bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signaling through CD16b in human neutrophils involves the Tec family of tyrosine kinases
Authors: Fernandes Maria J G , Lachance Geneviève , Paré Guillaume , Rollet-Labelle Emmanuelle , Naccache Paul H 
Published: May 2005

AbstractTec kinases belong to the second largest family of nonreceptor tyrosine kinases. Although these kinases are expressed in myeloid cells, little is known about their implication in neutrophil function. We recently reported the participation of Tec kinases in the responses of human neutrophils to the bacterial peptide N-formyl-l-methionyl-l-leucyl-l-phenylalanine via G-coupled protein receptors. In this study, we extended our investigations of Tec kinases to the signaling of the glycosylphosphatidylinositol-linked receptor CD16b, which is highly and specifically expressed in neutrophils. The results obtained indicate that Tec is translocated to the plasma membrane, phosphorylated, and activated upon CD16b cross-linking and that the activation of Tec is inhibited by Src-specific inhibitors as well as by the phosphatidylinositol-3 kinase inhibitor, wortmannin. As no specific inhibitor of Tec exists, the role of Tec kinases was further investigated using a-Cyano-b-hydroxy-b-methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13), a compound known to inhibit Bruton's tyrosine kinase. We show that this compound also inhibits the kinase activity of Tec and provide evidence that the mobilization of intracellular calcium and the tyrosine phosphorylation of phospholipase Cγ2 (PLCγ2) induced upon CD16b engagement are inhibited by LFM-A13. We also show that Tec kinases are important for CD16b-dependent degranulation of neutrophils. In summary, we provide direct evidence for the implication of Tec in CD16b signaling and suggest that Tec kinases are involved in the phosphorylation and activation of PLCγ2 and subsequently, in the mobilization of calcium in human neutrophils.
Cooperation between platelet-derived CD154 and CD4+ T cells for enhanced germinal center formation
Authors: Elzey Bennett D , Grant Julieann F , Sinn Haley W , Nieswandt Bernhard , Waldschmidt Thomas J , Ratliff Timothy L 
Published: May 2005

AbstractIt has been demonstrated previously that platelet-derived CD154 communicates with the adaptive immune compartment, enhancing B and T cell responses in CD154−/− mice. The presence of platelets was also shown to be necessary for optimal production of immunoglobulin G (IgG) in normal C57BL/6 mice. These data led us to hypothesize that platelets perform a sentinel function, quickly relaying activating signals to the adaptive immune compartment. Here, we report that platelet-derived CD154 increases serum IgG levels and germinal center formation under conditions where antigen-specific CD4+ T cell numbers are limiting. We propose that in the physiologic setting where antigen-specific B and T cells are rare, platelets function to enhance signals required for robust adaptive humoral immunity.
Histamine-3 receptor antagonists reduce superoxide anion generation and lipid peroxidation in rat brain homogenates
Authors: Badenhorst H E , Maharaj D S , Malan S F , Daya S , van Dyk S 
Published: May 2005

Abstract
Using a cyanide model to induce neurotoxic effects in rat brain homogenates, we examined the neuroprotective properties of three H3 antagonists, namely clobenpropit, thioperamide and impentamine, and compared them to aspirin, a known neuroprotective agent. Superoxide anion levels and malondialdehyde concentration were assessed using the nitroblue tetrazolium and lipid peroxidation assays. Clobenpropit and thioperamide significantly reduced superoxide anion generation and lipid peroxidation. Impentamine reduced lipid peroxidation at all concentrations used, but only reduced superoxide anion generation at a concentration of 1 mM. In the lipid peroxidation assay, all the drugs compared favourably to aspirin. This study demonstrates the potential of these agents to be neuroprotective by exerting antioxidant effects.
Antinociceptive effect of proanthocyanidins from Croton celtidifolius bark
Authors: DalBó Silvia , Jürgensen Sofia , Horst Heros , Ruzza Ângelo Adolfo , Soethe Douglas Nihues , Santos Adair Roberto Soares , Pizzolatti Moacir Geraldo , Ribeiro-do-Valle Rosa Maria 
Published: May 2005

