bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bronchodilatory effects of the aqueous extract of Gynostemma pentaphyllum and gypenosides III and VIII in anaesthetized guinea-pigs
Authors: Circosta Clara , de Pasquale Rita , Palumbo Dora R , Occhiuto Francesco 
Published: July 2005

Abstract
The bronchodilatory activity of the aqueous extract of Gynostemma pentaphyllum Makino leaves was investigated in anaesthetized guinea-pigs and compared with two of its isolated gypenosides (III and VIII). The results showed that the intravenous administration of the decoction of G. pentaphyllum (2.5, 5 or 10 mg kg−1) decreased bronchial resistance in basal conditions and significantly (P&lt;0.01) reduced (68% inhibition) the bronchoconstrictor action of histamine. Furthermore, the extract antagonized (80% inhibition) the bronchoconstrictor response induced by the antigen in sensitized guinea-pigs. Gypenosides III (0.7 mg kg−1, i.v.) and VIII (0.3 mg kg−1, i.v.) caused a similar protective effect in both experimental models used; however, the duration and the intensity of the action was less than that of the extract containing corresponding quantities of gypenosides III and VIII. This study confirmed the validity of the traditional use of this plant in the treatment of asthma and other respiratory disorders.
Protective effects of baicalin on oxygen/glucose deprivation- and NMDA-induced injuries in rat hippocampal slices
Authors: Liu Lu-Ying , Wei Er-Qing , Zhao Yan-Min , Chen Fang-Xue , Wang Meng-Ling , Zhang Wei-Ping , Chen Zhong 
Published: July 2005

Abstract
Baicalin is a flavonoid derivative from Scutellaria baicalensis Georgi with various pharmacological effects. Recently, the neuroprotective effect of baicalin was reported. To confirm this effect and explore the possible mechanism, we have investigated the protective effect of baicalin on ischaemiclike or excitotoxic injury and the activation of protein kinase Cα (PKCα) in rat hippocampal slices. In-vitro ischaemic-like injury was induced by oxygen/glucose deprivation (OGD) and the excitotoxic injury by N-methyl-d-aspartate (NMDA). The viability and swelling of the slices were detected by triphenyltetrazolium chloride (TTC) staining and image analysis of light transmittance (LT), respectively. The translocation of PKCα was measured by immunoblotting. Baicalin was added during both injuries. Baicalin (0.1, 1, and 10 μmolL−1) concentration-dependently inhibited OGD-induced viability reduction and acute neuron swelling, and inhibited the increased portion of PKCα present in the membrane fraction over the total PKCα. Baicalin ameliorated NMDA-induced viability reduction (not LT elevation) and inhibited the NMDA-increased membrane portion of PKCα at 1 μmolL−1. We concluded that baicalin had a protective effect on ischaemic-like or excitotoxic injury in rat hippocampal slices, which might have been partly related to inhibition of PKCα translocation.
Determination of intraluminal theophylline concentrations after oral intake of an immediate-and a slow-release dosage form
Authors: Brouwers Joachim , Ingels Françoise , Tack Jan , Augustijns Patrick 
Published: July 2005

Abstract
The purpose of this study was to evaluate a protocol which enables determining luminal drug concentrations after oral drug administration in man. Human intestinal fluids were aspirated from two sampling sites (duodenum and jejunum) at different time points after oral intake of theophylline; an immediate- and a slow-release dosage form were used to demonstrate the feasibility of discriminating between different formulations. Osmolarity and pH of the aspirates were measured and theophylline concentrations were determined by HPLC-UV. After intake of the immediate-release formulation of theophylline, duodenal maximum concentrations up to 3 mm were reached within 30 min. Theophylline appeared to be almost completely absorbed before it reached the second sampling site in the jejunum, as observed jejunal concentrations were lower than 10% of the maximal duodenal concentrations. These results are in agreement with fast dissolution and fast absorption through the intestinal mucosa, which could be expected as theophylline belongs to class I of the Biopharmaceutical Classification System. In contrast to the immediate-release formulation, administering the slow-release dosage form resulted in a gradual appearance of theophylline, reaching maximal intestinal concentrations below 300 μm. The proposed methodology can be used to assess luminal drug concentrations and to monitor the time- and site-dependent composition of intestinal fluids after intake of an oral dosage form. This approach may contribute to a better understanding of the behaviour of oral drug formulations in the gastrointestinal tract and may be exploited to further unravel the complexity of the gastrointestinal absorption process. In addition, knowledge of luminal drug concentrations may assist in the selection of drug concentrations applied in in-vitro permeability assays.
Suppressive activity of epinastine hydrochloride on TARC production from human peripheral blood CD4+ T cells in-vitro
Authors: Kanai Ken-ichi , Asano Kazuhito , Hisamitsu Tadashi , Suzaki Harumi 
Published: July 2005

