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Jouni Uitto - One of the best experts on this subject based on the ideXlab platform.
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restricting Dietary magnesium accelerates ectopic connective tissue mineralization in a mouse model of pseudoxanthoma elasticum abcc6
Experimental Dermatology, 2012Co-Authors: Qiujie Jiang, Jouni UittoAbstract:Abstract Ectopic mineralization, linked to a number of diseases, is a major cause of morbidity and mortality in humans. Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by calcium phosphate deposition in various tissues. The mineral content of Diet has been suggested to modify the disease severity in PXE. The aim of this study is to explore the role of Diet with reduced magnesium in modifying tissue mineralization in a mouse model of PXE. Abcc6(-/-) mice were placed on either standard rodent Diet (control) or an Experimental Diet low in magnesium at weaning (4 weeks) and examined for mineralization in the skin and internal organs at the ages of 1.5, 2 or 6 months by computerized morphometric analysis of histopathological sections and by chemical assay of calcium and phosphate. Abcc6(-/-) mice on Experimental Diet demonstrated an accelerated, early-onset mineralization of connective tissues, as compared to control mice. Wild-type or heterozygous mice on Experimental Diet did not show evidence of mineralization up to 6 months of age. All mice on Experimental Diet showed decreased urinary calcium, increased urinary phosphate and elevated parathyroid serum levels. However, no difference in bone density at 6 months of age was noted. Our findings indicate that the mineral content, particularly magnesium, can modify the extent and the onset of mineralization in Abcc6(-/-) mice and suggest that Dietary magnesium levels may contribute to the phenotypic variability of PXE. The control of mineralization by Dietary magnesium may have broader implications in general population in the context of vascular mineralization.
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magnesium carbonate containing phosphate binder prevents connective tissue mineralization in abcc6 mice potential for treatment of pseudoxanthoma elasticum
Clinical and Translational Science, 2009Co-Authors: Qiaoli Li, Jennifer Larusso, Alix E Grandpierre, Jouni UittoAbstract:Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues primarily in the skin, eyes, and the cardiovascular system. PXE is caused by mutations in the ABCC6 gene. While PXE is associated with considerable morbidity and mortality, there is currently no effective or specific treatment. In this study, we tested oral phosphate binders for treatment of a mouse model of PXE which we have developed by targeted ablation of the corresponding mouse gene (Abcc6-/-). This “knock-out” (KO) mouse model recapitulates features of PXE and demonstrates mineralization of a number of tissues, including the connective tissue capsule surrounding vibrissae in the muzzle skin which serves as an early biomarker of the mineralization process. Treatment of these mice with a magnesium carbonate-enriched Diet (magnesium concentration being 5-fold higher than in the control Diet) completely prevented mineralization of the vibrissae up to six months of age, as demonstrated by computerized morphometric analysis of histopathology as well as by calcium and phosphate chemical assays. The magnesium carbonate-enriched Diet also prevented the progression of mineralization when the mice were placed on that Experimental Diet at three months of age and followed up to six months of age. Treatment with magnesium carbonate was associated with a slight increase in the serum concentration of magnesium, with no effect on serum calcium and phosphorus levels. In contrast, concentration of calcium in the urine was increased over ten-fold while the concentration of phosphorus was markedly decreased being essentially undetectable after long term (> 4 month) treatment. No significant changes were noted in the serum parathyroid hormone levels. Computerized axial tomography scan of bones in mice placed on magnesium carbonate-enriched Diet showed no differences in the bone density compared to mice on the control Diet, and chemical assays showed a small increase in the calcium and phosphate content of the femurs by chemical assay, in comparison to mice on control Diet. Similar experiments with another Experimental Diet supplemented with lanthanum carbonate did not interfere with the mineralization process in Abcc6-/- mice. These results suggest that magnesium carbonate may offer a potential treatment modality for PXE, a currently intractable disease, as well as for other conditions characterized by ectopic mineralization of connective tissues.
