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PubMed2002

Development of theophylline sustained release dosage form based on Kollidon SR.

Sustained release theophylline matrix tablets constituting Kollidon SR (Polyvinyl acetate and povidone based matrix retarding polymer) were developed in this study in an attempt to design a dosage form that manifests desirable release profile and thorough adherence to official monographs. Four matrix tablet formulations were prepared by dry blending and direct compression of Kollidon SR and HPMC-15cps (hydroxypropylmethylcellulose) in varying proportion with fixed percentage of theophylline. Tablets containing only Kollidon SR with the active ingredient demonstrated a rapid rate of drug release with an initial burst effect. Incorporation of HPMC-15cps in the matrix tablet prolonged the release of drug with subsequent minimization of burst effect as confirmed by mean dissolution time, T50 and Higuchi release rate data. Among the batches containing HPMC-15 cps, a direct relationship was obtained between release rate and the percentage of HPMC used. A suitable controlled release profile was obtained with the matrix tablets containing 20% Kollidon SR and 30% HPMC-15cps. The formulation showed close resemblance to commercial products and compliance with USP specification. The results were explored and explained by the difference of physico-chemical property and hydration characteristics of the polymers. In addition to this result, the exponential model was applied to characterize the drug release behaviour from polymeric systems. It was found that, Fickian release is predominant in tablets containing Kollidon SR alone and non-Fickian mechanism plays an important role in the release of drug from HPMC containing tablets with a trend towards zero-order or case II release. In vitro release profile of two commercial brands were also undertaken for comparison and modulation of the experimental batches.

Journal Article↗
PubMedDate not supplied

Measuring the wealth of nations.

The sustainability of development is closely linked to changes in total per capita wealth. This paper presents estimates of the wealth of nations for nearly 100 countries, broken down into produced assets, natural resources and human resources. While the latter is the dominant form of wealth in virtually all countries, in low income natural resource exporters the share of natural resources in total wealth is equal to the share of produced assets. For low income countries in general, cropland forms the vast majority of natural wealth. The analysis suggests the process of development can be viewed as one of portfolio management: sustainable development entails saving the rents from exhaustible resources, managing renewable resources sustainably, and investing savings in both produced assets and human resources.

Conservation of Natural Resources↗
PubMed2002

The role of multilateral institutions.

In line with its mission of alleviating poverty through support for environmentally and socially sustainable economic development, The World Bank (along with some other multilateral development banks) is working to help developing countries capture a share of the emerging global market in greenhouse-gas-emissions reductions ('carbon trading'). Under the Kyoto Protocol of the United Nations Framework Convention on Climate Change (UNFCCC), the Joint Implementation instrument and the Clean Development Mechanism now provide an opening for substantial international resource transfers and potential for supporting sustainable development through the transfer of cleaner technologies or sustainable forestry and agro-forestry practices. For example, carbon sequestration represents a non-extractive non-consumptive sustainable use of living natural resources that can be incorporated within a multiple-use 'integrated ecosystem management' approach. The World Bank initiated the Prototype Carbon Fund (PCF) in April 2000, to help spur the development of a global carbon market and to 'learn by doing' how to use carbon-purchase transactions across a range of energy-sector technologies (and some forestry applications) to achieve environmentally credible and cost-effective emissions reductions that benefit developing countries and economies in transition. Building on the success of the PCF ($145 million raised from public and private-sector investors), The World Bank expects to launch two new funds in 2002: the Biocarbon Fund and the Community Development Carbon Fund. These funds will target synergies between carbon markets and objectives such as biodiversity conservation, combating desertification and small-scale community-driven development. Experience from the PCF shows that developing countries can have a comparative advantage in supplying this global market, as emissions reductions can be achieved in developing countries in the range of $3-$5 per ton of CO(2) equivalent, compared with a marginal abatement cost of $10-$15 per ton of CO(2) equivalent in most countries within the Organization for Economic Cooperation and Development. However, realizing this economic potential over the next decade, and targeting the market to the rural poor, will require substantial assistance with project development and government legal and institutional capacity building. Specific needs include raising awareness of the potential of carbon markets at all levels (particularly in energy and land-use sectors), clarifying property rights, particularly in the case of communally held land and resources, ensuring the existence of an attractive investment climate, eliminating policies that create perverse incentives and constraints, and mitigating logistical, political and 'reputational' risks that could deter private-sector investors. It will also be necessary to find ways to reconcile the short-term needs of the rural poor and the typically long-term revenue stream associated with carbon sequestration.

