bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and Pharmacodynamics of Ceftizoxime in Patients with Dosages Adjusted for Renal Function
Authors: Neuhauser Melinda M. , McKinnon Peggy S. , Hershberger Ellie , Rybak Michael J. 
Published: June 2004

Study Objective. Our institution developed dosing guidelines for patients with renal impairment based on pharmacokinetic data and class‐specific pharmacodynamics. Ceftizoxime was chosen as a model agent to evaluate if the modified guidelines achieved similar minimal plasma concentration (Cpmin) and time above the minimum inhibitory concentration of the infecting organism (T>MIC) in patients with renal impairment versus those with normal renal function.Design. Prospective pharmacokinetic and pharmacodynamic evaluation of ceftizoxime dosages.Setting. University‐affiliated hospital.Patients. Forty‐three patients with suspected or documented infection were enrolled and classified into four groups based on creatinine clearance (Clcr; ml/min): group 1, above 100; group 2, 61–99; group 3, 31–60; and group 4, 15–30.Interventions. Ceftizoxime serum concentrations were obtained at steady state.Measurements and Main Results. Pharmacokinetic and pharmacodynamic parameters were calculated. As expected, clearance and elimination rate constant were reduced, and half‐life tended to be greater in patients with renal impairment. The Cpmin and area under the concentration‐time curve over 24 hours were similar between groups (p=0.39, p=0.42). The T>MIC was 100% for all patient isolates, and 90% or more versus our clinical strain for all groups. Clinical outcomes were similar among all groups.Conclusion. Our dosing guidelines achieved similar Cpmin among all groups of patients. Our results support that recommendations for dosing adjustments should be based on pharmacokinetic data and must also consider pharmacodynamic parameters.
Systemic exposure to proteasome inhibitors causes a progressive model of Parkinson's disease
Authors: McNaught Kevin St. P. , Perl Daniel P. , Brownell Anna‐Liisa , Olanow C. Warren 
Published: June 2004

AbstractEnvironmental toxins have been implicated in the etiology of Parkinson's disease. Recent findings of defects in the ubiquitin‐proteasome system in hereditary and sporadic forms of the illness suggest that environmental proteasome inhibitors are candidate PD‐inducing toxins. Here, we systemically injected six doses of naturally occurring (epoxomicin) or synthetic (Z‐lle‐Glu(OtBu)‐Ala‐Leu‐al [PSI]) proteasome inhibitors into adult rats over a period of 2 weeks. After a latency of 1 to 2 weeks, animals developed progressive parkinsonism with bradykinesia, rigidity, tremor, and an abnormal posture, which improved with apomorphine treatment. Positron emission tomography demonstrated reduced carbon‐11‐labeled 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane (CFT) binding to dopaminergic nerve terminals in the striatum, indicative of degeneration of the nigrostriatal pathway. Postmortem analyses showed striatal dopamine depletion and dopaminergic cell death with apoptosis and inflammation in the substantia nigra pars compacta. In addition, neurodegeneration occurred in the locus coeruleus, dorsal motor nucleus of the vagus, and the nucleus basalis of Meynert. At neurodegenerative sites, intracytoplasmic, eosinophilic, α‐synuclein/ubiquitin–containing, inclusions resembling Lewy bodies were present in some of the remaining neurons. This animal model induced by proteasome inhibitors closely recapitulates key features of PD and may be valuable in studying etiopathogenic mechanisms and putative neuroprotective therapies for the illness. Ann Neurol 2004
Reaktionen zwischen und in Molekülkristallen
Authors: Braga Dario , Grepioni Fabrizia 
Published: June 2004

AbstractReaktionen in und zwischen Molekülkristallen, insbesondere mechanisch ausgelöste Umsetzungen, werden in diesem Kurzaufsatz diskutiert. Den Schwerpunkt bilden Prozesse innerhalb oder zwischen Festkörpern, die vor allem durch supramolekulare Wechselwirkungen gesteuert werden: Templatcycloadditionen, Bildung von Einschlussverbindungen, Reaktionen von Molekülkristallen mit Umorganisation nichtkovalenter Bindungen und Bildung von Komplexen und Koordinationsverbindungen. Lösungsmittelfreie mechanochemische Verfahren wie Mahlen und Kneten bieten sich als umweltschonende Methoden zur Synthese von molekularen und supramolekularen Feststoffen an.
Sulfotransferases: Structure, Mechanism, Biological Activity, Inhibition, and Synthetic Utility
Authors: Chapman Eli , Best Michael D. , Hanson Sarah R. , Wong Chi‐Huey 
Published: June 2004

