L-carnitine: a partner between immune response and lipid metabolism ?

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Giuseppe Famularo

1993-01-01

Full Text Available The authors demonstrated that in vivo administered L-carnitine strongly ameliorated the immune response in both healthy individuals receiving Intralipid and ageing subjects with cardiovascular diseases, as shown by the enhancement of mixed lymphocyte reaction. Notably, in the latter group L-carnitine treatment also resulted in a significant reduction of serum levels of both cholesterol and triglycerides. Therefore, the hypothesis is that L-carnitine supplementation could ameliorate both the dysregulated immune response and the abnormal lipid metabolism in several conditions.

Effect of [L-Carnitine] on acetyl-L-carnitine production by heart mitochondria

International Nuclear Information System (INIS)

Bieber, L.L.; Lilly, K.; Lysiak, W.

1986-01-01

The authors recently reported a large efflux of acetyl-L-carnitine from rat heart mitochondria during state 3 respiration with pyruvate as substrate both in the presence and absence of malate. In this series of experiments, the effect of the concentration of L-carnitine on the efflux of acetyl-L-carnitine and on the production of 14 CO 2 from 2- 14 C-pyruvate was determined. Maximum acetylcarnitine production (approximately 25 n moles/min/mg protein) was obtained at 3-5 mM L-carnitine in the absence of added malate. 14 CO 2 production decreased as the concentration of L-carnitine increased; it plateaued at 3-5 mM L-carnitine. These data indicate carnitine can stimulate flux of pyruvate through pyruvate dehydrogenase and can reduce flux of acetyl CoA through the Krebs cycle by acting as an acceptor of the acetyl moieties of acetyl CoA generated by pyruvate dehydrogenase

Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial.

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Badrasawi, M; Shahar, Suzana; Zahara, A M; Nor Fadilah, R; Singh, Devinder Kaur Ajit

2016-01-01

Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia. This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile. The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine ( P <0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention. L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults.

Efficacy of L-carnitine supplementation on frailty status and its biomarkers, nutritional status, and physical and cognitive function among prefrail older adults: a double-blind, randomized, placebo-controlled clinical trial

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Badrasawi, M; Shahar, Suzana; Zahara, AM; Nor Fadilah, R; Singh, Devinder Kaur Ajit

2016-01-01

Background Frailty is a biological syndrome of decreased reserve and resistance to stressors due to decline in multiple physiological systems. Amino acid deficiency, including L-carnitine, has been proposed to be associated with its pathophysiology. Nevertheless, the efficacy of L-carnitine supplementation on frailty status has not been documented. Thus, this study aimed to determine the effect of 10-week L-carnitine supplement (1.5 g/day) on frailty status and its biomarkers and also physical function, cognition, and nutritional status among prefrail older adults in Klang Valley, Malaysia. Methodology This study is a randomized, double-blind, placebo-controlled clinical trial conducted among 50 prefrail subjects randomized into two groups (26 in L-carnitine group and 24 in placebo group). Outcome measures include frailty status using Fried criteria and Frailty Index accumulation of deficit, selected frailty biomarkers (interleukin-6, tumor necrosis factor-alpha, and insulin-like growth factor-1), physical function, cognitive function, nutritional status and biochemical profile. Results The results indicated that the mean scores of Frailty Index score and hand grip test were significantly improved in subjects supplemented with L-carnitine (P<0.05 for both parameters) as compared to no change in the placebo group. Based on Fried criteria, four subjects (three from the L-carnitine group and one from the control group) transited from prefrail status to robust after the intervention. Conclusion L-carnitine supplementation has a favorable effect on the functional status and fatigue in prefrail older adults. PMID:27895474

Patients with medium-chain acyl-coenzyme a dehydrogenase deficiency have impaired oxidation of fat during exercise but no effect of L-carnitine supplementation

DEFF Research Database (Denmark)

Madsen, K L; Preisler, N; Orngreen, M C

2013-01-01

It is not clear to what extent skeletal muscle is affected in patients with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD). l-Carnitine is commonly used as a supplement in patients with MCADD, although its beneficial effect has not been verified.......It is not clear to what extent skeletal muscle is affected in patients with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD). l-Carnitine is commonly used as a supplement in patients with MCADD, although its beneficial effect has not been verified....

Regulation of carnitine status in ruminants and efficacy of carnitine supplementation on performance and health aspects of ruminant livestock: a review.

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Ringseis, Robert; Keller, Janine; Eder, Klaus

2018-02-01

Carnitine has long been known to play a critical role for energy metabolism. Due to this, a large number of studies have been carried out to investigate the potential of supplemental carnitine in improving performance of livestock animals including ruminants, with however largely inconsistent results. An important issue that has to be considered when using carnitine as a feed additive is that the efficacy of supplemental carnitine is probably dependent on the animal's carnitine status, which is affected by endogenous carnitine synthesis, carnitine uptake from the gastrointestinal tract and carnitine excretion. The present review aims to summarise the current knowledge of the regulation of carnitine status and carnitine homeostasis in ruminants, and comprehensively evaluate the efficacy of carnitine supplementation on performance and/or health in ruminant livestock by comparing the outcomes of studies with carnitine supplementation in dairy cattle, growing and finishing cattle and sheep. While most of the studies show that supplemental carnitine, even in ruminally unprotected form, is bioavailable in ruminants, its effect on either milk or growth performance is largely disappointing. However, supplemental carnitine appears to be a useful strategy to offer protection against ammonia toxicity caused by consumption of high levels of non-protein N or forages with high levels of soluble N both, in cattle and sheep.

Carnitine Deficiency and Pregnancy

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Anouk de Bruyn

2015-01-01

Full Text Available We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, supplementation with carnitine is advised. This supplementation should be continued throughout pregnancy according to plasma concentrations.

Marked elevation in plasma trimethylamine-N-oxide (TMAO in patients with mitochondrial disorders treated with oral l-carnitine

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H.D. Vallance

2018-06-01

Full Text Available Oral supplementation with l-carnitine is a common therapeutic modality for mitochondrial disorders despite limited evidence of efficacy. Recently, a number of studies have demonstrated that a gut microbiota-dependent metabolite of l-carnitine, trimethylamine oxide (TMAO, is an independent and dose-dependent risk factor for cardiovascular disease (CVD. Given the limited data demonstrating efficacy with oral l-carnitine therapy and the newly raised questions of potential harm, we assessed plasma TMAO levels in patients with mitochondrial disease with and without oral l-carnitine supplementation. Nine subjects were recruited and completed the study. Eight out of 9 subjects at baseline had plasma TMAO concentrations <97.5th percentile (<15.5 μM. One subject with stage 3 renal disease, had marked elevation in plasma TMAO (pre 33.98 μm versus post 101.6 μm. Following at least 3 months of l-carnitine supplementation (1000 mg per day, plasma TMAO levels were markedly increased in 7out of 9 subjects; overall, plasma TMAO significantly increased 11.8-fold (p < 0.001 from a baseline median level of 3.54 μm (interquartile range (IQR 2.55–8.72 to 43.26 (IQR 23.99–56.04 post supplementation. The results of this study demonstrate that chronic oral l-carnitine supplementation markedly increases plasma TMAO levels in subjects with mitochondrial disorders. Further studies to evaluate both the efficacy and long term safety of oral l-carnitine supplementation for the treatment of mitochondrial disorders are warranted. Keywords: l-carnitine, Trimethylamine N-oxide, Mitochondrial disorders

Effects of Supplementation Time of L-Carnitine and Garlic Powder on Performance and Carcass Characteristics of Broiler Chickens

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Ali Khatibjoo

2016-08-01

Full Text Available Introduction Carnitine has several roles in lipid oxidation, immunomodulation function and enhancing antibody responses. L-carnitine has been found to exhibit immunomodulatory effects. It enhances serum primary antibody response to sheep red blood cells (SRBC and subsequent humoral immunity using 100 mg L-carnitine/ kg diet compared with control group in Leghorn chickens (Deng et al., 2006. It was reported that only the immediate effects of dietary carnitine on immunocompetence is known while comparing long and short-term effects on early life on the immune system of broiler chickens is unknown. The organic allyl sulfur components in garlic (mainly allicin were implicated to mediate its biological activity. The biological activities of these compounds may be related to their SH modification and antioxidant properties (Prasad et al., 1996. AGE treatment prevented the reduction of the antibody production response in thymectomized mice and improved the thymectomy-induced deterioration of learning behaviors in passive avoidance performance and in a spatial memory task (Zhang et al., 1998. Materials and Methods Four hundred Arian one-day-old broiler chicks were used. This experiment was conducted in order to consider the effects of L-Carnitine and garlic powder on broiler chicken performance, blood metabolites and carcass characteristics in a 2×5 factorial arrangement in randomized complete design with 5 dietary treatments, 4 replicates and 12 birds in each and two periods: short (first 3 weeks and long time (total production period. Dietary treatments were 1 Basal diet (BD: no supplementation, 2 ration having 0.02% flavomycin (positive control, 3 ration having 1.5% garlic powder, 4 ration having 0.025% L-Carnitine and 5 ration having 0.025% L-Carnitine plus 1.5% garlic powder. The birds were kept under conventional conditions for vaccination, temperature, ventilation, and lighting based on Ross catalogue recommendations. Standard management

Effects of a therapeutic lifestyle change diet and supplementation with Q10 plus L-carnitine on quality of life in patients with myocardial infarction: A randomized clinical trial

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Mohammad Hossein Sharifi

2017-03-01

Conclusion: Both TLC diet and supplementation with Q10 and L- carnitine had a positive effect on the physical and emotional subscales of MacNew questionnaire and may improve post-MI prognosis. Based on the results, combination of Q10 plus L-carnitine and TLC die can be a potential intervention for improving QoL and secondary prevention.

Effect of different levels of L-carnitine and lysine-methionine on broiler blood parameters

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Babak Hosseintabar

2015-09-01

Full Text Available Objetive. In the present study a completely randomized 3×3 factorial design was used to analyze the effects of different levels of L-Carnitine, lysine(Lys and methionine (Met on the blood concentrations of energy, protein and lipid metabolites of male broiler chickens. Materials and methods. A total of 270 newly hatched male broiler chickens (Ross 308 were randomly assigned to 9 groups (ten broilers per replicate and three replicates per treatment. The control group was fed a basal diet, whereas the treatment groups were fed basal diets supplemented with L-Carnitine (0 mg/kg, 75 mg/kg and 150 mg/kg and lysine-methionine (0, 15 and 30% for 42 days. On day 42, one bird was randomly chosen per replication, a blood sample was taken and the blood concentrations of glucose (GLU, uric acid (UAc, triglyceride (TG, VLDL, HDL, LDL, total protein (TP, albumin (Alb and total cholesterol (TC were analyzed. Results. Dietary L-carnitine supplementation had a significant effect (p<0.05 on uric acid (UAc, HDL, LDL, and total cholesterol (TC. The birds feed L-carnitine plus Lys and Met presented the highest plasmatic UAc level and the lowest plasmatic TC and LDL level. Moreover, L-carnitine significantly reduced total cholesterol (TC when compared with both the control group and the birds feed Lys and Met without L-carnitine. Conclusions. A diet with 150 mg/kg L-carnitine plus 15% Lys and Met seems to be enough to sustain low plasmatic TC, LDL and HDL concentrations on male broiler.

Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency

OpenAIRE

de Boer, L.; Kluijtmans, L. A. J.; Morava, E.

2012-01-01

Although the diagnosis of a primary carnitine deficiency is usually based on a very low level of free and total carnitine (free carnitine: 1–5 μM, normal 20–55 μM) (Longo et al. 2006), we detected a patient via newborn screening with a total carnitine level 67 % of the normal value. At the age of 1 year, after interruption of carnitine supplementation for a 4-week period the carnitine profile was assessed and the free carnitine level had dropped to 10.4 μmol/l (normal: 20–55 μM) and total car...

l-Carnitine and heart disease.

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Wang, Zhong-Yu; Liu, Ying-Yi; Liu, Guo-Hui; Lu, Hai-Bin; Mao, Cui-Ying

2018-02-01

Cardiovascular disease (CVD) is a key cause of deaths worldwide, comprising 15-17% of healthcare expenditure in developed countries. Current records estimate an annual global average of 30 million cardiac dysfunction cases, with a predicted escalation by two-three folds for the next 20-30years. Although β-blockers and angiotensin-converting-enzymes are commonly prescribed to control CVD risk, hepatotoxicity and hematological changes are frequent adverse events associated with these drugs. Search for alternatives identified endogenous cofactor l-carnitine, which is capable of promoting mitochondrial β-oxidation towards a balanced cardiac energy metabolism. l-Carnitine facilitates transport of long-chain fatty acids into the mitochondrial matrix, triggering cardioprotective effects through reduced oxidative stress, inflammation and necrosis of cardiac myocytes. Additionally, l-carnitine regulates calcium influx, endothelial integrity, intracellular enzyme release and membrane phospholipid content for sustained cellular homeostasis. Carnitine depletion, characterized by reduced expression of "organic cation transporter-2" gene, is a metabolic and autosomal recessive disorder that also frequently associates with CVD. Hence, exogenous carnitine administration through dietary and intravenous routes serves as a suitable protective strategy against ventricular dysfunction, ischemia-reperfusion injury, cardiac arrhythmia and toxic myocardial injury that prominently mark CVD. Additionally, carnitine reduces hypertension, hyperlipidemia, diabetic ketoacidosis, hyperglycemia, insulin-dependent diabetes mellitus, insulin resistance, obesity, etc. that enhance cardiovascular pathology. These favorable effects of l-carnitine have been evident in infants, juvenile, young, adult and aged patients of sudden and chronic heart failure as well. This review describes the mechanism of action, metabolism and pharmacokinetics of l-carnitine. It specifically emphasizes upon the beneficial

Creatine, L-carnitine, and ω3 polyunsaturated fatty acid supplementation from healthy to diseased skeletal muscle.

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D'Antona, Giuseppe; Nabavi, Seyed Mohammad; Micheletti, Piero; Di Lorenzo, Arianna; Aquilani, Roberto; Nisoli, Enzo; Rondanelli, Mariangela; Daglia, Maria

2014-01-01

Myopathies are chronic degenerative pathologies that induce the deterioration of the structure and function of skeletal muscle. So far a definitive therapy has not yet been developed and the main aim of myopathy treatment is to slow the progression of the disease. Current nonpharmacological therapies include rehabilitation, ventilator assistance, and nutritional supplements, all of which aim to delay the onset of the disease and relieve its symptoms. Besides an adequate diet, nutritional supplements could play an important role in the treatment of myopathic patients. Here we review the most recent in vitro and in vivo studies investigating the role supplementation with creatine, L-carnitine, and ω3 PUFAs plays in myopathy treatment. Our results suggest that these dietary supplements could have beneficial effects; nevertheless continued studies are required before they could be recommended as a routine treatment in muscle diseases.

Creatine, L-Carnitine, and ω3 Polyunsaturated Fatty Acid Supplementation from Healthy to Diseased Skeletal Muscle

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D'Antona, Giuseppe; Nabavi, Seyed Mohammad; Micheletti, Piero; Aquilani, Roberto; Nisoli, Enzo; Rondanelli, Mariangela; Daglia, Maria

2014-01-01

Myopathies are chronic degenerative pathologies that induce the deterioration of the structure and function of skeletal muscle. So far a definitive therapy has not yet been developed and the main aim of myopathy treatment is to slow the progression of the disease. Current nonpharmacological therapies include rehabilitation, ventilator assistance, and nutritional supplements, all of which aim to delay the onset of the disease and relieve its symptoms. Besides an adequate diet, nutritional supplements could play an important role in the treatment of myopathic patients. Here we review the most recent in vitro and in vivo studies investigating the role supplementation with creatine, L-carnitine, and ω3 PUFAs plays in myopathy treatment. Our results suggest that these dietary supplements could have beneficial effects; nevertheless continued studies are required before they could be recommended as a routine treatment in muscle diseases. PMID:25243159

Role of carnitine in disease

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Flanagan Judith L

2010-04-01

Full Text Available Abstract Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.

Marked elevation in plasma trimethylamine-N-oxide (TMAO) in patients with mitochondrial disorders treated with oral l-carnitine

OpenAIRE

H.D. Vallance; A. Koochin; J. Branov; A. Rosen-Heath; T. Bosdet; Z. Wang; S.L. Hazen; G. Horvath

2018-01-01

Oral supplementation with l-carnitine is a common therapeutic modality for mitochondrial disorders despite limited evidence of efficacy. Recently, a number of studies have demonstrated that a gut microbiota-dependent metabolite of l-carnitine, trimethylamine oxide (TMAO), is an independent and dose-dependent risk factor for cardiovascular disease (CVD). Given the limited data demonstrating efficacy with oral l-carnitine therapy and the newly raised questions of potential harm, we assessed pla...

Aplicações clínicas da suplementação de L-carnitina Clinical uses of L-carnitine supplementation

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Christianne de Faria Coelho

2005-10-01

Full Text Available A carnitina, uma amina quaternária (3-hidroxi-4-N-trimetilamino-butirato, é sintetizada no organismo (fígado, rins e cérebro a partir de dois aminoácidos essenciais: lisina e metionina, exigindo para sua síntese a presença de ferro, ácido ascórbico, niacina e vitamina B6. Tem função fundamental na geração de energia pela célula, pois age nas reações transferidoras de ácidos graxos livres do citosol para mitocôndrias, facilitando sua oxidação e geração de adenosina Trifosfato. A concentração orgânica de carnitina é resultado de processos metabólicos - como ingestão, biossíntese, transporte dentro e fora dos tecidos e excreção - que, quando alterados em função de diversas doenças, levam a um estado carencial de carnitina com prejuízos relacionados ao metabolismo de lipídeos. A suplementação de L-carnitina pode aumentar o fluxo sangüíneo aos músculos devido também ao seu efeito vasodilatador e antioxidante, reduzindo algumas complicações de doenças isquêmicas, como a doença arterial coronariana, e as conseqüências da neuropatia diabética. Por esse motivo, o objetivo do presente trabalho foi descrever possíveis benefícios da suplementação de carnitina nos indivíduos com necessidades especiais e susceptíveis a carências de carnitina, como os portadores de doenças renais, neuropatia diabética, síndrome da imunodefeciência adquirida e doenças cardiovasculares.Carnitine, a quaternary amine (3-hidroxy-4-n-trimethylaminobutyrate is synthesized in the body (liver, kidney and brain from lysine and methionine, two essential amino acids, in the presence of iron, ascorbate, niacin and vitamin B6. Carnitine plays a central role in the cellular energy metabolism because it transports long-chain fatty acids from the cytosol to the mitochondria for oxidation and adenosine 5'-triphosphate generation. The organic concentration of carnitine is a result of several metabolic pathways such as ingestion

Effect of Different Levels of L-Carnitine on the Productive Performance, Egg Quality, Blood Parameters and Egg Yolk Cholesterol in Laying Hens

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Kazemi-Fard M

2015-12-01

Full Text Available This experiment was conducted to investigate the effects of different levels of L-carnitine on productive performance, egg quality and blood parameters in laying hens. Forty-eight Hy-Line W-36 egg Layers were weighed at 90 weeks of age and randomly allocated into 16 cages (three hens per cage. Four dietary treatments were prepared by supplementing L-carnitine (0, 50, 100 and 150 mg/kg of diet to corn-soybean meal diet and offered ad libitum to hens. After two weeks of acclimatization, the eggs were weighed daily and feed intake as well as egg quality traits were measured biweekly. At the end of the experiment, two hens from each cage were selected to determine blood parameters and two eggs from each replicate were collected for cholesterol analysis. Results showed that L-carnitine supplementation at 100 and 150 mg/kg significantly increased egg production and egg mass, but decreased yolk cholesterol content. Laying hens receiving diet containing 50 mg/kg L-carnitine had significantly higher Hough unit, but lower progesterone than the hens fed control diet (P < 0.05. The results of this study showed that supplementing hens' diet with L-carnitine had beneficial effects on productive performance and decreased yolk cholesterol concentration; so it can be used as an effective supplement in the diet of laying hens.

Primary Carnitine deficiency in the Faroe Islands

DEFF Research Database (Denmark)

Rasmussen, Jan; Køber, Lars; Lund, Allan M

2014-01-01

BACKGROUND: Carnitine deficiency can cause cardiomyopathy and cardiac arrhythmia. The prevalence in the Faroe Islands is the highest reported in the world (1:300). A nationwide screening program identified 76 Faroese adult patients (15-80 years) with Primary Carnitine Deficiency (PCD). We describe...... prior and current health status and symptoms in these patients, especially focusing on cardiac characteristics. METHODS: Upon identification, patients were immediately admitted for physical examination, ECG, blood tests and initiation of L-carnitine supplementation. Medical records were reviewed...... and patients were interviewed. Echocardiography and blood tests were performed in 35 patients before and after L-carnitine supplementation. RESULTS: All patients were either asymptomatic or had minor symptoms when diagnosed. Echocardiography including LVEF, global longitudinal strain and dimensions were normal...

The effect of fermented buckwheat on producing l-carnitine- and γ-aminobutyric acid (GABA)-enriched designer eggs.

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Park, Namhyeon; Lee, Tae-Kyung; Nguyen, Thi Thanh Hanh; An, Eun-Bae; Kim, Nahyun M; You, Young-Hyun; Park, Tae-Sub; Kim, Doman

2017-07-01

The potential of fermented buckwheat as a feed additive was studied to increase l-carnitine and γ-aminobutyric acid (GABA) in designer eggs. Buckwheat contains high levels of lysine, methionine and glutamate, which are precursors for the synthesis of l-carnitine and GABA. Rhizopus oligosporus was used for the fermentation of buckwheat to produce l-carnitine and GABA that exert positive effects such as enhanced metabolism, antioxidant activities, immunity and blood pressure control. A novel analytical method for simultaneously detecting l-carnitine and GABA was developed using liquid chromatography/mass spectrometry (LC/MS) and LC/MS/MS. The fermented buckwheat extract contained 4 and 34 times more l-carnitine and GABA respectively compared with normal buckwheat. Compared with the control, the fermented buckwheat extract-fed group showed enriched l-carnitine (13.6%) and GABA (8.4%) in the yolk, though only l-carnitine was significantly different (P < 0.05). Egg production (9.4%), albumen weight (2.1%) and shell weight (5.8%) were significantly increased (P < 0.05). There was no significant difference in yolk weight, and total cholesterol (1.9%) and triglyceride (4.9%) in the yolk were lowered (P < 0.05). Fermented buckwheat as a feed additive has the potential to produce l-carnitine- and GABA-enriched designer eggs with enhanced nutrition and homeostasis. These designer eggs pose significant potential to be utilized in superfood production and supplement industries. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Crystal Structure of an L-Carnitine Complex with Pyrogallol[4]arene

International Nuclear Information System (INIS)

Fujisawa, I; Takeuchi, D; Kitamura, Y; Okamoto, R; Aoki, K

2012-01-01

L-Carnitine is essential for the transport of long-chain fatty acids from cytosol into mitochondria for generating metabolic energy. The survey of crystal structures of carnitine-containing proteins in the Protein Data Bank reveals that carnitine can take several conformations with the quarternary trimethylammonium terminal being always bound to aromatic residues through cation-π interactions in acyltransferases or carnitine-binding proteins. In order to demonstrate the importance of cation-π interaction as a carnitine recognition mechanism in the artificial receptor-ligand system that mimics the carnitine-binding sites, we have determined the crystal structure of a complex formed between L-carnitine and pyrogallol[4]arene (pyrogallol cyclic tetramer: PCT) as a carnitine receptor, 2PCT·2(L-carnitine)·4EtOH. There form two crystallographically independent monomeric [PCT·L-carnitine] substructures, which further form an obliquely arranged capsule-like dimeric [PCT·L-carnitine] 2 structure through a pair of O-H (PCT)···O (L-carnitine) hydrogen bonds. This is the first report of PCT complex with chiral molecules. In each of the two monomeric [PCT·L-carnitine] substructures, the L-carnitine molecule takes the elongated form with an intramolecular hydrogen bond between the hydroxyl group and the carboxylate oxygen, and the cationic trimethylammonium moiety is incorporated into the cavity of the bowl-shaped PCT molecule through cation-π interactions. These features are similar to those at the D-carnitine-binding site in the crystal structure of the glycine betaine/carnitine/choline-binding protein complex.

Role of L-carnitine in Ameliorating the Cadmium Chloride and/or Irradiation-Induced Testicular Toxicity

International Nuclear Information System (INIS)

Ramadan, L.A.

2003-01-01

The role of oxidative stress in chronic administration of CdCl2 and/or irradiation toxicity and its prevention by pretreatment with L-carnitine was investigated. Adult male rats were administered with CdCl2 (3 mg/kg S.C. three times a week for three weeks) and /or irradiated at (2 Gy) dose level of gamma radiation. CdCl2 administration and/or irradiation induced cellular damage was indicated by significant decrease in lactate dehydrogenase isoenzyme (LDH-X), glutathione level (GSH) and glutathione peroxidase enzyme activity (GSH-PX) as well as significant increase in malonaldehyde (MDA) in testicular tissues. Administration of L-carnitine (200 mg/kg I.P.) 1 hr before CdCl2 and/or irradiation, ameliorated the decrease in LDH-X, GSH and GSH-PX and the increase in MDA induced by CdCl2 and/or irradiation indicating the prophylactic action of L-carnitine on CdCl2 and /or irradiation toxicity. Various studies have indicated that cadmium is a potent heavy metal carcinogen in experimental animals (Poirier et al., 1983 and Waalkes et al..,1988) and is possibly carcinogenic in human populations exposed either occupationally or environmentally (Bako et al., 1982). Target sites for cadmium carcinogenesis in rodents have been shown to include testes after parenteral exposure (Poirier et al., 1983 and Waalkes et al., 1988) and lung after chronic inhalation (Takenaka et al., 1983)

L-carnitine and cancer cachexia. I. L-carnitine distribution and metabolic disorders in cancer cachexia.

Science.gov (United States)

Szefel, Jarosław; Kruszewski, Wiesław Janusz; Ciesielski, Maciej; Szajewski, Mariusz; Kawecki, Krzysztof; Aleksandrowicz-Wrona, Ewa; Jankun, Jerzy; Lysiak-Szydłowska, Wiesława

2012-07-01

Cancer cachexia (CC), a progressive loss of body mass, is associated with decreased energy production. Abnormally low levels of L-carnitine (LC) in skeletal muscle means that mitochondrial β-oxidation of long-chain fatty acids (LCFA) does not occur efficiently in patients with CC. We assessed the influence of CC on LC distribution and the effects of parenteral lipid emulsions on plasma LC levels and urinary excretion. Fifty patients with CC were randomly assigned to total parenteral nutrition (TPN) with long-chain triglycerides (LCTs), or LCTs plus medium-chain triglycerides (MCTs) as 50/50. Patients were further separated into those with body-mass index (BMI) ≤ 19 kg/m(2) and BMI >19 kg/m(2). Plasma concentrations of total LC (TC) and free LC (FC) and their urinary excretion were measured, along with skeletal muscle LC levels. On average, plasma FC and TC were higher than reference values in all patients. Patients with BMI ≤ 19 kg/m(2) had lower plasma FC and TC than those with BMI >19 kg/m(2). Skeletal muscle FC in the BMI ≤ 19 kg/m(2) group was lower than reference value, but within the normal range in others. LC and FC urinary excretion was higher than reference values. Plasma LC and its urinary excretion were higher in patients administered pure LCTs relative to those given MCTs/LCTs. A decrease in skeletal muscle LC in cancer patients with CC (BMI ≤ 19 kg/m(2)) correlates with an increase in its plasma levels and increased renal excretion. A diet of MCTs/LCTs reduces LC release from muscle to plasma and urine more effectively than LCTs.

Gender differences in locomotor and stereotypic behavior associated with l-carnitine treatment in mice.

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Benvenga, Salvatore; Itri, Elenora; Hauser, Peter; De Tolla, Louis; Yu, Sui-Foh; Testa, Giuseppe; Pappalardo, Maria Angela; Trimarchi, Francesco; Amato, Antonino

2011-02-01

The carnitines exert neuroprotective and neuromodulatory actions, and carnitine supplementation increases locomotor activity (LMA) in experimental animals. We measured 13 indexes of LMA and 3 indexes of stereotypic activity (STA) in adult male and female caged mice. In a randomized 4-week trial, 10 males and 10 females received 50 mg/kg body weight PO l-carnitine, and another 10 males and 10 females received placebo. Compared with placebo-treated females, placebo-treated males had a greater number of stereotypies (NSTs), stereotypy counts (STCs), stereotypy time (STT), and right front time (RFT), but smaller total distance traveled (TDT), margin distance (MD), number of vertical movements (NVMs), and left rear time (LRT). Compared with placebo-treated males, carnitine-treated males had greater horizontal activity (HA), movement time (MT), NVM, STT, TDT, STC, MD, LRT, and clockwise revolutions (CRs), but smaller left front time (LFT) and RFT. Compared with placebo-treated females, carnitine-treated females had greater NST, STC, STT, LFT, and RFT, but smaller NM, HA, NVM, VA, MT, anticlockwise revolutions (ACRs), CR, TDT, and MD; right rear time (RRT) remained statistically insignificant across all comparisons. In summary, l-carnitine caused gender differences to persist for STC, diminish for NST and STT, disappear for LRT and NVM, change in the opposite direction for TDT and MD, appear de novo for HA, VA, NM, MT, and LFT, and remain absent for RRT and ACR. Some indexes of LMA and STA are sexually dimorphic in adult mice, and l-carnitine differentially maintains, diminishes/cancels, inverts, or creates the sexual dimorphism of particular indexes. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.

Stereoselective synthesis of L-[4-13C]carnitine

International Nuclear Information System (INIS)

Unkefer, C.J.; Ehler, D.S.

1991-01-01

The stereoselective synthesis of L-[4- 13 C]carnitine was achieved in 5 steps. The label was introduced from K 13 CN into an easily separated diastereomeric pair of 3-deoxy-D-[1- 13 C]aldohexoses. Reductive amination of the labeled aldohexose yielded the corresponding D-1-(dimethylamino)[1- 13 C]alditol which was oxidized in two steps and alkylated with iodomethane to yield L-[4- 13 C]carnitine. The stereochemical integrity at C-2 of the 3-deoxy-D-[1- 13 C]glucose precursor was maintained throughout the synthesis of L-[4- 13 C]carnitine. (author)

Synthesis of O-[11C]acetyl CoA, O-[11C]acetyl-L-carnitine, and L-[11C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey

International Nuclear Information System (INIS)

Jacobson, Gunilla B.; Watanabe, Yasuyoshi; Valind, Sven; Kuratsune, Hirohiko; Laangstroem, Bengt

1997-01-01

The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with 11 C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1- 11 C]acetyl CoA and O-[2- 11 C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1- 11 C]acetyl-L-carnitine and O-[2- 11 C]acetyl-L-carnitine in 70-80% yield, based on [1- 11 C]acetate or [2- 11 C]acetate, respectively. By an N-methylation reaction with [ 11 C]methyl iodide, L-[methyl- 11 C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl- 11 C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [ 11 C]methyl iodide. Initial data of the kinetics of the different 11 C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented

L-carnitine protects against testicular dysfunction caused by gamma irradiation in mice.

Science.gov (United States)

Ahmed, Mohamed Mohamed; Ibrahim, Zein Shaban; Alkafafy, Mohamed; El-Shazly, Samir Ahmed

2014-07-01

This study was conducted on mice to evaluate the radioprotective role of L-carnitine against γ-ray irradiation-induced testicular damage. Adult male mice were exposed to whole body irradiation at a total dose of 1 Gy. Radiation exposure was continued 24 h a day (0.1 Gy/day) throughout the 10 days exposure period either in the absence and/or presence of L-carnitine at an i.p. dose of 10 mg/kg body weight/day. Results revealed that γ-rays irradiation suppressed the expression of ABP and CYP450SCC mRNA, whereas treatment with L-carnitine prior and throughout γ-rays irradiation exposure inhibited this suppression. Treatment with γ-ray irradiation or L-carnitine down-regulated expression of aromatase mRNA. With combined treatment, L-carnitine significantly normalized aromatase expression. γ-Ray irradiation up-regulated expression of FasL and Cyclin D2 mRNA, while L-carnitine inhibited these up-regulations. Results also showed that γ-ray-irradiation up-regulated TNF-α, IL1-β and IFN-γ mRNA expressions compared to either controls or the L-carnitine treated group. Moreover, γ-irradiation greatly reduced serum testosterone levels, while L-carnitine, either alone or in combination with irradiation, significantly increased serum testosterone levels compared to controls. In addition, γ-irradiation induced high levels of sperm abnormalities (43%) which were decreased to 12% in the presence of L-carnitine. In parallel with these findings, histological examination showed that γ-irradiation induced severe tubular degenerative changes, which were reduced by L-carnitine pre-treatment. These results clarified the immunostimulatory effects of L-carnitine and its radioprotective role against testicular injury. Copyright © 2014 Elsevier GmbH. All rights reserved.

Ameliorative effects of l-carnitine on rats raised on a diet supplemented with lead acetate

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El-Said El-Sherbini

2017-09-01

Conclusion:l-Carnitine may play an important role in reversing the undesirable effects of lead intoxication. Future studies should be conducted to see whether such an effect is applicable in humans exposed to lead poising.

Effect of propionyl-L-carnitine on human endothelial cells

NARCIS (Netherlands)

Hinsbergh, V.W.M. van; Scheffer, M.A.

1991-01-01

A possible protective effect of propionyl-L-carnitine on human endothelial cells was studied both under basal culture conditions and in the presence of agents capable of influencing oxidative damage, such as glucose/glucose oxidase and oxidized low-density lipoproteins. Propionyl-L-carnitine had no

Survey of Synergistic Effect of L-carnitine with Glutamine on Body Composition and Dietary Intake in Soccer Players: A Double-blind, Randomized Clinical Trial

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Mohammad Hozoori

2016-10-01

Full Text Available Background: The present study was conducted to investigate the possible effects of L-carnitine and glutamine and their synergistic effects on male soccer athletes. Methods: 28 male soccer players (21.1 ± 0.7 y were enrolled in a randomized pre and post intervention, double-blind design. Before the intervention, their performances were assessed by Bruce protocol, and their body composition was measured with the body composition analyzer. Then, athletes were randomly allocated into four groups: 2 g L-glutamine, 2 g L-carnitine, 2 g L-carnitine + 2 g L-glutamine and placebo. Supplements were prescribed for 21 days and after three weeks, athletes' performances and body composition were re-evaluated. Results: The results showed that body weight, body fat percentage, lean muscle mass, and dietary intake made no significant changes in different groups of athletes. In between groups comparison, results did not significantly change in any performance indices. However, in L-carnitine supplement group, the results of pre and post intervention showed that the running distance and maximal oxygen uptake (VO2max increased significantly while the subjective sense of fatigue decreased significantly. Conclusions: Based on our findings, a three-week prescription of separateor combined glutamine and L-carnitine, had no effects on body composition or dietary intake in soccer players. But, the athletes' energy intake was more than the one reported in other studies. Although further studies are required to assess these effects on athletic performance.

Preparation of radioactive acetyl-l-carnitine by an enzymatic exchange reaction

International Nuclear Information System (INIS)

Emaus, R.; Bieber, L.L.

1982-01-01

A rapid method for the preparation of [1- 14 C]acetyl-L-carnitine is described. The method involves exchange of [1- 14 C]acetic acid into a pool of unlabeled acetyl-L-carnitine using the enzymes acetyl-CoA synthetase and carnitine acetyltransferase. After isotopic equilibrium is attained, radioactive acetylcarnitine is separated from the other reaction components by chromatography on Dowex 1 (C1 - ) anion exchange resin. One of the procedures used to verify the product [1- 14 C]acetyl-L-carnitine can be used to synthesize (3S)-[5- 14 C]citric acid

Synthesis of O-[{sup 11}C]acetyl CoA, O-[{sup 11}C]acetyl-L-carnitine, and L-[{sup 11}C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey

Energy Technology Data Exchange (ETDEWEB)

Jacobson, Gunilla B.; Watanabe, Yasuyoshi; Valind, Sven; Kuratsune, Hirohiko; Laangstroem, Bengt

1997-07-01

The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with {sup 11}C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1-{sup 11}C]acetyl CoA and O-[2-{sup 11}C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1-{sup 11}C]acetyl-L-carnitine and O-[2-{sup 11}C]acetyl-L-carnitine in 70-80% yield, based on [1-{sup 11}C]acetate or [2-{sup 11}C]acetate, respectively. By an N-methylation reaction with [{sup 11}C]methyl iodide, L-[methyl-{sup 11}C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl-{sup 11}C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [{sup 11}C]methyl iodide. Initial data of the kinetics of the different {sup 11}C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented.

Does left ventricular function improve with L-carnitine after acute myocardial infarction?

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Iyer R

1999-04-01

Full Text Available A double blind randomized placebo controlled clinical trial was carried out to assess the efficacy and safety of L-carnitine in patients suffering from acute anterior wall myocardial infarction with respect to left ventricular function. Sixty patients (34 men, 26 women, mean age 56+11 yr. with acute anterior wall myocardial infarction were randomized to placebo and L-carnitine. All the patients were given intravenous L-carnitine / placebo in the dose of 6gm/day for the first seven days followed by oral L-carnitine / placebo 3 gm/day in three divided doses for a period of three months. Echocardiography was performed for regional wall motion abnormality, left ventricular end systolic volume (ESV, end diastolic volume (EDV and ejection fraction (EF on admission, after seven days and after three months of the infarction. Forty-four patients completed the study. There were three deaths, two in the placebo and one in the L-carnitine group (p>0.05. Thirteen patients were lost to follow up. Echo parameters in both groups were comparable (p>0.05. The duration of chest pain prior to initiation of the I.V. L-carnitine was 7.5 + 5.2 hrs in the L-carnitine group and 7 + 4 hrs in the placebo group (p>0.05. There was no statistical difference in the EF, ESV and EDV on admission, at discharge and after three months in the L-carnitine and the placebo groups (p>0.05. No significant adverse effects were noted. L-carnitine, though a safe drug, does not affect the left ventricular function in patients with myocardial infarction.

