bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apoptosis inducing activity of viscin, a lipophilic extract from Viscum album L.
Authors: Urech K , Scher J M , Hostanska K , Becker H 
Published: December 2004

Abstract
Detection of antiproliferative activity and bioactivity-guided fractionation of viscin, a lipophilic extract from Viscum album L., led to the isolation of betulinic acid, oleanolic acid and ursolic acid as active components. Viscin, betulinic acid, oleanolic acid and ursolic acid inhibited growth and induced apoptotic cell death in Molt4, K562 and U937 leukaemia cells. The growth inhibitory effect of viscin was more pronounced in Molt4 and U937 cells (IC50 (concentration that inhibited cell proliferation by 50%): 118 ± 24 and 138 ± 24 μg mL−1) than in K562 cells (IC50: 252 ± 37 μg mL−1). Oleanolic acid was the least effective in all cell lines (7.5–45.5% inhibition at 10 μg mL−1) and ursolic acid the most active in Molt4 and U937 cells (81.8 and 97.8% inhibition, respectively, at 5 μg mL−1). A dose-dependent loss of membrane phospholipid asymmetry associated with apoptosis was induced in all cell lines as shown in flow cytometry by the externalization of phosphatidylserine and morphological changes in cell size and granularity. There were differences in individual cell lines' response towards the apoptosis-inducing effect of viscin, betulinic acid, oleanolic acid and ursolic acid. The triterpenoids β-amyrin, β-amyrinacetate, lupeol, lupeolacetate, β-sitosterol and stigmasterol, and the fatty acids oleic acid, linoleic acid, palmitic acid and stearic acid were also present in the lipophilic extract.
Transport of prostaglandin E1 across the blood-brain barrier in rats
Authors: Taogoshi T , Nomura A , Murakami T , Nagai J , Takano M 
Published: December 2004

Abstract
The transport of prostaglandin E1 (PGE1) across the blood-brain barrier (BBB) was characterized using an in-situ rat brain perfusion technique. The uptake of [3H]PGE1 was not affected by short-chain monocarboxylic acids (butyric acid and valeric acid). On the other hand, uptake of [3H]PGE1 was significantly inhibited by medium-chain monocarboxylic acids such as hexanoic acid, enanthic acid and octanoic acid. These medium-chain monocarboxylic acids showed a more potent inhibitory effect on [3H]PGE1 uptake with increasing number of carbon atoms. In contrast, there was no decrease in [3H]PGE1 transport by any dicarboxylic acids with 5–8 carbon atoms. Valproic acid decreased [3H]PGE1 uptake, whereas p-aminohippuric acid, a substrate for the organic anion transporter family, did not inhibit [3H]PGE1 transport. Bromocresol green, an inhibitor of prostaglandin transporter (PGT), strongly decreased [3H]PGE1 transport across the BBB. In addition, digoxin and taurocholate, substrates for organic anion transporting polypeptide subtype 2 (Oatp2), significantly inhibited [3H]PGE1 uptake. RT-PCR analysis revealed that PGT mRNA and Oatp2 mRNA are expressed in a capillary-rich fraction from rat brain. Thus, it is suggested that PGE1 transport across the BBB is mediated by some specific transport systems, possibly by the members of the Oatp family.
Stability of Ala 125 recombinant human interleukin-2 in solution
Authors: Reyes Nuria , Ruiz Llamil , Aroche Kethia , Gerónimo Haydee , Brito Olga , Hardy Eugenio , Gonzälez L R 
Published: December 2004

Abstract
Herein, we describe the preformulation study of Ala 125-recombinant human interleukin-2 (rhIL-2A125) in solution. This modified form of the natural human IL-2 is obtained by the replacement of cysteine with alanine at position 125. The compatibility of this rhIL-2A125 with type I borosilicate glass vials showed no significant adsorption at liquid-vial interface. The effect of single excipients on the stability of this lymphokine was evaluated through RP-HPLC, SDS-PAGE and biological activity assay. Polysorbate 80 at high concentrations decreased the stability of rhIL-2A125 in solution. On the other hand, the use of antioxidants (methionine and EDTA Na2) diminished the oxidation rate of the active ingredient. Additionally, a group of amino acids (glutamine, alanine, glycine and histidine) stabilized rhIL-2A125 in different grades, and glycine at 5 mg mL−1 allowed for the best stability behaviour. Taken together, these preformulation results can be used to design an adequate liquid vehicle for rhIL-2A125 to be manufactured for human use.
Prostaglandins in non-insectan invertebrates: recent insights and unsolved problems
Authors: Rowley Andrew F. , Vogan Claire L. , Taylor Graham W. , Clare Anthony S. 
Published: December 2004

