bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered dose-to-effect of propofol due to pharmacokinetics in rats with experimental diabetes mellitus
Authors: Leal N , Calvo R , Agrad F Z , Lukas J C , de la Fuente L , Suarez E 
Published: March 2005

Abstract
Pathology related alterations in the pharmacokinetics or the pharmacodynamics of propofol could contribute to the observed large variability in the hypnotic dose. We have tested the influence of diabetes mellitus on the induction dose and the pharmacokinetics and pharmacodynamics of propofol in rats. Diabetes was induced in rats by administration of streptozotocin (60 mg kg−1, i.p.) while control rats received vehicle intraperitoneally. All animals had glucose, cholesterol, triglycerides and albumin levels measured. In-vitro protein binding was determined by ultrafiltration. Rats were randomly split into set 1 (dose-concentration-effect study) with control and streptozotocin rats, and set 2 (pharmacokinetic study), with control and streptozotocin rats. Rats in the effect set received either a variable infusion of 6 mg kg−1 min−1 propofol until onset (induction dose) of the hypnotic effect (loss of the righting reflex), or a 15 mg kg−1 bolus to assess offset time (recovery of the righting reflex). Blood (Cblood) and brain (Cbrain) propofol concentrations at onset and offset were assayed by HPLC. In the pharmacokinetic study, propofol was administered intravenously at 6 mg kg−1 min−1 for 2 min. Arterial blood samples were collected between 0.5 and 540 min and assayed for propofol. A mixed effects compartmental pharmacokinetic modelling method (NONMEM) was used to analyse the observations and variabilities. The dose necessary for onset differed between streptozotocin and controls, and so did the pharmacokinetics with two- and three-compartment descriptions, respectively. Cblood and Cbrain at onset and offset were similar, possibly rejecting changes in pharmacodynamics. The total and unbound volume of distribution was significantly lower in the streptozotocin group with no differences in clearance (CL) between streptozotocin and controls, (mean (inter-animal CV%)) CL = 0.026 (17%) and 0.025 (62%) L min−1, respectively. Individual Bayes Vdss (volume of distribution at steady state) were different, (mean (s.d.)) Vdss = 7.7 (2.67) and 1.11 (0.09) L, respectively. The pharmacokinetic model was validated by comparison with the data from set 1. Simulations of total and unbound Cblood, for both groups, at the hypnotic dose for the controls, revealed differences throughout the time course of the pharmacokinetics. The difference observed in the induction dose of propofol to streptozotocin and control rats was due to alterations in the pharmacokinetics, secondary to the pathology.
Myosin light chain kinase and Rho-kinase participate in P2Y receptor-mediated acceleration of permeability through the endothelial cell layer
Authors: Tanaka Naoko , Nejime Namie , Kubota Yoko , Kagota Satomi , Yudo Keiko , Nakamura Kazuki , Kunitomo Masaru , Takahashi Koichi , Hashimoto Michio , Shinozuka Kazumasa 
Published: March 2005

Abstract
We have shown that P2Y receptor stimulation accelerates macromolecular permeation through the endothelial cell layer. To elucidate the mechanism of this acceleration, we examined the effects of ML-9, a myosin light chain kinase inhibitor, and Y-27632, a Rho-kinase inhibitor, on fluorescein isothiocyanate dextran (FD-4) permeation across the human umbilical vein endothelial cell monolayer. FD-4 permeation was analysed by high-performance liquid chromatography fluorescence detection. A P2Y receptor agonist, 2meS-ATP, enhanced the permeability of FD-4, which was inhibited by pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), a P2Y-receptor antagonist. The 2meS-ATP-induced increase in the permeability of FD-4 was significantly inhibited by ML-9. Also, Y-27632 prevented the 2meS-ATP-induced increase in the permeability of FD-4. Neither ML-9 nor Y-27632 influenced the spontaneous permeation of FD-4. These results suggest that phosphorylation of the myosin light chain may play an important role in the purinergic regulation of macromolecular permeation through the vascular endothelium.
Lectin of Pisum arvense seeds induces in-vivo and in-vitro neutrophil migration
Authors: Alencar V B M , Assreuy A M S , Alencar N M N , Meireles A V P , Mota M R L , Aragão K S , Cajazeiras J B , Nagano C S , Brito G A C , Silva L I M M , Pinto V P T , Sampaio A H , Debray H , Cavada B S , Ribeiro R A 
Published: March 2005

