bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dronedarone: An Amiodarone Analog for the Treatment of Atrial Fibrillation and Atrial Flutter
Authors: Dale Krista M , White C Michael 
Published: March 2007

Objective:To review the pharmacology, pharmacokinetics, clinical efficacy, and safety profile of dronedarone for the treatment of atrial fibrillation.Data Sources:A literature search was conducted using the search terms dronedarone, SR 33589, atrial fibrillation, and antiarrhythmic medication in MEDLINE (1966–February 2007), International Pharmaceutical Abstracts (1970–February 2007), and EMBASE (1990–February 2007). References from the identified trials and selected review articles were evaluated. Additional information, including abstracts and posters, was obtained from Sanofi-Aventis.Study Selection and Data Extraction:Published studies and meeting abstracts evaluating the effects of dronedarone in humans and animals were reviewed.Data Synthesis:Dronedarone is a novel antiarrhythmic medication to treat atrial fibrillation. Dronedarone has a multifaceted mechanism of action similar to that of amiodarone. Dronedarone works by blocking potassium, sodium, and calcium channels and exhibits antiadrenergic properties. The drug has been evaluated at doses of 400, 600, and 800 mg twice daily. It prolonged the time to atrial fibrillation recurrence to 60–158 days compared with 5–59 days with placebo and decreased heart rate during atrial fibrillation by 12–25 beats/min in clinical trials. Major adverse events include gastrointestinal side effects and risk of proarrhythmia. Dronedarone may increase the risk of mortality in patients with congestive heart failure.Conclusions:Dronedarone is a new antiarrhythmic agent for the treatment of atrial fibrillation. Further studies are needed to better define dronedarone's safety profile and place in therapy.
Use of Atypical Antipsychotics in the Treatment of Autistic Disorder
Authors: Stachnik Joan M , Nunn-Thompson Cheryl 
Published: March 2007

Objective: To review clinical trials and reports describing the efficacy and safety of atypical antipsychotics (olanzapine, ziprasidone, quetiapine, aripiprazole) in the treatment of autistic or other pervasive developmental disorders. Data Sources: English-language publications from the MEDLINE database (1966–February 2007) including clinical trials, case reports, and retrospective series were reviewed. Study Selection and Data Extraction: Relevant data were extracted from studies of selected atypical antipsychotics in the treatment of autistic disorder in children, adolescents, and adults. Most literature found was in the form of case reports or case series; however, several open-label and double-blind trials were also identified. Data Synthesis: Autistic disorder is a chronic neurodevelopmental disorder with limited treatment options. Nonpharmacologic approaches may be the most beneficial, but pharmacologic agents are needed for some patients with significant behavioral manifestations of the disorder. The atypical antipsychotics (olanzapine, ziprasidone, quetiapine, aripiprazole) have shown some efficacy in improving certain behavioral symptoms of autistic disorder—primarily aggressiveness, hyperactivity, and self-injurious behavior. Efficacy was based on observation or changes from baseline in behavioral rating scores. Data appear to be strongest for olanzapine compared with quetiapine, with several open-label trials suggesting its efficacy. Weight gain and sedation were frequently reported adverse events with both agents. Aripiprazole has demonstrated efficacy in limited case series, with minimal adverse effects reported. Conclusions: Atypical antipsychotics represent a treatment option for symptoms associated with autistic disorder. However, these drugs do not affect the core symptoms of autistic disorder and are associated with potentially significant adverse effects. In addition, there is a lack of randomized controlled trials to determine the true efficacy and long-term safety of these agents in the pediatric population.
The Role of Statin Therapy in Sepsis
Authors: Chua Doson , Tsang Ruth S , Kuo I Fan 
Published: March 2007