SUMMARYProstaglandins (PG) are oxygenated derivatives of C20 polyunsaturated fatty acids including arachidonic and eicosapentaenoic acids. In mammals, these compounds have been shown to play key roles in haemostasis, sleep-wake regulation, smooth muscle tone, and vaso-, temperature and immune regulation. In invertebrates, PGs have been reported to perform similar roles and are involved in the control of oogenesis and spermatogenesis, ion transport and defence. Although there is often a detailed understanding of the actions of these compounds in invertebrates such as insects, knowledge of their mechanism of biosynthesis is often lacking. This account provides a critical review of our current knowledge on the structure and modes of biosynthesis of PGs in invertebrates, with particular reference to aquatic invertebrates. It emphasises some of the most recent findings, which suggest that some PGs have been misidentified.Prostaglandins in invertebrates can be categorised into two main types; the classical forms, such as PGE2 and PGD2 that are found in mammals, and novel forms including clavulones, bromo- and iodo-vulones and various PGA2 and PGE2 esters. A significant number of reports of PG identification in invertebrates have relied upon methods such as enzyme immunoassay that do not have the necessary specificity to ensure the validity of the identification. For example, in the barnacle Balanus amphitrite, although there are PG-like compounds that bind to antibodies raised against PGE2, mass spectrometric analysis failed to confirm the presence of this and other classical PGs. Therefore, care should be taken in drawing conclusions about what PGs are formed in invertebrates without employing appropriate analytical methods. Finally, the recent publication of the Ciona genome should facilitate studies on the nature and mode of biosynthesis of PGs in this advanced deuterostomate invertebrate.
Joint work and power associated with acceleration and deceleration in tammar wallabies (Macropus eugenii)
Authors: McGowan C. P. , Baudinette R. V. , Biewener A. A. 
Published: December 2004

SUMMARYMeasurements of joint work and power were determined using inverse dynamics analysis based on ground reaction force and high-speed video recordings of tammar wallabies as they decelerated and accelerated while hopping over a force platform on level ground. Measurements were obtained over a range of accelerations ranging from -6 m s-2 to 8 m s-2. The goal of our study was to determine which joints are used to modulate mechanical power when tammar wallabies change speed. From these measurements, we also sought to determine which hind limb muscle groups are the most important for producing changes in mechanical work. Because our previous in vivoanalyses of wallaby distal muscle function indicated that these muscle-tendon units favor elastic energy savings and perform little work during steady level and incline hopping, we hypothesized that proximal muscle groups operating at the hip and knee joint are most important for the modulation of mechanical work and power. Of the four hind limb joints examined, the ankle joint had the greatest influence on the total limb work, accounting for 89% of the variation observed with changing speed. The hip and metatarsophalageal (MP) joints also contributed to modulating whole limb work, but to a lesser degree than the ankle, accounting for 28% (energy production) and -24% (energy absorption) of the change in whole limb work versus acceleration, respectively. In contrast, the work produced at the knee joint was independent of acceleration. Based on the results of our previous in vivo studies and given that the magnitude of power produced at the ankle exceeds that which these muscles alone could produce, we conclude that the majority of power produced at the ankle joint is likely transferred from the hip and knee joints viaproximal bi-articular muscles, operating in tandem with bi-articular ankle extensors, to power changes in hopping speed of tammar wallabies. Additionally, over the observed range of performance, peak joint moments at the ankle (and resulting tendon strains) did not increase significantly with acceleration, indicating that having thin tendons favoring elastic energy storage does not necessarily limit a tammar wallaby's ability to accelerate or decelerate.
Ion-selective microelectrode analysis of salicylate transport by the Malpighian tubules and gut ofDrosophila melanogaster
Authors: O'Donnell Michael J. , Rheault Mark R. 
Published: December 2004

