bluuebunny/crossref_metadata_2025 huggingface dataset:
Utilizing intraluminal pressure differences to predict esophageal bolus flow dynamics
Authors: Ghosh Sudip K. , Kahrilas Peter J. , Lodhia Nilesh , Pandolfino John E.
Published: September 2007

Successful esophageal emptying depends on the generation of a sustained intrabolus pressure (IBP) sufficient to overcome esophagogastric junction (EGJ) obstruction. Our aim was to develop a manometric analysis paradigm that describes the bolus driving pressure difference and the flow permissive time for esophageal bolus transit. Twenty normal subjects were studied with a 36-channel manometry assembly (1-cm spacing) during two 5- and one 10-ml barium swallows and concurrent fluoroscopy. Bolus domain pressure plots were generated by plotting bolus domain pressure (BDP) and EGJ relaxation pressure. BDP was defined as the pressure midway between the peristaltic ramp-up and the proximal margin of the EGJ. The flow permissive time was defined as the period where the BDP was ≥ EGJ relaxation pressure. The mean BDP was 11.7 ± 1.0 mmHg (SE), and the mean flow permissive time was 3.9 ± 0.4 s for 5-ml swallows in normal controls. The mean BDP difference during flow was 4.0 ± 1.0 mmHg. There was no significant difference in the fluoroscopic transit time and the flow permissive time calculated from the BDP plots (5 ml: fluoroscopy 3.4 ± 0.2 s; BDP 3.9 ± 0.4 s, P > 0.05). BDP plots provide a reliable measurement of IBP and its relationship with EGJ relaxation. The time available for flow can be readily delineated from this analysis, and the driving pressure responsible for flow can be accurately described and quantified. This may help predict abnormal bolus transit and the underlying mechanical properties of the EGJ.
HIF-1α in endurance training: suppression of oxidative metabolism
Authors: Mason Steven D. , Rundqvist Helene , Papandreou Ioanna , Duh Roger , McNulty Wayne J. , Howlett Richard A. , Olfert I. Mark , Sundberg Carl Johan , Denko Nicholas C. , Poellinger Lorenz , Johnson Randall S.
Published: September 2007

During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress. The primary transcriptional response factor for acclimation to hypoxic stress is hypoxia-inducible factor-1α (HIF-1α), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1α in endurance training, we have created mice specifically lacking skeletal muscle HIF-1α and subjected them to an endurance training protocol. We found that only wild-type mice improve their oxidative capacity, as measured by the respiratory exchange ratio; surprisingly, we found that HIF-1α null mice have already upregulated this parameter without training. Furthermore, untrained HIF-1α null mice have an increased capillary to fiber ratio and elevated oxidative enzyme activities. These changes correlate with constitutively activated AMP-activated protein kinase in the HIF-1α null muscles. Additionally, HIF-1α null muscles have decreased expression of pyruvate dehydrogenase kinase I, a HIF-1α target that inhibits oxidative metabolism. These data demonstrate that removal of HIF-1α causes an adaptive response in skeletal muscle akin to endurance training and provides evidence for the suppression of mitochondrial biogenesis by HIF-1α in normal tissue.
Manipulation of the Potassium Channel Kv1.1 and Its Effect on Neuronal Excitability in Rat Sensory Neurons
Authors: Chi Xian Xuan , Nicol G. D.
Published: September 2007

Potassium channels play a critical role in regulating many aspects of action potential (AP) firing. To establish the contribution of the voltage-dependent potassium channel Kv1.1 in regulating excitability, we used the selective blocker dendrotoxin-K (DTX-K) and small interfering RNA (siRNA) targeted to Kv1.1 to determine their effects on AP firing in small-diameter capsaicin-sensitive sensory neurons. A 5-min exposure to 10 nM DTX-K suppressed the total potassium current ( IK) measured at +40 mV by about 33%. DTX-K produced a twofold increase in the number of APs evoked by a ramp of depolarizing current. Associated with increased firing was a decrease in firing threshold and rheobase. DTX-K did not alter the resting membrane potential or the AP duration. A 48-h treatment with siRNA targeted to Kv1.1 reduced the expression of this channel protein by about 60% as measured in Western blots. After treatment with siRNA, IKwas no longer sensitive to DTX-K, indicating a loss of functional protein. Similarly, after siRNA treatment exposure to DTX-K had no effect on the number of evoked APs, firing threshold, or rheobase. However, after siRNA treatment, the firing threshold had values similar to those obtained after acute exposure to DTX-K, suggesting that the loss of Kv1.1 plays a critical role in setting this parameter of excitability. These results demonstrate that Kv1.1 plays an important role in limiting AP firing and that siRNA may be a useful approach to establish the role of specific ion channels in the absence of selective antagonists.
Using Constraints on Neuronal Activity to Reveal Compensatory Changes in Neuronal Parameters
Authors: Olypher Andrey V. , Calabrese Ronald L.
Published: September 2007

