bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse events, bone mineral density and discontinuation associated with generic alendronate among postmenopausal women previously tolerant of brand alendronate: a retrospective cohort study
Authors: Grima Daniel T , Papaioannou Alexandra , Airia Parisa , Ioannidis George , Adachi Jonathan D
Published: April 2010

Background

A rise in gastrointestinal (GI) adverse events (AEs) and a decline in bone mineral density (BMD) was observed in patients previously tolerant to brand alendronate shortly after generic versions were introduced in July 2005 to the Canadian market. The objective of our study was to quantify changes in AE rates and BMD scores, as well as associated alendronate discontinuation among patients before and after switch from brand to generic alendronate.

Methods

A chart review of postmenopausal women 50 years of age and older between 2003 and 2007 was conducted in two specialized tertiary care referral centers. Patients on alendronate both before and after July 2005 were included. The change in the number of AEs, changes in BMD and associated alendronate discontinuation was compared before and after the switch from brand to generic alendronate.

Results

301 women with an average age of 67.6 years (standard deviation (SD) = 9.5) had a total of 47 AEs between July 2003 and December 2007 that resulted in discontinuation of the medication. There was a significant increase in the rate of AEs per patient-months-at-risk from 0.0001 before to 0.0044 after October 2005 (p < 0.001). The most common AEs were GI in nature (stomach pain, GI upset, nausea, and reflux). In addition, 23 patients discontinued alendronate due to BMD reduction after January 2006. In these patients, BMD scores were significantly reduced from their prior BMD measures (change of -0.0534, p < 0.001 for spine BMD and change of -0.0338, p = 0.01 for femur BMD). Among patients who discontinued due to BMD reduction, BMD was stable in the period prior to January 2006 (change of -0.0066, p = 0.5 for spine BMD and change of 0.0011, p = 0.9 for femur BMD); however, testing for reduction after January 2006 in BMD measures (one-sided T-test) revealed there was a significant reduction in BMD scores for both anatomic sites (change of -0.0321, p = .005 for spine, change of -0.0205, p = 0.05 for femur).

Conclusions

Patients who were previously stable on doses of brand alendronate experienced an increase in AEs causing discontinuation after introduction of automatic substitution to generic alendronate. In addition, reductions in BMD were observed in some patients who had stable BMDs before January 2006. Given the substantial increase in AEs, generic alendronate may not be as well tolerated as brand alendronate.
CD7 in acute myeloid leukemia: correlation with loss of wild-type CEBPA, consequence of epigenetic regulation
Authors: Röhrs Sonja , Scherr Michaela , Romani Julia , Zaborski Margarete , Drexler Hans G , Quentmeier Hilmar
Published: April 2010

Background

CD7 is a negative prognostic marker in myeloid malignancies. In acute myeloid leukemia (AML), an inverse correlation exists between expression of wild-type CEBPA and CD7. Aim of this study was to find out whether C/EBPα is a negative regulator of CD7 and which other regulatory mechanisms might be involved.

Results

As already described for primary AML cells, the majority of AML cell lines tested were either C/EBPα+/CD7- or C/EBPα-/CD7+. However, the existence of isolated CD7+ cell lines expressing wild-type C/EBPα challenges the notion that C/EBPα acts as a unique repressor of CD7. Furthermore, ectopic expression of CEBPA did not reduce CD7 in CD7+ cells and knock-down of C/EBPα failed to induce CD7 in CD7- cells. In contrast, the DNA demethylating agent Aza-2'deoxycytidine triggered CD7 expression in CD7- AML and in T-cell lines suggesting epigenetic regulation of CD7. Bisulfite sequencing data confirmed that CpGs in the CD7 exon1 region are methylated in CD7- cell lines, and unmethylated in CD7+ cell lines.

Conclusion

We confirmed an inverse correlation between the expression of wild-type CEBPA and of CD7 in AML cells. Our results contradict the hypothesis that C/EBPα acts as repressor for CD7, and instead show that epigenetic mechanisms are responsible for CD7 regulation, in AML cells as well as in T-cells, the typical CD7 expressing cell type.
Effects of different fibrinogen concentrations on blood loss and coagulation parameters in a pig model of coagulopathy with blunt liver injury
Authors: Grottke Oliver , Braunschweig Till , Henzler Dietrich , Coburn Mark , Tolba Rene , Rossaint Rolf
Published: April 2010

Introduction

The early application of fibrinogen could potentially reverse haemodilution-induced coagulopathy, although the impact of varying concentrations of fibrinogen to reverse dilutional coagulopathy has not been studied in vivo. We postulated that fibrinogen concentration is correlated with blood loss in a pig model of coagulopathy with blunt liver injury.

Methods

Coagulopathy was induced in 18 anaesthetized pigs (32 ± 1.6 kg body weight) by replacing 80% of blood volume with hydroxyethylstarch 130/0.4 and Ringer's lactated solution, and re-transfusion of erythrocytes. Animals were randomly assigned to receive either 70 mg kg-1 (F-70) or 200 mg kg-1 (F-200) fibrinogen or placebo before inducing blunt liver injury using a force of 225 ± 26 Newton. Haemodynamics, coagulation parameters and blood loss were monitored for 2 hours. After death, histological examination of internal organs was performed to assess the presence of emboli and the equality of liver injury.

