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Biomedical subjects

A A Poltera

Publications and source records attributed to A A Poltera.

At least 37 records · Page 2Linked to original sources
PubMed1990

The influence of food on the pharmacokinetics of CGP 6140 (amocarzine) after oral administration of a 1200 mg single dose to patients with onchocerciasis.

Eleven male patients from Mali with Onchocerca volvulus infections received in random order a 1200 mg single oral dose of CGP 6140 after an overnight fast and after food intake. The concentrations of CGP 6140 and of its N-oxide metabolite, CGP 13231, were measured in plasma and urine. Mean (+/- s.d.) AUC CGP 6140 values were 67.0 +/- 10.8 mumol l-1 h in fed and 22.0 +/- 17.2 mumol l-1 h in fasting patients. The mean maximum concentrations (Cmax) in plasma +/- s.d. were 12.7 +/- 2.8 mumol l-1 in fed and 4.7 +/- 4.1 mumol l-1 in fasting patients. The median time to Cmax was 3 h in fed and 2 h in fasting patients. Mean (+/- s.d.) AUC of the N-oxide metabolite was 59.9 +/- 10.7 mumol l-1 h in fed and 23.4 +/- 16.2 mumol l-1 h in fasting patients. The urinary recovery was less than 0.5% of dose for CGP 6140 in both fed and fasting conditions. It was 30.1 +/- 11.5 and 11.4 +/- 8.0% of the dose for the N-oxide metabolite in fed and fasting conditions, respectively. Variability in plasma concentrations and urinary recovery of CGP 6140 and of the N-oxide metabolite was greater in fasted patients. The low solubility of CGP 6140 in aqueous solutions at neutral pH and its higher solubility at acidic pH might explain the increase in bioavailability after food intake. The administration of CGP 6140 after food intake is therefore recommended for an optimal systemic effect.

Administration, Oral↗
PubMed1988

The in vitro determination of the visual resolution in onchocercal nodules of bovine and human origin by a portable ophthalmologic ultrasound scanner.

A portable ophthalmologic real-time ultrasound linear scanner (Ophthascan) was used to determine the optic resolution of excised onchocercal nodules of Onchocerca volvulus and O. gibsoni origin. Fresh, thawed and fixed nodules were used. Following macroscopic and histologic examination it became apparent that the Ophthascan could clearly distinguish between echogenic worm coils and non-echogenic areas of necrosis. The fibrotic nodular capsule was more echogenic than the worm coils inside the nodule. The optic resolution did not permit to distinguish the internal organ structures within a worm segment. This in vitro determination of the visual resolution of an opthalmologic real-time ultrasound linear scanner is in accordance with in vivo results of an ongoing trial with a new macrofilaricide. Thus sonography can be used to visualise the interior of superficial onchocercal nodules in vivo and to follow their evolution with or without chemotherapy. The non-invasive diagnostic and sequential assessment of onchocercal nodules by sonography will be a valuable contribution in onchocerciasis, especially for the assessment of macrofilaricides.

Animals↗
PubMed1988

Antifilarial activity of CGP 20,376 in chimpanzees (Pan t. troglodytes) naturally infected with Dipetalonema vanhoofi.

CGP 20,376, a benzthiazole and new antifilarial agent, was investigated at CIRMF in eight wild born chimpanzees naturally infected with Dipetalonema vanhoofi. Single oral doses (3.75, 7.5, 11 and 15 mg/kg) were administered. Drug levels during the first hour after administration were assessed in seven chimpanzees at 10 minute intervals in the blood. Levels of unchanged drug (CGP 20,376) were higher than those of its metabolite (CGP 20,308). However, there was considerable variation between individuals, although the results for each animal were consistent. Because of investigational limitations a complete drug profile could not be established. Unsheathed microfilariae of D. vanhoofi were monitored during the first hour following drug administration in seven chimpanzees. In five the microfilaraemia dropped to low counts within 10 minutes and remained below the initial values for the next 50 minutes while in two other chimpanzees it showed a more irregular reduction. Periodic microfilarial counts over the next 20 months, at roughly 30 day intervals, showed that three chimpanzees, treated with 7.5, 11 and 15 mg/kg respectively, remained free of circulating microfilariae from Day 1 to Day 600, the chimpanzee treated with 3.75 mg/kg remained microfilaremic and, in three chimpanzees low numbers of microfilariae reappeared within one year, whereas in the remaining ape they reappeared after one year. No major clinical adverse effects were observed, but liver function tests showed mild reversible changes at the 11 and 15 mg/kg doses. CGP 20,376 was therefore microfilaricidal, except for the lowest dose, and it was possibly macrofilaricidal in those chimpanzees which remained free of microfilariae for 600 days. Clinically CGP 20,376 was well tolerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Immunopathological aspects of trypanosomal meningoencephalitis in vervet monkeys after relapse following Berenil treatment.

