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1.
Pediatr Radiol ; 44(12): 1548-56, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24859357

ABSTRACT

BACKGROUND: Few standards exist for reporting results of voiding cystourethrogram (VCUG). OBJECTIVE: To assess the variation in reporting of VCUG findings from different facilities using a standardized assessment tool. MATERIALS AND METHODS: VCUG reports were evaluated for demographic, technical, anatomical and functional information. Reports were categorized by age, gender, indication and vesicouretal reflux (VUR) status. Institutions were classified as a free-standing pediatric hospital (n = 3), pediatric hospital within a hospital (n = 11), or non-pediatric facility (n = 24) and reports were classified as having been read by a pediatric radiologist or not. Each category of outside reports (n = 152) was randomly matched with a twice-larger group of Hospital A reports from the same category (n = 304). Multivariate linear regression was used to analyze the association between the primary outcome (percentage of items described in dictated VCUG report) and the type of radiologist and institution. RESULTS: Of the 456 studies, 66% were in girls, 56% were in those <12 months old, and the indication was urinary tract infection (UTI) in 81%. The mean percentage of items reported was 67 ± 14% (74 ± 7% at free-standing pediatric hospitals, 61 ± 10% at pediatric hospitals within a hospital, and 48 ± 11% at non-pediatric facilities). In multivariate analysis, VCUG reports generated at non-pediatric facilities had 17% fewer items included (95% CI: 14.5-19.7%, P < 0.0001), and pediatric hospitals within a hospital had 9% fewer items included (5.9-12.5%, P < 0.0001) when compared to free-standing pediatric hospitals. Reports read by a pediatric radiologist had 12% more items included (9.1-15.3%, P < 0.0001) compared to those read by a non-pediatric radiologist. CONCLUSION: More complete VCUG reports were observed when generated at free-standing pediatric hospitals and when interpreted by a pediatric radiologist.


Subject(s)
Documentation/standards , Image Processing, Computer-Assisted/statistics & numerical data , Medical Records/standards , Urinary Bladder/diagnostic imaging , Urinary Tract Infections/diagnostic imaging , Urography , Animals , Female , Hospitals/statistics & numerical data , Hospitals, Pediatric/statistics & numerical data , Humans , Hydronephrosis/diagnostic imaging , Image Processing, Computer-Assisted/methods , Infant , Kidney/diagnostic imaging , Male , Medical Records/statistics & numerical data , Reproducibility of Results , Urinary Tract , Urinary Tract Infections/complications , Urination , Urography/methods , Vesico-Ureteral Reflux/complications , Vesico-Ureteral Reflux/diagnostic imaging
2.
PLoS Negl Trop Dis ; 18(6): e0012020, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38924064

ABSTRACT

Bovine trypanosomosis, caused by Trypanosoma vivax, currently affects cattle and has a significant economic impact in sub-Saharan Africa and South America. The development of new diagnostic antigens is essential to improve and refine existing methods. Our study evaluated the efficacy of two recombinant antigens in detecting specific antibodies in cattle. These antigens are derivatives of an invariant surface glycoprotein (ISG) from T. vivax. A fraction of a previously described antigen (TvY486_0045500), designated TvISGAf, from an African strain was evaluated, and a new ISG antigen from an American isolate, TvISGAm, was identified. The two antigens were expressed as fusion proteins in Escherichia coli: TvISGAf was fused to the MBP-His-tag, and TvISGAm was obtained as a His-tag fused protein. An ELISA evaluation was conducted using these antigens on 149 positive and 63 negative bovine samples. The diagnostic performance was enhanced by the use of a combination of both antigens (referred to as TvISG-based ELISA), achieving a sensitivity of 89.6% and specificity of 93.8%. Following the validation of the TvISG-based ELISA, the seroprevalence of T. vivax infection in 892 field samples from cattle in the central region of Argentina was determined. The mean seroprevalence of T. vivax was 53%, with variation ranging from 21% to 69% among the six departments studied. These results support the use of the TvISG ELISA as a valuable serological tool for the detection and monitoring of T. vivax infection in cattle. Furthermore, we report for the first time the seroprevalence of T. vivax in Argentina, which highlights the widespread endemic nature of the disease in the region. In order to effectively manage the increasing spread of T. vivax in the vast livestock production areas of South America, it is essential to implement consistent surveillance programs and to adopt preventive strategies.


Subject(s)
Antigens, Protozoan , Cattle Diseases , Enzyme-Linked Immunosorbent Assay , Serologic Tests , Trypanosoma vivax , Animals , Cattle , Argentina/epidemiology , Trypanosoma vivax/immunology , Trypanosoma vivax/genetics , Trypanosoma vivax/isolation & purification , Serologic Tests/methods , Serologic Tests/veterinary , Cattle Diseases/diagnosis , Cattle Diseases/epidemiology , Cattle Diseases/parasitology , Antigens, Protozoan/immunology , Antigens, Protozoan/genetics , Enzyme-Linked Immunosorbent Assay/methods , Enzyme-Linked Immunosorbent Assay/veterinary , Antibodies, Protozoan/blood , Sensitivity and Specificity , Trypanosomiasis, African/diagnosis , Trypanosomiasis, African/veterinary , Trypanosomiasis, African/epidemiology , Livestock/parasitology
3.
J Lipid Res ; 51(2): 406-15, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19744920

