bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensitization and Translocation of TRPV1 by Insulin and IGF-I
Authors: Van Buren Jeremy J , Bhat Satyanarayan , Rotello Rebecca , Pauza Mary E , Premkumar Louis S
Published: April 2005

Insulin and insulin-like growth factors (IGFs) maintain vital neuronal functions. Absolute or functional deficiencies of insulin or IGF-I may contribute to neuronal and vascular complications associated with diabetes. Vanilloid receptor 1 (also called TRPV1) is an ion channel that mediates inflammatory thermal nociception and is present on sensory neurons. Here we demonstrate that both insulin and IGF-I enhance TRPV1-mediated membrane currents in heterologous expression systems and cultured dorsal root ganglion neurons. Enhancement of membrane current results from both increased sensitivity of the receptor and translocation of TRPV1 from cytosol to plasma membrane. Receptor tyrosine kinases trigger a signaling cascade leading to activation of phosphatidylinositol 3-kinase (PI(3)K) and protein kinase C (PKC)-mediated phosphorylation of TRPV1, which is found to be essential for the potentiation. These findings establish a link between the insulin family of trophic factors and vanilloid receptors.
Reported use of data monitoring committees in the main published reports of randomized controlled trials: a cross-sectional study
Authors: Sydes Matthew R , Altman Douglas G , Babikera Abdel B , Parmar Mahesh KB , Spiegelhalter David J ,   DAMOCLES group
Published: April 2005

Background We describe a review of published main reports of randomized controlled trials (RCTs), in order to measure the frequency of reported use of data monitoring committees (DMCs) and factors associated with reported DMC use. Methods Twenty-four higher impact general and specialist medical journals were handsearched for main reports of RCTs in order to provide a cross-sectional sample of trials published in the year 2000. Additionally, the same general medical journals were handsearched for 1990 to allow a comparison across time.

Results Of 662 RCTs published in 2000, 120 (18%) explicitly reported using a DMC, while 107 (16%) reported planned interim analyses. Overall, about a quarter (24%) reported at least one of these. A higher proportion of trials reported using a DMC in 2000 than 1990 (70/282, 25% versus 21/204, 10%) in the general medical journals. Logistic regression models suggested the more important variables associated with increased reported DMC use were: later year of publication, publication in general medical journal, survival-based endpoint, multicentre trial, increasing number of patients recruited, at least one arm involving a placebo, at least one arm involving a drug, factorial design and USA involvement in the trial.

Conclusions In 2000, about a quarter of main RCT reports mention use of a DMC. Actual use of DMCs is likely to be somewhat greater. Reporting use of a DMC was more likely for larger and longer trials among other factors. We believe the factors affecting reported use affect actual use. It is recommended that when a DMC oversees a trial, brief details should be explicitly included in the main trial paper. Standard nomenclature for DMCs is recommended.
Systematic qualitative review of the literature on data monitoring committees for randomized controlled trials
Authors: Sydes Matthew R , Spiegelhalter David J , Altman Douglas G , Babiker Abdel B , Parmar Mahesh KB ,   DAMOCLES Group
Published: April 2005

Aims To systematically review the published literature on data monitoring committees (DMCs) for randomized controlled trials (RCT) and summarize information and opinions on best practice. This was part of the DAMOCLES project. Methods A systematic and comprehensive search of five online bibliographic databases was performed, identifying 4007 potentially relevant articles. These were assessed in two stages by the authors. The 84 most relevant articles were agreed and were supplemented with extracts from 16 books: ultimately, 100 sources were reviewed. A series of 23 questions plus subquestions were developed to structure the data extraction and interpretation process.

Results Much has been written about DMCs but by a rather small community of authors. The papers included some results of surveys, but were mainly opinion pieces based on the authors' beliefs, practices and experiences. There is a lack of empirical evidence for many aspects of DMCs. There was a great range of detail in the literature relating to the prespecified questions. It was generally agreed that interim monitoring of accumulating data was necessary in some form for most trials. Questions such as membership of the DMC featured widely in the literature with opinions and practice ranging from 3–20 members, of whom between none and all should be independent. There was a consensus that formal statistical methods should be used as tools to guide decision making rather than as hard rules. Conversely, topics such as the training and experience required for DMC membership were discussed in very few papers.

Conclusions There is a consensus in the published literature in a number of areas, although there are many different models for structure and functions of a DMC. While uncertainty remains about some issues, it is strongly recommended that an explicit set of guidelines (Charter) is prepared for each DMC prior to the start of the trial specifying clearly how it will operate.
Sensitivity analysis of causal inference in a clinical trial subject to crossover
Authors: Xie Hui , Heitjan Daniel F
Published: April 2005

In many clinical trials it is possible for some subjects to cross over between treatment arms. One can evaluate the effect of crossover by modeling it as a missing-data problem, where for subjects who cross over, one treats the unobserved value of the outcome in the original randomization arm as the missing data. The as-treated analysis is invalid if the crossover is nonignorable, in the sense that the crossovers represent a nonrandom sample of the randomized subjects [1,2]. A recent area of general interest is the development of methods for measuring the sensitivity of inferences to nonignorability in the missing-data mechanism; one such approach is that of Troxel et al. [3]. In this paper we apply their method to the problem of measuring sensitivity to nonignorable crossover in randomized trials, extending it to the case where the crossover mechanism may differ between arms. Our method allows us to identify circumstances under which the as-treated analysis may be more or less sensitive to nonignorable crossover. We illustrate it with the example of a randomized clinical trial (RCT) in multiple sclerosis and a study of the effect of military service on income.
Breast cancer cells induce stromal fibroblasts to express MMP-9 via secretion of TNF-α and TGF-β
Authors: Stuelten Christina H. , Byfield Stacey DaCosta , Arany Praveen R. , Karpova Tatiana S. , Stetler-Stevenson William G. , Roberts Anita B.
Published: April 2005

