bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischemic Preconditioning Attenuates Portal Venous Plasma Concentrations of Purines following Warm Liver Ischemia in Man
Authors: Choukèr A. , Martignoni A. , Schauer R.J. , Rau H.G. , Volk A. , Heizmann O. , Dugas M. , Messmer K. , Peter K. , Thiel M.
Published: August 2005

Background/Aims: Degradation of adenine nucleotides to adenosine has been suggested to play a critical role in ischemic preconditioning (IPC). Thus, we questioned in patients undergoing partial hepatectomy whether (i) IPC will increase plasma purine catabolites and whether (ii) formation of purines in response to vascular clamping (Pringle maneuver) can be attenuated by prior IPC. Methods: 75 patients were randomly assigned to three groups: group I underwent hepatectomy without vascular clamping; group II was subjected to the Pringle maneuver during resection, and group III was preconditioned (10 min ischemia and 10 min reperfusion) prior to the Pringle maneuver for resection. Central, portal venous and arterial plasma concentrations of adenosine, inosine, hypoxanthine and xanthine were determined by high-performance liquid chromatography. Results: Duration of the Pringle maneuver did not differ between patients with or without IPC. Surgery without vascular clamping had only a minor effect on plasma purine concentrations. After IPC, plasma concentrations of purines transiently increased. After the Pringle maneuver alone, purine plasma concentrations were most increased. This strong rise in plasma purines caused by the Pringle maneuver, however, was significantly attenuated by IPC. When portal venous minus arterial concentration difference was calculated for inosine or hypoxanthine, the respective differences became positive in patients subjected to the Pringle maneuver and were completely prevented by preconditioning. Conclusion: These data demonstrate that (i) IPC increases formation of adenosine, and that (ii) the unwanted degradation of adenine nucleotides to purines caused by the Pringle maneuver can be attenuated by IPC. Because IPC also induces a decrease of portal venous minus arterial purine plasma concentration differences, IPC might possibly decrease disturbances in the energy metabolism in the intestine as well.
Association of Interleukin-8 and Plasminogen Activator System in the Progression of Colorectal Cancer
Authors: Terada H. , Urano T. , Konno H.
Published: August 2005

The aim of this study was to investigate the relationship of Interleukin-8 (IL-8) with vascular endothelial growth factor (VEGF) and plasminogen activator system (PA system) in the progression of colorectal cancer (CRC). In eighty-seven patients with CRC, the levels of IL-8, and VEGF as representative angiogenic factors and urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), plasminogen activator inhibitor-1 (PAI-1), and PAI-2 as representative invasive factors were quantitatively assayed in tumor and adjacent normal tissues. The levels of IL-8, VEGF, and PA system factors in tumor tissues were all significantly higher than those in normal tissues. The IL-8 level was significantly associated with tumor size, depth of infiltration, Dukes stage, and liver metastasis, and also significantly correlated with the levels of VEGF, uPAR, uPA, and PAI-1. The VEGF level was significantly associated with tumor size, vascular involvement. The levels of uPAR and PAI-1 were significantly associated with tumor size and depth of infiltration, and the uPAR level was associated with liver metastasis. The VEGF level was significantly correlated with the levels of uPAR and PAI-1. These results reveal that IL-8, VEGF, and PA system factors are contributed to tumor growth, invasion, and metastasis in CRC. Univariate analysis revealed that high levels of IL-8, VEGF, and uPAR were significantly associated with a shorter overall survival time; however, multivariate analysis identified only liver metastasis as an independent prognostic factor. In conclusion, IL-8 is responsible to tumor progression and liver metastasis of CRC, and the activation of PAS induced by IL-8 as well as VEGF may play an important role in the progression of CRC.
TC21/R-Ras2 Upregulation in Esophageal Tumorigenesis: Potential Diagnostic Implications
Authors: Sharma Rinu , Sud Neetu , Chattopadhyay Tushar Kant , Ralhan Ranju
Published: August 2005

Objectives: Early detection of esophageal cancer is hampered by paucity of molecular markers for diagnosis of this aggressive gastrointestinal malignancy in early stages. We recently identified TC21/R-Ras2, a small GTP-binding protein (SMG) in esophageal squamous cell carcinomas (ESCCs) by differential display. This study was designed to test the hypothesis that differential expression of TC21 in normal, dysplastic and malignant esophageal tissues may be of clinical relevance in esophageal tumorigenesis. Methods:Immunohistochemical analysis of TC21 was carried out in 83 ESCCs, 37 dysplasias and 29 matched histologically normal esophageal tissues and correlated with clinicopathological parameters. The cellularlocalization of TC21 was determined by confocal microscopy. Results: Expression of TC21 protein was observed in 60/83 (73%) ESCCs predominantly localized in tumor nuclei. Intriguingly, intense TC21 immunoreactivity was observed in all endoscopic biopsies with histological evidence of dysplasia (16 cases) as well as in dysplastic areas distant to ESCCs (21 cases), while matched distant histologically normal epithelia did not show detectable TC21 expression. Immunoblotting and semi-quantitative RT-PCR confirmed TC21 expression in dysplastias and ESCCs. Confocal microscopy showed nuclear as well as cytoplasmic TC21 expression in ESCCs and TE13 cells. Conclusions: To our knowledge, this is the first report demonstrating differential expression of TC21 in normal, dysplastic and ESCC tissues, suggesting that TC21 expression is associated with early stages of esophageal tumorigenesis. Nuclear localization of TC21 makes it the third of over 100 small SMGs identified to be localized in the nucleus.
Lactational Transfer of Cadmium from  Meriones shawi shawi Mothers to Their Pups and Its Effects on Calcium Homeostasis and Bone Calcium in Pups
Authors: Haouem Samir , Sakly Rachid
Published: August 2005

