Biomedical subjects
Publications and source records attributed to G Goethals.
Steroidal glycoalkaloids of many Solanum species have recognized biological activities, especially those containing the glycosyl moiety alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-D-glucopyranose (chacotriose) whose peracetate is here synthesized and characterized by complete 1H and 13C NMR assignment.
Glycosyl-1,4-benzodiazepin-2,5-diones were prepared by coupling polyhydroxylated groups at N-1 of the corresponding benzodiazepine. The groups include 1-deoxy-D,L-xylit-1-yl, 6-deoxy-D-glucopyranos-6-yl, and 6-deoxy-3-OR-D-glucopyranos-6-yl (R = n-CnH(2n +1); n = 8, 12, and 16). The structural variations of the sugar group allowed comparison of such amphiphilic data as water solubility (Sw), critical micelle concentration (CMC), and corresponding surface tension (gamma) values. At 25 degrees C, unsubstituted benzodiazepines have Sw values from 0.9 to 4.2 10(-3) mol L(-1), whereas xylit-1-yl and 6-deoxy-D-glucopyranos-6-yl derivatives are, respectively, 7.4-25 and 58-204 times more soluble. Also, compounds with R = n-C8H17 are more soluble than corresponding benzodiazepines (1.4-5.8 times) and give micelles with CMC from 2.7 to 5.6 10(-3) mol L(-1) and corresponding gamma from 29 to 37 mN m(-1). In contrast, compounds with R = n-C12H25 and n-C16H33 are not soluble enough to reach the critical micelle concentration.
Poly(3-hydroxybutyrate) (PHB) quantification has been developed mostly using acidic methanolysis followed by GC analysis of the 3-hydroxybutyrate methyl ester. However, under our experimental conditions, only 62% of the ester was detected by GC analysis. Following the study of the different steps involved in this method (i.e., hydrolysis, esterification, and recovery of the ester), the recovery was shown to be limiting. Addition of water to the organic phase, required for its purification before injection, led to the partition of the ester between the organic and the aqueous phase. The influence of the length of acidic methanolysis time on the amount of ester detected was also investigated. NMR analysis was used to show that secondary products were absent in both phases, regardless of heating time. Moreover, increasing acid concentration and the use of lyophilized cells were shown to lead to the decrease of the treatment time. Concerning internal standard choice, methyl benzoate was found to meet all the requirements to correct injection volume errors or to follow organic phase volume changes as a function of acid and water concentrations. The validity of the method was checked on Rhizobium meliloti M5N1 cells, which are shown to produce about 60% PHB (w/w) when cultivated with fructose as the carbon source.
Using pharmacokinetic data from healthy human volunteers in a bicompartmental pharmacokinetic model, a repeated dose scheme for pralidoxime methylsulphate (Contrathion) was developed producing plasma levels remaining above the assumed "therapeutic concentration" of 4 mg.l-1. Using the same data, it was found that a concentration of 4 mg.l-1 could also be obtained by a loading dose of 4.42 mg.kg-1 followed by a maintenance dose of 2.14 mg.kg-1.h-1. In order to study the pharmacokinetic behaviour of pralidoxime in poisoned patients, this continuous infusion scheme was then applied in nine cases of organophosphorus poisoning (agents: ethyl parathion, ethyl and methyl parathion, dimethoate and bromophos), and the pralidoxime plasma levels were determined. The mean plasma levels obtained in the various patients varied between 2.12 and 9 mg.l-1. Pharmacokinetic data were calculated, giving a total body clearance of 0.57 +/- 0.27 l.kg-1.h-1 (mean +/- SD), an elimination half-life of 3.44 +/- 0.90 h, and a volume of distribution of 2.77 +/- 1.45 l.kg-1.
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Gastric endoscopy of a 40 year old woman suffering from ill-defined epigastralgy revealed a carcinoid tumor apparently located at the mucous membrane. The tumor was neither argyrophil nor argentaffin. Immunohistochemical tests for VIP, gastrin and serotonin were negative. Biological examinations indicated hypochrome anemia and hypergastrinemia (greater than 800 pg/ml). The excision was completed by a gastrectomy of 2/3 with a Pean anastomosis. No residual tumor was detected but the fundic mucous membrane showed considerable atrophic gastritis together with a marked hyperplasia of endocrine cells giving an aspect of microcarcinoidosis. Immunohistochemical studies showed that most of the cells produced serotonin while a few cells produced gastrin or VIP. Control biopsies of the stump showed similar hyperplasia of the endocrine cells and ultrastructural studies confirmed the polymorphism of the islets. The present observation is compared to analogous cases cited in the literature. The pathogenic mechanism possibly linked to the capacity of gastrin in stimulating endocrine cells is discussed. The prognosis in these carcinoid tumors appears to be the same as in other gastric carcinoid tumors. In particular, a recent observation (Goldman et al., 1981) illustrated their aptitude to lead to metastases.
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Fifty patients stricken by giardiosis were treated by a single dose administration of Tinidazole -- 50 mg./kg. for children and 2 g. for adults per os. Fifteen days after treatment, 84 0/0 of the patients had negative coprologic exams for giardiosis. The product was well-tolerated by the digestive tract as was demonstrated by a coprologic examination for digested food reside; however, minor digestive inconveniences were noted in 87 0/0 of the patients. There were no perturbations of hematologic or hepatic tests. This product would thus appear to be a treatment of choice in the management of giardiosis.
About one case of massive strongyloidosis becoming out of any immunosuppressive treatment and without travel out of France in a 40 year-old-woman, the authors study the different possibilities of contamination and set the problem of a drug-resistance to Thiabendazole.