesity is also associated with reduced plasma testosterone levels, which contributes to hypogonadism and increases the risk of vascular pathology. Endothelial dysfunction and androgen deficiency have previously been linked to the pathophysiological mechanisms of erectile dysfunction. The underlying pathophysiological mechanisms of endothelial dysfunction and testosterone deficiency include penile vascular insufficiency as a result of the loss of nitric oxide synthase expression and activity and the loss of tissue compliance, resulting in reduced hemodynamic properties. Recent progress in the field of sexual medicine has recognized the impact of vascular disease and hypogonadism on the management of patients with erectile dysfunction. We suggest that visceral obesity, a component of the metabolic syndrome, adversely affects endothelial function and testosterone levels, contributing to hypogandism and erectile dysfunction. Thus, clinical screening for the risk of erectile dysfunction in obese patients should include the assessment of waist circumference, testosterone levels, body mass index and physical inactivity.
The Pseudomonas aeruginosa nirE gene encodes the S‐adenosyl‐L‐methionine‐dependent uroporphyrinogen III methyltransferase required for heme d1 biosynthesis
Authors: Storbeck Sonja , Walther Johannes , Müller Judith , Parmar Vina , Schiebel Hans Martin , Kemken Dorit , Dülcks Thomas , Warren Martin J. , Layer Gunhild
Published: September 2009

Biosynthesis of heme d1, the essential prosthetic group of the dissimilatory nitrite reductase cytochrome cd1, requires the methylation of the tetrapyrrole precursor uroporphyrinogen III at positions C‐2 and C‐7. We produced Pseudomonas aeruginosa NirE, a putative S‐adenosyl‐l‐methionine (SAM)‐dependent uroporphyrinogen III methyltransferase, as a recombinant protein in Escherichia coli and purified it to apparent homogeneity by metal chelate and gel filtration chromatography. Analytical gel filtration of purified NirE indicated that the recombinant protein is a homodimer. NirE was shown to be a SAM‐dependent uroporphyrinogen III methyltransferase that catalyzes the conversion of uroporphyrinogen III into precorrin‐2 in vivo and in vitro. A specific activity of 316.8 nmol of precorrin‐2 h−1·mg−1 of NirE was found for the conversion of uroporphyrinogen III to precorrin‐2. At high enzyme concentrations NirE catalyzed an overmethylation of uroporphyrinogen III, resulting in the formation of trimethylpyrrocorphin. Substrate inhibition was observed at uroporphyrinogen III concentrations above 17 μm. The protein did bind SAM, although not with the same avidity as reported for other SAM‐dependent uroporphyrinogen III methyltransferases involved in siroheme and cobalamin biosynthesis. A P. aeruginosa nirE transposon mutant was not complemented by native cobA encoding the SAM‐dependent uroporphyrinogen III methyltransferase involved in cobalamin formation. However, bacterial growth of the nirE mutant was observed when cobA was constitutively expressed by a complementing plasmid, underscoring the special requirement of NirE for heme d1 biosynthesis.
The thioflavin T fluorescence assay for amyloid fibril detection can be biased by the presence of exogenous compounds
Authors: Hudson Sean A. , Ecroyd Heath , Kee Tak W. , Carver John A.
Published: September 2009

Thioflavin T (ThT) dye fluorescence is used regularly to quantify the formation and inhibition of amyloid fibrils in the presence of anti‐amyloidogenic compounds such as polyphenols. However, in this study, it was shown, using three polyphenolics (curcumin, quercetin and resveratrol), that ThT fluorescence should be used with caution in the presence of such exogenous compounds. The strong absorptive and fluorescent properties of quercetin and curcumin were found to significantly bias the ThT fluorescence readings in both in situ real‐time ThT assays and single time‐point dilution ThT‐type assays. The presence of curcumin at concentrations as low as 0.01 and 1 μm was sufficient to interfere with the ThT fluorescence associated with fibrillar amyloid‐β(1‐42) (0.5 μm) and fibrillar reduced and carboxymethylated κ‐casein (50 μm), respectively. The ThT fluorescence associated with fibrillar amyloid‐β(1‐42) was also biased using higher concentrations of resveratrol, a polyphenol that is not spectroscopically active at the wavelengths of ThT fluorescence, implying that there can be direct interactions between ThT and the exogenous compound and/or competitive binding with ThT for the fibrils. Thus, in all cases where ThT is used in the presence of an exogenous compound, biases for amyloid‐associated ThT fluorescence should be tested, regardless of whether the additive is spectroscopically active. Simple methods to conduct these tests were described. The Congo red spectral shift assay is demonstrated as a more viable spectrophotometric alternative to ThT, but allied methods, such as transmission electron microscopy, should also be used to assess fibril formation independently of dye‐based assays.

