RESUMO
This article describes a case report on a rare cause of acute respiratory failure. The patient suffered from a rapidly progressing respiratory insufficiency due to intoxication with a neurotoxin (botulism). A rapid diagnosis proved to be very difficult due to the rarity of the disease itself and the difficulties encountered in the clinical examination caused by early initiation of intubation, artificial ventilation and analgosedation.
Assuntos
Botulismo/complicações , Insuficiência Respiratória/etiologia , Antitoxina Botulínica , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Síndrome do Desconforto RespiratórioRESUMO
We report on a 79 years old female patient with slowly progressive painful weakness of the proximal upper and lower limbs. CK was slightly elevated (242 U 7 l). MRI guided biopsy of the proximal lower limbs revealed the rare findings of nemaline myopathy.
Assuntos
Miopatias da Nemalina/diagnóstico , Idoso , Biópsia , Creatina Quinase/sangue , Diagnóstico Diferencial , Eletromiografia , Feminino , Humanos , Extremidade Inferior/patologia , Imageamento por Ressonância Magnética , Debilidade Muscular/etiologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Miopatias da Nemalina/patologia , Extremidade Superior/patologiaRESUMO
BACKGROUND: Hyperhomocysteinaemia is a metabolic disorder associated with the development of premature atherosclerosis. Among the determinants which predispose to premature thromboembolic and atherothrombotic events, serum activity of paraoxonase 1, mainly synthesized in the liver, has been shown to be a predictor of cardiovascular disease and to be negatively correlated with serum homocysteine levels in human. Even though treatments of hyperhomocysteinaemic patients ongoing cardiovascular complications are commonly used, it still remains unclear above which homocysteine level a preventive therapy should be started. MATERIALS AND METHODS: In order to establish a threshold of plasma homocysteine concentration we have analyzed the hepatic cystathionine beta synthase and paraoxonase 1 activities in a moderate to intermediate murine model of hyperhomocysteinaemia. Using wild type and heterozygous cystathionine beta synthase deficient mice fed a methionine enriched diet or a control diet, we first studied the link between cystathionine beta synthase and paraoxonase 1 activities and plasma homocysteine concentration. RESULTS: Among the animals used in this study, we observed a negative correlation between plasma homocysteine level and cystathionine beta synthase activity (rho=-0.52, P=0.0008) or paraoxonase 1 activity (rho=-0.49, P=0.002). Starting from these results, a homocysteine cut-off value of 15 microm has been found for both cystathionine beta synthase (P=0.0003) and paraoxonase 1 (P=0.0007) activities. CONCLUSIONS: Our results suggest that both cystathionine beta synthase and paraoxonase 1 activities are significantly decreased in mice with a plasma homocysteine value greater than 15 microm. In an attempt to set up preventive treatment for cardiovascular disease our results indicate that treatments should be started from 15 microm of plasma homocysteine.
Assuntos
Arildialquilfosfatase/metabolismo , Cistationina beta-Sintase/metabolismo , Homocisteína/sangue , Hiper-Homocisteinemia/metabolismo , Animais , Modelos Animais de Doenças , Fígado/metabolismo , CamundongosRESUMO
The sudden onset of hearing impairment or hearing loss can be a characteristic sign of a vertebrobasilar circulatory disturbance. We report on a 65 year old male patient with an acute left-sided tinnitus followed by hearing loss as an initial symptom of an infarction of the left anterior inferior cerebellar artery (AICA). Successively, additional symptoms with vertigo, nausea, vomiting and a transient dysarthria and ataxia of the left upper extremity occurred. In the course of the illness, the hearing loss, ataxia and dysarthria completely recovered. MRI of the brain showed an infarction in the area of the anterior inferior cerebellar artery; neurosonographic examination of the basilar and vertebral arteries was normal. Therefore, in patients with acute hearing impairment or hearing loss, an AICA-ischemia should be considered and the patient carefully examined for additional brainstem symptoms, since this can be the first sign of an life-threatening basilar artery thrombosis.
