title: Development of an Intraruminal Controlled-Release Device

authors: McLellan, Bradley John

subjects: gas-producing cell

abstract: Slow-release devices retained in the rumen, are a simple method for continuous administration of bioactives to ruminant animals.  To satisfy regulatory requirements and avoid waste of bioactive due to under- or over-dosing, it is advantageous to have a constant and predictable release rate.  Existing intraruminal controlled-release technologies cannot easily be adapted for different bioactives or rates of release and can be influenced by the variable physiological environment in the rumen.  Some existing commercial products use the pressure generated by a hydrogen gas-producing cell to extrude fluids from a syringe-like device.  This technology may provide advantages for ruminal controlled-release as the gas production rate is unaffected by environment in the rumen and can be easily adjusted using electrical resistance applied to the gas cell.  This technology was adapted for use in the rumen in these studies.
Initial experiments identified the need for greater understanding of the rate that hydrogen is produced by the gas cell and the rate that gas diffuses through the barrel walls.  Gas production rate was found to be inversely proportional to the resistance applied to the gas-producing cell.  Factors affecting gas diffusion rate from the device were studied and a polymer was identified that reduced hydrogen diffusion to 5% of that for the initial components used.  A relationship was developed to predict the release profile of a device.  Controlled-release devices were constructed from selected materials.  They released blank formulation at in vitro at a constant rate, which was within experimental variation of predicted values.  Release rates from the devices used in vivo were slightly higher than predicted.  The presence of rumen gases inside in vivo devices suggested that the difference may be due to inward diffusion of these gases; these may be eliminated by further study of barrel materials.  Recommendations on the redesign of this technology for use as a generic intraruminal delivery system are given.

text: Development of an Intraruminal Controlled-Release Device Slow-release devices retained in the rumen, are a simple method for continuous administration of bioactives to ruminant animals.  To satisfy regulatory requirements and avoid waste of bioactive due to under- or over-dosing, it is advantageous to have a constant and predictable release rate.  Existing intraruminal controlled-release technologies cannot easily be adapted for different bioactives or rates of release and can be influenced by the variable physiological environment in the rumen.  Some existing commercial products use the pressure generated by a hydrogen gas-producing cell to extrude fluids from a syringe-like device.  This technology may provide advantages for ruminal controlled-release as the gas production rate is unaffected by environment in the rumen and can be easily adjusted using electrical resistance applied to the gas cell.  This technology was adapted for use in the rumen in these studies.
Initial experiments identified the need for greater understanding of the rate that hydrogen is produced by the gas cell and the rate that gas diffuses through the barrel walls.  Gas production rate was found to be inversely proportional to the resistance applied to the gas-producing cell.  Factors affecting gas diffusion rate from the device were studied and a polymer was identified that reduced hydrogen diffusion to 5% of that for the initial components used.  A relationship was developed to predict the release profile of a device.  Controlled-release devices were constructed from selected materials.  They released blank formulation at in vitro at a constant rate, which was within experimental variation of predicted values.  Release rates from the devices used in vivo were slightly higher than predicted.  The presence of rumen gases inside in vivo devices suggested that the difference may be due to inward diffusion of these gases; these may be eliminated by further study of barrel materials.  Recommendations on the redesign of this technology for use as a generic intraruminal delivery system are given.

year: 2007

title: Translating MDG 3: Gender, Empowerment and the Adolescent Girl in Maharashtra, India

authors: Nandedkar, Lalitgauri

subjects: Adolescent Girls

abstract: This thesis is an exploration of Millennium Development Goal (MDG) 3, tracing its path from a global aspiration to its translation into a developing world context. Adopted in 2001 by the United Nations, the eight MDGs represented a global effort to address issues such as poverty, health, social injustice and environmental degradation. Goal 3 specifically was aimed at gender equality and women’s empowerment. Despite an extensive scholarship on the MDGs in general and on the specific issue of women’s empowerment in the development context, there has been little scholarly attention directed at the place and role of adolescent girls in the context of gender equality and empowerment. Similarly, there is a critical need to examine how policy formulated at the global level is translated into local contexts and with what consequences. This research undertakes a qualitative, in-depth, small-scale case study of a gender empowerment programme located in rural Maharashtra, India, to examine how a broad goal of gender empowerment is translated into a UNICEF-funded local programme for adolescent girls. 

