Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 12 de 12
Filter
1.
Musculoskelet Sci Pract ; 61: 102595, 2022 10.
Article in English | MEDLINE | ID: mdl-35688012

ABSTRACT

BACKGROUND: Adolescent Idiopathic Scoliosis (AIS) is a three-dimensional deformity of the spine associated with pain and aesthetic changes. Various health care professionals may be led to evaluate and/or manage adolescents presenting AIS. There is no compiling of the studies evaluating the level of knowledge on AIS conservative management among undergraduate students in healthcare. OBJECTIVE: To identify and map the current studies evaluating the level of knowledge of health profession students on AIS conservative management. DESIGN: Scoping review. METHODS: The search strategy was conducted in Scopus database. Three concepts were included: "Adolescent idiopathic scoliosis", "Knowledge" and "Undergraduate students studying in a healthcare field". Studies identification included (1) duplicates removing, (2) title and abstract screening, and (3) full-text screening. The quality of the included studies was assessed. Studies' characteristics were extracted, and results were summarized. RESULTS: Searches yielded the identification of 245 citations. After duplicates removal and abstract screening, three full-text articles were identified. Following full-text review, two full-text articles were finally included. Both studies evaluated students in physiotherapy, but using distinct questionnaires. Both studies reported an unsatisfactory level of knowledge. CONCLUSION: Knowledge of future health professionals about the conservative management of AIS has been barely evaluated. Therefore, no conclusion can be drawn regarding the level of knowledge of undergraduate health professions' students on AIS conservative management. The development a standardized questionnaire to adequately assess this knowledge across institutions and professions is required.


Subject(s)
Kyphosis , Scoliosis , Adolescent , Conservative Treatment , Delivery of Health Care , Humans , Scoliosis/therapy , Students
2.
J Manipulative Physiol Ther ; 43(6): 655-666, 2020.
Article in English | MEDLINE | ID: mdl-32709518

ABSTRACT

OBJECTIVE: Lumbopelvic pain (LBPP) affects 45% to 81% of pregnant women, and 25% to 43% of these women report persistent LBPP beyond 3 months after giving birth. The objective of this study was to investigate the association of physical activity, weight status, anxiety, and evolution of LBPP symptoms in postpartum women. METHODS: This was a prospective observational cohort study with 3 time-point assessments: baseline (T0), 3 months (T3), and 6 months (T6). Women with persistent LBPP 3 to 12 months after delivery were recruited. At each time point, pain disability was assessed with the Pelvic Girdle Questionnaire and the Oswestry Disability Index (ODI), physical activity with Fitbit Flex monitors, and anxiety with the French-Canadian version of the State-Trait Anxiety Inventory. Weight was recorded using a standardized method. Pain intensity (numerical rating scale, 0-100) and frequency were assessed using a standardized text message on a weekly basis throughout the study. RESULTS: Thirty-two women were included (time postpartum: 6.6 ± 2.0 months; maternal age: 28.3 ± 3.8 years; body weight: 72.9 ± 19.1 kg), and 27 completed the T6 follow-up. Disability, pain intensity, and pain frequency improved at T6 (P < .001). Participants lost a mean of 1.9 ± 4.5 kg at T6, and this weight loss was correlated with reduction in LBPP intensity (r = 0.479, P = .011) and LBPP frequency (r = 0.386, P = .047), Pelvic Girdle Questionnaire score (r = 0.554, P = .003), and ODI score (r = 0.494, P = .009). Improvement in ODI score at T6 was correlated with the number of inactive minutes at T3 (r = -0.453, P = .026) and T6 (r = -0.457, P = .019), and with daily steps at T6 (r = 0.512, P = .006). CONCLUSION: Weight loss is associated with positive LBPP symptom evolution beyond 3 months postpartum, and physical activity is associated with reduction in pain disability.


Subject(s)
Anxiety Disorders/physiopathology , Exercise/physiology , Low Back Pain/physiopathology , Pelvic Girdle Pain/physiopathology , Postpartum Period/physiology , Pregnancy Complications/physiopathology , Weight Loss/physiology , Adult , Canada , Cohort Studies , Disability Evaluation , Female , Follow-Up Studies , Humans , Pregnancy , Prospective Studies , Surveys and Questionnaires
3.
Complement Ther Med ; 43: 196-200, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30935530

