bluuebunny/crossref_metadata_2025 huggingface dataset:
A PET-CT study on the specificity of acupoints through acupuncture treatment in migraine patients
Authors: Yang Jie , Zeng Fang , Feng Yue , Fang Li , Qin Wei , Liu Xuguang , Song Wenzhong , Xie Hongjun , Chen Ji , Liang Fanrong
Published: August 2012

Background

In the field of acupuncture research, the topic of acupoint specificity has received increasing attention, but no unified conclusion has been reached on whether or not acupoint specificity exists. Furthermore, the majority of previous acupuncture neuroimaging studies have been performed using healthy subjects. In this study, patients with migraine were used to investigate acupoint specificity.

Methods

Thirty patients with migraine were enrolled and randomized into three groups: Traditional Acupuncture Group (TAG), Control Acupuncture Group (CAG), and Migraine Group (MG). The TAG was treated by acupuncture stimulation at Waiguan (TE5), Yang Lingquan (GB34), and Fengchi (GB20). The CAG was treated at Touwei (ST8), Pianli (LI6), and Zusanli (ST36). The MG received no treatment. Positron emission tomography with computed tomography (PET-CT) was used to test for differences in brain activation between the TAG and CAG versus MG, respectively.

Results

Traditional acupuncture treatment was more effective for pain reduction than control acupuncture treatment. The TAG showed higher brain metabolism than the MG in the middle temporal cortex (MTC), orbital frontal cortex (OFC), insula, middle frontal gyrus, angular gyrus, post-cingulate cortex (PCC), the precuneus, and the middle cingulate cortex (MCC). Metabolism decreased in the parahippocampus, hippocampus, fusiform gyrus, postcentral gyrus, and cerebellum in the TAG compared with the MG. In the CAG, metabolism increased compared with the MG in the MTC, supratemporal gyrus, supramarginal gyrus, and MCC, whereas metabolism decreased in the cerebellum.

Conclusions

Acupuncture stimulation of different points on similar body regions in migraine patients reduced pain and induced different levels of cerebral glucose metabolism in pain-related brain regions. These findings may support the functional specificity of migraine- treatment-related acupoint.

Trial registration

The number of our clinical trial registration is: ChiCTR-TRC-11001813, and the protocol and inclusion criteria have already been registered as ChiCTR-TRC-11001813.
Effect of green tea extracts on oxaliplatin-induced peripheral neuropathy in rats
Authors: Lee Jung Soo , Kim Yoon Tae , Jeon Eun Kyoung , Won Hye Sung , Cho Young-Seok , Ko Yoon Ho
Published: August 2012

Background

A common side effect of oxaliplatin is peripheral neurotoxicity. Oxidative stress to dorsal root ganglion (DRG) may be one of important pathogenic mechanisms. Green tea contains four polyphenol catechins, which are known to be potent antioxidants. The present work is aimed to determine whether green tea extracts have neuroproective or palliative effects on neurotoxicity symptoms induced by oxaliplatin.

Methods

We conducted behavioral tests including sensory and thermal thresholds, an electrophysiological study, and TUNEL staining to assess neurotoxicity during the experimental period using animal models.

Results

A total of 14 adult rats were randomly allocated into two groups. Oxaliplatin (4 mg/kg) with or without green tea (300 mg/kg orally once daily) was administered intraperitoneally twice per week for 6 weeks. At 4 and 6 weeks after oxaliplatin administration, sensory threshold values were significantly decreased and at 6 weeks after oxaliplatin administration, thermal threshold values were significantly increased in oxaliplatin-treated rats compared with those in rat treated with oxaliplatin and green tea extracts. The electrophysiological assessment, including sensory nerve conduction and H-reflex-related sensory nerve conduction velocity, revealed no significant changes in the two groups. TUNEL staining showed no significant difference in the number of apoptotic-featured cells between the two experimental groups in the DRG or peripheral nerves, but the number of apoptotic-featured cells in DRG was higher than that in sciatic nerves within each group.

Conclusions

Green tea extracts may be a useful adjuvant to alleviate sensory symptoms after oxaliplatin administration, such as allodynia, but did not prevent morphometric or electrophysiological alterations induced by oxaliplatin.
Predicting active school travel: The role of planned behavior and habit strength
Authors: Murtagh Shemane , Rowe David A , Elliott Mark A , McMinn David , Nelson Norah M
Published: August 2012

Background

Despite strong support for predictive validity of the theory of planned behavior (TPB) substantial variance in both intention and behavior is unaccounted for by the model’s predictors. The present study tested the extent to which habit strength augments the predictive validity of the TPB in relation to a currently under-researched behavior that has important health implications, namely children’s active school travel.

Method

Participants (N = 126 children aged 8–9 years; 59 % males) were sampled from five elementary schools in the west of Scotland and completed questionnaire measures of all TPB constructs in relation to walking to school and both walking and car/bus use habit. Over the subsequent week, commuting steps on school journeys were measured objectively using an accelerometer. Hierarchical multiple regressions were used to test the predictive utility of the TPB and habit strength in relation to both intention and subsequent behavior.

Results

The TPB accounted for 41 % and 10 % of the variance in intention and objectively measured behavior, respectively. Together, walking habit and car/bus habit significantly increased the proportion of explained variance in both intention and behavior by 6 %. Perceived behavioral control and both walking and car/bus habit independently predicted intention. Intention and car/bus habit independently predicted behavior.

