bluuebunny/crossref_metadata_2025 huggingface dataset:
eClasSkeduler: A Course Scheduling System for the Executive Education Unit at the Universidad de Chile
Authors: Miranda Jaime
Published: February 2010

Each October, the Executive Education Unit at the Universidad de Chile develops its course schedules for the following year. By 2008, the complexities of increasing enrollments and course offerings had rendered its manual timetabling process unmanageable. Inconvenient and inflexible scheduling decisions were causing discontent among instructors and students, making the need for a more efficient system of assigning classrooms patent. Three characteristics distinguish the unit's situation from the classic university course timetabling problem. First, its courses vary in duration, ranging between 15 and 30 weeks. Second, its course start dates are spread over the academic year. Finally, each course's start date is flexible and must fall within a window defined by the earliest and latest start dates. This paper presents an automated computational system that generates optimal timetables and classroom assignments for all the unit's courses, minimizing both operating costs and schedule conflicts. When we compared the schedules it generated with the unit's manually generated timetables, we found that our system yielded average cost savings of 35 percent; in addition, it reduced execution times (for generating schedules) from two weeks to less than 30 minutes.
A Customer Management Dilemma: When Is It Profitable to Reward One's Own Customers?
Authors: Shin Jiwoong , Sudhir K.
Published: February 2010

This study attempts to answer a basic customer management dilemma facing firms: when should the firm use behavior-based pricing (BBP) to discriminate between its own and competitors' customers in a competitive market? If BBP is profitable, when should the firm offer a lower price to its own customers rather than to the competitor's customers? This analysis considers two features of customer behavior up to now ignored in BBP literature: heterogeneity in customer value and changing preference (i.e., customer preferences are correlated but not fixed over time). In a model where both consumers and competing firms are forward-looking, we identify conditions when it is optimal to reward the firm's own or competitor's customers and when BBP increases or decreases profits. To the best of our knowledge, we are the first to identify conditions in which (1) it is optimal to reward one's own customers under symmetric competition and (2) BBP can increase profits with fully strategic and forward-looking consumers.
Cyclosporine-Induced Pain Syndrome; Amlodipine-Induced Myoclonus; Probable Amlodipine-Induced Angioedema; Liver Injury with Clopidogrel; Sunitinib-Induced Myxedema Coma; Review: Sexual Dysfunction, Depression, and Antidepressants
Authors: Shuster Joel
Published: February 2010

The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers.
Cefepime-Induced Neurotoxicity: A Review of the Evidence
Authors: Zemrak Wesley R.
Published: February 2010

Purpose

Cefepime-induced neurotoxicity is a relatively underappreciated and unrecognized adverse event in current clinical practice. Because cefepime is widely used in many hospitals, it is vital that clinicians be aware of this adverse event.

Methods

A systematic review of the literature was conducted to highlight the current evidence linking cefepime and neurotoxicity.

Results

More than 40 case reports were identified and analyzed for evidence of cefepime-induced neurotoxicity. Confusion, encephalopathy, coma, myoclonus, nonconvulsive status epilepticus, and frank seizures have been described. Most cases occurred in patients with impaired renal function. Onset of neurotoxicity ranged from 1 to 16 days. On discontinuation of cefepime, neurologic function returned to baseline.

Conclusions

Cefepime-induced neurotoxicity occurs primarily in patients with impaired renal function; however, several cases have occurred in patients with normal renal function. Most cases of neurotoxicity have arisen in patients who did not receive appropriate dose adjustment for renal impairment. The range of toxicity and latency are broad, thus clinicians must be aware of this adverse event and take all of the necessary steps to prevent the occurrence of neurotoxicity.
Dronedarone: Emergence of a New Therapeutic Option for the Treatment of Atrial Fibrillation
Authors: Howard Patricia A.
Published: February 2010

This continuing feature updates readers on recent developments in cardiovascular pharmacotherapy. Cardiovascular disease remains the number 1 killer in the United States, and more clinical outcome trials have been conducted in cardiology than in any other field of medicine. Given this rapidly expanding knowledge base, if pharmacists stay current with developments in drug therapy, they can have a significant impact on prevention and treatment.
Melphalan, Prednisone, and Thalidomide (MPT) Regimen for Multiple Myeloma
Authors: Waddell J. Aubrey , Solimando Dominic A.
Published: February 2010

The complexity of cancer chemotherapy requires that pharmacists be familiar with the complicated regimens and highly toxic agents used. This column reviews various issues related to preparing, dispensing, and administering antineoplastic therapy and to the agents, commercially available and investigational, used to treat malignant diseases.
Colchicine: Primary Amyloidosis
Authors: Generali Joyce A. , Cada Dennis J.
Published: February 2010

This Hospital Pharmacy feature is extracted from Off-Label Drug Facts, a quarterly publication available from Wolters Kluwer Health. Off-Label Drug Facts is a practitioner-oriented resource for information about specific drug uses that are unapproved by the US Food and Drug Administration. This new guide to the literature enables the health care professional or clinician to quickly identify published studies on off-label uses and determine if a specific use is rational in a patient care scenario. A summary of the most relevant data is provided, including background, study design, patient population, dosage information, therapy duration, results, safety, and therapeutic considerations. References direct the reader to the full literature for more comprehensive information before patient care decisions are made. Direct questions or comments regarding Off-Label Drug Uses to hospital pharmacy@drugfacts.com .
Reevaluation of Emergency Drug Management in a Tertiary Care Mother-Child Hospital
Authors: Bussières Jean-François , Scharr Karin , Marquis Christopher , Saindon Sophie , Toledano Baruch , Diliddo Lydia , Charrette Sylvie
Published: February 2010

Purpose

To evaluate the management of emergency drugs in a mother-child teaching hospital.

