bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulatory effects of Aloe vera leaf gel extract on oxidative stress in rats treated with streptozotocin
Authors: Rajasekaran S , Sivagnanam K , Subramanian S 
Published: January 2005

Abstract
Oxidative stress is currently suggested as a mechanism underlying diabetes and diabetic-related complications. Oxidative stress results from an imbalance between radical-generating and radical-scavenging systems. Many secondary plant metabolites have been reported to possess antioxidant activity. This study was designed to evaluate the potential antioxidative activity of the ethanolic extract from Aloe vera leaf gel in the plasma and pancreas of streptozotocin (STZ)-induced diabetic rats. Glibenclamide was used as a standard reference drug. Oral administration of ethanolic extract at a concentration of 300 mg kg−1 body weight for 21 days resulted in a significant reduction in fasting blood glucose, thiobarbituric acid reactive substances, hydroperoxides and alpha-tocopherol and significant improvement in ascorbic acid, reduced glutathione and insulin in the plasma of diabetic rats. Similarly, the treatment also resulted in a significant reduction in thiobarbituric acid reactive substances, hydroperoxides, superoxide dismutase, catalase and glutathione peroxidase and significant improvement in reduced glutathione in the pancreas of STZ-induced diabetic rats when compared with untreated diabetic rats. The ethanolic extract appeared to be more effective than glibenclamide in controlling oxidative stress. Thus, this study confirms the ethnopharmacological use of Aloe vera in ameliorating the oxidative stress found in diabetes.
In-vivo effects of the 1,2,4-piperazine derivatives MM5 and MC1, putative 5-HT agonists, on dopamine and serotonin release in rat prefrontal cortex
Authors: Iskra-Jopa Joanna , Golembiowska Krystyna , Dziubina Anna , Cybulski Marcin , Duszynńska Beata , Chilmonczyk Zdzislaw 
Published: January 2005

Abstract
Two 1,2,4-substituted derivatives of piperazine were tested for their effect on dopamine and serotonin (5-HT) release in rat prefrontal cortex. Both compounds, 1-[4-(4-chinolin-2-yl-piperazin-1-yl)-butyl]piperidin-2-on (MM5) and 1-[4-(2-methyl-4-chinolin-2-yl-piperazin-1-yl)-butyl]-8-azaspiro [4.5]decano-7,9-dion (MC1), produced hypothermia in mice and showed affinity for 5-HT1A receptors in-vitro. Like the selective 5-HT1A agonist 8-OH-DPAT (0.1 mg kg−1), MM5 given peripherally (30 mg kg−1) decreased the extracellular 5-HT level in rat prefrontal cortex, while MC1 suppressed 5-HT release at a higher dose (40 mg kg−1), but not at a lower one (30 mg kg−1). The effect of both compounds on 5-HT release was abolished by WAY 100635 (0.3 mg kg−1). MC1 (30 and 40 mg kg−1), but not MM5, raised cortical dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and extracellular homovanillic acid (HVA) levels. The effect of MC1 on dopamine release was reversed by neither WAY 100635 nor the non-selective 5-HT2 antagonist ritanserin (2 mg kg−1). However, ritanserin prevented the effect of the higher dose of MC1 on 5-HT release. The results of this study suggest that MM5 exhibits the profile of a 5-HT1A agonist devoid of dopaminergic activity. MC1 seems to possess moderate agonist activity at 5-HT1A and 5-HT2A receptors, while acting on 5-HT release in the rat prefrontal cortex. However, the facilitation of dopamine release by this compound does not seem to be related to its affinity for 5-HT1A and 5-HT2A receptors.
The metallopeptide antibiotic bacitracin inhibits interleukin-12 αβ and β2 secretion
Authors: Alloza I , Vandenbroeck K 
Published: January 2005

Abstract
The metalloantibiotic bacitracin is a known inhibitor of protein disulfide isomerase (PDI). The disulfide-linked interleukin-12 (IL-12) αβ-heterodimer and β2-homodimer forms are crucial mediators of cell-mediated immune responses and inflammatory reactions. Bacitracin was found to potently block secretion of both the αβ- and β2-dimer forms of IL-12, while it did not affect secretion of the β-monomer. This inhibition coincided with a reduction in the intracellular amount of PDI found in complex with the β-chain during intracellular transit. Bacitracin did not affect mRNA levels of the α- and β-chain. Similar to bacitracin, N-acetylcysteine blocked αβ- and β2-secretion as well as PDI-β-chain complex formation. Thus, blocking PDI or shifting the endoplasmic reticulum towards a more reduced status disrupts the oxidative folding pathway or assembly of IL-12 dimer forms. The assembly stage of cytokines in the endoplasmic reticulum may represent a novel target for pharmacological intervention.
A pharmacokinetic/pharmacodynamic model for a platelet activating factor antagonist based on data arising from Phase I studies
Authors: Evans Lynne , Aarons Leon , Brearley Chris 
Published: January 2005