Structured digital abstract

MINT‐7259867: RCMκ‐CN (uniprotkb:P02668) and RCMκ‐CN (uniprotkb:P02668) bind (MI:0407) by electron microscopy (MI:0040)

MINT‐7258930: RCMκ‐CN (uniprotkb:P02668) and RCMκ‐CN (uniprotkb:P02668) bind (MI:0407) by fluorescence technologies (MI:0051)

MINT‐7259878: Amyloid beta (uniprotkb:P05067) and Amyloid beta (uniprotkb:P05067) bind (MI:0407) by fluorescence technologies (MI:0051)
Disulfide bridge regulates ligand‐binding site selectivity in liver bile acid‐binding proteins
Authors: Cogliati Clelia , Tomaselli Simona , Assfalg Michael , Pedò Massimo , Ferranti Pasquale , Zetta Lucia , Molinari Henriette , Ragona Laura
Published: September 2009

Bile acid‐binding proteins (BABPs) are cytosolic lipid chaperones that play central roles in driving bile flow, as well as in the adaptation to various pathological conditions, contributing to the maintenance of bile acid homeostasis and functional distribution within the cell. Understanding the mode of binding of bile acids with their cytoplasmic transporters is a key issue in providing a model for the mechanism of their transfer from the cytoplasm to the nucleus, for delivery to nuclear receptors. A number of factors have been shown to modulate bile salt selectivity, stoichiometry, and affinity of binding to BABPs, e.g. chemistry of the ligand, protein plasticity and, possibly, the formation of disulfide bridges. Here, the effects of the presence of a naturally occurring disulfide bridge on liver BABP ligand‐binding properties and backbone dynamics have been investigated by NMR. Interestingly, the disulfide bridge does not modify the protein‐binding stoichiometry, but has a key role in modulating recognition at both sites, inducing site selectivity for glycocholic and glycochenodeoxycholic acid. Protein conformational changes following the introduction of a disulfide bridge are small and located around the inner binding site, whereas significant changes in backbone motions are observed for several residues distributed over the entire protein, both in the apo form and in the holo form. Site selectivity appears, therefore, to be dependent on protein mobility rather than being governed by steric factors. The detected properties further establish a parallelism with the behaviour of human ileal BABP, substantiating the proposal that BABPs have parallel functions in hepatocytes and enterocytes.
Ocular abnormalities in mice lacking the immunoglobulin superfamily member Cdo
Authors: Zhang Wei , Mulieri Philip J. , Gaio Ursula , Bae Gyu‐Un , Krauss Robert S. , Kang Jong‐Sun
Published: September 2009

Vertebrate eye development requires a series of complex morphogenetic and inductive events to produce a lens vesicle centered within the bilayered optic cup and a posteriorly positioned optic stalk. Multiple congenital eye defects, including microphthalmia and coloboma, result from defects in early eye morphogenesis. Cdo is a multifunctional cell surface immunoglobulin superfamily member that interacts with and mediates signaling by cadherins and netrins to regulate myogenesis. In addition, Cdo plays an essential role in early forebrain development by functioning as coreceptor for sonic hedgehog. It is reported here that Cdo is expressed in a dynamic, but dorsally restricted, fashion during early eye development, and that mice lacking Cdo display multiple eye defects. Anomalies seen in Cdo−/− mice include coloboma (failure to close the optic fissure); failure to form a proper boundary between the retinal pigmented epithelium and optic stalk; defective lens formation, including failure to separate from the surface ectoderm; and microphthalmia. Consistent with this wide array of defects, developing eyes of Cdo−/− mice show altered expression of several regulators of dorsoventral eye patterning, including Pax6, Pax2, and Tbx5. Taken together, these findings show that Cdo is required for normal eye development and is required for normal expression of patterning genes in both the ventral and dorsal domains. The multiple eye development defects seen in Cdo−/− mice suggest that mutations in human Cdo could contribute to congenital eye anomalies, such as Jacobsen syndrome, which is frequently associated with ocular defects, including coloboma and Peters’ anomaly.
Risk Factors for Individual Domains of Female Sexual Function
Authors: Jiann Bang-Ping , Su Cheng-Chen , Yu Chia-Cheng , Wu Tony T. , Huang Jong-Khing
Published: September 2009

Introduction

Female sexual function contains four major subtypes of desire, arousal, orgasm, and pain. Few studies used validated instruments to determine the dysfunction in these areas and assess their risk factors.

Aim

To assess the prevalence of and risk factors for individual components of sexual difficulty in women.

Methods

A self-administered questionnaire containing the Female Sexual Function Index (FSFI) was given to 2,159 woman employees of two hospitals to assess their sexual function and its correlates.

Main Outcome Measures

The associations between female sexual difficulty in individual domains defined by the FSFI domain scores and potential risk factors assessed by simple questions.

Results

Among the 1,580 respondents, 930 women’s data were eligible for analysis with a mean age of 36.1 years (range 20–67). Of them, 43.8% had sexual difficulty in one or more domains, including low desire in 31.3%; low arousal, 18.2%; low lubrication, 4.8%; low orgasmic function, 10.4%; low satisfaction, 7.3%; and sexual pain, 10.5%. Compared with the younger women (20–49 years), the oldest age group (50–67 years) had a significantly higher prevalence in low desire, low arousal, and low lubrication, but not in the other domains. Based on multivariate logistic regression analyses, poor relationship with the partner and perception of partner’s sexual dysfunction were major risk factors for low desire, low arousal, low orgasmic function, and low satisfaction. Age and urge urinary incontinence were associated with low lubrication and sexual pain. Most comorbidities were not related to these difficulties, except diabetes being related to low desire.

