bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrical and Mechanical Modulations by Oxygen-derived Free-radical Generating Systems in Guinea-pig Heart Muscles
Authors: Satoh Hiroyasu , Matsui Kazunori 
Published: April 2011

Abstract
The effects of free-radical generating systems and angiotensin-converting enzyme (ACE) inhibitors on the action potentials and contractile force in guinea-pig cardiac muscles were examined using conventional microelectrode and whole-cell voltage-clamp methods at 36°C.
Hydrogen peroxide (30–100 μm) prolonged 50%, 75% and 90% repolarization of action-potential duration (APD) approximately 15–25 min after its application. But the longer exposure reversed the APD shortening in a concentration-dependent manner. Other action-potential parameters were not altered to a significant extent. The contractile force was increased. Longer exposure inhibited the enhanced force (but it was still larger than control). The effects on the spontaneous action potential from right atrial muscle were almost the same. In whole-cell voltage-clamp experiments, H2O2 (100 μm) inhibited l-type Ca2+ current and enhanced delayed rectifier K+ current. The effects of light-activated rose bengal (10–100 nm) on the APD were similar to, but more potent than, those of H2O2. The response was observed rapidly after a light illumination. During exposure to rose bengal (100 nm), abnormal spontaneous action potentials or arrhythmias such as a bigeminy occurred, presumably because of early and delayed afterdepolarizations. The responses were irreversible. At 300 μm ACE inhibitors, captopril and enalapril, protected the changes induced by these free radicals.
These results indicate that H2O2 has a dual, time-dependent, action on the APD and rose bengal with light illumination produced the responses rapidly. The oxygen-derived free radicals increased [Ca]i and then cellular Ca2+ overload occurred. These responses were protected by ACE inhibitors.
Effects of ATP on Phosphoinositide Hydrolysis and Prostaglandin E2 Generation in Rabbit Astrocytes
Authors: Ishimoto Hiromi , Nakahata Norimichi , Matsuoka Isao , Nakanishi Hironori 
Published: April 2011

Abstract
Extracellular ATP secreted from stimulated nerves plays a role in neurotransmission. This study examined the effects of extracellular ATP on phospholipase A2 and C signalling pathways in rabbit astrocytes.
ATP caused prostaglandin E2 (PGE2) generation and phosphoinositide hydrolysis in a time- and concentration-dependent manner. A P2y purinoceptor-selective agonist, 2-methylthio-ATP also caused phosphoinositide hydrolysis, but not PGE2 generation. A P2x purinoceptor-selective agonist, α,β-methylene-ATP did not cause either phosphoinositide hydrolysis or PGE2 generation. Although pertussis toxin had no effect on 2-methylthio-ATP-induced phosphoinositide hydrolysis, it markedly decreased ATP-induced PGE2 generation, with significant inhibition of phosphoinositide hydrolysis. Dexamethasone and indomethacin which potently inhibited ATP-induced PGE2 generation, caused partial inhibition of phosphoinositide hydrolysis, suggesting that pertussis toxin-sensitive component of ATP-induced phospholipase C activation is mediated by cyclo-oxygenase metabolites of arachidonic acid.
These results suggest that a stimulation of P2y receptor results in phospholipase C activation in a pertussis toxin-insensitive manner, and that a P2 receptor other than the P2y or P2x subtypes is involved in ATP-induced phospholipase A2 activation via a pertussis toxin-sensitive G protein.
Some Histamine-related Compounds Interacting with the Benzylamine-oxidizing Activity of Rat White Adipocytes
Authors: Raimondi Laura , Conforti Laura , Banchelli Grazia , Sgromo Lucia , Pirisino Renato 
Published: April 2011

Abstract
In rat white adipocytes histamine is oxidized by a semicarbazide-sensitive amine oxidase which has benzylamine or preferential substrate (Bz-SSAO). To determine whether Bz-SSAO could control the extracellular levels of histamine and other histamine-related compounds active in lipid mobilization, a series of histaminergic compounds was screened as possible substrates or inhibitors of Bz-SSAO activity.
Histaminergic compounds with imidazolo or thiazolo groups are oxidized by rat white-adipocyte Bz-SSAO whereas S-isothiourea derivatives, with two- or three-carbon-atom alkyl chains between the isothiourea and the N,N-dimethyl residue are, instead, inhibitors of the enzyme. Amtamine has been identified as a selective, high affinity substrate for rat white adipocyte Bz-SSAO. This enzymatic degradation might represent a catabolic pathway for the drug.
These results show that the histaminase property of the rat white-adipocyte enzyme Bz-SSAO also extends to other histamine derivatives active at histamine receptors.
Mechanisms Involved in the Antinociceptive Effect in Mice of the Hydroalcoholic Extract of Siphocampylus verticillatus
Authors: Trentin Ana P , Santos Adair R S , Miguel Obdúlio G , Pizzolatti Moacir G , Yunes Rosendo A , Calixto João B 
Published: April 2011