Abstract
Thymus- and activation-regulated chemokine (TARC) is an important molecule in the development and maintenance of allergic diseases. However, there is little information about the influence of anti-allergic agents on TARC production. The aim of this study is to examine the influence of epinastine hydrochloride, an H1-receptor antagonist, on TARC production from human peripheral blood CD4+ T cells using an in-vitro cell culture technique. CD4+ T cells prepared from healthy subjects were cultured in wells coated with a combination of OKT3 and anti-CD28 monoclonal antibody in the presence or absence of epinastine HCl for 24 h. The cells were also stimulated with interleukin (IL)-4 in a similar manner. Levels of TARC and IL-4 in culture supernatants were examined by ELISA. The addition of epinastine HCl exerted a dose-dependent suppressive effect on the production of both TARC and IL-4 from CD4+ T cells under co-stimulatory molecule stimulation. The minimum concentration of the agent showing a significant suppressive effect on TARC and IL-4 production was 5.0 μm and 2.5 μm, respectively. Epinastine HCl also suppressed the ability of cells to produce TARC in response to IL-4 stimulation, when the agent was added to cell cultures at more than 2.5 μm. It was concluded that this inhibitory action of epinastine HCl may be partially responsible for epinastine's attenuating effect on allergic diseases.
Gastroprotective effect of Astragaloside IV: role of prostaglandins, sulfhydryls and nitric oxide
Authors: Navarrete Andrés , Arrieta Jesús , Terrones Liliana , Abou-Gazar Hassan , Calis Ihsan 
Published: July 2005

Abstract
This investigation evaluated the gastroprotective activity of Astragaloside IV, a cycloartane-type triterpene glycoside isolated from Astragalus zahlbruckneri. Gastric mucosal damage was induced in rats by intragastric ethanol (1 mL/rat). Rats treated orally with Astragaloside IV suspended in Tween 80 at 3, 10 and 30 mg kg−1, showed 15, 37 and 52% gastroprotection, respectively. The gastroprotection observed at 30 mg kg−1 for this compound was attenuated in rats pretreated with NG-nitro-l-arginine methyl ester (70 mg kg−1, i.p), a nitric oxide (NO)-synthase inhibitor, suggesting that the gastroprotective mechanism of this glycoside involves, at least in part, the participation of NO. The gastroprotective effect of Astragaloside IV was not affected by the inhibition of prostaglandin synthesis with indometacin (10 mg kg−1, s.c.) nor by the block of endogenous sulfhydryls with N-ethylmaleimide (NEM, 10 mg kg−1, s.c.). Carbenoxolone was used as a gastroprotective model drug and showed a dose-dependent gastroprotective effect (25, 43 and 88% of gastroprotection, at 3, 10 and 30 mg kg−1, respectively). The partial participation of prostaglandins, sulfhydryls and NO was observed in the gastroprotective mechanism of carbenoxolone.
Modification of gamma radiation induced response of peritoneal macrophages and splenocytes by Hippophae rhamnoides (RH-3) in mice
Authors: Prakash H , Bala Madhu , Ali A , Goel H C 
Published: July 2005