ABSTRACT

Niemann-Pick type C1 disease (NPC1) is an autosomal recessive lysosomal storage disorder characterized by neonatal jaundice, hepatosplenomegaly, and progressive neurodegeneration. The present study provides the lipid profiles, mutations, and corresponding associations with the biochemical phenotype obtained from NPC1 patients who participated in the National NPC1 Disease Database. Lipid profiles were obtained from 34 patients (39%) in the survey and demonstrated significantly reduced plasma LDL cholesterol (LDL-C) and increased plasma triglycerides in the majority of patients. Reduced plasma HDL cholesterol (HDL-C) was the most consistent lipoprotein abnormality found in male and female NPC1 patients across age groups and occurred independent of changes in plasma triglycerides. A subset of 19 patients for whom the biochemical severity of known NPC1 mutations could be correlated with their lipid profile showed a strong inverse correlation between plasma HDL-C and severity of the biochemical phenotype. Gene mutations were available for 52 patients (59%) in the survey, including 52 different mutations and five novel mutations (Y628C, P887L, I923V, A1151T, and 3741_3744delACTC). Together, these findings provide novel information regarding the plasma lipoprotein changes and mutations in NPC1 disease, and suggest plasma HDL-C represents a potential biomarker of NPC1 disease severity.


Subject(s)
Databases, Factual , Lipid Metabolism , Mutation , Niemann-Pick Disease, Type C/epidemiology , Phenotype , Adolescent , Adult , Child , Child, Preschool , Cohort Studies , Female , Humans , Infant , Lipoproteins/blood , Male , Niemann-Pick Disease, Type C/diagnosis , Niemann-Pick Disease, Type C/genetics , Niemann-Pick Disease, Type C/metabolism , United States , Young Adult
4.
Arch Argent Pediatr ; 117(1): 6-11, 2019 02 01.
Article in English, Spanish | MEDLINE | ID: mdl-30652440

ABSTRACT

INTRODUCTION: Multidrug resistant Gramnegative (MDRGN) infections are an increasing problem in neonatal intensive care units. The objective of this study was to establish the epidemiological, clinical, microbiological, and evolutionary characteristics of carbapenem-resistant MDRGN infections and the risk factors for them at the Division of Neonatology of a tertiary care hospital. POPULATION AND METHOD: A retrospective cohort study was done in this Division in patients with a documented MDRGN infection between 4/24/2013 and 4/29/2015. RESULTS: Twenty-one patients were included. Their median gestational age and birth weight were 35 weeks and 2070 g, respectively. Eighteen patients (86 %) had a positive blood culture; the most commonly isolated microorganism was Acinetobacter baumannii (17 patients, 81 %), followed by carbapenemase-producing Klebsiella pneumoniae (3 patients, 14 %) and Enterobacter cloacae (1 patient, 5 %).The median age at diagnosis was 28 days and all patients had risk factors for infection, including surgery, assisted mechanical ventilation, parenteral nutrition, central venous line, and antibiotics. The definite antibiotic therapy included colistin in all cases; in combination, in 84 %. Five patients (24 %) died due to the infection. Prematurity and a birth weight < 2000 g were statistically significant risk factors associated with mortality (p = 0.03 and 0.01, respectively). CONCLUSION: MDRGN infections were observed in patients with predisposing factors. Acinetobacter baumannii was the main etiologic agent. Mortality was high and related to prematurity and a low birth weight.


Introducción. Las infecciones por bacilos Gram-negativos multirresistentes (BGN-MR) constituyen un problema creciente en las unidades de cuidado intensivo neonatal. El objetivo del estudio fue conocer las características epidemiológicas, clínicas, microbiológicas, evolutivas y los factores de riesgo de infección por BGN-MR resistentes a carbapenemes en el Servicio de Neonatología de un hospital de alta complejidad. Población y método. Se realizó un estudio de cohorte retrospectivo en dicho Servicio, donde se incluyeron los pacientes con infección documentada por BGN-MR del 24/4/2013 al 29/4/2015. Resultados. Se incluyeron 21 pacientes. La mediana de edad gestacional y peso de nacimiento fue 35 semanas y 2070 gramos, respectivamente. Dieciocho pacientes (86 %) tuvieron hemocultivos positivos y el aislamiento microbiológico más frecuente fue Acinetobacter baumannii (17 pacientes, 81 %), seguido por Klebsiella pneumoniae productora de carbapenemasa (3 pacientes, 14 %) y Enterobacter cloacae (1 paciente, 5 %). La mediana de edad al momento del diagnóstico fue de 28 días y todos tenían factores de riesgo para la infección, como cirugía, asistencia respiratoria mecánica, nutrición parenteral, catéter central y antibióticos. El tratamiento antibiótico definitivo fue colistina en todos los casos, combinado en el 84 %. Cinco pacientes (24 %) fallecieron por la infección. La prematurez y el peso < 2000 g fueron factores de riesgo estadísticamente significativos asociados a la mortalidad (p = 0,03 y 0,01, respectivamente). Conclusión. Las infecciones por BGN-MR se presentaron en pacientes con factores predisponentes. Acinetobacter baumannii fue el primer agente etiológico. La mortalidad fue elevada y relacionada con prematurez y bajo peso al nacer.