SUMMARYTransport of the organic anion salicylate by the Malpighian tubules and gut of larval and adult fruit flies was studied using two salicylate-selective microelectrode methods. The first method combined the high selectivity of tridodecylmethylammonium-based electrodes for salicylate with the self-referencing ion-selective microelectrode technique for non-invasive spatial and temporal analysis of salicylate flux. Measurements with this technique revealed secretion of salicylate across the main and distal segments of the Malpighian tubule as well as the midgut, ileum and rectum. The second method used a salicylate-selective microelectrode to measure the concentration of salicylate in fluid droplets secreted by isolated DrosophilaMalpighian tubules set up in a Ramsay secretion assay. Transepithelial salicylate flux was calculated as the product of fluid secretion rate and secreted fluid salicylate concentration. Measurements with this method revealed that salicylate transport was active and saturable; the kinetic parameters Jmax and Kt were 2.72 pmol min-1 tubule-1 and 0.046 mmol l-1,respectively. Measurements of transepithelial salicylate flux determined by both microelectrode methods were in good agreement. Transepithelial flux measurements measured by microelectrodes were also validated by comparing them with measurements of radiolabelled salicylate levels in secreted droplets. Salicylate concentrations in haemolymph samples were measured with salicylate-selective microelectrodes after injection of salicylate into the haemocoel or after insects were fed salicylate-rich diets. The rate of salicylate secretion by Malpighian tubules in vitro was sufficient to account for the measured rate of decline of salicylate concentration in the haemolymph in vivo.
Consumptive coagulopathy complicating juvenile angiofibroma
Authors: Baguley Campbell , Sandhu Guri , O’Donnell James , Howard David 
Published: December 2004

Objective: To investigate the incidence and clinical significance of deranged clotting results among patients with juvenile (nasopharyngeal) angiofibroma.Methods: Twenty consecutive patients treated for juvenile angiofibroma between March 1998 and July 2002 in whom preoperative coagulation tests were performed were selected. Results were compared with normal laboratory values, and clinical and histological records were retrospectively analysed.Results: Four out of 20 patients were found to have abnormal tests, consistent with concurrent consumptive coagulopathies. One patient was found to have a raised D-dimer level. This resolved following removal of the lesion.Conclusions:The association between larger arterio-venous malformations and disseminated intravascular coagulopathy is well described (Kasabach–Merritt syndrome). Our findings suggest that low-grade consumptive coagulopathies may also complicate smaller juvenile angiofibromas, implying that preoperative coagulation screening tests may have a role in ensuring optimal perioperative haemostasis.
Volumetric analysis of maxillary sinuses of Zulu and European crania by helical, multislice computed tomography
Authors: Fernandes C.L. 
Published: December 2004

Introduction: The volumes of the maxillary sinuses are of interest to surgeons operating endoscopically as variation in maxillary sinus volume may mean variation in anatomical landmarks. Other surgical disciplines, such as dentistry, maxillo-facial surgery and plastic surgery, may benefit from this information.Objectives: To compare the maxillary sinus volumes of dried crania from cadavers of European and Zulu descent, with respect to ethnic group and gender.Methodology: Helical, multislice computed tomography (CT) was performed using 1-mm coronal slices. The area
for each slice was obtained by tracing the outline of each slice. The CT machine calculated a volume by totalling the slices for each sinus.Results: Ethnic and gender variations were found in the different groups. It was found that European crania had significantly larger antral volumes
than Zulu crania and men had larger volumes than women. Race and gender interaction was also assessed, as was maxillary sinus side.Conclusion: A variation in maxillary sinus volume between different ethnic groups and genders exists, and surgeons operating in this region should be aware of this.
Repair of subtotal tympanic membrane perforations with Seprafilm®
Authors: Konakçi Ersin , Koyuncu Mehmet , Ünal Recep , Tekat Atilla , Uyar Melek 
Published: December 2004

Objectives: We studied the experimental use of Seprafilm, a sheet-like filmform of hyaluronic acid, in the repair of subtotal perforations of the tympanic membrane (TM), and the durability of such repairs.Method: The research was conducted on 42 Sprague–Dawley rats. Right TMs of all rats were subtotally and thermally perforated in the same fashion. Seprafilm was applied to the perforated TMs of the 21 rats comprising the experiment group. The perforated TMs of the remaining 21rats, the control group, were left to heal spontaneously.Results: The mean healing times were recorded as 7.8 ± 0.6 days for the Seprafilm group and 14.9 ± 1.1 days for the control group (p < 0.001).Conclusions: These results suggest that Seprafilm may be a possible first choice (before thedecision to operate) in subtotal perforations, considering its easy application and patient follow-up.
Evaluation of Drug Interaction Software to Identify Alerts for Transplant Medications
Authors: Smith Wendy D , Hatton Randy C , Fann Amy L , Baz Maher A , Kaplan Bruce 
Published: December 2004