Four quarantined vervet monkeys were treated with intramuscular Berenil in patent CNS infection after experimental trypanosome inoculation with Trypanosoma brucei rhodesiense or T. brucei brucei. All four animals relapsed in the post-therapeutic survival time of 37 to 209 days when they had fully developed meningoencephalitis in histological sections with the presence of interstitial intracerebral trypanosomes, which were confirmed in two monkeys by electron microscopy. In both, sequential samples of the serum and cerebrospinal fluid were analysed for circulating immune complexes, immunoglobulins and albumin. From these results the intracerebral IgG synthesis and the impairment of the blood-brain-barrier were calculated, both being present in advanced infection. Circulating immune complexes were present in the serum, but could not be demonstrated in the cerebrospinal fluid. The monkey model therefore permits the study of various aspects of cerebral trypanosomiasis. Berenil treatment is inefficient in patent CNS infection and leads to a protracted, less virulent disease course with terminal meningoencephalitis and intracerebral "persister" trypanosomes. This drug-induced trypanosome shift with meningoencephalitis could be used for chemotherapeutic purposes to test new compounds in late stage disease.

Amidines↗
PubMed1985

Trypanosomal cardiac valvulitis in vervet monkeys.

Quarantined vervet monkeys (Cercopithecus aethiops) were infected with Trypanosoma brucei (10(4) parasites/animal) in a tsetse free area. Thirteen monkeys (11 infected with T.b. rhodesiense and 2 with T.b. brucei) were studied. Animals became parasitaemic within one week after infection. The infection time lasted between 21 and 129 days; in 8 monkeys it was between 50 and 70 days. Macroscopically massive pericarditis was observed in one, pericardial effusion in one, small apical aneurysms in three. Microscopically all had pancarditis of moderate to marked degree including all 4 chambers, the apices and the valvular appendages. Trypanosomes and inflammatory cells were found in the interstitium of the 3 cardiac layers. Lymphatic drainage of trypanosomes and inflammatory cells was seen in all hearts, the lymphatic vessels showing signs of stasis. By light microscopy trypanosomes and inflammatory cells were also shown to occur in all four types of heart valves implicating diffuse valvulitis. In two instances electron microscopy confirmed the intact presence of the trypanosomes clustering in great numbers in the pars elastica of the valves. In the collagenous part, some intact single trypanosomes were seen between collagen fibres. No amastigotes were observed. These results point to select sites in organ topography which in turn may be relevant to active disease, chemotherapy and healing. The possibility of hiding places within the heart - protecting trypanosomes from the host defense and/or chemotherapeutic agents - ought to be considered.

Animals↗
PubMed1983

Cardiac lymph drainage in experimental African trypanosomiasis in vervet monkeys.

In group I (15 monkeys) the infection time was less than 70 days with one exception and histologically 14 had trypanosomal pancarditis with morphological evidence of lymph stasis. Trypanosomes served as markers of the dilated cardiac lymphatics seen at apices, atrioventricular junctions, near the His bundle, at the base of cardiac valves and around the root of the aorta and pulmonary artery. 3 hearts had apical aneurysms. In group II (6 monkeys) the infection time exceeded 130 days and despite specific non-arsenical treatment all relapsed. Histologically focal cardiac fibrosis and extravascular trypanosomes within the brain were seen (encephalitis), the latter was absent in group I. The impairment of the cardiac lymph flow is contributory to the development of pericarditis, valvulitis, myocytolysis, apical aneurysm as well as fibrosis, and it may well be a common denominator in the pathogenesis for cardiopathies induced by various pathogenes .

Animals↗
PubMed1982

Trypanosoma brucei gambiense: cerebral immunopathology in mice.

Ninety outbred white adult female mice were infected with Trypanosoma brucei gambiense (GUMS 2, alias LUMP 1237) originating from a Zairian patient and known to produce a low parasitaemia in rodents. The development of cerebral trypanosomiasis was independent upon the number of parasites inoculated per mouse. Trypanosomes appeared in the circulating blood about four months after infection, when some mice started to show the first signs of paresis which subsequently led to cachexia. A clinical test to stage such a development is described. 57 mice were sacrificed at various intervals after infection, starting from one to 22 months. The morphological changes in the brain consisted of a diffuse meningoencephalitis in 45 mice, (78.9%) often associated with parasites, the latter being best visualised in 21 mice (36.8%) by immunofluorescence using a specific antitrypanosome antibody. The trypanosomes showed a predominantly extravascular distribution in the cerebral parenchyma, to a lesser extent in the meninges and only rarely in the choroid plexuses. Deposits of immunoglobulins in the choroid plexuses and cerebral infiltrations by plasma cells were mild. The level of circulating immune complexes was found to be increased. Adequate intravenous Melarsoprol did not prevent the disease from progressing to advanced stages, and there is limited morphological evidence that it did not eradicate the parasite from the host. The immunofluorescent use of an antitrypanosome antibody to demonstrate the persistence of tissue parasites after chemotherapy is recommended. Murine models seem therefore to be suitable for drug screening in cerebral trypanosomiasis since all three trypanosomes of the brucei group can be adapted to mice.