Methods

A physical inventory of all the resuscitation carts, emergency carts, and emergency boxes was taken. Fifteen compliance criteria were established to evaluate partial trays of emergency medications. The contents of full and partial emergency medication trays and boxes were revised, and an improved process was implemented based on a review of the literature. The research team included 2 pharmacists, 1 anesthetist, 1 intensivist, 1 emergency doctor, 1 nurse, and 1 research assistant.

Results

Before the harmonization process, there were 11 full resuscitation carts with 48 items and 30 partial emergency carts with an average item count of 15.4 ± standard deviation 4.4, as well as 16 pediatric boxes and 3 emergency boxes in pediatrics and obstetrics, respectively. During the evaluation process, 1,911 distribution units were checked, 2.5% of which had expired. Following the process there were 14 identical resuscitation carts with 43 items and 25 emergency carts with 21 items.

Conclusion

There are few examples of steps that can be taken to evaluate and update the management of emergency medications in health care facilities. This evaluative study outlines an approach that entailed taking a physical inventory, evaluating the process, and improving the management model within a tertiary care university hospital center. A review of the new process will be performed in 12 months' time.
Hyperglycemia Management in the Hospital: The Pharmacists Role
Authors: Eppley Melody A. , Serr Garrett
Published: February 2010

Hyperglycemia is prevalent in the inpatient setting and is associated with increased morbidity and mortality in patients with diabetes and in those without diabetes. Too often hyperglycemia is underrecognized, under-reported, and undermanaged. Insulin is the treatment of choice for most patients who have hyperglycemia and are hospitalized, and pharmacists are often responsible for ensuring its safe and effective use. Improving hyperglycemia management in patients who are hospitalized provides pharmacists with an opportunity to positively affect patient outcomes and health care costs. This article discusses the pharmacist's role in managing blood glucose levels; current recommendations for target blood glucose concentrations; the evolution of insulin treatment from sliding scale to algorithms/protocols to computer-guided decision-support systems; discharge planning; and patient education.
Developing a Meaningful Strategic Plan
Authors: Sanborn Michael
Published: February 2010

The Director's Forum series is written and edited by Michael Sanborn and Robert Weber and is designed for guiding pharmacy leaders in establishing patient-centered services in hospitals and health systems. Another specific goal of this column is addressing many of the key challenges that pharmacy directors currently face, while also providing information that will foster growth in pharmacy leadership and patient safety. Previous articles in this series have discussed the many different aspects of pharmacy management and leadership challenges. This feature addresses the importance of developing and effectively executing a pharmacy strategic plan.
Analysis of the water vapour sorption behaviour of Sitka spruce [Picea sitchensis (Bongard) Carr.] based on the parallel exponential kinetics model
Authors: Hill Callum A.S. , Norton Andrew , Newman Gary
Published: February 2010

The water vapour sorption behaviour of Sitka spruce was analysed based on the parallel exponential kinetics (PEK) model. The PEK model deconvolutes the sorption kinetics curve into two exponential kinetics processes (fast and slow) which have characteristic times and moisture contents associated with them. The sorption kinetics was examined at different temperatures enabling the determination of activation energies for the sorption kinetic processes throughout the hygroscopic range (from 5% to 95% relative humidities). The physical interpretation of the PEK model is also discussed.
Water sorption in wood and modified wood at high values of relative humidity. Part 2: Appendix. Theoretical assessment of the amount of capillary water in wood microvoids
Authors: Engelund Emil Tang , Thygesen Lisbeth G. , Hoffmeyer Preben
Published: February 2010

A theoretical study of the amount of moisture held in wood as capillary condensed water in the relative humidity (RH) range of 90–99.9% is carried out. The study is based on idealized geometries of the softwood structure related to micrographs. It is confined to structural elements such as bordered pits and the pointed ends of tracheids. The theoretical amount of water in these elements is found by employing the Kelvin equation. An equal amount of earlywood and latewood cells with different geometries and with different amounts of pits is assumed. The effect of pit aspiration is considered, and different degrees of pit aspiration are assigned to earlywood and latewood. We suggest based on the results that capillary condensation makes only a very small contribution to the equilibrium moisture content. At 99.9% RH the contribution amounts to less than 0.0035 kg water per kg dry wood. This is in line with the experimental results presented in Part 1 of this study.
Neuronal Stability and Drift across Periods of Sleep: Premotor Activity Patterns in a Vocal Control Nucleus of Adult Zebra Finches
Authors: Rauske Peter L. , Chi Zhiyi , Dave Amish S. , Margoliash Daniel
Published: February 2010