In this study, we developed a general description of parameter combinations for which specified characteristics of neuronal or network activity are constant. Our approach is based on the implicit function theorem and is applicable to activity characteristics that smoothly depend on parameters. Such smoothness is often intrinsic to neuronal systems when they are in stable functional states. The conclusions about how parameters compensate each other, developed in this study, can thus be used even without regard to the specific mathematical model describing a particular neuron or neuronal network. We showed that near a generic point in the parameter space there are infinitely many other points, or parameter combinations, for which specified characteristics of activity are the same as in the original point. These parameter combinations form a smooth manifold. This manifold can be extended as long as the gradients of characteristics are defined and independent. All possible variations of parameters compensating each other are simply all possible charts of the same manifold. The number of compensating parameters (but not parameters themselves) is fixed and equal to the number of the independent characteristics maintained. The algorithm that we developed shows how to find compensatory functional dependencies between parameters numerically. Our method can be used in the analysis of the homeostatic regulation, neuronal database search, model tuning and other applications.
Macrophage-mediated neuroprotection and neurogenesis in the olfactory epithelium
Authors: Borders A. S. , Hersh M. A. , Getchell M. L. , van Rooijen N. , Cohen D. A. , Stromberg A. J. , Getchell T. V.
Published: September 2007

Resident and recruited olfactory epithelial macrophages participate in the regulation of the survival, degeneration, and replacement of olfactory sensory neurons (OSNs). We have reported that liposome-encapsulated clodronate (Lip-C) induced selective and statistically significant depletion of macrophages in the OE of sham and 48 h OBX mice (38 and 35%, respectively) that resulted in increased OSN apoptosis and decreased numbers of mature OSNs and proliferating basal cells compared to controls (Lip-O). The aim of this study was to identify molecular mechanisms by which the selective depletion of macrophages in the OE resulted in these cellular changes by using a microarray expression pattern analysis. A 2×2 ANOVA identified 4,085 overall significantly ( P < 0.01) regulated genes in the OE of Lip-O and Lip-C sham and 48 h OBX mice, and further statistical analysis using pairwise comparisons identified 4,024 genes that had either a significant ( P < 0.01) treatment main effect ( n = 2,680), group main effect ( n = 778), or interaction effect ( n = 980). The mean hybridization signals of immune response genes, e.g., Cxcr4, and genes encoding growth factors and neurogenesis regulators, e.g., Hdgf and Neurod1, respectively, were primarily lower in Lip-C mice compared with Lip-O mice. Apoptosis genes, e.g., Bak1, were also differentially regulated in Lip-C and/or OBX mice. Expression patterns of selected genes were validated with real-time RT-PCR; immunohistochemistry was used to localize selected gene products. These results identified the differential regulation of several novel genes through which alternatively activated macrophages regulate OSN progenitor cell proliferation, differentiation, and maturation, and the survival of OSNs.
Characterization of Cu(II)-ACC Complexes and Conversion of the Bound ACC into Ethylene in the Presence of Hydrogen Peroxide. Detection of a Brown Intermediate at Low Temperature
Authors: Ghattas Wadih , Giorgi Michel , Gaudin Christian , Rockenbauer Antal , Réglier Marius , Simaan A. Jalila
Published: September 2007

Two copper(II)-ACC complexes were prepared and characterized: [Cu(bpy)(ACC)(H2O)]⋅CO4(1) and[Cu(ACC)2]3⋅4H2O(2). Their crystallographic structures are described and analyzed. Spectroscopic characterizations (UV-visible and EPR) confirm that the structure is maintained in solution. These complexes are able to produce ethylene in the presence of hydrogen peroxide in an “ACC Oxidase-like” reaction in water and in methanol. The conversion of ACC into ethylene depends on the amount of base, and, in methanol, 3 equivalents of NaOH are needed for optimum activity. The base is proposed to play a role inH2O2deprotonation. The presence of an exogenic ligand (bpy) is important for the reactivity and may stabilize a reaction intermediate. Indeed, a brown intermediate with an absorption band centered at 433 nm can be detected at low temperature when1is treated with 10 equivalents ofH2O2.
Common Fixed Point Theorems for Hybrid Pairs of Occasionally Weakly Compatible Mappings Satisfying Generalized Contractive Condition of Integral Type
Authors: Abbas Mujahid , Rhoades BE
Published: September 2007

We obtain several fixed point theorems for hybrid pairs of single-valued and multivalued occasionally weakly compatible maps defined on a symmetric space satisfying a contractive condition of integral type. The results of this paper essentially contain every theorem on hybrid and multivalued self-maps of a metric space as a special case.

Erratumhttp://dx.doi.org/10.1155/2008/274793
Necessary Conditions for the Solutions of Second Order Non-linear Neutral Delay Difference Equations to Be Oscillatory or Tend to Zero
Authors: Rath R. N. , Dix J. G. , Barik B. L. S. , Dihudi B.
Published: September 2007

We find necessary conditions for every solution of the neutral delay difference equationΔ(rnΔ(yn−pnyn−m))+qnG(yn−k)=fnto oscillate or to tend to zero asn→∞, whereΔis the forward difference operatorΔxn=xn+1−xn, andpn, qn, rnare sequences of real numbers withqn≥0, rn>0. Different ranges of{pn}, includingpn=±1, are considered in this paper. We do not assume thatGis Lipschitzian nor nondecreasing withxG(x)>0forx≠0. In this way, the results of this paper improve, generalize, and extend recent results. Also, we provide illustrative examples for our results.
Nessi: An EEG-Controlled Web Browser for Severely Paralyzed Patients
Authors: Bensch Michael , Karim Ahmed A. , Mellinger Jürgen , Hinterberger Thilo , Tangermann Michael , Bogdan Martin , Rosenstiel Wolfgang , Birbaumer Niels
Published: September 2007

