Recent trends in cancer survival.
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Biomedical subjects
Publications and source records attributed to J Kerner.
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The right ventricles of pig heart were perfused with hypoxic blood and the left ventricles were perfused with normally ventilated arterial blood. Free carnitine and short-chain acylcarnitines in hypoxic ventricles were lower than in perfused controls, and much lower than in non-perfused heart. Acetylcarnitine levels decreased and the branched-chain acylcarnitines and propionylcarnitine were elevated in the hypoxic perfused ventricles. These data indicate that both hypoxia and anaesthesia caused loss of carnitine and short-chain acylcarnitines from the heart and hypoxia also changed the distribution of short-chain acylcarnitines in the heart.
Medium-chain acylcarnitines were isolated from human urine using a combination of chloroform-methanol extraction, silicic acid column and molecular sieving chromatography and preparative HPLC. Three purified acylcarnitines were analyzed by fast atom bombardment mass spectrometry and were also saponified and the free fatty acids analyzed by gas chromatography and mass spectrometry. Combined electron impact mass spectrometry and fast atom bombardment mass spectrometry and periodate oxidation for location of double bonds, demonstrated the occurrence of delta 6-octenylcarnitine, 2-methyloctanylcarnitine and 2-methyl-delta 6-octenylcarnitine. These acylcarnitines were present in the thirteen urines obtained from normal humans, but were not detected in urines from three individuals who had been on total parenteral nutrition for more than a year. The occurrence of alpha-methyl medium-chain acylcarnitines in human urine indicates a role for carnitine in excretion (detoxification) of these acyl derivatives.
Obesity-producing, hypothalamic knife cuts and ventromedial hypothalamic (VMH) lesions in ad libitum-fed adult rats increased intake of a high-fat diet (123 and 130%) and energy retention (880 and 1,099%) during the 4-wk period postsurgery; even when pair fed to control rats, energy retention of the knife-cut and lesioned rats was still elevated (105 and 155%). Thermogenic capacity of brown adipose tissue (BAT), estimated from guanosine diphosphate (GDP) binding to BAT mitochondria, was unchanged in hyperphagic knife-cut and VMH-lesioned rats and was reduced approximately 50% when these rats were pair fed to controls. Urinary excretion of norepinephrine (NE) was approximately twofold higher in ad libitum-fed, knife-cut, and lesioned rats than in control rats; restriction of energy intake decreased NE excretion to control values. Rates of NE turnover in heart paralleled urinary NE excretion, whereas NE turnover in BAT was generally not increased in the hyperphagic rats. Urinary epinephrine excretion, an index of adrenal medullary activity, was depressed in all knife-cut and VMH-lesioned rats. Hyperphagia coupled with a lack of increased heat production in BAT causes gross obesity in ad libitum-fed, knife-cut, and VMH-lesioned rats, whereas obesity in pair-fed rats develops in part at least as a result of reduced heat production by BAT.
As part of a project to determine if newborn piglets contain less than optimal amounts of carnitine, the carnitine and acylcarnitine content of colostrum, milk and serum of sows and of serum, liver, heart and muscle of newborn and 2-day-old piglets was measured. Colostrum contained high amounts (370 nmol/ml) total carnitine, with greater than 95% being acylated. The principal acylcarnitines (approx. 45% each) were acetyl- and isovalerylcarnitine . In contrast, serum from lactating or nonpregnant nonlactating sows and from piglets all contained primarily free carnitine and some acetylcarnitine but only traces of isovalerylcarnitine . At birth, the blood and liver of piglets contained very low amounts of total carnitine, which increased two- and fourfold, respectively, after 2 days of suckling. These data show that newborn piglet liver and blood are carnitine poor and indicate that the high levels in colostrum and milk are a source of tissue carnitine. The large amounts of acetyl- and isovalerylcarnitine in colostrum and milk might facilitate secretion of available carnitine.