How stable are neural activity patterns compared across periods of sleep? We evaluated this question in adult zebra finches, whose premotor neurons in the nucleus robustus arcopallialis (RA) exhibit sequences of bursts during daytime singing that are characterized by precise timing relative to song syllables. Each burst has a highly regulated pattern of spikes. We assessed these spike patterns in singing that occurred before and after periods of sleep. For about half of the neurons, one or more premotor bursts had changed after sleep, an average of 20% of all bursts across all RA neurons. After sleep, modified bursts were characterized by a discrete, albeit modest, loss of spikes with compensatory increases in spike intervals, but not changes in timing relative to the syllable. Changes in burst structure followed both interrupted bouts of sleep (1.5–3 h) and full nights of sleep, implicating sleep and not circadian cycle as mediating these effects. Changes in burst structure were also observed during the day, but far less frequently. In cases where multiple bursts in the sequence changed in a single cell, the sequence position of those bursts tended to cluster together. Bursts that did not show discrete changes in structure also showed changes in spike counts, but not biased toward losses. We hypothesize that changes in burst patterns during sleep represent active sculpting of the RA network, supporting auditory feedback-mediated song maintenance.
Segregation of Acute Leptin and Insulin Effects in Distinct Populations of Arcuate Proopiomelanocortin Neurons
Authors: Williams Kevin W. , Margatho Lisandra O. , Lee Charlotte E. , Choi Michelle , Lee Syann , Scott Michael M. , Elias Carol F. , Elmquist Joel K.
Published: February 2010

Acute leptin administration results in a depolarization and concomitant increase in the firing rate of a subpopulation of arcuate proopiomelanocortin (POMC) cells. This rapid activation of POMC cells has been implicated as a cellular correlate of leptin effects on energy balance. In contrast to leptin, insulin inhibits the activity of some POMC neurons. Several studies have described a “cross talk” between leptin and insulin within the mediobasal hypothalamus via the intracellular enzyme, phosphoinositol-3-kinase (PI3K). Interestingly, both insulin and leptin regulate POMC cellular activity by activation of PI3K; however, it is unclear whether leptin and insulin effects are observed in similar or distinct populations of POMC cells. We therefore used dual label immunohistochemistry/in situhybridization and whole-cell patch-clamp electrophysiology to map insulin and leptin responsive arcuate POMC neurons. Leptin-induced Fos activity within arcuate POMC neurons was localized separate from POMC neurons that express insulin receptor. Moreover, acute responses to leptin and insulin were largely segregated in distinct subpopulations of POMC cells. Collectively, these data suggest that cross talk between leptin and insulin occurs within a network of cells rather than within individual POMC neurons.
Cilia Organize Ependymal Planar Polarity
Authors: Mirzadeh Zaman , Han Young-Goo , Soriano-Navarro Mario , García-Verdugo Jose Manuel , Alvarez-Buylla Arturo
Published: February 2010

Multiciliated epithelial cells, called ependymal cells, line the ventricles in the adult brain. Most ependymal cells are born prenatally and are derived from radial glia. Ependymal cells have a remarkable planar polarization that determines orientation of ciliary beating and propulsion of CSF. Disruption of ependymal ciliary beating, by injury or disease, results in aberrant CSF circulation and hydrocephalus, a common disorder of the CNS. Very little is known about the mechanisms guiding ependymal planar polarity and whether this organization is acquired during ependymal cell development or is already present in radial glia. Here we show that basal bodies in ependymal cells in the lateral ventricle walls of adult mice are polarized in two ways: (1) rotational; angle of individual basal bodies with respect to their long axis and (2) translational; the position of basal bodies on the apical surface of the cell. Conditional ablation of motile cilia disrupted rotational orientation, but translational polarity was largely preserved. In contrast, translational polarity was dramatically affected when radial glial primary cilia were ablated earlier in development. Remarkably, radial glia in the embryo have a translational polarity that predicts the orientation of mature ependymal cells. These results suggest that ependymal planar cell polarity is a multistep process initially organized by primary cilia in radial glia and then refined by motile cilia in ependymal cells.
Homeostatic Regulation of Synaptic Excitability: Tonic GABAAReceptor Currents ReplaceIhin Cortical Pyramidal Neurons of HCN1 Knock-Out Mice
Authors: Chen Xiangdong , Shu Shaofang , Schwartz Lauren C. , Sun Chengsan , Kapur Jaideep , Bayliss Douglas A.
Published: February 2010

Homeostatic control of synaptic efficacy is often mediated by dynamic regulation of excitatory synaptic receptors. Here, we report a novel form of homeostatic synaptic plasticity based on regulation of shunt currents that control dendritosomatic information transfer. In cortical pyramidal neurons from wild-type mice, HCN1 channels underlie a dendritic hyperpolarization-activated cationic current (Ih) that serves to limit temporal summation of synaptic inputs. In HCN1 knock-out mice, as expected,Ihis reduced in pyramidal neurons and its effects on synaptic summation are strongly diminished. Unexpectedly, we found a markedly enhanced bicuculline- and L-655,708-sensitive background GABAAcurrent in these cells that could be attributed to selective upregulation of GABAAα5 subunit expression in the cortex of HCN1 knock-out mice. Strikingly, despite diminishedIh, baseline sublinear summation of evoked EPSPs was unchanged in pyramidal neurons from HCN1 knock-out mice; however, blocking tonic GABAAcurrents with bicuculline enhanced synaptic summation more strongly in pyramidal cells from HCN1 knock-out mice than in those cells from wild-type mice. Increasing tonic GABAAreceptor conductance in the context of reducedIh, using computational or pharmacological approaches, restored normal baseline synaptic summation, as observed in neurons from HCN1 knock-out mice. These data indicate that upregulation of α5 subunit-mediated GABAAreceptor tonic current compensates quantitatively for loss of dendriticIhin cortical pyramidal neurons from HCN1 knock-out mice to maintain normal synaptic summation; they further imply that dendritosomatic synaptic efficacy is a controlled variable for homeostatic regulation of cortical neuron excitabilityin vivo.
Redox Dysregulation Affects the Ventral But Not Dorsal Hippocampus: Impairment of Parvalbumin Neurons, Gamma Oscillations, and Related Behaviors
Authors: Steullet Pascal , Cabungcal Jan-Harry , Kulak Anita , Kraftsik Rudolf , Chen Ying , Dalton Timothy P. , Cuenod Michel , Do Kim Q.
Published: February 2010

