Pentosan Polysulfate: Oral Versus Subcutaneous Injection in Mucopolysaccharidosis Type I Dogs
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{"title"=>"Pentosan polysulfate: Oral versus subcutaneous injection in mucopolysaccharidosis type I dogs", "type"=>"journal", "authors"=>[{"first_name"=>"Calogera M.", "last_name"=>"Simonaro", "scopus_author_id"=>"6602972154"}, {"first_name"=>"Shunji", "last_name"=>"Tomatsu", "scopus_author_id"=>"7005241812"}, {"first_name"=>"Tracy", "last_name"=>"Sikora", "scopus_author_id"=>"55174933600"}, {"first_name"=>"Francyne", "last_name"=>"Kubaski", "scopus_author_id"=>"55357869000"}, {"first_name"=>"Michael", "last_name"=>"Frohbergh", "scopus_author_id"=>"55363604400"}, {"first_name"=>"Johana M.", "last_name"=>"Guevara", "scopus_author_id"=>"43761090200"}, {"first_name"=>"Raymond Y.", "last_name"=>"Wang", "scopus_author_id"=>"57148773000"}, {"first_name"=>"Moin", "last_name"=>"Vera", "scopus_author_id"=>"55261766000"}, {"first_name"=>"Jennifer L.", "last_name"=>"Kang", "scopus_author_id"=>"56982126800"}, {"first_name"=>"Lachlan J.", "last_name"=>"Smith", "scopus_author_id"=>"14122339400"}, {"first_name"=>"Edward H.", "last_name"=>"Schuchman", "scopus_author_id"=>"7004364820"}, {"first_name"=>"Mark E.", "last_name"=>"Haskins", "scopus_author_id"=>"7006857674"}], "year"=>2016, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84963813656", "doi"=>"10.1371/journal.pone.0153136", "issn"=>"19326203", "pui"=>"609727104", "isbn"=>"2012177778", "pmid"=>"27064989", "scopus"=>"2-s2.0-84963813656"}, "id"=>"37a11e63-d881-3fa4-b1cb-7d533ab1277a", "abstract"=>"BACKGROUND We previously demonstrated the therapeutic benefits of pentosan polysulfate (PPS) in a rat model of mucopolysaccharidosis (MPS) type VI. Reduction of inflammation, reduction of glycosaminoglycan (GAG) storage, and improvement in the skeletal phenotype were shown. Herein, we evaluate the long-term safety and therapeutic effects of PPS in a large animal model of a different MPS type, MPS I dogs. We focused on the arterial phenotype since this is one of the most consistent and clinically significant features of the model. METHODOLOGY/PRINCIPAL FINDINGS MPS I dogs were treated with daily oral or biweekly subcutaneous (subQ) PPS at a human equivalent dose of 1.6 mg/kg for 17 and 12 months, respectively. Safety parameters were assessed at 6 months and at the end of the study. Following treatment, cytokine and GAG levels were determined in fluids and tissues. Assessments of the aorta and carotid arteries also were performed. No drug-related increases in liver enzymes, coagulation factors, or other adverse effects were observed. Significantly reduced IL-8 and TNF-alpha were found in urine and cerebrospinal fluid (CSF). GAG reduction was observed in urine and tissues. Increases in the luminal openings and reduction of the intimal media thickening occurred in the carotids and aortas of PPS-treated animals, along with a reduction of storage vacuoles. These results were correlated with a reduction of GAG storage, reduction of clusterin 1 staining, and improved elastin integrity. No significant changes in the spines of the treated animals were observed. CONCLUSIONS PPS treatment led to reductions of pro-inflammatory cytokines and GAG storage in urine and tissues of MPS I dogs, which were most evident after subQ administration. SubQ administration also led to significant cytokine reductions in the CSF. Both treatment groups exhibited markedly reduced carotid and aortic inflammation, increased vessel integrity, and improved histopathology. We conclude that PPS may be a safe and useful therapy for MPS I, either as an adjunct or as a stand-alone treatment that reduces inflammation and GAG storage.", "link"=>"http://www.mendeley.com/research/pentosan-polysulfate-oral-versus-subcutaneous-injection-mucopolysaccharidosis-type-i-dogs", "reader_count"=>16, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>2, "Student > Master"=>2, "Other"=>4, "Student > Bachelor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>2, "Student > Master"=>2, "Other"=>4, "Student > Bachelor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>4, "Agricultural and Biological Sciences"=>4, "Medicine and Dentistry"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>2, "Chemistry"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Chemistry"=>{"Chemistry"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"United States"=>2}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/4936270"], "description"=>"<p>Quantification of the Lumen and Intimal Thickness of the Aorta In Normal, Untreated and PPS Treated MPS I Dogs.</p>", "links"=>[], "tags"=>["Oral Versus Subcutaneous Injection", "CSF", "Conclusions PPS treatment", "GAG storage", "MPS", "VI", "IL", "clusterin 1 staining"], "article_id"=>3170752, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Ecology", "Immunology", "Cancer", "Infectious Diseases"], "users"=>["Calogera M. Simonaro", "Shunji Tomatsu", "Tracy Sikora", "Francyne Kubaski", "Michael Frohbergh", "Johana M. Guevara", "Raymond Y. Wang", "Moin Vera", "Jennifer L. Kang", "Lachlan J. Smith", "Edward H. Schuchman", "Mark E. Haskins"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153136.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Quantification_of_the_Lumen_and_Intimal_Thickness_of_the_Aorta_In_Normal_Untreated_and_PPS_Treated_MPS_I_Dogs_/3170752", "title"=>"Quantification of the Lumen and Intimal Thickness of the Aorta In Normal, Untreated and PPS Treated MPS I Dogs.", "pos_in_sequence"=>9, "defined_type"=>3, "published_date"=>"2016-04-11 07:51:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/4936144"], "description"=>"<p>(A) Normal (B) Storage (arrowhead) and elastin fragmentation (arrow) is evident in the aortas of untreated 12-month-old MPS I dogs (B) Reduced storage (arrowheads) and fragmentation was observed in MPS I animals treated with oral PPS (daily) for 17 months. (C) Little or no storage or fragmentation was evident in the subQ treated animals (biweekly for 12 months). (20X magnification).</p>", "links"=>[], "tags"=>["Oral Versus Subcutaneous Injection", "CSF", "Conclusions PPS treatment", "GAG storage", "MPS", "VI", "IL", "clusterin 1 staining"], "article_id"=>3170689, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Ecology", "Immunology", "Cancer", "Infectious Diseases"], "users"=>["Calogera M. Simonaro", "Shunji Tomatsu", "Tracy Sikora", "Francyne Kubaski", "Michael Frohbergh", "Johana M. Guevara", "Raymond Y. Wang", "Moin Vera", "Jennifer L. Kang", "Lachlan J. Smith", "Edward H. Schuchman", "Mark E. Haskins"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153136.g005", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Elastin_staining_in_the_descending_aorta_of_normal_untreated_and_PPS_treated_MPS_I_dogs_/3170689", "title"=>"Elastin staining in the descending aorta of normal, untreated and PPS-treated MPS I dogs.", "pos_in_sequence"=>6, "defined_type"=>1, "published_date"=>"2016-04-11 07:51:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/4935916", "https://ndownloader.figshare.com/files/4935919", "https://ndownloader.figshare.com/files/4935928"], "description"=>"<div><p>Background</p><p>We previously demonstrated the therapeutic benefits of pentosan polysulfate (PPS) in a rat model of mucopolysaccharidosis (MPS) type VI. Reduction of inflammation, reduction of glycosaminoglycan (GAG) storage, and improvement in the skeletal phenotype were shown. Herein, we evaluate the long-term safety and therapeutic effects of PPS in a large animal model of a different MPS type, MPS I dogs. We focused on the arterial phenotype since this is one of the most consistent and clinically significant features of the model.