Results

Plasma dilution caused severe coagulopathy. Measured by thromboelastography fibrinogen restored coagulation dose-dependently. Total blood loss was significantly lower and survival better in both fibrinogen groups as compared to controls (P < 0.05). Between the F-70 (1317 ± 113 ml) and the F-200 group (1155 ± 232 ml) no significant difference in total blood loss could be observed, despite improved coagulation parameters in the F-200 group (P < 0.05). Microscopy revealed even injury pattern and no (micro) thrombi for either group.

Conclusions

Restoring fibrinogen with 70 or 200 mg kg-1 after severe dilutional coagulopathy safely improved coagulation and attenuated blood loss after experimental blunt liver trauma. The higher dosage of fibrinogen was not associated with a further reduction in blood loss.
Reconstructing the evolutionary history of the centriole from protein components
Authors: Hodges Matthew E. , Scheumann Nicole , Wickstead Bill , Langdale Jane A. , Gull Keith
Published: April 2010

Centrioles are highly conserved structures that fulfil important cellular functions, such as nucleation of cilia and flagella (basal-body function) and organisation of pericentriolar material to form the centrosome. The evolution of these functions can be inferred from the distribution of the molecular components of extant centrioles and centrosomes. Here, we undertake an evolutionary analysis of 53 proteins known either for centriolar association or for involvement in cilia-associated pathologies. By linking protein distribution in 45 diverse eukaryotes with organism biology, we provide molecular evidence to show that basal-body function is ancestral, whereas the presence of the centrosome is specific to the Holozoa. We define an ancestral centriolar inventory of 14 core proteins, Polo-like-kinase, and proteins associated with Bardet-Biedl syndrome (BBS) and Meckel-Gruber syndrome. We show that the BBSome is absent from organisms that produce cilia only for motility, predicting a dominant and ancient role for this complex in sensory function. We also show that the unusual centriole of Caenorhabditis elegans is highly divergent in both protein composition and sequence. Finally, we demonstrate a correlation between the presence of specific centriolar proteins and eye evolution. This correlation is used to predict proteins with functions in the development of ciliary, but not rhabdomeric, eyes.
Aspirin Dosing for the Prevention and Treatment of Ischemic Stroke: An Indication-Specific Review of the Literature
Authors: Ansara Alexander J , Nisly Sarah A , Arif Sally A , Koehler Julia M , Nordmeyer Sarah T
Published: April 2010

OBJECTIVE:

To evaluate the efficacy of aspirin for the treatment and prevention of ischemic stroke and identify the minimum dose proven to be effective for each indication.

DATA SOURCES:

PubMed and MEDLINE searches (up to January 2010) were performed to identify primary literature, using search terms including aspirin, stroke prevention, acute ischemic stroke, acetylsalicylic acid, atrial fibrillation, myocardial infarction, and carotid endarterectomy. Additionally, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION:

Articles published in English were evaluated and relevant primary literature evaluating the efficacy of aspirin in the prevention of stroke was included in this review.

DATA SYNTHESIS:

Antiplatelet therapy is the benchmark for the prevention of ischemic stroke. Aspirin has been proven to prevent ischemic stroke in a variety of settings. Despite the frequency at which aspirin continues to be prescribed in patients at risk of ischemic stroke, there remains confusion in clinical practice as to what minimum dose is required in various at-risk patients. A thorough review of the primary literature suggests that low-dose (50-81 mg daily) aspirin is insufficient for some indications. Acute ischemic stroke treatment requires 160-325 mg, while atrial fibrillation and carotid arterial disease require daily doses of 325 and 81-325 mg, respectively.

CONCLUSIONS:

Available evidence suggests that aspirin dosing must be individualized according to indication. Recommendations provided by national guidelines at times recommend lower doses of aspirin than have been proven effective. Higher doses are indicated for stroke prevention in atrial fibrillation (325 mg) and acute ischemic stroke patients (160-325 mg). Aspirin has not yet been proven effective for primary prevention of strokes in men, and a minimum dose for these patients cannot be determined from the available data.
Dust particles in low-pressure plasmas: Formation and induced phenomena
Authors: Mikikian Maxime , Cavarroc Marjorie , Couëdel Lénaïc , Tessier Yves , Boufendi Laïfa
Published: April 2010

Formation of dust particles is a common mechanism in low-pressure plasmas. These big particles (in comparison with other plasma species) are sometimes the desired final products of the process, but they may also constitute a severe drawback in certain contexts. In either situation, it is necessary to understand growth mechanisms well, in order to control or avoid dust particle formation. One of the problems that has to be overcome is that dust particle growth is usually a continuous mechanism: once started, it can enter into a cyclic regime where new generations of dust particles are succeeding one after the other. This cyclic phenomenon often induces a side effect consisting of instabilities of a few tens of Hz. This paper discusses the main characteristics of dust successive generations, and particularly the importance of dust-free spaces (void) involved in this process. Finally, some aspects related to deposition when several generations coexist will be presented.
Risk taker extraordinaire: An interview with Elvera Voth
Authors: Cohen Mary L
Published: April 2010

