bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low sodium and furosemide‐induced stimulation of the renin system in man is mediated by cyclooxygenase 2
Authors: Kammerl Martin C. , Nüsing Rolf M. , Schweda Frank , Endemann Dierk , Stubanus Mike , Kees Frieder , Lackner Karl J. , Fischereder Michael , Krämer Bernhard K. 
Published: December 2004

The aim of this study was to examine the effects of highly selective inhibition of cyclooxygenase 2 (COX‐2) with rofecoxib on the renin system during long‐term stimulation and after short‐term stimulation. Six healthy male volunteers received, in a randomized crossover design, a low‐sodium diet for days 1 through 9 with or without 25 mg rofecoxib twice daily on days 5 through 9 and, in addition, 20 mg of furosemide intravenously on day 8. Plasma renin activity increased 2 to 3 times over baseline with a low‐sodium diet and 5 times over baseline 30 minutes after intravenous furosemide; it was still elevated nearly 5 times on day 9. These effects were completely blocked by rofecoxib. Plasma aldosterone and urinary aldosterone concentrations basically reflected the findings with plasma renin activity. Urinary sodium excretion decreased during a low‐sodium diet and increased after intravenous furosemide without being significantly affected by rofecoxib. We have concluded that low‐sodium and furosemide‐stimulated renin and aldosterone secretion is completely blocked in healthy volunteers during COX‐2 inhibition with rofecoxib, suggesting that intact COX‐2 is of major importance for stimulation of the renin system under these conditions in man.Clinical Pharmacology & Therapeutics (2001) 70, 468–474; doi: 10.1016/S0009‐9236(01)49789‐X
Ethnicity influences morphine pharmacokinetics and pharmacodynamics
Authors: Cepeda M. Soledad , Farrar John T. , Roa Jairo H. , Boston Ray , Meng Qing C. , Ruiz Franklin , Carr Daniel B. , Strom Brian L. 
Published: December 2004

ObjectiveOur objective was to evaluate ethnic differences in response to morphine and to determine whether any detectable differences were pharmacokinetically based.MethodsThis cohort study was carried out in a teaching hospital. Sixty‐six young, healthy male subjects from 3 ethnic groups (Caucasians, native Indians, and Latinos; n = 22 in each group) consented to participate. All subjects received an intravenous morphine bolus of 0.08 mg/kg followed by 0.002 mg/kg · min infused for 30 minutes. Respiratory response was evaluated with the carbon dioxide rebreathing method before and at 25, 95, 180, and 360 minutes after morphine administration. Vital signs and opioid side effects were recorded, and serial blood samples were analyzed for morphine, morphine‐3‐glucuronide, and morphine‐6‐glucuronide (M6G).ResultsAll 3 groups had suppression of the ventilatory response to hypercapnia, but the degree of blunting of the ventilatory response differed among groups. Compared with Caucasians, native Indians had an additional 18% reduction in ventilatory response after morphine administration (95% confidence interval, −35% to −2%). The incidence of side effects was similar in all groups (P = .18). Caucasians had higher plasma levels of M6G than did native Indians or Latinos. M6G areas under 6‐hour concentration‐versus‐time curve were as follows: Caucasians, 12,065 ± 4354; native Indians, 8464 ± 4809; and Latinos, 9156 ± 3764 ng · min/mL (P = .03).ConclusionsEthnicity influences the response to morphine. Native Indians are more susceptible to morphine depression of the ventilatory response than Caucasians, despite the higher serum M6G levels in Caucasians.Clinical Pharmacology & Therapeutics (2001) 70, 351–361; doi: 10.1016/S0009‐9236(01)51508‐8
A population pharmacokinetic‐pharmacodynamic analysis and model validation of azimilide
Authors: Phillips Luann , Grasela Thaddeus H. , Agnew Jeffrey R. , Ludwig Elizabeth A. , Thompson Gary A. 
Published: December 2004

