title: Chemical aspects of saponin bioactivity and ovine photosensitization diseases

authors: Loader, Jared I.

abstract: A general review of saponin chemistry, bioactivities and of chemical aspects of saponin-associated hepatogenous photosensitization of ruminants (sheep, goats, and cattle) is presented. 
A field trial was undertaken to explore the genin dose/response hypothesis that saponins produced by the plant Narthecium ossifragum may be the direct cause of the toxicity leading to the photosensitization disease alveld seen in Norwegian lambs grazing N. ossifragum containing pastures. The genin content of N. ossifragum leaves from 2 control and 2 outbreak pasture areas, in a region of Norway known for periodic livestock outbreaks of alveld, ranged from 4553 to 10879 mg/kg DM. No significant statistical differences in the mean sapogenin content from the 2 control and 2 outbreak pasture areas were found. Total faecal sapogenin levels determined for lambs grazing the 2 control and 2 outbreak areas ranged from 973 to 36314 mg/kg DM. No obvious relationships between faecal sapogenin levels of lambs exhibiting external alveld symptoms and lambs not exhibiting symptoms were identified. The data does not support the hypothesis that saponins are the sole causative agent for the development of alveld disease symptoms in lambs grazing pastures containing N. ossifragum. 
Genin levels in Scottish collections of N. ossifragum plant material, gathered from pasture on which sheep were photosensitized, were determined. Elevated levels of sarsasapogenin and smilagenin containing saponins were found in flower heads (ca. 18000 mg/kg DM). Significant levels of free genins were found in plant roots (832-1184 mg/kg DM). The percentage contribution (ca. 45-65%) of smilagenin (a 25R-genin) in the Scottish samples was typically 2-4 times greater than is the case for Norwegian collections of N. ossifragum (typically ca. 10-15%). 
A field trial involving the daily intraruminal administration of a 1:4 mixture of [2,2,4,4-2H4]sarsasapogenin and [2,2,4,4-2H4]episarsasapogenin to 4 ewes, their twin lambs, and to 3 weaned lambs over a 21 day period was undertaken in Norway. The results showed that the isotope-dilution methodology can be applied under field conditions to estimate the uptake of sapogenins from plant material under conditions characteristically associated with the development of al veld. 
Mother ewes, on average, consumed 2-3 times the daily weight of N. ossifragum (ca. 700-750 g DM/day) consumed by the lambs (ca. 200-250 g DM/day). Percentage deuterium ratios, determined using SIM GC-MS protocols, while lower that anticipated, were consistent across the animals involved in the trial (between ca. 2-3%). Average N. ossifragum intakes, calculated relative to live-weights, were determined for all sheep involved in the trial. No correlation between the quantity of N. ossifragum consumed and live-weight (g DM day/kg) and the development of alveld was identified. 
The synthesis of sarsasapogenin β-D-galactoside, episarsasapogenin β-D-glucoside, episarsasapogenin β-D-galactoside, betulin 3-(β-D-glucoside) and betulin 3,28-(β-D-diglucoside), was performed via Koenig-Knorr coupling of sarsasapogenin, episarsasapogenin, or betulin with 2,3,4,6-tetra-0-acetyl-α-D-glucopyranosyl bromide, or the corresponding galactoside, followed by hydrolysis of the resulting tetra-0-acetyl-β-Dglycosides.Structures of intermediates, and product glycosides were established using a combination of ES-MS and one- and two-dimensional NMR spectral data. 
The synthesized sarsasapogenin, episarsasapogenin and betulin saponins, 4-methoxyfuran-2(5H)-one 5-(β-D-glucoside), Yucca schidigera 70° Brix extract, a methanol conjugate extract of N. ossifragum leaves and the active triketone fraction (triketone oil) from East Cape Manuka oil were subjected to a bioactivity evaluation against a range of bacterial and fungal organisms using the agar gel well diffusion technique. A possible structure-activity relationship amongst the synthesized saponins is discussed. 
The activity of triketone oil against two fish-pathogenic strains of Saprolegnia parasiticawas evaluated. The evaluation, performed in vitro, required the use of small percentages of water-miscible organic solvents and phosphate buffer solutions to obtain homogenous aqueous solutions. Inhibition of S. parasitica growth was seen at triketone oil concentrations of: (i) 150 and 200 ppm using aqueous solutions containing 0.5% and 1.0% pyrrolidinone, each containing 0.5% Tween 80 and (ii) at 150 and 200 ppm, at both pH 7 .0 and 7.5 of a 0.25 molL-1  phosphate buffer solution. An in vivo toxicity trial found that East Cape triketone oil at 200 ppm was acutely toxic to Atlantic salmon fry, with a 50% mortality rate after a 2 h single dose static bath exposure.