Conclusions

Relationship factors had substantial impact on female sexual function in desire, arousal, orgasm, and satisfaction. On the other hand, women’s lubrication problem and sexual pain were related predominantly with biological factors. These are initial results and future research is needed to confirm them.
Female Youth Who Sexually Coerce: Prevalence, Risk, and Protective Factors in Two National High School Surveys
Authors: Kjellgren Cecilia , Priebe Gisela , Svedin Carl Göran , Mossige Svein , Långström Niklas
Published: September 2009

Introduction

Sexual coercion is recognized as a serious societal problem. Correlates and risk factors of sexually abusive behavior in females are not well known.

Aim

Etiological theory and empirical study of female perpetrators of sexual coercion are usually based on small or highly selected samples. Specifically, population-based data are needed to elucidate risk/protective factors.

Main Outcome Measures

Main outcome measures include a self-report questionnaire containing 65 items tapping socio-demographic and health conditions, social relations, sexual victimization, conduct problems and a set of normative and deviant sexual cognitions, attitudes, and behaviors.

Methods

We used a 2003–2004 survey of sexual attitudes and experiences among high school students in Norway and Sweden to identify risk factors and correlates to sexually coercive behavior (response rate 80%); 4,363 females participated (Mean = 18.1 years).

Results

Thirty-seven women (0.8%) reported sexual coercion (ever talked someone into, used pressure, or forced somebody to have sex). Sexually coercive compared with non-coercive women were similar on socio-demographic variables, but reported less parental care and more parental overprotection, aggression, depressive symptoms, and substance misuse. Also, sexually coercive females reported more sexual lust, sex partners, penetrative sexual victimization, rape myths, use of violent porn, and friends more likely to use porn. When using the Swedish subsample to differentiate risk factors specific for sexual coercion from those for antisocial behavior in general, we found less cannabis use, but more sexual preoccupation, pro-rape attitudes, and friends using violent porn in sexually coercive compared with non-sex conduct problem females.

Conclusions

Sexually coercive behavior in high school women was associated with general risk/needs factors for antisocial behavior, but also with specific sexuality-related risk factors. This differential effect has previously been overlooked, agrees with similar findings in men, and should have substantial etiological importance.
The Management of Erectile Dysfunction with Placebo Only: Does it Work?
Authors: De Araujo Artur Carvalho , Da Silva Fernando Gomes , Salvi Fernando , Awad Monique Carvalho , Da Silva Eloísio Alexsandro , Damião Ronaldo
Published: September 2009

Introduction

Randomized clinical trials (RCT) remain the gold standard in providing scientific evidence in medical practice in spite of the significant placebo effect in the treatment of several disorders. Although the first-line therapy for erectile dysfunction (ED) is oral phosphodiesterase type-5 inhibitor (iPDE5), the placebo effect in RCT of iPDE5 for ED occurs at a rate as high as 50%.

Aims

To evaluate the role of therapeutic illusion in the oral treatment for ED.

Methods

A prospective, controlled, single-blind, parallel-group study was performed at single-center. One hundred and twenty-three patients with ED were randomly assigned into three groups and received different letters: Group 1 (G1) was informed to be receiving a substance for ED treatment; Group 2 (G2) was informed that they could be receiving an active drug or placebo; Group 3 (G3) was conscious to be using placebo. Starch capsules were dispensed to all patients. Median follow up was 12 weeks.

Main Outcome Measures

ED improvement was assessed after 8 weeks of the intervention by the erectile function domain of the International Index of Erectile Function (IIEF) and the Quality of Erection Questionnaire. ED severity was classified by the IIEF erectile function (IIEF-EF) domain score into five categories: no ED (score of 26–30), mild (22–25), mild to moderate (17–21), moderate (11–16), and severe (6–10). Improvement in IIEF-EF domain was considered as a change in category of severity.

Results

ED severity improved in all three groups (G1 = 31.7%, P = 0.039; G2 = 36.8%, P = 0.028; G3 = 36.8%, P = 0.002) and no difference was found among groups (P = 0.857). Improvement of quality of erection score was only significant in G2 (P = 0.005) and G3 (P < 0.001).

Conclusions

Written-suggested therapeutic illusion for patients with ED has no major influence in the outcomes. However, treatment of ED with oral placebo capsules demonstrates clinical effects, improving erectile function and quality of erection.
Female Sexual Arousal Disorder with and without a Distress Criterion: Prevalence and Correlates in a Representative Czech Sample
Authors: Weiss Petr , Brody Stuart
Published: September 2009

Introduction

Sexual medicine would benefit from large representative surveys examining the prevalence of genital female sexual arousal disorder (FSAD) symptoms (with and without the increasingly controversial distress criterion), as well as novel FSAD correlates and potential “protective” factors.