BackgroundPharmacokinetic (PK) and pharmacodynamic (PD) models for azimilide were developed and validated with sparse blood sampling and QTc interval data obtained during three clinical trials of azimilide for prevention of supraventricular arrhythmia recurrence.MethodsPatients were orally administered placebo or azimilide dihydrochloride, 35, 50, 75, 100, or 125 mg/d, for 6 to 9 months. NONMEM was used for data fitting and assessment of selected patient covariates and concomitant medication classes for PK/PD relationships.ResultsResults indicate that azimilide clearance (CL) was dependent on body weight (WTKG), gender, and current tobacco use, where CL (L/h) = 3.92 × (WTKG − 43)0.208, with a 17% increase for male subjects and a 15.5% increase for current tobacco use. Volume of distribution (V) was also dependent on WTKG and total bilirubin (BIL), where V (L) = 9.88 × (WTKG − 43) + 717 × (BIL)0.348. The PK/PD analysis indicated that the baseline QTc interval was dependent on gender, New York Heart Association Class, digoxin, and paced artificial pacemaker spike, whereas the 50% effective concentration (EC50) was dependent on the serum potassium (K) level, where EC50 = 107 × K. The change in EC50 was not clinically significant within the normal range for potassium. The mean Emax (maximum increase in the QTc interval for the Emax models) was a 61.7 ms increase from baseline. At 125 mg/d the predicted percent increase in the QTc interval at the maximum plasma drug concentration at steady state was 9% and 10% for male and female patients, respectively. The values of the median prediction error were −3% and −0.4% for the PK and PK/PD models, respectively, and the values of the absolute prediction error were 21% and 4% for the PK and PK/PD models, respectively, indicating that both models are essentially unbiased and acceptably accurate.ConclusionsAzimilide PK parameters are dependent on body weight, gender, smoking status, and bilirubin and are independent of the coadministration of digoxin, warfarin, and cytochrome P4503A4 inhibitors and inducers. The relationship between azimilide concentration and change in QTc is primarily dependent on serum potassium.Clinical Pharmacology & Therapeutics (2001) 70, 370–383; doi: 10.1016/S0009‐9236(01)56650‐3
Different effects of St John's Wort on the pharmacokinetics of simvastatin and pravastatin
Authors: Sugimoto Koh‐ichi , Ohmori Masami , Tsuruoka Shuichi , Nishiki Kenta , Kawaguchi Atsuhiro , Harada Ken‐ichi , Arakawa Masashi , Sakamoto Koh‐ichi , Masada Mikio , Miyamori Isamu , Fujimura Akio 
Published: December 2004

ObjectiveSt John's Wort, a widely used herbal product, is an inducer of CYP3A4 and it decreases blood concentrations of CYP3A4 substrates. The effects of St John's Wort on the pharmacokinetics of 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors simvastatin (an inactive lactone pro‐drug) and pravastatin were determined in this study.MethodsSixteen healthy male subjects (n = 8 in group 1 and n = 8 in group 2) took a St John's Wort caplet (300 mg) or matching placebo three times a day for 14 days in a double‐blind, crossover study. On day 14, a single oral dose of 10 mg simvastatin and 20 mg pravastatin was given to subjects in group 1 and group 2, respectively. Blood samples were obtained during a 24‐hour period after the administration of each drug.ResultsRepeated St John's Wort treatment tended to lower plasma simvastatin concentration and significantly (P < .05) lowered concentrations of simvastatin hydroxy acid, its active metabolite. The peak concentration in plasma (ratio, 0.72 of placebo) of simvastatin hydroxy acid tended to be decreased and its area under the plasma concentration‐time curve between time zero and 24 hours after administration (ratio, 0.48 of placebo) was significantly decreased (P < .05) by St John's Wort. On the other hand, St John's Wort did not influence plasma pravastatin concentration. No significant differences were observed in the elimination half‐life of simvastatin or pravastatin between the placebo and St John's Wort trials.ConclusionsThis study showed that St John's Wort decreases plasma concentrations of simvastatin but not of pravastatin. Because simvastatin is extensively metabolized by CYP3A4 in the intestinal wall and liver, which are induced by St John's Wort, it is likely that this interaction is partly caused by the enhancement of the CYP3A4‐mediated first‐pass metabolism of simvastatin in the small intestine and liver.Clinical Pharmacology & Therapeutics (2001) 70, 518–524; doi: 10.1016/S0009‐9236(01)64092‐X
Angioplasty increases target site concentrations of ciprofloxacin in patients with peripheral arterial occlusive disease
Authors: Joukhadar Christian , Klein Nikolas , Frossard Martin , Minar Erich , Stass Heino , Lackner Edith , Herrmann Markus , Riedmüller Eva , Müller Markus 
Published: December 2004