Elvera Voth has been a role model and mentor for me since I first saw her conduct the East Hill Singers in 2003. After her professional choral career in Anchorage, Alaska, she returned to her native state of Kansas with an idea to teach prisoners to sing. In 1995 she founded the East
Hill Singers, a men's chorus comprised of minimum security prisoners incarcerated at the Lansing Correctional Facility and of male community volunteer singers. After Robert Shaw led a singalong to support her prison choir, the non-profit organization Arts in Prison, Inc. began in 1998 in order
to help develop other arts-based courses for prisoners. In this interview she reflects on her time conducting the East Hill Singers and the West Wall Singers (a chorus in the maximum unit at Lansing), prison education and her newest community music project.
On punishment and music education: Towards a practice for prisons and schools
Authors: Shieh Eric
Published: April 2010

Reflecting on the successes and challenges of his work as a prison music educator in four correctional facilities, the author suggests a framework for a music education that resists authoritarianism, allows for agency and engages with society. Focusing particularly on the societal context
and consequences of prison as a place of punishment, he argues that such a framework must take as its point of departure a democratic and a critical pedagogical orientation that opposes the deficit models present in most US prison education programmes. Characteristic of this orientation, then,
would be conceptualizations of the teacher as facilitator, musical knowledge as creative expression, classroom as community and performance as action. These conceptualizations further make visible the limitations of traditional approaches to school music education, and draw attention to the
degree to which traditional approaches to schooling problematically approach prisons in their disciplinary function.
Music for mothers and babies living in a prison: A report on a special production of BebBab
Authors: Rodrigues Helena , Leite Anabela , Faria Cristina , Monteiro Irene , Rodrigues Paulo Maria
Published: April 2010

BbBb is a project that combines education and artistic performance in a process that is centred on music, babies and their parents. We discovered that previous productions resulted in a very strong bonding among parents and babies, families and the community. In 2008 we implemented a special production in a prison in Oporto where mothers live with their own children until the age of four. Here we describe the ideas, goals and strategies of the project, we look at its artistic aspects and we report the impact it had on the participants, based on interviews conducted after the project was concluded. The report of this practical work is integrated in a reflection about the general issue of music in prison, and we explain why we believe BebBab can be a case study helping to establish guidelines for future work, particularly in the case of imprisoned mothers and babies.
Reviews
Authors: Krebs Katja
Published: April 2010

FOUND IN TRANSLATION GREEK DRAMA IN ENGLISH, J. MICHAEL WALTON (2007) Cambridge: Cambridge University Press, p. 320, ISBN: 978-0-521-86110-6, Hardback, 65
Reviews
Authors: Sommer Kerstin
Published: April 2010

ENTERTAINING TELEVISION: THE BBC AND POPULAR TELEVISION CULTURE IN THE 1950s, SU HOLMES (2008) Manchester: Manchester University Press, 232 pp., ISBN 978-07-1907-791-3, Hardback, 50.00
Horrifying adaptations: Ringu, The Ring, and the cultural contexts of copying
Authors: Phu Thy
Published: April 2010

Focusing on the figure of the copy in Hideko Sadaka's Ringu and its Gore Verebinksi's The Ring, this article traces one of the sources of horror in these films to the fluidity of this figure. Manifest variously as a form of technological reproduction that, in turn, serves
as a way of screening fears associated with biological reproduction as well as the parental responsibilities that this process occasions and as a means by which cultural memory might be preserved, the figure of the copy serves as a vexed symbolic vehicle for exploring the relationship between
cultural texts and the disparate national contexts that shape them. Ultimately, the figure of the copy functions as an apt means of self-reflexively commenting on the possibilities and limitations that might characterize the process of adaptation itself.
The commercial effects of the adaptation of novels into films in the United Kingdom, 19101940
Authors: Barnett Vincent L
Published: April 2010

Although there has been much general discussion in the academic literature about the influence of cross-media adaptations on the success or otherwise of the additional media outputs that result, there has been less actual empirical investigation of this hypothesized link using quantitative data to test the arguments being made. This article consequently examines the commercial effects of the release of film adaptations on the sales and printing of the original books in question, by first analysing data on the outputs of two well-known popular novelists of the inter-war period (A. E.W. Mason and Baroness Orczy). It then examines this topic from a company history perspective, documenting the fate of a specific British film production company (Stoll Picture Productions Limited) that specialized in this type of literary adaptation. Finally, some more general observations about the cultural economics of cross-media productions are deduced.
Infinite exchange: The social ontology of the photographic image
Authors: Osborne Peter
Published: April 2010

This paper approaches the problem of the ontology of the photographic image post-digitalization historically, via a conception of photography as the historical totality of photographic forms. It argues, first, that photography is not best understood as a particular art or medium, but
rather in terms of the form of the image it produces; second, that the photographic image is the main social form of the digital image (the current historically dominant form of the image in general); and third, that there is no fundamental ontological distinction regarding indexicality between
photographically generated digital images and those of chemically based photography. The anxiety about the real produced by digital imagery has its origins elsewhere, in the ontological peculiarities of the social form of value in societies based on relations of exchange. Distinguishing between
the event of capture and the event of visualization, it is argued that it is in its potential for an infinite multiplication of visualizations that the distinctiveness of the digital image lies. In the digital image, the infinite possibilities for social exchange generated by the abstraction
of value from use finds an equivalent visual form.
Combined Adaptiveness of Specific Motor Cortical Ensembles Underlies Learning
Authors: Arce Fritzie , Novick Itai , Mandelblat-Cerf Yael , Israel Zvi , Ghez Claude , Vaadia Eilon
Published: April 2010