Subject(s)
Carbapenems/pharmacology , Carbapenems/therapeutic use , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria/drug effects , Gram-Negative Bacterial Infections/drug therapy , Cohort Studies , Female , Gram-Negative Bacterial Infections/epidemiology , Gram-Negative Bacterial Infections/microbiology , Humans , Infant, Newborn , Intensive Care Units, Neonatal , Male , Retrospective Studies
5.
Lipids ; 43(5): 467-70, 2008 May.
Article in English | MEDLINE | ID: mdl-18350327

ABSTRACT

Renal handling of major HDL components was studied by analyzing urine from patients with Fanconi syndrome, a rare renal proximal tubular reabsorption failure, including dysfunction of the kidney HDL receptor, cubilin. A high urinary excretion of apolipoprotein A-I and A-IV corresponding to a major part of the metabolism of these proteins was measured. In contrast, no urinary excretion of apolipoprotein A-II which is more hydrophobic and tighter bound to HDL was found. Control urines displayed absence of the three apolipoproteins. Urinary excretion of phospholipids, triglycerides, cholesterol and cholesterol esters in patients was as low as in controls. In conclusion, these data indicate that the human kidney is a major site for filtered nascent apolipoprotein A-I and A-IV but not for HDL particles.


Subject(s)
Apolipoprotein A-II/metabolism , Apolipoprotein A-I/metabolism , Apolipoproteins A/metabolism , Kidney/physiology , Fanconi Syndrome/metabolism , Fanconi Syndrome/physiopathology , Fanconi Syndrome/urine , Humans , Immunohistochemistry , Kidney/metabolism , Kidney/physiopathology , Kidney Tubules, Proximal/metabolism
6.
J Clin Invest ; 110(1): 35-42, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12093886

ABSTRACT

The ABC transporter ABCA1 plays a key role in the first steps of the reverse cholesterol transport pathway by mediating lipid efflux from macrophages. Previously, it was demonstrated that human ABCA1 overexpression in vivo in transgenic mice results in a mild elevation of plasma HDL levels and increased efflux of cholesterol from macrophages. In this study, we determined the effect of overexpression of ABCA1 on atherosclerosis development. Human ABCA1 transgenic mice (BAC(+)) were crossed with ApoE(-/-) mice, a strain that spontaneously develop atherosclerotic lesions. BAC(+)ApoE(-/-) mice developed dramatically smaller, less-complex lesions as compared with their ApoE(-/-) counterparts. In addition, there was increased efflux of cholesterol from macrophages isolated from the BAC(+)ApoE(-/-) mice. Although the increase in plasma HDL cholesterol levels was small, HDL particles from BAC(+)ApoE(-/-) mice were significantly better acceptors of cholesterol. Lipid analysis of HDL particles from BAC(+)ApoE(-/-) mice revealed an increase in phospholipid levels, which was correlated significantly with their ability to enhance cholesterol efflux.


Subject(s)
ATP-Binding Cassette Transporters/metabolism , Arteriosclerosis/prevention & control , ATP Binding Cassette Transporter 1 , ATP-Binding Cassette Transporters/genetics , Animals , Apolipoprotein A-I/blood , Apolipoproteins A/blood , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Arteriosclerosis/etiology , Arteriosclerosis/metabolism , Arteriosclerosis/pathology , Biological Transport, Active , Cholesterol/metabolism , Humans , Lipoproteins, HDL/blood , Macrophages/metabolism , Mice , Mice, Knockout , Mice, Transgenic , Phospholipids/blood , Tissue Distribution
7.
Rev. científica memoria del posgrado. ; 3(1): 37-41, 2022. ilus.
Article in Spanish | LILACS | ID: biblio-1401894

ABSTRACT

OBJETIVO. Determinar la asociación que existe entre las valoraciones de la articulación atlantooccipital durante la valoración preanestésica y la valoración del Cormack Lehane durante la intubación para predecir una vía aérea difícil en el paciente pediátrico de 0 a 12 años de edad que ingresaron a quirófano del Hospital Municipal Boliviano Holandés en los meses de agosto a octubre de la Gestión 2017. MATERIAL Y METODOS. Es un diseño observacional descriptivo de corte transversal, en 70 pacientes de 0 a 12 años de edad que siguiendo criterios estrictos de inclusión se evaluó la clasificación de vía aérea difícil pediátrica analizando la concordancia entre la asociación de la valoración de la articulación atlantooccipital con la escala de Cormack-Lehane. RESULTADOS. Se evaluaron pacientes entre 0 a 12 años, la Escala de Bellhouse Dore encontrada fue Grado I 39%, Grado III 29%, Grado II 24% y Grado IV 8% y el Cormack Lehane encontrado es grado I 39%, grado III 29%, grado II 24% y el grado IV 8%. La asociación de ambas escalas determinó como predictor de vía aérea normal al 63%, potencialmente difícil 29% y vía aérea difícil 8%. CONCLUSIÓN. Existe asociación entre las valoraciones de la articulación atlantooccipital durante la valoración preanestesica y la valoración del Cormack Lehane durante la intubación como predictor de una vía aérea difícil en el paciente pediátrico de 0 a 12 años de edad.


OBJECTIVE. To determine the association that exists between the assessments of the atlanto-occipital joint during the preanesthetic assessment and the assessment of the Cormack Lehane during intubation to predict a difficult airway in pediatric patients aged 0 to 12 who were admitted to the Municipal Boliviano Holandés Hospital in the months of August to October of the Management 2017. MATERIAL AND METHODS. It is an observational descriptive crosssectional design, in 70 patients from 0 to 12 years of age who, following strict inclusion criteria, evaluated the classification of pediatric difficult airway, analyzing the concordance between the association of the atlanto-occipital joint assessment with the Cormack-Lehane scale. RESULTS. Patients between 0 to 12 years old were evaluated, the Bellhouse Dore Scale found was Grade I 39%, Grade III 29%, Grade II 24% and Grade IV 8% and the Cormack Lehane found is grade I 39%, grade III 29 %, grade II 24% and grade IV 8%. The association of both scales determined a 63% normal airway as a predictor, 29% potentially difficult and 8% difficult airway. CONCLUSION. There is an association between the assessments of the atlanto-occipital joint during the pre-anesthetic assessment and the assessment of the Cormack Lehane during intubation as a predictor of a difficult airway in pediatric patients 0 to 12 years of age.


