bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcome of treatment of vocally disruptive behaviour in nursing home residents
Authors: Draper Brian , Turner Jane , McMinn Bryan , Gonskl Peter , Mcintosh Helen , Latham Linda , Snowdon John , Draper Deborah , Luscombe Georgina , Meares Susanne
Published: December 2008

Objective: To determine the outcome of treatments for vocally disruptive behaviour (VDB) in nursing homes provided by psychogeriatric and geriatric outreach services.

Method: Nursing home residents referred to six psychogeriatric and geriatric outreach services for treatment of VDB were examined pre‐ treatment and followed‐up for three months by a research nurse. All recommended treatments for VDB and the effects of implementation were recorded. Main outcome measures were the Cornell Scale for Depression in Dementia, the Dementia Behaviour Disturbance Scale and measures of nurse satisfaction.

Results: Three‐month outcome data was available for 22 residents, of whom four had died. Of the remainder, six (33%) had objective improvement in VDB. The nursing home staff rated the outreach teams as at least ‘somewhat’ helpful in 61% of cases surviving three months and was particularly satisfied with medication advice. No specific treatment appeared to be more effective.

Conclusions: Reduction in VDB obtained through interventions by psychogeriatric and geriatric outreach teams was modest, but nursing home staff found most of the teams to be helpful. Aged care outreach services should provide support to nursing home staff in the management of challenging behaviours.
Perceptions of bereavement care in consultant geriatricians and advanced trainees in geriatric medicine
Authors: Boyatzis Irene , Blight Joanne , Vieira Barry Ian , Flicker Leon
Published: December 2008

Objectives: To examine the perceptions of practising aged care physicians with respect to bereavement care.

Method: A questionnaire survey was sent to 427 Consultant Geriatricians and Advanced Trainees in Geriatric Medicine.

Results: Ninety eight percent of respondents believed it was important to provide bereavement care for patients and their families. Fifty six percent did not feel it was their role to provide this support. For those who provided bereavement care (33%), most used a combination of hospital and community based resources. Fifty nine percent of respondents believed that they had inadequate training in bereavement care. Seventy one percent of respondents were not aware of resources available to fellow colleagues experiencing difficulties coping with the death of a patient.

Conclusions: Aged care physicians differ in their approaches to bereavement care. Aged care physicians may need further education in bereavement care.
Gambling and older people in Australia
Authors: McCormack John , Jackson Alun C. , Thomas Shane A.
Published: December 2008

Objectives: There is a dearth of studies on the gambling behaviour of older people in Australia. This study aims to address that gap in local knowledge by investigating the gambling activity of older people in the general community, as well as the situation of older gamblers who attend counselling services for people with problem gambling behaviour.

Method: The study draws on a recent national gambling survey to review older peoples' gambling in the general community, and then uses data from Victorian Gamblers' Help counselling services to review the gambling problems and treatment needs of older problem gamblers.

Results: Older people gamble at a slightly lower rate than younger groups in the general community. Older problem gamblers similarly appear to have less serious problems than younger groups although there is a small group with quite severe problems as a result of gambling. There are more older female problem gamblers in counselling than males, but older men present more serious problems. Treatment responses appear to be effective for this age group.

Conclusion: As older age is currently characterised by a low fixed income and thus greater vulnerability to the adverse consequences of gambling, research should continue to monitor the gambling impact on older people as our population ages.
Effect of age and visual contrast on gait during obstacle negotiation
Authors: Crosbie Jack , Gan Neesha
Published: December 2008

Background: Obstacle avoidance and negotiation may pose significant difficulties for older people. Of particular interest is the fluency with which they can negotiate obstacles which contrast poorly with their surroundings.

Methods: Two groups of healthy subjects, one young group of mean age 22 years and an older group of mean age 73 years, were tested while walking at a preferred and a fast walking speed under conditions of high and low contrast obstacle. Data were collected using a video‐camera to derive values for step length, duration and velocity while subjects ambulated over a 20m track and stepped on to and over a low wooden block.

Results: In essence, there was no difference between these young and old subjects in their gait strategies nor in the fluency with which they approached the obstacle. Older subjects did, however, walk slower than younger subjects at the “fast” pace. The subjects did not appear to be influenced by the contrast of the obstacle with its surroundings.

Conclusions: Healthy older subjects do not show any inherent loss of fluency or hesitation in negotiating a simple obstacle, irrespective of the contrast of the obstacle with its surroundings.
Dietary and health supplement use among older Australians: results from a national survey
Authors: Brownie Sonya , Myers Stephen
Published: December 2008

Objectives: To measure the extent of dietary and health supplement use among older Australians and to contrast older supplement users from older non‐supplement users.

Method: Survey participants (n= 1,263) provided information related to demographic, health and lifestyle features. The target population were Australians aged 65 years and over, randomly chosen from the Australian Electoral Commission. Data was obtained using a 12‐page self‐administered, mail questionnaire.

Results: Forty‐three percent (n=548) of the sample reported using at least one dietary and health supplement, 52% of females and 35% of males. Supplement use was significantly related to several demographic and lifestyle features including: gender, educational level, smoking status and number of visits to complementary health therapists.

Conclusions: Clearly, supplements were chosen more for their perceived ability to attenuate or modify ailments, rather than their role in correcting nutritional deficiencies. Older Australians appear intent on taking health matters in their own hands. Approximately one third of them rarely inform their doctor about the supplements they use, which raises concerns about the safety and appropriateness of this action.
Effects of ambient baroque music on patients with dementia
Authors: Heim Christian , Nair B. Kichu , Mowbray Denise , Tavender Janelle
Published: December 2008

Objective: To determine the effect of ambient baroque music on the behaviour of patients with dementia in a nursing home.