Abstract
PAL is a glucose/mannose-specific lectin isolated from Pisum arvense seeds. Previously, we demonstrated the capacity of other leguminous lectins to induce oedema formation and neutrophil stimulation. To investigate the potential pro-inflammatory activity of PAL, we have studied its ability to induce neutrophil migration into peritoneal cavities of rats and neutrophil chemotaxis in-vitro. The role of resident cells and sugar residues on PAL activity was analysed. PAL or saline (control) were administered intraperitoneally to rats, and total and differential leucocyte (macrophages, neutrophils and mast cells) counts were performed. The role of resident cells on the PAL effect was evaluated using three strategies: reducing the total resident cell population by lavage of rat cavities with saline; increasing macrophage population by treating animals with thioglycolate; and depleting mast cell population by subchronic treatment of rats with compound 48/80. PAL induced in-vitro and in-vivo neutrophil migration. In-vivo, PAL (50, 100, 200 and 300 μg) significantly (P &lt; 0.05) and dose-dependently increased neutrophil migration by 600, 740, 900 and 940%, respectively, showing maximal effect 4 h after injection. PAL induced mononuclear cell migration. The neutrophil stimulatory effect of PAL was potentiated in animals treated with both thioglycolate and compound 48/80. The indirect lectin chemotactic effect was shown in rats injected with supernatant from cultured macrophages stimulated by PAL. In conclusion, PAL was shown to exhibit in-vivo and in-vitro proinflammatory activity. The in-vivo effect seemed to occur by a dual mechanism that was independent, but also dependent, on resident cells.
In-vitro anti-inflammatory activity of Pinus sylvestris and Plantago lanceolata extracts: effect on inducible NOS, COX-1, COX-2 and their products in J774A.1 murine macrophages
Authors: Vigo E , Cepeda A , Gualillo O , Perez-Fernandez R 
Published: March 2005

Abstract
Extracts of the plant species Pinus sylvestris L. and Plantago lanceolata L. have been used in traditional medicine for the treatment of certain respiratory diseases, but little is known about their precise effects and mechanisms of action. In this study, we investigated the effect of these plant extracts on the production of nitric oxide (NO) and prostaglandin E2, NO synthase (NOS) type II, cyclooxygenase-1 (COX-1) and COX-2 mRNA expression in the murine macrophage cell line J774A.1. We found that Pinus sylvestris and Plantago lanceolata extracts inhibited NO production in a concentration-dependent manner in this cell line, without obvious cytotoxic effects as tested by MTT assay. The Plantago lanceolata extract at all doses used, and the Pinus sylvestris extract at high doses, showed significant scavenging of NO radicals released by the NO donor PAPA-NONOate. Our data also show that pre-treatment with these extracts significantly inhibits inducible NOS (iNOS) mRNA production in this cell line, without affecting COX-1 mRNA expression. COX-2 mRNA levels and PGE2 levels induced by lipopolysaccharide/interferon-γ were not modified upon pre-treatment with the extracts. Thus, our results suggest that the anti-inflammatory properties of Pinus sylvestris and Plantago lanceolata extracts may reflect decreased NO production, possibly due to inhibitory effects on iNOS gene expression or to NO-scavenging activity.
Mucoadhesive microspheres for nasal administration of an antiemetic drug, metoclopramide: in-vitro/ex-vivo studies
Authors: Gavini Elisabetta , Rassu Giovanna , Sanna Vanna , Cossu Massimo , Giunchedi Paolo 
Published: March 2005

Abstract
Microparticulate delivery systems designed for the nasal administration of an antiemetic drug, metoclopramide hydrochloride, were prepared. Microspheres composed of sodium alginate, chitosan hydrochloride, or both, were obtained using a spray-drying method; some batches of drug-free microparticles were prepared as a comparison. The morphology, in-vitro swelling behaviour, mucoadhesive properties and drug release from microparticles were evaluated. Ex-vivo drug permeation tests were carried out using sheep nasal mucosa; permeation test of the drug solution was peformed as comparison. During ex-vivo permeation tests, transmission electron microscopy (TEM) analyses were carried out on the nasal mucosa to study the morphological changes of epithelial cells and tight junctions, while the change in microsphere morphology was examined using photostereo microscopy (PM). Spray-dried microparticles had a mean diameter (dvs) in the range of about 3–10 μm. They showed good in-vitro mucoadhesive properties. In-vitro release profiles and swelling behaviour depended on their composition: the drug release occurred in 1–3 h. Ex-vivo studies showed that drug permeation through the mucosa from microparticles based on chitosan was higher than from those consisting of alginate alone. This can be related to the penetration enhancing properties of chitosan. Complexation of chitosan with alginate led to a control of the drug release. Microscopy observation of microspheres during the permeation tests revealed that microparticles swelled and gelled, maintaining their shape. TEM analyses of the mucosa after exposure to the microparticles consisting of alginate/chitosan showed opened tight junctions. This preliminary study shows that alginate/chitosan spray-dried microspheres have promising properties for use as mucoadhesive nasal carriers of an antiemetic drug.
Metabolism of pantoprazole involving conjugation with glutathione in rats
Authors: Zhong Dafang , Xie Zhiyong , Chen Xiaoyan 
Published: March 2005

