bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of design‐based stereology to evaluate volumes and numbers in the liver: a review with practical guidelines
Authors: Marcos Ricardo , Monteiro Rogério A.F. , Rocha Eduardo 
Published: February 2012

AbstractStereology offers a number of tools for the analysis of sections in microscopy (which usually provide only two‐dimensional information) for the purpose of estimating geometric quantities, such as volume, surface area, length or number of particles (cells or other structures). The use of these tools enables recovery of the three‐dimensional information that is inherent in biological tissues. This review uses the liver as a paradigm for summarizing the most commonly used state‐of‐the‐art methods for quantitation in design‐based stereology. Because it is often relevant to distinguish hyperplasia and hypertrophy in liver responses, we also focus on potential pitfalls in the sampling and processing of liver specimens for stereological purposes, and assess the existing methods for volume and number estimation. With respect to volume, we considered whole liver volume (V), volume density (VV) and so‐called local volumes, including the number‐weighted volume () and the volume‐weighted volume (). For number, we considered the total number (N) and the numerical density (NV). If correctly applied, current stereological methods guarantee that no bias is introduced in the estimates, which will be therefore accurate; additionally, methods can be tuned for obtaining precise quantitative estimates that can reveal subtle changes in the volume or number of selected hepatic cells. These methods have already detailed the effects of some substances and specific diets on the liver, and should be routinely included in the toolbox of liver research.
Inhibitory effect of cannabichromene, a major non‐psychotropic cannabinoid extracted from Cannabis sativa, on inflammation‐induced hypermotility in mice
Authors: Izzo Angelo A , Capasso Raffaele , Aviello Gabriella , Borrelli Francesca , Romano Barbara , Piscitelli Fabiana , Gallo Laura , Capasso Francesco , Orlando Pierangelo , Di Marzo Vincenzo 
Published: February 2012

BACKGROUND AND PURPOSE Cannabichromene (CBC) is a major non‐psychotropic phytocannabinoid that inhibits endocannabinoid inactivation and activates the transient receptor potential ankyrin‐1 (TRPA1). Both endocannabinoids and TRPA1 may modulate gastrointestinal motility. Here, we investigated the effect of CBC on mouse intestinal motility in physiological and pathological states.EXPERIMENTAL APPROACH Inflammation was induced in the mouse small intestine by croton oil. Endocannabinoid (anandamide and 2‐arachidonoyl glycerol), palmitoylethanolamide and oleoylethanolamide levels were measured by liquid chromatography‐mass spectrometry; TRPA1 and cannabinoid receptors were analysed by quantitative RT‐PCR; upper gastrointestinal transit, colonic propulsion and whole gut transit were evaluated in vivo; contractility was evaluated in vitro by stimulating the isolated ileum, in an organ bath, with ACh or electrical field stimulation (EFS).KEY RESULTS Croton oil administration was associated with decreased levels of anandamide (but not 2‐arachidonoyl glycerol) and palmitoylethanolamide, up‐regulation of TRPA1 and CB1 receptors and down‐regulation of CB2 receptors. Ex vivo CBC did not change endocannabinoid levels, but it altered the mRNA expression of TRPA1 and cannabinoid receptors. In vivo, CBC did not affect motility in control mice, but normalized croton oil‐induced hypermotility. In vitro, CBC reduced preferentially EFS‐ versus ACh‐induced contractions. Both in vitro and in vivo, the inhibitory effect of CBC was not modified by cannabinoid or TRPA1 receptor antagonists.CONCLUSION AND IMPLICATIONS CBC selectively reduces inflammation‐induced hypermotility in vivo in a manner that is not dependent on cannabinoid receptors or TRPA1.
Does terfenadine‐induced ventricular tachycardia/fibrillation directly relate to its QT prolongation and Torsades de Pointes?
Authors: Lu Hua Rong , Hermans An N , Gallacher David J 
Published: February 2012

