NITRIC OXIDE SYNTHASE INHIBITION ATTENUATES L-DOPA-INDUCED DYSKINESIAS IN A RODENT MODEL OF PARKINSON`S DISEASE

Chronic L-DOPA pharmacotherapy in Parkinson`s disease is often, accompanied by the development of abnormal and excessive movements known as L-DOPA-induced dyskinesia. Rats with 6-hydroxydopamine lesion of dopaminergic neurons chronically treated with L-DOPA develop a rodent analog of this dyskinesia characterized by severe axial, limb, locomotor and orofacial abnormal involuntary movements. While the mechanisms by which these effects occur are not clear, they may involve the nitric oxide system. In the present study we investigate if nitric oxide synthase inhibitors can prevent dyskinesias induced by repeated administration Of L-DOPA in rats with unilateral 6-hydroxydopamine lesion. Chronic L-DOPA (high fixed dose, 100 mg/kg; low escalating dose, 10-30 mg/kg) treatment induced progressive dyskinesia changes. Two nitric oxide synthase inhibitors, 7-nitroindazole (1-30 mg/kg) and NG-nitro-L-arginine (50 mg/kg), given 30 min before L-DOPA, attenuate dyskinesia. 7-Nitroindazolee also improved motor performance of these animals in the rota-rod test. These results suggest the possibility that nitric oxide synthase inhibitors may be useful to treat L-DOPA.-Induced dyskinesia. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of a mixture of growth factors and proteins on the development of the osteogenic phenotype in human alveolar bone cell cultures

Strategies to promote bone repair have included exposure of cells to growth factor (GF) preparations from blood that generally include proteins as part of a complex mixture. This study aimed to evaluate the effects of such a mixture on different parameters of the development of the osteogenic phenotype in vitro. Osteoblastic cells were obtained by enzymatic digestion of human alveolar bone and cultured under standard osteogenic conditions until subconfluence. They were subcultured on Thermanox coverslips up to 14 days. Treated cultures were exposed during the first 7 days to osteogenic medium supplemented with a GFs + proteins mixture containing the major components found in platelet extracts [plate I et-derived growth factor-BB, transforming growth factor (TGF)-beta 1, TGF-beta 2, albumin, fibronectin, and thrombospondin] and to osteogenic medium alone thereafter. Control cultures were exposed only to the osteogenic medium. Treated cultures exhibited a significantly higher number of adherent cells from day 4 onward and of cycling cells at days 1 and 4, weak alkaline phosphatase (ALP) labeling, and significantly decreased levels of ALP activity and mRNA expression. At day 14, no Alizarin red-stained nodular areas were detected in cultures treated with GFs + proteins. Results were confirmed in the rat calvaria-derived osteogenic cell culture model. The addition of bone morphogenetic protein 7 or growth and differentiation factor 5 to treated cultures upregulated Runx2 and ALP mRNA expression, but surprisingly, ALP activity was not restored. These results showed that a mixture of GFs + proteins affects the development of the osteogenic phenotype both in human and rat cultures, leading to an increase in the number of cells, but expressed a less differentiated state.

The young women's network: A case study in community development

While young women have been found to be at additional risk for psychological morbidity after a breast cancer diagnosis, their specific needs in relation to support are not well described. A community development approach was utilized to develop the Young Women's Network, a peer support programme for young women who have been diagnosed with breast cancer that addresses their specific psychological and social needs, Central to this approach was the key role of the target group in both the definition of the problem and the generation of the solutions. This article describes the steps involved in developing this programme and guidelines for health professionals and community members who may wish to replicate either the Young Women's Network or this particular approach to programme development. Copyright (C), 2001 John Wiley & Sons, Ltd.