Urinary excretion of L-carnitine, acetyl-L-carnitine, propionyl-L-carnitine and their antioxidant activities after single dose administration of L-carnitine in healthy subjects

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Yu Cao

2013-03-01

Full Text Available The urine excretion of L-carnitine (LC, acetyl-L-carnitine (ALC and propionyl-Lcarnitine (PLC and their relations with the antioxidant activities are presently unknown. Liquid L-carnitine (2.0 g was administered orally as a single dose in 12 healthy subjects. Urine concentrations of LC, ALC and PLC were detected by HPLC. Superoxide dismutase (SOD, total antioxidative capacity (T-AOC, malondialdehyde (MDA and nitrogen monoxidum (NO activities were measured by spectrophotometric methods. The 0~2 h, 2~4 h, 4~8 h, 8~12 h, 12~24 h excretion of LC was 53.13±31.36 µmol, 166.93±76.87 µmol, 219.92±76.30 µmol, 100.48±23.89 µmol, 72.07±25.77 µmol, respectively. The excretion of ALC was 29.70±14.43 µmol, 80.59±32.70 µmol, 109.85±49.21 µmol, 58.65±18.55 µmol, and 80.43±35.44 µmol, respectively. The urine concentration of PLC was 6.63±4.50 µmol, 15.33±12.59 µmol, 15.46±6.26 µmol, 13.41±11.66 µmol and 9.67±7.92 µmol, respectively. The accumulated excretion rate of LC was 6.1% within 24h after its administration. There was also an increase in urine concentrations of SOD and T-AOC, and a decrease in NO and MDA. A positive correlation was found between urine concentrations of LC and SOD (r = 0.8277 or T-AOC (r = 0.9547, and a negative correlation was found between urine LC excretions and NO (r = -0.8575 or MDA (r = 0.7085. In conclusion, a single oral LC administration let to a gradual increase in urine L-carnitine excretion which was associated with an increase in urine antioxidant enzymes and the total antioxidant capacities. These data may be useful in designing therapeutic regimens of LC or its analogues in the future.A excreção urinária de L-carnitina (LC, acetil-L-carnitina (ALC e propionil-L-carnitine (PLC e as suas relações com as atividades antioxidantes são presentemente desconhecidos. Líquido de L-carnitina (2,0 g foi administrada por via oral como uma dose única em 12 indivíduos saudáveis. As concentra

The antidiabetic effect of L-carnitine in rats: the role of nitric oxide system

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Shaghayegh Hajian-Shahri

2017-11-01

Full Text Available Background: Nowadays, the use of L-carnitine in the treatment of diabetes is increasing. This study was conducted to investigate the effect of co-administration of L-arginine (precursor for the synthesis of nitric oxide and nitro-L-arginine (nitric oxide synthesis inhibitor on antidiabetic activity of L-carnitine in diabetic rats. Materials and Methods: In this study, 50 male rats weighing 180-201g were divided into five groups: (1 non diabetic control rats; (2 untreated diabetic rats; (3 diabetic rats treated with L-carnitine 300 mg/kg (4; diabetic rats treated with L-carnitine 300 mg/kg + L-arginine 300 mg/kg; and (5 diabetic rats treated with L-carnitine (300 mg/kg + nitro-L-arginine (1mg/kg. Type 1 diabetes was induced by a single intraperitoneal injection of 110 mg/kg body weight alloxan. After 30 days, liver malondialdehyde levels, lipid profile, serum glucose, and glycated hemoglobin serum levels were measured. Results: Blood glucose, liver enzymes, glycated hemoglobin, and liver malondialdehyde levels significantly decreased in diabetic rats treated with L-carnitine compared to the untreated diabetic group (P<0.05. The co-administration of L-arginine and L-carnitine led to a significant decrease in glycated hemoglobin levels and serum glucose, in a manner similar to the group received only L-carnitine. Also, L-arginine and nitro-l-arginine had similar effects on liver lipid peroxidation and serum biochemical parameters. Conclusion: The results suggest that the hypoglycemic effect of L-carnitine is mediated independently from nitric oxide pathways. The interaction between L-carnitine and L-arginine may not be synergistic. So, their combined administration is not recommended for the diabetic patients.

CHANGES IN MAXIMAL STRENGTH AND BODY COMPOSITION AFTER DIFFERENT METHODS OF DEVELOPING MUSCLE STRENGTH AND SUPPLEMENTATION WITH CREATINE, L-CARNITINE AND HMB

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M Kruszewski

2011-06-01

Full Text Available The aim of the present study was to assess the effects of bodybuilding training combined with administration of L-carnitine, weightlifting training combined with administration of creatine, and isometric training combined with administration of β-hydroxy-β-methylbutyrate (HMB on maximal strength and body composition of athletes. The studies were conducted on groups of beginners practising bodybuilding training (n=63 and isometric training (n=69 as well as on a group of advanced powerlifters (n=50 practising weightlifting training. The obtained results indicate that the most desirable and beneficial supportive effect in strength sports was exhibited by HMB. No significant differences in body composition of subjects practising bodybuilding training were detected between those who were given L-carnitine and those who received placebo, an observation confirming controversies over the capacity of the former to reduce fat content. However, significant differences in maximal strength were demonstrated between the examined groups of athletes. Significant differences in the examined parameters were also detected within the group of advanced powerlifters practising weightlifting between those who were supplemented with creatine and those who were given placebo. Thus, the use of creatine in the development of physical capacity in advanced athletes may be advisable.

Effects of L-carnitine administration on left ventricular remodeling after acute anterior myocardial infarction: The L-carnitine Ecocardiografia Digitalizzata Infarto Miocardico (CEDIM) trial

NARCIS (Netherlands)

S. Iliceto (Sabino); D. Scrutinio (Domenico); P. Bruzzi (P.); G. D'Ambrosio (Gaetano); A. Boni (Alejandro); M. Di Biase (Matteo); G. Biasco (Giuseppina); P.G. Hugenholtz (Paul); P. Rizzon (Paolo)

1995-01-01

textabstractObjectives. This study was performed to evaluate the effects of l-carnitine administration on long-term left ventricular dilation in patients with acute anterior myocardial infarction. Background. Carnitine is a physiologic compound that performs an essential role in myocardial energy

Production of L-carnitine by secondary metabolism of bacteria

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Iborra José L

2007-10-01

Full Text Available Abstract The increasing commercial demand for L-carnitine has led to a multiplication of efforts to improve its production with bacteria. The use of different cell environments, such as growing, resting, permeabilized, dried, osmotically stressed, freely suspended and immobilized cells, to maintain enzymes sufficiently active for L-carnitine production is discussed in the text. The different cell states of enterobacteria, such as Escherichia coli and Proteus sp., which can be used to produce L-carnitine from crotonobetaine or D-carnitine as substrate, are analyzed. Moreover, the combined application of both bioprocess and metabolic engineering has allowed a deeper understanding of the main factors controlling the production process, such as energy depletion and the alteration of the acetyl-CoA/CoA ratio which are coupled to the end of the biotransformation. Furthermore, the profiles of key central metabolic activities such as the TCA cycle, the glyoxylate shunt and the acetate metabolism are seen to be closely interrelated and affect the biotransformation efficiency. Although genetically modified strains have been obtained, new strain improvement strategies are still needed, especially in Escherichia coli as a model organism for molecular biology studies. This review aims to summarize and update the state of the art in L-carnitine production using E. coli and Proteus sp, emphasizing the importance of proper reactor design and operation strategies, together with metabolic engineering aspects and the need for feed-back between wet and in silico work to optimize this biotransformation.

Modulatory effects of l-carnitine plus l-acetyl-carnitine on neuroendocrine control of hypothalamic functions in functional hypothalamic amenorrhea (FHA).

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Genazzani, Alessandro D; Despini, Giulia; Czyzyk, Adam; Podfigurna, Agnieszka; Simoncini, Tommaso; Meczekalski, Blazej

2017-12-01

Functional hypothalamic amenorrhea (FHA) is a relatively frequent disease due to the combination of metabolic, physical, or psychological stressors. It is characterized by the low endogenous GnRH-induced gonadotropin secretion, thus triggering the ovarian blockade and a hypoestrogenic condition. Up to now various therapeutical strategies have been proposed, both using hormonal treatment as well as neuroactive compounds. Since carnitine, namely l-acetyl-carnitine (LAC), has been demonstrated to be effective in the modulation of the central hypothalamic control of GnRH secretion, we aimed to evaluate whether a combined integrative treatment for 12 weeks of LAC (250 mg/die) and l-carnitine (500 mg/die) was effective in improving the endocrine and metabolic pathways in a group of patients (n = 27) with FHA. After the treatment, interval mean LH plasma levels increased while those of cortisol and amylase decreased significantly. When patients were subdivided according to baseline LH levels, only hypo-LH patients showed the significant increase of LH plasma levels and the significant decrease of both cortisol and amylase plasma levels. The increased 17OHP/cortisol ratio, as index of the adrenal activity, demonstrated the reduced stress-induced adrenal activity. In conclusion, our data sustain the hypothesis that the integrative administration of LAC plus l-carnitine reduced both the metabolic and the neuroendocrine impairment of patients with FHA.

Safety Measures of L-Carnitine L-Tartrate Supplementation in Healthy Men.

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Rubin, Martyn R.; Volek, Jeff S.; Gomez, Ana L.; Ratamess, Nicholas A.; French, Duncan N.; Sharman, Matthew J.; Kraemer, William J.

2001-01-01

Examined the effects of ingesting the dietary supplement L- CARNIPURE on liver and renal function and blood hematology among healthy men. Analysis of blood samples indicated that there were no statistically significant differences between the L-CARNIPURE and placebo conditions for any variables examined, suggesting there are no safety concerns…

Oxygen Glucose Deprivation in Rat Hippocampal Slice Cultures Results in Alterations in Carnitine Homeostasis and Mitochondrial Dysfunction

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Rau, Thomas F.; Lu, Qing; Sharma, Shruti; Sun, Xutong; Leary, Gregory; Beckman, Matthew L.; Hou, Yali; Wainwright, Mark S.; Kavanaugh, Michael; Poulsen, David J.; Black, Stephen M.

2012-01-01

Mitochondrial dysfunction characterized by depolarization of mitochondrial membranes and the initiation of mitochondrial-mediated apoptosis are pathological responses to hypoxia-ischemia (HI) in the neonatal brain. Carnitine metabolism directly supports mitochondrial metabolism by shuttling long chain fatty acids across the inner mitochondrial membrane for beta-oxidation. Our previous studies have shown that HI disrupts carnitine homeostasis in neonatal rats and that L-carnitine can be neuroprotective. Thus, this study was undertaken to elucidate the molecular mechanisms by which HI alters carnitine metabolism and to begin to elucidate the mechanism underlying the neuroprotective effect of L-carnitine (LCAR) supplementation. Utilizing neonatal rat hippocampal slice cultures we found that oxygen glucose deprivation (OGD) decreased the levels of free carnitines (FC) and increased the acylcarnitine (AC): FC ratio. These changes in carnitine homeostasis correlated with decreases in the protein levels of carnitine palmitoyl transferase (CPT) 1 and 2. LCAR supplementation prevented the decrease in CPT1 and CPT2, enhanced both FC and the AC∶FC ratio and increased slice culture metabolic viability, the mitochondrial membrane potential prior to OGD and prevented the subsequent loss of neurons during later stages of reperfusion through a reduction in apoptotic cell death. Finally, we found that LCAR supplementation preserved the structural integrity and synaptic transmission within the hippocampus after OGD. Thus, we conclude that LCAR supplementation preserves the key enzymes responsible for maintaining carnitine homeostasis and preserves both cell viability and synaptic transmission after OGD. PMID:22984394

L-carnitine increases body lean in adult dogs and cats

OpenAIRE

Jewell, D.

2010-01-01

L-carnitine has been shown to be a repartitioning agent (i.e.,setting metabolism toward more protein and less fat accretion) in animals used for food production. The purpose of this study was to determine the effects on body composition repartitioning (i.e.,increasing lean body mass) of added dietary L-carnitine in adult dogs and cats.

L-carnitine plasma levels in dogs and cats. A diagnostic parameter?

International Nuclear Information System (INIS)

Fischer, J.

1993-04-01

The relation between levels of carnitine in plasma and lesions of organs should be demonstrated. 52 dogs and 58 cats examined in veterinary clinics for several reasons and routinely screened for blood chemistry also were analysed for free plasma carnitine by a radiocarbon method. Increased carnitine levels were observed in both species in case of heart, liver and kidney disorders. Additionally the influence of food intake on carnitine levels in dogs was studied. Postprandial changes were insignificant. Because of lack of information about carnitine levels in cats and changes with age plasma carnitine was determined in cats and kittens. The range of normal values was 8.2 to 24.2 μmol/l without any significance of age

Effects of Oral L-Carnitine on Liver Functions after Transarterial Chemoembolization in Intermediate-Stage HCC Patients

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Abeer Hassan

2015-01-01

Full Text Available Transarterial chemoembolization (TACE is usually followed by hepatic dysfunction. We evaluated the effects of L-carnitine on post-TACE impaired liver functions. Methods. 53 cirrhotic hepatocellular carcinoma patients at Osaka Medical College were enrolled in this study and assigned into either L-carnitine group receiving 600 mg oral L-carnitine daily or control group. Liver functions were evaluated at pre-TACE and 1, 4, and 12 weeks after TACE. Results. The L-carnitine group maintained Child-Pugh (CP score at 1 week after TACE and exhibited significant improvement at 4 weeks after TACE (P<0.01. Conversely, the control group reported a significant CP score deterioration at 1 week (P<0.05 and 12 weeks after TACE (P<0.05. L-carnitine suppressed serum albumin deterioration at 1 week after TACE. There were significant differences between L-carnitine and control groups regarding mean serum albumin changes from baseline to 1 week (P<0.05 and 4 weeks after TACE (P<0.05. L-carnitine caused prothrombin time improvement from baseline to 1, 4 (P<0.05, and 12 weeks after TACE. Total bilirubin mean changes from baseline to 1 week after TACE exhibited significant differences between L-carnitine and control groups (P<0.05. The hepatoprotective effects of L-carnitine were enhanced by branched chain amino acids combination. Conclusion. L-carnitine maintained and improved liver functions after TACE.

The effects of acute L-carnitine administration on ventilatory breakpoint and exercise performanceduring incremental exercise

OpenAIRE

Mojtaba Kaviani; Maryam Nourshahi; Farhad Shokoohi

2009-01-01

(Received 31 October, 2009 ; Accepted 10 March, 2010)AbstractBackground and purpose: Many athletes adopt nutritional manipulations to improve their performance. Among the substances generally consumed is carnitine (L-trimethyl-3-hydroxy-ammoniobutanoate) which has been used by athletes as an ergogenic aid, due to its role in the transport of long-chain fatty acids across mitochondrial membranes. Nutritional supplements containing carbohydrates, proteins, vitamins, and minerals have been widel...

Oral carnitine supplementation reduces body weight and insulin resistance in women with polycystic ovary syndrome: a randomized, double-blind, placebo-controlled trial.

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Samimi, Mansooreh; Jamilian, Mehri; Ebrahimi, Faraneh Afshar; Rahimi, Maryam; Tajbakhsh, Banafsheh; Asemi, Zatollah

2016-06-01

Limited data are available for evaluating the effects of oral carnitine supplementation on weight loss and metabolic profiles of women with polycystic ovary syndrome (PCOS). This study was designed to determine the effects of oral carnitine supplementation on weight loss, and glycaemic and lipid profiles in women with PCOS. In a prospective, randomized, double-blind, placebo-controlled trial, 60 overweight patients diagnosed with PCOS were randomized to receive either 250 mg carnitine supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at the beginning and the end of the study to quantify parameters of glucose homoeostasis and lipid concentrations. At the end of the 12 weeks, taking carnitine supplements resulted in a significant reduction in weight (-2·7 ± 1·5 vs +0·1 ± 1·8 kg, P weight, BMI, WC and HC, and beneficial effects on glycaemic control; however, it did not affect lipid profiles or free testosterone. © 2015 John Wiley & Sons Ltd.

Evaluating effects of L-carnitine on human bone-marrow-derived mesenchymal stem cells.

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Fujisawa, Koichi; Takami, Taro; Fukui, Yumi; Quintanilha, Luiz Fernando; Matsumoto, Toshihiko; Yamamoto, Naoki; Sakaida, Isao

2017-05-01

Mesenchymal stem cells (MSCs) are multipotent cells showing potential for use in regenerative medicine. Culture techniques that are more stable and methods for the more efficient production of MSCs with therapeutic efficacy are needed. We evaluate the effects of growing bone marrow (Bm)-derived MSCs in the presence of L-carnitine, which is believed to promote lipid metabolism and to suppress apoptosis. The presence of L-carnitine decreased the degree of drug-induced apoptosis and suppressed adipogenic differentiation. Metabolomic analysis by means of the exhaustive investigation of metabolic products showed that, in addition to increased β-oxidation and the expression of all carnitine derivatives other than deoxycarnitine (an intermediate in carnitine synthesis), polysaturated and polyunsaturated acids were down-regulated. An integrated analysis incorporating both serial analysis of gene expression and metabolomics revealed increases in cell survival, suggesting the utility of carnitine. The addition of carnitine elevated the oxygen consumption rate by BmMSCs that had been cultured for only a few generations and those that had become senescent following repeated replication indicating that mitochondrial activation occurred. Our exhaustive analysis of the effects of various carnitine metabolites thus suggests that the addition of L-carnitine to BmMSCs during expansion enables efficient cell production.

[Micronutrients in oncology. Current data about vitamin D, selenium, L-carnitine and vitamin C].

Science.gov (United States)

Gröber, Uwe; Mücke, Ralph; Holzhauer, Peter; Kisters, Klaus

2013-04-01

Many patients receiving cancer treatment use micronutrient supplements, with the intention to complement their cancer treatment, or help them cope with the therapy- and disease-associated side-effects. Up to 90% of the cancer patients are adding antioxidants without the knowledge of the treating physician. There are many concerns that antioxidants might decrease the effectiveness of chemotherapy, but increasing evidence suggests a benefit when antioxidants and other micronutrients, such as selenium, L-carnitine and vitamin D are added to conventional cytotoxic therapies. It is imperative that physicians discuss the use ofantioxidant and other micronutrient supplements with their cancer patients and educate them about potentially negative, but also potentially beneficial effects.

Carnitine

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Carnitine (L-g-trimethylamino-ß-hydroxybutyrate) functions metabolically as a covalent molecular chaperone of acyl compounds esterified to its hydroxyl moiety (1,2). The quintessentialmetabolic function of L-carnitine is to shuttle long-chain FAs (LCFAs)2 across the inner mitochondrial membrane to t...

The Effect of Acetyl-L-Carnitine Administration on Persons with Down Syndrome

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Pueschel, Siegfried M.

2006-01-01

Since previous investigations reported improvements in cognition of patients with dementia after acetyl-L-carnitine therapy and since there is an increased risk for persons with Down syndrome to develop Alzheimer disease, this study was designed to investigate the effect of acetyl-L-carnitine administration on neurological, intellectual, and…

Acetyl L-Carnitine Modulating Irradiation Induced Cardio-Pulmonary Toxicity in Rats

International Nuclear Information System (INIS)

Gharib, O.A.

2006-01-01

In The Present study male adult Wister albino rats were irradiated at 4 Gy whole body gamma irradiation and Acetyl L-carnitine (ALC) was evaluated as a potential radio-protector under conditions that would model the oxidative stress syndrome. ALC protect the heart and lung from the depletion of SOD, GSHPx activities and GSH content followed radiation exposure. Protection from the increase of malonaldehyde (MDA) in heart and lung tissues as well as serum creatine phosphokinase (CPK), AST and LDH has been observed. These results imply that ALC can act as a radio-protector against many aspects of oxidative damage. ALC is an ester of the tri methylated amino acid L-carnitine, and is synthesized endogenously in the human brain, liver and kidney by the enzyme ALC transferase or obtained from dietary sources (Goa and Brogden, 1987). L carnitine and short chain derivatives are essential cofactors for mitochondrial transport and oxidation of long chain fatty acid and act also as scavengers of oxygen free radicals in mammalian tissue (Izgut-Uysal et al., 2001). The transport of ALC and PLC occurs more easily than L-carnitine through the lipid component of the intestinal barrier suggesting possible better oral bioavailability of the esters than L-carnitine (Marciniani et al., 1991). ALC has antioxidant activity towards oxidative stress via an inhibition of the increase in lipid hydro peroxidation (Yasui et al., 2002). ALC significantly enhances the regenerative capacity of neurons that survive peripheral nerve trauma (Marciniani et al., 1991) and has also shown neuro-protective effect in rats (Bigini et al., 2002)

L-CARNITINE-INDUCED MODULATION OF PLASMA FATTY ACIDS METABOLISM IN HYPERLIPIDEMIC RABBITS

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Frank Hernández Rosales PhD

2006-02-01

mejoramiento del metabolismo de las lipoproteínas. ABSTRACTThe present study was designed to examine whether the hipocholesterolemic effect of L-carnitine supplementation is related with lipoprotein fatty acid metabolism. Fatty acid compositional and cholesterol content changes were measured in lipoproteins of six different groups of rabbits. Group 1, rabbits fed a standard diet; group 2, rabbits fed standard diet plus L-carnitine 80 mg/kg bw; group 3, rabbits fed a 0.5 % cholesterol diet; group 4, rabbits fed a 0.5 % cholesterol diet plus L-carnitine 80 mg/kg b.w. These four groups were fed their diets during 126 days. Group 5 and 6 were fed the same diet as group 4 in a previous period of 126 days, and after this time, group 5 was fed the same diet as group 1, and group 6 fed the same diet as group 2, during a second period of 65 days.However, the progression of hypercholesterolemia was reduced 50 % by L-carnitine administration in those animals fed cholesterol diet. Fatty acid compositional changes in lipoprotein-cholesteryl esters were found in all groups of animals supplemented with L-carnitine. During the standard-fed period the saturated and unsaturated fatty acid ratio was increased in VLDL and HDL particles whereas was decreased in LDL. In the hyperlipidemia progression period the saturated to unsaturated fatty acid ratio in HDL fraction was slightly enhanced and in the VLDL+LDL modified particle was diminished. In the hyperlipidemia regression period, plasma cholesterol level was additionally reduced in a 33 % in the group 6; and the saturated to unsaturated fatty ratio had the same behaviour from that observed in the progression period for HDL and VLDL+LDL particles. A remarkable reduction (75% of aorta atherosclerotic plaques in the group 6 was found. From these results we concluded that L-carnitine, in this experimental model, induces an improved lipoprotein metabolism.

Effects of vitamin C and L-carnitine on lipid profile and oxidative ...

African Journals Online (AJOL)

The roles of vitamin C and L-carnitine on lipid profile and oxidative stress parameters in the brain of rats during fasting and re-feeding were investigated. Sixty male Sprague-Dawley rats (170-180 g) were divided into four groups of control, fasting, fasting + vitamin C and fasting + L-carnitine. The test groups were further ...

L-carnitine prevents memory impairment induced by chronic REM-sleep deprivation.

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Alzoubi, Karem H; Rababa'h, Abeer M; Owaisi, Amani; Khabour, Omar F

2017-05-01

Sleep deprivation (SD) negatively impacts memory, which was related to oxidative stress induced damage. L-carnitine is a naturally occurring compound, synthesized endogenously in mammalian species and known to possess antioxidant properties. In this study, the effect of L-carnitine on learning and memory impairment induced by rapid eye movement sleep (REM-sleep) deprivation was investigated. REM-sleep deprivation was induced using modified multiple platform model (8h/day, for 6 weeks). Simultaneously, L-carnitine was administered (300mg/kg/day) intraperitoneally for 6 weeks. Thereafter, the radial arm water maze (RAWM) was used to assess spatial learning and memory. Additionally, the hippocampus levels of antioxidant biomarkers/enzymes: reduced glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG ratio, glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD) and thiobarbituric acid reactive substance (TBARS) were assessed. The results showed that chronic REM-sleep deprivation impaired both short- and long-term memory (Psleep deprivation induced reduction in the hippocampus ratio of GSH/GSSG, activity of catalase, GPx, and SOD. No change was observed in TBARS among tested groups (P>0.05). In conclusion, chronic REM-sleep deprivation induced memory impairment, and treatment with L-carnitine prevented this impairment through normalizing antioxidant mechanisms in the hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

EVALUATING THE EFFECTIVENESS OF ELKAR (L-CARNITINE IN PREMATURE INFANTS

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Svetlana V. Garina

2016-06-01

Full Text Available Introduction. Recently in Russia there is a tendency to increase the proportion of premature infants, prolonged postnatal adaptation which may be associated with carnitine deficiency Early diagnosis and correction of carnitine deficiency in premature infants is possible to reserve the prevention of pathological conditions of the prenatal period in these patients. Materials and Methods. 98 newborn infants have been examined with the help of clinical laboratory methods. Results. It has been stated that the overwhelming majority of newborn infants irrespective of their gestational age and body mass at the moment of birth had reference ranges of crude carnitine and higher degree of floating carnitine in their peripheral blood within the first days of their lives. These changes are particularly characteristic for small pre-mature infants. Statistically significant differences between the levels of crude carnitine and floating carnitine depended on the gender of newborn infants have been revealed. Directly correlated dependence of the level of crude carnitine on the body mass at the moment of birth of small premature infants has been stated. Discussion and Conclusions. It has been proved that implementing L-carnitine into the development care plan for premature infants facilitates quick body weight gain, significantly cuts down the period of tube feeding, lowers frequency of anemia development of premature infants and duration of neonatal jaundice. The ability of Elkar to correct functional diseases of cardio vascular system of premature infants has been shown.

Evaluation of serum l-carnitine level in children with acute bronchial asthma

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Eman Ramadan

2014-07-01

Conclusion: According to our study, it could be concluded that l-carnitine decrease is linked to the occurrence of attack of bronchial asthma. Accordingly, it is recommended to make further studies to find out if there is a beneficial role of carnitine intake in the prophylaxis & treatment of attacks of bronchial asthma. The recommended studies should search for the most suitable dose & side effects of carnitine as a potential pharmaceutical agent.

Acetyl-L-carnitine improves aged brain function.

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Kobayashi, Satoru; Iwamoto, Machiko; Kon, Kazuo; Waki, Hatsue; Ando, Susumu; Tanaka, Yasukazu

2010-07-01

The effects of acetyl-L-carnitine (ALCAR), an acetyl derivative of L-carnitine, on memory and learning capacity and on brain synaptic functions of aged rats were examined. Male Fischer 344 rats were given ALCAR (100 mg/kg bodyweight) per os for 3 months and were subjected to the Hebb-Williams tasks and AKON-1 task to assess their learning capacity. Cholinergic activities were determined with synaptosomes isolated from brain cortices of the rats. Choline parameters, the high-affinity choline uptake, acetylcholine (ACh) synthesis and depolarization-evoked ACh release were all enhanced in the ALCAR group. An increment of depolarization-induced calcium ion influx into synaptosomes was also evident in rats given ALCAR. Electrophysiological studies using hippocampus slices indicated that the excitatory postsynaptic potential slope and population spike size were both increased in ALCAR-treated rats. These results indicate that ALCAR increases synaptic neurotransmission in the brain and consequently improves learning capacity in aging rats.

[Therapy of arrhythmia induced by myocardial ischemia. Association of L-carnitine, propafenone and mexiletine].

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Mondillo, S; Faglia, S; D'Aprile, N; Mangiacotti, L; Campolo, M A; Agricola, E; Palazzuoli, V

1995-12-01

To assess the anti-arrythmic effect of L-carnitina, propafenone and mexiletine, we tested the drugs in 50 patients with effort angina and ventricular ectopic beats (VEB). The patients were randomized in 5 groups: Group A: was treated with oral L-carnitine at the dose of 2 g x 3 for two weeks. Group B: oral propafenone at the dose of 300 mg x 3 for two weeks. Group C: as group B+L-carnitine+g x 3 at the second weeks. Group D: oral mexiletine at the dose of 200 mg x 3 for two weeks. Group E: as group D+L-carnitine 2 gr x 3 at the second week. After 7 and 14 days of treatment, in all patients an Holter examination was performed. Our results show that L-carnitine exerts a significant reduction of the VEB and its administration potentiates the anti-arrythmic effect of propafenone and mexiletine.

Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport

International Nuclear Information System (INIS)

Rebouche, C.J.; Engel, A.G.

1984-01-01

The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine was administered intravenously to six normal subjects, one patient with primary muscle carnitine deficiency (MCD), and four patients with primary systemic carnitine deficiency (SCD). Specific radioactivity was followed in plasma for 28 d. A three-compartment model (extracellular fluid, muscle, and ''other tissues'') was adopted. Rate constants, fluxes, pool sizes, and turnover times were calculated. Results of these calculations indicated reduced transport of carnitine into muscle in both forms of primary carnitine deficiency. However, in SCD, the reduced rate of carnitine transport was attributed to reduced plasma carnitine concentration. In MCD, the results are consistent with an intrinsic defect in the transport process. Abnormal fluctuations of the plasma carnitine, but of a different form, occurred in MCD and SCD. The significance of these are unclear, but in SCD they suggest abnormal regulation of the muscle/plasma carnitine concentration gradient. In 8 of 11 subjects, carnitine excretion was less than dietary carnitine intake. Carnitine excretion rates calculated by kinetic compartmental analysis were higher than corresponding rates measured directly, indicating degradation of carnitine. However, we found no radioactive metabolites of L-[methyl-3H]carnitine in urine. These observations suggest that dietary carnitine was metabolized in the gastrointestinal tract

The effect of L-carnitine on lipid metabolism in patients on chronic haemodialysis

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Yderstræde, Knud Bonnet; Pedersen, Fritz Bangsgaard; Dragsholt, C.

1987-01-01

Twenty-one patients (median 49 years; range 20-72 years) on chronic haemodialysis (median: 54 months; range 16-154 months) were examined in a clinical controlled trial for the effect of carnitine on hyperlipoproteinaemia. Initial values of serum carnitine were within the normal range. Carnitine...... was added to the dialysis fluid to a final concentration of 100 mumol/l. The trial was carried out for 6 months, and the serum of fasting patients was analysed at monthly intervals for carnitine, triglycerides, HDL-cholesterol, LDL-cholesterol and apolipoprotein A and B. The loss of carnitine...... to the dialysis fluid also was examined, as was the retained amount in those receiving carnitine. We could not confirm the findings of others that carnitine produces lowering of serum triglycerides and increases of serum HDL-cholesterol. The study was extended for another year with ten patients; however...

EFECTO DE L-CARNITINA SOBRE EL PESO, NIVELES DE TRIGLICÉRIDOS Y COLESTEROL DE RATONES SOMETIDOS A DIETAS NORMO E HIPERCALÓRICAS | EFFECT OF L-CARNITINE ON WEIGHT, CHOLESTEROL AND TRIGLYCERIDES LEVELS OF MICE RECEIVING NORMAL AND HIGH CALORIC DIETS

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Luis Ojeda

2016-11-01

Full Text Available An experimental study was conducted to determine the effect of L-carnitine on weight and serum lipid levels (triglycerides and total cholesterol on NMRI mice. To do so, a factorial arrangement of treatments 22 under a completely randomized design was carried out. Factors considered were the diet (normal and hypercaloric and the inclusion or not of the L-carnitine supplement. L-carnitine was orally administered at a rate of 2 mg/day. Weight [g], serum triglyceride concentrations [mg·dL-1] and total cholesterol [mg·dL-1] were evaluated. Analysis of variance test and Tukey mean comparisons were applied. Non significant differences were found between the type of diet for weight (F = 4.00; p = 0.0575, and cholesterol (F = 0.09; p = 0.7722, or for the administration of L-carnitine for the weight (F = 1.08; p = 0.3096, and cholesterol (F = 0.13; p = 0.7255. For triglycerides, significant differences between the type of diet (F = 12.73; p = 0.0016, and significant interaction between type of diet and the administration of L-carnitine (F = 5.95; p = 0.0228, were found. This effect suggests that the amino acid combined with a low calorie diet could be considered as an alternative to treat cases of hypertriglyceridemia.

Role of l-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study

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Topcu-Tarladacalisir, Yeter; Kanter, Mehmet [Trakya University, Department of Histology and Embryology, Faculty of Medicine, Edirne (Turkey); Uzal, Mustafa Cem [Trakya University, Department of Radiation Oncology, Faculty of Medicine, Edirne (Turkey)

2009-08-15

The present study, we hypothesized that l-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma ({gamma})-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal {gamma}-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + l-carnitine group received scrotal {gamma}-irradiation plus 200 mg/kg i.p. l-carnitine. l-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of {gamma}-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, l-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy. (orig.)

Role of l-carnitine in the prevention of seminiferous tubules damage induced by gamma radiation: a light and electron microscopic study

International Nuclear Information System (INIS)

Topcu-Tarladacalisir, Yeter; Kanter, Mehmet; Uzal, Mustafa Cem

2009-01-01

The present study, we hypothesized that l-carnitine can minimize germ-cell depletion and morphological features of late cell damage in the rat testis following gamma (γ)-irradiation. Wistar albino male rats were divided into three groups. Control group received physiological saline 0.2 ml intraperitoneally (i.p.), as placebo. Radiation group received scrotal γ-irradiation of 10 Gy as a single dose plus physiological saline. Radiation + l-carnitine group received scrotal γ-irradiation plus 200 mg/kg i.p. l-carnitine. l-carnitine starting 1 day before irradiation and 21 days (three times per week) after irradiation. Testis samples of the all groups were taken at day 21, 44 and 70 post-irradiation. All samples were processed at the light and electron microscopic levels. Morphologically, examination of γ-irradiated testis revealed presence of marked disorganization and depletion of germ cells, arrest of spermatogenesis, formation of multinucleated giant cells, and vacuolization in the germinal epithelium. The type and extent of these changes varied at different post-treatment intervals. The damage was evident at the 21st day and reached maximum level by the 44th day. By day 44 post-irradiation, the changes were most advanced, and were associated with atrophied seminiferous tubules without germ cells, the increase in the number and size of vacuolizations in germinal epithelium, and the absent multinucleated giant cells due to spermatids had completely disappeared. The increase in nucleus invaginations, the dilatation of smooth endoplasmic reticulum cysternas and the increase in the number and size of lipid droplets in the Sertoli cells were determined at the electron microscopic level. In conclusion, l-carnitine supplementation during the radiotherapy would be effective in protecting against radiation-induced damages in rat testis, and thereby may improve the quality of patient's life after the therapy. (orig.)

Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats

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Malone Michael A

2006-01-01

Full Text Available Abstract Background Streptozotocin-induced diabetes (STZ-D in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement. Aim The purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats. Methods Wistar rats (48 were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24 were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks. Results The heart rates for the STZ-D rats (290 ± 19 bpm were less than control rats (324 ± 20 bpm (p Conclusion Thus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model.

Protective effect of L-carnitine and L-arginine against busulfan-induced oligospermia in adult rat.

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Abd-Elrazek, A M; Ahmed-Farid, O A H

2018-02-01

Busulfan is an anticancer drug caused variety of adverse effects for patients with cancer. But it could cause damage to the male reproductive system as one of its adverse effects. This study aimed to investigate the protective effect of L-carnitine and L-arginine on semen quality, oxidative stress parameters and testes cell energy after busulfan treatment. Adult male rats were divided into four groups: control (Con), busulfan (Bus), busulfan plus L-arginine (Bus + L-arg) and busulfan plus L-carnitine (Bus + L-car). After 28 days, the semen was collected from the epididymis and the testes were assessed. Sperm count, motility and velocity were measured by CASA, and smears were prepared for assessment of sperm morphology. Serum and testes supernatants were separated for DNA metabolites, oxidative stress and cell energy parameters. Testes tissues also subjected for caspase-3. The results showed significant improvement in sperm morphology, motility, velocity and count in the groups treated with L-arginine and L-carnitine and accompanied with an increase in MDA, GSSG and ATP, reduction in GSH, AMP, ADP, NO and 8-OHDG also recorded. These results are supported by caspase-3. Administration of L-arg and L-car attenuated the cytotoxic effects of busulfan by improving semen parameters, reducing oxidative stress and maintaining cell energy. © 2017 Blackwell Verlag GmbH.

Secondary Carnitine Deficiency in Dialysis Patients: Shall We Supplement It?

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Ronald J.A. Wanders; Tim Ulinski; Stephanie E. Reuter; Asha Moudgil

2016-01-01

Carnitine, essential for fatty acid β-oxidation, is obtained from diet and through de novo biosynthesis. The organic cation/carnitine transporter 2 (OCTN2) facilitates carnitine cellular transport and kidney resorption. Carnitine depletion occurs in OCTN2-deficient patients, with serious clinical complications including cardiomyopathy, myopathy, and hypoketotic hypoglycaemia. Neonatal screening can detect OCTN2 deficiency. OCTN2-deficiency is also known as primary carnitine deficiency. Carnit...

Selenium supplementation in pediatric patients using parenteral nutrition: Is it time to do something?