Conclusions

The TPB significantly predicts children’s active school travel. However, habit strength augments the predictive validity of the model. The results indicate that school travel is controlled by both intentional and habitual processes. In practice, interventions could usefully decrease the habitual use of motorized transport for travel to school and increase children’s intention to walk (via increases in perceived behavioral control and walking habit, and decreases in car/bus habit). Further research is needed to identify effective strategies for changing these antecedents of children’s active school travel.
On "Equation missing" -equivalence of impulsive differential equations and its applications to partial impulsive differential equations
Authors: Georgieva A , Kostadinov S , Stamov GT , Alzabut JO
Published: August 2012

By means of the Schauder-Tychonoff principle,

L
p

(
k
)

-equivalence are established between linear and nonlinear perturbed impulsive differential equations with an unbounded linear part in an arbitrary Banach space. The feasibility of our theoretical results is illustrated by an example involving partial impulsive differential equations of the parabolic type.

MSC:34A37, 35Q72, 47H10.
Phylogenetic analysis of HDV isolates from HBsAg positive patients in Karachi, Pakistan
Authors: Perveen Shadab , Nasir Muhammad Israr , Shahid Syed M , Azhar Abid , Khan Obaid Yusuf
Published: August 2012

Background

In spite of a high occurrence of Hepatitis Delta in the province of Sindh in Pakistan, no genetic study of Hepatitis Delta virus (HDV) isolates from this region was carried out. The aim of this study is to analyze the genetic proximity within local HDV strains, and relationship with other clades of HDV, using phylogenetic analysis.

Results

Phylogenetic analysis of nucleotide sequences of the Hepatitis Delta Antigen (HDAg) R0 region obtained in this study, showed considerable diversity among the local strains with a potential subgroup formation within clade I. The multiple sequence alignment of predicted amino acids within clade I showed many uncommon amino acid substitutions within some conserved regions that are crucial for replication and assembly of HDV.

Conclusions

The studied strains showed a range of genetic diversity within HDV clade I. There is clustering of sequences into more than one group, along with formation of potential subgroup within clade I. Clustering shows the genetic closeness of strains and indicates a common origin of spread of HDV infection. Further phylogeny-based studies may provide more information about subgroup formation within clade I and may be used as an effective tool in checking and/or preventing the spread of hepatitis D virus infection in this region.
CO2 flagging - an improved method for the collection of questing ticks
Authors: Gherman Călin M , Mihalca Andrei D , Dumitrache Mirabela O , Györke Adriana , Oroian Ioan , Sandor Mignon , Cozma Vasile
Published: August 2012

Background

Most epidemiological studies on tick-borne pathogens involve collection of ticks from the environment. An efficient collection method is essential for large sample pools. Our main aim was to evaluate the efficacy of a new method, where traditional flagging was enhanced by the use of CO2 dispersed into the white flannel. The CO2 was spread through a rubber hose network inserted into the flag blanket. The research was conducted in spring, in March-April 2011 in two locations from Cluj County, Romania.

Methods

The research was conducted in March-April 2011 in two locations from Cluj County, Romania. The flag to be tested contained a fine silicone rubber hose network which dispersed the CO2 in the shaft. On each collection site n=30 samplings were performed. Each sampling consisted in the simultaneous use of both flags (with and without CO2) by two persons. The CO2 concentration level on the flag canvas surface was measured. The efficacy of the method was determined by counting comparatively the total number of ticks and separate developmental stage count.

Results

Using the CO2 improved flag, 2411 (59%) Ixodes ricinus and 100 (53.8%) Dermacentor marginatus ticks were captured, while the CO2-free flag accounted for the collection of 1670 I. ricinus (41%) and 86 (46.2%) D. marginatus ticks. The addition of CO2 prompted a concentration difference on the surface of the flag ranging between 756.5 and 1135.0 ppm with a mean value of 848.9 ppm.

Conclusion

The study showed that the CO2 enhanced sweep flag increased the ability of I. ricinus (p < 0001) but not of D. marginatus to be attracted to the flag blanket.
Molecular characterisation of Galba truncatula, Lymnaea neotropica and L. schirazensis from Cajamarca, Peru and their potential role in transmission of human and animal fascioliasis
Authors: Bargues M Dolores , Artigas Patricio , Khoubbane Messaoud , Ortiz Pedro , Naquira Cesar , Mas-Coma Santiago
Published: August 2012

Background

Human and animal fascioliasis is emerging in many world regions, among which Andean countries constitute the largest regional hot spot and Peru the country presenting more human endemic areas. A survey was undertaken on the lymnaeid snails inhabiting the hyperendemic area of Cajamarca, where human prevalences are the highest known among the areas presenting a "valley transmission pattern", to establish which species are present, genetically characterise their populations by comparison with other human endemic areas, and discuss which ones have transmission capacity and their potential implications with human and animal infection.

Methods

Therefore, ribosomal DNA ITS-2 and ITS-1, and mitochondrial DNA 16S andcox1 were sequenced by the dideoxy chain-termination method.

Results

Results indicate the presence of three, morphologically similar, small lymnaeid species belonging to theGalba/Fossariagroup:Galba truncatula,Lymnaea neotropicaandL. schirazensis. Only one combined haplotype for each species was found. The ITS-1, 16S andcox1 haplotypes ofG. truncatulaare new. No new haplotypes were found in the other two species. This scenario changes previous knowledge, in which onlyL. viator(=L. viatrix) was mentioned.Galba truncatulaappears to be the most abundant, with high population densities and evident anthropophyly including usual presence in human neighbourhood. Infection byFasciola hepaticalarval stages were molecularly confirmed in two populations of this species. The nearness betweenG. truncatulapopulations presenting liver fluke infection and both human settings and schools for children, together with the absence of populations of other lymnaeid species in the locality, suggest a direct relationship with human infection.