Abstract
Alcoholic extract of Hippophae rhamnoides, RH-3, reported to render &gt;80% survival against lethal whole body Co-60-gamma irradiation (10 Gy) in mice, was investigated for its immunostimulatory effects. In comparison with un-irradiated control, whole body irradiation did not reduce peritoneal macrophage counts at 24 h post-irradiation. RH-3 treatment (30 mg kg−1 body weight) alone or 30 min before whole-body irradiation enhanced viable counts of macrophages significantly (P≤0.05) compared with both un-irradiated control and irradiated groups. Whole-body irradiation reduced the number of viable splenocytes significantly (P≤0.05) compared with un-irradiated control at 24 h post-irradiation. RH-3 treatment alone or before whole-body irradiation appreciably countered radiation-induced decrease in splenocyte count. 3H-thymidine uptake method revealed that whole-body irradiation reduced splenocyte proliferation significantly (159 ± 45 counts min−1/106 cells; P±0.05) in comparison with control (607 ± 142 counts min−1) at 24 h after irradiation but RH-3 treatment before irradiation reduced the steep decrease and maintained it as 444 ± 153 counts-min−1. After whole-body irradiation, the ratio of spleen weight/mouse weight decreased to 1.5 ± 04 compared with 2.9 ± 0.32 in un-irradiated control at 24 h post-irradiation. Similarly, total protein content in splenocytes also decreased to 48 ± 6 μg/106 cells in comparison with 368 ± 16 μg/106 cells of un-irradiated control. RH-3 treatment before irradiation countered radiation-induced decrease in both spleen weight/mouse weight ratio (4.0 ± 0.35) and total protein content (360 ± 13 μg/106 splenocytes). In the supernatant of peritoneal macrophage cultures exposed to 2 Gy Co-60-gamma radiation ex-vivo, the total nitrite content was enhanced significantly (P&lt;0.05) to 5.72 ± 0.09 μm in comparison with un-irradiated control (1.64 ± 0.09 μm). RH-3 treatment (30 μg mL−1) before irradiation reduced total nitrite significantly (0.93 ± 0.3; P≤0.05) in comparison with irradiated control group. At 24 h after whole body irradiation, the CD4+/CD8+ ratio reduced to 1.5 in comparison with un-irradiated control (1.9) but RH-3 treatment before irradiation restored the ratio to 2.1. These findings explicitly reveal the immunostimulatory activity of RH-3, which may play an important role in the manifestation of its radioprotective efficacy.
Absorption characteristics of model compounds from the small intestinal serosal surface and a comparison with other organ surfaces
Authors: Nishida Koyo , Kuma Akiko , Fumoto Shintaro , Nakashima Mikiro , Sasaki Hitoshi , Nakamura Junzo 
Published: July 2005

Abstract
We examined the absorption of phenolsulfonphthalein (PSP) and fluorescein isothiocyanate dextrans (FD-4, MW 4400; FD-10, MW 9500; FD-40, MW 40500) as model compounds through the small intestinal serosal surface. After application to the rat small intestinal serosal surface using a cylindrical diffusion cell, each compound was absorbed at different rates. The absorption ratios in 6 h after PSP, FD-4, FD-10 and FD-40 application were calculated to be 89.2, 34.6, 14.9 and 2.1% of dose, respectively. Elimination profiles of PSP, FD-4 and FD-10 from the small intestinal serosal surface obeyed first-order kinetics. Moreover, we calculated the apparent permeability coefficient Papp for comparison to other organ surfaces. The kidney had the highest absorption efficiency, as shown by having more than 1.5 times significantly higher Papp values of PSP, FD-4 and FD-10. Similar to the other organ surfaces, a correlation was observed between the Papp of the small intestine and the molecular weight of these hydrophilic compounds. In addition, the small intestine is likely to contribute largely to hydrophilic compound absorption from the peritoneal cavity, judging from absorption clearance, CLa, calculated using the peritoneal organ surface area.
Further investigations on the role of ascorbic acid in stratum corneum lipid models after UV exposure
Authors: Trommer Hagen , Böttcher Rolf , Huschka Christoph , Wohlrab Wolfgang , Neubert Reinhard H H 
Published: July 2005

Abstract
This study is the continuation of our research into vitamin C and its possible effects on human skin after topical administration. The effects of ascorbic acid, iron ions and UV irradiation on stratum corneum lipid models were investigated. The lipid models used were: a simple system (linolenic acid dispersion), a complex system (liposomes consisting of dipalmitoylphosphatidylcholine, cholesterol and linolenic acid) and complex systems with additionally incorporated ceramides (types III and IV). The lipid peroxidation was quantified by the thiobarbituric acid assay. A human adult low-calcium high-temperature (HaCaT) keratinocytes cell culture was used as a second in-vitro model. The amount of intracellular peroxides was determined by measuring the fluorescence intensity using the dihydrorhodamine 123 assay. Electron paramagnetic resonance spectroscopy was used to study the influence of ascorbic acid and iron ions on the signal intensity of 5-doxylstearic acid during UV exposure. Ascorbic acid showed prooxidative properties in the thiobarbituric acid assay whereas cell protection was measured in the HaCaT keratinocytes experiments. Electron paramagnetic resonance investigations revealed different extents of free radical production generated by iron ions, ascorbic acid and UV irradiation. In evaluating the results from this study new aspects of the mechanism of lipid damage caused by these three factors were suggested, transcending the simple redox behaviour of ascorbic acid.
Daubertand the Proper Role for the Courts in Health, Safety, and Environmental Regulation
Authors: McGarity Thomas O. 
Published: July 2005

