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Background: Hearing loss, occurring in 1-3/1,000 newborns in the well-babies population, is one of the most common congenital diseases, and hearing screening at birth still represents the only means for its early detection. Since 2011 the Emilia Romagna Regional Health Agency has recommended Newborn Hearing Screening for all babies at its birth points and for newborns moving to the region. The aims of this study are to analyze the results of this regional-based Newborn Hearing Screening program and to discuss the impact of the legislative endorsement on the organization. Material and methods: This is an observational retrospective chart study. The recordings of well-babies and babies at Neonatal Intensive Care Units were collected during the period from January 1st 2015 to December 31st 2020. The following data were included: Newborn Hearing Screening coverage, percentage of refer at otoacoustic emissions, prevalence and entity of hearing loss, unilateral/bilateral rate, presence of audiological risk factors. Results: More than 99% of a total of 198,396 newborns underwent the Newborn Hearing Screening test during the period January 1st 2015 to December 31st 2020, with a coverage ranging between 99.6% and 99.9%. Overall, the percentage of confirmed hearing loss cases was about 17-30 % of refer cases, 745 children received a diagnosis of hearing loss (prevalence 3.7/1,000). Considering profound hearing loss cases, these represent 13% of bilateral hearing loss. Conclusion: A regional-based Newborn Hearing Screening program is valuable and cost-effective. In our experience, the centralization of the data system and of the data control is crucial in order to implement its efficiency and effectiveness. Healthcare policies, tracking systems and public awareness are decisive for a successful programme implementation.
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Potenciales Evocados Auditivos del Tronco Encefálico , Pérdida Auditiva , Lactante , Niño , Recién Nacido , Humanos , Estudios Retrospectivos , Pérdida Auditiva/diagnóstico , Pérdida Auditiva/epidemiología , Pruebas Auditivas/métodos , Emisiones Otoacústicas Espontáneas , Tamizaje Neonatal/métodosRESUMEN
BACKGROUND: Alterations in thyroid function and structure have been reported in obesity. Function reverses to normal after weight loss, but nothing is known about structure. AIM: To evaluate the effect of weight loss on thyroid function and structure in obese children. SUBJECTS AND METHODS: The study was conducted in 72 overweight and obese children. Measurement of free T(3) (fT(3)), free T4 (fT(4)), TSH, antithyroid- antibodies and a thyroid ultrasound was performed at the beginning (phase 1) and after a period of 1.8±1.0 yr of lifestyle intervention (phase 2). RESULTS: Height SD score (SDS), body mass index SDS, total fat mass did not change from phase 1 to phase 2. Percentage of fat free mass decreased significantly (p<0.05). Waist/height ratio decreased (0.6±0.1 vs 0.5±0.1; p<0.05) as well as waist/hip ratio (0.9±0.1 vs 0.8±0.1; p<0.05). In phase 1, TSH was 2.8±1.7 mU/l; in phase 2, it was 2.2±0.9 mU/l (p<0.05); 17.2% of children showed a TSH level above the normal range (3.6 mU/l) in phase 1, and 6.2% in phase 2 (p<0.05). fT(4) was 10.8±2.2 pg/ml in phase 1 and 10.7±1.9 pg/ml in phase 2. fT(3) was 4.4±1.3 pg/ml (phase 1) and 3.9±1.1 pg/ml (phase 2) (p<0.05). Thyroid volume was -0.5±0.8 SDS (phase 1) and -0.5±1 SDS (phase 2). A non-significant improvement in thyroid structure was observed. CONCLUSIONS: In conclusion, healthier lifestyle improves body composition, thyroid function, and structure.