Elevated oxidative stress and alteration in antioxidant systems, including glutathione (GSH) decrease, are observed in schizophrenia. Genetic and functional data indicate that impaired GSH synthesis represents a susceptibility factor for the disorder. Here, we show that a genetically compromised GSH synthesis affects the morphological and functional integrity of hippocampal parvalbumin-immunoreactive (PV-IR) interneurons, known to be affected in schizophrenia. A GSH deficit causes a selective decrease of PV-IR interneurons in CA3 and dendate gyrus (DG) of the ventral but not dorsal hippocampus and a concomitant reduction of β/γ oscillations. Impairment of PV-IR interneurons emerges at the end of adolescence/early adulthood as oxidative stress increases or cumulates selectively in CA3 and DG of the ventral hippocampus. Such redox dysregulation alters stress and emotion-related behaviors but leaves spatial abilities intact, indicating functional disruption of the ventral but not dorsal hippocampus. Thus, a GSH deficit affects PV-IR interneuron's integrity and neuronal synchrony in a region- and time-specific manner, leading to behavioral phenotypes related to psychiatric disorders.
Presynaptic GABABReceptors Regulate Experience-Dependent Development of Inhibitory Short-Term Plasticity
Authors: Takesian Anne E. , Kotak Vibhakar C. , Sanes Dan H.
Published: February 2010

Short-term changes in synaptic gain support information processing throughout the CNS, yet we know little about the developmental regulation of such plasticity. Here we report that auditory experience is necessary for the normal maturation of synaptic inhibitory short-term plasticity (iSTP) in the auditory cortex, and that presynaptic GABABreceptors regulate this development. Moderate or severe hearing loss was induced in gerbils, and iSTP was characterized by measuring inhibitory synaptic current amplitudes in response to repetitive stimuli. We reveal a profound developmental shift of iSTP from depressing to facilitating after the onset of hearing. Even moderate hearing loss prevented this shift. This iSTP change was mediated by a specific class of inhibitory interneurons, the low-threshold spiking cells. Further, using paired recordings, we reveal that presynaptic GABABreceptors at interneuron-pyramidal connections regulate iSTP in an experience-dependent manner. This novel synaptic mechanism may support the emergence of mature temporal processing in the auditory cortex.
eIF2α Phosphorylation-Dependent Translation in CA1 Pyramidal Cells Impairs Hippocampal Memory Consolidation without Affecting General Translation
Authors: Jiang Zhihong , Belforte Juan E. , Lu Yuan , Yabe Yoko , Pickel James , Smith Carolyn Beebe , Je Hyun-Soo , Lu Bai , Nakazawa Kazu
Published: February 2010

Protein synthesis inhibitor antibiotics are widely used to produce amnesia, and have been recognized to inhibit general or global mRNA translation in the basic translational machinery. For instance, anisomycin interferes with protein synthesis by inhibiting peptidyl transferase or the 80S ribosomal function. Therefore,de novogeneral or global protein synthesis has been thought to be necessary for long-term memory formation. However, it is unclear which mode of translation—gene-specific translation or general/global translation—is actually crucial for the memory consolidation process in mammalian brains. Here, we generated a conditional transgenic mouse strain in which double-strand RNA-dependent protein kinase (PKR)-mediated phosphorylation of eIF2α, a key translation initiation protein, was specifically increased in hippocampal CA1 pyramidal cells by the chemical inducer AP20187. Administration of AP20187 significantly increased activating transcription factor 4 (ATF4) translation and concomitantly suppressed CREB-dependent pathways in CA1 cells; this led to impaired hippocampal late-phase LTP and memory consolidation, with no obvious reduction in general translation. Conversely, inhibition of general translation by low-dose anisomycin failed to block hippocampal-dependent memory consolidation. Together, these results indicated that CA1-restricted genetic manipulation of particular mRNA translations is sufficient to impair the consolidation and that consolidation of memories in CA1 pyramidal cells through eIF2α dephosphorylation depends more on transcription/translation of particular genes than on overall levels of general translation. The present study sheds light on the critical importance of gene-specific translations for hippocampal memory consolidation.
Coordination between Extrinsic Extracellular Matrix Cues and Intrinsic Responses to Orient the Centrosome in Polarizing Cerebellar Granule Neurons
Authors: Gupta Shailesh Kumar , Meiri Karina F. , Mahfooz Kashif , Bharti Upasna , Mani Shyamala
Published: February 2010

Successful axon targeting during development is critically dependent on directionality of axon extension and requires coordination between the extrinsic cues that provide spatial information to the axon and the intrinsic responses that regulate structural specification of the axon during neuronal polarization. How these responses are coordinated is unclear but are known to involve aligning the centrosome with the base of the emerging axon. We have used a novelin vitromicropatterning assay that spatially segregates the extrinsic cues used by polarizing cerebellar granule cells to orient axon extension and used it to investigate the signaling mechanisms responsible for coordinating centrosome positioning with intrinsic responses. The results show that, when laminin and/or vitronectin are used as spatially restricted cues in association with substrate-associated sonic hedgehog, they are sufficient to induce cell cycle arrest, that laminin and vitronectin then induce integrin-mediated signaling that upregulates phosphoinositide-3 kinase and PKC function to produce phosphatidylinositol 3,4,5-trisphosphate (PIP3) that is associated with the centrosome, that this PIP3 can interact with PKC-phosphorylated growth-associated protein GAP-43, and that PKC-phosphorylated GAP-43 in turn is required for positioning Par6, Cdc42, and IQGAP1, all intrinsic response components, in proximity to the centrosome, such that, in the absence of GAP-43, they are mislocalized and microtubules are not oriented appropriately. We conclude from these results that GAP-43 plays an important role in coordinating extrinsic signaling and intrinsic responses in polarizing cerebellar granule neurons.
Activation of the T1 Neuronal Circuit is Necessary and Sufficient to Induce Sexually Dimorphic Mating Behavior inDrosophila melanogaster
Authors: Ronderos David S. , Smith Dean P.
Published: February 2010

