Comparison of methods to determine glucose kinetics and measurement of recycling and lactose formation in lactating cows.

Several investigators have suggested that the conventional multicompartmental exponential analysis of in vivo glucose metabolism is arbitrary and possibly not the most accurate description of glucose kinetics, especially in the large animal. In support of that hypothesis, we found that in a systematic comparison of 3 methods, blood-specific radioactivity data in single-injection studies of glucose metabolism in lactating cows was better described graphically, or by a hybrid polynomial-biexponential curve fit, than by an exclusively exponential curve fit. We hypothesized that this finding was attributable to partial failure of linearity and steady-state assumptions that underlie the exponential model. Second, using both an irreversible tracer (3H-labeled glucose) and reversible tracer (14C-labeled glucose), we found that glucose carbon recycling had no effect during the first 2 hours, but became significant in lactating cows 7 hours after injection. Finally, we determined that approximately 52 to 55% of the glucose replacement rate was being used to generate lactose.

Influence of microinjection of insulin into the ventromedial hypothalamus on acetate metabolism in rumen epithelium of sheep.

Injections of 50 microU insulin into the ventromedial hypothalamic nuclei (VMH) in intact sheep decreased the rates of 14C transfer from 14C-1-acetate into CO2, glucose, ketone bodies, and increased the rates into triglyceride and phospholipids in rumen epithelium of sheep. Insulin injections into the parietal cortex of intact sheep or into the VMH of sheep with VMH lesions had no effect on the acetate metabolism in rumen epithelium as compared with the control groups which received saline injections into the same brain regions. These results support the view that the VMH serves as an integral part of an insulin-sensitive brain regulatory system in the acetate metabolism of rumen epithelium.

Partitioning of amino acids in lactating cows: oxidation to carbon dioxide.

The rate and extent of oxidation of 20 different amino acids has been evaluated as part of a study on partitioning of amino acids in normal lactating cows. Only four amino acids--glutamate, aspartate, alanine and glutamine--were extensively oxidized, and when expressed as a percentage of the injected dose oxidized during 3 h after intravenous injection, the value for these four amino acids was not significantly different from those obtained with the volatile fatty acids. The oxidation of all other amino acids was significantly slower, effectively prolonging their availability for protein synthesis. The pattern of oxidation among the amino acids supports the hypothesis that catabolized protein can provide a protracted source of anaplerotic precursors that augment the metabolic role of the tricarboxylic acid cycle and would have survival advantage in both acute and chronic exigencies. Glutamate and aspartate provide the earliest and largest influx to the tricarboxylic acid cycle, with alanine and, especially, glutamine appearing to serve as reservoirs of amino-nitrogen. Several dispensable amino acids are metabolized as slowly as the indispensable ones, indicating that metabolic conservation is not restricted to the latter group.

Leucine turnover and oxidation in trained rats during exercise.

The effects of training on leucine turnover and oxidation were studied during rest and exercise in young, postabsorptive female rats. Relationships were primarily studied by the continuous infusion method, using [1-14C]leucine. Arterial blood was assayed for leucine specific activity and expired air was monitored for O2 consumption, CO2 production, and the specific activity of 14CO2. The rate of leucine turnover in trained rats was 70% greater than the rate of leucine turnover in untrained rats and was not affected by exercise. By virtue of a higher turnover, the rate of leucine oxidation was 40% greater in trained rats during both rest and exercise. Moreover, leucine oxidation was proportional to the metabolic rate and represented 30% of the leucine turnover at rest and 40-60% of the leucine turnover during exercise. In the same animals leucine turnover was secondarily assessed by measuring the fraction of the [1-14C]leucine dose contained in the hemoglobin pool 4 wk after infusion (occupancy tracer method). Occupancy values for leucine turnover were not different from those determined by the continuous infusion method. The results show that whole body leucine turnover is increased by training and that leucine oxidation is increased by both training and exercise.

Severe cytomegalovirus infection in multiply transfused, splenectomized, trauma patients.

During a 2-year period 5 previously healthy young men who had undergone splenectomy and received multiple transfusions for trauma had severe cytomegalovirus (CMV) infection. Their illness was characterised by a long period of high fever, severe interstitial pneumonitis with dyspnoea and hypoxaemia, and an unusually high lymphocytosis (12 000-26 000 cells/microliter) with numerous atypical forms. The presumptive diagnosis was based on the patients' seroconversion and viral excretion, on the clinical and haematological findings which were typical of severe CMV infection, and on the absence of other infective organisms. In 1 case widespread CMV pneumonitis was confirmed at necropsy. These observations raise the possibility that splenectomy increases the severity and modifies the pattern of CMV infection, since during the same period no other case of severe CMV infection was observed among a large number of patients who had received multiple transfusions but had not undergone splenectomy.

Estimation of plasma histidine flux in cows.