ABSTRACT

OBJECTIVES: To assess chiropractic (DC) and naturopathic doctors' (ND) pediatric care natural health product (NHP) recommendations. DESIGN: Surveys were developed in collaboration with DC and ND educators, and delivered as an on-line national survey. NHP dose, form of delivery, and indications across pediatric age ranges (from newborn to 16 years) for each practitioner's top five NHPs were assessed. Data were analyzed using descriptive statistics, t-tests, and non-parametric tests. RESULTS: Of the 421 respondents seeing one or more pediatric patients per week, 172 (41%, 107 DCs, 65 NDs) provided 440 NHP recommendations, categorized as: vitamins and minerals (89 practitioners, 127 recommendations), probiotics (110 practitioners, 110 recommendations), essential fatty acids (EFAs: 72 practitioners, 72 recommendations), homeopathics (56 practitioners, 66 recommendations), botanicals (29 practitioners, 31 recommendations), and other NHPs (33 practitioners, 34 recommendations). Indications for the NHP recommendations were tabulated for NHPs with 10 or more recommendations in any age category: 596 total indications for probiotics, 318 indications for essential fatty acids, 138 indications for vitamin D, and 71 indications for multi-vitamins. CONCLUSIONS: This is the first study documenting the pediatric NHP recommendations of two popular complementary medicine professions. Common NHPs at standard doses are the most frequently recommended products, with use and doses adjusted according to age. High-quality evidence regarding the efficacy, safety, and dosing for NHP use in children is scarce; development of evidence-informed pediatric guidelines is recommended, particularly for the most commonly used and recommended NHPs.


Subject(s)
Biological Products/therapeutic use , Chiropractic/statistics & numerical data , Dietary Supplements/statistics & numerical data , Naturopathy/statistics & numerical data , Adolescent , Attitude of Health Personnel , Canada , Child , Child, Preschool , Complementary Therapies/statistics & numerical data , Female , Health Care Surveys/statistics & numerical data , Humans , Infant , Infant, Newborn , Male
4.
J Manipulative Physiol Ther ; 41(3): 234-241, 2018.
Article in English | MEDLINE | ID: mdl-29456093

ABSTRACT

OBJECTIVE: Pain in the pelvic girdle area is commonly reported during pregnancy and the postpartum period, and its impact on quality of life is considerable. The Pelvic Girdle Questionnaire (PGQ), developed in 2011 in Norway, is the only condition-specific tool assessing pelvic girdle pain-related symptoms and disability. The questionnaire was recently translated and adapted for the French-Canadian population. The objective of this study was to assess the measurement properties of the previously translated French-Canadian PGQ. METHODS: Eighty-two women with pelvic girdle pain were included in this validation study. The French-Canadian PGQ, pain intensity Numeric Rating Scale, and Oswestry Disability Index were completed by participants at baseline, 48 hours later, and 3 to 6 months later to assess test-retest reliability, construct validity, responsiveness, floor and ceiling effects, and internal consistency. RESULTS: Reliability analyses indicated an intraclass correlation coefficient of 0.841 (95% confidence interval [CI] 0.750-0.901) for the global score. Construct validity analyses indicated a Spearman rank correlation coefficient of 0.696 with the Oswestry Disability Index. Responsiveness analyses identified an effect size of 0.908 (95% CI 0.434-1.644) and an area under the receiver operating characteristics curve of 0.823 (95% CI 0.692-0.953). There was no floor or ceiling effect, and internal consistency analyses indicated a Cronbach α of .933 for the activity subscale and .673 for the symptom subscale. CONCLUSION: Overall, the French-Canadian version of the PGQ is reliable, valid, and responsive, suggesting that it can be implemented in both research and clinical settings to assess functional limitations in pregnant and postpartum women.


Subject(s)
Pelvic Girdle Pain/diagnosis , Pregnancy Complications/diagnosis , Surveys and Questionnaires/standards , Adult , Canada , Female , Humans , Male , Pelvic Pain/diagnosis , Postpartum Period , Pregnancy , Psychometrics , ROC Curve , Reproducibility of Results , Translating
5.
BMC Complement Altern Med ; 17(1): 512, 2017 Dec 01.
Article in English | MEDLINE | ID: mdl-29191235