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Composición Corporal , Estilo de Vida , Obesidad/terapia , Glándula Tiroides/anatomía & histología , Glándula Tiroides/fisiología , Programas de Reducción de Peso/métodos , Adolescente , Autoanticuerpos/sangre , Niño , Femenino , Humanos , Masculino , Obesidad/patología , Obesidad/fisiopatología , Sobrepeso/patología , Sobrepeso/fisiopatología , Sobrepeso/terapia , Evaluación de Programas y Proyectos de Salud , Tirotropina/sangre , Tiroxina/sangre , Resultado del Tratamiento , Triyodotironina/sangre , Programas de Reducción de Peso/organización & administraciónRESUMEN
BACKGROUND: Health behavior change interventions delivered by social media allow for real-time, dynamic interaction, peer social support, and experimenter-provided content. AIMS: We tested the feasibility, acceptability, and preliminary efficacy of a novel Twitter-based walking break intervention with daily behavior change strategies and prompts for social support, combined with a Fitbit, vs. Fitbit alone. METHODS: In a 2-group pilot, 45 sedentary women from a heart clinic were randomized to Twitter + Fitbit activity tracker (Tweet4Wellness, n = 23) or Fitbit-only (control, n = 22). All received a Fitbit and 13 weeks of tailored weekly step goals. Tweet4Wellness consisted of a private Twitter support group, with daily automated behavior change "tweets" informed by behavior change theory, and encouragement to communicate within the group. Feasibility outcomes included recruitment and enrollment numbers, implementation challenges, and number and type of help requests from participants throughout the study period. Preliminary efficacy outcomes provided by Fitbit data were sedentary minutes, number of hours with >250 steps, maximum sitting bout, weighted sedentary median bout length, total steps, intensity minutes (>3.0 METS), and ratio of time spent sitting-to-moving. Acceptability outcomes included level of Twitter participation within Tweet4Wellness, and Likert scale plus open-ended survey questions on enjoyment and perceived effectiveness of intervention components. Survey data on acceptability of the features of the intervention were collected at 13 weeks (end-of-treatment [EOT]) and 22 weeks (follow-up). RESULTS: The study was feasible, with addressable implementation challenges. Tweet4Wellness participants changed significantly from baseline to EOT relative to control participants on number of active hours p = .018, total steps p = .028, and ratio of sitting-to-moving, p = .014. Only sitting-to-moving was significant at follow-up (p = .047). Among Tweet4Wellness participants, each tweet sent during treatment was associated with a 0.11 increase in active hours per day (p = .04) and a 292-step increase per day (p < .001). Tweet4Wellness participants averaged 54.8 (SD = 35.4) tweets, totaling 1304 tweets, and reported liking the accountability and peer support provided by the intervention. CONCLUSION: A Twitter-delivered intervention for promoting physical activity among inactive women from a heart clinic was feasible, acceptable, and demonstrated preliminary efficacy in increasing daily active hours, daily total steps, and the ratio of sitting-to-moving from pre to post for the intervention compared with the control. Lessons learned from this pilot suggest that the next study should expand the recruitment pool, refine the intervention to increase group engagement, and select active hours, total steps, and ratio of sitting-to-movement as primary sedentary behavior measures.
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BACKGROUND AND AIM: Hyperfibrinogenemia, a cardiovascular risk factor, is frequent in hypertension and largely unexplained. In this study, we measured fibrinogen production and whole-body protein turnover under both basal and hyperinsulinemic states, in hypertensive [H] and control [C] subjects, using a leucine stable isotope tracer and precursor-product relationships. METHODS AND RESULTS: Since hypertension is often a feature of the "metabolic", insulin resistance syndrome, which in turn affects both fibrinogen kinetics and whole-body protein turnover, we selected hypertensive subjects without the metabolic syndrome. Following basal measurements, an euglycemic, approximately euaminoacidemic, hyperinsulinemic clamp was performed, with plasma insulin raised to 700-900 pmol/L. In H, rates of the fractional and absolute synthesis (FSR and ASR, respectively) of fibrinogen were 30%-40% greater (p<0.05 or less) than in C in both states, whereas leucine turnover was normal. Hyperinsulinemia did not modify fibrinogen synthesis in either group with respect to baseline, whereas it suppressed leucine appearance from endogenous proteolysis by approximately 40% to same extent in both groups. Amino acid clearance was similar in both the H and C subjects. In H, the insulin-mediated glucose disposal (M) was approximately 25% lower, (although insignificantly) than in controls, showing no overall insulin resistance. There was an inverse correlation between M and fibrinogen FSR during the clamp. CONCLUSIONS: In essential hypertension fibrinogen production is increased, is not further stimulated by insulin, and is inversely related to insulin sensitivity at high-physiological insulin concentrations. Amino acid disposal and basal as well as insulin-responsive protein degradation rates are instead normal.
