The Experts below are selected from a list of 294 Experts worldwide ranked by ideXlab platform

M Meaney - One of the best experts on this subject based on the ideXlab platform.

  • Fasciola hepatica: ultrastructural effects of a combination of triclabendazole and Clorsulon against mature fluke
    Parasitology Research, 2007
    Co-Authors: M Meaney, A B Forbes, G. P. Brennan, J. Allister, B. Mckinstry, K. Mclaughlin, I Fairweather
    Abstract:

    A study has been carried out to investigate the ultrastructural effects of triclabendazole (TCBZ) at half-normal concentration, Clorsulon at half-normal concentration, and a combination of these two drugs against mature Fasciola hepatica. The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 μg/ml), Clorsulon (5 μg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (5 mg/kg body weight), Clorsulon (5 mg/kg body weight), or a combination of the two drugs, and flukes recovered after 48 h. Fine structural changes within the tegumental syncytium and tegumental cells were assessed by transmission electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-normal concentrations, both in vivo and in vitro; also than TCBZ.SO at normal concentration in vitro. The changes observed aid in the understanding of the gross changes to the tegumental surface described previously (Meaney M, Allister J, McKinstry B, McLaughlin K, Brennan GP, Forbes AB, Fairweather I. Parasitol Res 99:609–621, 2006 ). The results indicate that there are additive effects between TCBZ and Clorsulon and suggest that the use of drug combinations would be of value in the treatment of TCBZ-resistant fluke.

  • Fasciola hepatica: morphological effects of a combination of triclabendazole and Clorsulon against mature fluke
    Parasitology Research, 2006
    Co-Authors: M Meaney, A B Forbes, G. P. Brennan, J. Allister, B. Mckinstry, K. Mclaughlin, I Fairweather
    Abstract:

    A study has been carried out to investigate the morphological effects of half-strength triclabendazole (TCBZ), half-strength Clorsulon, and a combination of these two drugs against mature Fasciola hepatica . The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 μg/ml), Clorsulon (5 μg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (6.25 mg/kg body weight), Clorsulon (5 mg/kg body weight), or a combination of the two drugs and flukes recovered after 48 h. Surface changes to the flukes were assessed by scanning electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-strength, both in vivo and in vitro. Disruption to the tegument of the flukes induced by the individual drugs at half-strength was relatively minor and less than that caused by the drugs at full-strength. The results suggest that there are additive effects between TCBZ and Clorsulon, which may be indicative of synergy: the use of drug combinations would be of value in the treatment of triclabendazole-resistant fluke.

  • Ultrastructural observations on oral ingestion and trans-tegumental uptake of Clorsulon by the liver fluke, Fasciola hepatica
    Parasitology Research, 2005
    Co-Authors: M Meaney, G. P. Brennan, S. Haughey, I Fairweather
    Abstract:

    Three experiments have been carried out in vitro to determine the effect of oral and trans-tegumental uptake of Clorsulon on the fine structure of the tegument and gut of Fasciola hepatica. Changes were assessed by transmission electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in Clorsulon (10 μg/ml). Limited swelling of the basal infolds was observed in the tegumental syncytium. Swollen mitochondria were present in the syncytium, the underlying tegumental cells and in the gastrodermal cells. Swelling and vesiculation of the cisternae of the granular endoplasmic reticulum (ger) was evident in the gastrodermal cells, together with a reduction in secretory activity. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with Clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. There was severe swelling of the basal infolds in the tegumental syncytium and swelling of mitochondria in the syncytium, tegumental cells and gastrodermal cells. In the tegumental cells there was a decrease in the number of Golgi complexes as well. A number of changes were evident in the gastrodermal cells: swelling of the ger cisternae, an increase in the number of autophagic vacuoles, a reduction in the number of secretory bodies and disruption of the lamellae projecting from the surface of the cells. In the third experiment, flukes were incubated for 24 h in Clorsulon (10 μg/ml), with both absorptive surfaces being available for drug uptake. There was severe swelling of the basal infolds in the tegumental syncytium and large autophagic vacuoles were present. Swollen mitochondria were a feature of the tegument, tegumental cells and gastrodermal cells, as were swollen cisternae of ger in the tegumental and gastrodermal cells. Fewer Golgi complexes were observed in the tegumental cells and in the gastrodermal cells there were fewer secretory bodies and an increased number of autophagic vacuoles. Overall, the gastrodermal cells were more severely affected than the tegument. Greater disruption of the tegument occurred when the oral route of uptake was available. The results support those of previous studies which point to oral uptake of Clorsulon being the major route of entry into the fluke.