Animals↗
PubMed1981

Trypanosoma brucei brucei: the response to Melarsoprol in mice with cerebral trypanosomiasis. An immunopathological study.

A murine model for cerebral trypanosomiasis was adapted to study the efficacy of Melarsoprol which was apparently curative in high intravenous doses (10 mg/kg, 3 x 10 mg/kg, 20 mg/kg) in advanced infection (6th week); only one relapse occurred, but observation time was limited. Deposits of Ig and C3 in the choroid plexuses tended to disappear after successful treatment. Circulating immune complexes increased in the 1st week after therapy and returned to normal values in the 2nd week. Such an increase could temporarily be prevented by chloroquine, which may explain the reported reduction of side-effects from Melarsoprol in man after use of chloroquine in sleeping sickness. Melarsoprol (3 x 3.6 mg/kg) given intraperitoneally showed apparent cures but also relapses. Melarsoprol in high intraperitoneal doses (3 x 10 mg/kg) showed an increasing number of relapses if related to the duration of infection. Morphologically, a diffuse interstitial distribution of the parasites appeared in the CNS after relapse had occurred (shift), contrasting with the preferential localization of the parasites in the choroid plexuses of untreated mice. Such a shift was best visualized by immunofluorescence using specific antitrypanosomal antibodies. Relapse-mice invariably showed increased levels of circulating immune complexes suggesting this serological test for early detection of relapses. Tissue parasites appeared to be a likely cause of relapses, irrespective of the duration of infection. A short observation time with no circulating blood parasites is no guarantee of cure. Benznidazole (3 x 1 g/kg) was ineffective in advanced infection.

Animals↗
PubMed1980

A model for cardiopathy induced by Trypanosoma brucei brucei in mice. A histologic and immunopathologic study.

The successful induction of pancarditis in mice by the use of Trypanosoma brucei brucei is reported. The sequential analysis of whole-organ sections demonstrated the presence of trypanosomes in the cardiac structures from the fourth week after infection. Parasites predominated on the endocardial and epicardial side but were also present in the valves, the conducting system, and the lymphatic system draining the heart, the latter being particularly evident in late infection. At the time of parasite invasion, deposits of IgM and IgG and of complement (C3) appeared in the tissues. Also at this time parasitemia reached a plateau, and the circulating specific antitrypanosomal antibodies, the serum Ig and C3, as well as the Clq activity, reached pathologic levels. Cellular response followed parasite invasion and appeared to be similar to that described in human African trypanosomiasis. In late infection, the draining lymph nodes showed a marked histiocytic proliferation, and the vessels became convoluted and distended. The suggested pathogenic mechanisms involve immunologic and mechanical factors. It is possible that the immunologic process prepares for a simultaneous or subsequent parasite invasion of the tissues with an associated inflammatory response. The partial obstruction of the lymphatic cardiac draining system probably accounts at least in part for the peculiar distribution of the parasite-induced lesions. A therapeutic trial was unsuccessful, but the persistence of trypanosomes in the tissues when circulating parasites were no longer detectable may account for relapses.

Animals↗
PubMed1980

Trypanosoma brucei brucei: a model for cerebral trypanosomiasis in mice--an immunological, histological and electronmicroscopic study.

The successful induction of cerebral trypanosomiasis in ordinary laboratory mice using Trypanosoma brucei brucei is reported. Sequential studies demonstrated the presence of trypanosomes in the interstitium of the choroid plexus at the fourth week after infection which correlated with the appearance of anti-trypanosomal antibodies, a rise of IgM and IgG serum levels and a rise of Clq binding activity as well as a decrease of C3 levels. Electronmicroscopic studies showed that the parasites were flagellated and localized extracellularly mainly in the interstitium of the choroid plexus. Granular immunofluorescent deposits of Ig and C3 were most marked in the choroid plexus. Electron-dense deposits suggestive of immune complexes were seen in subendothelial, interstitial and subependymal areas of the choroid plexus. Since autoantibodies to the brain were found in the serum of some mice, the possible involvement of autoimmune manifestations in the pathogenesis of cerebral lesions has to be considered. The pattern of inflammatory foci at the eighth week after infection was very similar to that observed in cerebral African trypanosomiasis in man. After treatment with ethidium bromide, trypanosomes persisted in the tissues when circulating parasites could no longer be detected. These observations suggest a sequential involvement of brain structures during African trypanosomiasis. Trypanosomes may first migrate from the vascular compartment into the interstitium of the choroid plexus, possible favoured by increased vascular permeability. Circulating immune complexes and complement activation may be involved at this state. Trypanosomes localized in the choroid plexus may then trigger a local immunologically mediated inflammatory reaction favouring the migration of trypanosomes into the CSF and further invasion of other cerebral structures.

Animals↗