bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison between in vitro rat and human and in vivo rat skin absorption studies
Authors: Van Ravenzwaay B , Leibold E 
Published: September 2004

In vitro skin penetration rates in rat and man were compared to those obtained in vivo in rats. Saturation of absorption was frequently observed at higher exposure levels in in vitro and in vivo. Lipophilic compounds showed the highest penetration rates through rat skin in vitro. In all cases in vitro dermal penetration through rat skin was higher than in vivo. Thus, the in vitro study may serve as a first tier test. The in vivo data suggest an inverse relationship between molecular weight and the rate of dermal absorption for lipophilic as well as hydrophilic compounds. Rat skin was more permeable to all tested substances than human skin (mean difference 10.9-fold). Thus, the systemic exposure of humans may be significantly overestimated if risk assessment is based only on the results of an in vivo rat study, because human skin is less permeable than rat skin. It would appear, therefore, that an estimate of actual dermal penetration through human skin should be based on the combined use of in vivo and in vitro data, using the following equation: %Human dermal penetration =(%rat in vivo dermal penetration) (See PDF for Formula)
Phase II Study of Denileukin Diftitox for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma
Authors: Dang Nam H. , Hagemeister Fredrick B. , Pro Barbara , McLaughlin Peter , Romaguera Jorge E. , Jones Dan , Samuels Barry , Samaniego Felipe , Younes Anas , Wang Michael , Goy Andre , Rodriguez Maria A. , Walker Pamela L. , Arredondo Yolanda , Tong Ann T. , Fayad Luis 
Published: September 2004

Purpose Denileukin diftitox is a fusion protein combining diphtheria toxin and interleukin-2 (IL-2) that targets tumor cells expressing the IL-2 receptor. Its efficacy has been shown in CD25+ cutaneous T-cell lymphoma, but not in B-cell non-Hodgkin's lymphoma (NHL). A phase II study was performed to evaluate the efficacy and tolerability of denileukin diftitox for relapsed or refractory B-cell NHL. Patients and Methods Patients with relapsed or refractory B-cell NHL were eligible. Tumor CD25 expression was determined by immunohistochemistry or flow cytometry. Denileukin diftitox was administered intravenously at a dose of 18 μg/kg once daily for 5 days every 3 weeks, up to eight cycles. Results Of the 45 patients assessable for response, 32 (71%) were refractory to the last chemotherapy treatment, and all were previously treated with rituximab. Three complete responses (6.7%) and eight partial responses (17.8%) were observed, for an overall response rate of 24.5%. Nine patients (20%) had stable disease. Objective response rates were similar in CD25+ (22%) and CD25− histologies (29%), as were stable disease rates (22% and 18%, respectively). For responding patients, the median time to treatment failure was 7 months, with a median follow-up in survivors of 18 months (range, 9 to 28 months), and the projected progression-free survival at 20 months was 24% (95% CI, 0% to 60%). Most toxicities were low-grade and transient. Conclusion Denileukin diftitox seems to be effective in relapsed or refractory, CD25+ and CD25− B-cell NHL and is well-tolerated at the dosage evaluated. Evaluation of denileukin diftitox in combination with other agents may be warranted.
Outcome of Treatment in Adults With Acute Lymphoblastic Leukemia: Analysis of the LALA-94 Trial
Authors: Thomas Xavier , Boiron Jean-Michel , Huguet Françoise , Dombret Hervé , Bradstock Ken , Vey Norbert , Kovacsovics Tibor , Delannoy André , Fegueux Nathalie , Fenaux Pierre , Stamatoullas Aspasia , Vernant Jean-Paul , Tournilhac Olivier , Buzyn Agnès , Reman Oumedaly , Charrin Christiane , Boucheix Claude , Gabert Jean , Lhéritier Véronique , Fiere Denis 
Published: September 2004