Abstract
A nonlinear mixed-effects modelling approach was used to analyse pharmacokinetic and pharma-codynamic data from two Phase I studies of a platelet activating factor (PAF) antagonist under development for the treatment of seasonal allergic rhinitis. Data for single-dose (8 subjects) and multiple-dose (9 subjects) administration were available for analysis with a program based on an EM algorithm. Pharmacokinetic analyses of plasma drug concentrations were performed using a biexponential model with first-order absorption. PAF response data were modelled with a hyperbolic Emax model. The drug showed nonlinear pharmacokinetics, with the clearance decreasing from 46.0 to 27.1 L h−1 over a dose range of 160–480 mg. There was an apparent dose dependency within the C50 (concentration producing 50% of the maximum effect) but at higher doses most of the data was above the estimated C50 and when the data was analysed simultaneously a value of 17.57 ng mL−1 was obtained for C50, with considerable intersubject variability (103%). Consistent results were obtained from the two studies and the population and individual pharmacodynamic parameter estimates from the analyses provided predicted responses that were in good agreement with the observed data. The results were used to simulate a 320-mg twice-daily dosing regimen.
Gastroprotective activity of a new semi-synthetic solidagenone derivative in mice
Authors: Rodríguez Jaime A , Theoduloz Cristina , Sánchez Marianela , Yáñez Tania , Razmilic Iván , Schmeda-Hirschmann Guillermo 
Published: January 2005

Abstract
The gastroprotective activity of the new semi-synthetic solidagenone derivative 15,16-epoxy-8(9),13(16),14-labdatrien-7β-methoxy-6β-ol (ELMO) has been assessed on the model of HCl/EtOH-induced gastric lesions in mice. Human gastric epithelial cells (AGS) and fibroblasts (MRC-5) were used to determine its mode of action. The effect of ELMO on the prostaglandin E2 content, cellular reduced glutathione (GSH) and protection against damage induced by sodium taurocholate was assessed against AGS cells. The effect of ELMO on the growth of AGS and fibroblast cultures was evaluated. The superoxide anion scavenging capacity of the compound was studied also. The cytotoxicity of ELMO, expressed as cell viability, was assessed using two independent endpoints: neutral red uptake (NRU) and the reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) for MRC-5 fibroblasts and NRU for AGS cells. A single oral dose of ELMO (10 and 20 mg kg−1) inhibited the appearance of gastric lesions in mice displaying similar values to lansoprazole at 20 mg kg−1. At 40 μm ELMO increased the prostaglandin E2 content but not GSH in AGS cells. The compound showed no effect on sodium taurocholate-induced damage and was devoid of superoxide anion scavenging activity. Concentrations of 0.5, 1, 2 and 4 μm stimulated fibroblast but not AGS cell proliferation. The compound showed weak cytotoxicity with values (IC50) of 411 (NRU) and 418 μm (MTT) for fibroblasts and 261 μm (NRU) for AGS cells. The results support further pharmacological study of this compound as a potential new anti-ulcerogenic drug.
Alteration of the pharmacokinetics of theophylline by rutaecarpine, an alkaloid of the medicinal herb Evodia rutaecarpa, in rats
Authors: Ueng Yune-Fang , Tsai Tung-Hu , Don Ming-Jaw , Chen Ruei-Ming , Chen Ta-Liang 
Published: January 2005