The molecular and cellular events mediating complex behaviors in animals are largely unknown. Elucidating the circuits underlying behaviors in simple model systems may shed light on how these circuits function. In drosophila, courtship behavior provides a tractable model for studying the underlying basis of innate behavior. The male-specific pheromone 11-cis-vaccenyl acetate (cVA) modulates courtship behavior and is detected by T1 neurons, located on the antenna of male and female flies. The T1 neurons express the odorant receptor Or67d and are exquisitely tuned to cVA pheromone. However, cVA-induced changes in mating behavior have also been reported upon manipulation of olfactory neurons expressing odorant receptor Or65a. These findings raise the issue of whether multiple olfactory-driven circuits underlie cVA-induced behavioral responses and what role these circuits play in behavior. Here, we engineered flies in which the Or67d circuit is specifically activated in the absence of cVA to determine the role of this circuit in behavior. We created transgenic flies that express a dominant-active, pheromone-independent variant of the extracellular pheromone receptor, LUSH. We found that, similar to the behaviors elicited by cVA, engineered male flies have dramatically reduced courtship, whereas engineered females showed enhanced courtship. cVA exposure did not enhance the dominant LUSH-triggered effects on behavior in the engineered flies. Finally, we show the effects of both cVA and dominant LUSH on courtship are reversed by genetically removing Or67d. These findings demonstrate that the T1/Or67d circuit is necessary and sufficient to mediate sexually dimorphic courtship behaviors.
Saccade Suppression by Electrical Microstimulation in Monkey Caudate Nucleus
Authors: Watanabe Masayuki , Munoz Douglas P.
Published: February 2010

It has been suggested that the caudate nucleus, the input stage of the basal ganglia, facilitates and suppresses saccade initiation based on its anatomical characteristics. Although the involvement of the caudate nucleus in saccade facilitation has been shown previously, it is still unclear whether the caudate nucleus is also involved in saccade suppression. Here, we revealed the direct involvement of the caudate nucleus in saccade suppression by electrical microstimulation in behaving monkeys. We delivered microstimulation to the caudate nucleus while monkeys performed the prosaccade (look toward a peripheral visual stimulus) and antisaccade (look away from the stimulus) paradigm. The reaction times of contralateral saccades were prolonged on both prosaccade and antisaccade trials. The suppression effects on reaction times were stronger on prosaccade trials compared with antisaccade trials. The analysis of reaction time distributions using the linear approach to threshold with ergodic rate model (LATER model) revealed that microstimulation prolonged reaction times by reducing the rate of rise to the threshold for saccade initiation. Microstimulation also worsened correct performance rates for contralateral saccades. The same microstimulation prolonged and/or shortened the reaction times of ipsilateral saccades, although the effects were not as consistent as those on contralateral saccades. We conclude that caudate signals are sufficient to suppress contralateral saccades and influence saccadic decision by controlling contralateral and ipsilateral saccade commands at the same time.
Inhibition of FK506 Binding Proteins Reduces α-Synuclein Aggregation and Parkinson's Disease-Like Pathology
Authors: Gerard Melanie , Deleersnijder Angélique , Daniëls Veronique , Schreurs Sarah , Munck Sebastian , Reumers Veerle , Pottel Hans , Engelborghs Yves , Van den Haute Chris , Taymans Jean-Marc , Debyser Zeger , Baekelandt Veerle
Published: February 2010

α-Synuclein (α-SYN) is a key player in the pathogenesis of Parkinson's disease (PD). In pathological conditions, the protein is present in a fibrillar, aggregated form inside cytoplasmic inclusions called Lewy bodies. Members of the FK506 binding protein (FKBP) family are peptidyl-prolyl isomerases that were shown recently to accelerate the aggregation of α-SYNin vitro. We now established a neuronal cell culture model for synucleinopathy based on oxidative stress-induced α-SYN aggregation and apoptosis. Using high-content analysis, we examined the role of FKBPs in aggregation and apoptotic cell death. FK506, a specific inhibitor of this family of proteins, inhibited α-SYN aggregation and neuronal cell death in this synucleinopathy model dose dependently. Knockdown of FKBP12 or FKBP52 reduced the number of α-SYN aggregates and protected against cell death, whereas overexpression of FKBP12 or FKBP52 accelerated both aggregation of α-SYN and cell death. Thus, FK506 likely targets FKBP members in the cell culture model. Furthermore, oral administration of FK506 after viral vector-mediated overexpression of α-SYN in adult mouse brain significantly reduced α-SYN aggregate formation and neuronal cell death. Our data explain previously described neuroregenerative and neuroprotective effects of immunophilin ligands and validate FKBPs as a novel drug target for the causative treatment of PD.
Diacylglycerol Lipase Is Not Involved in Depolarization-Induced Suppression of Inhibition at Unitary Inhibitory Connections in Mouse Hippocampus
Authors: Min Rogier , Testa-Silva Guilherme , Heistek Tim S. , Canto Cathrin B. , Lodder Johannes C. , Bisogno Tiziana , Di Marzo Vincenzo , Brussaard Arjen B. , Burnashev Nail , Mansvelder Huibert D.
Published: February 2010