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Fibrinógeno/metabolismo , Hiperinsulinismo/metabolismo , Hipertensión/metabolismo , Insulina/administración & dosificación , Adulto , Biomarcadores/metabolismo , Glucemia/metabolismo , Estudios de Casos y Controles , Deuterio , Fibrinógeno/biosíntesis , Glucosa/administración & dosificación , Técnica de Clampeo de la Glucosa , Humanos , Hiperinsulinismo/sangre , Hipertensión/sangre , Técnicas de Dilución del Indicador , Infusiones Intravenosas , Insulina/sangre , Cinética , Leucina/administración & dosificación , Masculino , Persona de Mediana Edad , Péptido Hidrolasas/metabolismo , Regulación hacia ArribaRESUMEN
Satellite cells are the main source of myogenic progenitors in postnatal skeletal muscle, but their use in cell therapy for muscle disorders is limited because these cells cannot be delivered through circulation and they are rapidly exhausted in severe myopathies. The search for alternative donor cells is ongoing, but none of the candidates so far show all the features required for successful colonization and repair of diseased muscle. In this study, we show that bisperoxovanadium, a phospho-tyrosine phosphatase inhibitor, induces myogenic cells to acquire a gene expression profile and a differentiation potential consistent with the phenotype of a circulating precursors, while maintaining their myogenic potential. These effects are mediated, at least in part, by NF-kappaB activation through the Tyr42-IkappaB-alpha phosphorylation, as shown by the expression of the dominant negative mutant form of the p50 NF-kappaB subunit. Moreover, when bisperoxovanadium-treated cells are injected into the femoral artery of alpha-sarcoglican null dystrophic mice, they are able to circulate and to reach muscle tissue; importantly, they contribute to muscle regeneration, as shown by the expression of alpha-sarcoglican in some fibers. Our observations indicate that bisperoxovanadium, or similar compounds, may prove very valuable to obtain and to expand, from committed cells, multipotent cell populations suitable for gene-cell therapy applications and may help to understand the molecular basis of genome reprogramming and "stem-ness."
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Inhibidores Enzimáticos/farmacología , Corazón/efectos de los fármacos , Miocardio/citología , Células Madre Pluripotentes/citología , Proteínas Tirosina Fosfatasas/antagonistas & inhibidores , Compuestos de Vanadio/farmacología , Animales , Secuencia de Bases , Ciclo Celular , Línea Celular , Cartilla de ADN , Citometría de Flujo , Técnica del Anticuerpo Fluorescente , Expresión Génica , Ratones , Miocardio/metabolismo , Fenotipo , Células Madre Pluripotentes/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Two patients (brother and sister, 41 and 39 yr of age, respectively) have been shown to have marked elevation of plasma triglycerides and chylomicrons, decreased low density lipoproteins (LDL) and high density lipoproteins (HDL), a type I lipoprotein phenotype, and a deficiency of plasma apolipoprotein C-II (apo C-II). The male patient had a history of recurrent bouts of abdominal pain often accompanied by eruptive xanthomas. The female subject, identified by family screening, was asymptomatic. Hepatosplenomegaly was present in both subjects. Analytical and zonal ultracentrifugation revealed a marked increase in triglyceride-rich lipoproteins including chylomicrons and very low density lipoproteins, a reduction in LDL, and the presence of virtually only the HDL3 subfraction. LDL were heterogeneous with the major subfraction of a higher hydrated density than that observed in plasma lipoproteins of normal subjects. Apo C-II levels, quantitated by radioimmunoassay, were 0.13 mg/dl and 0.12 mg/dl, in the male and female proband, respectively. A variant of apo C-II (apo C-IIPadova) with lower apparent molecular weight and more acidic isoelectric point was identified in both probands by two-dimensional gel electrophoresis. The marked hypertriglyceridemia and elevation of triglyceride-rich lipoproteins were corrected by the infusion of normal plasma or the injection of a biologically active synthesized 44-79 amino acid residue peptide fragment of apo C-II. The reduction in plasma triglycerides after the injection of the synthetic apo C-II peptide persisted for 13-20 d. These results definitively established that the dyslipoproteinemia in this syndrome is due to a deficiency of normal apo C-II. A possible therapeutic role for replacement therapy of apo C-II by synthetic or recombinant apo C-II in those patients with severe hypertriglyceridemia and recurrent pancreatitis may be possible in the future.
