RESUMO
AIM: Stromelysin (MMP3), through its action on collagen and other matrix metalloproteinases, influences arterial wall remodeling. In healthy subjects, the 5A/6A polymorphism located in the promoter of the MMP3 gene is associated with common carotid remodeling, 6A/6A subjects having increased arterial diameter, wall thickness (intima-media thickness, IMT) and decreased wall shear stress (WSS). In the present study, we have investigated the influence of the 5A/6A polymorphism on common carotid remodeling in subjects with diabetes mellitus. METHODS: Diabetic subjects (N.=136) and age-matched healthy male controls (N.=101) have been studied. Common carotid diameter, IMT and flow velocity have been measured by echo-Doppler. Blood viscosity has been measured by a cone/plate viscometer. WSS has been calculated. RESULTS: Diabetic patients had increased common carotid diameter, IMT, and decreased flow velocity and WSS (all P<0.05), compared with controls. In controls, subjects homozygous for the 6A allele had increased diameter, IMT and decreased WSS. In diabetics, no difference was observed in vascular parameters among the three genotypes. CONCLUSION: The 5A/6A polymorphism of the MMP3 gene influences arterial remodeling of the common carotid artery in healthy subjects, but not in patients with diabetes mellitus. Therefore, the significance of the 5A/6A polymorphism as a marker of risk in this high cardiovascular risk population seems to be somehow blunted.
Assuntos
Artéria Carótida Primitiva/patologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Metaloproteinase 3 da Matriz/genética , Polimorfismo Genético/genética , Adulto , Doenças Cardiovasculares/etiologia , Artéria Carótida Primitiva/diagnóstico por imagem , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas/genética , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/patologia , Túnica Média/diagnóstico por imagem , Túnica Média/patologia , UltrassonografiaRESUMO
The presence of specific mRNAs in dendrites and at synapses is well established, but a direct and reliable demonstration that they are associated with polysomes is still missing. To address this point we analyzed the polysomal association of the mRNAs for the alpha-subunit of Ca(2+)/calmodulin-dependent protein kinase II (alpha-CaMKII), for type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1) and for the activity-regulated cytoskeleton-associated protein (Arc) in a synaptosomal preparation devoid of contaminating material from neuronal and glial perikarya. We show that a fraction of alpha-CaMKII, InsP3R1, and Arc mRNAs present in synaptosomes is indeed associated with polysomes. Moreover, we show that polysomal association of alpha-CaMKII mRNA, but not InsP3R1 and Arc mRNAs, increases with depolarization of the synaptosomal membrane. Finally, we show that the synthesis of alpha-CaMKII protein increases with stimulation. Dendritic mRNA recruitment onto polysomes in response to synaptic stimulation might represent one of the mechanisms underlying the processes of learning and memory.
Assuntos
Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Polirribossomos/metabolismo , RNA Mensageiro/metabolismo , Sinaptossomos/metabolismo , Animais , Encéfalo/ultraestrutura , Canais de Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Proteínas do Citoesqueleto/metabolismo , Técnicas In Vitro , Receptores de Inositol 1,4,5-Trifosfato , Camundongos , Camundongos Endogâmicos C57BL , Microscopia Eletrônica , Proteínas do Tecido Nervoso/metabolismo , Polirribossomos/enzimologia , Cloreto de Potássio/farmacologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Estimulação Química , Sinaptossomos/enzimologiaRESUMO
In order to assess the efficacy of gemfibrozil on lipid and haemostatic parameters in patients with plurimetabolic syndrome, a multicenter double-blind placebo controlled, parallel study was carried out in 56 patients with primary hypertriglyceridemia and glucose intolerance. These patients had elevated PAI activity and antigen and t-PA antigen levels at rest and after venous occlusion. Gemfibrozil reduced plasma triglyceride levels (P<0.001), whereas it increased free fatty acids (P<0.05) and high density lipoprotein cholesterol levels (P<0.05). In those patients reaching normalization of plasma triglyceride levels (triglyceride reduction > or =50%) (n=15), insulin levels (P<0.05) as well as the insulin resistance index were reduced by gemfibrozil treatment, suggesting an improvement of the insulin resistance index in this patient subgroup. Gemfibrozil treatment did not affect plasma fibrinolysis or fibrinogen levels, despite marked reduction of plasma triglycerides and improvement of the insulin sensitivity associated with triglyceride normalization.
