RESUMO
Factor X (FX) is a vitamin K-dependent plasma protein required for the intrinsic and extrinsic pathways of blood coagulation. FXSanto Domingo is a hereditary FX deficiency which is characterized clinically by a severe bleeding diathesis. The proposita has a FX activity of less than 1% and a FX antigen of less than 5%. We have determined the molecular basis of the defect in the FXSanto Domingo gene by amplification of all eight exons with polymerase chain reaction and subsequent sequence analysis. The patient is homozygous for a G----A transition in exon I at codon -20 (numbering the alanine at the NH2 terminus of the mature protein as +1), resulting in the substitution of arginine for glycine in the carboxy-terminal part of the signal peptide. This amino acid change occurs near the presumed cleavage site of the signal peptidase. We hypothesized that the mutation might prevent cleavage by the signal peptidase which in turn would impair proper secretion of the FX protein. To test this hypothesis, we compared the expression of wild type and mutant FX cDNA in a human kidney cell line. Wild type and mutant constructs in the expression vector pCMV4 were introduced into the human embryonic kidney cell line 293 by calcium phosphate transfection. FX antigen levels in the supernatant of the cells harboring the wild type construct were 2.4 micrograms/10(7) cells per 24 h, whereas antigen levels in media from cells containing the FXSanto Domingo construct were undetectable. No FX antigen was detected in the cell lysates of cells transfected with the mutant construct. To insure that the difference in protein levels was not due to a difference in steady state levels of mRNA, Northern analysis was performed on RNA from the cell lysates of both constructs. The results showed a transcript of the same size, present in roughly equal amounts, in both cases. Thus, the defect in the signal sequence of FXSanto Domingo exerts its effect posttranscriptionally. FXSanto Domingo is the first described example of a bleeding diathesis due to a mutation in the signal sequence.
Assuntos
Deficiência do Fator X/genética , Mutação , Adolescente , Sequência de Aminoácidos , Sequência de Bases , Fator X/análise , Fator X/genética , Feminino , Humanos , Dados de Sequência Molecular , FenótipoRESUMO
The aim of this multicentre, prospective, randomised, dose-ranging study was to compare the safety and efficacy of subcutaneous recombinant hirudin (HBW 023) against intravenous sodium heparin in acute lower limb deep venous thrombosis (DVT). Patients were randomized to treatment with either HBW 023 or heparin for 5 +/- 1 days. HBW 023 was given according to body-weight in three dose groups. Thromboembolic disease was assessed by phlebography and ventilation/perfusion (V/Q) scanning on Day 1 and Day 5 +/- 1. One hundred and fifty-five patients were enrolled, of these 121 were evaluable for efficacy analysis. Significantly fewer patients on HBW 023 developed new V/Q abnormalities during the treatment period, (p = 0.006). There was no difference between the groups in thrombus extension or regression, major bleeding complications or serious adverse events. There were significantly fewer findings of new V/Q mismatch after treatment with HBW 023, and anticoagulant control was superior in these patients.
Assuntos
Fibrinolíticos/uso terapêutico , Heparina/uso terapêutico , Terapia com Hirudina , Tromboflebite/tratamento farmacológico , Adulto , Idoso , Relação Dose-Resposta a Droga , Feminino , Fibrinolíticos/efeitos adversos , Fibrinolíticos/farmacocinética , Heparina/efeitos adversos , Heparina/farmacocinética , Hirudinas/efeitos adversos , Hirudinas/farmacocinética , Humanos , Infusões Intravenosas , Injeções Intravenosas , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Prospectivos , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/uso terapêuticoRESUMO
Nitric oxide (NO) exerts its vasodilator and antiaggregatory effects through activation of soluble guanylate cyclase and the consequent increase in the concentration of cGMP in target cells. We conducted this study in order to evaluate relationships between intraplatelet cGMP levels and risk factors for atherosclerosis in middle aged subjects. Intraplatelet cGMP was determined by radioimmunoassay and related to age, BMI, blood pressure, antihypertensive treatment, total, LDL and HDL cholesterol, triglycerides, blood glucose, HbA1c, smoking habit and intimal thickness of the common carotid artery in 265 subjects participating in a health survey (age 59 +/- 6 years, range 48-68 years, 121 females, 144 males). Intraplatelet cGMP concentration was inversely correlated with total serum cholesterol (r = -0.18; p < 0.01) and HDL cholesterol (r = -0.14, p < 0.05) as well as with platelet count (r = -0.29; p < 0.001). When platelet count was adjusted for, only the correlation between total serum cholesterol and cGMP remained significant. No significant correlations could be demonstrated between intraplatelet cGMP levels and measurable parameters of atherosclerosis. Lower levels of the vasodilating and antiaggregating mediator cGMP in platelets are related to higher levels of serum total cholesterol. These results favour the hypothesis of a relationship between lipid levels and NO associated vasodilator and antiaggregating function in atherosclerosis.