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Apolipoproteínas C/deficiencia , Lipasa/sangre , Lipoproteínas/sangre , Triglicéridos/sangre , Adulto , Apolipoproteína C-II , Apolipoproteínas C/genética , Apolipoproteínas C/uso terapéutico , Quilomicrones/sangre , Femenino , Variación Genética , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , MasculinoRESUMEN
Erythroid differentiation involves the activation of a number of erythroid-specific genes, most of which, including the globin genes and the erythropoietin receptor (Epo-R) gene, are, at least in part, regulated by the transcription factor GATA-1. In order to understand the relationship, if any, between expression of GATA-1, response to Epo and erythroid differentiation, we analyzed the expression of GATA-1, Epo-R and globin genes in an Epo-dependent human cell line, UT-7 Epo. The results were compared to those obtained with the parental granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell line, UT-7, which has a predominantly megakaryoblastic phenotype and is unable to proliferate continuously in the presence of Epo. UT-7 Epo and UT-7 expressed similar levels of GATA-1 mRNA and binding activity. The two lines also expressed comparable levels of Epo-R mRNA while the number of Epo-binding sites on UT-7 Epo cells was one-sixth the number of UT-7 cells (2400 +/- 3 vs. 13,800 +/- 300). This difference in the number of binding sites could be due to differences in cell surface (UT-7 cells are 20% smaller than the parental UT-7 cells) or in receptor turnover. By Northern analysis, UT-7 cells expressed detectable levels of beta- and gamma-globin but not alpha-globin. In comparison, UT-7 Epo cells expressed alpha-globin and higher levels of gamma-globin (5-fold) and beta-globin (from barely to clearly detectable). Globin chains (alpha, beta and gamma) were clearly detectable by affinity chromatography in UT-7 Epo but not in UT-7 cells. The frequency of the cells which expressed beta- and gamma-globin genes in the two cell populations was measured by immunofluorescence with beta- and gamma-specific antibodies. The number of gamma-positive cells and their fluorescence intensity were higher in UT-7 Epo than in UT-7 cells (0 to 17% barely positive cells and 23 to 40% clearly positive cells, respectively), indicating that the increase in globin mRNA observed in UT-7 Epo is due to both an increase of gene expression per cell and an increase in numbers of cells containing gamma-globin. The levels of GATA-1, Epo-R and globin mRNA expressed were not affected by a 24-hour incubation of either cell line with Epo, GM-CSF or interleukin-3 (IL-3).(ABSTRACT TRUNCATED AT 400 WORDS)
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Células Precursoras Eritroides/citología , Eritropoyetina/farmacología , Northern Blotting , Diferenciación Celular , División Celular , Línea Celular , Proteínas de Unión al ADN/genética , Células Precursoras Eritroides/metabolismo , Factores de Unión al ADN Específico de las Células Eritroides , Técnica del Anticuerpo Fluorescente , Factor de Transcripción GATA1 , Expresión Génica , Globinas/biosíntesis , Globinas/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Humanos , Interleucina-3/metabolismo , Interleucina-3/farmacología , Receptores de Eritropoyetina/genética , Factores de Transcripción/genéticaRESUMEN
Stemness was recently depicted as a dynamic condition in normal and tumor cells. We found that the embryonic protein Cripto-1 (CR1) was expressed by normal stem cells at the bottom of colonic crypts and by cancer stem cells (CSCs) in colorectal tumor tissues. CR1-positive populations isolated from patient-derived tumor spheroids exhibited increased clonogenic capacity and expression of stem-cell-related genes. CR1 expression in tumor spheroids was variable over time, being subject to a complex regulation of the intracellular, surface and secreted protein, which was related to changes of the clonogenic capacity at the population level. CR1 silencing induced CSC growth arrest in vitro with a concomitant decrease of Src/Akt signaling, while in vivo it inhibited the growth of CSC-derived tumor xenografts and reduced CSC numbers. Importantly, CR1 silencing in established xenografts through an inducible expression system decreased CSC growth in both primary and metastatic tumors, indicating an essential role of CR1 in the regulation the CSC compartment. These results point to CR1 as a novel and dynamically regulated effector of stem cell functions in colorectal cancer.
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Neoplasias Colorrectales/metabolismo , Proteínas Ligadas a GPI/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/metabolismo , Animales , Neoplasias Colorrectales/fisiopatología , Femenino , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/fisiología , Regulación Neoplásica de la Expresión Génica , Genes src , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Péptidos y Proteínas de Señalización Intercelular/fisiología , Ratones , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/fisiología , Células Madre Neoplásicas/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Esferoides Celulares , Células Tumorales CultivadasRESUMEN
Incubation of trifluoperazine, a local anaesthetic, at concentrations higher than the cmc with Sendai virus particles produces the selective solubilization of the haemagglutinin neuraminidase (HN) and matrix (M) proteins. This phenomenon involves aggregation of the Sendai virions and therefore the separation of HN and M from the rest of the particle can be performed by bench centrifugation. The supernatant contains the HN and M proteins and HN, once inserted into liposomes, elicits its own biological activities. Therefore, the method seems suitable for purifying large amounts of HN.
