Combining Metabolomics and Gene Expression Analysis Reveals that Propionyl- and Butyryl- Carnitines Are Involved in Late Stages of Arbuscular Mycorrhizal Symbiosis

The arbuscular mycorrhizal （AM） symbiosis is a widespread mutualistic association between soil fungi （Glomeromycota） and the roots of most plant species. AM fungi are obligate biotrophs whose development is partially under the control of their plant host. We explored the possibility to combine metabolomic and transcriptomic approaches to find putative mycorrhiza-associated metabolites regulating AM fungal development. Methanol extracts of Medicago truncatula roots colonized or not with the AM fungus Rhizophagus irregularis were analyzed and compared by ultra- high-performance liquid chromatography （UHPLC）, high-resolution mass spectrometry （Q-TOF）, and multivariate statisti- cal discrimination. We detected 71 mycorrhiza-associated analytes exclusively present or at least 10-fold more abundant in mycorrhizal roots. To identify among these analytes those that could regulate AM fungal development, we fraction- ated by preparative and semi-preparative HPLC the mycorrhizal and non-mycorrhizal root extracts and established how the 71 analytes were distributed among the fractions. Then we tested the activity of the fractions on germinating spores of R. irregularis by quantifying the expression of 96 genes known for their diverse in planta expression patterns. These investigations reveal that propionyl- and butyryl-carnitines accumulated in mycorrhizal roots. The results suggest that these two molecules regulate fungal gene expression in planta and represent interesting candidates for further biologi- cal characterization.

Rethinking neurodegenerative diseases:neurometabolic concept linking lipid oxidation to diseases in the central nervous system

Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.

Carnitine palmitoyltransferase-II inactivity promotes malignant progression of metabolic dysfunction-associated fatty liver disease via liver cancer stem cell activation

BACKGROUND Metabolic dysfunction-associated fatty liver disease(MAFLD)is one of the main chronic liver diseases.However,the roles of mitochondrial carnitine palmitoyl transferase-II(CPT-II)downregulation and liver cancer stem cell(LCSC)activation remain to be identified.AIM To investigate the dynamic alterations in CPT-II inactivity and LCSC activation during the malignant progression of MAFLD.METHODS Dynamic models of mouse MAFLD were generated via the consumption of a high-fat diet or the addition of 2-fluorenylacetamide for hepatocarcinogenesis.The mice were divided into groups on the basis of hematoxylin and eosin staining.Biochemistries,CPT-II,intrahepatic T cells,and LCSCs were determined and confirmed in clinical samples.The mitochondrial membrane potential(MMP)was analyzed.Differentially expressed genes were screened via RNA sequencing and enriched in KEGG pathways or GO functions.RESULTS Dynamic models of MAFLD malignant transformation were successfully generated on the basis of pathological examination.Hepatic lipid accumulation was associated with the loss of mitochondrial CPT-II activity and alterations in the MMP,with decreases in liver CD3+or CD4+T cells and increased AFP levels.In the lipid accumulation microenvironment,mitochondrial CPT-II was inactivated,followed by aberrant activation of CD44+or CD24+LCSCs,as validated in MAFLD or hepatocellular carcinoma patient samples.In terms of mechanism,the biological process category focused mainly on the metabolic regulation of cells in response to external stimuli.The enriched molecular functions included protein binding,cell apoptosis,and cell proliferation.CONCLUSION CPT-II inactivity promotes the malignant progression of MAFLD via the loss of innate immune function and abnormal LCSC activation.

