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Alan W Stitt - One of the best experts on this subject based on the ideXlab platform.
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prevention of retinal Capillary Basement Membrane thickening in diabetic dogs by a non steroidal anti inflammatory drug
Diabetologia, 2003Co-Authors: T A Gardiner, Heather Anderson, D B Archer, Thorsten P Degenhardt, Suzanne R Thorpe, John W Baynes, Alan W StittAbstract:To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology. Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status. Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p≤0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p≤0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal Capillary Basement Membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p≤0.0001). This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.
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inhibition of advanced glycation end products protects against retinal Capillary Basement Membrane expansion during long term diabetes
The Journal of Pathology, 2003Co-Authors: T A Gardiner, Heather Anderson, Alan W StittAbstract:The purpose of this study was to investigate the advanced glycation end-product (AGE)-inhibitory properties of aminoguanidine and to determine whether treatment in long-term diabetic rats can prevent Basement Membrane lesions of diabetic retinopathy. Four groups of male Wistar rats were studied: untreated diabetics injected with 45 mg/kg streptozotocin, aminoguanidine-treated diabetics, untreated controls, and aminoguanidine-treated controls. After 12 months' diabetes, the retinas from six animals were processed for electron microscopy or the retinal microvasculature was isolated using the trypsin digest technique. Stereological analysis was used to estimate quantitative ultrastructural changes in the retinal Capillary-associated Basement Membrane. Serum AGEs were quantified by competitive AGE-ELISA, while microvascular-associated, immunoreactive AGEs were analysed on retinal trypsin digests. Aminoguanidine significantly reduced serum AGEs in the diabetic group (p < 0.001). In the retinal capillaries, there was a marked reduction in AGE immunoreactivity in the aminoguanidine-treated diabetics when compared with untreated diabetics. The surface area and absolute volume of the retinal Capillary Basement Membrane were significantly increased in the diabetic rats when compared with non-diabetic controls (p < 0.001 and p < 0.001, respectively). Aminoguanidine treatment of diabetic rats protected against Basement Membrane expansion when compared with untreated diabetic counterparts. Aminoguanidine treatment prevents the development of diabetes-induced Basement Membrane expansion in retinal capillaries. The AGE inhibition properties of aminoguanidine suggest that AGEs play an important role in the complex pathogenesis of Basement Membrane thickening during diabetic retinopathy. Copyright © 2003 John Wiley & Sons, Ltd.
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inhibition of advanced glycation end products protects against retinal Capillary Basement Membrane expansion during long term diabetes
The Journal of Pathology, 2003Co-Authors: T A Gardiner, Heather A Anderson, Alan W StittAbstract:The purpose of this study was to investigate the advanced glycation end-product (AGE)-inhibitory properties of aminoguanidine and to determine whether treatment in long-term diabetic rats can prevent Basement Membrane lesions of diabetic retinopathy. Four groups of male Wistar rats were studied: untreated diabetics injected with 45 mg/kg streptozotocin, aminoguanidine-treated diabetics, untreated controls, and aminoguanidine-treated controls. After 12 months' diabetes, the retinas from six animals were processed for electron microscopy or the retinal microvasculature was isolated using the trypsin digest technique. Stereological analysis was used to estimate quantitative ultrastructural changes in the retinal Capillary-associated Basement Membrane. Serum AGEs were quantified by competitive AGE-ELISA, while microvascular-associated, immunoreactive AGEs were analysed on retinal trypsin digests. Aminoguanidine significantly reduced serum AGEs in the diabetic group (p < 0.001). In the retinal capillaries, there was a marked reduction in AGE immunoreactivity in the aminoguanidine-treated diabetics when compared with untreated diabetics. The surface area and absolute volume of the retinal Capillary Basement Membrane were significantly increased in the diabetic rats when compared with non-diabetic controls (p < 0.001 and p < 0.001, respectively). Aminoguanidine treatment of diabetic rats protected against Basement Membrane expansion when compared with untreated diabetic counterparts. Aminoguanidine treatment prevents the development of diabetes-induced Basement Membrane expansion in retinal capillaries. The AGE inhibition properties of aminoguanidine suggest that AGEs play an important role in the complex pathogenesis of Basement Membrane thickening during diabetic retinopathy.