Assuntos
Genfibrozila/uso terapêutico , Hemostasia/efeitos dos fármacos , Hipertrigliceridemia/tratamento farmacológico , Hipertrigliceridemia/fisiopatologia , Hipolipemiantes/uso terapêutico , Resistência à Insulina , Adulto , Idoso , Glicemia/análise , Método Duplo-Cego , Ácidos Graxos não Esterificados/sangue , Teste de Tolerância a Glucose , Humanos , Hipertrigliceridemia/sangue , Insulina/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
An acquired platelet functional defect was found to be present in eight patients who presented with various clinical conditions--three with renal allograft rejection, three with the hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, one with acute consumption coagulopathy due to an incompatible transfusion and one with systemic lupus erythematosus. They showed defective platelet aggregation and reduced levels of adenine nucleotides and serotonin with abnormal uptake and storage of the amine. The bleeding time was more prolonged than predicted from the platelet count. These abnormalities were strikingly similar to those occurring in patients with congenital storage pool deficiency. The acquired defect is thought to be related to the presence in the circulation of "exhausted" platelets following their in vivo exposure to inducers of the release reaction such as damaged endothelium, thrombin and immune complexes. The bleeding tendency of the underlying diseases might be aggravated by the impairment of platelet function.
Assuntos
Transtornos Plaquetários/etiologia , Plaquetas/fisiologia , Difosfato de Adenosina/sangue , Trifosfato de Adenosina/sangue , Adulto , Complexo Antígeno-Anticorpo , Transtornos Plaquetários/imunologia , Plaquetas/metabolismo , Criança , Feminino , Rejeição de Enxerto , Humanos , Doenças do Sistema Imunitário/sangue , Masculino , Agregação Plaquetária , Testes de Função Plaquetária , Serotonina/sangueRESUMO
Derivatives of cyclic nucleotides were evaluated for their ability to inhibit platelet aggregation and the release reaction. Derivatives substituted in position 8 (mainly 8-Br-cyclic GMP) were more active than 3'-5' cyclic AMP, and their relative potency in inhibiting platelet aggregation and 14C-serotonin release was comparable to that of N62-0'-dibutyryl-cyclic AMP. Compounds substituted in position 6 or 2'-0 were not effective. The active compounds, which were also tested for their ability to stimulate platelet adenylate cyclase or to inhibit cyclic AMP phosphodiesterase, did not modify the intracellular levels of cyclic AMP. Since previous animal experiments have shown that these derivatives cause less side effects than cyclic AMP and its dibutyryl derivative in animals, it is suggested that modification of the cyclophosphate molecule might make it possible to find compounds active only on platelet function without interfering with other biological systems.
Assuntos
Plaquetas/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Bucladesina/farmacologia , AMP Cíclico/farmacologia , GMP Cíclico/farmacologia , Epinefrina/farmacologia , Humanos , Serotonina/metabolismoRESUMO
Fifty-two patients with chronic myeloproliferative disorders (13 with polycythemia vera; 23 with primary thrombocythemia; 6 with myelofibrosis and 10 with chronic granulocytic leukemia) had low platelet levels of adenine nucleotides and serotonin and abnormal uptake and storage of the amine. The storage pool deficiency was confined to the substances contained in the platelet dense bodies, because alpha-granule and lysosome markers were present in normal amounts. In chronic granulocytic leukemia the storage defect was usually less marked but was accompanied by a decreased formation of thromboxane B2 and normal platelet aggregation in response to arachidonic acid. There was no clearcut relationship of these biochemical abnormalities to prolongation of bleeding time or to thrombotic and hemorrhagic symptoms. The defect was still present in 15 patients after treatment had returned the cell counts to the normal range. Normal levels of 5HT and adenine nucleotides were observed in 8 patients whose platelet counts were high after splenectomy for non-hematological reasons. These findings suggest that biochemical abnormalities are related to the presence in the bone marrow of abnormal clones, resulting in the production of defective platelets.