ABSTRACT

BACKGROUND: To assess chiropractic (DC) and naturopathic doctors' (ND) knowledge, attitudes, and behaviour with respect to the pediatric patients in their practice. METHODS: Cross-sectional surveys were developed in collaboration with DC and ND educators. Surveys were sent to randomly selected DCs and NDs in Ontario, Canada in 2004, and a national online survey was conducted in 2014. Data were analyzed using descriptive statistics, t-tests, non-parametric tests, and linear regression. RESULTS: Response rates for DCs were n = 172 (34%) in 2004, n = 553 (15.5%) in 2014, and for NDs, n = 171 (36%) in 2004, n = 162 (7%) in 2014. In 2014, 366 (78.4%) of DCs and 83 (61%) of NDs saw one or more pediatric patients per week. Pediatric training was rated as inadequate by most respondents in both 2004 and 2014, with most respondents (n = 643, 89.9%) seeking post-graduate training by 2014. Respondents' comfort in treating children and youth is based on experience and post-graduate training. Both DCs and NDs that see children and youth in their practices address a broad array of pediatric health concerns, from well child care and preventative health, to mild and serious illness. CONCLUSIONS: Although the response rate in 2014 is low, the concerns identified a decade earlier remain. The majority of responding DCs and NDs see infants, children, and youth for a variety of health conditions and issues, but self-assess their undergraduate pediatric training as inadequate. We encourage augmented pediatric educational content be included as core curriculum for DCs and NDs and suggest collaboration with institutions/organizations with expertise in pediatric education to facilitate curriculum development, especially in areas that affect patient safety.


Subject(s)
Chiropractic/statistics & numerical data , Health Personnel/psychology , Health Personnel/statistics & numerical data , Naturopathy/statistics & numerical data , Pediatrics/statistics & numerical data , Adult , Attitude of Health Personnel , Canada , Chiropractic/education , Colic/therapy , Cross-Sectional Studies , Female , Fever/therapy , Health Personnel/education , Humans , Infant, Newborn , Male , Middle Aged , Otitis Media/therapy , Pediatrics/education
6.
Biochim Biophys Acta ; 1791(8): 764-71, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19362162

ABSTRACT

Mice have been used widely to define the mechanism of action of fibric acid derivatives. The fibrates are pharmacological agonists of the peroxisome proliferator-activated receptor alpha (PPARalpha), whose activation in human subjects promotes potent reduction in plasma levels of triglycerides (TG) with concomitant increase in those of HDL-cholesterol. The impact of PPARalpha agonists on gene expression in humans and rodents is however distinct; such distinctions include differential regulation of key genes of lipid metabolism. We evaluated the question as to whether the human and murine genes encoding apolipoprotein apoAV, a regulator of plasma concentrations of TG-rich lipoproteins, might be differentially regulated in response to fibrates. Fenofibrate, a classic PPARalpha agonist, repressed expression of mouse Apoa5 in vivo in a mouse model transgenic for the human APOA5 gene; by contrast, expression of the human ortholog was up-regulated. Our findings are consistent with the presence of a functional PPAR-binding element in the promoter of the human APOA5 gene; this element is however degenerate and non-functional in the corresponding mouse Apoa5 sequence, as demonstrated by reporter assays and gel shift analyses. These data further highlights the distinct mechanisms which are implicated in the metabolism of TG-rich lipoproteins in mice as compared to man. They equally emphasize the importance of the choice of a mouse model for investigation of the impact of pharmaceutical modifiers on hypertriglyceridemia.


Subject(s)
Apolipoproteins A/genetics , Apolipoproteins/genetics , Gene Expression Regulation , Hypertriglyceridemia/drug therapy , PPAR alpha/metabolism , Animals , Apolipoprotein A-V , Base Sequence , Cell Line, Tumor , Clofibric Acid/pharmacology , Down-Regulation/drug effects , Gene Expression Regulation/drug effects , Humans , Lipoproteins/blood , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Transgenic , Molecular Sequence Data , Response Elements/genetics , Up-Regulation/drug effects
7.
Arterioscler Thromb Vasc Biol ; 27(7): 1625-31, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17446440

ABSTRACT

OBJECTIVE: Premature atherosclerosis is a characteristic feature of systemic lupus erythematosus, a prototypic autoimmune disease. The principle cellular and molecular mechanisms which underlie such accelerated atherosclerosis are indeterminate. METHODS AND RESULTS: The pathophysiology of lupus-mediated atherogenesis was evaluated in a novel animal model involving transplantation of bone marrow cells from the lupus prone strain gld into Ldl-r(-/-) mice. Diet-induced atherogenesis in lethally-irradiated Ldl-r(-/-) mice transplanted with gld bone marrow cells resulted in accelerated atherosclerosis (+65%) as compared with control mice transplanted with wild-type marrow cells. Enhanced atherogenesis was associated with enhanced activation of both B and T lymphocytes and with arterial inflammation involving endothelial cell activation, monocyte recruitment, and accumulation of apoptotic debris, macrophages, and CD4 T cells, but was independent of plasma lipid levels and renal function. CONCLUSIONS: Our data support the contention that despite the absence of both disturbed cholesterol homeostasis and renal dysfunction in autoimmune gld-->Ldl-r(-/-) mice, lupus disease induces enhanced activation of the immune system and acts locally on the vasculature to induce inflammation, together with accumulation of apoptotic debris, macrophages, and CD4 T cells, thereby accelerating plaque progression.