Assuntos
Plaquetas/química , Colesterol/sangue , GMP Cíclico/sangue , Fatores Etários , Idoso , Anti-Hipertensivos/farmacologia , Arteriosclerose/sangue , Glicemia/análise , Pressão Sanguínea , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus/sangue , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Radioimunoensaio , Fatores de Risco , Fumar/sangue , Triglicerídeos/sangueRESUMO
Renal revascularization by splenic artery implantation was performed in 5 dogs using a temporary arteriovenous fistula in the distal end of the implanted artery for the purpose of increasing the blood flow and counteracting the thrombus formation in the artery. Following creation of renal artery stenosis, the revascularization process was evaluated by serial consecutive splenic arteriographies and by estimation of blood flow through the implanted arteries. The experimental animals survived occlusion of the ipsilateral renal artery and contralateral nephrectomy with maintenance of a reasonably good renal function. The present study also indicates a facilitation of a vascularization from the implanted artery when the initial thrombus formation within the artery was prevented by creation of such a fistula.
Assuntos
Derivação Arteriovenosa Cirúrgica , Rim/irrigação sanguínea , Artéria Esplênica/transplante , Angiografia , Animais , Circulação Colateral , Creatinina/sangue , Cães , Nefrectomia , Obstrução da Artéria Renal/fisiopatologia , Trombose/prevenção & controle , Transplante AutólogoRESUMO
The PiZ genetic variant of alpha 1-antitrypsin in its homozygous form is associated with an increased risk for chronic lung and liver disease. About 5% of the population are carriers of one PiZ deficiency gene resulting in intermediate levels of plasma alpha 1-antitrypsin (PiMZ, PiSZ, PiPZ). We report the preparation of a hybridoma cell line, ATZ 11, produced by fusion of spleen cells from BALB/c mice immunized with a purified liver PiZ alpha 1-antitrypsin and Sp 2/0 Ag 14 mouse myeloma cells. ATZ 11 produces monoclonal antibodies (IgG1 kappa) specifically interacting with PiZ alpha 1-antitrypsin. These antibodies were used in an ELISA procedure permitting easy and accurate identification of PiZ gene carriers. The method is especially well-suited for studying large population samples concerning the putative relationship between intermediate alpha 1-antitrypsin deficiency and disease.
Assuntos
Genes , Mutação , alfa 1-Antitripsina/genética , Animais , Anticorpos Monoclonais , Ensaio de Imunoadsorção Enzimática , Epitopos/análise , Feminino , Variação Genética , Homozigoto , Hepatopatias/genética , Pneumopatias/genética , Camundongos , Camundongos Endogâmicos BALB C , Risco , alfa 1-Antitripsina/análiseRESUMO
The existence of two genetic variants (allotypes) of normal human factor IX is used for carrier detection in three families with severe and one with mild haemophilia B. By analysis of IX:Ag with two different monoclonal antibodies in 93 members of the families, allelic assignment is shown to be a complement in carrier diagnosis to genotypic DNA studies. Allelic assignment makes possible a reliable diagnosis based on phenotypic studies, though its usefulness is limited due to ethnic variation in allelic frequency. Determination of factor IX allotypes should be useful for carrier detection in many Swedish families with haemophilia B.