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Freitas, Renata Germano Borges de Oliveira Nascimento; Nogueira, Roberto José Negrão; Hessel, Gabriel

2018-03-01

To analyze the nutritional status of selenium and verify the effect of its supplementation in pediatric patients during 14 days of parenteral nutrition (PN). This is a series of cases with patients followed for two weeks while using PN. Data collection was performed at the beginning (T0), in the 7th (T1) and 14th days of PN (T2). The supplemented group received 2 µg/kg/day of selenous acid. Weight and height were measured for nutritional status assessment. Tests requested: plasma selenium, albumin, pre-albumin, C-reactive protein (CRP), total cholesterol and HDL-cholesterol. Fourteen (14) patients with inflammatory process and with low or very low weight for their ages were evaluated. In both groups (with and without supplementation), all patients had low selenium levels. Median plasma selenium concentrations were 17.4 µg/L (T0), 23.0 µg/L (T1) and 20.7 µg/L (T2). Increase and reduction of selenium occurred both in patients with high CRP and in those presenting normalization of this parameter. Lower plasma selenium levels have been detected since the start of the research and supplementation (2 µg/kg/day of selenous acid) was not to enough to approach the reference values.

Efeitos da suplementação oral de L-carnitina associada ao treinamento físico na tolerância ao exercício de pacientes com doença pulmonar obstrutiva crônica Influence of oral L-carnitine supplementation combined with physical training on exercise tolerance in patients with chronic obstructive pulmonary disease

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Audrey Borghi Silva

2003-12-01

Full Text Available INTRODUÇÃO: Pacientes portadores de doença pulmonar obstrutiva crônica apresentam redução da tolerância ao exercício físico, principalmente devido à limitação ventilatória. A L-carnitina tem sido utilizada com o objetivo de melhorar a capacidade aeróbia de pacientes com doenças crônicas, porém não existem estudos em pacientes portadores de doença pulmonar obstrutiva crônica. OBJETIVO: Avaliar a influência da suplementação de L-carnitina, associada ao treinamento físico por seis semanas, três vezes por semana em pacientes portadores de doença pulmonar obstrutiva crônica. MÉTODO: A amostra foi constituída de 30 pacientes portadores de doença pulmonar obstrutiva crônica (69 ± 7 anos com volume expiratório forçado no primeiro segundo BACKGROUND: Patients with chronic obstructive pulmonary disease usually present intolerance to physical exertion due to ventilatory limitation. L-carnitine has been used to enhance aerobic capacity in patients with chronic diseases, but no study seems to be available for this patient population. OBJECTIVE: To evaluate the influence of L-carnitine supplementation (2 g/day in chronic obstructive pulmonary disease patients undergoing physical training three times a week for six weeks. METHOD: Patients (mean age 69 ± 7 years, n = 30 with stable chronic obstructive pulmonary disease and < 65% of predicted forced expiratory volume in 1 second (FEV1 were separated into three groups of 10 patients each. Group 1 (G1, n = 10 received physical training and L-carnitine (2 g/day, group 2 (G2, n = 10 received physical training and placebo, and group 3 (G3, n = 10 received only L-carnitine (2 g/day. Spirometry and a 6-minute walking distance test were performed before and after intervention. Plasma levels of free carnitine were measured at the beginning and end of the study. RESULTS: A significant increase in walking distance was found only in G1 and G2 (421 ± 100 to 508 ± 80.7 and 496 ± 78.7 to

Sibutramine and L-carnitine compared to sibutramine alone on insulin resistance in diabetic patients.

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Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Gravina, Alessia; Mereu, Roberto; D'Angelo, Angela; Palumbo, Ilaria; Randazzo, Sabrina; Cicero, Arrigo F G

2010-01-01

To evaluate the effects of one year of treatment with sibutramine plus L-carnitine compared to sibutramine on body weight, glycemic control, and insulin resistance state in type 2 diabetic patients. Two hundred and fifty-four patients with uncontrolled type 2 diabetes mellitus (T2DM) [glycated hemoglobin (HbA(1c)) >8.0%] in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, high sensitivity-C reactive protein (Hs-CRP). There was a decrease in body weight, BMI, HbA(1c), FPI, HOMA-IR, and RBP-4 in both groups, even when the values obtained with sibutramine plus L-carnitine were lower than the values obtained in sibutramine group. There was a faster decrease of FPG, PPG, TC, LDL-C, resistin and Hs-CRP with sibutramine plus L-carnitine even when no differences between the two groups were obtained. Furthermore, only sibutramine plus L-carnitine improved Tg, and visfatin. Sibutramine plus L-carnitine gave a faster improvement of lipid profile, insulin resistance parameters, glycemic control, and body weight compared to sibutramine.

Efficacy of a novel formulation of L-Carnitine, creatine, and leucine on lean body mass and functional muscle strength in healthy older adults: a randomized, double-blind placebo-controlled study.

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Evans, Malkanthi; Guthrie, Najla; Pezzullo, John; Sanli, Toran; Fielding, Roger A; Bellamine, Aouatef

2017-01-01

Progressive decline in skeletal muscle mass and function are growing concerns in an aging population. Diet and physical activity are important for muscle maintenance but these requirements are not always met. This highlights the potential for nutritional supplementation. As a primary objective, we sought to assess the effect of a novel combination of L-Carnitine, creatine and leucine on muscle mass and performance in older subjects. Forty-two healthy older adults aged 55-70 years were randomized to receive either a novel L-Carnitine (1500 mg), L-leucine (2000 mg), creatine (3000 mg), Vitamin D3 (10 μg) (L-Carnitine-combination) product ( n  = 14), L-Carnitine (1500 mg) ( n  = 14), or a placebo ( n  = 14) for eight weeks. We evaluated body mass by DXA, upper and lower strength by dynamometry, and walking distance by a 6-min walk test at baseline and after eight weeks of intervention. These measures, reflecting muscle mass, functional strength and mobility have been combined to generate a primary composite score. Quality of life, blood safety markers, and muscle biopsies for protein biomarker analysis were also conducted at baseline and the end of the study. The primary composite outcome improved by 63.5 percentage points in the L-Carnitine-combination group vs. placebo ( P  = 0.013). However, this composite score did not change significantly in the L-Carnitine group ( P =  0.232), and decreased slightly in the placebo group ( P =  0.534). Participants supplemented with the L-Carnitine-combination showed a 1.0 kg increase in total lean muscle mass ( P  = 0.013), leg lean muscle mass (0.35 kg, P =  0.005), and a 1.0 kg increase in lower leg strength ( P  = 0.029) at week 8. In addition, these increases were significant when compared to the placebo group (P =  0.034, P =  0.026, and P =  0.002, respectively). Total mTOR protein expression was increased in participants in the L-Carnitine-combination group at the end of

L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model with upregulation of mitochondrial pathway.

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Hisashi Ishikawa

Full Text Available Non-alcoholic steatohepatitis (NASH is a severe form of non-alcoholic fatty liver disease characterized by lobular inflammation, hepatocellular ballooning, and fibrosis with an inherent risk for progression to cirrhosis and hepatocellular carcinoma (HCC. Mitochondrial dysfunction appears to play a role in the progression from simple steatosis to NASH. L-carnitine (L-b-hydroxy-g-N-trimethylaminobutyric acid, an essential nutrient that converts fat into energy in mitochondria, has been shown to ameliorate liver damage. The aim of the present study was to explore the preventive and therapeutic effect of L-carnitine in NASH model mice. Eight-week-old male STAM mice, a NASH-cirrhosis-hepatocarcinogenic model, were divided into 3 experimental groups and fed as follows: 1 high-fat diet (HFD (control group; 2 HFD mixed with 0.28% L-carnitine (L-carnitine group; and 3 HFD mixed with 0.01% α-tocopherol (α-tocopherol group. After 4 or 8 weeks, mice were sacrificed. Blood samples and livers were collected, and hepatic tumors were counted and measured. Livers were subjected to histological study, immunohistochemical staining of 4-hydroxynonenal and ferritin, determination of 8-OHdG levels, mRNA and protein expressions for multiple genes, and metabolomic analysis. The intestinal microbiome was also analyzed. L-carnitine increased hepatic expression of genes related to long-chain fatty acid transport, mitochondrial β-oxidation, and antioxidant enzymes following suppression of hepatic oxidative stress markers and inflammatory cytokines in NASH, and mice treated with L-carnitine developed fewer liver tumors. Although α-tocopherol resulted in NASH improvement in the same manner as L-carnitine, it increased periodontitis-related microbiotic changes and hepatic iron transport-related gene expression and led to less effective for anti-hepatocarcinogenesis. Conclusion: L-carnitine prevents progression of non-alcoholic steatohepatitis in a mouse model by

Radiolysis of D(+)-carnitine by 60Co-γ-radiation and formation of L(+)-β-methylcholine

International Nuclear Information System (INIS)

Loester, Heinz; Strack, Erich; Seim, Hermann

1986-01-01

The radiolysis of D(+)-carnitine by 60 Co-γ-radiation was examined to obtain optically active β-methylcholine. It was found that the radiolysis leads to a number of trimethylammonium bases but to no other betaines. (+)-β-Methylcholine and acetonyltrimethylammonium could be identified by means of common analytical methods. The amounts of methylamines formed by irradiation were very small. Racemization of the D(+)-carnitine did not occur during irradiation, L(-)-carnitine was not found when an enzymatical determination method was used. The fact that (+)-β-methylcholine was formed from D(+)-carnitine is pharmacologically important, because acetyl-L(+)-β-methylcholine has a strong interaction with muscarinic receptors. (author)

Serum carnitine concentration is decreased in patients with Lyme borreliosis

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Alina Kępka

2016-03-01

Full Text Available Background: Lyme borreliosis (LB is a serious infectious disease. Carnitine plays a crucial role in metabolism and inflammatory responses. Carnitine may be important in improving neuronal dysfunction and loss of neurons. Aim: To evaluate serum carnitine concentration in adult patients with various clinical types of LB. Material/Methods: Groups: 1 patients with erythema migrans (EM, n=16, 2 neuroborreliosis (NB, n=10, 3 post-Lyme disease (PLD, n=22 and healthy controls (HC, n=32. Total (TC and free (FC carnitine were determined with the spectrophotometric method. Results: TC levels (44.9±10.4, 28.0±8.4, 35.9±15.6 μmol/L in the EM, NB and PLD patients were lower than in HC (54.0±11.4 μmol/L, p < 0.001. FC levels (32.7±7.7, 23.6±6.8, 26.3±11.2 μmol/L in the EM, NB and PLD patients were lower than in HC (40.5±7.6 μmol/L, p < 0.001. AC levels (12.2±5.2, 4.4±2.6, 9.6±7.4 μmol/L in the EM, NB and PLD patients were lower in the NB and PLD patients than in HC (13.5±8.40 μmol/L, p <0.001. AC/FC ratio was 0.31±0.14, 0.18±0.09, 0.39±0.33 in the EM, NB and PLD patients. Conclusions: LB patients exhibit a significant decrease of their serum carnitine concentrations. The largest changes were in the NB and PLD patients. To prevent late complications of the disease a possibility of early supplementation with carnitine should be considered. Further studies are required to explain the pathophysiological significance of our findings.

Synthesis and biological evaluation of cyclic analogs of L-carnitine as potential agents in the treatment of myocardial ischemia

International Nuclear Information System (INIS)

Woster, P.M.

1987-01-01

The purpose of this research was to synthesize a number of cyclic, rigid analogs of L-carnitine, having a variety of predetermined positional and stereochemical orientations, to be used as probes into the spatial and conformational requirements of the enzyme known as carnitine/acylcarnitine translocase. The ability of these analogs to serve as substrates for this enzyme was to be determined by assessing the degree to which they initiate efflux of 14 C-L-carnitine from isolated heart mitochondria. Toward this end, synthesis of several such analogs was attempted, resulting in the isolation and characterization of 9 cyclic analogs of carnitine, 5 of which are previously unreported. Bioevaluation of these synthetic carnitine analogs was conducted in a previously described assay system. Rat heart mitochondria were isolated by differential centrifugation and prepared for the study by incubation with 14 C-L-carnitine. Efflux of radiolabeled carnitine was then monitored in the presence of the compound being evaluated. This represents the first instance in which non-naturally occurring analogs of L-carnitine have been shown to undergo transport via this mitochondrial translocase, suggesting the possibility that cyclic carnitine analogs may find utility as agents in the treatment of myocardial ischemia

Effects of L-carnitine against oxidative stress in human hepatocytes: involvement of peroxisome proliferator-activated receptor alpha

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Li Jin-Lian

2012-03-01

Full Text Available Abstract Background Excessive oxidative stress and lipid peroxidation have been demonstrated to play important roles in the production of liver damage. L-carnitine is a natural substance and acts as a carrier for fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. It is also an antioxidant that reduces metabolic stress in the cells. Recent years L-carnitine has been proposed for treatment of various kinds of disease, including liver injury. This study was conducted to evaluate the protective effect of L-carnitine against hydrogen peroxide (H2O2-induced cytotoxicity in a normal human hepatocyte cell line, HL7702. Methods We analyzed cytotoxicity using MTT assay and lactate dehydrogenase (LDH release. Antioxidant activity and lipid peroxidation were estimated by reactive oxygen species (ROS levels, activities and protein expressions of superoxide dismutase (SOD and catalase (CAT, and malondialdehyde (MDA formation. Expressions of peroxisome proliferator-activated receptor (PPAR-alpha and its target genes were evaluated by RT-PCR or western blotting. The role of PPAR-alpha in L-carnitine-enhanced expression of SOD and CAT was also explored. Statistical analysis was performed by a one-way analysis of variance, and its significance was assessed by Dennett's post-hoc test. Results The results showed that L-carnitine protected HL7702 cells against cytotoxity induced by H2O2. This protection was related to the scavenging of ROS, the promotion of SOD and CAT activity and expression, and the prevention of lipid peroxidation in cultured HL7702 cells. The decreased expressions of PPAR-alpha, carnitine palmitoyl transferase 1 (CPT1 and acyl-CoA oxidase (ACOX induced by H2O2 can be attenuated by L-carnitine. Besides, we also found that the promotion of SOD and CAT protein expression induced by L-carnitine was blocked by PPAR-alpha inhibitor MK886. Conclusions Taken together, our findings suggest that L-carnitine could protect HL

Propionyl-l-carnitine: Labelling in the N-methyl position with Carbon-11 and pharmacokinetic studies in rats

International Nuclear Information System (INIS)

Davenport, Raymond J.; Law, Marilyn P.; Pike, Victor W.; Osman, Safiye; Poole, Keith G.

1995-01-01

The prospective therapeutic, propionyl-l-carnitine, was labelled in the N-methyl position with the positron-emitter, carbon-11 (t (1(2)) = 20.4 min), with a view to studying its pharmacokinetics in humans using PET. Labelling was achieved by methylating nor-propionyl-l-carnitine hydrochloride with no-carrier-added [ 11 C]iodomethane (produced from cyclotron-produced [ 11 C]carbon dioxide) in ethanol in the presence of 1,2,2,6,6,-pentamethylpiperidine. HPLC of the reaction mixture on a strong cation exchange column provided high purity [N-methyl- 11 C]propionyl-l-carnitine in 62% radiochemical yield (decay-corrected from [ 11 C]iodomethane), ready for intravenous administration within 35 min from the end of radionuclide production. [N-methyl- 11 C]Propionyl-l-carnitine, given intravenously to rats, cleared rapidly from plasma. A slow uptake of radioactivity into myocardium and striated muscle was observed. In plasma, unchanged tracer represented 84% of the radioactivity at 2.5 min and 2.5% of the radioactivity at 60 min. In heart, unchanged tracer represented 18% of radioactivity at 2.5 min and 2.4% at 15 min. The remainder of radioactivity detected in plasma and heart was identified as [N-methyl- 11 C]l-carnitine and [N-methyl- 11 C]acetyl-l-carnitine

Update on critical evidence for use of carnitine analogs in clinical practice in CNS disorders

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Traina G

2011-04-01

Full Text Available Giovanna TrainaDepartment of Economics and Food Sciences, University of Perugia, Perugia, ItalyAbstract: L-carnitine (LC is part of the carnitine shuttle system at the mitochondrial inner membrane (MIM and transports long chain fatty acids over the MIM route. Acetyl-L -carnitine (ALC, the acetyl ester of LC, plays an essential role in intermediary metabolism. To ALC are ascribed neurotrophic actions, antioxidant and antiapoptotic activity, positive effects on mitochondrial metabolism, and stabilization of intracellular membranes. Acylcarnitine and LC supplementation have shown beneficial effects in the treatment of aging, chronic degenerative pathologies and the slowing of the progression of mental deterioration in neurodegenerative diseases, and painful neuropathies. ALC is reported to affect brain energy and phospholipid metabolism and to interact with cell membranes, proteins, and enzymes. It also shows a neuromodulatory effect on synaptic morphology and neurotransmitter synaptic transmission, including that of acetylcholine and dopamine. All these data suggest that ALC can affect several targets in the central nervous system. The roles and effects of LC and ALC have led researchers to investigate carnitine's involvement in a variety of neuropathological states and treatments, including autism, Parkinson's disease, Alzheimer's disease, Down's syndrome, Huntington's disease, cerebellar ataxia, age-associated mental decline, hepatic encephalopathy, and ammonia neurotoxicity. This review summarizes evidence that carnitine analogs play many roles in serious neurological pathologies.Keywords: L-carnitine, acetyl-L-carnitine, brain, neural disorders

L-Carnitine for the treatment of a calcium channel blocker and metformin poisoning.

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St-Onge, Maude; Ajmo, Ian; Poirier, Diane; Laliberté, Martin

2013-09-01

The object of the current communication is to discuss the theory and the evidence for the use of L-carnitine in calcium channel blocker and metformin poisonings. A 68-year-old male known for hypertension and type II diabetes was admitted to the critical care unit of a community hospital following an overdose of amlodipine and metformin. The patient was intubated, ventilated, and hemodynamically supported with vasopressors. Despite calcium, glucagon, high-dose insulin (HDI), and lipid emulsion for calcium channel blocker and bicarbonate for metabolic acidosis, the patient remained hemodynamically unstable. The patient was considered too unstable to initiate continuous renal replacement therapy; and without access to extracorporeal life support, the administration of L-carnitine was administered as a last resort. One hour after L-carnitine, the norepinephrine requirements started to decrease, the patient began to improve and was subsequently extubated successfully without apparent sequelae in less than 4 days. L-Carnitine combined with HDI may have helped with the calcium channel blocker (CCB) poisoning by decreasing insulin resistance, promoting intracellular glucose transport, facilitating the metabolism of free fatty acids, and increasing calcium channel sensitivity. It may have also stimulated oxidative utilization of glucose instead of converting pyruvate into lactate and contributed to decrease lactate production with metformin poisoning.

The Effect of Creatin and Carnitine Supplementation on 5 kmClassic and 10 km Free Styles Race Performance of Cross Country Skiers

OpenAIRE

Ebru ÇETİN

2004-01-01

This İnvestigation examined the effect of creatin and carnitine supplementation on 5 km classic and 10 km free styles race performance of competitive cross country skiers.Eighteen highly trained (12 male and 6 female) cross country skiers aged 13-16 years seperated into 3 equal groups. All groups participated in the 5 km classic and 10 km free races styles in Erciyes at 2200m altitude ski center before the carnitine and creatine loading. After the race subjects were seperated into carnitine, ...

The Effect of L-Carnitine, Hypotaurine, and Taurine Supplementation on the Quality of Cryopreserved Chicken Semen

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Agnieszka Partyka

2017-01-01

Full Text Available The objective of this study was to investigate the effect of L-carnitine (LC, hypotaurine (HT, and taurine (T on the quality of frozen-thawed chicken semen. Pooled semen samples were divided into seven aliquots (control, 1 mM LC, 5 mM LC, 1 mM HT, 10 mM HT, 1 mM T, and 10 mM T and subjected to cryopreservation. Postthaw sperm motility was determined by IVOS system and sperm characteristics were assessed with fluorochromes and flow cytometry. The highest sperm motility and the highest percentage of viable sperm were in the HT1 group (P<0.01 and P<0.05 following cryopreservation. After thawing, we observed a higher percentage of sperm without apoptosis and membrane reorganization changes in the LC1 and T1 group when compared to the control (P<0.05. There was a higher percentage of live sperm without lipid peroxidation (LPO in all treatments (P<0.01; P<0.05, when compared to the control group. The percentage of sperm with high mitochondrial potential significantly increased with LC1, T1, and T10 (P<0.05. Supplementation of the diluent with LC1, LC5, and T1 significantly (P<0.05 reduced DNA susceptibility to fragmentation, compared to the control and HT1 groups. These results indicate that the addition of examined antioxidants improves the quality of cryopreserved chicken semen.

The Effect of L-Carnitine, Hypotaurine, and Taurine Supplementation on the Quality of Cryopreserved Chicken Semen.

Science.gov (United States)

Partyka, Agnieszka; Rodak, Olga; Bajzert, Joanna; Kochan, Joanna; Niżański, Wojciech

2017-01-01

The objective of this study was to investigate the effect of L-carnitine (LC), hypotaurine (HT), and taurine (T) on the quality of frozen-thawed chicken semen. Pooled semen samples were divided into seven aliquots (control, 1 mM LC, 5 mM LC, 1 mM HT, 10 mM HT, 1 mM T, and 10 mM T) and subjected to cryopreservation. Postthaw sperm motility was determined by IVOS system and sperm characteristics were assessed with fluorochromes and flow cytometry. The highest sperm motility and the highest percentage of viable sperm were in the HT1 group ( P < 0.01 and P < 0.05) following cryopreservation. After thawing, we observed a higher percentage of sperm without apoptosis and membrane reorganization changes in the LC1 and T1 group when compared to the control ( P < 0.05). There was a higher percentage of live sperm without lipid peroxidation (LPO) in all treatments ( P < 0.01; P < 0.05), when compared to the control group. The percentage of sperm with high mitochondrial potential significantly increased with LC1, T1, and T10 ( P < 0.05). Supplementation of the diluent with LC1, LC5, and T1 significantly ( P < 0.05) reduced DNA susceptibility to fragmentation, compared to the control and HT1 groups. These results indicate that the addition of examined antioxidants improves the quality of cryopreserved chicken semen.

[The hypotriglyceridemic action of the combination of L-carnitine + simvastatin vs. L-carnitine and vs. simvastatin].

Science.gov (United States)

Savica, V; Bellinghieri, G; Lamanna, F

1992-01-01

Previous studies had determined the role played by L-carnitine and simvastatin in the treatment of altered lipidemia in dialyzed patients with chronic uremia. The authors carried out a study on the above substances either singly or together administered to the same patients with chronic uremia in hemodialysis. This study was aimed at demonstrating the possible synergic normolipidemic action of both substances in comparison with their single administration, because their different mechanism of action could be metabolically enhanced. The obtained results demonstrated that the therapeutic association proposed is preferable to the use of the single substances. Moreover, a higher and more rapid normolipidemic effect was obtained after using L-carnitina associated with simvastatin with respect to the separated substances.

L-carnitine pretreatment protects slow-twitch skeletal muscles in a rat model of ischemia-reperfusion injury.

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Demirel, Mert; Kaya, Burak; Cerkez, Cem; Ertunc, Mert; Sara, Yildirim

2013-10-01

Ischemia-reperfusion (I/R) injury negatively affects the outcome of surgical interventions for amputated or severely traumatized extremities. This study aimed to evaluate the protective role of l-carnitine on the contractile properties of fast-twitch (extensor digitorum longus [EDL]) and slow-twitch (soleus [SOL]) skeletal muscles following I/R-induced injury in a rat model. Rats were divided into 4 groups (1) saline pretreatment, (2) l-carnitine pretreatment, (3) saline pretreatment and I/R, and (4) l-carnitine pretreatment and I/R. Twitch and tetanic contractions in the EDL and SOL muscles in each group were recorded. Additionally, a fatigue protocol was performed in these muscles. Twitch and tetanic contraction amplitudes were lower in the EDL and SOL muscles in which I/R was induced (P contraction amplitude in the SOL muscles following I/R (P muscles. l-Carnitine pretreatment did not alter the fatigue response in any of the muscles.

The plasma carnitine concentration regulates renal OCTN2 expression and carnitine transport in rats

OpenAIRE

Schürch, R; Todesco, L; Novakova, K; Mevissen, M; Stieger, B; Krähenbühl, S

2010-01-01

Previous findings in rats and in human vegetarians suggest that the plasma carnitine concentration and/or carnitine ingestion may influence the renal reabsorption of carnitine. We tested this hypothesis in rats with secondary carnitine deficiency following treatment with N-trimethyl-hydrazine-3-propionate (THP) for 2 weeks and rats treated with excess L-carnitine for 2 weeks. Compared to untreated control rats, treatment with THP was associated with an approximately 70% decrease in plasma car...

epsilon-N-trimethyllysine availability regulates the rate of carnitine biosynthesis in the growing rat

International Nuclear Information System (INIS)

Rebouche, C.J.; Lehman, L.J.; Olson, L.

1986-01-01

Rates of carnitine biosynthesis in mammals depend on the availability of substrates and the activity of enzymes subserving the pathway. This study was undertaken to test the hypothesis that the availability of epsilon-N-trimethyllysine is rate-limiting for synthesis of carnitine in the growing rat and to evaluate diet as a source of this precursor for carnitine biosynthesis. Rats apparently absorbed greater than 90% of a tracer dose of [methyl- 3 H]epsilon-N-trimethyllysine, and approximately 30% of that was incorporated into tissues as [ 3 H]carnitine. Rats given oral supplements of epsilon-N-trimethyllysine (0.5-20 mg/d), but no dietary carnitine, excreted more carnitine than control animals receiving no dietary epsilon-N-trimethyllysine or carnitine. Rates of carnitine excretion increased in a dose-dependent manner. Tissue and serum levels of carnitine also increased with dietary epsilon-N-trimethyllysine supplementation. There was no evidence that the capacity for carnitine biosynthesis was saturated even at the highest level of oral epsilon-N-trimethyllysine supplementation. Common dietary proteins (casein, soy protein and wheat gluten) were found to be poor sources of epsilon-N-trimethyllysine for carnitine biosynthesis. The results of this study indicate that the availability of epsilon-N-trimethyllysine limits the rate of carnitine biosynthesis in the growing rat

Protective effects of vitamins E, B and C and L-carnitine in the prevention of cisplatin-induced ototoxicity in rats.

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Tokgöz, S Alicura; Vuralkan, E; Sonbay, N D; Çalişkan, M; Saka, C; Beşalti, Ö; Akin, İ

2012-05-01

This experimental study aimed to investigate the effects of vitamins E, B and C and L-carnitine in preventing cisplatin-induced ototoxicity. Twenty-five adult, male, Wistar albino rats were randomly allocated to receive intraperitoneal cisplatin either alone or preceded by vitamins B, E or C or L-carnitine. Auditory brainstem response (i.e. hearing thresholds and wave I-IV intervals) and distortion product otoacoustic emissions (i.e. signal-to-noise ratios) were recorded before and 72 hours after cisplatin administration. The following statistically significant differences were seen: control group pre- vs post-treatment wave I-IV interval values (p vitamin E and B groups' I-IV interval values (p vitamin E vs vitamin B and C and L-carnitine groups' hearing thresholds (p vitamin B vs vitamin C and L-carnitine groups' hearing thresholds (p vitamin B and L-carnitine groups (2000 and 3000 Hz; p Vitamins B, E and C and L-carnitine appear to reduce cisplatin-induced ototoxicity in rats. The use of such additional treatments to decrease cisplatin-induced ototoxicity in humans is still under discussion.

Effects of ICRF-187 and L-Carnitine on bleomycin-induced lung toxicity in rats

International Nuclear Information System (INIS)

Shouman, Samia A.; Abdel-Hamid, M.A.; Hassan, Zeinab A.; Mansour, Heba H.

2002-01-01

The possible modulatory effects of ICRF-187 and L-carnitine against bleomycin-induced pulmonary toxicity in male rats were investigated. Repeated administration of bleomycin (10 mg/kg, twice weekly for 6 consecutive weeks) produced significant lung toxicity. The toxicity was manifested by significant increase in normal contents of lipid peroxide (LPO, 91.7%) reduced glutathione (GSH, 73.2%) and oxidized glutathione (GSSG, 135.4%) as well as the activity of superoxide dismutase (SOD, 222.7%). Thirty minutes prior to bleomycin treatment, other groups of rats received either ICRF-187 (95 mg/kg) or L-carnitine (500 mg/kg) adopting the same schedule of treatment as in bleomycin-treated group. L-carnitine decreased bleomycin-induced elevations in SOD activity, GSH and GSSG contents, however, it failed to suppress the increase in LPO level. On the other hand, treatment with ICRF-187 returned back all the elevated biochemical parameters induced by bleomycin to nearly normal levels. In conclusion, the results of this study showed a potential capability of ICRF-187 to mitigate the bleomycin-induced lung injury. Moreover, despite the inability of L-carnitine to change the elevated LPO content, it was able however, to decrease the elevated endogenous antioxidant parameters. (author)

Effects of short- and long-term feeding of L-carnitine and congeners on the production of eicosanoids from rat peritoneal leucocytes

NARCIS (Netherlands)

I.M. Garrelds (Ingrid); G.R. Elliott (G.); F.J. Zijlstra (Freek); I.L. Bonta

1994-01-01

textabstractThe effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids front in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A

Kinetic compartmental analysis of carnitine metabolism in the human carnitine deficiency syndromes. Evidence for alterations in tissue carnitine transport.

OpenAIRE

Rebouche, C J; Engel, A G

1984-01-01

The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle. The problem was approached by mathematical modeling, by using the technique of kinetic compartmental analysis. A tracer dose of L-[methyl-3H]carnitine wa...

Effects of exercise on l-carnitine and lipid metabolism in African catfish (Clarias gariepinus) fed different dietary l-carnitine and lipid levels

NARCIS (Netherlands)

Ozorio, R.O.A.; Ginneken, van V.J.T.; Bessa, R.J.B.; Verstegen, M.W.A.; Verreth, J.A.J.; Huisman, E.A.

2010-01-01

African catfish (Clarias gariepinus) were fed four isonitrogenous diets (34 % crude protein), each containing one of two lipid (100 or 180 g/kg) and two l-carnitine (15 or 1000 mg/kg) levels. After 81 d of feeding, thirty-two fish (body weight 32 g) from each dietary group were randomly selected,

Supplemental parenteral nutrition in critically ill patients: a study protocol for a phase II randomised controlled trial.

Science.gov (United States)

Ridley, Emma J; Davies, Andrew R; Parke, Rachael; Bailey, Michael; McArthur, Colin; Gillanders, Lyn; Cooper, David J; McGuinness, Shay

2015-12-24

Nutrition is one of the fundamentals of care provided to critically ill adults. The volume of enteral nutrition received, however, is often much less than prescribed due to multiple functional and process issues. To deliver the prescribed volume and correct the energy deficit associated with enteral nutrition alone, parenteral nutrition can be used in combination (termed "supplemental parenteral nutrition"), but benefits of this method have not been firmly established. A multi-centre, randomised, clinical trial is currently underway to determine if prescribed energy requirements can be provided to critically ill patients by using a supplemental parenteral nutrition strategy in the critically ill. This prospective, multi-centre, randomised, stratified, parallel-group, controlled, phase II trial aims to determine whether a supplemental parenteral nutrition strategy will reliably and safely increase energy intake when compared to usual care. The study will be conducted for 100 critically ill adults with at least one organ system failure and evidence of insufficient enteral intake from six intensive care units in Australia and New Zealand. Enrolled patients will be allocated to either a supplemental parenteral nutrition strategy for 7 days post randomisation or to usual care with enteral nutrition. The primary outcome will be the average energy amount delivered from nutrition therapy over the first 7 days of the study period. Secondary outcomes include protein delivery for 7 days post randomisation; total energy and protein delivery, antibiotic use and organ failure rates (up to 28 days); duration of ventilation, length of intensive care unit and hospital stay. At both intensive care unit and hospital discharge strength and health-related quality of life assessments will be undertaken. Study participants will be followed up for health-related quality of life, resource utilisation and survival at 90 and 180 days post randomisation (unless death occurs first). This trial

Effects of acute L-carnitine intake on metabolic and blood lactate levels of elite badminton players.

Science.gov (United States)

Eroğlu, Hüseyin; Senel, Omer; Güzel, Nevin A

2008-04-01

Purpose of this study is to research the effects of acute L-Carnitine intake on badminton players' metabolic and blood lactate values. A total of 16 Turkish national badminton players (8 male, 8 female) were voluntarily participated into study. MaxVO2, MET, energy consumption, HR (heart rate), VE (minute ventilation), R (respiratory exchange ratio), AT (anaerobic threshold), oxygen pulse and blood lactate (LA) of subjects were measured by Sensormedics VmaxST and Accutrend Lactate Analyzer. The participants were subjected to the test protocol twice before and after 2g of L-Carnitine intake. The data were evaluated by the use of SPSS 13.0 for Windows. No significant differences were found between 1st. (without L-Carnitine intake) and 2nd. (with L-Carnitine intake) measurements of female participants as regards to all measured parameters. There was a significant difference in EMHR (exercise maximum heart rate) of males between two measurements (p0.05). Respiratory exchange ratio of males was significantly different at anaerobic threshold (pbadminton players.

l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70.

Science.gov (United States)

Hussein, Abdelaziz M; Adel, Mohamed; El-Mesery, Mohamed; Abbas, Khaled M; Ali, Amr N; Abulseoud, Osama A

2018-03-14

l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal) (negative control) or pentylenetetrazole (PTZ) 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car) (100 mg/kg/day × 4 weeks) (PTZ + l-Car), while the second group received saline (PTZ + Sal). Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score ( p = 0.0002) that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure ( p l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA) ( p l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 ( p l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.

Synthesis of carboxy-labelled 1-carnitine

International Nuclear Information System (INIS)

Goodfellow, D.B.; Hoppel, C.L.; Turkaly, J.S.

1982-01-01

A method for the production of carboxy-labelled l-carnitine is described. The first step is the chemical synthesis of 4-N-trimethylammoniobutanoate (butyrobetaine) from the precursors 4-aminobutanoate and iodomethane. The second step involves the hydroxylation of butyrobetaine to form l-carnitine using butyrobetaine hydroxylase partially purified from bovine calf liver. The method also can be used to synthesize Me-labelled and uniformly-chain-labelled l-carnitine. (author)

Iodine Supplementation for Pediatric Patients Receiving Long-Term Parenteral Nutrition.

Science.gov (United States)

Santoro, Jonathan D; Nespor, Colleen; Poole, Robert L; Kerner, John A

2016-04-01

Patients dependent on parenteral nutrition (PN) are among a group at risk of developing iodine deficiency. Supplementation with iodine in this population has been debated in a number of studies, resulting in variable clinical practices. The Committee on Clinical Practice Issues of the American Society for Clinical Nutrition recommends a dose of 1 mcg/kg/d of parenteral iodine for patients receiving PN. At our institution, PN trace elements do not include iodine, although this is not the case internationally. Our study sought to assess iodine levels and thyroid function in a cohort of PN-dependent pediatric patients. A retrospective analysis studied 32 pediatric patients with a variety of medical diagnoses who received PN as a primary means of nutrition for 6 months or longer. Patients received variable proportions of their total caloric intake as PN, which ranged from 14%-100%. Iodine and thyroid function levels were obtained by serum sampling. No patient in our cohort of 32 demonstrated thyroid dysfunction or developed iodine deficiency. The length of time on PN and the percentage of total nutrition intake as PN were not associated with iodine levels (P Parenteral and Enteral Nutrition.

Therapeutic effects of Laser and L-carnitine against amiodarone ...

African Journals Online (AJOL)

Pulmonary toxicity is considered a life- threatening complication of ... Research Center, Faculty of Medicine, Ain .... Laser therapy restores the balance between oxidants and ... No conflict of interest associated with this work. Contribution of .... Fitness. 2014; 149-159. 21. Lee BJ, Lin JS, Lin YC, Lin PT. Effects of L-carnitine.

Effect of short- and long-term feeding of L-carnitine and its congeners on the production of eicosanoids from rat peritoneal leukocytes

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Garrelds, I.M.; Elliott, G.R.; Zijlstra, F.; Bonta, I.

1994-01-01

The effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids from in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A lower number

Effect of telmisartan in combined with L-carnitine on peritoneal dialysis patients

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Effect of telmisartan in combined with L-carnitine on peritoneal dialysis patients

2016-07-01

Full Text Available Objective: To observe the therapeutic effect of telmisartan in combined with L-carnitine on the peritoneal dialysis (PD patients in order to guide the clinical medication. Methods: A total of 80 patients with chronic renal failure (CRF who were admitted in our hospital from November, 2011 to January, 2014 for PD were included in the study and randomized into the treatment group and the control group. The patients in the two groups were routinely performed with PD. The patients in the treatment group were given L-carnitine oral liquid, 10mL/time, 3 times/d, and telmisartan, 80 mg/time, 1 time/d. The patients in the control group were given L-carnitine oral liquid, 10mL/time, 3 times a day. The patients in the two groups were treated for 24 weeks continuously. The serum SCr and BUN levels before and after treatment in the two groups were observed. RRF was calculated. The changes of daily average urine volume and blood pressure before and after treatment in the two groups were observed. Results: After treatment, the reduced degree of SCr and BUN in the treatment group was significantly greater than that in the control group, while the reduced degree of RRF was significantly less than that in the control group (P<0.05. After treatment, the daily urine volume was reduced, but the reduced degree in the treatment group was significantly less than that in the control group (P<0.05. After treatment, SBP and DBP were reduced, but the reduced degree in the treatment group was significantly superior to that in the control group (P<0.05. Conclusions: Telmisartan in combined with L-carnitine applied in PD patients can effectively delay the loss of RRF and the reduction of urine volume, and regulate the blood pressure in order to alleviate the clinical symptoms and improve the patients’ living qualities.