ObjectivePatients with peripheral arterial occlusive disease are prone to soft tissue infections and frequently require antibiotics. To date, however, it is not known whether improvement of arterial blood flow by angioplasty of stenosis increases antibiotic concentrations in ischemic lesions.Patients and methodsAll patients were scheduled to undergo elective percutaneous transluminal angioplasty (n = 10). Following a single, 400‐mg dose of ciprofloxacin, drug concentrations in plasma, ischemic and healthy soft tissue; arterial peak systolic velocity; and ankle‐brachial pressure index were assessed before and after angioplasty. Unbound ciprofloxacin concentrations were measured at the site of infection with use of in vivo microdialysis.ResultsAngioplasty increased peak systolic velocity and ankle‐brachial pressure index compared with base‐line (P < .002). Before angioplasty area under concentration‐time curve (AUC0–300) values for ciprofloxacin were lower in ischemic tissue than in healthy tissue, with median values of 7.1 mg·h/L (range, 3.5–13.0) and 11.3 mg·h/L (range, 3.4–19.0), respectively (P = .03). After angioplasty AUC0–300 values were identical in ischemic and healthy adipose tissue; median AUC0–300 values were 8.0 mg·h/L (range, 4.0–20.7) and 8.5 mg·h/L (range, 4.4–22.9), respectively (P = .7). A combined in vivo pharmacokinetic/in vitro pharmacodynamic simulation based on tissue concentration data indicates that this difference in pharmacokinetics is also reflected in antimicrobial effect.ConclusionAntibiotic concentrations are reduced significantly in ischemic lesions compared to those of healthy adipose tissue in patients with peripheral arterial occlusive disease. From the present data it might be speculated that improvement of arterial blood flow at the affected extremity is associated with increased cure rates of soft tissue infections in these patients.Clinical Pharmacology & Therapeutics (2001) 70, 532–539; doi: 10.1016/S0009‐9236(01)74143‐4
Assessment of cytochrome P450 activity by a five‐drug cocktail approach
Authors: Zhu Bing , Ou‐Yang Dong‐Sheng , Chen Xiao‐Ping , Huang Song‐Lin , Tan Zhi‐Rong , He Nan , Zhou Hong‐Hao 
Published: December 2004

ObjectivesOur goal was to establish and validate a modified cocktail approach including probe drugs caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam for simultaneous phenotyping of CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A.MethodsThe study was conducted in 14 healthy, nonsmoking male volunteers with a cocktail of 5 drugs consisting of 100 mg caffeine, 200 mg chlorzoxazone, 100 mg mephenytoin, 100 mg metoprolol, and 7.5 mg midazolam in a randomized manner with a 7 × 7 Latin square design. Plasma was obtained at 1, 4, and 6 hours, and urine was collected from 0 to 8 hours after oral drug administration.ResultsThe phenotypic indexes determined for caffeine, chlorzoxazone, mephenytoin, metoprolol, and midazolam were not significantly different when the drugs were given in different combinations. There were no metabolic interactions or analytic interference of these probe drugs.ConclusionsThis cocktail approach can simultaneously provide independent in vivo phenotypic measures for the cytochrome P450 (CYP) enzymes CYP1A2, CYP2E1, CYP2C19, CYP2D6, and CYP3A.Clinical Pharmacology & Therapeutics (2001) 70, 455–461; doi: 10.1016/S0009‐9236(01)92726‐2
Severe phenytoin intoxication in a subject homozygous for CYP2C9*3
Authors: Brandolese Renato , Scordo Maria Gabriella , Spina Edoardo , Gusella Milena , Padrini Roberto 
Published: December 2004

A 31‐year‐old woman who had a severe head injury was treated with oral phenytoin (100 mg 3 times a day) to prevent posttraumatic seizures. On day 10 of phenytoin treatment, 3 hours after the morning dose, the patient manifested neurologic signs compatible with phenytoin intoxication. Thus drug serum concentrations were monitored daily for 12 days. The elimination half‐life was 103 hours, namely, about 5 times longer than the mean value generally quoted (22 hours). In the absence of any acquired predisposing factor for phenytoin toxicity, genetic mutations in the cytochrome P450 (CYP) enzymes responsible for phenytoin metabolism (CYP2C9 and CYP2C19) were suspected. Genotyping revealed that the patient was homozygous for the CYP2C9*3 allele (CYP2C9*3/*3) and heterozygous for the CYP2C19*2 allele (CYP2C19*1/*2). In view of the markedly reduced metabolic activity of CYP2C*3 in comparison with the wild‐type enzyme (about one fifth) and of the minor role of CYP2C19 in phenytoin metabolism, it is likely that CYP2C9*3 mutation was largely responsible for drug overdose.Clinical Pharmacology & Therapeutics (2001) 70, 391–394; doi: 10.1016/S0009‐9236(01)95478‐5
Studies on crystallization behaviors and crystal morphology of polyamide 66/clay nanocomposites
Authors: Kang Xin , He Suqin , Zhu Chengshen , Wang Liuyang , Lüˇ Liyun , Guo Jianguo 
Published: December 2004