Methylmalonic Acidemia: An Unusual Cause of Chronic Renal Disease in Adults

Background: Methylmalonic aciduria (MMA) is a genetic disorder of aminoacid metabolism, due to mutations in methylmalonyl-CoA mutase, which leads to the accumulation of methylmalonic acid in body fluids. Patients typically present at the age of 1 month to 1 year with dehydration, renal impairment as well as neurologic manifestations viz. seizure, encephalopathy, strokes and disease in the globus pallidi. The case: a 26-year-old man presented with severe acute on top of chronic renal disease with serum creatinine at 590 umol/L and bilateral 8 cm kidneys with thin and echogenic cortex. He had: (a) hypernatremic dehydration, metabolic acidosis and high ammonia level with (b) a history of multiple similar attacks since the age of 8 months. Diagnosis of MMA was confirmed by high serum and urine enzymatic levels as well as genetic testing. His initial management included support with replacements of fluids, electrolytes, and bicarbonates as well as intravenous dextrose, vitamin B12 and broad-spectrum antibiotic (Meropenem) for his chest infection. Subsequently, he received 1) CARBAGLU (carglumic acid) for 7 days to lower his ammonia level to Conclusion: Untreated homozygous MMA variants, can achieve adulthood with significant renal disease yet their morbidity and mortality can be ameliorated with diet and specific therapy.

Case Report: Carnitine Palmitoyl Transferase II (CPT II) Deficiency

Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting and the accumulation of the long chain fatty in the body. There are three types of CPT II deficiency, the myopathic form, the severe infantile hepatocardiomuscular form and the lethal neonatal form. They are all inherited as an autosomal recessive. Diagnosis of the CPTII are 1) tandem mass spectrometry (MS/MS) in adult form and 2) CPTII polymorphism (F352C), which is linked to reducing the activity of CPTII in infantile form [1]. Glucose is the primary management and medium-chain fatty acid is an alternative due to the bypass of the CPTII enzyme in the pathway. For the prevention of CPTII deficiency are to avoid long chain fatty acid (C12-fatty acid), fasting, prolonged exercise, known triggers, and certain medications such as anti-epileptics and general anesthesia. During the rhabdomyolysis and myoglobinuria attack, it is very important to maintain hydration to avoid acute renal failure. If, however, renal failure occurs, dialysis is recommended. We present a case of a 27-year-old African American woman with the significant past medical history of CPT II deficiency leading to recurrent rhabdomyolysis and myoglobinuria. Together with all the research studies from diagnosis to treatment of CPTII deficiency will help in clinical management of patients. And this case report will add to the existing case reports of patients who have CPTII deficiency in terms of how we diagnose, how we treat, and how we prevent symptoms from re-occurring.

Establishment of a metabolite diagnostic model for the risk of diabetic nephropathy in type 2 diabetic population:Based on a cross-sectional study in China

Introduction:This study aimed to investigate the correlation between various plasma metabolites and the likelihood of developing diabetic nephropathy(DN)and construct a diagnostic model for DN in Chinese patients with type 2 diabetes mellitus(T2DM).Methods:A cross-sectional investigation was conducted in a hospital setting.Based on medical data,a total of 743 patients from a tertiary hospital were selected and categorized into two groups:the diabetic nephropathy group(DN group)and the non-diabetic nephropathy group(non-DN group).Plasma levels of metabolites,including amino acids and acylcarnitines,were determined using a laser counter measurement system(LC-MS).Subsequently,partial least-squares regression was used to assess the significance of these metabolites.Receiver operating characteristic(ROC)curves were generated for factors that ranked highest in terms of relevance.Model performance was assessed using the curve(AUC).Results:Of the 743 patients with T2DM admitted to the hospital,145 had DN.Compared with the non-DN group,the DN group exhibited elevated systolic blood pressure(P=0.001),high-density lipoprotein cholesterol(P=0.01),and low-density lipoprotein cholesterol(P=0.042).Additionally,the DN group had a higher prevalence of stroke patients(P<0.001)and diabetic retinopathy patients(P<0.001).Finally,a risk model that included citrulline,leucine,tyrosine,valine,propionylcarnitine(C3),and palmitoylcarnitine(C16)was developed.This model achieved an AUC of 0.709,with a 95%confidence interval(CI)ranging from 0.626 to 0.793.Conclusions:A diagnostic model consisting of six plasma metabolites to assess the risk of DN in Chinese patients with T2DM may provide clues for future research.