The absence of adolescent girls in the gender and development and feminist scholarship has meant that existing feminist analytical frameworks are inadequate for this study. Hence, I draw on a range of scholarship on Third World feminism, the women, culture and development paradigm, the social relations framework, as well as on youth and citizenship to develop an adolescent girl and development perspective. Deploying this perspective as an analytical tool serves to provide a fresh insight into how Goals conceptualised at the global level translate to influence policy affecting the lived realities of adolescent girls in rural India. 

The empirical case study, grounded in feminist qualitative research methodology, employs this perspective to undertake a thematic analysis of primary documents and transcripts of interviews and focus groups to illustrate how themes and ideas about empowerment, responsibility and development play out in the neoliberal context of development in India. In deploying this framework, the thesis seeks to understand how well-intentioned programmes, such as the Deepshikha programme in rural Maharashtra, often become the site of neoliberal development initiatives that maintain rather than challenge power structures. In addition, it explores the implications of excluding adolescent boys from development interventions. 

The analysis demonstrates that while the Deepshikha programme offers many avenues to political, social, economic, and personal empowerment for adolescent girls, it is not without its contestations. Embedded in narratives of self-responsibilisation, adolescent girls are burdened by multiple pressures in their daily lives. Although often socially perceived as a person of lesser value, the adolescent girl, nonetheless, becomes an object of investment through which she is meant to uplift herself. The thesis examines how, through processes of volunteerism and instrumentalism embedded in notions of the active citizen, the adolescent girl fulfils her duties within family and community while continuing to challenge established hierarchical and structural forms of power. 

This research is significant as there is a paucity of academic scholarship on adolescent girls in the development context. It demonstrates how the translation of a global policy initiative, MDG 3, into a local empowerment programme affects the dynamics of gender relations, with specific reference to adolescent girls and boys in rural Maharashtra. It also contributes to a critical scholarship in the area of gender and development that explores the structural and hierarchical oppression that adolescent girls face and the implications this has for their communities.

text: Translating MDG 3: Gender, Empowerment and the Adolescent Girl in Maharashtra, India This thesis is an exploration of Millennium Development Goal (MDG) 3, tracing its path from a global aspiration to its translation into a developing world context. Adopted in 2001 by the United Nations, the eight MDGs represented a global effort to address issues such as poverty, health, social injustice and environmental degradation. Goal 3 specifically was aimed at gender equality and women’s empowerment. Despite an extensive scholarship on the MDGs in general and on the specific issue of women’s empowerment in the development context, there has been little scholarly attention directed at the place and role of adolescent girls in the context of gender equality and empowerment. Similarly, there is a critical need to examine how policy formulated at the global level is translated into local contexts and with what consequences. This research undertakes a qualitative, in-depth, small-scale case study of a gender empowerment programme located in rural Maharashtra, India, to examine how a broad goal of gender empowerment is translated into a UNICEF-funded local programme for adolescent girls. 

The absence of adolescent girls in the gender and development and feminist scholarship has meant that existing feminist analytical frameworks are inadequate for this study. Hence, I draw on a range of scholarship on Third World feminism, the women, culture and development paradigm, the social relations framework, as well as on youth and citizenship to develop an adolescent girl and development perspective. Deploying this perspective as an analytical tool serves to provide a fresh insight into how Goals conceptualised at the global level translate to influence policy affecting the lived realities of adolescent girls in rural India. 

The empirical case study, grounded in feminist qualitative research methodology, employs this perspective to undertake a thematic analysis of primary documents and transcripts of interviews and focus groups to illustrate how themes and ideas about empowerment, responsibility and development play out in the neoliberal context of development in India. In deploying this framework, the thesis seeks to understand how well-intentioned programmes, such as the Deepshikha programme in rural Maharashtra, often become the site of neoliberal development initiatives that maintain rather than challenge power structures. In addition, it explores the implications of excluding adolescent boys from development interventions. 