AbstractThe sulfonation (also known as sulfurylation) of biomolecules has long been known to take place in a variety of organisms, from prokaryotes to multicellular species, and new biological functions continue to be uncovered in connection with this important transformation. Early studies of sulfotransferases (STs), the enzymes that catalyze sulfonation, focused primarily on the cytosolic STs, which are involved in detoxification, hormone regulation, and drug metabolism. Although known to exist, the membrane‐associated STs were not studied as extensively until more recently. Involved in the sulfonation of complex carbohydrates and proteins, they have emerged as central players in a number of molecular‐recognition events and biochemical signaling pathways. STs have also been implicated in many pathophysiological processes. As a result, much interest in the complex roles of STs and in their targeting for therapeutic intervention has been generated. Progress in the elucidation of the structures and mechanisms of sulfotransferases, as well as their biological activity, inhibition, and synthetic utility, are discussed in this Review.
Astrometry of the 1572 supernova (B Cassiopeiae)
Authors: Green D. W. E. 
Published: June 2004

AbstractContemporary European measurements of the Milky Way supernova of 1572 (B Cas) have been analyzed to compute a modern position for the star in 1572. This work adds to that done by previous 20th‐century authors by using a new procedure and previously unused astrometry by 16th‐century European observers. Comparison is made with earlier analyses and to modern positional data on the supernova remnant (3C 10). (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
New variable stars among or near to H‐alpha emission stars
Authors: Kohoutek L. , Wehmeyer R. 
Published: June 2004

AbstractThis paper is dealing with the discovery of 11 new or new suspected variables, found as a by‐product during the preparation of our Catalogue of Stars in the Northern Milky Way Having H‐alpha in Emission. We give: (1) The coordinates of the variables and of the respective comparison stars; (2) the maximum and the minimum brightnesses of the observed m(pg), which were determined by visual estimation using the brightnesses in Catalogue USNO A2.0; (3) finding charts of the variables together with their comparison stars used (in electronic form only). (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Possible connection between period change and magnetic activity of the very short‐period binary VZ Piscium
Authors: Qian S. B. , Soonthornthum B. , Xiang F. Y. , Zhu L. Y. , He J. J. 
Published: June 2004

AbstractNew times of light minimum of the short‐period (P = 0d.26) close binary system, VZ Psc, are presented. A period investigation of the binary star, by combining the three new eclipse times with the others collected from the literatures, shows that the variation of the period might be in an alternate way. Under the hypothesis that the variation of the orbital period is cyclic, a period of 25 years and an amplitude of 0.d0030 for the cyclic change are determined. If this periodic variation is caused by the presence of a third body, the mass of the third body (m3) should be no less than 0.081M⊙. Since both components of VZ Psc are strong chromospherically active and the level of activity of the secondary component is higher than that of the primary one, the period may be more plausibly explained by cyclic magnetic activity of the less massive component. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Harnessing the potential of chemical defenses from antimicrobial activities
Authors: Lu Chunhua , Shen Yuemao 
Published: June 2004

AbstractResistance to the drugs used in the treatment of many infectious diseases is increasing, while microbial infections are being found to be responsible for more life‐threatening diseases than previously thought. Despite a large investment in the invention and application of high‐throughput screening techniques involving miniaturization and automation, and a diverse array of strategies for designing and constructing various chemical libraries, relatively few new drugs have resulted. Natural products, however, have been a major source of drugs for centuries. Since some of them are produced by organisms as a result of selection in favour of improved defense against competing deleterious microorganisms, in principle they would be less likely to incur resistance. Furthermore, the production of those defensive secondary metabolites is inducible because their original function is a response to environmental challenges. Moreover, symbioses, co‐habitation associations between two or more different species of organisms, are universal in nature, and the production of secondary metabolites by symbiotic microbes may be an important adaptation allowing microbes to affect their hosts. Therefore, co‐culture strategies, using combinations of plant cell–pathogenic microbes, plant cell–endophytes (or symbionts), and symbiont–pathogenic microbes, based on the principles of chemical defense and the known mechanisms of organism interactions, may be an efficient general approach in the search for new anti‐microbial drugs. BioEssays 26:808–813, 2004. © 2004 Wiley Periodicals, Inc.
Glutamine breakdown in rapidly dividing cells: waste or investment?
Authors: Aledo J. Carlos 
Published: June 2004