  • A scanning electron microscope study on the route of entry of Clorsulon into the liver fluke, Fasciola hepatica
    Parasitology Research, 2005
    Co-Authors: M Meaney, G. P. Brennan, S. Haughey, I Fairweather
    Abstract:

    Three experiments were carried out in vitro to determine the roles of the tegument and gut of Fasciola hepatica in the uptake of the flukicidal drug, Clorsulon. Changes to the two surfaces were assessed by scanning electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in Clorsulon (10 μg/ml). The gastrodermal surface remained normal and few changes to the tegumental surface were observed. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with Clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. The gastrodermal surface was severely disrupted and the gut lamellae were disorganised and necrotic. Swelling of the tegument and blebbing on the tegumental surface were evident, but the changes were not severe. More severe swelling of the tegument was observed in the third experiment, in which flukes were incubated for 24 h in Clorsulon (10 μg/ml), with both absorptive surfaces being available for drug uptake. The gastrodermal surface was badly disrupted and the gut lamellae were disorganised and necrotic. Taking the results of the three experiments together, the gastrodermal surface was more affected than the tegument and the greatest disruption to the two surfaces was seen when both routes of entry were available to the fluke. The data support a previous study which indicated that entry of Clorsulon into the fluke in vivo is principally by the oral ingestion of drug bound to the red blood cells.

  • Transmission electron microscope study of the ultrastructural changes induced in the tegument and gut of Fasciola hepatica following in vivo drug treatment with Clorsulon
    Parasitology Research, 2004
    Co-Authors: M Meaney, I Fairweather, G. P. Brennan, A B Forbes
    Abstract:

    Using transmission electron microscopy (TEM), both the tegument and gut of Fasciola hepatica were examined in an effort to identify and characterise the ultrastructural changes induced following treatment with the flukicidal drug Clorsulon. Male Sprague-Dawley rats infected with F. hepatica were dosed orally at 8–8.5 weeks post-infection with Clorsulon at a concentration of 12.5 mg/kg body weight. After 24, 48 and 72 h, rats were sacrificed by cervical dislocation and mature flukes recovered from the bile ducts. After 24 h treatment in vivo, disruption of the tegumental syncytium was concentrated at the apex of the syncytium where a dark band consisting of numerous secretory bodies was present. Some blebbing of the apex had also occurred, “open” bodies were present in this region and the mitochondria were slightly swollen. In the cell bodies, swelling of the mitochondria and their cristae had also occurred and the Golgi complexes appeared to be smaller than normal. The disruption seen after 48 h treatment in vivo was similar but more severe: the frequency of blebbing had increased, as had the number of “open” bodies and the swelling of the mitochondria. Vacuoles had begun to appear in the syncytium—both autophagic and electron-lucent—and swelling of the mucopolysaccharide masses around the basal infolds had occurred. Lipid droplets were observed occasionally. In the cell bodies, autophagic vacuoles had begun to appear and swelling of the mitochondria had increased in severity. After 72 h treatment in vivo, more severe disruption was seen in the tegumental syncytium in which widespread swelling and blebbing of the apex was apparent. The basal infolds had become very badly swollen in a number of specimens and damage to the spines was evident. The mitochondria remained swollen, as did the mucopolysaccharide masses around the basal infolds. Lipid droplets were more frequently observed in the syncytium. In the tegumental cells, swelling of the mitochondria was greater and an increase in the number of autophagic vacuoles was apparent. The gut showed signs of disruption after 24 h treatment in vivo, in that the surface lamellae were disrupted and a build-up of autophagic vacuoles at the apex of the cells had taken place. Swelling of the mitochondria and the cisternae of granular endoplasmic reticulum (gER) was evident. There was a decrease in the number of secretory bodies. After 48 h treatment in vivo, the number of autophagic vacuoles in the gastrodermal cells had increased, the mitochondria and gER remained swollen and the disruption seen to the lamellae was still evident. In the 72 h-treated specimens, the disruption seen in the gastrodermal cells had increased significantly, with severe vacuolation of the apical cytoplasm. An increase in the number of autophagic vacuoles was evident, the mitochondria and the gER remained swollen and lipid droplets were present in the cells.

I Fairweather - One of the best experts on this subject based on the ideXlab platform.