Method: An observational study involving 14 dementia patients in a nursing home for six weeks. We measured adverse patient behaviours such as episodes of calling out, wandering, aggression, talking to self, verbal abuse and signs of agitation, as well as need for night sedation.

Results: Adverse behaviours decreased by over 40% during the intervention period.

Conclusions: A strong positive result was obtained in this pilot study. Potential benefits of the intervention are considerable as it is non‐invasive, cost‐effective and pleasant for patients and staff alike. Larger, randomised controlled studies are warranted.
Effect of Clonidine on Tyrosine Hydroxylase Activity in the Adrenal Medulla and Brain of Spontaneously Hypertensive Rats
Authors: Moura Eduardo , Afonso Joana , Serrão Maria Paula , Vieira‐Coelho Maria Augusta
Published: December 2008

Abstract:  In the present study, we evaluated the effect of the α2‐adrenoceptor agonist clonidine on tyrosine hydroxylase activity in adrenal medulla and brain of spontaneously hypertensive rats and Wistar Kyoto rats. Six‐week‐old animals were treated with clonidine (100 µg/kg body weight, daily, i.p.) for 4 weeks. Treatment with clonidine significantly reduced mean arterial blood pressure in spontaneously hypertensive rats to values similar to normotensive Wistar Kyoto rats. In the adrenal medulla of spontaneously hypertensive rats, clonidine treatment produced a significant increase in tyrosine hydroxylase activity with higher Vmax values and no changes in KM values. This effect was accompanied by a significant increase in tyrosine hydroxylase protein expression and of noradrenaline and adrenaline levels. In the brain of spontaneously hypertensive rats, treatment with clonidine produced a significant decrease in tyrosine hydroxylase activity with lower Vmax values and no changes in KM values accompanied by a significant decrease in tyrosine hydroxylase protein expression and of dopamine and noradrenaline levels. In Wistar Kyoto rats, clonidine treatment had no effect on tyrosine hydroxylase activity and protein expression or catecholamine levels in adrenal medulla or brain. Clonidine treatment significantly reduced noradrenaline and adrenaline plasma levels in spontaneously hypertensive rats and Wistar Kyoto rats. In conclusion, treatment with the α2‐adrenoceptor agonist clonidine prevented the increase in mean arterial blood pressure in young spontaneously hypertensive rats. This effect was accompanied by opposite effects on tyrosine hydroxylase activity in spontaneously hypertensive rat adrenal medulla and brain: an increase in adrenal medulla and a decrease in brain, bringing sympathetic function to a similar profile found in normotensive Wistar Kyoto rats.
Endothelial Nitric Oxide Synthase Regulation in Female Genital Tract Structures
Authors: Musicki Biljana , Liu Tongyun , Lagoda Gwen A. , Bivalacqua Trinity J. , Strong Travis D. , Burnett Arthur L.
Published: December 2008

Introduction

Female sexual arousal disorder (FSAD) is a major component of female sexual dysfunctions, affecting 25–70% of women. The mechanisms of FSAD are poorly understood. Estrogen contributes to the control of genital blood flow during the sexual response. Vascular effects of estrogen are mostly attributed to its regulation of endothelial nitric oxide (NO) production. However, the role of endothelial NO synthase (eNOS) and the mechanisms that regulate eNOS in female genital tract structures are largely unknown.

Aim

To review available evidence of the mechanisms of eNOS regulation in female genital tract structures.

Methods

This article reviews the literature that relates to the role of NO and eNOS in female sexual arousal and its modulation by estrogen.

Main Outcome Measures

Association between female sexual arousal, NO, and eNOS.

Results

The NO/cyclic guanosine monophosphate pathway is believed to have a primary role in the regulation of clitoral and vaginal blood flow, and smooth muscle relaxation during sexual arousal. Estrogen is critical for maintaining vaginal and clitoral blood flow and vaginal transudate production. Estrogen regulates eNOS by genomic mechanisms, involving augmented mRNA transcription and protein synthesis, and by non-genomic mechanisms, which occur without alterations in gene expression. However, limited studies have evaluated the physiological role of endothelial NO and the molecular mechanisms of eNOS regulation in the female genital tract.

Conclusions

The effects of estrogen on increasing genital blood flow and smooth muscle relaxation have been attributed mostly to regulation of eNOS. However, the exact mechanisms of eNOS regulation in female genital tract structures and the molecular basis for the eNOS defect with aging and vascular diseases warrant further investigation.
Epothilones in the treatment of breast cancer: Review of clinical experience
Authors: XU Binghe
Published: December 2008

The author will be discussing the off label use of ixabepilane in the management of metastatic breast cancer in this review.