Subject(s)
Atherosclerosis/immunology , Atherosclerosis/physiopathology , Cytokines/metabolism , Lupus Erythematosus, Systemic/immunology , Animals , Antibodies, Antiphospholipid/blood , Apoptosis/immunology , Apoptosis/physiology , Bone Marrow Transplantation , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , Cytokines/immunology , Disease Models, Animal , Immune System/physiology , Lipid Metabolism , Lipoproteins/metabolism , Lupus Erythematosus, Systemic/physiopathology , Macrophages/cytology , Macrophages/immunology , Male , Mice , Mice, Inbred C57BL , Probability , Radiation Chimera , Reference Values , Sensitivity and Specificity
8.
J Clin Invest ; 116(10): 2767-76, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16964311

ABSTRACT

Scavenger receptor SR-BI has been implicated in HDL-dependent atheroprotective mechanisms. We report the generation of an SR-BI conditional knockout mouse model in which SR-BI gene targeting by loxP site insertion produced a hypomorphic allele (hypomSR-BI). Attenuated SR-BI expression in hypomSR-BI mice resulted in 2-fold elevation in plasma total cholesterol (TC) levels. Cre-mediated SR-BI gene inactivation of the hypomorphic SR-BI allele in hepatocytes (hypomSR-BI-KO(liver)) was associated with high plasma TC concentrations, increased plasma free cholesterol/TC (FC/TC) ratio, and a lipoprotein-cholesterol profile typical of SR-BI-/- mice. Plasma TC levels were increased 2-fold in hypomSR-BI and control mice fed an atherogenic diet, whereas hypomSR-BI-KO(liver) and SR-BI-/- mice developed severe hypercholesterolemia due to accumulation of FC-rich, VLDL-sized particles. Atherosclerosis in hypomSR-BI mice was enhanced (2.5-fold) compared with that in controls, but to a much lower degree than in hypomSR-BI-KO(liver) (32-fold) and SR-BI-/- (48-fold) mice. The latter models did not differ in either plasma lipid levels or in the capacity of VLDL-sized lipoproteins to induce macrophage cholesterol loading. However, reduced atherosclerosis in hypomSR-BI-KO(liver) mice was associated with decreased lesional macrophage content as compared with that in SR-BI-/- mice. These data imply that, in addition to its major atheroprotective role in liver, SR-BI may exert an antiatherogenic role in extrahepatic tissues.


Subject(s)
Atherosclerosis/genetics , Liver/metabolism , Scavenger Receptors, Class B/genetics , ATP Binding Cassette Transporter, Subfamily G, Member 1 , ATP-Binding Cassette Transporters/genetics , Alleles , Animals , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Apolipoproteins/blood , Atherosclerosis/etiology , Atherosclerosis/metabolism , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cholesterol, VLDL/blood , Diet, Atherogenic , Female , Gene Expression/genetics , Interleukin-6/blood , Lipoproteins/blood , Lipoproteins/chemistry , Lipoproteins/genetics , Liver/pathology , Macrophages/chemistry , Macrophages/pathology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Scavenger Receptors, Class B/deficiency , Scavenger Receptors, Class B/metabolism , Sex Factors , Triglycerides/blood
9.
Arterioscler Thromb Vasc Biol ; 24(12): 2358-64, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15486308

ABSTRACT

OBJECTIVE: The human scavenger receptor class B type I (Cla-1) plays a key role in cellular cholesterol movement in facilitating transport of cholesterol between cells and lipoproteins. Indirect evidence has suggested that Cla-1 gene expression is under the feedback control of cellular cholesterol content. To define the molecular mechanisms underlying such putative regulation, we evaluated whether Cla-1 is a target gene of the sterol regulatory element binding protein (SREBP) transcription factor family. METHODS AND RESULTS: Transient transfections demonstrated that SREBP factors induce Cla-1 promoter activity and that SREBP-2 is a more potent inducer than the SREBP-1a isoform. The 5'-deletion analysis of 3 kb of the 5'-flanking sequence of the Cla-1 gene, combined with site-directed mutagenesis and electrophoretic mobility shift assay, allowed identification of a unique sterol responsive element. SREBP-mediated Cla-1 regulation was confirmed in stably transfected human embryonic kidney 293 cells expressing the active form of SREBP-2 at incremental levels. In these cell lines, Cla-1 mRNA and protein levels were increased in direct proportion to the level of SREBP-2 expression. CONCLUSIONS: These findings provide evidence that SREBP-2, a key regulator of cellular cholesterol uptake through modulation of the expression of the low-density lipoprotein receptor gene, may influence cellular cholesterol homeostasis via regulation of Cla-1 gene expression.