Conclusions

The geographical overlap of three lymnaeid species poses problems for epidemiological studies and control action. First, a problem in classifying lymnaeid specimens in both field and laboratory activities, given their transmission capacity differences:G. truncatulamainly involved in transmission to humans,L neotropicatypically responsible for livestock infection, andL. schirazensisunable for transmission. Although several phenotypic characteristics may be helpful for a preliminary specimen classification, a definitive classification can only be obtained by marker sequencing. Aditionally,L. schirazensisincreases the confusion, owing to its ability to mix with otherGalba/Fossariaspecies and distort fascioliasis data such as transmission capacity and infection susceptibility. Second, a problem for epidemiological analysis, surveillance and control by methods as mathematical modelling and Remote Sensing - Geographical Information Systems. In Cajamarca, low resolution mapping may be insufficient, as already verified in Andean areas where different lymnaeid species overlap.
The involvement of the wnt signaling pathway and TCF7L2 in diabetes mellitus: The current understanding, dispute, and perspective
Authors: Ip Wilfred , Chiang Yu-ting Alex , Jin Tianru
Published: August 2012

The Wnt signaling pathway was initially discovered for its role in tumorigenesis and the development ofDrosophilaand other eukaryotic organisms. The key effector of this pathway, the bipartite transcription factor β-cat/TCF, is formed by free β-catenin (β-cat) and a TCF protein, including TCF7L2. Extensive recent investigations have highlighted the role of the Wnt signaling pathway in metabolic homeostasis and its implication in diabetes and other metabolic diseases. Genome-wide association studies have shown that several key components of the Wnt signaling pathway are implicated in metabolic homeostasis and the development of type 2 diabetes (T2D). Despite controversial observations regarding the role of Wnt signaling in the development and function of pancreatic islets, the discovery of the association between certain single nucleotide polymorphisms of TCF7L2 and T2D susceptibility has fueled great efforts to explore the role of Wnt signaling in the function of pancreatic β-cells and glucose homeostasis. Here we have introduced our basic understanding of the canonical Wnt signaling pathway, summarized our current knowledge on its implication in metabolic homeostasis and T2D, discussed the work on TCF7L2 as a T2D susceptibility gene, and presented the controversial role of Wnt signaling and TCF7L2 in pancreatic islets as well as their potential metabolic function in other organs. We then expanded our view into the crosstalk among Wnt, insulin and FOXO signaling cascades, which further illustrates the complexity of the Wnt signaling pathway in metabolic homeostasis. Finally, we have presented our perspectives.
Dynamic fluorescence imaging of the free radical products of X-ray absorption in live cells
Authors: Rappole Catherine A , Mitra Kasturi , Wen Han
Published: August 2012

The immediate products of x-ray absorption in aqueous biological samples are free radicals including *OH, H2O2, *H and solvated electrons. Because their lifetimes and diffusion ranges are dependent on the local bio-molecular environment, imaging these free radicals in real-time while they are produced by a scanning x-ray nanobeam may provide a biological microscopy method of high resolution. As a first step towards this goal, we investigated the feasibility of imaging the initial free radical products of x-ray absorption in live cells using fluorescent free radical sensors. We selected six commercially available fluorescent sensors for screening tests of their sensitivities towards x-ray radiation in solution form. Two of the six dyes were found to have high sensitivities. One of the two was successfully used for dynamic confocal fluorescence imaging of x-ray generated free radicals in the intracellular space of mouse embryonic fibroblasts. Time series of fluorescence images before and during x-ray radiation were acquired. The rate of increase of cellular fluorescence showed both the initial production of free radicals by the physical ionization events as well as stimulated biological production of reactive oxygen species later on. The implications of the results for future development of microscopy techniques are discussed.
Factor H autoantibodies and deletion of Complement Factor H-Related protein-1 in rheumatic diseases in comparison to atypical hemolytic uremic syndrome
Authors: Foltyn Zadura Anna , Zipfel Peter F , Bokarewa Maria I , Sturfelt Gunnar , Jönsen Andreas , Nilsson Sara C , Hillarp Andreas , Saxne Tore , Trouw Leendert A , Blom Anna M
Published: August 2012

Introduction

Complement activation is involved in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and atypical hemolytic uremic syndrome (aHUS). Autoantibodies to complement inhibitor factor H (FH), particularly in association with deletions of the gene coding for FH-related protein 1 (CFHR1), are associated with aHUS.

Methods

Autoantibodies against FH, factor I (FI) and C4b-binding protein (C4BP) were measured by ELISA, while CFHR1 homozygous deletion was determined with Western blotting of sera. Epitopes for FH autoantibodies were mapped using recombinant fragments of FH.

Results

FH autoantibodies were detected in SLE (6.7%, n = 60, RA patients (16.5%, n = 97 in the Swedish cohort and 9.2%, n = 217 in the Dutch cohort) and thrombosis patients positive for the lupus anticoagulants (LA+) test (9.4%, n = 64) compared with aHUS patients (11.7%, n = 103). In the control groups (n = 354), an average of 4% of individuals were positive for FH autoantibodies. The frequencies observed in both RA cohorts and LA+ patients were statistically significantly higher than in controls. We also found that an average of 15.2% of the FH-autoantibody positive individuals in all studied disease groups had homozygous deficiency of CFHR1 compared with 3.8% of the FH autoantibody negative patients. The levels of FH autoantibodies varied in individual patients over time. FH autoantibodies found in LA+, SLE and RA were directed against several epitopes across FH in contrast to those found in aHUS, which bound mainly to the C-terminus. Autoantibodies against FI and C4BP were detected in some patients and controls but they were not associated with any of the diseases analyzed in this study.