BACKGROUND AND PURPOSE Terfenadine has been reported to cause cardiac death. Hence, we investigated its pro‐arrhythmic potential in various in vitro models.EXPERIMENTAL APPROACH Pro‐arrhythmic effects of terfenadine were investigated in rabbit isolated hearts and left ventricular wedge preparations. Also, using whole‐cell patch‐clamp recording, we examined its effect on the human ether‐à‐go‐go‐related gene (hERG) current in HEK293 cells transfected with hERG and on the INa current in rabbit ventricular cells and human atrial myocytes.KEY RESULTS Terfenadine concentration‐ and use‐dependently inhibited INa in rabbit myocytes and in human atrial myocytes and also inhibited the hERG. In both the rabbit left ventricular wedge and heart preparations, terfenadine at 1 µM only slightly prolonged the QT‐ and JT‐intervals but at 10 µM, it caused a marked widening of the QRS complex, cardiac wavelength shortening, incidences of in‐excitability and non‐TdP‐like ventricular tachycardia/fibrillation (VT/VF) without prolongation of the QT/JT‐interval. At 10 µM terfenadine elicited a lower incidence of early afterdepolarizations versus non‐ Torsades de Pointes (TdP)‐like VT/VF (100% incidence), and did not induce TdPs. Although the concentration of terfenadine in the tissue‐bath was low, it accumulated within the heart tissue.CONCLUSION AND IMPLICATIONS Our data suggest that: (i) the induction of non‐TdP‐like VT/VF, which is caused by slowing of conduction via blockade of INa (like Class Ic flecainide), may constitute a more important risk for terfenadine‐induced cardiac death; (ii) although terfenadine is a potent hERG blocker, the risk for non‐TdP‐like VT/VF exceeds the risk for TdPs; and (iii) cardiac wavelength (λ) could serve as a biomarker to predict terfenadine‐induced VT/VF.
Nociceptive and pro‐inflammatory effects of dimethylallyl pyrophosphate via TRPV4 activation
Authors: Bang S , Yoo S , Yang TJ , Cho H , Hwang SW 
Published: February 2012

BACKGROUND AND PURPOSE Sensory neuronal and epidermal transient receptor potential ion channels (TRPs) serve an important role as pain sensor molecules. While many natural and synthetic ligands for sensory TRPs have been identified, little is known about the endogenous activator for TRPV4. Recently, we reported that endogenous metabolites produced by the mevalonate pathway regulate the activities of sensory neuronal TRPs. Here, we show that dimethylallyl pyrophosphate (DMAPP), a substance produced by the same pathway is an activator of TRPV4.EXPERIMENTAL APPROACH We examined the effects of DMAPP on sensory TRPs using Ca2+ imaging and whole‐cell electrophysiology experiments with a heterologous expression system (HEK293T cells transfected with individual TRP channels), cultured sensory neurons and keratinocytes. We then evaluated nociceptive behavioural and inflammatory changes upon DMAPP administration in mice in vivo.KEY RESULTS In the HEK cell heterologous expression system, cultured sensory neurons and keratinocytes, µM concentrations of DMAPP activated TRPV4. Agonistic and antagonistic potencies of DMAPP for other sensory TRP channels were examined and activation of TRPV3 by camphor was found to be inhibited by DMAPP. In vivo assays, intraplantar injection of DMAPP acutely elicited nociceptive flinches that were prevented by pretreatment with TRPV4 blockers, indicating that DMAPP is a novel pain‐producing molecule through TRPV4 activation. Further, DMAPP induced acute inflammation and noxious mechanical hypersensitivities in a TRPV4‐dependent manner.CONCLUSIONS AND IMPLICATIONS Overall, we found a novel sensory TRP acting metabolite and suggest that its use may help to elucidate the physiological role of TRPV4 in nociception and associated inflammation.
Transforming growth factor‐β impairs glucocorticoid activity in the A549 lung adenocarcinoma cell line
Authors: Salem S , Harris T , Mok JSL , Li MYS , Keenan CR , Schuliga MJ , Stewart AG 
Published: February 2012