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Hemaglutininas Virales/aislamiento & purificación , Virus de la Parainfluenza 1 Humana/análisis , Proteínas de la Matriz Viral/aislamiento & purificación , Virión/análisis , Animales , Embrión de Pollo , Detergentes , Neuraminidasa/aislamiento & purificación , Virus de la Parainfluenza 1 Humana/enzimología , Solubilidad , Trifluoperazina , Virión/enzimologíaRESUMEN
The Sendai virus fuses with host cell membranes in a pH-independent manner through an unknown mechanism. Here we report that mild trypsin pre-treatments of Sendai virions, for example 15 min at 4 degrees C, give Sendai virions the ability to fuse at a rate up to 10-fold higher than control. By using human erythrocytes as host cell membranes, viral fusion was assessed by hemolysis as well as fluorescence dequenching of octadecyl rhodamine B chloride. The mild protease treatment strikingly shortens the lag time taken by the virus to start the fusion process. Similar data were obtained on reconstituted Sendai virus envelope. Among proteases, tested as fusion enhancer, trypsin is more effective than either endoproteinase Lys-C, chymotrypsin, or endoproteinase Arg-C. After removal of trypsin from treated virions the fusion rate enhancement remains for hours at room temperature. The lack of protease specificity, together with the impossibility to detect any new N-terminal products, suggests that only a small percentage of viral envelope components are cleaved, still a large enough number to set the envelope in a ready-to-fuse state.
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Endopeptidasas/farmacología , Respirovirus/metabolismo , Quimotripsina/metabolismo , Eritrocitos/metabolismo , Colorantes Fluorescentes/metabolismo , Humanos , Cinética , Fusión de Membrana/fisiología , Metaloendopeptidasas/metabolismo , Rodaminas/metabolismo , Serina Endopeptidasas/metabolismo , Tripsina/metabolismo , Proteínas del Envoltorio Viral/metabolismoRESUMEN
Results related to long term treatment with Colestipol (a new resin sequestering bile acids) in 23 subjects with familial hypercholesterolaemia, 12 with Type IIA, 8 with Type IIB and 3 homozygotes are reported. Patients were given 15 g/day active drug for a period of 12 months and a double dose (30 g/day) for a successive period of 4 months along with a low cholesterol, low saturated fat, polyunsaturated fat-rich diet. Mean cholesterol decrease was --42 +/- 18 mg/dl (P less than 0.05) after 12 months of 15 g/day Colestipol and --69 +/- 17 mg/dl (P less than 0.01) after the following 4 months of 30 g/day Colestipol. The difference between the two periods of treatment (15 g and 30 g/day was not statistically significant. A slight but not significant increase in triglyceride levels was observed. Serum uric acid showed a significant increase throughout the entire period of treatment. No malabsorption syndrome or signs of toxicity were seen. Most frequent side effects were constipation, nausea, and metheorism which, with the exception of 4 cases which were withdrawn from the study, were reported as being transitory and mild.
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Anticolesterolemiantes/farmacología , Colestipol/farmacología , Hipercolesterolemia/genética , Lípidos/sangre , Poliaminas/farmacología , Adulto , Colestipol/administración & dosificación , Colestipol/efectos adversos , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Evaluación de Medicamentos , Femenino , Humanos , Hipercolesterolemia/dietoterapia , Hipercolesterolemia/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Ácido Úrico/sangreRESUMEN
In order to evaluate the relationship between triglyceride-rich lipoproteins (chylomicrons and VLDL) and HDL during alimentary lipaemia, 12 healthy volunteers, 6 male and 6 female (aged 20--40 yrs), were studied. Cholesterol, phospholipid, triglyceride and protein were evaluated in whole serum, VLDL, LDL and HDL (successively subfractionated in HDL2 and HDL3). Blood samples were collected in a fasting state, 4.5 and 9 h after a 1500 calorie meal (20% protein, 40% carbohydrate, 40% fat). A striking increase in triglyceride-rich lipoproteins after 4.5 h was observed in both sexes, but was more pronounced in males. An increase in phospholipid and triglyceride as well as a slight reduction in cholesterol was evident in HDL after 4.5 h. At the same time both lipids and proteins were decreased in HDL3 and increased in HDL2. This phenomenon is more evident in females, who showed a significantly higher basal HDL2 level. These results suggest a possible metabolic relationship in the post-prandial phase between triglyceride-rich lipoproteins and HDL, and an inverse correlation between HDL2 and HDL3.