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magnesium carbonate containing phosphate binder prevents connective tissue mineralization in abcc6 mice potential for treatment of pseudoxanthoma elasticum
Clinical and Translational Science, 2009Co-Authors: Jennifer Larusso, Alix E Grandpierre, Jouni UittoAbstract:Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues primarily in the skin, eyes, and the cardiovascular system. PXE is caused by mutations in the ABCC6 gene. While PXE is associated with considerable morbidity and mortality, there is currently no effective or specific treatment. In this study, we tested oral phosphate binders for treatment of a mouse model of PXE which we have developed by targeted ablation of the corresponding mouse gene (Abcc6(-/-)). This "knock-out" (KO) mouse model recapitulates features of PXE and demonstrates mineralization of a number of tissues, including the connective tissue capsule surrounding vibrissae in the muzzle skin which serves as an early biomarker of the mineralization process. Treatment of these mice with a magnesium carbonate-enriched Diet (magnesium concentration being 5-fold higher than in the control Diet) completely prevented mineralization of the vibrissae up to 6 months of age, as demonstrated by computerized morphometric analysis of histopathology as well as by calcium and phosphate chemical assays. The magnesium carbonate-enriched Diet also prevented the progression of mineralization when the mice were placed on that Experimental Diet at 3 months of age and followed up to 6 months of age. Treatment with magnesium carbonate was associated with a slight increase in the serum concentration of magnesium, with no effect on serum calcium and phosphorus levels. In contrast, concentration of calcium in the urine was increased over 10-fold while the concentration of phosphorus was markedly decreased, being essentially undetectable after long-term (> 4 month) treatment. No significant changes were noted in the serum parathyroid hormone levels. Computerized axial tomography scan of bones in mice placed on magnesium carbonate-enriched Diet showed no differences in the bone density compared to mice on the control Diet, and chemical assays showed a small increase in the calcium and phosphate content of the femurs by chemical assay, in comparison to mice on control Diet. Similar experiments with another Experimental Diet supplemented with lanthanum carbonate did not interfere with the mineralization process in Abcc6(-/-) mice. These results suggest that magnesium carbonate may offer a potential treatment modality for PXE, a currently intractable disease, as well as for other conditions characterized by ectopic mineralization of connective tissues.
S Ravikumar - One of the best experts on this subject based on the ideXlab platform.
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changes in biochemical histological and specific immune parameters in catla catla ham by cynodon dactylon l
Journal of King Saud University - Science, 2012Co-Authors: B Kaleeswaran, Soundharrajan Ilavenil, S RavikumarAbstract:Abstract Indian major carp, Catla catla (Ham.), was fed with ethanolic extract of Cynodon dactylon (L.) mixed Diet with 0.05% (group A), 0.5% (group B) and 5% (group C) extract for 60 days with an interval of 10 days. Significant ( P > 0.05) alterations were observed in the haematological and biochemical parameters such as white blood cell counts, red blood cell counts, haemoglobin content, serum glucose, cholesterol, protein, albumin, globulin, albumin/globulin ratio and RNA/DNA ratio in the Experimental Diet and control fishes. Non-specific immune response was assessed by the anti-protease activity, which was significantly increased in the Experimental Diet groups. The specific immune response of fish was evaluated by antibody response against heat-killed Aeromonas hydrophila for 28 days by using ELISA and bacterial agglutination assay. Aggregation of melanomacrophage centres (MMC) and considerable modifications were observed in the histological analysis of the spleen of Experimental Diet groups. These results suggested that C. dactylon (L.) could combat the microbial infection by stimulating the immune response in fish.