Assuntos
Alelos , Fator IX/genética , Triagem de Portadores Genéticos , Hemofilia B/genética , Feminino , Humanos , Masculino , LinhagemRESUMO
Factor IX antigen (IX:Ag) was measured with three different immunoradiometric assays (IRMAs) in 30 healthy people and 43 patients with haemophilia B of varying severity. Two of the IRMAs were based on monoclonal antibodies capable of differentiating between two genetically determined molecular variants of normal factor IX. Most patients with severe hemophilia B lacked demonstrable IX:Ag. The factor IX variant that is undetectable with one of the monoclonal antibodies used was present in 2 out of 6 families with moderate haemophilia B and in 1 out of 6 families with mild haemophilia B. The existence of allotypes of factor IX in hemophilia B may have practical implications for carrier detection and prenatal diagnosis.
Assuntos
Alelos , Fator IX/análise , Hemofilia B/sangue , Variação Genética , Hemofilia B/genética , Hemofilia B/fisiopatologia , Humanos , Concentração Osmolar , RadioimunoensaioRESUMO
Both glucocorticoids and cyclosporine are used to prevent rejection in organ transplant recipients. However, long-term treatment with these drugs is known to induce hyperlipidemia and premature development of atherosclerosis. In previous studies, we have shown that the immunosuppressive drug cyclosporine inhibits catabolism of low-density lipoproteins (LDL) mainly by reducing the expression of LDL-receptor messenger RNA (mRNA), thus explaining the increased plasma levels of LDL cholesterol observed in patients treated with cyclosporine. In the present study, our objective was to investigate the mechanism by which glucocorticoids increase plasma levels of LDL cholesterol. We studied the catabolism of LDL in the human hepatoma cell line HepG2. Our results show that hydrocortisone at physiologically relevant concentrations inhibits LDL binding, uptake, and degradation in a dose-dependent way. Moreover, hydrocortisone also reduces the expression of LDL-receptor mRNA in a dose-dependent way. Cyclosporine also has an additive inhibitory effect on hydrocortisone in the catabolism of LDL. The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin reverses the inhibitory effect of both hydrocortisone and cyclosporine. We conclude that treatment with hydrocortisone and/or cyclosporine induces increased plasma levels of LDL cholesterol because of reduced hepatic LDL receptor activity. HMG-CoA reductase inhibitors reverse this undesirable effect and thus reduce the risk of the development of atherosclerosis in patients subjected to immunosuppressive treatment.
Assuntos
Ciclosporina/farmacologia , Hidrocortisona/farmacologia , Imunossupressores/farmacologia , Receptores de LDL/antagonistas & inibidores , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Humanos , Lipoproteínas LDL/metabolismo , RNA Mensageiro/análise , Receptores de LDL/genética , Receptores de LDL/metabolismo , Células Tumorais CultivadasRESUMO
Previously we have shown that cyclosporine inhibits low-density lipoprotein (LDL) catabolism in HepG2 cells. This inhibition mainly occurs through reduced LDL-receptor activity. 3-Hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors up-regulate LDL receptor activity with a subsequent increase in LDL uptake and degradation. In this study, in HepG2 cells, we investigated the effects of HMG-CoA reductase inhibitors on cellular LDL catabolism in the presence of cyclosporine. Different concentrations of cyclosporine and HMG-CoA reductase inhibitors, which were within the range of therapeutic concentrations used in humans, were added to the culture medium and the cellular LDL receptor activity was then measured. The results show that HMG-CoA reductase inhibitors reverse the down-regulatory effect of cyclosporine on LDL receptor activity, thus further supporting our previous findings and also providing a rationale for the already established treatment in cyclosporine-induced hypercholesterolemia with HMG-CoA reductase inhibitors.