Learning motor skills entails adaptation of neural computations that can generate or modify associations between sensations and actions. Indeed, humans can use different strategies when adapting to dynamic loads depending on available sensory feedback. Here, we examined how neural activity in motor cortex was modified when monkeys made arm reaches to a visual target and locally adapted to curl force field with or without visual trajectory feedback. We found that firing rates of a large subpopulation of cells were consistently modulated depending on the distance of their preferred direction from the learned movement direction. The newly acquired activity followed a cosine-like function, with maximal increase in directions that opposed the perturbing force and decrease in opposite directions. As a result, the combined neuronal activity generated an adapted population vector. The results suggest that this could be achieved without changing the tuning properties of the cells. This population directional signal was however altered in the absence of visual feedback; while the cosine pattern of modulation was maintained, the population distributions of modulated cells differed across feedback consistent with the different trajectory shapes. Finally, we predicted generalization patterns of force-field learning based on the cosine-like modulation. These conformed to reported features of generalization in humans, suggesting that the generalization function was related to the observed rate modulations in the motor cortex. Overall, the findings suggest that the new combined activation of neuronal ensembles could underlie the change in the internal model of movement dynamics in a way that depends on available sensory feedback and chosen strategy.
No Increase of the Blood Oxygenation Level-Dependent Functional Magnetic Resonance Imaging Signal with Higher Field Strength: Implications for Brain Activation Studies
Authors: Seehafer Jörg U. , Kalthoff Daniel , Farr Tracy D. , Wiedermann Dirk , Hoehn Mathias
Published: April 2010

Experimental data up to 7.0 T show that the blood oxygenation level-dependent (BOLD) signal of functional magnetic resonance imaging (fMRI) increases with higher magnetic field strength. Although several studies at 11.7 T report higher BOLD signal compared with studies at 7.0 T, no direct comparison at these two field strengths has been performed under the exact same conditions. It therefore remains unclear whether the expected increase of BOLD effect with field strength will still continue to hold for fields >7.0 T. To examine this issue, we compared the BOLD activation signal at 7.0 and 11.7 T with the two common sequences, spin-echo (SE) and gradient-echo (GE) echo planar imaging (EPI). We chose the physiologically well controlled rat model of electrical forepaw stimulation under medetomidine sedation. While a linear to superlinear increase in activation with field strengths up to 7.0 T was reported in the literature, we observed no significant activation difference between 7.0 and 11.7 T with either SE or GE. Discussing the results in light of the four-component model of the BOLD signal, we showed that at high field only two extravascular contributions remain relevant, while both intravascular components vanish. Constancy of the BOLD effect is discussed due to motional narrowing, i.e., susceptibility gradients become so strong that phase variance of diffusing spins decreases and therefore the BOLD signal also decreases. This finding will be of high significance for the planning of future human and animal fMRI studies at high fields and their quantitative analysis.
Importin-β11 Regulates Synaptic Phosphorylated Mothers Against Decapentaplegic, and Thereby Influences Synaptic Development and Function at theDrosophilaNeuromuscular Junction
Authors: Higashi-Kovtun Misao E. , Mosca Timothy J. , Dickman Dion K. , Meinertzhagen Ian A. , Schwarz Thomas L.
Published: April 2010

Importin proteins act both at the nuclear pore to promote substrate entry and in the cytosol during signal trafficking. Here, we describe mutations in theDrosophilageneimportin-β11, which has not previously been analyzed genetically. Mutants ofimportin-β11died as late pupae from neuronal defects, and neuronal importin-β11 was present not only at nuclear pores but also in the cytosol and at synapses. Neurons lacking importin-β11 were viable and properly differentiated but exhibited discrete defects. Synaptic transmission was defective in adult photoreceptors and at larval neuromuscular junctions (NMJs). Mutant photoreceptor axons formed grossly normal projections and synaptic terminals in the brain, but synaptic arbors on larval muscles were smaller while still containing appropriate synaptic components. Bone morphogenic protein (BMP) signaling was the apparent cause of the observed NMJ defects.Importin-β11interacted genetically with the BMP pathway, and at mutant synaptic boutons, a key component of this pathway, phosphorylated mothers against decapentaplegic (pMAD), was reduced. Neuronal expression of animportin-β11transgene rescued this phenotype as well as the other observed neuromuscular phenotypes. Despite the loss of synaptic pMAD, pMAD persisted in motor neuron nuclei, suggesting a specific impairment in the local function of pMAD. Restoring levels of pMAD to mutant terminals via expression of constitutively active type I BMP receptors or by reducing retrograde transport in motor neurons also restored synaptic strength and morphology. Thus, importin-β11 function interacts with the BMP pathway to regulate a pool of pMAD that must be present at the presynapse for its proper development and function.
Ca2+-Dependent Facilitation of Cav1.3 Ca2+Channels by Densin and Ca2+/Calmodulin-Dependent Protein Kinase II
Authors: Jenkins Meagan A. , Christel Carl J. , Jiao Yuxia , Abiria Sunday , Kim Kristin Y. , Usachev Yuriy M. , Obermair Gerald J. , Colbran Roger J. , Lee Amy
Published: April 2010