Abstract
The antinociception caused by the hydroalcoholic extract of Siphocampylus verticillatus (Campanulaceae) has been investigated in chemical and thermal models of nociception in mice. We have also assessed some of the mechanisms underlying the antinociceptive effect of the extract.
The hydroalcoholic extract of S. verticillatus (60–1000 mg kg−1, i.p. or p.o.) produced dose-related, significant and long-lasting (6 to 8 h) inhibition of acetic acid-induced abdominal constriction in mice, with ID50 values of 204 and ∼1000 mg kg−1, respectively. In the formalin test, the extract (100–1000 mg kg−1), given either intraperitoneally or orally, resulted in graded inhibition of both phases of formalin-induced pain, being about 2- to 4-fold more potent in attenuating the second phase of the pain. The calculated mean ID50 (mg kg−1) values for the earlier and the later phases were: 491 and 186 and 640 and 441, respectively. In addition, the extract (60–1000 mg kg−1, i.p. or p.o.) caused marked and dose-related inhibition of capsaicin-induced neurogenic pain with mean ID50 values of 420 and 485 mg kg−1, respectively. The hydroalcoholic extract, at the same doses, did not significantly affect the performance of animals in the rota-rod test, nor did it have any analgesic effect in the tail-flick or hot-plate tests. The treatment of animals with naloxone (5 mg kg−1, s.c.) significantly reversed the analgesic effect of both morphine (5 mg kg−1, s.c.) and the extract (300 mg kg−1, i.p.) when assessed against acetic acid-induced abdominal constrictions. The treatment of animals with l-arginine (600 mg kg−1, i.p.) significantly attenuated the antinociceptive effects of NG-nitro-l-arginine (l-NOARG) (75 mg kg−1, i.p.), of the hydroalcoholic extract (600 mg kg−1, i.p.) or of morphine (5 mgkg−1, s.c.), when analysed against the formalin test. In addition, adrenalectomy of animals 7 days before the tests significantly reversed the antinociception caused by the hydroalcoholic extract (300 mg kg−1, i.p.) in the formalin-induced pain.
These data show that the hydroalcoholic extract of S. verticillatus has significant and long-lasting oral antinociception when assessed against both neurogenic and inflammatory models of nociception in mice. The precise mechanism responsible for the analgesic effect of the extract still remains unclear, but a great part of this effect seems to be partly related to an opioid-like action and involvement of the l-arginine-nitric oxide pathway. Finally, the antinociception caused by the hydroalcoholic extract of S. verticillatus is modulated by adrenal hormones.
Analysis of Rabbit Vascular Responses to DBI, an Ingol Derivative Isolated from Euphorbia canariensis
Authors: Miranda Francisco J , Alabadí José A , Pérez Pedro , Ortí Marta , Centeno Jose M , Yuste Alberto , Sanz-Cervera Juan F , Marco J Alberto , Alborch Enrique 
Published: April 2011

Abstract
We have analysed the effects of 7,12-O-diacetyl-8-O-benzoil-2,3-diepiingol (DBI), an ingol derivative isolated from E. canariensis, on isometric tension developed by isolated rabbit basilar and carotid arteries.
Concentration-response curves to DBI (10−8 - 3 × 10−5 m) were obtained cumulatively in both arteries at resting tension and active tone (KC1, 50 mm). At resting tension, DBI induced a concentration-dependent contraction, which was not inhibited in Ca2+-free medium. H7 (1-(5-isoquinoline sulphonyl)-2-methylpiperazine dichloride) (10−4 m) inhibited the DBI-induced contraction both in basilar and in carotid arteries. Calmidazolium (10−4 m) inhibited the maximum contraction of the carotid artery to DBI, and completely abolished the response in the basilar artery. In pre-contracted basilar arteries DBI induced a concentration-dependent relaxation that was not modified by incubation with NG-nitro-l-arginine (l-NOARG; 10−5 m) or indomethacin (10−5 m). In the carotid artery with active tone DBI induced further contractions, which were not significantly modified by l-NOARG (10−5 m) and were potentiated by indomethacin (10−5 m).
These results suggest that DBI contracts rabbit basilar and carotid arteries by a mechanism that is independent of extracellular Ca2+ and involves the participation both of protein kinase C and of calmodulin. DBI relaxes basilar but not carotid arteries by a mechanism independent of the liberation of nitric oxide and prostacyclin. In the carotid artery prostacyclin but not nitric oxide partially counteracts the contractile action of DBI.
Peter Howard El worthy (1933–1995): a Biographical Note
Authors: Florence A T 
Published: April 2011

