bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolution of the Stabilis® Database: Creation of a Level of Evidence for Stability Studies
Authors: D’Huart Elise , Lider Pauline , Vigneron Jean , Demoré Béatrice 
Published: April 2018

Abstract

Background
Stabilis® is an international database on stability and compatibility of drugs. The stability data comes mainly from publications of pharmaceutical journals. As the quality of the published stability studies is not equivalent, the objective of this work was to propose a level of evidence for the physico-chemical stability studies selected for the database.

Methods
At first, we evaluated the main pharmacological class consulted by the users. This work was then divided into 5 steps: (1) updating of the criteria to validate a stability study, (2) creating a grid rating articles, (3) rating of the articles of stability studies for anticancer, antifungal and antiviral drugs by 2 evaluators, (4) creation of new screens in the database to enter rating, to visualize the pictograms and commentaries by the users, (5) creation of a guideline to explain the different levels of evidence.

Results
The main pharmacological class consulted by Stabilis® users is the anticancer drugs and then antiinfectives. We have selected anticancer, antifungal and antiviral drugs for our study. Two hundred and forty publications were evaluated. The highest level attributed was A for anticancer and antifungal drugs and C for antiviral drugs. This difference can be explained by the fact that the majority of publications about antiviral drugs were older.
The most frequent anomalies in the rating of articles were an incomplete or imperfect validation of the analytical method (high value of the coefficient of variation) and a defect in the evaluation of the stability indicating capacity.
It must be noted that the level of evidence is not the quality level of the analytical method but the mixture of the quality of the method validation and of the results. This aspect was a choice of the Stabilis® team and seems important because the security of the patient is impacted by both aspects.

Conclusions
This new function contributes to help the Stabilis® users to evaluate the stability data published and to take a decision for their use in daily practice. This function will be progressively extended to other pharmacological classes of injectable drugs and then for non-injectable preparations.
Formulation of a 3-months Stability Oral Viscous Budesonide Gel and Development of an Indicating Stability HPLC Method
Authors: Bonnet Mathilde , Dermu Marine , Roessle Clara , Bellaiche Marc , Abarou Tarik , Vasseur Véronique , Benakouche Samira , Storme Thomas 
Published: April 2018

Abstract

Background
Eosinophilic Esophagitis is an increasing pathology which can cause stomach symptom like dysphagia, vomiting, food blockage. The treatment consists in dietary therapy and topical corticosteroid therapy to avoid the important number of side effects of the oral corticosteroids. There is presently no available topical form adapted for treating esophageal pathology.

Methods
The aim of this work was to develop an oral viscous budesonide gel (OVBG). A focus on palatability was made in order to use OVBG in children. A stability indicating HLPC method able to quantify budesonide contained in our OVBG has been developed.

Results
Previous work of Hefner and Al. showed that xanthan gum had a longer esophageal mucosal contact time than sucralose. This encouraged the development of a xanthan gum-based formulation. This OVBG has also the advantage to facilitate compliance thanks to its taste and pleasant texture. The stability length of the preparation can be extended over a 3-months period, stored in a refrigerator at 2–8 °C.

Conclusions
An adapted pediatric formulation with a 3-months stability was developed. Furthermore, the formulation can be easily reproduced in community pharmacy. Regarding the increasing number of patients concerned OVBG is a good answer to a real clinical need.
The influence of isometric exercise on endogenous pain modulation: comparing exercise-induced hypoalgesia and offset analgesia in young, active adults
Authors: Harris Samuel , Sterling Michele , Farrell Scott F. , Pedler Ashley , Smith Ashley D. 
Published: April 2018

Abstract

Background and aims
Impairment of endogenous analgesia has been associated with the development, maintenance and persistence of pain. Endogenous analgesia can be evaluated using exercise-induced hypoalgesia (EIH) and offset analgesia (OffA) paradigms, which measure temporal filtering of sensory information. It is not clear if these paradigms are underpinned by common mechanisms, as EIH and OffA have not previously been directly compared. A further understanding of the processes responsible for these clinically relevant phenomena may have future diagnostic and therapeutic utility in management of individuals with persistent pain conditions. The primary aim of this study was to investigate if there is a correlation between the magnitudes of EIH and OffA. The secondary aim of the study was to examine whether exercise influences OffA.

