Biomedical subjects
Publications and source records attributed to C Bories.
The use of ivermectin for mass treatment in human onchocerciasis is justified, because no other drug was available. But, as this compound is ineffective on adult filariae and as the emergence of drug resistance is quite possible, the evaluation of new chemical compounds for their macrofilaricidal activity should be continued. Several new compounds of interest are presented.
Arsenical compounds are the main therapeutic way, effective in the neurological phase of trypanosomiasis. Unfortunately, their important toxicity prevents their easy administration. Structural cyclization of arsonic acid derivatives has led to a class of non-toxic compounds: spiroarsoranes. A 47 compound primary screening on an in vivo murine model of Trypanosoma brucei brucei resulted in the isolation of a very effective derivative after a single subcutaneous injection of 30 mg.kg-1 body weight (Chemotherapeutic Index = 21). In this study, trypanocidal activity of this compound was evaluated on an in vivo sheep model of trypanosomiasis by T. brucei brucei, according to experimental model of the Institute of Neurological Epidemiology and Tropical Neurology of Limoges (France). A single subcutaneous injection of 30 and 100 mg.kg-1 b.w., and 30 and 60 mg.kg-1 b.w. was given respectively during first and second phase of trypanosomiasis. Ovine pharmacokinetics of this compound will be evaluated in a further study.
New compounds containing 5,6-dihydro imidazo[2,1-b]thiazole, 2,3,5,6-tetrahydro imidazo[2,1-b]thiazole and 2,3-dihydro imidazo[2,1-b]benzothiazole rings, substituted by heterocycles analogue to chromones, were synthesized and screened against three nematodes, in vitro. The results indicate moderate anthelmintic properties, compared to levamisole; nevertheless, some products exhibit a significant degree of activity.
Two series of 2-substituted 1,2-epoxyethanesulfonamides 2 and ethynesulfonamides 5 were synthesized and evaluated for their antifilarial activity. The trans epoxides 2T were stereospecifically prepared by a Darzens reaction between aldehydes and halomethanesulfonamides. The cis isomers 2c were obtained from ethynesulfonamides 5 by semihydrogenation followed by KOCl epoxidation. 2-Substituted ethynesulfonamides 5 were synthesized from appropriate trans-ethenesulfonamides by a bromination/dehydrobromination sequence. These products, as well as several synthetic intermediates, were evaluated for antifilarial activity against Molinema dessetae either in vivo in its natural host, the rodent Proechimys oris, or in vitro by a new test using cultures of the infective larvae. Most of the epoxides 2T and acetylenic derivatives 5 bearing a 2-aryl substituent were active in vitro. Among these compounds, four epoxides 2T and one acetylenic derivative 5 showed marked macrofilaricidal activity in vivo without any microfilaricidal activity. The differences between the in vivo and in vitro results may be due, in part, to the low chemical stability of the epoxy sulfonamides 2T. Despite this limitation, the activities observed in this reliable animal model suggest further development and testing of both series 2T and 5 as macrofilaricides.
The potential use of polyisobutylcyanoacrylate nanoparticles in antiparasitic chemotherapy is described. The nanoparticles on their own proved to have trypanocidal activity against Trypanosoma brucei brucei in-vitro but not against Trichomonas vaginalis or Entamoeba histolytica. The trypanocidal activity was partly confirmed in-vivo with T. brucei-infected mice.
The effects of parenteral nutrition in the treatment of patients with severe chronic radiation enterocolitis is not known. We retrospectively studied 19 adult patients who received parenteral nutrition during 8.6 +/- 2.4 months (mean +/- SEM), including 6 cases in our home-parenteral nutrition-program. Parenteral nutrition was started 49 +/- 12 months after radiation therapy; follow-up after parenteral nutrition was 22 +/- 7 months. Indication for parenteral nutrition was malnutrition (weight = 73 +/- 2 p. 100 of ideal body weight, serum albumin level = 27 +/- 1 g/l) due to multifocal gastrointestinal radiation injuries with stenoses (n = 12), fistulae (n = 3) and short bowel syndrome (n = 4). Parenteral nutrition was given during the peri-operative period in 15 patients. Neither fistulae nor stenoses resolved with parenteral nutrition alone (n = 7) or in association with steroids (n = 5). There was a 57 p. 100 mortality rate (11 patients): 10 p. 100 were postoperative (2 of the 3 patients with fistulae), 21 p. 100, due to radiation complications and 26 p. 100, due to progression of cancer. In those patients with severe and multifocal chronic radiation enteropathy, parenteral nutrition did not influence the lesions in the digestive tract. Nutritional support could, however, be considered as an useful adjunct with a low perioperative mortality rate. In the 14 patients without superimposed unresponsive cancer, parenteral nutrition followed by curative abdominal surgery seemed to be associated with the best prognosis and in 7 of the 8 survivors, parenteral nutrition has been discontinued without reappearance of clinical malnutrition.