</p><p>Methodology/Principal Findings</p><p>MPS I dogs were treated with daily oral or biweekly subcutaneous (subQ) PPS at a human equivalent dose of 1.6 mg/kg for 17 and 12 months, respectively. Safety parameters were assessed at 6 months and at the end of the study. Following treatment, cytokine and GAG levels were determined in fluids and tissues. Assessments of the aorta and carotid arteries also were performed. No drug-related increases in liver enzymes, coagulation factors, or other adverse effects were observed. Significantly reduced IL-8 and TNF-alpha were found in urine and cerebrospinal fluid (CSF). GAG reduction was observed in urine and tissues. Increases in the luminal openings and reduction of the intimal media thickening occurred in the carotids and aortas of PPS-treated animals, along with a reduction of storage vacuoles. These results were correlated with a reduction of GAG storage, reduction of clusterin 1 staining, and improved elastin integrity. No significant changes in the spines of the treated animals were observed.</p><p>Conclusions</p><p>PPS treatment led to reductions of pro-inflammatory cytokines and GAG storage in urine and tissues of MPS I dogs, which were most evident after subQ administration. SubQ administration also led to significant cytokine reductions in the CSF. Both treatment groups exhibited markedly reduced carotid and aortic inflammation, increased vessel integrity, and improved histopathology. We conclude that PPS may be a safe and useful therapy for MPS I, either as an adjunct or as a stand-alone treatment that reduces inflammation and GAG storage.</p></div>", "links"=>[], "tags"=>["Oral Versus Subcutaneous Injection", "CSF", "Conclusions PPS treatment", "GAG storage", "MPS", "VI", "IL", "clusterin 1 staining"], "article_id"=>3170563, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Ecology", "Immunology", "Cancer", "Infectious Diseases"], "users"=>["Calogera M. Simonaro", "Shunji Tomatsu", "Tracy Sikora", "Francyne Kubaski", "Michael Frohbergh", "Johana M. Guevara", "Raymond Y. Wang", "Moin Vera", "Jennifer L. Kang", "Lachlan J. Smith", "Edward H. Schuchman", "Mark E. Haskins"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0153136.s001", "https://dx.doi.org/10.1371/journal.pone.0153136.s002", "https://dx.doi.org/10.1371/journal.pone.0153136.s003"], "stats"=>{"downloads"=>1, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Pentosan_Polysulfate_Oral_Versus_Subcutaneous_Injection_in_Mucopolysaccharidosis_Type_I_Dogs/3170563", "title"=>"Pentosan Polysulfate: Oral Versus Subcutaneous Injection in Mucopolysaccharidosis Type I Dogs", "pos_in_sequence"=>1, "defined_type"=>4, "published_date"=>"2016-04-11 07:51:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/4935970"], "description"=>"<p>IL-8 and TNF-alpha were quantified at the end of the PPS treatment (17 months with daily oral treatment and 12 months with biweekly subQ) by ELISA assays as described in the Materials and Methods. (A) Serum IL-8 and TNF-alpha in untreated (black), oral (white), and subQ (grey) groups. * = p<0.005 when comparing treated to untreated animals. Dashed lines represent normal levels. (B) CSF IL-8 and TNF-alpha in the treated and untreated groups. * = p<0.03; ** = p<0.005. The vertical lines in each column indicate the ranges for the individual animals with each group (n = 5/group).