Objective: To systematically review the evidence evaluating the role of statin therapy in sepsis. Data Sources: MEDLINE, EMBASE, and PubMed were searched (1980–January 2007) for English-language clinical trials that evaluated the use of statins and the development and treatment of sepsis in human subjects. Search terms included statin, HMG-CoA reductase inhibitor, bacteremia, sepsis, septic shock, septicemia, and severe sepsis. In addition, pertinent references from identified articles were obtained. Study Selection and Data Extraction: Only clinical trials with primary efficacy outcomes of mortality, incidence of sepsis, and severe sepsis were included. Data Synthesis: Seven retrospective and 2 prospective cohort studies were included in this review. One was excluded because the patient population was not experiencing sepsis. Three studies demonstrated a reduced mortality with statin use while 2 other studies did not demonstrate this mortality benefit. One study suggested increased mortality with statin use in sepsis. Three studies showed a reduced incidence of development of sepsis or sepsis-related outcomes, while one study did not. The observational and retrospective nature of these studies and the higher rate of cardiovascular comorbidities in the statin groups may have allowed for a confounding influence. The conflicting results and heterogeneity between the studies makes the observed association between statin use and incidence of sepsis and sepsis-related mortality inconclusive. The clinical benefit of statin therapy in sepsis remains to be determined. Conclusions: There is an association between statin use and a lower incidence of sepsis and sepsis-related mortality. However, a causal relationship between stalin use and reduced sepsis-related mortality has not yet been established. Currently, statins cannot be recommended for sepsis prevention or treatment until controlled trials are performed.
Medicine Use Among 11- and 13-Year-Olds: Agreement Between Parents' Reports and Children's Self-Reports
Authors: Andersen Anette , Krølner Rikke , Holstein Bjørn E , Due Pernille , Hansen Ebba Holme 
Published: March 2007

Background: The validity of children's self-reports on medicine use has not been reported. Objective: To determine the agreement between parents' and children's reports of medicine use for 5 common complaints and to analyze predictors for disagreement. Methods: We used the child–parent validation survey from the research project Health Behaviour in School-Aged Children. Three hundred ninety-three 11- and 13-year-old Danish children and their parents responded to identical questionnaires. The main outcome measures were self-reported medicine use during the previous month for headache, stomachache, difficulties in falling asleep, nervousness, and asthma. Results: The percent agreement was lowest with medicine use for headache (64.6%), but was very high for the other 4 complaints (85.3–91.8%). The simple κ coefficients were moderate to good for medicine use for headaches, stomachache, and asthma (0.31–0.58) but poor for difficulties in falling asleep and nervousness. Children who had the specific complaint during the previous month were more likely than their parents to report more frequent medicine use. Conclusions: We have some confidence in young adolescents' self-reports of medicine use, as the results of this study are in keeping with other studies on the validity of children's reports of health-related behaviors. Furthermore, the findings suggest that such data can be used in epidemiologic studies that aim to categorize children into groups with and without medicine use.
Effect of Nesiritide Infusion Duration on Renal Function in Acutely Decompensated Heart Failure Patients
Authors: Chow Sheryl L , Peng Jessica T , Okamoto Mark P , Heywood J Thomas 
Published: March 2007

Background: Nesiritide, a synthetic B-type natriuretic peptide, is used for the treatment of patients with acutely decompensated heart failure. Although nesiritide has been reported to worsen renal function, as reflected by significant elevations in serum creatinine (SCr), the impact of infusion duration on renal function has not been evaluated. Objective: To investigate the effect of nesiritide infusion duration (<24 h vs ≥24 h) on worsening renal function in patients with acutely decompensated heart failure. Methods: Medical records of hospitalized patients receiving nesiritide were retrospectively reviewed, and 84 consecutive charts of patients with acute decompensated heart failure and available renal function tests were identified for the study. SCr and blood urea nitrogen (BUN) were documented at baseline and during infusion. Worsening renal function was defined as an increase in SCr of 0.5 mg/dL or more or BUN 10 mg/dL or more from baseline. Results: Univariate analysis showed a significant association between nesiritide infusion duration of 24 hours or more (26.1% vs 2.6%; p = 0.003), high diuretic doses (61.5% vs 32.4%; p = 0.045), and baseline SCr (2.0 ± 0.8 vs 1.5 ± 0.7 mg/dL; p = 0.04) with increases in SCr of 0.5 mg/dL or more. However, only infusion duration of 24 hours or more was statistically significant on multivariate analysis, after adjusting for baseline SCr (OR 10.46; 95% CI 1.26 to 86.72; p = 0.03). Longer duration of infusion was also a consistent variable in both univariate and multivariate analysis when elevated BUN was evaluated (34.8 vs 2.6%; p < 0.001 and OR 19.73; 95% CI 2.47 to 157.46; p = 0.005, respectively). Conclusions: Nesiritide infusion of 24 hours or more appears to be significantly associated with elevated markers of worsening renal function in patients with acutely decompensated heart failure compared with infusion of less than 24 hours; however, prospective studies are needed to corroborate this finding.
Pharmaceutical Care in Community Pharmacies: Practice and Research in Denmark
Authors: Herborg Hanne , Sørensen Ellen Westh , Frøkjær Bente 
Published: March 2007