Cadmium (Cd) was given to Meriones shawi shawi dams in the diet (1 g CdCl2/1.5 kg of diet) from day 1 to day 21 of lactation. Pups were killed at 5, 10, 14 and 21 days of lactation. Thereafter, liver, kidney, femur and stomach content were removed and plasma was collected to element analyses. Cd in stomach content, kidney, liver and femur and calcium (Ca) in stomach content, femur and plasma were determined in pups by atomic absorption spectrophotometer. The results indicate that Cd was transferred to the suckling and it was detected in the liver, the kidney and the femur from the 5th, the 10th and the 14th days of age, respectively. Stomach content of Ca was increased significantly from the 10th day to the end of lactation, whereas Ca levels increase in plasma and femur only at day 10 of lactation.
Empirical Reflections on Academic Training Programs in Counseling Psychology
Authors: Neimeyer Greg J. , Goodyear Rodney K.
Published: August 2005

The three main articles in the Major Contribution of the September issue of The Counseling Psychologist address academic training programs in counseling psychology, focusing on their institutional contexts and commitments. Each article examines one key issue, provides empirical data concerning this issue, and traces the practical implications of these data for future research, training, or policymaking in the field of counseling psychology.
The Shifting Sands of Counseling Psychology Programs’ Institutional Contexts
Authors: Blustein David L. , Goodyear Rodney K. , Perry Justin C. , Cypers Scott
Published: August 2005

Despite strong indicators of the robustness of counseling psychology, the specialty seems somewhat vulnerable, as evidenced by the fact that several solid programs have been forced to phase out or to convert to combined-integrated programs. In fact, analyzing the trends among counseling psychology programs reveals that 30% of programs that have been accredited have been phased out. This article provides a context for understanding the accreditation history of counseling psychology programs. We then offer solutions and strategies to reduce this particular vulnerability. The proximal and distal solutions that are presented may help ensure the continued flourishing of counseling psychology across institutional, programmatic, and national levels.
A Broad View of Education and Training
Authors: Cornish Jennifer A. Erickson , Riva Maria T.
Published: August 2005

This reaction responds to the three core articles in the Major Contribution in the September 2005issue of The Counseling Psychologist regarding (a) how counseling psychology programs fit within academic structures, (b) how our training models relate to student and faculty outcomes, and (c) how much progress has been made toward increasing the diversity of our faculty. The authors (a director/internship director in a university counseling center and a training director of a counseling psychology program) share a belief in the continued need for teachers and trainers in counseling psychology to work together, not only within departments and colleges but across campuses and throughout the field. The importance of collaboration between graduate programs and college counseling centers is highlighted, and support for a closer fit with colleges of education is stressed, along with a commitment to children and adolescents. This Major Contribution will hopefully reinvigorate other cooperative efforts.
Feminist Identity and Theories as Correlates of Feminist Supervision Practices
Authors: Szymanski Dawn M.
Published: August 2005

Although feminist supervision approaches have been advanced in the literature as alternatives or adjuncts to traditional supervision models, little is known about those who utilize feminist supervision practices. This study was designed to examine if feminist supervision practices were related to one’s own feminist identity and various beliefs regarding feminism in general in a sample of 135 clinical supervisors. Results revealed that feminist supervision was significantly negatively correlated with passive acceptance of traditional gender roles and positively correlated with feelings of anger over sexism, connection with women’s communities, commitment to feminist activism, and beliefs that are consistent with five prominent feminist philosophies. Multiple regression analysis found that greater use of feminist supervision practices was uniquely related to being a woman; being lesbian, gay, or bisexual; and having a greater commitment to feminist activism. Research and practice implications are discussed.
Partly Cloudy With a Chance of Rain
Authors: Neimeyer Greg J. , Goodyear Rodney K.
Published: August 2005

The three reactions in the September 2005 issue of The Counseling Psychologist provide a context for extending and deepening our understanding of key issues surrounding counseling psychology training programs. This rejoinder (a) comments on their reflections and suggestions, (b) offers a tabular summary of the suggestions made by the various contributors and discussants, and (c) concludes with the hope that this collection of articles and reactions will contribute to an ongoing process of development that will help ensure counseling psychology’s continued viability.
Dealing with Diversity
Authors: Greene Victor
Published: August 2005