Cav1 (L-type) channels and calmodulin-dependent protein kinase II (CaMKII) are key regulators of Ca2+signaling in neurons. CaMKII directly potentiates the activity of Cav1.2 and Cav1.3 channels, but the underlying molecular mechanisms are incompletely understood. Here, we report that the CaMKII-associated protein densin is required for Ca2+-dependent facilitation of Cav1.3 channels. While neither CaMKII nor densin independently affects Cav1.3 properties in transfected HEK293T cells, the two together augment Cav1.3 Ca2+currents during repetitive, but not sustained, depolarizing stimuli. Facilitation requires Ca2+, CaMKII activation, and its association with densin, as well as densin binding to the Cav1.3 α1subunit C-terminal domain. Cav1.3 channels and densin are targeted to dendritic spines in neurons and form a complex with CaMKII in the brain. Our results demonstrate a novel mechanism for Ca2+-dependent facilitation that may intensify postsynaptic Ca2+signals during high-frequency stimulation.
Neuregulin-ErbB Signaling Promotes Microglial Proliferation and Chemotaxis Contributing to Microgliosis and Pain after Peripheral Nerve Injury
Authors: Calvo Margarita , Zhu Ning , Tsantoulas Christoforos , Ma Zhenzhong , Grist John , Loeb Jeffrey A. , Bennett David L. H.
Published: April 2010

A key component in the response of the nervous system to injury is the proliferation and switch to a “proinflammatory” phenotype by microglia (microgliosis). In situations where the blood–brain barrier is intact, microglial numbers increase via the proliferation and chemotaxis of resident microglia; however, there is limited knowledge regarding the factors mediating this response. After peripheral nerve injury, a dorsal horn microgliosis develops, which directly contributes to the development of neuropathic pain. Neuregulin-1 (NRG-1) is a growth and differentiation factor with a well characterized role in neural and cardiac development. Microglia express the NRG1 receptors erbB2, 3, and 4, and NRG1 signaling via the erbB2 receptor stimulated microglial proliferation, chemotaxis, and survival, as well as interleukin-1β releasein vitro. Intrathecal treatment with NRG1 resulted in microglial proliferation within the dorsal horn, and these cells developed an activated morphology. This microglial response was associated with the development of both mechanical and cold pain-related hypersensitivity. Primary afferents express NRG1, and after spinal nerve ligation (SNL) we observed both an increase in NRG1 within the dorsal horn as well as activation of erbB2 specifically within microglia. Blockade of the erbB2 receptor or sequestration of endogenous NRG after SNL reduced the proliferation, the number of microglia with an activated morphology, and the expression of phospho-P38 by microglia. Furthermore, consequent to such changes, the mechanical pain-related hypersensitivity and cold allodynia were reduced. NRG1-erbB signaling therefore represents a novel pathway regulating the injury response of microglia.
The Differential Axonal Degradation of Ret Accounts for Cell-Type-Specific Function of Glial Cell Line-Derived Neurotrophic Factor as a Retrograde Survival Factor
Authors: Tsui Cynthia C. , Pierchala Brian A.
Published: April 2010

Glial cell line-derived neurotrophic factor (GDNF) is a neuronal growth factor critical for the development and maintenance of central and peripheral neurons. GDNF is expressed in targets of innervation and provides support to several populations of large, projection neurons. To determine whether GDNF promotes retrograde survival over long axonal distances to cell bodies, we used a compartmentalized culture system. GDNF supported only modest and transient survival of postnatal sympathetic neurons when applied to their distal axons, in contrast to dorsal root ganglion (DRG) sensory neurons in which GDNF promoted survival equally well from either distal axons or cell bodies. Ret, the receptor tyrosine kinase for GDNF, underwent rapid proteasomal degradation in the axons of sympathetic neurons. Interestingly, the level of activated Ret in DRG neurons was sustained in the axons and also appeared in the cell bodies, suggesting that Ret was not degraded in sensory axons and was retrogradely transported. Pharmacologic inhibition of proteasomes only in the distal axons of sympathetic neurons caused an accumulation of activated Ret in both the axons and cell bodies during GDNF stimulation. Furthermore, exposure of the distal axons of sympathetic neurons to both GDNF and proteasome inhibitors, but neither one alone, promoted robust survival, identical to GDNF applied directly to the cell bodies. This differential responsiveness of sympathetic and sensory neurons to target-derived GDNF was attributable to the differential expression and degradation of the Ret9 and Ret51 isoforms. Therefore, the local degradation of Ret in axons dictates whether GDNF family ligands act as retrograde survival factors.
Exogenous Brain-Derived Neurotrophic Factor Rescues Synaptic Dysfunction inMecp2-Null Mice
Authors: Kline David D. , Ogier Michael , Kunze Diana L. , Katz David M.
Published: April 2010

