bluuebunny/crossref_metadata_2025 huggingface dataset:
Kinetics of heavy metal desorption from three soils using citric acid, tartaric acid, and EDTA
Authors: Wasay S.A. , Barrington S. , Tokunagal S. , Prasher S.
Published: December 2007

Organic acids are relatively new soil heavy metal leaching agents requiring the development of desorption kinetics before being applied. The objective was to determine the heavy metal desorption rates for three heavily contaminated soils (clay loam, loam, and sandy clay loam), treated under optimum conditions with either citric acid, tartaric acid, or EDTA for comparison. A two-rate reaction (fast and slow) model was defined to describe desorption kinetics, where both first order rates were assumed irreversible and reversible, respectively. Experimental data were collected by initially subjecting the three soils to batch experiments at optimum leaching agent level, for up to 36 h. The results indicated that citric acid was a more consistent leaching agent compared to tartaric acid and EDTA, which were efficient mainly in treating the clay loam and the sandy clay loam, respectively. The two-rate reaction model fitted the data but its empirical coefficients need to be defined for each individual soil to be treated. For Pb common to all three experimental soils, k1, representing the fast desorption rate, increased with the ratio of metal equivalence fraction: soil CEC. The coefficients k2and α0, representing the slower rate of desorption and the proportion of Pb involved in this slow rate, respectively, increased with the mass of Pb held by the oxide and organic matter fractions. The coefficient m1, related to the relative rate of the backward reaction from the slow to the fast, varied according to the mass of Pb held by the exchangeable site. Despite the empirical values associated with the kinetics coefficients, their correspondence with individual processes indicate that organic acid remediation can be modeled using the two rate kinetic equation proposed in this project.
Phosphorus adsorption and oven dried alum residual solids in fixed bed column experiments
Authors: Mortula M.M. , Gagnon G.A.
Published: December 2007

In this study, fixed bed columns were used to evaluate the effectiveness of phosphorus adsorption on oven dried alum residual solids. The effect of key operating parameters (pH, particle size, and initial phosphorus concentration) on the effectiveness of phosphorus removal was investigated. The results indicated that phosphorus removal using oven dried alum residual solids was effective and comparable to granular activated carbon. Statistical analysis showed that the effect of particle size on the breakthrough pore volume processed was significant, but the effect of pH was inconclusive. Aluminum leaching was found to be higher than 20 mg/L for an influent pH level of 3. The effectiveness of phosphorus removal was affected by initial phosphorus concentration. However, initial phosphorus concentration did not appear to have any considerable effect on aluminum and organic leaching.
Bacterial cultures capable of facultative growth on methane under thermophilic or thermotolerant conditions
Authors: Laursen Andrew E. , Kulpa Charles F. , Niedzielski Maksymilian F. , Estable Mario C.
Published: December 2007

Bacteria cultured from thermal features (cultures OS and 44) and from sedimentary rock of the continental margin (SA) are capable of growth on methane as a sole carbon source under thermotolerant (OS and 44) to thermophilic (SA) conditions. All three grew better on enriched medium, suggesting methane is not a preferred substrate. Sequencing (16S rDNA) suggests OS and 44 are primarily Brevibacillus and SA is primarily Geobacillus , not members of described methanotrophic genera. These cultures appear pure based on cell morphology, however they may be consortia of tightly syntrophic bacteria. Growth on 13C-methane demonstrated that these bacteria incorporate carbon from methane. Labeling (δδ13C) was greatest when cultures were grown on methane only. When medium was supplemented with yeast extract (0.05%) labeling was less intense, however total methane incorporation was greater due to increased bacterial biomass. These bacterial cultures could have application for methane removal from waste streams at high temperatures.
Performance evaluation of fabric aided slow sand filter in drinking water treatment
Authors: Mondal Pulin Kumar , Seth Rajesh , Biswas Nihar
Published: December 2007

In this study, an assessment of the performance of slow sand filter (SSF) aided with non-woven fabric (NWF) was carried out. Several laboratory-scale SSF columns were tested with simulated raw water containing varying levels of turbidity and total organic carbon (TOC). The results show that in filters with NWF, the fabric layers captured most of the incoming solids and extended the filter run time for the sand bed. The run time for the sand bed increased with the increasing of the fabric thickness from 8.9 to 44.5 mm. Turbidity, TOC, and bacterial removal efficiencies of the filters with fabric were comparable to that without fabric and representing conventional SSF. The study thus demonstrates that operation of SSF with NWF can be a feasible option for simplifying the operation of and extending the viability of the SSF process to a wider range of raw water turbidity values than that considered economical for conventional SSF.
Polycyclic aromatic hydrocarbons emitted from a hot-mix drum, asphalt plant: study of the influence from use of recycled bitumen
Authors: Ventura Anne , Jullien Agnès , Monéron Pierre
Published: December 2007