We used 2D-cocultures employing fibroblasts of different genetic backgrounds and MCF10A-derived human breast epithelial cells of increasingly malignant potential to investigate tumor-stroma interactions in breast cancer and to identify possible signaling pathways involved. Tumor cells induced expression of matrix-metalloproteinase 9 (MMP-9) in fibroblasts in a pattern dependent on the degree of their malignancy. In-situ zymography localized the main gelatinolytic activity around stromal cells in cocultures and xenografted tumors. Use of Smad3 knockout fibroblasts, small molecule inhibitors, and neutralizing antibodies showed that MMP-9 expression was induced by tumor cell-derived TNF-α and TGF-β, dependent on Smad-, Ras-, and PI3-kinase-signaling, and likewise modulated by subsequent HGF- and EGF-signaling. Together, our results indicate that MMP-9 levels in tumor fibroblasts are regulated by a complex tumor-stroma cross-talk, involving multiple ligands and cellular signaling pathways.
Functional contribution of Pds5 to cohesin-mediated cohesion in human cells and Xenopus egg extracts
Authors: Losada Ana , Yokochi Tomoki , Hirano Tatsuya
Published: April 2005

Sister chromatid cohesion is essential for proper segregation of the genome in mitosis and meiosis. Central to this process is cohesin, a multi-protein complex conserved from yeast to human. Previous genetic studies in fungi have identified Pds5/BimD/Spo76 as an additional factor implicated in cohesion. Here we describe the biochemical and functional characterization of two Pds5-like proteins, Pds5A and Pds5B, from vertebrate cells. In HeLa cells, Pds5 proteins physically interact with cohesin and associate with chromatin in a cohesin-dependent manner. Depletion of the cohesin subunit Scc1 by RNA interference leads to the assembly of chromosomes with severe cohesion defects. A similar yet milder set of defects is observed in cells with reduced levels of Pds5A or Pds5B. In Xenopus egg extracts, mitotic chromosomes assembled in the absence of Pds5A and Pds5B display no discernible defects in arm cohesion, but centromeric cohesion is apparently loosened. Unexpectedly, these chromosomes retain an unusually high level of cohesin. Thus, Pds5 proteins seem to affect the stable maintenance of cohesin-mediated cohesion and its efficient dissolution during mitosis. We propose that Pds5 proteins play both positive and negative roles in sister chromatid cohesion, possibly by directly modulating the dynamic interaction of cohesin with chromatin. This idea would explain why cells lacking Pds5 function display rather complex and diverse phenotypes in different organisms.
Effect of accommodating sucking and nosing on the behaviour of artificially reared piglets
Authors: Widowski T M , Yuan Y , Gardner J M
Published: April 2005

Neonatal piglets are often used in biomedical research applications that require artificial rearing. Social housing can be problematic because the piglets develop belly nosing, navel and ear sucking that can result in injury. Our objective was to determine the effectiveness of using feeding devices that provide various opportunities for sucking and nosing behaviour on reducing piglet-directed behaviour of group-housed laboratory piglets. Fifteen piglets were used in each of four trials. The piglets nursed their dam for approximately 72 h to obtain passive immunity before transfer to a laboratory facility where they were allotted, five per group, to one of three stainless steel isolator units. Each unit featured a different style of feeding system for the delivery of milk replacer: a plastic trough (T), a nipple (N) mounted on a smooth plexiglass wall, or a nipple mounted on a pliant bag of sterile water (artificial udder [AU]). Each system had five feeding spaces so that all piglets fed simultaneously. Milk was provided at 6-h intervals, and behaviour was recorded on alternate days for 12 days post-weaning. Although trough-fed piglets began to eat much sooner than those piglets fed from nipples, time spent nosing, chewing or sucking on pen-mates and belly nosing were markedly higher in T piglets than in either N or AU, overall (mean: P <0.05) and over time (quadratic: P <0.05). Over time, N piglets developed a stereotypic snout rubbing on the wall behind the nipples, while AU piglets massaged and often fell asleep in contact with the udder from day 2 of the trial. Resting patterns were also affected. N and AU piglets settled down to rest more quickly (P <0.01) and spent significantly more time resting in the hour following feeding than T piglets (P <0.05). A feeding device that accommodates both sucking and massage can significantly reduce piglet-directed behaviour and may facilitate social housing of artificially reared piglets.
Development of a gut perfusion model as an alternative to the use of live fish
Authors: Nematollahi Amin , Decostere Annemie , Ducatelle Richard , Haesebrouck Freddy , Pasmans Frank
Published: April 2005