BACKGROUND: The ability of computerized physician order entry (CPOE) systems to identify clinically significant drug interactions is dependent upon the integrity of the drug information populating the software. A CPOE system with incomplete or inaccurate drug information will fail to identify clinically important drug interactions and, therefore, fail to reduce preventable adverse drug events (pADEs). OBJECTIVE: To evaluate, from the prescribers' perspective, the ability of a common drug interaction database to identify clinically important drug interactions involving drugs used in transplantation. METHODS: The clinical significance of drug interactions involving 5 transplant drugs was evaluated by an expert panel to determine whether alerts should be generated for physicians not involved in the transplant at the time of order entry. Drug interactions included in the analysis were generated from the expert panel, a common drug interaction database, and 2 standard drug interaction references. Responses on the clinical significance were used to calculate the sensitivity, specificity, and positive and negative predictive values for each severity setting of a common electronic drug interaction database. RESULTS: Overall, the database failed to identify approximately 70% of interactions considered significant by the expert panel. Of the alerts that were generated, >85% were considered clinically significant. The database was most deficient in identifying interactions resulting from additive toxicity. CONCLUSIONS: To expect a decrease in pADEs caused by drug interactions, the information used to populate CPOE systems must be validated. Establishing consistency and integrity of this information may be a future role for pharmacists.
Conversion of the Modulatory Actions of Dopamine on Spinal Reflexes from Depression to Facilitation in D3Receptor Knock-Out Mice
Authors: Clemens Stefan , Hochman Shawn 
Published: December 2004

Descending monoaminergic systems modulate spinal cord function, yet spinal dopaminergic actions are poorly understood. Using thein vitrolumbar cord, we studied the effects of dopamine and D2-like receptor ligands on spinal reflexes in wild-type (WT) and D3-receptor knock-out mice (D3KO).Low dopamine levels (1 μm) decreased the monosynaptic “stretch” reflex (MSR) amplitude in WT animals and increased it in D3KO animals. Higher dopamine concentrations (10-100 μm) decreased MSR amplitudes in both groups, but always more strongly in WT. Like low dopamine, the D3receptor agonists pergolide and PD 128907 reduced MSR amplitude in WT but not D3KO mice. Conversely, D3receptor antagonists (GR 103691 and nafadotride) increased the MSR in WT but not in D3KO mice. In comparison, D2-preferring agonists bromocriptine and quinpirole depressed the MSR in both groups. Low dopamine (1-5 μm) also depressed longer-latency (presumably polysynaptic) reflexes in WT but facilitated responses in D3KO mice. Additionally, in some experiments (e.g., during 10 μmdopamine or pergolide in WT), polysynaptic reflexes were facilitated in parallel to MSR depression, demonstrating differential modulatory control of these reflex circuits. Thus, low dopamine activates D3receptors to limit reflex excitability. Moreover, in D3ligand-insensitive mice, excitatory actions are unmasked, functionally converting the modulatory action of dopamine from depression to facilitation.Restless legs syndrome (RLS) is a CNS disorder involving abnormal limb sensations. Because RLS symptoms peak at night when dopamine levels are lowest, are relieved by D3agonists, and likely involve increased reflex excitability, the D3KO mouse putatively explains how impaired D3activity could contribute to this sleep disorder.
Hippocampal Structures Among Japanese Adolescents Before and After the COVID-19 Pandemic
Authors: Cai Lin , Maikusa Norihide , Zhu Yinghan , Nishida Atsushi , Ando Shuntaro , Okada Naohiro , Kasai Kiyoto , Nakamura Yuko , Koike Shinsuke 
Published: February 2024