Air Pollution↗
PubMed2000

Cerebral metabolic response to traumatic brain injury sustained early in development: a 2-deoxy-D-glucose autoradiographic study.

Following fluid percussion (FP) traumatic brain injury (TBI), adult rats exhibit dynamic regional changes in cerebral glucose metabolism characterized by an acute (hours) increase and subsequent chronic (weeks) decrease in metabolic rates. The injury-induced hyperglycolysis is the result of ionic fluxes across cell membranes and the degree and extent of metabolic depression is predictive of neurobehavioral deficits. Given that younger animals appear to exhibit similar physiological responses to injury yet show an improved rate of recovery compared to adults, we wanted to determine if this injury-induced dynamic metabolic response to TBI is different if the injury is sustained early in life. Local cerebral metabolic rates for glucose (ICMRglc: micromol/100 g/min) using [14C]2-deoxy-D-glucose were measured immediately, 30 min, 1 day, and 3 days following a mild to moderate level of lateral FP injury in postnatal day 17 (P17) rats. Even though gross morphological damage was not evident, injured pups exhibited ipsilateral hyperglycolysis immediately after injury, predominantly in cortical regions (ranging from 59.2% to 116.5% above controls). This hyperglycolytic state subsided within 30 min, and by 1 day all cerebral structures, except the ipsilateral cerebellar cortex, showed lower rates of glucose metabolism (ranging from 5.7% to 63.0% below controls). This period of posttraumatic metabolic depression resolved within 3 days for all structures measured. Compared to previous adult studies these results suggest that the young rat pup, although exhibiting acute hyperglycolysis, is not subjected to a prolonged period of metabolic depression, which supports the findings that at this level of injury severity, these young animals show remarkable neurological sparing following TBI.

Age Factors↗
PubMed2000

From psycho-social theory to sustainable classroom practice: developing a research-based teacher-delivered sex education programme.

This paper describes the development of a theoretically based sex education programme currently undergoing a randomized controlled trial in the UK. It considers some of the practical difficulties involved in translating research-based conclusions into acceptable, replicable and potentially effective classroom lessons. The discussion acknowledges that the implications of social psychological research and the requirements of rigorous evaluation may conflict with accepted principles inherent in current sex education practice. It also emphasizes that theoretical ideas must be carefully embedded in lessons which are informed by an awareness of classroom culture, and the needs and skills of teachers. For example, the use of same-sex student groups to reflect on the gendered construction of sexuality may be problematic. Materials must be tailored to recipients' circumstances, which may require substituting for limited experience with the use of detailed scripts and scenarios. Furthermore, role-play techniques for sexual negotiation that work elsewhere may not be effective in the UK. The use of trigger video sessions and other techniques are recommended. Finally, the problems involved in promoting condom-related skills are discussed. The paper concludes that, if an intervention is to be sustainable beyond the research stage, it must be designed to overcome such problems while remaining theoretically informed.

Adolescent↗
PubMed2004

Investing in sustainable catchments.

