Detection and alterations of acetylcarnitine (AC) in human liver by 1 H MRS at 3T after supplementation with l-carnitine.

PURPOSE: Acetylcarnitine can be assessed in vivo using proton MRS (1 H-MRS) with long TEs and this has been previously applied successfully in muscle. The aim of this study was to evaluate a 1 H-MRS technique for liver acetylcarnitine quantification in healthy humans before and after l-carnitine supplementation. METHOD: Baseline acetylcarnitine levels were quantified using a STEAM sequence with prolonged TE in 15 healthy adults. Using STEAM with four different TEs was evaluated in phantoms. To assess reproducibility of the measurements, five of the participants had repeated 1 H-MRS without receiving l-carnitine supplementation. To determine if liver acetylcarnitine could be changed after l-carnitine supplementation, acetylcarnitine was quantified 2 h after intravenous l-carnitine supplementation (50 mg/kg body weight) in the other 10 participants. Hepatic lipids were also quantified from the 1 H-MRS spectra. RESULTS: There was good separation between the acetylcarnitine and fat in the phantoms using TE = 100 ms. Hepatic acetylcarnitine levels were reproducible (coefficient of reproducibility = 0.049%) and there was a significant (p < 0.001) increase in the relative abundance after a single supplementation of l-carnitine. Hepatic allylic, methyl, and methylene peaks were not altered by l-carnitine supplementation in healthy volunteers. CONCLUSION: Our results demonstrate that our 1 H-MRS technique could be used to measure acetylcarnitine in the liver and detect changes following intravenous supplementation in healthy adults despite the presence of lipids. Our techniques should be explored further in the study of fatty liver disease, where acetylcarnitine is suggested to be altered due to hepatic inflexibilities.

L-Carnitine Stimulates In Vivo Carbohydrate Metabolism in the Type 1 Diabetic Heart as Demonstrated by Hyperpolarized MRI.

The diabetic heart is energetically and metabolically abnormal, with increased fatty acid oxidation and decreased glucose oxidation. One factor contributing to the metabolic dysfunction in diabetes may be abnormal handling of acetyl and acyl groups by the mitochondria. L-carnitine is responsible for their transfer across the mitochondrial membrane, therefore, supplementation with L-carnitine may provide a route to improve the metabolic state of the diabetic heart. The primary aim of this study was to use hyperpolarized magnetic resonance imaging (MRI) to investigate the effects of L-carnitine supplementation on the in vivo metabolism of [1-13C]pyruvate in diabetes. Male Wistar rats were injected with either vehicle or streptozotocin (55 mg/kg) to induce type-1 diabetes. Three weeks of daily i.p. treatment with either saline or L-carnitine (3 g/kg/day) was subsequently undertaken. In vivo cardiac function and metabolism were assessed with CINE and hyperpolarized MRI, respectively. L-carnitine supplementation prevented the progression of hyperglycemia, which was observed in untreated streptozotocin injected animals and led to reductions in plasma triglyceride and ß-hydroxybutyrate concentrations. Hyperpolarized MRI revealed that L-carnitine treatment elevated pyruvate dehydrogenase flux by 3-fold in the diabetic animals, potentially through increased buffering of excess acetyl-CoA units in the mitochondria. Improved functional recovery following ischemia was also observed in the L-carnitine treated diabetic animals.

The Importance of the Fatty Acid Transporter L-Carnitine in Non-Alcoholic Fatty Liver Disease (NAFLD).

L-carnitine transports fatty acids into the mitochondria for oxidation and also buffers excess acetyl-CoA away from the mitochondria. Thus, L-carnitine may play a key role in maintaining liver function, by its effect on lipid metabolism. The importance of L-carnitine in liver health is supported by the observation that patients with primary carnitine deficiency (PCD) can present with fatty liver disease, which could be due to low levels of intrahepatic and serum levels of L-carnitine. Furthermore, studies suggest that supplementation with L-carnitine may reduce liver fat and the liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST) in patients with Non-Alcoholic Fatty Liver Disease (NAFLD). L-carnitine has also been shown to improve insulin sensitivity and elevate pyruvate dehydrogenase (PDH) flux. Studies that show reduced intrahepatic fat and reduced liver enzymes after L-carnitine supplementation suggest that L-carnitine might be a promising supplement to improve or delay the progression of NAFLD.

Nosocomial Infections Caused by Acinetobacter baumannii: Are We Losing the Battle?

BACKGROUND: The incidence of nosocomial infections caused by multi-drug- and extended-drug resistant strains of Acinetobacter is constantly increasing all over the world, with a high mortality rate. We analyzed the in-hospital data on the sensitivity of Acinetobacter baumannii isolates and correlated them with antibiotic treatment and clinical outcomes of nosocomial infections over a 17-mo period. METHODS: Retrospective analysis was performed at the Clinical Center "Bezanijska kosa," Belgrade, Serbia. Microbiologic data (number and sensitivity of A. baumannii isolates) and clinical data (medical records of 41 randomly selected patients who developed nosocomial infection caused by A. baumannii) were matched. RESULTS: Acinetobacter baumannii, detected in 279 isolates and obtained from 19 patients (12% of all samples), was resistant to almost all antibiotics tested, including carbapenems, with the exception of colistin and tigecycline. It was obtained most often from the respiratory tract samples. Empiric treatment of the nosocomial infections (pneumonia in 75% of cases) involved cephalosporins, metronidazole, and carbapenems (80%, 66%, and 61% of patients, respectively), whereas tigecyclin and colistin were used primarily in targeted therapy (20% and 12% of patients, respectively). The mortality rate of patients treated empirically was significantly higher (p < 0.01), reaching 100% in the elderly. CONCLUSIONS: Nosocomial A. baumannii infections represent a significant clinical problem because of their high incidence, lack of susceptibility to the most commonly used antibiotics, and the often inappropriate treatment, which favors the development of multi-drug-resistant strains.

[Importance of breast-feeding in antioxidant defence].

We investigated the importance of two enzymes (superoxide dismutase--SOD and glutathione peroxidase--GSH-Px) in the antioxidant defence of newborns and analysed their activity in: human colostrum and milk (from 63 mothers, after normal delivery, without complications or signs of infection), gastric fluid (from 10 breast-fed newborns, 7-28 days after birth; and from 15 artificially-fed newborns, with no signs of infection, 7-28 days after birth), and plasma (from 10 newborns, 1-28 days old, with no signs of infection, and 10 newborns, 1-28 days old, with signs of neonatal sepsis). The results of the study showed that there was statistically significant increased activity of SOD (p<0.001) in colostrum compared to mature milk. There was no statistically important difference in the activity of GSH-Px between those two samples. The activity of SOD in the gastric fluid of the artificially-fed newborns was statistically significantly lower than in the breast-fed newborns (p<0.001). The same results were found for mature mother's milk. We discovered a significant increase of SOD plasma activity in the newborns with sepsis, compared to the breast-fed newborns, with no signs of infection. The negative correlation between the activities of SOD and GSH-Px in the gastric fluid samples of the breast-fed and the artificially-fed newborns and the newborns with sepsis, showed that the activities of both enzymes were important for adequate antioxidant defence during the neonatal period. Breast-feeding with both colostrum and mature human milk is probably very important for adequate antioxidant defence in newborns.