Antimicrotubule agents have emerged as a critical component of our armamentarium of chemotherapeutic drugs for breast cancer treatment. The taxanes paclitaxel and docetaxel are among the most widely used agents because of their proven efficacy in both the metastatic and adjuvant settings. Although the taxanes represented a significant advance for breast cancer treatment, the clinical utility of these drugs may be limited by the rapid emergence of drug resistance as conferred by cellular P‐glycoprotein and alterations in β‐tubulin. The search for the next generation of metastatic tumor antigens has resulted in the discovery of the epothilones, a novel class of microtubule‐stabilizing agents. Although the epothilones possess a mechanism of action that is similar to that of the taxanes, they are structurally unrelated and several members of this novel class of antimicrotubule agents, such as epothilone B and its derivatives, demonstrate greater therapeutic indices and lower susceptibility to multidrug resistance than do the taxanes in preclinical studies. At the time of writing, several epothilones are under clinical investigation for the treatment of cancer patients. Of these, ixabepilone, a semi‐synthetic analog of natural epothilone B, has demonstrated anti‐tumor activity alone or as part of a combination of therapy in patients with taxane‐ and multidrug‐resistant metastatic breast cancer. This article reviews the clinical experience to date with the epothilones with a focus on locally advanced breast cancer and metastatic disease. Clinical experience with second‐generation epothilones under clinical development will be discussed as well.
The end of progressive politics?
Authors: Oppenheim Carey , Harker Lisa
Published: December 2008

Progressive politics has reached a stumbling block on its path to social change and it is time to identify new ways forward, say Carey Oppenheim and Lisa Harker.
To the left, to the right…?
Authors: Curtice John
Published: December 2008

John Curtice argues that although the Liberal Democrats have taken a risky gamble in changing their position on tax and spend, it may not translate into gains in the next election.
Limiting conflict in the Caucasus
Authors: Rayfield Donald
Published: December 2008

Donald Rayfield argues that the situation in Georgia is not as black‐and‐white as it may have appeared in recent media coverage, and that the best option for the republic would be to recognise the independence of South Ossetia and Abkhazia.
Is gender equality legislation becoming counter‐productive?
Authors: Hakim Catherine
Published: December 2008

Catherine Hakim argues that social and family policy must now be gender‐neutral, but should cater for diversity in lifestyle preferences.
The special relationship
Authors: Lloyd John
Published: December 2008

The continued closeness of the political and media world post‐Blair is ruinous to both, argues John Lloyd. But it cannot be undone without a cultural revolution of global scale.
Don't sneer at suburbia
Authors: Huq Rupa
Published: December 2008

Politicians have ignored the suburbs to their detriment, argues Rupa Huq. Here lies the true Englishness Brown wishes to promote, but a policy agenda to support suburban regeneration is long overdue.
Plasma Carboxy‐Terminal Peptide of Procollagen Type I Is an Independent Predictor of Diastolic Function in Patients With Advanced Systolic Heart Failure
Authors: Roongsritong Chanwit , Sadhu Ashish , Pierce Mika , Raj Rishi , Simoni Jan
Published: December 2008

Severe diastolic dysfunction has important clinical implications in advanced systolic heart failure. The authors investigated whether a marker of fibrosis, serum carboxy‐terminal peptide of procollagen type I (PICP) is a major determinant of diastolic function in 40 patients with heart failure and ejection fraction <35%. Patients with unstable heart failure or ischemic symptoms were excluded. The authors found PICP to be an independent predictor of diastolic function in addition to age and pulmonary artery systolic pressure. The authors’ findings suggest that studies evaluating whether therapy that improves myocardial fibrosis could have a favorable impact on diastolic function in this population are warranted.
Short‐Term Effects of Right Ventricular Pacing on Cardiorespiratory Function in Patients With a Biventricular Pacemaker
Authors: Toggweiler Stefan , Kobza Richard , Zuber Michel , Erne Paul
Published: December 2008

The intention of this study was to evaluate the short‐term effect of right ventricular (RV) pacing on cardiorespiratory function in patients with a biventricular pacemaker. A group of 26 patients with a biventricular pacemaker was enrolled in this cross‐over, single‐blind study. All patients underwent spiroergometry and electrocardiography in RV and biventricular pacing mode. Peak work capacity (102±32 W and 107±34 W for RV and biventricular pacing mode, respectively; P<.01) and peak oxygen consumption (21.4±6.7 mL/min/kg and 22.6±7.0 mL/min/kg for RV and biventricular pacing mode, respectively; P<.01) were significantly lower in the RV pacing mode. Heart rate at rest was significantly higher with active RV pacing. Short‐term RV pacing in patients with a biventricular pacemaker resulted in a higher heart rate at rest, a lower peak work capacity, and a lower peak oxygen consumption compared with that in the biventricular pacing mode.
Barriers to Antihypertensive Medication Adherence Among Adults— United States, 2005
Authors: Vawter Lemuel , Tong Xin , Gemilyan Manik , Yoon Paula W.
Published: December 2008

Antihypertensive agents are one of the most commonly prescribed classes of medications in the country, but patient adherence rates are low. To better understand why rates are low, the authors used data from the 2005 HealthStyles survey and found that among the 1432 respondents who received prescriptions for antihypertensive medications, 407 (28.4%) reported having difficulty taking their medication. ``Not remembering'' was the most common reason reported (32.4%), followed by cost (22.6%), having no insurance (22.4%), side effects (12.5%), other reasons (12.3%), not thinking there is any need (9.3%), and having no health care provider (4.7%). In a multivariate model, younger age, lower income, having mental function impairment, and having had a blood pressure check more than 6 months earlier were factors significantly associated with reporting difficulty taking prescribed antihypertensive drugs. Control of hypertension is a significant public health issue, and alleviating barriers to medication adherence should be a major goal toward hypertension management.
Early Antihypertensive Efficacy of Olmesartan Medoxomil
Authors: Saito Ikuo , Kushiro Toshio , Ishikawa Mayumi , Matsushita Yasuyuki , Sagawa Kei , Hiramatsu Katsutoshi , Komiya Masahiro
Published: December 2008