Assuntos
Plaquetas/metabolismo , Transtornos Mieloproliferativos/metabolismo , Nucleotídeos de Adenina/análise , Ácidos Araquidônicos/metabolismo , Tempo de Sangramento , Doença Crônica , Humanos , Transtornos Mieloproliferativos/sangue , Agregação Plaquetária , Serotonina/metabolismoRESUMO
It is already known that activation of the coagulation and fibrinolytic system occurs in patients undergoing cardiopulmonary bypass (CPB). We have thus studied twenty patients (10 treated with aprotinin during CPB and 10 untreated) both during the intraoperative period and during thirty days follow up. In untreated patients D-dimer levels increased 4-fold during CPB and the levels were above baseline for the whole follow up (p < 0.0001). D-dimer levels were reduced in aprotinin treated patients in comparison to untreated patients (p = 0.0172); levels then gradually increased to the values of the untreated patients over the following 24 h later and remained higher during the thirty day follow up. The behavior of haemostatic variables in the 24 h after CPB did not vary between untreated and aprotinin treated patients. In particular, five minutes after protamine sulphate administration, levels of F1 + 2 and TAT rose significantly (p = 0.0054, p = 0.0022 respectively), whereas fibrinogen significantly decreased (p < 0.0001) and PAI-1 antigen levels were reduced. Two days after CPB the concentrations of F1 + 2 and TAT lowered, whereas fibrinogen and PAI-1 antigen levels increased. On the 5th, 8th and 30th days after CPB, F1 + 2 and TAT levels remained higher than those reported at baseline in both groups of patients, whereas fibrinogen levels increased over basal levels in aprotinin treated patients only. Thus, in addition to the activation of the coagulation and fibrinolytic system occurring during the intraoperative period, in patients undergoing CPB, there are alterations of haemostatic variables up to thirty days from surgery.
Assuntos
Aprotinina/farmacologia , Hemostasia , Anastomose de Artéria Torácica Interna-Coronária , Idoso , Antitrombina III/análise , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Fibrinogênio/análise , Fibrinólise , Seguimentos , Hemostasia/efeitos dos fármacos , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Peptídeo Hidrolases/análise , Inibidor 1 de Ativador de Plasminogênio/sangue , Período Pós-Operatório , Protrombina/análiseRESUMO
In this study the effects of different aggregating agents on platelet rich plasma (PRP) and whole blood (WB) aggregation, as determined by the optical and the impedance method, are evaluated. While the response of PRP to PAF, epinephrine and sodium arachidonate was comparable using the two methods, significantly greater amounts of collagen and ADP were required to obtain 50% aggregation of PRP. In addition, when the response of WB to the aggregation induced by different agents was compared to that of PRP (impedance method), no difference between WB and PRP was detected, with exception for ADP and sodium arachidonate induced aggregation. In vitro data on the aggregation of PRP induced by collagen and ADP in the presence of different concentrations of red cells and of white cells, suggest that WC and RC may affect PRP aggregation only in selected experimental conditions.
