RESUMEN
Peripheral arterial disease (PAD) is by far the most common cause of intermittent claudication. This disease can greatly reduce the affected individual's walking capacity and can seriously affect daily life activities. Few therapeutic options are aimed at improving walking capacity. This was a randomized, doubleblind, placebo-controlled, multicenter trial, performed in 24 Italian centers. Two hundred seventeen patients with intermittent claudication (stages IIa and IIb of Fontaine's PAD classification) were randomly assigned to heparan sulfate (40 mg orally twice a day) or placebo for 6 months. The primary end-point was an increase in pain-free walking distance [initial claudication distance (ICD)] during the 24 weeks of treatment. The pain-free and the absolute walking distance (ACD) were monitored by standardized treadmill test at baseline and at 4, 12 and 24 weeks. The change in initial claudication distance during treatment, expressed as integrated change over time, was significantly greater with heparan sulfate than with placebo (306 +/- 494 vs. 250 +/- 510 meters x months, p = 0.019). Significantly fewer treated patients worsened during treatment (decreased initial claudication distance) compared with controls (9.1% vs. 19.6%; p = 0.027). Functional recovery in the most severely affected subgroup of patients (stage IIb of Fontaine's classification) was more clearly detected and significantly greater among treated than among control patients (absolute increase in ICD: 70 +/- 113 vs. 58 +/- 172 meters, p = 0.028; integrated increase: 304 +/- 422 vs. 208 +/- 503 meters x months; p = 0.004). Heparan sulfate appeared to increase the walking capacity of patients with intermittent claudication to a significantly greater extent than did placebo. The treatment was well tolerated.
Asunto(s)
Anticoagulantes/uso terapéutico , Heparitina Sulfato/uso terapéutico , Claudicación Intermitente/tratamiento farmacológico , Anciano , Anticoagulantes/efectos adversos , Método Doble Ciego , Femenino , Hemodinámica/efectos de los fármacos , Heparitina Sulfato/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Factores de Tiempo , CaminataRESUMEN
The fibrinolytic and anticoagulant activities of heparan sulphate (HS) and dermatan sulphate (DS) were compared with those of heparin using in vitro tests. Our results demonstrate that HS has higher profibrinolytic activity than heparin and DS. Although 50 times less potent than heparin in inhibiting factor IIa, HS is three times more active than DS. The action of HS resides in HCH-mediated factor IIa inhibition combined with an ATIII-mediated inhibition. DS has no action on ATIII-mediated inhibition of factor IIa. The comparison of the anticoagulant activities of the three compounds confirmed the very limited anticoagulant effect of both HS and DS in comparison with heparin.
Asunto(s)
Dermatán Sulfato/farmacología , Heparina/farmacología , Heparitina Sulfato/farmacología , Animales , Anticoagulantes/farmacología , Coagulación Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Fibrinólisis/efectos de los fármacos , Técnicas In Vitro , Masculino , Peso Molecular , Conejos , Ratas , Ratas WistarRESUMEN
Sixty patients, recognized as chronic alcoholics on the grounds of the case history and with a score above 11 of the Munich Alcoholism Test (MALT) have been treated with metadoxine or placebo for thirty days according to a double blind randomized design. In the group treated with active drug there has been a significant reduction higher than in the controls of the scores relating to the abstinence symptomatology, in particular regarding the neuropsychic residual symptomatology (anxiety, depression, insomnia) after the first week of treatment, a reduced requirement of benzodiazepines and/or neuroleptics, and a significant decrement higher than in the controls of the score of MALT at the end of treatment. Furthermore, metadoxine seems to make easy the maintenance of abstinence, at least at short term.