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estimation of the surface area and volume of the retinal Capillary Basement Membrane using the stereologic method of vertical sections
Analytical and Quantitative Cytology and Histology, 1994Co-Authors: Heather A Anderson, T A Gardiner, Alan W Stitt, D B ArcherAbstract:The modern stereologic method of vertical sections was applied to the retina as a means of generating unbiased estimates of three-dimensional structure. The method is illustrated with real data on the volume and surface area of the Capillary Basement Membrane from the central retina of the rat. Novel methods of estimating the volume of retina sampled and of creating accurate vertical sections are described. The advantages of using stereologic methods to generate quantitative information on the three-dimensional structure of the retina are discussed and compared to those of previous quantitative methods that provide data on two-dimensional structure only.
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diabetic retinopathy quantitative variation in Capillary Basement Membrane thickening in arterial or venous environments
British Journal of Ophthalmology, 1994Co-Authors: Alan W Stitt, T A Gardiner, Heather Anderson, D B ArcherAbstract:Diabetes mellitus was induced in male beagles by a single injection of an alloxan and streptozotocin cocktail and fasting blood sugar levels maintained between 15 and 20 mmol/l. Five years after induction of diabetes, three diabetic animals were sacrificed, together with sex and age-matched controls, and the retinas fixed for either transmission electron microscopy (TEM) or trypsin digestion. In TEM specimens, capillaries in close proximity to the major vessels were designated as either AE (arterial environment) or VE (venous environment) and the thickness of their Basement Membranes (BMs) measured using an image analyser based two dimensional morphometric analysis system. Results show that the BMs of retinal capillaries from the diabetic dogs were significantly thicker than those from control dogs. Furthermore, within the diabetic group the AE capillaries had thicker BMs than VE capillaries (p < or = 0.05). The controls, however, showed no significant difference in BM thickness between AE and VE capillaries. Although many of the capillaries designated as AE or VE would actually have been derived from the opposite side of the circulation, with respect to BM thickness, they conformed to values of their specific group. The conclusion is that diabetic capillaries are more vulnerable to BM thickening in an arterial environment than in a venous environment.
Diana Maria Lopategui - One of the best experts on this subject based on the ideXlab platform.
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rethinking peritubular Capillary Basement Membrane multilayering in renal transplant pathology a case report
Pediatric Nephrology, 2017Co-Authors: Rita Van Dammelombaerts, Diana Maria Lopategui, Elena Levtchenko, Evelyne Lerut, Maarten Naesens, Noel KnopsAbstract:Background Severe multilayering (ML) of the peritubular Capillary Basement Membranes in kidney allografts is considered to be an ultrastructural hallmark of chronic antibody-mediated rejection (CAMR). We describe here the unexpected findings in a young male adolescent with underlying focal segmental glomerulosclerosis who underwent a living-related donor transplant procedure, a case which brought into question the specificity of ML.
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rethinking peritubular Capillary Basement Membrane multilayering in renal transplant pathology a case report
Pediatric Nephrology, 2017Co-Authors: Diana Maria Lopategui, Elena Levtchenko, Evelyne Lerut, Maarten Naesens, Rita Van Dammelombaerts, Noel KnopsAbstract:Severe multilayering (ML) of the peritubular Capillary Basement Membranes in kidney allografts is considered to be an ultrastructural hallmark of chronic antibody-mediated rejection (CAMR). We describe here the unexpected findings in a young male adolescent with underlying focal segmental glomerulosclerosis who underwent a living-related donor transplant procedure, a case which brought into question the specificity of ML. The patient received a kidney from his mother, whose donor screening was unremarkable. He developed nephrotic-range proteinuria shortly after the procedure. Biopsies performed within the first 6 months after transplantation demonstrated ML (5–6 layers). Since there were no other criteria for CAMR, electron microscopic analysis of the baseline biopsy was performed, which in retrospect also demonstrated ML. The donor is still asymptomatic after 7 years of follow-up, with normal renal function and no proteinuria. We discuss the phenomenon of ML in renal disease and together with the findings in our case would like to draw attention to the fact that ML in the setting of renal transplantation is not specific to CAMR, as it can exist in several kidney diseases and even in asymptomatic donors.
T A Gardiner - One of the best experts on this subject based on the ideXlab platform.
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prevention of retinal Capillary Basement Membrane thickening in diabetic dogs by a non steroidal anti inflammatory drug
Diabetologia, 2003Co-Authors: T A Gardiner, Heather Anderson, D B Archer, Thorsten P Degenhardt, Suzanne R Thorpe, John W Baynes, Alan W StittAbstract:To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology. Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status. Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p≤0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p≤0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal Capillary Basement Membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p≤0.0001). This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.