Purpose We analyzed the benefits of a risk-adapted postremission strategy in adult lymphoblastic leukemia (ALL), and re-evaluated stem-cell transplantation (SCT) for high-risk ALL. Patients and Methods A total of 922 adult patients entered onto the trial according to risk groups: standard-risk ALL (group 1), high-risk ALL (group 2), Philadelphia chromosome-positive ALL (group 3), and CNS-positive ALL (group 4). All received a standard four-drug/4-week induction course. Patients from group 1 who achieved a complete remission (CR) after one course of induction therapy were randomly assigned between intensive and less intensive postremission chemotherapy, whereas those who achieved CR after salvage therapy were then included in group 2. Patients in groups 2, 3, and 4 with an HLA-identical sibling were assigned to allogeneic SCT. In groups 3 and 4, autologous SCT was offered to all other patients, whereas in group 2 they were randomly assigned between chemotherapy and autologous SCT. Results Overall, 771 patients achieved CR (84%). Median disease-free survival (DFS) was 17.5 months, with 3-year DFS at 37%. In group 1, the 3-year DFS rate was 41%, with no difference between arms of postremission randomization. In groups 2 and 4, the 3-year DFS rates were 38% and 44%, respectively. In group 2, autologous SCT and chemotherapy resulted in comparable median DFS. Patients with an HLA-matched sibling (groups 2 and 4) had improved DFS. Three-year DFS was 24% in group 3. Conclusion Allogeneic SCT improved DFS in high-risk ALL in the first CR. Autologous SCT did not confer a significant benefit over chemotherapy for high-risk ALL.
Age-Dependent Regulation of Lipogenesis in Human and Rat Adipocytes
Authors: Kamel Ashraf F. , Norgren Svante , Strigård Karin , Thörne Anders , Fakhrai-Rad Hossein , Galli Joakim , Marcus Claude 
Published: September 2004

The regulation of adipocyte metabolism is of importance for adipose tissue growth and therefore also for the development of obesity. This study was designed to investigate the regulation of basal and insulin-induced lipogenesis, glucose transport, and glucose transporter protein expression in human and rat adipocytes from different age groups.The study included 21 infants, 21 children, nine adults, and 80 male weaned and 20 male adult Fischer rats. The lipogenesis experiments were performed under conditions at which glucose transport is rate limiting. Basal lipogenesis was approximately three times higher in infants and children than in adults, whereas insulin-induced lipogenesis was two times higher in infants than in children and adults. In rats, basal lipogenesis, insulin-induced lipogenesis, and insulin sensitivity were two times higher in weaned than in adult animals. Moreover, basal and insulin-induced glucose transport were two times higher in weaned than in adult rats. No differences were detected in GLUT1 or GLUT4 content between any of the age groups in human or in rat adipocytes.In conclusion, basal and insulin-stimulated lipogenesis are increased in adipocytes early in life. This may promote adipose tissue growth in early age. The data indicate that age-dependent variation in basal and insulin-stimulated lipogenesis is differently regulated.
ACTISEAT: Active vehicle seat for acceleration compensation
Authors: Frechin M M , Ariño S B , Fontaine J 
Published: September 2004

This paper describes an active vehicle seat to isolate the equipment and passengers in a vehicle from vibration and to compensate, to a certain extent, for acceleration in all directions. The main objective of this system is to reduce the negative effects of vibration and acceleration on embarked equipment and passengers. The active seat is composed of three main subsystems: A motion sensor unit installed on the vehicle body, to acquire the main motion parameters of the vehicle: speeds, accelerations, inclinations, etc. A small motion base attached to the seat. This platform moves actively, driven by a set of actuators. A control system for the overall system command. The seat has been extensively tested and the main results are presented.
The Renal Protective Effects of Angiotensin II Receptor Blockers in Type 2 Diabetes Mellitus
Authors: Coyle James D , Gardner Stephanie F , White C Michael 
Published: September 2004

OBJECTIVE To review the renal protective effects of angiotensin II receptor blockers (ARBs) in patients with type 2 diabetes mellitus. DATA SOURCES A MEDLINE search (1966-March 2004) was completed using irbesartan, candesartan, losartan, valsartan, eprosartan, olmesartan, telmisartan, renal protection, nephropathy, albuminuria, and type 2 diabetes mellitus as key words. STUDY SELECTION AND DATA EXTRACTION All identified English-language articles were reviewed. References of the identified sources were used to identify additional articles. Articles representative of the subject matter of our review were included. DATA SYNTHESIS ARBs have extensive data showing their renal protective benefits in hypertensive type 2 diabetic patients with microalbuminuria or proteinuria. The benefits are over and above that of blood pressure reduction alone and extend to normotensive diabetic patients as well. Maximizing the ARB dose before adding additional therapies or another renal-protecting agent (angiotensin-converting enzyme [ACE] inhibitor or non-dihydropyridine calcium-channel blocker) may be superior to adding another class of antihypertensive, even if similar blood pressures can be achieved. CONCLUSIONS ARBs are an important therapy for hypertensive type 2 diabetic patients and can benefit normotensive diabetic patients as well. ARB dosage optimization or the addition of a second renoprotective agent (ACE inhibitor or non-dihydropyridine calcium-channel blocker) may be important for optimal renoprotection, although further research is clearly needed in this area.
Age-Related Functional Changes of Prefrontal Cortex in Long-Term Memory: A Repetitive Transcranial Magnetic Stimulation Study
Authors: Rossi Simone , Miniussi Carlo , Pasqualetti Patrizio , Babiloni Claudio , Rossini Paolo M. , Cappa Stefano F. 
Published: September 2004