Methods
Thirty-six healthy, pain-free participants were recruited. EIH was evaluated using pressure pain thresholds (PPT) and pain ratings to suprathreshold pressure stimuli over tibialis anterior and the cervical spine. OffA evaluation utilised a three-step protocol, whereby individualised heat pain thermal stimuli [Numerical Rating Scale (NRS)=50/100] were applied (T1), before increasing 1 °C (T2), followed by 1 °C reduction (T3). The magnitude of OffA was calculated as the percentage reduction in the NRS from T2 to T3. PPT/suprathreshold pain ratings and OffA measures were recorded, before and after 5 min of isometric quadriceps exercise performed at 20–25% maximum voluntary contraction (MVC); and following a 15 min rest period. Data were analysed using repeated measures (RM) ANCOVA and correlational analyses.

Results
There was no correlation between EIH measures (PPTs or pain ratings to suprathreshold pressure stimuli over tibialis anterior or the cervical spine) and OffA (p>0.11 for all). OffA was induced and not modulated by exercise (p=0.28).

Conclusions
Five minutes of 20–25% MVC lower limb isometric exercise provided non-pharmacological pain modulation in young, active adults. Magnitude of EIH was not correlated with that of OffA, and exercise did not influence magnitude of OffA.

Implications
These results suggest that in young, pain-free individuals, separate testing of these two paradigms is required to comprehensively evaluate efficacy of endogenous analgesia. If these results are replicated in patient populations, alternative or complementary methods to exercise interventions may be required to modulate impaired OffA.
Wie nah ist uns die Zwischenkriegszeit?
Authors: Raithel Thomas 
Published: April 2018

Abstract
The interwar period was a phase of the formation of new states and of democratic awakening, but also a time of crises and the failure of democracies as well as the establishment of authoritarian and dictatorial systems. Until recently, it was largely overlooked by research and the general public. Given the recent increase of right-wing populist currents and authoritarian tendencies in Europe, interest has once again grown. The second “Contemporary History Podium” is thus dedicated to the question of how akin we are to the interwar period. How is it perceived in different countries which constituted themselves as democracies at the end of the First World War after the fall of the Romanov, Habsburg and Hohenzollern Empires? Also what is the relevance of this history for the present? Ota Konrád (Charles University Prague), Ekaterina Makhotina (University of Bonn), Anton Pelinka (Central European University Budapest), Thomas Raithel (Institute for Contemporary History Munich-Berlin) und Krzysztof Ruchniewicz (Willy Brandt Center, Wrocław University) look into these questions utilising the examples of Czechoslovakia, Lithuania, Austria, Germany and Poland.
n-Type Cu2O/α-Fe2O3 Heterojunctions by Electrochemical Deposition: Tuning of Cu2O Thickness for Maximum Photoelectrochemical Performance
Authors: Gahlawat Soniya , Rashid Nusrat , Ingole Pravin P. 
Published: April 2018

Abstract
Here, we report the enhanced photoelectrochemical performance of surface modified hematite thin films with n-type copper oxide nanostructures (Cu2O/Fe2O3) obtained through simple electrochemical deposition method. The thickness and amount of cuprous oxide layer were varied by simply changing the number of electrodeposition cycles (viz. 5, 10, 25, 50 and 100) in order to understand its thermodynamic and kinetic influence on the photoelectrochemical activity of the resultant nano-heterostructures. Structural and morphological characteristics of the obtained Cu2O/Fe2O3 films have been studied by absorption spectroscopy, X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy analysis. Electrochemical investigations such as linear sweep voltammetry, Mott–Schottky analysis, and electrochemical impedance spectroscopy suggested the formation of n-type Cu2O layers over the hematite films with varying charge-carrier densities, ranging from 0.56×1019 to 3.94×1019 cm−3, that varies with the number of cycles of electrochemical deposition. Besides, the thickness of deposited cuprous oxide layer is noted to alter the net electrochemical and photo-electrochemical response of the base material. An interesting, peak event was recorded for a particular thickness of the cuprous oxide layer (obtained after 25 cycles of electrochemical deposition) below and above which the efficiency of catalyst was impaired. The heterojunction obtained thus, followed well known Z-scheme and gave appreciable increment in the photocurrent response.
Retinal Ganglion Cell Axons Recognize Specific Guidance Cues Present in the Deafferented Adult Rat Superior Colliculus
Authors: Bähr Mathias , Wizenmann Andrea 
Published: April 2018