Assuntos
Infarto Encefálico/complicações , Infarto Encefálico/diagnóstico , Doenças Cerebelares/complicações , Doenças Cerebelares/diagnóstico , Cerebelo/irrigação sanguínea , Perda Auditiva Súbita/diagnóstico , Perda Auditiva Súbita/etiologia , Idoso , Humanos , Masculino , Zumbido/diagnóstico , Zumbido/etiologiaRESUMO
A lot of methods are now available for total plasma homocysteine (tHcy) determination. Commercial kits using immunoassay, easier to use, begin to supplant in-house laboratory methods. Our aim is to evaluate the interchangeability of tHcy measurements in 9 French hospital laboratories. Six different method types were used: 2 gas chromatography-mass spectrometry (GC-MS), 2 HPLC with fluorescence detection subdivided in one in-house method and one commercial kit (Bio-Rad ), 3 fluorescence polarization immunoassays (FPIA), 1 enzyme immunoassay, 1 amino acid analyser, 1 capillary electrophoresis coupled with laser-induced fluorescence detection (EC-LIF). Each laboratory analysed 41 patient's plasma samples in which 8 samples contained added homocystine. Results were analysed for imprecision, recovery, and methodological differences. The mean among-laboratory imprecision (CV) ranged from 12.5 to 18% in function of plasma sample type and was identical to the mean among-method variation. In terms of recovery, we obtained underestimated results with immunoassays. The bias relative to the GC-MS method was less than 12.5% except for two laboratories, one using FPIA assay and the other EC-LIF. In conclusion, the interchangeability of tHcy results between laboratories is not satisfactory and does not allow us to evaluate cardiovascular risk linked to moderate increases of tHcy.
Assuntos
Análise Química do Sangue/métodos , Homocisteína/sangue , Laboratórios Hospitalares , Análise Química do Sangue/normas , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Eletroforese Capilar , Fluorescência , Imunoensaio de Fluorescência por Polarização , França , Humanos , Técnicas Imunoenzimáticas , Laboratórios Hospitalares/normas , Lasers , Espectrometria de Massas , Kit de Reagentes para DiagnósticoRESUMO
AIM: Fabry disease is an X-linked inborn error of glycosphingolipid metabolism due to the deficient activity of alpha-galactosidase A, a lysosomal enzyme. It is a multisystem disorder characterized by progressive renal insufficiency, with added morbidity from cardio- and cerebrovascular involvement. The recent availability of genetically engineered enzyme offers an effective targeted treatment approach, but also emphasizes the need for surrogate markers to delineate organ damage and monitor the efficacy of enzyme replacement therapy (ERT). METHODS: Multiple endothelial factors and plasma homocysteine concentrations were investigated in 12 consecutive hemizygous males with classic Fabry disease and 15 controls as part of an exhaustive baseline evaluation prior to ERT. RESULTS: Compared with the controls, plasma concentrations of homocysteine were significantly (p < 0.01) higher in patients with Fabry disease in the absence of chronic renal failure or vitamin deficiency. Plasma concentrations of vascular cell adhesion molecule-1 were also significantly (p < 0.05) higher in the patients, and there was a trend for decreased endothelin-1 levels. No difference was found in serum intercellular adhesion molecule-1, plasma P-selectin, serum E-selectin and plasma thrombomodulin between the patients and controls. CONCLUSIONS: The results do not reveal measurable evidence for endothelial and leukocyte activation that could reliably serve as surrogate markers for routine monitoring of the efficacy of ERT in patients with Fabry disease. While the exact origin and clinical significance of hyperhomocysteinaemia in Fabry disease remains to be studied in a larger cohort of patients carefully monitored for their concurrent medications, especially carbamazepine, we suggest that patients may benefit from folic acid or multivitamin therapy to treat this additional vascular risk factor, when present.
Assuntos
Endotelina-1/sangue , Doença de Fabry/sangue , Doença de Fabry/complicações , Homocisteína/sangue , Doenças Vasculares/sangue , Doenças Vasculares/etiologia , Adolescente , Adulto , Estudos de Coortes , Creatinina/sangue , Selectina E/sangue , Doença de Fabry/terapia , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , Selectina-P/sangue , Trombomodulina/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Doenças Vasculares/terapiaRESUMO
The increased cardiovascular risk associated with hyperhomocysteinemia has been partly related to homocysteine (Hcy)-induced endothelial cell dysfunction. However, the intra or extracellular starting point of the interaction between Hcy and endothelial cells, leading to cellular dysfunction, has not yet been identified. We investigated the effects of both intracellular and extracellular Hcy accumulation on endothelin-1 (ET-1) synthesis by cultured human endothelial cells. Incubation of cultures with methionine (1.0 mmol x L(-1)) for 2 h induced a slight increase in cellular Hcy content but no change in ET-1 production. Incubation of cells with Hcy (0.2 mmol x L(-1)) led to a significant fall in ET-1 generation, accompanied by a significant increase in cellular Hcy content. Addition of the amino-acid transport system L substrate 2-amino-2-norbornane carboxylic acid had no effect on the Hcy-induced decrease in ET-1 production but significantly inhibited the Hcy-induced increase in the cellular Hcy content. Incubation of cells with a lower Hcy concentration (0.05 mmol x L(-1)) also reduced ET-1 production without increasing the cellular Hcy content. Co-incubation with extracellular free-radical inhibitors (superoxide dismutase, catalase and mannitol) markedly reduced the effect of Hcy on ET-1 production. Thus, it is extracellular Hcy accumulation that triggers the decrease in ET-1 production by endothelial cells through oxidative products.