  • Fasciola hepatica: ultrastructural effects of a combination of triclabendazole and Clorsulon against mature fluke
    Parasitology Research, 2007
    Co-Authors: M Meaney, A B Forbes, G. P. Brennan, J. Allister, B. Mckinstry, K. Mclaughlin, I Fairweather
    Abstract:

    A study has been carried out to investigate the ultrastructural effects of triclabendazole (TCBZ) at half-normal concentration, Clorsulon at half-normal concentration, and a combination of these two drugs against mature Fasciola hepatica. The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 μg/ml), Clorsulon (5 μg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (5 mg/kg body weight), Clorsulon (5 mg/kg body weight), or a combination of the two drugs, and flukes recovered after 48 h. Fine structural changes within the tegumental syncytium and tegumental cells were assessed by transmission electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-normal concentrations, both in vivo and in vitro; also than TCBZ.SO at normal concentration in vitro. The changes observed aid in the understanding of the gross changes to the tegumental surface described previously (Meaney M, Allister J, McKinstry B, McLaughlin K, Brennan GP, Forbes AB, Fairweather I. Parasitol Res 99:609–621, 2006 ). The results indicate that there are additive effects between TCBZ and Clorsulon and suggest that the use of drug combinations would be of value in the treatment of TCBZ-resistant fluke.

  • Fasciola hepatica: morphological effects of a combination of triclabendazole and Clorsulon against mature fluke
    Parasitology Research, 2006
    Co-Authors: M Meaney, A B Forbes, G. P. Brennan, J. Allister, B. Mckinstry, K. Mclaughlin, I Fairweather
    Abstract:

    A study has been carried out to investigate the morphological effects of half-strength triclabendazole (TCBZ), half-strength Clorsulon, and a combination of these two drugs against mature Fasciola hepatica . The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 μg/ml), Clorsulon (5 μg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (6.25 mg/kg body weight), Clorsulon (5 mg/kg body weight), or a combination of the two drugs and flukes recovered after 48 h. Surface changes to the flukes were assessed by scanning electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-strength, both in vivo and in vitro. Disruption to the tegument of the flukes induced by the individual drugs at half-strength was relatively minor and less than that caused by the drugs at full-strength. The results suggest that there are additive effects between TCBZ and Clorsulon, which may be indicative of synergy: the use of drug combinations would be of value in the treatment of triclabendazole-resistant fluke.

  • Ultrastructural observations on oral ingestion and trans-tegumental uptake of Clorsulon by the liver fluke, Fasciola hepatica
    Parasitology Research, 2005
    Co-Authors: M Meaney, G. P. Brennan, S. Haughey, I Fairweather
    Abstract:

    Three experiments have been carried out in vitro to determine the effect of oral and trans-tegumental uptake of Clorsulon on the fine structure of the tegument and gut of Fasciola hepatica. Changes were assessed by transmission electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in Clorsulon (10 μg/ml). Limited swelling of the basal infolds was observed in the tegumental syncytium. Swollen mitochondria were present in the syncytium, the underlying tegumental cells and in the gastrodermal cells. Swelling and vesiculation of the cisternae of the granular endoplasmic reticulum (ger) was evident in the gastrodermal cells, together with a reduction in secretory activity. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with Clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. There was severe swelling of the basal infolds in the tegumental syncytium and swelling of mitochondria in the syncytium, tegumental cells and gastrodermal cells. In the tegumental cells there was a decrease in the number of Golgi complexes as well. A number of changes were evident in the gastrodermal cells: swelling of the ger cisternae, an increase in the number of autophagic vacuoles, a reduction in the number of secretory bodies and disruption of the lamellae projecting from the surface of the cells. In the third experiment, flukes were incubated for 24 h in Clorsulon (10 μg/ml), with both absorptive surfaces being available for drug uptake. There was severe swelling of the basal infolds in the tegumental syncytium and large autophagic vacuoles were present. Swollen mitochondria were a feature of the tegument, tegumental cells and gastrodermal cells, as were swollen cisternae of ger in the tegumental and gastrodermal cells. Fewer Golgi complexes were observed in the tegumental cells and in the gastrodermal cells there were fewer secretory bodies and an increased number of autophagic vacuoles. Overall, the gastrodermal cells were more severely affected than the tegument. Greater disruption of the tegument occurred when the oral route of uptake was available. The results support those of previous studies which point to oral uptake of Clorsulon being the major route of entry into the fluke.

  • A scanning electron microscope study on the route of entry of Clorsulon into the liver fluke, Fasciola hepatica
    Parasitology Research, 2005
    Co-Authors: M Meaney, G. P. Brennan, S. Haughey, I Fairweather
    Abstract:

    Three experiments were carried out in vitro to determine the roles of the tegument and gut of Fasciola hepatica in the uptake of the flukicidal drug, Clorsulon. Changes to the two surfaces were assessed by scanning electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in Clorsulon (10 μg/ml). The gastrodermal surface remained normal and few changes to the tegumental surface were observed. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with Clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. The gastrodermal surface was severely disrupted and the gut lamellae were disorganised and necrotic. Swelling of the tegument and blebbing on the tegumental surface were evident, but the changes were not severe. More severe swelling of the tegument was observed in the third experiment, in which flukes were incubated for 24 h in Clorsulon (10 μg/ml), with both absorptive surfaces being available for drug uptake. The gastrodermal surface was badly disrupted and the gut lamellae were disorganised and necrotic. Taking the results of the three experiments together, the gastrodermal surface was more affected than the tegument and the greatest disruption to the two surfaces was seen when both routes of entry were available to the fluke. The data support a previous study which indicated that entry of Clorsulon into the fluke in vivo is principally by the oral ingestion of drug bound to the red blood cells.