An alternative fish model with the principal aim of studying the interaction between fish pathogens and the intestinal tissue was developed. The preparation consisted of an excised gut tractus from rainbow trout ( Oncorhynchus mykiss), perfused through cannulation of the aorta intestinalis ventralis with filtered and heparinized Cortland + dextran 1% as the perfusion fluid. This perfusion fluid was delivered by means of a drip. The perfused gut tractus was suspended in a circular bath filled with Ringer solution, which was aerated and kept at a constant temperature of 12°C. Unperfused gut placed in Ringer solution at the same temperature served as the negative control. Perfusion was effective in maintaining the gut in a healthy condition for at least 60 min with only slight oedema and sloughing of the epithelium. Conversely, the unperfused gut revealed excessive tissue degeneration and severe necrosis.
The isolated working heart model in infarcted rat hearts
Authors: Itter G , Jung W , Schoelkens B A , Linz W
Published: April 2005

Congestive heart failure (CHF) is one of the most common causes of death in western countries. The aim of this study was to establish and validate the working heart model in rat hearts with CHF. In the rat model the animals show parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The focus of attention was the evaluation of cardiodynamics (e.g.contractility) in the isolated 'working heart' model. The geometric properties of the left ventricle were measured by planimetry (stereology). Formulae available in the past for determining certain parameters in the working heart model (e.g.external heart work) have to be fitted to the circumstances of the infarcted rat hearts with its different organ properties.

CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive rats (SHR/NHsd) by creating a permanent (8 week) occlusion of the left coronary artery, 2 mm distal to the origin from the aorta, by a modified technique (Itter et al. 2004). This resulted in a large infarction of the free left ventricular wall.

We were able to establish and adapt a new and predictive working heart model in spontaneously hypertensive rat hearts with myocardial infarction (MI) 8–12 weeks after coronary artery ligation. At this stage the WKY rat did not show any symptoms of CHF. The SHR rat represented characteristic parameters and symptoms that could be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III–IV). Upon inspection, severe clinical symptoms of CHF such as dyspnoea, subcutaneous oedema, palebluish limbs and impaired motion were prominent. On necropsy the SHR showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. In the working heart model the infarcted animals showed reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd than in the Wistar Kyoto rat (WKY/NHsd).

The aim for the future is to find a causal therapy of heart failure treatment. At present, only palliative therapy is possible for patients with heart failure. For this reason the working heart model in CHF rat hearts should provide a valuable method for early testing of new therapeutic approaches for patients with CHF.
Biopsy of the mouse prostate
Authors: Harmelin A , Danon T , Kela I , Brenner O
Published: April 2005

Many transgenic and knockout mouse models of prostate cancer have become available over the past decade. In this paper we describe a simple biopsy technique of the murine prostate. This technique allows sequential follow-up of the prostate in an individual mouse. Its use could also reduce the number of mice used in studies of the prostate gland.
Blood sampling from the cranial vena cava in the Norway rat (Rattus norvegicus)
Authors: Jekl Vladimír , Hauptman Karel , Jeklová Edita , Knotek Zdeněk
Published: April 2005

This paper describes blood sampling from the cranial vena cava (CVC) in the Norway rat. In order to limit stress, the blood sampling should be done under short-term inhalation anaesthesia, for example, an oxygen/isoflurane mixture. The injection site is just cranial to the first rib, 0.3–0.8 cm lateral to the manubrium when the animal is in dorsal recumbency. The needle, attached to a syringe, is inserted at 30° in the direction of the opposite femoral head. After penetration of the skin, negative pressure is developed in the syringe and the insertion of the needle is continued for another 0.2–1 cm in the given direction until blood begins to flow. The amount of blood sampled ranges from 0.8 to 2.5 mL depending on the body weight of the patient. A trial on 50 rats aged 5–24 months included 25 rats sampled once, eight rats sampled twice with an interval of seven days, 11 rats sampled twice with an interval of three weeks and four rats sampled four times with intervals of four weeks – a total of 87 blood samplings. The serious complications quoted in association with blood sampling from the CVC in other experimental animals (vascular lacerations, heart puncture, serious haemorrhage, tracheal and throat trauma) were not observed in our study. There were only four blood samplings (4.5%) with mild haemorrhage from the injection site, due to erroneous sampling from the jugular vein.
A novel method for activity monitoring in small non-human primates
Authors: Mann T M , Williams K E , Pearce P C , Scott E A M
Published: April 2005

Patterns of spontaneous activity are valuable reflections of well-being in animals and humans and, because of this, investigations have frequently incorporated some form of activity monitoring into their studies. It is widely believed that activity monitoring, alongside assessments of general behaviour, should be included in initial CNS safety pharmacology screening. As the number of marmoset studies having actimetry as their focus, or as an adjunct, is increasing, we wished to evaluate an alternative approach to those commonly used. The method is based on miniaturized accelerometer technologies, currently used for human activity monitoring.