Subject(s)
DNA-Binding Proteins/physiology , Gene Expression Regulation/physiology , Receptors, Immunologic/genetics , Transcription Factors/physiology , Binding Sites/genetics , CCAAT-Enhancer-Binding Proteins/metabolism , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism , Kidney/chemistry , Kidney/cytology , Kidney/embryology , Kidney/metabolism , Mutagenesis, Site-Directed/genetics , Promoter Regions, Genetic/genetics , Receptors, Immunologic/metabolism , Receptors, Scavenger , Recombinant Proteins/genetics , Scavenger Receptors, Class B , Sterol Regulatory Element Binding Protein 1 , Sterol Regulatory Element Binding Protein 2 , Transcription Factors/chemistry , Transcription Factors/genetics , Transcription Factors/metabolism , Transfection/methods
10.
Arterioscler Thromb Vasc Biol ; 23(9): 1633-9, 2003 Sep 01.
Article in English | MEDLINE | ID: mdl-12842837

ABSTRACT

OBJECTIVE: The apolipoprotein(a) [apo(a)] gene locus is the major determinant of the circulating concentration of the atherothrombogenic lipoprotein Lp(a). In vitro analysis of the intergenic region between the apo(a) and plasminogen genes revealed the presence of a putative apo(a) transcription control region (ACR) approximately 20 kb upstream of the apo(a) gene that significantly increases the minimal promoter activity of the human apo(a) gene. METHODS AND RESULTS: To examine the function of the ACR in its natural genomic context, we used the Cre-loxP recombination system to generate 2 nearly identical apo(a)-yeast artificial chromosome transgenic mouse lines that possess a single integration site for the human apo(a) transgene in the mouse genome but differ by the presence or absence of the ACR enhancer. Analysis of the 2 groups of animals revealed that the deletion of the ACR was associated with 30% reduction in plasma and mRNA apo(a) levels. Apo(a)-yeast artificial chromosome transgenic mice with and without the ACR sequence were similar in all other aspects of apo(a) regulation, including liver-specific apo(a) expression and alteration in expression levels in response to sexual maturation and a high-fat diet. CONCLUSIONS: This study provides the first experimental in vivo evidence for a functional role of the ACR enhancer in determining levels of apo(a) expression.


Subject(s)
5' Untranslated Regions/physiology , Apolipoproteins A/genetics , Chromosomes, Artificial, Yeast/genetics , Enhancer Elements, Genetic/physiology , Gene Expression Regulation/physiology , Promoter Regions, Genetic/genetics , Transcription, Genetic/physiology , Transgenes , 5' Untranslated Regions/genetics , Animals , Blastocyst/chemistry , Blastocyst/metabolism , Chimera , Diet, Atherogenic , Dietary Fats/pharmacology , Enhancer Elements, Genetic/drug effects , Female , Gene Expression Regulation/drug effects , Gene Expression Regulation/genetics , Gene Transfer Techniques , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic/genetics , Organ Specificity/genetics , Transcription, Genetic/genetics , Transgenes/genetics
11.
Atherosclerosis ; 164(2): 305-11, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12204802