A reliable and sensitive method for the quantitation of picomole amounts of acetylcarnitine, propionylcarnitine, aliphatic 4-carbon, and 5-carbon acylcarnitines has been developed. The procedure requires the measurement of the amounts of carnitine and acid-soluble carnitine and then the enzymatic exchange of 3H- or 14C-labeled L-carnitine into the acylcarnitine pool using commercial carnitine acetyltransferase, essentially free of acyl-CoA hydrolase activity. After isotopic equilibrium is obtained, the radioactive acylcarnitines are separated using either HPLC or thin-layer chromatography. Procedures for both are described. After separation, the amounts of radioactivity in the acylcarnitines are determined and the amount of individual acylcarnitines can be calculated from the specific activity of the initial total carnitine pool or from the ratio of dpm in the acylcarnitine fraction/dpm in free carnitine X (nanomoles L-carnitine) in the sample. The method has several advantages over current procedures, including rapidity, use of small sample sizes, simplicity, and reliability.
Liver carnitine level decreased from 249 +/- 16.1 nmoles/g (mean +/- SEM) control value to 148 +/- 9.8 nmoles/g (59.4%) in ascorbic acid deficient guinea-pigs, while in the underfed ('pair-fed') group it decreased to 181 +/- 14.1 nmoles/g (72.6%). Underfeeding also resulted in lower ascorbic acid levels; the depression of carnitine in the underfed animals could be prevented by an overdose (200 mg daily) of ascorbic acid.
Time courses for the effect of electrical stimulation, fasting and sampling mode (anesthesia vs decapitation) on the quantitative distribution of carnitine and its esters in fast white and fast red skeletal muscle fibres of rats were determined. Both fibre types responded similarly to electrical stimulation with respect to changes in acetyl- and propionylcarnitine, but the time course was very different. The proportion of esterified carnitine decreased with fasting and anesthesia in both fibres compared to the fed decapitated group. This shift in the acylation state of carnitine was mainly due to the decrease of acetylcarnitine levels. The data show that the use of anesthetics may induce significant quantitative changes in specific acylcarnitine levels, presumably reflecting changes in specific acylcoenzyme A levels.
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The concentration of total carnitine in human breast milk remained at a constant mean level near 62.9 range: 56.0-69.8/nmoles/ml during the first 21 days postpartum. The carnitine level fell significantly to 35.2 +/- 1.26 nmoles/ml until the 40-50th day. The carnitine concentrations did not depend on the secreted volume of milk. In comparison, fresh and commercial pasteurized cow's milk contained 206.2 (range: 192-269) nmoles/ml and 160.0 (range: 158-200) nmoles/ml carnitine, respectively. In the sera of nursing mothers, the concentration of total carnitine was lower on the first day after delivery (27.2 +/- 1.19 nmoles/ml) but returned to normal by the 21st day postpartum (38.8 +/- 2.97 nmoles/ml).
Food ingestion of male guinea-pigs was restricted to 10 g/day. Total carnitine content of liver of the underfed animals fell to 3.75 mumoles per liver (46.1% of control). Serum level of total carnitine was 35.0 nmoles/ml (64.4%) in the underfed animals while they developed high ketonemia, 384.2 nmoles/ml (555.2%). In "restricted' animals the carnitine levels also decreased in the muscles.
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Authors performed on rabbits experimental tubular pedicles and pedicle transfers investigating by means of fill up angiography the changes occuring in the arterial network. They conclude that in the tubular pedicles the adapting of blood supply to the changed circumstances result in transformation of arterial network. There are similar alterations after transposition of the tubular pedicles. Details of changes in vascularisation are given.
The hospital-based alternative birth center answers the needs of many low-risk patients. At the same time, it provides safety factors that cannot be approached by home delivery. A home-like environment facilitates labor, simplifies delivery, and strengthens the family unit.
Buformin at a concentration of 1--2.5 mM stimulates solubilized carnitine palmitoyltransferase by reducing the inhibitory effect of palmitoyl-CoA. Neither buformin nor metformin inhibits the solubilized carnitine palmitoyltransferase.
We investigated the effect of denervation upon the concentration of carnitine, the activity of carnitine palmityltransferase and carnitine acetyltransferase in the "red" soleus and "white" extensor digitorum longus muscles of the rat. Soon after denervation a marked drop in the amount of muscle carnitine was observed, that was more pronounced in the "red" soleus. The activity of both CPT and CAT decreased in both types of muscle, but CPT activity decreased to a greater extent in the soleus than in the EDL. These data may be indicative of a more impaired fat combustion in the "red" than in the "white" muscle following denervation.
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