Neuroimaging findings suggest that the lateralization of prefrontal cortex activation associated with episodic memory performance is reduced by aging. It is still a matter of debate whether this loss of asymmetry during encoding and retrieval reflects compensatory mechanisms or de-differentiation processes. We addressed this issue by the transient interference produced by repetitive transcranial magnetic stimulation (rTMS), which directly assesses causal relationships between performance and stimulated regions. We compared the effects of rTMS (a rapid-rate train occurring simultaneously to the presentation of memoranda) applied to the left or right dorsolateral prefrontal cortex (DLPFC) on visuospatial recognition memory in 66 healthy subjects divided in two classes of age (<45 and >50 years).In young subjects, rTMS of the right DLPFC interfered with retrieval more than left DLPFC stimulation. The asymmetry of the effect progressively vanished with aging, as indicated by bilateral interference effects on recognition performance. Conversely, the predominance of left DLPFC effect during encoding was not abolished in elders, thus probing its causal role for encoding along the life span. Findings confirm that the neural correlates of retrieval modify along aging, suggesting that the bilateral engagement of the DLPFC has a compensatory role on the elders' episodic memory performance.
Lasting Blood-Brain Barrier Disruption Induces Epileptic Focus in the Rat Somatosensory Cortex
Authors: Seiffert Ernst , Dreier Jens P. , Ivens Sebastian , Bechmann Ingo , Tomkins Oren , Heinemann Uwe , Friedman Alon 
Published: September 2004

Perturbations in the integrity of the blood-brain barrier have been reported in both humans and animals under numerous pathological conditions. Although the blood-brain barrier prevents the penetration of many blood constituents into the brain extracellular space, the effect of such perturbations on the brain function and their roles in the pathogenesis of cortical diseases are unknown.In this study we established a model for focal disruption of the blood-brain barrier in the rat cortex by direct application of bile salts. Exposure of the cerebral cortexin vivoto bile salts resulted in long-lasting extravasation of serum albumin to the brain extracellular space and was associated with a prominent activation of astrocytes with no inflammatory response or marked cell loss. Using electrophysiological recordings in brain slices we found that a focus of epileptiform discharges developed within 4-7 d after treatment and could be recorded up to 49 d postoperatively in >60% of slices from treated animals but only rarely (10%) in sham-operated controls. Epileptiform activity involved both glutamatergic and GABAergic neurotransmission. Epileptiform activity was also induced by direct cortical application of native serum, denatured serum, or albumin-containing solution. In contrast, perfusion with serum-adapted electrolyte solution did not induce abnormal activity, thereby suggesting that the exposure of the serum-devoid brain environment to serum proteins underlies epileptogenesis in the blood-brain barrier-disrupted cortex. Although many neuropathologies entail a compromised blood-brain barrier, this is the first direct evidence that it may have a role in the pathogenesis of focal cortical epilepsy, a common neurological disease.
Gas Chromatographic — Mass Spectrometric Determination of Phenylacetic Acid in Human Blood
Authors: Mangani Giovanna , Canestrari Franco , Berloni Arnaldo , Maione Michela , Pagliarani Silvia , Mangani Filippo 
Published: September 2004