Catchments constitute logical units for management of the water cycle. Patterns of development uninformed by sustainability concerns have degraded catchment integrity and associated ecosystem functions, imposing largely unquantified costs. Ecosystem functions are central to sustainable social and economic progress; their protection or restoration may be the only sustainable form of investment in catchments. Despite growing use of catchment functions in some policy areas, a shortfall in awareness and pragmatic tools limits progress with policies and practical tools to support sustainable development in catchments, perpetuating damaging practices. This paper reviews methods of economic valuation of riverine systems. Valuation of ecosystem functions is revealed as particularly pertinent to sustainable development, as an indicator of the benefits of ecological processes to social and economic progress. A range of practical projects, targeted at restoration of riverine habitat in the UK with the intent of improving both river ecology and the social and economic advantages that flow from it, is also reviewed. Emerging principles and themes are discussed in terms of their potential contribution to policies and practices that promote sustainability. Review of these projects highlights the importance of planning at adequately broad scales--spatial, temporal and disciplinary--to identify integrated solutions, and to maximise community "buy-in" and total benefits. In several cases, economic analyses demonstrate strongly positive benefit-cost ratios stemming from habitat improvement. However, major reform of regulatory and economic instruments is needed to promote sustainable catchment development, since prevalent "perverse" incentives continue to degrade ecosystem functions. Measures to recognise and reward ecosystem service as legitimate outputs from agricultural land use constitute a particular priority. There is a need simultaneously to address both "big picture" structural adjustments and locally-appropriate solutions, from which clear local benefits flow. Pragmatic measures that contribute to systemic outcomes must also be attractive to local decision-makers and land managers, and yield benefits that ensure they are sustained once intervention ceases. Cost need not be a barrier, as current environmentally-damaging subsidies may instead be redirected towards sensitive land use and/or measures to protect biodiversity and ecosystem functioning, particularly where targeted upon habitat of disproportionate importance to functioning of catchments as whole systems. Internalisation of the costs of damage to ecosystem functioning will promote valuation of the natural capital of catchments as a primary resource for social and economic progress.

Conservation of Natural Resources↗
PubMed2003

Development of a sustainable treatment technology for domestic sewage.

We propose an integrated chemical-physical-biological treatment concept for the low-cost treatment of domestic wastewater. Domestic wastewater was subjected to a chemically enhanced primary sedimentation (CEPS), followed by treatment in an upflow anaerobic sludge blanket (UASB) reactor. In addition, a regenerable zeolite was used to remove NH4+, either after CEPS pretreatment or after biological treatment in the UASB reactor. The CEPS pretreatment consisted of the addition of a coagulant (FeCl3) and an anionic organic flocculant and removed on average 73% of the total chemical oxygen demand (CODt), 85% of the total suspended solids, and 80% of PO4(3-) present in the wastewater. The UASB system, which consequently received a low CODt input of approximately 140 mg/L, was operated using a volumetric loading rate of 0.4 g CODt/L.d (hydraulic retention time [HRT] = 10 h) and 0.7 g CODt/L.d (HRT = 5 h). For these conditions, the system removed about 55% of the CODt in its influent, thus producing an effluent with a low CODt of approximately 50 mg/L. The zeolite, when applied in batch mode before the UASB reactor, removed approximately 45% of the NH4+, whereas its application as a post-treatment cartridge resulted in almost 100% NH4+ removal. The simple design and relatively low operating costs, due to low costs of added chemicals and low energy input (estimated at Euro 0.07-0.1 per m3 wastewater treated), combined with excellent treatment performance, suggest that this system can be used as a novel domestic wastewater treatment system for developing countries. Therefore, the system is called a Low-cost, Integrated Sewage Treatment (LIST) system.

Animals↗
PubMed2001

Ends versus means: the role of markets in expanding access to contraceptives.

Achieving and sustaining universal access to contraceptives are key policy goals of interventions supplying contraceptive commodities. Donor support for contraceptive supplies is substantial and many public and national programmes rely on donated and subsidized supplies of contraceptives. Sustainability of programme benefits is a concern to both national governments and donor agencies. At the same time, market-based provision of contraceptives has become a major source of contraceptives for individuals in a number of countries. While the goals or 'ends' of policy are to increase and sustain universal access to contraceptives, there is debate about the role of markets and their negative impacts on equity and universality. There is also concern that while public programmes supplying free contraceptives may, in the medium-term, achieve high coverage, they may hamper the achievement of long-term sustainability and the development of commercial markets. This paper focuses on the tension between the public health and market paradigms, and uses economic analysis as a framework in order to examine the relative roles or 'means' for subsidized public and commercial private sector supply of contraceptives. The review of the theory and evidence focuses on the trade-offs between public sector and market provision of contraceptives, examining the role for the public sector given the potential for market failures, the impact of public provision on the development of markets, and the role of price in demand. However, because of the potential conflict between these policy objectives, we argue that strategies to deliver contraceptives should be based on the specific characteristics of the context. In particular four variables (contraceptive prevalence rates, HIV prevalence, income level of country, size and geographic spread of private sector development) are important in characterizing this context, and these are highlighted in a matrix of programme priorities. Public choices need to take into account the ways in which they will affect the potential for development of sustainable private sources of supply. Undertaking a 'market assessment' should be a key stage in the analysis of policy options. Such an assessment should address demand factors, health priorities, actual and potential sources of supply and the relationships between public and private supply. Clearly the development of markets for contraceptives is not an end in itself, but may prove an important means of improving the health of women and men.