Asphalt mixing is an industrial activity of which energy consumption can reach 60% of the total energy consumed by the construction and maintenance of a road over a 30-year service life. Hot mix asphalt plant represents the most common process found in the road sector. Hot bitumen fumes however contain polycyclic aromatic hydrocarbon (PAH) compounds, and, moreover, the use of recycled bitumen can lead to generating various emissions. Polycyclic aromatic hydrocarbons may also be emitted from the process itself, a step that requires warming and drying aggregate through combustion. In the aim of minimizing emissions, it has become necessary to identify the set of major influential parameters. A joint research program involving several institutions has been laid out to conduct an experimental campaign on the Blois Hot Mix Asphalt plant, with quantification of the 16 PAH listed by the USEPA. Variations in asphalt recycling rate favour emissions of heavy molecular weight PAH, among those analysed.
Application of artificial neural networks to effluent phosphate prediction in struvite recovery
Authors: Forrest Alexander L. , Fattah Kazi P. , Mavinic Donald S. , Koch Frederic A.
Published: December 2007

In advanced wastewater treatment plants (AWWTP), the recovery of phosphorus (P) has become a recent focus of the wastewater engineering industry. The potential economic savings behind improved sludge management and the control of struvite encrustation in AWWTP are two of the primary driving forces behind this. Process control of phosphorus (struvite) recovery systems has only been partially successful because: (1) key control variables have yet to be identified and (2) there is no adequate performance evaluation model that is applicable to struvite recovery technologies. In process control, two different types of modeling are most commonly seen: mechanistic and “black-box” style models. In recent years, varying models have been developed to try to predict the formation of struvite in both sludge digestion process lines and P-recovery technologies designed for struvite removal. All of these are strictly mechanistic models, based on either the chemical equilibrium of the system or the associated kinetic parameters, with varying degrees of complexity. Artificial neural networks (ANN), as a type of black-box modeling, have seen limited application in wastewater treatment with regards to phosphate recovery. The analysis of several historical daily operational databases evaluated the predictive ability of two mechanistic and one ANN models. It was determined that the newly developed ANN model was not site specific and had the highest predictive ability of the three. This would be beneficial for the development of an automated control system for struvite removal package treatment processes.
Potential side effects of using ammonia to inhibit bromate formation during the ozonation of drinking water
Authors: Hofmann R. , Andrews R.C.
Published: December 2007

This note identifies potential side effects of using ammonia to inhibit bromate formation during the ozonation of drinking water, and makes preliminary predictions of their significance. Based on kinetic calculations, it is expected that ammonia would not exert a significant ozone demand and consequently would have little impact on the ozonation process. The ammonia needed to inhibit bromate formation is also not expected to promote nitrification in distribution systems, since the ammonia would either typically be removed through breakpoint chlorination or would be used to form chloramines. However, the impact of ammonia on biologically active filters, which often follow ozonation, is more difficult to evaluate since the issue has not been directly studied, and the role of nitrogen in the biological processes in such an environment is complex. Further, if chlorine were being used for secondary disinfection, any ammonia that persisted in the treated water would exert a demand and would have to be considered.
Autothermal thermophilic aerobic digestion (ATAD) — Part II: Review of research and full-scale operating experiences
Authors: Layden Noreen M. , Kelly Harlan G. , Mavinic Donald S. , Moles Richard , Bartlett John
Published: December 2007

Autothermal thermophilic aerobic digestion (ATAD) is an exothermic process where sludge is subjected to temperatures greater than 55 °C for at least 4 hours, over 6–10 days. Organic solids are degraded and the heat released during the microbial degradation is used to bring the process temperature within the thermophilic range. It produces a biologically stable product, achieving a reduction in biomass, while using smaller digesters, compared to mesophilic aerobic and anaerobic digestion. There are no regulatory requirements in North America and Europe for the reduction of the volume of total solids in sludge processing. However, a reduction in the volume of material for final disposal has cost benefits. By virtue of the residual mass, volume reductions are easily made through dewatering or dehydrating steps following ATAD. Despite the apparent advantages of ATAD, limited information on the process is available in the literature. Concerns still exist about documented cases of odour issues, problems with sludge dewaterability, foaming, excess use of polymers and high-energy consumption. This article presents some relevant bench-scale and pilot ATAD study data, with appropriate discussion. It also assembles information from a range of sources and provides an insight into actual application and experiences with full-scale ATAD.
A Bayesian Framework for Multimodel Regression
Authors: DelSole Timothy
Published: December 2007

This paper presents a framework based on Bayesian regression and constrained least squares methods for incorporating prior beliefs in a linear regression problem. Prior beliefs are essential in regression theory when the number of predictors is not a small fraction of the sample size, a situation that leads to overfitting—that is, to fitting variability due to sampling errors. Under suitable assumptions, both the Bayesian estimate and the constrained least squares solution reduce to standard ridge regression. New generalizations of ridge regression based on priors relevant to multimodel combinations also are presented. In all cases, the strength of the prior is measured by a parameter called the ridge parameter. A “two-deep” cross-validation procedure is used to select the optimal ridge parameter and estimate the prediction error.