This article is a history of howMilwaukee urban leaders treated their diverse, ethnic communities by “ Americanizing” them. The Milwaukee experience with their immigrants was both similar to and distinctive of other American cities. Basing their reception on the German tradition of fellowship as other midwestern centers, Milwaukeeans were unique throughout in combining a love for promoting the ethnic diversity of dress, music, and dance with teaching foreigners the English language and American democratic principles. Therefore, from especially the 1920s on, Americanizing foreigners in tax-supported, school social centers meant teaching them to be loyal Americans while offering training in and promotion of cultural differences.
Reflections on the Pedagogy of Place in Planning and Urban Design
Authors: Arefi Mahyar , Triantafillou Menelaos
Published: August 2005

This article revisits the concept of place in planning and urban design and proposes a conceptual framework consisting of four ontological constructs of place as a set of visual attributes, product, process, and meaning. The article discusses the theoretical underpinnings of each concept and explores the advantages of a continuum between these terms to help bridge the gap between policy planning and physical design and to move toward a meaningful urban design. The study also examines the application of the proposed constructs of place to a sophomore-planning studio, focusing on the University of Cincinnati campus, which was offered at the School of Planning during the fall quarter of 2002.
Spatial and Transportation Mismatch in Los Angeles
Authors: Ong Paul M. , Miller Douglas
Published: August 2005

This article compares the impacts of spatial mismatch (the geographic separation of workers and jobs) and transportation mismatch (the lack of access to a private automobile) on neighborhood employment-to-population ratios and unemployment rates. The study uses tract-level data for the Los Angeles metropolitan area. The analysis uses an instrumental-variable approach to correct for the simultaneity of employment and car ownership. Results indicate that transportation mismatch is the more important factor in generating poor labor-market outcomes, particularly for disadvantaged neighborhoods. Areas with relatively more jobs increase female employment rates but not male employment rates. On the other hand, lower car ownership rates significantly decrease the employment ratio and increase the unemployment rate for both sexes.
Framing a Conflict in a Community-University Partnership
Authors: Prins Esther
Published: August 2005

Tension and conflict are inherent in community-university partnerships, yet they can also lead to learning and growth. This article shows how four members of a partnership framed a dispute in rural California and examines how they resolved tacit, divergent expectations about communication, decision making, and authority. The dispute prompted a transition from informal to intentional decision making and helped members clarify their expectations of each other. Unclear purposes and practices lead to confusion, but deliberation and a willingness to learn enable partners to gain understanding and work together more effectively. The article concludes with implications for improving working relationships in community-university partnerships and collaborative planning.
Toward Postmodern Urbanism?
Authors: Hirt Sonia A.
Published: August 2005

This article analyzes the meaning of postmodernism in planning through the in-depth study of the evolution of planning and zoning in Cleveland, Ohio. Cleveland was selected because of its innovative and highly visible planning tradition, which has weaved through the main historic stages of American planning, and has served as a planning laboratory nationwide. The article investigates whether a postmodern planning transition in Cleveland is detectable and what its key aspects and contradictions are. It concludes that the postmodern shift in Cleveland is notably stronger in planning discourses than in planning policies. In so doing, the article demonstrates a key characteristic of the postmodern shift generally and in terms of planning, more specifically, that postmodernism is still more about a shift in attitudes than in actions.
The “Studio Abroad” as a Mode of Transcultural Engagement in Urban Planning Education
Authors: Abramson Daniel Benjamin
Published: August 2005

This article reviews the dynamics and achievements of a ten-year series of collaborative planning studios and field research between faculty and students from urban planning and design programs in Canadian and Chinese universities, with additional perspective gained by observations of other collaborations. Focusing on the pedagogical and cross-cultural communicative aspects of the experience, the article suggests some key features of successful international educational collaborations and assesses the special role that physical design can play in facilitating engagement between students from different “planning cultures.”
The Electoral College, Mobilization, and Turnout in the 2000 Presidential Election
Authors: Hill David , McKee Seth C.
Published: August 2005

This study takes a two-stage approach to examining the impact of the electoral college on turnout in the 2000 presidential election. First, we examine whether battleground states received more media spending and visits by the candidates and their party committees compared to nonbattleground states. Second, we examine whether media spending and candidate visits were related to state-level turnout. The results of the project show that the battleground states did receive significantly more media expenditures and candidate visits from the two major party campaigns than nonbattleground states. Furthermore, when controlling for state-level contextual and political factors, the more media expenditures and candidate visits a state received the higher the state turnout. Finally, the analysis reveals that state battleground status indirectly impacted state-level turnout through its effect on media spending and candidate visits.
Ralph Nader's Campaign Strategy in the 2000 U.S. Presidential Election
Authors: Burden Barry C.
Published: August 2005

Those observing the 2000 presidential campaign agreed that Ralph Nader could not win the presidency but disagreed about his actual strategy. Many Democrats contended that he was playing the role of “spoiler” in an attempt to attract attention or affect the election outcome. Others argued that he was trying to earn 5% of the popular vote to secure matching funds for the Green Party in the next presidential election. Count models find that Nader's travel schedule, unlike Gore's, was unresponsive to the closeness of the major-party race. Nader's appearances were driven primarily by opportunities for attracting a large number of voters, suggesting that earning 5% was indeed a central campaign goal. Data on television advertising produce a parallel result. This finding resolves an ongoing debate about Nader in particular, but also points to broader differences between major and minor-party campaign strategies.
COPASAAR – A database for proteomic analysis of single amino acid repeats
Authors: Depledge Daniel P , Dalby Andrew R
Published: August 2005

Background

Single amino acid repeats make up a significant proportion in all of the proteomes that have currently been determined. They have been shown to be functionally and medically significant, and are associated with cancers and neuro-degenerative diseases such as Huntington's Chorea, where a poly-glutamine repeat is responsible for causing the disease. The COPASAAR database is a new tool to facilitate the rapid analysis of single amino acid repeats at a proteome level. The database aims to simplify the comparison of repeat distributions between proteomes in order to provide a better understanding of their function and evolution.