text: Chemical aspects of saponin bioactivity and ovine photosensitization diseases A general review of saponin chemistry, bioactivities and of chemical aspects of saponin-associated hepatogenous photosensitization of ruminants (sheep, goats, and cattle) is presented. 
A field trial was undertaken to explore the genin dose/response hypothesis that saponins produced by the plant Narthecium ossifragum may be the direct cause of the toxicity leading to the photosensitization disease alveld seen in Norwegian lambs grazing N. ossifragum containing pastures. The genin content of N. ossifragum leaves from 2 control and 2 outbreak pasture areas, in a region of Norway known for periodic livestock outbreaks of alveld, ranged from 4553 to 10879 mg/kg DM. No significant statistical differences in the mean sapogenin content from the 2 control and 2 outbreak pasture areas were found. Total faecal sapogenin levels determined for lambs grazing the 2 control and 2 outbreak areas ranged from 973 to 36314 mg/kg DM. No obvious relationships between faecal sapogenin levels of lambs exhibiting external alveld symptoms and lambs not exhibiting symptoms were identified. The data does not support the hypothesis that saponins are the sole causative agent for the development of alveld disease symptoms in lambs grazing pastures containing N. ossifragum. 
Genin levels in Scottish collections of N. ossifragum plant material, gathered from pasture on which sheep were photosensitized, were determined. Elevated levels of sarsasapogenin and smilagenin containing saponins were found in flower heads (ca. 18000 mg/kg DM). Significant levels of free genins were found in plant roots (832-1184 mg/kg DM). The percentage contribution (ca. 45-65%) of smilagenin (a 25R-genin) in the Scottish samples was typically 2-4 times greater than is the case for Norwegian collections of N. ossifragum (typically ca. 10-15%). 
A field trial involving the daily intraruminal administration of a 1:4 mixture of [2,2,4,4-2H4]sarsasapogenin and [2,2,4,4-2H4]episarsasapogenin to 4 ewes, their twin lambs, and to 3 weaned lambs over a 21 day period was undertaken in Norway. The results showed that the isotope-dilution methodology can be applied under field conditions to estimate the uptake of sapogenins from plant material under conditions characteristically associated with the development of al veld. 
Mother ewes, on average, consumed 2-3 times the daily weight of N. ossifragum (ca. 700-750 g DM/day) consumed by the lambs (ca. 200-250 g DM/day). Percentage deuterium ratios, determined using SIM GC-MS protocols, while lower that anticipated, were consistent across the animals involved in the trial (between ca. 2-3%). Average N. ossifragum intakes, calculated relative to live-weights, were determined for all sheep involved in the trial. No correlation between the quantity of N. ossifragum consumed and live-weight (g DM day/kg) and the development of alveld was identified. 
The synthesis of sarsasapogenin β-D-galactoside, episarsasapogenin β-D-glucoside, episarsasapogenin β-D-galactoside, betulin 3-(β-D-glucoside) and betulin 3,28-(β-D-diglucoside), was performed via Koenig-Knorr coupling of sarsasapogenin, episarsasapogenin, or betulin with 2,3,4,6-tetra-0-acetyl-α-D-glucopyranosyl bromide, or the corresponding galactoside, followed by hydrolysis of the resulting tetra-0-acetyl-β-Dglycosides.Structures of intermediates, and product glycosides were established using a combination of ES-MS and one- and two-dimensional NMR spectral data. 
The synthesized sarsasapogenin, episarsasapogenin and betulin saponins, 4-methoxyfuran-2(5H)-one 5-(β-D-glucoside), Yucca schidigera 70° Brix extract, a methanol conjugate extract of N. ossifragum leaves and the active triketone fraction (triketone oil) from East Cape Manuka oil were subjected to a bioactivity evaluation against a range of bacterial and fungal organisms using the agar gel well diffusion technique. A possible structure-activity relationship amongst the synthesized saponins is discussed. 
The activity of triketone oil against two fish-pathogenic strains of Saprolegnia parasiticawas evaluated. The evaluation, performed in vitro, required the use of small percentages of water-miscible organic solvents and phosphate buffer solutions to obtain homogenous aqueous solutions. Inhibition of S. parasitica growth was seen at triketone oil concentrations of: (i) 150 and 200 ppm using aqueous solutions containing 0.5% and 1.0% pyrrolidinone, each containing 0.5% Tween 80 and (ii) at 150 and 200 ppm, at both pH 7 .0 and 7.5 of a 0.25 molL-1  phosphate buffer solution. An in vivo toxicity trial found that East Cape triketone oil at 200 ppm was acutely toxic to Atlantic salmon fry, with a 50% mortality rate after a 2 h single dose static bath exposure.