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Quilomicrones , Lipoproteínas HDL/sangre , Lipoproteínas VLDL/sangre , Triglicéridos/sangre , Adulto , Ingestión de Alimentos , Femenino , Humanos , Lípidos/sangre , Masculino , Factores de TiempoRESUMEN
Twenty subjects with familial hypercholesterolemia (12 Type IIa and 8 Type IIb), previously treated with Colestipol for 16 months, were subjected to therapy with Colestipol (15 g/day) + clofibrate (2 g/day) for 15 months. During the second treatment period these patients continued to follow the isocaloric hypocholesterolemic diet initiated during the original trial. In Type IIa patients, the association of these drugs enhanced the decrease in plasma cholesterol levels. The total mean decrease was -40 +/- 17 mg/dl (P less than 0.05). In Type IIb patients, on the other hand, the association of clofibrate with Colestipol induced an increase in plasma cholesterol levels. The total mean increase was +24 +/- 7 mg/dl (P less than 0.05). A markedly significant decrease in plasma triglyceride levels was observed in this group (- 107 +/- 30; P less than 0.01). These results seem to indicate that, in Type IIa, clofibrate increased the resin's hypocholesterolemic effect. In Type IIb, on the other hand, the association of these drugs did not seem to be indicated since a marked hypotriglyceridemic effect was accompanied by an increase in plasma cholesterol levels. These results are briefly discussed in the light of recent data obtained on the effects of Colestipol and clofibrate on lipoprotein metabolism.
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Colestipol/administración & dosificación , Hipercolesterolemia/genética , Poliaminas/administración & dosificación , Adulto , Colesterol/sangre , Ensayos Clínicos como Asunto , Clofibrato/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Hipercolesterolemia/sangre , Hipercolesterolemia/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Factores de Tiempo , Triglicéridos/sangreRESUMEN
Twelve patients with mild and 3 with severe hypercholesterolemia were stabilized with an isocaloric diet containing less than 300 mg cholesterol daily with a P/S ratio of 1.8, and placebo period of 4 weeks. They were administered 1000 mg probucol daily for 12 weeks, followed by placebo for 6 weeks. In patients with mild disease, a significant cholesterol reduction was achieved in serum, LDL, and HDL (maximum decrease, 17%, 13%, and 31%, respectively). While HDL3 cholesterol was reduced significantly throughout the period (P less than 0.001), HDL2 cholesterol showed a significant decrease only at the 4th week of treatment (P less than 0.001), and returned to basal levels at the 8th and 12th treatment weeks. Serum apo B levels decreased only slightly, but the HDL-apo A-I fall was significant with a reduction in the HDL-CH/HDL-apo A-I ratio throughout the treatment period. In 3 patients with severe disease, cholesterol decrease in serum and in VLDL, LDL and HDL fractions varied, but on the whole was lower than in patients with mild disease. A decrease in VLDL-CH and HDL-CH was present in all 3, but LDL-CH levels were only slightly lowered in 2 patients, and unchanged in the third. Serum probucol levels fell 66% from the 4th to the 12th treatment week, and in parallel, the percentage of lipoprotein-bound drug increased about 2-fold. It is suggested that these changes in pharmacokinetics as well as the cholesterol-lowering effect of the drug may be due to a change in lipoprotein composition or structure.