AbstractTumours, and in general rapidly dividing cells, behave as dissipative devices that apparently waste glutamine, since its consumption seems to exceed both energetic and nitrogen needs. Although not conclusive, there is compelling evidence suggesting that the consumption of such large amounts of glutamine is essential to sustain high rates of cellular proliferation. Herein, I first review the experimental evidence linking proliferation with high rates of glutamine breakdown. Then, the current knowledge on the proteins and activities involved in this high glutamine consumption will be summarized. Finally, the significance of the apparent waste of glutamine will be discussed on bioenergetic grounds. The discussion leads to the hypothesis that glutamine breakdown might energize some endergonic processes, as well as accelerating other exergonic processes related to cellular proliferation. BioEssays 26:778–785, 2004. © 2004 Wiley Periodicals, Inc.
Eye development: a view from the retina pigmented epithelium
Authors: Ramón Martínez‐Morales Juan , Rodrigo Isabel , Bovolenta Paola 
Published: June 2004

AbstractThe retina pigment epithelium (RPE) is a highly specialised epithelium that serves as a multifunctional and indispensable component of the vertebrate eye. Although a great deal of attention has been paid to its transdifferentiation capabilities and its ancillary functions in neural retina development, little is known about the molecular mechanisms that specify the RPE itself. Recent advances in our understanding of the genetic network that controls the progressive specification of the eye anlage in vertebrates have provided some of the initial cues to the mechanisms responsible for RPE patterning. Here, we have outlined many recent findings that suggest that a limited number of transcription factors, including Otx2, Mitf and Pax6 and a few signalling cascades, are the elements required for the onset of RPE specification in vertebrates. Furthermore, using this information and the data available on the specification of the pigmented cells of primitive chordates, we have ventured some hypotheses on the origin of RPE cells during evolution. BioEssays 26:766–777, 2004. © 2004 Wiley Periodicals, Inc.
Tumour necrosis factor α production by polymorphonuclear neutrophils treated with mouse anti‐human CD19 monoclonal antibody
Authors: Nishimura Motoko 
Published: June 2004

AbstractPolymorphonuclear neutrophils (PMNs) play pivotal roles as phagocytic cells in immune defence against bacteria and parasites, exerting their effects by production of reactive oxygen species, several cytokines, chemokines and by phagocytotic reaction. In our investigation of properties of activated PMNs, we discovered that one of the two kinds of mouse anti‐human CD19 monoclonal antibodies (mAbs) clone SJ25‐C1, weakly binds to freshly prepared PMNs. Moreover, the treatment of freshly prepared PMNs with anti‐CD19 mAb (clone SJ25‐C1) at 37°C for 6 h induces the production and the secretion of tumour necrosis factor α (TNF α) by PMNs in vitro which was detectable in culture supernatants by bioassay using mouse cell line L929 cells. The concentration of TNF α secreted into the culture supernatant of PMNs cultured in the presence of anti‐CD19 mAb (clone SJ25‐C1) was higher than those of PMNs treated at 37°C for 6 h with various PMN activators, such as anti‐CD24 mAb, granulocytes‐macrophage colony stimulation factor (GM‐CSF) or interferon γ (IFN γ). In contrast, another clone of anti‐CD19 mAb, HD37, did not bind to freshly prepared PMNs and failed to produce TNF α. To confirm that anti‐CD19 mAb (clone SJ25‐C1)‐treated PMNs definitely produce TNF α, we measured the levels of intracellular expression of TNF α in PMNs permeabilized by saponin. These cells were treated with fluorescence‐conjugated mouse anti‐human TNF α mAb for detection of intracellular TNF α expression. Consequently, large amounts of intracellular TNF α were detected in PMNs treated with anti‐CD19 mAb (clone SJ25‐C1) but not in those treated with anti‐CD19 mAb (clone HD37). Copyright © 2004 John Wiley & Sons, Ltd.
Effect of new and known 1,4‐dihydropyridine derivatives on blood glucose levels in normal and streptozotocin‐induced diabetic rats
Authors: Briede Janīna , Stivriņa Māra , Stoldere Dzintra , Bisenieks Egīls , Uldriķis Jānis , Poikāns Jānis , Makarova Natālija , Duburs Gunārs 
Published: June 2004