-
inhibition of advanced glycation end products protects against retinal Capillary Basement Membrane expansion during long term diabetes
The Journal of Pathology, 2003Co-Authors: T A Gardiner, Heather Anderson, Alan W StittAbstract:The purpose of this study was to investigate the advanced glycation end-product (AGE)-inhibitory properties of aminoguanidine and to determine whether treatment in long-term diabetic rats can prevent Basement Membrane lesions of diabetic retinopathy. Four groups of male Wistar rats were studied: untreated diabetics injected with 45 mg/kg streptozotocin, aminoguanidine-treated diabetics, untreated controls, and aminoguanidine-treated controls. After 12 months' diabetes, the retinas from six animals were processed for electron microscopy or the retinal microvasculature was isolated using the trypsin digest technique. Stereological analysis was used to estimate quantitative ultrastructural changes in the retinal Capillary-associated Basement Membrane. Serum AGEs were quantified by competitive AGE-ELISA, while microvascular-associated, immunoreactive AGEs were analysed on retinal trypsin digests. Aminoguanidine significantly reduced serum AGEs in the diabetic group (p < 0.001). In the retinal capillaries, there was a marked reduction in AGE immunoreactivity in the aminoguanidine-treated diabetics when compared with untreated diabetics. The surface area and absolute volume of the retinal Capillary Basement Membrane were significantly increased in the diabetic rats when compared with non-diabetic controls (p < 0.001 and p < 0.001, respectively). Aminoguanidine treatment of diabetic rats protected against Basement Membrane expansion when compared with untreated diabetic counterparts. Aminoguanidine treatment prevents the development of diabetes-induced Basement Membrane expansion in retinal capillaries. The AGE inhibition properties of aminoguanidine suggest that AGEs play an important role in the complex pathogenesis of Basement Membrane thickening during diabetic retinopathy. Copyright © 2003 John Wiley & Sons, Ltd.
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inhibition of advanced glycation end products protects against retinal Capillary Basement Membrane expansion during long term diabetes
The Journal of Pathology, 2003Co-Authors: T A Gardiner, Heather A Anderson, Alan W StittAbstract:The purpose of this study was to investigate the advanced glycation end-product (AGE)-inhibitory properties of aminoguanidine and to determine whether treatment in long-term diabetic rats can prevent Basement Membrane lesions of diabetic retinopathy. Four groups of male Wistar rats were studied: untreated diabetics injected with 45 mg/kg streptozotocin, aminoguanidine-treated diabetics, untreated controls, and aminoguanidine-treated controls. After 12 months' diabetes, the retinas from six animals were processed for electron microscopy or the retinal microvasculature was isolated using the trypsin digest technique. Stereological analysis was used to estimate quantitative ultrastructural changes in the retinal Capillary-associated Basement Membrane. Serum AGEs were quantified by competitive AGE-ELISA, while microvascular-associated, immunoreactive AGEs were analysed on retinal trypsin digests. Aminoguanidine significantly reduced serum AGEs in the diabetic group (p < 0.001). In the retinal capillaries, there was a marked reduction in AGE immunoreactivity in the aminoguanidine-treated diabetics when compared with untreated diabetics. The surface area and absolute volume of the retinal Capillary Basement Membrane were significantly increased in the diabetic rats when compared with non-diabetic controls (p < 0.001 and p < 0.001, respectively). Aminoguanidine treatment of diabetic rats protected against Basement Membrane expansion when compared with untreated diabetic counterparts. Aminoguanidine treatment prevents the development of diabetes-induced Basement Membrane expansion in retinal capillaries. The AGE inhibition properties of aminoguanidine suggest that AGEs play an important role in the complex pathogenesis of Basement Membrane thickening during diabetic retinopathy.
-
estimation of the surface area and volume of the retinal Capillary Basement Membrane using the stereologic method of vertical sections
Analytical and Quantitative Cytology and Histology, 1994Co-Authors: Heather A Anderson, T A Gardiner, Alan W Stitt, D B ArcherAbstract:The modern stereologic method of vertical sections was applied to the retina as a means of generating unbiased estimates of three-dimensional structure. The method is illustrated with real data on the volume and surface area of the Capillary Basement Membrane from the central retina of the rat. Novel methods of estimating the volume of retina sampled and of creating accurate vertical sections are described. The advantages of using stereologic methods to generate quantitative information on the three-dimensional structure of the retina are discussed and compared to those of previous quantitative methods that provide data on two-dimensional structure only.