Conclusions

Autoantibodies against FH are not specific for aHUS but are present at a significant frequency in rheumatic diseases where they could be involved in pathophysiological mechanisms.
Toll-like receptors in the host defense against Pseudomonas aeruginosa respiratory infection and cystic fibrosis
Authors: McIsaac Shayla M , Stadnyk Andrew W , Lin Tong-Jun
Published: August 2012

Review of innate cell TLR activation by Pseudomonas aeruginosa to explain lung inflammation during cystic fibrosis, and the prospects of preventing infection.

TLRs function in innate immunity by detecting conserved structures present in bacteria, viruses, and fungi. Although TLRs do not necessarily distinguish pathogenic organisms from commensals, in the context of compromised innate immunity and combined with pathogensˈ effector molecules, TLRs drive the host response to the organism. This review will discuss the evidence and role(s) of TLRs in the response to the opportunistic bacterial pathogen, Pseudomonas aeruginosa, as it relates to respiratory infection and CF, in which innate immune mechanisms are indeed compromised. Outer membrane lipoproteins, LPS, flagellin, and nucleic acids all serve as ligands for TLR2, -4, -5, and -9, respectively. These TLRs and their respective downstream effector molecules have proven critical to the host response to P. aeruginosa, although the protective effects of TLRs may be impaired and in some cases, enhanced in the CF patient, contributing to the particular susceptibility of individuals with this disease to P. aeruginosa infection.
Tissue Platinum Concentration and Tumor Response in Non–Small-Cell Lung Cancer
Authors: Kim Eric S. , Lee J. Jack , He Guangan , Chow Chi-Wan , Fujimoto Junya , Kalhor Neda , Swisher Stephen G. , Wistuba Ignacio I. , Stewart David J. , Siddik Zahid H.
Published: August 2012

Purpose

Platinum resistance is a major limitation in the treatment of advanced non–small-cell lung cancer (NSCLC). Reduced intracellular drug accumulation is one of the most consistently identified features of platinum-resistant cell lines, but clinical data are limited. We assessed the effects of tissue platinum concentrations on response and survival in NSCLC.

Patients and Methods

We measured total platinum concentrations by flameless atomic absorption spectrophotometry in 44 archived fresh-frozen NSCLC specimens from patients who underwent surgical resection after neoadjuvant platinum-based chemotherapy. Tissue platinum concentration was correlated with percent reduction in tumor size on post- versus prechemotherapy computed tomography scans. The relationship between tissue platinum concentration and survival was assessed by univariate and multicovariate Cox proportional hazards regression model analysis and Kaplan-Meier analysis.

Results

Tissue platinum concentration correlated significantly with percent reduction in tumor size (P < .001). The same correlations were seen with cisplatin, carboplatin, and all histology subgroups. Furthermore, there was no significant impact of potential variables such as number of cycles and time lapse from last chemotherapy on platinum concentration. Patients with higher platinum concentration had longer time to recurrence (P = .034), progression-free survival (P = .018), and overall survival (P = .005) in the multicovariate Cox model analysis after adjusting for number of cycles.

Conclusion

This clinical study established a relationship between tissue platinum concentration and response in NSCLC. It suggests that reduced platinum accumulation might be an important mechanism of platinum resistance in the clinical setting. Further studies investigating factors that modulate intracellular platinum concentration are warranted.
Against the Period
Authors: Kates Joshua
Published: August 2012

This essay returns to part 2, chapter 4 of Louis Althusser and Étienne Balibar’s landmark text Reading Capital to interrogate some of the historiographical concepts upon which literary studies continues to rely, especially that of the period. Althusser’s profound critique of the period remains cogent, this article argues, for a field in which individual events and texts and large-scale social and political formations are often bound together by no framework other than their putative belonging to one and the same block of time—that is, a period. Aiming to reform this concept in order to institute a more complex historiography, Althusser invents a version of what came to be known simply as “theory.” (Théorie was the name of Althusser’s series at Maspero, in which Reading Capital and many of his subsequent works appeared.) Thus, while this essay, on the one hand, discloses the limits of Althusser’s own practice of theory (in its ambivalent relation to structuralism), it concludes, on the other, that no genuine reworking is possible of the historical horizon we all presuppose, apart from the revival of theory or one of its avatars or successors. As in Althusser’s example, theory’s task, as yet unfulfilled, is to recast thought and knowledge’s relation to time and history.
Diffusion tensor imaging in spinal cord compression
Authors: Wang Wei , Qin Wen , Hao Nanxin , Wang Yibin , Zong Genlin
Published: August 2012

Background

Although diffusion tensor imaging has been successfully applied in brain research for decades, several main difficulties have hindered its extended utilization in spinal cord imaging.

Purpose

To assess the feasibility and clinical value of diffusion tensor imaging and tractography for evaluating chronic spinal cord compression.