Effects of oral L-carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial.

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Taku Miyagawa

Full Text Available UNLABELLED: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM sleep abnormalities. A genome-wide association study (GWAS identified a novel narcolepsy-related single nucleotide polymorphism (SNP, which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP. In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral L-carnitine for the treatment of narcolepsy, we performed a clinical trial administering L-carnitine (510 mg/day to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial. Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02. L-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. L-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration. Differences in the Japanese version of the Epworth Sleepiness Scale (ESS and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36 vitality and mental health subscales did not reach statistical significance between L-carnitine and placebo. This study suggests that oral L-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN UMIN000003760.

Radioiodinated fatty acid carnitine ester: synthesis and biodistribution of 15-(p-iodo[131I]-phenyl)pentadecanoyl-D,L-carnitine chloride

International Nuclear Information System (INIS)

Eisenhut, M.; Liefhold, J.

1986-01-01

After the uptake into heart muscle cells long chain fatty acids enter predominantly into the triglyceride and phospholipid pool before they are degraded in the mitochondria by β-oxidation. Therefore the formation of fatty acid esters with glycerine obscures the functional ability of the heart namely to catabolize free fatty acids. The sum of the two reaction pathways are visualized by sequential heart scintigraphy with e.g. 131 I labeled 15-(p-iodo-phenyl)-pentadecanoic acid (IPPA). Before the fatty acids can be degraded by β-oxidation they are bound to carnitine for mitochondrial membrane transport. Thus IPPA would not participate in lipid formation, if it is offered as 15-(p-iodo[ 131 I]-phenyl)-pentadecanoyl-D,L-carnitine chloride (IPPA-CE) to the heart muscle cells. Additionally carnitine esters of fatty acids are known to be better substrates for β-oxidation than free fatty acids. We were therefore interested in the biochemical fate of radioiodinated IPPA-CE in rats. (author)

Effect of supplementation of lecithin and carnitine on growth performance and nutrient digestibility in pigs fed high-fat diet

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Arathy Saseendran

2017-02-01

Full Text Available Aim: To study the effect of dietary supplementation of lecithin and carnitine on growth performance and nutrient digestibility in pigs fed high-fat diet. Materials and Methods: A total of 30 weaned female large white Yorkshire piglets of 2 months of age were selected and randomly divided into three groups allotted to three dietary treatments, T1 - Control ration as per the National Research Council nutrient requirement, T2 - Control ration plus 5% fat, and T3 - T2 plus 0.5% lecithin plus 150 mg/kg carnitine. The total dry matter (DM intake, fortnightly body weight of each individual animal was recorded. Digestibility trial was conducted toward the end of the experiment to determine the digestibility coefficient of various nutrients. Results: There was a significant improvement (p0.05 among the three treatments on average daily gain, feed conversion efficiency, and nutrient digestibility during the overall period. Conclusion: It was concluded that the dietary inclusion of animal fat at 5% level or animal fat along with lecithin (0.5% and carnitine (150 mg/kg improved the growth performance in pigs than non-supplemented group and from the economic point of view, dietary incorporation of animal fat at 5% would be beneficial for improving growth in pigs without dietary modifiers.

Musculus soleus of rats at physical activity and L-carnitine and creatine phosphate effect

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Irina A. Khutorskaya

2017-09-01

Full Text Available Introduction: The study of the effect of metabolic drugs on the histochemical characteristics of soleus muscle is relevant for solving the problem of providing the training process in Russia with non-doping drugs for safe correction of the consequences of intense physical activity in athletes. Materials and Methods: Dynamic physical activity in rats (n = 24 was simulated by swimming “to the limit” with weighting of 10 % of body weight (20 days, 1 time per day. The experimental animals were divided into four groups (6 animals each: № 1 – control, № 2 – swimming + isotonic NaCl solution, № 3 and № 4 – swimming + L-carnitine or creatine phosphate 100.0 mg/kg daily intraperitoneally. The object of the study was musculus soleus. Differentiation of muscle fibers was carried out by the intensity of histochemical activity of succinate dehydrogenase (SDG and alkaline stable adenosine triphosphate (ATP of myosin. The percentage of muscle fibers was evaluated and their diameter was defined by the direct morphometry. The obtained data were treated statistically by Student’s T-test. Results: Swimming of the animals “to the limit” do not affect the ratio of fibers with different phenotypes in the soleus muscle. This indicator is genetically determined and was not modified by L-carnitine and creatine phosphate. Dynamic physical activity promotes the development of hypertrophy of muscle fibers of various types. The investigated medicaments of the metabolic type either do not influence on the formation of exerciseinduced hypertrophy (predominantly creatine phosphate or reduce the intensity of the hypertrophic process (predominantly L-carnitine under dynamic physical activity. Discussion and Conclusions: The obtained data indicate L-carnitine and creatine phosphate do not have an anabolic effect. Taking into account the relevant data on ability of L-carnitine and creatine phosphate to effectively correct a negative effects of intensive

Carnitine derivatives: clinical usefulness.

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Malaguarnera, Mariano

2012-03-01

Carnitine and its derivatives are natural substances involved in both carbohydrate and lipid metabolism. This review summarizes the recent progress in the field in relation to the molecular mechanisms. The pool of different carnitine derivatives is formed by acetyl-L-carnitine (ALC), propionyl-L-carnitine (PLC), and isovaleryl-carnitine. ALC may have a preferential effect on the brain tissue. ALC represents a compound of great interest for its wide clinical application in various neurological disorders: it may be of benefit in treating Alzheimer's dementia, depression in the elderly, HIV infection, chronic fatigue syndrome, peripheral neuropathies, ischemia and reperfusion of the brain, and cognitive impairment associated with various conditions. PLC has been demonstrated to replenish the intermediates of the tricarboxylic acid cycle by the propionyl-CoA moiety, a greater affinity for the sarcolemmal carrier, peripheral vasodilator activity, a greater positive inotropism, and more rapid entry into myocytes. Most studies of the therapeutic use of PLC are focused on the prevention and treatment of ischemic heart disease, congestive heart failure, hypertrophic heart disease, and peripheral arterial disease. ALC and PLC are considered well tolerated without significant side-effects. A number of therapeutic effects possibly come from the interaction of carnitine and its derivatives with the elements of cellular membranes.

Performance of juvenile turbot (Scophthalmus maximus fed varying dietary L-carnitine levels at different stocking densities Desempenho de juvenis de pregado (Scophthalmus maximus em função da densidade de estocagem e de níveis dietéticos de L-carnitina

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José Fernando Magalhães Gonçalves

2010-04-01

Full Text Available Commercial farming of turbot (Scophthalmus maximus at high stocking densities may lead to growth depression and increasing production costs. Moreover, the high levels of accumulated waste in an intensive system may cause rapid deterioration of water quality, which may undermine the production. L-carnitine is known as a growth-enhancer which shows promise as mitigator of crowding effects. The effects of stocking densities (4, 8, 11 and 14 kg m² on growth performance, feed utilization and body composition were evaluated during 75 days on turbot (75.6 ± 2.8 g fed two dietary L-carnitine levels (40 or 240 mg kg¹. At the end of the feeding trial, total ammonia excretion (TAN was measured postprandially for 24h. Specific growth rate and weight gain decreased with increasing stocking density. Fish held at 4 kg m² had higher final body weight (94-96 g than fish held at higher densities (80-87 g. Protein efficiency ratio was higher in fish held at 4 kg m² (1.33-1.36, in comparison to fish stocked at 8 kg m² (0.98 or 14 kg m² (0.45. Voluntary feed intake decreased from 0.70 to 0.56% BW with increasing stocking density. Dietary L-carnitine supplementation did not affect growth performance and body composition, except for body L-carnitine content which increased from 75 to 128 mg kg¹ BW with supplementation. Fish fed 240 mg L-carnitine supplements had lower TAN that the ones fed 40 mg L-carnitine (p A aquicultura de pregado (Scophthalmus maximus utilizando elevadas densidades pode reduzir o crescimento e aumentar os custos de produção. Elevados níveis de metabolitos gerados nestes sistemas intensivos provocam rápida deterioração da qualidade da água, podendo também comprometer a performance da produção. A L-carnitina atua como potenciadora do crescimento parecendo ser promissora por atenuar alguns desses efeitos. Os efeitos de densidades (4, 8, 11 e 14 kg m² no desempenho do crescimento, composição corporal foram avaliados em pregados

Carnitine deficiency presenting with a decreased mental state in a patient with amyotrophic lateral sclerosis receiving long-term tube feeding: a case report.

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Isse, Naohi; Miura, Yoh; Obata, Toshiyuki; Takahara, Noriko

2013-12-30

L-carnitine is an important metabolic mediator involved in fatty acid transport. It is obtained from the diet, particularly from animal products, such as red meat. Previous reports have revealed that long-term tube feeding with a commercial product containing no or low levels of carnitine can lead to an altered mental state caused by hyperammonemia. A 72-year-old Japanese man had a 12-year history of amyotrophic lateral sclerosis. He was bedridden and had required mechanical ventilation and enteral tube feeding for 10 years at home. His main enteral solution was a commercial product that contained low carnitine levels, and he sometimes received coffee and homemade products such as miso soup. Our patient's ability to communicate gradually deteriorated over a period of one year. His serum total carnitine level was abnormally low, at 26.7μmol/L (normal range, 45 to 91μmol/L), but his ammonium level was normal. His mental state improved dramatically after starting L-carnitine supplementation (600mg twice daily). This case highlights the importance of avoiding carnitine deficiency in patients with amyotrophic lateral sclerosis undergoing long-term tube feeding. These patients experience progressive muscle atrophy that might cause impaired carnitine storage and might manifest as communication difficulties. Carnitine deficiency can be misdiagnosed as a progression of systemic muscle atrophy. Clinicians should be aware of this disorder and should consider periodically measuring carnitine levels, regardless of the patient's serum ammonium levels.

The effects of L-carnitin in Budd-Chiari syndrome in a domestic cat

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Aliye Sağkan Öztürk

2016-03-01

Full Text Available This paper describes a thrombosis in the vena cava caudalis of a 15 year-old cat with ascites. Trauma and eventually feline enteric corona virus infection in the cat were not detected. In the intrahepatic region, a blockage of vena cava caudalis was brought to light by ultrasonographic imaging. An aspirate of abdominal fl uid revealed modified transudate. Liver enzyme levels were increased in the serum sample of the cat. The levels of total oxidant status (TOS and total antioxidant status (TAS were elevated in the peritoneal fluid. Liver protection diet with L-carnitine, diuretic therapy and antimicrobial drugs were administrated for treatment of the cat. During the continuous treatment, the amount of abdominal fluid decreased, but never completely absorbed. L-carnitine was administered to the cat during the time of treatment, and subsequently the levels of liver enzymes decreased. However, the cat died because of recurrent ascites and persistent thrombosis. In conclusion, ultrasonographic examination was very reliable, non-invasive and highly useful diagnostic method for BCS and L-carnitine has crucial effects on the quality of life, energy metabolism and liver enzyme levels. However, the blockage of the vena cava caudalis could not completely respond to medical treatment and thrombosis should be eliminated by surgical intervention.

Oral carnitine therapy in children with cystinosis and renal Fanconi syndrome

International Nuclear Information System (INIS)

Gahl, W.A.; Bernardini, I.; Dalakas, M.; Rizzo, W.B.; Harper, G.S.; Hoeg, J.M.; Hurko, O.; Bernar, J.

1988-01-01

11 children with either cystinosis or Lowe's syndrome had a reduced content of plasma and muscle carnitine due to renal Fanconi syndrome. After treatment with oral L-carnitine, 100 mg/kg per d divided every 6 h, plasma carnitine concentrations became normal in all subjects within 2 d. Initial plasma free fatty acid concentrations, inversely related to free carnitine concentrations, were reduced after 7-20 mo of carnitine therapy. Muscle lipid accumulation, which varied directly with duration of carnitine deficiency (r = 0.73), improved significantly in three of seven rebiopsied patients after carnitine therapy. One Lowe's syndrome patient achieved a normal muscle carnitine level after therapy. Muscle carnitine levels remained low in all cystinosis patients, even though cystinotic muscle cells in culture took up L-[ 3 H]carnitine normally. The half-life of plasma carnitine for cystinotic children given a single oral dose approximated 6.3 h; 14% of ingested L-carnitine was excreted within 24 h. Studies in a uremic patient with cystinosis showed that her plasma carnitine was in equilibrium with some larger compartment and may have been maintained by release of carnitine from the muscle during dialysis. Because oral L-carnitine corrects plasma carnitine deficiency, lowers plasma free fatty acid concentrations, and reverses muscle lipid accumulation in some patients, its use as therapy in renal Fanconi syndrome should be considered. However, its efficacy in restoring muscle carnitine to normal, and the optimal dosage regimen, have yet to be determined

Protective Effects of Ibuprofen and L-Carnitine Against Whole Body Gamma Irradiation-Induced Duodenal Mucosal Injury

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Meryem Akpolat

2011-03-01

Full Text Available Objective: Ibuprofen and L-carnitine have been demonstrated to provide radioprotective activity to the hamster against whole body sublethal irradiation. The purpose of this study is to test those antioxidant drugs, each of which has the capacity of inhibiting mucosal injury, as topical radioprotectants for the intestine. Material and Methods: The male hamsters were divided into the following four groups (n=6: group 1: control group, received saline, 1 ml/100 g by gavage, as placebo. Group 2: irradiated-control group, received whole body irradiation of 8 Gy as a single dose plus physiological saline. The animals in groups 3 and 4 were given a daily dose of 10 mg/kg of ibuprofen and 50 mg/kg of L-carnitine for 15 days respectively, before irradiation with a single dose of 8 Gy. Twenty-four hours after radiation exposure, the hamsters were sacrificed and samples were taken from the duodenum, and the histopatological determinations were carried out. Results: Morphologically, examination of the gamma irradiated duodenum revealed the presence of shortening and thickening of villi and flattening of enterocytes, massive subepithelial lifting. Pretreatment of ibuprofen and L-carnitine with irradiation reduced these histopathological changes. Conclusion: Ibuprofen and L-carnitine administrated by the oral route may be a good radioprotector against small intestinal damage in patients undergoing radiotherapy.

Protective effects of l-carnitine and piracetam against mitochondrial permeability transition and PC3 cell necrosis induced by simvastatin.

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Costa, Rute A P; Fernandes, Mariana P; de Souza-Pinto, Nadja C; Vercesi, Aníbal E

2013-02-15

Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. Here we investigated the pathways leading to simvastatin-induced prostate cancer cell death as well as the mechanisms of cell death protection by l-carnitine or piracetam. These compounds are known to prevent and/or protect against cell death mediated by oxidative mitochondrial damage induced by a variety of conditions, either in vivo or in vitro. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either l-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, l-carnitine and piracetam acted at concentrations significantly lower than they act individually. These results shed new light into both the cytotoxic mechanisms of statins and the mechanisms underlying the protection against MPT and cell death by the compounds l-carnitine and piracetam. Copyright © 2013 Elsevier B.V. All rights reserved.

Effects of combination of sibutramine and L-carnitine compared with sibutramine monotherapy on inflammatory parameters in diabetic patients.

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Derosa, Giuseppe; Maffioli, Pamela; Salvadeo, Sibilla A T; Ferrari, Ilaria; Gravina, Alessia; Mereu, Roberto; D'Angelo, Angela; Palumbo, Ilaria; Randazzo, Sabrina; Cicero, Arrigo F G

2011-03-01

The aim of the study was to evaluate the effects of 12-month treatment with sibutramine plus L-carnitine compared with sibutramine alone on body weight, glycemic control, insulin resistance, and inflammatory state in type 2 diabetes mellitus patients. Two hundred fifty-four patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA(1c)] >8.0%) in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomized to take sibutramine 10 mg plus L-carnitine 2 g or sibutramine 10 mg in monotherapy. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA(1c), fasting plasma glucose, postprandial plasma glucose, fasting plasma insulin, homeostasis model assessment of insulin resistance index, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, leptin, tumor necrosis factor-α, adiponectin, vaspin, and high-sensitivity C-reactive protein. Sibutramine plus L-carnitine gave a faster improvement of fasting plasma glucose, postprandial plasma glucose, lipid profile, leptin, tumor necrosis factor-α, and high-sensitivity C-reactive protein compared with sibutramine alone. Furthermore, there was a better improvement of body weight, HbA(1c), fasting plasma insulin, homeostasis model assessment of insulin resistance index, vaspin, and adiponectin with sibutramine plus L-carnitine compared with sibutramine alone. Sibutramine plus L-carnitine gave a better and faster improvement of all the analyzed parameters compared with sibutramine alone without giving any severe adverse effect. Copyright © 2011 Elsevier Inc. All rights reserved.

Does carnitine have a role in fat absorption?

International Nuclear Information System (INIS)

Leichter, J.; Ottem, A.; Hahn, P.

1987-01-01

The effect of D-carnitine and tetradecylglycidic acid (TDGA), an inhibitor of carnitine palmitoyltransferase, on intestinal absorption of palmitic acid was determined. The proximal intestinal segment was ligated in adult male rats and filled with 0.5 μCi of 14 C-palmitic acid alone or with either D-carnitine or TDGA. Thirty minutes alter the radioactivity was determined in the intestinal lumen, intestinal wall and plasma. The absorption of palmitic acid was decreased in the presence of D-carnitine (10 mg/ml) as evidenced by significantly lower levels of radioactivity in the gut wall and the plasma and by significantly greater residual radioactivity in the lumenal contents. L-carnitine had no effect on plasma radioactivity but if D- and L-carnitine were given together the effect of D-carnitine was still in evidence. TDGA also inhibited intestinal absorption of palmitic acid. 8 references, 2 tables

Carnitine Profile and Effect of Suppletion in Children with Renal Fanconi Syndrome due to Cystinosis

OpenAIRE

Besouw, M.; Cornelissen, E.; Cassiman, D.; Kluijtmans, L.; van den Heuvel, L.; Levtchenko, E.

2014-01-01

Background: Cystinosis is an autosomal recessive disorder marked by intralysosomal cystine accumulation. Patients present with generalized proximal tubular dysfunction called renal Fanconi syndrome. Urinary carnitine loss results in plasma and muscle carnitine deficiency, but no clinical signs of carnitine deficiency have been described. Also, the optimal dose of carnitine supplementation is undefined. This study aimed to determine whether currently recommended carnitine doses result in adequ...

Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia

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Sapere, Nadia; La Marca, Giancarlo; Angiolillo, Antonella; Vitale, Michela; Corbi, Graziamaria; Scapagnini, Giovanni; Intrieri, Mariano; Russo, Claudio

2016-01-01

This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer’s disease. Twenty-nine patients with probable Alzheimer’s disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L) to subjective memory complaint (4.3±0.9 μmol/L), mild cognitive impairment (4.0±0.53 μmol/L), up to Alzheimer’s disease (3.5±0.6 μmol/L) group (p<0.001). The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer’s disease group; and subjective memory complaint vs. Alzheimer’s disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer’s disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer’s disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer’s disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal

Serum Levels of Acyl-Carnitines along the Continuum from Normal to Alzheimer's Dementia.

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Adriana Cristofano

Full Text Available This study aimed to determine the serum levels of free L-carnitine, acetyl-L-carnitine and 34 acyl-L-carnitine in healthy subjects and in patients with or at risk of Alzheimer's disease. Twenty-nine patients with probable Alzheimer's disease, 18 with mild cognitive impairment of the amnestic type, 24 with subjective memory complaint and 46 healthy subjects were enrolled in the study, and the levels of carnitine and acyl-carnitines were measured by tandem mass spectrometry. The concentrations of acetyl-L-carnitine progressively decreased passing from healthy subjects group (mean±SD, 5.6±1.3 μmol/L to subjective memory complaint (4.3±0.9 μmol/L, mild cognitive impairment (4.0±0.53 μmol/L, up to Alzheimer's disease (3.5±0.6 μmol/L group (p<0.001. The differences were significant for the comparisons: healthy subjects vs. subjective memory complaint, mild cognitive impairment or Alzheimer's disease group; and subjective memory complaint vs. Alzheimer's disease group. Other acyl-carnitines, such as malonyl-, 3-hydroxyisovaleryl-, hexenoyl-, decanoyl-, dodecanoyl-, dodecenoyl-, myristoyl-, tetradecenoyl-, hexadecenoyl-, stearoyl-, oleyl- and linoleyl-L-carnitine, showed a similar decreasing trend, passing from healthy subjects to patients at risk of or with Alzheimer's disease. These results suggest that serum acetyl-L-carnitine and other acyl-L-carnitine levels decrease along the continuum from healthy subjects to subjective memory complaint and mild cognitive impairment subjects, up to patients with Alzheimer's disease, and that the metabolism of some acyl-carnitines is finely connected among them. These findings also suggest that the serum levels of acetyl-L-carnitine and other acyl-L-carnitines could help to identify the patients before the phenotype conversion to Alzheimer's disease and the patients who would benefit from the treatment with acetyl-L-carnitine. However, further validation on a larger number of samples in a longitudinal

l-Carnitine Modulates Epileptic Seizures in Pentylenetetrazole-Kindled Rats via Suppression of Apoptosis and Autophagy and Upregulation of Hsp70

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Abdelaziz M. Hussein

2018-03-01

Full Text Available l-Carnitine is a unique nutritional supplement for athletes that has been recently studied as a potential treatment for certain neuropsychiatric disorders. However, its efficacy in seizure control has not been investigated. Sprague Dawley rats were randomly assigned to receive either saline (Sal (negative control or pentylenetetrazole (PTZ 40 mg/kg i.p. × 3 times/week × 3 weeks. The PTZ group was further subdivided into two groups, the first received oral l-carnitine (l-Car (100 mg/kg/day × 4 weeks (PTZ + l-Car, while the second group received saline (PTZ + Sal. Daily identification and quantification of seizure scores, time to the first seizure and the duration of seizures were performed in each animal. Molecular oxidative markers were examined in the animal brains. l-Car treatment was associated with marked reduction in seizure score (p = 0.0002 that was indicated as early as Day 2 of treatment and continued throughout treatment duration. Furthermore, l-Car significantly prolonged the time to the first seizure (p < 0.0001 and shortened seizure duration (p = 0.028. In addition, l-Car administration for four weeks attenuated PTZ-induced increase in the level of oxidative stress marker malondialdehyde (MDA (p < 0.0001 and reduced the activity of catalase enzyme (p = 0.0006 and increased antioxidant GSH activity (p < 0.0001. Moreover, l-Car significantly reduced PTZ-induced elevation in protein expression of caspase-3 (p < 0.0001 and β-catenin (p < 0.0001. Overall, our results suggest a potential therapeutic role of l-Car in seizure control and call for testing these preclinical results in a proof of concept pilot clinical study.

L-carnitine mitigates UVA-induced skin tissue injury in rats through downregulation of oxidative stress, p38/c-Fos signaling, and the proinflammatory cytokines.

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Salama, Samir A; Arab, Hany H; Omar, Hany A; Gad, Hesham S; Abd-Allah, Gamil M; Maghrabi, Ibrahim A; Al Robaian, Majed M

2018-04-01

UVA comprises more than 90% of the solar UV radiation reaching the Earth. Artificial lightening lamps have also been reported to emit significant amounts of UVA. Exposure to UVA has been associated with dermatological disorders including skin cancer. At the molecular level, UVA damages different cellular biomolecules and triggers inflammatory responses. The current study was devoted to investigate the potential protective effect of L-carnitine against UVA-induced skin tissue injury using rats as a mammalian model. Rats were distributed into normal control group (NC), L-carnitine control group (LC), UVA-Exposed group (UVA), and UVA-Exposed and L-carnitine-treated group (UVA-LC). L-carnitine significantly attenuated UVA-induced elevation of the DNA damage markers 8-oxo-2'-deoxyguanosine (8-oxo-dG) and cyclobutane pyrimidine dimers (CPDs) as well as decreased DNA fragmentation and the activity of the apoptotic marker caspase-3. In addition, L-carnitine substantially reduced the levels of lipid peroxidation marker (TBARS) and protein oxidation marker (PCC) and significantly elevated the levels of the total antioxidant capacity (TAC) and the antioxidant reduced glutathione (GSH) in the skin tissues. Interestingly, L-carnitine upregulated the level of the DNA repair protein proliferating cell nuclear antigen (PCNA). Besides it mitigated the UVA-induced activation of the oxidative stress-sensitive signaling protein p38 and its downstream target c-Fos. Moreover, L-carnitine significantly downregulated the levels of the early response proinflammatory cytokines TNF-α, IL-6, and IL-1β. Collectively, our results highlight, for the first time, the potential attenuating effects of L-carnitine on UVA-induced skin tissue injury in rats that is potentially mediated through suppression of UVA-induced oxidative stress and inflammatory responses. Copyright © 2018 Elsevier B.V. All rights reserved.

[ACTION OF L-CARNITINE, CORVITIN AND THEIR COMBINATION ON FUNCTIONAL STATE OF LIVER IN EXPERIMENTAL MODEL OF REYE SYNDROME IN RATS].

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Ghonghadze, M; Antelava, N; Liluashvili, K; Okujava, M; Pachkoria, K

2017-02-01

Administration of Aacetylsalicylic acid in children with viral infections (influence B, chickenpox) can be related with development of Reye syndrome - severe encephalopathy and liver insufficiency with mortality in 50% of cases. During Reye syndrome most important is deficiency of carnitine and hepatocyte damage. Decreased amount of carnitine impairs the energy function of mitochondria and gluconeogenesis as well as production of urea. As a result develops toxic encephalopathy and liver insufficiency. The goal of the research was assessment of efficacy of L-Carnitine, Corvitin and their combination on functional state of liver in experimental model of Reye Syndrome in rats. The study was performed on mature white male Wistar rates with body mass 150-180g. 50 rats were randomly divided into 5 groups (10 rats in each group). The model of Reye syndrome was induced in accordance with A.Vengersky's method. Intraperitoneal administration of 4-pentenoic acid was performed once daily during seven days, the used dosage was 20mg/kg. The treatment of toxic hepatitis was carried with intraperitoneal administration of L-Carnitine 300mg/kg, Corvitine 100mg/kg and concurrent administration of these drugs. Monotherapy with Corvitin and L-Carnitin successfully improved liver function and equally decreased indicators of hepatocyte's cytolyses and increased levels of glucose and urea. The markers of cholestasis was slightly more improved during use of L-Carnitine. Simultaneous use of both drugs was effective in rats with Reye syndrome, indicators of liver damage normalized and herewith, no mortality outcome was observed. The most pronounced hepatoprotective effect of concurrent administration of L-Carnitine and Corvitin may be due to synergic action of these drugs and such regime can be recommended for correction of liver function during Reye syndrome.

Carnitine for fatigue in multiple sclerosis.

Science.gov (United States)

Tejani, Aaron M; Wasdell, Michael; Spiwak, Rae; Rowell, Greg; Nathwani, Shabita

2012-05-16

Fatigue is reported to occur in up to 92% of patients with multiple sclerosis (MS) and has been described as the most debilitating of all MS symptoms by 28% to 40% of MS patients. To assess whether carnitine (enteral or intravenous) supplementation can improve the quality of life and reduce the symptoms of fatigue in patients with MS-related fatigue and to identify any adverse effects of carnitine when used for this purpose. A literature search was performed using Cochrane MS Group Trials Register (09 September 2011), Cochrane Central Register of Controlled Trials (CENTRAL) "The Cochrane Library 2011, issue 3", MEDLINE (PubMed) (1966-09 September 2011), EMBASE (1974-09 September 2011), and www.clinicaltrials.gov for ongoing trials retrieval. Reference lists of review articles and primary studies were also screened. A hand search of the abstract book of recent relevant conference symposia was also conducted. Personal contact with MS experts and a manufacturer (Source Naturals, United States) of carnitine formulation was contacted to determine if they knew of other clinical trials. No language restrictions were applied. Full reports of published and unpublished randomized controlled trials and quasi-randomized trials of any carnitine intervention in adults affected by multiple sclerosis with a clinical diagnosis of fatigue associated with multiple sclerosis were included. Data from the eligible trials was extracted and coded using a standardized data extraction form and entered into RevMan 5. Discrepancies were to be resolved by discussion with a third reviewer, however this was not necessary.The quality items to be assessed were method of randomization, allocation concealment, blinding (participants, investigators, outcome assessors and data analysis), intention-to-treat analysis and completeness of follow up. The search identified one ongoing randomized, placebo-controlled, cross-over trial (expected completion 2013) and one completed randomized, active

Myocardial Protective Effects of L-Carnitine on Ischemia-Reperfusion Injury in Patients With Rheumatic Valvular Heart Disease Undergoing Cardiac Surgery.

Science.gov (United States)

Li, Ming; Xue, Li; Sun, Haifeng; Xu, Suochun

2016-12-01

The authors used L-carnitine as an ingredient in cardioplegic solution during valve replacement surgery to investigate the protective effect of L-carnitine on myocardial ischemia-reperfusion injury (MIRI) and its possible mechanism. Prospective, randomized study. A tertiary-care hospital. The study comprised 90 patients undergoing valve replacement under cardiopulmonary bypass. Patients were divided randomly into 3 groups. L-carnitine was added to the crystalloid cardioplegic solution for experimental group 1 (3 g/L) and experimental group 2 (6 g/L), whereas no L-carnitine was used in the control group. The remainder of the treatment was identical for all 3 groups. Serum was collected from each patient 1 hour before the surgery and at 2, 6, 24, and 72 hours after unclamping the aorta, and tissue samples were obtained before cardiac arrest and after unclamping the aorta. The postoperative levels of serum aspartate aminotransferase, creatine kinase, creatine kinase-MB isozyme, and lactic acid dehydrogenase and the apoptotic index were all lower in the 2 experimental groups than those in the control group. In addition, each of the aforementioned serum enzyme levels and the apoptotic index in all 3 groups significantly increased after unclamping the aorta compared with baseline levels taken before surgery. Bcl-2 expression was higher and Bax was lower in the 2 experimental groups compared with those of the control group after unclamping the aorta. However, there was no significant difference in all the postoperative indices between the 2 experimental groups. L-carnitine may reduce cardiopulmonary bypass-induced myocardial apoptosis through modulating the expressions of Bcl-2 and Bax, resulting in a protective effect from MIRI. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats

International Nuclear Information System (INIS)

Anwar, M. K.; Hussain, M. M.; Khan, M. A.; Ahmad, T.

2013-01-01

Objective: To compare the effects of combined and individual supplementation of cholecalciferol and levo carnitine on plasma glucose, plasma insulin and insulin resistance in type 2 diabetic rats. Methods: The randomised controlled trial was conducted at the Department of Physiology, Army Medical College, Rawalpindi, between October 2010 and April 2011. It comprised 80 healthy Sprague Dawley rats who were divided into four groups (n = 20 each). Rats were fed high-fat diet for 2 weeks followed by an intraperitoneal injection of streptozocin to induce type 2 diabetes mellitus. Group I served as diabetic control; group II was given cholecalciferol; group III; levo carnitine; and group IV was administered cholecalciferol and levo carnitine together. After 6 days of supplementation, terminal intracardiac blood extraction was done and samples were analysed for fasting plasma glucose and plasma insulin. Insulin resistance was calculated by homeostatic model assessment for insulin resistance. SPSS 17.0 was used for statistical analysis. Results: Fasting plasma glucose levels were significantly decreased (p <0.001) in the combined supplementation group compared to the diabetic control and individual supplementation groups. Combined supplementation showed a significant increase in fasting plasma insulin levels when compared with diabetic control and levo carnitine groups (p <0.001), and the effect of combined supplementation on ameliorating insulin resistance was significantly better (p <0.001) as compared to the individual supplementation of cholecalciferol and levo carnitine. Conclusions: The combined supplementation of cholecalciferol and levo carnitine for 6 days markedly improved the glycaemic control, insulin secretion and insulin resistance in type 2 diabetic rats on high-fat diet. A prolonged supplementation by both the compounds along with caloric restriction may yield a more promising outcome. (author)

Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

OpenAIRE

Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

1985-01-01

We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in...

Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

Science.gov (United States)

Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

1985-06-01

We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in tumour cells exposed to 5 microM-methylglyoxal bis(guanylhydrazone) for only 7 h. Electron-microscopic examination of the drug-exposed cells revealed that more than half of the mitochondria were severely damaged. Similar exposure of the leukaemia cells to the drug in the presence of carnitine not only abolished the inhibition of fatty acid oxidation but almost completely prevented the drug-induced mitochondrial damage. The protection provided by carnitine appeared to depend on the intracellular concentration of methylglyoxal bis(guanylhydrazone), since the mitochondria-sparing effect disappeared at higher drug concentrations.

Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

International Nuclear Information System (INIS)

Deusing, Dorothé Jenni; Beyrer, Melanie; Fitzenberger, Elena; Wenzel, Uwe

2015-01-01

Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation

Carnitine protects the nematode Caenorhabditis elegans from glucose-induced reduction of survival depending on the nuclear hormone receptor DAF-12

Energy Technology Data Exchange (ETDEWEB)

Deusing, Dorothé Jenni, E-mail: Dorothe.J.Deusing@ernaehrung.uni-giessen.de; Beyrer, Melanie, E-mail: m.beyrer@web.de; Fitzenberger, Elena, E-mail: Elena.Fitzenberger@ernaehrung.uni-giessen.de; Wenzel, Uwe, E-mail: uwe.wenzel@ernaehrung.uni-giessen.de

2015-05-08

Besides its function in transport of fatty acids into mitochondria in order to provide substrates for β-oxidation, carnitine has been shown to affect also glucose metabolism and to inhibit several mechanisms associated with diabetic complications. In the present study we used the mev-1 mutant of the nematode Caenorhabditis elegans fed on a high glucose concentration in liquid media as a diabetes model and tested the effects of carnitine supplementation on their survival under heat-stress. Carnitine at 100 μM completely prevented the survival reduction that was caused by the application of 10 mM glucose. RNA-interference for sir-2.1, a candidate genes mediating the effects of carnitine revealed no contribution of the sirtuin for the rescue of survival. Under daf-12 RNAi rescue of survival by carnitine was abolished. RNA-interference for γ-butyrobetaine hydroxylase 2, encoding the key enzyme for carnitine biosynthesis did neither increase glucose toxicity nor prevent the rescue of survival by carnitine, suggesting that the effects of carnitine supplementation on carnitine levels were significant. Finally, it was demonstrated that neither the amount of lysosomes nor the proteasomal activity were increased by carnitine, excluding that protein degradation pathways, such as autophagy or proteasomal degradation, are involved in the protective carnitine effects. In conclusion, carnitine supplementation prevents the reduction of survival caused by glucose in C. elegans in dependence on a nuclear hormone receptor which displays high homologies to the vertebrate peroxisomal proliferator activated receptors. - Highlights: • Carnitine protects from glucose-induced reduction of stress-resistance. • Carnitine acts via the PPAR homolog DAF-12 on glucose toxicity. • Carnitine protects from glucose toxicity independent of protein degradation.

Parenteral nutrition in the critically ill.

Science.gov (United States)

Gunst, Jan; Van den Berghe, Greet

2017-04-01

Feeding guidelines have recommended early, full nutritional support in critically ill patients to prevent hypercatabolism and muscle weakness. Early enteral nutrition was suggested to be superior to early parenteral nutrition. When enteral nutrition fails to meet nutritional target, it was recommended to administer supplemental parenteral nutrition, albeit with a varying starting point. Sufficient amounts of amino acids were recommended, with addition of glutamine in subgroups. Recently, several large randomized controlled trials (RCTs) have yielded important new insights. This review summarizes recent evidence with regard to the indication, timing, and dosing of parenteral nutrition in critically ill patients. One large RCT revealed no difference between early enteral nutrition and early parenteral nutrition. Two large multicenter RCTs showed harm by early supplementation of insufficient enteral nutrition with parenteral nutrition, which could be explained by feeding-induced suppression of autophagy. Several RCTs found either no benefit or harm with a higher amino acid or caloric intake, as well as harm by administration of glutamine. Although unanswered questions remain, current evidence supports accepting low macronutrient intake during the acute phase of critical illness and does not support use of early parenteral nutrition. The timing when parenteral nutrition can be initiated safely and effectively is unclear.

Phase II Randomized Study of Plitidepsin (Aplidin, Alone or in Association with L-carnitine, in Patients with Unresectable Advanced Renal Cell Carcinoma

Directory of Open Access Journals (Sweden)

Patrick Schöffski

2009-03-01

Full Text Available This randomized phase II study evaluated two schedules of the marine compound Plitidepsin with or without co-administration of L-carnitine in patients with renal cell carcinoma. Patients had adequate performance status and organ function.The primary endpoint was the rate of disease control (no progression at 12 weeks (RECIST.Other endpoints included the response rate and time dependent efficacy measures.The trial also assessed the efficacy of L-carnitine to prevent Plitidepsin-related toxicity. The two regimes given as 24 hour infusion every two weeks showed hints of antitumoral activity. Disease control at 12 weeks was 15.8% in Arm A (5mg/m2, no L-carnitine and 11,1% in Arm B (7mg/m2 with L-carnitine. Two partial responses were observed in Arm A (19 patients, none in Arm B (20 patients. Both schedules had the same progression-free interval (2.1 months.The median overall survival was 7.0 and 7.6 months.The safety profile was similar in both arms of the trial and adverse events were mainly mild to moderate (NCI CTC version 2.0. Increasing the dose to 7mg/m2 did not increase the treatment efficacy but the incidence of transaminase and CPK elevations and serious AEs. Coadministration of L-carnitine did not prevent muscular toxicity or CPK-elevation associated with Plitidepsin.