Endocannabinoids control hippocampal inhibitory synaptic transmission through activation of presynaptic CB1receptors. During depolarization-induced suppression of inhibition (DSI), endocannabinoids are synthesized upon postsynaptic depolarization. The endocannabinoid 2-arachidonoylglycerol (2-AG) may mediate hippocampal DSI. Currently, the best studied pathway for biosynthesis of 2-AG involves the enzyme diacylglycerol lipase (DAGL). However, whether DAGL is necessary for hippocampal DSI is controversial and was not systematically addressed. Here, we investigate DSI at unitary connections between CB1receptor-containing interneurons and pyramidal neurons in CA1. We found that the novel DAGL inhibitor OMDM-188, as well as the established inhibitor RHC-80267, did not affect DSI. As reported previously, effects of the DAGL inhibitor tetrahydrolipstatin depended on the application method: postsynaptic intracellular application left DSI intact, while incubation blocked DSI. We show that all DAGL inhibitors tested block slow self-inhibition in neocortical interneurons, which involves DAGL. We conclude that DAGL is not involved in DSI at unitary connections in hippocampus.
Evidence for the existence of a PbCO3-II phase from high pressure X-ray measurements
Authors: Minch Robert , Peters Lars , Ehm Lars , Knorr Karsten , Siidra Oleg I. , Prakapenka Vitali , Dera Przemyslaw , Depmeier Wulf
Published: February 2010

The high-pressure room temperature behavior of PbCO3 was investigated by angle-dispersive synchrotron powder diffraction up to 16.16(5) GPa. A phase transition to a high-pressure polymorph II of lead carbonate was observed at a pressure of approximately p
c = 8.7 GPa. Thereby, the symmetry is reduced from orthorhombic Pmcn to monoclinic P121/c1. The cell parameters at p = 8.90(5) GPa are a = 5.101(1) Å, b = 8.303(3) Å, c = 5.602(2) Å, β = 89.51(4)°, Z = 4. The transformation is supposed to be of 2nd order.
Structures of (pyrazinecarbonyl)hydrazones of substituted benzaldehydes: different supramolecular arrangements from C—H···X (X = O, N, π) hydrogen bonds
Authors: Howie R. Alan , da Silva Lima Camilo H. , Kaiser Carlos R. , de Souza Marcus V. N. , Wardell James L. , Wardell Solange M. S. V.
Published: February 2010

The crystal structures of six (pyrazinecarbonyl)hydrazone di-substituted benzaldehyde derivatives [N2C4H3CONHN = CHC6H3XY: X,Y = 2,3-Cl2; 2,3-(MeO)2; 2,4-F2; 2,4-Me2; 3-HO—4-MeO; 3-MeO—4-HO] and one tri-substituted benzaldehyde derivative, [N2C4H3CONHN = CHC6H2X3: X3 = 3,4,5-(MeO)3] are reported. In all cases extensive intermolecular C—H···X (X = O, N or π-ring) hydrogen-bonding is present in which the the oxygen atoms of OH and OMe substituents act as hydrogen-bond acceptors and C—H bonds of methyl groups act as hydrogen-bond donors. The connectivity attained is one-dimensional in chains or ribbons in the 2,3-(OMe)2 and 2,4-Me2 derivatives, three dimensional only in the case of the 3-MeO—4-HO derivative and two dimensional in layers of molecules otherwise. It is concluded, therefore, that the bulky nature of the substituents limits the connectivity attainable in this series of compounds.
Repair of Extensive Thoracoabdominal Aortic Aneurysm with a Tetrafurcate Graft: Midterm Results of 63 Cases
Authors: Cheng Lijian , Huang Fuhua , Chang Qian , Zhu Junming , Yu Cuntao , Liu Yongmin , Zhang Haitao , Zheng Jun , Sun Li-Zhong
Published: February 2010

Objective: The objective is to present a method for maintaining the spinal cord blood supply and our midterm results for using a tetrafurcate graft in extensive thoracoabdominal aortic aneurysm (TAAA) repair.Methods: From August 2003 to October 2007, we used a tetrafurcate graft to perform repairs to TAAAs of Crawford extent II in 63 consecutive patients. The mean age of this group of patients was 39.98 10.62 years, and 46 (73%) of them were male. All of the procedures were performed under profound hypothermia with a short interval of circulatory arrest. T6 to T12 intercostal arteries were reconstructed as a "neo-intercostal artery" (N-IA) and were connected to an 8-mm sidearm of the graft to maintain the spinal cord blood supply. Visceral arteries were joined into a patch and were anastomosed to the end of the main graft. The left renal artery was anastomosed to an 8-mm sidearm or joined to the patch. The other 10-mm sidearms were anastomosed to iliac arteries.Results: With 100% follow-up, the early-mortality rate was 7.94%. The incidence of cerebral complications was 9.52%. Temporary paraplegia was observed in 2 patients, and paraparesis occurred in 1 patient. Pulmonary complication was the most common morbidity in this group (25.40%). Two patients with Marfan syndrome had N-IA artery pseudoaneurysms during follow-up. The mean survival time of this group was 50.64 2.13 months, with survival rates of 92.06% after 1 year, 88.38% after 2 years, and 86.11% after 3 years.Conclusion: The N-IA may play an important role in spinal cord protection, and N-IA pseudoaneurysm should be avoided in Marfan syndrome patients. The use of a tetrafurcate graft is a reliable method for TAAA repair, with satisfactory midterm results.
Dipyridamole and Low Doses of Heparin as a New Successful Physiopathologic and Therapeutic Approach in 2 Cases of Disseminated Intravascular Coagulation
Authors: Gomes Otoni M. , Gomes Eros S.
Published: February 2010