Material and Methods

Single-shot spin-echo echo-planar DT sequences were scanned in 42 spinal cord compression patients and 49 healthy volunteers. The mean values of the apparent diffusion coefficient and fractional anisotropy were measured in region of interest at the cervical and lower thoracic spinal cord. The patients were divided into two groups according to the high signal on T2WI (the SCC-HI group and the SCC-nHI group for with or without high signal). A one-way ANOVA was used. Diffusion tensor tractography was used to visualize the morphological features of normal and impaired white matter.

Results

There were no statistically significant differences in the apparent diffusion coefficient and fractional anisotropy values between the different spinal cord segments of the normal subjects. All of the patients in the SCC-HI group had increased apparent diffusion coefficient values and decreased fractional anisotropy values at the lesion level compared to the normal controls. However, there were no statistically significant diffusion index differences between the SCC-nHI group and the normal controls. In the diffusion tensor imaging maps, the normal spinal cord sections were depicted as fiber tracts that were color-encoded to a cephalocaudal orientation. The diffusion tensor images were compressed to different degrees in all of the patients.

Conclusion

Diffusion tensor imaging and tractography are promising methods for visualizing spinal cord tracts and can provide additional information in clinical studies in spinal cord compresion.
Laparotomy for a patient with warfarin-induced large bowel obstruction
Authors: Pericleous S , Maguire N , Cumming J G
Published: August 2012

Many commonly prescribed drugs can interact with warfarin and prolong bleeding time beyond therapeutic limits. We report a patient who developed a rectus sheath haematoma following inadvertent over anticoagulation. Despite conservative management, the patient went on to develop large bowel obstruction from the expanding haematoma and operative intervention became necessary.
Plasticity of Metabotropic Glutamate Receptor-Dependent Long-Term Depression in the Anterior Cingulate Cortex after Amputation
Authors: Kang SukJae Joshua , Liu Ming-Gang , Chen Tao , Ko Hyoung-Gon , Baek Gi-Chul , Lee Hye-Ryeon , Lee Kyungmin , Collingridge Graham L. , Kaang Bong-Kiun , Zhuo Min
Published: August 2012

Long-term depression (LTD) is a key form of synaptic plasticity important in learning and information storage in the brain. It has been studied in various cortical regions, including the anterior cingulate cortex (ACC). ACC is a crucial cortical region involved in such emotion-related physiological and pathological conditions as fear memory and chronic pain. In the present study, we used a multielectrode array system to map cingulate LTD in a spatiotemporal manner within the ACC. We found that low-frequency stimulation (1 Hz, 15 min) applied onto deep layer V induced LTD in layers II/III and layers V/VI. Cingulate LTD requires activation of metabotropic glutamate receptors (mGluRs), while L-type voltage-gated calcium channels and NMDA receptors also contribute to its induction. Peripheral amputation of the distal tail impaired ACC LTD, an effect that persisted for at least 2 weeks. The loss of LTD was rescued by priming ACC slices with activation of mGluR1 receptors by coapplying (RS)-3,5-dihydroxyphenylglycine and MPEP, a form of metaplasticity that involved the activation of protein kinase C. Our results providein vitroevidence of the spatiotemporal properties of ACC LTD in adult mice. We demonstrate that tail amputation causes LTD impairment within the ACC circuit and that this can be rescued by activation of mGluR1.
Bidirectional Plasticity of Intrinsic Excitability Controls Sensory Inputs Efficiency in Layer 5 Barrel Cortex Neuronsin Vivo
Authors: Mahon Séverine , Charpier Stéphane
Published: August 2012

Responsiveness of cortical neurons to sensory inputs can be altered by experience and learning. While synaptic plasticity is generally proposed as the underlying cellular mechanism, possible contributions of activity-dependent changes in intrinsic excitability remain poorly investigated. Here, we show that periods of rhythmic firing in rat barrel cortex layer 5 pyramidal neurons can trigger a long-lasting increase or decrease in their membrane excitabilityin vivo. Potentiation of cortical excitability consisted of an increased firing in response to intracellular stimulation and a reduction in threshold current for spike initiation. Conversely, depression of cortical excitability was evidenced by an augmented firing threshold leading to a reduced current-evoked spiking. The direction of plasticity depended on the baseline level of spontaneous firing rate and cell excitability. We also found that changes in intrinsic excitability were accompanied by corresponding modifications in the effectiveness of sensory inputs. Potentiation and depression of cortical neuron excitability resulted, respectively, in an increased or decreased firing probability on whisker-evoked synaptic responses, without modifications in the synaptic strength itself. These data suggest that bidirectional intrinsic plasticity could play an important role in experience-dependent refinement of sensory cortical networks.
Opioid Activation of Toll-Like Receptor 4 Contributes to Drug Reinforcement
Authors: Hutchinson M. R. , Northcutt A. L. , Hiranita T. , Wang X. , Lewis S. S. , Thomas J. , van Steeg K. , Kopajtic T. A. , Loram L. C. , Sfregola C. , Galer E. , Miles N. E. , Bland S. T. , Amat J. , Rozeske R. R. , Maslanik T. , Chapman T. R. , Strand K. A. , Fleshner M. , Bachtell R. K. , Somogyi A. A. , Yin H. , Katz J. L. , Rice K. C. , Maier S. F. , Watkins L. R.
Published: August 2012