Abstract
Rutaecarpine is a main active alkaloid present in the medicinal herb, Evodia rutaecarpa. The cyto-chrome P450 (CYP) 1A2 substrate, theophylline, is an important therapeutic agent for the treatment of asthma, but has a narrow therapeutic index. To evaluate the pharmacokinetic interaction of theophyl-line with rutaecarpine, the effects of rutaecarpine on CYP1A2 activity and theophylline pharmaco-kinetics were investigated. Oral treatment of Sprague-Dawley rats with 50 mg kg−1 rutaecarpine for three days through a gastrogavage caused a 4- and 3-fold increase in liver microsomal 7-ethoxyresorufin O-deethylation (EROD) and 7-methoxyresorufin O-demethylation activity, respectively. In the kidney, rutaecarpine treatment caused a 3-fold increase in EROD activity. In the lungs, EROD activity was elevated from an undetectable to a detectable level by rutaecarpine. Pharmacokinetic parameters of theophylline were determined using a microdialysis sampling method. Rutaecarpine pre-treatment increased the clearance of theophylline in a dose-dependent manner. Pre-treatment of rats with 50 mg kg−1 rutaecarpine caused a 3-fold increase in theophylline clearance and a 70%, 68% and 68% decrease in the area under the concentration-time curve (AUC), mean residence time (MRT) and half-life, respectively. These results demonstrated that rutaecarpine treatment elevated CYP1A2 catalytic activity and theophylline excretion in rats. In patients taking theophylline, adverse effects might be noticed when a rutaecarpine-containing herbal preparation is used concomitantly.
Rats are able to navigate in virtual environments
Authors: Hölscher C. , Schnee A. , Dahmen H. , Setia L. , Mallot H. A. 
Published: January 2005

SUMMARYVirtual reality (VR) systems are useful tools that enable users to alter environmental settings and the location of landmarks in an accurate and fast way. Primates have been shown to be able to navigate in virtual environments. For rodents, however, all previous attempts to develop VR systems in which rats behave in the same way as in corresponding 3-D environments have failed. The question arises as to whether, in principle, rodents can be trained to navigate in a properly designed virtual environment (VE), or whether this peculiarity is limited to primates and humans. We built a virtual reality set-up that takes the wide-angle visual system of rats into account. We show for the first time that rats learn spatial tasks in this VE quite readily. This set-up opens up new opportunities for investigations of information processing in navigation (e.g. the importance of optic flow or vestibular input).
A distinct carbonic anhydrase in the mucus of the colon of humans and other mammals
Authors: Kleinke Tanja , Wagner Siegfried , John Harald , Hewett-Emmett David , Parkkila Seppo , Forssmann Wolf-Georg , Gros Gerolf 
Published: January 2005

SUMMARYWe have collected gastrointestinal, mainly colonic, mucus from humans,guinea pigs, rats, and normal and carbonic anhydrase II (CAII)-deficient mice. In the mucus of all species, substantial CA activity was present. Using antibodies against human CA isoforms we found that the human mucus CA differs from cytosolic CAI and CAII, membrane-bound CAIV, and the secreted CAVI of saliva. The high sensitivity of mucus CA to acetazolamide rules out its identity with cytosolic CAIII. Partial sequences obtained from the purified human mucus CA show similarity, but not identity, with human CAI, and clear differences from the other known CAs. Additional evidence concerning the CA isoform present in mucus was obtained for the mucus CA of other species and was derived from: (1) the mucus of CAII-deficient mice, whose high CA activity confirms that it is not CAII that is responsible; (2) the inhibitory effect of iodide, which shows that mucus CA from mice, guinea pig and humans does not have the high anion sensitivity of CAI; (3) the inactivating effect of 0.2%SDS on guinea pig, mouse and human mucus CA, ruling out the SDS-resistant CAIV; and (4) the partitioning of guinea-pig mucus CA into the water phase in Triton X114 phase separation experiments, which also argues against its identity with membrane-bound CAs, such as CAIV. A comparison of colonic mucus CA activity in normal and germ-free rats indicates that the mucus CA is not of bacterial origin but is produced by the gastrointestinal tissues. We conclude(from its immunoreactivity, from iodide inhibition and from partial amino acid sequences) that mucus CA of human origin probably represents an isozyme, which is specific for mucus and is not identical with the known CA isozymes. The results obtained for mucus CA of other species collectively point in the same direction.
Dynamic flight stability of a hovering bumblebee
Authors: Sun Mao , Xiong Yan 
Published: January 2005