AbstractPhenyl acetic acid, a metabolite of 2—phenyl ethylamine, acts as a neuromodulator in the nigrostriatal dopaminergic pathway neuromodulator stimulating the release of dopamine. The evaluation of phenyl acetic acid concentration in the biological fluid reflects phenyl ethylamine levels thus allowing the assessment of the modulatory role of this endogenous substance. Changes in biological fluids levels of 2—phenylethylamine and/or in its metabolite have been reported in affective disorders, such as depression and schizophrenia. Recently, the occurrence of the “attention deficit hyperactivity syndrome” has been frequently reported in childhood population and involvement of dopaminergic dysfunction in this disease has been suspected. A fast, reliable and reproducible method for the determination of phenyl acetic acid in human blood, is therefore needed in order to have a screening tool for monitoring both healthy childhood population and suspected “attention deficit hyperactivity syndrome” patients. The gas chromatographicmass spectrometric method here described makes use of a deuterated internal standard in order to overcome problems related to the lack of reproducibility often encountered when a derivatization step is performed.
Improved Analysis of Polycyclic Aromatic Hydrocarbons in Atmospheric Particulate Matter by HPLC—Fluorescence
Authors: Bacaloni Alessandro , Cafaro Claudia , de Giorgi Loretta , Ruocco Roberta , Zoccolillo Lelio 
Published: September 2004

AbstractAn improved method is reported for determination of Polycyclic Aromatic Hydrocarbons (PAHs) in atmospheric particulate matter by HPLC—FLD. The sampling step (air volume collected during each sampling period varies in the range 10≑13 m3) is carried out by means of a mediumflow pumping system (15 L min—1) on a glass fiber filter (47 mm diameter) placed as collecting substrate in the samplingcassette. After sampling, the filter is extracted with 3 ml of acetonitrile in an ultrasonic bath for 30 minutes. As for extraction of PAHs from loaded filters a new criterion here is proposed to evaluate the recovery efficiency of PAHs from the sample, instead of the usual spiking method of standard solution. The extract was then reduced to 100 μL and analysed by HPLC—FLD on line spectra system. The method is rapid (about one hour for extraction and analysis), reproducible and enables to measure with good accuracy the atmospheric concentration of benzo(b) fluoranthene (BbF), benzo(k)fluoranthene (BkF), benzo(a)pyrene (BaP), benzo(ghi) perylene (BghiP), carcinogenic compounds always present in the urban airborne particulate matter. So it is useful for routine pollution studies and suitable to substitute the official method used now. Monthly average air concentrations, for the four PAHs above mentioned, measured in Rome from July 2001 to June 2002, are reported.
Biomass accumulation and clogging in trickle‐bed bioreactors
Authors: Iliuta Ion , Larachi Faïçal 
Published: September 2004

AbstractExcessive biomass formation in two‐phase flow trickle‐bed bioreactors induces clogging and leads to the progressive obstruction of the bed that is accompanied with a buildup in pressure drop and flow channeling. Currently, physical models linking the two‐phase flow to the space‐time evolution of biological clogging are virtually nonexistent. An attempt has been made with this contribution to fill in this gap by developing a unidirectional dynamic multiphase flow model based on the volume‐average mass, momentum, and species balance equations. Phenol biodegradation by Pseudomonas putida as the predominant species immobilized on activated carbon was chosen as a case study to illustrate the consequences of formation of excessive amounts of biomass. Furthermore, in developing the transient model, the following basic processes were assumed to occur and have been accounted for in the mathematical model: oxygen transport from gas into liquid bulks, phenol, and oxygen transport from the liquid phase to the biofilm surface, simultaneous diffusion and reaction of phenol and oxygen within biofilm, as well as their simultaneous diffusion and adsorption within the porous supporting particles. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2541–2551, 2004
A simultaneous method for two‐ and three‐liquid–phase stability determination
Authors: Guo Minqiang , Wang Shuqing , Repke Jens‐Uwe , Wozny Günter 
Published: September 2004

AbstractThe methods for multiphase stability determination are generally based on Gibbs free energy minimization. However, a novel and efficient method is proposed in this work for one‐, two‐, and particularly three‐liquid‐phase stability identification in ternary mixtures. The method is designated the extended general line‐length (EGL) method, which is based on our previous GL method. Both the EGL and GL methods are equation‐solving approaches. The EGL method is easy to understand and can be performed fast. Only parameters of the thermodynamic models, such as UNIQUAC and NRTL, are required for the stability determination. The thermodynamic model applied does not influence the rapidness and validity of the EGL method. Graphical techniques and simultaneous computation are adopted in this method. Its applicability and efficiency are exemplified by three typical examples. For each example, three different phase configurations, consisting of one‐, two‐, and up to a three‐liquid phase, are tested. The results show that the EGL method can be used for the determination of multiphase stability in all liquid‐phase configurations of ternary systems. © 2004 American Institute of Chemical Engineers AIChE J, 50: 2571–2582, 2004
Skeletal age, dental age, and the maturation of KNM‐WT 15000
Authors: Smith Shelley L. 
Published: September 2004