Results

A comparative analysis of all proteomes in the database (currently 244) shows that single amino acid repeats account for about 12–14% of the proteome of any given species. They are more common in eukaryotes (14%) than in either archaea or bacteria (both 13%). Individual analyses of proteomes show that long single amino acid repeats (6+ residues) are much more common in the Eukaryotes and that longer repeats are usually made up of hydrophilic amino acids such as glutamine, glutamic acid, asparagine, aspartic acid and serine.

Conclusion

COPASAAR is a useful tool for comparative proteomics that provides rapid access to amino acid repeat data that can be readily data-mined. The COPASAAR database can be queried at the kingdom, proteome or individual protein level. As the amount of available proteome data increases this will be increasingly important in order to automate proteome comparison. The insights gained from these studies will give a better insight into the evolution of protein sequence and function.
Effect of neutrophil depletion on gelatinase expression, edema formation and hemorrhagic transformation after focal ischemic stroke
Authors: Harris Alex K , Ergul Adviye , Kozak Anna , Machado Livia S , Johnson Maribeth H , Fagan Susan C
Published: August 2005

Background

While gelatinase (MMP-2 and -9) activity is increased after focal ischemia/reperfusion injury in the brain, the relative contribution of neutrophils to the MMP activity and to the development of hemorrhagic transformation remains unknown.

Results

Anti-PMN treatment caused successful depletion of neutrophils in treated animals. There was no difference in either infarct volume or hemorrhage between control and PMN depleted animals. While there were significant increases in gelatinase (MMP-2 and MMP-9) expression and activity and edema formation associated with ischemia, neutrophil depletion failed to cause any change.

Conclusion

The main finding of this study is that, in the absence of circulating neutrophils, MMP-2 and MMP-9 expression and activity are still up-regulated following focal cerebral ischemia. Additionally, neutrophil depletion had no influence on indicators of ischemic brain damage including edema, hemorrhage, and infarct size. These findings indicate that, at least acutely, neutrophils are not a significant contributor of gelatinase activity associated with acute neurovascular damage after stroke.
Electronic properties of amino acid side chains: quantum mechanics calculation of substituent effects
Authors: Dwyer Donard S
Published: August 2005

Background

Electronic properties of amino acid side chains such as inductive and field effects have not been characterized in any detail. Quantum mechanics (QM) calculations and fundamental equations that account for substituent effects may provide insight into these important properties. PM3 analysis of electron distribution and polarizability was used to derive quantitative scales that describe steric factors, inductive effects, resonance effects, and field effects of amino acid side chains.

Results

These studies revealed that: (1) different semiempirical QM methods yield similar results for the electronic effects of side chain groups, (2) polarizability, which reflects molecular deformability, represents steric factors in electronic terms, and (3) inductive effects contribute to the propensity of an amino acid for α-helices.

Conclusion

The data provide initial characterization of the substituent effects of amino acid side chains and suggest that these properties affect electron density along the peptide backbone.
The health impacts of globalisation: a conceptual framework
Authors: Huynen Maud MTE , Martens Pim , Hilderink Henk BM
Published: August 2005

This paper describes a conceptual framework for the health implications of globalisation. The framework is developed by first identifying the main determinants of population health and the main features of the globalisation process. The resulting conceptual model explicitly visualises that globalisation affects the institutional, economic, social-cultural and ecological determinants of population health, and that the globalisation process mainly operates at the contextual level, while influencing health through its more distal and proximal determinants. The developed framework provides valuable insights in how to organise the complexity involved in studying the health effects resulting from globalisation. It could, therefore, give a meaningful contribution to further empirical research by serving as a 'think-model' and provides a basis for the development of future scenarios on health.
Effect of Larrea tridentata (creosote bush) on cholesterol gallstones and bile secretion in hamsters
Authors: Arteaga Silvia , Carmona Agustín , Andrade-Cetto Adolfo , Cárdenas René , Luis Juana
Published: August 2005