Operative: We report 2 cases of disseminated intravascular coagulation (DIC) successfully treated with the combination of the platelet adhesiveness blocker dipyridamole and low doses of intravenous heparin.Methods: The first patient was a 17-year-old boy with septic arthritis; the second patient was a 12-year-old boy with a liver abscess. Both had hemocultures positive for Staphylococcus aureus. The diagnosis of DIC was defined by clinical signs of septicemia with fever, tachypnea, peripheral vasoconstriction, and low platelet counts (67,000/mm3 and 47,000/mm3, respectively). The second patient also presented with acute ischemia of the fingers and toes. General care was provided in the intensive care unit, and high doses of antibiotics were provided continuously (metronidazole and oxacillin or ceftriaxone). A 5% glucose solution containing dipyridamole (Persantine; Istituto De Angeli/Boheringer Ingelheim, Reggello, Italy) was administered by continuous intravenous infusion (20 mg/24 hours). In addition, regular heparin (Liquemin; Roche, Indianapolis, IN, USA) was administered at a dosage of 250 mg/kg per hour or 25 IU/kg per hour (6 mg/kg per 24 hours). These heparin doses are not able to promote complete blood anticoagulation. Treatment with heparin and dipyridamole was maintained for 10 days in the first patient and for 18 days in the second.Results: By 48 hours after treatment with dipyridamole and low-dose heparin, both patients recovered and presented with a good clinical condition and increased numbers of circulating platelets. Both patients were discharged in a safe clinical condition in the second month after hospital admission.Conclusion: Successful clinical recovery of 2 young patients with DIC with an unfavorable clinical evolution and a prognosis for a lethal outcome was achieved with the combination of a continuous infusion of dipyridamole and low doses of heparin.
Preventive and therapeutic methods against the toxic effects of mycotoxins — A review
Authors: Mézes Miklós , Balogh Krisztián , Tóth Katalin
Published: February 2010

Ingredients used in animal feeds and their contamination with undesirable substances, such as mycotoxins, are fundamentally important both in terms of the quality of animal products and the potential human health impacts associated with the animal-based food production chain. Feed ingredients contaminated with mycotoxins may have a wide range of toxicological effects on animals. Therefore, mycotoxin contamination of feed ingredients constituting complete feed products represents an important potential hazard in farm animal production. This review summarises the potential effects of some preventive methods used during the storage of cereal grains as well as of nutritive (e.g. antioxidants, amino acids, fats) or non-nutritive compounds (e.g. pharmacological substances, carbon- or silica-based polymers) and detoxifying enzymes recommended for use against the toxic effects of different mycotoxins.
Inflammation- and axotomy-induced changes in galanin-like immunoreactive (GAL-LI) nerve structures in the porcine descending colon
Authors: Gonkowski Sławomir , Burliński Piotr , Skobowiat Cezary , Majewski Mariusz , Całka Jarosław
Published: February 2010

This study reports on changes caused by chemically driven inflammation and axotomy in galanin-like immunoreactive (GAL-LI) nerve structures in the porcine descending colon. The distribution pattern of GAL-LI structures was studied using the immunofluorescence technique in the circular muscle layer, the myenteric (MP), outer submucous (OSP) and inner submucous plexuses (ISP), and also in the mucosal layer. Under physiological conditions GAL-LI perikarya were shown to constitute 3.68 ± 0.32%, 7.02 ± 0.93% and 10.99 ± 0.71% in MP, OSP and ISP, respectively. Both colitis and axotomy caused an increase in GAL-like immunoreactivity, which was different in particular parts of the bowel segment studied. The numbers of GAL-LI perikarya increased to 14.16 ± 0.49%, 16.78 ± 1.09% and 37.46 ± 1.18% during colitis and 7.92 ± 0.72%, 10.44 ± 0.71% and 16.20 ± 0.96% after axotomy in MP, OSP and ISP, respectively. Both these processes caused an increase in the number of GAL-LI nerve fibres in the circular muscle and mucosal layers as well as the appearance of a population of GAL-LI cells in the mucosa.
The influence of transfer gun passage time through the uterine cervix on pregnancy rate in recipient heifers
Authors: Jaśkowski Jędrzej , Urbaniak Krzysztof , Antosik Paweł , Włodarczyk Renata
Published: February 2010