SUMMARYThe longitudinal dynamic flight stability of a hovering bumblebee was studied using the method of computational fluid dynamics to compute the aerodynamic derivatives and the techniques of eigenvalue and eigenvector analysis for solving the equations of motion.For the longitudinal disturbed motion, three natural modes were identified:one unstable oscillatory mode, one stable fast subsidence mode and one stable slow subsidence mode. The unstable oscillatory mode consists of pitching and horizontal moving oscillations with negligible vertical motion. The period of the oscillations is 0.32 s (approx. 50 times the wingbeat period of the bumblebee). The oscillations double in amplitude in 0.1 s; coupling of nose-up pitching with forward horizontal motion (and nose-down pitching with backward horizontal motion) in this mode causes the instability. The stable fast subsidence mode consists of monotonic pitching and horizontal motions, which decay to half of the starting values in 0.024 s. The stable slow subsidence mode is mainly a monotonic descending (or ascending) motion, which decays to half of its starting value in 0.37 s.Due to the unstable oscillatory mode, the hovering flight of the bumblebee is dynamically unstable. However, the instability might not be a great problem to a bumblebee that tries to stay hovering: the time for the initial disturbances to double (0.1 s) is more than 15 times the wingbeat period (6.4 ms), and the bumblebee has plenty of time to adjust its wing motion before the disturbances grow large.
Cell volume control inParamecium: factors that activate the control mechanisms
Authors: Iwamoto Masaaki , Sugino Kazuyuki , Allen Richard D. , Naitoh Yutaka 
Published: January 2005

SUMMARYA fresh water protozoan Paramecium multimicronucleatum adapted to a given solution was found to swell until the osmotic pressure difference between the cytosol and the solution balanced the cytosolic pressure. The cytosolic pressure was generated as the cell swelled osmotically. When either one or both of these pressures was somehow modified, cell volume would change until a new balance between these pressures was established. A hypothetical osmolyte transport mechanism(s) was presumably activated when the cytosolic pressure exceeded the threshold value of ∼1.5 × 105 Pa as the cell swelled after its subjection to a decreased osmolarity. The cytosolic osmolarity thereby decreased and the volume of the swollen cell resumed its initial value. This corresponds to regulatory volume decrease (RVD). By contrast, another hypothetical osmolyte transport mechanism(s) was activated when the cell shrank after its subjection to an increased osmolarity. The cytosolic osmolarity thereby increased and volume of the shrunken cell resumed its initial value. This corresponds to regulatory volume increase (RVI). The osmolyte transport mechanism responsible for RVD might be activated again when the external osmolarity decreases further, and the cytosolic osmolarity thereby decreases to the next lower level. Similarly, another osmolyte transport mechanism responsible for RVI might be activated again when the external osmolarity increases further, and the cytosolic osmolarity thereby increases to the next higher level. Stepwise changes in the cytosolic osmolarity caused by a gradual change in the adaptation osmolarity found in P. multimicronucleatum is attributable to these osmolyte transport mechanisms. An abrupt change in the amount of fluid discharged from the contractile vacuole seen immediately after changing the external osmolarity reduces an abrupt change in cell volume and thereby protects the cell from the disruption of the plasma membrane by excessive stretch or dehydration during shrinkage.
Pigmentation in the sensory organs of the ascidian larva is essential for normal behavior
Authors: Jiang Di , Tresser Jason W. , Horie Takeo , Tsuda Motoyuki , Smith William C. 
Published: January 2005

SUMMARYFree-living animals and their larvae utilize light and gravity as cues to navigate in open space. Detection and response to these environmental stimuli are important for the dispersal and settlement of ascidian larvae. Two pigmented structures in the brain of the ascidian larva, the ocellus and the otolith, have been shown to function as the photoreceptive and gravity sensitive organs, respectively. Here, we show that pigmentation is essential for proper phototactic and geotactic behavior in larvae of the ascidian species Ciona savignyi. Two recessive and complementing mutant lines of C. savignyi, immaculate and spotless, that specifically disrupt the pigmentation of the sensory organs during larval development are described. Homozygous mutant larvae are unable to respond properly to gravity and illumination cues while settling. Genetic analysis shows that spotless is caused by a point mutation within the tyrosinase gene that creates a premature stop codon, while the molecular nature of immaculate is unknown. Although the role of pigmentation in the ocellus of C. savignyi is similar to that in vertebrate visual systems, our results demonstrate a novel use of melanin in geotactic behavior.
Circadian rhythms of behavioral cone sensitivity and long wavelength opsin mRNA expression: a correlation study in zebrafish
Authors: Li Ping , Temple Shelby , Gao Yan , Haimberger Theordore J. , Hawryshyn Craig W. , Li Lei 
Published: January 2005