year: 2004

title: Special educational needs: a contextualised perspective

authors: Lupton, Ruth

subjects: special educational needs (SEN)

abstract: The paper examines variations in the extent of special education needs (SEN) in different socio-economic contexts, drawing on data from 46 English primary schools. It examines the implications of variations in SEN for individual pupils and for school organisation and processes. It reviews funding allocations for SEN and what they mean for the provision of support in different settings.

text: Special educational needs: a contextualised perspective The paper examines variations in the extent of special education needs (SEN) in different socio-economic contexts, drawing on data from 46 English primary schools. It examines the implications of variations in SEN for individual pupils and for school organisation and processes. It reviews funding allocations for SEN and what they mean for the provision of support in different settings.

year: 2010

title: Reimagining community resilience through a Te Ao Maori worldview

authors: Boston, Megan

abstract: Efforts to improve community resilience have seen universal efforts to grow capabilities in disaster management for the built environment. Although comprehensive frameworks exist, the perspective used to derive these frameworks fails to address marginalised communities' vulnerabilities, including Indigenous Māori people. Colonization and socio-economic deprivation on Māori mean community response frameworks fail to reflect their values and specific needs when preparing and responding to natural disasters. The nature of Māori culture and values presents an opportunity to reimagine the scope of community resilience for an inclusive framework. The Māori history has resilient practices weaved into the very fabric of their culture, which knowledge has survived through the oral transmission of waiata, whakataukī, whakairo, and pūrakau. The practice of community resilience amongst ancient Māori was not consigned to singular events but instead is a holistic perspective to the manner of living. Sourcing and qualifying this information from people aligned and immersed in nature is the knowledge required to improve the frameworks to respond to natural disasters while expanding the literature on community resilience. A comprehensive analysis of traditional Māori resilience is conducted by evaluating a variety of Mātauranga Māori that relate to the resilient nature of Māori. This information is compared to modern Māori perceptions of community resilience using a derived earthquake scenario for the local Iwi Ngati Toa, located in the city of Porirua within the Wellington region. This information will enable a comprehensive definition of community resilience and improve disaster response frameworks to be more inclusive, safe, sustainable, and resilient.

text: Reimagining community resilience through a Te Ao Maori worldview Efforts to improve community resilience have seen universal efforts to grow capabilities in disaster management for the built environment. Although comprehensive frameworks exist, the perspective used to derive these frameworks fails to address marginalised communities' vulnerabilities, including Indigenous Māori people. Colonization and socio-economic deprivation on Māori mean community response frameworks fail to reflect their values and specific needs when preparing and responding to natural disasters. The nature of Māori culture and values presents an opportunity to reimagine the scope of community resilience for an inclusive framework. The Māori history has resilient practices weaved into the very fabric of their culture, which knowledge has survived through the oral transmission of waiata, whakataukī, whakairo, and pūrakau. The practice of community resilience amongst ancient Māori was not consigned to singular events but instead is a holistic perspective to the manner of living. Sourcing and qualifying this information from people aligned and immersed in nature is the knowledge required to improve the frameworks to respond to natural disasters while expanding the literature on community resilience. A comprehensive analysis of traditional Māori resilience is conducted by evaluating a variety of Mātauranga Māori that relate to the resilient nature of Māori. This information is compared to modern Māori perceptions of community resilience using a derived earthquake scenario for the local Iwi Ngati Toa, located in the city of Porirua within the Wellington region. This information will enable a comprehensive definition of community resilience and improve disaster response frameworks to be more inclusive, safe, sustainable, and resilient.

year: 2023