Actiwatch®-Minis were used to monitor the activity of two groups of differently housed marmosets for 14 consecutive days. Group A consisted of four mixed-sex pairs of animals and group B comprised eight group-housed males. Activity profiles were generated for weekday and weekend periods. The devices captured quantifiable data which showed differences in total activity between the two differently housed groups and revealed intragroup variations in the temporal spread of activity between weekdays and weekends. The Actiwatch®-Mini has been shown to generate retrospective, data-logged activity counts recorded from multiple animals in a single arena by means of non-invasive monitoring.
Quantitative assessment of mouse skin transplant rejection using digital photography
Authors: Schwoebel F , Barsig J , Wendel A , Hamacher J
Published: April 2005

Mouse skin transplantation is an established in vivo model used to investigate the T-cell-mediated immune response of acute allograft rejection. The critical endpoint of this model is complete rejection of the allograft. However, visual judgement of this end stage of rejection is an arbitrary process and difficult to standardize. To overcome this problem, we established a monitoring method based on digital photography. Serial pictures from skin allografts of individual animals (C57BL/6 on BALB/c) were taken with a digital camera mounted on a microsurgical microscope. Thereby, the description and the correct assessment of early stages of rejection were possible due to the magnification of grafts by the microscope. Rejection scores were introduced to describe different stages from retained to completely rejected grafts. With cyclosporine A as a standard immunosuppressive treatment, we showed that early stages of skin rejection were unambiguously identified. This procedure allows the earlier termination of the experiment and reduction of animal distress, and it can be re-evaluated anywhere and any time after completion.

This study demonstrates the suitability of monitoring experimental skin allograft rejection by digital photography, entailing several refinements in animal experimentation, both for the researcher and for the animal.
Mycotoxins in laboratory rodent feed
Authors: Waldemarson A Halldén , Hedenqvist P , Salomonsson A-C , Häggblom P
Published: April 2005

Twenty-one batches of fixed-formula rodent diets from three feed manufacturers were tested for the presence of five mycotoxins: deoxynivalenol (DON), nivalenol (NIV), HT-2 toxin, T-2 toxin and ochratoxin A (OTA). Five batches were also tested for the presence of zearalenone (ZEN) and six batches for aflatoxins. Detectable levels of DON (up to 298 μg/kg), NIV (up to 118 μg/kg), OTA (up to 3.1 μg/kg) or ZEN (up to 26.7 μg/kg) were found in samples from all manufacturers. Three batches contained two (DON or NIV and OTA or ZEN) and one batch contained three (DON, OTA and ZEN) different mycotoxins. Aflatoxins, T-2 and HT-2 were not detected in any of the batches. The concentrations of mycotoxins detected in the feed were low, but indicated that feed ingredients, probably the cereal ingredients, were contaminated by mycotoxins. Since mycotoxins are known to have toxic and/or immunosuppressive effects, non-contaminated ingredients should be used for production of laboratory animal feed. The results imply that an improved quality control of ingredients used for laboratory rodent feed should be implemented.
Indicators for post-surgery recovery in Mongolian gerbils (Meriones unguiculatus)
Authors: Weinandy R , Fritzsche P , Weinert D , Wenkel R , Gattermann R
Published: April 2005

Telemetric investigations of various parameters are widely used to estimate an animal's state. However, the implantation of the transmitters includes anaesthesia and surgery and has short and longer lasting impacts on the studied object. The aim of the present paper was to evaluate these effects in Mongolian gerbils, namely the hypothermia caused by the anaesthetic and the enduring disturbance of daily rhythmicity until complete recovery. The surgery associated with the implantation of the transmitters differed both in severity and type of anaesthesia. Whereas normal values of body temperature were restored within hours, restoration of daily rhythm required several days, depending on the severity of the surgical procedure. Also, the sensitivity of the body temperature to activity changes was different until the rhythms were re-established. A method based on the rhythm magnitude and shape was proposed to estimate the time until complete recovery of the animals.
A Model of Organizational Integration, Implementation Effort, and Performance
Authors: Barki Henri , Pinsonneault Alain
Published: April 2005

The notion of integration is central to the understanding of organizations in general as well as of contemporary phenomena such as e-commerce, virtual organizations, virtual teams, and enterprise resource planning (ERP) implementation. Yet, the concept of integration is ill-defined in the literature, and the impact of achieving high levels of integration is not well understood. The present paper addresses these issues. Drawing on the literature of several fields, this paper proposes the concept of organizational integration (OI), which is defined as the extent to which distinct and interdependent organizational components constitute a unified whole. Six types of OI are identified: two intraorganizational OI (internal-operational, internal-functional) and four interorganizational OI (external-operational-forward, external-operational-backward, external-operational-lateral, and external-functional). This paper then presents a model and develops 14 propositions to predict (1) the effort needed to implement different types of OI, (2) the impact different types of OI will have on organizational performance, and (3) how six factors (interdependence, barriers to OI, mechanisms for achieving OI, environmental turbulence, complexity reduction mechanisms, and organizational configurations) influence the relationship between OI types, implementation effort, and organizational performance. The OI framework and model are then used to develop 14 propositions for ERP implementation research and to explain the findings of recent research on integration.
Anticoagulation Monitoring Part 1: Warfarin and Parenteral Direct Thrombin Inhibitors
Authors: Spinler Sarah A , Nutescu Edith A , Smythe Maureen A , Wittkowsky Ann K
Published: April 2005

OBJECTIVE:

To review the availability, mechanisms, limitations, and clinical application of point-of-care (POC) devices used in the management of warfarin and parenteral direct thrombin inhibitors.

DATA SOURCES:

Scientific articles were identified through a MEDLINE search (1966–August 2004), manufacturer Web sites, additional references listed in articles and Web sites, and abstracts from scientific meetings.

STUDY SELECTION AND DATA EXTRACTION:

English-language literature from clinical trials was reviewed to evaluate the accuracy, reliability, and clinical application of POC monitoring devices.