Assigning a Daubert-like gatekeeper role to courts engaged in judicial review of risk assessments prepared by federal agencies is a profoundly bad idea.I describe the role of courts in reviewing regulatory agency decisionmaking and explore the potential impact of incorporating Daubert principles into administrative law. A Daubert form of judicial review will prevent agencies from employing a “weight of the evidence” approach, forcing them to adopt a “corpuscular” approach that rewards efforts by regulatees to find and exaggerate flaws in individual scientific studies.Consequently, applying Daubert to federal agency decisionmaking will have a predictable impact on regulatory policy that runs directly counter to the precautionary policies that animate most health, safety, and environmental statutes.
Expert Evidence, the Adversary System, and the Jury
Authors: Vidmar Neil 
Published: July 2005

Many assertions have been made about the competence of juries in dealing with expert evidence. I review the types of expert evidence that jurors hear and the impact of adversary legal procedure on the form and manner in which evidence is presented. Empirical research indicates that jurors understand the adversary process, that they do not automatically defer to the opinions of experts, and that their verdicts appear to be generally consistent with external criteria of performance. Conflicts between the American adversary system and changes in trial procedures that might assist the jury in its task are also considered here.
What Has a Decade of Daubert Wrought?
Authors: Berger Margaret A. 
Published: July 2005

There have been changes within the judicial system that may be attributable to opinions on the admissibility of expert testimony that began with the Supreme Court’s 1993 decision in Daubert v Merrell Dow Pharmaceuticals, Inc. After surveying Daubert and subsequent related Supreme Court opinions, I examine a number of questions. Do the factors courts apply post-Daubert in ruling on the admissibility of expert testimony make scientific sense? Has Daubert had an impact on the willingness of scientists to become expert witnesses? What do we know about Daubert’s impact on improving science in the court room? What has been Daubert’s effect on access to the courts? Does Daubert further public policy objectives of protecting the public against harm?
Scientific Inferences in the Laboratory and the Law
Authors: Cranor Carl 
Published: July 2005

Following the Supreme Court’s Daubert v Merrell Dow Pharmaceuticals, Inc decision, courts have struggled in reviewing scientific evidence and appear to have appreciated insufficiently the nature of scientific reasoning. To assist their evidentiary reviews, courts need to appreciate both scientific complexity and ignorance about human toxicity caused by the universe of chemical substances. Conscientious, well-motivated, respectable experts can come to different conclusions about scientific evidence without making obvious mistakes and without being charlatans. So that justice is done between parties, courts need to allow for reasonable scientific disagreement to avoid excluding from trials respectable experts and all relevant scientific evidence. The public health community can assist courts to understand ranges of scientific evidence and to recognize the reasonableness of scientific disagreements.
Regulatory Parallels to Daubert: Stakeholder Influence, “Sound Science,” and the Delayed Adoption of Health-Protective Standards
Authors: Neff Roni A. , Goldman Lynn R. 
Published: July 2005

There is broad agreement that regulatory decisions should be based on evidence. But interested parties have used the “sound science” mantle to demand extended research, analysis, and review of evidence for the sole purpose of delaying health-protective regulation. This historical review shows how the forces behind the “sound science” reasoning leading to the Daubert v Merrell Dow Pharmaceuticals, Inc decision on science in the courtroom have operated in parallel in environmental regulation. Like Daubert, certain “sound science” regulatory tools can be used to improve decision quality. However, these tools can also challenge the federal government’s ability to safeguard the public’s health and well-being. Most recently, political tampering with science provides the foundation for some policymakers to disregard science completely in the environmental regulatory process.
Law’s Knowledge: Science for Justice in Legal Settings
Authors: Jasanoff Sheila 
Published: July 2005