The proposed regression estimates are tested on the Development of a European Multimodel Ensemble System for Seasonal to Interannual Prediction (DEMETER) hindcasts of seasonal mean 2-m temperature over land. Surprisingly, none of the regression models proposed here can consistently beat the skill of a simple multimodel mean, despite the fact that one of the regression models recovers the multimodel mean in a suitable limit. This discrepancy arises from the fact that methods employed to select the ridge parameter are themselves sensitive to sampling errors. It is plausible that incorporating the prior belief that regression parameters are “large scale” can reduce overfitting and result in improved performance relative to the multimodel mean. Despite this, results from the multimodel mean demonstrate that seasonal mean 2-m temperature is predictable for at least three months in several regions.
From mountain trade to jungle politics
Authors: Moran Arik
Published: December 2007

This article explores the interaction between a kingdom on the Himalayan frontier and colonial rule. Drawing on recent anthropological research regarding the local expression of political sovereignty through ‘government by deity’ (devta ka raj), it aims to reinterpret the actions taken by Bashahr's ruling class in relation to their colonial superiors. As British interests in modernisation and forestry challenged the rulers’ power base, the latter devised alternative methods in order to retain their authority. The increasing contestation of power in the latter half of the nineteenth century gradually polarised the kingdom's ruling strata between those advocating accommodation to British rule and those bent on retaining their independence. The culmination of this process saw a transformed kingship in early twentieth-century Bashahr.
‘Delinquent subjects’
Authors: Bhukya Bhangya
Published: December 2007

This article examines how dacoities in colonial India began largely during famines, and how they were perpetuated by the state's cruel practices of detention and surveillance. When dacoity was seen to be a threat to civil society and the state, the authorities deployed a variety of methods to put down, control, punish and reform the dacoits, many of who were considered to belong to ‘criminal tribes/communities’. The creation of a body of anthropological knowledge about the ‘criminal’ communities was important in this respect, as it helped the state to separate supposedly ‘delinquent’ from ‘honest’ subjects. It also conferred a specific social identity upon such groups, thereby socially stigmatising them. The creation of a surveillance society served colonial ends. The Criminal Tribes Act (CTA) of 1871 provided for those designated as criminal tribes to be registered with local police stations, to be confined to specific villages, fined, punished, and put in reformatories. Groups that suffered such a fate thereafter found it so difficult to earn an honest livelihood that they became even more likely to commit dacoities. The itinerant Lambadas of Hyderabad state who were so incarcerated were particularly hard hit.
The shaping of land revenue policy in Madras Presidency
Authors: Mustafa Mohammed
Published: December 2007

There were a number of systems of settlements in Madras Presidency when the East India Company assumed administrative charges at the end of the eighteenth century. The Company government did not know which system was suitable and should be adopted for the whole of the Presidency. It initiated permanent settlement in 1802 in some areas, and found it unsuitable to be applied to other regions. Thus, it began a series of experiments in different districts in order to find a suitable system of settlement. These revenue experiments finally led the Company government to adopt the ryotwari system in many regions. It is these revenue experiments that the present article examines in relation to Chittoor district, and brings out the factors responsible for changing government policies during the period of experiments. The study shows how the settlements made with different types of landlords led to the formation of separate groups in rural areas and, in turn, planted the seeds of factional politics in the later period in the present Rayalseema region, which roughly coincides with the erstwhile ceded districts. It also throws light on the policy of discrimination against the cultivators, which led to a deterioration in the conditions of these people.
A Spatial Model of Competitive Bidding for Government Grants: Why Efficiency Gains Are Limited
Authors: Ward Hugh , John Peter
Published: December 2007

With a view to improving public sector efficiency many governments now make public sector bodies competitively bid for funding. We model the bidding process as a game of spatial competition. Using Monte Carlo simulations we show that in efficient equilibria many bidding groups will not be under competitive pressure. The model suggests that this is because their ideal projects are inherently valuable for the funding agency and other groups cannot match this without departing so far from their ideal that they would rather not be successful. We test the hypothesis that competition will be limited largely to groups whose preferred projects are of medium quality on data from the UK Single Regeneration Budget. Using resubmitted bids to track the impact of competition, we find evidence consistent with this hypothesis.
Hindu–Muslim Brotherhood
Authors: Williams Philippa
Published: December 2007

The rise of Hindu nationalism in India in recent decades has stimulated a body of academic interest emphasising the irreconcilable differences between Hindus and Muslims on the subcontinent. This article shifts the focus on Hindu–Muslim relations away from conflict to that of everyday peace, where peace is perceived as an active process towards the non-violent resolution of communal conflict. The terrorist attacks in Varanasi, north India, in March 2006 created an atmosphere of anticipated communal tension. Despite expectations that communal violence would result, peace was maintained in the city. This article draws on ethnographic research conducted in Varanasi during April and May 2006 to explore the role of the ‘state’, ‘civil society’ and ‘agency’, and examines the mechanisms that enabled communal peace to prevail in light of existing theoretical literature on communal violence. These findings confirm the centrality of ‘civil society’ in minimising the potential for communal violence, but most importantly emphasise the vital role of human agency in understanding the processes by which peace is maintained.
Out of School and (Probably) in Work
Authors: Jayaraj D. , Subramanian S.
Published: December 2007