  • Transmission electron microscope study of the ultrastructural changes induced in the tegument and gut of Fasciola hepatica following in vivo drug treatment with Clorsulon
    Parasitology Research, 2004
    Co-Authors: M Meaney, I Fairweather, G. P. Brennan, A B Forbes
    Abstract:

    Using transmission electron microscopy (TEM), both the tegument and gut of Fasciola hepatica were examined in an effort to identify and characterise the ultrastructural changes induced following treatment with the flukicidal drug Clorsulon. Male Sprague-Dawley rats infected with F. hepatica were dosed orally at 8–8.5 weeks post-infection with Clorsulon at a concentration of 12.5 mg/kg body weight. After 24, 48 and 72 h, rats were sacrificed by cervical dislocation and mature flukes recovered from the bile ducts. After 24 h treatment in vivo, disruption of the tegumental syncytium was concentrated at the apex of the syncytium where a dark band consisting of numerous secretory bodies was present. Some blebbing of the apex had also occurred, “open” bodies were present in this region and the mitochondria were slightly swollen. In the cell bodies, swelling of the mitochondria and their cristae had also occurred and the Golgi complexes appeared to be smaller than normal. The disruption seen after 48 h treatment in vivo was similar but more severe: the frequency of blebbing had increased, as had the number of “open” bodies and the swelling of the mitochondria. Vacuoles had begun to appear in the syncytium—both autophagic and electron-lucent—and swelling of the mucopolysaccharide masses around the basal infolds had occurred. Lipid droplets were observed occasionally. In the cell bodies, autophagic vacuoles had begun to appear and swelling of the mitochondria had increased in severity. After 72 h treatment in vivo, more severe disruption was seen in the tegumental syncytium in which widespread swelling and blebbing of the apex was apparent. The basal infolds had become very badly swollen in a number of specimens and damage to the spines was evident. The mitochondria remained swollen, as did the mucopolysaccharide masses around the basal infolds. Lipid droplets were more frequently observed in the syncytium. In the tegumental cells, swelling of the mitochondria was greater and an increase in the number of autophagic vacuoles was apparent. The gut showed signs of disruption after 24 h treatment in vivo, in that the surface lamellae were disrupted and a build-up of autophagic vacuoles at the apex of the cells had taken place. Swelling of the mitochondria and the cisternae of granular endoplasmic reticulum (gER) was evident. There was a decrease in the number of secretory bodies. After 48 h treatment in vivo, the number of autophagic vacuoles in the gastrodermal cells had increased, the mitochondria and gER remained swollen and the disruption seen to the lamellae was still evident. In the 72 h-treated specimens, the disruption seen in the gastrodermal cells had increased significantly, with severe vacuolation of the apical cytoplasm. An increase in the number of autophagic vacuoles was evident, the mitochondria and the gER remained swollen and lipid droplets were present in the cells.

A B Forbes - One of the best experts on this subject based on the ideXlab platform.

  • Fasciola hepatica: ultrastructural effects of a combination of triclabendazole and Clorsulon against mature fluke
    Parasitology Research, 2007
    Co-Authors: M Meaney, A B Forbes, G. P. Brennan, J. Allister, B. Mckinstry, K. Mclaughlin, I Fairweather
    Abstract:

    A study has been carried out to investigate the ultrastructural effects of triclabendazole (TCBZ) at half-normal concentration, Clorsulon at half-normal concentration, and a combination of these two drugs against mature Fasciola hepatica. The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 μg/ml), Clorsulon (5 μg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (5 mg/kg body weight), Clorsulon (5 mg/kg body weight), or a combination of the two drugs, and flukes recovered after 48 h. Fine structural changes within the tegumental syncytium and tegumental cells were assessed by transmission electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-normal concentrations, both in vivo and in vitro; also than TCBZ.SO at normal concentration in vitro. The changes observed aid in the understanding of the gross changes to the tegumental surface described previously (Meaney M, Allister J, McKinstry B, McLaughlin K, Brennan GP, Forbes AB, Fairweather I. Parasitol Res 99:609–621, 2006 ). The results indicate that there are additive effects between TCBZ and Clorsulon and suggest that the use of drug combinations would be of value in the treatment of TCBZ-resistant fluke.