Malonylcarnitine in Newborns with Non-syndromic Cleft Lip with or without Cleft Palate

Aim Malonyl-CoA is regarded as a key signaling molecule in mammalian ceils. It is converted to acetyl-CoA, and to a lesser extent, to malonyl acid and malonylcamitine （C3DC）. Availability of carnitine has been reported to be essential for the developing fetus. The objectives of the present study were to analyze associations of malonylcarnitine, acetylcarnitine （C2）, and free carnitine （CO） in subjects with orofacial clefts. Methodology We performed a retrospective analysis of carnitine concentration obtained from a newborn screening program carried out in our institution. Concentrations of whole blood malonylcarnitine, acetylcarnitine, and free carnitine were measured using tandem mass spectrometry. The study group consisted of 51 children with nonsyndromic cleft lip with or without cleft palate. In total, 106 healthy children without congenital anomalies served as controls. Cut-off points were established using likeli-hood ratio values. Results The mean concentration of malonylcarnitine in the cleft group was lower than that of the control group, 0.048 μmol.L^1 vs. 0.058 μmol.L^-1, respectively （P=-0.009）. In patients with orofacial cleft, low malonylcarnitine levels （〈0.047 μmol.L-1） were 1.7 times more predominant than in healthy individuals （P=-0.03）. The mean concentration of acetylcarnitine was also lower in affected newborns in comparison to controls, 33.8 μol.L^-1 vs. 37.8 μmol·L^-1, respectively （P=-0.026）. After analysis of acetylearnitine and free carnitine concentrations, the likelihood ratio test did not indicate valuable cut-offpoints. Conclusion The study provides initial data indicating a potential association between decreased malonylcarnitine and abnormal palatogenesis.

左卡尼汀在新生儿的临床应用

肉碱（carnitine）音译为＂卡尼汀＂,其有生物活性的异构体为左卡尼汀（levocarnitine）,是哺乳动物能量代谢必需的体内天然物质。研究表明,左卡尼汀是新生儿一种条件性必需营养素[1-2]。左卡尼汀最重要的代谢功能是能协助长链脂肪酸（long-chain fatty aicds,LCFAs）转运至线粒体内进行β-氧化和产能[3]。

Effects of L-carnitine in patients with hepatic encephalopathy

AIM： To evaluate the influence of Locarnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy （HE）. METHODS： One hundred and fifty patients （10 patients with alcoholism, 41 patients with hepatitis virus B infection, 78 patients with hepatitis C virus infection, 21 patients with cryptogenetic cirrhosis） meeting the inclusion criteria were randomized into group A receiving a 90-d treatment with L-carnitine （2 g twice a day） or into group B receiving placebo in double blind. RESULTS： At the end of the study period, a significant decrease in NI-14 fasting serum levels was found in patients with hepatic encephalopathy （P〈0.0S） after the treatment with levocarnitine （LC）. Significant differences were also found between symbol digit modalities test and block design in patients with hepatic encephalopathy （P〈0.0S）. CONCLUSION： Results of our study suggest an important protective effect of L-carnitine against ammonia-precipitated encephalopathy in cirrhotic patients.

OCTN and CARD15 gene polymorphism in Chinese patients with inflammatory bowel disease

AIM： To investigate the single nucleotide polymorphism （SNPs） distribution of NOD2/CARD15 （R702W, G908R）, OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease （IBD）. METHODS： A total of 61 patients with Crohn＇s disease （CD）, 151 patients with ulcerative colitis （UC）, and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction （PCR-SSP） or by restriction fragment length polymorphism （PCR-RFLP） analysis. RESULTS： Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 （0/61 with CD） and 1.3% （2/151 with UC）. CONCLUSION： Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients.