Objective: To review the current status of Danish community pharmacy in both practice and research and discuss future trends. Findings: Denmark has a social welfare system that provides health care, social services, and pensions to its population. Medical care and surgery are free. Prescription medicines are reimbursed by an average of 56%. Community pharmacies are privately owned, but the health authorities regulate drug prices and the number of pharmacies. At present, Denmark has 322 pharmacies, corresponding to 1 pharmacy per 16 700 inhabitants. All pharmacies provide prescription and over-the-counter products, advice about medicine use, dose dispensing, generic substitutions, and administration of individual reimbursement registers. Except for very simple processes, compounding is centralized at 3 pharmacies. Many pharmacies offer measurement of blood glucose, blood pressure, and cholesterol, and 60% offer inhalation counseling, a reimbursed service. Research in pharmacy practice is well established and conducted primarily at universities and at Pharmakon A/S, which is owned by the Danish Pharmaceutical Association. Discussion: Extended services in clinical pharmacy are priorities for all Danish pharmacy organizations. Reimbursement is sought at the national level, as well as from payers in the new local authority structures in Denmark. The trend in research focuses on collaborative health care, on developing and documenting the value of community pharmacy services, and on optimizing services and strengthening implementation. Conclusions: Denmark has few, but large, community pharmacies and a long tradition of research and development resulting in several well-documented cognitive and clinical services. However, few services are reimbursed and implementation is still a challenge.
Critical Care: Multicenter Treatment and Outcome Evaluation of Aspiration Syndromes in Critically III Patients
Authors: Kane-Gill Sandra L , Olsen Keith M , Rebuck Jill A , Rea Rhonda S , Boatwright D Wesston , Smythe Maureen A , Walker Terrence R , Lager Stephanie L , Hodgman Tudy 
Published: March 2007

Background: Aspiration syndromes (pneumonia and pneumonitis) have significantly different processes. An evaluation of treatment and outcomes for these different syndromes has not been reported previously. Objective: To characterize and assess antimicrobial prescribing patterns for aspiration syndromes in intensive care unit (ICU) patients and describe outcomes of those patients. Methods: A retrospective, observational evaluation was conducted using a convenience sample of patients at 27 hospitals in North America; these patients were admitted to an adult ICU with a diagnosis of suspected/confirmed aspiration or had a suspected/confirmed aspiration while in the ICU. Hospital demographic, diagnosis, treatment, and clinical outcome data were collected. Results: Over a 12 month period, 187 patients were observed. Aspiration syndromes included suspected aspiration (31%; n = 58), aspiration pneumonitis (12%; n = 23), aspiration pneumonia (55%; n = 103), and diagnosis not available (1.6%; n = 3). Antimicrobial management for the aspiration syndromes was as follows: suspected aspiration: 59% single agent, 38% multiple agents, and 3% no therapy; aspiration pneumonitis; 48% single agent, 39% multiple agents, and 13% no therapy; aspiration pneumonia: 48% single agent. 52% multiple agents, and 0% no therapy. Antimicrobial therapy was prescribed in patients with suspected (97%) and confirmed (100%) aspiration. Antibiotic therapy duration was significantly longer for aspiration pneumonia (9.1 ± 7.5 days) than for aspiration pneumonitis (5.2 ± 3.6 days; p = 0.013). Length of ICU stay was similar across patient groups. Conclusions: Antimicrobial agents are frequently prescribed to treat aspiration syndromes despite the lack of demonstrated efficacy for aspiration pneumonitis. Outcomes between aspiration syndromes were similar with the exception of duration of antibiotic treatment.
Characterisation of novel splicing variants of the tyrosine hydroxylase C-terminal domain in human neuroblastic tumours
Authors: Roma Josep , Saus Ester , Cuadros Marc , Reventós Jaume , Sánchez de Toledo Josep , Gallego Soledad 
Published: March 2007

