Renewal of the membrane complex of Schistosoma mansoni is closely associated with lipid metabolism

Metabolic pathways leading to lipid biosynthesis in four different developmental stages of Schistosoma mansoni were explored and quantified by incubation in the presence of labeled precursors in a chemically defined medium. At the schistosomulum stage and in male, female, or paired worms, glycerol and oleate incorporation into neutral lipids, mainly in the form of triacylglycerols, was greater than into phospholipids, whereas in 11-and 15-day-old worms, synthesis mainly led to phospholipids. Incorporation into phospholipids was recovered largely in phosphatidylcholine, and distribution into other phospholipids depended on the developmental stage. Incorporation of choline and ethanolamine into their respective phospholipids represented up to 15% of the parasitic phospholipid content. The formation of phosphatidylcholine by phosphatidylethanolamine methylation occurred mainly in the immature parasitic stages. Inositol incorporation was also measurable, whereas [14C]serine incorporation was low or undetectable. Addition of 1-palmitoyl-2-[14C]oleyl phosphatidylcholine revealed a very high uptake of this phospholipid by the immature stages but further metabolism was not detectable. In contrast, adult S. mansoni were completely unable to take up or absorb this exogenous phospholipid. The most striking aspect of this study was the relatively high metabolic activity in 11-day-old worms and the lower but sustained activity on day 15 and at the schistosomulum stage. By comparison, biosynthetic activity in adult S. mansoni, on which research studies have been focused until now, was very low. We also discuss the participation of lipid metabolism in the constant renewal of the membrane complex which is essential to parasitism by S. mansoni.     

Influence of dietary protein level on protein self-selection and plasma and brain amino acid concentrations

Control of protein intake was studied in young rats that were allowed to choose between either protein-free and 55% casein diets or 15% and 55% casein diets. Animals on the protein-free vs. 55% casein regimen exhibited a lower weight gain, a lower cumulative energy intake and a greater cumulative total protein intake during the 13-day study compared to rats selecting between 15% and 55% casein. The daily average proportion of total food selected as casein by animals choosing between protein-free and 55% casein diets increased from 15% to 38% during the course of the study. In contrast, rats choosing between 15% and 55% casein chose 18-22% of total food as protein throughout the entire study. Long-term protein intake or protein selection did not correlate significantly with whole-brain contents of 5-HT or 5-HIAA. Our results suggest that protein intake is not regulated at a constant proportion of total calories, but is controlled between a minimum level that will support rapid growth and a maximum that, if exceeded, would require the animal to undergo substantial metabolic adaptation. The mechanism controlling protein selection may involve diet-induced changes in the brain content of total free indispensable amino acids.     

Regional brain variations of cytochrome oxidase activity and motor coordination in Lurcher mutant mice

Lurcher mutant mice are characterized by massive degeneration of cerebellar Purkinje cells and granule cells and by deficits in motor coordination. Regional brain variations of cytochrome oxidase (CO) activity were analyzed to identify those brain regions with abnormal metabolic activity as a secondary consequence of the cerebellar atrophy and to establish the relationship between CO activity and motor deficits. Lurcher mutants had higher CO activity in all three cerebellar deep nuclei than normal littermate controls of the same background strain. Higher CO activity was also found in Lurcher mutants in brain regions directly connected to the cerebellum, such as the lateral vestibular nucleus, the cochlear nucleus, the red nucleus, the ventrolateral thalamus, the dorsal raphe, the interpeduncular nucleus, and the inferior colliculus. By contrast, there was a sharp decrease in CO activity in the inferior olive. As for brain regions not directly connected to the cerebellum, higher CO activity was observed in the trigeminal motor nucleus and the CA1 molecular layer of the hippocampus, which highlights probable transsynaptic alterations as a secondary consequence of cerebellar atrophy. A positive correlation between CO activity in the red nucleus and latencies before falling in two motor-coordination tests indicates that a compensatory increase of metabolic activity in a cerebellar efferent region is associated with improved behavior. Received: 15 September 1997 / Accepted: 3 March 1998     

Ischaemic episodes of less than 5 minutes produce preconditioning but not stunning in the isolated rat heart