ABSTRACT

The effect of statins on Lp(a) levels is controversial; furthermore, the potential action of statins on apo(a) fragmentation is indeterminate. We therefore determined the circulating levels of Lp(a) and of apo(a) fragments in hypercholesterolemic patients before and after treatment (6 weeks) with Atorvastatin 10 mg/day (A10) or Simvastatin 20 mg/day (S20). In a double blind study, hypercholesterolemic patients (n=391) at high cardiovascular risk (LDL-C>=4.13 mmol/l; TG<2.24 mmol/l; 34% with documented CHD; 45% hypertensive; and 29% current smokers) were assigned to treatment with A10 (n=199) or S20 (n=192). Plasma Lp(a) and apo(a) fragment levels (n=206) were measured prior to and after treatment. At baseline, A10 and S20 groups did not differ in plasma levels of lipids, Lp(a) (A10: 0.45+/-0.48 mg/ml, S20: 0.46+/-0.5), and apo(a) fragments (A10: 3.88+/-5.22 microg/ml; S20: 3.25+/-3), and equally in apo(a) isoform size (A10: 26+/-5 kr, S20: 25.5+/-5.3). After treatment, both statins significantly reduced Lp(a) levels (A10: 0.42+/-0.47 mg/ml, 6% variation, P<0.001; S20: 0.45+/-0.53 mg/ml, 0.02% variation, P=0.046). A10 and S20 did not significantly differ in their efficacy to lower Lp(a) levels. In a multivariate logistic regression analysis, the reduction of Lp(a) levels was independently associated with Lp(a) baseline concentration, but not to other variables, including LDL-C reduction. Plasma levels of apo(a) fragments were not modified by either statin. In conclusion, both A10 and S20 significantly lowered Lp(a), although this effect was of greater magnitude in atorvastatin-treated patients.


Subject(s)
Apolipoproteins A/blood , Apolipoproteins A/drug effects , Cardiovascular Diseases/prevention & control , Heptanoic Acids/administration & dosage , Hypercholesterolemia/drug therapy , Lipoprotein(a)/blood , Lipoprotein(a)/drug effects , Pyrroles/administration & dosage , Simvastatin/administration & dosage , Adult , Aged , Atorvastatin , Cardiovascular Diseases/etiology , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Female , Follow-Up Studies , Humans , Hypercholesterolemia/complications , Logistic Models , Male , Middle Aged , Probability , Reference Values , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Statistics, Nonparametric , Treatment Outcome
12.
J Am Soc Nephrol ; 11(3): 507-513, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10703674

ABSTRACT

Plasma levels of lipoprotein(a) (Lp(a)), an atherogenic particle, are elevated in kidney disease, which suggests a role of this organ in the metabolism of Lp(a). Additional evidence for a role of the kidney in the clearance of Lp(a) is provided by the fact that circulating N-terminal fragments of apolipoprotein(a) (apo(a)) are processed and eliminated by the renal route. To further understand the mechanism underlying such renal excretion, the levels of apo(a) fragments in plasma and urine relative to plasma Lp(a) levels were determined in patients with nephrotic syndrome (n = 15). In plasma, the absolute (24.7 +/- 20.4 versus 2.16 +/- 2.99 microg/ml, P < 0.0001) as well as the relative amounts of apo(a) fragments (4.6 +/-3.4% versus 2.1 +/- 3.3% of total Lp(a), P < 0.0001) were significantly elevated in nephrotic patients compared with a control, normolipidemic population. In addition, urinary apo(a) excretion in patients with nephrotic syndrome was markedly elevated compared with that in control subjects (578 +/- 622 versus 27.7 +/- 44 ng/ml per mg creatinine, P < 0.001). However, the fractional catabolic rates of apo(a) fragments were similar in both groups (0.68 +/- 0.67% and 0.62 +/- 0.47% in nephrotic and control subjects, respectively), suggesting that increased plasma concentrations of apo(a) fragments in nephrotic subjects are more dependent on the rate of synthesis rather than on the catabolic rate. Molecular analysis of apo(a) immunoreactive material in urine revealed that the patterns of apo(a) fragments in nephrotic patients were distinct from those of control subjects. Full-length apo(a), large N-terminal apo(a) fragments similar in size to those present in plasma, as well as C-terminal fragments of apo(a) were detected in urine from nephrotic patients but not in urine from controls. All of these apo(a) forms were in addition to smaller N-terminal apo(a) fragments present in normal urine. This study also demonstrated the presence of Lp(a) in urine from nephrotic patients by ultracentrifugal fractionation. These data suggest that in nephrotic syndrome, Lp(a) and large fragments of apo(a) are passively filtered by the kidney through the glomerulus, whereas smaller apo(a) fragments are secreted into the urine.


Subject(s)
Lipoprotein(a)/blood , Lipoprotein(a)/urine , Nephrotic Syndrome/blood , Nephrotic Syndrome/urine , Adult , Apolipoproteins/blood , Apolipoproteins/urine , Apoprotein(a) , Electrophoresis, Gel, Two-Dimensional , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoblotting , Lipids/blood , Male , Middle Aged , Peptide Fragments/blood , Peptide Fragments/urine , Ultracentrifugation
SELECTION OF CITATIONS
SEARCH DETAIL
...