Aims

To examine the extent to which genital FSAD symptoms, with and without a distress criterion, are associated with both historical and current aspects of sexual behavior.

Methods

In a representative sample of the Czech population (aged 15–88), 1,000 women were asked whether they currently have impaired lubrication and vaginal swelling (and if so, if this produces marked distress or interpersonal difficulty). They provided details of vaginal orgasm (induced by penile–vaginal intercourse [PVI] without clitoral masturbation) consistency, feelings during their first PVI, estimates of their typical foreplay and PVI durations, their degree of mental focus on vaginal sensations during PVI, among other factors.

Main Outcome Measures

The current prevalence of FSAD with and without a distress criterion and their associations with current and antecedent sexual behaviors and responses.

Results

The current prevalence of FSAD was 10.3% without, plus 7.5% with a distress criterion (which tended to be associated with more impairments than without distress). History of vaginal orgasm (odds ratio = 2.78), never masturbating (odds ratio = 2.4), not having felt pain and discomfort on first PVI (odds ratio = 2.27), and not having frequent anal intercourse are protective against FSAD with distress, but not without distress. Age (especially over 50) and inadequate focusing of mental attention on vaginal sensations during PVI are associated with increased FSAD risk both with and without distress.

Conclusions

FSAD with and without distress appear to be different entities to some extent, with the distressed group showing more long-term signs of psychosexual impairment. We suggest that FSAD with and without distress be considered two different disorders.
Design and Application of a New Rat-Specific Vacuum Erectile Device for Penile Rehabilitation Research
Authors: Yuan Jiuhong , Westney O. Lenaine , Wang Run
Published: September 2009

Introduction

Radical prostatectomy has a potential negative impact on penile health. The vacuum erection device (VED) has been used to promote the recovery of penile function and to maintain penile length. However, there is skepticism in the urological community due to its elusive mechanisms in penile rehabilitation.

Aim

To design a rat-specific VED and assess its application and safety.

Methods

Based on rat penile measurement and the principle of human VED, the rat-specific VED was designed, and the application for rats was evaluated.

Main Outcome Measures

The vacuum pressure of the rat-specific VED was measured. The VED application on rat penis and its side effects were studied.

Results

The rat-specific VED is a safe and applicable device to study the mechanism of VED in penile rehabilitation.

Conclusions

The newly designed rat-specific VED is a good simulator of the human VED. The application of this device on bilateral cavernous nerve crush rat model will be used to study the mechanisms of the VED in the penile rehabilitation.
Assessment of Emotions: Anxiety, Anger, Depression, and Curiosity
Authors: Spielberger Charles D. , Reheiser Eric C.
Published: September 2009

Anxiety, anger, depression, and curiosity are major indicators of psychological distress and well‐being that require careful assessment. Measuring these psychological vital signs is of critical importance in diagnosis, and can facilitate treatment by directly linking intense emotions to the events that give rise to them. The historical background regarding theory and research on anxiety, anger, depression, and curiosity is briefly reviewed, and the nature and assessment of these emotional states and personality traits are examined. The construction and development of the State‐Trait Anxiety Inventory (STAI), the State‐Trait Anger EXpression Inventory (STAXI‐2), and the State‐Trait Personality Inventory (STPI) to assess anxiety, anger, depression, and curiosity, and the major components of these emotional states and personality traits, are described in detail. Findings demonstrating the diverse utility and efficacy of these measures are also reported, along with guidelines for their interpretation and utilisation in research and clinical practice. Research with the STAI, STAXI and STPI over the last 40 years has contributed to understanding vitally important measurement concepts that are especially applicable to the assessment of emotions. These concepts included the state–trait distinction, item intensity specificity, and the importance of items that describe the presence or absence of emotions.
If One is Looking for Meaning in Life, Does it Help to Find Meaning in Work?
Authors: Steger Michael F. , Dik Bryan J.
Published: September 2009

People experience well‐being at both global (life) and domain (e.g. careers) levels, and presumably people experience meaning on both levels as well. Two studies assessed whether finding meaning on one level “satisfies” people's search for meaning at the other level. Study 1 assessed this question by analysing survey responses from 231 undergraduate students, finding a significant interaction such that people seeking global‐level meaning in life reported greater well‐being and self‐efficacy in choosing a career if they experienced domain‐level meaning in their careers. Study 2 used both calling‐focused and traditional career workshops in an effort to experimentally induce a sense of domain‐level meaning in careers in a sample of 91 undergraduate students. There was a trend for people seeking global‐level meaning in life to report greater reductions in depressive symptoms and increased domain‐level meaning in their careers following the workshops. Together these studies suggest that people seeking global‐level meaning in life are, indeed, satisfied by experiencing meaning in their careers. We discuss these results in terms of how career and workplace interventions might be tailored according to how intently people are seeking meaning.
Are Deterrent Pictures Effective? The Impact of Warning Labels on Cognitive Dissonance in Smokers
Authors: Glock Sabine , Kneer Julia
Published: September 2009