We have previously demonstrated that an EEG-controlled web browser based on self-regulation of slow cortical potentials (SCPs) enables severely paralyzed patients to browse the internet independently of any voluntary muscle control. However, this system had several shortcomings, among them that patients could only browse within a limited number of web pages and had to select links from an alphabetical list, causing problems if the link names were identical or if they were unknown to the user (as in graphical links). Here we describe a new EEG-controlled web browser, called Nessi, which overcomes these shortcomings. In Nessi, the open source browser, Mozilla, was extended by graphical in-place markers, whereby different brain responses correspond to different frame colors placed around selectable items, enabling the user to select any link on a web page. Besides links, other interactive elements are accessible to the user, such as e-mail and virtual keyboards, opening up a wide range of hypertext-based applications.
Efficacy and Tolerability of Naltrexone in the Treatment of Alcohol Dependence: Oral versus Injectable Delivery
Authors: Roozen Hendrik G. , de Waart Ranne , van den Brink Wim
Published: September 2007

Oral naltrexone, an opioid antagonist, reduces relapse and heavy drinking in alcohol-dependent patients. However, oral delivery is associated with poor compliance and adverse events. To enhance treatment outcome and reduce side effects, injectable extended-release naltrexone formulations have been developed. Currently, there are no studies available directly comparing oral and injectable formulations of naltrexone in alcohol-dependent patients. This paper reviews the efficacy and adverse events of oral versus injectable extended-release naltrexone. Therefore, data were extracted from two recently published reviews about oral naltrexone in the treatment of alcohol dependence. Pooled outcomes were compared with reported outcomes of recent studies on injectable extended-release naltrexone. Injectable naltrexone seems to be effective in the management of alcohol dependence. Although inconclusive, the available results indicate that the expected advantages of injectable naltrexone over oral naltrexone still have to be proven. Randomized studies with direct comparisons of oral and injectable naltrexone are urgently needed.
Individual Variation in Coping with Stress: A Multidimensional Approach of Ultimate and Proximate Mechanisms
Authors: Koolhaas Jaap M. , de Boer Sietse F. , Buwalda Bauke , van Reenen Kees
Published: September 2007

Ecological studies on feral populations of mice, fish and birds elucidate the functional significance of phenotypes that differ individually in their behavioral and neuroendocrine response to environmental challenge. Within a species, the capacity to cope with environmental challenges largely determines individual survival in the natural habitat. Recent studies indicate that individual variation within a species may buffer the species for strong fluctuations in the natural habitat. A conceptual framework will be presented that is based on the view that individual variation in aggressive behavior can be considered more generally as a variation in actively coping with environmental challenges. Highly aggressive individuals adopt a proactive coping style whereas low levels of aggression indicate a more passive or reactive style of coping. Coping styles have now been identified in a range of species and can be considered as trait characteristics that are stable over time and across situations. The dimension of coping style seems to be independent of an emotionality dimension. Hence, in the analysis of the proximate mechanisms of stress and adaptation, one has to consider the possibility that the mechanisms which determine the type of stress response might be independent from those underlying the magnitude of the response. The two coping styles differ in a number of important neurobiological and neuroendocrine systems. For example, proactive males differ significantly from reactive males in the homeostatic control of serotonergic activity resulting in completely opposite dose response relationships of various serotonergic drugs. The results so far show that proactive coping is characterized by a strong inhibitory control of the 5-HT neuron via its somatodendritic 5-HT1A autoreceptor. It is hypothesized that the regulation of serotonin release is causally related to coping style rather than emotionality. Understanding the functional individual variation as it occurs in nature and the underlying neurobiology and neuroendocrinology is fundamental in understanding individual vulnerability to stress related disease.
Genetically Determined Variation in Stress Responsiveness in Rainbow Trout: Behavior and Neurobiology
Authors: Schjolden Joachim , Winberg Svante
Published: September 2007

It is becoming increasingly recognized that the diversity in stressors, their intensity, predictability and the context in which they are experienced, will result in behavioral and physiological responses just as diverse. In addition, stress responses are characterized by individual variations where the physiological and behavioral reactions are associated in such a manner that distinct stress coping styles encompassing suites of correlated traits can be identified. These are often referred to as proactive and reactive stress coping styles. Proactive coping is characterized by more aggression, higher general activity and higher sympathetic activation, whereas reactive coping is characterized by immobility, lack of initiative and a higher parasympathetic/hypothalamic activation. Stable coping styles appear to coexist within populations, and these strategies appear to be largely innate. Moreover, the physiological and behavioral traits of coping styles appear to be heritable. These stress coping styles have proven to play a major role in competitive ability and subsequent social position in different species of vertebrates. However, there are also studies showing that social position can affect parameters encompassing the stress coping style of individuals. In this regard it is important, but not always easy, to distinguish between causes and effects of behavioral and physiological responses to stressors. The question raised is to what extent and rigidness stress coping styles are guided by genetic factors.
Genomic Responses to Behavioral Interactions in an African Cichlid Fish: Mechanisms and Evolutionary Implications
Authors: Burmeister Sabrina S.
Published: September 2007