Larrea tridentata (Sesse and Moc. ex DC.) Coville is used for the treatment of gallstones in traditional Mexican medicine. The possible prevention or elimination of gallstones by ethanolic and aqueous extracts of the leaves and twigs of L. tridentata was tested in hamsters fed a rich carbohydrate, fat-free diet. In addition, the effects of the ethanolic extract and its main metabolite, nordihydroguaiaretic acid, on bile secretion in the perfused liver were tested. In the experiment on prevention of gallstones, the dry ethanolic extract at a level of 0.5% of diet completely inhibited gallstone formation, lowered biliary moles percent cholesterol and increased the proportion of chenodeoxycholic acid of hepatic bile. The dry aqueous extract at a level of 1% of diet did not affect gallstone frequency or biliary parameters. In the experiment on elimination of gallstones, the ethanolic extract significantly reduced gallstone frequency, gallbladder bile cholesterol concentration and moles percent cholesterol. Both the ethanolic extract and nordihydroguaiaretic acid had cholestatic effects in the perfused liver, with an EC50 of 34 and 28 mg dL−1, respectively, when perfused for 10 min. This effect was reversible with concentrations up to 40 mg dL−1. The results indicate that L. tridentata could be useful in the treatment of gallstone disease, however care must be taken due to its hepatotoxicity.
Antitumour activity of 3-chlorodeoxylapachol, a naphthoquinone from Avicennia germinans collected from an experimental plot in southern Florida
Authors: Jones William P , Lobo-Echeverri Tatiana , Mi Qiuwen , Chai Heebyung , Lee Dongho , Soejarto Djaja D , Cordell Geoffrey A , Pezzuto John M , Swanson Steven M , Kinghorn A Douglas
Published: August 2005

As part of an ongoing collaborative effort to discover new anticancer agents from plants, an extract obtained from the leaves and twigs of Avicennia germinans, collected in a coastal area of southern Florida, was identified as possessing cytotoxic activity in a panel of human cancer cell lines. Fractionation of the petroleum ether partition, using cytotoxicity to guide the fractionation, led to the isolation of 3-chlorodeoxylapachol. The antitumour potential of 3-chlorodeoxylapachol was demonstrated with the in-vivo hollow fibre assay, a model of antitumour activity using human cancer cell-filled fibres implanted into mice. The possibility that this compound is an artefact of the isolation procedure was ruled out by liquid chromatography—mass spectrometry analysis of extracts prepared without the use of chlorinated solvent. In conclusion, 3-chlordeoxylapachol, a secondary metabolite obtained from the chloroform-soluble extract of a mangrove tree, was cytotoxic in a panel of human cancer cells, and active against KB human cancer cells in the murine hollow fibre antitumour model, with selectivity in KB cells for the intravenous site at lower doses, indicating possible metabolic activation.
Antimycobacterial agents from selected Mexican medicinal plants
Authors: Rivero-Cruz Isabel , Acevedo Laura , Guerrero José A , Martínez Sergio , Pereda-Miranda Rogelio , Mata Rachel , Bye Robert , Franzblau Scott , Timmermann Barbara N
Published: August 2005

As part of the ICBG program Bioactive Agents from Dryland Biodiversity of Latin America, the present investigation was undertaken to explore the possible antimycobacterial potential of compounds derived from selected Mexican medicinal plants. Bioassay-guided fractionation of the crude extracts of Rumex hymenosepalus (Polygonaceae), Larrea divaricata (Zygophyllaceae), Phoradendron robinsonii (Loranthaceae) and Amphipteryngium adstringens (Julianiaceae) led to the isolation of several antimycobacterial compounds. Four stilbenoids, two flavan-3-ols and three anthraquinones were isolated from R. hymenosepalus. Two flavonols and nordihydroguaiaretic acid were obtained from L. divaricata. Sakuranetin was the antimycobacterial agent isolated from P. robinsonii. Two known triterpenoids and the novel natural product 3-dodecyl-1,8-dihydroxy-2-naphthoic acid were obtained from A. adstringens. In general, the isolates were identified by spectral means. The antimycobacterial activity of the secondary compounds isolated from the analysed species, as well as that of nine pure compounds previously isolated in our laboratories, was investigated; the MIC values ranged from 16 to 128μ mL−1. Among the tested compounds, the glycolipids, sesquiterpenoids and triterpenoids showed the best antimycobacterial activity. The antimycobacterial property of the glycolipids is reported for the first time. Although the tested compounds showed moderate antimycobacterial activity, their presence in the analysed species provides the rationale for their traditional use in the treatment of tuberculosis.
Historical and modern medicinal plant uses — the example of the Ch'orti‘ Maya and Ladinos in Eastern Guatemala
Authors: Kufer Johanna , Heinrich Michael , Förther Harald , Pöll Elfriede
Published: August 2005

Local empirical knowledge about medicinal properties of plants is the basis for their use as home remedies. Particularly in developing countries such remedies still are an indispensable resource for everyday health care. They form the basis for numerous studies on drugs from natural sources. Like other indigenous groups across the world, the Ch'orti' Maya in Eastern Guatemala are currently experiencing a phase of dramatic cultural change, with their traditional knowledge about plants being in great danger of disappearing. During 17 months of fieldwork, medicinal plant uses were documented using a semi-quantitative approach and analysed using ethnopharmacological methods. The most important groups of illnesses treated with plants were gastrointestinal complaints and illnesses associated with pain and fever. Field data were compared with mostly unpublished historical data collected in the 1930s by the anthropologist Charles Wisdom. This comparison showed that medicinal plant uses that are more consistent over time are also shared by a larger number of people. A literature search on the most frequently mentioned medicinal plants showed that, even for widely used medicinal species, phytochemical and pharmacological data are insufficient for fully understanding their therapeutic profile. Whereas a few examples of potentially dangerous practices were encountered, the limited amount of information available mostly supports local medicinal plant usage.
In-vitro corneal permeation of cannabinoids and their water-soluble phosphate ester prodrugs
Authors: Juntunen Juha , Järvinen Tomi , Niemi Riku
Published: August 2005