</p>", "links"=>[], "tags"=>["Oral Versus Subcutaneous Injection", "CSF", "Conclusions PPS treatment", "GAG storage", "MPS", "VI", "IL", "clusterin 1 staining"], "article_id"=>3170599, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Ecology", "Immunology", "Cancer", "Infectious Diseases"], "users"=>["Calogera M. Simonaro", "Shunji Tomatsu", "Tracy Sikora", "Francyne Kubaski", "Michael Frohbergh", "Johana M. Guevara", "Raymond Y. Wang", "Moin Vera", "Jennifer L. Kang", "Lachlan J. Smith", "Edward H. Schuchman", "Mark E. Haskins"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153136.g001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Serum_and_CSF_inflammatory_markers_in_age_matched_untreated_and_PPS_treated_MPS_I_dogs_/3170599", "title"=>"Serum and CSF inflammatory markers in age-matched untreated and PPS-treated MPS I dogs.", "pos_in_sequence"=>2, "defined_type"=>1, "published_date"=>"2016-04-11 07:51:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/4936105"], "description"=>"<p>Representative images (H&E staining) are shown for untreated, oral, and subQ PPS-treated MPS I dogs (17 months with daily oral treatment and 12 months with biweekly subQ). (A) The intima media of both the descending aorta and carotid is thickened (arrows) in the untreated MPS I dog due to lysosomal storage, resulting in narrowing of the lumen (*) (magnification 1X). PPS treatment decreased the thickness of the intimal media and increased the diameter of the lumen with both modes of administration, but was more significant with subQ treatment (see Tables <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153136#pone.0153136.t002\" target=\"_blank\">2</a> and <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0153136#pone.0153136.t003\" target=\"_blank\">3</a>) (B) Higher magnification (10X) of the descending aorta and carotid artery in untreated and PPS-treated MPS I dogs revealed reduced vacuolization/storage in the treated animals when compared to untreated (arrows). (C) Total GAGs were determined in the descending aorta of normal, untreated and PPS-treated MPS I dogs. PPS treatment significantly reduced GAG storage with both modes of treatment, consistent with the histological evidence of storage reduction. Black columns, untreated MPS I dogs; white columns, oral PPS-treated MPS I dogs; grey columns, subQ PPS-treated MPS I dogs. The vertical lines in each column indicate the ranges. * p = 0.0041</p>", "links"=>[], "tags"=>["Oral Versus Subcutaneous Injection", "CSF", "Conclusions PPS treatment", "GAG storage", "MPS", "VI", "IL", "clusterin 1 staining"], "article_id"=>3170668, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Ecology", "Immunology", "Cancer", "Infectious Diseases"], "users"=>["Calogera M. Simonaro", "Shunji Tomatsu", "Tracy Sikora", "Francyne Kubaski", "Michael Frohbergh", "Johana M. Guevara", "Raymond Y. Wang", "Moin Vera", "Jennifer L. Kang", "Lachlan J. Smith", "Edward H. Schuchman", "Mark E. Haskins"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153136.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Analysis_of_the_descending_aorta_and_carotid_in_untreated_and_PPS_treated_MPS_I_dogs_/3170668", "title"=>"Analysis of the descending aorta and carotid in untreated and PPS-treated MPS I dogs.", "pos_in_sequence"=>5, "defined_type"=>1, "published_date"=>"2016-04-11 07:51:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/4936222"], "description"=>"<p>Safety Profiles of Oral and Subcutaneous PPS Treatment in MPS I Dogs.</p>", "links"=>[], "tags"=>["Oral Versus Subcutaneous Injection", "CSF", "Conclusions PPS treatment", "GAG storage", "MPS", "VI", "IL", "clusterin 1 staining"], "article_id"=>3170734, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Ecology", "Immunology", "Cancer", "Infectious Diseases"], "users"=>["Calogera M. Simonaro", "Shunji Tomatsu", "Tracy Sikora", "Francyne Kubaski", "Michael Frohbergh", "Johana M. Guevara", "Raymond Y. Wang", "Moin Vera", "Jennifer L. Kang", "Lachlan J. Smith", "Edward H. Schuchman", "Mark E. Haskins"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153136.t001", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Safety_Profiles_of_Oral_and_Subcutaneous_PPS_Treatment_in_MPS_I_Dogs_/3170734", "title"=>"Safety Profiles of Oral and Subcutaneous PPS Treatment in MPS I Dogs.", "pos_in_sequence"=>8, "defined_type"=>3, "published_date"=>"2016-04-11 07:51:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/4936075"], "description"=>"<p>Mass