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Dietary supplementation with cynodon dactylon l enhances innate immunity and disease resistance of indian major carp catla catla ham
Fish & Shellfish Immunology, 2011Co-Authors: B Kaleeswaran, Soundharrajan Ilavenil, S RavikumarAbstract:Indian major carp (Catla catla) was subjected to study the immunostimulatory effects when the grass Cynodon dactylon(L) ethanolic extract administrated as feed supplement. C. catla was fed with 0% (Control), 0.05% (group I), 0.5% (group II) and 5% (group III) extract provided for 60 days. Blood samples were collected at every 10 days of interval up to 60 days for analyzing the non-specific humoral (lysozyme activity, antiprotease activity and haemolytic complement) and cellular (production of reactive oxygen and nitrogen species, myeloperoxidase activity) immune response study. The results indicate that C. dactylon ethanolic extract administered as feed supplement significantly (P < 0.05) enhanced most of the non-specific immune parameters tested. Among the Experimental Diet groups, significantly increased response of non-specific immunity was seen in group III (5%). Disease resistant analysis against Aeromonas hydrophila was performed in control group and plant extract treated fish for 7, 14, 21 and 28 days. Relative percent survival rate (RPS) was observed in treated samples, which is directly proportional to concentration of the extract. Additionally, electron microscopic studies and gelatin zymography for Matrix Metalo Proteinase (MMPs) were examined in spleen at 7th and 28th days of feeding. Administration of C. dactylon mixed Diet delayed the lymphocyte destruction with positive ultrastructural changes. An induced stress (A. hydrophila infection) was observed by using MMPs expression, which was reduced in the Experimental Diet groups than the control. All these Experimental results prove that C. dactylon ethanolic extract enhances the immunity of Catla fish.
Fernando Gomezpinilla - One of the best experts on this subject based on the ideXlab platform.
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Dietary omega 3 fatty acids normalize bdnf levels reduce oxidative damage and counteract learning disability after traumatic brain injury in rats
Journal of Neurotrauma, 2004Co-Authors: Zhe Ying, Fernando GomezpinillaAbstract:Omega-3 fatty acids (i.e., docosahexaenoic acid; DHA) regulate signal transduction and gene expression, and protect neurons from death. In this study we examined the capacity of Dietary omega- 3 fatty acids supplementation to help the brain to cope with the effects of traumatic injury. Rats were fed a regular Diet or an Experimental Diet supplemented with omega-3 fatty acids, for 4 weeks before a mild fluid percussion injury (FPI) was performed. FPI increased oxidative stress, and impaired learning ability in the Morris water maze. This type of lesion also reduced levels of brainderived neurotrophic factor (BDNF), synapsin I, and cAMP responsive element-binding protein (CREB). It is known that BDNF facilitates synaptic transmission and learning ability by modulating synapsin I and CREB. Supplementation of omega-3 fatty acids in the Diet counteracted all of the studied effects of FPI, that is, normalized levels of BDNF and associated synapsin I and CREB, reduced oxidative damage, and counteracted learning ...
B Kaleeswaran - One of the best experts on this subject based on the ideXlab platform.
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changes in biochemical histological and specific immune parameters in catla catla ham by cynodon dactylon l
Journal of King Saud University - Science, 2012Co-Authors: B Kaleeswaran, Soundharrajan Ilavenil, S RavikumarAbstract:Abstract Indian major carp, Catla catla (Ham.), was fed with ethanolic extract of Cynodon dactylon (L.) mixed Diet with 0.05% (group A), 0.5% (group B) and 5% (group C) extract for 60 days with an interval of 10 days. Significant ( P > 0.05) alterations were observed in the haematological and biochemical parameters such as white blood cell counts, red blood cell counts, haemoglobin content, serum glucose, cholesterol, protein, albumin, globulin, albumin/globulin ratio and RNA/DNA ratio in the Experimental Diet and control fishes. Non-specific immune response was assessed by the anti-protease activity, which was significantly increased in the Experimental Diet groups. The specific immune response of fish was evaluated by antibody response against heat-killed Aeromonas hydrophila for 28 days by using ELISA and bacterial agglutination assay. Aggregation of melanomacrophage centres (MMC) and considerable modifications were observed in the histological analysis of the spleen of Experimental Diet groups. These results suggested that C. dactylon (L.) could combat the microbial infection by stimulating the immune response in fish.