Phenotypic plasticity in Astatotilapia burtoni allows individual males to alternate between dominant and subordinate status, two physiologically and behaviorally distinct phenotypes. Because these phenotypes are completely reversible, they provide an excellent model for studying the molecular mechanisms of phenotypic plasticity. The ability to express alternate phenotypes in A. burtoni depends on the ability to regulate gene expression on both short- and long-term time scales. Previous studies have demonstrated that dominant males, who have increased reproductive capacity, have higher expression of several genes involved in reproduction (e.g., genes for steroid receptors). These differences in gene expression and reproductive physiology are controlled by interactions among males. Recently, it was found that the same interactions that lead to stable long-term changes in gene expression also induce short-term and transient changes in expression of egr-1, an immediate-early gene transcription factor. This immediate-early gene response is part of a general mechanism for mediating changes in gene expression that underlie phenotypic plasticity. Longer stable changes in gene expression must involve other mechanisms, such as dynamic modifications of the epigenome. Recent data suggests a direct link between the immediate-early gene response and epigenetic modifications. These mechanisms which link behavioral interactions to changes in gene expression allow phenotypic variation to occur without corresponding changes in the genome and, as a consequence, they have implications for evolution. In the case of A. burtoni, phenotypic plasticity is likely to slow evolution because it produces highly adapted phenotypes under the primary niches encountered in the life-history of the species and the plasticity itself is likely to be an adaptive trait.
Generic and Disease-Specific Health-Related Quality of Life in Women with Coital Incontinence: A Prospective, Multicenter Study
Authors: Oh Seung-June , Choo Myung-Soo , Kim Hong Sik , Kim Joon Chul , Lee Jeong Gu , Yun Jong Min , Kim Duk Yoon , Paick Jae-Seung , Lee Ji Youl , Chung Byung Soo , Min Kweon Sik , Kim Young-Ho , Jung Hee Chang , Son Hwancheol , Jeong Jeong Yun , Rho Joon , Lee Kyu-Sung , Park Won-Hee , Ku Ja Hyeon
Published: September 2007

Objective: This study was carried out to evaluate the impact of coital incontinence on health-related quality of life (HRQOL) in women with lower urinary tract symptoms. Methods: A total of 180 women with sexual activity were evaluated. To obtain HRQOL assessments, patients were asked to fill out the Bristol Female Lower Urinary Tract Symptoms and the Medical Outcomes Study Short Form (SF-36) questionnaires. Results: The coital incontinence group had more frequently symptoms including urgency, urge incontinence, bladder pain, stress incontinence, unpredictable incontinence, nocturnal incontinence, reduced stream, and stopping flow than the no coital incontinence group. The frequency of incontinence and volume of leakage were also higher in the coital incontinence group than the no coital incontinence group. All symptom questions regarding sexual matters and quality of life except cutting down on fluid were more frequent in patients with coital incontinence than those without coital incontinence. Of the eight domains in the SF-36 questionnaire, five domains, namely, Physical functioning, Role-physical functioning, Social functioning, Role-emotional functioning, and Mental health were significantly different between the two groups. When comparing the Bristol Female Lower Urinary Tract Symptoms scores in the two groups, the scores in all domains except Voiding symptoms in the coital incontinence group were significantly higher than those in the no coital incontinence group. Patients with coital incontinence had more HRQOL impairment than those without coital incontinence. Conclusions: Our study reveals that more emphasis should be placed on coital incontinence in the terminology of urinary incontinence.
AL Amyloidosis with Renal Involvement
Authors: Ryšavá Romana
Published: September 2007

Primary (AL amyloidosis) is a systemic disease characterized by an amyloid deposition process in many organs, with unsatisfactory survival of patients. The monoclonal light chains form the fibrils that deposit and accumulate in tissues. Renal involvement is very frequent in AL amyloidosis and could lead to development of nephrotic syndrome followed by the renal failure in many cases. Classic therapeutic combination melphalan and prednisone has been supplemented with drugs with different mechanisms of action in this group of patients: high-dose dexamethasone, high-dose dexamethasone with melphalan, combination of vincristine, doxorubicin, and dexamethasone or newly high-dose melphalan supported by peripheral blood stem cell transplantation. This progressive therapy leads to the better survival and prognosis in the majority of patients. Alternative therapeutic approaches include thalidomide (alone or in combination with cyclophosphamide), lenalidomide, iododoxorubicin, etanercept and rituximab. The development of immunotherapy is expected in the near future.
Penetration of Pollen Proteins into the Skin
Authors: Jacobi U. , Engel K. , Patzelt A. , Worm M. , Sterry W. , Lademann J.
Published: September 2007

Atopic dermatitis is a chronic remittent skin disease. In the extrinsic form of atopic dermatitis, type IgE-mediated reactions play an important pathophysiological role. The aim of the present study was to examine whether type I allergens can penetrate into the skin. Therefore, pollen proteins were labeled with fluorescein isothiocyanate (FITC), and their penetration profile was studied qualitatively. Solutions of FITC-labeled pollen proteins were applied in vitro on porcine skin and in vivo on human skin. In vitro, the FITC-labeled proteins were observed within the complete stratum corneum (SC) and inside the hair follicles even 15 min after application. They were also distributed inside the dermis around the hair follicles. In vivo, a similar pattern of distribution within the SC and the hair follicles was observed. These results indicate penetration via the SC lipid layers and a faster penetration via the hair follicles. The FITC-labeled proteins entered the dermis via the follicular pathway. Therefore, the follicular penetration should be considered in the development of skin protection strategies. To evaluate such strategies, the developed method can be used, and further studies in atopic dermatitis patients are necessary to determine whether the penetration of type I allergens is increased.
Daptomycin Does Not Exert Immunomodulatory Effects in an Experimental Endotoxin Model of Human Whole Blood
Authors: Thallinger Christiane , Rothenburger Markus , Marsik Claudia , Wuenscher Sonja , Popovic Martin , Endler Georg , Wagner Oswald , Joukhadar Christian
Published: September 2007