Assuntos
Células Sanguíneas/fisiologia , Testes de Coagulação Sanguínea , Coagulantes , Agregação Plaquetária/efeitos dos fármacos , Adulto , Testes de Coagulação Sanguínea/métodos , Plaquetas/fisiologia , Colágeno , Condutividade Elétrica , Eritrócitos/fisiologia , Feminino , Humanos , Leucócitos/fisiologia , Masculino , Pessoa de Meia-Idade , Nefelometria e Turbidimetria , Plasma/fisiologiaRESUMO
The newly developed method, based on the quantitation of changes in electrical impedance, to determine platelet aggregation in whole blood was applied to the evaluation of the effects of Indobufen, a well known inhibitor of platelet rich plasma aggregation. The platelet antiaggregatory activity of the drug after single (200 or 400 mg) and repeated doses (200 mg or 200 mg b.i.d. for 1 week) was determined on whole blood aggregation and thromboxane B2 formation by platelet rich plasma of 16 patients with high risk of atherosclerosis. At 2 hr after the single dose treatments, Indobufen significantly reduced the whole blood aggregation induced by 0.5-2 micrograms/ml collagen. At 24 hr from the intake of the drug the aggregation was significantly inhibited in patients who ingested the 400 mg dose only. As far as the repeated administrations are concerned, it appears that the inhibition of whole blood aggregation and thromboxane B2 formation by platelets reached 12 hr after the last drug administration was comparable to the degree of inhibition achieved 2 hr after Indobufen intake. It is concluded that Indobufen orally administered to patients with high risk of atherosclerosis is a potent inhibitor of whole blood aggregation.
Assuntos
Arteriosclerose/prevenção & controle , Coagulação Sanguínea/efeitos dos fármacos , Fenilbutiratos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Adulto , Idoso , Arteriosclerose/sangue , Relação Dose-Resposta a Droga , Feminino , Humanos , Isoindóis , Masculino , Pessoa de Meia-Idade , Fenilbutiratos/administração & dosagem , Inibidores da Agregação Plaquetária/administração & dosagem , Fatores de Risco , Tromboxano B2/biossíntese , Tromboxano B2/sangueRESUMO
This investigation sought to determine how different components of the hemostatic system affect the development of venous thrombosis in rats displaying hyperlipidemia, either on a genetic basis or secondary to metabolic disorders. On employing an experimental model of collagen-triggered venous thrombosis, both spontaneously hyperlipidemic (Yoshida strain) and streptozotocin-induced diabetic rats generated about 2.3-fold greater thrombi than normolipidemic controls. This was associated with significant platelet activation, as revealed by increased levels of serum thromboxane B2 in diabetics (1.5-fold) as well as in Yoshida (8-fold) rats, in comparison with controls. In contrast, ex vivo total fibrinolytic activity, as measured by euglobulin lysis time, did not differ between normo- and hyperlipidemic or diabetic animals. Plasminogen activator inhibitor activity was lower in both Yoshida and diabetic rats than in controls. However, tissue-type plasminogen activator activity was differently affected by the genetic or the diabetes-related hyperlipidemia, showing significantly lower values in Yoshida (-26%), but significantly higher values in diabetic rats (+29%) than in normolipidemic controls. We conclude that platelet activation, rather than consistent modifications of the fibrinolytic system, is likely to influence the enhanced thrombus development associated with primary or secondary forms of hyperlipidemia.
Assuntos
Hiperlipidemias/sangue , Ativação Plaquetária , Tromboflebite/sangue , Tromboflebite/etiologia , Animais , Modelos Animais de Doenças , Fibrinólise , Masculino , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos , Ratos Sprague-Dawley , Tromboxano B2/sangueRESUMO
A circular dichroism study has been performed to investigate the conformational properties of lysozyme adsorbed onto new and worn hydrophilic contact lenses. Whereas the native state of the protein is retained immediately after adsorption, lysozyme appears to be substantially denatured in worn lenses. These findings support the hypothesis of an immune response, due to lysozyme denaturation, for reported eye diseases in contact lens wearing patients. Regeneration processes to remove adsorbed proteins leave on the lens traces of potentially noxious materials. A reasonably frequent lens replacement is accordingly recommended.