The aim of the present study was to examine whether ischaemic episodes of less than 5 min could induce preconditioning or stunning in the isolated rat heart. Hearts were subjected to total global ischaemia of 1, 2 and 4 min followed by 10 min of reperfusion before an 18-min main ischaemic period and 30 min of reperfusion. The effects on physiology, purine metabolism and anaerobic glycolysis were compared with a control group subjected to the main ischaemia only. The brief ischaemic episodes did not produce stunning based on the recovery of left ventricular developed pressure (LVDP) and heart rate (HR) product during the first reperfusion. Preconditioning of 11–14% increased recovery of LVDP x HR during the second reperfusion was observed in the 1- and 4-min group. In the 2-min group a low repayment of flow debt during the first reperfusion was associated with a slightly reduced recovery of LVDP x HR compared to the other preconditioned groups during the second reperfusion. Only in the 4-min group was preconditioning associated with fewer breakdown products of the purine nucleotide pool (adenosine) and anaerobic glycolysis (lactate) in both tissue and effluate after the main ischaemia. Preconditioning (reflected in recovery of function) could be produced with ischaemic episodes of less than 5 min that did not produce stunning. Thus, stunning is probably not the primary cause of preconditioning.     

Post-competition blood lactate concentrations in collegiate swimmers

Summary The purpose of this investigation was to quantitate post-competition lactate (LA) concentrations of swimmers during a competitive collegiate meet. Blood LA was measured by an enzymatic method on 23 subjects 5 min after each race event. The largest mean LA concentration of 25.7 mM/L was observed in swimmers after competing in the 200-yd individual medley. Swimmers in the 200-yd butterfly, back, breast and freestyle races had similar mean blood LA concentrations (ranging from 16.4 to 20.6 mM/L). Swimmers in the two longest events, the 500-yd and 1,000-yd free style races, had mean LA concentrations of 15.6 and 10.0 mM/L, respectively. To account for the effects of motivation, LA concentrations were measured following maximal effort noncompetitive 100 and 200-yd swims. LA concentrations were slightly greater in conjunction with faster performances for the competitive as compared to the noncompetitive 100 and 200-yd swims.     

Peroxisomal fatty acid oxidation capacity is more resistant to ischaemic and reperfusion injury than mitochondrial fatty acid oxidation capacity in feline hearts

We investigated ischaemic and postischaemic mitochondrial and peroxisomal fatty acid oxidation capacity, ATP levels and regional function in 40 anaesthetized open chest cats subjected to 10 or 40 min of regional myocardial ischaemia with or without 3 h of reperfusion (n=10 in each situation). Following 10 min of ischaemia, the mitochondrial fatty acid oxidation capacity measured in tissue extracts from ischaemic tissue (nmol min^-1 mg protein^-1) was reduced in both subepi- and subendocardium, but was normalized in reperfused tissue extracts from both wall layers (0.29±0.03 and 0.30±0.04 vs. 0.57±0.05 and 0.59±0.05, P<0.05). Peroxisomal fatty acid oxidation capacity in tissue extracts was unaffected by ischaemia and reperfusion. ATP levels and regional function measured in the LAD region was partly restored transmurally. After 40 min of LAD occlusion, mitochondrial fatty acid oxidation capacity was reduced, with higher activity in subepi- than in subendocardium (0.27±0.05 vs. 0.19±0.04, P<0.05). Reperfusion did not restore mitochondrial fatty acid oxidation capacity. Peroxisomal fatty acid oxidation capacity was increased in the ischaemic subendocardium compared with levels in non-ischaemic subendocardium (0.53±0.02 vs. 0.45±0.03, P<0.05), with normalization at the end of reperfusion. ATP levels were non-uniformly reduced during ischaemia and not repleted during reperfusion. Regional function recovered in circumferential segments but not in longitudinal segments following 40 min of ischaemia. In conclusion fatty acid oxidation enzymes seem to be more resistant to ischaemia in peroxisomes than in mitochondria. Mitochondrial fatty acid oxidation is fully reversible following shortlasting ischaemia, but remains depressed following prolonged ischaemia and reperfusion.     

Endocrine and metabolic abnormalities following kidney transplantation

Summary Various endocrine and metabolic disturbances associated with long standing uremia persist after kidney transplantation or arise from the use of immunosuppressive drugs. Hyperlipidemia for long time being implicated as the cause of corticosteroids is also observed in renal transplant recipients treated with cyclosporin A monotherapy. After conversion from cyclosporin to azathioprine serum cholesterol and triglyceride concentration fall, and elevation of LDL-cholesterol may also be reversed. There is a tendency for higher HDL-cholesterol in azathioprine and prednisolone treated transplant patients. Those patients who are at risk for clinically significant cholesterol elevations can be predicted by their pretransplant lipid levels, specifically the LDL-fraction. Risk-benefit ratio of conversion and of treatment with lipid-lowering drugs, especially with lovastatin, should be carefully examined, also in view of glucose intolerance.Higher incidence of diabetes mellitus requiring insulin therapy in cyclosporin treated transplant recipients has been reported. Cyclosporin may cause toxic effects on pancreatic beta-cells resulting in inhibition of insulin secretion. High doses of cyclosporin induce inhibition of glycogen synthesis in rat liver. Glucose intolerance is reversible after reduction of cyclosporin dose or conversion to azathioprine. Therefore glucose metabolism in kidney transplant recipients treated with cyclosporin should be carefully followed.Immunosuppressive therapy may affect reproductive function, arachidonate metabolism and renin-angiotensin-aldosterone system as well as posttransplant calcium and phophate metabolism.Endocrine and metabolic abnormalities are associated with long standing uremia. After successful kidney transplantation several observations are normalized but further complications arise from the use of immunosuppressive drugs. The present paper reviews various endocrine and metabolic disturbances described following renal transplantation.     