A tracer method is described for estimating the plasma amino acid flux in animals during steady state, and its application is illustrated using lactating cows that were injected intravenously with 14C- or 3H-labeled histidine. The method involves an extension of the occupancy principle in which the fraction of tracer recovered in a metabolic sink, casein or hemoglobin, provides the basis for calculating the amino acid flux. The plasma histidine flux was 25 g/day based on recovery of isotope in hemoglobin.

Melanoma in New South Wales: an epidemiologic surgery 1970--76.

This survey of the incidence of melanoma in New South Wales, Australia, from 1970 to 1976 revealed a doubling of incidence in the seven year period. The most marked rise occurred in 1972. A marked preponderance of leg melanoma in women and trunk melanoma in men was noted. The incidence of melanoma in men continues to rise throughout life while the incidence in women levels out after the age of 50 years. A recent rapid rise in elderly men was noted. A cumulative exposure to sunlight in a susceptible population is the most likely explanation of both the rise in incidence and the site distribution of the reported melanomas.

Evaluation of structured and unstructured training for general practice.

Twenty-four general-practice trainees were assessed at the beginning and end of their training year. They improved significantly in their factual recall and problem-solving ability. Sixteen young principals who had had an unstructured training for general practice were assessed at the same time and were initially of the same standard but their results showed no difference over the same year.

The behavior of muscle phosphorylase as a reservoir for vitamin B6 in the rat.

Current belief that vitamin B6 deficiency causes depletion of muscle phosphorylase in animals appears to be erroneous. We present evidence that vitamin B6 deficiency is ineffective in reducing total phosphorylase in gasttocnemius muscle of young rats over a period of at least 8 weeks. Rats that had accumulated high levels of muscle phosphorylase while ingesting diets containing normal or excess amounts of the vitamin retained their phosphorylase after transfer to a vitamin B6 deficient diet. Prolonged deficiency did ultimately lead to enzyme depletion but this was after anorexia had developed and weight loss had occurred. When rats were partially starved for 1 to 4 days (fed 10% of normal energy intake) they lost muscle phosphorylase while retaining alanine and aspartate aminotransferases. When totally starved, the rats lost more phosphorylase than during partial starvation, but completely retained alanine aminotransferase, and lost some aspartate aminotrasferase. We conclude that the behavior of muscle phosphorylase is consistent with the Krebs-Fischer proposal that it acts as a reservoir for vitamin B6 and that starvation, but not vitamin B6 deficiency per se, causes depletion of muscle phosphorylase. It appears that phosphorylase may function as an adjunct ot adipose tissue necessary for the animal to efficiently meet the exigencies of starvation.

Increased muscle phosphorylase in rats fed high levels of vitamin B6.

The present study was undertaken to test the hypothesis that muscle phosphorylase may function as a repository for vitamin B6 in the animal. Since a repository would be expected to accumulate surplus material, one would predict that phosphorylase, which contains stoichio-metric amounts or pyridoxal phosphate, would increase in muscle of animals surfeited with the vitamin. Rats were fed a vitamin B6-free diet supplemented with pyridoxine providing levels 10, 1.0 and 0.1 of those recommended by the National Research Council (NRC). At the high intake level, muscle phosphorylase and total muscle vitamin B6 increased steadily and in almost constant ratio for at least 6 weeks, whereas both alanine and aspartate transaminase increased initially, but reached a plateau within 2 weeks. At the intermediate level of pyridoxine intake, muscle phosphorylase also increased, but less rapidly than in rats fed the higher level. When vitamin B6 intake was restricted to 10% of the NRC-recommended level, no increase in phosphorylase concentration occurred during a period of 10 weeks. These results support the hypothesis that muscle phosphorylase acts as a reservoir for vitamin B6 in the animal and provide experimental evidence that muscle enzyme content expands as vitamin is accumulated during high dietary intake.

Effect of glucose load on synthesis of plasma glucose in lactating cows.

We assess the effect of an intravenous glucose load on production of glucose in lactating dairy cows. Isotope dilution techniques were utilized to measure transfer rate of plasma glucose (with tritiated glucose) and gluconeogenesis (with carbon-14 labeled propionate or carbon dioxide). A glucose load equivalent to the cow's normal transfer rate decreased endogenous glucose output two-thirds and decreased gluconeogenesis by half. Glucose concentration and transfer rate were higher within 2 h after glucose load started while carbon-14 transfer to plasma glucose became increasingly depressed and persisted for at least 1 h after loading terminated. Reduced plasma glucose synthesis from propionate during loading was associated with increased transfer of propionate carbon to plasma phospholipids, triglycerides, and cholesterol esters, and with increased plasma insulin concentration. It appears that glucogenic precursors are utilized for greater synthesis of lipid (and presumably glycogen) and that loading leads to metabolic changes causing net reduction in gluconeogenic capacity. These changes could have important implications for use of intravenous glucose in treating hypoglycemic metabolic conditions.