AbstractAlternative splicing of human tyrosine hydroxylase (hTH) transcripts appears to occur mainly in the N-terminal domain, giving rise to at least eight different isoforms. We recently reported the existence of hTH transcript variants resulting from splicing of exons 8 and 9, within a region previously thought to be constant. The mRNA distribution of these novel hTH isoforms in neuroblastic tumours and in foetal adrenal glands was analysed by conventional and real-time RT-PCR. The presence of the target protein was determined by Western blotting, immunoprecipitation and protein analysis. Transcripts lacking exons 8 and 9 were widely distributed in the tissues analysed. Characterisation of full-length mRNA revealed that splicing of exons 8 and 9 was always associated with splicing of exons 2 (hTH-Δ2,8,9) or 1b and 2 (hTH-Δ1b,2,8,9). In addition, one variant detected on Western blots in several tumours fits the predicted size (58 kDa) of the isoforms lacking exons 8 and 9. In conclusion, the two novel isoforms reported here (hTH-Δ2,8,9 and hTH-Δ1b,2,8,9) represent the first full-length isoforms with alternative splicing in the hTH C-terminal domain. These results demonstrate for the first time the existence of hTH isoforms Δ2,8,9 and Δ1b,2,8,9. Their general distribution in neuroblastoma and adrenal glands and translation into protein suggest a significant functional role for these novel hTH isoforms, which merit further study.
N.BspD6I DNA nickase strongly stimulates template-independent synthesis of non-palindromic repetitive DNA by Bst DNA polymerase
Authors: Zyrina Nadezhda V. , Zheleznaya Lyudmila A. , Dvoretsky Eugene V. , Vasiliev Victor D. , Chernov Andrei , Matvienko Nicholas I. 
Published: March 2007

Abstract
Highly efficient DNA synthesis without template and primer DNAs occurs when N.BspD6I DNA nickase is added to a reaction mixture containing deoxynucleoside triphosphates and the large fragment of Bst DNA polymerase. Over a period of 2 h, virtually all the deoxynucleoside triphosphates (dNTPs) become incorporated into DNA. Inactivation of N.BspD6I nickase by heating inhibits DNA synthesis. Optimal N.BspD6I activity is required to achieve high yields of synthesized DNA. Electron microscopy data revealed that the majority of DNA molecules have a branched structure. Cloning and sequencing of the fragments synthesized demonstrated that the DNA product mainly consists of multiple hexanucleotide non-palindromic tandem repeats containing nickase recognition sites. A possible mechanism is discussed that addresses template-independent DNA synthesis stimulated by N.BspD6I nickase.
Insulin-regulated aminopeptidase: analysis of peptide substrate and inhibitor binding to the catalytic domain
Authors: Ye Siying , Chai Siew Yeen , Lew Rebecca A. , Albiston Anthony L. 
Published: March 2007

Abstract
Peptide inhibitors of insulin-regulated aminopeptidase (IRAP) accelerate spatial learning and facilitate memory retention and retrieval by binding competitively to the catalytic site of the enzyme and inhibiting its catalytic activity. IRAP belongs to the M1 family of Zn2+-dependent aminopeptidases characterized by a catalytic domain that contains two conserved motifs, the HEXXH(X)18E Zn2+-binding motif and the GXMEN exopeptidase motif. To elucidate the role of GXMEN in binding peptide substrates and competitive inhibitors, site-directed mutagenesis was performed on the motif. Non-conserved mutations of residues G428, A429 and N432 resulted in mutant enzymes with altered catalytic activity, as well as divergent changes in kinetic properties towards the synthetic substrate leucine β-naphthalamide. The affinities of the IRAP inhibitors angiotensin IV, Nle1-angiotensin IV, and LVV-hemorphin-7 were selectively decreased. Substrate degradation studies using the in vitro substrates vasopressin and Leu-enkephalin showed that replacement of G428 by either D, E or Q selectively abolished the catalysis of Leu-enkephalin, while [A429G]IRAP and [N432A]IRAP mutants were incapable of cleaving both substrates. These mutational studies indicate that G428, A429 and N432 are important for binding of both peptide substrates and inhibitors, and confirm previous results demonstrating that peptide IRAP inhibitors competitively bind to its catalytic site.
HIRIP3 is a nuclear phosphoprotein interacting with and phosphorylated by the serine-threonine kinase CK2
Authors: Assrir Nadine , Filhol Odile , Galisson Frédéric , Lipinski Marc 
Published: March 2007

Abstract
The HIRIP3 protein had been identified from its interaction with the HIRA histone chaperone. Experiments using anti-peptide antisera indicated that this 556-aa protein is nuclear throughout the cell cycle and excluded from condensed chromatin during mitosis. Based on its electrophoretic migration and sensitivity to phosphatase treatment, endogenous HIRIP3 was found to be heavily phosphorylated. HIRIP3 can be phosphorylated in vitro by a recombinant form of the serine-threonine kinase CK2. Moreover, HIRIP3 protein was found to co-purify with a CK2 activity. Together, these data prompt us to propose HIRIP3 as a new member of the growing list of CK2 substrates with a possible role in chromatin metabolism.
Enzymatic properties of human kallikrein-related peptidase 12 (KLK12)
Authors: Memari Nader , Jiang Weiping , Diamandis Eleftherios P. , Luo Liu-Ying 
Published: March 2007