DISORDERS OF CARNITINE TRANSPORT AND THE CARNITINE CYCLE

OpenAIRE

Longo, Nicola; di San Filippo, Cristina Amat; Pasquali, Marzia

2006-01-01

Carnitine plays an essential role in the transfer of long-chain fatty acids across the inner mitochondrial membrane. This transfer requires enzymes and transporters that accumulate carnitine within the cell (OCTN2 carnitine transporter), conjugate it with long chain fatty acids (carnitine palmitoyl transferase 1, CPT1), transfer the acylcarnitine across the inner plasma membrane (carnitine-acylcarnitine translocase, CACT), and conjugate the fatty acid back to Coenzyme A for subsequent beta ox...

The effect of L-carnitine on carbonic anhydrase level in rats exposed ...

African Journals Online (AJOL)

It plays an important regulatory role in the mitochondria and is required for the transport of fatty acids from the cytosol into the mitochondria during the breakdown of lipids or fats for the generation of metabolic energy. The functions of L-carnitine in skeletal muscle are critical to sustaining normal bioenergetics during exercise ...

Mechanisms for altered carnitine content in hypertrophied rat hearts

International Nuclear Information System (INIS)

Reibel, D.K.; O'Rourke, B.; Foster, K.A.

1987-01-01

Carnitine levels are reduced in hypertrophied hearts of rats subjected to aortic constriction (banding) and evaluated in hypertrophied hearts of spontaneously hypertensive rats (SHR). In an attempt to determine the mechanisms for these alterations, L-[ 14 C]carnitine transport was examined in isolated perfused hearts. Total carnitine uptake was significantly reduced by ∼20% in hypertrophied hearts of banded rats at all perfusate carnitine concentrations employed. The reduction in total uptake was due to a 40% reduction in carrier-mediated carnitine uptake with no difference in uptake by diffusion. In contrast, carnitine uptake was not altered in isolated hypertrophied hearts of SHR. However, serum carnitine levels were elevated in SHR, which could result in increased myocardial carnitine uptake in vivo. The data suggest that altered carnitine content in hypertrophied hearts of aortic-banded rats is due to an alteration in the carrier-mediated carnitine transport system in the myocardium. However, altered carnitine content in hypertrophied hearts of SHR is not due to a change in the carnitine transport system per se but may rather be due to a change in serum carnitine levels

Uptake of carnitine by red blood cells

International Nuclear Information System (INIS)

Campa, M.; Borum, P.

1986-01-01

A significant amount of blood carnitine (70% of cord blood and 40% of blood from healthy adults) is partitioned into the red blood cell compartment of whole blood. Data indicate that the plasma compartment and the red blood cell compartment of whole blood represent different metabolic pools of carnitine. There are no data to indicate that red blood cells synthesize carnitine, but our understanding of the uptake of carnitine by red blood cells is negligible. Red blood cells were obtained from healthy adults, washed twice with normal saline, and used for uptake experiments. When the cells were incubated at 37 0 C in the presence of 14 C-carnitine, radioactivity was found both in the soluble cytosolic and membrane fractions of the cells following lysis. The uptake was dependent upon the time of incubation, temperature of incubation, and carnitine concentration in the incubation medium. Washed red blood cell membranes incubated with 14 C-carnitine showed specific binding of radioactivity. These data are consistent with the hypothesis that red blood cells have an uptake mechanism for L-carnitine

[Can the treatment with L-carnitine improve the inflammation in chronic hemodialysis patients?].

Science.gov (United States)

Grazi, G; Meriggioli, M; Donati, G

2004-01-01

Inflammation in patients on chronic hemodialysis (HD) is related to malnutrition and atherosclerosis; anemia is also often present in these patients. It has been demonstrated that l-carnitina treatment, in addition to reducing the need for erythropoietin (EPO), improves nutritional parameters and cardiac performance. To evaluate the effect of l-carnitine on the inflammatory pathology in patients on chronic HD, we studied 11 patients with no sure signs of malnutrition, flogistic and infective pathologies and with C-reactive protein (CRP) <2 mg/dL. We evaluated at baseline, after 6 and 12 months CRP, serum albumin, hemoglobin (Hb),nPCR and EPO weekly requirement. We observed a reduction in CRP (from 0.88 +/- 0.65 to 0.42 +/- 0.17 mg/dL after 6 months and to 0.50 + 0.36 mg/dL after 12 months), an increase in serum albumin (from 10.9 +/- 1.23 to 2.08 +/- 1.88 and to 11.8 +/- 1.15 g/dL) and an increase in nPCR (from 0.96 +/- 0.09 to 1.15 +/- 0.2 and to 1.16 +/- 0.18 g/kg/die); EPO weekly requirement decreased (from 7363 +/- 2941 to 5909 +/- 3207 units after 6 months and to 5363 +/- 3139 units after 12 months). These results seem to underline a positive effect of l-carnitine on the inflammatory pathology of patients on chronic hemodialytic treatment.

Usefulness of L-carnitine, a naturally occurring peripheral antagonist of thyroid hormone action, in iatrogenic hyperthyroidism: a randomized, double-blind, placebo-controlled clinical trial.

Science.gov (United States)

Benvenga, S; Ruggeri, R M; Russo, A; Lapa, D; Campenni, A; Trimarchi, F

2001-08-01

Old studies in animals and unblinded studies in a few hyperthyroid patients suggested that L -carnitine is a periferal antagonist of thyroid hormone action at least in some tissues. This conclusion was substantiated by our recent observation that carnitine inhibits thyroid hormone entry into the nucleus of hepatocytes, neurons, and fibroblasts. In the randomized, double-blind, placebo-controlled 6-month trial reported here, we assessed whether 2 or 4 g/d oral L-carnitine were able to both reverse and prevent/minimize nine hyperthyroidism- related symptoms. We also evaluated changes on nine thyroid hormone-sensitive biochemical parameters and on vertebral and hip mineral density (bone mineral density). Fifty women under a fixed TSH-suppressive dose of L -T(4) for all 6 months were randomly allocated to five groups of 10 subjects each. Group 0 associated placebo for 6 months; groups A2 and A4 started associating placebo (first bimester), substituted placebo with 2 or 4 g/d carnitine (second bimester), and then returned to the association with placebo. Groups B2 and B4 started associating 2 and 4 g/d carnitine for the first two bimesters, and then substituted carnitine with placebo (third bimester). Symptoms and biochemical parameters worsened in group 0. In group A, symptoms and biochemical parameters worsened during the first bimester, returned to baseline or increased minimally during the second bimester (except osteocalcin and urinary OH-proline), and worsened again in the third bimester. In group B, symptoms and biochemical parameters (except osteocalcin and urinary OH-proline) did not worsen or even improved over the first 4 months; they tended to worsen in the third bimester. In both the A and B groups, the two doses of carnitine were similarly effective. At the end of the trial, bone mineral density tended to increase in groups B and A (B > A). In conclusion, L-carnitine is effective in both reversing and preventing symptoms of hyperthyroidism and has a

Reduction of apoptosis through the mitochondrial pathway by the administration of acetyl-L-carnitine to mouse fibroblasts in culture

International Nuclear Information System (INIS)

Pillich, Rudolf Tito; Scarsella, Gianfranco; Risuleo, Gianfranco

2005-01-01

It is shown in literature that stress, such as deprivation of trophic factors and hypoxia, induces apoptosis in cultured cells and in tissues. In light of these results, we explored the possibility of protecting cells from programmed death by improving the metabolism of the mitochondrion. To this end, acetyl-L-carnitine was administered at various concentrations under conditions of serum deprivation. The choice of this drug was based on the accepted notion that acetyl-L-carnitine is able to stabilize mitochondrial membranes and to increase the supply of energy to the organelle. The results presented here indicate that the drug protects cells from apoptotic death: this is demonstrated by a lower positivity to the TUNEL reaction and by a strong reduction of the apoptotic DNA ladder in serum-deprived cells. The involvement of the mitochondrial apoptotic pathway was assessed by cytochrome C release and immunoreactivity to caspase 3. Moreover, acetyl-L-carnitine stimulates cell proliferation

Failure of carnitine in improving hepatic nitrogen content in alcoholic and non-alcoholic malnourished rats

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Luciana P. Rodrigues

2010-01-01

Full Text Available AIMS: To investigate the effect of carnitine supplementation on alcoholic malnourished rats' hepatic nitrogen content. METHODS: Malnourished rats, on 50% protein-calorie restriction with free access to water (malnutrition group and malnourished rats under the same conditions with free access to a 20% alcohol/water solution (alcohol group were studied. After the undernourishment period (4 weeks with or without alcohol, both groups were randomly divided into two subgroups, one of them nutritionally recovered for 28 days with free access to a normal diet and water (recovery groups and the other re-fed with free access to diet and water plus carnitine (0.1 g/g body weight/day by gavage (carnitine groups. No alcohol intake was allowed during the recovery period. RESULTS: The results showed: i no difference between the alcohol/no alcohol groups, with or without carnitine, regarding body weight gain, diet consumption, urinary nitrogen excretion, plasma free fatty acids, lysine, methionine, and glycine. ii Liver nitrogen content was highest in the carnitine recovery non-alcoholic group (from 1.7 to 3.3 g/100 g, P.05 was highest in the alcoholic animals. CONCLUSION: Carnitine supplementation did not induce better nutritional recovery.

Synthesis of radioactively methyl-labelled (1)-carnitine

International Nuclear Information System (INIS)

Ingalls, S.T.; Hoppel, C.L.; Turkaly, J.S.

1982-01-01

Commercial (l)-carnitine chloride was N-demethylated by the action of sodium benzenemercaptide in warm N,N-dimethylformamide. The product 4-(N,N-dimethylammonio)-3-hydroxybutanoic acid chloride salt was isolated in good yield by ion exchange chromatography. Methylation of the product by 14 C -iodomethane in dry methanol produced biologically active 4-N-Me- 14 C -(l)-carnitine chloride of high specific activity in excellent yield. (author)

ESPEN Guidelines on Parenteral Nutrition: gastroenterology

DEFF Research Database (Denmark)

A., Van Gossum; Cabre, E.; Hebuterne, X.

2009-01-01

. There is a lack of data supporting specific nutrients in these conditions. Parenteral nutrition is mandatory in case of intestinal failure, at least in the acute period. In patients with short bowel, specific attention should be paid to water and electrolyte supplementation. Currently, the use of growth hormone......-based recommendations for the indications, application and type of parenteral formula to be used in acute and chronic phases of illness. Parenteral nutrition is not recommended as a primary treatment in CD and UC. The use of parenteral nutrition is however reliable when oral/enteral feeding is not possible...

O papel da L-carnitina no estado nutricional e na evolução ecocardiográfica da cardiomiopatia dilatada idiopática da infância The role of L-carnitine in nutritional status and echocardiographic parameters in idiopathic dilated cardiomyopathy in children

Directory of Open Access Journals (Sweden)

Vitor M. P. Azevedo

2005-10-01

impact of L-carnitine supplementation on the nutritional status and echocardiogram parameters of children with idiopathic dilated cardiomyopathy. METHODS: This was an open label cohort of 11 patients who received L-carnitine (100 mg/kg/day plus the conventional medical treatment, compared with 40 controls, matched for gender and age. The L-carnitine group was weighed 118 times and the controls 264 times. Additionally, the L-carnitine group underwent 65 two-dimensional echocardiograms and the controls 144. Chi-square, Student's t test, Pearson correlation and ANOVA were calculated with alpha = 0.05. RESULTS: For the L-carnitine group: age at presentation = 3.82 years old, 72.7% (p = 0.033 were females younger than 2 years and 90.9% (p = 0.0001 were in functional classes III and IV. There were no deaths during this period. At presentation, no differences were observed in weight percentile (31.2±8.74 vs. 19.6±21.2 (p = 0.29 or z score (-0.68±1.05 vs. -1.16±0.89 (p = 0.24. Increases were observed in both the percentile (p = 0.026 and z score (p = 0.033 after the introduction of L-carnitine. At presentation, there were no differences in ejection fraction (54.9%±3.8 vs. 49.3%±6.6 (p = 0.19, but LV mass/BSA were greater in the L-carnitine group (169.12 g/m²±26.24 vs. 110.67 g/m²±15.62 (p = 0.0005. After the introduction of L-carnitine an increase in ejection fraction (48.3±7 to 67.2±7 (p = 0.044 was observed. LV mass/BSA decreased (164.29g/m²±28.14 to 110.88g/m²±28.88, but without significance (p = 0.089 CONCLUSION: In children with idiopathic dilated cardiomyopathy, supplementation of L-carnitine may be helpful for nutritional and echocardiographic improvement.

Changes in fatty acid concentrations in tissues of African catfish, Clarias gariepinus, as a consequence of dietary carnitine, lysine and lipid supplements

NARCIS (Netherlands)

Ozorio, E.O.A.; Uktolseja, J.L.A.; Huisman, E.A.; Verreth, J.A.J.

2001-01-01

A study was undertaken to examine the effect of different dietary carnitine (200 and 1000 mg/kg diet) and fat (90 and 190 g/kg diet) supplementation on growth and fatty acid concentrations of fish fed either with a low- (13 g/kg) or a high-lysine (21 g/kg) diet. African catfish (22?7 g/fish),

Serum carnitine levels in bone marrow transplant recipients.

Science.gov (United States)

Kirvelä, O; Antila, H; Heinonen, O; Toivanen, A

1990-12-01

This study investigated plasma carnitine levels in patients undergoing allogenic bone marrow transplantation. The patients received fat-based TPN (50% fat, 50% CHO; calorie: nitrogen ratio 125:1) for an average of 33 +/- 7.5 days. TPN was started before transplantation and stopped when patients were able to eat. Caloric needs were estimated using the Harris-Benedict equation; 150% of the estimated BEE was given for the first two weeks after transplantation. The amount of TPN was gradually decreased as patients resumed their oral intake. All patients had low-normal serum carnitine levels before transplantation. There was no significant change in total or free serum carnitine levels during the course of TPN. However, in patients who had symptoms of graft vs. host reaction (GVH), the highest carnitine values during GVH (total 72.3 +/- 6.5 and free 61.2 +/- 12.4 mumol/l) were significantly higher (p < 0.001) than the baseline values (total 27.1 +/- 9.3 and free 24.9 +/- 9.6 mumol/l) or the highest non GVH values after transplantation (total 32.0 +/- 10.7 and free 29.0 +/- 10.7 mumol/l, respectively). The serum triglyceride, total cholesterol, and HDL cholesterol remained within normal range. In conclusion, bone marrow transplant patients receiving fat-based TPN have normal circulating levels of carnitine. GVH reaction caused an increase in the carnitine levels, which was probably due to increased tissue catabolism.

Effects of Carnitine on Sperm Parameters of Infertile Males with Idiopathic Asthenospermia

Directory of Open Access Journals (Sweden)

I Amiri

2008-01-01

Full Text Available ABSTRACT: Introduction & Objective: Studies confirm that a number of nutritional and environmental factors may negatively affect spermatogenesis and cause male infertility. Carnitine is an important factor for sperm motility. Carnitine deficiency decreases sperm motility and may cause male infertility. The aim of this study was to assess the effects of carnitine on sperm parameters in infertile males with idiopathic asthenospermia. Materials & Methods: This study is a before and after clinical trial performed on 40 asthenospermia men who were treated with 750 mg per/day carnitine in Fatemieh infertility research center in years 2006-2007. Sperm parameters were assessed before and after treatment. The obtained data were analyzed using SPSS10 and paired T-test Results: The results showed a significant increase in sperm concentration, morphology, sperm total motility and rapid progressive motility after treatment by carnitine (p<0.05. Conclusion: Carnitine supplementation has a significant effect on sperm parameters in men with idiopathic asthenospermia.

Primary Carnitine (OCTN2) Deficiency Without Neonatal Carnitine Deficiency

NARCIS (Netherlands)

Boer, L. de; Kluijtmans, L.A.J.; Morava, E.

2013-01-01

Although the diagnosis of a primary carnitine deficiency is usually based on a very low level of free and total carnitine (free carnitine: 1-5 muM, normal 20-55 muM) (Longo et al. 2006), we detected a patient via newborn screening with a total carnitine level 67 % of the normal value. At the age of

Gbu Glycine Betaine Porter and Carnitine Uptake in Osmotically Stressed Listeria monocytogenes Cells

Science.gov (United States)

Mendum, Mary Lou; Smith, Linda Tombras

2002-01-01

The food-borne pathogen Listeria monocytogenes grows actively under high-salt conditions by accumulating compatible solutes such as glycine betaine and carnitine from the medium. We report here that the dominant transport system for glycine betaine uptake, the Gbu porter, may act as a secondary uptake system for carnitine, with a Km of 4 mM for carnitine uptake and measurable uptake at carnitine concentrations as low as 10 μM. This porter has a Km for glycine betaine uptake of about 6 μM. The dedicated carnitine porter, OpuC, has a Km for carnitine uptake of 1 to 3 μM and a Vmax of approximately 15 nmol/min/mg of protein. Mutants lacking either opuC or gbu were used to study the effects of four carnitine analogs on growth and uptake of osmolytes. In strain DP-L1044, which had OpuC and the two glycine betaine porters Gbu and BetL, triethylglycine was most effective in inhibiting growth in the presence of glycine betaine, but trigonelline was best at inhibiting growth in the presence of carnitine. Carnitine uptake through OpuC was inhibited by γ-butyrobetaine. Dimethylglycine inhibited both glycine betaine and carnitine uptake through the Gbu porter. Carnitine uptake through the Gbu porter was inhibited by triethylglycine. Glycine betaine uptake through the BetL porter was strongly inhibited by trigonelline and triethylglycine. These results suggest that it is possible to reduce the growth of L. monocytogenes under osmotically stressful conditions by inhibiting glycine betaine and carnitine uptake but that to do so, multiple uptake systems must be affected. PMID:12406761

Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats.

Science.gov (United States)

Amin, Kamal A; Nagy, Mohamed A

2009-10-16

Obesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity. To investigate the development of obesity in response to a high fat diet (HFD) and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF) (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice) on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats. White male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr), 30 rats fed a high-fat diet (HFD) for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD), the 2nd group HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10th week (start time for treatments) for 4 weeks.Body weight, lipid profile & renal function (urea, uric acid creatinine) ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB) the oxidative stress marker reduced glutathione (GSH), and Malondialdehyde (MDA) catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed. Data showed that feeding HFD diet significantly increased final body weight, triglycerides (TG), total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile.Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia, hyperinsulinemia, and high insulin resistance (IR

Effect of Carnitine and herbal mixture extract on obesity induced by high fat diet in rats

Directory of Open Access Journals (Sweden)

Amin Kamal A

2009-10-01

Full Text Available Abstract Background Obesity-associated type 2 diabetes is rapidly increasing throughout the world. It is generally recognized that natural products with a long history of safety can modulate obesity. Aim To investigate the development of obesity in response to a high fat diet (HFD and to estimate the effect of L-carnitine and an Egyptian Herbal mixture formulation (HMF (consisting of T. chebula, Senae, rhubarb, black cumin, aniseed, fennel and licorice on bodyweight, food intake, lipid profiles, renal, hepatic, cardiac function markers, lipid Peroxidation, and the glucose and insulin levels in blood and liver tissue in rats. Method White male albino rats weighing 80-90 gm, 60 days old. 10 rats were fed a normal basal diet (Cr, 30 rats fed a high-fat diet (HFD for 14 weeks during the entire study. Rats of the HFD group were equally divided into 3 subgroups each one include 10 rats. The first group received HFD with no supplement (HFD, the 2nd group HFD+L-carnitine and the third group received HFD+HMF. Carnitine and HMF were administered at 10th week (start time for treatments for 4 weeks. Body weight, lipid profile & renal function (urea, uric acid creatinine ALT & AST activities, cardiac markers, (LDH, C.K-NAC and MB the oxidative stress marker reduced glutathione (GSH, and Malondialdehyde (MDA catalase activity, in addition to glucose, insulin, and insulin resistance in serum & tissues were analyzed. Results Data showed that feeding HFD diet significantly increased final body weight, triglycerides (TG, total cholesterol, & LDL concentration compared with controls, while significantly decreasing HDL; meanwhile treatment with L-carnitine, or HMF significantly normalized the lipid profile. Serum ALT, urea, uric acid, creatinine, LDH, CK-NAC, CK-MB were significantly higher in the high fat group compared with normal controls; and administration of L-carnitine or herbal extract significantly lessened the effect of the HFD. Hyperglycemia

Molecular enzymology of carnitine transfer and transport

NARCIS (Netherlands)

Ramsay, RR; Gandour, RD; van der Leij, FR

2001-01-01

Carnitine (L-3-hydroxy-4-N-trimethylaminobutyric acid) forms esters with a wide range of acyl groups and functions to transport and excrete these groups. It is found in most cells at millimolar levels after uptake via the sodium-dependent carrier, OCTN2. The acylation state of the mobile carnitine

Perioperative Alanyl-Glutamine-Supplemented Parenteral Nutrition in Chronic Radiation Enteritis Patients With Surgical Intestinal Obstruction: A Prospective, Randomized, Controlled Study.

Science.gov (United States)

Yao, Danhua; Zheng, Lei; Wang, Jian; Guo, Mingxiao; Yin, Jianyi; Li, Yousheng

2016-04-01

A prospective, randomized, controlled study was performed to evaluate the effects of perioperative alanyl-glutamine-supplemented parenteral nutrition (PN) support on the immunologic function, intestinal permeability, and nutrition status of surgical patients with chronic radiation enteritis (CRE)-induced intestinal obstruction. Patients who received 0.4 g/kg/d alanyl-glutamine and isonitrogenous PN were assigned to an alanyl-glutamine-supplemented PN (Gln-PN) group and a control group, respectively. Serum levels of alanine aminotransferase and glutamine, body fat mass (FM), immunologic function, and intestinal permeability were measured before and after surgery. Serum glutamine levels of the Gln-PN group significantly exceeded that of the control group (P nutrition state and intestinal motility of surgical patients with CRE-induced intestinal obstruction. © 2015 American Society for Parenteral and Enteral Nutrition.

Altered carnitine transport in pressure-overload hypertrophied rat hearts

International Nuclear Information System (INIS)

O'Rourke, B.; Foster, K.; Reibel, D.K.

1986-01-01

The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L- 14 C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 μM carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. The reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 μM carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart

Muscle contraction increases carnitine uptake via translocation of OCTN2

Energy Technology Data Exchange (ETDEWEB)

Furuichi, Yasuro [Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa (Japan); Sugiura, Tomoko; Kato, Yukio [Faculty of Pharmacy, Kanazawa University, Kanazawa (Japan); Takakura, Hisashi [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan); Hanai, Yoshiteru [Nagoya Institute of Technology, Nagoya (Japan); Hashimoto, Takeshi [Ritsumeikan University, Kusatsu (Japan); Masuda, Kazumi, E-mail: masuda@ed.kanazawa-u.ac.jp [Faculty of Human Sciences, Kanazawa University, Kanazawa (Japan)

2012-02-24

Highlights: Black-Right-Pointing-Pointer Muscle contraction augmented carnitine uptake into rat hindlimb muscles. Black-Right-Pointing-Pointer An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. Black-Right-Pointing-Pointer Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. Black-Right-Pointing-Pointer OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL{sub uptake}) of L-[{sup 3}H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL{sub uptake} of [{sup 14}C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL{sub uptake} of L-[{sup 3}H]carnitine in the contracting muscles increased 1.4-1.7-fold as compared to that in the contralateral resting muscles (p < 0.05). The CL{sub uptake} of [{sup 14}C]IAP was much higher than that of L-[{sup 3}H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly

Muscle contraction increases carnitine uptake via translocation of OCTN2

International Nuclear Information System (INIS)

Furuichi, Yasuro; Sugiura, Tomoko; Kato, Yukio; Takakura, Hisashi; Hanai, Yoshiteru; Hashimoto, Takeshi; Masuda, Kazumi

2012-01-01

Highlights: ► Muscle contraction augmented carnitine uptake into rat hindlimb muscles. ► An increase in carnitine uptake was due to an intrinsic clearance, not blood flow. ► Histochemical analysis showed sarcolemmal OCTN2 was emphasized after contraction. ► OCTN2 protein in sarcolemmal fraction was increased in contracting muscles. -- Abstract: Since carnitine plays an important role in fat oxidation, influx of carnitine could be crucial for muscle metabolism. OCTN2 (SLC22A5), a sodium-dependent solute carrier, is assumed to transport carnitine into skeletal muscle cells. Acute regulation of OCTN2 activity in rat hindlimb muscles was investigated in response to electrically induced contractile activity. The tissue uptake clearance (CL uptake ) of L-[ 3 H]carnitine during muscle contraction was examined in vivo using integration plot analysis. The CL uptake of [ 14 C]iodoantipyrine (IAP) was also determined as an index of tissue blood flow. To test the hypothesis that increased carnitine uptake involves the translocation of OCTN2, contraction-induced alteration in the subcellular localization of OCTN2 was examined. The CL uptake of L-[ 3 H]carnitine in the contracting muscles increased 1.4–1.7-fold as compared to that in the contralateral resting muscles (p uptake of [ 14 C]IAP was much higher than that of L-[ 3 H]carnitine, but no association between the increase in carnitine uptake and blood flow was obtained. Co-immunostaining of OCTN2 and dystrophin (a muscle plasma membrane marker) showed an increase in OCTN2 signal in the plasma membrane after muscle contraction. Western blotting showed that the level of sarcolemmal OCTN2 was greater in contracting muscles than in resting muscles (p < 0.05). The present study showed that muscle contraction facilitated carnitine uptake in skeletal muscles, possibly via the contraction-induced translocation of its specific transporter OCTN2 to the plasma membrane.

Oral cobalamin supplementation in cats with hypocobalaminaemia: a retrospective study.

Science.gov (United States)

Toresson, Linda; Steiner, Joerg M; Olmedal, Gunilla; Larsen, MajBritt; Suchodolski, Jan S; Spillmann, Thomas

2017-12-01

Objectives The objective of the study was to evaluate whether oral cobalamin supplementation can restore normocobal-aminaemia in cats with hypocobalaminaemia and clinical signs of gastrointestinal disease. Methods This was a retrospective study based on a computerised database search for client-owned cats treated at Evidensia Specialist Animal Hospital, Helsingborg, Sweden, during the period December 2013 to August 2016. Inclusion criteria were cats with clinical signs of chronic enteropathy, an initial serum cobalamin concentration ⩽250 pmol/l (reference interval 214-738 pmol/l) and oral treatment with cobalamin tablets. Results Twenty-five cats met the inclusion criteria. The cats were treated with 0.25 mg cyanocobalamin tablets once daily. Serum cobalamin concentration was rechecked 27-94 days after continuous oral cobalamin supplementation. All cats had serum cobalamin concentrations above the reference interval after oral cobalamin supplementation. Median (range) serum cobalamin concentration was 128 pmol/l (111-250 pmol/l) prior to treatment and 2701 pmol/l (738-16,359 pmol/l) after supplementation. This difference was statistically significant ( P cats with hypocobalaminaemia. Thus, oral cobalamin supplementation is a promising alternative to parenteral administration. Prospective comparative studies in cats being treated with parenteral vs oral cobalamin supplementation in a larger number of patients are warranted before oral supplementation can be recommended for routine use.

Carnitine levels in 26,462 individuals from the nationwide screening program for primary carnitine deficiency in the Faroe Islands

DEFF Research Database (Denmark)

Rasmussen, Jan; Nielsen, Olav W; Janzen, Nils

2014-01-01

BACKGROUND: Primary carnitine deficiency (PCD) is an autosomal recessive disorder of fatty acid oxidation and has been associated to episodes of sudden death in the Faroe Islands. Data are presented from the nationwide population based Faroese screening program to find people with low carnitine...... levels indicating PCD. METHODS: Whole blood samples from dried blood spots were analysed by tandem mass spectrometry with and without butylation. Genetic analyses were performed in all people with non-butylated free carnitine (fC0) below 7 μmol/L. RESULTS: 55 % (n = 26,462) of the entire population...

Synthesis of [methyl-14C]crotonobetaine from DL-[methyl-14C]carnitine

International Nuclear Information System (INIS)

Loester, H.; Seim, H.

1996-01-01

The causes of carnitine deficiency syndromes are not completely understood, but decomposition of L-carnitine in vivo is likely to be involved. Carnitine is metabolized to γ-butyrobetaine, and crotonobetaine is probably an intermediate in this pathway. To validate experimentally the precursor-product relationship between the three physiologically occuring γ-betaines - L-carnitine, crotonobetaine, γ-butyrobetaine - labelling with stable or radioactive isotopes became necessary. Methyl-labelled carnitine isomers (L(-)-, D(+)- or DL-) or γ-butyrobetaine can be easily synthesized by methylation of 4-amino-3-hydroxybutyric acid isomers or 4-aminobutyric acid, respectively. Because of problems with the 4-aminocrotonic acid, we synthesized labelled crotonbetaine from labelled carnitine. Thus, DL-[methyl- 14 C]carnitine was dehydrated by reaction with concentrated sulfuric acid. After removal of the latter the products were separated and purified by ion exchange chromatography on DOWEX 50 WX8 (200 - 400 mesh) and gradient elution with hydrochloric acid. In addition to the labelled main product [methyl- 14 C]crotonobetaine (yield about 50 %), [methyl- 14 C]glycine betaine and [methyl- 14 C]acetonyl-trimethylammonium (ATMA) were formed. The end products were identified by combined thin layer chromatography/autoradiography and quantified by liquid scintillation counting. (Author)

Effects of telmisartan in combined with L-carnitine on the oxidative stress and micro-inflammation status in peritoneal dialysis patients

Directory of Open Access Journals (Sweden)

Jin-Xiu Cheng

2016-06-01

Full Text Available Objective: To explore the effects of telmisartan in combined with L-carnitine on the oxidative stress and micro-inflammation status in peritoneal dialysis (PD patients. Methods: A total of 80 patients with chronic renal failure (CRF who were admitted in our hospital from November, 2011 to January, 2014 for PD were included in the study and randomized into the treatment group and the control group. The patients in the two groups were routinely performed with PD. The patients in the treatment group were given L-carnitine oral liquid, 10 mL/time, 3 times/d, and telmisartan, 80 mg/time, 1 time/d. The patients in the control group were given L-carnitine oral liquid, 10 mL/time, 3 times a day. The patients in the two groups were treated for 24 weeks continuously. A volume of 5 mL morning fasting venous blood before and after treatment was extracted, and centrifuged for serum. The levels of hs-CRP, IL-6, IL-8, TNF-α, MDA, and GSH-Px were determined. Results: After treatment, the levels of hs-CRP, IL-6, IL-8, and TNF-α were reduced, and the reduced degree in the treatment group was significantly superior to that in the control group. After treatment, MDA was reduced, GSH-Px was elevated, and the reduced degree and elevated degree in the treatment group were significantly superior to those in the control group. Conclusions: Telmisartan in combined with L-carnitine can probably become an ideal therapeutic measure for inhibiting the micro-inflammation state and oxidative stress reaction in PD patients, thus reducing the risk of cardiovascular events, which can provide an evidence for the clinical application in the future.

Propionyl-L-carnitine as a potential protective agent against radiation-induced cardiotoxicity

International Nuclear Information System (INIS)

Ramadan, L.A.

2003-01-01

In this study, propiony-L-carnitine (PLC); a natural short-chain derivative of L-carnitine, has been tested as a potential protective agent against radiation-induced cardio-toxicity. Cardiotoxicity was assessed in the homo-genate of the heart by measuring the plasma levels of creatine phosphokinase (CPK), lactic acid dehydrogenase (LDH), aspartate aminotransferase (AST), as well as malon-dialdehyde (MDA), glutathione content (GSH), glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), adenosine triphosphate (ATP) and nitric oxide (NO) production, whole body gamma-irradiation (2 and 6Gy ) of rats significantly increased CPK, LDH, AST,MDA, and NO and significantly decreased GSH,GSH-PX, SOD and ATP. Daily administration (one week) of PLC before whole body irradiation caused significant recovery for the serum enzyme CPK, LDH, AST and MDA, GSH, GSH-PX, SOD, ATP and NO levels in cardiac tissue. The protective effect PLC was attributed to it's antioxidant properties. Radiation therapy, likewise, is a valuable method of treatment for a variety of intrathoracic neoplasms. During radiotherapy of thoracic tumorus, the heart is often included in the primary treatment volume and chronic impairment of myocadial function occurs (cilliers and lochner, 1993; benderitter et al., 1995). Irradiation causes numerous changes in different metabolic reactions within the cardiac cells with major adverse undersirable effects that involve cardiotoxicity

Retinal Pigment Epithelial Cell Culture and Cooperation of L-carnitine in Reducing Stress Induced Cellular Damage

International Nuclear Information System (INIS)

Shamsi, Farrukh A.; Al-Rajhi, Ali A.; Athmanathan, S.; Boulton, M.; Chaudhry, Imtiaz A.

2006-01-01

Purpose was to show that L-carnitine (LC) is capable of reducing non-oxidative stress in the retinal pigment epithelial cells (RPE) of the human eye. The RPE cells were cultured from donor eyes, obtained immediately after post-mortem. The interaction between bovine serum albumin (BSA) and non-oxidative (sodium hydroxide and methyl methane sulphonate) stress-inducers was observed by recording the change in the absorption profiles of the interacting molecules after incubation in light for 5 hours and after treatment with LC. The isolated and cultured RPE cells from the human eyes were treated with sodium hydroxide or methyl methane sulphonate and/or LC for 5 hours under light, and the qualitative effect on cell morphology after treatment was analyzed by staining cells with Giemsa and visualization by light microscopy. The cell morphology was also qualitatively analyzed by scanning electron microscopy (SEM). L-carnitine and stress-inducers interact with BSA and bring about changes in the spectral profile of the interacted molecules. Light microscopy as well as SEM show that the changes in the cellular morphology, induced by 100 uM concentrations of non-oxidative stress-inducers, are considerably reduced in the presence of 100 uM LC. However, L-carnitine alone does not cause any qualitative damage to the cell morphology during incubation under similar conditions. The results give a preliminary indication that LC has ability to reduce the changes brought about by the non-oxidative stress-inducers in the RPF cells in culture. (author)

Effect of Magnetic Field Exposure on Testicular function and Prophylactic Role of Coenzyme Q10 and L-Carnitine in Mice

International Nuclear Information System (INIS)

Ramadan, L.A.; Abd-Allah, A.R.A.; Aly, H.A.A.

2004-01-01

The protective effect of L-carnitine or Co enzyme Q 10 (Co Q 10) against high magnetic field (20 mt) induced testicular toxicity in mice was evaluated. Animals were injected with L-carnitine (200 mg/kg i.p.) or Co Q 10(200 mg/kg per o.s.) 1 hr before exposure to fractionated doses (1/2 h/day, 3 times per week for 2 weeks) or acute dose (3 hr) of magnetic field. Total sperm count motility, daily sperm production and testicular LDH-X activity as well as histopathological examination were investigated. Exposure of mice to fractionated doses of magnetic field caused a significant decrease in sperm count, motility, daily sperm production and LDH-X activity,which were more pronounced than those of acute dose. Moreover,marked testicular histopathological changes were observed after exposure to fractionated doses of magnetic field. Pretreatment of mice with L-carnitine or Co Q 10 1 hr before exposure to the magnetic field caused a significant recovery of testicular damage induced by high magnetic field (20 mT)

Immunomodulatory effects of L-carnitine and q10 in mouse spleen exposed to low-frequency high-intensity magnetic field

International Nuclear Information System (INIS)

Arafa, Hossam M.M.; Abd-Allah, Adel R.A.; El-Mahdy, Mohamad A.; Ramadan, Laila A.; Hamada, Farid M.A.

2003-01-01

In the current study, we have investigated the bioeffects of repeated exposure to low-frequency (50 Hz) high-intensity (20 mT; 200 G) electromagnetic field (EMF) on some immune parameters in mice. The animals were exposed to EMF daily for 30 min three times per week for 2 weeks. We also studied the possible immunomodulatory effects of two anti-radical substances known to have non-specific immunostimulant effects namely, L-carnitine (200 mg/kg body weight i.p.) and Q10 (200 mg/kg body weight, p.o.). Both drugs were given 1 h prior to each EMF exposure. Immune endpoints included total body weight, spleen/body weight ratio, splenocytes viability, total and differential white blood cell (WBCs; lymphocytes, monocytes, neutrophils) counts, as well as the lymphocyte proliferation induced by the mitogens; phytohaemagglutinin (PHA), concanavalin-A (Con-A) and lipoploysaccharide (LPS). Magnetic field decreased splenocyte viability, WBCs count, as well as mitogens-induced lymphocyte proliferation. L-carnitine, but not Q10 could ameliorate the adverse effects of EMF on the vast majority of the immune parameters tested, suggesting a possible immunoprotective role of L-carnitine under the current experimental conditions

New perspective for nutritional support of cancer patients: Enteral/parenteral nutrition.

Science.gov (United States)

Akbulut, Gamze

2011-07-01

Cancer and its treatment result in severe biochemical and physiological alterations associated with a deterioration of quality of life (QoL). Cancer-related malnutrition may evolve into cancer cachexia due to complex interactions between pro-inflammatory cytokines and the host metabolism. Depending on the type of cancer treatment (either curative or palliative), the clinical condition of the patient and nutritional status, adequate and patient-tailored nutritional intervention should be prescribed (diet counseling, oral supplementation, enteral or total parenteral nutrition). Nutritional support has been widely advocated as adjunctive therapy for a variety of underlying illnesses, including surgery and medical oncotherapy (radiation or chemotherapy for cancer). Glutamine, n-3 fatty acids and probiotics/prebiotics are therapeutic factors that potentially modulate gastrointestinal toxicity related to cancer treatments. Enteral and parenteral nutrition may help improve patient survival, functional status and QoL, yet the benefits appear to be primarily limited to patients with good functional status and with gastrointestinal disease affecting nutritional intake. Parenteral nutrition offers the possibility of increased or maintenance of the nutrient intake in patients for whom normal food intake is inadequate and for whom enteral nutrition is not feasible, is contraindicated or is not accepted by the patient. This article reviews evidence on issues relevant to enteral and parenteral nutrition in patients with cancer.