BACKGROUND AND PURPOSE The lung adenocarcinoma cell line, A549, undergoes epithelial‐mesenchymal cell transition (EMT) in response to TGF‐β. Glucocorticoids do not prevent the EMT response, but TGF‐β induced resistance to the cytokine‐regulatory action of glucocorticoids. We sought to characterize the impairment of glucocorticoid response in A549 cells.EXPERIMENTAL APPROACH A549 cells were exposed to TGF‐β for up to 96 h before glucocorticoid treatment and challenge with IL‐1α to assess glucocorticoid regulation of IL‐6 and CXCL8 production. Nuclear localization of the glucocorticoid receptor α (GRα) was ascertained by immunofluorescence and Western blotting. Transactivation of the glucocorticoid response element (GRE) was measured with a transfected GRE‐secreted human placental alkaline phosphatase reporter.KEY RESULTS TGF‐β (40–400 pM) reduced the maximum inhibitory effect of dexamethasone on IL‐1α‐induced IL‐6 and CXCL8 production. The impaired glucocorticoid response was detected with 4 h of TGF‐β (40 pM) exposure (and 4 h IL‐1α to induce CXCL8 expression) and therefore was not secondary to EMT, a process that requires longer incubation periods and higher concentrations of TGF‐β. TGF‐β also impaired dexamethasone regulation of granulocyte‐macrophage colony‐stimulating factor in thrombin‐stimulated BEAS‐2B epithelial cells. Impaired regulation of CXCL8 was associated with markedly reduced GRE transactivation and reduced induction of mRNA for IκBα, the glucocorticoid‐inducible leucine zipper and the epithelial sodium channel (SCNN1A). The expression, cellular levels and nuclear localization of GRα were reduced by TGF‐β.CONCLUSIONS AND IMPLICATIONS We have identified mechanisms underlying the impairment of responses to glucocorticoids by TGF‐β in the A549 and BEAS‐2B cell lines.
Hydrogen sulfide‐induced mechanical hyperalgesia and allodynia require activation of both Cav3.2 and TRPA1 channels in mice
Authors: Okubo Kazumasa , Matsumura Midori , Kawaishi Yudai , Aoki Yuka , Matsunami Maho , Okawa Yasumasa , Sekiguchi Fumiko , Kawabata Atsufumi 
Published: February 2012

BACKGROUND AND PURPOSEHydrogen sulfide, a gasotransmitter, facilitates somatic pain signals via activation of Cav3.2 T‐type calcium channels in rats. Given evidence for the activation of transient receptor potential ankyrin‐1 (TRPA1) channels by H2S, we asked whether TRPA1 channels, in addition to Cav3.2 channels, contribute to the H2S‐induced mechanical hyperalgesia and allodynia in mice.EXPERIMENTAL APPROACHMechanical hyperalgesia and allodynia were evaluated by the von Frey test in mice. Cav3.2 or TRPA1 channels in the sensory neurons were silenced by repeated intrathecal administration of antisense oligodeoxynucleotides in mice.KEY RESULTSIntraplantar administration of NaHS evoked hyperalgesia and allodynia in mice, an effect attenuated or abolished by NNC 55–0396 or mibefradil, T‐type calcium channel blockers, and by ascorbic acid or zinc chloride, known to selectively inhibit Cav3.2 channels, out of the three isoforms of T‐type calcium channels. Silencing of Cav3.2 channels in the sensory neurons also prevented the NaHS‐induced hyperalgesia and allodynia in mice. The NaHS‐induced hyperalgesia and allodynia in mice were significantly suppressed by AP18, a TRPA1 channel blocker, and by silencing of TRPA1 channels in the sensory neurons.CONCLUSIONS AND IMPLICATIONSMechanical hyperalgesia and allodynia induced by NaHS/H2S required activation of both Cav3.2 and TRPA1 channels in mice.
Abdominal ultrasonographic findings at diagnosis of osteosarcoma in dogs and association with treatment outcome
Authors: Sacornrattana O. , Dervisis N. G. , McNiel E. A. 
Published: February 2012

AbstractThe purpose of this study was to describe abdominal ultrasonographic findings present at diagnosis of osteosarcoma (OSA) in dogs and to investigate for associations with treatment outcome. Medical records from 118 dogs diagnosed withOSAthat had abdominal ultrasonography performed as part of their initial evaluation were reviewed. Fifty‐seven percent had ultrasonographic abnormalities identified. The organ with the highest frequency of ultrasonographic changes was the spleen. While most sonographic changes were considered to be either benign or of unknown clinical consequences, metastases were identified in three dogs (2.5%), two of which (1.7%) did not have other evidence of metastasis. Dogs with any ultrasonographic abnormality were less likely to receive definitive therapy (P= 0.005) and exhibited shorter survival, although the latter observation was not statistically significant (P= 0.071). However, the identification of lesions in either the liver (P= 0.021) or the kidney (P= 0.003) was statistically associated with shorter survival.
Discrimination, Crypticity, and Incipient Taxa in Entamoeba
Authors: Espinosa Avelina , Paz‐Y‐Miño‐C. Guillermo 
Published: February 2012