DATA SYNTHESIS:

The prothrombin time expressed as the international normalized ratio (PT—INR) is a well-established test for monitoring warfarin anticoagulation. Multiple devices are available for POC testing. Because there is no universally accepted standard, the performance of each device is typically tested against a standard test performed in a reference laboratory. Performance of currently available devices, as measured by correlations to a standard reference laboratory PT—INR, may be considered very good and acceptable for use in patient care. Utilization of patient self-testing and patient self-monitoring of warfarin anticoagulation using POC devices is increasing. Parenteral direct thrombin inhibitors are typically monitored using a standard laboratory activated partial thromboplastin time. Some research has shown that POC monitoring of direct thrombin inhibitors using the ecarin clotting time is helpful for patients undergoing cardiopulmonary bypass surgery, although that test is not readily available.

CONCLUSIONS:

POC testing for anticoagulation therapy has been available for >20 years. Multiple POC devices are available to monitor warfarin. There is some variability in results between devices and between reagents used in the same device. Despite these limitations, POC monitoring of warfarin via the PT—INR is an integral part of clinical practice. Additional research evaluating POC monitoring of direct thrombin inhibitors is necessary.
Potential Elevation of Tacrolimus Trough Concentrations with Concomitant Metronidazole Therapy
Authors: Lee Page Robert , Klem Patrick M , Rogers Christin
Published: April 2005

OBJECTIVE:

To report the occurrence of a potential tacrolimus elevation in a renal transplant recipient after adding metronidazole to the medication regimen.

CASE SUMMARY:

A 24-year-old white man status post living-related renal transplant who had been stabilized on tacrolimus 4 mg twice daily (trough concentrations 7–10 ng/mL) for 2 months and prednisone 20 mg daily presented to the clinic with severe diarrhea. Stool cultures were positive for Clostridium difficile, and therapy with metronidazole 500 mg 4 times daily was initiated. Between days 4 and 14 of metronidazole therapy, the patient's tacrolimus trough concentration and serum creatinine level increased to maximum levels of 26.3 ng/mL and 3.3 mg/dL (baseline 1.6–1.8 mg/dL), respectively. Tacrolimus was withheld for one dose and then decreased to 1 mg twice daily. Two days after metronidazole discontinuation, tacrolimus trough concentrations dropped to 9.4 ng/mL and serum creatinine to 2.3 mg/dL, warranting a tacrolimus dose increase to 3 mg daily.

DISCUSSION:

As of April 15, 2005, one other case has been reported documenting an elevation in tacrolimus concentrations with the addition of metronidazole. The possible mechanism may be related to metronidazole's weak inhibition of CYP3A4 and, possibly, P-glycoprotein. According to the Naranjo probability scale, metronidazole was the probable cause of this adverse reaction.

CONCLUSIONS:

Coadministration of tacrolimus with metronidazole may result in elevated tacrolimus concentrations, possibly leading to tacrolimus toxicity. Practitioners should be aware of this potential interaction and closely monitor tacrolimus concentrations and renal function.
Efficacy of Sucrose to Reduce Pain in Premature Infants during Eye Examinations for Retinopathy of Prematurity
Authors: Gal Peter , Kissling Grace E , Young William O , Dunaway Kimberly K , Marsh Virginia A , Jones Susan M , Shockley Dawn H , Weaver Nicole L , Carlos Rita Q , Ransom J Laurence
Published: April 2005

BACKGROUND:

Eye examinations for retinopathy of prematurity (ROP) are painful to the neonate. The use of topical anesthetic for eye examinations to evaluate ROP is routine in our neonatal intensive care unit (NICU), but does not completely suppress painful responses. Sweet solutions have been shown to reduce procedural pain in newborns.

OBJECTIVE:

To examine whether the addition of sucrose 24% to topical anesthetic improves procedural pain control during the ROP eye examination.

METHODS:

Neonates born at ⩽30 weeks' gestation were included in this placebo-controlled, double-blind, crossover study. Patients were randomly assigned to receive treatment with either proparacaine HCl ophthalmic solution 0.5% plus 2 mL of sucrose 24% or proparacaine HCl ophthalmic solution 0.5% plus 2 mL of sterile water (placebo) prior to an eye examination. In a subsequent eye examination, each patient received the alternate treatment. Oral sucrose and sterile water were prepared in the pharmacy in identical syringes, and physicians, nurses, and pharmacists in the NICU were blinded to the treatment given. Pain was measured using the Premature Infant Pain Profile (PIPP) scoring system, which measures both physical and physiologic measures of pain, and the scores were simultaneously assessed by 2 study nurses. PIPP scores were recorded 1 and 5 minutes before and after the eye examination and during initial placement of the eye speculum. The same ophthalmologist performed all eye examinations. Several different definitions of a pain response were investigated.

RESULTS:

Twenty-three infants were studied, with 12 receiving sucrose and 11 receiving placebo as the first treatment. For 3 of the 5 definitions of pain response, patients experienced significantly less pain at speculum insertion with sucrose than with placebo. After the ROP examination, pain responses were similar with either sucrose or placebo.