Subject(s)
Humans , Atlanto-Occipital Joint
8.
Arterioscler Thromb Vasc Biol ; 24(3): 504-10, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14707038

ABSTRACT

OBJECTIVE: Uptake of modified low-density lipoprotein (LDL) by macrophages through scavenger receptors results in lipid droplets accumulation and foam cell formation. Excess lipid deposition in macrophages has been reported to modulate expression of several genes including adipophilin. In this study, we investigated the function of adipophilin in lipid accumulation and cholesterol efflux in THP-1 macrophages. METHODS AND RESULTS: Adipophilin mRNA expression was 3.5-fold higher in human atherosclerotic plaques compared with healthy areas of the same arteries. Moreover, in the presence of acetylated LDL (AcLDL), triglycerides and cholesteryl esters were increased in macrophages overexpressing adipophilin by 40% and 67%, respectively, whereas their accumulation was reduced when endogenous cellular adipophilin was depleted using siRNA approach. In addition, neither overexpression nor downregulation of adipophilin altered expression of genes involved in lipid efflux. However, the affinity and the number of AcLDL receptors were not affected. After 24-hour incubation of lipid-loaded macrophages with apolipoprotein A-I, cholesterol efflux was reduced by 47% in adipophilin transfected cells versus control cells. CONCLUSIONS: Our results showed that stimulation of adipophilin expression in macrophages by modified LDL promotes triglycerides and cholesterol storage and reduces cholesterol efflux. Therefore, adipophilin might contribute, in vivo, to lipid accumulation in the intima of the arterial wall.


Subject(s)
Carotid Artery Diseases/metabolism , Lipid Metabolism , Macrophages/drug effects , Peptides/physiology , Apolipoprotein A-I/pharmacology , Carotid Artery Diseases/etiology , Carotid Artery Diseases/surgery , Cell Differentiation/drug effects , Cell Line/drug effects , Cell Line/metabolism , Cholesterol/metabolism , Cholesterol Esters/metabolism , DNA, Complementary/genetics , Endarterectomy, Carotid , Foam Cells/metabolism , Gene Silencing , Humans , Lipoproteins, LDL/pharmacology , Macrophages/metabolism , Membrane Proteins , Monocytes/drug effects , Peptides/genetics , Perilipin-2 , RNA, Messenger/biosynthesis , RNA, Small Interfering/pharmacology , Receptors, Immunologic/metabolism , Receptors, Scavenger , Tetradecanoylphorbol Acetate/pharmacology , Transfection , Triglycerides/metabolism
9.
Arterioscler Thromb Vasc Biol ; 24(4): 756-61, 2004 Apr.
Article in English | MEDLINE | ID: mdl-14751811

ABSTRACT

OBJECTIVE: Expression of human apolipoprotein (h-apo) A-IV in apoE-deficient (apoE(0)) mice (h-apoA-IV/E(0)) reduces susceptibility to atherosclerosis. Chronic infection mimicked by exposure to lipopolysaccharide (LPS) increases the size of atherosclerosis lesions in apoE(0) mice. Thus, we used h-apoA-IV/E(0) mice to determine whether h-apoA-IV plays a protective role after LPS administration. METHODS AND RESULTS: We injected apoE(0), h-apoA-IV/E(0), and C57Bl/6 (wild-type) mice intraperitoneally with either LPS or phosphate-buffered saline (PBS) every week for 10 weeks. Atherosclerotic lesions were significantly smaller in h-apoA-IV/E(0) mice treated with LPS than in their apoE(0) counterparts. The titers of IgG2a and IgG2b autoantibodies to oxidized low-density lipoprotein (LDL) were higher in the LPS-group of h-apoA-IV/E(0) mice than in apoE(0) mice, suggesting that the Th1 response is stronger in the presence of h-apoA-IV. Lymphocytes from the blood, liver, spleen, and thymus of h-apoA-IV/E(0) mice treated with LPS produced less IL-4, INF-gamma, and TNF-alpha proinflammatory cytokines than their apoE(0) counterparts. Furthermore, we demonstrated that recombinant h-apoA-IV blocks the LPS-induced stimulation of monocytes. CONCLUSIONS: The expression of h-apoA-IV in apoE(0) mice reduces the susceptibility to atherogenesis and decreases the secretion of proinflammatory cytokines after LPS administration.


Subject(s)
Apolipoproteins A/physiology , Arteriosclerosis/prevention & control , Cytokines/metabolism , Animals , Apolipoproteins A/genetics , Apolipoproteins E/deficiency , Apolipoproteins E/genetics , Arteriosclerosis/blood , Arteriosclerosis/genetics , Arteriosclerosis/pathology , Autoantibodies/blood , Autoantibodies/immunology , Blood Cells/metabolism , Cytokines/biosynthesis , Humans , Infections , Lipids/blood , Lipopolysaccharides/pharmacology , Lipopolysaccharides/toxicity , Lipoproteins, LDL/immunology , Liver/metabolism , Liver/pathology , Lymphocyte Subsets/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Animal , Monocytes/drug effects , Monocytes/physiology , Recombinant Fusion Proteins/physiology , Spleen/metabolism , Spleen/pathology , Thymus Gland/metabolism , Thymus Gland/pathology
10.
FEBS Lett ; 572(1-3): 294-8, 2004 Aug 13.
Article in English | MEDLINE | ID: mdl-15304365