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Dietary supplementation with cynodon dactylon l enhances innate immunity and disease resistance of indian major carp catla catla ham
Fish & Shellfish Immunology, 2011Co-Authors: B Kaleeswaran, Soundharrajan Ilavenil, S RavikumarAbstract:Indian major carp (Catla catla) was subjected to study the immunostimulatory effects when the grass Cynodon dactylon(L) ethanolic extract administrated as feed supplement. C. catla was fed with 0% (Control), 0.05% (group I), 0.5% (group II) and 5% (group III) extract provided for 60 days. Blood samples were collected at every 10 days of interval up to 60 days for analyzing the non-specific humoral (lysozyme activity, antiprotease activity and haemolytic complement) and cellular (production of reactive oxygen and nitrogen species, myeloperoxidase activity) immune response study. The results indicate that C. dactylon ethanolic extract administered as feed supplement significantly (P < 0.05) enhanced most of the non-specific immune parameters tested. Among the Experimental Diet groups, significantly increased response of non-specific immunity was seen in group III (5%). Disease resistant analysis against Aeromonas hydrophila was performed in control group and plant extract treated fish for 7, 14, 21 and 28 days. Relative percent survival rate (RPS) was observed in treated samples, which is directly proportional to concentration of the extract. Additionally, electron microscopic studies and gelatin zymography for Matrix Metalo Proteinase (MMPs) were examined in spleen at 7th and 28th days of feeding. Administration of C. dactylon mixed Diet delayed the lymphocyte destruction with positive ultrastructural changes. An induced stress (A. hydrophila infection) was observed by using MMPs expression, which was reduced in the Experimental Diet groups than the control. All these Experimental results prove that C. dactylon ethanolic extract enhances the immunity of Catla fish.
Konrad Dabrowski - One of the best experts on this subject based on the ideXlab platform.
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optimization of dipeptide protein mixtures in Experimental Diet formulations for rainbow trout oncorhynchus mykiss alevins
Aquaculture, 2006Co-Authors: Bendik F. Terjesen, Kyeong-jun Lee, Yongfang Zhang, Mark L. Failla, Konrad DabrowskiAbstract:Abstract It has previously been shown that Diets in which the amino acid portion is based on synthetic dipeptides result in positive growth of rainbow trout alevins. However, the protein-based Diets used as a control performed significantly better. One objective of the present study was to identify a protein–dipeptide mixture ratio that results in comparable growth to a protein-based control, in alevins over the first 6 weeks of feeding. Seven Diets were tested, including the casein–gelatin control, three Diets with differing proportions of the casein–gelatin replaced with synthetic dipeptides (50P, 75P and 100P), one Diet based on free amino acids and one reference commercial Diet. In the seventh Diet, arginine-containing dipeptides were withdrawn from the 100P dipeptide-based Diet. To evaluate the Diets, effects on growth, survival, feed intake and free amino acid (FAA) concentrations in muscle tissues were studied. The results on rainbow trout alevin performance using synthetic dipeptide (100P)-based Diets resulted in a relative growth of 34% of the growth observed when alevins were fed the casein–gelatin control Diet. The free amino acid (FAA)-based Diet, however, resulted in a negative growth of the alevins. In contrast, a 1:1 ratio of synthetic dipeptides to casein–gelatin (50P Diet) resulted in similar growth as the casein–gelatin control Diet fed fish. Furthermore, the 50P Diet resulted in a survival that was not significantly different from that found when using a commercial Diet, which showed the highest survival. The concentrations of indispensable FAA (IAA) in muscle were with few exceptions similar in the control and 50P group, while the 100P dipeptide- or free amino acid-based Diet fed fish showed lower levels of free IAA in muscle. Alevins fed dipeptide-based Diets without arginine (100P w/o Arg) showed high mortality within 2 weeks and negative or minimal growth. This Dietary group was restarted at 2 and 4 weeks, and similar results were obtained. In conclusion, the present study indicates that a 50% replacement of the protein portion with synthetic dipeptides is an acceptable Diet formulation for rainbow trout alevins in terms of growth, survival and muscle levels of indispensable FAA. The effects of arginine-containing dipeptide withdrawal on fish growth and survival indicates that arginine is an indispensable amino acid in first-feeding alevins, despite their expression of the ornithine–urea cycle and related enzymes that may function in net de novo synthesis of arginine. The synthetic dipeptide Diets used here were able to identify such limiting amino acids and may be further used to re-evaluate indispensable amino acid requirements in fish early life stages characterized with high growth.