Topically administered cannabinoids have been shown to reduce intraocular pressure by interacting with the ocular cannabinoid receptor. Most cannabinoids have very poor aqueous solubility, which limits their pharmaceutical development and usefulness. In this study, permeation of three cannabinoids (arachidonylethanolamide, R-methanandamide and noladin ether) and their water-soluble phosphate ester prodrugs across isolated rabbit cornea was investigated in vitro. Hydroxypropyl-β-cyclodextrin (HP-β-CD) was used to solubilize the parent cannabinoids in permeation studies to achieve the required concentration in donor and receiving cells. Highest fluxes were obtained with lipophilic parent compounds administered with HP-β-CD, and the fluxes of phosphate esters were 45–70% that of their corresponding parent compounds. Phosphate esters hydrolysed on the surface of the cornea or during the permeation to release the lipophilic parent compound, which further permeated the cornea. No phosphate esters were detected on the endothelial side of the cornea. Although the phosphate esters had lower fluxes than their corresponding parent compounds in these HP-β-CD formulations, the results are promising and the fluxes of phosphate esters are significantly higher than the fluxes of parent compounds administered as a suspension (due to their low aqueous solubility) without HP-β-CD.
Effect of charge and lipid concentration on in-vivo percutaneous absorption of methyl nicotinate from liposomal vesicles
Authors: Puglia Carmelo , Rizza Luisa , Bonina Francesco , Esposito Elisabetta , Menegatti Enea , Cortesi Rita , Nastruzzi Claudio
Published: August 2005

We have investigated the influence of charge and lipid concentration on the in-vivo percutaneous absorption of a model compound, methyl nicotinate (MN), from liposomal vesicles. MN-loaded liposomes were produced by the reverse-phase evaporation method (REV) using different concentrations of phosphatidyl choline (PC), in association with surfactants such as dioctadecyl dimethyl ammonium bromide (DDAB18) and dicetyl phosphate (DCP), which impart a positive or negative charge to the systems, respectively. The liposomal suspensions were then processed to hydrogels and used to study in-vivo the MN permeation profile. MN was chosen as the model compound since it was capable of causing cutaneous erythema, the intensity and duration of which was proportional to the amount entering the living epidermis over time. The extent of the erythema was monitored by reflectance spectrophotometry, a non-invasive technique. In-vivo findings showed an interesting MN delayed release, which was proportional to the amount of phospholipids in each liposomal formulation. Furthermore, it could be noted that the erythematous effect was more prolonged when MN was delivered from neutral or negatively-charged liposomal forms.
Mannosylated niosomes as carrier adjuvant system for topical immunization
Authors: Jain Sanyog , Vyas S P
Published: August 2005

The aim of this study was to develop mannosylated niosomes as a topical vaccine delivery carrier and adjuvant for the induction of both humoral and cellular immunity. Bovine serum albumin (BSA)-loaded niosomes composed of sorbitan monostearate/sorbitan trioleate (Span 60/Span 85), cholesterol and stearylamine as constitutive lipids were prepared by the reverse-phase evaporation method. The niosomes were coated with a modified polysaccharide O-palmitoyl mannan (OPM) to target them to Langerhan's cells, the major antigen presenting cells found in abundance beneath the stratum corneum. Prepared niosomes were characterized in-vitro for their size, shape, entrapment efficiency and ligand binding specificity. The immune stimulating activity was studied by measuring serum IgG titre and its subclasses (IgG2a/IgG1 ratio) following topical application of various niosomal formulations in albino rats. The results were compared with alum-adsorbed BSA following topical application and intramuscular injection. It was observed that niosomal formulations elicited a significantly higher serum IgG titre upon topical application as compared with topically applied alum adsorbed BSA (P<0.05). The serum IgG levels were significantly higher for the mannosylated niosomes as compared with plain uncoated niosomes (P<0.05). All formulations displayed a combined serum IgG2a/IgG1 response, which suggested that the formulations were capable of eliciting both humoral and cellular responses. The study signified the potential of OPM-coated niosomes as a topical vaccine delivery carrier and adjuvant. The proposed system would be simple, stable, and cost effective and might be clinically acceptable.
Long-term treatment with Hachimi-jio-gan attenuates kidney damage in spontaneously diabetic WBN/Kob rats
Authors: Nakagawa Takako , Yokozawa Takako , Yamabe Noriko , Goto Hirozo , Shibahara Naotoshi , Rhyn Dong Young , Shimada Yutaka
Published: August 2005