AbstractAnalysis of the effect of several 1,4‐DHP Ca2+ channel antagonists on experimental and clinical diabetes shows that structurally similar Ca2+ channel antagonists can exert opposite effects on Ca2+ influx, glucose homeostasis and insulin secretion. The influence of the Ca2+ channel antagonists on pancreatic β cell functions is dependent on lipophilicity, interactions with the cell membrane lipid bilayer, with SNAREs protein complexes in cell and vesicle membranes, with intracellular receptors, bioavailability and time of elimination from several organs and the bloodstream. In the present work we studied the effect at several doses of new compounds synthesized in the Latvian Institute of Organic Synthesis on blood glucose levels in normal and STZ‐induced diabetic rats. The compounds tested were: 1,4‐DHP derivatives cerebrocrast (1), etaftoron (2), OSI‐1190 (3), OSI‐3802 (4), OSI‐2954 (5) and known 1,4‐DHP derivatives: niludipine (6), nimodipine (7) and nicardipine (8) which possess different lipophilicities. Analysis of the structure–function relationships of the effect of 1,4‐DHP derivatives on glucose metabolism showed that cerebrocrast could evoke qualitative differences in activity. Insertion of an OCHF2 group in position 2 of the 4‐phenylsubstituent and propoxyethylgroup R in ester moieties in positions 3 and 5 of the DHP structure, as well as an increase in the number of carbon atoms in the ester moiety, significantly modified the properties of the compound. Thereby cerebrocrast acquired high lipophilicity and membranotropic properties. Cerebrocrast, in a single administration at low doses (0.05 and 0.5 mg kg−1, p.o.), significantly decreased the plasma level of glucose in normal rats and in STZ‐induced diabetic rats returned plasma glucose to basal levels. This effect was characterized by a slow onset and a powerful long‐lasting influence on glucose metabolism, especially in STZ‐induced diabetic rats. Copyright © 2004 John Wiley & Sons, Ltd.
Antioxidant‐associated chemoprevention by sodium selenite in N‐nitrosodiethylamine‐induced and phenobarbital‐promoted hepatocarcinogenesis in rats
Authors: Thirunavukkarasu C. , Babu E. , Ebrahim A. S. , Chandramohan N. , Sakthisekaran D. 
Published: June 2004

AbstractThe anticarcinogenic/antioxidant potential of sodium selenite (Se), a micronutrient, was evaluated on liver tumourigenesis induced by N‐nitrosodiethylamine (DEN) and promoted by phenobarbital (PB; 0.05% in diet). Male, albino rats of the Wistar strain were exposed intravenously to a single dose of DEN (200 mg kg−1 body weight). Se (4 ppm in drinking water) was supplemented before initiation, or during initiation and/or during the promotion period of carcinogenesis. At the end of 16 weeks (after DEN administration) nodular incidence, the total number of nodules and non‐enzymic antioxidants such as vitamin E, vitamin C, total thiol, protein thiol and non‐protein thiol contents were measured in hepatoma, surrounding tissue and kidney tissue of control and experimental groups. In hepatoma‐bearing animals the above biochemical changes were decreased when compared with normal control animals. On Se treatment throughout the study, (20 weeks) the above biochemical changes reverted to normal levels. Pre‐ and post‐treatment with Se also shows a tendency to reverse the above changes. The results indicate that prior application of Se significantly reverses the adverse changes produced during the tumourigenesis. Furthermore, prior applications of Se significantly reduced the cumulative number of tumours per tumour‐bearing animals. The present study reveals the antitumour potential of Se against DEN‐induced liver carcinogenesis. Copyright © 2004 John Wiley & Sons, Ltd.
Protein kinase A activity is associated with metacyclogenesis in Leishmania amazonensis
Authors: Genestra Marcelo , Cysne‐Finkelstein Léa , Leon Leonor 
Published: June 2004

