bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of 1α,25-Dihydroxyvitamin D<sub>3</sub> in Normal Mice after Systemic Exposure to Effective and Safe Antitumor Doses
Authors: Muindi Josephia R. , Modzelewski Ruth A. , Peng Yibing , Trump Donald L. , Johnson Candace S. 
Published: March 2004

<i>Objective:</i> Calcitriol, 1α,25-dihydroxyvitamin D<sub>3</sub> (1,25-D<sub>3</sub>) has potent antiproliferative effects and potentiates the antitumor activity of many other cytotoxic drugs. 1,25-D<sub>3</sub> plasma pharmacokinetic (PK) parameters associated with antitumor activity in experimental animal models are unknown. The objective of this study was to determine plasma calcitriol PK in normal mice at doses of calcitriol which are active in suppressing tumor growth. <i>Methods:</i> Plasma 1,25-D<sub>3</sub> PK were examined in normal C3H/HeJ mice after a single intraperitoneal dose of 0.125 or 0.5 µg 1,25-D<sub>3</sub>/mouse. PK blood samples were collected from groups of 5–9 mice at each time point up to 24 h after 1,25-D<sub>3</sub> administration. Plasma 1,25-D<sub>3</sub> concentrations were measured by radioimmunoassy. Plasma 1,25-D<sub>3</sub> concentration diurnal variation was determined in blood samples from untreated animals collected in the morning (9:00–11:00 a.m.) and in the evening (4:00–9:00 p.m.). <i>Results:</i> Median baseline plasma 1,25-D<sub>3</sub> concentration measured in the morning and in the evening were 0.082 ng/ml (CI 95%, 0.076–0.099) and 0.067 ng/ml (CI 95%, 0.058–0.075), respectively (p = 0.004). After 0.125 and 0.5 µg dosing, peak plasma 1,25-D<sub>3</sub> concentrations (Cp<sub>max</sub>) were 12.0 ng/ml (CI 95%, 10.8–12.6) and 41.6 ng/ml (CI 95%, 40.8–53.6), respectively. The corresponding areas under the curve (AUC<sub>0–>24 h</sub>) were 47.0 (CI 95%, 43.2–51.1) and 128.0 (CI 95%, 127.0–130.0) ng·h/ml. No dose-related changes in time to Cp<sub>max</sub> and apparent total plasma clearance were observed. <i>Conclusions:</i> These results demonstrate diurnal variation in baseline plasma 1,25-D<sub>3</sub> concentrations in mice. Plasma 1,25-D<sub>3</sub> PK in mice receiving doses that are effective in slowing tumor growth, inducing cell cycle arrest and apoptosis, and potentiating taxanes and platinum analogue antitumor activity are at least 5–10 times higher than those easily achieved and nontoxic in patients receiving high-dose intermittent oral therapy.
Suppression of N-Methyl-N-Nitrosourea-Induced Photoreceptor Apoptosis in Rats by Docosahexaenoic Acid
Authors: Moriguchi Kaei , Yoshizawa Katsuhiko , Shikata Nobuaki , Yuri Takashi , Takada Hideho , Hada Takahiko , Tsubura Airo 
Published: March 2004