This article explores the hypothesis that the phenomenon of child labour is explicable in terms of poverty that compels a household to keep its children out of school and put them to work in the cause of the household's survival. In exploring the link between child labour and poverty in the Indian context, the article advances the view that the nature of the connection is more readily apprehended if both the variables under study are defined more expansively and inclusively than is customarily the case. Specifically, the suggestion is that it may be realistic to include those children who are conventionally categorised as ‘non-workers not attending school’ within the count of child labourers. It is also suggested that poverty is meaning fully measured in terms of a multidimensional approach to the problem, wherein the aim is to assess generalised capability failure—arising from want of access to elementary infrastructural facilities and essential amenities—with respect to a number of basic human functionings. The core of the article's argument is presented by means of a simple analytical model of child labour and deprivation, and the issues emerging from it are studied in the Indian context with the support of both primary and secondary data.
Changing Patron–Client Relations Favourable to New Opportunities for Landless Labourers in Rural Bangladesh
Authors: Makita Rie
Published: December 2007

Recent agrarian changes such as the casualisation of employment, an overall decrease in agricultural employment, the lack of agricultural labourers in the peak seasons, and increasing non-farm activities by landowners have resulted in declining patron–client relationships between landless labourers and landowning employers. Drawing on a local NGO's income-generating programme, this article explores how landless labourers avail themselves of an opportunity given under changing labour buyer–seller relationships, and how the NGO's intervention influences the relationships between landed and landless groups. The case study shows that, combined with proper intervention, the outcome of such agrarian changes can be transformed from increased vulnerability into an enabling environment for landless labourers to diversify their livelihoods and so achieve upward economic mobility through the new opportunity. Furthermore, when the intervention for the landless also stimulates the livelihood diversification of landowners, a new equal relationship emerges between the two groups.
Victims and agents
Authors: Ganguly-Scrase Ruchira
Published: December 2007

Scholarly accounts of children of the urban poor in South Asia often decry the exploitative conditions of child labour — the harsh and debilitating environmental conditions. At the same time, these accounts treat young people merely as victims and consequently leave out the felt experiences of working-class children and youth. Based on fieldwork among a marginalized leather worker community in an urban neighbourhood in India, this article aims to go beyond countering homogenizing perspectives and the challenge to the exploitation narrative. In doing so, I examine their specificity through ethnographic accounts of the ways in which young people actively construct their own identities, and reinterpret and negotiate adult notions of labour, caste, and community solidarity. Significantly these perspectives help us to comprehend the nature of youth discontent towards their traditional occupation. I analyse their discontent with the general declining employment opportunities in a globalizing Indian economy. Focusing on the youth cultures in the neighbourhood, I explore the conflicts within and between genders and generations emanating from the changing economic conditions.
New technology and young people's consumer identitites
Authors: Wilska Terhi-anna , Pedrozo Sueila
Published: December 2007

This article investigates new definitions of the self and identity vis-à-vis digital media and consumption styles among young people. The research is based on an empirical survey conducted in Finland in 2001 and re-done in Rio de Janeiro, Brazil in 2003–04. The main goal of this study is how information and communication technology (ICT) relates to young people's consumer identities in two very different countries. In Finland, equal access to new technology is widespread. In Brazil, digital exclusion is predominant due to social inequalities in income distribution. The results showed that young people's use of and attitudes towards ICT are surprisingly similar in both countries, and in both countries we found connections between consumer identities and ICT use and related attitudes. However, in Brazil, the father's educational level explained attitudes towards ICT better than consumer identities did. In Finland, gender was a more powerful determinant than in Brazil, which is a bit surprising. However, social and cultural differences make this comparison a bit difficult and the results must be treated with caution.
‘We can't just sit the whole day watching TV’
Authors: Hagen Ingunn
Published: December 2007

Media use is often a source of negotiations between children and their parents. Children's and young people's ideas about how much and what they want to watch on TV may differ from those of their parents. In addition, there might be disagreements in the family regarding who should use the computer and for what purpose. With new media like cable TV and computers/Internet increasingly available to modern families, there is intensified public pressure on parents to monitor and regulate their children's media use. The purpose of this article is to discuss questions related to these negotiations and regulations.
Basic skills and transitions to adulthood
Authors: Simpson Donald , Cieslik Mark
Published: December 2007