Opioid action was thought to exert reinforcing effects solely via the initial agonism of opioid receptors. Here, we present evidence for an additional novel contributor to opioid reward: the innate immune pattern-recognition receptor, toll-like receptor 4 (TLR4), and its MyD88-dependent signaling. Blockade of TLR4/MD2 by administration of the nonopioid, unnatural isomer of naloxone, (+)-naloxone (rats), or two independent genetic knock-outs of MyD88-TLR4-dependent signaling (mice), suppressed opioid-induced conditioned place preference. (+)-Naloxone also reduced opioid (remifentanil) self-administration (rats), another commonly used behavioral measure of drug reward. Moreover, pharmacological blockade of morphine-TLR4/MD2 activity potently reduced morphine-induced elevations of extracellular dopamine in rat nucleus accumbens, a region critical for opioid reinforcement. Importantly, opioid-TLR4 actions are not a unidirectional influence on opioid pharmacodynamics, sinceTLR4−/−mice had reduced oxycodone-induced p38 and JNK phosphorylation, while displaying potentiated analgesia. Similar to our recent reports of morphine-TLR4/MD2 binding, here we provide a combination ofin silicoand biophysical data to support (+)-naloxone and remifentanil binding to TLR4/MD2. Collectively, these data indicate that the actions of opioids at classical opioid receptors, together with their newly identified TLR4/MD2 actions, affect the mesolimbic dopamine system that amplifies opioid-induced elevations in extracellular dopamine levels, therefore possibly explaining altered opioid reward behaviors. Thus, the discovery of TLR4/MD2 recognition of opioids as foreign xenobiotic substances adds to the existing hypothesized neuronal reinforcement mechanisms, identifies a new drug target in TLR4/MD2 for the treatment of addictions, and provides further evidence supporting a role for central proinflammatory immune signaling in drug reward.
Topography of Native SK Channels Revealed by Force Nanoscopy in Living Neurons
Authors: Maciaszek Jamie L. , Soh Heun , Walikonis Randall S. , Tzingounis Anastasios V. , Lykotrafitis George
Published: August 2012

The spatial distribution of ion channels is an important determinant of neuronal excitability. However, there are currently no quantitative techniques to map endogenous ion channels with single-channel resolution in living cells. Here, we demonstrate that integration of pharmacology with single-molecule atomic force microscopy (AFM) allows for the high-resolution mapping of native potassium channels in living neurons. We focus on calcium-activated small conductance (SK) potassium channels, which play a critical role in brain physiology. By linking apamin, a toxin that specifically binds to SK channels, to the tip of an AFM cantilever, we are able to detect binding events between the apamin and SK channels. We find that native SK channels from rat hippocampal neurons reside primarily in dendrites as single entities and in pairs. We also show that SK channel dendritic distribution is dynamic and under the control of protein kinase A. Our study demonstrates that integration of toxin pharmacology with single-molecule AFM can be used to quantitatively map individual native ion channels in living cells, and thus provides a new tool for the study of ion channels in cellular physiology.
Characterization of Multiple Exon 1 Variants in Mammalian HuD mRNA and Neuron-Specific Transcriptional Control via Neurogenin 2
Authors: Bronicki Lucas M. , Bélanger Guy , Jasmin Bernard J.
Published: August 2012

The RBP (RNA-binding protein) and Hu/ELAV family member HuD regulates mRNA metabolism of genes directly or indirectly involved in neuronal differentiation, learning and memory, and several neurological diseases. Given the important functions of HuD in a variety of processes, we set out to determine the mechanisms that promote HuD mRNA expression in neurons using a mouse model. Through several complementary approaches, we determined that the abundance of HuD mRNA is predominantly under transcriptional control in developing neurons. Bioinformatic and 5′RACE (rapid amplification of cDNA ends) analyses of the 5′ genomic flanking region identified eight conserved HuD leader exons (E1s), two of which are novel. Expression of all E1 variants was determined in mouse embryonic (E14.5) and adult brains. Sequential deletion of the 5′ regulatory region upstream of the predominantly expressed E1c variant revealed a well conserved 400 bp DNA region that contains five E-boxes and is capable of directing HuD expression specifically in neurons. Using EMSA (electrophoretic mobility shift assay), ChIP (chromatin immunoprecipitation), and 5′ regulatory region deletion and mutation analysis, we found that two of these E-boxes are targets of Neurogenin 2 (Ngn2) and that this mechanism is important for HuD mRNA induction. Together, our findings reveal that transcriptional regulation of HuD involves the use of alternate leader exons and Ngn2 mediates neuron-specific mRNA expression. To our knowledge, this is the first study to identify molecular events that positively regulate HuD mRNA expression.
Regulation of Postnatal Forebrain Amoeboid Microglial Cell Proliferation and Development by the Transcription Factor Runx1
Authors: Zusso Morena , Methot Laurent , Lo Rita , Greenhalgh Andrew D. , David Samuel , Stifani Stefano
Published: August 2012

Microglia are the immune cells of the nervous system, where they act as resident macrophages during inflammatory events underlying many neuropathological conditions. Microglia derive from primitive myeloid precursors that colonize the nervous system during embryonic development. In the postnatal brain, microglia are initially mitotic, rounded in shape (amoeboid), and phagocytically active. As brain development proceeds, they gradually undergo a transition to a surveillant nonphagocytic state characterized by a highly branched (ramified) morphology. This ramification process is almost recapitulated in reverse during the process of microglia activation in the adult brain, when surveillant microglia undergo a ramified-to-amoeboid morphological transformation and become phagocytic in response to injury or disease. Little is known about the mechanisms controlling amoeboid microglial cell proliferation, activation, and ramification during brain development, despite the critical role of these processes in the establishment of the adult microglia pool and their relevance to microglia activation in the adult brain. Here we show that the mouse transcription factor Runx1, a key regulator of myeloid cell proliferation and differentiation, is expressed in forebrain amoeboid microglia during the first two postnatal weeks. Runx1 expression is then downregulated in ramified microglia. Runx1 inhibits mouse amoeboid microglia proliferation and promotes progression to the ramified state. We show further that Runx1 expression is upregulated in microglia following nerve injury in the adult mouse nervous system. These findings provide insight into the regulation of postnatal microglia activation and maturation to the ramified state and have implications for microglia biology in the developing and injured brain.
Earlier Speech Exposure Does Not Accelerate Speech Acquisition
Authors: Peña Marcela , Werker Janet F. , Dehaene-Lambertz Ghislaine
Published: August 2012