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HDL-Colesterol/sangre , LDL-Colesterol/sangre , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Fenoles/uso terapéutico , Probucol/uso terapéutico , Adulto , Apolipoproteína A-I , Apolipoproteínas A/sangre , Apolipoproteínas B/sangre , Femenino , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas HDL2 , Lipoproteínas HDL3 , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Masculino , Persona de Mediana Edad , Probucol/efectos adversos , Probucol/sangre , Probucol/farmacologíaRESUMEN
Plasma lipids, lipoproteins, tissue lipoprotein lipase (LPL) and hepatic lipase (H-TGL) were studied in 7 patients with familial hyperchylomicronemia from four different families. Their first-degree relative were also studied. The patients were heterogeneous for the genetic defect; LPL activity was absent in five patients (LPL deficiency) but normal in two. However, these two did not have apo C-II, the physiological activator of LPL (C-II deficiency). There were no significant differences in the clinical picture between patients with LPL deficiency and C-II deficiency. In both mutants, marked hypertriglyceridemia was due to an accumulation of lipoproteins of density less than 1.006 g/ml. The LDL fraction was very reduced and abnormal in composition, presenting a CH/TG ratio of 0.5. The plasma apolipoprotein B (apo B) level was low (67 +/- 5.5 mg/dl) and was transported mainly in the VLDL fraction (26 +/- 3.2 mg/dl) rather than in the LDL fraction (15 +/- 1.4 mg/dl). Very low levels of cholesterol and apolipoprotein A-I in HDL subfractions HDL2 and HDL3 were also recorded. Only 3 out of the 24 first-degree relatives of patients with LPL deficiency showed even a small increase in plasma triglycerides, but 15 had low or low to normal LPL values. H-TGL levels were normal in all subjects. The 4 first-degree relatives of C-II deficiency patients showed normal levels of plasma lipids. LPL and H-TGL, and 2 children of 1 patient showed normal distribution of apo C peptides in their VLDL. A block in chylomicron catabolism, due to the absence of LPL or apo C-II, may lead to a massive accumulation of lipoproteins with a density less than 1.006 g/ml, and a drastic reduction in the LDL and HDL fractions. Low LPL values in the first-degree relatives of LPL deficiency patients might represent a biochemical marker for healthy carriers of LPL deficiency.
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Hiperlipoproteinemia Tipo I/sangre , Hiperlipoproteinemias/sangre , Tejido Adiposo/enzimología , Adulto , Apolipoproteínas/sangre , Preescolar , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Lipoproteínas HDL , Lipoproteínas VLDL/sangre , Hígado/enzimología , Masculino , Persona de Mediana EdadRESUMEN
We compared five immunoassays for lipoprotein(a) (Lp(a)) determination (end-point immunonephelometry, two-site IRMA and three different ELISA methods) in order to verify their agreement. Since it has been demonstrated that human apo(a) structure is closely similar to that of plasminogen, cross-reactivity of apo(a) antibodies with plasminogen represents an important technical problem in serum Lp(a) quantification. On this account we used a plasminogen-free fraction obtained by one-step ultracentrifugation at a density of 1.125 g/ml, in which no plasminogen activity was found. A satisfactory correlation between serum and plasminogen-free fraction Lp(a) values was found for all the methods; the limits of agreement were too high, however, to use serum and fraction interchangeably. Furthermore, it emerged that the different assays were more comparable and individual Lp(a) differences between methods were less spread when plasminogen-free fraction was used instead of serum.
Asunto(s)
Análisis Químico de la Sangre/métodos , Inmunoensayo/métodos , Lipoproteína(a)/sangre , Plasminógeno/análisis , Análisis de Varianza , Análisis Químico de la Sangre/estadística & datos numéricos , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática/métodos , Estudios de Evaluación como Asunto , Humanos , Inmunoensayo/estadística & datos numéricos , Ensayo Inmunorradiométrico/métodos , Lipoproteína(a)/inmunología , Nefelometría y Turbidimetría/métodos , Plasminógeno/inmunologíaRESUMEN
Gidez et al described a double precipitation method with polyanions to separate high density lipoprotein (HDL) subfractions, using sodium heparin to precipitate very low density lipoprotein (VLDL) and low density lipoprotein (LDL) first, and dextran sulphate 15000 to precipitate HDL2 from total HDL afterwards. This method has shown a very good correlation with the data from the analytical and preparative ultracentrifuge. The aim of this work is to use this method to analyse HDL2 and HLD3 levels in a population living in our district. We studied 163 subjects considered as 'normal' on the basis of anamnestic and clinical evaluation and routine analysis and 47 subjects with familial hyperlipoproteinemia (types IIa, IIb, and IV). The results obtained confirmed both the difference in HDL and particularly HDL2 levels between the sexes which other authors had observed with reference methods, and the significant negative correlation between plasma triglycerides and HDL2 levels. This method may be applied easily, is rather cheap and, therefore, may be used more often in future.
