110: 259 -269, 2002). Heptanoate and C 5-ketone bodies derived from its partial oxidation in liver are precursors of anaplerotic propionyl-CoA in peripheral tissues. It was hypothesized that increasing anaplerosis in peripheral tissues would boost energy production. In the present study, we tested the potential of a triheptanoin emulsion as an intravenous nutrient. Normal rats were infused with triheptanoin intravenously or intraduodenally at up to 40% of caloric requirement. The blood concentration ratio (heptanoate/C 5-ketone bodies) was high with intravenous and low with intraduodenal triheptanoin infusion. During intravenous infusion of triheptanoin, lipolysis was stimulated but appeared compensated by fatty acid reesterification. During intraduodenal infusion of triheptanoin, lipolysis was not stimulated. Our data support the hypothesis that intravenous triheptanoin could be used to treat decompensated patients with long-chain fatty acid oxidation disorders.heptanoate; C 5-ketone bodies; fatty acid oxidation disorders; anaplerosis INHERITED FATTY ACID OXIDATION DISORDERS (FOD) include defects of the cell membrane carnitine transporter, the "carnitine cycle" (CPT I, translocase, CPT II), or the mitochondrial ␤-oxidation spiral. The most common disorders of ␤-oxidation affect very-long-chain acyl-CoA dehydrogenase, mitochondrial trifunctional protein, isolated long-chain hydroxyacylCoA dehydrogenase, and medium-and short-chain acyl-CoA dehydrogenase. Patients with long-chain FOD commonly present with recurrent hypoketotic hypoglycemia, hypertrophic or dilated cardiomyopathy, cardiac arrhythmias, rhabdomyolysis, muscle weakness, and hypotonia, (for a review, see Ref. 21). There is considerable phenotypic variation associated with nearly all of these disorders.The classical chronic treatment of long-chain FOD involves frequent feeding with a diet adjusted so as to lower long-chain fat intake from the usual 30 -35% of total kilocalories to ϳ20%, including essential fatty acids. The decrease in energy from long-chain fats is partly compensated by an increase in carbohydrates, often with cornstarch at bed time. In addition, even carbon medium-chain triglycerides (trioctanoin/tridecanoin) are added to the diet. This is because fatty acids with 8 -10 carbons enter the mitochondrion as carboxylates, which, after activation, require only those ␤-oxidative enzymes with medium-and short-chain length specificity. The dietary treatment with medium-chain triglycerides is obviously restricted to long-chain disorders and is contraindicated for medium-and short-chain deficiencies.A new strategy was recently conceived for the dietary treatment of long-chain FOD, i.e., providing about one-third of the calories as triheptanoin (22). The catabolism of heptanoate yields anaplerotic propionyl-CoA in addition to acetyl-CoA. It was hypothesized that part of the energy deficit in FOD patients results from a decrease in the concentration of citric acid cycle intermediates in muscle and heart cells. These intermediates carry the carb...

In this study, we tested whether lipolysis induced by triheptanoin infusion is accompanied by the potentially harmful release of long-chain fatty acids. Rats were infused with heptanoate Ϯ glycerol or triheptanoin. Intravenous infusion of triheptanoin at 40% of caloric requirement markedly increased glycerol endogenous Ra but not oleate endogenous Ra. Thus, the activation of lipolysis was balanced by fatty acid reesterification in the same cells. The liver acyl-CoA profile showed the accumulation of intermediates of heptanoate ␤-oxidation and C5-ketogenesis and a decrease in free CoA but no evidence of metabolic perturbation of liver metabolism such as propionyl overload. Our data suggest that triheptanoin, administered either intravenously or intraduodenally, could be used for intensive care and nutritional support of metabolically decompensated long-chain fatty acid oxidation disorders.INHERITED FATTY ACID OXIDATION DISORDERS (FOD) can affect the carnitine transporter, the "carnitine cycle" [carnitine palmitoyltransferase (CPT) I, translocase, CPT II], or the mitochondrial ␤-oxidation spiral (for a review, see Ref. 17). Although the phenotype of long-chain FOD is variable, patients often suffer from muscle weakness, hypotonia, cardiac arrhythmia, and cardiomyopathy. Acute episodes, triggered by an infection or trauma, often involve hypoketotic hypoglycemia, massive rhabdomyolysis with release of creatine kinase in plasma, shock, and death (22).Since the early 1980s, the chronic dietary treatment of long-chain FOD involved 1) a moderately high-carbohydrate diet with cornstarch at bed time, 2) decreasing long-chain fats to about 20% of the calories, including essential fatty acids, and 3) providing medium-chain triglycerides (1) since the corresponding C 8 and C 10 fatty acids enter mitochondria as carboxylates, which, after activation, require only those ␤-oxidation enzymes with medium-and short-chain specificity (10). The treatment with medium-chain triglycerides is restricted to long-chain FOD and is contraindicated for medium-and shortchain FOD (17).In 2002, we proposed to replace the even-medium-chain triglycerides with odd-chain triheptanoin (19). Heptanoate, like octanoate, enters mitochondria without passing through the CPT system (10). Unlike octanoate, which is ␤-oxidized to acetyl-CoA, heptanoate is oxidized to acetyl-CoA and propionyl-CoA (Fig. 1). The latter is anaplerotic for the citric acid cycle. We reasoned that, during episodes of metabolic decompensation, such as long-chain FOD, the release of large molecules from cells, e.g., creatine kinase, is probably accompanied by the release of small molecules, including citric acid cycle intermediates. The latter carry acetyl groups as they are oxidized to CO 2 . This would explain the muscle weakness often encountered in long-chain FOD patients. Chronic anaplerotic therapy with triheptanoin improved the clinical status and quality of life of a number of patients (18,20).In another study (8), we explored the metabolism of triheptanoin administered to r...

Automated Cleansing Device may be useful for standardized evaluation of the cleansing effectiveness and parallel assessment of the corresponding irritancy potential of industrial skin cleansers. This will allow objectifying efficacy and safety of industrial skin cleansers, thus enabling market transparency and facilitating rational choice of products.

Intra- and inter-device specific test results of an in vivo model of skin cleansing using the automated cleansing device (ACiD) were reproducible. The long-term aim is a standardized classification of occupational skin cleansing products comparing their skin cleansing effectiveness in relation to their skin irritancy. This might then provide the basis for a rational specific product selection by consumers and may be used as a tool for future product development by manufacturers.

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