spectrometric quantification of GAG-derived disaccharides was performed as described in the Material and Methods. Urine GAGs were measured at the end of the treatment; 17 months with oral daily PPS and 12 months with biweekly subQ PPS. Black columns, untreated MPS I dogs; white columns, oral PPS-treated MPS I dogs; grey columns, subQ PPS-treated MPS I dogs. The vertical lines in each column indicate the ranges. Dashed lines represent normal levels. (A) The dermatan sulfate disaccharide (Di-6S) was significantly reduced with both modes of PPS administration, with subQ treatment being more significant. * p = 0.0232 comparing untreated to oral and p = 0.0141 comparing untreated to subQ. (B) Heparan sulfate disaccharides (DiHS-OS, DiHS-6S, and DiHS-NS) also were reduced with PPS treatment when compared to untreated animals, although the reductions were not significant.</p>", "links"=>[], "tags"=>["Oral Versus Subcutaneous Injection", "CSF", "Conclusions PPS treatment", "GAG storage", "MPS", "VI", "IL", "clusterin 1 staining"], "article_id"=>3170641, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Ecology", "Immunology", "Cancer", "Infectious Diseases"], "users"=>["Calogera M. Simonaro", "Shunji Tomatsu", "Tracy Sikora", "Francyne Kubaski", "Michael Frohbergh", "Johana M. Guevara", "Raymond Y. Wang", "Moin Vera", "Jennifer L. Kang", "Lachlan J. Smith", "Edward H. Schuchman", "Mark E. Haskins"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153136.g003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Mass_spectrometric_analysis_of_urine_GAGs_in_age_matched_normal_untreated_and_PPS_treated_MPS_I_dogs_/3170641", "title"=>"Mass spectrometric analysis of urine GAGs in age-matched normal, untreated and PPS-treated MPS I dogs.", "pos_in_sequence"=>4, "defined_type"=>1, "published_date"=>"2016-04-11 07:51:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/4936312"], "description"=>"<p>Quantification of the Lumen and Intimal Thickness of the Carotid In Normal, Untreated and PPS Treated MPS I Dogs.</p>", "links"=>[], "tags"=>["Oral Versus Subcutaneous Injection", "CSF", "Conclusions PPS treatment", "GAG storage", "MPS", "VI", "IL", "clusterin 1 staining"], "article_id"=>3170776, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Ecology", "Immunology", "Cancer", "Infectious Diseases"], "users"=>["Calogera M. Simonaro", "Shunji Tomatsu", "Tracy Sikora", "Francyne Kubaski", "Michael Frohbergh", "Johana M. Guevara", "Raymond Y. Wang", "Moin Vera", "Jennifer L. Kang", "Lachlan J. Smith", "Edward H. Schuchman", "Mark E. Haskins"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153136.t003", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Quantification_of_the_Lumen_and_Intimal_Thickness_of_the_Carotid_In_Normal_Untreated_and_PPS_Treated_MPS_I_Dogs_/3170776", "title"=>"Quantification of the Lumen and Intimal Thickness of the Carotid In Normal, Untreated and PPS Treated MPS I Dogs.", "pos_in_sequence"=>10, "defined_type"=>3, "published_date"=>"2016-04-11 07:51:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/4936186"], "description"=>"<p>(A) Immunohistochemical analysis of clusterin, a marker of inflammation, in the descending aorta of untreated MPS I dogs. High-level expression (brown) of clusterin in aortic plaques and the inner and outer borders of the vessel were observed in the untreated dogs (arrows). PPS-treated animals (17 months with daily oral and 12 months with biweekly subQ) did not show plaque formation and exhibited reduced clusterin staining similar to normal. Magnification 2X. (B) Western blot analysis showing reduced clusterin expression in the descending aorta of PPS-treated animals. Two representative animals are shown for each treatment group. Nor = age-matched normal animal, PPS-O = MPS I dogs treated with daily oral PPS for 17 months. PPS-SQ = MPS dogs treated with biweekly subQ with PPS for 12 months.