AbstractX‐ray diffraction methods, DSC thermal analysis, and polarized light microscopy (PLM) were used to investigate the structural changes of nylon 66/clay nanocomposites. PA 66/clay nanocomposites were prepared by the method of melt intercalation. The results indicate that the addition of the intercalated organo‐montmorillonite (OMMT) can induce generation of the β‐form crystal of PA 66 and substantially affect the arrangement of molecules in the α‐form crystal, although the crystallinity scarcely changes. Also, the DSC results indicate that the addition of OMMT in the PA 66 matrix leads to increases of crystallization temperatures and the full width at half maximum (FWHM) of the exothermic peaks. Moreover, the viscosity factor is the main influence on FWHM of the exothermic peaks of PA 66/clay nanocomposites. The results of nonisothermal crystallization kinetics show that OMMT has the effect of heterogeneous nucleation and leads to the decrease of the size of the spherocrystal. The heterogeneous nucleation effects of OMMTs influence the mechanism of crystallization and the growth mode of PA 66 crystals. PLM photographs verify that the size of spherocrystal is decreased and visually confirm the theory of crystallization kinetics. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 756–763, 2005
Studies on physico‐mechanical and optical properties, and WAXS of castor oil based polyurethane/polyacrylates interpenetrating polymer networks
Authors: Siddaramaiah  , Mallu P. , Roopa S. , Somashekarappa H. , Somashekar R. 
Published: December 2004

AbstractInterpenetrating polymer networks (IPNs) of polyurethane (PU)/polyacrylates have been synthesized by sequential polymerization of castor oil, methylene diisocyanate (MDI), and acrylate monomers such as methyl acrylate (MA), methyl methacrylate (MMA), and ethyl acrylate (EA); with benzoyl peroxide (BPO) and ethylene glycol dimethyl acrylate (EGDM) as an initiator and crosslinker, respectively. The physico‐mechanical properties, such as density, surface hardness, tensile strength, percentage elongation at break, and tear strength; and the optical properties, like total transmittance and haze, of PU/polyacrylate IPNs have been reported. Microcrystalline parameters of IPNs have been computed by using wide angle X‐ray scattering (WAXS) recordings. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 764–773, 2005
KiSS‐1 expression and metastin‐like immunoreactivity in the rat brain
Authors: Brailoiu G. Cristina , Dun Siok L. , Ohsawa Masahiro , Yin Deling , Yang Jun , Chang Jaw Kang , Brailoiu Eugen , Dun Nae J. 
Published: December 2004

AbstractMetastin, the gene product of metastasis suppressor gene KiSS‐1, is the endogenous ligand for the G‐protein‐coupled receptor GPR54 (or AXOR12, or OT7T175). The expression of KiSS‐1 gene and peptide and the distribution of metastin were studied in the rat central nervous system by reverse transcriptase‐polymerase chain reaction, Western blotting, and immunohistochemical methods. KiSS‐1 gene and peptide expression was higher in the hypothalamus than in the brainstem and spinal cord. In the brain, metastin‐like immunoreactivity (irMT) was found mainly in three groups of cells: dorsomedial hypothalamic nucleus, nucleus of the solitary tract, and caudal ventrolateral medulla. Immunoreactive fibers of varying density were noted in bed nucleus of stria terminalis, septal nuclei, nucleus accumbens, caudate putamen, diagonal band, amygdala, hypothalamus, zona incerta, thalamus, periaqueductal gray, raphe nuclei, lateral parabrachial nucleus, locus coeruleus, spinal trigeminal tract, rostral ventrolateral medulla, and medullary reticular nucleus. Preabsorption of the antiserum with metastin peptide fragment (45–54)‐NH2 (1 μg/ml) resulted in no staining in any of the sections. The biological activity of metastin was assessed by monitoring intracellular calcium [Ca2+]i in cultured hippocampal neurons, which are known to express GPR54. Metastin increased [Ca2+]i in a population of cultured hippocampal neurons. The results show that metastin is biologically active in rat central neurons, and its anatomical distribution suggests a possible role in nociception and autonomic and neuroendocrine functions. J. Comp. Neurol. 481:314–329, 2005. © 2004 Wiley‐Liss, Inc.
Regional, cellular, and subcellular localization of RGS10 in rodent brain
Authors: Waugh Jeff L. , Lou Angela C. , Eisch Amelia J. , Monteggia Lisa M. , Muly E. Chris , Gold Stephen J. 
Published: December 2004