Abstract
The chemical composition of the chromatography 63 subfraction (63SF) from the ethyl acetate soluble fraction of the crude extract of Croton celtidifolius bark presented a high content of total proanthocyanidins (75.0 ± 2.3%). HPLC analysis of 63SF revealed a dimeric profile (e.g. catechin-(4α → 8)-catechin and gallocatechin-(4α → 8)-catechin) and polymeric proanthocyanidins. In pharmacological investigations, 63SF administered intraperitoneally exhibited dose-dependent antinociceptive activity against several chemical stimuli, including the intraperitoneal injection of acetic acid (ID50 (the dose of 63SF which was able to reduce the nociceptive response by 50% relative to the control value) = 0.9 (0.5–1.6)) and the intraplantar injection of capsaicin (ID50 = 13.0 (10.0–17.0)), glutamate (ID50 = 4.0 (2.0–7.0)) and formalin (ID50 first phase = 36.0 (24.0–53.0) and late phase = 11.0 (8.0–14.0)). 63SF administered orally exhibited an antinociceptive effect in the formalin test (ID50 first phase = 125.0 (89.0–177.0) and late phase = 65.0 (33.0–95.0)). In the same test, 63SF was effective when given soon after the first phase, as well as exhibiting therapeutic activity. Furthermore, 63SF was effective in models of thermal nociception including tail-flick and hot-plate tests. When the mice were treated in the neonatal period with capsaicin, the antinociceptive effect of 63SF in the first phase of the formalin test was abolished, but pretreatment with naltrexone did not change the antinociceptive effect of 63SF. Together, these results provide evidence that 63SF exerted a pronounced systemic antinociception against chemical (acetic acid, formalin, glutamate and capsaicin tests) and thermal (hot-plate and tail-flick tests) nociceptive models of pain in mice at a dose that did not interfere with the locomotor activity. The mechanism by which this sub-fraction produced antinociception remains unclear, but it is unlikely to involve the activation of the opioid system. However, unmyelinated C-fibres sensitive to treatment with capsaicin are likely to participate in antinociception caused by 63SF.
Site-specific delivery of anti-inflammatory drugs in the gastrointestinal tract: an in-vitro release model
Authors: Klein Sandra , Stein Jürgen , Dressman Jennifer 
Published: May 2005

Abstract
Mesalazine and budesonide are anti-inflammatory drugs that are used to induce and maintain remission of inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis. Both drug substances are intended to act locally at the inflamed sites of the gastrointestinal tract. The therapeutic objective for per oral treatment with these drugs is to achieve a high concentration of the active drug at the sites of inflammation while minimizing systemic absorption. The aim of this study was to develop a test system able to reflect the changing environment that a dosage form incorporating the anti-inflammatory agent is exposed to as it moves through the gastrointestinal tract. The USP dissolution apparatus 3 was used for all experiments. Compendial, as well as biorelevant, media were used to simulate passage through the gastrointestinal tract under various physiological conditions. Different dosage forms of mesalazine (5-aminosalicylic acid, 5-ASA) and budesonide available on the German market were tested. Although all dosage forms were indicated for the same therapeutic objectives, each of the dosage forms exhibited a characteristic release pattern under in-vitro conditions simulating a passage through the fasted-state gastrointestinal tract. Results from this test series indicate that, in the case of various dosage forms of mesalazine and budesonide used for the therapy of Crohn's disease and ulcerative colitis, release patterns as the dosage form moves through the gastrointestinal tract may vary widely. As the various phenotypes of IBD have different requirements in terms of pattern of distribution of the inflamed sites, and because other aspects of gastrointestinal physiology vary within the patient population, the test methods and approach described here should be very useful in designing therapy tailored to the needs of each individual patient.
Hydrolysis kinetics and QSAR investigation of soft antimicrobial agents
Authors: Loftsson Thorsteinn , Thorsteinsson Thorsteinn , Másson Már 
Published: May 2005