The authors assessed the early antihypertensive efficacy of olmesartan medoxomil (OM) in a 12‐week prospective observational study. Of 2221 patients with untreated hypertension who received OM (mainly 10 or 20 mg), 331 patients whose blood pressure (BP) was measured at 1 week after initiation of treatment were defined as the ``early BP determination group,'' whereas the remaining 1890 patients were defined as the ``standard BP determination group.'' Baseline characteristics, doses of OM, concomitant drugs used, and BP during treatment did not differ between the 2 groups. The achievement rate of BP target (<140/90 mm Hg) was 28.4% at 1 week in the early BP determination group and 28.3% at 2 weeks in the standard BP determination group (P=NS). Rates of adverse drug reactions in the 2 groups were similar. The present study suggests that OM is safe and effective in reducing BP at an early time point of treatment.
Calculations of Polarizabilities and Their Gradients for Electron Energy-Loss Spectroscopy
Authors: Paidarová Ivana , Čurík Roman , Sauer Stephan P. A.
Published: December 2008

We illustrate for a set of small hydrocarbons, CH4, C2H4, C3H6 and C3H8, the important role of the electric dipole polarizability tensor and its geometric derivatives in theoretical models of electron energy-loss spectra (EELS). The coupled cluster linear response method together with Sadlej's polarized valence triple zeta basis set of atomic orbitals were used to calculate the polarizabilities and polarizability gradients. Incorporation of these ab initio data into the discrete momentum representation method (DMR) leads to perfect agreement between theory and collision experiments.
Coupled Cluster Study of Polycyclopentanes: Structure and Properties of C5H2n, n = 0-4
Authors: Veis Libor , Čársky Petr , Pittner Jiří , Michl Josef
Published: December 2008

The title hydrocarbons have been examined by the CCSD(T)/cc-pVTZ (singlets) and UMP2/cc-pVTZ (triplets) methods. They were confirmed to represent local minima on the singlet potential energy surface, while 1,3-biradical, 1,4-biradical, or carbene structures were found on the triplet surface, including an intermediate for the triplet energy transfer from one to the other double bond of 1,4-pentadiene. Bonding is discussed in terms of Weinhold's NBO theory and the absence of a simple correlation between bond strength and bond length in these highly strained systems is pointed out. Predictions of NMR, IR, and Raman spectra are provided.
EXACT ANALYTICAL EXPRESSIONS AND NUMERICAL VALUES OF DIAGONAL MATRIX ELEMENTS nlj, ,  AND  WITH DIRAC'S RADIAL FUNCTIONS g(r) and f(r) OF H-LIKE ATOMS AND THE SYMMETRY OF APPELL'S FUNCTION F2(1, 1)
Authors: TARASOV V. F.
Published: December 2008

This article deals with the connection between a.m. the diagonal matrix elements with the P. A. M. Dirac radial functions g(r) and f(r) and the diagonal matrix elements nl with the E. R. Schrödinger radial functions Rnl(r) of H-like atoms (as Z=1, n≤8 and -7≤k≤4) and new properties of the P. E. Appell function F2(x,y) to the vicinity of the singular point (1, 1). In Tables 1–4, exact numerical values of these integrals are first given here, i.e., actually for all the D. I. Mendeleev table. (The author has all values of these integrals and graphs of Dirac's radial functions for the arbitrary nlj-states of H-like atoms and Z ≤ 137).
PREPARATION AND ELECTRO-THERMOCONDUCTIVE CHARACTERISTICS OF MAGNETORHEOLOGICAL SUSPENSIONS
Authors: BICA IOAN , CHOI HYOUNG JIN
Published: December 2008

We review both synthesis and magnetorheological (MR) characteristics of magnetic particles concerning electro-thermoconductive MR suspensions. Various MR systems from nanoparticles to microparticles of iron, iron oxides and metallic solids with and without additives or modifications with polymers are summarized. Methods for electro-thermoconductive MR suspensions and mechanisms that lend them these properties, experimental results and discussions on them are presented.
METAL–INSULATOR TRANSITION IN 3D QUANTUM PERCOLATION
Authors: TRAVĚNEC IGOR
Published: December 2008

We present the metal–insulator transition study of a quantum site percolation model on simple cubic lattice. Transfer matrix method is used to calculate transport properties — Landauer conductance — for the binary distribution of energies. We calculate the mobility edge in disorder (ratio of insulating sites) — energy plane in detail and we find the extremal critical disorder somewhat closer to the classical percolation threshold than formerly reported. We calculate the critical exponent ν along the mobility edge and find it constant and equal to the one of 3D Anderson model, confirming common universality class. Possible exception is the center of the conduction band, where either the single-parameter scaling is not valid anymore, or finite size effects are immense. One of the reasons for such statement is the difference between results from arithmetic and geometric averaging of conductance at special energies. Only the geometric mean yields zero critical disorder in band center, which was theoretically predicted.
Loss of p21Waf1/Cip1/Sdi1enhances intestinal stem cell survival following radiation injury
Authors: George Robert J. , Sturmoski Mark A. , May Randal , Sureban Sripathi M. , Dieckgraefe Brian K. , Anant Shrikant , Houchen Courtney W.
Published: December 2008