Assuntos
Ciclosporina/farmacologia , Inibidores Enzimáticos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases , Receptores de LDL/antagonistas & inibidores , Receptores de LDL/efeitos dos fármacos , Anticolesterolemiantes/farmacologia , Transporte Biológico Ativo , Ciclosporina/efeitos adversos , Regulação para Baixo/efeitos dos fármacos , Ácidos Graxos Monoinsaturados/farmacologia , Fluvastatina , Humanos , Hipercolesterolemia/induzido quimicamente , Hipercolesterolemia/tratamento farmacológico , Indóis/farmacologia , Lipoproteínas LDL/metabolismo , Lovastatina/análogos & derivados , Lovastatina/farmacologia , Receptores de LDL/metabolismo , Células Tumorais Cultivadas , Regulação para Cima/efeitos dos fármacosRESUMO
The aim of this study was to elucidate the possible causes of elevated low-density lipoprotein (LDL)-cholesterol levels in transplanted patients treated with the immunosuppressant drug, cyclosporine. HepG2 cells, from a well-differentiated cell-line of hepatoma cells, were cultured and used as a model for in vitro hepatocytic LDL uptake. Different concentrations of cyclosporine, which were within the range of concentrations found in humans treated with cyclosporine, were added to tissue culture medium together with 125I-LDL. The results showed that cyclosporine reduced LDL uptake and degradation in HepG2 cells by about 25%. The cells were also pretreated with cyclosporine for 1 to 24 hours and then incubated with new medium containing labeled LDL for 2 hours at 4 degrees C in an LDL-binding assay. The data showed that cyclosporine reduced the subsequent LDL binding. Cyclosporine has no toxic effects on HepG2 cells, as shown by unchanged growth capacity of the cells. By means of a 50-fold excess of unlabeled LDL, a monoclonal anti-LDL receptor antibody, and dextran sulfate, we also evaluated if this inhibition of LDL binding occurred through the LDL receptor-mediated pathway, through non-LDL receptor-mediated pathways, or through both. The results show that cyclosporine reduces LDL binding and uptake by mainly inhibiting the LDL receptor-mediated pathway. We also studied the effect of the LDL-cyclosporine complex on the binding of labelled LDL. The presence of cyclosporine in the LDL particle does not influence the binding behaviour of LDL to its receptor. We also found that cyclosporine reduces the expression of the LDL receptor messenger RNA (mRNA) by about 40%. Thus, the interpretation of this study is that cyclosporine can cause an increase in LDL-cholesterol in the plasma of transplantation patients by reducing the catabolism of LDL in the liver by inhibiting mainly the LDL receptor-mediated catabolism through an effect on LDL receptor synthesis.
Assuntos
Carcinoma Hepatocelular/metabolismo , Ciclosporina/farmacologia , Lipoproteínas LDL/antagonistas & inibidores , Neoplasias Hepáticas/metabolismo , Carcinoma Hepatocelular/patologia , Ciclosporina/metabolismo , Humanos , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacocinética , Neoplasias Hepáticas/patologia , RNA Mensageiro/metabolismo , Receptores de LDL/genética , Receptores de LDL/metabolismo , Células Tumorais CultivadasRESUMO
Here we report the production of four different monoclonal antibodies against factor VIII/von Willebrand factor (F VIII/vWF) and the use of these antibodies in immunoradiometric assay (IRMA), crossed immunoelectrophoresis (CIE) and multimeric sizing (MS) for analysing the various types of von Willebrand's disease. None of the antibodies inactivated factor VIII coagulant activity and one (R1) of them partly inhibited the ristocetin co-factor activity. One monoclonal antibody (R2) was radiolabelled and compared with 125I rabbit affinity purified antibody against F VIII/vWF. The two IRMA techniques gave similar results in 26 normals and 22 samples representing all variants of von Willebrand's disease. This monoclonal antibody could also be used in multimeric sizing and not only produced patterns identical to those obtained with the rabbit affinity purified antibody, but also gave better resolution. Further advantages of using monoclonal antibodies in these tests are: practically unlimited access to the same specific antibody, time-consuming affinity purification of the rabbit antibody can be avoided and the overall use of radioactivity reduced. This study demonstrates that one (R2) of the four monoclonal antibodies is suitable for routine analysis of F VIII/vWF and the use of this antibody simplifies the laboratory work in classifying von Willebrand's disease.