AbstractPersistent difficulties in resolving clear lineages in diverging populations of prokaryotes or unicellular eukaryotes (protistan polyphyletic groups) are challenging the classical species concept. Although multiple integrated approaches would render holistic taxonomies, most phylogenetic studies are still based on single‐gene or morphological traits. Such methodologies conceal natural lineages, which are considered “cryptic.” The concept of species is considered artificial and inadequate to define natural populations. Social organisms display differential behaviors toward kin than to nonrelated individuals. In “social” microbes, kin discrimination has been used to help resolve crypticity. Aggregative behavior could be explored in a nonsocial protist to define phylogenetic varieties that are considered “cryptic.” Two Entamoeba invadens strains, IP‐1 and VK‐1:NS are considered close populations of the same “species.” This study demonstrates that IP‐1 and VK‐1:NS trophozoites aggregate only with alike members and discriminate members of different strains based on behavioral and chemical signals. Combined morphological, behavioral/chemical, and ecological studies could improve Archamoebae phylogenies and define cryptic varieties. Evolutionary processes in which selection acted continuously and cumulatively on ancestors of Entamoeba populations gave rise to chemical and behavioral signals that allowed individuals to discriminate nonpopulation members and, gradually, to the emergence of new lineages; alternative views that claim a “Designer” or “Creator” as responsible for protistan diversity are unfounded.
The conclusiveness of less‐invasive imaging techniques (computer tomography, X‐ray) with regard to their identification of bone diseases in a primate model (Callithrix jacchus)
Authors: Grohmann J. , Taetzner S. , Theuss T. , Kuehnel F. , Buchwald U. , Einspanier A. 
Published: February 2012

AbstractBackground  Although common marmosets seem to be appropriate animal models to examine bone diseases, no data about the conclusiveness of less‐invasive techniques are available. Therefore, the aim was to combine different techniques to analyse changes in bone metabolism of common marmosets with bone diseases.Methods  Five monkeys were examined by X‐ray, computer tomography (CT), histology and immunohistochemistry (IHC).Results  Monkeys with lowest bone mineral density (BMD) showed increased bone marrow, decreased cancellous bone and decreased contrast in X‐ray. Highest alkaline phosphatase (AP)‐levels were detected in bones with low elastic modulus. Expression of osteopontin (OPN), osteocalcin (OC) and runt‐related transcriptions factor 2 (RUNX 2) was detected in bones with high modulus. No expression was present in bones with lower modulus. Collagen type I and V were found in every bone.Conclusions  In conclusion, CT, X‐ray and AP are useful techniques to detect bone diseases in common marmosets. These observations could be confirmed by IHC.
The effect of various concentrations of iodine potassium iodide on the antimicrobial properties of mineral trioxide aggregate – a pilot study
Authors: Saatchi Masoud , Hosseini Hananeh Sadat , Farhad Ali Reza , Narimany Tahmineh 
Published: February 2012

Abstract –  Background: Mineral trioxide aggregate (MTA) is a multi‐purpose dental material with various uses in dentistry. Iodine potassium iodide (IKI) is the most commonly used iodine compound in endodontics. We aimed to assess the antimicrobial activity of tooth‐colored ProRoot MTA combined with IKI. Materials and methods: The antimicrobial activity of IKI was assessed at three concentrations (1%, 2%, and 4%) as the mixing agents combined with MTA against Enterococcus faecalis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans. For each microorganism, three plates were inoculated with 100 μl of a microbial suspension (McFarland 0.5). Four wells were prepared in each plate. MTA (70 mg) was mixed with any of the three concentrations of IKI (25 μl) or sterile distilled water (25 μl) and placed in each well. The plates were incubated for 24 h at 37°C. Zones of inhibition (ZOI) were measured in millimeters by a blinded observer. Data were analyzed using analysis of variance and the Dunnett t‐test. Results: All MTA mixtures with water or IKI solutions showed inhibitory zones. The mean ZOI of each MTA/IKI mixture was not significantly different from MTA/water mixture (P > 0.05). MTA/1% IKI had smaller ZOI than MTA/water against E. coli, E. faecalis, and C. albicans. MTA/2% IKI showed larger ZOI only against P. aeruginosa. MTA/4% IKI showed larger ZOI against P. aeruginosa and E. coli (P < 0.05). Conclusions: Substitution of IKI solutions (1%, 2%, and 4%) for water did not significantly increase the antimicrobial activity of MTA.
Contact dermatitis to para‐phenylenediamine in hair dye following sensitization to black henna tattoos – an ongoing problem
Authors: Kind Fabiola , Scherer Kathrin , Bircher Andreas J. 
Published: February 2012