We evaluated the effects of dietary intake of docosahexaenoic acid (DHA) on photoreceptor cell apoptosis caused by N-methyl-N-nitrosourea (MNU). Five-week-old female Sprague-Dawley rats were fed basal diet (AIN-76A) or DHA diet (modified AIN-76A containing 9.5% DHA) for 2 weeks, and then received a single intraperitoneal injection of 60 mg/kg body weight MNU at 50 days of age. Then, rats continued to receive the same diet or were switched to the opposite diet: group 1, basal diet before and after MNU injection; group 2, DHA diet before MNU injection and basal diet after MNU injection; group 3, basal diet before MNU injection and DHA diet after MNU injection; group 4, DHA diet before and after MNU injection (10 rats in each group). Rats were starved for 24 h, then sacrificed 3 or 7 days after MNU. Morphologically, at 3 days after MNU injection, photoreceptor cell apoptosis was advanced in group 1 compared with group 4. At this time point, as evaluated by retinal damage ratio [(length of retina less than 4 photoreceptor cells thick/whole retinal length) ×100], retinal damage was highest in group 1 (82.4 ± 5.1%), followed by group 2 (41.1 ± 7.3%), group 3 (24.7 ± 11.5%), and group 4 (6.6 ± 6.6%); severity tended to be inversely correlated with serum DHA composition. At 7 days after MNU injection, active signs of photoreceptor cell apoptosis ended in all MNU-treated groups, and retinal damage ratio was high in group 1 (88.4 ± 2.8%), whereas it remained low in groups 2, 3 and 4 (38.4 ± 15.2, 45.7 ± 9.8 and 46.9 ± 11.2%, respectively). High DHA composition during induction/signaling phase and/or effector phase of photoreceptor cell apoptosis can delay the onset of apoptosis and counteract progression of MNU retinotoxicity in rat retina. DHA may play a role in the suppression of MNU-induced photoreceptor cell apoptosis in rat retina.
Effect of N-Acetylcysteine on Serum Creatinine Concentration in Patients with Chronic Renal Insufficiency Who Are Undergoing Coronary Angiography
Authors: Agrawal Malay , Wodlinger Anna M. , Huggins Chad E. , Tudor Gail E. , Pieper John A. , O’Reilly Kevin P. , Denu-Ciocca Cynthia J. , Stouffer George A. , Ohman E. Magnus 
Published: March 2004

<i>Background:</i> Prior studies have produced conflicting results on whether N-acetylcysteine (NAC) reduces the incidence of contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CA). The dosing regimens of NAC in these studies seemed impractical for everyday clinical practice. <i>Objective:</i><i></i>We studied the effect of NAC, with a novel dosing strategy, on serum creatinine concentration (SCr), and the incidence of CIN, in patients who were undergoing CA and/or percutaneous coronary intervention (PCI). <i>Methods:</i> Twenty-five subjects with baseline renal insufficiency who were undergoing CA and/or PCI were randomized to either NAC or placebo.<i></i>The treatment schedule was 800 mg of NAC 12 h prior to angiography, 600 mg of NAC 2 h prior to angiography, and 600 mg of NAC 6 h after angiography or matching placebo. All subjects were hydrated with 1 ml/kg of 0.45% saline and received non-ionic contrast for angiography. The primary endpoint was change in SCr and the secondary endpoint was the incidence of CIN as defined by an increase of 0.5 mg/dl or 25% in SCr at 48 h. <i>Results:</i><i></i>The average SCr at enrollment was 1.7 mg/dl and average dye exposure was 171 ml. The average change in SCr in the NAC and placebo groups was 0.14 and 0.06 mg/dl, respectively (p = 0.60). The incidence of CIN was 18 and 14% in the NAC and placebo groups, respectively (p = 1.0). <i>Conclusion:</i> In this small study, there was no significant difference in the change in<i></i>SCr nor the incidence of CIN in patients with baseline renal insufficiency undergoing CA and/or PCI who were treated with NAC or placebo.
What Is the Lowest Dose of Aspirin for Maximum Suppression of in vivo Thromboxane Production after a Transient Ischemic Attack or Ischemic Stroke?
Authors: Dippel Diederik W.J. , van Kooten Fop , Leebeek Frank W.G. , van Vliet Huub H.D.M. , Mehicevic Ajnira , Li Simon S.C. , Koudstaal Peter J. 
Published: March 2004