The microcolony assay following gamma irradiation (IR) is a functional assay of intestinal stem cell fate. The cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1/Sdi1(p21) regulates cell cycle arrest following DNA damage. To explore the role of p21 on stem cell fate, we examined the effects of p21 deletion on intestinal crypt survival following IR and expression of the stem/progenitor cell marker Musashi-1 (Msi-1) and the antiapoptotic gene survivin. Intestinal stem cell survival in adult wild-type (WT) and p21−/−mice was measured using the microcolony assay. Msi-1, p21, and survivin mRNA were measured using real-time PCR and immunohistochemical analysis. Laser capture microdissection (LCM) was used to isolate mRNA from the crypt stem cell zone. No differences in radiation-induced apoptosis were observed between WT and p21−/−mice. However, increased crypt survival (3.0-fold) was observed in p21−/−compared with WT mice 3.5 days after 13 Gy. Msi-1 and survivin mRNA were elevated 12- and 7.5-fold, respectively, in LCM-dissected crypts of p21−/−compared with WT mice. In conclusion, deletion of p21 results in protection of crypt stem/progenitor cells from IR-induced cell death. Furthermore, the increase in crypt survival is associated with increased numbers of Msi-1- and survivin-expressing cells in regenerative crypts.
Functional coupling of the downregulated in adenoma Cl−/base exchanger DRA and the apical Na+/H+exchangers NHE2 and NHE3
Authors: Musch Mark W. , Arvans Donna L. , Wu Gary D. , Chang Eugene B.
Published: December 2008

Non-nutrient-dependent salt absorption across the brush-border membrane of intestinal epithelial cells is primarily mediated by coupled apical Na+/H+(aNHE) and anion exchange transport, with the latter suspected of being mediated by DRA (downregulated in adenoma; SLC26A3) that is defective in congenital chloridorrhea. To investigate DRA in greater detail and determine whether DRA and NHE activities can be coupled, we measured22Na+and36Cl−uptake in Caco2BBE colon cells infected with the tet-off-inducible DRA transgene. Under basal conditions, DRA activity was low in normal and infected Caco2BBE cells in the presence of tetracycline, whereas NHE activities could be easily detected. When apical NHE activity was increased by transfection or serum-induced expression of the aNHE isoforms NHE2 and NHE3, increased36Cl−uptake was observed. Inhibition of DRA activity by niflumic acid was greater than that by DIDS as well as by the NHE inhibitor dimethylamiloride and the carbonic anhydrase inhibitor methazolamide. DRA activity was largely aNHE-dependent, whereas a component of DRA-independent aNHE uptake continued to be observed. Coupled aNHE and DRA activities were inhibited by increased cellular cAMP and calcium and were associated with synaptotagmin I-dependent, clathrin-mediated endocytosis. In summary, these data support the role of DRA in electroneutral NaCl absorption involving functional coupling of Cl−/base exchange and apical NHE.
Transplantation of basic fibroblast growth factor-pretreated adipose tissue-derived stromal cells enhances regression of liver fibrosis in mice
Authors: Kamada Yoshihiro , Yoshida Yuichi , Saji Yukiko , Fukushima Juichi , Tamura Shinji , Kiso Shinichi , Hayashi Norio
Published: December 2008

Adipose tissue-derived stromal cells (ADSC) potentially differentiate into various cell types similar to bone marrow-derived mesenchymal stromal cells (BMSC). Unlike BMSC, ADSC can be harvested easily and repeatedly. However, the advantages of ADSC for cell transplantation in liver disease remain unclear. To investigate this, we developed a novel culture system for ADSC, as well as effective methods for transplantation of ADSC into mice liver. ADSC were isolated from subcutaneous adipose tissues of male C57BL6/J mice and cultured on plastic dishes with or without basic fibroblast growth factor (bFGF). In the in vivo study, ADSC isolated from green fluorescent protein-transgenic mice were transplanted into carbon tetrachloride-injured C57BL6/J mice liver. bFGF-treated ADSC expressed several liver-specific marker genes and demonstrated liver-related functions such as albumin secretion, glycogen synthesis, urea production, and low-density lipoprotein uptake. Importantly, pretreatment of ADSC with bFGF for 1 wk enhanced the repopulation rate of ADSC in mice liver, attenuated liver fibrosis, and restored normal serum alanine aminotransferase and albumin levels. The results indicate that basic FGF facilitates transdifferentiation of ADSC into hepatic lineage cells in vitro and that transplantation of bFGF-pretreated ADSC reduced hepatic fibrosis in mice. ADSC are a potentially valuable source of cells for transplantation therapy.
Continuous cardiac output and left atrial pressure monitoring by long time interval analysis of the pulmonary artery pressure waveform: proof of concept in dogs
Authors: Xu Da , Olivier N. Bari , Mukkamala Ramakrishna
Published: December 2008

We developed a technique to continuously (i.e., automatically) monitor cardiac output (CO) and left atrial pressure (LAP) by mathematical analysis of the pulmonary artery pressure (PAP) waveform. The technique is unique to the few previous related techniques in that it jointly estimates the two hemodynamic variables and analyzes the PAP waveform over time scales greater than a cardiac cycle wherein wave reflections and inertial effects cease to be major factors. First, a 6-min PAP waveform segment is analyzed so as to determine the pure exponential decay and equilibrium pressure that would eventually result if cardiac activity suddenly ceased (i.e., after the confounding wave reflections and inertial effects vanish). Then, the time constant of this exponential decay is computed and assumed to be proportional to the average pulmonary arterial resistance according to a Windkessel model, while the equilibrium pressure is regarded as average LAP. Finally, average proportional CO is determined similar to invoking Ohm's law and readily calibrated with one thermodilution measurement. To evaluate the technique, we performed experiments in five dogs in which the PAP waveform and accurate, but highly invasive, aortic flow probe CO and LAP catheter measurements were simultaneously recorded during common hemodynamic interventions. Our results showed overall calibrated CO and absolute LAP root-mean-squared errors of 15.2% and 1.7 mmHg, respectively. For comparison, the root-mean-squared error of classic end-diastolic PAP estimates of LAP was 4.7 mmHg. On future successful human testing, the technique may potentially be employed for continuous hemodynamic monitoring in critically ill patients with pulmonary artery catheters.
Muscle fatigue examined at different temperatures in experiments on intact mammalian (rat) muscle fibers
Authors: Roots H. , Ball G. , Talbot-Ponsonby J. , King M. , McBeath K. , Ranatunga K. W.
Published: December 2008

