Perchloroethylene: Effects on Body and Organ Weights and Plasma Butyrylcholinesterase Activity in Mice

Abstract: The effects of continuous and intermittent inhalation of perchloroethylene (PCE) on plasma butyrylcholinesterase (BuChE) activity, organ weights, liver morphology and motor activity in mice (strain NMRI) were tested. PCE exposure increased plasma BuChE activity in a time- and concentration dependent manner in both sexes. The increase was statistically significant at 37 p.p.m. in animals continuously exposed for 30 days. BuChE increased approximately 1.5 times in females and 2.5 times in males after 120 days exposure to 150 p.p.m. After rehabilitation of animals exposed for 30 days to 150 p.p.m., BuChE levels returned to normal. Liver weight also increased in a time and concentration dependent manner. Both sexes exhibited significant liver enlargement at 9 p.p.m. The increase was about 2.3 in females and 1.9 in males after continuous exposure to 150 p.p.m. for 120 days. After rehabilitation (120 days) of animals exposed to 150 p.p.m. for 30 days, a 10% increase still remained. A decrease in body weight gain was seen in both sexes after exposure to concentrations above 75 p.p.m. Female kidney weight was slightly increased. No clear effect on spleen weight could be detected. When the same time-weighted average concentration was used, intermittent exposure for 30 days had similar effects on liver weight and BuChE activity as continuous exposure, even when exposures lasted for only one hour per day. Liver cell morphology was changed after PCE exposure. The alterations could be observed already at 9 p.p.m. but disappeared after rehabilitation.     

In vitro sensitivity of Plasmodium falciparum field isolates to extracts from Cameroonian Annonaceae plants

In a search for new plant-derived antimalarial extracts, 19 fractions were obtained from three Annonaceae species, Uvariopsis congolana (leaf, stem), Polyalthia oliveri (stem bark), and Enantia chlorantha (stem, stem bark) with yields ranging from 0.33% to 4.60%. The extracts were prepared from 500 g of each plant part, using organic solvents to afford five methanolic fractions (acetogenin rich), five water fractions, five hexane fractions, and four interface precipitates. Evaluation of the activity of fractions in vitro against field isolates of the malaria parasite Plasmodium falciparum showed that acetogenin-rich fractions and interface precipitates were the most potent, with IC₅₀ values ranging from 0.05 to 8.09 μg/ml. Sensitivity of parasite isolates to plant extracts varied greatly, with over 100-fold difference from isolate to isolate in some cases. The active acetogenin-rich fractions and interface precipitates were assessed in combination with chloroquine in the same conditions, and showed additive interaction in the huge majority of cases. Synergistic interactions were found in some cases with acetogenin-rich fractions. Acute toxicity of promising fractions was evaluated through oral administration in Swiss albino mice. Tested fractions appeared to be safe, with LD₅₀ values higher than 2 g/kg. In summary, acetogenin-rich fractions from Annonaceae species showed high potency against P. falciparum field isolates and safety by oral administration in mice, supporting their detailed investigation for antimalarial drug discovery.     

Unusual familial cardiomyopathy with storage of intermediate filaments in the cardiac muscular cells

Summary Unusual histological and ultrastructural changes in cardiac muscle cells have been found in 3 brothers with progressive myocardial deficiency. Histologically, this cardiomyopathy was characterized by massive storage of PAS-negative proteinaceous material in most cardiac muscle cells. The electron microscope showed that this material consisted of sinuous filaments, 7–10 nm in diameter, similar to the intermediate filaments normally present in cardiac muscle cells. Filament storage coincided with the disintegration of neighbouring myofibrils, with particular change in Z bands giving rise to rod-like bodies and more complex structures formed by the association of Z band material and sarcoplasmic reticulum (SR) tubules. Filament storage and myofibrillar disintegration always occurred in areas where the SR developed and involuted extensively. Relatively high glycogen accumulation also occurred, in close relation to the SR changes. Discrete SR proliferation, glycogen overload and filament deposits were observed in a few skeletal fibres.These observations suggest that disturbance in the metabolism of desmin (protein subunit of intermediate filaments and a fundamental component of Z bands) might be involved in this type of cardiomyopathy. The influence of a chronic defect in calcium regulation might also be envisaged in view of the marked SR abnormalities.     

Histidinaemia in Sweden

Histidinaemia screening was included in the epidemiological survey of the Swedish neonatal screening programme, 1971-72. Dried blood samples on filter paper collected neonatally from 171,000 infants were analysed by the Guthrie method. A blood histidine level above 0.96 mmol/l (15 mg per 100 ml) was regarded as a positive test and was found in 639 infants – i.e., 1/270. No further diagnostic measures were taken until 1977 when stored dried blood samples from 273 infants with a positive screening test were analysed for urocanic acid. Four children had undetectable blood urocanic acid. They were studied and histidinaemia was confirmed in two children, and excluded in two. Both histidinaemic children had normal psychomotor development at 7 years of age, in spite of the fact that no dietary treatment was given. The incidence of histidinaemia in Sweden was estimated as 1/37,000, on the basis of neonatal screening. In addition, histidinaemia was diagnosed in four individuals who were not detected in the neonatal screening programme; of these, only one had an IQ less than 85. At present, general neonatal screening for histidinaemia in Sweden does not seem justified.