Assuntos
Endotelina-1/metabolismo , Espaço Extracelular/efeitos dos fármacos , Homocisteína/metabolismo , Homocisteína/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Linhagem Celular , Endotelina-1/biossíntese , Endotélio/citologia , Endotélio/efeitos dos fármacos , Endotélio/metabolismo , Espaço Extracelular/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Líquido Intracelular/metabolismo , Metionina/metabolismo , Metionina/farmacologia , Oxidantes/metabolismo , Oxidantes/farmacologia , Oxirredução/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismoRESUMO
Venous blood flow rate in the lower extremity after applying different pneumatic compression devices was evaluated. Five healthy individuals, aged 21-35, were recruited for this study. The ability of six different pneumatic compression devices to increase femoral venous blood flow velocity was analyzed and compared to that of active and passive foot dorsiflexion. Baseline venous blood flow velocity was measured using an ATL Duplex Doppler before leg compression. Venous blood flow velocity was then monitored before, during, and after each compression cycle. Average peak venous velocity increased >200% on dorsiflexion of the ankle. Among the investigated devices, the increase in venous velocity varied significantly. Design of compression chambers enabling compression on the lateral and medial aspects of the calf produced an increase in venous velocity closest to active foot dorsiflexion. Foot compression devices produced the smallest increase in venous velocity. The relative effectiveness of pneumatic compression devices, particularly with respect to increasing venous blood flow in the lower extremity, may correlate well with how closely the device simulates the physiologic contraction of the calf muscles. Clinical trials are needed to further compare the effectiveness of these devices, as other less readily measured factors play a role in thromboprophylaxis.
Assuntos
Bandagens , Trombose Venosa/prevenção & controle , Adulto , Velocidade do Fluxo Sanguíneo , Desenho de Equipamento , Segurança de Equipamentos , Feminino , Veia Femoral/fisiologia , Humanos , Perna (Membro) , Masculino , Valores de Referência , Sensibilidade e Especificidade , Trombose Venosa/fisiopatologiaAssuntos
Linguagem Infantil , Comportamento Verbal , Pré-Escolar , Humanos , Fala , Medida da Produção da FalaRESUMO
An increase in homocysteine, a sulphur amino acid, is nowdays considered as a risk factor for cardiovascular diseases, and is independent of other risk factors. Reference range for total plasma homocysteine level in adults is usually 5-15 mmol/l. Hyperhomocysteinemia is defined as a fasting total plasma homocysteine level > 15 mmol/l. There may be also graded increased risks for subjects with homocysteinemia from 10 to 15 mmol/l. However, no threshold has been defined, partly because of the lack of standardization in pre-analytical and analytical steps. The aim of the present work was to evaluate three pre-analytical parameters on plasma homocysteine levels: i) the influence of three anticoagulants (EDTA, sodium citrate and lithium heparin); ii) the delay period of blood sample on ice before centrifugation; and iii) the advantages of strong acidic citrate at room temperature. The mean concentrations of total plasma homocysteine were different in function of the anticoagulant. These differences (EDTA minus lithium heparin or EDTA minus sodium citrate) were less than 10% however the used methods and could explain the good correlation between the results. However we recommend to keep the anticoagulant constant in the same study. When EDTA blood samples were immediately put on crushed ice, the maximum delay period before centrifugation could reach 4 hours. If ice is unavailable, strong acidic citrate at room temperature is a good alternative until for 4 hours.