Abstract
Quaternary ammonium surfactants, such as benzalkonium chloride and cetylpyridinium chloride, are commonly used as antibacterial agents for disinfectants and for general environmental sanitation, as well as in surfactants, penetration enhancers and preservatives in pharmaceutical and cosmetic formulations. However, these agents are known to cause various side-effects and toxic reactions that are believed to be associated with their chemical stability. Soft analogues of the long-chain quaternary ammonium compounds were synthesized according to the soft drug approach and their physicochemical properties investigated, such as their hydrolytic rate constant, surface activity and lipophilicity. Structure-activity studies showed that the antimicrobial activity of the compounds was strongly influenced by their lipophilicity and chemical stability, the activity increasing with increasing lipophilicity and stability. However, in soft drug design structure-activity relationships are combined with structure-inactivation relationships during the lead optimization. The safety index (SI) of compounds was defined as the hydrolytic rate constant divided by the minimum inhibitory concentration. The SI of the soft antibacterial agents was found to increase with increasing lipophilicity but optimum SI was obtained when their hydrolytic t1/2, at pH 6 and 60°C, was about 11 h. Optimization of the soft antibacterial agents through SI optimization resulted in potent but chemically unstable quaternary ammonium antibacterial agents.
Interaction of baicalin and baicalein with antibiotics in the gastrointestinal tract
Authors: Xing Jie , Chen Xiaoyan , Sun Yuming , Luan Yan , Zhong Dafang 
Published: May 2005

Abstract
To clarify the absorption mechanism of baicalin and to investigate the interaction between baicalin and antibiotics, the pharmacokinetics of baicalin and its aglycone baicalein in normal rats and in antibiotic-treated (with a mixture of neomycin and streptomycin) rats were investigated. A method of liquid chromatography-tandem mass spectrometry with a selected reaction monitoring mode was used to determine the plasma concentrations of baicalin and baicalein. The plasma concentration of total baicalein was determined after treatment of β-glucuronidase/sulfatase. Unpaired Student's t-test was used for statistical comparison. After oral administration of baicalin, the absolute bioavailability of baicalin, based on the AUC of the baicalin parent form, was 2.2 ± 0.2% in normal rats, which decreased to 1.5 ± 0.2% in antibiotic-treated rats. Based on the AUC of total baicalein after enzymatic hydrolysis, the absorption of baicalin was 28.0 ± 5.7%, which significantly decreased to 7.7 ± 1.2% in antibiotic-treated rats. After oral administration of baicalein, the glucuronides/sulfates of baicalein were predominant in plasma. Based on the AUC of total baicalein after enzymatic hydrolysis, the absorption of baicalein was 36.1 ± 4.4% in normal rats, which did not differ markedly from that in antibiotic-treated rats (P &gt; 0.05). The presence of baicalin isomer in plasma after oral administration of baicalin indicated that baicalin was transformed, at least in part, to baicalein before absorption, then to its conjugated metabolites in rats. Aminoglycosides decreased the absorption of baicalin, but not of baicalein, which indicated that antibiotics decreased the decomposition of baicalin to baicalein by inhibiting intestinal flora, and further influenced the absorption, metabolism and efficacy of baicalin. These interactions should be paid attention to in clinical studies when baicalin is administered in combination with antibiotics.
Ecabet sodium raises plasma levels of calcitonin gene-related peptide and substance P in healthy humans
Authors: Katagiri Fumihiko , Inoue Shin , Sato Yuhki , Itoh Hiroki , Takeyama Masaharu 
Published: May 2005

