bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time‐dependent Effect of Kainate‐induced Seizures on Glutamate Receptor GluR5, GluR6, and GluR7 mRNA and Protein Expression in Rat Hippocampus
Authors: Ullal Gautam , Fahnestock Margaret , Racine Ronald 
Published: April 2005

Summary:  Purpose: Glutamate receptor 6 is strongly implicated in human refractory epilepsy and in kainic acid (KA)‐induced status epilepticus (SE). In vitro pharmacologic studies with newer antiepileptic drugs (AEDs) are increasingly indicating the role of glutamate receptor 5 (GluR5) in epilepsy. Glutamate receptor 7 (GluR7) has been the least investigated in the context of epilepsy. We studied the messenger ribonucleic acid (mRNA) and protein expression of GluR5, GluR6, and GluR7 in rat hippocampus 72 h, 90 days, and 180 days after KA‐induced SE. Methods: SE was induced by injecting KA intraperitoneally (i.p.) into adult rats. The hippocampi were isolated 72 h, 90 days, and 180 days after SE. Reverse transcription–polymerase chain reaction (RT‐PCR) was performed for mRNA expression. Western blots determined the protein expression. Results: A significant increase was noted in GluR5 expression in KA‐treated animals compared with controls at 72 h and 180 days, with no significant difference at the intervening 90‐day point. Protein levels for GluR5 increased at 72 h and remained elevated until 180 days. GluR7 mRNA showed a significant decrease at 90 days after seizures. Neither the mRNA expression nor the protein levels of GluR6 differed from controls at any of the times after SE. Conclusions: KA‐induced SE leads to an upregulation of GluR5 mRNA and protein and a downregulation of GluR7 mRNA in rat hippocampus, with no change in GluR6 mRNA or protein expression.
Cost‐effectiveness of First‐line Antiepileptic Drug Treatments in the Developing World: A Population‐level Analysis
Authors: Chisholm Dan ,   WHO‐CHOICE
Published: April 2005

Summary: Purpose:To establish the population‐level costs and cost‐effectiveness of first‐line antiepileptic drug (AED) treatments for reducing the treatment gap in developing countries.Methods:A population model was applied to nine World Health Organization (WHO) developing subregions to estimate the impact of four first‐line AEDs in the primary care management of (ICD‐10 defined) idiopathic epilepsy and epileptic syndromes: phenobarbitone (PB), phenytoin (PHT), carbamazepine (CBZ), and valproic acid (VPA). The efficacy of treatment was gauged in terms of improvements to both disability and recovery, subsequently adjusted for treatment coverage, response, and adherence. Total population‐level treatment effects (measured in disability‐adjusted life years or DALYs averted) and treatment costs (measured in international dollars; I$) were combined to form ratios of cost‐effectiveness.Results:Across nine developing WHO subregions, extending AED treatment coverage to 50% of primary epilepsy cases would avert between 150 and 650 DALYs per one million population (equivalent to 13–40% of the current burden), at an annual cost per capita of I$ 0.20–1.33. Older first‐line AEDs (PB, PHT) were most cost‐effective on account of their similar efficacy but lower acquisition cost (I$ 800–2,000 for each DALY averted).Conclusions:A significant proportion of the current burden of epilepsy in developing countries is avertable by scaling‐up the routine availability of low‐cost AEDs. Critical factors in the successful implementation of such a scaled‐up level of service delivery, apart from renewed political support and investment, relate to appropriate training and continuity of drug supply.
Biting Behavior, Aggression, and Seizures
Authors: Alberto Tassinari Carlo , Tassi Laura , Calandra‐Buonaura Giovanna , Stanzani‐Maserati Michelangelo , Fini Nicola , Pizza Fabio , Sartori Ivana , Michelucci Roberto , Lo Russo Giorgio , Meletti Stefano 
Published: April 2005