The analysis demonstrates that while the Deepshikha programme offers many avenues to political, social, economic, and personal empowerment for adolescent girls, it is not without its contestations. Embedded in narratives of self-responsibilisation, adolescent girls are burdened by multiple pressures in their daily lives. Although often socially perceived as a person of lesser value, the adolescent girl, nonetheless, becomes an object of investment through which she is meant to uplift herself. The thesis examines how, through processes of volunteerism and instrumentalism embedded in notions of the active citizen, the adolescent girl fulfils her duties within family and community while continuing to challenge established hierarchical and structural forms of power. 

This research is significant as there is a paucity of academic scholarship on adolescent girls in the development context. It demonstrates how the translation of a global policy initiative, MDG 3, into a local empowerment programme affects the dynamics of gender relations, with specific reference to adolescent girls and boys in rural Maharashtra. It also contributes to a critical scholarship in the area of gender and development that explores the structural and hierarchical oppression that adolescent girls face and the implications this has for their communities.

year: 2017

title: In vitro cell culture to study microglial inflammation

authors: Newland, Julia

subjects: CNs

abstract: Inflammation of the central nervous system (CNS) characterised by release of cytokines such as tumour necrosis factor-alpha (TNF-a) and interleukin-1 (IL-1) is an event that is often detrimental to neuronal cells and is thought to contribute to the neuronal loss observed during neurodegeneration.
One objective of this study was to investigate the potential anti-inflammatory properties of kawakawa leaf extracts using in vitro model cell systems. Kawakawa leaf extracts anti-inflammatory properties have anecdotally been documented in traditional Maori medicinal practices (Rangoa). However, before this aspect could be carried out, experiments were undertaken to investigate the effects the kawakawa leaf extracts had on the growth rates of two mammalian cell lines (HeLa and THP-1 cells).
Interestingly, the growth assays showed that the extracts to have both a stimulatory and inhibitory effect on cell growth. Toxicity of cells can be categorised as either necrotic or apoptotic cell death. In this study, HeLa cells and THP-1 cells were incubated under standard growth conditions with various concentrations (10 to 100ug/ml) of Kawakawa leave extracts prepared at room temperature or 60OC.
Growth data as seen in figures 2 and 3 typically have a long lag phase before they start to reach exponential growth between days 4 and 5. The extract having the largest stimulatory effect on HeLa cells as shown by figure 6 was 25 ug/ml at 60OC and the largest inhibitory effect seen on HeLa cells was seen at 50 ug/ml RT shown by figure 6. The extract which has the largest stimulatory effect on THP-1 cells is 25 ug/ml 60OC as shown by figure 11 whereas the extract producing the largest inhibitory effect is 25 ug/ml RT.

Apoptotic and necrotic cell death mechanisms were examined by using in vitro biochemistry techniques. Assessments were largely made based on biochemical changes of HeLa cells and THP-1 cells post treatment of Kawakawa leave extracts.
Measurement of lactate dehydrogenase (LDH assays) in the growth media of cells that were shown to be growth inhibited during exposure to Kawakawa extracts indicated that the growth inhibition resulting from exposure to the extracts was not due to necrotic cell death processes. (ie that cells maintained their membrane integrity) When compared to the control, a lower amount of cytosolic LDH was seen in THP-1 cell lines. However, HeLa cell lines produced a high level of cytosolic LDH which may be due to mycoplasma contamination. On average, Kawakawa concentrations at 12.5ug/ml and 25ug/ml yielded less lysed cells percentage across both cell lines.
The demonstrated cell growth inhibition was unlikely to be due to necrosis and because of this it was decided to see if cell death was caused by mitochondrial processes that would further support apoptotic cell death. The biochemical assay MTT indirectly measures mitochondrial dehydrogenase activity in the presence of kawakawa leave extracts.
The MTT data illustrated mitochondrial impairment where HeLa cells exposed to Kawakawa 60OC concentrations 6.25 ug/ml and 12.5 ug/ml had the lowest average mitochondrial activity. THP-1 cells exposed to Kawakawa 60OC concentrations 12.5 ug/ml and 50 ug/ml had the lowest average mitochondrial activity.
The main results of this study include, the treatment of HeLa and THP-1 cells with kawakawa extracts demonstrated that cytotoxicity was not due to necrosis. The most interesting finding of this study is when kawakawa extracts inhibit cell growth there is no increase in LDH. This is suggestive that the cellular membrane remains intact when exposed to the extract.