An experiment was conducted to investigate the impact of cigarette warning labels on cognitive dissonance in smokers. Smokers' and non‐smokers' risk perceptions with regard to smoking‐related diseases were measured with ratings as well as with response latencies before and after presentation of warning labels. Results indicated an influence of warning labels on smokers' ratings, revealing cognitive dissonance reducing strategies after confrontation with warning labels. Response latencies showed an impact of confrontation with smoking‐related health risks rather than an impact of warning labels. Findings are discussed in terms of cognitive dissonance theory.
Biogeographic diversification inNolana(Solanaceae), a ubiquitous member of the Atacama and Peruvian Deserts along the western coast of South America
Authors: DILLON Michael O. , TU Tieyao , XIE Lei , QUIPUSCOA SILVESTRE Victor , WEN Jun
Published: September 2009

Abstract The present paper reconstructs the biogeographic diversification forNolanaL.f. (Solanaceae), a genus of 89 endemic species largely restricted to fog‐dependent desertlomasformations of coastal Peru and Chile. Previous efforts have reconstructed a phylogenetic estimate forNolanausing a combination of molecular markers. Herein, we expand on those results to examine hypotheses of biogeographic origins and diversification patterns.Nolanaoccupies habitats within a continuous coastal desert and forms a terrestrial archipelago of discrete “islands” unique in size, topography, and species composition. Each locality contains at least oneNolanaspecies and many contain multiple species in sympatry. The genus has a Chilean origin, with the basal clades confined to Chile with wide geographic and ecological distributions. Peru contains two strongly supported clades, suggesting two introductions with subsequent radiation. A Chilean clade of shrubby, small‐flowered species appears to have had its origins from the same ancestors of the second line that radiated in Peru and northern Chile.Nolana galapagensisis endemic to the Islas Galápagos, with origins traced to Peruvian taxa with a divergence time of 0.35 mya. Rates of diversification over the past 4.02 mya inNolana, in one of the driest habitats on Earth, suggest rapid adaptive radiation in several clades. Success inNolanamay be attributed to characters that confer a competitive advantage in unpredictable and water‐dependent environments, such as succulent leaf anatomy and ecophysiology, and the reproductive mericarp unique toNolana. The processes affecting or shaping the biota of western South America are discussed.
Serum α‐1‐acid glycoprotein concentration in clinically healthy puppies and adult dogs and in dogs with various diseases
Authors: Yuki Masashi , Itoh Hiroshi , Takase Katsuaki
Published: September 2009

Background:α‐1‐acid glycoprotein (AGP) is an acute‐phase protein and a serum marker of inflammation and neoplasia in humans. AGP concentrations in diseased dogs and the potential effects of age, breed, and sex have not been elucidated.

Objective:The purpose of this study was to examine differences in AGP concentration based on age, sex, and breed in a large population of clinically healthy dogs and to compare AGP concentrations in dogs with various diseases.

Methods:Serum was obtained from clinically healthy puppies (n=74) and adults (n=172) of both sexes, and included mongrels (n=205) and Beagles (n=41). Serum also was obtained from 192 dogs with various diseases, including 8 with pyometra that were sampled before, and 1, 2, 3, and 10 days after surgery. AGP concentration was measured by single radial immunodiffusion. Statistical comparisons were made among age, sex, breed, and disease groups.

Results:Serum AGP in healthy adult mongrels was 364±106 mg/L (reference interval, 152–576 mg/L). AGP was lowest in newborns (n=11, 122±54 mg/L) and gradually increased to adult levels by 3 months of age. Median AGP concentration was highest in dogs with parvovirus (n=17, 2100 mg/L), distemper (n=7, 1250 mg/L), and pyometra (n=18, 2480 mg/L) and was also significantly higher in dogs with acute filariasis, renal failure, urolithiasis, pancreatitis, hepatitis, trauma, hyperadrenocorticism, and immune‐mediated hemolytic anemia. Dogs with acute filariasis and acute hepatopathy had significantly higher AGP concentrations than dogs with chronic filariasis and chronic hepatopathy. Serum AGP concentration decreased gradually following surgery for pyometra but remained increased after 10 days (896±175 mg/L).

Conclusions:Because of significantly lower AGP in puppies, the age of dogs should be considered when using AGP as a marker of disease. Serum AGP may be a useful marker of inflammatory disease in dogs and may help differentiate acute and chronic stages of disease.
Activation of M2 muscarinic receptors leads to sustained suppression of hippocampal transmission in the medial prefrontal cortex
Authors: Wang Lang , Yuan Li‐Lian
Published: September 2009