  • Fasciola hepatica: morphological effects of a combination of triclabendazole and Clorsulon against mature fluke
    Parasitology Research, 2006
    Co-Authors: M Meaney, A B Forbes, G. P. Brennan, J. Allister, B. Mckinstry, K. Mclaughlin, I Fairweather
    Abstract:

    A study has been carried out to investigate the morphological effects of half-strength triclabendazole (TCBZ), half-strength Clorsulon, and a combination of these two drugs against mature Fasciola hepatica . The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 μg/ml), Clorsulon (5 μg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (6.25 mg/kg body weight), Clorsulon (5 mg/kg body weight), or a combination of the two drugs and flukes recovered after 48 h. Surface changes to the flukes were assessed by scanning electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-strength, both in vivo and in vitro. Disruption to the tegument of the flukes induced by the individual drugs at half-strength was relatively minor and less than that caused by the drugs at full-strength. The results suggest that there are additive effects between TCBZ and Clorsulon, which may be indicative of synergy: the use of drug combinations would be of value in the treatment of triclabendazole-resistant fluke.

  • Transmission electron microscope study of the ultrastructural changes induced in the tegument and gut of Fasciola hepatica following in vivo drug treatment with Clorsulon
    Parasitology Research, 2004
    Co-Authors: M Meaney, I Fairweather, G. P. Brennan, A B Forbes
    Abstract:

    Using transmission electron microscopy (TEM), both the tegument and gut of Fasciola hepatica were examined in an effort to identify and characterise the ultrastructural changes induced following treatment with the flukicidal drug Clorsulon. Male Sprague-Dawley rats infected with F. hepatica were dosed orally at 8–8.5 weeks post-infection with Clorsulon at a concentration of 12.5 mg/kg body weight. After 24, 48 and 72 h, rats were sacrificed by cervical dislocation and mature flukes recovered from the bile ducts. After 24 h treatment in vivo, disruption of the tegumental syncytium was concentrated at the apex of the syncytium where a dark band consisting of numerous secretory bodies was present. Some blebbing of the apex had also occurred, “open” bodies were present in this region and the mitochondria were slightly swollen. In the cell bodies, swelling of the mitochondria and their cristae had also occurred and the Golgi complexes appeared to be smaller than normal. The disruption seen after 48 h treatment in vivo was similar but more severe: the frequency of blebbing had increased, as had the number of “open” bodies and the swelling of the mitochondria. Vacuoles had begun to appear in the syncytium—both autophagic and electron-lucent—and swelling of the mucopolysaccharide masses around the basal infolds had occurred. Lipid droplets were observed occasionally. In the cell bodies, autophagic vacuoles had begun to appear and swelling of the mitochondria had increased in severity. After 72 h treatment in vivo, more severe disruption was seen in the tegumental syncytium in which widespread swelling and blebbing of the apex was apparent. The basal infolds had become very badly swollen in a number of specimens and damage to the spines was evident. The mitochondria remained swollen, as did the mucopolysaccharide masses around the basal infolds. Lipid droplets were more frequently observed in the syncytium. In the tegumental cells, swelling of the mitochondria was greater and an increase in the number of autophagic vacuoles was apparent. The gut showed signs of disruption after 24 h treatment in vivo, in that the surface lamellae were disrupted and a build-up of autophagic vacuoles at the apex of the cells had taken place. Swelling of the mitochondria and the cisternae of granular endoplasmic reticulum (gER) was evident. There was a decrease in the number of secretory bodies. After 48 h treatment in vivo, the number of autophagic vacuoles in the gastrodermal cells had increased, the mitochondria and gER remained swollen and the disruption seen to the lamellae was still evident. In the 72 h-treated specimens, the disruption seen in the gastrodermal cells had increased significantly, with severe vacuolation of the apical cytoplasm. An increase in the number of autophagic vacuoles was evident, the mitochondria and the gER remained swollen and lipid droplets were present in the cells.

  • Fasciola hepatica: effects of the fasciolicide Clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes
    Parasitology Research, 2003
    Co-Authors: M Meaney, I Fairweather, L S L Mcdowell, G. P. Brennan, A B Forbes
    Abstract:

    The ultrastructural changes in Fasciola hepatica induced by the fasciolicide Clorsulon were assessed using scanning electron microscopy. At 8 and 44 weeks post-infection, male Sprague-Dawley rats infected with F. hepatica were dosed orally with Clorsulon at a concentration of 12.5 mg/kg and mature flukes recovered from the bile duct after 24 h, 48 h, and 72 h in both experiments. An in vitro incubation was also set up using mature fluke (8 weeks old) incubated with Clorsulon for 24 h at a concentration of 10 μg/ml. After 24 h in vivo, the young-mature flukes (8 weeks old) showed significant disruption to the tegumental surface, particularly in the anterior mid-body region, where a distinct band of swelling and blebbing was evident. The band began just behind the ventral sucker and ran posteriorly along both margins. The apical cone region of the fluke was characterised by swelling and blebbing of the surface between the spines. Similar changes were evident after 48 h in vivo, but the disruption was more severe and the mid-body band had spread posteriorly. In approximately half of the specimens recovered after 72 h in vivo, widespread disruption had occurred, with sloughing of the apical membrane or the entire syncytium, over almost all of the oral cone and anterior mid-body. For all time periods, the anterior half of the fluke was more severely affected than the posterior half. No differences were seen between the dorsal and ventral surfaces. Old-mature flukes (44 weeks old) showed regionally similar, but more severe and widespread disruption than that seen in the young-mature flukes. The onset of surface changes occurred more quickly in old-mature flukes as well. Eight-week-old flukes which had been incubated for 24 h in vitro showed surprisingly little disruption, but this may be due to the method by which the drug is taken up by the fluke.

  • fasciola hepatica effects of the fasciolicide Clorsulon in vitro and in vivo on the tegumental surface and a comparison of the effects on young and old mature flukes
    Parasitology Research, 2003
    Co-Authors: M Meaney, Ian Fairweather, Gerard Brennan, L S L Mcdowell, A B Forbes
    Abstract:

    The ultrastructural changes in Fasciola hepatica induced by the fasciolicide Clorsulon were assessed using scanning electron microscopy. At 8 and 44 weeks post-infection, male Sprague-Dawley rats infected with F. hepatica were dosed orally with Clorsulon at a concentration of 12.5 mg/kg and mature flukes recovered from the bile duct after 24 h, 48 h, and 72 h in both experiments. An in vitro incubation was also set up using mature fluke (8 weeks old) incubated with Clorsulon for 24 h at a concentration of 10 μg/ml.

G. P. Brennan - One of the best experts on this subject based on the ideXlab platform.

  • Fasciola hepatica: ultrastructural effects of a combination of triclabendazole and Clorsulon against mature fluke
    Parasitology Research, 2007
    Co-Authors: M Meaney, A B Forbes, G. P. Brennan, J. Allister, B. Mckinstry, K. Mclaughlin, I Fairweather
    Abstract:

    A study has been carried out to investigate the ultrastructural effects of triclabendazole (TCBZ) at half-normal concentration, Clorsulon at half-normal concentration, and a combination of these two drugs against mature Fasciola hepatica. The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 μg/ml), Clorsulon (5 μg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (5 mg/kg body weight), Clorsulon (5 mg/kg body weight), or a combination of the two drugs, and flukes recovered after 48 h. Fine structural changes within the tegumental syncytium and tegumental cells were assessed by transmission electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-normal concentrations, both in vivo and in vitro; also than TCBZ.SO at normal concentration in vitro. The changes observed aid in the understanding of the gross changes to the tegumental surface described previously (Meaney M, Allister J, McKinstry B, McLaughlin K, Brennan GP, Forbes AB, Fairweather I. Parasitol Res 99:609–621, 2006 ). The results indicate that there are additive effects between TCBZ and Clorsulon and suggest that the use of drug combinations would be of value in the treatment of TCBZ-resistant fluke.

  • Fasciola hepatica: morphological effects of a combination of triclabendazole and Clorsulon against mature fluke
    Parasitology Research, 2006
    Co-Authors: M Meaney, A B Forbes, G. P. Brennan, J. Allister, B. Mckinstry, K. Mclaughlin, I Fairweather
    Abstract:

    A study has been carried out to investigate the morphological effects of half-strength triclabendazole (TCBZ), half-strength Clorsulon, and a combination of these two drugs against mature Fasciola hepatica . The Cullompton TCBZ-susceptible isolate was used for these experiments. Flukes were incubated for 24 h in vitro in TCBZ sulphoxide (7.5 μg/ml), Clorsulon (5 μg/ml), or a combination of the two drugs. For the in vivo experiment, rats were dosed with TCBZ (6.25 mg/kg body weight), Clorsulon (5 mg/kg body weight), or a combination of the two drugs and flukes recovered after 48 h. Surface changes to the flukes were assessed by scanning electron microscopy. Treatment with the combination of drugs produced greater disruption to the flukes than the individual drugs at half-strength, both in vivo and in vitro. Disruption to the tegument of the flukes induced by the individual drugs at half-strength was relatively minor and less than that caused by the drugs at full-strength. The results suggest that there are additive effects between TCBZ and Clorsulon, which may be indicative of synergy: the use of drug combinations would be of value in the treatment of triclabendazole-resistant fluke.