SUMMARY
Using a behavioral assay based on visually mediated escape responses, we measured long-wavelength-sensitive red cone (LC) sensitivities in zebrafish. In a 24 h period, the zebrafish were least sensitive to red light in the early morning and most sensitive in the late afternoon. To investigate if the fluctuation of behavioral cone sensitivity correlates with opsin gene expression, we measured LC opsin mRNA expression at different times in the day and night under different lighting conditions. Under a normal light–dark cycle, the expression of LC opsin mRNA determined by real-time RT–PCR was low in the early morning and high in the late afternoon, similar to the fluctuation of behavioral cone sensitivity. This rhythm of LC opsin mRNA expression, however, dampened out gradually in constant conditions. After 24 h of constant light (LL), the expression of LC opsin mRNA dropped to levels similar to those determined in the early morning in control animals. By contrast, when the zebrafish were kept in constant dark (DD), the expression of LC opsin mRNA increased, to levels about 30-fold higher than the expression in the early morning in control animals. This day–night fluctuation in LC opsin mRNA expression was correlated to changes in opsin density in the outer segment of cone photoreceptor cells. Microspectrophotometry (MSP)measurements found significant differences in red cone outer segment optical density with a rhythm following the behavioral sensitivity. Furthermore,dopamine modulated the circadian rhythms in expression of LC opsin mRNA. Administration of dopamine increased LC opsin mRNA expression, but only in the early morning.
Desalting, Concentration, and Buffer Exchange by Dialysis and Ultrafiltration
Authors: Phillips Allen T. , Signs Mark W. 
Published: January 2005

AbstractThis unit includes a variety of dialysis and ultrafiltration techniques that can be used for desalting, concentration, or buffer exchange. Standard dialysis by diffusion across cellulose tubing is described as a technique for desalting or buffer exchange. Ultrafiltration under pressure can be used either for concentrating protein or, where the sample volume is replenished with a desired buffer, for desalting/buffer exchange (i.e., diafiltration). A variation is ultrafiltration by tangential flow, which serves the same purposes as ultrafiltration under pressure but is better suited to handling large volumes of solution. Yet another variation is an ultrafiltration technique employing centrifugal microconcentrators, which allows concentration of very small volumes of solution.
Preparation and Extraction of Insoluble (Inclusion‐Body) Proteins from Escherichia coli
Authors: Palmer Ira , Wingfield Paul T. 
Published: January 2005

AbstractHigh‐level expression of many recombinant proteins in Escherichia coli leads to the formation of highly aggregated protein commonly referred to as inclusion bodies. Inclusion bodies are normally formed in the cytoplasm; alternatively, if a secretion vector is used, they can form in the periplasmic space. Inclusion bodies can be recovered from cell lysates and this unit describes preparation of washed pellets and solubilization of the protein using guanidine⋅HCl. The extracted protein, which is unfolded, is either directly folded as described in UNIT here or further purified by gel filtration in the presence of guanidine⋅HCl as idescribed here. A support protocol describes the removal of guanidine⋅HCl from column fractions so they can be monitored by SDS‐PAGE.
Determining the Fluorescence Spectrum of a Protein
Authors: Pain Roger H. 
Published: January 2005

AbstractFluorescence spectra of proteins are determined chiefly by the polarity of the environment of the tryptophan and tyrosine residues and by their specific interactions. A thorough consideration of fluorescence spectrometers and their calibration is provided along with important information regarding spectrometer cells, buffers and clarification of samples. Protocols are provided for recording fluorescence spectra and for measuring fluorescence quenching to probe the accessibility of tryptophan residues to small molecules (to yield information about the structural environment of the tryptophan). The technique involves quantifying the decrease in protein fluorescence intensity in the presence of increasing concentrations of quencher, followed by analysis of the data to give details of the interaction of the quencher with the tryptophan residue. Finally, agives details on how to interpret fluorescence spectra.
Overview of Approaches to the Identification of Inhibitors of Cytokine Action
Authors: Woska, Joseph R. , Magram Jeanne 
Published: January 2005

AbstractCytokines are key regulatory molecules that serve as critical mediators of cell‐to‐cell communication. They play a central role in immune function and are important molecular targets for drug discovery because of their dysregulation in immune disease. Initial attempts to develop agents that block the actions of cytokines focused on identifying small‐molecule antagonists that would directly compete with these cytokines for their cognate receptors. These efforts were, for the most part, unsuccessful. Outlined in this unit are strategies for developing new approaches. The first section describes strategies for how one might build a conceptual framework to approach this problem. The second section focuses on the technical approaches that can be utilized to accomplish the strategies outlined in the first section. These concepts are illustrated using interleukin‐2 (IL‐2) as a prototype, since there is a substantial body of knowledge regarding this cytokine, including information on its functions, signaling pathways, and physiological effects in normal and diseased tissue.