Summary: Purpose:To describe the semiologic features of aggressive behaviors observed in human epileptic seizures with particular reference to the act of biting a conspecific.Methods:We analyzed the biting behavior (BB) and other aggressive gestures occurring in a group of 11 patients retrospectively selected from >1,000 patients subjected to video‐EEG/SEEG monitoring for presurgical evaluation of drug‐resistant seizures.Results:Patients displaying BB showed (a) a male sex predominance, (b) heterogeneous etiologies and lesion locations, and (c) seizures involving the frontotemporal regions of both hemispheres. The act of biting was a rapid motor action, lasting ∼600 ms, occurring in the context of strong emotional arousal, fear, and anger, with various bodily gestures with aggressive connotation. BB was mainly a “reflexive” behavior, in that biting acts were evoked (both during and after seizures) by actions of people in close contact with the patient. The sole intrusion of the examiner's hand in the space near the patient's face was effective in triggering BB. Rarely, self‐directed or object‐directed biting acts were not triggered by external stimuli. Intracranial data (SEEG) obtained in one subject showed that the amygdala/hippocampal region plus the orbitomedial prefrontal cortex had to be involved by ictal activity to observe BB.Conclusions:Anatomic and electrophysiologic data in our patients suggest that a model of dual—temporal and frontal—dysfunction could account for the occurrence of ictal/postictal BB. Behavioral data suggest also that BB and related aggressive gestures can be considered as the emergence of instinctive behaviors with an adaptative significance of defense of the peripersonal space.
PROPERTIES OF CARICA PAPAYA L. (PAPAYA) SEED OIL FOLLOWING EXTRACTIONS USING SOLVENT AND AQUEOUS ENZYMATIC METHODS
Authors: PUANGSRI T. , ABDULKARIM S.M. , GHAZALI H.M. 
Published: April 2005

ABSTRACT The physico‐chemical properties of oil from Carica papaya were determined following extraction with petroleum ether and aqueous‐enzymatic methods. Four commercial enzymes were used for the enzymatic extraction, namely, Termamyl 120 L, Type L (α‐Amylase), Neutrase®0.8 L (Neutral protease), Celluclast®1.5 L FG (Cellulase) and Pectinex®Ultra SP‐L (Pectinase). The melting point of the oil was 9.7–10.5C and showed that there was no significant difference (P > 0.05) between the oil obtained from enzyme and solvent extractions. Generally, the color of the oil was reddish yellow. Solvent‐extracted oil tended to have more yellow and red color (24 Y + 4.0 R) compared to enzyme‐extracted oil (20 Y + 3.0 R). The iodine and the saponification values of the solvent‐extracted oil were found to be 66.0 and 154.7, respectively, while those of the enzyme extracted oil were 66.2–69.3 and 154.2–161.7, respectively. The unsaponifiable matter of the oil extracted using different enzymes ranged between 2.07 and 2.90% and were significantly different (P < 0.05) from that of the solvent‐extracted oil (1.39%). The predominant fatty acid in the oil was oleic acid (72–78%), with some palmitic (12–14%), stearic (4–5%) and linoleic (2.5–3.5%) acids with no significant difference in fatty acid compositions between oil extracted using solvent and enzymes. The main triacylglycerols (TAGs) were sn‐glycerol‐oleate‐oleate‐oleate (OOO) (43.5–45.5%) and 1‐palmitoyl‐dioleoyl glycerol (POO) +stearoyl‐oleoyl‐linoleoyl glycerol (SOL) (29.5–30.5%).
RHEOLOGICAL BEHAVIOR OF POMEGRANATE (PUNICA GRANATUM L.) JUICE AND CONCENTRATE
Authors: ALTAN AYLİN , MASKAN MEDENİ 
Published: April 2005

ABSTRACT The rheological behavior of pomegranate juice (Punica granatum L.), prepared from fresh pomegranates, was studied as a function of solids concentration in the range 17.5–75°Brix at 10–55C, using a controlled stress rheometer. Concentration methods did not influence flow behavior. There were no significant differences (P > 0.05) between viscosity and activation energy values for the pomegranate juices concentrated by different methods. The juices exhibited Newtonian behavior regardless of the concentration method. The effect of temperature was described by an Arrhenius‐type equation with an activation energy in the range 5.34–32.2 kJ/mol depending on concentration. An exponential model described better the effect of the soluble solids on the viscosity and Eavalues. A simple equation was proposed for describing the combined effect of temperature and soluble solids content on the juice viscosity.
EFFECT OF ADDED SALT ON TEXTURAL PROPERTIES OF HEAT‐INDUCED GELS MADE FROM GUM–PROTEIN MIXTURES
Authors: TOTOSAUS A. , GUERRERO I. , MONTEJANO J.G. 
Published: April 2005