Diabetes mellitus is now the most common cause of end-stage renal failure. In this study, the effects of Hachimi-jio-gan on diabetic kidney damage in spontaneously diabetic WBN/Kob rats were examined. Oral administration of Hachimi-jio-gan to WBN/Kob rats for 25 weeks significantly suppressed urinary protein excretion. It did not affect body weight loss or blood glucose levels, whereas it reversed the increase in kidney weight of WBN/Kob rats. Hachimi-jio-gan also reduced fibronectin and transforming growth factor β1 (TGF-β1) protein expression in the renal cortex. Furthermore, renal lipid peroxidation levels of WBN/Kob rats given Hachimi-jio-gan were significantly lower than those of untreated controls. Renal superoxide dismutase activity was elevated by Hachimi-jio-gan treatment in a dose-dependent manner. These results suggested that Hachimi-jio-gan could prevent diabetic kidney damage by reducing renal oxidative injury and expression of fibronectin and TGF-β1 proteins, which are all involved in the pathophysiology of diabetic nephropathy.
Puckered, aDrosophilaMAPK phosphatase, ensures cell viability by antagonizing JNK-induced apoptosis
Authors: McEwen Donald G. , Peifer Mark
Published: August 2005

MAPK phosphatases (MKPs) are important negative regulators of MAPKs in vivo, but ascertaining the role of specific MKPs is hindered by functional redundancy in vertebrates. Thus, we characterized MKP function by examining the function of Puckered (Puc), the sole Drosophila Jun N-terminal kinase (JNK)-specific MKP, during embryonic and imaginal disc development. We demonstrate that Puc is a key anti-apoptotic factor that prevents apoptosis in epithelial cells by restraining basal JNK signaling. Furthermore, we demonstrate that JNK signaling plays an important role inγ-irradiation-induced apoptosis, and examine how JNK signaling fits into the circuitry regulating this process. Radiation upregulates both JNK activity and puc expression in a p53-dependent manner, and apoptosis induced by loss of Puc can be suppressed by p53 inactivation. JNK signaling acts upstream of both Reaper and effector caspases. Finally, we demonstrate that JNK signaling directs normal developmentally regulated apoptotic events. However, if cell death is prevented, JNK activation can trigger tissue overgrowth. Thus, MKPs are key regulators of the delicate balance between proliferation, differentiation and apoptosis during development.
Polycomb group protein complexes exchange rapidly in livingDrosophila
Authors: Ficz Gabriella , Heintzmann Rainer , Arndt-Jovin Donna J.
Published: August 2005

Fluorescence recovery after photobleaching (FRAP) microscopy was used to determine the kinetic properties of Polycomb group (PcG) proteins in whole living Drosophila organisms (embryos) and tissues (wing imaginal discs and salivary glands).

PcG genes are essential genes in higher eukaryotes responsible for the maintenance of the spatially distinct repression of developmentally important regulators such as the homeotic genes. Their absence, as well as overexpression, causes transformations in the axial organization of the body. Although protein complexes have been isolated in vitro, little is known about their stability or exact mechanism of repression in vivo.

We determined the translational diffusion constants of PcG proteins,dissociation constants and residence times for complexes in vivo at different developmental stages. In polytene nuclei, the rate constants suggest heterogeneity of the complexes. Computer simulations with new models for spatially distributed protein complexes were performed in systems showing both diffusion and binding equilibria, and the results compared with our experimental data. We were able to determine forward and reverse rate constants for complex formation. Complexes exchanged within a period of 1-10 minutes, more than an order of magnitude faster than the cell cycle time,ruling out models of repression in which access of transcription activators to the chromatin is limited and demonstrating that long-term repression primarily reflects mass-action chemical equilibria.
Gata4 regulates the formation of multiple organs
Authors: Holtzinger Audrey , Evans Todd
Published: August 2005

We have developed a loss-of-function model for Gata4 in zebrafish, in order to examine broadly its requirement for organogenesis. We show that the function of Gata4 in zebrafish heart development is well conserved with that in mouse, and that, in addition, Gata4 is required for development of the intestine, liver, pancreas and swim bladder. Therefore, a single transcription factor regulates the formation of many organs. Gata6 is a closely related transcription factor with an overlapping expression pattern. We show that zebrafish depleted of Gata6 show defects in liver bud growth similar to mouse Gata6 mutants and zebrafish Gata4 morphants, and that zebrafish embryos depleted of both Gata4 and Gata6 display an earlier block in liver development, and thus completely lack liver buds. Therefore, Gata4 and Gata6 have distinct non-redundant functions in cardiac morphogenesis, but are redundant for an early step of liver development. In addition, both Gata4 and Gata6 are essential and non-redundant for liver growth following initial budding.
Two-dimensional gel analysis of the heat-shock response in marine snails(genusTegula): interspecific variation in protein expression and acclimation ability
Authors: Tomanek Lars
Published: August 2005