In experiments on small bundles of intact fibers from a rat fast muscle, in vitro, we examined the decline in force in repeated tetanic contractions; the aim was to characterize the effect of shortening and of temperature on the initial phase of muscle fatigue. Short tetanic contractions were elicited at a control repetition rate of 1/60 s, and fatigue was induced by raising the rate to 1/5 s for 2–3 min, both in isometric mode (no shortening) and in shortening mode, in which each tetanic contraction included a ramp shortening at a standard velocity. In experiments at 20°C ( n = 12), the force decline during a fatigue run was 25% in the isometric mode but was significantly higher (35%) in the shortening mode. In experiments at different temperatures (10–30°C, n = 11), the tetanic frequency and duration were adjusted as appropriate, and for shortening mode, the velocity was adjusted for maximum power output. In isometric mode, fatigue of force was significantly less at 30°C (∼20%) than at 10°C (∼30%); the power output (force × velocity) was >10× higher at 30°C than at 10°C, and power decline during a fatigue run was less at 30°C (∼20–30%) than at 10°C (∼50%). The finding that the extent of fatigue is increased with shortening contractions and is lower at higher temperatures is consistent with the view that force depression by inorganic phosphate, which accumulates within fibers during activity, may be a primary cause of initial muscle fatigue.
New insights into ocular blood flow at very high altitudes
Authors: Bosch Martina M. , Merz Tobias M. , Barthelmes Daniel , Petrig Benno L. , Truffer Frederic , Bloch Konrad E. , Turk Alex , Maggiorini Marco , Hess Thomas , Schoch Otto D. , Hefti Urs , Sutter Florian K. P. , Pichler Jacqueline , Huber Andreas , Landau Klara
Published: December 2008

Little is known about the ocular and cerebral blood flow during exposure to increasingly hypoxic conditions at high altitudes. There is evidence that an increase in cerebral blood flow resulting from altered autoregulation constitutes a risk factor for acute mountain sickness (AMS) and high-altitude cerebral edema (HACE) by leading to capillary overperfusion and vasogenic cerebral edema. The retina represents the only part of the central nervous system where capillary blood flow is visible and can be measured by noninvasive means. In this study we aimed to gain insights into retinal and choroidal autoregulatory properties during hypoxia and to correlate circulatory changes to symptoms of AMS and clinical signs of HACE. This observational study was performed within the scope of a high-altitude medical research expedition to Mount Muztagh Ata (7,546 m). Twenty seven participants underwent general and ophthalmic examinations up to a maximal height of 6,800 m. Examinations included fundus photography and measurements of retinal and choroidal blood flow, as well as measurement of arterial oxygen saturation and hematocrit. The initial increase in retinal blood velocity was followed by a decrease despite further ascent, whereas choroidal flow increase occurred later, at even higher altitudes. The sum of all adaptational mechanisms resulted in a stable oxygen delivery to the retina and the choroid. Parameters reflecting the retinal circulation and optic disc swelling correlated well with the occurrence of AMS-related symptoms. We demonstrate that sojourns at high altitudes trigger distinct behavior of retinal and choroidal blood flow. Increase in retinal but not in choroidal blood flow correlated with the occurrence of AMS-related symptoms.
Locomotor exercise induces long-lasting impairments in the capacity of the human motor cortex to voluntarily activate knee extensor muscles
Authors: Sidhu Simranjit K. , Bentley David J. , Carroll Timothy J.
Published: December 2008

Muscle fatigue is a reduction in the capacity to exert force and may involve a “central” component originating in the brain and/or spinal cord. Here we examined whether supraspinal factors contribute to impaired central drive after locomotor endurance exercise. On 2 separate days, 10 moderately active individuals completed a locomotor cycling exercise session or a control session. Brief (2 s) and sustained (30 s) isometric knee extension contractions were completed before and after locomotor exercise consisting of eight, 5-min bouts of cycling at 80% of maximum workload. In the control session, subjects completed the isometric contractions in a rested state. Twitch responses to supramaximal motor nerve stimulation and transcranial magnetic stimulation were obtained to assess peripheral force-generating capacity and voluntary activation. Maximum voluntary contraction (MVC) force during brief contractions decreased by 23 ± 6.3% after cycling exercise and remained 12 ± 2.8% below baseline 45 min later ( F1,9 > 15.5; P < 0.01). Resting twitch amplitudes declined by ∼45% ( F1,9 = 28.3; P < 0.001). Cortical voluntary activation declined from 90.6 ± 1.6% at baseline to 80.6 ± 2.1% after exercise ( F1,9 = 28.0; P < 0.001) and remained significantly reduced relative to control 30–45 min later (80.6 ± 3.4%; F1,9 = 10.7; P < 0.01). Thus locomotor exercise caused a long-lasting impairment in the capacity of the motor cortex to drive the knee extensors. Force was reduced more during sustained MVC after locomotor exercise than in the control session. Peripheral mechanisms contributed relatively more to this force reduction in the control session, whereas supraspinal fatigue played a greater role in sustained MVC reduction after locomotor exercise.
Influence of priming exercise on pulmonary O2uptake kinetics during transitions to high-intensity exercise at extreme pedal rates
Authors: DiMenna Fred J. , Wilkerson Daryl P. , Burnley Mark , Bailey Stephen J. , Jones Andrew M.
Published: December 2008