ABSTRACT Large deformation rheological tests were employed to determine the textural differences in heat‐induced gel systems. Three different large deformation rheological methods (viscosity index and apparent elasticity, texture profile analysis (TPA) and torsional fracture) were employed to study the dependence of the ion type on the textural properties of heat‐induced mixed protein–gum gels. Protein–gum mixed solutions were prepared with bovine serum albumin (BSA) or egg white albumin (EWA) (20% w/v) with κ‐carrageenan (KCG), gellan (GLN) or xanthan gums (XNT) (0.5% w/v) at 0.1 M sodium chloride (NaCl), potassium chloride (KCl) or no added salt. Despite inherent differences in protein type, the main effect on the textural properties evaluated was for the kind of salt added, since potassium ions, with a strong influence on KCG and GLN gelation, affected the parameters related to the structure or hardness of the samples. There was no significant effect on parameters associated with sample ductility or elasticity. GLN formed stronger gels than KCG, whereas XNT did not perform as well in gel formation since it does not contribute to protein matrix formation. The results indicated that potassium may be substituted for sodium ions at low ionic strengths in foods where the incorporation of KCG or GLN helps to improve texture and related features.
Clinically Relevant Genotype Interpretation of Resistance to Didanosine
Authors: Marcelin Anne-Geneviève , Flandre Philippe , Pavie Juliette , Schmidely Nathalie , Wirden Marc , Lada Olivier , Chiche Dan , Molina Jean-Michel , Calvez Vincent 
Published: April 2005

ABSTRACTWe analyzed the didanosine (ddI) arm of the randomized, placebo-controlled Jaguar trial in order to define a genotypic score for ddI associated with virologic response. In this arm, 111 patients experiencing virologic failure received ddI in addition to their current combination therapy for 4 weeks. The impact of mutations in the reverse transcriptase gene on the virologic response to ddI was studied in univariate analysis. Genotypic score was constructed using step-by-step analyses first including only mutations associated to poorer virologic response (scored as +1), while secondarily, mutations associated to a better response (scored as −1) were also eligible. Eight mutations were associated with a reduced response to ddI, M41L, D67N, T69D, L74V, V118I, L210W, T215Y/F, and K219Q/E, and two mutations were associated with a better response, K70R and M184V/I. The best prediction of the virologic response to ddI was obtained with a composite score comprising mutations added and subtracted (set II, M41L + T69D + L74V+ T215Y/F + K219Q/E − K70R − M184V/I;P= 4.5 × 10−9) and by comparing that to only mutations added (set I, M41L + T69D + L74V + L210W + T215Y/F + K219Q/E;P= 1.2 × 10−7). Patients had a human immunodeficiency virus RNA reduction of 1.24, 0.84, 0.61, 0.40, and 0.07 log10copies/ml when they were ranked as having a genotypic score II of −2, −1, or 0 or 1 and 2 mutations or more, respectively. In conclusion, we developed and validated a genotypic score, taking into account mutations negatively and positively impacting the virologic response to ddI.
Molecular Characterization of MexL, the Transcriptional Repressor of the
mexJK
Multidrug Efflux Operon in
Pseudomonas aeruginosa
Authors: Chuanchuen Rungtip , Gaynor Jared B. , Karkhoff-Schweizer RoxAnn , Schweizer Herbert P. 
Published: April 2005

ABSTRACT

The
Pseudomonas aeruginosa mexJK
efflux operon is constitutively expressed in mutants with defects in the upstream
mexL
gene, which encodes a repressor of the TetR family. MexL and a MexL
A47D
mutant protein were purified from
Escherichia coli
as fusion proteins with carboxy-terminal hexahistidine tags. Native polyacrylamide gel electrophoresis and size exclusion chromatography revealed that MexL is a tetramer in solution. MexL and MexL
A47D
oligomerization was confirmed using a genetic approach, and the MexL
A47D
mutant protein was not impaired in multimerization. Gel mobility shift and footprinting assays demonstrated that MexL, but not MexL
A47D
, binds specifically to the 94-bp
mexL-mexJ
intergenic region to sequences located between positions −84 and −20 from the
mexJ
initiation codon. MexL protected about 60 nucleotides on each strand, and the protected regions overlapped almost perfectly, a finding consistent with MexL regulating the expression of both
mexL
and
mexJK
, which was ascertained by gene fusion analyses. The protected region contains predicted −10 and −35 promoter sequences for both
mexL
and
mexJ
, with partially overlapping −10 regions. The
mexL
promoter assignment was verified by mapping the
mexL
transcription start site, and the
mexJ
promoter was localized to the predicted regions using
lacZ
fusions. The MexL-protected region contains two inverted GTATTT repeats, and their location in the protected region and overlap with the
mexL
and
mexJ
promoter sequences strongly support a role in MexL binding.
Evaluation by Monte Carlo Simulation of the Pharmacokinetics of Two Doses of Meropenem Administered Intermittently or as a Continuous Infusion in Healthy Volunteers
Authors: Krueger Wolfgang A. , Bulitta Jurgen , Kinzig-Schippers Martina , Landersdorfer Cornelia , Holzgrabe Ulrike , Naber Kurt G. , Drusano George L. , Sörgel Fritz 
Published: April 2005