Critical periods in language acquisition have been discussed primarily with reference to studies of people who are deaf or bilingual. Here, we provide evidence on the opening of sensitivity to the linguistic environment by studying the response to a change of phoneme at a native and nonnative phonetic boundary in full-term and preterm human infants using event-related potentials. Full-term infants show a decline in their discrimination of nonnative phonetic contrasts between 9 and 12 months of age. Because the womb is a high-frequency filter, many phonemes are strongly degradedin utero. Preterm infants thus benefit from earlier and richer exposure to broadcast speech. We find that preterms do not take advantage of this enriched linguistic environment: the decrease in amplitude of the mismatch response to a nonnative change of phoneme at the end of the first year of life was dependent on maturational age and not on the duration of exposure to broadcast speech. The shaping of phonological representations by the environment is thus strongly constrained by brain maturation factors.
Passivitätsbasierte Regelung schaltender nichtlinearer Systeme
Authors: Kloiber Tobias , Kotyczka Paul
Published: August 2012

Es wird eine konstruktive Reglerentwurfsmethode für schaltende nichtlineare steuerungssaffine Systeme vorgestellt, die dem geschlossenen Regelkreis eine schaltende Port-Hamiltonsche Struktur mit gemeinsamer Energiefunktion zuweist und so (asymptotische) Stabilität der Ruhelage erzielt. Die Methode generiert alle schaltenden Zustandsrückführungen, welche die Strecke unter beliebigem Schalten asymptotisch stabilisieren. Für eine spezielle Systemklasse wird ein systematisches Vorgehen für den Reglerentwurf präsentiert. Dabei wird ein neues Ergebnis zur Matrixgleichung
AX+X

T

A

T
=Q
vorgestellt.
Beobachterbasierte Zustandsrückführungen für hyperbolische verteiltparametrische Systeme
Authors: Woittennek Frank
Published: August 2012

Der Beitrag behandelt den Entwurf von Zustandsrückführungen für hyperbolische Systeme mit örtlich verteilten Parametern in einer Ortsdimension. Grundlage für den Entwurf sind hyperbolische Regelungs- und Beobachterformen. Die Transformation in diese speziellen Zustandsdarstellungen wird mit Hilfe flachheitsbasierter Methoden berechnet und anhand eines einfachen Beispiel erläutert. Der Nutzen der Methode wird in Simulationsstudien nachgewiesen.
Dexmedetomidine for Transport of a Spontaneously Breathing Combative Child
Authors: Watt Kevin M. , Walgos Jason , Cheifetz Ira M. , Turner David A.
Published: August 2012

Interhospital transport presents a challenge for pediatricians, and airway protection is often a significant concern. The severely agitated child without respiratory compromise poses an extremely difficult dilemma, as most sedative agents can cause respiratory depression. Intubation offers definitive control of the airway but is not without risk, especially in an environment where experience and resources for pediatric intubation may be limited. Dexmedetomidine may be used for sedation in certain circumstances for the transport of a child without the need for intubation and mechanical ventilation.
Recent options in drug therapy after solid organ transplantation
Authors: Pőcze Balázs , Németh Péter , Langer Róbert
Published: August 2012

Solid organ transplantation has shown improvement in patient and graft survival rates due to the development of immunosuppression in the last fifty years; however only the last two decades led to the development of new, baseline immunosuppressive drugs that avoid the unlikely side effects of calcineurin inhibitors, especially nephrotoxicity. The transplanted organ is foreign to the host and, therefore, it induces a complex immune response of the recipient. In this review, a brief outline of immune response is given, followed by the introduction of new immunosuppressive drugs acting via variant pathways. These are compounds which are already in use or becoming shortly available and are potential future alternatives for the calcineurin inhibitors. This paper highlights the role of co-stimulation blockade with belatacept and the recently even more intensively studied field of tolerance induction. Orv. Hetil., 2012, 153, 1294–1301.
Gynecological screening or cervical screening? Conflicts between clinical and public health viewpoints
Authors: Döbrőssy Lajos , Kovács Attila , Budai András , Cornides Ágnes
Published: August 2012

The ”gynecological screening” that is composed of complex gynecological examination including colposcopy and cytological examinations has traditionally been incorporated into the gynecological protocol and practice. Over the past few decades, unfortunately, this screening practice has entrenched in the mind both of the gynecological community and the general public. As a result, the government-supported, organized cervical screening program of the population has come to a standstill. In order to adjust the cervical screening practice to the international public health recommendations in which cytology is the only screening test applied, the authors decided to involve primary care nurses and health visitors in smear taking, and to refer those with abnormal findings to a gynecologist for further clinical examination. Orv. Hetil., 2012, 153, 1302–1313.
Concentrações séricas eficazes após doses únicas de drogas anti-epiléticas: conceito de dose carga
Authors: Bittencourt Paulo R.M. , Richens Alan
Published: August 2012