Assuntos
Anticorpos Monoclonais/análise , Fatores de Coagulação Sanguínea/análise , Fator VIII/análise , Fator de von Willebrand/análise , Animais , Anticorpos Monoclonais/biossíntese , Linhagem Celular , Fator VIII/imunologia , Humanos , Imunoeletroforese Bidimensional , Imunoglobulina G/análise , Cadeias kappa de Imunoglobulina/análise , Cadeias lambda de Imunoglobulina/análise , Camundongos , Radioimunoensaio , Doenças de von Willebrand/sangue , Fator de von Willebrand/imunologiaRESUMO
The polymorphism is located within exon 5 of the human coagulation factor VII gene and is silent at the amino acid level. The distribution pattern is similar in Caucasians and African Americans. This polymorphism may be useful for restriction fragment length polymorphism (RFLP) diagnosis of factor X deficiency as well as factor VII deficiency, since the factor X gene is closely linked to the factor VII locus.
Assuntos
Fator VII/genética , Polimorfismo Genético , Sequência de Bases , Primers do DNA , Desoxirribonucleases de Sítio Específico do Tipo II , Frequência do Gene , Ligação Genética , Humanos , Dados de Sequência MolecularRESUMO
It has been suggested that a number of molecules associated with inflammation are involved in the pathogenesis of Alzheimer's disease (AD). We measured the levels of alpha(1)-antichymotrypsin (ACT), alpha(1)-antitrypsin (AAT), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and oxidised low-density lipoprotein (oxLDL) in matched cerebrospinal fluid (CSF) and plasma of 141 patients with probable AD. We found a significant relationship between CSF and plasma levels of ACT (r = 0.4, p < 0.001), IL-6 (r = 0.74, p < 0.001), MCP-1 (r = 0.71, p < 0.001), and a borderline relationship between CSF and plasma oxLDL (r = 0.22, p < 0.05). In addition, linear regression analysis revealed a positive correlation between levels of CSF-ACT and oxLDL (p < 0.001), but an inverse relation between levels of CSF ACT, CSF AAT and MCP-1 (p < 0.001). A significant correlation was also found between levels of CSF ACT, oxLDL and the ratio of CSF to serum albumin, which is used as a measure of the blood-brain barrier function. Our data extend previous reports regarding the inflammatory markers in the plasma and CSF of patients with AD and provide good evidence that levels of ACT, IL-6, MCP-1 and oxLDL in plasma and CSF might be candidates as biomarkers for monitoring the inflammatory process in AD.
Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/líquido cefalorraquidiano , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Inflamação/metabolismo , Alelos , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Peptídeos beta-Amiloides/sangue , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Apolipoproteínas E/genética , Barreira Hematoencefálica , Quimiocina CCL2/sangue , Quimiocina CCL2/líquido cefalorraquidiano , Cognição , Humanos , Interleucina-6/sangue , Interleucina-6/líquido cefalorraquidiano , Lipoproteínas LDL/sangue , Lipoproteínas LDL/líquido cefalorraquidiano , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/líquido cefalorraquidiano , alfa 1-Antiquimotripsina/sangue , alfa 1-Antiquimotripsina/líquido cefalorraquidianoRESUMO
Two patients with life-threatening disseminated intravascular coagulation (DIC) syndrome, one caused by Gram-negative bacteria and one by premature separation of the placenta, are described. Specific substitution was given by antithrombin III concentrate and AHF-Kabi, a low purity factor VIII concentrate containing native von Willebrand factor and factor XIII. The treatment quickly returned the extremely low levels of antithrombin III, factor VIII:C, fibrinogen and factor XIII, initially found, to normal, and also returned the multimeric pattern of von Willebrand factor to normal. This resulted in diminished bleeding, enabling surgical treatment of the underlying disease.