CONCLUSIONS:

Oral sucrose may reduce the immediate pain response in premature infants undergoing eye examination for ROP.
Liquefaction of CCA-treated wood and elimination of metals from the solvent by precipitation
Authors: Lin Lianzhen , Hse Chung-Yun
Published: April 2005

Spent chromated copper arsenate (CCA)-treated wood was liquefied in polyethylene glycol 400/glycerin (2:1w/w). Sulfuric acid (95–98%) and ferrous salts (FeSO4·7H2O or FeCl2·4H2O) were used as catalysts and additives, respectively. The resulting liquefied CCA-treated wood was diluted with aqueous solvents and was then mixed with complexion/precipitation agents, followed by precipitation or filtration to remove the toxic metal-bearing sediment. As a result, more than 90% of Cu, Cr or As was removed.
Direct measurement of strain distribution along a wood bond line. Part 1: Shear strain concentration in a lap joint specimen by means of electronic speckle pattern interferometry
Authors: Müller Ulrich , Sretenovic Aleksandra , Vincenti Angela , Gindl Wolfgang
Published: April 2005

Phenol-resorcinol-formaldehyde (PRF) and one-component polyurethane (PUR) resins were used to manufacture single lap joint samples corresponding to EN 302-1. 3D electronic speckle pattern interferometry (ESPI), which enables measurement of spatial displacement of less than 0.1 μm, was used during tensile shear experiments to observe full-field in-plane and out-of-plane deformation of the lap joint samples and to detect strain concentrations in the vicinity of glue lines. Finite element analysis was performed to validate ESPI measurements. In general, ESPI measurements showed that in a lap joint experiment a very small volume of material close to the ends of the overlapping area is highly strained. ESPI and finite element analysis pointed out that PUR glue lines are characterised by much higher shear deformations than PRF glue lines, especially at the ends of the overlapping area. However, due to the lower Young's modulus of PUR resin compared to PRF, higher shear strains but lower shear stress concentrations can be expected in PUR, which was confirmed by the FE model.
Differentiation of indoor wood decay fungi with MALDI-TOF mass spectrometry
Authors: Schmidt Olaf , Kallow Wibke
Published: April 2005

MALDI-TOF MS differentiated mycelia within pairs each of the closely related indoor wood decay fungi Serpula lacrymans, S. himantioides, Coniophoraputena, C. marmorata, and Antrodia vaillantii, A. sinuosa. The method is thus suitable to identify unknown samples by spectrum comparison.
Identification of Glyoxalase-I as a Protein Marker in a Mouse Model of Extremes in Trait Anxiety
Authors: Krömer Simone A. , Keßler Melanie S. , Milfay Dale , Birg Isabel N. , Bunck Mirjam , Czibere Ludwig , Panhuysen Markus , Pütz Benno , Deussing Jan M. , Holsboer Florian , Landgraf Rainer , Turck Christoph W.
Published: April 2005

For >15 generations, CD1 mice have been selectively and bidirectionally bred for either high-anxiety-related behavior (HAB-M) or low-anxiety-related behavior (LAB-M) on the elevated plus-maze. Independent of gender, HAB-M were more anxious than LAB-M animals in a variety of additional tests, including those reflecting risk assessment behaviors and ultrasound vocalization, with unselected CD1 “normal” control (NAB-M) and cross-mated (CM-M) mice displaying intermediate behavioral scores in most cases. Furthermore, in both the forced-swim and tail-suspension tests, LAB-M animals showed lower scores of immobility than did HAB-M and NAB-M animals, indicative of a reduced depression-like behavior. Using proteomic and microarray analyses, glyoxalase-I was identified as a protein marker, which is consistently expressed to a higher extent in LAB-M than in HAB-M mice in several brain areas. The same phenotype-dependent difference was found in red blood cells with NAB-M and CM-M animals showing intermediate expression profiles of glyoxalase-I. Additional studies will examine whether glyoxalase-I has an impact beyond that of a biomarker to predict the genetic predisposition to anxiety- and depression-like behavior.
Using Functional Magnetic Resonance Imaging to Assess Adaptation and Size Invariance of Shape Processing by Humans and Monkeys
Authors: Sawamura Hiromasa , Georgieva Svetlana , Vogels Rufin , Vanduffel Wim , Orban G. A.
Published: April 2005

Functional magnetic resonance imaging in awake monkeys and humans was used to compare object adaptation in shape-sensitive regions of these two species under identical and different size conditions. Object adaptation was similar in humans and monkeys under both conditions. Neither species showed complete size invariance, in agreement with single-cell studies. Both the macaque inferotemporal (IT) complex and human lateral occipital complex (LOC) displayed an anteroposterior gradient in object adaptation and size invariance, with the more anterior regions being more adaptable and size invariant. The results provide additional evidence for the homology between the macaque IT cortex and human LOC but also add to the growing list of differences between human and monkey intraparietal sulcus regions.
Glutamate Receptors in Perirhinal Cortex Mediate Encoding, Retrieval, and Consolidation of Object Recognition Memory
Authors: Winters Boyer D. , Bussey Timothy J.
Published: April 2005