Legal developments following Daubert v Merrell Dow Pharmaceuticals, Inc indicate a growing need to reevaluate the decision’s fundamental assumptions about law, science, and their interactions.I argue that in Daubert and two successor cases, the Supreme Court misconceived both the nature of scientific practice and its links to legal fact-finding. The decisions endorsed a separatist model of law and science, presupposing a sharper boundary between the institutions than exists or should exist.A better approach is to recognize that law and science are both knowledge-generating institutions, but that fact-making serves different functions in these two settings. The important question for the law is not how judges can best do justice to science, but rather how courts can better render justice under conditions of uncertainty and ignorance.
Legislating “Sound Science”: The Role of the Tobacco Industry
Authors: Baba Annamaria , Cook Daniel M. , McGarity Thomas O. , Bero Lisa A. 
Published: July 2005

In the late 1990s, in an effort to dispute the link between secondhand smoke and lung cancer, Philip Morris initiated a campaign to legislate “sound science.” The campaign involved enacting data access and data quality laws to obtain previously confidential research data in order to reanalyze it based on industry-generated data quality standards. Philip Morris worked with other corporate interests to form coalitions and workgroups, develop a “data integrity” outreach program, sponsor symposia on “research integrity,” and draft language for the new acts. The tobacco industry played a role in establishing laws that increase corporate influence on public health and regulatory policy decisions.
The (Near) Irrelevance of Daubert to Criminal Justice and Some Suggestions for Reform
Authors: Neufeld Peter J. 
Published: July 2005

Daubert v Merrell Dow Pharmaceuticals, Inc should have an extraordinary impact on criminal litigation, because there is rarely a criminal trial that does not rely on some form of expert testimony. In fact, it is almost irrelevant. Despite the frequency of prosecution proffered scientific and expert testimony in criminal cases, Daubert is rarely invoked to challenge it. In civil cases, when expert testimony is challenged in criminal proceedings, the outcome could not be more different. Because most violent crimes are committed by the poor, their court appointed advocates—overworked and underfinanced—are not up to the challenge. In the absence of a system of effective representation, Daubert will not improve scientific evidence in criminal cases. The only way to guard against the misapplication of forensic science is to impose controls and reforms long before the cases come to court.
Causation and Causal Inference in Epidemiology
Authors: Rothman Kenneth J. , Greenland Sander 
Published: July 2005

Concepts of cause and causal inference are largely self-taught from early learning experiences. A model of causation that describes causes in terms of sufficient causes and their component causes illuminates important principles such as multicausality, the dependence of the strength of component causes on the prevalence of complementary component causes, and interaction between component causes. Philosophers agree that causal propositions cannot be proved, and find flaws or practical limitations in all philosophies of causal inference. Hence, the role of logic, belief, and observation in evaluating causal propositions is not settled. Causal inference in epidemiology is better viewed as an exercise in measurement of an effect rather than as a criterion-guided process for deciding whether an effect is present or not.
Science and Regulation: Current Impasse and Future Solutions
Authors: Hoppin Polly J. , Clapp Richard 
Published: July 2005

We reflect on four articles that examine the Supreme Court’s Daubert v Merrell Dow Pharmaceuticals, Inc decision and efforts by private interests to derail public health and environmental regulations. The articles’ authors make the case that the impact of Daubert and related decisions in court settings pale by comparison to the threat that Daubert-like thinking poses in the regulatory arena. A growing number of companies, however, have made substantial changes in practice and in culture by embracing a philosophy where health and environment are priorities. Mechanisms could be established to encourage firms to pledge to use science to meet public health and environmental goals, as well as channel the ingenuity of the private sector towards ecological, economical, and equitable systems of production.
Synthesis of 6‐Substituted 7‐Bomoazabicyclo[2.2.1]heptanes via Nucleophilic Addition to 3‐Bromo‐1‐azoniatricyclo[2.2.1.0]‐heptane Bromide
Authors: Gayet Arnaud , Andersson Pher G. 
Published: July 2005

AbstractWe describe herein an efficient method for the preparation of a functionalised bicyclic framework (6‐substituted 7‐bromo‐aza‐bicyclo[2.2.1]heptane) through the selective opening of the aziridium 2 with organocuprates in up to 90% yield. These interesting chiral building blocks were then utilised as novel ligands in the rearrangement of epoxides to afford chiral allylic alcohols.