Assuntos
Antitrombina III/uso terapêutico , Coagulação Intravascular Disseminada/terapia , Fator XIII/uso terapêutico , Complicações Hematológicas na Gravidez/terapia , Fator de von Willebrand/uso terapêutico , Adulto , Cistadenoma/complicações , Cistadenoma/cirurgia , Coagulação Intravascular Disseminada/etiologia , Feminino , Humanos , Gravidez , Teratoma/complicações , Teratoma/cirurgiaRESUMO
BACKGROUND: Familial hypercholesterolaemia, an autosomal co-dominant disorder caused by defects in the low-density lipoprotein receptor gene, is strongly associated with premature development of cardiovascular disease. METHODS: In this study, we have applied a gene screening method in a population of familial hypercholesterolaemia patients in order to describe the genetic background of the disease in southern Sweden. These patients were studied with the aim of relating the presence of the different mutations to the clinical expression of the disease and to the response to pharmacological treatment. RESULTS: In 16 out of 21 patients, potentially disease-causing low-density lipoprotein receptor gene defects were found, including five not previously described alterations (C240-->F, C122-->stop, C356-->Y, 785insG, 165delG). No defects in apolipoprotein B were found. One group of patients (n = 4) carried the mutation C122-->stop and another group of patients (n = 4) a mutation causing the substitution W66-->G. Patients in the two genotype subgroups were very similar with respect to lipid levels before treatment. CONCLUSION: A tendency towards differential susceptibility to treatment with statins was observed for the patient groups, encouraging further comparative studies of heterozygous FH patients.
Assuntos
Hiperlipoproteinemia Tipo II/genética , Mutação , Receptores de LDL/genética , Adulto , Anticolesterolemiantes/uso terapêutico , Análise Mutacional de DNA , Primers do DNA/genética , Feminino , Humanos , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Hiperlipoproteinemia Tipo II/metabolismo , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Polimorfismo Conformacional de Fita Simples , Prognóstico , SuéciaRESUMO
There is increasing evidence that lipoproteins are involved in the progression of kidney diseases and in the deterioration of kidney transplant function, although the exact mechanism is still not known. Common polymorphisms of apolipoprotein E genotype associate with the variability of lipoprotein levels and composition. We have, therefore, determined the apolipoprotein E genotype in a group of 112 renal transplant patients, of whom 27 had had an episode of acute vascular rejection, while 85 had not. We found no difference in apolipoprotein E genotype distribution or in relative allele frequency in the vascular rejection group as compared with the group without vascular rejection. The apolipoprotein E genotype distribution in the transplant group was also compared with that in a group of 407 healthy Swedish individuals. The E3/E4 genotype occurred with a significantly increased frequency in the transplant group: 38.3 versus 16% in the control group (p < 0.001). The prevalence of individuals carrying the epsilon4 allele among the transplant group was also significantly higher (44%) as compared with the control group (30%; p < 0.01). This increase was entirely due to the predominant increase of E3/E4, as the E4/E4 genotype was less frequent in transplant recipients than in normal controls (3.5 vs. 10.6%; p < 0.05). The relative frequencies of epsilon2 (0.044), epsilon3 (0.716), and epsilon4 (0.238) alleles in the renal transplant group were not different from those of normal controls (0. 078, 0.718, and 0.202, respectively). With regard to the prevalence of E4/E4 in the two groups, the lack of difference in the relative frequency of the epsilon4 allele must be interpreted with caution. The results thus suggest that the E3/E4 genotype may be associated with the progression of kidney disease leading to renal insufficiency. However, the apolipoprotein E genotype does not seem to influence the risk of vascular rejection among transplant recipients.