Object recognition is consistently impaired in human amnesia and animal models thereof. Results from subjects with permanent brain damage have revealed the importance of the perirhinal cortex to object recognition memory. Here, we report evidence from rats for interdependent but distinct stages in object recognition memory (encoding, retrieval, and consolidation), which require glutamate receptor activity within perirhinal cortex. Transient blockade of AMPA receptor-mediated synaptic transmission within perirhinal cortex disrupted encoding for short- and long-term memory as well as retrieval and consolidation. In contrast, transient NMDA receptor blockade during encoding affected only long-term object recognition memory; NMDA receptor activity was also necessary for consolidation but not retrieval. These results further demonstrate the importance of perirhinal cortex for object recognition memory and suggest that, as in the hippocampus, AMPA and NMDA receptors mediate synaptic transmission and activity-dependent synaptic plasticity, respectively, in several stages of memory processing.
Voluntary Exercise Decreases Amyloid Load in a Transgenic Model of Alzheimer's Disease
Authors: Adlard Paul A. , Perreau Victoria M. , Pop Viorela , Cotman Carl W.
Published: April 2005

Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there are few therapeutics that affect the underlying disease mechanism. Recent epidemiological studies, however, suggest that lifestyle changes may slow the onset/progression of AD. Here we have used TgCRND8 mice to examine directly the interaction between exercise and the AD cascade. Five months of voluntary exercise resulted in a decrease in extracellular amyloid-β (Aβ) plaques in the frontal cortex (38%;p= 0.018), the cortex at the level of the hippocampus (53%;p= 0.0003), and the hippocampus (40%;p= 0.06). This was associated with decreased cortical Aβ1-40 (35%;p= 0.005) and Aβ1-42 (22%;p= 0.04) (ELISA). The mechanism appears to be mediated by a change in the processing of the amyloid precursor protein (APP) after short-term exercise, because 1 month of activity decreased the proteolytic fragments of APP [for α-C-terminal fragment (α-CTF), 54% andp= 0.04; for β-CTF, 35% andp= 0.03]. This effect was independent of mRNA/protein changes in neprilysin and insulin-degrading enzyme and, instead, may involve neuronal metabolism changes that are known to affect APP processing and to be regulated by exercise. Long-term exercise also enhanced the rate of learning of TgCRND8 animals in the Morris water maze, with significant (p< 0.02) reductions in escape latencies over the first 3 (of 6) trial days. In support of existing epidemiological studies, this investigation demonstrates that exercise is a simple behavioral intervention sufficient to inhibit the normal progression of AD-like neuropathology in the TgCRND8 mouse model.
Aldolases A and C Are Ribonucleolytic Components of a Neuronal Complex That Regulates the Stability of the Light-Neurofilament mRNA
Authors: Cañete-Soler Rafaela , Reddy Konda S. , Tolan Dean R. , Zhai Jinbin
Published: April 2005

A 68 nucleotide segment of the light neurofilament (NF-L) mRNA, spanning the translation termination signal, participates in regulating the stability of the transcriptin vivo. Aldolases A and C, but not B, interact specifically with this segment of the transcriptin vitro. Aldolases A and C are glycolytic enzymes expressed in neural cells, and their mRNA binding activity represents a novel function of these isozymes. This unsuspected new activity was first uncovered by Northwestern blotting of a brainstem/spinal cord cDNA library. It was confirmed by two-dimensional fractionation of mouse brain cytosol followed by Northwestern hybridization and protein sequencing. Both neuronal aldolases interact specifically with the NF-L but not the heavy neurofilament mRNA, and their binding to the transcript excludes the poly(A)-binding protein (PABP) from the complex. Constitutive ectopic expression of aldolases A and C accelerates the decay of a neurofilament transgene (NF-L) driven by a tetracycline inducible system. In contrast, mutant transgenes lacking mRNA sequence for aldolase binding are stabilized. Our findings strongly suggest that aldolases A and C are regulatory components of a light neurofilament mRNA complex that modulates the stability of NF-L mRNA. This modulation likely involves endonucleolytic cleavage and a competing interaction with the PABP. Interactions of aldolases A and C in NF-L expression may be linked to regulatory pathways that maintain the highly asymmetrical form and function of large neurons.
Involvement of a Rac Activator, P-Rex1, in Neurotrophin-Derived Signaling and Neuronal Migration
Authors: Yoshizawa Masato , Kawauchi Takeshi , Sone Masaki , Nishimura Yoshiaki V. , Terao Mami , Chihama Kaori , Nabeshima Yo-ichi , Hoshino Mikio
Published: April 2005

Rho-family GTPases play key roles in regulating cytoskeletal reorganization, contributing to many aspects of nervous system development. Their activities are known to be regulated by guanine nucleotide exchange factors (GEFs), in response to various extracellular cues. P-Rex1, a GEF for Rac, has been mainly investigated in neutrophils, in which this molecule contributes to reactive oxygen species formation. However, its role in the nervous system is essentially unknown. Here we describe the expression profile and a physiological function of P-Rex1 in nervous system development.In situhybridization revealed thatP-Rex1is dynamically expressed in a variety of cells in the developing mouse brain, including some cortical and DRG neurons. In migrating neurons in the intermediate zone, P-Rex1 protein was found to localize in the leading process and adjacent cytoplasmic region. When transfected in pheochromocytoma PC12 cells, P-Rex1 can be activated by NGF, causing an increase in GTP-bound Rac1 and cell motility. Deletion analyses suggested roles for distinct domains of this molecule. Experiments using a P-Rex1 mutant lacking the Dbl-homology domain, a dominant-negative-like form, and small interfering RNA showed that endogenous P-Rex1 was involved in cell migration of PC12 cells and primary cultured neurons from the embryonic day 14 cerebral cortices, induced by extracellular stimuli (NGF, BDNF, and epidermal growth factor). Furthermore,in uteroelectroporation of the mutant protein into the embryonic cerebral cortex perturbed radial neuronal migration. These findings suggest that P-Rex1, which is expressed in a variety of cell types, is activated by extracellular cues such as neurotrophins and contributes to neuronal migration in the developing nervous system.
Protein-Protein Coupling/Uncoupling Enables Dopamine D2Receptor Regulation of AMPA Receptor-Mediated Excitotoxicity
Authors: Zou Shengwei , Li Lei , Pei Lin , Vukusic Brian , Van Tol Hubert H. M. , Lee Frank J. S. , Wan Qi , Liu Fang
Published: April 2005