AbstractThe skeleton of theHomo erectusboy from West Lake Turkana, Kenya (KNM‐WT 15000), is remarkably complete, and this individual has thus provided a case study for several researchers examiningHomo erectusgrowth. Using data from a longitudinal study of Montreal French‐Canadian children, it is shown that while dental and skeletal ages match reasonably well at the level of a sample of children, individuals can display differences between skeletal and dental ages of 2 years or more. Furthermore, the relationship between these two markers may change over time in individual children. It is also possible to find children with patterns of dental maturation similar to KNM‐WT 15000's pattern in the Montreal sample. Therefore, neither the discrepancy between skeletal age and dental age alone nor the pattern of dental maturation as assessed by dental stages precludes a human‐like pattern of growth, including an adolescent growth spurt, for this individual. Some indicators (e.g., estimated body size for predicted age, and enamel formation) do suggest possible growth‐patterning differences from modern humans, and therefore earlier maturation is a reasonable hypothesis, but caution is warranted, given the large degree of modern human variation in developmental markers and the inherent uncertainty in precise estimation of KNM‐WT 15000's maturational parameters. Am J Phys Anthropol, 2004. © 2004 Wiley‐Liss, Inc.
Estimation of the most likely number of individuals from commingled human skeletal remains
Authors: Adams Bradley J. , Konigsberg Lyle W. 
Published: September 2004

AbstractThis study examines quantification techniques applicable to human skeletal remains, and in particular the Lincoln index (LI), the minimum number of individuals (MNI), and what we refer to as the most likely number of individuals (MLNI), which is a modification of the LI by Chapman ([1951] Univ. Calif. Publ. Stat. 1:131–159). As part of the study, a test of pair‐matching between commingled homologous elements, e.g., right and left femora, was performed based on gross morphology. The results show that pair‐matching can be accurately performed, and that the MLNI is a useful technique for dealing with well‐preserved commingled remains recovered from archaeological excavations and/or forensic investigations. Our results show that it is potentially misleading to draw population conclusions based on the MNI, except in instances where recovery is near 100%. The MLNI was found to be the best method to compensate for the potential underestimates of the MNI and potential bias in the original LI estimates resulting from small sample sizes. We demonstrate the use of MLNI in estimating the number of individuals from Lodge 21 at the Larson site, a late protohistoric structure at which the inhabitants were massacred and subsequently had their skeletal elements commingled by further taphonomic processes. We also show how to calculate estimates and standard errors for the recovery probabilities of skeletal elements. Am J Phys Anthropol, 2004. © 2004 Wiley‐Liss, Inc.
Crystalline morphology and isothermal crystallization kinetics of poly(ethylene terephthalate)/clay nanocomposites
Authors: Wan Tong , Chen Ling , Chua Yang Choo , Lu Xuehong 
Published: September 2004

AbstractA poly(ethylene terephthalate) (PET)/montmorillonite clay nanocomposite was synthesized via in situ polymerization. Microscopic studies revealed that in an isothermal crystallization process, some crystallites in the nanocomposite initially were rod‐shaped and later exhibited three‐dimensional growth. The crystallites in the nanocomposite were irregularly shaped, rather than spherulitic, being interlocked together without clear boundaries, and they were much smaller than those of neat PET. With Avrami analysis, the isothermal crystallization kinetic parameters (the Avrami exponent and constant) were obtained. The rate constants for the nanocomposite demonstrated that clay could greatly increase the crystallization rate of PET. The results for the Avrami exponent were consistent with the observation of the rodlike crystallites in the PET/clay nanocomposite during the initial stage. Wide‐angle X‐ray scattering and Fourier transform infrared studies showed that, in comparison with neat PET, the crystal lattice parameters and crystallinity of the nanocomposite did not change significantly, whereas more defects may have been present in the crystalline regions of the nanocomposite because of the presence of the clay. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 1381–1388, 2004