Abstract
We have investigated the metabolism of pantoprazole and have provided an explanation for the formation mechanism of its metabolites. Metabolites found in the urine of rats after oral administration of pantoprazole sodium (25 mg kg−1) were analysed by liquid chromatography/ion trap mass spectrometry (LC/MSn). The N-acetylcysteine derivatives of benzimidazole (M1) and pyridine (M2), four pyridine-related metabolites (M3–M6), and three benzimidazole-related metabolites (M7–M9) were found, none of which had been reported previously. Five of the metabolites (M1, M2, M3, M7, and M8) were isolated from the urine of rats after oral administration of pantoprazole sodium by semi-preparative HPLC. Structures of these metabolites were identified by a combination analysis of LC/MSn and 1H NMR spectra. Structures of the remaining four metabolites (M4, M5, M6, and M9) were tentatively assigned through LC/MSn. The metabolites M2, M3, M4, M5 and M6 and the other metabolites (M1, M7, M8, and M9) reflected the fate of the pyridine moiety and the benzimidazole moiety, respectively. The proposed formation route of M3–M6 was via initial reduction to mercaptopyridine followed by S-methylation, O-demethylation, and S-oxidation to the corresponding sulfoxide or sulfone. Meanwhile, M8 and M9 were formed via initial reduction to the 5-difluoromethoxy-1H-benzoimidazole-2-thiol (M7) followed by hydroxylation and S-methylation. The metabolism of pantoprazole included an attack by glutathione on the benzimidazole-2-carbon and pyridine-7′-carbon. It is an important metabolic pathway of pantoprazole in rats.
The stereoselective biotransformation of the anti-obesity drug sibutramine in rat liver microsomes and in primary cultures of rat hepatocytes
Authors: Link Marek , Novotná Romana , Suchanová Bohumila , Skálová Lenka , Wsól Vladimír , Szotáková Barbora 
Published: March 2005

Abstract
Sibutramine is an anti-obesity drug sold as a racemic mixture under the trademark Meridia or Reductil. With the aim of evaluating the stereoselectivity in phase I of sibutramine biotransformation, the formation of the main metabolites from R-sibutramine, S-sibutramine and rac-sibutramine was studied in rat microsomes and primary cultures of hepatocytes. A novel analytical method for the determination of sibutramine and its phase I metabolites in culture medium and microsomal incubates using isocratic reversed-phase liquid chromatography with UV detection was developed. Only two metabolites, mono-desmethylsibutramine (M1) and di-desmethylsibutramine (M2), were found in the rat microsomes incubated with sibutramine and NADPH. The kinetics of M1 and M2 formation slightly differed depending on the enantiomeric form of the sibutramine used. The stereoselectivity in sibutramine biotransformation was much more evident in primary cultures of rat hepatocytes. While R-sibutramine incubation led to the formation of M1 and M2 metabolites only, the incubation of S-sibutramine or rac-sibutramine (to a lesser extent) resulted in four major metabolites (M1, M2, M3 and M4) and 2 or 3 minor metabolites. On the basis of our results, R-sibutramine might represent the more advantageous sibutramine enantiomer from the pharmacokinetic standpoint.
Discordance Analysis Characteristics as a New Method to Compare the Diagnostic Accuracy of Tests: Example of Complexed Versus Total Prostate-Specific Antigen
Authors: Keller Thomas , Butz Hermann , Lein Michael , Kwiatkowski Maciej , Semjonow Axel , Luboldt Hans-Joachim , Hammerer Peter , Stephan Carsten , Jung Klaus 
Published: March 2005