During development, retinal ganglion cell axons establish a topographically ordered projection from the retina to the superior colliculus (SC). The putative guidance activities for retinal axons that operate during embryonic development are not detectable in the normal adult SC. However, these cues reappear upon transection of the optic nerve of adult rats. In the present study, we used a modified version of the “stripe assay,” in which membranes from either anterior or posterior SC alternated with laminin stripes. Temporal embryonic retinal axons consistently avoid membranes from embryonic posterior SC, but only rarely from adult deafferented SC. However, they are attracted to membranes from both embryonic and adult deafferented anterior SC. Nasal retinal axons only show a significant preference for membranes from posterior SC after deafferentation. When retinal axons were offered a choice to grow on membranes either from their embryonic or their deafferented target regions, they showed a preference for the deafferented SC. On carpets consisting of laminin and membranes from normal SC (not deafferented) or nontarget regions (inferior colliculus), temporal and nasal axons grow either in a random fashion or show preferences for the laminin stripes.Our modified version of the classic stripe assay shows specific growth preferences of embryonic retinal axons for membrane lanes from their appropriate embryonic or deafferented adult target regions. These findings suggest that the deafferentation of the SC in adult rats triggers the reexpression of specific guidance activities for retinal axons. Those “attractive” guidance cues appear to be differentially expressed in the developing and deafferented SC.
Collateral Sprouting of Uninjured Primary Afferent A-Fibers into the Superficial Dorsal Horn of the Adult Rat Spinal Cord after Topical Capsaicin Treatment to the Sciatic Nerve
Authors: Mannion Richard J. , Doubell Tim P. , Coggeshall Richard E. , Woolf Clifford J. 
Published: April 2018

That terminals of uninjured primary sensory neurons terminating in the dorsal horn of the spinal cord can collaterally sprout was first suggested by Liu and Chambers (1958), but this has since been disputed. Recently, horseradish peroxidase conjugated to the B subunit of cholera toxin (B-HRP) and intracellular HRP injections have shown that sciatic nerve section or crush produces a long-lasting rearrangement in the organization of primary afferent central terminals, with A-fibers sprouting into lamina II, a region that normally receives only C-fiber input (Woolf et al., 1992). The mechanism of this A-fiber sprouting has been thought to involve injury-induced C-fiber transganglionic degeneration combined with myelinated A-fibers being conditioned into a regenerative growth state.In this study, we ask whether C-fiber degeneration and A-fiber conditioning are both necessary for the sprouting of A-fibers into lamina II. Local application of the C-fiber-specific neurotoxin capsaicin to the sciatic nerve has previously been shown to result in C-fiber damage and degenerative atrophy in lamina II. We have used B-HRP to transganglionically label A-fiber central terminals and have shown that 2 weeks after topical capsaicin treatment to the sciatic nerve, the pattern of B-HRP staining in the dorsal horn is indistinguishable from that seen after axotomy, with lamina II displaying novel staining in the identical region containing capsaicin-treated C-fiber central terminals.These results suggest that after C-fiber injury,uninjuredA-fiber central terminals can collaterally sprout into lamina II of the dorsal horn. This phenomenon may help to explain the pain associated with C-fiber neuropathy.
Late Compartments of Amyloid Precursor Protein Transport in SY5Y Cells Are Involved in β-Amyloid Secretion
Authors: Peraus Gisela C. , Masters Colin L. , Beyreuther Konrad 
Published: April 2018