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diabetic retinopathy quantitative variation in Capillary Basement Membrane thickening in arterial or venous environments
British Journal of Ophthalmology, 1994Co-Authors: Alan W Stitt, T A Gardiner, Heather Anderson, D B ArcherAbstract:Diabetes mellitus was induced in male beagles by a single injection of an alloxan and streptozotocin cocktail and fasting blood sugar levels maintained between 15 and 20 mmol/l. Five years after induction of diabetes, three diabetic animals were sacrificed, together with sex and age-matched controls, and the retinas fixed for either transmission electron microscopy (TEM) or trypsin digestion. In TEM specimens, capillaries in close proximity to the major vessels were designated as either AE (arterial environment) or VE (venous environment) and the thickness of their Basement Membranes (BMs) measured using an image analyser based two dimensional morphometric analysis system. Results show that the BMs of retinal capillaries from the diabetic dogs were significantly thicker than those from control dogs. Furthermore, within the diabetic group the AE capillaries had thicker BMs than VE capillaries (p < or = 0.05). The controls, however, showed no significant difference in BM thickness between AE and VE capillaries. Although many of the capillaries designated as AE or VE would actually have been derived from the opposite side of the circulation, with respect to BM thickness, they conformed to values of their specific group. The conclusion is that diabetic capillaries are more vulnerable to BM thickening in an arterial environment than in a venous environment.
Noel Knops - One of the best experts on this subject based on the ideXlab platform.
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rethinking peritubular Capillary Basement Membrane multilayering in renal transplant pathology a case report
Pediatric Nephrology, 2017Co-Authors: Rita Van Dammelombaerts, Diana Maria Lopategui, Elena Levtchenko, Evelyne Lerut, Maarten Naesens, Noel KnopsAbstract:Background Severe multilayering (ML) of the peritubular Capillary Basement Membranes in kidney allografts is considered to be an ultrastructural hallmark of chronic antibody-mediated rejection (CAMR). We describe here the unexpected findings in a young male adolescent with underlying focal segmental glomerulosclerosis who underwent a living-related donor transplant procedure, a case which brought into question the specificity of ML.
-
rethinking peritubular Capillary Basement Membrane multilayering in renal transplant pathology a case report
Pediatric Nephrology, 2017Co-Authors: Diana Maria Lopategui, Elena Levtchenko, Evelyne Lerut, Maarten Naesens, Rita Van Dammelombaerts, Noel KnopsAbstract:Severe multilayering (ML) of the peritubular Capillary Basement Membranes in kidney allografts is considered to be an ultrastructural hallmark of chronic antibody-mediated rejection (CAMR). We describe here the unexpected findings in a young male adolescent with underlying focal segmental glomerulosclerosis who underwent a living-related donor transplant procedure, a case which brought into question the specificity of ML. The patient received a kidney from his mother, whose donor screening was unremarkable. He developed nephrotic-range proteinuria shortly after the procedure. Biopsies performed within the first 6 months after transplantation demonstrated ML (5–6 layers). Since there were no other criteria for CAMR, electron microscopic analysis of the baseline biopsy was performed, which in retrospect also demonstrated ML. The donor is still asymptomatic after 7 years of follow-up, with normal renal function and no proteinuria. We discuss the phenomenon of ML in renal disease and together with the findings in our case would like to draw attention to the fact that ML in the setting of renal transplantation is not specific to CAMR, as it can exist in several kidney diseases and even in asymptomatic donors.
Heather Anderson - One of the best experts on this subject based on the ideXlab platform.