ABSTRACT

We have generated transgenic rabbits that express the entire human apoA-I/C-III/A-IV gene cluster. As in humans, h-apoA-I and h-apoC-III were expressed in liver and intestine, whereas h-apoA-IV mRNA was detected in intestine only. Transgenic rabbits had significantly higher plasma total cholesterol, HDL-cholesterol and total phospholipid concentrations than non-transgenic littermates. In contrast to similar transgenic mice previously generated, which have gross hypertriglyceridemia, triglyceride concentrations were only moderately raised in transgenic rabbits. Plasma and HDL from transgenic rabbits were more effective than those from controls in promoting cholesterol efflux from cultured hepatoma cells. They had lower LCAT, lower CETP and higher PLTP activities than non-transgenic littermates. Cholesterol-feeding produced major increases in plasma lipids. The qualitative response to the diet was not modified by cluster expression. Human apoA-I concentration was halved by cholesterol-feeding, whereas h-apoC-III and h-apoA-IV concentrations were not significantly altered. Cholesterol efflux from hepatoma cells to plasma and HDL was not altered by the diet. Since lipoprotein metabolism of rabbits closely resembles that of humans, human apoA-I/C-III/A-IV transgenic rabbits may provide a reliable model for studies of the transcriptional regulation of the cluster, and for evaluating the effects of different agents on the expression of the three genes.


Subject(s)
Apolipoprotein A-I/genetics , Apolipoproteins A/genetics , Apolipoproteins C/genetics , Cholesterol, Dietary/pharmacology , Gene Expression Regulation/genetics , Animal Feed , Animals , Animals, Genetically Modified , Apolipoprotein C-III , Carcinoma, Hepatocellular , Cholesterol/blood , Diet , Gene Expression Regulation/drug effects , Humans , Intestinal Mucosa/metabolism , Liver/metabolism , Liver Neoplasms , Mice , Multigene Family , Organ Specificity , RNA, Messenger/genetics , Rabbits
11.
FEBS Lett ; 557(1-3): 39-44, 2004 Jan 16.
Article in English | MEDLINE | ID: mdl-14741338

ABSTRACT

Various studies have correlated apolipoprotein (apo) A-I, the major component high-density lipoprotein, with protection against development of cardiovascular disease. Although apoA-I expression has been previously detected in the liver and intestine, we have discovered that the human apoA-I gene is also expressed in the heart. Using transgenic (Tg) mice generated with the human apoA-I/C-III/A-IV gene cluster and Tg mice produced with just the 2.2 kb human apoA-I gene, we have detected significant levels of apoA-I expression in the heart. Furthermore, the detection of apoA-I expression in the hearts of human apoA-I Tg mice indicates that the minimal regulatory elements necessary for cardiac expression of the gene are located near its coding sequence. To determine if the apoA-I gene is also expressed in the human heart, similar analyses were performed, where apoA-I expression was found in both adult and fetal hearts. Furthermore in-depth investigation of the various regions of human and Tg mouse hearts revealed that the apoA-I mRNA was present in the ventricles and atria, but not in the aorta. In situ hybridization of Tg mouse hearts revealed that apoA-I expression was restricted to the cardiac myocyte cells. Finally, heart explants and cardiac primary culture experiments with Tg mice showed secretion of particles containing the human apoA-I protein, and metabolic labeling experiments have also detected a 28 kDa human apoA-I protein secreted from the heart. From these novel findings, new insights into the role and function of apoA-I can be extrapolated.


Subject(s)
Apolipoprotein A-I/genetics , Heart/metabolism , Myocardium/metabolism , Animals , Apolipoprotein A-I/metabolism , Base Sequence , DNA Primers , Gene Expression Regulation, Enzymologic , Humans , Mice , Mice, Inbred C57BL , Mice, Transgenic , Polymerase Chain Reaction , RNA, Messenger/genetics
12.
Am J Clin Nutr ; 75(3): 484-91, 2002 Mar.
Article in English | MEDLINE | ID: mdl-11864853

ABSTRACT

BACKGROUND: The fatty acid content and saturation degree of the diet can modulate HDL composition and cholesterol efflux. OBJECTIVE: We studied the modifications in plasma lipoprotein particles and serum capacity to stimulate cholesterol efflux induced by different fatty acids. DESIGN: Seventeen women and 24 men followed in the same sequence 4 diets containing 35% of total energy as fat. The saturated fat diet contained 17% palm oil; the monounsaturated fat diet, 20.9% olive oil; the n-6 polyunsaturated fat diet, 12.5% sunflower oil; and the n-3 polyunsaturated fat diet, sunflower oil supplemented with 4-4.5 g fish oil/d. Each phase lasted 4-5 wk. RESULTS: In both sexes, apolipoprotein (apo) A-I concentrations were significantly lower with unsaturated fat diets than with the saturated fat diet, but concentrations of lipoproteins containing only apo A-I (Lp A-I) were lower only in the men. Concentrations of lipoproteins containing both apo A-I and apo A-II (Lp A-I:A-II) were lower with both polyunsaturated fat diets in the women but significantly higher in the men. Lp E concentrations were significantly higher with the 2 polyunsaturated fat diets. Lp E non-B particle concentrations were not modified in the men but were significantly higher in the women in both polyunsaturated fat phases. Lp C-III concentrations were higher with the saturated fat diet only in the men. The serum samples taken after the n-3 polyunsaturated fat phase were the most efficient for extracting cellular cholesterol in both sexes. CONCLUSIONS: The monounsaturated and polyunsaturated fat diets were healthier, producing a better lipid profile. The n-3 polyunsaturated fat diet increased the capacity of serum to promote the efflux of cholesterol from cells in culture.