AbstractBackground: ROC curve analysis is used to compare the overall diagnostic accuracy of tests, but its application to subgroups selected by a concentration range of only one marker may show severe biases. We developed a new approach, which we have named discordance analysis characteristics (DAC).Methods: The DAC method is based on a generalization of the McNemar test so that for a given pair of cutoff values only those patients are analyzed who are categorized differently by the two tests compared. The analyses are performed for all cutoff pairs that deliver identical sensitivities for both tests. We used data for total (tPSA) and complexed prostate-specific antigen (cPSA) from a recently published multicenter study to demonstrate the DAC method.Results: The example shows that ROC analyses of subgroups can give contradictory results about the diagnostic accuracy of two markers, depending on the marker used for the selection of subgroups. The DAC method avoids artifacts attributable to questionable selection of subgroups and facilitates overall and local comparisons of the diagnostic accuracy of tests. The DAC results of the analyzed data set suggest that cPSA has higher diagnostic accuracy than does tPSA.Conclusions: The DAC method is a suitable tool for comparing the clinical usefulness of laboratory markers. The DAC method could be considered as an additional tool to ROC analysis and could replace comparative ROC analyses of diagnostic tests, especially within subgroups defined by only one of the markers.
Does Melanoma Behave Differently in Younger Children Than in Adults? A Retrospective Study of 33 Cases of Childhood Melanoma From a Single Institution
Authors: Ferrari Andrea , Bono Aldo , Baldi Marzia , Collini Paola , Casanova Michela , Pennacchioli Elisabetta , Terenziani Monica , Marcon Ilaria , Santinami Mario , Bartoli Cesare 
Published: March 2005

Objective.To ascertain whether childhood melanoma presents any peculiar clinical features or differences in prognosis with respect to adults, we retrospectively analyzed the data from 33 patients who were up to 14 years of age and treated for cutaneous melanoma at the Istituto Nazionale Tumori, Milan, over a 25-year period.
Methods.Primary lesions were amelanotic in half of the cases and raised in 73%. Lower extremities were the most common primary sites. Histologically, 9 cases were classified as nodular type, and median thickness was 2.5 mm. Nine children had nodal involvement at diagnosis, 2 in-transit metastases, and 1 distant spread. Surgery was the mainstay of treatment; 9 patients underwent lymph node dissection, 3 received chemotherapy, and 2 received radiotherapy.
Results.With a median follow-up of 122 months, 5-year event-free survival and overall survival were 60% and 70%, respectively. Age seemed to correlate with survival, event-free survival being 90% in children under 10 and 47% in older patients, although the initial microstaging seemed worse in the former.
Conclusion.By comparison with adult cases, childhood melanoma can have a higher percentage of atypical clinical features (amelanotic and raised lesions), nodular histotype, and thick lesions. Although we have no data to support any suggestion of biological differences between young children and adolescents or adults, our findings give the impression that melanoma behaves differently in the younger age group.
Asthma Phenotypes, Risk Factors, and Measures of Severity in a National Sample of US Children
Authors: Kelley Colleen F. , Mannino David M. , Homa David M. , Savage-Brown Amanda , Holguin Fernando 
Published: March 2005

Objective. To examine a nationally representative sample of US children aged 6 to 16 years old and determine whether there are differences in risk factors and measures of severity between children with different asthma phenotypes.
Methods. We analyzed data from the Third National Health and Nutrition Examination Survey. We used questionnaire and skin-prick testing data to separate children into the following mutually exclusive categories: atopic asthma, nonatopic asthma, resolved asthma, frequent respiratory symptoms with no asthma diagnosis, and normal. We used multivariate regression to determine whether demographic or potential risk factors varied between phenotypes and whether measures of severity varied by phenotype.
Results. We found that 4.8% of children had atopic asthma, 1.9% had nonatopic asthma, 3.4% had resolved asthma, and 4.3% had frequent respiratory symptoms. Risk factors varied by phenotype, for example, the mean BMI was higher among children with nonatopic asthma, prenatal maternal smoking was a risk factor for resolved asthma, and child care attendance was a risk factor for frequent respiratory symptoms with no asthma diagnosis. Patients with atopic and nonatopic asthma were similar for most measures of asthma severity (medication use, health status, and lung function impairment). In contrast, patients with resolved asthma had fewer symptoms but a similar level of lung function impairment to that seen in patients with current asthma, whereas children with frequent respiratory symptoms but no asthma diagnosis had normal lung function.
Conclusions. Asthma risk factors and measures of severity vary between children with different asthma phenotypes.
Provider and Practice Characteristics Associated With Antibiotic Use in Children With Presumed Viral Respiratory Tract Infections
Authors: Gaur Aditya H. , Hare Marion E. , Shorr Ronald I. 
Published: March 2005