The degree to which temperature acclimation modifies the acute synthesis of the entire heat-shock protein (Hsp) complement is still unknown, but it may constitute an important mechanism for understanding the differences in acclimation ability among closely related ectothermic species that occupy widely varying thermal environments. In general, eurythermal (heat-tolerant)species modify physiological function in response to an increase in acclimation temperature to a greater extent than stenothermal (heat-sensitive)species. In the present work I used 35S-labelled amino acids and two-dimensional gel electrophoresis to test this assumption for how acclimation affects acute Hsp expression (referred to as phenotypic plasticity) in two heat-sensitive, low-intertidal to subtidal zone turban snails, Tegula brunnea and T. montereyi, in comparison to a heat-tolerant, mid- to low-intertidal zone congener, T. funebralis. I was able (i) to detect the synthesis of over 30 proteins in gill tissue,primarily in the 70 kDa range, in response to an increase in temperature(13°C, 24°C, 27°C and 30°C), (ii) to assess the effect of acclimation (13°C vs 22°C) on acute Hsp synthesis, and (iii)to compare this effect among the three Tegula congeners. After increasing acclimation temperature from 13°C to 22°C, synthesis of the most highly expressed Hsps decreased more in T. brunnea and T. montereyi than in T. funebralis. Two highly expressed proteins of molecular mass 71 and 74 kDa, however, were also synthesized constitutively at 13°C and changed with increasing acclimation temperature in all three species. Although similar in phenotypic plasticity, T. brunnea and T. montereyi synthesized either a 76 or a 72 kDa cluster of proteins,respectively, and differed in how acclimation affected the acute synthesis of several 77 kDa proteins. Thus, in Tegula, the effect of acclimation on Hsp expression is (i) Hsp-specific, (ii) dependent on a protein's expression pattern (constitutive and inducible vs only inducible),(iii) and is actually limited in the more eurythermal mid- to low-intertidal congener. These results contradict the general assumption that greater heat tolerance correlates with an increased ability to modify physiological function in response to acclimation.
Tracing heme in a living cell: hemoglobin degradation and heme traffic in digest cells of the cattle tickBoophilus microplus
Authors: Lara F. A. , Lins U. , Bechara G. H. , Oliveira P. L.
Published: August 2005

Heme is present in all cells, acting as a cofactor in essential metabolic pathways such as respiration and photosynthesis. Moreover, both heme and its degradation products, CO, iron and biliverdin, have been ascribed important signaling roles. However, limited knowledge is available on the intracellular pathways involved in the flux of heme between different cell compartments. The cattle tick Boophilus microplus ingests 100 times its own mass in blood. The digest cells of the midgut endocytose blood components and huge amounts of heme are released during hemoglobin digestion. Most of this heme is detoxified by accumulation into a specialized organelle, the hemosome.

We followed the fate of hemoglobin and albumin in primary cultures of digest cells by incubation with hemoglobin and albumin labeled with rhodamine. Uptake of hemoglobin by digest cells was inhibited by unlabeled globin,suggesting the presence of receptor-mediated endocytosis. After endocytosis,hemoglobin was observed inside large digestive vesicles. Albumin was exclusively associated with a population of small acidic vesicles, and an excess of unlabeled albumin did not inhibit its uptake. The intracellular pathway of the heme moiety of hemoglobin was specifically monitored using Palladium–mesoporphyrin IX (Pd-mP) as a fluorescent heme analog. When pulse and chase experiments were performed using digest cells incubated with Pd-mP bound to globin (Pd-mP-globin), strong yellow fluorescence was found in large digestive vesicles 4 h after the pulse. By 8 h, the emission of Pd-mP was red-shifted and more evident in the cytoplasm, and at 12 h most of the fluorescence was concentrated inside the hemosomes and had turned green. After 48 h, the Pd-mP signal was exclusively found in hemosomes. In methanol, Pd-mP showed maximal emission at 550 nm, exhibiting a red-shift to 665 nm when bound to proteins in vitro.

The red emission in the cytosol and at the boundary of hemosomes suggests the presence of heme-binding proteins, probably involved in transport of heme to the hemosome. The existence of an intracellular heme shuttle from the digestive vesicle to the hemosome acting as a detoxification mechanism should be regarded as a major adaptation of ticks to a blood-feeding way of life. To our knowledge, this is the first direct observation of intracellular transport of heme in a living eukaryotic cell. A similar approach, using Pd-mP fluorescence, could be applied to study heme intracellular metabolism in other cell types.
Behavioural discrimination of polarized light in the damselfishChromis viridis(family Pomacentridae)
Authors: Mussi Martina , Haimberger Theodore J. , Hawryshyn Craig W.
Published: August 2005

In this study, we demonstrate the capacity for damselfish (green chromis, Chromis viridis) to discriminate between different e-vector orientations of ultraviolet polarized light. We examined the ability of green chromis to resolve small differences in e-vector orientation of ultraviolet polarized light. Fish were successfully trained to swim towards an e-vector orientation of polarized light using a behavioural chamber. C. viridis was able to discriminate between the horizontal and the vertical plane of ultraviolet polarized light independent of brightness content of the stimuli. However, e-vector discrimination capability disappeared when the ultraviolet portion of the light stimuli was removed, indicating that the presence of ultraviolet light was critical for e-vector discrimination. Fish could also distinguish between relatively small e-vector orientations of ultraviolet polarized light. Functional implications for high e-vector discriminative capabilities could be used in functional domains such as feeding and communication.