Postnatal deficits in brain-derived neurotrophic factor (BDNF) are thought to contribute to pathogenesis of Rett syndrome (RTT), a progressive neurodevelopmental disorder caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MeCP2). InMecp2-null mice, a model of RTT, BDNF deficits are most pronounced in structures important for autonomic and respiratory control, functions that are severely affected in RTT patients. However, relatively little is known about how these deficits affect neuronal function or how they may be linked to specific RTT endophenotypes. To approach these issues, we analyzed synaptic function in the brainstem nucleus tractus solitarius (nTS), the principal site for integration of primary visceral afferent inputs to central autonomic pathways and a region in which we found markedly reduced levels of BDNF inMecp2mutants. Our results demonstrate that the amplitude of spontaneous miniature and evoked EPSCs in nTS neurons is significantly increased inMecp2-null mice and, accordingly, that mutant cells are more likely than wild- type cells to fire action potentials in response to primary afferent stimulation. These changes occur without any increase in intrinsic neuronal excitability and are unaffected by blockade of inhibitory GABA currents. However, this synaptopathy is associated with decreased BDNF availability in the primary afferent pathway and can be rescued by application of exogenous BDNF. On the basis of these findings, we hypothesize that altered sensory gating in nTS contributes to cardiorespiratory instability in RTT and that nTS is a site at which restoration of normal BDNF signaling could help reestablish normal homeostatic controls.
Dlx5andDlx6Regulate the Development of Parvalbumin-Expressing Cortical Interneurons
Authors: Wang Yanling , Dye Catherine A. , Sohal Vikaas , Long Jason E. , Estrada Rosanne C. , Roztocil Tomas , Lufkin Thomas , Deisseroth Karl , Baraban Scott C. , Rubenstein John L. R.
Published: April 2010

Dlx5andDlx6homeobox genes are expressed in developing and mature cortical interneurons. Simultaneous deletion ofDlx5and6results in exencephaly of the anterior brain; despite this defect, prenatal basal ganglia differentiation appeared largely intact, while tangential migration ofLhx6+andMafb+interneurons to the cortex was reduced and disordered. The migration deficits were associated with reducedCXCR4expression. Transplantation of mutant immature interneurons into a wild-type brain demonstrated that loss of eitherDlx5orDlx5&6preferentially reduced the number of mature parvalbumin+interneurons; those parvalbumin+interneurons that were present had increased dendritic branching.Dlx5/6+/−mice, which appear normal histologically, show spontaneous electrographic seizures and reduced power of gamma oscillations. Thus,Dlx5&6appeared to be required for development and function of somal innervating (parvalbumin+) neocortical interneurons. This contrasts withDlx1, whose function is required for dendrite innervating (calretinin+, somatostatin+, and neuropeptide Y+) interneurons (Cobos et al., 2005).
Rett Syndrome Microglia Damage Dendrites and Synapses by the Elevated Release of Glutamate
Authors: Maezawa Izumi , Jin Lee-Way
Published: April 2010

MECP2, an X-linked gene encoding the epigenetic factor methyl-CpG-binding protein-2, is mutated in Rett syndrome (RTT) and aberrantly expressed in autism. Most children affected by RTT are heterozygousMecp2−/+females whose brain function is impaired postnatally due to MeCP2 deficiency. Recent studies suggest a role of glia in causing neuronal dysfunction via a non-cell-autonomous effect in RTT. Here we report a potent neurotoxic activity in the conditioned medium (CM) obtained fromMecp2-null microglia. Hippocampal neurons treated with CM fromMecp2-null microglia showed an abnormal stunted and beaded dendritic morphology, and signs of microtubule disruption and damage of postsynaptic glutamatergic components within 24 h. We identified that the toxic factor in the CM is glutamate, because (1)Mecp2-null microglia released a fivefold higher level of glutamate, (2) blockage of microglial glutamate synthesis by a glutaminase inhibitor abolished the neurotoxic activity, (3) blockage of microglial glutamate release by gap junction hemichannel blockers abolished the neurotoxic activity, and (4) glutamate receptor antagonists blocked the neurotoxicity of theMecp2-null microglia CM. We further identified that increased levels of glutaminase and connexin 32 inMecp2-null microglia are responsible for increased glutamate production and release, respectively. In contrast, the CM from highly pureMecp2-null astrocyte cultures showed no toxic effect. Our results suggest that microglia may influence the onset and progression of RTT and that microglia glutamate synthesis or release could be a therapeutic target for RTT.
Brain-Derived Neurotrophic Factor Is Associated with Age-Related Decline in Hippocampal Volume
Authors: Erickson Kirk I. , Prakash Ruchika Shaurya , Voss Michelle W. , Chaddock Laura , Heo Susie , McLaren Molly , Pence Brandt D. , Martin Stephen A. , Vieira Victoria J. , Woods Jeffrey A. , McAuley Edward , Kramer Arthur F.
Published: April 2010

Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain-derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age, and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood.
Essential Role of the Redox-Sensitive Kinase p66shcin Determining Energetic and Oxidative Status and Cell Fate in Neuronal Preconditioning
Authors: Brown Jacquelynn E. , Zeiger Stephanie L. H. , Hettinger Jane C. , Brooks Joshua D. , Holt Benjamin , Morrow Jason D. , Musiek Erik S. , Milne Ginger , McLaughlin BethAnn
Published: April 2010