Temporal relationship between the auditory brainstem response and focal responses of auditory nerve root and cochlear nucleus during development in the tammar wallaby (Macropus eugenii)

Thirty-two pouch-young tammar wallabies were used to discover the generators of the auditory brainstem response (ABR) during development by the use of simultaneous ABR and focal brainstem recordings. A click response from the auditory nerve root (ANR) in the wallaby was recorded from postnatal day (PND) 101, when no central auditory station was functional, and coincided with the ABR, a simple positive wave. The response of the cochlear nucleus (CN) was detected from PND 110, when the ABR had developed 1 positive and 1 negative peak. The dominant component of the focal ANR response, the N-1 wave, coincided with the first half of the ABR P wave, and that of the focal CN response, the N-1 wave, coincided with the later two thirds. In older animals, the ANR response coincided with the ABR's N-1, wave, while the CN response coincided with the ABR's P-2, N-2 and P-3 waves, with its contribution to the ABR P-2 dominant. The protracted development of the marsupial auditory system which facilitated these correlations makes the tammar wallaby a particularly suitable model. Copyright (C) 2001 S. Karger AG, Basel.

Growth regime map for liquid-bound granules: further development and experimental validation

An attempt was made to quantify the boundaries and validate the granule growth regime map for liquid-bound granules recently proposed by Iveson and Litster (AlChE J. 44 (1998) 1510). This regime map postulates that the type of granule growth behaviour is a function of only two dimensionless groups: the amount of granule deformation during collision (characterised by a Stokes deformation number, St(def)) and the maximum granule pore saturation, s(max). The results of experiments performed with a range of materials (glass ballotini, iron ore fines, copper chalcopyrite powder and a sodium sulphate and cellulose mixture) using both drum and high shear mixer granulators were examined. The drum granulation results gave good agreement with the proposed regime map. The boundary between crumb and steady growth occurs at St(def) of order 0.1 and the boundary between steady and induction growth occurs at St(def) of order 0.001. The nucleation only boundary occurs at pore saturations that increase from 70% to 80% with decreasing St(def). However, the high shear mixer results all had St(def) numbers which were too large. This is most likely to be because the chopper tip-speed is an over-estimate of the average impact velocity granules experience and possibly also due to the dynamic yield strength of the materials being significantly greater than the yield strengths measured at low strain rates. Hence, the map is only a useful tool for comparing the granulation behaviour of different materials in the same device. Until we have a better understanding of the flow patterns and impact velocities in granulators, it cannot be used to compare different types of equipment. Theoretical considerations also revealed that several of the regime boundaries are also functions of additional parameters not explicitly contained on the map, such as binder viscosity. (C) 2001 Elsevier Science B.V. All rights reserved.

An orthotopic xenograft model of human nonseminomatous germ cell tumour

We have established the first example of an orthotopic xenograft model of human nonseminomatous germ cell tumour (NSGCT). This reproducible model exhibits many clinically relevant features including metastases to the retroperitoneal lymph nodes and lungs, making it an ideal tool for research into the development and progression of testicular germ cell tumours.

An aggregate sales model for consumer durables incorporating a time-varying mean replacement age

Forecasting category or industry sales is a vital component of a company's planning and control activities. Sales for most mature durable product categories are dominated by replacement purchases. Previous sales models which explicitly incorporate a component of sales due to replacement assume there is an age distribution for replacements of existing units which remains constant over time. However, there is evidence that changes in factors such as product reliability/durability, price, repair costs, scrapping values, styling and economic conditions will result in changes in the mean replacement age of units. This paper develops a model for such time-varying replacement behaviour and empirically tests it in the Australian automotive industry. Both longitudinal census data and the empirical analysis of the replacement sales model confirm that there has been a substantial increase in the average aggregate replacement age for motor vehicles over the past 20 years. Further, much of this variation could be explained by real price increases and a linear temporal trend. Consequently, the time-varying model significantly outperformed previous models both in terms of fitting and forecasting the sales data. Copyright (C) 2001 John Wiley & Sons, Ltd.

Regulation of male sexual development by Sry and Sox9

Sry, a gene from the Y chromosome, is known to initiate testis formation and subsequent male differentiation in mammals. A related gene, Sox9, also plays a critical role in testis determination, possibly in all vertebrates. A number of models have been presented regarding the molecular modes of action of these two genes. However, details regarding their regulation, regulatory target genes, and interacting protein factors and co-factors have not been established with any certainty. In this review, we examine new evidence and re-examine existing evidence bearing on these issues, in an effort to build up an integrative model of the network of gene activity centred around Sry and Sox9. J. Exp. Zool. 290:463-474, 2001. (C) 2001 Wiley-Liss, Inc.