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prevention of retinal Capillary Basement Membrane thickening in diabetic dogs by a non steroidal anti inflammatory drug
Diabetologia, 2003Co-Authors: T A Gardiner, Heather Anderson, D B Archer, Thorsten P Degenhardt, Suzanne R Thorpe, John W Baynes, Alan W StittAbstract:To investigate the effect of treatment with the non-steroidal anti-inflammatory drug Sulindac on the early vascular pathology of diabetic retinopathy in the dog, and it's effect on recognised biochemical indices of hyperglycaemia-related pathophysiology. Experimental diabetes (streptozotocin/alloxan) was induced in 22 male beagle dogs and 12 of the animals were assigned at random to receive oral Sulindac (10 mg/kg daily). Age- and sex-matched control animals were maintained as non-diabetic controls. After 4 years, several morphological parameters were quantified in the retinal microvasculature of each animal group using an established stereological method. Also, the following diabetes-associated biochemical parameters were analysed: accumulation of advanced glycation end products (AGEs), red blood cell polyol levels and antioxidant status. Diabetes increased red blood cell sorbitol levels when compared to non-diabetic controls (p≤0.05), however, there was no difference in sorbitol levels between the untreated and the treated diabetic animals. No significant differences were found in red blood cell myoinositol levels between the three groups of animals. Pentosidine and other AGEs were increased two- to three-fold in the diabetic animals (p≤0.001) although treatment with Sulindac did not affect their accumulation in diabetic skin collagen or alter diabetes-induced rises in plasma malondialdehyde. Retinal Capillary Basement Membrane volume was significantly increased in the untreated diabetic dogs compared to non-diabetic controls or Sulindac-treated diabetic animals (p≤0.0001). This study has confirmed the beneficial effect of a non-steroidal anti-inflammatory drug on the early vascular pathology of diabetic retinopathy. However the treatment benefit was not dependent on inhibition of polyol pathway activity, advanced glycation, or oxidative stress.
-
inhibition of advanced glycation end products protects against retinal Capillary Basement Membrane expansion during long term diabetes
The Journal of Pathology, 2003Co-Authors: T A Gardiner, Heather Anderson, Alan W StittAbstract:The purpose of this study was to investigate the advanced glycation end-product (AGE)-inhibitory properties of aminoguanidine and to determine whether treatment in long-term diabetic rats can prevent Basement Membrane lesions of diabetic retinopathy. Four groups of male Wistar rats were studied: untreated diabetics injected with 45 mg/kg streptozotocin, aminoguanidine-treated diabetics, untreated controls, and aminoguanidine-treated controls. After 12 months' diabetes, the retinas from six animals were processed for electron microscopy or the retinal microvasculature was isolated using the trypsin digest technique. Stereological analysis was used to estimate quantitative ultrastructural changes in the retinal Capillary-associated Basement Membrane. Serum AGEs were quantified by competitive AGE-ELISA, while microvascular-associated, immunoreactive AGEs were analysed on retinal trypsin digests. Aminoguanidine significantly reduced serum AGEs in the diabetic group (p < 0.001). In the retinal capillaries, there was a marked reduction in AGE immunoreactivity in the aminoguanidine-treated diabetics when compared with untreated diabetics. The surface area and absolute volume of the retinal Capillary Basement Membrane were significantly increased in the diabetic rats when compared with non-diabetic controls (p < 0.001 and p < 0.001, respectively). Aminoguanidine treatment of diabetic rats protected against Basement Membrane expansion when compared with untreated diabetic counterparts. Aminoguanidine treatment prevents the development of diabetes-induced Basement Membrane expansion in retinal capillaries. The AGE inhibition properties of aminoguanidine suggest that AGEs play an important role in the complex pathogenesis of Basement Membrane thickening during diabetic retinopathy. Copyright © 2003 John Wiley & Sons, Ltd.
-
diabetic retinopathy quantitative variation in Capillary Basement Membrane thickening in arterial or venous environments
British Journal of Ophthalmology, 1994Co-Authors: Alan W Stitt, T A Gardiner, Heather Anderson, D B ArcherAbstract:Diabetes mellitus was induced in male beagles by a single injection of an alloxan and streptozotocin cocktail and fasting blood sugar levels maintained between 15 and 20 mmol/l. Five years after induction of diabetes, three diabetic animals were sacrificed, together with sex and age-matched controls, and the retinas fixed for either transmission electron microscopy (TEM) or trypsin digestion. In TEM specimens, capillaries in close proximity to the major vessels were designated as either AE (arterial environment) or VE (venous environment) and the thickness of their Basement Membranes (BMs) measured using an image analyser based two dimensional morphometric analysis system. Results show that the BMs of retinal capillaries from the diabetic dogs were significantly thicker than those from control dogs. Furthermore, within the diabetic group the AE capillaries had thicker BMs than VE capillaries (p < or = 0.05). The controls, however, showed no significant difference in BM thickness between AE and VE capillaries. Although many of the capillaries designated as AE or VE would actually have been derived from the opposite side of the circulation, with respect to BM thickness, they conformed to values of their specific group. The conclusion is that diabetic capillaries are more vulnerable to BM thickening in an arterial environment than in a venous environment.