Asunto(s)
Alcoholismo/tratamiento farmacológico , Piridoxina/uso terapéutico , Ácido Pirrolidona Carboxílico/uso terapéutico , Intoxicación Alcohólica/tratamiento farmacológico , Método Doble Ciego , Combinación de Medicamentos , Evaluación de Medicamentos , Femenino , Departamentos de Hospitales , Humanos , Italia , Masculino , Persona de Mediana Edad , Síndrome de Abstinencia a Sustancias/tratamiento farmacológicoRESUMEN
The effects of metadoxine (pyrrolidone-carboxylic acid; PCA) and pyridoxine on the locomotor responses to ethanol in mice were compared. Metadoxine (200 and 400 mg/kg i.p.) and PCA (86 and 172 mg/kg) prevented, in a dose-related manner, the locomotor stimulant effect of a low dose of ethanol (1.5 g/kg i.p.), whereas pyridoxine (228 mg/kg i.p.) was completely ineffective. Neither compound modified the sedative effect of a high ethanol dose (2.5 g/kg i.p.). The results indicate that the antagonistic effect of metadoxine on ethanol stimulant response is due to the PCA component of the molecule.
Asunto(s)
Etanol/antagonistas & inhibidores , Actividad Motora/efectos de los fármacos , Piridoxina/farmacología , Ácido Pirrolidona Carboxílico/farmacología , Animales , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Etanol/farmacología , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
The paper aims to evaluate the effects of metadoxine on liver function tests in chronic alcohol abusers without a clear alcohol dependence, by means of an open trial carried out in 7 hospitals in Tuscany. The study comprised 72 patients with a daily alcohol intake of at least 80 g for men and 30 g for women, over a period of at least 5 years. The patients were urgently requested to stop drinking, and were randomly divided into 2 groups, of which the first (52 subjects) was treated with metadoxine (500 mg twice a day) and the second (20 subjects) received only some vitamins. Interviews and blood tests were performed 1 and 2 months after the trial began. Statistical calculations were made using the chi-square and Student's tests. Metadoxine induced a more rapid reduction of SGOT and SGPT and, possibly, of Gammagt; these effects were especially evident, and were associated with a significant reduction of MCV, in 20 patients (12 in the first group and 8 in the second) in whom blood test abnormalities were greatest. No unfavorable side effects were observed that could be attributed to the drug. Metadoxine can therefore be considered a valuable resource in the treatment of alcoholic liver disease.
Asunto(s)
Alcoholismo/tratamiento farmacológico , Combinación de Medicamentos , Hepatopatías Alcohólicas/tratamiento farmacológico , Hígado/efectos de los fármacos , Piridoxina/farmacología , Ácido Pirrolidona Carboxílico/farmacología , Adulto , Anciano , Femenino , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Piridoxina/uso terapéutico , Ácido Pirrolidona Carboxílico/uso terapéutico , Factores de TiempoRESUMEN
The effects of metadoxine (pyrrolidone carboxylate of pyridoxine), a compound with central benzodiazepine-like properties, were evaluated in two groups of chronic alcoholics (inpatients) presenting a mild withdrawal syndrome. According to a double-blind study design 20 patients received metadoxine 900 mg twice daily eluted in 500 ml of saline infusion, while 20 (the control group) were given 500 ml of saline infusion twice daily with equivalent doses of pyridoxine (40 mg/die) every morning over a 10-day period. The results indicate that metadoxine treatment was able to control alcohol abstinence, thus allowing a reduction in the needs for standard benzodiazepine therapy. The central activity of gamma-aminobutyric acid of this compound might play a crucial role in the clinical effects demonstrated.
Asunto(s)
Etanol , Piridoxina/uso terapéutico , Ácido Pirrolidona Carboxílico/uso terapéutico , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Adulto , Ansiolíticos/uso terapéutico , Benzodiazepinas , Método Doble Ciego , Combinación de Medicamentos , Humanos , Masculino , Persona de Mediana Edad , Piridoxina/efectos adversos , Ácido Pirrolidona Carboxílico/efectos adversosRESUMEN
We report a new method of fluorangiography employing a polypeptide fraction from bovine factor VIII that has shown remarkable affinity to the endothelial surface of microvessels. Rabbits injected with this compound, labeled with fluorescein isothiocyanate, show a very delayed disappearance time of fluorescence in retinal vessels when compared with those injected with ordinary fluorescein. This allows a good observation of the late time, which is of great diagnostic advantage for several pathological conditions.