The influence of passage time of the transfer gun through the uterine cervix and body to the embryo insertion site on pregnancy rate was analysed in 248 recipient heifers (mean age: 15–17 months). Embryos (90 fresh and/or 88 and 70 frozen in glycerol and ethylene glycol, respectively, grades 4 and 5, stage 1 or 2) were transferred to the ipsilateral uterine horn on day 7. Two different transfer guns were used in this experiment: a sterilisable steel transfer instrument to be used without sheaths with a removable tip made of gold-plated stainless steel (Wörrlein Minitüb) or a transfer stylet with sheaths with a metal tip and a side opening (Cassou gun, IMV Technologies). The time of passage of the instruments through the uterine cervix and body to the site of embryo deposition in the uterine horn was measured in the study. In order to randomise the risk of errors, all manipulations were carried out by the same experienced operator. The average time needed for the insertion of embryos into the uterus was 50.6 seconds (s) and it was longer for the transfer gun with sheaths than for the metal-tipped transfer gun (60.1 and 40.8 s, respectively) (P < 0.001). The average conception rate was 45.6%. If the time needed to insert embryos into the uterus was 10-60 s, the conception rate was 53.4% (up to 20, 21–30, 31–40, 41–50 and 51–60 s − 57.7, 52.5, 50, 51.5 and 50%, respectively). In contrast, if the time needed to insert the embryo in the uterine horn was longer than 60 s, the conception rate was 20.4% (61–80, 80.1–120 and > 120 s − 28.0, 6.0 and 24.9%, respectively). Thus, it cannot be excluded that the type of the applied transfer gun may influence pregnancy rate in recipient cows due to its effect on cervical passage time.
A pulsed-field gel electrophoresis study of the genetic diversity of Campylobacter jejuni and Campylobacter coli in poultry flocks in Slovenia
Authors: Gruntar Igor , Ocepek Matjaž , Avberšek Jana , Mićunović Jasna , Pate Mateja
Published: February 2010

Campylobacter jejuni
and
C. coli
have recently become the most frequent cause of bacterial foodborne enteric infection in most industrialised countries. Consumption and handling of undercooked contaminated poultry meat was identified as an important risk factor for human campylobacteriosis. The aim of this study was to ascertain the genetic diversity of
C. jejuni
and
C. coli
strains isolated from poultry in Slovenia. A total of 68 isolates (42
C. jejuni
, 26
C. coli
) from faeces (n = 48), meat (n = 15) and skin/carcasses (n = 5) of chicken (n = 60) and turkey samples (n = 5) were analysed by pulsed-field gel electrophoresis.
Sma
I macrorestriction discriminated between
C. jejuni
and
C. coli
isolates.
C. jejuni
isolates exhibited a higher degree of diversity compared to
C. coli
isolates. In the
C. jejuni
group, a number of small clusters were apparent, while
C. coli
strains formed less but larger clusters. Additional
Kpn
I digestion of selected isolates resulted in poor subtyping. Strains with identical or very similar profiles were found on different farms, either in the same or different regions and time periods. Some of the clones indicated possible cross-contamination at slaughterhouses.
Hepatitis and hydropericardium syndrome associated with adenovirus infection in goslings
Authors: Ivanics Éva , Palya Vilmos , Markos Béla , Dán Ádám , Ursu Krisztina , Harrach Balázs , Kaján Győző , Glávits Róbert
Published: February 2010

Two outbreaks of severe acute disease characterised by hepatitis and hydropericardium were observed in young goslings on large-scale farms in Hungary. Histological examination revealed multifocal necrotic areas and two types of intranuclear inclusion bodies adjacent to necrotic areas in the liver. The most prominent type of inclusion bodies showed strong basophilic staining and completely filled the enlarged nucleus. The other type was eosinophilic and occupied the centre of the nucleus, which had margination of chromatin. In the heart, haemorrhage was associated with multifocal necrosis in the myocardium. The presence of fowl adenovirus DNA in different organs of the naturally infected goslings was detected by polymerase chain reaction (PCR). The virus was isolated, and identified as a goose adenovirus by genomic analysis. This is the first report on the involvement of a goose adenovirus in severe acute disease associated with hepatitis and hydropericardium.
First description of papillary carcinoma in the thyroid gland of a Red-eared slider ( Trachemys scripta elegans )
Authors: Gál János , Csikó György , Pásztor István , Bölcskey-Molnár Antal , Albert Mihály
Published: February 2010

Postmortem examination of the carcass of an approximately 10-year-old male Red-eared slider (
Trachemys scripta elegans
) was performed. The thyroid gland was enlarged, showed follicular structure, and shifted the base of the heart caudally. Histology revealed differently shaped and sized follicles in the thyroid gland. Based on the macroscopic appearance and histopathological changes of the thyroid gland, the pathological process was established as a papillary-cystic carcinoma. Neoplasia of the endocrine organs, especially of the thyroid gland, is rare in reptiles. The current case seems to be the first report of thyroid carcinoma in a Red-eared slider.
Prediction of the disease course in inflammatory bowel diseases
Authors: Kiss Lajos Sándor , Lakatos Péter László
Published: February 2010

A Crohn-betegség (CD) és a colitis ulcerosa (UC) klinikai megjelenése igen változatos lehet a betegség megjelenésekor és a betegség lefolyása során. A legtöbb Crohn-betegnél a betegség lefolyása során különböző szövődmények jelennek meg, szűkület alakulhat ki, illetve perforáció jelentkezhet. A szövődmények miatt a betegek egy része végül sebészi kezelésre szorul. Az utóbbi években éppen ezért a kutatások egyik középpontjába került a betegség progresszióját előrejelző faktorok vizsgálata. Mivel a potenciálisan súlyos lefolyású betegekben a korai immunmodulátor és/vagy biológiai kezelés indokolt, fontos a prediktív faktorok ismerete és minél korábbi meghatározása. Ebben az összefoglaló közleményben a szerzők az irodalomban elérhető azon klinikai, endoszkópiás, laboratóriumi és genetikai faktorokra vonatkozó adatokat szeretnék áttekinteni, amelyek segítséget nyújthatnak a mindennapi gyakorlatban a klinikusok számára a megfelelő kezelési stratégia kiválasztásához.