Assuntos
Apolipoproteínas E/genética , Frequência do Gene , Transplante de Rim , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Alelos , Apolipoproteína E3 , Apolipoproteína E4 , Feminino , Genótipo , Rejeição de Enxerto/genética , Humanos , Masculino , Pessoa de Meia-Idade , SuéciaRESUMO
The aim of this study was to investigate whether consumption of a newly developed oat milk deprived of insoluble fiber would result in lower serum cholesterol and low-density lipoprotein (LDL) cholesterol levels in men with moderate hypercholesterolemia. The study had a randomized, controlled double-blind design, and oat milk was compared with an identically flavored control drink. Sixty-six men were recruited from a screening program and were randomly assigned to two groups. Each group took either oat milk or a control drink (rice milk) for 5 weeks (0.75 liters/day) and then switched to the other drink regimen for another 5-week period with a 5-week washout period between the test periods. The oat milk contained more dietary fiber, especially beta-glucan (0.5 g/100 g), than the control drink (<0.02 g/100 g). Both drinks were well appreciated and got similar sensory evaluation, indicating that the double-blind design had been attained. In the final analysis 52 subjects remained. Compared with the control drink, intake of oat milk resulted in significantly lower serum total cholesterol (6%, p = 0.005) and LDL cholesterol (6%, p = 0.036) levels. The decrease in LDL cholesterol was more pronounced if the starting value was higher (r = -0.55, p < 0.001). The concentration of high-density lipoprotein cholesterol was not significantly different after consumption of the two drinks. Serum triglycerides did not change significantly after intake of oat milk, but a significant increase was observed after intake of the control drink (p = 0.003). It is concluded that also oat milk deprived of insoluble fiber has cholesterol-reducing properties.
Assuntos
Avena , LDL-Colesterol/sangue , Colesterol/sangue , Hipercolesterolemia/dietoterapia , Idoso , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Dieta , Método Duplo-Cego , Humanos , Hipercolesterolemia/sangue , Masculino , Pessoa de Meia-Idade , PaladarRESUMO
The distribution of 1,198 Malmö alleles was examined in 822 men from 16 indigenous populations and 188 women from 7 of the ethnic groups. Subjects were from several European countries, the Mediterranean, East Asia, and the USA (Anglo- and African-Americans). The frequencies of the rarer (Malmö B) allele were approximately equal across Europe, the highest frequencies (0.36) being in the French and Anglo-Americans; no population was observed with clearly the highest frequency. They diminished slightly at moderate distances from Europe (Tunisia, Ethiopia) and greatly at longer distances (East Asia and West Africa). In Orientals, the frequencies ranged from 0.07 (East Indians) to 0.03 (the Chinese) and from 0.0 to 0.15 in African-Americans. Assuming selective neutrality, the data are consistent with the European origin of the 'B' allele when the population was small and outward spread.
Assuntos
Fator IX/genética , Genética Populacional , Polimorfismo Genético , África do Norte/etnologia , Alelos , Ásia/etnologia , População Negra/genética , Europa (Continente)/etnologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Ilhas do Mediterrâneo/etnologia , Pigmentação da Pele/genética , SuéciaRESUMO
Hemophilia B is an X-chromosomal recessive disease due to deficiency of coagulation factor IX. Three monoclonal antibodies against factor IX were prepared and used to develop immunoradiometric assays (IRMAs) of factor IX antigen (IX-Ag). IX-Ag was measured in 65 normal individuals with one IRMA based on polyclonal anti-IX antibodies and two IRMAs based on three monoclonal anti-IX antibodies. One of the monoclonal antibodies differed in specificity since it neutralized less than 50% of the clotting activity of factor IX (IX-C), whereas the other two monoclonal antibodies neutralized 80-95%. When the former antibody was used as the solid phase in IRMA, two groups of normal individuals were distinguished: group A with measurable IX-Ag, and group B without demonstrable IX-Ag. There were no differences between the groups either in IX-C or in IX-Ag measured with polyclonal antibodies. A subgroup comprising only women could be distinguished in group A, in whom intermediate IX-Ag concentrations were found. Family studies showed the group B variant of normal factor IX to be transmitted according to the pattern of X-linked recessive inheritance. The allelic frequency of group A was 0.66, and that of group B was 0.34.