Proline biosynthesis by Fasciola hepatica at different developmental stages in vivo and vitro.

The ability of Fasciola hepatica to produce proline was assessed by measuring activity of the proline biosynthesis enzyme ornithine-delta-transaminase, and the arginine-dependent production of proline in vitro. This was related to the changes in bile proline of rats during the course of infection. It was found that the total production of proline and total enzyme activity per fluke increased as the fluke increased in size. However, while the specific enzyme activity remained constant throughout development, there was a preferential increase in proline production relative to protein content of the flukes just prior to their migration into the bile ducts. This early amplification of proline production could provide the stimulus to induce hyperplasia in the bile duct in preparation for fluke entry as proline production relative to protein content of fluke dropped markedly after migration into the bile ducts and never again reached the pre-migration level.

Studies of the effect of diamphenethide and oxyclozanide on the metabolism of Fasciola hepatica.

Studies were made of the effects of diamphenethide-amine on glucose transport, glycogen breakdown, adenine nucleotides, metabolites and excretory products in both parenchymal and bile duct flukes in vitro and in bile duct flukes in vivo. The most consistent and pronounced effect observed was an elevation of malate levels. There appeared to be no differences between responses of parenchymal and of bile duct flukes to diamphenethide-amine. For comparative purposes the effect of oxydozanide was assessed on most of these parameters in bile duct flukes in vitro. Not all the changes caused by oxyclozanide were characteristic of an uncoupler; however, the pattern of changes in the metabolites was markedly different from that caused by diamphenethide-amine.

Protection of Fasciola hepatica against flukicidal action of the amine of diamphenethide in vitro.

A variety of compounds structurally related to serotonin and dopamine were tested for their ability to protect adult liver flukes against the flukicidal effect in vitro of an active metabolite of diamphenethide (diamphenethide-amine). The most effective was dopamine. The protective effect of dopamine was also assessed by analysis of the metabolite and adenine nucleotide levels and excretory products of flukes exposed to diamphenethide-amine in vitro. Most notably, dopamine appeared to depress considerably the large elevation of internal malate which is a characteristic effect of diamphenethide-amine on liver flukes.

The nature and role of pregnancy-associated antigens and the endocrinology of early pregnancy in the ewe.

Depite descriptions of many of the physiological events of early pregnancy in the ewe, the way in which the immunological and endocrine adjustments are brought about is not well understood. Obviously, specific effects--for example, maintenance of the corpus luteum--are brought about by the presence of a conceptus in the uterus. This has led to a search for substances produced by the conceptus or induced by the presence of the conceptus in the uterus which could be involved in establishing pregnancy. This paper describes the presence in sheep of substances associated with pregnancy and discusses the origin and characterization of these substances and their role in ovine pregnancy.

Synthesis and removal of different cholesterol esters by aortic smooth muscle cells in culture.

The incorporation of 3H-labelled oleic acid and of 14C-labelled linoleic acid into phospholipid, triglyceride and cholesterol ester in smooth muscle cells grown in incubation medium supplemented with either 5% normal or 5% hyperlipemic serum has been studied. Both fatty acids were incorporated into cholesterol esters to a greater extent when cells grown in incubation medium containing hyperlipemic serum. Oleic acid was incorporated into cholesterol esters in preference to linoleic acid. The addition of hyperlipemic serum to the incubation medium did not increase the incorporation fo either 3H-labelled oleic acid or of 14C-labelled linoleic acid into phospholipid or triglyceride. The removal of labelled lipid fractions has also been followed for four days in cells pulse labelled for 24 hours with 3H-labelled oleic acid and 14C-labelled linoleic acid. Both 3H- and 14C-labelled cholesterol esters were removed more rapidly when the smooth muscle cells were grown in medium containing normal serum than in medium containing hyperlipemic serum. The removal of both phospholipid and triglyceride was similar in normal and hyperlipemic serum. Comparison of the 3H/14C ratio indicated that the cholesterol oleate and cholesterol linoleate were removed at similar rates.

Pre- and post-operative studies of fibrinolysis and prothrombin in cyanotic congenital heart disease.

Multiple components of the fibrinolytic mechanism (plasminogen, plasmin, antiplasmin, fibrinogen, fibrin degradation products) and factor II (prothrombin) levels were studied in 40 children with cyanotic congenital heart disease (CCHD) prior to corrective surgery. Seven of these were also studied post-operatively. A further 17 children were studied after corrective surgery only. Pre-operatively, increased fibrinolysis could bedemonstrated in only 7.5-12% of patients, and there was no correlation between the levels of fibrinolytic components and the severity of polycythemia or post-operative blood loss. There was no evidence of fibrinolysis post-operatively. Pre-operatively, low prothrombin levels were common (25%), were correlated with the amount of post-operative bloodloss and were restored to normal by corrective surgery. Hypoprothrombinaemia is one of the most significant haematological abnormalities in CCHD.