There is considerable evidence that dopamine D2receptors can modulate AMPA receptor-mediated neurotoxicity. However, the molecular mechanism underlying this process remains essentially unclear. Here we report that D2receptors inhibit AMPA-mediated neurotoxicity through two pathways: the activation of phosphoinositide-3 kinase (PI-3K) and downregulation of AMPA receptor plasma membrane expression, both involving a series of protein-protein coupling/uncoupling events. Agonist stimulation of D2receptors promotes the formation of the direct protein-protein interaction between the third intracellular loop of the D2receptor and the ATPaseN-ethylmaleimide-sensitive factor (NSF) while uncoupling the NSF interaction with the carboxyl tail (CT) of the glutamate receptor GluR2 subunit of AMPA receptors. Previous studies have shown that full-length NSF directly couples to the GluR2CTand facilitates AMPA receptor plasma membrane expression. Furthermore, the CT region of GluR2 subunit is also responsible for several other intracellular protein couplings, including p85 subunit of PI-3K. Therefore, the direct coupling of D2-NSF and concomitant decrease in the NSF-GluR2 interaction results in a decrease of AMPA receptor membrane expression and an increase in the interaction between GluR2 and the p85 and subsequent activation of PI-3K. Disruption of the D2-NSF interaction abolished the ability of D2receptor to attenuate AMPA-mediated neurotoxicity by blocking the D2activation-induced changes in PI-3K activity and AMPA receptor plasma membrane expression. Furthermore, the D2-NSF-GluR2-p85 interactions are also responsible for the D2inhibition of ischemia-induced cell death. These data may provide a new avenue to identify specific targets for therapeutics to modulate glutamate receptor-governed diseases, such as stroke.
A Novel Positive Allosteric Modulator of the α7 Neuronal Nicotinic Acetylcholine Receptor:In VitroandIn VivoCharacterization
Authors: Hurst Raymond S. , Hajós Mihaly , Raggenbass Mario , Wall Theron M. , Higdon Nicole R. , Lawson Judy A. , Rutherford-Root Karen L. , Berkenpas Mitchell B. , Hoffmann W. E. , Piotrowski David W. , Groppi Vincent E. , Allaman Geraldine , Ogier Roch , Bertrand Sonia , Bertrand Daniel , Arneric Stephen P.
Published: April 2005

Several lines of evidence suggest a link between the α7 neuronal nicotinic acetylcholine receptor (nAChR) and brain disorders including schizophrenia, Alzheimer's disease, and traumatic brain injury. The present work describes a novel molecule, 1-(5-chloro-2,4-dimethoxy-phenyl)-3-(5-methyl-isoxazol-3-yl)-urea (PNU-120596), which acts as a powerful positive allosteric modulator of the α7 nAChR. Discovered in a high-throughput screen, PNU-120596 increased agonist-evoked calcium flux mediated by an engineered variant of the human α7 nAChR. Electrophysiology studies confirmed that PNU-120596 increased peak agonist-evoked currents mediated by wild-type receptors and also demonstrated a pronounced prolongation of the evoked response in the continued presence of agonist. In contrast, PNU-120596 produced no detectable change in currents mediated by α4β2, α3β4, and α9α10 nAChRs. PNU-120596 increased the channel mean open time of α7 nAChRs but had no effect on ion selectivity and relatively little, if any, effect on unitary conductance. When applied to acute hippocampal slices, PNU-120596 increased the frequency of ACh-evoked GABAergic postsynaptic currents measured in pyramidal neurons; this effect was suppressed by TTX, suggesting that PNU-120596 modulated the function of α7 nAChRs located on the somatodendritic membrane of hippocampal interneurons. Accordingly, PNU-120596 greatly enhanced the ACh-evoked inward currents in these interneurons. Systemic administration of PNU-120596 to rats improved the auditory gating deficit caused by amphetamine, a model proposed to reflect a circuit level disturbance associated with schizophrenia. Together, these results suggest that PNU-120596 represents a new class of molecule that enhances α7 nAChR function and thus has the potential to treat psychiatric and neurological disorders.
The soul danced into the body: Nation and improvisation in Istanbul
Authors: Bryant Rebecca
Published: April 2005

In this article, I examine the politics and practices of apprenticeship in the “traditions” of Turkish folk music through playing the bag˘lama, or saz. The saz has become iconically representative of a folk music collected and preserved in the era of nationalism, and I examine the meaning of such a self‐conscious and reflexive tradition's claims to traditionality. I outline the ways in which that tradition is acquired as an aesthetics of self, requiring one to consciously shape the self to become the type of person who can play the saz and, hence, improvise within the sensibility of a tradition.