ABSTRACT

Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The pharmacokinetics of meropenem were studied in two groups, each comprising eight healthy volunteers who received the following doses: 500 mg as an intravenous infusion over 30 min three times a day (t.i.d.) versus a 250-mg loading dose followed by a 1,500 mg continuous infusion over 24 h for group A and 1,000 mg as an intravenous infusion over 30 min t.i.d. versus a 500-mg loading dose followed by a 3,000-mg continuous infusion over 24 h for group B. Meropenem concentrations in plasma and urine were determined by liquid chromatography-mass spectrometry/mass spectrometry and high-performance liquid chromatography with UV detection, respectively. Pharmacokinetic calculations were done by use of a two-compartment open model, and the data were extrapolated by Monte Carlo simulations for 10,000 simulated subjects for pharmacodynamic evaluation. There were no significant differences in total clearance and renal clearance between group A and group B or between the intermittent treatment and the continuous infusion. The analyses of the probability of target attainment by MIC for the high- and low-dose continuous infusions were robust up to MICs of 4 mg/liter and 2 mg/liter, respectively. The corresponding values for intermittent infusions were only 0.5 mg/liter and 0.25 mg/liter. When these observations were correlated with MICs obtained from the MYSTIC database, intermittent infusion results in adequate activity against two of the most common nosocomially acquired pathogens,
Klebsiella pneumoniae
and
Enterobacter cloacae
. However, against
Pseudomonas aeruginosa
, the evaluation shows a clear advantage of high-dose therapy administered as a continuous infusion. We believe that in the empirical therapy situation, the continuous-infusion mode of administration is most worth the extra efforts. We conclude that clinical trials for evaluation of the continuous infusions of meropenem in critically ill patients are warranted.
Behavior of Thymidylate Kinase toward Monophosphate Metabolites and Its Role in the Metabolism of 1-(2′-Deoxy-2′-Fluoro-β-
l
-Arabinofuranosyl)-5-Methyluracil (Clevudine) and 2′,3′-Didehydro-2′,3′-Dideoxythymidine in Cells
Authors: Hu Rong , Li Ling , Degrève Bart , Dutschman Ginger E. , Lam Wing , Cheng Yung-Chi 
Published: April 2005

ABSTRACT

l
-Nucleoside analogs are a new class of antiviral and anticancer agents, several of which are currently used in the clinic. The phosphorylation of these agents to the triphosphate form is thought to be important for exertion of their pharmacological activities. 1-(2′-Deoxy-2′-fluoro-β-
l
-arabinofuranosyl)-5-methyluracil (
l
-FMAU; Clevudine) is a thymidine analog that is currently under phase III clinical trials as an anti-human hepatitis B virus agent. We examined the behavior of its monophosphate metabolite with human recombinant thymidylate kinase (TMPK) and showed that
l
-FMAU monophosphate (
l
-FMAUMP) is a poorer substrate than its
d
-configuration anomer (
d
-FMAUMP). The phosphorylation efficiency of
l
-FMAUMP is similar to that of the monophosphate of 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T), an anti-human immunodeficiency virus analog, both of which are approximately 1% TMP. To clarify the role of human TMPK in the phosphorylation of
l
-FMAUMP to the diphosphate metabolite in cells, a Tet-On inducible human TMPK cell line system was established. In this system, the expression of TMPK is closely regulated in response to various concentrations of doxycycline. When the cells were treated with
l
-FMAU or d4T, the amounts of the diphosphate and triphosphate metabolites of these analogs were increased, in accordance with an increase in human TMPK activity in cells. In conclusion, this is the first demonstration of the behavior of TMPK toward
l
-FMAUMP. This study indicates that human TMPK can phosphorylate
l
-FMAUMP and play a critical role in
l
-FMAU metabolism in cells.
Seven Novel Variants of the Staphylococcal Chromosomal Cassette
mec
in Methicillin-Resistant
Staphylococcus aureus
Isolates from Ireland
Authors: Shore Anna , Rossney Angela S. , Keane Conor T. , Enright Mark C. , Coleman David C. 
Published: April 2005