Cholinergic innervation of the prefrontal cortex is critically involved in arousal, learning and memory. Dysfunction of muscarinic acetylcholine receptors and their downstream signalling pathways has been identified in mental retardation. To assess the role played by the muscarinic receptors at the hippocampal–frontal cortex synapses, an important relay in information storage, we used a newly developed frontal slice preparation in which hippocampal afferent fibres are preserved. Transient activation of muscarinic receptors by carbachol results in a long‐lasting depression of synaptic efficacy at the hippocampal but not cortical pathways or local circuitry. On the basis of a combination of electrophysiological, pharmacological and anatomical results, this input‐specific muscarinic modulation can be partially attributed to the M2 subtype of muscarinic receptors, possibly through a combination of pre‐ and postsynaptic mechanisms.
Loose coupling between calcium channels and sites of exocytosis in chromaffin cells
Authors: Wu Minnie M. , Llobet Artur , Lagnado Leon
Published: September 2009

Calcium microdomains generated by tight clusters of calcium channels regulate fusion of small vesicles at the synaptic terminal and have also been suggested to trigger exocytosis of large dense‐core vesicles from neuroendocrine cells. To test this idea, we have compared sites of exocytosis and the spatial distribution of calcium channels in chromaffin cells. Fusion of individual vesicles was visualized using interference reflection microscopy and the submembranous calcium signal was assessed using total internal reflection fluorescence microscopy. Depolarization triggered a burst of exocytosis from up to seven sites in a membrane area of 11 μm2, but these sites did not colocalize with calcium microdomains. Instead, calcium influx occurred in large patches (averaging 34 μm2) containing a mixture of P/Q‐ and N‐type channels. About 20% of fusion events occurred outside calcium channel patches. Further, the delay between the onset of stimulation and a burst of exocytosis was prolonged for several seconds by increasing the concentration of the slow calcium chelator EGTA from 1.5 to 5 mm. These results demonstrate that while calcium channels and release sites tend to congregate in specialized regions of the surface membrane, these have dimensions of several micrometres. The dominant calcium signal regulating release in chromaffin cells is generated by the cooperative action of many channels operating over distances of many micrometres rather than discrete clusters of calcium channels generating localized microdomains.
Agonist and blocking actions of choline and tetramethylammonium on human muscle acetylcholine receptors
Authors: Lape Remigijus , Krashia Paraskevi , Colquhoun David , Sivilotti Lucia G.
Published: September 2009

Choline has been used widely as an agonist for the investigation of gain‐of‐function mutants of the nicotinic acetylcholine receptor. It is useful because it behaves like a partial agonist. The efficacy of choline is difficult to measure because choline blocks the channel at concentrations about four times lower than those that activate it. We have fitted activation mechanisms to single‐channel activity elicited from HEK‐expressed human recombinant muscle nicotinic receptors by choline and by tetramethylammonium (TMA). Channel block by the agonist was incorporated into the mechanisms that were fitted, and block was found not to be selective for the open state. The results also suggest that channel block is very fast and that the channel can shut almost as fast as normal when the blocker was bound. Single‐channel data are compatible with a mechanism in which choline is actually a full agonist, its maximum response being limited only by channel block. However, they are also compatible with a mechanism incorporating a pre‐opening conformation change (‘flip’) in which choline is a genuine partial agonist. The latter explanation is favoured by concentration jump experiments, and by the fact that only this mechanism fits the TMA data. We propose that choline, like TMA, is a partial agonist because it is very ineffective (approximately 600‐fold less than acetylcholine) at eliciting the initial, pre‐opening conformation change. Once flipping has occurred, all agonists, even choline, open the channel with similar efficiency.
Activation of the retrotrapezoid nucleus by posterior hypothalamic stimulation
Authors: Fortuna Michal G. , Stornetta Ruth L. , West Gavin H. , Guyenet Patrice G.
Published: September 2009

The retrotrapezoid nucleus (RTN) contains chemically defined neurons (ccRTN neurons) that provide a pH‐regulated excitatory drive to the central respiratory pattern generator. Here we test whether ccRTN neurons respond to stimulation of the perifornical hypothalamus (PeF), a region that regulates breathing during sleep, stress and exercise. PeF stimulation with gabazine increased blood pressure, phrenic nerve discharge (PND) and the firing rate of ccRTN neurons in isoflurane‐anaesthetized rats. Gabazine produced an approximately parallel upward shift of the steady‐state relationship between ccRTN neuron firing rate and end‐tidal CO2, and a similar shift of the relationship between PND and end‐tidal CO2. The central respiratory modulation of ccRTN neurons persisted after gabazine without a change in pattern. Morphine administration typically abolished PND and reduced the discharge rate of most ccRTN neurons (by 25% on average). After morphine administration, PeF stimulation activated the ccRTN neurons normally but PND activation and the central respiratory modulation of the ccRTN neurons were severely attenuated. In the same rat preparation, most (58%) ccRTN neurons expressed c‐Fos after exposure to hypercapnic hyperoxia (6–7% end‐tidal CO2; 3.5 h; no hypothalamic stimulation) and 62% expressed c‐Fos under hypocapnia (∼3% end‐tidal CO2) after PeF stimulation. Under baseline conditions (∼3% end‐tidal CO2, hyperoxia, no PeF stimulation) few (11%) ccRTN neurons expressed c‐Fos. In summary, most ccRTN neurons are excited by posterior hypothalamic stimulation while retaining their normal response to CNS acidification. ccRTN neurons probably contribute both to the chemical drive of breathing and to the feed‐forward control of breathing associated with emotions and or locomotion.
Reduction of low grade inflammation restores blunting of postprandial muscle anabolism and limits sarcopenia in old rats
Authors: Rieu Isabelle , Magne Hugues , Savary‐Auzeloux Isabelle , Averous Julien , Bos Cécile , Peyron M. A. , Combaret Lydie , Dardevet Dominique
Published: September 2009