Abstract
Peter Elworthy had a considerable influence on pharmaceutical science, education and practice, in the UK. He died in December 1995 at the early age of 62, but he had retired from full time academic work from his post as Professor of Pharmacy and Head of the Department of Pharmacy in the University of Manchester twelve years earlier. Concerned about his health but also not a little disillusioned by the multiple pressures placed even then on senior academics, he foresaw the era of cuts and the central oversight and restrictions. His heart was elsewhere. In his 1976 Harrison Memorial Lecture (reproduced in this issue) he said: “Looking back, I have the feeling of having been very lucky. ‘Much have I travell'd in the realms of gold, and many goodly states and kingdoms seen.’ My main interest has been in the phenomenon of micellization. The subject has been of absorbing interest, and continually shows new bright facets which lead to new scientific advances. Travelling in the realms of gold has nothing to do with gold, but to me it means travelling in sunlight, which illuminates things brightly, and makes visible new facts, which have been invisible before. Occasionally dark clouds form; they are the disappointments and frustrations, but we need them in order to be able to recognize the sunlight by contrast.”
Variation in Cetostearyl Alcohol and Lecithin from Different Sources: Evaluation by Dielectric Analysis
Authors: Rowe R C 
Published: April 2011

Abstract
Dielectric analysis has been used to evaluate the variation with source of both cetostearyl alcohol (when used in aqueous gels prepared with cetostearyl alcohol and cetrimide) and lecithin (when used in oil-in-water emulsions).
In both examples differences in the dielectric response were detected for samples prepared using excipients from different sources, despite the failure of other tests to detect any difference.
The differences seen could be related to changes in the structures of the samples.
Aggregation and Surface Properties of Synthetic Double-chain Non-ionic Surfactants in Aqueous Solution
Authors: Lawrence M Jayne , Lawrence Simon M , Barlow David J 
Published: April 2011

Abstract
Double-chain non-ionic surfactants have been synthesized with the general formula 2CnMPEG750, where n is the number of carbons in the alkyl chains and 750 is the molecular weight of the monomethoxypolyoxyethylene (MPEG) head group. The aggregation and surface properties in dilute aqueous solution (&lt;1.0% w/w) of surfactants with n = 8, 10 and 12 have been determined.
Each of the surfactants formed clear, foaming, non-birefringent solutions. Total-intensity light scattering indicated the presence of micelles with aggregation numbers of 36, 68 and 74 for the 2C8, 2C10 and 2C12 surfactants, respectively, whereas photon-correlation studies yielded radii, assuming spherical aggregates, of 59–103 Å. Surface-tension measurements gave critical micelle concentrations for the surfactants in the range 1–15–7–24 × 10−6 m; these, as expected, decreased when the number of carbon atoms in the alkyl chains was increased.
Such studies are important in the design of new surfactants as vehicles for drug delivery because it is imperative to be able to predict the type of aggregate formed by a surfactant.
The Influence of Gamma Irradiation on the Physicochemical Properties of a Novel Triblock Copolymer of β-Caprolactone and Ethylene Oxide
Authors: Martini Luigi , Collett John H , Attwood David 
Published: April 2011

Abstract
A novel triblock copolymer of ε-caprolactone (CL) and ethylene oxide (E), CL6E90CL6, intended for use in implantable drug-delivery systems, has been subjected to gamma irradiation, in the solid state and in aqueous solution, under different controlled environmental conditions, to assess its stability to a radiation sterilization process.
When copolymer matrices were irradiated with doses of irradiation up to 72 kGy in the presence of oxygen, negligible changes were observed in the molar mass, molecular mobility (assessed by pulsed nuclear magnetic resonance spectroscopy) and thermal properties. However, irradiation of matrices in the absence of oxygen (anoxia) induced the formation of cross-links, as indicated by a reduction in the molecular mobility of the copolymer, but without affecting its molar mass and thermal properties. Gamma irradiation of aqueous solutions of CL6E90CL6 in the presence of oxygen induced random polymer chain scission, as evidenced by a reduction in the molar mass, and the formation of a distribution of copolymer chain lengths in solution. Nuclear magnetic resonance relaxation studies showed that irradiation of solutions of CL6E90CL6 at concentrations greater than 4% w/v under anoxic conditions with doses of 54 kGy produced polymer gels with a network structure.
These differences in the effects of gamma irradiation on the physicochemical properties of CL6E90CL6 might be germane to the method selected for sterilization of the polymer before its use in implantable drug-delivery systems.
Influence of Hydroxypropyl β-Cyclodextrin on the Stability of Benzylpenicillin in Chloroacetate Buffer
Authors: Ong J K , Sunderland V B , McDonald C 
Published: April 2011