A study of the ameliorating effects of carnitine on hepatic steatosis induced by total parenteral nutrition in rats

AIM To investigate the effects of carnitine on ameliorating hepatic steatosis induced by total parenteral nutrition (TPN) in animal model. METHODS Eighteen normal Wistar rats and 19 cirrhotic Wistar rats induced by carbon tetrachloride were randomly divided into three groups, i.e., free access to food and drink (group A), TPN (group B) and TPN+carnitine (group C) for one week, respectively. Hepatic function, histology and its fat content were determined on the 7th day. RESULTS Hepatic triglyceride (TG) and cholesterol (CHO) contents were significantly higher in groups B and C than in group A, and significantly lower in group C than in group B in both normal and cirrhotic rats (all P <0 05). Histopathological examinations revealed that hepatic steatosis was more severe in group B than in group C in both normal and cirrhotic rats. CONCLUSION Carnitine can ameliorate hepatic steatosis associated with TPN in both non cirrhotic and cirrhotic rats.

Mitochondrial carnitine palmitoyl transferase-Ⅱ inactivity aggravates lipid accumulation in rat hepatocarcinogenesis

AIM To investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase Ⅱ(CPT-Ⅱ) expression during malignant transformation of rat hepatocytes.METHODS Sprague-Dawley male rats were fed with normal, high fat(HF), and HF containing 2-fluorenylacetamide(2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, pre-cancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-Ⅱ alterations were analyzed by immunohistochemistry, and compared with CPT-Ⅱ specific concentration(μg/mg protein). Levels of total cholesterol(Tch), triglyceride(TG), and aminotransferases [alanine aminotransferase(ALT), aspartate aminotransferase(AST)] were determined by the routine methods.RESULTS After intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls(P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher(4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-Ⅱ in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-Ⅱ levels in the cancer group than in any of the other groups(P < 0.05).CONCLUSION Low CPT-Ⅱ expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.

Role of CARD15,DLG5 and OCTN genes polymorphisms in children with inflammatory bowel diseases

AIM: To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predispo- sition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD). METHODS: Two hundred patients with Crohn’s disease (CD), 186 ulcerative colitis (UC) patients, 434 par- ents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated. RESULTS: Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more com- mon in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an in- creased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was morefrequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed. CONCLUSION: Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric on- set of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.

A simplified LC-MS/MS method for the quantification of the cardiovascular disease biomarker trimethylamine-N-oxide and its precursors

Trimethylamine-N-oxide(TMAO)has emerged as a potential biomarker for atherosclerosis and the development of cardiovascular diseases(CVDs).Although several clinical studies have shown striking associations of TMAO levels with atherosclerosis and CVDs,TMAO determinations are not clinical routine yet.The current methodology relies on isotope-labeled internal standards,which adds to pre-analytical complexity and costs for the quantification of TMAO and its precursors carnitine,betaine or choline.Here,we report a liquid chromatography-tandem mass spectrometry based method that is fast(throughput up to 240 samples/day),consumes low sample volumes(e.g.,from a finger prick),and does not require isotope-labeled standards.We circumvented the analytical problem posed by the presence of endogenous TMAO and its precursors in human plasma by using an artificial plasma matrix for calibration.We cross-validated the results obtained using an artificial matrix with those using mouse plasma matrix and demonstrated that TMAO,carnitine,betaine and choline were accurately quantified in’reallife’human plasma samples from healthy volunteers,obtained either from a finger prick or from venous puncture.Additionally,we assessed the stability of samples stored at-20℃and room temperature.Whereas all metabolites were stable at-20℃,increasing concentrations of choline were determined when stored at room temperature.Our method will facilitate the establishment of TMAO as a routine clinical biomarker in hematology in order to assess the risk for CVDs development,or to monitor disease progression and intervention effects.