Abstract
Ecabet sodium (ecabet), a cytoprotective drug, produces an increase in mucosal blood flow. One of the gastrointestinal motility regulatory factors has been assumed to be the induction of changes in the levels of peptides (gastrin, somatostatin and motilin) in plasma. On the other hand, recently, capsaicin-sensitive afferent nerves were shown to play an important role in gastric mucosal defensive mechanism. Capsaicin stimulates afferent nerves and enhances the release of calcitonin gene-related peptide (CGRP) and substance P in the stomach. We studied the effect of ecabet on human plasma gastrin-, somatostatin-, motilin-, CGRP- and substance P-like immunoreactive substance (IS) in healthy subjects. Ecabet sodium at a dose of 3.0 g, or placebo, was orally administered in five healthy males. The blood samples were taken before and at 20, 40, 60, 90, 120, 180 and 240 min after administration, subjected to extracting procedures, and submitted to a highly sensitive enzyme immunoassay system. Single administration of ecabet caused significant (P &lt; 0.05) increases in plasma CGRP-, substance P- and somatostatin-IS concentration compared with placebo. Ecabet significantly decreased plasma gastrin-IS levels compared with placebo. In this study, we hypothesized that ecabet might stimulate capsaicin-sensitive afferent nerves indirectly and improve mucosal blood flow; this might be a key mechanism underlying its gastroprotective action.
Immuno-stimulating complexes prepared by ethanol injection
Authors: Lendemans Dirk G , Myschik Julia , Hook Sarah , Rades Thomas 
Published: May 2005

Abstract
This study describes the formulation of immuno-stimulating complexes (ISCOMs) utilising the ethanol injection technique. Cholesterol and phosphatidylcholine were dissolved in ethanol and the resulting solution was rapidly injected into a stirred, aqueous solution of the triterpene-saponin mixture Quil-A. The reversed experiment was also carried out by adding the aqueous Quil-A solution to a solution of cholesterol/phosphatidylcholine dissolved in ethanol. This was done by either rapid injection or dropwise addition of the aqueous Quil-A solution. The colloidal dispersions obtained by ethanol injection and reversed addition were compared with formulations obtained by the dialysis and lipid-film hydration methods. In a further experiment, the preparation of ISCOMs from liposomes as precursor structures was investigated. Transmission electron microscopy was used to analyse the resulting colloidal dispersions. Samples were also compared with respect to homogeneity of obtained particle species. The ethanol injection technique led to formation of ISCOMs in high numbers within 2h post formulation. The reversed rapid injection resulted in a similar colloidal dispersion, differing from the former mainly due to the presence of some helical micellar structures. The reversed, dropwise addition led to the formation of helices as the predominant colloidal structure. Of the three previously established methods, only dialysis led to the formation of ISCOMs within 48 h. The lipid-film hydration method and the approach using liposomes as precursor structures did not produce ISCOMs under the conditions and within the time periods investigated. However, it is known that dispersions prepared by the hydration method equilibrate towards ISCOMs after longer storage. Ethanol injection and reversed rapid injection are simple, cost-effective and quick methods to produce ISCOMs.
Involvement of P-glycoprotein in regulating cellular levels of Ginkgo flavonols: quercetin, kaempferol, and isorhamnetin
Authors: Wang Yi , Cao Jiang , Zeng Su 
Published: May 2005

Abstract
Quercetin, kaempferol, and isorhamnetin were the most important flavonoid constituents in extracts from Ginkgo biloba leaves. Transport studies of Ginkgo flavonols were performed in Caco-2 cell mono-layers. Their apparent permeability in absorptive and secretion directions was determined, and quercetin, kaempferol and isorhamnetin displayed polarized transport, with the Papp,B-A being higher than the Papp,A-B (P &lt; 0.01 for quercetin, P &lt; 0.001 for kaempferol and isorhamnetin, Student's t-test). Bcap37/MDR1 cells, which were transfected with a P-glycoprotein (P-gp) gene construct, were treated with quercetin, kaempferol or isorhamnetin. The concentrations of Ginkgo flavonol in Bcap37/MDR1 cells were lower than those in parent cells (P &lt; 0.05 for quercetin, P &lt; 0.01 for isorhamnetin, Mann-Whitney U test). The concentrations of the flavonol in transfected cells increased when incubated with the P-gp inhibitor verapamil (P &lt; 0.05 for kaempferol, Mann-Whitney U test). A colorometric assay for ATPase activity was applied to the detection of interaction of flavonol with P-gp. Quercetin and kaempferol inhibited the ATPase activity, and isorhamnetin stimulated the ATPase activity (P &lt; 0.05 for isorhamnetin, Mann Whitney U test). The results indicated that Ginkgo flavonols quercetin, kaempferol and isorhamnetin were substrates of P-gp. The P-gp type efflux pump might limit the bioavailability of Ginkgo flavonols.
High participation rates are not necessary for cost-effective colorectal cancer screening
Authors: Howard Kirsten , Salkeld Glenn , Irwig Les , Adelstein Barbara-Ann 
Published: May 2005