Doses únicas de fenitoína (500 a l.OOOmg), carbamazepina (400 e l.OOOmg) e valproato de sódio (600mg) foram administradas oralmente a 5 voluntários normais jovens e concentrações séricas foram determinadas entre 1 e 8 horas após administração. A técnica foi duplo-cega, controlada por placebo. Concentrações séricas "terapêuticas" foram obtidas após valproato de sódio e após a dose de l.OOOmg de carbamazepina. Os resultados sugerem que doses-carga de fenitoína (1.500-2.000mg) e carbamazepina (800mg) são úteis no controle sub-agudo de crises epilépticas freqüentes em pacientes de ambulatório e que carbamazepina pode ser utilizada para o controle crônico de estado de mal epiléptico inicialmente tratado com diazepam ou outra preparação de ação rápida.
Neurocriptococose e imunossupressão: modelo experimental, em camundongos
Authors: Machado L. R. , Fecchio Denise , Limongi J. C. P. , Berger A. , Livramento J. A. , Spina-França A.
Published: August 2012

Com o objetivo de padronizar modelo experimental de imunossupressão foram selecionados dois lotes de 50 camundongos impúberes, cada um dividido em grupos de 10, e submetidos a ação de dexametasona. O estudo foi dividido em dois experimentos. No primeiro experimento foi utilizado o primeiro lote de animais e foram estabelecidas as condições para obtenção de modelo de imunossupressão em camundongos mediante administração de dexametasona diluída na água de consumo e ingerida ad libitum pelos animais. Entre os critérios utilizados para avaliar a vigência de imunossupressão são realçados: a ocorrência de eriçamento de pelos, leucopenia por diminuição do número de linfócitos e hipotrofia do baço comparativamente aos controles, com hipoplasia intensa de todas as estruturas linfóides. No segundo experimento foi empregado o segundo lote de animais e foi estudado o comportamento do modelo experimental estabelecido. Os animais receberam, por via intraperitonial, número aproximado delO6 leveduras com os caracteres morfológicos do Cryptococcus neoformans, provenientes de culturas de cepas patogênicas ao homem e isoladas do líquido cefalorraqueano de pacientes com neurocriptococose. Apesar de haverem sido identificadas leveduras em cortes histológicos de pulmão, fígado e baço em todos os camundongos inoculados, somente ocorreu o óbito naqueles em que havia acometimento do sistema nervoso central pela levedura (aproximadamente 50% dos animais). A discussão dos resultados obtidos e seu significado inclui considerações sobre o possível papel desempenhado pela função barreira hêmato-encefálica no evento constatado.
Hematomas intracerebrais hipertensivos: a propósito de 50 casos
Authors: Lynch José Carlos , Alves Ricardo , Ribeiro Ricardo , Lima José Geraldo
Published: August 2012

São analisados 50 pacientes com hematomas hipertensivos supratentoriais. A literatura pertinente é revista. As várias proposições de tratamento desta patologia são apresentadas e analisadas. Os autores também propõem uma rotina de tratamento para os hematomas hipertensivos supratentoriais.
Intoxicação por difenilhidantoína: em monoterapia e em combinação com outros anticonvulsivantes
Authors: Schelp A. O. , Weisner B.
Published: August 2012

Entre julho de 1979 e julho de 1984 foram determinadas as concentrações plasmáticas de difenilhidantoína de 1.000 pacientes que faziam uso do medicamento como única droga ou em associação com outros anticonvulsivantes. Sob monoterapia encontramos um percentual de 3,3% com níveis séricos acima de 24mg/l e 0,4% com sinais clínicos de efeitos colaterais. Entre os pacientes em utilização de associação medicamentosa foi determinada elevação dos níveis séricos de difenilhidantoína em 9,1% dos pacientes e sinais clínicos de intoxicação em 4,6%. Não foi constatado predomínio de qualquer das diferentes associações medicamentosas na frequência de sinais clínicos de intoxicação. Os dados reforçam a assertiva de que devemos esgotar todas as possibilidades de controle com uma única droga, antes de tentar a utilização de um segundo medicamento.
Hemorragia cerebral como primeira manifestação do lupus eritematoso sistêmico: estudo clínico e histopatológico de dois casos
Authors: Nascimento Osvaldo J. M. , Freitas Marcos R. G. de , Cavalcanti José Luiz S. , Barretto Netto Manoel
Published: August 2012

Os autores apresentam duas pacientes que iniciaram a doença lúpica com quadro de hemorragia cerebral. Na primeira realizou-se estudo tomográfico que revelou área compatível a sangramento no parênquima nervoso. Na segunda paciente, da gravidade do quadro decorreu o óbito, tendo sido realizado estudo anatomopatológico. São feitas considerações sobre a baixa incidência de hemorragia no SNC em pacientes com LES, a importância no presente de estudos tomográficos e a possível fisiopatogenia do quadro hemorrágico nessa colagenose.
Polimioclonia-opsoclono: síndrome de Kinsbourne. Relato de um caso
Authors: Vieira João Batista Arruda , Rosa Evandro Diniz
Published: August 2012

Registro de um caso de polimioclonia-opsoclono, síndrome de Kinsbourne, em paciente pertencente a grupo etário superior ao normalmente citado na literatura. O aparecimento da polimioclonia foi marcado por característica incomum, a de apresentar-se de forma ascendente. O tratamento instituído baseou-se no uso de dexametasona, havendo evolução clínica favorável.