Objective. Although overuse of antibiotics in children has been well documented, relatively little information is known about provider and facility characteristics associated with this prescribing practice. This study was done to evaluate the differences in overuse of antibiotics among staff physicians and resident/interns (housestaff [HS]) who work in hospital-based outpatient clinics.
Methods. This cross-sectional study involved patient encounters in outpatient departments that were included in the US National Hospital Ambulatory Medical Care Survey database from 1995 to 2000. Encounters with patients who were aged &lt;18 years and had a primary diagnosis suggestive of viral respiratory tract infection were evaluated. Patients with comorbid conditions that might justify antibiotic use were excluded.
Results. This study included 1952 patient encounters with a primary diagnosis suggestive of a viral infection and 33.2% of these patients receiving antibiotics. Overall, antibiotic use was significantly less among HS (19.5%) than staff physicians (36.4%; odds ratio [OR]: 0.44; 95% confidence interval [CI]: 0.33–0.59). This difference between HS (19.5%) and staff physicians (32.5%) persisted even within teaching hospitals (OR: 0.5; 95% CI: 0.4-0.7). Among staff physicians, antibiotic use was greater among those who work in nonteaching (39.6%) compared with teaching hospitals (32.5%; OR: 1.51; 95%: CI 1.15-1.98). Controlling for other patient and provider variables, antibiotic use occurred less among HS than among staff physicians in teaching hospitals (OR: 0.53; 95% CI: 0.38-0.75).
Conclusions. Antibiotic prescribing in the context of an outpatient visit for a diagnosis suggestive of a viral respiratory tract illness occurs more commonly among staff physicians than trainees and among staff physicians more commonly in nonteaching compared with teaching institutions.
Home Use of the GlucoWatch G2 Biographer in Children With Diabetes
Authors: Hathout Eba , Patel Nina , Southern Christina , Hill Julie , Anderson Reginald , Sharkey Jeannine , Hadley-Scofield Merrilee , Tran Long , Leptien Amy , Lopatin Margarita , Wang Betty , Mace John , Eastman Richard 
Published: March 2005

Objective. To evaluate usability, accuracy, and hypoglycemia detection of the GlucoWatch G2 Biographer (GW2B) in children aged 1 to 17 years.
Methods. After a 15-hour study of device accuracy, 46 children (15 &lt;7 years, 31 ≥7 years) with type 1 diabetes were enrolled for an extended-wear outcome study: 2 daytime and 2 nighttime 15-hr wear periods each week and blood glucose monitoring 4 times daily for 3 months.
Results. A total of 531 paired GW2B/meter readings were available for accuracy assessment. The correlation coefficients were 0.58 and 0.74 (ages &lt;7 and ≥7 years, respectively). There was no significant change in hemoglobin A1C or weight-adjusted insulin dose at 3 months after biographer use. Forty-two episodes of hypoglycemia were detected by the GW2B, 33 of which were confirmed by blood glucose meters. Sensitivity and specificity of audible low-glucose alerts were ∼79% and 83%, respectively. No significant side effects were reported.
Conclusion. The GW2B is usable and safe in children who are &lt;7 years or older in the home setting. The GW2B can detect asymptomatic nocturnal hypoglycemia in younger children.
Physician and Dentist Tobacco Use Counseling and Adolescent Smoking Behavior: Results From the 2000 National Youth Tobacco Survey
Authors: Shelley Donna , Cantrell Jennifer , Faulkner Dorothy , Haviland Lyndon , Healton Cheryl , Messeri Peter 
Published: March 2005

Objective. The present study describes patterns of tobacco use counseling among physicians and dentists as reported by adolescents and determines the association between provider advice to quit and cessation activities among current smokers.
Methods. Data were analyzed from the 2000 National Youth Tobacco Survey, an anonymous, self-administered, school-based survey. The National Youth Tobacco Survey was administered to a nationally representative sample of 35828 students in grades 6 to 12 in 324 schools.
Results. Thirty-three percent of adolescents who visited a physician or a dentist in the past year reported that a physician counseled them about the dangers of tobacco use, and 20% reported that a dentist provided a similar message. Among students who smoked in the past year, 16.4% received advice to quit from a physician and 11.6% received advice to quit from a dentist. Physician or dentist advice to quit was correlated with 1 or more quit attempts in the past 12 months.
Conclusion. On the basis of adolescent reports, physician and dentist practice patterns remain well below recommended guidelines. Results suggest that provider advice to quit is associated with cessation activity. Additional studies are needed to confirm whether the low prevalence of brief provider tobacco use counseling is a missed opportunity to affect adolescent smoking behavior.