Assuntos
Lentes de Contato de Uso Prolongado , Lentes de Contato Hidrofílicas , Proteínas do Olho/metabolismo , Lágrimas/metabolismo , Adsorção , Humanos , Conformação ProteicaRESUMO
Plant sterols lower serum cholesterol concentration. Available data have confirmed the lipid-lowering efficacy in adults, while there is a relative dearth of data in children and almost exclusively restricted to subjects with familial hypercholesterolemia (FH). Aim of the present study was to evaluate the efficacy, tolerability and safety of plant sterol supplementation in children with different forms of primary hyperlipidemias. The effect of plant sterol consumption on plasma lipids was evaluated in 32 children with heterozygous FH, 13 children with Familial Combined Hyperlipidemia (FCH) and 13 children with Undefined Hypercholesterolemia (UH) in a 12-week open-label intervention study using plant sterol-enriched yoghurt. Plasma lipids and apolipoproteins were measured by routine methods. Markers of cholesterol synthesis (lathosterol) and absorption (campesterol and sitosterol) were measured by GC-MS. Tolerability and adherence to recommended regimen was very high. A significant reduction was observed in LDL-cholesterol in the three groups (10.7, 14.2 and 16.0% in FH, FCH and UH, respectively). Lathosterol concentrations were unchanged, reflecting a lack of increased synthesis of cholesterol. Of the two absorption markers, only sitosterol showed a slight but significant increase. Daily consumption of plant sterol dairy products favorably changes lipid profile by reducing LDL-cholesterol. To our knowledge, this is the first report of the use of plant sterols-enriched foods in treating children with primary hyperlipidemia such as FCH and UH, likely to be the most frequent form also in the young age in the western populations.
Assuntos
Biomarcadores/sangue , Colesterol/metabolismo , Suplementos Nutricionais , Hiperlipidemias/dietoterapia , Lipídeos/sangue , Fitosteróis/administração & dosagem , Absorção , Adolescente , Anticolesterolemiantes/administração & dosagem , Criança , Colesterol/biossíntese , Colesterol/farmacocinética , Feminino , Alimentos Fortificados , Humanos , Hiperlipidemias/sangue , Masculino , IogurteAssuntos
Antitrombinas/sangue , Testes de Coagulação Sanguínea , Testes de Função Hepática , Animais , Biópsia , Doença Crônica , Feminino , Hepatite/sangue , Humanos , Soros Imunes , Imunoensaio , Indicadores e Reagentes , Fígado/patologia , Cirrose Hepática/sangue , Masculino , Métodos , Coelhos/imunologiaRESUMO
BACKGROUND: Sitosterolaemia is a rare autosomal recessive disorder characterised by elevated plasma levels of plant sterols and cholesterol. Sitosterolaemia is caused by gene mutations in either of two ATP-binding cassette (ABC) half transporters, ABCG5 and ABCG8. The plasma sterol profile and genetic analysis of a 10-year-old girl who had tuberous xanthomas is the subject of this report. MATERIALS AND METHODS: Genomic DNA was isolated from white blood cells from the proband, her family and a control group of healthy people. All exons of ABCG5 and ABCG8 were sequenced. Plasma cholesterol and triglycerides were measured by routine methods. All other plasma sterols were measured by Gas Chromatography coupled to Mass Spectrometry. RESULTS: The proband was found to be homozygous for a single nucleotide mutation in exon 10 of the ABCG5 gene, consisting of a C to T transition at nucleotide 1336 of the coding sequence, which results in the premature termination of the ABCG5 protein at amino acid 446 (Arg446X). Her mother and brother were also homozygous for the same mutation and all had elevated plasma beta-sitosterol levels. The father was heterozygous and showed normal beta-sitosterol levels. This mutation was not found in healthy normolipidaemic subjects. CONCLUSIONS: We describe a novel nonsense mutation in exon 10 of the ABCG5 gene in a 10-year-old girl showing clinical and biochemical features of sitosterolaemia. This family study broadens the spectrum of the ABCG5/ABCG8 mutations causing sitosterolaemia and helps highlight the correlations between such gene mutations, biochemical phenotype and the development of cardiovascular disease.
Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Éxons/genética , Lipoproteínas/genética , Membro 5 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Adulto , Criança , Colesterol/sangue , Família , Feminino , Humanos , Irã (Geográfico)/etnologia , Masculino , Pessoa de Meia-Idade , Mutação , Sitosteroides/sangue , Esteróis/sangue , Triglicerídeos/sangue , Xantomatose/etiologiaRESUMO
Lysinuric protein intolerance (LPI) is a disorder of dibasic amino acid transport secondary to mutation of the SLC7A7 gene characterized by renal failure, pulmonary alveolar proteinosis, lupus-like autoimmune symptoms and usually increased plasma citrulline. In order to better understand the underlying mechanism, we studied the plasma and urinary nitrite/nitrate (NO2-/NO3-) concentrations in three LPI patients and the in vitro NO2- production in cultured fibroblasts. Our data show that NO3- levels are increased in the plasma of patients with LPI. Similarly, NO2- release in the medium of cultured fibroblasts was increased. On this basis, we hypothesize that some of the poorly understood clinical signs of LPI could be related to the activation of the NO-citrulline pathway.
Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/metabolismo , Lisina/metabolismo , Óxido Nítrico/metabolismo , Adolescente , Erros Inatos do Metabolismo dos Aminoácidos/genética , Sistema y+L de Transporte de Aminoácidos , Células Cultivadas , Criança , Citrulina/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Cadeias Leves da Proteína-1 Reguladora de Fusão/genética , Humanos , Nitratos/sangue , Nitratos/urina , Óxido Nítrico Sintase/metabolismo , Óxido Nítrico Sintase Tipo II , Nitritos/sangue , Nitritos/urinaRESUMO
A relation between elevated triglyceride (TG) levels and alterations of the fibrinolytic system has been recognized in studies of patients with coronary heart disease. In this investigation, the total fibrinolytic activity and the levels of specific components of the fibrinolytic system were evaluated in plasma samples from a highly selected group of patients with type IV hyperlipoproteinemia before and after a dietary treatment aimed at reducing TG levels. The fibrinolytic response of type IV patients was comparable to that of normolipidemic subjects, whereas tissue-type plasminogen activator antigen levels before and after venous occlusion (p less than 0.01) and resting plasminogen activator inhibitor-1 (PAI-1) antigen (p less than 0.01) and activity (p less than 0.01) were significantly higher in hypertriglyceridemic subjects compared with controls. After dietary treatment, a 22% reduction in TG levels was attained in type IV patients, with no appreciable modification of fibrinolytic parameters. The analysis of the single-patient data revealed a tendency toward normalization of PAI-1 levels only in those patients who showed a TG reduction greater than or equal to 20%. Very low density lipoproteins (VLDLs) from both normal and type IV patients concentration-dependently stimulated PAI-1 release by endothelial cells and HepG2 cells, with the effect of VLDL from type IV patients being more pronounced on HepG2 cells. The release of PAI-1 induced by VLDL in competent cells may thus account for the elevated levels of this antifibrinolytic protein that occur in hypertriglyceridemic patients.