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) isolates recovered in Irish hospitals between 1971 and 2002 were characterized using multilocus sequence typing (MLST) (
n
= 130) and SCC
mec
typing (
n
= 172). Where atypical SCC
mec
typing results were obtained, PCR amplification of entire SCC
mec
elements, analysis of amplimer mobility, and nucleotide sequencing were undertaken. MLST revealed that 129/130 isolates had the same genotypes as internationally spread MRSA clones, including ST239, ST247, ST250, ST5, ST22, ST36, and ST8. A novel genotype, ST496, was identified in one isolate. Half of the isolates (86/172) had SCC
mec
type I, IA, II, III, or IV. The remaining 86 isolates harbored novel SCC
mec
variants in three distinct genetic backgrounds: (i) 74/86 had genotype ST8 and either one of five novel SCC
mec
II (IIA, IIB, IIC, IID, and IIE) or one of two novel SCC
mec
IV (IVE and IVF) variants; (ii) 3/86 had genotype ST239 and a novel SCC
mec
III variant; (iii) 9/86 had a novel SCC
mec
I variant associated with ST250. SCC
mec
IVE and IVF were similar to SCC
mec
IVc and IVb, respectively, but differed in the region downstream of
mecA
. The five SCC
mec
II variants were similar to SCC
mec
IVb in the region upstream of the
ccr
complex but otherwise were similar to SCC
mec
II, except for the following regions: SCC
mec
IIA and IID had a novel
mec
complex, A.4 (Δ
mecI
-IS
1182-
Δ
mecI-mecR1-mecA-
IS
431mec
); SCC
mec
IIC and IIE had a novel
mec
complex, A.3 (IS
1182
-Δ
mecI
-
mecR1-mecA-
IS
431mec
); SCC
mec
IID and IIE lacked pUB110; SCC
mec
IIC and IIE lacked a region of DNA between Tn
554
and the
mec
complex; and SCC
mec
IIB lacked Tn
554
. This study has demonstrated a hitherto-undescribed degree of diversity within SCC
mec
.
Prevalence and Characterization of Invasive Isolates of
Streptococcus pyogenes
with Reduced Susceptibility to Fluoroquinolones
Authors: Powis Jeff , McGeer Allison , Duncan Carla , Goren Ryan , de Azavedo Joyce C. S. , Bast Darrin J. , Pong-Porter Sylvia , Mazzulli Tony , Green Karen , Willey Barbara , Low Donald E. 
Published: April 2005

ABSTRACT

Fluoroquinolone susceptibility testing was performed on invasive group A streptococcus isolates from 1992-1993 and 2003 from Ontario, Canada. None were nonsusceptible to levofloxacin. Two of 153 (1.3%) from 1992-1993 and 7 of 160 (4.4%) from 2003 had a levofloxacin MIC of 2 μg/ml; all nine had
parC
mutations, and eight were serotype M6.
Discovery of Small-Molecule Human Immunodeficiency Virus Type 1 Entry Inhibitors That Target the gp120-Binding Domain of CD4
Authors: Yang Quan-en , Stephen Andrew G. , Adelsberger Joseph W. , Roberts Paula E. , Zhu Weimin , Currens Michael J. , Feng Yaxiong , Crise Bruce J. , Gorelick Robert J. , Rein Alan R. , Fisher Robert J. , Shoemaker Robert H. , Sei Shizuko 
Published: April 2005

ABSTRACTThe interaction between human immunodeficiency virus type 1 (HIV-1) gp120 and the CD4 receptor is highly specific and involves relatively small contact surfaces on both proteins according to crystal structure analysis. This molecularly conserved interaction presents an excellent opportunity for antiviral targeting. Here we report a group of pentavalent antimony-containing small molecule compounds, NSC 13778 (molecular weight, 319) and its analogs, which exert a potent anti-HIV activity. These compounds block the entry of X4-, R5-, and X4/R5-tropic HIV-1 strains into CD4+cells but show little or no activity in CD4-negative cells or against vesicular stomatitis virus-G pseudotyped virions. The compounds compete with gp120 for binding to CD4: either immobilized on a solid phase (soluble CD4) or on the T-cell surface (native CD4 receptor) as determined by a competitive gp120 capture enzyme-linked immunosorbent assay or flow cytometry. NSC 13778 binds to an N-terminal two-domain CD4 protein, D1/D2 CD4, immobilized on a surface plasmon resonance sensor chip, and dose dependently reduces the emission intensity of intrinsic tryptophan fluorescence of D1/D2 CD4, which contains two of the three tryptophan residues in the gp120-binding domain. Furthermore, T cells incubated with the compounds alone show decreased reactivity to anti-CD4 monoclonal antibodies known to recognize the gp120-binding site. In contrast to gp120-binders that inhibit gp120-CD4 interaction by binding to gp120, these compounds appear to disrupt gp120-CD4 contact by targeting the specific gp120-binding domain of CD4. NSC 13778 may represent a prototype of a new class of HIV-1 entry inhibitors that can break into the gp120-CD4 interface and mask the gp120-binding site on the CD4 molecules, effectively repelling incoming virions.