Assuntos
Homocisteína/sangue , Anticoagulantes/farmacologia , Centrifugação , Ácido Cítrico , Criopreservação , Homocisteína/efeitos dos fármacos , Humanos , Temperatura , Fatores de TempoRESUMO
BACKGROUND AND PURPOSE: The diagnosis and quantification of microangiopathy in dementia is difficult. The assessment of small-vessel disease requires expensive and sophisticated nuclear medicine techniques. This study was performed to identify microangiopathy related to the integrity of cerebral microcirculation by sonographic measurements (arteriovenous cerebral transit time [cTT]). METHODS: We performed transcranial color-coded duplex sonography in 40 patients with vascular dementia, 20 patients with Alzheimer's disease or Lewy body disease, and 25 age-matched controls. The clinical diagnosis was established by history of dementia and neuroimaging findings. Cognitive impairment was assessed by the Mini-Mental State Examination and Alzheimer's Disease Assessment Scale. cTT is defined as the time required by an ultrasound contrast agent to pass from a cerebral artery to a vein. This was measured by recording the power-Doppler intensity curves in the P2 segment of the posterior cerebral artery and the vein of Galen. Previous studies have shown a prolongation of cTT in patients with cerebral microangiopathy. RESULTS: cTT was substantially prolonged in patients with vascular dementia (5.8 seconds; 25th percentile 4.5; 75th percentile 7.5; U test, P<0.001) compared with controls (3.1 seconds; 2.3; 3.4) but not in patients with degenerative dementia (3.7 seconds; 3.7; 4.2). In patients with vascular dementia, cTT was significantly correlated with cognitive impairment. CONCLUSIONS: cTT may be useful tool to disclose small-vessel disease in demented patients. Examination is noninvasive and quickly performed. It may be also useful in follow-up examinations in patients undergoing therapy.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Demência Vascular/diagnóstico por imagem , Doença por Corpos de Lewy/diagnóstico por imagem , Ultrassonografia Doppler Transcraniana , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Estudos de Casos e Controles , Veias Cerebrais/diagnóstico por imagem , Transtornos Cognitivos/diagnóstico , Meios de Contraste , Feminino , Seguimentos , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Microcirculação/fisiologia , Pessoa de Meia-Idade , Polissacarídeos , Artéria Cerebral Posterior/diagnóstico por imagem , Fatores de Tempo , Ultrassonografia Doppler em Cores , Ultrassonografia Doppler DuplaRESUMO
This double-blind, randomized, placebo-controlled clinical trial evaluated the impact on withdrawal symptoms of (i) combining naltrexone with a 4-day buprenorphine taper for short opioid detoxification (NB Group), compared to (ii) using a 4-day buprenorphine taper alone, followed by naltrexone on day 8 (PB Group). Sublingual buprenorphine was administered on days 1-4 (26 mg total). For the NB Group (n = 32) escalating doses of oral naltrexone were given on days 2-8 (placebo day 1). For the PB Group (n = 28) placebo was given on days 1-7 and naltrexone on day 8. Main outcome measures were Observed Opioid Withdrawal scores (OOW, 0-30) and use of medications to treat opioid withdrawal. Of 32 patients in the NB group, 59% experienced clinically relevant withdrawal (defined as OOW > or = 5) on day 2, but, after day 5, none experienced withdrawal. In the PB group, the number of patients experiencing withdrawal increased over time. The first naltrexone dose induced comparable withdrawal in both groups: peak OOW scores were (mean +/- SD) 5.2 +/- 3.3 on day 2 for the NB group, and 4.0 +/- 3.9 on day 8 for the PB group (NS), though, on day 2, 7 patients dropped out in the NB group and none in the PB group, while only one patient dropped out in the PB group on day 8. Throughout the 8-day study, patients in both groups received similar amount of adjunct medication: 0.64 +/- 0.07 mg (NB group) of clonidine vs 0.73 +/- 0.15 mg (PB group; NS). Only 25% of patients required use of sedatives (up to 20 mg diazepam). Starting naltrexone on day 2 appeared to abolish withdrawal symptoms after day 5 and, thus, to shorten the duration of withdrawal symptoms. Peak withdrawal symptoms after naltrexone were of moderate intensity, suggesting that naltrexone combined with buprenorphine is an acceptable and safe treatment for shortened opioid detoxification and induction of naltrexone maintenance.