Developing a meta model for the Bunge-Wand-Weber ontological constructs

At the core of the analysis task in the development process is information systems requirements modelling, Modelling of requirements has been occurring for many years and the techniques used have progressed from flowcharting through data flow diagrams and entity-relationship diagrams to object-oriented schemas today. Unfortunately, researchers have been able to give little theoretical guidance only to practitioners on which techniques to use and when. In an attempt to address this situation, Wand and Weber have developed a series of models based on the ontological theory of Mario Bunge-the Bunge-Wand-Weber (BWW) models. Two particular criticisms of the models have persisted however-the understandability of the constructs in the BWW models and the difficulty in applying the models to a modelling technique. This paper addresses these issues by presenting a meta model of the BWW constructs using a meta language that is familiar to many IS professionals, more specific than plain English text, but easier to understand than the set-theoretic language of the original BWW models. Such a meta model also facilitates the application of the BWW theory to other modelling techniques that have similar meta models defined. Moreover, this approach supports the identification of patterns of constructs that might be common across meta models for modelling techniques. Such findings are useful in extending and refining the BWW theory. (C) 2002 Elsevier Science Ltd. All rights reserved.

Long-run growth effects of taxation in a non-scale growth model with innovation

In previous studies, taxing income or consumption hinders long-run growth. Incorporating saving and leisure into the non-scale Schumpeterian model of [Journal of Political Economy 107 (1999) 715-730], we show that the usual growth effects of taxing consumption and labor income do not exist. (C) 2002 Elsevier Science B.V. All rights reserved.

A model of factors affecting an information system's change in state

Management are keen to maximize the life span of an information system because of the high cost, organizational disruption, and risk of failure associated with the re-development or replacement of an information system. This research investigates the effects that various factors have on an information system's life span by understanding how the factors affect an information system's stability. The research builds on a previously developed two-stage model of information system change whereby an information system is either in a stable state of evolution in which the information system's functionality is evolving, or in a state of revolution, in which the information system is being replaced because it is not providing the functionality expected by its users. A case study surveyed a number of systems within one organization. The aim was to test whether a relationship existed between the base value of the volatility index (a measure of the stability of an information system) and certain system characteristics. Data relating to some 3000 user change requests covering 40 systems over a 10-year period were obtained. The following factors were hypothesized to have significant associations with the base value of the volatility index: language level (generation of language of construction), system size, system age, and the timing of changes applied to a system. Significant associations were found in the hypothesized directions except that the timing of user changes was not associated with any change in the value of the volatility index. Copyright (C) 2002 John Wiley Sons, Ltd.

Pathways to Melanoma Development: Lessons from the Mouse

Because of subtle differences between mouse and human skin, mice have traditionally not been an ideal model to study melanoma development. Understanding of the molecular mechanisms of melanoma predisposition, however, has been greatly improved by modeling various pathway defects in the mouse. This review analyzes the latest developments in mouse models of melanoma, and summarizes what these may indicate about the development of this neoplasm in humans. Mutations of genes involved in human melanoma have been recapitulated with some unexpected results, particularly with respect to the role of the two transcripts (Ink4a and Arf) encoded by the Cdkn2a locus. Both the Ink4a/pRb and Arf/p53 pathways are involved in melanoma development in mice, and possible mechanisms of cross-talk between the two pathways are discussed. We also know from mouse models that Ras/mitogen-activated protein kinase pathway activation is very important in melanoma development, either through direct activation of Ras (e.g., Hras G12V), or via activation of Ras-effector pathways by other oncogenes (e.g., Ret, Hgf/Sf). Ras can cooperate with the Arf/p53 pathway, and probably the Ink4a/Rb pathway, to induce melanoma. These three growth regulation pathways (Ink4a/pRb, Arf/p53, and Ras/mitogen-activated protein kinase) seem to represent three major axes of melanoma development in mice. Finally, we summarize experiments using genetically modified mice that have given indications of the intensity and timing of ultraviolet radiation exposure that may be most responsible for melanoma development.