We investigated the pedal rate dependency of the effect of priming exercise on pulmonary oxygen uptake (V̇o2) kinetics. Seven healthy men completed two, 6-min bouts of high-intensity cycle exercise (separated by 6 min of rest) using different combinations of extreme pedal rates for the priming and criterion exercise bouts (i.e., 35→35, 35→115, 115→35, and 115→115 rev/min). Pulmonary gas exchange and heart rate were measured breath-by-breath, and muscle oxygenation was assessed using near-infrared spectroscopy. When the priming bout was performed at 35 rev/min (35→35 and 35→115 conditions), the phase II V̇o2time constant (τ) was not significantly altered ( bout 1: 31 ± 7 vs. bout 2: 30 ± 5 s and bout 1: 48 ± 16 vs. bout 2: 46 ± 21 s, respectively). However, when the priming bout was performed at 115 rev/min (115→35 and 115→115 conditions), the phase II τ was significantly reduced ( bout 1: 31 ± 7 vs. bout 2: 26 ± 5 s and bout 1: 48 ± 16 vs. bout 2: 39 ± 9 s, respectively, P < 0.05). Muscle oxygenation was significantly higher after priming exercise in all four conditions, but significant effects on V̇o2kinetics were only evident when muscle O2extraction (measured as Δ[deoxyhemoglobin]/ΔV̇o2) was elevated in the fundamental response phase. These data indicate that prior high-intensity exercise at a high pedal rate can speed V̇o2kinetics during subsequent high-intensity exercise, presumably through specific priming effects on type II muscle fibers.
Skin blood flow and nitric oxide during body heating in type 2 diabetes mellitus
Authors: Sokolnicki Lynn A. , Strom Nicholas A. , Roberts Shelly K. , Kingsley-Berg Shirley A. , Basu Ananda , Charkoudian Nisha
Published: December 2008

Individuals with type 2 diabetes mellitus (T2DM) often exhibit microvascular dysfunction that may contribute to impaired thermoregulation, but potential mechanisms remain unclear. Our goals were to quantify skin blood flow responses and nitric oxide-mediated vasodilation during body heating in individuals with T2DM compared with nondiabetic control subjects of similar age. We measured skin blood flow (laser-Doppler flowmetry) in conjunction with intradermal microdialysis of NG-nitro-l-arginine methyl ester (l-NAME; nitric oxide synthase inhibitor) or vehicle during 45–60 min of whole body heating (WBH) in 10 individuals with T2DM and 14 control subjects. In six individuals from each group, we also measured forearm blood flow (FBF) by venous occlusion plethysmography on the contralateral forearm. FBF responses showed diminished absolute cutaneous vasodilation during WBH in the T2DM group ( PANOVA < 0.01; peak FBF in control 13.1 ± 1.7 vs. T2DM 9.0 ± 1.6 ml·100 ml−1·min−1). However, the relative contribution of nitric oxide to the cutaneous vasodilator response (expressed as % of maximal cutaneous vascular conductance) was not different between groups ( P > 0.05). We conclude that cutaneous vasodilator responses to WBH are decreased in individuals with T2DM, but the contribution of nitric oxide to this smaller vasodilation is similar between T2DM and control individuals. This decrease in cutaneous vasodilation is likely an important contributor to impaired thermoregulation in T2DM.
SR-A, MARCO and TLRs Differentially Recognise Selected Surface Proteins from Neisseria meningitidis: an Example of Fine Specificity in Microbial Ligand Recognition by Innate Immune Receptors
Authors: Plüddemann Annette , Mukhopadhyay Subhankar , Sankala Marko , Savino Silvana , Pizza Mariagrazia , Rappuoli Rino , Tryggvason Karl , Gordon Siamon
Published: December 2008

Macrophages express various classes of pattern recognition receptors involved in innate immune recognition of artificial, microbial and host-derived ligands. These include the scavenger receptors (SRs), which are important for phagocytosis, and the Toll-like receptors (TLRs) involved in microbe sensing. The class A macrophage scavenger receptor (SR-A) and macrophage receptor with a collagenous structure (MARCO) display similar domain structures and ligand-binding specificity, which has led to the assumption that these two receptors may be functionally redundant. In this study we show that SR-A and MARCO differentially recognise artificial polyanionic ligands as well as surface proteins from the pathogenic bacterium Neisseria meningitidis. We show that, while acetylated low-density lipoprotein (AcLDL) is a strong ligand for SR-A, it is not a ligand for MARCO. Of the neisserial proteins that were SR ligands, some were ligands for both receptors, while other proteins were only recognised by either SR-A or MARCO. We also analysed the potential of these ligands to act as TLR agonists and assessed the requirement for SR-A and MARCO in pro-inflammatory cytokine induction. SR ligation alone did not induce cytokine production; however, for proteins that were both SR and TLR ligands, the SRs were required for full activation of TLR pathways.
The Interleukin-1 Receptor-Associated Kinase M Selectively Inhibits the Alternative, Instead of the Classical NFκB Pathway
Authors: Su Jianmin , Zhang Tongli , Tyson John , Li Liwu
Published: December 2008