Abstract
Hydroxypropyl β-cyclodextrin (HPβCyD) has been shown to stabilize a wide variety of chemically distinct pharmaceutical entities through inclusion-complex formation between drug and cyclodextrin. The effect of HPβCyD on the acid-catalysed hydrolysis of benzylpenicillin (penicillin G) was evaluated in chloroacetate buffer at pH 2.20.
At penicillin G: cyclodextrin molar concentration ratios from 1:1 to 1:10, HPβCyD effected stabilization of penicillin G by 1.56- to 5.21-fold. At all temperatures, the observed first-order rate constant (kobs) values assumed a non-linear, Michaelis-Menten type decrease as a function of increasing HPβCyD concentration. Degradation of penicillin G complexed with HPβCyD (penicillin G-HPβCyD), was approximately ninefold slower than uncomplexed penicillin G. The proportion of penicillin G degrading in either of these forms was, in turn, determined by the equilibrium constant for the complexation. The apparent thermodynamic and activation parameters for the complexation between penicillin G and HPβCyD have also been evaluated. The negative standard enthalpy change (ΔH°) for the complexation implied that the penicillin G-HPβCyD complex would be predisposed towards enhanced stability, and thus the kobs value for the hydrolysis of penicillin G decreased with reduction of temperature in these systems. The lack of difference between the enthalpies of activation (ΔH‡) for the hydrolysis of uncomplexed and complexed penicillin G seemed to be compensated by the significant difference between the entropies of activation (ΔS‡) for these hydrolytic reactions.
The results indicate that HPβCyD represents a viable means of stabilization of penicillin G solutions at the pH employed in this study.
Isolation of a polysaccharide with antiproliferative, hypoglycemic, antioxidant and HIV-1 reverse transcriptase inhibitory activities from the fruiting bodies of the abalone mushroom Pleurotus abalonus
Authors: Wang Chang Rong , Ng Tzi Bun , Li Le , Fang Jin Cen , Jiang Yun , Wen Ting Yi , Qiao Wen Tao , Li Ning , Liu Fang 
Published: April 2011

Abstract

Objective
The intent of this study was to purify and characterize a polysaccharide named LA from the fruiting bodies of the edible mushroom Pleurotus abalones.

Methods
The 120-kDa polysaccharide was obtained by extraction with boiling water, ethanol precipitation, ion exchange chromatography on Diethylaminoethyl-cellulose and gel filtration on Sephadex G-200.

Key findings
The LA was composed of glucose, rhamnose, glucuronic acid, xylose, galactose and arabinose in the molar ratio of 26.3 : 2.7 : 1 : 1.4 : 1.8 : 1.2. The FITR and 1H-NMR spectrum of LA disclosed that it was a saccharide with an α-configuration. Its 13C-NMR spectrum revealed that its main chain was [→6)-α-d-Gly(1→]n. The LA exhibited antioxidant activities, especially in scavenging 1,1- diphenyl-2-picryl-hydrazyl radicals and hydroxyl radicals. It manifested antiproliferative activity towards breast cancer MCF7 cells with an IC50 of 3.7 µm, and also exerted some antiproliferative activity against HepG2 cells. It manifested a hypoglycemic action on diabetic mice. It inhibited HIV-1 reverse transcriptase with an IC50 of 8.7 × 10−2 µm.

Conclusions
The polysaccharide from the abalone mushroom.
Immunization with Bacillus Spores Expressing Toxin A Peptide Repeats Protects against Infection with Clostridium difficile Strains Producing Toxins A and B
Authors: Permpoonpattana Patima , Hong Huynh A. , Phetcharaburanin Jutarop , Huang Jen-Min , Cook Jenny , Fairweather Neil F. , Cutting Simon M. 
Published: April 2011