Abstract
Human kallikrein-related peptidase 12 (KLK12) is a new member of the human tissue kallikrein family. Preliminary studies suggest that KLK12 is differentially expressed in breast cancer and may have potential use as a cancer biomarker. It has been predicted that KLK12 is a secreted serine protease. However, the enzymatic properties of this protein have not been reported so far. Here, we report the production of recombinant KLK12 and analyses of its enzymatic characteristics, including zymogen activation, substrate specificity, and regulation of its activity. KLK12 is secreted as an inactive pro-enzyme, which is able to autoactivate to gain enzymatic activity. Through screening of a panel of fluorogenic and chromogenic peptide substrates, we establish that active KLK12 possesses trypsin-like activity, cleaving peptide bonds after both arginine and lysine. Active KLK12 quickly loses its activity due to autodegradation, and its activity can also be rapidly inhibited by zinc ions and by α2-antiplasmin through covalent complex formation. Furthermore, we demonstrate that KLK12 is able to activate KLK11 zymogen in vitro. Our results indicate that KLK12 may participate in enzymatic cascades involving other kallikreins.
Glutamic acid-141: a heme ‘bodyguard’ in anionic tobacco peroxidase
Authors: Hushpulian Dmitri M. , Poloznikov Andrew A. , Savitski Pavel A. , Rozhkova Alexandra M. , Chubar Tatyana A. , Fechina Victoria A. , Orlova Marina A. , Tishkov Vladimir I. , Gazaryan Irina G. , Lagrimini L. Mark 
Published: March 2007

Abstract
The role of the conserved glutamic acid residue in anionic plant peroxidases with regard to substrate specificity and stability was examined. A Glu141Phe substitution was generated in tobacco anionic peroxidase (TOP) to mimic neutral plant peroxidases such as horseradish peroxidase C (HRP C). The newly constructed enzyme was compared to wild-type recombinant TOP and HRP C expressed in E. coli. The Glu141Phe substitution supports heme entrapment during the refolding procedure and increases the reactivation yield to 30% compared to 7% for wild-type TOP. The mutation reduces the activity towards ABTS, o-phenylenediamine, guaiacol and ferrocyanide to 50% of the wild-type activity. No changes are observed with respect to activity for the lignin precursor substrates, coumaric and ferulic acid. The Glu141Phe mutation destabilizes the enzyme upon storage and against radical inactivation, mimicking inactivation in the reaction course. Structural alignment shows that Glu141 in TOP is likely to be hydrogen-bonded to Gln149, similar to the Glu143-Lys151 bond in Arabidopsis A2 peroxidase. Supposedly, the Glu141-Gln149 bond provides TOP with two different modes of stabilization: (1) it prevents heme dissociation, i.e., it ‘guards’ heme inside the active center; and (2) it constitutes a shield to protect the active center from solvent-derived radicals.
SUMOylation modulates transcriptional repression by TRPS1
Authors: Kaiser Frank J. , Lüdecke Hermann-Josef , Weger Stefan 
Published: March 2007

Abstract
Mutations or deletions of the TRPS1 gene on human chromosome 8q.24.1 cause the tricho-rhino-phalangeal syndromes (TRPS), which are characterized by craniofacial and skeletal malformations. The gene encodes a transcription factor that functions as a repressor for GATA-mediated transcription. The activity of transcription factors is often controlled by posttranslational modifications. We show here that TRPS1 is SUMOylated at multiple sites, both in vivo and in vitro, through interaction with UBC9. Overexpression of wild-type UBC9 enhances TRPS1-mediated transcriptional repression. In contrast, a SUMOylation-deficient UBC9 mutant, which nevertheless still binds TRPS1, has no effect. Of the five potential TRPS1 SUMO-target sites, which were predicted based on a minimal SUMOylation consensus sequence (MCS), two are located within the C-terminal repression domain (RD) at lysine residues 1192 (termed S4) and 1201 (S5). S5 was identified as the major acceptor site within this region, and a point mutation of S5 strongly decreases TRPS1-RD-mediated transcriptional repression. Additional mutation of S4 results in abrogation of SUMOylation at the TRPS1-RD and almost complete loss of the repressive properties of TRPS1. These results identify SUMOylation at the TRPS1-RD as a major mechanism that regulates the function of TRPS1.