Subject(s)
Apolipoproteins/blood , Cardiovascular Diseases/etiology , Cholesterol/metabolism , Dietary Fats/administration & dosage , Lipids/blood , Lipoproteins, HDL/blood , Apolipoproteins/analysis , Cardiovascular Diseases/blood , Cardiovascular Diseases/epidemiology , Cells, Cultured , Cross-Over Studies , Diet , Dietary Fats, Unsaturated/administration & dosage , Fatty Acids/administration & dosage , Fatty Acids, Monounsaturated/administration & dosage , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-6 , Fatty Acids, Unsaturated/administration & dosage , Female , Humans , Incidence , Lipoproteins, HDL/analysis , Male , Middle Aged , Patient Compliance , Plant Oils/administration & dosage , Sex Characteristics , Spain/epidemiology
13.
Atherosclerosis ; 166(1): 31-40, 2003 Jan.
Article in English | MEDLINE | ID: mdl-12482548

ABSTRACT

Scavenger receptor class B, type I (SR-BI) mediates the selective uptake of high-density lipoprotein- (HDL-) associated cholesteryl esters (CE), i.e. lipid uptake independent from HDL holo-particle internalisation. This pathway contributes to the HDL-mediated CE delivery to the liver. From human plasma HDL, two major lipoprotein subfractions can be isolated: one contains apolipoprotein (apo) A-I and apo A-II (LpA-I:A-II) as dominant protein components, whereas in the other population apo A-II is absent (LpA-I). In this investigation the role of SR-BI in selective CE uptake from HDL, LpA-I and LpA-I:A-II was explored. HDL(3) (d=1.125-1.21 g/ml), LpA-I and LpA-I:A-II were isolated from human plasma and radiolabeled in the protein (125I) as well as in the CE moiety ([3H]). Baby hamster kidney (BHK) cells were stably transfected with the full-length human SR-BI cDNA and these cells demonstrate SR-BI expression in immunoblots. In contrast, no SR-BI protein was detectable in control BHK cells (vector). To investigate lipoprotein uptake, cells incubated (37 degrees C, 4 h) in medium containing radiolabeled HDL(3), LpA-I or LpA-I:A-II and finally cellular tracer content was determined. For both types of BHK cells, the rate of apparent lipoprotein particle uptake according to the lipid tracer ([3H]) was in substantial excess over that due to the protein tracer (125I) demonstrating selective CE uptake ([3H]-(125)I) from HDL(3), LpA-I and LpA-I:A-II. SR-BI expression increased cellular selective CE uptake from labeled HDL(3) up to 24-fold. In BHK cells without SR-BI expression, selective CE uptake was higher from LpA-I compared with LpA-I:A-II. Analogously, in BHK cells with SR-BI expression, the rate of selective CE uptake was higher from LpA-I compared with LpA-I:A-II. In summary, SR-BI significantly increases selective CE uptake from HDL(3), LpA-I and LpA-I:A-II. Concerning HDL subfractions, the rate of SR-BI-mediated selective CE uptake is greater from LpA-I compared with LpA-I:A-II and this result suggests that SR-BI preferentially facilitates the CE transfer from LpA-I lipoprotein particles to cells.


Subject(s)
Apolipoprotein A-II/metabolism , Apolipoprotein A-I/metabolism , CD36 Antigens/metabolism , Cholesterol Esters/metabolism , Kidney/metabolism , Membrane Proteins , Receptors, Immunologic , Receptors, Lipoprotein/metabolism , Animals , Cells, Cultured , Cricetinae , Receptors, Scavenger , Scavenger Receptors, Class B
14.
Metabolism ; 53(10): 1262-7, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15375780

ABSTRACT

It is widely accepted that aerobic physical activity is associated with a less atherogenic lipid and lipoprotein profile and, consequently, with a reduced cardiovascular risk. Both cross-sectional studies and prospective-interventional trials show that the most frequent modification observed consists of a slight but significant increase in high-density lipoprotein cholesterol (HDL-C) levels. Nevertheless, only few studies made an attempt to elucidate if this quantitative modification was accompanied by an improvement in any of HDL antiatherogenic functions. The purpose of this study was to evaluate the main steps of reverse cholesterol transport, the best known antiatherogenic function performed by HDL, in a group of well-trained soccer players (n = 35) in comparison to sedentary controls (n = 15). Average HDL-C levels were 12.5% higher in the sportsmen, in large part because of greater HDL2-C concentration. No statistically significant differences were observed in the other lipid- and lipoprotein-related parameters. The capacity to promote cholesterol efflux from Fu5AH cells was significantly higher in the soccer players than in the control individuals (20.5% +/- 0.4% v 15.9% +/- 1.2%, respectively, P < .001). However, lecithin:cholesterol acyltransferase (LCAT; 2.6 +/- 0.9 v 1.4 +/- 0.3%/mL.h, respectively) and cholesteryl ester transfer protein (CETP; 69.5 +/- 8.3 v 62.7 +/- 14.8%/mL.h, respectively) activities did not reach statistically significant difference between both groups. Correlation analysis showed that cholesterol efflux induced by serum samples was directly related to HDL-C (r = 0.59, P < .001), HDL2-C (r = 0.37, P < .01), and lipoprotein (Lp)A-I (r = 0.44, P < .05). On the other hand, negative correlations were observed with waist/hip ratio (r = -0.36, P < .05), low-density lipoprotein cholesterol (LDL-C; r = -0.33, P < .05), apolipoprotein B (apo B; r = -0.42, P < .05), and LpA-I;A-II (r = -0.51, P < .005). In conclusion, the well-known cardioprotective benefit of regular exercise could be based, at least in part, on a less atherogenic lipid and lipoprotein profile and an enhanced cellular cholesterol efflux.