Ageing is characterized by a decline in muscle mass that could be explained by a defect in the regulation of postprandial muscle protein metabolism. Indeed, the stimulatory effect of food intake on protein synthesis and its inhibitory effect on proteolysis is blunted in old muscles from both animals and humans. Recently, low grade inflammation has been suspected to be one of the factors responsible for the decreased sensitivity of muscle protein metabolism to food intake. This study was undertaken to examine the effect of long‐term prevention of low grade inflammation on muscle protein metabolism during ageing. Old rats (20 months of age) were separated into two groups: a control group and a group (IBU) in which low grade inflammation had been reduced with a non‐steroidal anti inflammatory drug (ibuprofen). After 5 months of treatment, inflammatory markers and cytokine levels were significantly improved in treated old rats when compared with the controls: −22.3% fibrinogen, −54.2%α2‐macroglobulin, +12.6% albumin, −59.6% IL6 and −45.9% IL1β levels. As expected, food intake had no effect on muscle protein synthesis or muscle proteolysis in controls whereas it significantly increased muscle protein synthesis by 24.8% and significantly decreased proteolysis in IBU rats. The restoration of muscle protein anabolism at the postprandial state by controlling the development of low grade inflammation in old rats significantly decreased muscle mass loss between 20 and 25 months of age. In conclusion, the observations made in this study have identified low grade inflammation as an important target for pharmacological, nutritional and lifestyle interventions that aim to limit sarcopenia and muscle weakness in the rapidly growing elderly population in Europe and North America.
Dynamic aspects of functional regulation of the ATP receptor channel P2X2
Authors: Kubo Yoshihiro , Fujiwara Yuichiro , Keceli Batu , Nakajo Koichi
Published: September 2009

The P2X2 channel is a ligand‐gated channel activated by ATP. Functional features that reflect the dynamic flexibility of the channel include time‐dependent pore dilatation following ATP application and direct inhibitory interaction with activated nicotinic acetylcholine receptors on the membrane. We have been studying the mechanisms by which P2X2 channel functionality is dynamically regulated. Using a Xenopus oocyte expression system, we observed that the pore properties, including ion selectivity and rectification, depend on the open channel density on the membrane. Pore dilatation was apparent when the open channel density was high and inward rectification was modest. We also observed that P2X2 channels show voltage dependence, despite the absence of a canonical voltage sensor. At a semi‐steady state after ATP application, P2X2 channels were activated upon membrane hyperpolarization. This voltage‐dependent activation was also [ATP] dependent. With increases in [ATP], the speed of hyperpolarization‐induced activation was increased and the conductance–voltage relationship was shifted towards depolarized potentials. Based on analyses of experimental data and various simulations, we propose that these phenomena can be explained by assuming a fast ATP binding step and a rate‐limiting voltage‐dependent gating step. Complete elucidation of these regulatory mechanisms awaits dynamic imaging of functioning P2X2 channels.
Beyond epidemiology: field studies and the physiology laboratory as the whole world
Authors: Nose Hiroshi , Morikawa Mayuko , Yamazaki Toshiaki , Nemoto Ken‐ichi , Okazaki Kazunobu , Masuki Shizue , Kamijo Yoshi‐ichiro , Gen‐no Hirokazu
Published: September 2009

There is no exercise training regimen broadly available in the field to increase physical fitness and prevent lifestyle‐related diseases in middle‐aged and older people. We have developed interval walking training (IWT) repeating five or more sets of 3 min fast walking at ≥70% peak aerobic capacity for walking (w) per day with intervening 3 min slow walking at 40% w, for ≥4 days week−1, for ≥5 months. Moreover, to determine w in individuals and also to measure their energy expenditure even while incline walking, we have developed a portable calorimeter. Further, to instruct subjects on IWT even if they live remotely from the trainers, we have developed e‐Health Promotion System. This transfers individual energy expenditure during IWT stored on the meter to a central server through the internet; it sends back the achievement to individuals along with advice generated automatically by the sever according to a database on ≥4000 subjects. Where we found that 5 months of IWT increased physical fitness and improved the indices of lifestyle‐related diseases by 10–20% on average. Since our system is run at low cost with fewer staff for more subjects, it enables us to develop exercise prescriptions appropriate for individuals.
The diseasome of physical inactivity – and the role of myokines in muscle–fat cross talk
Authors: Pedersen Bente K.
Published: September 2009