<i>Background:</i> There is still worldwide disagreement about the optimal lowest dose of aspirin to be used in patients after a transient ischemic attack (TIA) or nondisabling stroke. We measured the urinary 11-dehydro-thromboxane-B<sub>2</sub> (uTXB<sub>2</sub>) excretion to compare the degree of suppression of in vivo platelet activation by various low doses of aspirin. <i>Methods:</i> 60 patients were randomly allocated to treatment with either 30, 50, 75 or 325 mg of aspirin. All patients received a 413-mg loading dose of carbasalate calcium (equivalent to 325 mg of aspirin) on day 0. The study population was stratified into a subgroup with acute ischemic stroke (AIS; n = 20; onset of symptoms <48 h) and a subgroup with a recent TIA or minor stroke (TIA/mS; n = 40) with onset of symptoms beyond 30 days, but less than a year previously. Urine samples were collected on day 0, 1, 5, 11 and 28 in patients with AIS, and on day 0, 11 and 28 in the patients with a TIA/mS. <i>Results:</i> On day 28, mean uTXB<sub>2</sub> levels were 241, 130, 217 and 187 pmol/mmol creatinine in the four treatment groups (ANOVA, p = 0.43). In the AIS subgroup, uTXB<sub>2</sub> remained suppressed on days 5 and 11 in all except the patients with the lowest dose (mean uTXB<sub>2</sub> on days 5 and 11: 475 and 392 pmol/mmol creatinine; log-transformed ANOVA, p = 0.05). <i>Conclusion:</i> In patients with a TIA or nondisabling stroke, a daily dose of 30 mg of aspirin provides sufficient suppression of thromboxane synthesis. No indication of a dose-effect relationship was found. However, whether such a low dose adequately suppresses thromboxane synthesis in patients with acute stroke is uncertain.
<i>Mycoplasma pneumoniae</i> in Elderly Patients with Stroke
Authors: Ngeh Joseph , Gupta Sandeep , Goodbourn Colin , McElligott Geraldine 
Published: March 2004

<i>Background and Purpose:</i> Previous studies have suggested certain infections as potential risk factors for stroke. <i>Chlamydia pneumoniae,</i> an atypical respiratory pathogen, has been linked to atherosclerotic vascular diseases. <i>Mycoplasma pneumoniae,</i> another atypical respiratory micro-organism, can rarely cause stroke. We investigated whether serological markers of <i>M. pneumoniae</i> infection were associated with acute stroke or transient ischaemic attack (TIA) in elderly patients. <i>Methods:</i> This case-control study was nested within the C-PEPS study – a case-control study on the seroprevalence of <i>C. pneumoniae</i> in elderly stroke and medical patients. Ninety-five incident cases of patients admitted consecutively with acute stroke or TIA, and 82 control subjects admitted concurrently with acute non-cardiopulmonary, non-infective disorders, were included in this study (both groups aged 65 years or older). Using commercial enzyme-linked immunosorbent assay (ELISA) kits, the presence of <i>M. pneumoniae</i> immunoglobulins IgA, IgG and IgM in patients’ sera was determined. <i>Results:</i> The seroprevalence of <i>M. pneumoniae</i> IgA, IgG and IgM in the stroke or TIA group (median age = 80) were 79, 61 and 6%, respectively. In the control group (median age = 80), the seroprevalence of respective <i>M. pneumoniae</i> IgA, IgG and IgM were 84, 50 and 11%. Using a logistic regression statistical model, adjusting for history of hypertension, smoking, diabetes mellitus, age and sex, history of ischaemic heart disease, and ischaemic electrocardiogram, the odds ratios of having a stroke or TIA in relation to <i>M. pneumoniae</i> IgA, IgG and IgM were 0.63 (95% confidence interval (CI) = 0.26–1.52, p = 0.31), 1.32 (95% CI = 0.66–2.64, p = 0.43) and 0.52 (95% CI = 0.14–1.92, p = 0.32), respectively. <i>Conclusions:</i> The study showed a high seroprevalence of <i>M. pneumoniae</i> in an elderly hospital population, using ELISA. Although the study ruled out <i>M. pneumoniae</i> seropositivity as a major risk factor for stroke in this elderly population, a smaller effect could not be excluded due to the small sample size. Future larger studies may be required to determine the precise role of <i>M. pneumoniae</i> infection in the pathogenesis of different subtypes of ischaemic stroke, in all age groups, and in different ethnic populations.
Effects of Histamine and the H2 Receptor Antagonist Ranitidine on Ischemia-Induced Acute Renal Failure: Involvement of IL-6 and Vascular Endothelial Growth Factor
Authors: Vannay Ádám , Fekete Andrea , Müller Veronika , Strehlau Jürgen , Viklicky Ondrej , Veres Tibor , Reusz György , Tulassay Tivadar , Szabó Attila J. 
Published: March 2004