Subject(s)
Cholesterol/blood , Physical Fitness/physiology , Soccer/physiology , Adolescent , Adult , Animals , Apolipoproteins/blood , Apolipoproteins/metabolism , Biological Transport, Active , Carcinoma, Hepatocellular/metabolism , Carrier Proteins/metabolism , Cholesterol Ester Transfer Proteins , Glycoproteins/metabolism , Humans , Lipoproteins/blood , Lipoproteins/metabolism , Male , Phosphatidylcholine-Sterol O-Acyltransferase/metabolism , Rats , Tumor Cells, Cultured
15.
Metabolism ; 51(11): 1410-7, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12404190

ABSTRACT

Thirty healthy postmenopausal women were randomized into 2 groups that received a sequential combined hormone-replacement therapy (HRT) (n = 18; conjugated equine estrogen 0.625 mg/d for 28 days and 5 mg of medroxyprogesterone acetate during the last 14 days) or placebo (n = 12). Plasma samples were collected before and during treatment (days 0, 15, 43, 71). High-density lipoprotein (HDL) lipid content, lipoprotein (Lp)A-I and LpA-I:LpA-II concentration, lecithin:cholesterol acyl transferase activity (LCAT), phospholipid transfer protein (PLTP) activity, and the plasma capacity to carry out cholesterol efflux from Fu5AH cells were measured. Most significant changes were found within the first 15 days after HRT. After 71 days of HRT, we found an increase in LpA-I lipoparticles (27%) and the following HDL lipids: phospholipids (21%), triglycerides (45%), and free cholesterol (43%), as well as an increase in cholesterol efflux (12.5%). PLTP activity, on the other hand, decreased 21% after 71 days of treatment. No significant changes in LCAT activity, HDL-cholesterol ester or LpA-I:LpA-II particles were found. Positive correlation between cholesterol efflux and the variables LpA-I and HDL-phospholipids were observed. PLTP was negatively correlated with apolipoprotein (apo) A-I, LpA-I, and LpA-I:LpA-II. In summary, our study, performed during 3 hormonal cycles, shows that HRT not only modifies HDL-cholesterol level, but also its lipid composition and HDL lipoparticle distribution. HRT enhances the plasma capacity to carry out cholesterol efflux from the Fu5AH system and decreases the activity of PLTP, a key protein regulating HDL levels. Considering the protocol sampling, these results represent mainly the estrogenic effect of HRT.


Subject(s)
Cholesterol, HDL/blood , Estrogen Replacement Therapy/methods , Estrogens, Conjugated (USP)/administration & dosage , Medroxyprogesterone/administration & dosage , Postmenopause/blood , Double-Blind Method , Drug Administration Schedule , Female , Humans , Lipids/blood , Middle Aged
16.
Arch Med Res ; 35(3): 235-40, 2004.
Article in English | MEDLINE | ID: mdl-15163466

ABSTRACT

BACKGROUND: Previous studies have shown that high density lipoprotein (HDL)-deficient states are associated with reduced paraoxonase 1 (PON1) activity. However, HDL reduction caused by primary hypertriglyceridemia has not been fully explored. The aim of the present study was to evaluate whether PON1 and platelet-activating factor acetylhydrolase (PAF-AH), two antioxidant enzymes, were altered in patients with low HDL-cholesterol levels with or without primary hypertriglyceridemia in comparison with control normolipemic subjects. METHODS: We studied 24 patients with low HDL-cholesterol levels with (n=12) or without (n=12) primary hypertriglyceridemia in comparison with 12 control subjects who presented normal HDL-cholesterol and triglyceride levels. Paraoxon and phenylacetate were used as substrate for measuring PON1 activities and 1-hexadecyl-2-[3H]acetyl-glycero-3-phosphocholine for platelet-activating factor acetylhydrolase (PAF-AH) activity. Double substrate method was used to assign phenotypes. Lipid, lipoprotein, apolipoprotein, and lipoprotein particles were determined by standardized methods. RESULTS: Both PON1 activities were significantly reduced in patients with low HDL-cholesterol levels. This reduction could be selectively attributed to the hypertriglyceridemic subgroup. PAF-AH activity was not different between hypoalphalipoproteinemic patients and controls. PON1 activities correlated positively and significantly with HDL-cholesterol, HDL2-cholesterol, HDL3-cholesterol, HDL-phospholipids, apo A-I, apo A-II, and LpA-I:A-II. PAF-AH correlated positively and significantly with total and low density lipoprotein-cholesterol. CONCLUSIONS: Data from this study would suggest that in hypoalphalipoproteinemic syndrome, particularly when associated with hypertriglyceridemia, there is impairment in enzymatic antioxidant activity exclusively related with HDL.