Assuntos
Fibrinólise , Hiperlipoproteinemia Tipo IV/sangue , Adulto , Carcinoma Hepatocelular/metabolismo , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Feminino , Humanos , Hiperlipoproteinemia Tipo IV/dietoterapia , Lipoproteínas VLDL/farmacologia , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Inativadores de Plasminogênio/metabolismo , Soroglobulinas/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Triglicerídeos/sangue , Células Tumorais CultivadasRESUMO
We investigated the relationship between plasma levels of metabolic and fibrinolytic variables in 163 fasted patients attending a lipid clinic. Of these patients, 118 had hypertriglyceridaemia (HTG) and 45 had normotriglyceridaemia (NTG). In HTG, basal fibrinolytic activity, ie tissue plasminogen activator (t-PA) activity, was impaired as a result of high plasminogen activator inhibitor type 1 (PAI-1) antigen and activity. Multiple stepwise regression analysis identified insulin and triglyceride levels as independent determinants of plasma PAI-1 levels (R2 = 0.18; P = 0.0001). When the patients were stratified into tertiles according to their levels of triglyceride and insulin, PAI-1 antigen levels were found to increase with rising levels of triglyceride in each insulin tertile. In contrast, the increase of PAI-1 with rising insulin levels was evident in the highest triglyceride tertile. In addition, subjects in the lowest tertile of both triglyceride and insulin had the lowest PAI-1 antigen levels, and subjects in the highest tertile of both triglyceride and insulin had the highest levels of PAI-1. Both basal and stimulated levels of t-PA antigen were significantly higher in HTG than in NTG. Multiple stepwise regression analysis identified triglyceride level as the sole major determinant of t-PA antigen levels (R2 = 0.13; P = 0.00003). The observation that both insulin and triglycerides correlate with PAI-1, whereas triglycerides were involved only in the increased secretion of t-PA, suggests that these two proteins are regulated by different mechanisms.
Assuntos
Hiperlipidemias/sangue , Insulina/biossíntese , Inibidor 1 de Ativador de Plasminogênio/sangue , Ativadores de Plasminogênio/sangue , Ativador de Plasminogênio Tecidual/sangue , Triglicerídeos/biossíntese , Adolescente , Adulto , Idoso , Instituições de Assistência Ambulatorial , Feminino , Humanos , Hiperlipidemias/diagnóstico , Hiperlipidemias/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valores de Referência , Análise de Regressão , Sensibilidade e EspecificidadeRESUMO
Low dose metformin (500 mg b.i.d.) was tested in 11 patients with symptomatic peripheral vascular disease (PVD) in an open design. At -1, 0, 1, 4, 7 months the major lipid and lipoprotein parameters, arterial function, and fibrinolytic activity were monitored. Arterial function changes were similar to those found with a high dose (850 mg t.i.d.) metformin but plasma lipids did not change to an appreciable extent. Post-ischaemic blood flow, by plethysmography, rose 30%; the exercise capacity, evaluated by treadmill test, also increased significantly by 105.7% for relative and 53.3% for absolute claudication. Total fibrinolytic activity did not change during the treatment but the antigens of two of the major components of the fibrinolytic system, i.e. t-PA and PAI-1, were significantly reduced at the end of the study. This study gave results quite consistent with those obtained with higher metformin doses, associated with a potentially higher risk of lactic acidosis.
Assuntos
Metformina/uso terapêutico , Doenças Vasculares/tratamento farmacológico , Idoso , Teste de Esforço , Humanos , Lipídeos/sangue , Lipoproteínas/sangue , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , PletismografiaRESUMO
The effects of bezafibrate 400 mg/day (slow release formulation) on plasma lipids/lipoproteins and on selected haemostatic parameters were evaluated in a double blind cross-over study in patients with Type IIb and IV hyperlipoproteinaemia. Placebo treatment did not influence any of those parameters, but the drug significantly reduced plasma triglycerides (-45%) and VLDL cholesterol, as well as causing a 12% fall in total cholesterol and a 20% increase in HDL cholesterol. Apo AI levels were significantly increased following bezafibrate and Apo B was reduced by about 20%. In addition to changes in the plasma lipid profile, bezafibrate reduced the sensitivity of platelets to the aggregatory effect of collagen, with no effect on TXB2 production. Fibrinogen levels after bezafibrate treatment were significantly lowered, the effect being more marked in patients with hyperfibrinogenaemia. Bezafibrate did not influence the plasma fibrinolytic profile. It is concluded that bezafibrate, besides its beneficial effects on the plasma lipoprotein profile, can exert beneficial changes on specific haemostatic parameters.