This article reports on the findings of a qualitative research project conducted in the North East of England. This project involved interviews with 55 young adults in an attempt to explore the impact of poor basic skills on transitions to adulthood. Poor basic skills have been identifued across Europe as a problem facing nation states, groups and individuals. But apart from large-scale survey-based studies (Bynner and Parsons, 2001), previous youth research has neglected the process through which basic skills play a role in transitions to adulthood. Proposing a social theory of situated basic skills as communal and individual resources, the authors develop an approach that is sensitive to both structure and agency in theorizing the role of literacy, numeracy and oracy in transitions. They claim that the mobilization of basic skills resources and their role across the life-course can best be understood by using a conceptualization of agency that recognizes the importance of reflexivity as a mediating link between subjective (agential) and objective (structural) dimensions of transition.
Citizenship among young adult Somalis in Norway
Authors: Fangen Katrine
Published: December 2007

This article analyses young Somalis’ citizenship in the sense of their civic activities on different geographic levels, and the interrelationship between civic activity, class, ethnicity and age. What are the participatory roles of the young Somalis, and how do they relate to entities such as politics, nation and ethnicity? How does class influence different levels of orientation? Data were collected through semi-structured interviews with five Somalis who had returned to Somaliland after living in Norway for many years, and 45 Somalis in Norway, but this article is a case study of three of the latter. Somali organizations give young adult Somalis from all backgrounds an opportunity to become involved and feel that they are doing something for other Somalis. For some, participation in these organizations is a stepping-stone to further political involvement in Norway, in Somalia or internationally. We especially see this among Somalis with a higher education, whereas those with less education are mostly involved in activities on the community level. Being active within Somali organizations in Norway combines the aspect of being well integrated in the host society with maintaining a commitment to one's own background and culture. The young Somalis associate doing something for others to becoming an adult; however, they also regard this sense of responsibility as an integral part of being Somali.
European Liberalisms
Authors: Freeden Michael
Published: December 2007

After examining different liberal narratives and suggesting that liberalism is open to a range of legitimate methodologies, the fluidity of liberalism is offered as a basis for a study in comparative political thought. Ten propositions on liberalism's structural and semantic features are listed and brought to bear on its adaptations, appropriations and misappropriations in Europe. They are tested in relation to various combinations of liberal components within and outside the family of liberalisms. Different views about the role of the state in Eastern and Western Europe are considered, as is the distinction between constitutional and welfare liberalism in Western Europe. Individual development versions are contrasted with market versions, and the problematic role of civil society is discussed. Finally, some misappropriations are explored with a view to assessing their claims to represent liberal positions. European liberalism emerges as a loosely assembled yet durable ideology around a strong core of value-commitments.
Anti-Liberalism and the Liberal Legacy in Postwar European Constitutionalism
Authors: Pombeni Paolo
Published: December 2007

Was liberalism really an outdated ideology in post-1945 European political systems, as claimed by some scholars? The great success of socialism on one side and various forms of Christian Democracy on the other could make that claim appear reasonable. In fact a closer view shows how postwar constitutions in some countries (Italy, France and Germany) presented once again fundamental liberal values, reformulated in different words. One of the roots of that difference is the gap between the Anglo-Saxon approach to liberalism, which takes into account history and communities, and the continental tradition of liberalism, linked to an abstract philosophical approach and highly dependent on long-standing struggles between Churches and the body politic.
Fear and Freedom
Authors: Müller Jan-Werner
Published: December 2007

This article identifies a distinct strand of 20th-century liberal thought that was exemplified by Isaiah Berlin, Raymond Aron and, to a lesser extent, Karl Popper. I offer a stylized account of their common ideas and shared political sensibility, and argue that their primarily negative liberalism was a variety of what Judith Shklar called the `liberalism of fear' — which put the imperative to avoid cruelty and atrocity first. All three founded their liberalism on a `politics of knowledge' that was directed primarily against Marxist philosophies of history and less against the idea of bureaucratic planning, as, in contrast, was the case with Friedrich von Hayek's thought. Moreover, all three subscribed to more or less explicit versions of value pluralism, and claimed that, in the circumstances of modernity, Weber's `clash of values' was exacerbated and required a particularly prudential approach to politics; this prudential management of value conflicts in turn was best entrusted to cultivated bureaucratic elites. All shared an image of a tolerant and humane society — essentially an idealized version of Britain — but said perhaps too little on the question how societies without the appropriate traditions of moderation and compromise were to be liberalized.
The Organization of Liberty
Authors: te Velde Henk
Published: December 2007

The historiography of European liberalism has been dominated by large countries; this contribution focuses on the successful tradition of liberalism in the Netherlands. Just like German liberalism (but unlike the British 19th-century model), the spirit of Dutch 19th-century liberalism was constitutional (in the sense of being legal and juridical). It assumed that constitutional rules in a certain sense produced liberty, because liberty was not possible without a legally guaranteed context. Today the Dutch liberal party tries to combine classical liberalism with a mild populism, but recently the Pim Fortuyn upsurge of populism has hurt the liberal party. A direct democratic style of politics has become popular among more right-wing liberals. Perhaps it is time to re-evaluate the 19th-century doctrinaire liberal traditions. Their anti-democratic ideas have been superseded, but the constitutional organization of liberty is as important as ever.
Personal Liberty and Political Freedom
Authors: Dénes Iván Zoltán
Published: December 2007