Subject(s)
1-Alkyl-2-acetylglycerophosphocholine Esterase/physiology , Aryldialkylphosphatase/physiology , Cholesterol, HDL/metabolism , Hypertriglyceridemia/pathology , Adult , Aged , Antioxidants/pharmacology , Cholesterol, LDL/metabolism , Humans , Lipid Metabolism , Lipoproteins/metabolism , Male , Middle Aged , Phenotype , Time Factors
17.
Arch. argent. pediatr ; 117(1): 6-11, feb. 2019. tab
Article in English, Spanish | LILACS, BINACIS | ID: biblio-983770

ABSTRACT

Introducción. Las infecciones por bacilos Gram-negativos multirresistentes (BGN-MR) constituyen un problema creciente en las unidades de cuidado intensivo neonatal. El objetivo del estudio fue conocer las características epidemiológicas, clínicas, microbiológicas, evolutivas y los factores de riesgo de infección por BGN-MR resistentes a carbapenemes en el Servicio de Neonatología de un hospital de alta complejidad. Población y método. Se realizó un estudio de cohorte retrospectivo en dicho Servicio, donde se incluyeron los pacientes con infección documentada por BGN-MR del 24/4/2013 al 29/4/2015. Resultados. Se incluyeron 21 pacientes. La mediana de edad gestacional y peso de nacimiento fue 35 semanas y 2070 gramos, respectivamente. Dieciocho pacientes (86 %) tuvieron hemocultivos positivos y el aislamiento microbiológico más frecuente fue Acinetobacter baumannii (17 pacientes, 81 %), seguido por Klebsiella pneumoniae productora de carbapenemasa (3 pacientes, 14 %) y Enterobacter cloacae (1 paciente, 5 %). La mediana de edad al momento del diagnóstico fue de 28 días y todos tenían factores de riesgo para la infección, como cirugía, asistencia respiratoria mecánica, nutrición parenteral, catéter central y antibióticos. El tratamiento antibiótico definitivo fue colistina en todos los casos, combinado en el 84 %. Cinco pacientes (24 %) fallecieron por la infección. La prematurez y el peso < 2000 g fueron factores de riesgo estadísticamente significativos asociados a la mortalidad (p = 0,03 y 0,01, respectivamente). Conclusión. Las infecciones por BGN-MR se presentaron en pacientes con factores predisponentes. Acinetobacter baumannii fue el primer agente etiológico. La mortalidad fue elevada y relacionada con prematurez y bajo peso al nacer.


Introduction. Multidrug resistant Gramnegative (MDRGN) infections are an increasing problem in neonatal intensive care units. The objective of this study was to establish the epidemiological, clinical, microbiological, and evolutionary characteristics of carbapenem-resistant MDRGN infections and the risk factors for them at the Division of Neonatology of a tertiary care hospital. Population and method. A retrospective cohort study was done in this Division in patients with a documented MDRGN infection between 4/24/2013 and 4/29/2015. Results. Twenty-one patients were included. Their median gestational age and birth weight were 35 weeks and 2070 g, respectively. Eighteen patients (86 %) had a positive blood culture; the most commonly isolated microorganism was Acinetobacter baumannii (17 patients, 81 %), followed by carbapenemase-producing Klebsiella pneumoniae (3 patients, 14 %) and Enterobacter cloacae (1 patient, 5 %). The median age at diagnosis was 28 days and all patients had risk factors for infection, including surgery, assisted mechanical ventilation, parenteral nutrition, central venous line, and antibiotics. The definite antibiotic therapy included colistin in all cases; in combination, in 84 %. Five patients (24 %) died due to the infection. Prematurity and a birth weight < 2000 g were statistically significant risk factors associated with mortality (p = 0.03 and 0.01, respectively). Conclusion. MDRGN infections were observed in patients with predisposing factors. Acinetobacter baumannii was the main etiologic agent. Mortality was high and related to prematurity and a low birth weight.


Subject(s)
Humans , Male , Female , Infant, Newborn , Gram-Negative Bacterial Infections/metabolism , Gram-Negative Bacterial Infections/drug therapy , Gram-Negative Bacterial Infections/epidemiology , Epidemiology, Descriptive , Retrospective Studies , Drug Resistance, Multiple, Bacterial , Gram-Negative Bacteria/metabolism
18.
Arch Argent Pediatr ; 111(3): e78-81, 2013 Jun.
Article in Spanish | MEDLINE | ID: mdl-23732360

ABSTRACT

Ophthalmic compromise is infrequent in children with congenital Chagas disease. We present 3 patients under 2 months of age, with ocular involvement, all of them referred to the hospital for ophthalmic evaluation of the premature newborn. The ophthalmic finding was bilateral severe vitreitis (posterior uveitis) related to Chagas disease. They received antiparasitic therapy with a good outcome in all cases. Chagas disease must be considered as differential diagnosis of ocular pathology in those countries where the pathology is endemic, and fundoscopic evaluation must be done in those children with the diagnosis, especially those symptomatic and prematurely born.


Subject(s)
Chagas Disease/congenital , Chagas Disease/complications , Diseases in Twins/congenital , Diseases in Twins/complications , Uveitis/parasitology , Chagas Disease/diagnosis , Chagas Disease/drug therapy , Diseases in Twins/diagnosis , Diseases in Twins/drug therapy , Female , Humans , Infant , Uveitis/diagnosis , Uveitis/drug therapy
20.
Arch Argent Pediatr ; 110(1): e9-12, 2012.
Article in Spanish | MEDLINE | ID: mdl-22307432

ABSTRACT

Orbital cellulitis typically occurs in older children, but it can occasionally affect infants and neonates. Staphylococcus aureus is the main pathogen isolated. Outcome depends on an adequate initial approach. We report three neonates with orbital cellulitis caused by community-associated MRSA.


Subject(s)
Methicillin-Resistant Staphylococcus aureus , Orbital Cellulitis/microbiology , Staphylococcal Infections , Community-Acquired Infections/microbiology , Humans , Infant, Newborn , Male
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