Population health, environment and economic development

This paper studies the role of income distribution and technology transfer in the process of economic development. A novel aspect of the model is that the composition of human capital as well as the level affect economic growth. Utilizing an overlapping-generations model in which income distribution changes endogenously, we present an economic explanation for why some countries could not start modern economic growth; why some countries took off but have apparently stopped growing after some time; and why some countries have successfully developed and continue to grow

Development of a novel titration and off-gas analysis (TOGA) sensor for study of biological processes in wastewater treatment systems

The development of the new TOGA (titration and off-gas analysis) sensor for the detailed study of biological processes in wastewater treatment systems is outlined. The main innovation of the sensor is the amalgamation of titrimetric and off-gas measurement techniques. The resulting measured signals are: hydrogen ion production rate (HPR), oxygen transfer rate (OTR), nitrogen transfer rate (NTR), and carbon dioxide transfer rate (CTR). While OTR and NTR are applicable to aerobic and anoxic conditions, respectively, HPR and CTR are useful signals under all of the conditions found in biological wastewater treatment systems, namely, aerobic, anoxic and anaerobic. The sensor is therefore a powerful tool for studying the key biological processes under all these conditions. A major benefit from the integration of the titrimetric and off-gas analysis methods is that the acid/base buffering systems, in particular the bicarbonate system, are properly accounted for. Experimental data resulting from the TOGA sensor in aerobic, anoxic, and anaerobic conditions demonstrates the strength of the new sensor. In the aerobic environment, carbon oxidation (using acetate as an example carbon source) and nitrification are studied. Both the carbon and ammonia removal rates measured by the sensor compare very well with those obtained from off-line chemical analysis. Further, the aerobic acetate removal process is examined at a fundamental level using the metabolic pathway and stoichiometry established in the literature, whereby the rate of formation of storage products is identified. Under anoxic conditions, the denitrification process is monitored and, again, the measured rate of nitrogen gas transfer (NTR) matches well with the removal of the oxidised nitrogen compounds (measured chemically). In the anaerobic environment, the enhanced biological phosphorus process was investigated. In this case, the measured sensor signals (HPR and CTR) resulting from acetate uptake were used to determine the ratio of the rates of carbon dioxide production by competing groups of microorganisms, which consequently is a measure of the activity of these organisms. The sensor involves the use of expensive equipment such as a mass spectrometer and requires special gases to operate, thus incurring significant capital and operational costs. This makes the sensor more an advanced laboratory tool than an on-line sensor. (C) 2003 Wiley Periodicals, Inc.

Development and survival of the diamondback moth (Lepidoptera : Plutellidae) at constant and alternating temperatures

Survival and development time from egg to adult emergence of the diamondback moth, Plutella xylostella (L.), were determined at 19 constant and 14 alternating temperature regimes from 4 to 40degreesC. Plutella xylostella developed successfully front egg to adult emergence at constant temperatures from 8 to 32degreesC. At temperatures from 4 to 6degreesC or from 34 to 40degreesC, partial or complete development of individual stages or instars was possible, with third and fourth instars having the widest temperature limits. The insect developed successfully from egg to adult emergence under alternating regimes including temperatures as low as 4degreesC or as high as 38degreesC. The degree-day model, the logistic equation, and the Wang model were used to describe the relationships between temperature and development rate at both constant and alternating temperatures. The degree-day model described the relationships well from 10 to 30degreesC. The logistic equation and the Wang model fit the data well at temperatures 32degreesC. Under alternating regimes, all three models gave good simulations of development in the mid-temperature range, but only the logistic equation gave close simulations in the low temperature range, and none gave close or consistent simulations in the high temperature range. The distribution of development time was described satisfactorily by a Weibull function. These rate and time distribution functions provide tools for simulating population development of P. xylostella over a wide range of temperature conditions.