Noninvasive evaluation of adult onset myopathy from carnitine palmitoyl transferase II deficiency using proton magnetic resonance spectroscopy.

Science.gov (United States)

Videen, J S; Haseler, L J; Karpinski, N C; Terkeltaub, R A

1999-08-01

The adult onset metabolic myopathy of carnitine palmitoyl transferase II (CPT II) deficiency is under-recognized, in part due to variable degrees of enzyme deficiency and symptomatology, as well as limitations in means for noninvasive evaluation. We describe a proton magnetic resonance spectroscopy (MRS) technique, using a standard clinical magnetic resonance imaging scanner, to diagnose and help monitor the response to therapy in adult CPT II deficiency. A 53-year-old woman presented with a long standing history of diffuse aching and fatigue provoked by high fat intake, fasting, or prolonged exertion. Muscle biopsy revealed myopathic features and a deficiency (33% of control) of CPT II activity with elevated palmitoyl carnitine. Proton MRS of the soleus muscle was performed using a 1.5 Tesla scanner before and during dietary therapy. Proton MRS revealed shortening of the transverse relaxation time (T2), consistent with increased acetylation of the carnitine pool. The symptoms resolved completely by treatment with frequent feedings of a high carbohydrate diet low in long chain fatty acids supplemented with medium chain triglycerides and L-carnitine. Recovery of normal muscle MRS and carnitine T2 relaxation was documented by the third month of therapy. Proton MRS is a novel, potentially useful, and readily available adjunct in the diagnosis and therapeutic monitoring of muscle CPT II deficiency.

Simple determination of betaine, l-carnitine and choline in human urine using self-packed column and column-switching ion chromatography with nonsuppressed conductivity detection.

Science.gov (United States)

Wei, Dan; Zhu, Yan; Guo, Ming

2018-02-01

A sequential online extraction, clean-up and separation system for the determination of betaine, l-carnitine and choline in human urine using column-switching ion chromatography with nonsuppressed conductivity detection was developed in this work. A self-packed pretreatment column (50 × 4.6 mm, i.d.) was used for the extraction and clean-up of betaine, l-carnitine and choline. The separation was achieved using self-packed cationic exchange column (150 × 4.6 mm, i.d.), followed by nonsuppressed conductivity detection. Under optimized experimental conditions, the developed method presented good analytical performance, with excellent linearity in the range of 0.60-100 μg mL -1 for betaine, 0.75-100 μg mL -1 for l-carnitine and 0.50-100 μg mL -1 for choline, with all correlation coefficients (R 2 ) >0.99 in urine. The limits of detection were 0.15 μg mL -1 for betaine, 0.20 μg mL -1 for l-carnitine and 0.09 μg mL -1 for choline. The intra- and inter-day accuracy and precision for all quality controls were within ±10.32 and ±9.05%, respectively. Satisfactory recovery was observed between 92.8 and 102.0%. The validated method was successfully applied to the detection of urinary samples from 10 healthy people. The values detected in human urine using the proposed method showed good agreement with the measurement reported previously. Copyright © 2017 John Wiley & Sons, Ltd.

Amino acid composition in parenteral nutrition: what is the evidence?

Science.gov (United States)

Yarandi, Shadi S.; Zhao, Vivian M.; Hebbar, Gautam; Ziegler, Thomas R.

2011-01-01

Purpose of review Complete parenteral nutrition solutions contain mixed amino acid products providing all nine essential amino acids and a varying composition of nonessential amino acids. Relatively little rigorous comparative efficacy research on altered parenteral nutrition amino acid composition has been published in recent years. Recent findings Limited data from randomized, double-blind, adequately powered clinical trials to define optimal doses of total or individual amino acids in parenteral nutrition are available. An exception is the growing number of studies on the efficacy of glutamine supplementation of parenteral nutrition or given as a single parenteral agent. Parenteral glutamine appears to confer benefit in selected patients; however, additional data to define optimal glutamine dosing and the patient subgroups who may most benefit from this amino acid are needed. Although some promising studies have been published, little data are available in the current era of nutrition support on the clinical efficacy of altered doses of arginine, branched chain amino acids, cysteine, or taurine supplementation of parenteral nutrition. Summary Despite routine use of parenteral nutrition, surprisingly little clinical efficacy data are available to guide total or specific amino acid dosing in adult and pediatric patients requiring this therapy. This warrants increased attention by the research community and funding agencies to better define optimal amino acid administration strategies in patient subgroups requiring parenteral nutrition. PMID:21076291

Kinetic compartmental analysis of carnitine metabolism in the dog

International Nuclear Information System (INIS)

Rebouche, C.J.; Engel, A.G.

1983-01-01

This study was undertaken to quantitate the dynamic parameters of carnitine metabolism in the dog. Six mongrel dogs were given intravenous injections of L-[methyl-3H]carnitine and the specific radioactivity of carnitine was followed in plasma and urine for 19-28 days. The data were analyzed by kinetic compartmental analysis. A three-compartment, open-system model [(a) extracellular fluid, (b) cardiac and skeletal muscle, (c) other tissues, particularly liver and kidney] was adopted and kinetic parameters (carnitine flux, pool sizes, kinetic constants) were derived. In four of six dogs the size of the muscle carnitine pool obtained by kinetic compartmental analysis agreed (+/- 5%) with estimates based on measurement of carnitine concentrations in different muscles. In three of six dogs carnitine excretion rates derived from kinetic compartmental analysis agreed (+/- 9%) with experimentally measured values, but in three dogs the rates by kinetic compartmental analysis were significantly higher than the corresponding rates measured directly. Appropriate chromatographic analyses revealed no radioactive metabolites in muscle or urine of any of the dogs. Turnover times for carnitine were (mean +/- SEM): 0.44 +/- 0.05 h for extracellular fluid, 232 +/- 22 h for muscle, and 7.9 +/- 1.1 h for other tissues. The estimated flux of carnitine in muscle was 210 pmol/min/g of tissue. Whole-body turnover time for carnitine was 62.9 +/- 5.6 days (mean +/- SEM). Estimated carnitine biosynthesis ranged from 2.9 to 28 mumol/kg body wt/day. Results of this study indicate that kinetic compartmental analysis may be applicable to study of human carnitine metabolism

Automated chemoenzymatic synthesis of no-carrier-added [carbonyl-11C]propionyl L-carnitine for pharmacokinetic studies

International Nuclear Information System (INIS)

Davenport, R.J.; Pike, V.W.; Dowsett, K.; Turton, D.R.; Poole, K.

1997-01-01

Propionyl-L-carnitine (PLC) is under development as a therapeutic for the treatment of peripheral artery disease, coronary heart disease and chronic heart failure. Three methods were examined for labelling PLC in its propionyl group with positron-emitting carbon-11 (t 1/2 = 20.3 min), one chemical and two chemoenzymatic. The former was based on the preparation of [ 11 C]propionyl chloride as labelling agent via 11 C-carboxylation of ethylmagnesium bromide with cyclotron-produced [ 11 C]carbon dioxide and subsequent chlorination. Reaction of carrier-added [ 11 C]propionyl chloride with L-carnitine in trifluoroacetic acid gave [ 11 C]PLC in 12% radiochemical yield (decay-corrected) from cyclotron-produced [ 11 C]carbon dioxide. However, the radiosynthesis was unsuccessful at the no-carrier added (NCA) level of specific radioactivity. [ 11 C]Propionate, as a radioactive precursor for chemoenzymatic routes, was prepared via carboxylation of ethylmagnesium bromide with [ 11 C]carbon dioxide and hydrolysis. NCA [ 11 C]PLC was prepared in 68 min in 14% radiochemical yield (decay-corrected) from [ 11 C]propionate via sequential conversions catalysed by acetate kinase, phosphotransacetylase and carnitine acetyltransferase. A superior chemoenzymatic synthesis of NCA [ 11 C]PLC was developed, based on the use of a novel supported Grignard reagent for the synthesis of [ 11 C]propionate and conversions by S-acetyl-CoA synthetase and carnitine acetyltransferase. This gave an overall radiochemical yield of 30-48% (decay-corrected). This synthesis was automated for radiation safety and provides pure NCA [ 11 C]PLC in high radioactivities ready for intravenous administration within 25 min from radionuclide production. The [ 11 C]PLC is suitable for pharmacokinetic studies in human subjects with PET and the elucidation of the fate of the propionyl group of PLC in vivo. (Author)

Protective Role of L- Carnitine and Zinc against γ-Radiation induced Cardiac and testicular Disorders in Albino Rats

International Nuclear Information System (INIS)

Ramadan, F. L.; Abdel-Monem, D.D.; Ismail, N.H.

2013-01-01

L-Carnitine is a dipeptide amino acid necessary for fat metabolism, it provides energy by transporting long-chain fatty acids to mitochondria to act as a fuel and it is considered a powerful antioxidant. In addition, zinc is an essential mineral which helps to increase the secretion of male sex hormones and raises the sperm count, so its combination with L-carnitine is useful for the fertility process. The present study aims to evaluate the potency of L-carnitine and zinc as radio- protective and curative agent pre and after exposure to γ-radiation through biochemical, histological, morphological abnormalities of sperms and DNA damage in the sperms induced by γ-irradiation by comet assay. Animals received L-carnitine (LC) and zinc (Zn) orally at the dose 9.45 mg/100 gm body wt./day for successive 20 days and then exposed to whole body gamma radiation at the dose 4 Gy (1 Gy for 4 days, day after day) on the 7th day from treatment with antioxidant. Histological examinations of heart and testis tissues showed that administration of LC and Zn have attenuated radiation induced damage and improved tissues architecture. Moreover, the observed amelioration in the tissues was accompanied by a remarkable decrease of their lipid peroxide levels (malondialdehyde (MDA)), together with an increase in glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) activities. Hormonal determinations of serum testosterone (T), follicular stimulating hormone (FSH) and luteinizing hormone (LH) which carried out for fertility assessment showed that whole body γ-irradiation of rats induced significant decrease in serum testosterone while FSH and LH were significantly increased as compared with control group. On the other hand, irradiation caused significant elevation in the total number of abnormal head, and / or tail of sperms in comparison to the control rats. The comet assay showed that exposure to γ-radiation induced DNA damage of sperms (tail moment values).

Determination of betaine, l-carnitine, and choline in human urine using a self-packed column and column-switching ion chromatography with nonsuppressed conductivity detection.

Science.gov (United States)

Wei, Dan; Liu, Junwei; Guo, Ming; Zhu, Yan

2017-11-01

A simple method for the determination of betaine, l-carnitine, and choline in human urine was developed based on column-switching ion chromatography coupled with nonsuppressed conductivity detection by using a self-packed column. A pretreatment column (50 mm × 4.6 mm, id) packed with poly(glycidyl methacrylate-divinylbenzene) microspheres was used for the extraction and cleanup of analytes. Chromatographic separation was achieved within 10 min on a cationic exchange column (150 mm × 4.6 mm, id) using maleic anhydride modified poly(glycidyl methacrylate-divinylbenzene) as the particles for packing. The detection was performed by ion chromatography with nonsuppressed conductivity detection. Parameters including column-switching time, eluent type, flow rates of eluent, and interfering effects were optimized. Linearity (r 2 ≥ 0.99) was obtained for the concentration range of 0.50-100, 0.75-100, and 0.25-100 μg/mL for betaine, l-carnitine, and choline, respectively. Detection limits were 0.12, 0.20, and 0.05 μg/mL for betaine, l-carnitine, and choline, respectively. The intra- and interday accuracy and precision for all quality controls were within ±10.11%. Satisfactory recovery was observed between 92.5 and 105.0%. The validated method was successfully applied for the determination of betaine, l-carnitine, and choline in urine samples from healthy people. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plasma carnitine concentrations after chronic alcohol intoxication 

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Alina Kępka

2013-05-01

after chronic alcohol intoxication is caused by the uptake of blood carnitine by tissues such as liver or muscles. In alcoholics the supplementation of carnitine is recommended in the case of a low level of plasma carnitine.

New perspective for nutritional support of cancer patients: Enteral/parenteral nutrition

Science.gov (United States)

AKBULUT, GAMZE

2011-01-01

Cancer and its treatment result in severe biochemical and physiological alterations associated with a deterioration of quality of life (QoL). Cancer-related malnutrition may evolve into cancer cachexia due to complex interactions between pro-inflammatory cytokines and the host metabolism. Depending on the type of cancer treatment (either curative or palliative), the clinical condition of the patient and nutritional status, adequate and patient-tailored nutritional intervention should be prescribed (diet counseling, oral supplementation, enteral or total parenteral nutrition). Nutritional support has been widely advocated as adjunctive therapy for a variety of underlying illnesses, including surgery and medical oncotherapy (radiation or chemotherapy for cancer). Glutamine, n-3 fatty acids and probiotics/prebiotics are therapeutic factors that potentially modulate gastrointestinal toxicity related to cancer treatments. Enteral and parenteral nutrition may help improve patient survival, functional status and QoL, yet the benefits appear to be primarily limited to patients with good functional status and with gastrointestinal disease affecting nutritional intake. Parenteral nutrition offers the possibility of increased or maintenance of the nutrient intake in patients for whom normal food intake is inadequate and for whom enteral nutrition is not feasible, is contraindicated or is not accepted by the patient. This article reviews evidence on issues relevant to enteral and parenteral nutrition in patients with cancer. PMID:22977559

Effect of different levels of vitamin C and L-carnitine on performance and some blood and immune parameters of broilers under heat stress.

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Saeed Mirzapor Sarab

2016-08-01

Full Text Available Introduction: High Environmental temperature during summer months which leading to heat stress, is of great concern in all types of poultry production. Feed consumption, growth rate, hatchability, mortality, and other important traits governing the prosperity of the industry are adversely affected by severe heat stress. Literature suggests that the advantages of dietary L-carnitine and ascorbic acid have been particularly apparent under heat stress (8. L- carnitine is a zwitterionic compound synthesized in vivo from lysine and methonine, and is essential for the transport of long – chain fatty acid across the inner mitochondria membrane for β – oxidation and remove toxic accumulations of fatty acids from mitochondria (18. Vitamin C is an effective antioxidant, which is essential for collagen synthesis, helps to maintain various enzymes in their required reduced form, and participates in the biosynthesis of carnitine, norepinephrine and certain neuroendocrine peptides (11. Invertebrates, insects, most fishes, some birds, guinea-pigs, bats and primates are not able to synthesize ascorbic acid. Thus, these animals must depend upon a dietary supply of this vitamin C. In poultry, ascorbic acid has been demonstrated to be essential for growth (25. Materials and Methods: In this study, 396 of Ross 308 broiler chicks in a completely randomized design with 3 × 3 factorial arrangement with 4 replicates of 11 chicks in each replicate were used for 42 days. Treatments were 3 levels of vitamin C (0, 250 and 500 mg/ kg and 3 levels of L-carnitine (0, 50 and 100 mg kg. In the first 3 weeks of breeding, broilers were under normal temperature and heat stress was done from the beginning of forth week. Feed and water were provided ad-libitum. Performance parameters were recorded weekly. The 0.5 mL suspension of 5% SRBC was injected at 28 and 35 days of age in one bird of each pen. To determine the antibody titer, blood was collected 1 week after each

Automated chemoenzymatic synthesis of no-carrier-added [carbonyl-{sup 11}C]propionyl L-carnitine for pharmacokinetic studies

Energy Technology Data Exchange (ETDEWEB)

Davenport, R.J.; Pike, V.W.; Dowsett, K.; Turton, D.R.; Poole, K. [Hammersmith Hospital, London (United Kingdom). MRC Cyclotron Unit

1997-07-30

Propionyl-L-carnitine (PLC) is under development as a therapeutic for the treatment of peripheral artery disease, coronary heart disease and chronic heart failure. Three methods were examined for labelling PLC in its propionyl group with positron-emitting carbon-11 (t{sub 1/2} = 20.3 min), one chemical and two chemoenzymatic. The former was based on the preparation of [{sup 11}C]propionyl chloride as labelling agent via {sup 11}C-carboxylation of ethylmagnesium bromide with cyclotron-produced [{sup 11}C]carbon dioxide and subsequent chlorination. Reaction of carrier-added [{sup 11}C]propionyl chloride with L-carnitine in trifluoroacetic acid gave [{sup 11}C]PLC in 12% radiochemical yield (decay-corrected) from cyclotron-produced [{sup 11}C]carbon dioxide. However, the radiosynthesis was unsuccessful at the no-carrier added (NCA) level of specific radioactivity. [{sup 11}C]Propionate, as a radioactive precursor for chemoenzymatic routes, was prepared via carboxylation of ethylmagnesium bromide with [{sup 11}C]carbon dioxide and hydrolysis. NCA [{sup 11}C]PLC was prepared in 68 min in 14% radiochemical yield (decay-corrected) from [{sup 11}C]propionate via sequential conversions catalysed by acetate kinase, phosphotransacetylase and carnitine acetyltransferase. A superior chemoenzymatic synthesis of NCA [{sup 11}C]PLC was developed, based on the use of a novel supported Grignard reagent for the synthesis of [{sup 11}C]propionate and conversions by S-acetyl-CoA synthetase and carnitine acetyltransferase. This gave an overall radiochemical yield of 30-48% (decay-corrected). This synthesis was automated for radiation safety and provides pure NCA [{sup 11}C]PLC in high radioactivities ready for intravenous administration within 25 min from radionuclide production. The [{sup 11}C]PLC is suitable for pharmacokinetic studies in human subjects with PET and the elucidation of the fate of the propionyl group of PLC in vivo. (Author).

Glycine propionyl-L-carnitine produces enhanced anaerobic work capacity with reduced lactate accumulation in resistance trained males

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Orem Ihsan

2009-04-01

Full Text Available Abstract Background Recent research has indicated that short term administration of glycine propionyl-L-carnitine (GPLC significantly elevates levels of nitric oxide metabolites at rest and in response to reactive hyperaemia. However, no scientific evidence exists that suggests such supplementation enhances exercise performance in healthy, trained individuals. The purpose of this study was to examine the effects of GPLC on the performance of repeated high intensity stationary cycle sprints with limited recovery periods in resistance trained male subjects. Methods In a double-blind, placebo-controlled, cross-over design, twenty-four male resistance trained subjects (25.2 ± 3.6 years participated in two test sessions separated by one week. Testing was performed 90 minutes following oral ingestion of either 4.5 grams GPLC or 4.5 grams cellulose (PL, in randomized order. The exercise testing protocol consisted of five 10-second Wingate cycle sprints separated by 1-minute active recovery periods. Peak (PP and mean values (MP of sprint power output and percent decrement of power (DEC were determined per bout and standardized relative to body masss. Heart rate (HR and blood lactate (LAC were measured prior to, during and following the five sprint bouts. Results Significant main effects (p Conclusion These findings indicate that short-term oral supplementation of GPLC can enhance peak power production in resistance trained males with significantly less LAC accumulation.

Screening of carnitine and biotin deficiencies on tandem mass spectrometry.

Science.gov (United States)

Hagiwara, Shin-Ichiro; Kubota, Mitsuru; Nambu, Ryusuke; Kagimoto, Seiichi

2017-04-01

It is important to assess pediatric patients for nutritional deficiency when they are receiving specific interventions, such as enteral feeding. We focused on measurement of C0 and 3-hydroxyisovalerylcarnitine (C5-OH) with tandem mass spectrometry (MS/MS), which is performed as part of the newborn mass screening. The purpose of this study was to investigate the usefulness of MS/MS for screening carnitine and biotin deficiencies. Forty-two children (24 boys, 18 girls) were enrolled between December 2013 and December 2015. Blood tests, including measurement of serum free carnitine via the enzyme cycling method, and acylcarnitine analysis on MS/MS of dried blood spot (DBS), were performed for the evaluation of nutrition status. Median patient age was 2 years (range, 2 months-14 years). Mean serum free carnitine was 41.8 ± 19.2 μmol/L. In six of the 42 patients, serum free carnitine was 1.00 nmol/L. Therapy-resistant eczema was improved by treatment with additional biotin and a non-hydrolyzed formula. C0 and C5-OH, measured on MS/MS of DBS, were useful for screening carnitine and biotin deficiencies. © 2016 Japan Pediatric Society.

Severe Hypothyroidism From Iodine Deficiency Associated With Parenteral Nutrition.

Science.gov (United States)

Golekoh, Marjorie C; Cole, Conrad R; Jones, Nana-Hawa Yayah

2016-11-01

Parenteral nutrition is crucial for supply of nutrients in children who cannot tolerate a full enteral diet. In the United States, it is not standard of care to give iodine to children dependent on parenteral nutrition, hence iodine is not routinely included in the micronutrient package. Herein, we present a case of a boy with hypothyroidism secondary to iodine deficiency after prolonged exclusive use of parenteral nutrition. Our case highlights the importance of screening for iodine deficiency and administering timely iodine supplementation in these at-risk children to prevent iatrogenic hypothyroidism. © 2015 American Society for Parenteral and Enteral Nutrition.

Synthesis of [methyl-{sup 14}C]crotonobetaine from DL-[methyl-{sup 14}C]carnitine

Energy Technology Data Exchange (ETDEWEB)

Loester, H.; Seim, H. [Leipzig Univ. (Germany). Inst. of Clinical Chemistry and Pathobiochemistry

1996-02-01

The causes of carnitine deficiency syndromes are not completely understood, but decomposition of L-carnitine in vivo is likely to be involved. Carnitine is metabolized to {gamma}-butyrobetaine, and crotonobetaine is probably an intermediate in this pathway. To validate experimentally the precursor-product relationship between the three physiologically occuring {gamma}-betaines - L-carnitine, crotonobetaine, {gamma}-butyrobetaine - labelling with stable or radioactive isotopes became necessary. Methyl-labelled carnitine isomers (L(-)-, D(+)- or DL-) or {gamma}-butyrobetaine can be easily synthesized by methylation of 4-amino-3-hydroxybutyric acid isomers or 4-aminobutyric acid, respectively. Because of problems with the 4-aminocrotonic acid, we synthesized labelled crotonbetaine from labelled carnitine. Thus, DL-[methyl-{sup 14}C]carnitine was dehydrated by reaction with concentrated sulfuric acid. After removal of the latter the products were separated and purified by ion exchange chromatography on DOWEX 50 WX8 (200 - 400 mesh) and gradient elution with hydrochloric acid. In addition to the labelled main product [methyl-{sup 14}C]crotonobetaine (yield about 50 %), [methyl-{sup 14}C]glycine betaine and [methyl-{sup 14}C]acetonyl-trimethylammonium (ATMA) were formed. The end products were identified by combined thin layer chromatography/autoradiography and quantified by liquid scintillation counting. (Author).

Effect of L-Carnitine on Skeletal Muscle Lipids and Oxidative Stress in Rats Fed High-Fructose Diet

Directory of Open Access Journals (Sweden)

Panchamoorthy Rajasekar

2007-01-01

Full Text Available There is evidence that high-fructose diet induces insulin resistance, alterations in lipid metabolism, and oxidative stress in rat tissues. The purpose of this study was to evaluate the effect of L-carnitine (CAR on lipid accumulation and peroxidative damage in skeletal muscle of rats fed high-fructose diet. Fructose-fed animals (60 g/100 g diet displayed decreased glucose/insulin (G/I ratio and insulin sensitivity index (ISI0,120 indicating the development of insulin resistance. Rats showed alterations in the levels of triglycerides, free fatty acids, cholesterol, and phospholipids in skeletal muscle. The condition was associated with oxidative stress as evidenced by the accumulation of lipid peroxidation products, protein carbonyls, and aldehydes along with depletion of both enzymic and nonenzymic antioxidants. Simultaneous intraperitoneal administration of CAR (300 mg/kg/day to fructose-fed rats alleviated the effects of fructose. These rats showed near-normal levels of the parameters studied. The effects of CAR in this model suggest that CAR supplementation may have some benefits in patients suffering from insulin resistance.

Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal piglets

DEFF Research Database (Denmark)

Bartholome, Anne L; Albin, David M; Baker, David H

2004-01-01

BACKGROUND: Supplementation of total parenteral nutrition (TPN) with a mixture of short-chain fatty acids (SCFA) enhances intestinal adaptation in the adult rodent model. However, the ability and timing of SCFA to augment adaptation in the neonatal intestine is unknown. Furthermore, the specific...

Aminocarnitine and acylaminocarnitines: Carnitine acyltransferase inhibitors affecting long-chain fatty acid and glucose metabolism

International Nuclear Information System (INIS)

Clark, D.J.

1989-01-01

DL-Aminocarnitine (DL-3-amino-4-trimethylaminobutyrate) and the acylaminocarnitines acetyl-, decanoyl- and palmitoyl-DL-aminocarnitine have been synthesized and tested as inhibitors of carnitine palmitoyl-transferase and carnitine acetyltransferase in vitro and in vivo. Acetyl-DL-aaminocarnitine is the most potent reversible inhibitor of carnitine acetyltransferase reported to date, and is competitive with respect to acetyl-L-carnitine. Mice given acetyl-DL-aminocarnitine metabolize [U- 14 C]acetyl-L-carnitine at about 60% of the rate of control mice. Palmitoyl-DL-aminocarnitine is the most potent reversible inhibitor of carnitine palmitoyltransferase reported to date. Decanoyl-DL-aminocarnitine and DL-aminocarnitine are also very potent inhibitors; all compounds inhibit the catabolism of [ 14 C]palmitate to 14 CO 2 in intact mice by at least 50%. Carnitine palmitoyltransferase controls the entry of long-chain fatty acids into the mitochondrial matrix for β-oxidation. The inhibition of carnitine palmitoyltransferase by aminocarnitine or acylaminocarnitines in vivo prevents or reverses ketogenesis in fasted mice, and causes the reversible accumulation of triglycerides in liver, kidney and plasma. Administration of DL-aminocarnitine to streptozotocindiabetic mice lowers plasma glucose levels and improves the glucose tolerance test

Impact of Early Parenteral Nutrition on Metabolism and Kidney Injury

OpenAIRE

Gunst, Jan; Vanhorebeek, Ilse; Casaer, Michaël P.; Hermans, Greet; Wouters, Pieter J.; Dubois, Jasperina; Claes, Kathleen; Schetz, Miet; Van den Berghe, Greet

2013-01-01

A poor nutritional state and a caloric deficit associate with increased morbidity and mortality, but a recent multicenter, randomized controlled trial found that early parenteral nutrition to supplement insufficient enteral nutrition increases morbidity in the intensive care unit, including prolonging the duration of renal replacement therapy, compared with withholding parenteral nutrition for 1 week. Whether early versus late parenteral nutrition impacts the incidence and recovery of AKI is ...

Parenteral Nutrition-Associated Liver Disease: The Role of the Gut Microbiota.

Science.gov (United States)

Cahova, Monika; Bratova, Miriam; Wohl, Petr

2017-09-07

Parenteral nutrition (PN) provides life-saving nutritional support in situations where caloric supply via the enteral route cannot cover the necessary needs of the organism. However, it does have serious adverse effects, including parenteral nutrition-associated liver disease (PNALD). The development of liver injury associated with PN is multifactorial, including non-specific intestine inflammation, compromised intestinal permeability, and barrier function associated with increased bacterial translocation, primary and secondary cholangitis, cholelithiasis, short bowel syndrome, disturbance of hepatobiliary circulation, lack of enteral nutrition, shortage of some nutrients (proteins, essential fatty acids, choline, glycine, taurine, carnitine, etc.), and toxicity of components within the nutrition mixture itself (glucose, phytosterols, manganese, aluminium, etc.). Recently, an increasing number of studies have provided evidence that some of these factors are directly or indirectly associated with microbial dysbiosis in the intestine. In this review, we focus on PN-induced changes in the taxonomic and functional composition of the microbiome. We also discuss immune cell and microbial crosstalk during parenteral nutrition, and the implications for the onset and progression of PNALD. Finally, we provide an overview of recent advances in the therapeutic utilisation of pro- and prebiotics for the mitigation of PN-associated liver complications.

Protective Role of Carnitine against the Harmful Biological Effects of Paracetamol and Radiation Exposure in Male Albino Rats

International Nuclear Information System (INIS)

Abd El Rahman, N.A.

2012-01-01

L-carnitine, a natural component of mammalian tissue, is a necessary factor in the utilization of long-chain fatty acids to produce energy. Furthermore it has been shown to protect cells from per oxidative stress. The objective of the present study was to evaluate the efficacy of L-carnitine on hepatotoxicity and nephrotoxicity induced by paracetamol, γ-radiation, and paracetamol + γ-radiation. Male albino rats were divided into 8 groups. 1-Control group: rats not subject to any treatment, 2-Carnitine group: rats received L-carnitine (0.5 ml/Kg body weight) via intraperitoneal injection during 21 days, 3-Paracetamol group: rats received paracetamol (50 mg/kg body) via intraperi-toneal injection during 21 days, 4- Carnitine + Paracetamol group: rats received L-carnitine in parallel to paracetamol treatment, 5- Radiation groups: rats were whole body gamma irradiated with 7 Gy, 6- Carnitine + Radiation group: rats received L-carnitine for 21 days before whole body gamma irradiation with 7Gy, 7- Paracetamol + Radiation group: rats received paracetamol during 21 days before whole body gamma irradiation, 8- Carnitine + Paracetamol + Radiation group: rats received L-carnitine parallel to paracetamol during 21 days before whole body gamma irradiation.The results demonstrated that rats receiving paracetamol, as well as whole body gamma irradiated rats and rats receiving paracetamol and irradiated showed a significant increase of alanine amino transferase (ALT), aspartate amino transferase (AST), and alkaline phosphatase (ALP) activities, and a significant decrease of gamma-glutamyl transpeptidase (GGT) activity indicating liver injury. A significant increase of urea, creatinine and uric acid levels was recorded also indicating kidney damage. Alteration in liver and kidney functions was accompanied by a significant increase in the content of thiobarbituric acid reactive substances (TBARS) associated with a significant decrease in glutathione (GSH) content and superoxide

Primary Carnitine Deficiency

DEFF Research Database (Denmark)

Rasmussen, Jan; Hougaard, David M; Sandhu, Noreen

2017-01-01

Primary carnitine deficiency (PCD) causes low levels of carnitine in patients potentially leading to metabolic and cardiac symptoms. Newborn screening for PCD is now routine in many countries by measuring carnitine levels in infants. In this study we report Apgar scores, length and weight...... scores, length and weight compared to controls. Newborns with PCD and newborns born to mothers with PCD had significantly lower levels of free carnitine (fC0) than controls. Screening algorithms focusing only on fC0 had a high rate of detection of newborns with PCD. Sample collection 4-9 days after birth...

Glutamine supplementation of parenteral nutrition does not improve intestinal permeability, nitrogen balance, or outcome in newborns and infants undergoing digestive-tract surgery: results from a double-blind, randomized, controlled trial

NARCIS (Netherlands)

E.W. Steyerberg (Ewout); F.W.J. Hazebroek (Frans); M. Mourik; G.J.J.M. Borsboom (Gerard); T. Rietveld (Trinet); J.G.M. Huijmans (Jan); D. Tibboel (Dick); M.J.I.J. Albers (Marcel)

2005-01-01

textabstractOBJECTIVE: To assess the effect of isocaloric isonitrogenous parenteral glutamine supplementation on intestinal permeability and nitrogen loss in newborns and infants after major digestive-tract surgery. SUMMARY BACKGROUND DATA: Glutamine supplementation in critically

Effects of L-Carnitine Theraphy On Methabolic and Biochemical Changes Caused By Propofol Infusion in Rabbits Undergoing Mechanical Ventilation

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Savaş Yılbaş

2011-08-01

Full Text Available Objective: Increased lipid mass in the body secondary to long term and high doses of propofol infusion may cause carnitine deficiency. In this study; we aimed to investigate the effects of carnitine, given for treatment purposes and have not been analyzed before, during high doses of propofol infusion in rabbits. Materials and Methods: Following ethical committee approval; 2500-3500 grams weight, 3-4 months-old, healthy, male, white 20 New Zealand rabbits were included in the study. The rabbits were premedicated with xsilazine and atropine. After the preparation period including tracheostomy, monitorization, catheterization of the ear arteries and veins and urinary vesical; basal blood samples for biochemical and metabolic parameters included in the study were taken and rabbits were divided into 4 groups, 5 rabbits in each,randomly (Group P, Group PC, Group S, Group SC. For sedation 20 mg/kg/h propofol infusion was given to Group P, 20 mg/kg/h propofol and 100 mg/kg L-carnitine infusions were given simultaneously to Group PC, sevoflurane for sedation was given to Group S, sevoflurane and L-carnitine infusion were given simultaneously to Group SC. Their sedation levels were evaluated every 30 minutes and their vital signs were reported every 15 minutes. Every 2 hours arterial blood gases analysis and every 12 hours electrolytes and metabolic parameters were repeated. Euthanasia with high doses (60 mg/kg of ketamin is performed for rabbits that were alive at the end of 24 hours. Results: All groups were similar in weight, vital parameters, all parameters searched in arterial blood gases, life time, liver enzymes, lactate dehydrogenase, serum electrolytes, creatine kinase and renal function tests (p>0.05. However; amylase levels before death or euthanasia were lower in Group PC compared to other groups;myoglobin and CK-MB levels in Group P were higher compared to other groups; cholesterol levels at 12th hour, before death or euthanasia were higher

Effects of L-Carnitine and Taurine on associated biochemical ...

African Journals Online (AJOL)

carnitine and taurine in healthy and alloxan induced diabetes mellitus in rats. Results showed that diabetic rats had significant increase in the levels of plasma glucose, malondialdehyde (MDA), urea, creatinine and the activity of serum asparate ...

Correlation between L-Carnitine and alpha-1, 4-glucosidase activity in the semen of normal, infertile and vasectomized men.

Science.gov (United States)

Tremblay, R R; Chapdelaine, P; Roy, R; Thabet, M

1982-01-01

The semen content of L-carnitine and of alpha 1, 4-glucosidase has been measured in subjects consulting for evaluation of their fertility. A close correlation (r=0.684) was found between both parameters over the range of azoospermia to normal zoospermia. A significant number of patients with oligo or azoospermia displayed normal values of L-carnitine and of alpha-1, 4-glucosidase while approximately 50% showed levels in the low spectrum of vasectomized men. On the basis of these findings, an obstructive pathology at epididymal or vas deferens level was established by vasography and/or bilateral scrotal exploration in 9 patients with azoospermia. These 2 epididymal markers might thus be useful in the hands of the practicing andrologist who has to determine precisely the site of a dysfunction in the reproductive system which leads to infertility.

Carnitine biosynthesis in mammals

NARCIS (Netherlands)

Vaz, Frédéric M.; Wanders, Ronald J. A.

2002-01-01

Carnitine is indispensable for energy metabolism, since it enables activated fatty acids to enter the mitochondria, where they are broken down via beta-oxidation. Carnitine is probably present in all animal species, and in numerous micro-organisms and plants. In mammals, carnitine homoeostasis is

Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging

OpenAIRE

Janson, Michael

2006-01-01

Dietary supplements at high doses as part of medical therapy have been controversial, but the evidence suggests that they play a significant role in prevention and treatment of diseases as well as protection from accelerated aging that results from oxygen free-radical damage, inflammation, and glycation. This literature review examines several supplements that have documented roles in medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid, chromium, L-carnitine, and quer...

Effect of dietary lipid, carnitine and exercise on lipid profile in rat blood, liver and muscle.

Science.gov (United States)

Karanth, Jyothsna; Jeevaratnam, K

2009-09-01

Aim of this study was to investigate the influence of physical exercise on effects of the daily intake of vegetarian diet of either vegetable hydrogenated fat (HF) or peanut oil (PO) with or without carnitine on the lipid profile. Eight groups of male Wistar rats were fed HF-diet (4 groups) or PO-diet (4 groups), with or without carnitine for 24 weeks. One group for each diet acted as sedentary control while the other groups were allowed swimming for 1 hr a day, 6 days/week, for 24 weeks. Plasma triglycerides (TG), total cholesterol (TC), HDL-cholesterol, free fatty acids (FFA), liver and thigh muscle glycogen, total fat (TF), TG, TC and FFA were analyzed. HF-fed rats showed significantly increased plasma TC, VLDL+LDL-cholesterol and TG compared to PO-fed rats, wherein a lowered plasma TC, TG levels in all the groups with significantly increased liver cholesterol and decreased muscle cholesterol was observed. Physical exercise of moderate intensity reduced plasma TC and TG accompanied by significantly reduced tissue TG and cholesterol while FFA and glycogen increased in all the groups. The influence of exercise was less pronounced in carnitine supplemented rats since carnitine could significantly reduce TG in plasma and tissues of sedentary rats. Results from the present study showed that the intake of HF diet significantly increased the plasma and tissue lipid profile and MUFA-rich diet or carnitine supplementation and/or exercise may ameliorate the deleterious effects of HF.

Carnitine transport and fatty acid oxidation.