By freedom, classical liberals meant non-interference, independence from the state, the personal and proprietary liberty of the governed. It is negative freedom as the antithesis both to absolutism and anarchy. In the republican interpretations, the freedom of a free political community is made possible and guaranteed by the institutionalization of the liberty of the political community. Political liberty is the medium, stage and precondition for the freedom of its members. That, in turn, is conditional upon the readiness of its members to protect the liberty of their community and themselves, i.e. upon the virtue of the free citizen. In this article I engage with four different interpretations of both kinds of liberty concepts in different discourses of the 20th-century UK and US and 20th—21st-century Hungary.
Dosage plan of a flurbiprofen injection product using inhibition of protein binding by lipid emulsion in rats
Authors: Ogata Kenji , Takamura Norito , Tokunaga Jin , Kawai Keiichi , Arimori Kazuhiko , Higuchi Shun
Published: December 2007

Flurbiprofen-axetil (FP-ax), a bolus injection product of a non-steroidal anti-inflammatory drug (NSAID), is a prodrug of flurbiprofen, an NSAID. As flurbiprofen strongly binds to site II of human serum albumin (HSA), the free (unbound) concentration of flurbiprofen after injection of FP-ax is low. We have examined the inhibitory effect of free fatty acid (FFA), a binding inhibitor for site II of HSA, on the binding of flurbiprofen in-vitro and in-vivo by ultrafiltration, to establish an effective dosage of FP-ax. In-vitro, fatty acid mixtures (FAs) inhibited the binding of flurbiprofen to rat serum albumin. The free fraction of flurbiprofen was remarkably increased by FAs in rat serum. In-vivo, FP-ax was injected into a control group (low FFA concentration in serum) and a lipid emulsion group (high FFA concentration in serum). The area under the curve of the free concentration of flurbiprofen during the alpha phase and the distribution volume of the central compartment of flurbiprofen were significantly higher in the lipid emulsion group than the control group (5.0- and 1.2-times, respectively). When FP-ax was administered at high FFA concentration, the free concentration of flurbiprofen and distribution of flurbiprofen to tissues increased transiently. This administration method may be useful for patients with cancer pain, having a potent analgesic effect.
Synergistic effect of iontophoresis and soluble microneedles for transdermal delivery of methotrexate
Authors: Vemulapalli Viswatej , Yang Ye , Friden Phillip M , Banga Ajay K
Published: December 2007

The aim of this study was to investigate the transdermal iontophoretic delivery of methotrexate, alone or in combination with microneedles, in-vitro and in-vivo using intracutaneous microdialysis in the hairless rat. The average depth of the microdialysis probe in the skin was found to be 0.54 mm. Methotrexate was stable in the presence of an applied electric field as determined by cyclic voltammetry. A current density of 0.4 mA cm−2 applied for 60 min was used in combination with maltose microneedles to enhance delivery of methotrexate across the skin. Delivery was enhanced by iontophoresis and microneedles, both in-vitro and in-vivo. A synergistic 25-fold enhancement of delivery was observed in-vivo when a combination of microneedles and iontophoresis was used compared with either modality alone.
Effects of CYP inducers and inhibitors on the pharmacokinetics of intravenous theophylline in rats: involvement of CYP1A1/2 in the formation of 1,3-DMU
Authors: Yang Kyung H , Lee Joo H , Lee Myung G
Published: December 2007

The types of hepatic cytochrome P450 (CYP) isozymes responsible for the metabolism of theophylline and for the formation of 1,3-dimethyluric acid (1,3-DMU) in rats in-vivo does not seem to have been studied at the dose ranges of dose-independent metabolic disposition of theophylline in rats (up to 10 mg kg−1). Therefore, theophylline (5 mg kg−1) was administered i.v. to male Sprague—Dawley rats pretreated with various inducers and inhibitors of CYP isozymes. In rats pretreated with 3-methylcholanthrene (3-MC), orphenadrine or dexamethasone (main inducers of CYP1A1/2, CYP2B1/2 and CYP3A1/2, respectively, in rats), the time-averaged non-renal clearance (CLNR) of theophylline was significantly faster than in their respective controls (1260, 42.7 and 69.0% increases, respectively). However, in rats pretreated with troleandomycin (a major inhibitor of CYP3A1/2 in rats), CLNR was significantly slower than in the controls (50.7% decrease). The 24 h urinary excretion of 1,3-DMU was increased significantly only in rats pretreated with 3-MC. The ratio of area under the curve for 1,3-DMU and theophylline (AUC1,3-DMU/AUCtheophylline) was increased significantly in rats pretreated with 3-MC (160% increase) and decreased significantly in rats pretreated with troleandomycin (50.1% decrease); however, the ratio was not increased in rats pretreated with dexamethasone. These data suggest that theophylline is primarily metabolized via CYP1A1/2, CYP2B1/2, and CYP3A1/2, and that 1,3-DMU is primarily formed via CYP1A1/2, and possibly CYP3A1/2, in rats.
Involvement of Mrp2 (Abcc2) in biliary excretion of moxifloxacin and its metabolites in the isolated perfused rat liver
Authors: Ahmed Salwa , Vo Nha T P , Thalhammer Theresia , Thalhammer Florian , Gattringer Klaus-Bernhard , Jäger Walter
Published: December 2007