AbstractTheregulator ofGproteinsignaling type 10 (RGS10) modulates Gαi/o signaling by means of its GTPase accelerating activity and is abundantly expressed in brain and in immune tissues. To elucidate RGS10 function in the nervous system, we mapped RGS10 protein in rat and mouse brain using light microscopic (LM) and electron microscopic (EM) immunohistochemical techniques. The LM showed that RGS10‐like immunoreactivity (LIR) labels all cellular subcompartments of neurons and microglia, including their nuclei. There were several differences between RGS10‐LIR distributions in rat and mouse, the most striking of which were the far denser immunoreactivity in rat dentate gyrus and dorsal raphe. The EM analysis corroborated and extended our findings from LM. Thus, EM confirmed the presence of dense RGS10‐LIR in the euchromatin compartment of nuclei. The EM analysis also resolved dense staining on terminals at symmetric synapses onto pyramidal cell somata. Dual immunofluorescence showed that forebrain interneurons densely labeled with RGS10‐LIR partially colocalized with parvalbumin‐LIR. Dual‐labeling histochemistry in caudoputamen demonstrated that densely labeled striatal cells were biased to the indirect‐projecting output pathway. Dual‐labeling immunofluorescence also showed that densely labeled RGS10‐LIR cells in the dentate gyrus subgranular zone were not proliferating but that newly born cells could differentiate to express RGS10‐LIR. Taken together, these data support a role for RGS10 in diverse processes that include modulation of pre‐ and postsynaptic G‐protein signaling. Moreover, enrichment of RGS10 in transcriptionally active regions of the nucleus suggests an unforeseen role of RGS10 in modulating gene expression. J. Comp. Neurol. 481:299–313, 2005. © 2004 Wiley‐Liss, Inc.
Comparison of the expression patterns of five neural RNA binding proteins in the Xenopus retina
Authors: Amato Marcos A. , Boy Sébastien , Arnault Emilie , Girard Manon , Della Puppa Alice , Sharif Ariane , Perron Muriel 
Published: December 2004

AbstractAn increasing body of evidence indicates that gene expression can be modulated by posttranscriptional mechanisms. RNA binding proteins, for instance, control gene expression at many regulatory levels including RNA splicing, transport, stability, and translation. Although numerous RNA binding proteins have been identified, very few have been studied extensively in the context of developmental processes. We focused our study on five neural RNA binding proteins: one Musashi homolog, Nrp‐1, one member of the Bruno gene family, BruL‐1 (also known as Etr‐1), and three members of the ELAV/Hu family, ElrB, ElrC, and ElrD. As an initial step in addressing their function during Xenopus neurogenesis, we used in situ hybridization to determine their expression patterns during retinal development. We found that RNA binding proteins belonging to different families have distinct spatio‐temporal expression. These combinatorial expression patterns are reminiscent of previously described cell type‐specific expression patterns of transcription factors during retinal development. The distribution of RNA binding proteins within the retina suggests that these regulators of posttranscriptional events may play important roles in multiple steps of retinogenesis. J. Comp. Neurol. 481:331–339, 2005. © 2004 Wiley‐Liss, Inc.
Fibronectin adsorption and arrangement on copolymer surfaces and their significance in cell adhesion
Authors: Kowalczyńska Hanna M. , Nowak‐Wyrzykowska Małgorzata , Kołos Robert , Dobkowski Jacek , Kamiński Jarosław 
Published: December 2004

AbstractThe adsorption of fibronectin (FN) to (styrene/methyl methacrylate) copolymer surfaces, both sulfonated (hydrophilic) and nonsulfonated (hydrophobic), was studied by means of the radioisotope (125I‐FN) and ELISA assays; the latter employed monoclonal antibodies. It was found that the radioiodination‐derived isotherms did not follow the Langmuir‐type adsorption law within the FN concentration range studied; rather, a quasi‐linear FN surface density versus bulk concentration dependence was observed. These isotherms, and our recent ELISA measurements with polyclonal antibodies, allowed us to estimate saturative FN surface densities, which were, within the experimental error, similar on both types of surfaces. This suggested the amount of adsorbed FN to be not responsible for observed differences in leukaemia L1210 cell adhesion (FN‐coated sulfonated surfaces are far more pro‐adhesive than their nonsulfonated analogues). The presumption that these differences are induced by changes in the FN arrangement was confirmed by the use of monoclonal antibodies directed against distinct FN domains, and by the blocking of α5β1 integrin receptor with the synthetic Gly‐Arg‐Gly‐Asp‐Ser‐Pro (GRGDSP) peptide. The RGD sequence located within the FN cell‐binding domain seems to be masked in the structure adopted on nonsulfonated surfaces, which hinders the integrin–ligand interaction. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res 72A: 228–236, 2005