Science.gov (United States)

Longo, Nicola; Frigeni, Marta; Pasquali, Marzia

2016-10-01

Carnitine is essential for the transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent β-oxidation. It can be synthesized by the body or assumed with the diet from meat and dairy products. Defects in carnitine biosynthesis do not routinely result in low plasma carnitine levels. Carnitine is accumulated by the cells and retained by kidneys using OCTN2, a high affinity organic cation transporter specific for carnitine. Defects in the OCTN2 carnitine transporter results in autosomal recessive primary carnitine deficiency characterized by decreased intracellular carnitine accumulation, increased losses of carnitine in the urine, and low serum carnitine levels. Patients can present early in life with hypoketotic hypoglycemia and hepatic encephalopathy, or later in life with skeletal and cardiac myopathy or sudden death from cardiac arrhythmia, usually triggered by fasting or catabolic state. This disease responds to oral carnitine that, in pharmacological doses, enters cells using the amino acid transporter B(0,+). Primary carnitine deficiency can be suspected from the clinical presentation or identified by low levels of free carnitine (C0) in the newborn screening. Some adult patients have been diagnosed following the birth of an unaffected child with very low carnitine levels in the newborn screening. The diagnosis is confirmed by measuring low carnitine uptake in the patients' fibroblasts or by DNA sequencing of the SLC22A5 gene encoding the OCTN2 carnitine transporter. Some mutations are specific for certain ethnic backgrounds, but the majority are private and identified only in individual families. Although the genotype usually does not correlate with metabolic or cardiac involvement in primary carnitine deficiency, patients presenting as adults tend to have at least one missense mutation retaining residual activity. This article is part of a Special Issue entitled: Mitochondrial Channels edited by Pierre Sonveaux, Pierre Maechler

l-carnitine as a Potential Additive in Blood Storage Solutions: A Study on Erythrocytes

OpenAIRE

Soumya, R.; Carl, H.; Vani, R.

2015-01-01

Erythrocytes undergo various changes during storage (storage lesion) that in turn reduces their functioning and survival. Oxidative stress plays a major role in the storage lesion and antioxidants can be used to combat this stress. This study elucidates the effects of l-carnitine (LC) on erythrocytes of stored blood. Blood was obtained from male Wistar rats and stored (4 °C) for 20 days in CPDA-1 (citrate phosphate dextrose adenine) solution. Samples were divided into–(i) controls (ii) LC 10 ...

The Protective Effect of Proponyl-L-Carnitine Against Ultrastructural Alterations in Cardiac Muscle of Irradiated and / or diabetic Rats

International Nuclear Information System (INIS)

Abu Nour, S.M.; Abdel-Azeem, M.G.; El-Nashar, D.E.M.

2011-01-01

Heart dysfunction in chronic diabetes has been observed to be associated with depressed myofibrillar adenosine triphosphatase activities. Oxidative stress a factor implicated in the heart injury may contribute towards some of these alterations. The present study was designed to evaluate the efficacy of L-carnitine on gamma radiation and diabetes induced oxidative damage in the heart by investigating alterations in the ultrastructural level. Streptozotocin was intraperitoneally injected (i.p) to rats at a dose of 28 mg/Kg b.wt / day for 2 weeks pre-irradiation. In irradiated groups, animals were exposed to 6.5 Gy whole body gamma radiation. L-carnitine was intraperitoneally injected (i.p) to rats at a dose of 250 mg/Kg b.wt/day for 2 weeks pre-irradiation. Animals were sacrificed on the 7th day after irradiation. The results demonstrated that the whole body exposure of rats to ionizing radiation induce oxidative stress which showed alterations on the ultrastructural level included dis organization with mayofibrillolysis relatively intact z-band (Z), fibrosis, swollen mitochondria, apoptotic nuclei and thickened walls of capillaries. In diabetic rats cardio muscle focal loss of myofilaments, also swelling of mitochondria and rupture of sacroplasmic reticulum, apoptotic nuclei with dilation of capillaries were evident. Administration of L-carnitine pre-irradiation has improved the ultrastructural alterations of the heart tissue. It is proposed that the oxidative stress is associated with a deficit in the status of the antioxidant defense system which may play a critical role in subcellular remodeling, calcium-handling abnormalities and subsequent diabetic cardiomyopathy

Activity of D-carnitine and its derivatives on Trypanosoma infections in rats and mice

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Manganaro M.

2003-06-01

Full Text Available Little progress has been made in the treatment of African trypanosomiasis over the past decades. L-carnitine has a major role in glycolysis-based energy supply of blood trypanosomes for it stimulates constant ATP production. To investigate whether administration of the isomer D-carnitine could exert a competitive inhibition on the metabolic pathway of the L-form, possibily resulting in parasite replication inhibition, several formulations of this compound were tested on Trypanosoma lewisi and T. brucei rhodesiense in rodent models. High oral dosages of D-carnitine inner salt and proprionyl-D-carnitine were not toxic to animals and induced about 50 % parasite growth inhibition in reversible, i.e. competitive, fashion. A putative mechanism could be an interference in pyruvate kinase activity and hence ATP production. Considering both, lack of toxicity and inhibitory activity, D-carnitine may have a role in the treatment of African trypanosomiasis, in association with available trypanocidal drugs.

Partial muscle carnitine palmitoyltransferase-A deficiency

Energy Technology Data Exchange (ETDEWEB)

Ross, N.S.; Hoppel, C.L.

1987-01-02

After initiation of ibuprofen therapy, a 45-year-old woman developed muscle weakness and tenderness with rhabdomyolysis, culminating in respiratory failure. A muscle biopsy specimen showed a vacuolar myopathy, and markedly decreased muscle carnitine content and carnitine palmitoyltransferase activity. Following recovery, muscle carnitine content was normal but carnitine palmitoyltransferase activity was still abnormally low. The ratio of palmitoyl-coenzyme A plus carnitine to palmitoylcarnitine oxidation by muscle mitochondria isolated from the patient was markedly decreased. The authors conclude that transiently decreased muscle carnitine content interacted with partial deficiency of carnitine palmitoyltransferase-A to produce rhabdomyolysis and respiratory failure and that ibuprofen may have precipitated the clinical event.

Partial muscle carnitine palmitoyltransferase-A deficiency

International Nuclear Information System (INIS)

Ross, N.S.; Hoppel, C.L.

1987-01-01

After initiation of ibuprofen therapy, a 45-year-old woman developed muscle weakness and tenderness with rhabdomyolysis, culminating in respiratory failure. A muscle biopsy specimen showed a vacuolar myopathy, and markedly decreased muscle carnitine content and carnitine palmitoyltransferase activity. Following recovery, muscle carnitine content was normal but carnitine palmitoyltransferase activity was still abnormally low. The ratio of palmitoyl-coenzyme A plus carnitine to palmitoylcarnitine oxidation by muscle mitochondria isolated from the patient was markedly decreased. The authors conclude that transiently decreased muscle carnitine content interacted with partial deficiency of carnitine palmitoyltransferase-A to produce rhabdomyolysis and respiratory failure and that ibuprofen may have precipitated the clinical event

Serial changes in selected serum constituents in low birth weight infants on peripheral parenteral nutrition with different zinc and copper supplements.

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Lockitch, G; Pendray, M R; Godolphin, W J; Quigley, G

1985-07-01

One hundred and five infants of birth weight 2000 g or less who received peripherally administered parenteral nutrition for periods of three or more weeks, were randomly assigned to groups receiving different amounts of zinc and copper supplement. The blood concentrations of zinc, copper, retinol-binding protein, prealbumin, alkaline phosphatase and aspartate transaminase were followed weekly. Mean serum zinc, retinol-binding protein and prealbumin declined significantly over time while alkaline phosphatase rose. Only the group receiving the highest zinc supplement maintained a mean serum zinc concentration within the normal range at seven weeks. No difference in the protein or enzyme concentrations was found between the different zinc supplement groups. No difference was seen in serum copper or ceruloplasmin between copper dose groups although one intravenous supplement was double that of the other.

O uso da L-carnitina como adjuvante no tratamento da miocardiopatia dilatada em criança com Aids Usage of L-carnitine as adjuvant in the treatment of dilated cardiomyopathy in a child with Aids

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Lourdes Zélia Zanoni

2011-06-01

Full Text Available OBJETIVO: Apresentar a resposta cardiovascular à L-carnitina de um paciente com insuficiência cardíaca congestiva decorrente de miocardiopatia dilatada pelo vírus da imunodeficiência humana. DESCRIÇÃO DO CASO: Criança com quadro clínico de insuficiência cardíaca congestiva grave devido à miocardiopatia dilatada pela síndrome de imunodeficiência adquirida. O tratamento para as manifestações clínicas foi instituído, com pouca resposta clínica. Com objetivo de melhorar o desempenho energético/metabólico dos cardiomiócitos, foi instituída terapia com L-carnitina. Observou-se significativa melhora clínica do paciente, em relação ao desempenho cardíaco, mesmo antes do início do tratamento com os fármacos antirretrovirais. COMENTÁRIOS: A L-carnitina é um composto que facilita o transporte dos ácidos graxos de cadeia longa para dentro da mitocôndria. Nesse caso, o uso da L-carnitina parece ser clinica e bioquimicamente justificado.OBJECTIVE: To present the cardiovascular response to L-carnitine of a patient with congestive heart failure caused by dilated cardiomyopathy and human immunodeficiency virus. CASE DESCRIPTION: Child with a clinical history of severe congestive heart failure due to dilated cardiomyopathy caused by acquired immunodeficiency syndrome. The treatment for the symptoms resulted in a poor clinical response. In order to improve the energetic performance/metabolism of cardiomyocytes, therapy with L-carnitine was established. There was significant clinical improvement of the cardiac performance of the patient, even before starting the treatment with antiretroviral drugs. COMMENTS: L-carnitine is a compound that facilitates the transport of long-chain fatty acids into the mitochondria. In this case the administration of L-carnitine appears to be clinically and biochemical justified.

Glutamine Supplemented Parenteral Nutrition to Prevent Ventilator-Associated Pneumonia in the Intensive Care Unit

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Meltem Türkay Aydoğmuş

2012-12-01

Full Text Available Objective: Ventilator-associated pneumonia (VAP is a form of nosocomial pneumonia that increases patient morbidity and mortality, length of hospital stay, and healthcare costs. Glutamine preserves the intestinal mucosal structure, increases immune function, and reduces harmful changes in gut permeability in patients receiving total parenteral nutrition (TPN. We hypothesized that TPN supplemented by glutamine might prevent the development of VAP in patients on mechanical ventilator support in the intensive care unit (ICU. Material and Methods: With the approval of the ethics committee and informed consent from relatives, 60 patients who were followed in the ICU with mechanical ventilator support were included in our study. Patients were divided into three groups. The first group received enteral nutrition (n=20, and the second was prescribed TPN (n=20 while the third group was given glutamine-supplemented TPN (n=20. C-reactive protein (CRP, sedimentation rate, body temperature, development of purulent secretions, increase in the amount of secretions, changes in the characteristics of secretions and an increase in requirement of deep tracheal aspiration were monitored for seven days by daily examination and radiographs. Results: No statistically significant difference was found among groups in terms of development of VAP (p=0.622. Conclusion: Although VAP developed at a lower rate in the glutamine-supplemented TPN group, no statistically significant difference was found among any of the groups. Glutamine-supplemented TPN may have no superiority over unsupplemented enteral and TPN in preventing VAP.

Glutamine supplemented parenteral nutrition to prevent ventilator-associated pneumonia in the intensive care unit.

Science.gov (United States)

Aydoğmuş, Meltem Türkay; Tomak, Yakup; Tekin, Murat; Katı, Ismail; Hüseyinoğlu, Urfettin

2012-12-01

Ventilator-associated pneumonia (VAP) is a form of nosocomial pneumonia that increases patient morbidity and mortality, length of hospital stay, and healthcare costs. Glutamine preserves the intestinal mucosal structure, increases immune function, and reduces harmful changes in gut permeability in patients receiving total parenteral nutrition (TPN). We hypothesized that TPN supplemented by glutamine might prevent the development of VAP in patients on mechanical ventilator support in the intensive care unit (ICU). With the approval of the ethics committee and informed consent from relatives, 60 patients who were followed in the ICU with mechanical ventilator support were included in our study. Patients were divided into three groups. The first group received enteral nutrition (n=20), and the second was prescribed TPN (n=20) while the third group was given glutamine-supplemented TPN (n=20). C-reactive protein (CRP), sedimentation rate, body temperature, development of purulent secretions, increase in the amount of secretions, changes in the characteristics of secretions and an increase in requirement of deep tracheal aspiration were monitored for seven days by daily examination and radiographs. No statistically significant difference was found among groups in terms of development of VAP (p=0.622). Although VAP developed at a lower rate in the glutamine-supplemented TPN group, no statistically significant difference was found among any of the groups. Glutamine-supplemented TPN may have no superiority over unsupplemented enteral and TPN in preventing VAP.

PPAR alpha-activation results in enhanced carnitine biosynthesis and OCTN2-mediated hepatic carnitine accumulation

NARCIS (Netherlands)

van Vlies, Naomi; Ferdinandusse, Sacha; Turkenburg, Marjolein; Wanders, Ronald J. A.; Vaz, Frédéric M.

2007-01-01

In fasted rodents hepatic carnitine concentration increases considerably which is not observed in PPAR alpha-/- mice, indicating that PPAR alpha is involved in carnitine homeostasis. To investigate the mechanisms underlying the PPAR alpha-dependent hepatic carnitine accumulation we measured

Effect of oral acetyl L-carnitine arginate on resting and postprandial blood biomarkers in pre-diabetics

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Tucker Patrick S

2009-06-01

Full Text Available Abstract Background Resting and postprandial oxidative stress is elevated in those with metabolic disorders such as diabetes. Antioxidant supplementation may attenuate the rise in oxidative stress following feeding. Therefore we sought to determine the effects of acetyl L-carnitine arginate (ALCA on resting and postprandial biomarkers of glucose and lipid metabolism, as well as oxidative stress. Methods Twenty-nine pre-diabetic men and women were randomly assigned to either 3 g·day-1 of ALCA (n = 14; 31 ± 3 yrs or placebo (n = 15; 35 ± 3 yrs in a double-blind design, to consume for eight weeks. Fasting blood samples were taken from subjects both pre and post intervention. After each fasting sample was obtained, subjects consumed a high fat, high carbohydrate meal and additional blood samples were taken at 1, 2, 4, and 6 hours post meal. Samples were analyzed for a variety of metabolic variables (e.g., glucose, HbA1c, lipid panel, C-reactive protein, nitrate/nitrite, and several markers of oxidative stress. Area under the curve (AUC was calculated for each variable measured post meal, both pre and post intervention. Results ALCA, but not placebo, resulted in an increase in nitrate/nitrite (25.4 ± 1.9 to 30.1 ± 2.8 μmol·L-1 from pre to post intervention, with post intervention values greater compared to placebo (p = 0.01. No other changes of statistical significance were noted (p > 0.05, although ALCA resulted in slight improvements in glucose (109 ± 5 to 103 ± 5 mg·dL-1, HbA1c (6.6 ± 1.1 to 6.2 ± 1.2%, and HOMA-IR (3.3 ± 1.3 to 2.9 ± 1.2. AUC postprandial data were not statistically different between ALCA and placebo for any variable (p > 0.05. However, nitrate/nitrite demonstrated a moderate effect size (r = 0.35 for increase from pre (139.50 ± 18.35 μmol·L-1·6 hr-1 to post (172.40 ± 21.75 μmol·L-1·6 hr-1 intervention with ALCA, and the magnitude of decrease following feeding was not as pronounced as with placebo

Metabolic fate of dietary carnitine in human adults: Identification and quantification of urinary and fecal metabolites

International Nuclear Information System (INIS)

Rebouche, C.J.; Chenard, C.A.

1991-01-01

Results of kinetic and pharmacokinetic studies have suggested that dietary carnitine is not totally absorbed and is in part degraded in the gastrointestinal tract of humans. To determine the metabolic fate of dietary carnitine in humans, we administered orally a tracer dose of methyl- 3 H L-carnitine with a meal to subjects who had been adapted to a low-carnitine diet or a high-carnitine diet. Urinary and fecal excretion of radiolabeled carnitine and metabolites was monitored for 5 to 11 d following administration of the test dose. Total radioactive metabolites excreted ranged from 13 to 34% (low carnitine diet) and 27 to 46% (high carnitine diet) of the ingested tracer. Major metabolites found were [ 3 H]trimethylamine N-oxide (8 to 39% of the administered dose; excreted primarily in urine) and [ 3 H]gamma-butyrobetaine (0.09 to 8% of the administered dose; excreted primarily in feces). Urinary excretion of total carnitine was 42 to 95% (high carnitine diet) and 190 to 364% (low carnitine diet) of intake. These results indicate that oral carnitine is 54 to 87% bioavailable from normal Western diets; the percentage of intake absorbed is related to the quantity ingested

[When enteral nutrition is not possible in intensive care patients: whether to wait or use parenteral nutrition?

Science.gov (United States)

Habes, Q L M; Pickkers, P

2016-01-01

- Overfeeding of critically ill patients is associated with a higher incidence of infections and an increased length of ventilation. However, trophic nutrition or permissive underfeeding appears to have no negative effect on the patient and may even provide a survival benefit.- Initiation of enteral nutrition within 24-48 hours after Intensive Care Unit (ICU) admission may reduce the number of complications and increase the chance of survival.- Total parenteral nutrition is associated with a higher risk of infections than enteral nutrition. This seems to be related to the higher calorie intake with parenteral nutrition rather than the route of administration.- In previously well-nourished patients, in whom enteral nutrition is only partially successful, it is safe to wait for up to 8 days before initiating supplemental parenteral nutrition.- In critically ill children, it is also safe to start supplemental parenteral nutrition at a late (on the 8th day after admission) rather than an early stage (within 24 hours of admission). Late supplemental parenteral nutrition may even result in fewer infectious complications and shorter hospitalisation.

Mutations of OCTN2, an organic cation/carnitine transporter, lead to deficient cellular carnitine uptake in primary carnitine deficiency

NARCIS (Netherlands)

Tang, N. L.; Ganapathy, V.; Wu, X.; Hui, J.; Seth, P.; Yuen, P. M.; Wanders, R. J.; Fok, T. F.; Hjelm, N. M.

1999-01-01

Systemic primary carnitine deficiency (CDSP, OMIM 212140) is an autosomal recessive disease characterized by low serum and intracellular concentrations of carnitine. CDSP may present with acute metabolic derangement simulating Reye's syndrome within the first 2 years of life. After 3 years of age,

Role of mitochondrial dysfunction in neurotoxicity of MPP+: partial protection of PC12 cells by acetyl-L-carnitine.

Science.gov (United States)

Virmani, Ashraf; Gaetani, Franco; Binienda, Zbigniew; Xu, Alex; Duhart, Helen; Ali, Syed F

2004-10-01

The damage to the central nervous system that is observed after administration of either methamphetamine (METH) or 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), is known to be linked to dopamine (DA). The underlying neurotoxicity mechanism for both METH and MPP+ seem to involve free radical formation and impaired mitochondrial function. The MPP+ is thought to selectively kill nigrostriatal dopaminergic neurons by inhibiting mitochondrial complex I, with cell death being attributed to oxidative stress damage to these vulnerable DA neurons. In the present study, MPP+ was shown to significantly inhibit the response to MTT by cultured PC12 cells. This inhibitory action of MPP+ could be partially reversed by the co-incubation of the cells with the acetylated form of carnitine, acetyl-L-carnitine (ALC). Since at least part of the toxic action of MPP+ is related to mitochondrial inhibition, the partial reversal of the inhibition of MTT response by ALC could involve a partial restoration of mitochondrial function. The role carnitine derivatives, such as ALC, play in attenuating MPP+ and METH-evoked toxicity is still under investigation to elucidate the contribution of mitochondrial dysfunction in mechanisms of neurotoxicity.

L-carnitine significantly decreased aging of rat adipose tissue-derived mesenchymal stem cells.

Science.gov (United States)

Mobarak, Halimeh; Fathi, Ezzatollah; Farahzadi, Raheleh; Zarghami, Nosratollah; Javanmardi, Sara

2017-03-01

Mesenchymal stem cells are undifferentiated cells that have the ability to divide continuously and tissue regeneration potential during the transplantation. Aging and loss of cell survival, is one of the main problems in cell therapy. Since the production of free radicals in the aging process is effective, the use of antioxidant compounds can help in scavenging free radicals and prevent the aging of cells. The aim of this study is evaluate the effects of L-carnitine (LC) on proliferation and aging of rat adipose tissue-derived mesenchymal stem cells (rADSC). rADSCs were isolated from inguinal region of 5 male Rattus rats. Oil red-O, alizarin red-S and toluidine blue staining were performed to evaluate the adipogenic, osteogenic and chondrogenic differentiation of rADSCs, respectively. Flow cytometric analysis was done for investigating the cell surface markers. The methyl thiazol tetrazolium (MTT) method was used to determine the cell proliferation of rADSCs following exposure to different concentrations of LC. rADSCs aging was evaluated by beta-galactosidase staining. The results showed significant proliferation of rADSCs 48 h after treatment with concentrations of 0.2 mM LC. In addition, in the presence of 0.2 mM LC, rADSCs appeared to be growing faster than control group and 0.2 mM LC supplementation could significantly decrease the population doubling time and aging of rADSCs. It seems that LC would be a good antioxidant to improve lifespan of rADSCs due to the decrease in aging.

A multi-ingredient containing carbohydrate, proteins L-glutamine and L-carnitine attenuates fatigue perception with no effect on performance, muscle damage or immunity in soccer players.

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Fernando Naclerio

Full Text Available We investigated the effects of ingesting a multi-ingredient (53 g carbohydrate, 14.5 g whey protein, 5 g glutamine, 1.5 g L-carnitine-L-tartrate supplement, carbohydrate only, or placebo on intermittent performance, perception of fatigue, immunity, and functional and metabolic markers of recovery. Sixteen amateur soccer players ingested their respective treatments before, during and after performing a 90-min intermittent repeated sprint test. Primary outcomes included time for a 90-min intermittent repeated sprint test (IRS followed by eleven 15 m sprints. Measurements included creatine kinase, myoglobin, interleukine-6, Neutrophil; Lymphocytes and Monocyte before (pre, immediately after (post, 1 h and 24 h after exercise testing period. Overall, time for the IRS and 15 m sprints was not different between treatments. However, the perception of fatigue was attenuated (P<0.001 for the multi-ingredient (15.9±1.4 vs. placebo (17.8±1.4 but not for the carbohydrate (17.0±1.9 condition. Several changes in immune/inflammatory indices were noted as creatine kinase peaked at 24 h while Interleukin-6 and myoglobin increased both immediately after and at 1 h compared with baseline (P<0.05 for all three conditions. However, Myoglobin (P<0.05 was lower 1 h post-exercise for the multi-ingredient (241.8±142.6 ng·ml(-1 and CHO (265.4±187.8 ng·ml(-1 vs. placebo (518.6±255.2 ng·ml(-1. Carbohydrate also elicited lower neutrophil concentrations vs. multi-ingredient (3.9±1.5 10(9/L vs. 4.9±1.8 10(9/L, P = 0.016 and a reduced (P<0.05 monocytes count (0.36±0.09 10(9/L compared to both multi-ingredient (0.42±0.09 10(9/L and placebo (0.42±0.12 10(9/L. In conclusion, multi-ingredient and carbohydrate supplements did not improve intermittent performance, inflammatory or immune function. However, both treatments did attenuate serum myoglobin, while only carbohydrate blunted post-exercise leukocytosis.

SMA CARNIVAL TRIAL PART II: a prospective, single-armed trial of L-carnitine and valproic acid in ambulatory children with spinal muscular atrophy.

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John T Kissel

Full Text Available BACKGROUND: Multiple lines of evidence have suggested that valproic acid (VPA might benefit patients with spinal muscular atrophy (SMA. The SMA CARNIVAL TRIAL was a two part prospective trial to evaluate oral VPA and L-carnitine in SMA children. Part 1 targeted non-ambulatory children ages 2-8 in a 12 month cross over design. We report here Part 2, a twelve month prospective, open-label trial of VPA and L-carnitine in ambulatory SMA children. METHODS: This study involved 33 genetically proven type 3 SMA subjects ages 3-17 years. Subjects underwent two baseline assessments over 4-6 weeks and then were placed on VPA and L-carnitine for 12 months. Assessments were performed at baseline, 3, 6 and 12 months. Primary outcomes included safety, adverse events and the change at 6 and 12 months in motor function assessed using the Modified Hammersmith Functional Motor Scale Extend (MHFMS-Extend, timed motor tests and fine motor modules. Secondary outcomes included changes in ulnar compound muscle action potential amplitudes (CMAP, handheld dynamometry, pulmonary function, and Pediatric Quality of Life Inventory scores. RESULTS: Twenty-eight subjects completed the study. VPA and carnitine were generally well tolerated. Although adverse events occurred in 85% of subjects, they were usually mild and transient. Weight gain of 20% above body weight occurred in 17% of subjects. There was no significant change in any primary outcome at six or 12 months. Some pulmonary function measures showed improvement at one year as expected with normal growth. CMAP significantly improved suggesting a modest biologic effect not clinically meaningful. CONCLUSIONS: This study, coupled with the CARNIVAL Part 1 study, indicate that VPA is not effective in improving strength or function in SMA children. The outcomes used in this study are feasible and reliable, and can be employed in future trials in SMA. TRIAL REGSITRATION: Clinicaltrials.gov NCT00227266.

Iron supplementation in Switzerland - A bi-national, descriptive and observational study.

Science.gov (United States)

Biétry, Fabienne A; Hug, Balthasar; Reich, Oliver; Susan, Jick S; Meier, Christoph Rudolf

2017-07-11

Iron deficiency is the most common nutritional disorder in the world, and it is the only common nutrient deficiency in industrialised nations. It is thought to be the most common cause of anaemia. Use of iron supplementation in Switzerland has not been previously quantified in detail. We quantified use of iron supplementation from Swiss data and compared it with data from the UK. We assessed the frequency of serum ferritin and haemoglobin tests prior to newly started iron therapy to see whether use was based on documented low iron levels or blood parameters, especially in the case of parenteral iron supplementation. We conducted a retrospective descriptive study of prescription iron supplementation use, and compared use of oral or parenteral iron drugs between Switzerland (CH) and the UK. We retrieved Swiss data from the Swiss Health Insurance Helsana Group, and UK data were from the Clinical Practice Research Datalink (CPRD). The study period was 2012 to 2014. The 3-year prevalence of iron supplementation was 9.4% in Switzerland and 4.4% in the UK. Iron use increased slightly between 2012 and 2014 in both countries (CH +0.3%, UK +0.2%). Recorded parenteral iron administration was roughly a thousand times higher in Switzerland (1.9%) than in the UK in 2014. In Switzerland, iron supplements were mostly given to patients aged 20 to 49 years or older than of 80 years. In the UK, iron supplementation was less frequent in younger people, but more prevalent in the elderly. Prior to a first iron prescription, ferritin tests were done more frequently in Switzerland (oral 67.2%, parenteral 86.6%) than in the UK (oral 43.3%, parenteral 65.5%). Haemoglobin was measured before a new parenteral iron therapy rarely in Switzerland (oral 14.9%, parenteral 11.7%), but frequently in the UK (oral 77.4%, parenteral 85.6%). Iron supplementation is more common in Switzerland than in the UK, particularly parenteral iron supplementation. Haemoglobin measurements prior to a new parenteral

Peripheral parenteral nutrition: an option for patients with an indication for short-term parenteral nutrition La nutrición parenteral periférica, alternativa para los pacientes con indicación de nutrición parenteral durante poco tiempo

OpenAIRE

M. I. T. D. Correia; J. Guimarâes; L. Cirino de Mattos; K. C. Araújo Gurgel; E. B. Cabral

2004-01-01

Objective: The aim of this study was to examine and describe our experience with the use of peripheral parenteral nutrition (PPN). Methods: Patients with an indication for parenteral nutrition for less than 15 days received it via a peripheral vein via a short, 20 or 22 gauge French polyurethane catheter. Parenteral nutrition had a final osmolality of 993 mOsm/l and was administered by infusion pump. The nutritional status of patients was assessed by the Subjective Global Assessment (SGA) tec...

Novel localization of OCTN1, an organic cation/carnitine transporter, to mammalian mitochondria

International Nuclear Information System (INIS)

Lamhonwah, Anne-Marie; Tein, Ingrid

2006-01-01

Carnitine is a zwitterion essential for the β-oxidation of fatty acids. We report novel localization of the organic cation/carnitine transporter, OCTN1, to mitochondria. We made GFP- and RFP-human OCTN1 cDNA constructs and showed expression of hOCTN1 in several transfected mammalian cell lines. Immunostaining of GFP-hOCTN1 transfected cells with different intracellular markers and confocal fluorescent microscopy demonstrated mitochondrial expression of OCTN1. There was striking co-localization of an RFP-hOCTN1 fusion protein and a mitochondrial-GFP marker construct in transfected MEF-3T3 and no co-localization of GFP-hOCTN1 in transfected human skin fibroblasts with other intracellular markers. L-[ 3 H]Carnitine uptake in freshly isolated mitochondria of GFP-hOCTN1 transfected HepG2 demonstrated a K m of 422 μM and Western blot with an anti-GFP antibody identified the expected GFP-hOCTN1 fusion protein (90 kDa). We showed endogenous expression of native OCTN1 in HepG2 mitochondria with anti-GST-hOCTN1 antibody. Further, we definitively confirmed intact L-[ 3 H]carnitine uptake (K m 1324 μM), solely attributable to OCTN1, in isolated mitochondria of mutant human skin fibroblasts having <1% of carnitine acylcarnitine translocase activity (alternate mitochondrial carnitine transporter). This mitochondrial localization was confirmed by TEM of murine heart incubated with highly specific rabbit anti-GST-hOCTN1 antibody and immunogold labeled goat anti-rabbit antibody. This suggests an important yet different role for OCTN1 from other OCTN family members in intracellular carnitine homeostasis

Proximate Composition, and -Carnitine and Betaine Contents in Meat from Korean Indigenous Chicken

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Samooel Jung

2015-12-01

Full Text Available This study investigated the proximate composition and l-carnitine and betaine content of meats from 5 lines of Korean indigenous chicken (KIC for developing highly nutritious meat breeds with health benefits from the bioactive compounds such as l-carnitine and betaine in meat. In addition, the relevance of gender (male and female and meat type (breast and thigh meat was examined. A total of 595 F1 progeny (black [B], grey-brown [G], red-brown [R], white [W], and yellow-brown [Y] from 70 full-sib families were used. The moisture, protein, fat, and ash contents of the meats were significantly affected by line, gender, and meat type (p<0.05. The males in line G and females in line B showed the highest protein and the lowest fat content of the meats. l-carnitine and betaine content showed effects of meat type, line, and gender (p<0.05. The highest l-carnitine content was found in breast and thigh meats from line Y in both genders. The breast meat from line G and the thigh meat from line R had the highest betaine content in males. The female breast and thigh meats showed the highest betaine content in line R. These data could be valuable for establishing selection strategies for developing highly nutritious chicken meat breeds in Korea.

L-Carnitine in rooster semen cryopreservation: Flow cytometric, biochemical and motion findings for frozen-thawed sperm.

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Fattah, A; Sharafi, M; Masoudi, R; Shahverdi, A; Esmaeili, V; Najafi, A

2017-02-01

Rooster semen cryopreservation is not efficient for artificial insemination in breeder flocks. L-Carnitine (LC) has been evaluated for effectiveness in cryopreservation media on the characteristics of rooster sperm after freeze-thawing. Motility characteristics, membrane functionality, abnormal morphology, apoptotic like changes, mitochondria activity and lipid peroxidation of rooster sperms were assessed after freeze-thawing with different concentrations of LC in Beltsville medium. Semen samples were collected from 12 roosters, twice a week, and diluted in the extenders that contained different concentrations of LC. Supplementation of Beltsevile with 1 and 2 mM LC was found to result in higher total motility (68.2± 1.7% and 69.1± 1.7%, respectively), progressive motility (28.4± 1.6%, 29.8± 1.6%), membrane functionality (76.2± 1.9% and 75.9± 1.9%), viability (58.2 ± 1.1%, 59.1 ± 1.1%) and lower significant of lipid peroxidation (2.53 ± 0.08 nmol/ml, 2.49 ± 0.08 nmol/ml) compared to control group containing no LC. Lower motility, progressive motility, and viability were observed in frozen-thawed sperm in extender containing 8 mM LC (35.8± 1.7%, 9.6± 1.2% and 27.1 ± 1.2%, respectively) compared to control. Morphology and mitochondrial activity were not affected by different concentrations of LC. Our results showed that supplementation of Beltsville extender with 1 and 2 mM LC significantly improved the quality of rooster sperm quality after freeze-thawing. Copyright © 2016 Elsevier Inc. All rights reserved.

Suplementação oral de L-carnitina associada ao treinamento físico e muscular respiratório na doença pulmonar obstrutiva crônica: estudo preliminar Oral supplementation of L-carnitine combined with exercise and respiratory training in patients with chronic obstructive pulmonary disease: preliminary study

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Matheus Guedes Fernandes Silva

2012-12-01

Full Text Available Avaliar os efeitos da suplementação oral de L-carnitina associada ao treinamento físico e muscular respiratório na doença pulmonar obstrutiva crônica (DPOC. Participaram 14 voluntários com idade de 65±10,4 anos e diagnóstico clínico de DPOC moderado, classificados de acordo com a espirometria prévia. Os voluntários foram divididos em grupo treino esteira (GTE e grupo treino muscular respiratório (GTMR. Realizaram o teste de caminhada de seis minutos (TC6', teste de caminhada com carga progressiva (TCP, avaliação nutricional do índice de massa corpórea (IMC, dose diária recomendada de L-carnitina, pressões inspiratórias (PImáx e expiratórias máximas (PEmáx. Fizeram 30 min de caminhada em esteira, 3 vezes/semana por 10 semanas, e o GTMR realizou, ainda, 10 min de treinamento muscular inspiratório (Threshold® IMT e 10 min de treinamento muscular expiratório (Threshold® PEP à 50% da PImáx e PEmáx ajustados semanalmente. Após 10 semanas, foram reavaliados. No TC6' pré e pós-programa de treinamento físico, as variáveis alteradas foram: distância percorrida (DP, frequência cardíaca (FC final, pressão arterial sistólica (PAS final, pressão arterial diastólica (PAD final e Borg final no GTMR, no GTE as variáveis alteradas foram FC repouso, FC final, PAS final, Borg repouso e DP. Comparando os grupos no TC6, o GTE apresentou FC final, PAD final e Borg final maiores do que o GTMR na reavaliação; já no TCP, a FC final, PAS final, Borg final foram maiores no GTE, e DP foi maior no GTMR. Na avaliação respiratória, a PEmáx foi maior no GTMR na reavaliação. O treino aeróbio e suplementação de L-carnitina na DPOC otimizou a performance, a capacidade física e a tolerância ao esforço.To evaluate the effects of oral supplementation of L-carnitine associated with physical and respiratory muscles training in chronic obstructive pulmonary disease (COPD. Participated 14 COPD volunteers (65±10.4 years, divided

Effect of early supplemental parenteral nutrition in the paediatric ICU: a preplanned observational study of post-randomisation treatments in the PEPaNIC trial.

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Vanhorebeek, Ilse; Verbruggen, Sascha; Casaer, Michaël P; Gunst, Jan; Wouters, Pieter J; Hanot, Jan; Guerra, Gonzalo Garcia; Vlasselaers, Dirk; Joosten, Koen; Van den Berghe, Greet

2017-06-01

Large randomised controlled trials have shown that early supplemental parenteral nutrition in patients admitted to adult and paediatric intensive care units (PICUs) is harmful. Overdosing of energy with too little protein was suggested as a potential reason for this. This study analysed which macronutrient was associated with harm caused by early supplemental parenteral nutrition in the Paediatric Early versus Late Parenteral Nutrition In Critical Illness (PEPaNIC) randomised trial. Patients in the initial randomised controlled trial were randomly assigned to receive suppplemental parenteral nutrition (PN) within 24 h of PICU admission (early PN) or to receive such PN after 1 week (late PN) when enteral nutrition was insufficient. In this post-randomisation, observational study, doses of glucose, lipids, and aminoacids administered during the first 7 days of PICU stay were expressed as % of reference doses from published clinical guidelines for age and weight. Independent associations between average macronutrient doses up to each of the first 7 days and likelihood of acquiring an infection in the PICU, of earlier live weaning from mechanical ventilation, and of earlier live PICU discharge were investigated using multivariable Cox proportional hazard analyses. The three macronutrients were included in the analysis simultaneously and baseline risk factors were adjusted for. From June 18, 2012, to July 27, 2015, 7519 children aged between newborn and 17 years were assessed for eligibility. 6079 patients were excluded, and 1440 children were randomly assigned to receive either early PN (n=723) or late PN (n=717). With increasing doses of aminoacids, the likelihood of acquiring a new infection was higher (adjusted hazard ratios [HRs] per 10% increase between 1·043-1·134 for days 1-5, p≤0·029), while the likelihood of earlier live weaning from mechanical ventilation was lower (HRs 0·950-0·975 days 3-7, p≤0·045), and the likelihood of earlier live PICU

ACETYL-L-CARNITINE AFFECTS THE ELECTRICAL ACTIVITY OF MECHANOSENSORY NEURONS IN HIRUDO MEDICINALIS GANGLIA

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Giovanna Traina

2017-04-01

Full Text Available Was previously discovered that in the leech Hirudo medicinalis, acetyl-l-carnitine (ALC affects forms of non-associative learning, such as sensitization and dishabituation, due to nociceptive stimulation of the dorsal skin in the swim induction behavioural paradigm, likely through modulating the activity of the mechanosensory tactile (T neurons, which initiate swimming. Since was found that ALC impaired sensitization and dishabituation, both of which are mediated by the neurotransmitter serotonin, the present study analyzed how ALC may interfere with the sensitizing response. Was already found that ALC reduced the activity of nociceptive (N neurons, which modulate T cell activity through serotonergic mediation.