text: In vitro cell culture to study microglial inflammation Inflammation of the central nervous system (CNS) characterised by release of cytokines such as tumour necrosis factor-alpha (TNF-a) and interleukin-1 (IL-1) is an event that is often detrimental to neuronal cells and is thought to contribute to the neuronal loss observed during neurodegeneration.
One objective of this study was to investigate the potential anti-inflammatory properties of kawakawa leaf extracts using in vitro model cell systems. Kawakawa leaf extracts anti-inflammatory properties have anecdotally been documented in traditional Maori medicinal practices (Rangoa). However, before this aspect could be carried out, experiments were undertaken to investigate the effects the kawakawa leaf extracts had on the growth rates of two mammalian cell lines (HeLa and THP-1 cells).
Interestingly, the growth assays showed that the extracts to have both a stimulatory and inhibitory effect on cell growth. Toxicity of cells can be categorised as either necrotic or apoptotic cell death. In this study, HeLa cells and THP-1 cells were incubated under standard growth conditions with various concentrations (10 to 100ug/ml) of Kawakawa leave extracts prepared at room temperature or 60OC.
Growth data as seen in figures 2 and 3 typically have a long lag phase before they start to reach exponential growth between days 4 and 5. The extract having the largest stimulatory effect on HeLa cells as shown by figure 6 was 25 ug/ml at 60OC and the largest inhibitory effect seen on HeLa cells was seen at 50 ug/ml RT shown by figure 6. The extract which has the largest stimulatory effect on THP-1 cells is 25 ug/ml 60OC as shown by figure 11 whereas the extract producing the largest inhibitory effect is 25 ug/ml RT.

Apoptotic and necrotic cell death mechanisms were examined by using in vitro biochemistry techniques. Assessments were largely made based on biochemical changes of HeLa cells and THP-1 cells post treatment of Kawakawa leave extracts.
Measurement of lactate dehydrogenase (LDH assays) in the growth media of cells that were shown to be growth inhibited during exposure to Kawakawa extracts indicated that the growth inhibition resulting from exposure to the extracts was not due to necrotic cell death processes. (ie that cells maintained their membrane integrity) When compared to the control, a lower amount of cytosolic LDH was seen in THP-1 cell lines. However, HeLa cell lines produced a high level of cytosolic LDH which may be due to mycoplasma contamination. On average, Kawakawa concentrations at 12.5ug/ml and 25ug/ml yielded less lysed cells percentage across both cell lines.
The demonstrated cell growth inhibition was unlikely to be due to necrosis and because of this it was decided to see if cell death was caused by mitochondrial processes that would further support apoptotic cell death. The biochemical assay MTT indirectly measures mitochondrial dehydrogenase activity in the presence of kawakawa leave extracts.
The MTT data illustrated mitochondrial impairment where HeLa cells exposed to Kawakawa 60OC concentrations 6.25 ug/ml and 12.5 ug/ml had the lowest average mitochondrial activity. THP-1 cells exposed to Kawakawa 60OC concentrations 12.5 ug/ml and 50 ug/ml had the lowest average mitochondrial activity.
The main results of this study include, the treatment of HeLa and THP-1 cells with kawakawa extracts demonstrated that cytotoxicity was not due to necrosis. The most interesting finding of this study is when kawakawa extracts inhibit cell growth there is no increase in LDH. This is suggestive that the cellular membrane remains intact when exposed to the extract.

year: 2016