<i>Background:</i> Vascular endothelial growth factor (VEGF) exerts cytoprotective, antiapoptotic and proangiogenic effects; its synthesis is induced by hypoxia, several cytokines and histamine. The effects of histamine and the H2 receptor antagonist ranitidine on renal VEGF and IL-6 synthesis were investigated in a well-established rat model of renal ischemia/reperfusion injury. <i>Methods:</i> Following 7 days of pretreatment with histamine (H group; n = 12), ranitidine (R group; n = 10) or vehicle (controls; n = 13), the left vascular pedicle was clamped for 50 min in uninephrectomized male rats and survival assessed in the different treatment groups. Additionally, renal IL-6 mRNA expression, as well as VEGF mRNA and protein abundance were measured in the three treatment groups following pretreatment only, 2 and 16 h after 50 min of renal ischemia (n = 6/group/timepoint). <i>Results:</i> Ranitidine significantly increased, while histamine significantly decreased survival following renal ischemia. Renal IL-6 mRNA expression increased 2 h after reperfusion in all groups and decreased thereafter, with the lowest level observed in the R group. While VEGF mRNA did not change in controls, histamine increased, whereas ranitidine decreased its expression during the follow-up. Two hours after ischemia a twofold increase in renal VEGF protein abundance was observed in controls and the H group and significantly higher values were noted in the R group at this time point. A further increase in VEGF protein was only present in the H group 16 h after reperfusion. <i>Conclusion:</i> These results indicate an important role of histamine in kidney damage following renal ischemia. The beneficial effects of ranitidine were partly mediated by decreased IL-6 and VEGF mRNA expression and significant early increase in renal VEGF abundance.
A Solitary Peutz-Jeghers-Type Hamartomatous Polyp in the Duodenum
Authors: Kitaoka Fumio , Shiogama Toshiaki , Mizutani Akimasa , Tsurunaga Yasutaka , Fukui Hiroshi , Higami Yoshikazu , Shimokawa Isao , Taguchi Takashi , Kanematsu Takashi 
Published: March 2004

<i>Background/Aims:</i> We report a case of solitary Peutz-Jeghers-type hamartomatous polyp of the duodenum in a 22-year-old Japanese woman along with the results of genomic analysis. <i>Methods/Results:</i> The patient was almost asymptomatic, though endoscopic examination revealed a solitary lobular polypoid lesion measuring 3 cm in diameter in the first portion of the duodenum. The lesion was resected endoscopically. Histopathological examination showed hyperplasia with a tree branch-like extension of the lamina propria derived from the muscularis mucosae, consistent with histological features of polyps of Peutz-Jeghers syndrome (PJS). No mucocutaneous pigmentation of the skin was evident and family history was negative. Analysis of the loss of heterozygosity at the locus of 19p 13.3 and mutation analysis of the <i>STK11/LKB1</i> gene, which has recently been recognized as a susceptible gene in PJS, were performed. However, no evidence of genomic abnormality was found. <i>Conclusion:</i> The clinical and investigative findings in our case suggest that the solitary Peutz- Jeghers-type hamartomatous polyp can be regarded as a clinical entity separate from PJS.
Biocompatibility of Cellulosic and Synthetic Membranes Assessed by Leukocyte Activation
Authors: Hernández Maria Rosa , Galán Ana Maria , Cases Aleix , Lopez-Pedret Jose , Pereira Arturo , Tonda Raul , Bozzo Jordi , Escolar Gines , Ordinas Antonio 
Published: March 2004

