Endothelin-1 in children with chronic renal failure

Endothelin-1 (ET-1) was meansured after extraction from plasma of normal adults (5.9±1.9 pg/ml,n=22), normal children (7.1±1.86 pg/ml,n=29), nonhaemodialysed children with chronic renal failure (CRF) (11.1±1.8 pg/ml),n=10), renal graft recipients (9.5±3.4 pg/ml,n=37), haemodialysed children 24 h after a haemodialysis session (20.02±10.9 pg/ml,n=26) and haemodialysed children before and after a haemodialysis session (15.31±10.6 and 13.8±8.5 respectively,n=14). A sensitive and specific radioimmunoassay was used. ET-1 was significantly higher in non-haemodialysed CRF children and in renal graft recipients than in normal children (P<0.001 andP<0.01, respectively) and significantly higher in haemodialysed children when compared with normal children, non-haemodialysed CRF children and renal graft recipients (P<0.001). ET-1 concentrations were similar in normal children and normal adults. ET-1 was inversely correlated with glomerular filtration rate in non-haemodialysed CRF children (r=–0.39,P<0.01) and positively correlated with extracellular volume in haemodialysed children (r=0.435,P<0.03). After haemodialysis, ET-1 increased in 6 and decreased in 8 of the 14 children studied before and after a haemodialysis session.     

Cholera, 1991--old enemy, new face]

The cholera epidemics of the XIXth century are described and reviewed. The extent, incidence and case-fatality rate for the disease in the seventh pandemic are described. The global epidemiological situation and its trend at the end of 1991 are analysed. A review of cholera epidemiology highlights the factors that might explain the less tragic nature of the disease today. The role of water, food and direct contagion in transmission of cholera over the last 20 years is considered in the light of recent studies and with special reference to the epidemic in Latin America, where the intense emotion aroused by the disease has prompted vigorous action that could produce significant and lasting progress in the health field.     

Inhibition of serotonin-induced increase in canine external carotid blood flow by drugs that decrease the sympathetic outflow

1 The present study was designed to analyse the effect of the centrally-acting sympatho-inhibitory drugs, prazosin and ketanserin, on the increase in external carotid blood flow (external CBF) produced by 5-hydroxytryptamine (5-HT) in pentobarbital-anaesthetized dogs. 2 Intracarotid (i.c.) infusions of 5-HT (10 μ g min^?1 during 1 min) produced an increase in external CBF without changes in mean arterial blood pressure or heart rate. This response to 5-HT was dose-dependently blocked by intravenous (i.v.) administration of prazosin (1, 3, 10, 30 and 100 μg kg^?1) or ketanserin (10, 30, 100 and 300 μg kg^?1). 3 Furthermore, 5-HT-induced increase in external CBF was inhibited by either the ganglionic blocking agent, mecamylamine (0.03, 0.1, 0.3, 1, 3 and 10 mg kg^?1), the mixed 5-HT₁-like and 5-HT₂ receptor antagonist, methiothepin (3, 10 and 30 μ g kg^?1) or the 5-HT_1A ligand, spiroxatrine (10, 30, 100 and 300 μg kg^?1). In contrast, the selective 5-HT₂ and 5-HT_1C receptor antagonist, ritanserin (30 and 100 μg kg^?1, i.v.), was unable to block the above response to 5-HT. 4 It is concluded that the inhibition of 5-HT-induced increase in external CBF by prazosin, ketanserin, mecamylamine and spiroxatrine is due to a reduction in the sympathetic tone and not to a blockade of 5-HT receptors.     

Scintigraphy with J001X, a Klebsiella membrane glycolipid, for the early diagnosis of chronic berylliosis: results from an experimental model.

A glycolipid (J001X) isolated from the membrane proteoglycans of a non-pathogenic strain of Klebsiella pneumoniae was developed to bind selectively to macrophages. A scintigraphic technique could thus be developed and applied to an experimental model of lung berylliosis. Six baboons were injected intratracheally with a beryllium metal suspension. Three to 24 months later, they were submitted to both an anatomical and a functional respiratory evaluation. Two baboons were explored at the early stage of alveolitis and four baboons at a more advanced stage characterised by a granulomatous disorder. Scintigraphy was performed using J001X labelled with 99mtechnetium administered as an aerosol. In the six baboons, conventional imaging techniques (chest x ray film, computed tomography scan, gallium scintigraphy), failed to show either any lung abnormality or mediastinal lymph nodes consistent with beryllium disease. In the two recently contaminated baboons, J001X scintigraphy showed a well defined parenchymal fixation facing the contaminated lobe. In the four baboons who were at a more advanced stage of berylliosis, J001X fixation was always focused paratracheally without any significant involvement of the lung parenchyma. The subcarinal and laterotracheal lymph nodes seen at necropsy corresponded to J001X scintigraphic fixations. In conclusion, when compared with conventional techniques such as chest x ray film, computed tomography scan, magnetic resonance imaging, and gallium scintigraphy, J001X scintigraphy has proved its ability to detect occult lesions in experimental berylliosis in baboons. By comparison with gallium scintigraphy, scintigraphy with J001X appears to have superior sensitivity and can be performed in four hours.     

Stimulation of tumor growthin vitro andin vivo by suramin on the VX2 model

Suramin is an antitrypanosomal compound with confirmed efficacy against several human malignancies. It is generally assumed that its mechanism of action includes the interaction with different growth factors, unlike most of the anticancer drugs. Its anticancer activity has not been testedin vivo against squamous cell carcinoma. The purpose of this study was to assess the efficacy and toxicity of suraminin vivo andin vitro on the VX2 tumor model at therapeutic monitored plasma concentrations. We determined the pharmacokinetics of suramin in rabbits, and modelized its administration in order to obtain plasma concentrations between 150 and 300 μg/ml throughout the treatment course of 3 weeks. Under these conditions, antitumor effects of suramin were evaluatedin vivo by comparing liver tumor involvement in suramin-treated and control rabbits. Liver involvement was quantified by image analysis andin vitro effects were also determined at the same concentrations.In vivo, suramin promoted liver tumor growth significantly (p<0.05), compared to untreated controls.In vitro, suramin significantly stimulated tumor cell growth at concentrations above 200 μg/ml (p<0.01). Suramin may have stimulatory effects on tumor growth in squamous cell carcinoma at relevant plasma drug concentrations. Caution should be taken in further trials in patients with squamous cell carcinomas.     

Retinal pigment epithelial cells secrete urokinase-type plasminogen activator and its inhibitor PAI-1.

Secretion of plasminogen activators and their inhibitors was examined in cultures of human retinal pigment epithelial (RPE) cells. The methods employed were zymography and reverse zymography, solid-phase immunocapture assay, metabolic labeling followed by immunoprecipitation, and immunofluorescence. The results showed that these cells produce urokinase-type plasminogen activator (u-PA) and a plasminogen activator inhibitor (PAI) which is immunologically and biochemically similar to PAI-1. Tissue-type plasminogen activator activity (t-PA) was not detected, but we detected small amounts of t-PA in an inactive complex with inhibitor in RPE cell-conditioned media. We conclude that RPE cells have the potential to utilize u-PA-catalyzed plasminogen activation which is subject to regulation by PAI-1. These results may have a bearing on the pathogenesis of proliferative retinal diseases.