Amyloid plaques, composed mainly of the 39–43 amino acid βA4 peptide, are a characteristic feature of Alzheimer’s disease. Generation of βA4 by proteolytic processing of the amyloid precursor protein (APP) is thought to occur in a pathway that includes the activity of two as yet unknown proteases, with β-secretase cleaving at the N terminus and γ-secretase releasing the C terminus of βA4. Inhibition studies and the finding that cell surface APP can serve as a direct precursor of βA4 suggest that the endosomal/lysosomal compartment is involved in the proteolysis of APP into βA4.In this study we targeted APP695 chimeric proteins directly into the endosomal/lysosomal compartment. This decreased the amount of released βA4, while the generation of the βA4 N terminus continued. APP695 proteins were constructed also, which carried sorting signals responsible for recycling between thetrans-Golgi network (TGN) and the cell surface. These proteins were processed into secreted βA4 at even higher levels than wild-type APP695. Moreover, retention of APP695 proteins in the endoplasmic reticulum led to neither βA4 secretion nor to processing by β-secretase in human SH-SY5Y neuroblastoma cells.These data suggest that a β-cleavage activity resides in a late endosomal compartment and that a γ-cleavage occurs in early endosomes, resulting in the generation of βA4 peptides with the majority ending at residue 40.
The Stimulatory Action and the Development of Tolerance to Caffeine Is Associated with Alterations in Gene Expression in Specific Brain Regions
Authors: Svenningsson Per , Nomikos George G. , Fredholm Bertil B. 
Published: April 2018

We sought neurochemical correlates to the stimulatory action of caffeine in rats and to adaptations during development of tolerance. Acute intraperitoneal injections of caffeine (7.5 mg/kg) increased locomotion and NGFI-A mRNA, a marker of neuronal activity, in the hippocampal area CA1, but decreased NGFI-A mRNA in rostral striatum and nucleus accumbens. Rats that received caffeine (0.3 gm/l) in their drinking water for 14 d developed tolerance to the stimulatory effect of a challenge with caffeine (7.5 mg/kg) and responded with a less pronounced decrease of NGFI-A mRNA in rostral striatum and nucleus accumbens. Metabolism of caffeine to its active metabolites was increased in tolerant animals, but the total level of active metabolites in brain was not significantly altered. Thus, there are changes in caffeine metabolism after long-term caffeine treatment, but they cannot explain development of tolerance.Caffeine-tolerant animals had downregulated levels of adenosine A2Areceptors and the corresponding mRNA in rostral parts of striatum, but an increased expression of adenosine A1receptor mRNA in the lateral amygdala. No changes in mesencephalic tyrosine hydroxylase mRNA were found in caffeine-tolerant rats.Thus, we have identified neuronal pathways that are regulated by adenosine A1and/or A2Areceptors and are targets for the stimulatory action of caffeine. Furthermore, adaptive changes in gene expression in these brain areas were associated with the development of locomotor tolerance to caffeine.
Multiple and Opposing Roles of Cholinergic Transmission in the Main Olfactory Bulb
Authors: Castillo Pablo E. , Carleton Alan , Vincent Jean-Didier , Lledo Pierre-Marie 
Published: April 2018

The main olfactory bulb is a critical relay step between the olfactory epithelium and the olfactory cortex. A marked feature of the bulb is its massive innervation by cholinergic inputs from the basal forebrain. In this study, we addressed the functional interaction between cholinergic inputs and intrinsic bulbar circuitry. Determining the roles of acetylcholine (ACh) requires the characterization of cholinergic effects on both neural excitability and synaptic transmission. For this purpose, we used electrophysiological techniques to localize and characterize the diverse roles of ACh in mouse olfactory bulb slices. We found that cholinergic inputs have a surprising number of target receptor populations that are expressed on three different neuronal types in the bulb. Specifically, nicotinic acetylcholine receptors excite both the output neurons of the bulb, i.e., the mitral cells, as well as interneurons located in the periglomerular regions. These nicotine-induced responses in interneurons are short lasting, whereas responses in mitral cells are long lasting. In contrast, muscarinic receptors have an inhibitory effect on the firing rate of interneurons from a deeper layer, granule cells, while at the same time they increase the degree of activity-independent transmitter release from these cells onto mitral cells.Cholinergic signaling thus was found to have multiple and opposing roles in the olfactory bulb. These dual cholinergic effects on mitral cells and interneurons may be important in modulating olfactory bulb output to central structures required for driven behaviors and may be relevant to understanding mechanisms underlying the perturbations of cholinergic inputs to cortex that occur in Alzheimer's disease.
Involvement of Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) and p53 in Neuronal Apoptosis: Evidence That GAPDH Is Upregulated by p53
Authors: Chen Ren-Wu , Saunders Paul A. , Wei Huafeng , Li Zhuangwu , Seth Prem , Chuang De-Maw 
Published: April 2018