</p>", "links"=>[], "tags"=>["Oral Versus Subcutaneous Injection", "CSF", "Conclusions PPS treatment", "GAG storage", "MPS", "VI", "IL", "clusterin 1 staining"], "article_id"=>3170713, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Ecology", "Immunology", "Cancer", "Infectious Diseases"], "users"=>["Calogera M. Simonaro", "Shunji Tomatsu", "Tracy Sikora", "Francyne Kubaski", "Michael Frohbergh", "Johana M. Guevara", "Raymond Y. Wang", "Moin Vera", "Jennifer L. Kang", "Lachlan J. Smith", "Edward H. Schuchman", "Mark E. Haskins"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153136.g006", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Clusterin_expression_in_the_descending_aorta_of_normal_untreated_and_PPS_treated_MPS_I_dogs_/3170713", "title"=>"Clusterin expression in the descending aorta of normal, untreated and PPS-treated MPS I dogs.", "pos_in_sequence"=>7, "defined_type"=>1, "published_date"=>"2016-04-11 07:51:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/4936024"], "description"=>"<p>Total GAGs were measured in urine and tissue homogenates at the end of the treatment (17 months with daily oral and 12 months with biweekly subQ PPS. (A) Total urine GAGs were significantly reduced with both modes of PPS administration, with subQ treatment being more significant; * = p<0.02 comparing untreated to oral and * = p<0.01 comparing untreated to subQ. (B) Total GAGs in tissue extracts from the kidney (medulla and cortex), liver and spleen of untreated and PPS-treated animals. In all tissues, PPS significantly lowered GAG storage; as in urine the reductions were greater using subQ administration. * = p<0.05. Black columns, untreated MPS I dogs; white columns, oral PPS treated MPS I dogs; grey columns, subQ PPS-treated MPS I dogs. The vertical lines in each column indicate the ranges for the individual animals in each treatment group (n = 5/group). Dashed lines represent normal levels.</p>", "links"=>[], "tags"=>["Oral Versus Subcutaneous Injection", "CSF", "Conclusions PPS treatment", "GAG storage", "MPS", "VI", "IL", "clusterin 1 staining"], "article_id"=>3170623, "categories"=>["Biochemistry", "Medicine", "Cell Biology", "Physiology", "Pharmacology", "Ecology", "Immunology", "Cancer", "Infectious Diseases"], "users"=>["Calogera M. Simonaro", "Shunji Tomatsu", "Tracy Sikora", "Francyne Kubaski", "Michael Frohbergh", "Johana M. Guevara", "Raymond Y. Wang", "Moin Vera", "Jennifer L. Kang", "Lachlan J. Smith", "Edward H. Schuchman", "Mark E. Haskins"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0153136.g002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Analysis_of_total_GAGs_in_age_matched_untreated_and_PPS_treated_MPS_I_dogs_/3170623", "title"=>"Analysis of total GAGs in age-matched untreated and PPS-treated MPS I dogs.", "pos_in_sequence"=>3, "defined_type"=>1, "published_date"=>"2016-04-11 07:51:58"}

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  • {"unique-ip"=>"59", "full-text"=>"58", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"2"}
  • {"unique-ip"=>"63", "full-text"=>"63", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"3"}
  • {"unique-ip"=>"56", "full-text"=>"57", "pdf"=>"9", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"4"}
  • {"unique-ip"=>"66", "full-text"=>"72", "pdf"=>"4", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2020", "month"=>"5"}
  • {"unique-ip"=>"78", "full-text"=>"98", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"6"}
  • {"unique-ip"=>"55", "full-text"=>"64", "pdf"=>"6", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2020", "month"=>"7"}
  • {"unique-ip"=>"50", "full-text"=>"58", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2020", "month"=>"8"}

Relative Metric

{"start_date"=>"2016-01-01T00:00:00Z", "end_date"=>"2016-12-31T00:00:00Z", "subject_areas"=>[]}
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