ABSTRACT

Clostridium difficile
is a leading cause of nosocomial infection in the developed world. Two toxins, A and B, produced by most strains of
C. difficile
are implicated as virulence factors, yet only recently has the requirement of these for infection been investigated by genetic manipulation. Current vaccine strategies are focused mostly on parenteral delivery of toxoids. In this work, we have used bacterial spores (
Bacillus subtilis
) as a delivery vehicle to evaluate the carboxy-terminal repeat domains of toxins A and B as protective antigens. Our findings are important and show that oral immunization of the repeat domain of toxin A is sufficient to confer protection in a hamster model of infection designed to closely mimic the human course of infection. Importantly, neutralizing antibodies to the toxin A repeat domain were shown to be cross-reactive with the analogous domain of toxin B and, being of high avidity, provided protection against challenge with a
C. difficile
strain producing toxins A and B (A
+
B
+
). Thus, although many strains produce both toxins, antibodies to only toxin A can mediate protection. Animals vaccinated with recombinant spores were fully able to survive reinfection, a property that is particularly important for a disease with which patients are prone to relapse. We show that mucosal immunization, not parenteral delivery, is required to generate secretory IgA and that production of these neutralizing polymeric antibodies correlates with protection. This work demonstrates that an effective vaccine against
C. difficile
can be designed around two attributes, mucosal delivery and the repeat domain of toxin A.
Increased Disease Severity of Parasite-Infected TLR2−/−Mice Is Correlated with Decreased Central Nervous System Inflammation and Reduced Numbers of Cells with Alternatively Activated Macrophage Phenotypes in a Murine Model of Neurocysticercosis
Authors: Gundra Uma Mahesh , Mishra Bibhuti B. , Wong Kondi , Teale Judy M. 
Published: April 2011

ABSTRACTIn a murine model for neurocysticercosis (NCC), intracranial inoculation of the helminth parasiteMesocestoides cortiinduces multiple Toll-like receptors (TLRs), among which TLR2 is upregulated first and to a relatively high extent. Here, we report that TLR2−/−mice displayed significantly increased susceptibility to parasite infection accompanied by increased numbers of parasites in the brain parenchyma compared to infection in wild-type (WT) mice. This coincided with an increased display of microglial nodule formations and greater neuropathology than in the WT. Parasite-infected TLR2−/−brains exhibited a scarcity of lymphocytic cuffing and displayed reduced numbers of infiltrating leukocytes. Fluorescence-activated cell sorter (FACS) analyses revealed significantly lower numbers of CD11b+myeloid cells, γδ T cells, αβ T cells, and B cells in the brains of parasite-infected TLR2−/−mice. This correlated with significantly reduced levels of inflammatory mediators, including tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), CCL2, CCL3, and interleukin-6 (IL-6) in the central nervous system (CNS) of TLR2−/−mice. As TLR2 has been implicated in immune regulation of helminth infections and as alternatively activated macrophages (AAMs) are thought to play a profound regulatory role in such infections, induction of AAMs in infected TLR2−/−mice was compared with that in WT mice. Parasite-infected WT brains showed larger numbers of macrophages/microglia (CD11b+cells) expressing AAM-associated molecules such as YM1, Fizz1 (found in inflammatory zone-1 antigen), and arginase 1 than TLR2−/−brains, consistent with a protective role of AAMs during infection. Importantly, these results demonstrate that TLR2-associated responses modulate the disease severity of murine NCC.
Helicobacter pylori VacA Induces Programmed Necrosis in Gastric Epithelial Cells
Authors: Radin Jana N. , González-Rivera Christian , Ivie Susan E. , McClain Mark S. , Cover Timothy L. 
Published: April 2011

ABSTRACT

Helicobacter pylori
is a Gram-negative bacterium that colonizes the human stomach and contributes to the development of peptic ulcer disease and gastric cancer. The secreted pore-forming toxin VacA is one of the major virulence factors of
H. pylori
. In the current study, we show that AZ-521 human gastric epithelial cells are highly susceptible to VacA-induced cell death. Wild-type VacA causes death of these cells, whereas mutant VacA proteins defective in membrane channel formation do not. Incubation of AZ-521 cells with wild-type VacA results in cell swelling, poly(ADP-ribose) polymerase (PARP) activation, decreased intracellular ATP concentration, and lactate dehydrogenase (LDH) release. VacA-induced death of these cells is a caspase-independent process that results in cellular release of histone-binding protein high mobility group box 1 (HMGB1), a proinflammatory protein. These features are consistent with the occurrence of cell death through a programmed necrosis pathway and suggest that VacA can be included among the growing number of bacterial pore-forming toxins that induce cell death through programmed necrosis. We propose that VacA augments
H. pylori
-induced mucosal inflammation in the human stomach by causing programmed necrosis of gastric epithelial cells and subsequent release of proinflammatory proteins and may thereby contribute to the pathogenesis of gastric cancer and peptic ulceration.