Background: Recent studies have shown that distinct classes of antimicrobial agents might exert immunomodulatory effects in experimental settings. Daptomycin is the first member of the class of cyclic lipopeptide antibiotics, which exert their antimicrobial activity via a unique mode of action on the bacterial cytoplasmic membrane. Thus, we tested its ability to influence pro-inflammatory cytokines by use of an established experimental model of human endotoxemia. Methods: A controlled experimental study design with 4 parallel groups was used. Whole blood from 10 healthy male volunteers was incubated either with saline (negative control), daptomycin (40 µg/ml, control), lipopolysaccharide (LPS; 50 pg/ml, positive control), or the combination of daptomycin plus LPS for 4 h. Real-time polymerase chain reaction was utilized for the measurement of selected pro-inflammatory cytokines, namely IL-1β, IL-6 (high sensitivity) and TNF-α on the mRNA level. Protein concentrations of these respective cytokines were measured in the supernatant using a commercially available ELISA. Results: Incubation of whole blood with LPS significantly increased protein and mRNA levels of cytokines compared to baseline (p < 0.05). However, the combination of daptomycin plus LPS did not exert any significant effect on mRNA and protein levels of IL-1β, IL-6 (high sensitivity) and TNF-α after 2 and 4 h of incubation compared to LPS incubation alone. Conclusion: Daptomycin does not affect pro-inflammatory cytokines in the early phase of endotoxemia. This is most likely due to the unique mode of action of daptomycin, its low potential to penetrate into human cells and its high affinity to bacterial cytoplasmic membranes.
Mortality from Neurodegenerative Disease and Exposure to Extremely Low-Frequency Magnetic Fields: 31 Years of Observations on Swiss Railway Employees
Authors: Röösli Martin , Lörtscher Manfred , Egger Matthias , Pfluger Dominik , Schreier Nadja , Lörtscher Emanuel , Locher Peter , Spoerri Adrian , Minder Christoph
Published: September 2007

Aims: The objective of the present study was to investigate the relationship between extremely low-frequency magnetic field (ELF-MF) exposure and mortality from several neurodegenerative conditions in Swiss railway employees. Methods: We studied a cohort of 20,141 Swiss railway employees with 464,129 person-years of follow-up between 1972 and 2002. For each individual, cumulative exposure was calculated from on-site measurements and modelling of past exposure. We compared cause-specific mortality in highly exposed train drivers (mean exposure: 21 µT) with less exposed occupational groups (for example station masters: 1 µT). Results: The hazard ratio for train drivers compared to station masters was 1.96 [95% confidence interval (CI) = 0.98–3.92] for senile dementia and 3.15 (95% CI = 0.90–11.04) for Alzheimer’s disease. For every 10 µT years of cumulative exposure senile dementia mortality increased by 5.7% (95% CI = 1.3–10.4), Alzheimer’s disease by 9.4% (95% CI = 2.7–16.4) and amyotrophic lateral sclerosis by 2.1% (95% CI = –6.8 to 11.7). There was no evidence for an increase in mortality from Parkinson’s disease and multiple sclerosis. Conclusions: This study suggests a link between exposure to ELF-MF and Alzheimer’s disease and indicates that ELF-MF might act in later stages of the disease process.
Carotid Intima-Media Thickness and Cognitive Function in Elderly Women: A Population-Based Study
Authors: Komulainen Pirjo , Kivipelto Miia , Lakka Timo A. , Hassinen Maija , Helkala Eeva-Liisa , Patja Kristiina , Nissinen Aulikki , Rauramaa Rainer
Published: September 2007

Objective: Several vascular risk factors have been linked to cognitive decline. However, little is known about the association between the atherosclerotic process and cognitive impairment. We investigated whether carotid intima-media thickness (IMT) predicts the risk of cognitive impairment and whether the putative impairment is specific for some cognitive domains. Methods: A 12-year population-based follow-up study was performed for a total of 91 women, aged 60–70 years at baseline. Ultrasonographically assessed carotid artery IMT and the Mini-Mental State Examination test were performed at baseline and 12-year follow-up. A detailed cognitive evaluation for memory and cognitive speed was performed in 2003. The mean of left and right carotid bifurcation IMT was used in the analyses for association with the risk for poor cognitive speed and memory. Results: Increased IMT at baseline was an independent predictor for poor memory (β = –5.004, 95% confidence interval = –7.74 to –2.27; p = 0.001) and cognitive speed (β = 2.562, 95% confidence interval = 1.19–4.94; p = 0.035) at 12-year follow-up after adjustment for age, education, depression, plasma LDL cholesterol, systolic blood pressure, cardiovascular disease, hormone replacement therapy, smoking, alcohol consumption and physical activity. The risk for poor memory (p = 0.023 for linear trend) and cognitive speed (p = 0.070 for linear trend) increased with increasing IMT tertiles. Conclusions: Carotid IMT predicts an increased risk for cognitive impairment, particularly poor memory and cognitive speed, in elderly women.
Transport Barriers in Transscleral Drug Delivery for Retinal Diseases
Authors: Kim Stephanie H. , Lutz Robert J. , Wang Nam Sun , Robinson Michael R.
Published: September 2007