Type 2 diabetes, cardiovascular diseases, colon cancer, breast cancer, dementia and depression constitute a cluster of diseases, which defines ‘a diseasome of physical inactivity’. Both physical inactivity and abdominal adiposity, reflecting accumulation of visceral fat mass, are associated with the occurrence of the diseases within the diseasome. Physical inactivity appears to be an independent and strong risk factor for accumulation of visceral fat, which again is a source of systemic inflammation. Chronic inflammation is involved in the pathogenesis of insulin resistance, atherosclerosis, neurodegeneration and tumour growth. Evidence suggests that the protective effect of exercise may to some extent be ascribed to the anti‐inflammatory effect of regular exercise, which can be mediated via a reduction in visceral fat mass and/or by induction of an anti‐inflammatory environment with each bout of exercise. The finding that muscles produce and release myokines provides a conceptual basis to understand the mechanisms whereby exercise influences metabolism and exerts anti‐inflammatory effects. According to our theory, contracting skeletal muscles release myokines, which work in a hormone‐like fashion, exerting specific endocrine effects on visceral fat. Other myokines work locally within the muscle via paracrine mechanisms, exerting their effects on signalling pathways involved in fat oxidation.
Interactions between short‐interval intracortical inhibition and short‐latency afferent inhibition in human motor cortex
Authors: Alle Henrik , Heidegger Tonio , Kriváneková Lucia , Ziemann Ulf
Published: September 2009

Transcranial magnetic stimulation (TMS) allows the testing of various inhibitory processes in human motor cortex. Here we aimed at gaining more insight into the underlying physiology by studying the interactions between short‐interval intracortical inhibition (SICI) and short‐latency afferent inhibition (SAI). SICI and SAI were examined in a slightly contracting hand muscle of healthy subjects by measuring inhibition of a test motor‐evoked potential conditioned by a sub‐threshold motor cortical magnetic pulse (S1) or an electrical pulse (P) applied to the ulnar nerve at the wrist, respectively. SICI alone and SAI alone had similar magnitude when S1 intensity was set to 90% active motor threshold and P intensity to three times the perceptual sensory threshold. SICI was reduced or even disinhibited when P was co‐applied, and SAI was reduced or disinhibited when S1 was co‐applied. These interactions did not depend on the exact timing of arrival of P and S1 in motor cortex. A control experiment with a S1 intensity lowered to 70% active motor threshold excluded a contribution by short‐interval intracortical facilitation. Finally, SICI with co‐applied P correlated linearly with SICI alone with a slope of the regression line close to 1 whereas SAI did not correlate with SAI when S1 was co‐applied with a slope of the regression line close to zero. Data indicate that S1 largely eliminates the effects of P when applied together, suggesting dominance of S1 over P. Findings strongly support the idea that SICI and SAI are mediated through two distinct and reciprocally connected subtypes of GABAergic inhibitory interneurons with convergent projections onto the corticospinal neurons. Furthermore, dominance of S1 over P is compatible with the notion that the SICI interneurons target the corticospinal neurons closer to their axon initial segment than the SAI interneurons.
Elucidation of the gating of the GIRK channel using a spectroscopic approach
Authors: Raveh Adi , Riven Inbal , Reuveny Eitan
Published: September 2009

The traditional view of G protein‐coupled receptor (GPCR)‐mediated signalling puts the players in this signalling cascade, namely the GPCR, the G protein and its effector, as individual components in space, where the signalling specificity is obtained mainly by the interaction of the GPCR and the Gα subunits of the G protein. A question is then raised as to how fidelity in receptor signalling is achieved, given that many systems use the same components of the G protein signalling machinery. One possible mechanism for obtaining the specific flow of the downstream signals, from the activated G protein to its specific effector target, in a timely manner, is compartmentalization, a spatial arrangement of the complex in a rather restricted space. Here we review our recent findings related to these issues, using the G protein‐coupled potassium channel (GIRK) as a model effector and fluorescence‐based approaches to reveal how the signalling complex is arranged and how the G protein exerts its action to activate the GIRK channel in intact cells.
Elevated Temperature Low-Cycle Fatigue Strength of Butt Welded AISI 316 Steel Pipes
Authors: Manfredi E. , Vitale E.
Published: September 2009

This paper reviews the experimental activities that were performed in recent years at the Department of Mechanical and Nuclear Engineering (DCMN) of the University of Pisa, mainly during research programs sponsored by the Italian Committee for Nuclear Energy (ENEA), in the field of life assessment under high temperature low-cycle fatigue and creep-fatigue conditions in AISI 316 weldments. These activities comprised tests on tubular, welded model structures of AISI 316, carried out in air, under either uniaxial or biaxial loading conditions, at 550°C and 650°C. Small smooth specimen testing was also performed mainly for characterizing the stress-strain behavior of the weldments. Extensive post-test analysis was focused on correlating the experimental results with life predictions based on commonly used or recently proposed design rules. Some of the main results have already been published but a complete report has not yet been delivered to the international literature. This paper is therefore aimed at giving a fairly complete picture of both the experimental results and the life prediction work.