<i>Background/Aims:</i> The contact of blood with artificial surfaces may activate blood leukocytes and platelets and initiate the leukocyte inflammatory response. We have investigated the effect of a hemodialysis (HD) with a cellulosic- and a synthetic-based membrane on circulating leukocyte activation. <i>Methods:</i> Samples were obtained from patients with ESRD at baseline, and at 15 and 120 min of a hemodialysis session from both the arterial and venous lines. Leukocyte respiratory burst was analyzed by luminol chemiluminescence. Actin polymerization, expression of CD11b, and heterotypic aggregation were studied by flow cytometry, leukocyte labeling with NBD phallacidin and monoclonal antibodies, respectively. <i>Results:</i> HD with a cellulosic membrane induced a transient fall in neutrophil (1.2 ± 0.5 × 10<sup>9</sup> vs. 3.6 ± 0.6 × 10<sup>9</sup> cells/l; p < 0.05) and monocyte counts (0.2 ± 0.1 × 10<sup>9</sup> vs. 0.7 ± 0.1 × 10<sup>9</sup> cells/l; p < 0.05). There was also an increase in respiratory burst in the venous line during a HD with a cellulosic membrane, at 15 and 120 min (100 ± 41 and 143.2 ± 45.3 vs. 23.8 ± 15.7; p < 0.05). Polymerized actin, expressed as fluorescence arbitrary units, was increased in baseline samples from uremic patients versus control subjects (327.8 ± 60.8 for a cellulosic membrane, p < 0.005, and 205 ± 26.5 for a synthetic one, p < 0.05 vs. 97.8 ± 27.6 in controls). The percentage of CD11b+ cells increased in samples during a HD with a cellulosic membrane at the venous line at 15 and 120 min (9.6 ± 4.5 and 18.4 ± 7.1% vs. 3.3 ± 1.9%; p < 0.05%). Changes in heterotypic aggregation during HD did not reach statistical significance, but levels were higher in patients treated with a cellulosic membrane at all points than in patients dialyzed with a synthetic one. <i>Conclusion:</i> There is evidence of a priming state of leukocytes from uremic patients, which is more evident in patients dialyzed with a cellulosic membrane. Cellulosic membranes also induce greater leukocyte activation than synthetic membranes during hemodialysis.
Determination of pamidronate in human whole blood and urine by reversed‐phase HPLC with ﬂuorescence detection
Authors: Wong Jaime A. , Renton Kenneth W. , Crocker John F. S. , O'Regan Patrick A. , Acott Philip D. 
Published: March 2004

AbstractPamidronate is a bisphosphonate that is effective in treating bone disease including osteopenia and osteoporosis in adults. A sensitive and reliable method for the analysis of pamidronate in whole blood and urine is key to the development of this drug for use in children. A previously described method for pamidronate analysis serum and urine did not consistently detect the drug at satisfactory levels in whole blood. The procedure involves co‐precipitation of the bisphosphonates with calcium phosphate, pre‐column derivitization with ﬂuorescamine, HPLC utilizing a Nucleosil C18 column, and ﬂuorescence detection with excitation at 395 nm and emission at 480 nm.Changes to the original protocol included the use of a new internal standard (alendronate), the optimization of the concentration of ethylenediaminetetraacetic acid (EDTA) for dissolving the precipitate, and the elimination of the acidiﬁcation step prior to deproteinization. The optimum EDTA concentration, which had a signiﬁcant effect on the labeling capability of ﬂuorescamine, was determined to be 20 mm.A good separation between pamidronate and alendronate was achieved using a heated (40°C ) Nucleosil C18, 10 µm particle size column. The mobile phase was an aqueous solution of 1 mm Na2EDTA–methanol (97:3, v/v) adjusted to pH 6.5 using a ﬂow‐rate of 1 mL/min. Fluorescence detection was set at 395 nm for excitation and at 480 nm for emission. The limit of quantitation for pamidronate was 0.5 µg/mL in whole blood and 0.1 µg/mL in urine. The method was applied to both whole blood and urine samples from pediatric patients. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis and Conformational Analysis of Novel N(OCH3)‐linked Disaccharide Analogues
Authors: Peri Francesco , Jiménez–Barbero Jesús , García–Aparicio Víctor , Tvaroška Igor , Nicotra Francesco 
Published: March 2004