Transscleral delivery has emerged as an attractive method for treating retinal disorders because it offers localized delivery of drugs as a less invasive method compared to intravitreal administration. Numerous novel transscleral drug delivery systems ranging from microparticles to implants have been reported. However, transscleral delivery is currently not as clinically effective as intravitreal delivery in the treatment of retinal diseases. Transscleral drug delivery systems require drugs to permeate through several layers of ocular tissue (sclera, Bruch’s membrane-choroid, retinal pigment epithelium) to reach the neuroretina. As a result, a steep drug concentration gradient from the sclera to the retina is established, and very low concentrations of drug are detected in the retina. This steep gradient is created by the barriers to transport that hinder drug molecules from successfully reaching the retina. A review of the literature reveals 3 types of barriers hindering transscleral drug delivery: static, dynamic and metabolic. While static barriers have been examined in detail, the literature on dynamic and metabolic barriers is lacking. These barriers must be investigated further to gain a more complete understanding of the transport barriers involved in transscleral drug delivery.
Intrafamilial Clinical Heterogeneity Associated with a Novel Mutation of the Retinal Degeneration Slow/Peripherin Gene
Authors: Simonelli Francesca , Testa Francesco , Marini Valeria , Interlandi Emanuela , Rossi Settimio , Pognuz Derri Roman , Virgili Gianni , Garrè Cecilia , Bandello Francesco
Published: September 2007

Aims: To identify the phenotypic variations in 6 related individuals affected by a novel mutation in the retinal degeneration slow/peripherin gene. Methods: Ten family members underwent ophthalmologic assessment with slit-lamp biomicroscopy, dilated fundus examination, fundus photography, autofluorescence imaging and electrophysiological tests. Genomic DNA was extracted from blood samples of all family members (n = 15) using the standard salting-out procedure. Results: The novel C165R mutation was identified in 8 individuals. Of these 8 patients, only 6 gave consent to the clinical study. They had a retinal disease characterized by an adulthood onset of symptoms, and their best corrected visual acuity was between 20/50 and 20/20. Fundus examination showed that 3 patients had typical fundus flavimaculatus: 1 had butterfly-shaped pattern dystrophy and 2 had incipient retinal changes. Conclusion: We identified a novel mutation of the retinal degeneration slow/peripherin gene in a family affected by different patterns of retinal dystrophy. This is the first report of an association of fundus flavimaculatus with butterfly-shaped pattern dystrophy.
Clonal Pluralization of Self, Relatives and Others
Authors: Ranjan Sanjeev , Chandra Prabha S. , Gupta Arun K. , Prabhu Santosh
Published: September 2007

Delusional misidentification syndromes are a fascinating aspect of the psychopathology of psychotic patients. Recent psychiatric literature has mentioned a new variant of misidentification syndrome. Termed ‘clonal pluralization’, it differs from the typical misidentification syndromes. Essentially, the basic assumption of clonal pluralization is the belief that there are many physically and psychologically identical copies of a given original. This report presents a patient with schizophrenia who believed in triplicate copies of herself and others.
Year-to-Year Variation in Release of Bet v 1 Allergen from Birch Pollen: Evidence for Geographical Differences between West and South Germany
Authors: Buters Jeroen T.M. , Kasche Anna , Weichenmeier Ingrid , Schober Wolfgang , Klaus Sabrina , Traidl-Hoffmann Claudia , Menzel Annette , Huss-Marp Johannes , Krämer Ursula , Behrendt Heidrun
Published: September 2007

Background: The release of the aeroallergen Bet v 1 from pollen is a major determinant in the etiology of allergic airway disease due to birch pollen. Objective: We determined the release of the major birch pollen allergen Bet v 1 from pollen of birch trees growing in 2 different geographic regions in Germany for 2 consecutive years. Methods: Catkins were collected during pollination in 2002 and 2003 from 82 healthy trees in South (Munich) and West Germany (North Rhine-Westphalia). The release of Bet v 1 from pollen samples was determined by a Bet v 1-specific ELISA. Results: Pollen from South Germany released about 3 times more Bet v 1 than those from West Germany in both 2002 and 2003 (p = 0.034 and p = 0.007, respectively). This was independent of the number of pollen during the pollen flight season. In 2003, the release of Bet v 1 from pollen was more than 5 times higher than in 2002 in both regions (South Germany 6.1 times, p < 0.001; West Germany 5.4 times, p = 0.003). Conclusions: Despite large individual differences, there seem to be regional and year-to-year variations in Bet v 1 release from birch pollen. Therefore, the combination of pollen count and release of Bet v 1 from this pollen must be assessed to estimate Bet v 1 exposure reliably.
Dietary Supplementation with Lactic Acid Bacteria Attenuates the Development of Atopic Dermatitis-Like Skin Lesions in NC/Nga Mice in a Strain-Dependent Manner
Authors: Wakabayashi Hideyuki , Nariai Chie , Takemura Fumiyo , Nakao Wakako , Fujiwara Daisuke
Published: September 2007