  • Ultrastructural observations on oral ingestion and trans-tegumental uptake of Clorsulon by the liver fluke, Fasciola hepatica
    Parasitology Research, 2005
    Co-Authors: M Meaney, G. P. Brennan, S. Haughey, I Fairweather
    Abstract:

    Three experiments have been carried out in vitro to determine the effect of oral and trans-tegumental uptake of Clorsulon on the fine structure of the tegument and gut of Fasciola hepatica. Changes were assessed by transmission electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in Clorsulon (10 μg/ml). Limited swelling of the basal infolds was observed in the tegumental syncytium. Swollen mitochondria were present in the syncytium, the underlying tegumental cells and in the gastrodermal cells. Swelling and vesiculation of the cisternae of the granular endoplasmic reticulum (ger) was evident in the gastrodermal cells, together with a reduction in secretory activity. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with Clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. There was severe swelling of the basal infolds in the tegumental syncytium and swelling of mitochondria in the syncytium, tegumental cells and gastrodermal cells. In the tegumental cells there was a decrease in the number of Golgi complexes as well. A number of changes were evident in the gastrodermal cells: swelling of the ger cisternae, an increase in the number of autophagic vacuoles, a reduction in the number of secretory bodies and disruption of the lamellae projecting from the surface of the cells. In the third experiment, flukes were incubated for 24 h in Clorsulon (10 μg/ml), with both absorptive surfaces being available for drug uptake. There was severe swelling of the basal infolds in the tegumental syncytium and large autophagic vacuoles were present. Swollen mitochondria were a feature of the tegument, tegumental cells and gastrodermal cells, as were swollen cisternae of ger in the tegumental and gastrodermal cells. Fewer Golgi complexes were observed in the tegumental cells and in the gastrodermal cells there were fewer secretory bodies and an increased number of autophagic vacuoles. Overall, the gastrodermal cells were more severely affected than the tegument. Greater disruption of the tegument occurred when the oral route of uptake was available. The results support those of previous studies which point to oral uptake of Clorsulon being the major route of entry into the fluke.

  • A scanning electron microscope study on the route of entry of Clorsulon into the liver fluke, Fasciola hepatica
    Parasitology Research, 2005
    Co-Authors: M Meaney, G. P. Brennan, S. Haughey, I Fairweather
    Abstract:

    Three experiments were carried out in vitro to determine the roles of the tegument and gut of Fasciola hepatica in the uptake of the flukicidal drug, Clorsulon. Changes to the two surfaces were assessed by scanning electron microscopy. In the first experiment, the flukes were ligatured to prevent the oral ingestion of drug and treated for 24 h in Clorsulon (10 μg/ml). The gastrodermal surface remained normal and few changes to the tegumental surface were observed. In the second experiment, flukes were fed for 24 h on red blood cells isolated from rats dosed with Clorsulon at 12.5 mg/kg body weight; this experiment was designed to prevent the exposure of the tegumental surface to the drug. The gastrodermal surface was severely disrupted and the gut lamellae were disorganised and necrotic. Swelling of the tegument and blebbing on the tegumental surface were evident, but the changes were not severe. More severe swelling of the tegument was observed in the third experiment, in which flukes were incubated for 24 h in Clorsulon (10 μg/ml), with both absorptive surfaces being available for drug uptake. The gastrodermal surface was badly disrupted and the gut lamellae were disorganised and necrotic. Taking the results of the three experiments together, the gastrodermal surface was more affected than the tegument and the greatest disruption to the two surfaces was seen when both routes of entry were available to the fluke. The data support a previous study which indicated that entry of Clorsulon into the fluke in vivo is principally by the oral ingestion of drug bound to the red blood cells.

  • Transmission electron microscope study of the ultrastructural changes induced in the tegument and gut of Fasciola hepatica following in vivo drug treatment with Clorsulon
    Parasitology Research, 2004
    Co-Authors: M Meaney, I Fairweather, G. P. Brennan, A B Forbes
    Abstract:

    Using transmission electron microscopy (TEM), both the tegument and gut of Fasciola hepatica were examined in an effort to identify and characterise the ultrastructural changes induced following treatment with the flukicidal drug Clorsulon. Male Sprague-Dawley rats infected with F. hepatica were dosed orally at 8–8.5 weeks post-infection with Clorsulon at a concentration of 12.5 mg/kg body weight. After 24, 48 and 72 h, rats were sacrificed by cervical dislocation and mature flukes recovered from the bile ducts. After 24 h treatment in vivo, disruption of the tegumental syncytium was concentrated at the apex of the syncytium where a dark band consisting of numerous secretory bodies was present. Some blebbing of the apex had also occurred, “open” bodies were present in this region and the mitochondria were slightly swollen. In the cell bodies, swelling of the mitochondria and their cristae had also occurred and the Golgi complexes appeared to be smaller than normal. The disruption seen after 48 h treatment in vivo was similar but more severe: the frequency of blebbing had increased, as had the number of “open” bodies and the swelling of the mitochondria. Vacuoles had begun to appear in the syncytium—both autophagic and electron-lucent—and swelling of the mucopolysaccharide masses around the basal infolds had occurred. Lipid droplets were observed occasionally. In the cell bodies, autophagic vacuoles had begun to appear and swelling of the mitochondria had increased in severity. After 72 h treatment in vivo, more severe disruption was seen in the tegumental syncytium in which widespread swelling and blebbing of the apex was apparent. The basal infolds had become very badly swollen in a number of specimens and damage to the spines was evident. The mitochondria remained swollen, as did the mucopolysaccharide masses around the basal infolds. Lipid droplets were more frequently observed in the syncytium. In the tegumental cells, swelling of the mitochondria was greater and an increase in the number of autophagic vacuoles was apparent. The gut showed signs of disruption after 24 h treatment in vivo, in that the surface lamellae were disrupted and a build-up of autophagic vacuoles at the apex of the cells had taken place. Swelling of the mitochondria and the cisternae of granular endoplasmic reticulum (gER) was evident. There was a decrease in the number of secretory bodies. After 48 h treatment in vivo, the number of autophagic vacuoles in the gastrodermal cells had increased, the mitochondria and gER remained swollen and the disruption seen to the lamellae was still evident. In the 72 h-treated specimens, the disruption seen in the gastrodermal cells had increased significantly, with severe vacuolation of the apical cytoplasm. An increase in the number of autophagic vacuoles was evident, the mitochondria and the gER remained swollen and lipid droplets were present in the cells.

L S L Mcdowell - One of the best experts on this subject based on the ideXlab platform.

  • Fasciola hepatica: effects of the fasciolicide Clorsulon in vitro and in vivo on the tegumental surface, and a comparison of the effects on young- and old-mature flukes
    Parasitology Research, 2003
    Co-Authors: M Meaney, I Fairweather, L S L Mcdowell, G. P. Brennan, A B Forbes
    Abstract:

    The ultrastructural changes in Fasciola hepatica induced by the fasciolicide Clorsulon were assessed using scanning electron microscopy. At 8 and 44 weeks post-infection, male Sprague-Dawley rats infected with F. hepatica were dosed orally with Clorsulon at a concentration of 12.5 mg/kg and mature flukes recovered from the bile duct after 24 h, 48 h, and 72 h in both experiments. An in vitro incubation was also set up using mature fluke (8 weeks old) incubated with Clorsulon for 24 h at a concentration of 10 μg/ml. After 24 h in vivo, the young-mature flukes (8 weeks old) showed significant disruption to the tegumental surface, particularly in the anterior mid-body region, where a distinct band of swelling and blebbing was evident. The band began just behind the ventral sucker and ran posteriorly along both margins. The apical cone region of the fluke was characterised by swelling and blebbing of the surface between the spines. Similar changes were evident after 48 h in vivo, but the disruption was more severe and the mid-body band had spread posteriorly. In approximately half of the specimens recovered after 72 h in vivo, widespread disruption had occurred, with sloughing of the apical membrane or the entire syncytium, over almost all of the oral cone and anterior mid-body. For all time periods, the anterior half of the fluke was more severely affected than the posterior half. No differences were seen between the dorsal and ventral surfaces. Old-mature flukes (44 weeks old) showed regionally similar, but more severe and widespread disruption than that seen in the young-mature flukes. The onset of surface changes occurred more quickly in old-mature flukes as well. Eight-week-old flukes which had been incubated for 24 h in vitro showed surprisingly little disruption, but this may be due to the method by which the drug is taken up by the fluke.

  • fasciola hepatica effects of the fasciolicide Clorsulon in vitro and in vivo on the tegumental surface and a comparison of the effects on young and old mature flukes
    Parasitology Research, 2003
    Co-Authors: M Meaney, Ian Fairweather, Gerard Brennan, L S L Mcdowell, A B Forbes
    Abstract:

    The ultrastructural changes in Fasciola hepatica induced by the fasciolicide Clorsulon were assessed using scanning electron microscopy. At 8 and 44 weeks post-infection, male Sprague-Dawley rats infected with F. hepatica were dosed orally with Clorsulon at a concentration of 12.5 mg/kg and mature flukes recovered from the bile duct after 24 h, 48 h, and 72 h in both experiments. An in vitro incubation was also set up using mature fluke (8 weeks old) incubated with Clorsulon for 24 h at a concentration of 10 μg/ml.