Progression of diethylnitrosamine-induced hepatic carcinogenesis in carnitine-depleted rats

AIM:To investigate whether carnitine deficiency is a risk factor during the development of diethylnitrosamine (DENA)-induced hepatic carcinogenesis. METHODS:A total of 60 male Wistar albino rats were divided into six groups with 10 animals in each group.Rats in group 1(control group)received a single intraperitoneal(i.p.)injection of normal saline. Animals in group 2(carnitine-supplemented group) were given L-carnitine(200 mg/kg per day)in drinking water for 8 wk.Animals in group 3(carnitine-depleted group)were given D-carnitine(200 mg/kg per day)and mildronate(200 mg/kg per day)in drinking water for 8 wk.Rats in group 4(DENA group)were injected with a single dose of DENA(200 mg/kg,i.p.)and 2 wk later received a single dose of carbon tetrachloride(2 mL/kg) by gavage as 1:1 dilution in corn oil.Animals in group 5(DENA-carnitine depleted group)received the same treatment as group 3 and group 4.Rats in group 6 (DENA-carnitine supplemented group)received the same treatment as group 2 and group 4.RESULTS:Administration of DENA resulted in a significant increase in alanine transaminase(ALT), gamma-glutamyl transferase(G-GT),alkaline phosphatase(ALP),total bilirubin,thiobarbituric acid reactive substances(TBARS)and total nitrate/ nitrite(NOx)and a significant decrease in reduced glutathione(GSH),glutathione peroxidase(GSHPx), catalase(CAT)and total carnitine content in liver tissues.In the carnitine-depleted rat model,DENA induced a dramatic increase in serum ALT,G-GT,ALP and total bilirubin,as well as a progressive reduction in total carnitine content in liver tissues.Interestingly, L-carnitine supplementation resulted in a complete reversal of the increase in liver enzymes,TBARS and NOx,and a decrease in total carnitine,GSH,GSHPx, and CAT induced by DENA,compared with the control values.Histopathological examination of liver tissues confirmed the biochemical data,where L-carnitine prevented DENA-induced hepatic carcinogenesis while D-carnitine-mildronate aggravated DENA-induced hepatic damage. CONCLUSION:Data from this study suggest for the first time that:(1)carnitine deficiency is a risk factor and should be viewed as a mechanism in DENA- induced hepatic carcinogenesis;(2)oxidative stress plays an important role but is not the only cause of DENA-induced hepatic carcinogenesis;and(3) long-term L-carnitine supplementation prevents the development of DENA-induced liver cancer.

Effects of the dietary supplementation with fructooligosaccharides on the excretion of nitrogen and phosphorus in Miichthys miiuy fries

Effects of dietary supplementation with fructooligosaccharides on the excretion of nitrogen and phosphorus in Miichthys miiuy fries were investigated. Nine hundred Miichthys miiuy fries were divided into 3 groups, each with triplicates. The basal diet and the basal diet supplemented with carnitine groups were considered as the negative and positive controls respectively. Results showed that the nitrogen concentration in excreted feces decreased significantly in fries fed the diet supplementation with 1000×10?6 fructooligosaccharides and 200×10?6 carnitine (P<0.05). The ammonic-nitrogen concentration decreased significantly in the carnitine group only (P<0.05), indicating the decreasing tendency caused by the supplementation with fructooligosaccha-rides. Supplementation with both did not have significant effects on the concentration of phosphorus in feces of Miichthys miiuy fries.

Intestinal OCTN2-and MCT1-targeted drug delivery to improve oral bioavailability

Various drug transporters are widely expressed throughout the intestine and play important roles in absorbing nutrients and drugs,thus providing high quality targets for the design of prodrugs or nanoparticles to facilitate oral drug delivery.In particular,intestinal carnitine/organic cation transporter 2(OCTN2)and mono-carboxylate transporter protein 1(MCT1)possess high transport capacities and complementary distributions.Therefore,we outline recent developments in transporter-targeted oral drug delivery with regard to the OCTN2 and MCT1 proteins in this review.First,basic information of the two transporters is reviewed,including their topological structures,characteristics and functions,expression and key features of their substrates.Furthermore,progress in transporter-targeting prodrugs and nanoparticles to increase oral drug delivery is discussed,including improvements in the oral absorption of anti-inflammatory drugs,antiepileptic drugs and anticancer drugs.Finally,the potential of a dual transporter-targeting strategy is discussed.