Contraceptive Agents↗
PubMed1995

Development of a sustainable chick cell line infected with Marek's disease virus.

Marek's disease virus (MDV) is a highly infectious and cell-associated avian herpesvirus. Fully productive infections with MDV are restricted to feather follicle epithelium of afflicted birds. In culture, MDV infection of primary chick (CEF) and duck embryo fibroblast cells is semiproductive. Passage of MDV and production of MDV vaccines is limited to these primary cell-associated systems. The finite life span of primary avian cell cultures has hampered efforts to use positive selection in generation of recombinant MDV and complicates studies of temporal gene regulation. In this report, we describe continuous chick fibroblast cell lines (MDV OU2.2 and MDV OU2.1) which support MDV replication. Southern blot and PCR analyses demonstrate that these cell lines harbor MDV DNA. Western blot analyses indicate that MDV OU2.2 cells express at least a limited set of viral proteins, pp38 and pp14, similar to that seen in MDV-lymphoblastoid cells. Presence of distinct plaques in confluent MDV OU2.2 cell monolayers is consistent with cytolytic semiproductive infection, similar to that observed in primary CEF. MDV OU2.2 cells are capable of transferring MDV infection to primary CEF cultures and inducing clinical signs of Marek's disease in susceptible birds. MDV OU2.2 cells have maintained a MDV-positive phenotype for over 16 months of active culture. Southern blot hybridization of MDV OU2.2 cell DNA reveals a distinct expansion of the MDV BamHI H fragment in a subset of viral genomes following long-term cultivation.

Animals↗
PubMed2007

Metabolic processes and carbon nutrient exchanges between host and pathogen sustain the disease development during sunflower infection by Sclerotinia sclerotiorum.

Interactions between the necrotrophic fungus Sclerotinia sclerotiorum and one of its hosts, Helianthus annuus L., were analyzed during fungal colonization of plant tissues. Metabolomic analysis, based on (13)C- and (31)P-NMR spectroscopy, was used to draw up the profiles of soluble metabolites of the two partners before interaction, and to trace the fate of metabolites specific of each partner during colonization. In sunflower cotyledons, the main soluble carbohydrates were glucose, fructose, sucrose and glutamate. In S. sclerotiorum extracts, glucose, trehalose and mannitol were the predominant soluble carbon stores. During infection, a decline in sugars and amino acids was observed in the plant and fungus total content. Sucrose and fructose, initially present almost exclusively in plant, were reduced by 85%. We used a biochemical approach to correlate the disappearance of sucrose with the expression and the activity of fungal invertase. The expression of two hexose transporters, Sshxt1 and Sshxt2, was enhanced during infection. A database search for hexose transporters homologues in the S. sclerotiorum genome revealed a multigenic sugar transport system. Furthermore, the composition of the pool of reserve sugars and polyols during infection was investigated. Whereas mannitol was produced in vitro and accumulated in planta, glycerol was exclusively produced in infected tissues and increased during colonization. The hypothesis that the induction of glycerol synthesis in S. sclerotiorum exerts a positive effect on osmotic protection of fungal cells and favors fungal growth in plant tissues is discussed. Taken together, our data revealed the importance of carbon-nutrient exchanges during the necrotrophic pathogenesis of S. sclerotiorum.

Amino Acid Sequence↗
PubMed1988

Enhancement of radial maze performances in CD1 mice after prenatal exposure to oxiracetam: possible role of sustained investigative responses developed during ontogeny.