Assuntos
Buprenorfina/uso terapêutico , Dependência de Heroína/reabilitação , Heroína/efeitos adversos , Naltrexona/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Adulto , Analgésicos/uso terapêutico , Área Sob a Curva , Clonidina/uso terapêutico , Método Duplo-Cego , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Humanos , Masculino , Síndrome de Abstinência a Substâncias/fisiopatologiaRESUMO
In patients with end-stage renal disease, plasma homocysteine and cardiac mass are both increased and considered independent risk predictors for cardiovascular-specific morbidity and mortality. In order to establish a relationship between these two parameters, we determined cardiac mass and plasma homocysteine in 75 patients with end-stage renal disease undergoing chronic hemodialysis. We observed a statistically significant positive association between plasma homocysteine and cardiac mass index or either of its components. This was observed even after adjustment for age, sex, systolic blood pressure and hematocrit (p = 0.0027). The adjusted odds ratio for left ventricular hypertrophy was 6.6 (95% confidence interval 1.3-32.8) for subjects with the highest versus the lowest plasma homocysteine concentrations. This cross-sectional study is the first to show a statistical link between plasma homocysteine and cardiac structure, independently of mechanical factors. High plasma homocysteine concentrations are associated with an increased adjusted risk of left ventricular hypertrophy in end-stage renal disease patients.
Assuntos
Homocisteína/sangue , Hipertrofia Ventricular Esquerda/etiologia , Falência Renal Crônica/complicações , Pressão Sanguínea , Feminino , Ácido Fólico/sangue , Hematócrito , Humanos , Hipertrofia Ventricular Esquerda/sangue , Hipertrofia Ventricular Esquerda/fisiopatologia , Falência Renal Crônica/sangue , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prognóstico , Diálise Renal , Fatores de Risco , Vitamina B 12/sangueRESUMO
Hyperhomocysteinemia is believed to be responsible for the development of vascular disease via several mechanisms, including the impairment of endothelial-cell functionality. In-vitro studies have demonstrated that homocysteine decreases the production or bioavailability of vasodilator autacoids, such as prostacyclin and NO. Here, we show that the treatment of human endothelial cells with noncytotoxic homocysteine concentrations leads to a dose-dependent decrease in both the secretion of the vasoconstrictor agent endothelin-1 (ET-1) and the level of its mRNA. Homocysteine had an inhibitory effect at pathophysiological (0.1 and 0.5 mmol.L(-1)) and pharmacological noncytotoxic (1.0 and 2.0 mmol.L(-1)) concentrations. Mean percentage variation from control for ET-1 production was -36. 2 +/- 18.9% for 0.5 mmol.L(-1) homocysteine and -41.5 +/- 26.8% for 1.0 mmol.L(-1) homocysteine, after incubation for 8 h. Mean percentage variation from control for steady-state mRNA was -17.3 +/- 7.1% for 0.5 mmol.L(-1) homocysteine and -46.0 +/- 10.1 for 1.0 mmol.L(-1) homocysteine, after an incubation time of 2 h. ET-1 production was also reduced by incubation with various other thiol compounds containing free thiol groups, but not by incubation with thiol compounds with no free thiol group. Co-incubation of cells with homocysteine and the sulfhydryl inhibitor N-ethylmaleimide prevented the effect of homocysteine on ET-1 production, confirming a sulfhydryl-dependent mechanism. Based on the reciprocal feedback mechanism controlling the synthesis of vasoactive mediators, these preliminary data suggest a mechanism by which homocysteine may selectively impair endothelium-dependent vasodilation by primary inhibition of ET-1 production.
Assuntos
Endotelina-1/biossíntese , Endotélio Vascular/efeitos dos fármacos , Homocisteína/farmacologia , Mercaptoetanol , S-Nitrosotióis , Arteriosclerose/metabolismo , Linhagem Celular , Sobrevivência Celular , Relação Dose-Resposta a Droga , Endotelina-1/metabolismo , Endotélio Vascular/metabolismo , Epoprostenol/análise , Humanos , Compostos Nitrosos/análise , Fatores de TempoRESUMO
Studies of symptomatic patients have identified hyperhomocysteinemia as an independent risk factor for vascular disease. In case-control studies, a point mutation (C677T) in the gene encoding 5,10-methylenetetrahydrofolate reductase (MTHFR) has also been linked to an increased risk of vascular disease through its effect on homocysteinemia. Our aim was to extend these observations to asymptomatic subjects by studying the influence of both homocysteinemia and its mutation on carotid artery geometry. We examined 144 subjects free of atherosclerotic lesions. Fasting homocysteinemia was measured by high-performance liquid chromatography with fluorometric detection. MTHFR genotype was analyzed by polymerase chain reaction followed by HinfI digestion. Carotid artery geometry was characterized by internal diameter and intima-media thickness, as assessed by a high-resolution echo-tracking system. Subjects in the upper homocysteine tertile had a greater carotid internal diameter than did subjects in the middle and lower tertiles (6516+/-770 versus 6206+/-641 and 5985+/-558 microm, respectively; P<0.001). Subjects homozygous for the mutation had a smaller carotid artery internal diameter than did subjects heterozygous or homozygous for the wild-type allele (5846+/-785 versus 6345+/-673 and 6199+/-671 microm, respectively; P<0.05). Homocysteinemia was not significantly increased in subjects homozygous for the mutation. In multivariate regression analysis, homocysteinemia was independently and positively associated with lumen diameter (P=0.0008) and wall thickness (P=0.020). Conversely, homozygosity for the mutation was negatively associated with internal diameter (P=0.009). These preliminary data suggest that mildly elevated homocysteinemia and homozygosity for the MTHFR C677T mutation are associated with opposite preclinical modifications of carotid artery geometry. If confirmed, these results may have important implications for new treatment strategies for vascular disease before the onset of clinical manifestations.