Summary  Background: The increased frequency of case reports of allergic contact dermatitis from non‐permanent black henna tattoos in recent years shows the popularity of this form of body painting.Patients and methods: Seven patients presented with allergic contact dermatitis after initial hair or eyelash dyeing. They all had a history of a previous reaction from a black henna tattoo. All were patch tested with the European standard patch test series and the standard supplemental series, as well as special series for dyes and hairdressers.Results: All seven patients showed a positive reaction in patch testing with para‐phenylenediamine (PPD) (0.3 % and/or 1.0 % in pet.). Five patients also had positive reactions to other dyes such as aminophenol, para‐toluene diamine, disperse orange and yellow and four patients reacted to benzocaine. These were interpreted as cross‐reactions. The time from sensitization by the black henna tattoo to the onset of allergic contact dermatitis after hair dyeing was an average of 6.2 years.Conclusions: The most common cause of allergic contact dermatitis after black henna tattoos is PPD. Both the long skin contact and the high concentrations of PPD increase the risk of sensitization. Allergic contact dermatitis may be followed by post‐inflammatory hyper‐ or hypopigmentation, scarring and lifelong sensitization, which can have occupational impact, especially for hair dressers and cosmeticians.
Biotic homogenization of upland vegetation: patterns and drivers at multiple spatial scales over five decades
Authors: Ross Louise C. , Woodin Sarah J. , Hester Alison J. , Thompson Des B.A. , Birks H. John B. 
Published: February 2012

AbstractQuestionsIs there evidence for biotic homogenization of upland vegetation? Do the magnitude and nature of floristic and compositional change vary between vegetation types? What can be inferred about the drivers responsible for the observed changes?LocationUpland heath, mire and grassland communities of the northwest Highlands of Scotland, UK.MethodsWe re‐survey plots first described in a phytosociological study of 1956–1958 to assess the changes in plant species composition over the last 50 yr in five major upland vegetation types. Using a combination of multivariate analysis, dissimilarity measures, diversity metrics and published data on species attributes; we quantify, characterize and link potential drivers of environmental change with the observed changes in species composition.ResultsGrassland and heath vegetation declined in species richness and variation in community composition, while mires showed little change. Previously distinct vegetation types became more similar in composition, characterized by the increased dominance of generalist upland graminoids and reduced dwarf‐shrub, forb and lichen cover, although novel assemblages were not apparent. Species with an oceanic distribution increased at the expense of those with an arctic‐montane distribution. Temperature, precipitation and acidity were found to be potentially important in explaining changes in species composition: species that had undergone the greatest increases had a preference for warmer, drier and more acidic conditions.ConclusionsThe vegetation of the northwest Scottish Highlands has undergone marked biotic homogenization over the last 50 yr, manifested through a loss of various aspects of diversity at the local, community and landscape scales. The magnitude of change varies between vegetation types, although the nature of change shows many similar characteristics. Analyses of species attributes suggest these changes are driven by climate warming and acidification, although over‐grazing may also be important. This study highlights the importance of the link between the loss of plant diversity and homogenization at multiple scales, and demonstrates that boreal heath communities are particularly at risk from these processes.
Elevational advance of alpine plant communities is buffered by herbivory
Authors: Speed James D. M. , Austrheim Gunnar , Hester Alison J. , Mysterud Atle 
Published: February 2012

AbstractQuestionA warming climate has been linked to changes in the distribution of many species, yet the interactions between climate and other environmental drivers are relatively poorly understood. Mountain regions are expected to be particularly at risk in a warming climate, and in many upland regions land use has also changed dramatically over the past few decades, with densities of grazing livestock often decreasing. Does livestock grazing influence elevational shifts of plant communities?LocationSouthern Scandes, Norway.MethodsWe use a unique long‐term experimental study at the landscape scale along an altitudinal gradient to study elevational shifts of plant communities and species under high and low sheep densities and in ungrazed conditions.ResultsWe show that elevational advance of the whole alpine grassland plant community occurred in the absence of herbivores (with a 3 m elevational advance over 8 yr), but was suppressed at low sheep density. At high sheep density there was a downward shift in plant community composition of 4 m. The average change in median altitude across species was positive in the absence of herbivores, but not significantly different from zero under both grazing treatments. There was no convincing evidence that species from lower altitudes showed a greater elevational advance than species from higher altitudes.ConclusionsThis study presents evidence that grazing sheep suppressed an elevational advance of the plant community, suggesting that grazing can limit the altitude of the plant community. This implies that grazing management has the potential to buffer climate‐driven shifts in plant communities. Conversely, the widespread recent changes in land use, with reductions in large herbivore densities in alpine areas, could further increase the vulnerability of alpine communities to warming.