Decrease of serum carnitine levels in patients with or without gastrointestinal cancer cachexia

AIM： To evaluate the levels of serum carnitine in patients with cancer in digestive organs and to compare them with other cancers in order to provide new insights into the mechanisms of cachexia. METHODS： Fifthy-five cachectic patients with or without gastrointestinal cancer were enrolled in the present study. They underwent routine laboratory investigations, including examination of the levels of various forms of carnitine present in serum （i.e., long-chain acylcarnitine, short-chain acylcarnitine, free carnitine, and total carnitine）. These values were compared with those found in 60 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS： When the cachectic patients with gastrointestinal cancer were compared with the cachectic patients without gastrointestinal cancer, the difference was -6.8 μmol/L in free carnitine （P 〈 0.005）, 0.04 μmol/ L in long chain acylcarnitine （P 〈 0.05）, 8.7 μmol/L in total carnitine （P 〈 0.001）. In the cachectic patients with or without gastrointestinal cancer, the difference was 12.2 μmol/L in free carnitine （P 〈 0.001）, 4.60 μmol/L in short chain acylcarnitine （P 〈 0.001）, and 0.60 μmol/L in long-chain acylcarnitine （P 〈 0.005） and 17.4 μmol/L in total carnitine （P 〈 0.001）. In the cachectic patients with gastrointestinal cancer and the healthy control subjects, the difference was 15.5 μmol/L in free carnitine （P 〈 0.001）, 5.2 μmol /L in short-chain acylcarnitine （P 〈 0.001）, 1.0 μmol/L in long chain acylcarnitine （P 〈 0.001）, and 21.8 μmol/L in total carnitine （P 〈 0.001）. CONCLUSION： Low serum levels of carnitine in terminal neoplastic patients are decreased greatly due to the decreased dietary intake and impaired endogenous synthesis of this substance. These low serum carnitine levels also contribute to the progression of cachexia in cancer patients.

Autism and carnitine: A possible link

Patients with autism spectrum disorders(ASD) present deficits in social interactions and communication, they also show limited and stereotypical patterns of behaviors and interests. The pathophysiological bases of ASD have not been defined yet. Many factors seem to be involved in the onset of this disorder. These include genetic and environmental factors, but autism is not linked to a single origin, only. Autism onset can be connected with various factors such as metabolic disorders: including carnitine deficiency. Carnitine is a derivative of two amino acid lysine and methionine. Carnitine is a cofactor for a large family of enzymes: the carnitine acyltransferases. Through their action these enzymes(and L-carnitine) are involved in energy production and metabolic homeostasis. Some people with autism(less than 20%) seem to have L-carnitine metabolism disorders and for these patients, a dietary supplementation with Lcarnitine is beneficial. This review summarizes the available information on this topic.

Plasma carnitine ester profile in adult celiac disease patients maintained on long-term gluten free diet

AIM： To determine the fasting plasma carnitine ester in patients with celiac disease. METHODS： We determined the fasting plasma carnitine ester profile using ESI triple quadrupol mass spectrometry in 33 adult patients with biopsy-confirmed maturity onset celiac disease maintained on long term gluten free diet. RESULTS： The level of free camibine did not differ as the celiac disease patients were compared with the healthy controls, whereas the acetylcarnitine level was markedly reduced （4.703± 0.205 vs 10.227 ± 0.368 nmol/mL, P〈0.01）. The level of propionylcarnitine was 61.5%, butyrylcarnitine 56.9%, hexanoylcarnitine 75%, octanoylcarnitine 71.1%, octenoylcarnitine 52.1%, decanoylcarnitine 73.1%, cecenoylcarnitine 58.3%, lauroylcarnitine 61.5%, miristoylcarnitine 66.7%, miristoleylcarnitine 62.5% and oleylcarnitine 81.1% in the celiac disease patients compared to the control values, respectively （P〈0.01）. CONCLUSION： The marked decrease of circulating acetylcarnitine with 50-80 % decrease of 11 other carnitine esters shows that the carnitine ester metabolism can be influenced even in clinically asymptomatic and well being adult celiac disease patients, and gluten withdrawal alone does not necessarily normalize all elements of the disturbed carnitine homeostasis.