Ischemic preconditioning is a phenomenon in which low-level stressful stimuli upregulate endogenous defensive programs, resulting in subsequent resistance to otherwise lethal injuries. We previously observed that signal transduction systems typically associated with neurodegeneration such as caspase activation are requisite events for the expression of tolerance and induction of HSP70. In this work, we sought to determine the extent and duration of oxidative and energetic dysfunction as well as the role of effector kinases on metabolic function in preconditioned cells. Using anin vitroneuronal culture model, we observed a robust increase in Raf and p66Shcactivation within 1 h of preconditioning. Total ATP content decreased by 25% 3 h after preconditioning but returned to baseline by 24 h. Use of a free radical spin trap or p66shcinhibitor increased ATP content whereas a Raf inhibitor had no effect. Phosphorylated p66shcrapidly relocalized to the mitochondria and in the absence of activated p66shc, autophagic processing increased. The constitutively expressed chaperone HSC70 relocalized to autophagosomes. Preconditioned cells experience significant total oxidative stress measured by F2-isoprostanes and neuronal stress evaluated by F4-neuroprostane measurement. Neuroprostane levels were enhanced in the presence of Shc inhibitors. Finally, we found that inhibiting either p66shcor Raf blocked neuroprotection afforded by preconditioning as well as upregulation of HSP70, suggesting both kinases are critical for preconditioning but function in fundamentally different ways. This is the first work to demonstrate the essential role of p66shcin mediating requisite mitochondrial and energetic compensation after preconditioning and suggests a mechanism by which protein and organelle damage mediated by ROS can increase HSP70.
Lo Schiavetto (1612): Travestied Sound, Ethnic Performance, and the Eloquence of the Body
Authors: Wilbourne Emily
Published: April 2010

This article examines at the relationship between epistemologies of sound, repertoires of popular music, and markers of ethnic difference in early seventeenth-century Italy. The analysis concentrates on two scenes from the 1612 commedia dell'arte play Lo Schiavetto (“The Little Slave”). In one, an Italian nobleman disguises himself as a mute Jew, in the other, a young Italian noblewoman sings while cross-dressed as a black, male slave. Questions of embodiment are considered, as are the specific historical circumstances of the work's original performers, Virginia Ramponi Andreini, detta Florinda, and her husband, Giovan Battista Andreini, detto Lelio. Musical discussion focuses on the genre of the madrigal comedy (with particular attention to Orazio Vecchi's L'Amfiparnaso) and Giulio Caccini's Le nuove musiche e nuova maniera di scriverle (1614).
Expression of basigin in reproductive tissues of estrogen receptor-α or -β null mice
Authors: Chen Li , Bi Jiajia , Nakai Masaaki , Bunick David , Couse John F , Korach Kenneth S , Nowak Romana A
Published: April 2010

Basigin plays important roles in both male and female reproduction because basigin (Bsg) null male and female mice are infertile. The aim of the present study was to determine whether basigin expression in reproductive organs requires estrogen receptor-α (ESR1, ERα) or -β (ESR2, ERβ). Expression of basigin protein in the testis, ovary, and male and female reproductive tracts was studied in adult wild-type (WT),Esr1-null (αERKO), andEsr2-null (βERKO) mice by immunohistochemistry and immunoblotting. Basigin mRNA levels in ovary and uterus were examined by quantitative RT-PCR. In females, basigin protein expression was observed mainly in granulosa and interstitial cells of the ovary and epithelial cells of the proximal oviduct in all genotypes. Basigin protein was also expressed in the uterine epithelium at proestrus and estrus in WT and βERKO mice but not in αERKO mice. However, a higher level of basigin mRNA was observed in uteri of αERKO mice compared with WT and βERKO mice. In males, basigin was expressed in Leydig cells and all germ cells except spermatogonia in all genotypes. Basigin was present in epithelial cells lining the efferent ductules in WT and βERKO mice, but expression was greatly reduced in αERKO mice. In epididymal ducts, basigin expression was observed in epithelial cells in the caput and cauda in all genotypes. These data suggest that expression of basigin protein requires ESR1, but not ESR2, in the uterus and efferent ductules, but is independent of estrogen receptor in the ovary, oviduct, testis, and epididymis.
Reconstrução de trânsito intestinal após confecção de colostomia à Hartmann
Authors: Silva Rodrigo Gomes da , Castro Júnior Geraldo Rosendo de , Ferreira Carmencita Lívia Macartti , Luz Magda Maria Profeta da , Conceição Sérgio Alexandre da , Lacerda-Filho Antônio
Published: April 2010

OBJETIVO: O objetivo desse estudo foi avaliar as taxas de morbidade e de mortalidade da tentativa de reversão do procedimento de Hartmann. MÉTODOS: Foram estudados retrospectivamente 29 pacientes submetidos à operação para reconstrução do trânsito intestinal após procedimento de Hartmann no Hospital das Clínicas da Universidade Federal de Minas Gerais no período de janeiro de 1998 a dezembro de 2006. Foram avaliados dados pré-operatório, intra-operatórios e pós-operatórios. RESULTADOS: A média de idade dos pacientes submetidos à operação para reconstrução de trânsito intestinal após realização de colostomia a Hartmann foi de 52,6 anos, sendo 16 pacientes do sexo masculino (55,2%). O tempo médio da permanência da colostomia foi de 17,6 meses (variando de 1 a 84 meses). O tempo operatório médio foi de 300 minutos (variando de 180 a 720 minutos). O sucesso na reconstrução do trânsito intestinal foi alcançado em 27 pacientes (93%). Dois pacientes apresentaram fístula anastomótica (7%) e seis tiveram infecção de parede (22%). Ocorreu um óbito (3,4%) em paciente com fístula anastomótica e sepse abdominal. Dentre os fatores relacionados ao insucesso na reconstrução da colostomia a Hartmann observou-se associação estatisticamente significativa com a tentativa prévia de reconstrução (p = 0,007), a utilização prévia de quimioterapia (p = 0,037) e o longo tempo de permanência da colostomia (p = 0,025) CONCLUSÃO: O intervalo entre a confecção e a tentativa de reversão não deve ser muito longo e os pacientes devem ser alertados que, numa pequena porcentagem dos casos, a reconstrução do trânsito intestinal pode ser impossível devido às condições locais do reto excluído.
Colecistectomia laparoscópica em transplantados
Authors: Coelho Júlio Cezar Uili , Contieri Fabiana L.C. , Freitas Alexandre Coutinho Teixeira de , Silva Fernanda Cristina da , Kozak Vanessa Nascimento , Silva Junior Alzemir Santos da
Published: April 2010

