A critical analysis of commercially available latex particle reagents for C-reactive protein (CRP) slide agglutination tests

C-reactive protein (CRP) was assessed in pediatric serum samples using different commercial latex reagents, which were analyzed for species origin of the coating antibodies, homogeneity and density of the latex particles, and prozone agglutinating capacity. All reagents correctly agglutinated the positive and negative control sera. The antibodies coating the particles differed with regard to species origin: one was coated with rabbit, one with horse and goat, one with horse, goat, rabbit and swine, while the reference reagent had horse, goat and rabbit antibodies.Only the monospecies specific antibody-coated latex showed obvious prozoning; this reagent also had the smallest and most homogenous latex particles and showed the most clear-cut reactions. False agglutination was observed at 7–26% according to quantitation with the spot immunoprecipitate assay, which compared favorably with radial immunodiffusion measurements. The lowest percentage of false readings was noted for the rabbit antibody-coated particles; the highest for the reagent with particles coated using antibodies from 4 different species.No reagent had satisfactory precision for the low positive sera between 10 and 40 mg CRP/1.     

Antihypertensive mechanism of action of ketanserin and some ketanserin analogues in the spontaneously hypertensive rat

Summary Ketanserin is a new antihypertensive agent with affinity to serotonin (5-HT)₂ receptors and at higher concentrations also to ₁-adrenoceptors. The present study was designed to evaluate the relative functional importance of the antagonism of ₁-adrenoreceptors and 5-HT₂-receptors in the antihypertensive mechanism of action of ketanserin and analogues after acute administration. In the spontaneously hypertensive rat, ketanserin and the two ketanserin analogues, R56413 and R55667 (which have relatively weaker -adrenolytic properties) were studied with regard to their ability to reduce the blood pressure after acute administration in the conscious rat and their ability to shift the dose response curves for 5-HT and phenylephrine in the pithed rat. The agents tested reduced the blood pressure only in a dose range where they blocked ₁-adrenoceptors and there was a striking correlation between the degree of hypotension and the degree of inhibition of the phenylephrine induced pressor responses. 5-HT₂-receptor blockade alone did not influence basal blood pressure. However, following pretreatment with R55667 in a low dose the blood pressure reduction to prazosin was enhanced.It is concluded that following acute administration in the rat the major portion of the antihypertensive response to ketanserin is due to an ₁-adrenoceptor blockade but that the 5-HT₂-receptor blockade contributes.Abbreviations 5-HT 5-hydroxytryptamine - SHR spontaneously hypertensive rat - SNS sympathetic nervous stimulation     

Twenty-five years after Billroth II gastrectomy for duodenal ulcer

One thousand twenty-five patients underwent a Billroth II resection for duodenal ulcer between 1948 and 1956. The operative mortality rate was 2.4%. At follow-up between 22 and 30 years later, 522 had died and 423 patients were traced. Recurrent ulcer appeared in 2.6% of the cases. Postgastrectomy symptoms occurred with the following frequency: dumping 10%, diarrhea 5%, vomiting 7%, and pain 4%. Anemia developed in 18%, hypoalbuminemia and hypocalcemia in 40 and 15%, respectively. Eleven percent had lost more than 10 kg in weight. Tuberculosis was found in 3% of the cases. While 90% of the patients were satisfied with the result, 10% were failures. The overall mortality rate was significantly increased because of suicide. Gastric carcinoma was the cause of death no more often than expected.

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Resumen En años anteriores la gastrectomía Billroth II fue un procedimiento operatorio de uso común en el tratamiento de la úlcera duodenal. Los promisorios resultados de la vagotomía con drenaje, vagotomía y antrectomía y, especialmente, la vagotomía de células parietales han reducido el rol de la resección de tipo Bilroth II. El propósito del presente estudio es describir los resultados a largo plazo en un grupo de pacientes sometidos a gastrectomía Billroth II por úlcera duodenal aproximadamente 25 años antes.Entre 1948 y 1956, 1 025 pacientes consecutivos, 810 hombres y 190 mujeres, fueron sometidos a resección Billroth II por úlcera duodenal. La mortalidad operatoria fué de 2,4%. Durante el período de seguimiento entre 22 y 30 años, 522 pacientes habían muerto y 423 pacientes pudieron ser ubicados para seguimiento. Síntomas de post-gastrectomía fueron observados con la incidencia siguiente: dumping 10%, diarrea 5%, vómito 7% y dolor 4%. La anemia se presentó en el 18%, hipoalbuminemia e hipocalcemia en el 40% y en el 15% respectivamente. Se presentó tuberculosis en el 3% de los casos. El 90% de los pacientes se mostraron satisfechos con el resultado de la operación, pero el 10% restante indicó la falla del tratamiento. La mortalidad global resultó significativamente incrementada debido a una alta incidencia de suicidio. El carcinoma gástrico fue causa de muerte con una frecuencia no aumentada, o sea que no se encontró un mayor riesgo de muerte por carcinoma de esófago o del remanente gástrico.