Moxifloxacin is a novel antibacterial agent that undergoes extensive metabolism in the liver to the glucuronide M1 and the sulfate M2, which are eliminated via the bile. To investigate the role of the multidrug resistance-associated protein (Mrp2) as the hepatic transport system for moxifloxacin and its conjugates, livers of Wistar and Mrp2-deficient TR− rats were perfused with moxifloxacin (10 μM) in a single-pass system. Values for the hepatic extraction ratio (E) and clearance (Cl) were insignificantly higher in TR− rats than Wistar rats (0.193 ± 0.050 vs 0.245 ± 0.050 for E; 6.85 ± 1.96 vs 8.73 ± 1.82 mL min−1 for Cl), whereas biliary excretion and efflux into perfusate over 60 min were significantly lower in the mutant rat strain. Cumulative biliary excretion of M1, M2 and moxifloxacin was significantly reduced to 0.027%, 19.1%, and 29.6% in the TR− rats compared with Wistar rats, indicating that the biliary elimination of M1 is mediated exclusively by Mrp2, whereas that of M2 and moxifloxacin seems to depend mostly on Mrp2 and, to a smaller extent, a further unidentified canalicular transporter. Moxifloxacin stimulates bile flow by up to 11% in Wistar rats, but not in TR− rats, further supporting an efficient transport of this drug and its glucuronidated and sulfated metabolites by Mrp2. Moxifloxacin (10 μM) also reversibly inhibited the Mrp2-mediated biliary elimination of bromsulphthalein in Wistar rats by 34%, indicating competition with the elimination of Mrp2-specific substrates. In conclusion, we found that Mrp2 mediates the biliary elimination of moxifloxacin and its glucuronidated and sulfated metabolites in rats. MRP2 may therefore play a key role in the transport of moxifloxacin and its conjugates into bile in humans.
Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and implications for in-vivo experiments
Authors: McConnell Emma L , Basit Abdul W , Murdan Sudaxshina
Published: December 2007

To use rodent models effectively in in-vivo investigations on oral drug and vaccine delivery, the conditions in the gastrointestinal tract must be understood. Some fundamental information is currently unavailable or incomplete. We have investigated the pH, water content and lymphoid tissue distribution along the gastrointestinal tract, as well as the stomach volume, as these were critical to our investigations on pH-responsive drug delivery and colonic vaccination. The observed values were compared with those in man as an indication of the validity of the rodent model. The mouse stomach pH was 3.0 (fed) and 4.0 (fasted), and the corresponding values in the rat were 3.2 (fed) and 3.9 (fasted). The mean intestinal pH was lower than that in man (< pH 5.2 in the mouse; < pH 6.6 in the rat). This brings into question the use of rodents in investigations on enteric-coated drug carriers targeted to the large intestine/distal gut. The water content in the gastrointestinal tract in the fed and fasted mouse was 0.98 ± 0.4 and 0.81 ± 1.3 mL, respectively, and in the fed and fasted rat was 7.8 ± 1.5 and 3.2 ± 1.8 mL. When normalized for body weight, there was more water per kg body weight in the gastrointestinal tracts of the mouse and rat, than in man. The stomach capacity was found to be approximately 0.4 and 3.4 mL for mice and rats, respectively. The low fluid volume and stomach capacity have implications for the testing of solid dosage forms in these animal models. Substantial amounts of lymphoid tissue analagous to small intestinal Peyer's patches were measured in the rat and mouse colon, showing the feasibility of colonic vaccination, a route which might prove to have different applications to the more commonly studied oral vaccines. The existence of lymphoid tissue in the mouse and rat caecum has also been reported.
Percutaneous penetration of felbinac after application of transdermal patches: relationship with pharmacological effects in rats
Authors: Shinkai Norihiro , Korenaga Kazuko , Takizawa1 Hiromi , Mizu Hideo , Yamauchi Hitoshi
Published: December 2007