OBJETIVO: Apresentar a nossa experiência com a colecistectomia laparoscópica no tratamento da colelitíase em transplantados. MÉTODOS: Dados demográficos, medicamentos utilizados e dados operatórios e pós-operatórios de todos transplantados que foram submetidos à colecistectomia laparoscópica por colelitíase no nosso hospital foram obtidos. Resultados: Quinze pacientes (13 transplantes renais e dois transplantes de medula óssea) foram submetidos à colecistectomia laparoscópica. Todos pacientes foram internados no hospital no dia da operação. O esquema imunossupressor não foi modificado durante a hospitalização. A apresentação clínica da colelitíase foi cólica biliar (n=12), colecistite aguda (n=2) e icterícia (n=1). A colecistectomia transcorreu sem intercorrências em todos pacientes. Complicações pós-operatórias foram náusea e vômitos em dois pacientes, intubação traqueal prolongada em um, infecção de ferida operatória em um e hematoma superficial grande em um paciente. CONCLUSÃO: Colecistectomia laparoscópica é associada à baixa morbidade e mortalidade e bom prognóstico pós-operatório em pacientes transplantados com colecistite não complicada.
Atividade da catalase no pulmão, rim e intestino delgado não isquemiado de ratos após reperfusão intestinal
Authors: Ferro Camila de Oliveira , Chagas Vera Lucia Antunes , Oliveira Marcus Fernandes de , Oliveira Pedro Lagerblad de , Schanaider Alberto
Published: April 2010

OBJETIVO: Avaliar a atividade catalase, após lesão por isquemia e reperfusão intestinal e estudar as alterações deste antioxidante em órgãos situados à distância do insulto inicial. MÉTODOS: Utilizaram-se 18 ratos do tipo Wistar, aleatoriamente distribuídos em três grupos. 1-Controle, 2-Simulação e 3-Isquemia/Reperfusão. Neste último, realizou-se isquemia no íleo, por 60 minutos, seguida de reperfusão por 30 minutos. No grupo 2 efetuou-se apenas uma laparotomia. Foram retirados, de todos os animais, segmentos do intestino com e sem reperfusão, além do pulmão e rim direitos para exame com microscopia óptica. A atividade da catalase foi aferida em espectrofotômetro ajustado para 240 nm. Utilizaram-se os testes estatísticos Mann e Whitney e Kruskal Wallis. RESULTADOS: Observou-se aumento significante (p < 0.05), da atividade da catalase nas porções do intestino isquemiado e não isquemiado, além do pulmão. Houve redução da atividade enzimática no rim. No grupo com reperfusão observaram-se alteração nas vilosidades, infiltrado inflamatório em todas as vísceras, além de áreas de atelectasia pulmonar. CONCLUSÃO: O estresse oxidativo intestinal, em ratos, causa alterações bioquímicas à distância com mobilização dos mecanismos de defesa antioxidante pulmonar, em segmento intestinal não isquemiado e no rim, com esgotamento precoce das reservas deste último, no entanto, sem lesão celular relevante, destas vísceras.
Análise biomecânica da solidarização de tendões para reconstrução do ligamento cruzado anterior
Authors: Stieven Filho Edmar , Malafaia Osvaldo , Ribas-Filho Jurandir Marcondes , Diniz Otaviano Esteves dos Santos , Borges Paulo César , Albano Mauro , Kume Márcio , Silva João Luiz Vieira da , Namba Mario
Published: April 2010

OBJETIVO: Avaliar a diferença do comportamento mecânico de tendões flexores solidarizados e não solidarizados para verificar se a solidarização tem função efetiva. MÉTODOS: Vinte e quatro tendões digitais bovinos frescos foram usados. Para determinar a área da secção transversal utilizou-se alginato. Dez tendões foram solidarizados seguindo as orientações do fabricante; outros 10 pares não. Foram desenvolvidas garras para fixação dos enxertos à máquina universal para simulação da fixação, sendo a superior bipartida e de passagem controlada dos pinos e a inferior com dentes alternados. RESULTADOS: A carga máxima dos corpos de prova não solidarizados foi de 849,4 N ± 386,8 a área 30,4 mm²± 7,7, tensão de 29 ± 17 Mpa. Os solidarizados obtiveram carga máxima de 871,8 N ± 484,9 área 35 mm²± 5,8, tensão de 24 ± 10 Mpa. Não houve diferença estatística entre os dois grupos (p>0,05). CONCLUSÃO: A distribuição de probabilidade mostra que para 400 N os tendões não solidarizados apresentam confiabilidade de 83,8% e os solidarizados de 78,5%%.
Mulheres e cirurgiãs
Authors: Franco Talita , Santos Elizabeth Gomes dos
Published: April 2010

As autoras apresentam o panorama da inserção das mulheres nas Especialidades Cirúrgicas desde o final do século XIX até os dias atuais e analisam as dificuldades enfrentadas bem como o aumento desta inserção nos dias atuais.