Beta 2-microglobulin determinations in ascitic fluid (A) and serum (S) collected on the same day, were performed in 24 patients suffering from alcoholic liver cirrhosis. Ascitic beta 2-m concentration varied from 0.4 to 4.6 mg/l for patients with a normal renal function. Much higher values were found in patients with chronic renal failure. No correlation could be established between ascitic beta 2-m level and the clinical evolution of the cirrhosis. Comparative measurements of beta 2-m S/A ratio and albumin, transferrin, total protein S/A ratios suggests a local synthesis of beta 2-m in ascitic fluid. This is confirmed by an immuno-cytochemical technique which reveals the localisation of beta 2-m in the cytoplasm of peritoneal cells. The presence of beta 2-m in ascitic fluid seems to be related to an ultrafiltration across the peritoneal membrane as well as a local polyclonal activation of the immune system.
A 73-year-old woman developed abnormal electrolyte and water loss from an excluded rectosigmoid segment after surgical treatment of a volvulus of the sigmoid colon. Rectal discharges lasted almost for a year, until it spontaneously resolved after restoration of large bowel continuity. Despite extensive investigation, including endoscopic, radiologic, microscopic, bacteriologic and parasitic examinations, no satisfactory explanation of the diarrhea could be found. The histologic pattern of the excluded segment showed a striking increase in mucosal thickness and in number and height of goblet cells. These abnormalities disappeared after closure of the colostomy. Electrolyte composition of the rectal fluid, which contained 134 mmol potassium and 22 mmol sodium per liter was remarkable and similar to that of normal stool water and anal discharges of patients with ulcerative proctitis.
Iron status, folacin status, haemoglobinopathies, malarial infection and intestinal parasitosis frequencies were assessed in a representative sample of 586 subjects living in a rural district of South Benin. Anaemia according to WHO reference values for haemoglobin was observed in 42 per cent of subjects. The prevalence was higher in children and menstruating women. Iron deficiency, defined by two or more abnormal values in the four independent indicators of iron status used (transferrin saturation, erythrocyte protoporphyrin, serum ferritin, and mean corpuscular volume) was present in 30 per cent of subjects. Half of the anaemias were associated with iron deficiency. Folate deficiency was associated with anaemia in 20 per cent of subjects. Anaemia, iron and folacin status were not significantly related to the degree of malarial infection nor to the type of haemoglobin. Although hookworm infection was very common, there was no significant relationship between egg count and haemoglobin level or haematological parameters of iron and folacin status. The lack of correlation can be explained by the low wormload observed.
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Chronic diarrhoea is frequent in acquired immune deficiency syndrome (AIDS) but has been poorly investigated so far. We report four patients with AIDS in whom diarrhoea and malabsorption were outstanding features, and who underwent extensive digestive investigations. Diarrhoea was a presenting symptom in all subjects and was of secretory type in three of them. D-xylose and vitamin B12 were malabsorbed in all cases; steatorrhea was found in the two patients who could ingest significant amounts of fat. Faecal alpha 1-antitrypsin clearance was increased in all subjects. Search for digestive pathogens showed unusual protozoans in all patients: in case 1, optical and electron microscopy revealed the presence in the cytoplasm of villous enterocytes of Microsporidia protozoans still unreported in AIDS. Stool and jejunal fluid examination showed Isospora belli in case 2 and Cryptosporidium in cases 3 and 4. On histological and ultrastructural study the former was localised in the cytoplasm of a few enterocytes and the latter was scattered throughout the villus and crypt brush border. Otherwise small intestinal histology only showed minor non-specific changes and the enterocytes were ultrastructurally normal. In patient 3 the slow marker intestinal perfusion technique showed a profuse fluid secretion in the duodenum and proximal jejunum. All patients needed prolonged total parenteral nutrition. Cryptosporidium and Microsporidia could not be eradicated despite multiple drug trials. Isospora belli was transiently cured by pyrimethamine-sulphadiazine. Only patient 2 is presently at home, and patients 1, 3, and 4 died after two, six, and nine months of total parenteral nutrition, respectively.
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