Background: In many countries high participation is an explicit target in screening programmes. The desire for high participation often appears to drive screening policy, although it is increasingly recognized that encouraging high participation may impinge upon the rights of an individual to make an informed choice. One argument offered in support of high participation is that it improves the cost-effectiveness of screening. This is questionable on theoretical grounds, and empirically there are conflicting results. Two recent cost-effectiveness models of faecal occult blood test (FOBT) screening for colorectal cancer (CRC) showed that cost-effectiveness was improved, another showed that cost-effectiveness was worsened and a fourth indicated that cost-effectiveness was unaffected by increasing the participation rate. Methods: We assessed the extent to which different levels and patterns of participation affect cost-effectiveness, using decision modelling of three CRC screening with FOBT scenarios. We estimate the incremental cost-effectiveness (value for money) ratios for each scenario. Results: The way in which participation is modelled, particularly assumptions made about the subsequent screening behaviour of non-participants ('if' and 'when' a non-participant attends for subsequent screening), affects the cost-effectiveness estimates for FOBT screening programmes. 100% participation in all screening rounds gives a cost per life year saved (LYS) of US&dollar;9705. Cost-effectiveness is worst when people who do not take part in one screening round (initial or subsequent) never take part in any future rounds of screening. Under this scenario, a participation rate of 20% in second and subsequent rounds gives a cost per LYS of US&dollar;29,500. Under more realistic assumptions, for example the attendance of even a small proportion of non-participants in subsequent rounds, cost-effectiveness is more favourable and similar to that achieved for full participation: the scenario with a random participation rate of 20% in second and subsequent rounds for both participants and non-participants has a cost per LYS of US&dollar;11,270. Conclusions: Contrary to a commonly held view, high participation in screening programmes is not necessary to achieve cost-effectiveness. Setting high target participation rates in screening programmes does not guarantee cost-effectiveness and may in certain circumstances reduce the cost-effectiveness.
The immunochemical faecal occult blood test leads to higher compliance than the guaiac for colorectal cancer screening programmes: a cluster randomized controlled trial
Authors: Federici Antonio , Rossi Paolo Giorgi , Borgia Piero , Bartolozzi Francesco , Farchi Sara , Gausticchi Gabriella 
Published: May 2005

Introduction: We conducted a cluster-randomized trial aimed at assessing the effect of the type of faecal occult blood, guaiac or immunochemical test on screening compliance. Methods: We sampled 130 general practitioners (GPs) who consented to participate in the trial. We randomly allocated half of them to the guaiac (Hemo-Fec) and half to the immunochemical test (OC-Hemodia). We sampled 2/10 of the GPs' 50–75-year-old patients ( n=7332) and randomly divided this population into half. One half was invited to be screened at the GP's office and the other to the nearest gastroenterology ward. The principal outcome was the percentage of returned tests. Results: The immunochemical test had a compliance of 35.8% and the guaiac of 30.4% (relative risk [RR] 1.20; 95% confidence interval [CI] 1.02–1.44). The difference was mostly due to a higher probability of returning the sample: 93.8% and 88.6% for immunochemical and guaiac, respectively (RR 1.06; 95% CI 1.02–1.10). The guaiac test had a higher prevalence of positives (10.3% versus 6.3%, RR 0.603; 95% CI 0.433–0.837). There was a higher variability in the results obtained with the guaiac test compared with the immunochemical (F[1, 12] = 16.25; P=0.0017). Conclusions: Compliance is more likely with the immunochemical than the guaiac test, independent of the provider. Guaiac tests show a higher variability of the results among centres. The successful implementation of a screening programme requires a period of standardization of the test reading in order to avoid unexpected work overload for colonscopy services.