Renal metabolism of corticosteroid hormones

Summary IK and STF from male and female rats have been used to study in vitro the renal metabolism of B. in male rat tissue four lipid soluble metabolites (I–IV) have been found, I+II being more polar and III+IV being less polar than B. I and II have been identified as 11-dehydro-20-hydroxy-B and 20-hydroxy-B. The structure of III and IV remains to be determined. Renal tissue from female rats produced predominantly III indicating sexual variations of steroid metabolism in kidneys. — The literature has been reviewed which documents that the kidneys in addition to B metabolize A, cortisol, progesterone and other corticosteroids.

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Abbreviations A Aldosterone - B Corticosterone - Alb Albumin - CS Corticosteroids - MCS/GCS Mineralo-/gluco-CS - IK Isolated (perfused) kidney - STF Suspended tubular fragments Supported by Deutsche Forschungsgemeinschaft Hi 97/16     

Hepatic gluconeogenesis and Krebs cycle fluxes in a CCl4 model of acute liver failure

Acute liver failure was induced in rats by CCl4 administration and its effects on the hepatic Krebs cycle and gluconeogenic fluxes were evaluated in situ by 13C NMR isotopomer analysis of hepatic glucose following infusion of [U-13C]propionate. In fed animals, CCl4 injury caused a significant increase in relative gluconeogenic flux from 0.80+/-0.10 to 1.34 +/-0.24 times the flux through citrate synthase (p<0.01). In 24-h fasted animals, CCl4-injury also significantly increased relative gluconeogenic flux from 1.36+/-0.16 to 1.80+/-0.22 times the flux through citrate synthase (p<0.01). Recycling of PEP via pyruvate and oxaloacetate was extensive under all conditions and was not significantly altered by CCl4 injury. CCl4 injury significantly reduced hepatic glucose output by 26% (42.8+/-7.3 vs 58.1+/-2.4 micromol/kg/min, p=0.005), which was attributed to a 26% decrease in absolute gluconeogenic flux from PEP (85.6+/-14.6 vs 116+/-4.8 micromol/kg/min, p<0.01). These changes were accompanied by a 47% reduction in absolute citrate synthase flux (90.6+/-8.0 to 47.6+/-8.0 micromol/kg/min, p<0.005), indicating that oxidative Krebs cycle flux was more susceptible to CCl4 injury. The reduction in absolute fluxes indicate a significant loss of hepatic metabolic capacity, while the significant increases in relative gluconeogenic fluxes suggest a reorganization of metabolic activity towards preserving hepatic glucose output.     

Effects of muscle blood flow on muscle energy metabolism and contractility

Energy metabolism and contractility of rat’s femoral triceps muscles were investigated by varying blood flow levels with ligation of the femoral artery. The triceps were stimulated electrically to produce equivalent conditions as exercise loading, and phosphorus nuclear magnetic resonance (³¹P-NMR) spectra and muscle tension levels were monitored. The ratio of inorganic phosphate (Pi) to ‘Pi+phosphocreatine (PCr)’, i.e. Pi/(Pi+PCr), was obtained from ³¹P-NMR spectra. This ratio was related to the reduction of blood flow ratio (BFR) during and after the stimulation period, whereas before starting the stimulation, there was no significant correlation. These findings indicate: (i) muscle energy metabolism during decreased blood flow is influenced by the stimulation (loading) given to the muscle; and (ii) changes of muscle energy metabolism due to decreased muscle blood flow during the loading is evaluable by measuring ³¹P-NMR spectra. Muscle tension reached the plateau 8 min after starting the stimulation, regardless of BFR, but muscle tension ratio decreased as BFR became lower. This indicates that decreased blood flow diminishes muscle contractility, and then lowers muscle function levels. Our findings indicate that muscle blood flow plays an important role in muscle function, and blood flow and muscle function levels are evaluable by measuring ³¹P-NMR spectra of the muscle.