A longitudinal study aimed at analyzing the behavioral effects of prenatal exposure to the nootropic compound oxiracetam was carried out in CD1 mice. Two groups of females were injected either with oxiracetam or saline from the beginning of pregnancy until parturition. Examination of pups from birth until the first month of age revealed no-influence of the treatment on litter size, body weights, sensory motor reflexes and motility. When placed in the open field at one month of age, mice born by mothers exposed to oxiracetam displayed more self grooming and spent less time in freezing than control mice. Prenatally treated mice were then found more interactive with their environment since the introduction of a novel object in the open field was followed by increased ambulation and higher sniffing object and rearing object scores. At three months of age, mice from both groups were tested in a radial six-arm maze task. Choice accuracy was significantly higher in prenatally treated mice which also tended to optimize their exploratory sequences by frequently running the maze in a clock-wise fashion. These results suggest that the better learning performances observed in the experimental group could be viewed as a consequence of an enhanced cognitive development based upon the higher rate of interactions with the environment shown by prenatally treated mice during ontogeny.

Animals↗
PubMed2006

Medicines for Malaria Venture: sustaining antimalarial drug development.

The Medicines for Malaria Venture (MMV) is committed to discovering, developing and delivering new drugs for malaria. Founded in 1999 as a nonprofit organization bringing private sector management methods to bear on a global public health problem, MMV is today recognized as a leader among the public-private partnerships working on diseases for the developing world. Together with its many partners, MMV manages the world's largest malaria research and development portfolio, covering the innovation spectrum from basic drug discovery to late-stage development.

Antimalarials↗
PubMed2004

Development of a sustained release dosage form for alpha-lipoic acid. I. Design and in vitro evaluation.

The purpose of this study was the design and evaluation of a sustained release dosage form for the oral administration of alpha-lipoic acid. The cationic polymer chitosan was used in order to provide a controlled drug release based on ionic interactions with the anionic drug. The effect of such ionic interactions on the release of alpha-lipoic acid could be verified by diffusion studies. In vitro release studies with tablets (diameter: 10.0 mm; thickness: approximately 4 mm) containing 80% alpha-lipoic acid and 20% chitosan acetate showed a controlled drug release over a time period of 24 h. Raising the ratio of chitosan acetate in such delivery systems led to an even stronger retardation of drug release. In addition, permeation studies carried out in Ussing-type chambers with freshly excised intestinal mucosa from guinea pigs demonstrated no significant (p < 0.05) influence of the degree of drug ionization on its absorption behavior. The apparent permeability coefficient (Papp) for alpha-lipoic acid was determined to be 1.39 +/- 0.28 x 10(-5) cm/sec at pH 6.4 (means +/- SD). The use of a sustained delivery system for alpha-lipoic acid, which is based on ionic interactions, should therefore have no influence on the absorption behavior of the drug. The sustained release dosage forms described here might provide a constant plasma level of the drug being highly beneficial for various therapeutic reasons.

Algorithms↗
PubMed2004

Development of a sustained release dosage form for alpha-lipoic acid. II. Evaluation in human volunteers.

Within this study an oral sustained release dosage form of alpha-lipoic acid (thioctic acid) has been generated and evaluated in healthy volunteers. A granulate comprising 56.8% alpha-lipoic acid and 43.2% chitosan acetate was compressed to tablets (weight: 0.45 g; diameter: 10.0 mm; thickness: 4 mm). Three of these tablets were administered at once orally to each volunteer. Prior to administration and then every hour for 12 hours blood samples were taken from the antebrachial vein. alpha-Lipoic acid concentrations in plasma were quantified via precolumn derivatization and reversed-phase high-performance liquid chromatography (HPLC). Results demonstrated that an increased plasma level of alpha-lipoic acid can be achieved by this formulation for at least 12 hours. Within this time period at least two maximum plasma concentrations were reached. The first one is based on the release of alpha-lipoic acid, which is not ionically and therefore only loosely bound to chitosan, whereas a second maximum is based on the release of the drug during the enzymatic degradation of the chitosan matrix in the colon. The AUC(0-12) was determined to be 183.8 +/- 101.4 microg x min/mL (mean +/- SD; n = 8). Because of the pulsed sustained release of alpha-lipoic acid, the dosage form described here seems to be highly beneficial in order to stimulate the glucose uptake in the case of diabetes type II.

Adult↗