The innate immunity signaling process is controlled by numerous positive and negative regulators. The interleukin-1 receptor-associated kinase M (IRAK-M) is one of the negative regulators that contribute to the attenuation of NFκB activation. The molecular mechanism involved, however, is poorly defined. In this report, we observed that IRAK-M selectively suppresses the NIK-IKKα-mediated alternative NFκB pathway. Deletion of IRAK-M led to NIK stabilization, favored the formation of the IKKα/IKKα homodimer instead of the IKKα/IKKβ heterodimer, and enhanced RelB nuclear distribution. In contrast, p65 nuclear localization and phosphorylation was not affected by IRAK-M deficiency. IRAK-M-deficient cells exhibited increased expression of selected cytokines such as IL-6 and GM-CSF, as well as quickened resynthesis of IκBα. The increased expression of IL-6 and GM-CSF was ablated when RelB expression was knocked down using specific siRNA. We also demonstrated that the observed inhibitory effect of IRAK-M was primarily limited to the TLR2 ligand, instead of TLR4. Taken together, our findings suggest that IRAK-M negatively regulates the alternative NFκB pathway in a ligand-specific manner.
Blockade of LOX-1 Prevents Endotoxin-Induced Acute Lung Inflammation and Injury in Mice
Authors: Zhang Ping , Liu Ming-Cheh , Cheng Lili , Liang Mei , Ji Hong-long , Fu Jian
Published: December 2008

Lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1), a cell surface receptor expressed in endothelial cells, is known to mediate oxidized LDL-induced vascular inflammation and atherogenesis. Although the role of LOX-1 in vascular inflammation has been well established, its involvement in acute lung inflammation and injury remains unclear. In the present study, we examined the effects of a LOX-1-blocking antibody on lung inflammation in a mouse endotoxin lipopolysaccharide (LPS)-induced acute lung injury model. We demonstrated that intraperitoneal challenge with LPS induced a rapid and robust increase in LOX-1 expression in mouse lung. Pre-treatment of mice with anti-LOX-1-blocking antibody significantly inhibited LPS-induced lung inflammation as indicated by decreased neutrophil accumulation in the lung. Furthermore, anti-LOX-1 was capable of inhibiting LPS-induced inflammatory responses, including NF-κB activation, ICAM-1 expression and apoptotic signaling, in mouse lung. Collectively, these results indicate that LOX-1 may serve as a valuable therapeutic target in the prevention of acute lung inflammation and injury in sepsis.
Activation of Insect Phenoloxidase after Injury: Endogenous versus Foreign Elicitors
Authors: Bidla Gawa , Hauling Thomas , Dushay Mitchell S. , Theopold Ulrich
Published: December 2008

The enzyme phenoloxidase (PO) is one of the first immune molecules that was identified in invertebrates. Recently, the immune function of PO has been challenged. We tested how PO is activated following injury in 2 insects, i.e. the fruit fly Drosophila melanogaster and the wax moth Galleria mellonella. Rapid PO activation in Drosophila was limited to discrete areas of the hemolymph clot which forms after injury. Surprisingly, unlike systemic PO activation during bacterial sepsis, clot melanization was not sensitive to microbial elicitors in our assay. Instead, Drosophila clot melanization was activated by endogenous signals such as apoptotic cells and was superinduced by phosphatidylserine, a negatively charged phospholipid normally found on the inner surface of the plasma membrane and exposed during apoptosis. In contrast, melanization in G. mellonella hemolymph was stronger and more uniform and was sensitive to peptidoglycan. This shows that both exogenous and endogenous signals can trigger the same immune mechanism in species- and context-dependent ways. Our findings have implications for the evolutionary dynamics of immune mechanisms and are in agreement with recent comparisons of insect immune transcriptomes.
Non-Opsonic Recognition of Mycobacterium tuberculosis by Phagocytes
Authors: Schäfer Georgia , Jacobs Muazzam , Wilkinson Robert J. , Brown Gordon D.
Published: December 2008

The interactions between Mycobacterium tuberculosis and host phagocytes such as macrophages and dendritic cells are central to both immunity and pathogenesis. Many receptors have been implicated in recognition and binding of M. tuberculosis such as the mannose receptor, dendritic-cell-specific intercellular adhesion molecule-3 grabbing nonintegrin, dectin-1 and complement receptor 3 as well as Toll-like receptors, scavenger receptors and CD14. While in vitro studies have demonstrated clear roles for particular recep- tor(s), in vivo work in receptor-deficient animals often revealed only a minor, or no role, in infection with M. tuberculosis. The initial encounter of phagocytic cells with myco- bacteria appears to be complex and depends on various parameters. It seems likely that infection with M. tuberculosis does not occur via a single receptor-mediated pathway. Rather, multiple receptors play different roles in M. tuberculosis infection, and the overall effect depends on the expression and availability of a particular receptor on a particular cell type and its triggered downstream responses. Moreover, the role of membrane cholesterol for M. tuberculosis interactions with phagocytes adds to the complexity of mycobacterial recognition and response. This review summarizes current knowledge on non-opsonic receptors involved in binding of mycobacteria and discusses the contribution of individual receptors to the recognition process.