Assuntos
Artérias Carótidas/anatomia & histologia , Homocisteína/sangue , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Adulto , Idoso , Feminino , Genótipo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2) , Pessoa de Meia-Idade , Análise Multivariada , MutaçãoRESUMO
Epidemiological, clinical, and experimental studies have demonstrated that high density lipoproteins (HDL) are protective against atherosclerosis. However, the respective influence of two main HDL subfractions (HDL2 and HDL3) on atherosclerosis process is not yet clear. The present study was designed to determine, which HDL subfraction was antiatherogenic in terms of eicosanoid release by human umbilical vein endothelial cells (HUVEC). Endothelial cells were incubated for 4 hours with HDL2 or HDL3 and prostaglandins 6-keto-PGF1alpha, thromboxane B2 and prostaglandin E2 were measured by RIA in culture supernatant. HDL2 has a dose dependent stimulatory effect on 6-keto-PGF1alpha release without stimulatory effect on thromboxane B2 secretion. The 6-keto-PGF1alpha/thromboxane B2 ratio increased progressively from 1.65 to 4.65 for 0.39 to 6.25 mg HDL protein/ml. The pattern of prostanoid secretion under influence of HDL3 showed a predominant response in 6-keto-PGF1alpha and TxB2 release. As regards PGE2, both HDL subfractions stimulated considerably secretion of this prostanoid in a dose dependent manner. In terms of PGI2/TxA2 balance the better antiatherogenic effect was observed with HDL2 subfraction.
Assuntos
Eicosanoides/metabolismo , Endotélio Vascular/metabolismo , Lipoproteínas HDL/farmacologia , Células Cultivadas , Relação Dose-Resposta a Droga , HumanosRESUMO
The incremental elastic modulus of the common carotid and radial arteries is increased in patients with end-stage renal disease (ESRD), independently of blood pressure, wall stress, and the presence of atherosclerotic alterations. Whether biochemical factors may be involved in the arterial changes and related to renal dysfunction remain largely ignored. To assess this question, we measured aortic (carotid-femoral), upper-limb (carotid-radial), and lower-limb (femoral-tibial) pulse wave velocity (PWV) in 74 ESRD patients undergoing hemodialysis in comparison with 57 control subjects similar in age, sex ratio, and mean blood pressure. We evaluated arterial blood pressure by sphygmomanometry, aortic calcifications and cardiac mass by echography, and routine biochemical parameters, total plasma homocysteine, and plasma endothelin levels by standard techniques. In the population of patients with ESRD, on the basis of multiple stepwise regression analysis, aortic PWV was positively and independently correlated with systolic blood pressure (P<.0001), age (P<.0001), prevalence of aortic calcification (P=.0004), and the prevalence of diabetes mellitus (P=.0043). Upper-limb PWV was influenced exclusively by mean blood pressure (P<.0001). Lower-limb PWV was positively and independently correlated with plasma total homocysteine (P=.0004) and plasma endothelin (P=.0187) only. At any vascular site, PWV was not independently correlated with tobacco consumption; plasma levels of cholesterol, triglyceride, fibrinogen, or hemoglobin; body mass index; or the presence of bilateral nephrectomy. Finally, plasma homocysteine was independently correlated with cardiac mass (P=.0022). This study provides evidence that in ESRD patients, the stiffness of the arterial wall and cardiac mass are strongly influenced by biochemical factors related to the kidney alterations and are independent of age and blood pressure level. Increased plasma endothelin and homocysteine may be specifically involved in the vascular damage of lower limbs.