Asunto(s)
Colesterol/sangre , Hiperlipoproteinemias/sangre , Lipoproteínas HDL/sangre , Adulto , Precipitación Química , HDL-Colesterol , Femenino , Humanos , Hiperlipoproteinemias/genética , Masculino , Persona de Mediana Edad , Fenotipo , Triglicéridos/sangreRESUMEN
Cholesterol levels in high density lipoprotein subfractions (HDL2 and HDL3) were evaluated in 69 patients (55 males, average age +/- SD 58.3 +/- 8.8, and 14 females, average age +/- SD 63.1 +/- 10.3) with extra-coronary arteriosclerosis (lower limbs, supraaortic trunks and both sites), and in 79 healthy age-matched control subjects. HDL cholesterol was significantly reduced in male and female patients. The HDL cholesterol decrease was due to a fall in both HDL2 and HDL3 cholesterols; nonetheless, an analysis of the HDL2-cholesterol/HDL3-cholesterol ratio disclosed that HDL2 cholesterol was the most reduced. Slightly higher plasma cholesterol and triglyceride levels were found in the patients as well as a higher plasma cholesterol/HDL-cholesterol ratio. On the contrary, the HDL2-cholesterol/HDL3-cholesterol ratio was significantly reduced in the patients. These preliminary findings suggest that, as in ischemic heart disease, the HDL cholesterol reduction in cerebral and peripheral arteriosclerosis is also mainly due to a reduction in the HDL2 subfraction. These results also lend further support to the proposal that determination of the HDL subfractions is useful for a better assessment of the risk profile for arteriosclerosis.
Asunto(s)
Arteriosclerosis/sangre , Colesterol/sangre , Arteriosclerosis Intracraneal/sangre , Lipoproteínas HDL/sangre , Anciano , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The results of plasma lipid and lipoprotein analysis in two related patients, brother (R.U.) and sister (R.R.) with analbuminemia, and three first-degree relatives (parents and sister) are reported. Both patients showed a remarkable increase in cholesterol and phospholipid levels, and there was a corresponding increase in serum apo B and apo A-I. This hyperlipidemia is due to a selective increase in LDL and HDL concentrations. R.U. showed an increase in both HDL2- and HDL3-cholesterol, R.R. only in HDL3-cholesterol. VLDL concentration was reduced in R.U. and normal in R.R. The plasma lipoprotein electrophoretic pattern did not correspond to any of the phenotypes in Fredrickson's classification. Composition of the different lipoprotein fractions was normal in the patients and family members. Serum FFA level in R.R. was very low. An increase in the plasma protein fractions, particularly the transport fractions, was confirmed in both patients. The possible pathophysiology of the hypercholesterolemia in these patients is discussed. Unlike other reported cases, clinical signs of atherosclerotic complications were absent.
Asunto(s)
Trastornos de las Proteínas Sanguíneas/sangre , Hiperlipidemias/etiología , Albúmina Sérica/deficiencia , Adulto , Anciano , Trastornos de las Proteínas Sanguíneas/genética , Colesterol/sangre , HDL-Colesterol , Ácidos Grasos no Esterificados/sangre , Femenino , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas HDL2 , Lipoproteínas HDL3 , Lipoproteínas LDL/sangre , Lipoproteínas VLDL/sangre , Masculino , Persona de Mediana Edad , Fosfolípidos/sangre , Triglicéridos/sangreRESUMEN
BACKGROUND: We investigated the relationships between plasma lipids and lipoprotein fractions and carotid artery lesions (CAL) in 177 cerebro-vascularly asymptomatic subjects, of whom 107 were primary hypertensive patients and 70 normotensive controls. METHODS: The prevalence and severity of CAL, as assessed by calculating a score of severity (score of CAL) and the maximal stenosis of both sides, as well as the intimal-medial thickness (IMT) were evaluated with a high-resolution echo-Doppler technique. We measured total serum cholesterol, triglycerides, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, lipoprotein (a) [Lp(a)], Apo (apolipoprotein)AI, ApoAII, ApoB, and fibrinogen. RESULTS: Both the prevalence (59.4% vs 26.2%) and severity of sex- and age-adjusted and unadjusted CAL and IMT were significantly higher in hypertensive patients than in controls. Regression analysis showed different predictors of IMT and maximal stenosis. The variables that remained in the model were age, mean blood pressure (BP), and smoking for IMT; pulse pressure, known duration of hypertension (HT), fibrinogen, and ApoB for the score of CAL; and the last four variables along with age and mean BP for maximal stenosis. Furthermore, we identified a link between the atherogenic lipoprotein fractions Lp(a) and ApoB, fibrinogen and early carotid artery atherosclerotic changes. CONCLUSIONS: The different correlates of IMT, CAL, and maximal degree of stenosis suggest that they reflect different events occurring in the arterial wall in response to aging, HT, and other risk factors, rather than simply different stages of the same atherosclerotic process.