We have evaluated the percutaneous penetration of felbinac following application of topical patches using a microdialysis technique, and have examined correlations with pharmacological effects. A linear microdialysis probe with a 20-mm dialysis fibre was inserted into the skin of anaesthetized rats. Probe perfusion was started at 2.0 μL min−1 with physiological saline and after a 60-min baseline sampling of dialysate, 0.1 mL croton oil was applied to the skin surface at a concentration of 8%, v/v. A felbinac patch was then applied to the same point 60 min thereafter and dialysate was sampled at 60-min intervals up to 300 min after patch application, for determination of concentrations of felbinac and prostaglandin (PG) E2. Analgesic effects of felbinac patches in an iodoacetate-induced osteoarthritis model and an incisional pain model were evaluated using the weight bearing method. After application of patches, felbinac penetration into the skin was rapid, maximum concentrations in the dialysates with 0.07, 0.5 and 3.5% w/w felbinac patches being 0.046 ± 0.02, 0.104 ± 0.06 and 0.244 ± 0.2 μg mL−1, respectively. Dermal administration of croton oil caused an increment in PGE2 levels, which was significantly decreased by 0.5 and 3.5% felbinac patches 2–5 h after application. In pharmacological studies, 3.5% felbinac patches suppressed pain-associated behaviour induced by iodoacetate injection and plantar incision. These results suggested that the transdermal patch containing 3.5% felbinac may become a useful formulation.
Semi-mechanistic description of the in-vitro antiproliferative effect of different antitumour agents
Authors: Moreno Daniel , Trocóniz Iñaki F , Enguita Mónica , Bandrés Eva , García-Foncillas Jesús , Garrido María J
Published: December 2007

The aim of the present work was to describe the antiproliferative effect of camptothecin (CPT), topotecan (TPT) and cisplatin (CIS) in cultured cells using a semi-mechanistic pharmacodynamic approach. This effect on the growth of DHD-K12PROb cells was modelled as a function of drug concentration and time of exposure using the Gompertz framework. Models reflected two major processes: cell proliferation and cell death/degradation. Antiproliferative effect of CPT and TPT was described as inhibition of cell proliferation, while the effect of CIS was described as stimulation of cell death, including a signal transduction process, reflected as a delay in the onset of drug action. The half-life associated with such a transduction process was estimated to be approximately 27 h. Interestingly, the time profiles of the model predicted a signal transduction process that closely resembled the observed profiles of caspase-3, a protein implicated in CIS-mediated apoptosis. Therefore, the combination of a simple and sensitive design, together with an appropriated modelling strategy, allowed us to explore different mechanisms of action for antitumour agents in cultured cells and to obtain information about the dynamics of signal transduction and the potential use of biomarkers.
Glycyrrhizin prevents of lipopolysaccharide/D-galactosamine-induced liver injury through down-regulation of matrix metalloproteinase-9 in mice
Authors: Abe Kazuki , Ikeda Tadayuki , Wake Kenjiro , Sato Tetsuji , Sato Toshitsugu , Inoue Hideo
Published: December 2007

Glycyrrhizin, a biological active compound isolated from the liquorice root, has been used as a treatment for chronic hepatitis. We have examined the involvement of matrix metalloproteinase (MMP)-9 in the development of lipopolysaccharide (LPS) and D-galactosamine (GalN)-induced liver injury in mice. We also investigated the effect of glycyrrhizin on expression of MMP-9 in this model. Levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased after LPS/GalN treatment. Expression of MMP-9 mRNA and protein was markedly up-regulated in liver tissues 6–8 h after LPS/GalN treatment. Pretreatment with glycyrrhizin (50 mg kg−1) and the MMP inhibitor (5 mg kg−1) suppressed increases in serum levels of ALT and AST in mice treated with LPS/GalN. Furthermore, glycyrrhizin inhibited levels of both mRNA and protein for MMP-9. Immunohistochemical reaction for MMP-9 was observed in macrophages/monocytes infiltrated in the inflammatory area of liver injury. Glycyrrhizin reduced the infiltration of inflammatory cells and immunoreactive MMP-9 in liver injury. The results indicated that MMP-9 played a role in the development of LPS/GalN-induced mouse liver injury, and suggested that an inhibition by glycyrrhizin of the acute liver injury may have been due to a down-regulation of MMP-9.
Optimization and validation of a chromatographic method for the simultaneous quantification of six bioactive compounds in Rhizoma et Radix Polygoni Cuspidati
Authors: Qian Guangsheng , Leung Sik-Yuen , Lu GuangHua , Leung Kelvin Sze-Yin
Published: December 2007

A reverse-phase HPLC method was developed for simultaneous quantification of six bioactive compounds in Rhizoma et Radix Polygoni Cuspidati. These compounds — polydatin (1), resveratrol (2), rhein (3), emodin (4), chrysophanol (5) and physcion (6) — were analysed from 24 authentic samples of the herb using UV HPLC. Based on the UV absorption characteristics of the six compounds, absorption wavelengths of 306 nm were chosen to quantify compounds 1 and 2, and 290 nm for compounds 3–6. A reliable and reproducible quantitative HPLC method for analysing authentic samples of Rhizoma et Radix Polygoni Cuspidati from different cultivation regions was developed. The results showed that the concentration of compound 1 in samples from Sichuan was almost 2-fold higher than that of samples acquired in Guangxi. Furthermore, compounds 3 and 5 were not found in all the samples tested. Thus, instead of using polydatin (1) and emodin (4) as markers for quality assessment, as in conventional practice, these findings show that compounds 2 and 6 are more suited to act as marker compounds for a more specific assessment of the quality of this herb.