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Résumé De 1948 à 1956, 1 025 malades atteints d'ulcère duodénal ont subi une opération de Billroth II. La mortalité a été de 2,4%. Au cours de l'évolution de 22 à 30 ans après l'intervention, 522 opérés sont décédés et 423 ont été suivis. La fréquence de la récidive a été de 2,6%. Les symptômes après gastrectomie ont atteint les taux suivants: dumping 10%, diarrhée 5%, vomissements 7%, douleur 4%. L'anémie a été constatée dans 18% des cas, l'hypoalbuminémie dans 40% des cas et l'hypocalcémie dans 15% des cas, onze pour cent des opérés ont accusé une chute pondérale supérieure à 10 kg; 3% ont présenté une tuberculose. Au total 90% des malades se sont déclarés satisfaits de l'intervention, encore que certains opérés se soient suicidés, ce nombre intervenant dans la mortalité globale. La mortalité par cancer n'a pas dépassé le taux accusé par la population en général.

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Supported by grants from the Danish Medical Research Council (No. 512-8760) and Købmand i Odense Johann & Hanne Weimann, født Seedorffs legat.     

Dietary Supplementation with Selenium and Coenzyme Q10 Prevents Increase in Plasma D-Dimer While Lowering Cardiovascular Mortality in an Elderly Swedish Population

A low intake of selenium is associated with increased cardiovascular mortality. This could be reduced by supplementation with selenium and coenzyme Q₁₀. D-dimer, a fragment of fibrin mirroring fibrinolysis, is a biomarker of thromboembolism, increased inflammation, endothelial dysfunction and is associated with cardiovascular mortality in ischemic heart disease. The objective was to examine the impact of selenium and coenzyme Q₁₀ on the level of D-dimer, and its relationship to cardiovascular mortality. D-dimer was measured in 213 individuals at the start and after 48 months of a randomised double-blind placebo-controlled trial with selenium yeast (200 µg/day) and coenzyme Q₁₀ (200 mg/day) (n = 106) or placebo (n = 107). The follow-up time was 4.9 years. All included individuals were low in selenium (mean 67 μg/L, SD 16.8). The differences in D-dimer concentration were evaluated by the use of T-tests, repeated measures of variance and ANCOVA analyses. At the end, a significantly lower D-dimer concentration was observed in the active treatment group in comparison with those on placebo (p = 0.006). Although D-dimer values at baseline were weakly associated with high-sensitive CRP, while being more strongly associated with soluble tumour necrosis factor receptor 1 and sP-selectin, controlling for these in the analysis there was an independent effect on D-dimer. In participants with a D-dimer level above median at baseline, the supplementation resulted in significantly lower cardiovascular mortality compared to those on placebo (p = 0.014). All results were validated with a persisting significant difference between the two groups. Therefore, supplementation with selenium and coenzyme Q₁₀ in a group of elderly low in selenium and coenzyme Q₁₀ prevented an increase in D-dimer and reduced the risk of cardiovascular mortality in comparison with the placebo group. The obtained results also illustrate important associations between inflammation, endothelial function and cardiovascular risk.     

Glutathione conjugate mediated toxicities

Glutathione (gamma-glutamyl-L-cysteinylglycine: GSH) is present in high concentrations in most living cells and participates in a variety of vital cellular reactions. In particular, GSH protects cells from potentially toxic electrophiles formed via the metabolism of xenobiotics, and such reactions have long been associated with the process of detoxication (Baumann and Preusse, 1879; Jaffe, 1879). Compounds that form GSH conjugates are processed by gamma-glutamyl transpeptidase (gamma-GT) and dipeptidases to cysteine S-conjugates, which are usually excreted in urine as their corresponding mercapturic acids (S-substituted N-acetyl-L-cysteine conjugates). In addition, GSH peroxidase activity, whether catalyzed by the selenium-dependent GSH peroxidase or by the GSH S-transferases, serves to detoxify hydrogen peroxide and organic hydroperoxides. However, in recent years, evidence indicating that GSH conjugation plays an important role in the formation of toxic metabolites from a variety of chemicals has accumulated. Thus, several classes of compounds are converted, via conjugation with GSH, into either cytotoxic, genotoxic, or mutagenic metabolites. The purposes of the symposium on "Glutathione Conjugate Mediated Toxicities" presented at the 1990 Society of Toxicology Annual Meeting were to discuss recent findings in this rapidly moving field, to present ideas on the mechanisms and modulation of GSH conjugate-dependent toxicities, to present a consensus on the broader significance of this work, and to identify directions for future research. This paper summarizes these presentations. GSH conjugation reactions are involved in the bioactivation of several classes of xenobiotics, and four types of GSH-dependent bioactivation reactions can be identified: (1) directly toxic GSH conjugates may be formed from vicinal dihaloalkanes via formation of electrophilic sulfur mustards; (2) cysteine conjugate beta-lyase-dependent bioactivation is involved in the selective nephrotoxicity of haloalkenes; (3) GSH conjugates of hydroquinones and isothiocyanates may serve as transport and targeting metabolites; and (4) GSH-dependent reactions may be involved in the release of toxic agents from precursor organic thiocyanates and nitrosoguanidines (N-methyl-N'-nitro-N-nitroguanidine).