We recently reported that cytosine arabinoside (AraC)-induced apoptosis of cerebellar neurons involves the overexpression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The present study was undertaken to investigate whether p53 and/or Bax overexpression participates in the AraC-induced apoptosis of cerebellar granule cells and, if so, the relationship between p53 induction and GAPDH overexpression in these cells.AraC-induced apoptosis of cerebellar granule cells was preceded by an increase in levels of p53 mRNA and protein detected between 1 and 8 hr after treatment. The mRNA level for a p53 target gene, Bax, was also increased. The increase in GAPDH mRNA lasted longer than that of either p53 or Bax, and the level of GAPDH protein in the particulate fraction increased after induction of GAPDH mRNA. The antisense oligonucleotide to p53 protected granule cells from AraC-induced chromatin condensation, internucleosomal cleavage, and apoptotic death. The inhibition of p53 expression by the p53 antisense oligonucleotide not only blocked the expression of Bax but also partially suppressed the increased GAPDH mRNA and protein levels. Conversely, the suppression of GAPDH expression and subsequent attenuation of apoptosis of granule cells by GAPDH antisense oligonucleotide did not influence the expression of p53 or Bax. Cerebellar granule cells prepared from p53 knock-out mice were resistant to AraC toxicity, and the p53 gene knock-out suppressed AraC-upregulated GAPDH expression. Moreover, infection of PC12 cells with an adenoviral vector containing p53 gene dramatically increased GAPDH expression and triggered cell apoptosis. These results suggest that AraC-induced apoptosis of cerebellar granule cells involves the expression of both GAPDH and p53 and that, similar to Bax, GAPDH is upregulated by p53 after exposure to the apoptotic insult.
Granule Cells and Cerebellar Boundaries: Analysis ofUnc5h3Mutant Chimeras
Authors: Goldowitz Dan , Hamre Kristin M. , Przyborski Stefan A. , Ackerman Susan L. 
Published: April 2018

Mutations in theUnc5h3gene, a receptor for the netrin 1 ligand, result in abnormal migrations of both Purkinje and granule cells to regions outside the cerebellum and of granule cells to regions within the cerebellum. Because both Purkinje and granule cells express this molecule, we sought to determine whether one or both of these cell types are the primary target of the mutation.Chimeric mice were made between wild-type ROSA26 transgenic mouse embryos (whose cells express β-galactosidase) andUnc5h3mutant embryos. The resulting chimeric brains exhibited a range of phenotypes. Chimeras that had a limited expression of the extracerebellar phenotype (movement of cerebellar cells into the colliculus and midbrain tegmentum) and the intracerebellar phenotype (migration of granule cells into white matter) had a normal-appearing cerebellum, whereas chimeras that had more ectopic cells had attenuated anterior cerebellar lobules. Furthermore, the colonization of colliculus and midbrain tegmentum by cerebellar cells was not equivalent in all chimeras, suggesting different origins for extracerebellar ectopias in these regions.The granule cells of the extracerebellar ectopias were almost entirely derived fromUnc5h3/Unc5h3mutant embryos, whereas the ectopic Purkinje cells were a mixture of both mutant and wild-type cells. Intracerebellar ectopias in the chimera were composed exclusively of mutant granule cells. These findings demonstrate that both inside and outside the cerebellum, the granule cell is the key cell type to demarcate the boundaries of the cerebellum.