AbstractBecause of the importance of cell signalling processes in proliferation and differentiation, the adenylate cyclase pathway was studied, specifically the protein kinase A (PKA) in Leishmania amazonensis. The PKAs of soluble (SF) and enriched membrane fractions (MF) from infective/non‐infective promastigotes and axenic amastigotes were assayed. In order to purify the PKA molecule, fractions were chromatographed on DEAE‐cellulose columns and the phosphorylative activity was evaluated using [γ32P]‐ATP as the phosphate source. These experiments were performed in the presence of cyclic adenosine monophosphate (cAMP) and an inhibitor of PKA. Our data demonstrated that the PKA activity was significantly higher (about two times) in SF from promastigotes with a high concentration of metacyclic forms, when compared with the non‐infective promastigotes, suggesting an association of this activity and the metacyclogenesis process. A discrete phosphorylative activity in axenic amastigotes was observed. As the adenylate cyclase/cAMP pathway would be involved in the parasite–host interiorization, the PKA activity may constitute a good intracellular target for studies of leishmanicidal drugs. Copyright © 2004 John Wiley & Sons, Ltd.
Influence of diadenosine tetraphosphate (Ap4A) on lipid metabolism
Authors: Rüsing D. , Verspohl E. J. 
Published: June 2004

AbstractDiadenosine polyphosphates (ApxA) are physiologically released and may be partly involved in the pathogenesis of diabetes mellitus. Ap4A (diadenosine tetraphosphate) leads to an increase in blood glucose while it decreases insulin levels in plasma. A possible link between ApxA and diabetes mellitus‐associated diseases such as insulin resistance and hyperlipidemia (plasma free fatty acids, cholesterol and its biosynthesis, triacylglycerols) has not been investigated yet. Parameters such as free fatty acid and cholesterol content in blood were determined enzymically. The biosynthesis of cholesterol and triacylglycerols was determined in HepG2 cells using the radioactive precursor [14C]‐acetate and by using gas chromatography. Plasma free fatty acids were significantly decreased 5 and 10 min after an Ap4A bolus (0.75 mg kg−1 b.w.) given to rats. Plasma cholesterol was reduced 5 and 60 min after Ap4A administration. LPDS (lipoprotein‐deficient serum)‐stimulated cholesterol biosynthesis in HepG2 cells was significantly reduced after 1 h incubation with Ap4A. Triacylglycerol (TAG) biosynthesis in HepG2 cells was not significantly influenced by Ap4A; there was just a tendency for a concentration‐dependent decrease in TAG levels. In conclusion Ap4A as a diabetogenetic compound is not likely to be responsible for the development of insulin resistance or of hyperlipidemia. Parameters such as free fatty acids, cholesterol and triacylglycerols are not elevated by Ap4A, but are even decreased. Ap4A seems to be involved in the development of diabetes mellitus by increasing blood glucose and decreasing plasma insulin as shown earlier, but not in diabetes mellitus‐associated diseases such as insulin resistance or hyperlipidemia. Copyright © 2004 John Wiley & Sons, Ltd.
HCV infective virions can be carried by human platelets
Authors: Pugliese A. , Gennero L. , Cutufia M. , Enrietto M. , Morra E. , Pescarmona P. , Ponzetto A. 
Published: June 2004

AbstractIt has been previously demonstrated that platelets (PLTs) can bind and transport HIV‐1 infectious virions. Hepatitis C virus (HCV)–HIV‐1 co‐infection occurs frequently among users of illicit intravenous drugs, thereby increasing the severity of HIV disease and the evolution towards chronic active hepatitis and hepatocellular carcinoma of HCV‐related hepatitis. In the present study we investigated whether or not PLTs can carry HCV, and studied the binding mechanisms. Purified PLTs, obtained from healthy donors, HCV negative and HIV negative, were adsorbed with HCV‐containing serum and then employed to infect a THP‐1 monocytoid cell line. Replication of HCV was observed as shown by positivity for the E2 antigen within THP‐1 cells, by indirect immunofluorescence; moreover, HCV‐RNA was detected in supernatants of THP‐1 cells at day 7 post‐incubation with HCV‐adsorbed PLTs. The binding of HCV to PLTs seems to involve fibronectin (FN), as already shown in the case of HIV‐1. Indeed, treatment with RGD (Gly‐Arg‐Gly‐Asp‐Ser), the key oligopeptide of FN binding, inhibits the ability of HCV to be carried by PLTs in infective forms; the same phenomenon occurs with Mabs to FN. Moreover the infection of THP‐1 cells seems to increase FN surface expression, as demonstrated by immunofluorescence tests. Copyright © 2004 John Wiley & Sons, Ltd.