Background: Dietary supplementation with lactic acid bacteria (LAB) is a potential approach to the prevention and manipulation of allergic diseases such as atopic dermatitis (AD). However, the influence of different bacterial strains and their immunomodulating capacities is still largely unknown. Methods: AD-like skin lesions were induced by sensitization to and repeated challenges with picrylchloride in the Th2-skewed NC/Nga mouse strain. The effects of LAB supplementation were assessed over time by monitoring clinical scores and plasma IgE levels. In some cases, mast cell infiltration, cutaneous hypersensitivity responses and cytokine mRNA expression in auricles were also examined. Additionally, cytokine production in vitro and cytokine mRNA accumulation in major lymphoid tissues were measured, comparing Lactobacillus paracasei KW3110 with L. rhamnosus GG (LGG). Results: Supplementation with KW3110 significantly reduced the development of AD-like skin lesions, accompanied by less mast cell infiltration and lower plasma IgE levels. KW3110 also suppressed immediate hypersensitivity reactions and IL-4 mRNA expression in the auricles. These preventive effects sustained when supplementation was terminated; moreover, inhibitory effects were also observed even when supplementation was initiated after the onset of symptoms. In accordance with its effects on IL-12 and IL-4 production in vitro, KW3110 prevented the emergence of clinical symptoms more effectively than LGG in vivo. Conclusions: Supplementation with KW3110 significantly attenuated the onset and exacerbation of AD-like symptoms in NC/Nga mice. The effects were more prominent than those obtained with LGG, suggesting the importance of differences between LAB strains and their immunomodulating capacity.
IL-10-Inducing Adjuvants Enhance Sublingual Immunotherapy Efficacy in a Murine Asthma Model
Authors: Van Overtvelt Laurence , Lombardi Vincent , Razafindratsita Alain , Saint-Lu Nathalie , Horiot Stéphane , Moussu Hélène , Mascarell Laurent , Moingeon Philippe
Published: September 2007

Background: IL-10-inducing adjuvants could enhance the efficacy of allergy vaccines in establishing allergen-specific tolerance.The aim of this study wasto identify such adjuvants using in vitro cultures of human and murine cells and to evaluate them in a therapeutic murine model of sublingual immunotherapy (SLIT). Methods: Adjuvants stimulating IL-10 gene expression by human or murine immune cells were tested sublingually in BALB/c mice sensitized to ovalbumin (OVA), assessing the reduction in airway hyperresponsiveness (AHR) by whole-body plethysmography. The induction of regulatory T cells (Treg) was evaluated using phenotypic and functional assays. T-cell proliferation in cervical lymph nodes (LNs) was assessed following intravenous transfer of CFSE-labelled OVA-specific T cells and FACS analysis. Results: A combination of 1,25-dihydroxyvitamin D3 plus dexamethasone (VitD3/Dex) as well as Lactobacillus plantarum were found to induce IL-10 production by human and murine dendritic cells (DCs). The former inhibits LPS-induced DC maturation, whereas L. plantarum induces DC maturation. Following stimulation with VitD3/Dex-pretreated DCs, CD4+ naïve T cells exhibit a Treg profile.In contrast, a Th1/Treg pattern of differentiation is observed in the presence of DCs treated with L. plantarum. Both adjuvants significantly enhance SLIT efficacy in mice, in association with either induction of Foxp3+ Treg cells (for VitD3/Dex) or proliferation of OVA-specific T cells in cervical LNs (for L. plantarum). Conclusions: Both VitD3/Dex and L. plantarum polarize naïve T cells towards IL-10-expressing T cells, through distinct mechanisms. As adjuvants, they both enhance SLIT efficacy in a murine asthma model.
Ligation of Toll-Like Receptor 3 Differentially Regulates M2 and M3 Muscarinic Receptor Expression and Function in Human Airway Smooth Muscle Cells
Authors: Morishima Hirotaka , Kajiwara Keiichi , Akiyama Kazuo , Yanagihara Yukiyoshi
Published: September 2007

Background: Viral infection causes asthma exacerbations and airway hyperreactivity. Toll-like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA) of viral or synthetic origin in a fashion different from protein kinase R (PKR). The aim of this study was to examine the expression and function of TLR3 in human airway smooth muscle (ASM) cells. Methods: Expression of TLR3 and muscarinic receptor (MR), histamine receptor (HR), and cysteinyl leukotriene receptor (CysLTR) subtypes was analyzed by quantitative real-time PCR, flow cytometry, or Western blotting. It was assessed whether ASM cells respond to polyinosinic-polycytidylic acid (poly I:C), a synthetic analog of dsRNA, with alterations in M2R, M3R, H1R, and CysLT1R expression. The function of these subtypes was evaluated by cholinergic regulation of forskolin-stimulated cyclic AMP accumulation or by mobilization of intracellular calcium upon stimulation. Results: ASM cells expressed TLR3 and PKR, and intracellular TLR3 expression was demonstrated. Poly I:C caused decreased M2R and increased M3R expression, without affecting H1R and CysLT1R expression. Poly I:C-treated cells showed decreased cholinergic inhibition of forskolin-stimulated cyclic AMP accumulation and enhanced calcium flux in response to acetylcholine, but not to histamine and LTD4. These modulating effects of poly I:C were reversed by chloroquine, but not by 2-aminopurine. Conclusions: The data indicate that poly I:C internalized by ASM cells differentially regulates M2R and M3R expression and function by interacting with TLR3 rather than with PKR, suggesting that these changes may contribute to airway hyperreactivity.
Real-Time Monitoring of Streptococcus mutans Biofilm Formation Using a Quartz Crystal Microbalance
Authors: Tam K. , Kinsinger N. , Ayala P. , Qi F. , Shi W. , Myung N.V.
Published: September 2007