ImportanceFew studies have used a large-sample, longitudinal, population-based cohort study to examine whether the COVID-19 pandemic as a global major life event is associated with structural plasticity of the adolescent hippocampus.ObjectiveTo examine whether Japan's first state of emergency (SoE) during the COVID-19 pandemic was associated with alterations in the macrostructures and microstructures of the hippocampus during its development.Design, Setting, and ParticipantsThe population-neuroscience Tokyo TEEN Cohort study is a prospective cohort study with 4 consecutive waves in Tokyo, Japan. Due to the SoE, data collection was suspended between March 27, 2020, and July 30, 2020. Analyzed data, comprising 1149 brain structural scans obtained from 479 participants, of whom 336 participants had undergone 2 or more scans, were collected between October 2013 and November 2021. Data were analyzed from August 2022 to December 2023.ExposuresJapan’s first SoE (April 7 to May 25, 2020).Main Outcomes and MeasuresHippocampal volume, 12 hippocampal subfield volumes, and 7 microstructural measures of the hippocampus.ResultsA total of 1060 brain scans from 459 participants (214 female participants [47%]) including 246 participants from wave 1 (median [IQR] age, 11.3 [11.1-11.7] years), 358 from wave 2 (median [IQR] age, 13.8 [13.3-14.5] years), 304 from wave 3 (median [IQR] age, 15.9 [15.4-16.5] years), and 152 from wave 4 (median [IQR] age, 17.9 [17.5-18.4] years) were included in the final main analysis. The generalized additive mixed model showed a significant associations of the SoE with the mean hippocampal volume (β = 102.19; 95% CI, 0.61-203.77; P = .049). The generalized linear mixed models showed the main associations of the SoE with hippocampal subfield volume (granule cell and molecular layer of the dentate gyrus: β = 18.19; 95% CI, 2.97-33.41; uncorrected P = .02; CA4: β = 12.75; 95% CI, 0.38-25.12; uncorrected P = .04; hippocampus-amygdala transition area: β = 5.67; 95% CI, 1.18-10.17; uncorrected P = .01), and fractional anisotropy (β = 0.03; 95% CI, 0.00-0.06; uncorrected P = .04).Conclusions and RelevanceAfter the first SoE, a volumetric increase in the hippocampus and trend increase in 3 subfield volumes and microstructural integration of the hippocampus were observed, suggesting that the transient plasticity of the adolescent hippocampus was affected by a major life event along with the typical developmental trajectory.
Lipid droplets provide metabolic flexibility for cancer progression
Authors: Safi Rémi , Menéndez Pablo , Pol Albert 
Published: February 2024

A hallmark of cancer cells is their remarkable ability to efficiently adapt to favorable and hostile environments. Due to a unique metabolic flexibility, tumor cells can grow even in the absence of extracellular nutrients or in stressful scenarios. To achieve this, cancer cells need large amounts of lipids to build membranes, synthesize lipid‐derived molecules, and generate metabolic energy in the absence of other nutrients. Tumor cells potentiate strategies to obtain lipids from other cells, metabolic pathways to synthesize new lipids, and mechanisms for efficient storage, mobilization, and utilization of these lipids. Lipid droplets (LDs) are the organelles that collect and supply lipids in eukaryotes and it is increasingly recognized that the accumulation of LDs is a new hallmark of cancer cells. Furthermore, an active role of LD proteins in processes underlying tumorigenesis has been proposed. Here, by focusing on three major classes of LD‐resident proteins (perilipins, lipases, and acyl‐CoA synthetases), we provide an overview of the contribution of LDs to cancer progression and discuss the role of LD proteins during the proliferation, invasion, metastasis, apoptosis, and stemness of cancer cells.
The ecology of online hate speech: Mapping expert perspectives on the drivers for online hate perpetration with the Delphi method
Authors: Weber Ina , Vandebosch Heidi , Poels Karolien , Pabian Sara 
Published: February 2024

AbstractOnline hate speech (OHS) is a prevalent issue on social media with harmful consequences for individuals and society. Counteracting this issue requires a better understanding of the factors that drive behaviors such as posting hate speech or making hateful comments. The present study contributes to this need by investigating the personal, social, and digital determinants for OHS perpetration. By conducting a two‐round Delphi study, data was collected from an interdisciplinary sample of experts. Practitioners were included in this sample to bridge gaps between research and fieldwork on OHS. The first survey collected information through open‐ended questions, which was then organized in different themes and lists of determinants in a thematic analysis. These determinants were rated for relevance in a follow‐up survey. Data analysis of the second survey used nonparametric statistics. From a total list of 129 determinants, the participants reached a consensus on 27 determinants as most relevant (median > 4) for facilitating the production and dissemination of OHS. An ecological perspective was applied to interpret these findings. As a result, we propose an ecological model of personal, social, and digital determinants for online hate perpetration to illustrate their influence on individual behavior as well as their possible connections. The model provides a comprehensive overview of factors facilitating OHS perpetration, which can help to identify points for intervention.