AbstractN(OMe)‐linked disaccharide analogues, isosteric to the corresponding natural disaccharides, have been synthesized by chemoselective assembly of unprotected natural monosaccharides with methyl 6‐deoxy‐6‐methoxyamino‐α‐D‐glucopyranoside in an aqueous environment. The coupling reactions were found to be chemo‐ and stereoselective affording β‐(1→6) disaccharide mimics when using Glc and GlcNAc; in the case of Gal, the β‐anomer was prevalent (β:α=7:1). An iterative method for the synthesis of linear N(OMe) oligosaccharide analogues was demonstrated, based on the use of an unprotected monosaccharide building block in which an oxime functionality at C‐6 is converted during the synthesis into the corresponding methoxyamino group. The conformational analysis of these compounds was carried out by using NMR spectroscopy, ab initio, molecular mechanics, and molecular dynamics methods. Optimized geometries and energies of fourteen conformers for each compound have been calculated at the B3LYP/6‐31G* level. Predicted conformational equilibria were compared with the results based on NMR experiments and good agreement was found. It appears that N(OMe)‐linked disaccharide analogues exhibit a slightly different conformational behavior to their parent natural disaccharides.
A family of hyperbolic spin Calogero‐Moser systems and the spin Toda lattices
Authors: Li L.‐C. 
Published: March 2004

AbstractIn this paper, we continue to develop a general scheme to study a broad class of integrable systems naturally associated with the coboundary dynamical Lie algebroids. In particular, we present a factorization method for solving the Hamiltonian flows. We also present two important classes of new examples, a family of hyperbolic spin Calogero‐Moser systems and the spin Toda lattices. To illustrate our factorization theory, we show how to solve these Hamiltonian systems explicitly. © 2004 Wiley Periodicals, Inc.
Computational and Experimental NMR Definition of Differences in the Conformational Behavior of Free and Lectin‐Bound Glycomimetic Aza/Carba‐Lactosides
Authors: Fernández‐Alonso María del Carmen , Cañada F. Javier , Solís Dolores , Cheng Xuhong , Kumaran Govindaraj , André Sabine , Siebert Hans‐Christian , Mootoo David R. , Gabius Hans‐Joachim , Jiménez‐Barbero Jesús 
Published: March 2004

AbstractVersatile synthetic procedures make saccharide derivatives with substitution at various sites available. Because of the particular involvement of galactosides in biorecognition processes, with lectins affecting growth regulation and adhesion, lactose has become a popular starting point for systematic structure variation. Since shape and flexibility are key parameters for ligand binding, we studied the conformational behavior of aza/carba‐C/O analogues of lactose (compound 1, aza‐C; compound 2, carba‐O). Computational calculations and NMR spectroscopy revealed conspicuous differences between 1 and 2 in the extents of accessible conformational area and flexibility. The aza‐C derivative also revealed clear shifts in population density relative to lactose, attributable to the exo‐anomeric effect. The assumption that the derivatives can act as glycomimetics was substantiated by binding studies with a plant lectin. The aza‐C analogue 1 maintained a higher degree of flexibility when bound than the O‐glycosidically linked carbadisaccharide 2. The experimental detection of exclusive NOEs characteristic of different conformers of bound 1 [i.e., H1′/H4 (syn‐Φ), H1′/H3 (anti‐Ψ), and H2′/H4 (anti‐Φ) NOE cross‐peaks] argues in favor of the ligand still harboring a certain degree of flexibility when bound to mistletoe lectin (VAA). In contrast, there is unambiguous evidence for binding of the major exo‐anomeric conformer of 2 by VAA, as indicated by the presence of the exclusive NOE of H7eq′/H4. Evidently, structural variations between closely related compounds can translate into clear differences in the lectin‐bound states of glycomimetics. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)