The ability of Streptococcus mutans, a well-known etiological agent in dental caries, to attach and form a biofilm is an important key to its virulence. The effects of various environmental factors (i.e. sucrose concentration, flow rate and temperature as well as genetic manipulations) on the capability of S. mutans (UA 140) to attach, form and detach were monitored in situ using quartz crystal microbalance. The biofilm growth rate was much slower than that of planktonic growth. Greater availability of sucrose contributed to biofilms with less lag time, lower doubling times and earlier detachment. Flow rate experiments showed that as the shear stress was reduced, the maximum mass accumulated also decreased. However, the detachment process was independent of shear force, perhaps indicative of quorum sensing. Increasing the incubation temperature from 37 to 40°C extended the lag period and inhibited the ability of the biofilm to attach readily. Absence of either the ciaH, luxS, gtfB or gtfC genes also greatly affected the ability of the S. mutans to adhere to a surface in comparison to the wild type. Quartz crystal microbalance results indicate that the gtfC gene possibly has a greater contribution to biofilm attachment than the gtfB gene, that the presence of the luxS gene is critical for attachment and that the ciaH gene primarily affects the initial reversible attachment of the biofilm.
Histamine and the Regulation of Body Weight
Authors: Jørgensen Emilie A. , Knigge Ulrich , Warberg Jørgen , Kjær Andreas
Published: September 2007

Energy intake and expenditure is regulated by a complex interplay between peripheral and central factors. An exhaustive list of peptides and neurotransmitters taking part in this complex regulation of body weight exists. Among these is histamine, which acts as a central neurotransmitter. In the present article we review current evidence pointing at an important role of histamine in the regulation of appetite and metabolism. Studies using both knockout mouse models as well as pharmacological studies have revealed that histamine acts as an anorexigenic agent via stimulation of histamine H1 receptors. One effect of histamine in the regulation of appetite is to act as a mediator of the inhibitory effect of leptin on appetite. It seems that histamine may attenuate and delay the development of leptin resistance in high-fat-diet-induced obesity. Furthermore, histamine may also act to accelerate lipolysis. Based on the current evidence of the involvement of histamine in the regulation of body weight, the histaminergic system is an obvious target for the development of pharmacological agents to control obesity. At present, H3 receptor antagonists that stimulate the histaminergic system may be the most promising histaminergic drugs for antiobesity therapy.
Gene Polymorphisms and Serum Alpha-2-Heremans-Schmid Levels in Italian Haemodialysis Patients
Authors: Cozzolino Mario , Biondi Maria Luisa , Galassi Andrea , Gallieni Maurizio , Melzi d’Eril Gian Vico , Brancaccio Diego
Published: September 2007

Background: Vascular calcification (VC) and accelerated atherosclerosis are major causes of cardiovascular (CV) morbidity and mortality in haemodialysis (HD) patients. Inhibitory proteins are associated with reduced VC and may play a key role in preventing CV in chronic kidney disease (CKD) patients. Fetuin-A, also known as α2-Heremans-Schmid glycoprotein (AHSG), is a circulating plasma protein with inhibitory effects on VC that has been associated with inflammation and CV mortality in HD patients. In the present study, we investigated the associations between serum fetuin-A levels and its gene (AHSG) polymorphisms in an Italian HD population. Methods: Ninety-six patients on stable chronic HD treatment and 57 healthy controls were genotyped for the common polymorphisms on the AHSG (T256S). In addition, serum fetuin-A levels were tested. Results: In this study, serum fetuin-A levels were lower in HD patients (0.35 ± 0.11 g/l) compared with healthy controls (0.62 ± 0.31 g/l, p < 0.05). In both HD patients and the control group, the distribution of the AHSG gene did not show significant association between low serum fetuin-A levels and the Ser/Ser genotype, known to be associated with a higher CV mortality risk in the HD population. Moreover, the distribution of AHSG gene polymorphisms in HD patients and in healthy controls was similar. Conclusions: In contrast with previous reports, this study suggests that CKD patients on HD treatment have a similar polymorphism distribution of the AHSG gene compared with the normal population and that the reduction in serum fetuin-A levels in Italian HD patients is not associated with an alteration in the distribution of AHSG T256S polymorphisms.
Distribution of Diurnal Primate Species in Togo and Bénin
Authors: Campbell Geneviève , Teichroeb Julie , Paterson James D.
Published: September 2007

The Dahomey Gap, a strip of forest-savanna mosaic that interrupts the lowland rainforests of West Africa, is supposed to have acted as a natural barrier to the distribution of forest-dwelling mammals. However, few thorough mammal surveys have been conducted in this region. This study intended to gather distributional data and help clarify the distribution limits of diurnal primates occurring within this ‘Gap’. Southern Togo and Bénin were surveyed between June and November 2003. The surveys consisted of interviews with hunters and guards from parks and reserves, and walking surveys of forests. As a result, seven diurnal primate species are listed for Togo and Bénin.