Effect of L-carnitine on fatty acid oxidation of the muscle in hemodialysis patients

International Nuclear Information System (INIS)

Siami, G.; Clinton, M.; Borum, P.

1986-01-01

Muscle weakness is a major cause of morbidity in end stage renal disease (ESRD) patients on long term hemodialysis (HD). Carnitine (C) is important for transport of fatty acids into mitochondria. The kidney is a major site of C biosynthesis which may be compromised in ESRD. C is lost during dialysis and is reduced in plasma and muscle. Although the cause of muscle weakness is multifactorial, the effect of supplemental C was tested on a group of ESRD patients on HD. C (1 gm I.V. 3 x/wk) or placebo was given to HD patients for 6 months. Muscle biopsies were obtained before and after C supplementation and from control subjects. Muscle pathology was examined by histochemical light microscopy. Fatty acid oxidation (FAO) by homogenate of the biopsied muscle was measured using [ 14 C] palmitate. Plasma aluminum (AL) and parthyroid hormone (PTH) were also measured and patients were evaluated for the degree of muscle weakness. All Pts had abnormal muscle pathology and C supplementation did not improve it. FAO by 3 HD Pts who had received placebo was 639 +/- 285 (S.D.) dpm/mg protein while control subjects were 1487 +/- 267 and was statistically different (p < .003). FAO by 8 HD Pts receiving C was not different from placebo. Addition of C in vitro stimulated FAO 70 to 80%, but there was not difference between groups. The degree of FAO was inversely correlated with the severity of the muscle pathology, and was directly correlated with the concentration of C in muscle. Pts with high plasma AL had lower FAO, but there was no correlation between FAO and PTH

Differences in essential fatty acid requirements by enteral and parenteral routes of administration in patients with fat malabsorption

DEFF Research Database (Denmark)

Jeppesen, Palle B; Høy, Carl-Erik; Mortensen, Per B

1999-01-01

Background: Essential fatty acid (EFA) requirements of patients receiving home parenteral nutrition (HPN) are uncertain. Objective: The objective was to evaluate the influence of the route of administration (enteral compared with parenteral) on plasma phospholipid EFA concentrations. Design......: Intestinal absorption, parenteral supplement of EFAs, and plasma phospholipid EFA concentrations were investigated in balance studies in 4 groups (A, B, C, and D) of 10 patients with short-bowel syndrome and a fecal loss of >2000 kJ/d. Groups A (fat malabsorption 50%) did...... absorption was negligible in groups C and D. Thus, intestinal absorption of EFAs in group A. corresponded to parenteral EFA supplements in group C, whereas group D was almost totally deprived of EFAs. The median plasma phospholipid concentration of linoleic acid decreased by 21.9%, > 16.3%, >13.8%, 11...

Effect of propionyl-L-carnitine on L-type calcium channels in human heart sarcolemma

International Nuclear Information System (INIS)

Bevilacqua, M.; Vago, T.; Norbiato, G.

1991-01-01

Propionyl-L-carnitine (PC) protects perfused rat hearts against damage by ischemia-reperfusion. Activation of L-type calcium channel play a role on ischemia-reperfusion damage. Therefore, we studied the effect of PC on some properties of L-type calcium channels in an in vitro preparation from human myocardium sarcolemma (from patients with idiopathic dilated cardiomyopathy). Binding of the L-type calcium channel blockers isradipine [ 3 H]-PN 200-110 (PN) to plasma membrane preparations revealed a single population of binding sites (total number: Bmax = 213 +/- 34 fM/mg protein and affinity: Kd = 152 +/- 19 nM; n = 6). The characteristics of these binding sites were evaluated in the presence and in the absence of Ca 2+ and of calcium blockers (D-888, a verapamillike drug, and diltiazem). Incubation in a Ca 2+ -containing buffer increased the affinity of PN binding sites. Binding sites for PN were modulated by organic calcium channel blockers; in competition isotherms at 37 degree C, D-888 (desmethoxyverapamil) decreased the PN binding, whereas diltiazem increased it. These results strongly suggest that the site labelled by PN is the voltage-operated calcium channel of the human myocardium. The addition of PC (1 mM) to plasma membranes labelled with PN at 37 degree C decreased the affinity of the binding; this effect was counteracted by the addition of Ca 2+ to the medium. This result was consistent with a competition between Ca 2+ and PC. The effect of PC incubation at 4 degree C was the opposite; at this temperature PC increased the affinity of the binding sites and the effect was obscured by Ca 2+

Carnitine palmitoyltransferase IA polymorphism P479L is common in Greenland Inuit and is associated with elevated plasma apolipoprotein A-I

DEFF Research Database (Denmark)

Rajakumar, Chandheeb; Ban, Matthew R; Cao, Henian

2009-01-01

Carnitine palmitoyltransferase IA, encoded by CPT1A, is a key regulator of fatty acid metabolism. Previously, a loss of function mutation, namely c.1436 CT (p.P479L), was reported in CPT1A in the homozygous state in Canadian aboriginal male with presumed CPT1A deficiency. In order to determine...

Behavioral and dermatologic changes and low serum zinc and copper concentrations in two premature infants after parenteral alimentation.

Science.gov (United States)

Sivasubramanian, K N; Henkin, R I

1978-11-01

Two premature infants were observed to develop behavioral and dermatologic changes and low serum zinc and copper concentrations following cessation of prolonged parenteral alimentation, while being fed exclusively with human milk. Following treatment with exogenous oral zinc supplementation, prompt relief of symptoms and increases of serum zinc and copper concentrations were observed in both infants. These patients comprise about 5% of our premature infants who are treated with parenteral alimentation for more than two weeks. We recommend that premature infants on prolonged parenteral alimentation should be monitored for changes in serum zinc and copper concentrations and, if a marked fall is observed, supplementation should be considered.

Parenteral nutrition in the ICU setting: need for a shift in utilization.

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Oshima, Taku; Hiesmayr, Michael; Pichard, Claude

2016-03-01

The difficulties to feed the patients adequately with enteral nutrition alone have drawn the attention of the clinicians toward the use of parenteral nutrition, although recommendations by the recent guidelines are conflicting. This review focuses on the intrinsic role of parenteral nutrition, its new indication, and modalities of use for the critically ill patients. A recent trial demonstrated that selecting either parenteral nutrition or enteral nutrition for early nutrition has no impact on clinical outcomes. However, it must be acknowledged that the risk of relative overfeeding is greater when using parenteral nutrition and the risk of underfeeding is greater when using enteral nutrition because of gastrointestinal intolerance. Both overfeeding and underfeeding in the critically ill patients are associated with deleterious outcomes. Thus, early and adequate feeding according to the specific energy needs can be recommended as the optimal feeding strategy. Parenteral nutrition can be used to substitute or supplement enteral nutrition, if adequately prescribed. Testing for enteral nutrition tolerance during 2-3 days after ICU admission provides the perfect timing to start parenteral nutrition, if needed. In case of absolute contraindication for enteral nutrition, consider starting parenteral nutrition carefully to avoid overfeeding.

Mild synthesis of [N-methyl-11C]-isovaleroyl-(L)-carnitine. The usefulness of a tritium approach

International Nuclear Information System (INIS)

Angelini, G.; Carnevaletti, F.; Margonelli, A.; Corsi, G.; Ragni, P.; Fazio, F.; Todde, S.; Tinti, O.

1999-01-01

The title carnitine derivative was labelled both with [ 11 C]methyl iodide and [ 3 H]methyl iodide. The former was synthesized in order to improve the knowledge of the acyl carnitines fate in humans. The latter was synthesized, at approximately the same concentration level as that of the former, in order to optimize its radiosynthesis, taking advantage from the long half-life of the tritium

Effect of L-carnitine and pyruvate on equine sperm maintained at 5 ºC and 15 ºC during 24 h: preliminary results

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Avila G

2016-12-01

Full Text Available The aim of this study was to evaluate if the addition of L-carnitine and pyruvate to two semen transport extenders (Kenney and Kenney modified by Tyrodes is able to maintain sperm parameters for 24 h at 5 ºC and 15 ºC. Semen was obtained from 3 stallions (n=3; r=2 and at time 0 and after 24 h of cooling, the following parameters evaluated: total and progressive motility (CASA, viability and acrosome status (FITC-PNA-PI, membrane function (HOS, and DNA with Toluidine Blue stain (TB and the Sperm Chromatin Dispersion assay (SCD. Each temperature was individually analyzed using a factorial design with a 5% significance level. No interactions were observed. For the moment, the Kenney extender with the addition of L-carnitine and pyruvate showed the best results for maintaining most sperm parameters for 24 h at both 5 ºC and 15 ºC.

Propionyl-L-Carnitine Enhances Wound Healing and Counteracts Microvascular Endothelial Cell Dysfunction.

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Maria Giovanna Scioli

Full Text Available Impaired wound healing represents a high cost for health care systems. Endothelial dysfunction characterizes dermal microangiopathy and contributes to delayed wound healing and chronic ulcers. Endothelial dysfunction impairs cutaneous microvascular blood flow by inducing an imbalance between vasorelaxation and vasoconstriction as a consequence of reduced nitric oxide (NO production and the increase of oxidative stress and inflammation. Propionyl-L-carnitine (PLC is a natural derivative of carnitine that has been reported to ameliorate post-ischemic blood flow recovery.We investigated the effects of PLC in rat skin flap and cutaneous wound healing. A daily oral PLC treatment improved skin flap viability and associated with reactive oxygen species (ROS reduction, inducible nitric oxide synthase (iNOS and NO up-regulation, accelerated wound healing and increased capillary density, likely favoring dermal angiogenesis by up-regulation for iNOS, vascular endothelial growth factor (VEGF, placental growth factor (PlGF and reduction of NADPH-oxidase 4 (Nox4 expression. In serum-deprived human dermal microvascular endothelial cell cultures, PLC ameliorated endothelial dysfunction by increasing iNOS, PlGF, VEGF receptors 1 and 2 expression and NO level. In addition, PLC counteracted serum deprivation-induced impairment of mitochondrial β-oxidation, Nox4 and cellular adhesion molecule (CAM expression, ROS generation and leukocyte adhesion. Moreover, dermal microvascular endothelial cell dysfunction was prevented by Nox4 inhibition. Interestingly, inhibition of β-oxidation counteracted the beneficial effects of PLC on oxidative stress and endothelial dysfunction.PLC treatment improved rat skin flap viability, accelerated wound healing and dermal angiogenesis. The beneficial effects of PLC likely derived from improvement of mitochondrial β-oxidation and reduction of Nox4-mediated oxidative stress and endothelial dysfunction. Antioxidant therapy and

IODINE CONTENT OF ENTERAL AND PARENTERAL NUTRITION SOLUTIONS.

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Willard, Devina L; Young, Lorraine S; He, Xuemei; Braverman, Lewis E; Pearce, Elizabeth N

2017-07-01

Iodine is essential for thyroid hormone synthesis, and iodine deficiency may result in thyroid disorders including goiter and hypothyroidism. Patients on long-term enteral nutrition (EN) or parenteral nutrition (PN) may be at risk for micronutrient deficiencies. The recommended daily allowance for iodine intake is 150 μg for nonpregnant adults. However, there is no current consensus among scientific societies regarding the quantity of iodine to be added in adult EN and PN formulations. The objective of this study was to determine the iodine content of U.S. adult enteral and parenteral nutrition solutions. This study also aimed to determine whether adult patients in the United States who are receiving long-term artificial nutrition may be at risk for iodine deficiency. Ten enteral nutrition solutions and 4 parenteral nutrition solutions were evaluated. The iodine contents of these solutions were measured spectrophotometrically and compared to the labeled contents. Measured and labeled EN iodine contents were similar (range 131-176 μg/L and 106-160 μg/L, respectively). In contrast, PN formulas were found to contain small, unlabeled amounts of iodine, averaging 27 μg/L. Typical fluid requirements are 30 to 40 mL/kg/day for adults receiving either total EN (TEN) or total PN (TPN). Adults on long-term TEN likely consume enough servings to meet their daily iodine requirements. However, patients on long-term TPN would require on average 5.6 L PN/day to meet the recommended daily allowance of iodine. This volume of PN is far in excess of typical consumption. Thus, U.S. patients requiring long-term TPN may be at risk for iodine deficiency. EN = enteral nutrition; PN = parenteral nutrition; TEN = total enteral nutrition; TPN = total parenteral nutrition; UIC = urinary iodine concentration.

Response to parenteral iron therapy distinguish unexplained refractory iron deficiency anemia from iron-refractory iron deficiency anemia.

Science.gov (United States)

Akin, M; Sarbay, H; Guler, S; Balci, Y I; Polat, A

2016-04-01

We evaluated that response to parenteral iron therapy could be helpful in distinguishing the types of iron deficiency anemia. This study analyzed responses to IV iron sucrose therapy of 15 children with unexplained refractory iron deficiency anemia (URIDA). We compared the results at diagnosis, 6 weeks and 6 months after the therapy. Results were compared with responses of 11 patients' results with iron-refractory iron deficiency anemia (IRIDA) from our previous study. Six weeks after the start of treatment, ferritin, MCV, MCH and Hb values were in normal range in 10 patients. The increase in Hb, MCH, MCV, and ferritin values ranged 2.6-3.5 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. In five patients, Hb, MCH, and MCV mean (range) values [11.2 g/dL (11-12.2), 24.5 pg (24-25.6), and 67 fL (65-70)] were nearly normal but ferritin mean (range) values [9.8 ng/mL (8-11)] were below normal. Six weeks after the start of treatment, Hb, MCH, MCV and ferritin values of patients with IRIDA were increased. The increase in Hb, MCH, MCV, and ferritin values ranged 0.8-2.7 g/dL, 1.7-4.2 pg, 2-9 fL, and 13-25 ng/mL, respectively. IRIDA is only partially responsive to parenteral iron supplementation. In conclusion, this study demonstrated that the response to intravenous iron therapy for the URIDA cases improved blood parameters more effectively than hereditary IRIDA. Response to parenteral iron therapy would be helpful to distinguish unexplained refractory IDA from hereditary IRIDA for clinicians who do not have access to hepcidin or TMPRS6 mutation analysis. © 2016 John Wiley & Sons Ltd.

Temporal Trends in the Use of Parenteral Nutrition in Critically Ill Patients

Science.gov (United States)

Kahn, Jeremy M.; Wunsch, Hannah

2014-01-01

Background: Clinical practice guidelines recommend enteral over parenteral nutrition in critical illness and do not recommend early initiation. Few data are available on parenteral nutrition use or timing of initiation in the ICU or how this use may have changed over time. Methods: We used the Project IMPACT database to evaluate temporal trends in parenteral nutrition use (total and partial parenteral nutrition and lipid supplementation) and timing of initiation in adult ICU admissions from 2001 to 2008. We used χ2 tests and analysis of variance to examine characteristics of patients receiving parenteral nutrition and multilevel multivariate logistic regression models to assess parenteral nutrition use over time, in all patients and in specific subgroups. Results: Of 337,442 patients, 20,913 (6.2%) received parenteral nutrition. Adjusting for patient characteristics, the use of parenteral nutrition decreased modestly over time (adjusted probability, 7.2% in 2001-2002 vs 5.5% in 2007-2008, P nutrition use increased simultaneously (adjusted probability, 11.5% in 2001-2002 vs 15.3% in 2007-2008, P parenteral nutrition declined most rapidly in emergent surgical patients, patients with moderate illness severity, patients in the surgical ICU, and patients admitted to an academic facility (P ≤ .01 for all interactions with year). When used, parenteral nutrition was initiated a median of 2 days (interquartile range, 1-3), after ICU admission and > 90% of patients had parenteral nutrition initiated within 7 days; timing of initiation of parenteral nutrition did not change from 2001 to 2008. Conclusions: Use of parenteral nutrition in US ICUs declined from 2001 through 2008 in all patients and in all examined subgroups, with the majority of parenteral nutrition initiated within the first 7 days in ICU; enteral nutrition use coincidently increased over the same time period. PMID:24233390

Preparation of crystalline sodium norcarnitine: an easily handled precursor for the preparation of carnitine analogs and radiolabeled carnitine.

Science.gov (United States)

Colucci, W J; Turnbull, S P; Gandour, R D

1987-05-01

A procedure by which crystalline sodium norcarnitine can be prepared in large quantities and high yields has been developed. Carnitine is selectively demethylated by thiophenoxide ion in N,N-dimethylethanolamine. The reactive thiophenoxide ion is generated in situ by addition of thiophenol to this basic reaction solvent. Hence, sodium thiophenoxide, which has been used in similar applications, but is difficult to prepare, can be avoided. Accordingly, reaction of (R,S)-carnitine followed by aqueous azeotropic distillation of byproducts as well as excess starting materials and then by neutralization with sodium hydroxide gave sodium norcarnitine in 89% yield. (R)-Carnitine gave 91% yield of (R)-norcarnitine zwitterion before neutralization. A method for the facile preparation of radiolabeled (R)-carnitine is also described. Thus, methylation of sodium norcarnitine with methyl iodide in methanolic acetone produced carnitine, which precipitated, and sodium iodide, which was soluble.

Dietary Carnitine maintains energy reserves and delays fatigue of exercised African catfish (Clarias Gariepinus) fed high fat diets

NARCIS (Netherlands)

Ozorio, R.; Ginneken, van V.J.T.; Thillart, van den G.; Verstegen, M.W.A.; Verreth, J.A.J.

2005-01-01

Lipids, together with proteins, are traditionally considered as primary fuels during aerobic swimming. The effects of dietary fat and carnitine supplements and exercise on the energy metabolism of juvenile fish were investigated. One hundred African catfish (Clarias gariepinus) were fed four

Carnitine palmityl transferase I deficiency

NARCIS (Netherlands)

Al-Aqeel, A. I.; Rashed, M. S.; Ruiter, J. P.; Al-Husseini, H. F.; Al-Amoudi, M. S.; Wanders, R. J.

2001-01-01

Carnitine palmityl transferase I is the key enzyme in the carnitine dependent transport of long chain fatty acids across the mitochondrial inner membrane and its deficiency results in a decrease rate of fatty acids beta-oxidation with decreased energy production. We reported a family of 3 affected

L-carnitine is a survival factor for chilled storage of rooster semen for a long time.

Science.gov (United States)

Fattah, A; Sharafi, M; Masoudi, R; Shahverdi, A; Esmaeili, V

2017-02-01

Rooster sperm is sensitive to cooling, which restricts procedures to store sperms for extended periods of time for artificial insemination of commercial flocks. This study was conducted to evaluate the suitability of adding L-carnitine (LC) to chilled-storage of rooster sperm and its effects on sperm quality parameters and its fertility potential during storage at 5 °C. Pooled semen from roosters were divided into six equal aliquots and diluted with media supplemented with different concentrations of LC (0, 0.5, 1, 2, 4 and 8 mM LC). Diluted semen samples were cooled to 5 °C and stored over 48 h. Motility, viability, membrane functionality, lipid peroxidation and mitochondria activity of the sperm were assessed at 0, 24 and 48 h of storage. Moreover, fertility potential of chilled stored sperm was considered at 24 h of storage. While sperm quality was not affected by LC at the beginning of storage (0 h), supplementation of extender with 1 and 2 mM of LC significantly improved the percentage of sperm motility, viability, membrane integrity and mitochondria activity at 24 h and 48 h compared to other groups. Lipid peroxidation was significantly reduced in sperm samples diluted with 1 and 2 mM LC at 24 h (2.15 ± 0.52 nmol/ml and 2.21 ± 0.52 nmol/ml) and 48 h (3.42 ± 0.49 nmol/ml and 3.38 ± 0.49 nmol/ml) compared to other groups. Furthermore, fertility rates during artificial insemination using sperms cooled for 24 h in the presence of 1 and 2 mM LC were significantly higher (78%) than in the control group (64%). These findings suggest that optimum doses of LC could protect rooster sperm against cool storage-induced functional and structural damages. Copyright © 2016 Elsevier Inc. All rights reserved.

Utilization of endogenous fatty acid stores for energy production in bovine preimplantation embryos.

Science.gov (United States)

Sutton-McDowall, Melanie L; Feil, Deanne; Robker, Rebecca L; Thompson, Jeremy G; Dunning, Kylie R

2012-05-01

Although current embryo culture media are based on carbohydrate metabolism of embryos, little is known about metabolism of endogenous lipids. L-carnitine is a β-oxidation cofactor absent in most culture media. The objective was to investigate the influence of L-carnitine supplementation on bovine embryo development. Abattoir-derived bovine cumulus oocyte complexes were cultured and fertilized. Post-fertilization, presumptive zygotes were transferred into a basic cleavage medium ± carbohydrates (glucose, lactate and pyruvate) ± 5 mm L-carnitine and cultured for 4 days in vitro. In the absence of carbohydrates during culture, embryos arrested at the 2- and 4-cell stages. Remarkably, +L-carnitine increased development to the morula stage compared to +carbohydrates alone (P levels were higher and ATP: ADP ratio were 1.9-fold lower (main effect, P < 0.05) compared to embryos cultured in -L-carnitine. Therefore, we inferred that +L-carnitine embryos were more metabolically active, with higher rates of ATP-ADP conversion. In conclusion, L-carnitine supplementation supported precompaction embryo development and there was an additive effect of +L-carnitine +carbohydrates on early embryo development, most likely through increased β-oxidation within embryos. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Assessment of pharmacokinetic interaction between piracetam and l-carnitine in healthy subjects.

Science.gov (United States)

Mendes, Gustavo D; Zaffalon, Gabriela Traldi; Silveira, Antonio Sérgio; Ramacciato, Juliana Cama; Motta, Rogério Heládio Lopes; Gagliano-Jucá, Thiago; Lopes, Anibal Gil; de Almeida Magalhães, José Cássio; De Nucci, Gilberto

2016-04-01

A rapid, sensitive and specific method for quantifying piracetam in human plasma using Piracetam d-8 as the internal standard (IS) is described. The analyte and the IS were extracted from plasma by one-step precipitation of protein using an acetonitrile (100%). The extracts were analyzed by high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (HPLC-MS/MS). The method had a chromatographic run time of 3.8 min and a linear calibration curve over the range 0.5-50 µg/mL (r > 0.99). This LC-MS-MS procedure was used to assess the bioavailability of two piracetam formulations: piracetam + l-carnitine (Piracar®; 270/330 mg tablet) and piracetam (Nootropil®; 800 mg tablet) in healthy volunteers of both sexes. The geometric means with corresponding 90% confidence interval (CI) for test/reference percentage ratios were 88.49% (90% CI = 81.19 - 96.46) for peak concentration/dose and 102.55% (90% CI = 100.62 - 104.51) for AUCinf /dose. The limit of quantitation of 0.5 µg/mL is well suited for pharmacokinetic studies in healthy volunteers. It was concluded that piracetam (Piracar®; 270/330 mg tablet) has a bioavailability equivalent to the piracetam (Nootropil®; 800 mg tablet) formulation with regard to both the rate and the extent of absorption. Copyright © 2015 John Wiley & Sons, Ltd.

Orthomolecular medicine: the therapeutic use of dietary supplements for anti-aging.

Science.gov (United States)

Janson, Michael

2006-01-01

Dietary supplements at high doses as part of medical therapy have been controversial, but the evidence suggests that they play a significant role in prevention and treatment of diseases as well as protection from accelerated aging that results from oxygen free-radical damage, inflammation, and glycation. This literature review examines several supplements that have documented roles in medical therapy, including vitamins C and E, coenzyme Q10, alpha-lipoic acid, chromium, L-carnitine, and quercetin. The evidence shows benefits in diabetes, cardiovascular disease, hypertension, congestive heart failure, age-related deterioration of brain function and vision, and immune function, as well as other age-related health problems.

Acetyl-L-Carnitine as an Adjunctive Therapy in the Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents: A Placebo-Controlled Trial

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Abbasi, Seyed-Hesameddin; Heidari, Shahram; Mohammadi, Mohammad-Reza; Tabrizi, Mina; Ghaleiha, Ali; Akhondzadeh, Shahin

2011-01-01

The objective of this study was to test whether a previous observed Acetyl-L-carnitine (ALC) treatment effect could be repeated in an ALC adjunctive therapy treatment trial of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. This was a six-week, randomized clinical trial undertaken in an outpatient child and adolescent…

Solving manufacturing problems for L-carnitine-L-tartrate to improve the likelihood of successful product scale-up

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Badawi Aliaa A.

2017-12-01

Full Text Available L-carnitine-L-tartrate, a non-essential amino acid, is hygroscopic. This causes a problem in tablet production due to pronounced adhesion of tablets to punches. A 33 full factorial design was adopted to suggest a tablet formulation. Three adsorbents were suggested (Aerosil 200, Aerosil R972, talc to reduce stickiness at three concentrations (1, 3 and 5 %, and three fillers (mannitol, Avicel PH 101, Dibasic calcium phosphate were chosen to prepare 27 formulations. Micromeritic properties of formulations were studied, and tablets were prepared by wet granulation. Absence of picking, sticking or capping, recording of sufficient hardness, acceptable friability and tablet ejection force indicated formulation success. The resulting formulation prepared using Avicel PH 101 and 1 % Aerosil 200 was submitted to further investigation in order to choose the most suitable compression conditions using a 33 full factorial design. Variables included compression force, tableting rate and magnesium stearate (lubricant concentration. The formulation prepared at compression force of 25 kN, using 2 % magnesium stearate, at a production rate of 30 tablets/ minute, was found to be the most appropriate scale up candidate.

Mild synthesis of [N-methyl-{sup 11}C]-isovaleroyl-(L)-carnitine. The usefulness of a tritium approach

Energy Technology Data Exchange (ETDEWEB)

Angelini, G.; Carnevaletti, F.; Margonelli, A.; Corsi, G. [Istituto di Chimica Nucleare - C.N.R., C.P. 10, Rome (Italy); Ragni, P. [Istituto di Chimica Nucleare -- C.N.R., C.P. 10 -- 00016 Monterotondo Stazione, Roma, (Italy); Fazio, F.; Todde, S. [Istituto di Neuroscienze e Bioimmagini - C.N.R., H.S. Raffaele, Milan (Italy); Tinti, O. [Sigma-Tau, Industrie Farmaceutiche Riunite S.p.A., Pomezia, Rome (Italy)

1999-02-01

The title carnitine derivative was labelled both with [{sup 11}C]methyl iodide and [{sup 3}H]methyl iodide. The former was synthesized in order to improve the knowledge of the acyl carnitines fate in humans. The latter was synthesized, at approximately the same concentration level as that of the former, in order to optimize its radiosynthesis, taking advantage from the long half-life of the tritium.

Radioiodinated carnitine and acylcarnitine analogs as potential myocardial imaging agents

International Nuclear Information System (INIS)

McConnell, D.S.

1991-01-01

R-carnitine is extremely important in mammalian energy metabolism. Gamma-butyrobetaine, the immediate biosynthetic precursor to R-carnitine, is synthesized in many organs. However, only liver can hydroxylate gamma-butyrobetaine to carnitine. Thus the transport of carnitine from its site of synthesis to the site of utilization is of utmost importance. Carnitine is found in highest concentration in cardiac and skeletal muscle, where it is required for the transport of fatty acids into the mitochondria. Before fatty acids are utilized as fuel for the myocyte by beta-oxidation, they are bound to carnitine as an acylcarnitine ester at the 3-hydroxyl, and transported across the micochondrial membranes. R,S-Carnitine has been shown to be taken up by myocytes. The author has begun a study on the use of carnitine derivatives as potential carriers for the site-specific delivery of radioiodine to bidning sites in the myocardium. Such agents labeled with a gamma-emitting nuclide such as iodine-123 would be useful for the noninvasive imaging of these tissues. The aim was to synthesize a variety of radiolabeled analogs of carnitine and acylcarnitine to address questions of transport, binding and availability for myocardial metabolism. These analogs consist of N-alkylated derivatives of carnitine, acylcarnitine esters as well as carnitine amides and ethers. One C-alkylated derivative showed interesting biodistribution, elevated myocardial uptake and competition with carnitine for binding in the myocardium

Relative Carnitine Deficiency in Autism

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Filipek, Pauline A.; Juranek, Jenifer; Nguyen, Minh T.; Cummings, Christa; Gargus, J. Jay

2004-01-01

A random retrospective chart review was conducted to document serum carnitine levels on 100 children with autism. Concurrently drawn serum pyruvate, lactate, ammonia, and alanine levels were also available in many of these children. Values of free and total carnitine ([rho] less than 0.001), and pyruvate ([rho]=0.006) were significantly reduced…

The histopathological comparison of L-carnitine with amifostine for protective efficacy on radiation-induced acute small intestinal toxicity

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Murat Caloglu

2012-01-01

Full Text Available Background: The aim of the study was to compare the protective efficacy of l-carnitine (LC to amifostine on radiation-induced acute small intestine damage. Materials and Methods: Thirty, 4-week-old Wistar albino rats were randomly assigned to four groups - Group 1: control (CONT, n = 6, Group 2: irradiation alone (RT, n = 8, Group 3: amifostine plus irradiation (AMI+RT, n = 8, and Group 4: l-Carnitine plus irradiation (LC+RT, n = 8. The rats in all groups were irradiated individually with a single dose of 20 Gy to the total abdomen, except those in CONT. LC (300 mg/kg or amifostine (200 mg/kg was used 30 min before irradiation. Histopathological analysis of small intestine was carried out after euthanasia. Results: Pretreatment with amifostine reduced the radiation-induced acute degenerative damage (P = 0.009 compared to the RT group. Pretreatment with LC did not obtain any significant difference compared to the RT group. The vascular damage significantly reduced in both of the AMI+RT (P = 0.003 and LC+RT group (P = 0.029 compared to the RT group. The overall damage score was significantly lower in the AMI+RT group than the RT group (P = 0.009. There was not any significant difference between the LC+RT and RT group. Conclusions: Amifostine has a marked radioprotective effect against all histopathological changes on small intestinal tissue while LC has limited effects which are mainly on vascular structure.

L-Carnitine Ameliorates Immunological-induced Hepatitis in rats

International Nuclear Information System (INIS)

Abd-Allah, Adel R.A.

2006-01-01

Immunological mediated hepatitis can be initiated by bacterial product; Lipopolysaccharide (LPS). The later is increased during severe infection, bacterial overgrowth or translocation. LPS stimulates Kupffer cells. Activation of the kupffer cells contributes to the onset of liver injuries by producing and releasing cytotoxic agents, inflammatory cytokines and reactive oxygen species. In the present study, L-carnitine, a natural antioxidant and immunoprotective agent, is used to protect against LPS-induced hepatitis. Liver content of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) and the DNA adduct 8-hydroxydeoxyguanosine (8-HDG) are estimated. Serum activity of liver enzymes ALT, AST, and Gamma-GT, in addition to IL2 level are also estimated. Moreover, liver histopathological changes are determined. Results revealed that LPS (5mg/kg once i.p) significantly increased 8-HDG, MDA, NO and depleted GSH in the liver of the treated rats. It also increased serum IL2 and activity of all the estimated liver enzyme markers indicating massive hepatic cellular damage as also shown as a necrotic damage in liver histological sections. LCR administered (500mg/kg) 3h before LPS protected against LPS-induced lethality by 100%. LCR also prevented the increase in liver content of 8-HDG, MDA and NO. It reduced the depleted GSH and prevented the necrotic damage in the liver tissue as shown by normalization of ALT, AST and Gamma-Gt as well as IL2 and a remarkable improvement in liver histology. These data suggest that LCr could be used as an adjuvant therapy in severely infected and specific patients to counteract LPS-induced liver hepatitis. (author)

Plasma trace metals during total parenteral alimentation.

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Solomons, N W; Layden, T J; Rosenberg, I H; Vo-Khactu, K; Sandstead, H H

1976-06-01

The plasma concentrations of the trace metals zinc and copper were studied prospectively in 13 patients with gastrointestinal diseases treated with parenteral alimentation (TPA) for periods of from 8 days to 7 1/2 weeks. Plasma copper levels fell rapidly and consistently in all patients, with an overall rate of - 11 mug per 100 ml per week. Zinc concentrations declined in 10 of 13 patients at a more gradual rate. Analysis of the standard parenteral alimentation fluids revealed zinc content equivalent to 50% of the daily requirement and a negligible content of copper. From combined analysis of plasma zinc, hair zinc, and taste acuity, there is evidence that increased utilization or redistribution within the body may effect plasma concentrations in some patients. Neither an increase in urinary excretion nor a primary decrease in plasma binding proteins appeared to be a major factor in lowering plasma trace metal concentrations. These findings indicate that a marked decrease in plasma copper is regular and a decline in plasma zinc is common during TPA using fluids unsupplemented with trace metals. Supplementation of parenteral alimentation fluids with the trace metals zinc and copper is recommended.

Enzymology of the Carnitine Biosynthesis Pathway

NARCIS (Netherlands)

Strijbis, Karin; Vaz, Frédéric M.; Distel, Ben

2010-01-01

The water-soluble zwitterion carnitine is an essential metabolite in eukaryotes required for fatty acid oxidation as it functions as a carrier during transfer of activated acyl and acetyl groups across intracellular membranes. Most eukaryotes are able to synthesize carnitine endogenously, besides

Inulin Supplementation Does Not Reduce Plasma Trimethylamine N-Oxide Concentrations in Individuals at Risk for Type 2 Diabetes

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Mary Elizabeth Baugh

2018-06-01

Full Text Available Trimethylamine N-oxide (TMAO is associated with type 2 diabetes (T2DM and increased risk of adverse cardiovascular events. Prebiotic supplementation has been purported to reduce TMAO production, but whether prebiotics reduce fasting or postprandial TMAO levels is unclear. Sedentary, overweight/obese adults at risk for T2DM (n = 18 were randomized to consume a standardized diet (55% carbohydrate, 30% fat with 10 g/day of either an inulin supplement or maltodextrin placebo for 6 weeks. Blood samples were obtained in the fasting state and hourly during a 4-h high-fat challenge meal (820 kcal; 25% carbohydrate, 63% fat; 317.4 mg choline, 62.5 mg betaine, 8.1 mg l-carnitine before and after the diet. Plasma TMAO and trimethylamine (TMA moieties (choline, l-carnitine, betaine, and γ-butyrobetaine were measured using isocratic ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS. There were no differences in fasting or postprandial TMAO or TMA moieties between the inulin and placebo groups at baseline (all p > 0.05. There were no significant changes in fasting or postprandial plasma TMAO or TMA moiety concentrations following inulin or placebo. These findings suggest that inulin supplementation for 6 weeks did not reduce fasting or postprandial TMAO in individuals at risk for T2DM. Future studies are needed to identify efficacious interventions that reduce plasma TMAO concentrations.

Carnitine acetyltransferase

DEFF Research Database (Denmark)

Berg, Sofia Mikkelsen; Beck-Nielsen, Henning; Færgeman, Nils Joakim

2017-01-01

Carnitine acetyltransferase (CRAT) deficiency has previously been shown to result in muscle insulin resistance due to accumulation of long-chain acylcarnitines. However, differences in the acylcarnitine profile and/or changes in gene expression and protein abundance of CRAT in myotubes obtained...

Genetics Home Reference: carnitine-acylcarnitine translocase deficiency

Science.gov (United States)

... Email Facebook Twitter Home Health Conditions CACT deficiency Carnitine-acylcarnitine translocase deficiency Printable PDF Open All Close ... Javascript to view the expand/collapse boxes. Description Carnitine-acylcarnitine translocase (CACT) deficiency is a condition that ...

Modelling and analysis of central metabolism operating regulatory interactions in salt stress conditions in a L-carnitine overproducing E. coli strain.

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Guido Santos

Full Text Available Based on experimental data from E. coli cultures, we have devised a mathematical model in the GMA-power law formalism that describes the central and L-carnitine metabolism in and between two steady states, non-osmotic and hyperosmotic (0.3 M NaCl. A key feature of this model is the introduction of type of kinetic order, the osmotic stress kinetic orders (g(OSn, derived from the power law general formalism, which represent the effect of osmotic stress in each metabolic process of the model.By considering the values of the g(OSn linked to each metabolic process we found that osmotic stress has a positive and determinant influence on the increase in flux in energetic metabolism (glycolysis; L-carnitine biosynthesis production; the transformation/excretion of Acetyl-CoA into acetate and ethanol; the input flux of peptone into the cell; the anabolic use of pyruvate and biomass decomposition. In contrast, we found that although the osmotic stress has an inhibitory effect on the transformation flux from the glycolytic end products (pyruvate to Acetyl-CoA, this inhibition is counteracted by other effects (the increase in pyruvate concentration to the extent that the whole flux increases. In the same vein, the down regulation exerted by osmotic stress on fumarate uptake and its oxidation and the production and export of lactate and pyruvate are reversed by other factors up to the point that the first increased and the second remained unchanged.The model analysis shows that in osmotic conditions the energy and fermentation pathways undergo substantial rearrangement. This is illustrated by the observation that the increase in the fermentation fluxes is not connected with fluxes towards the tricaboxylic acid intermediates and the synthesis of biomass. The osmotic stress associated with these fluxes reflects these changes. All these observations support that the responses to salt stress observed in E. coli might be conserved in halophiles.Flux evolution

Serum total and free carnitine levels in children with asthma.

Science.gov (United States)

Asilsoy, Suna; Bekem, Ozlem; Karaman, Ozkan; Uzuner, Nevin; Kavukçu, Salih

2009-02-01

Serum carnitine is decreased in recurrent pulmonary infections. We aimed to evaluate serum carnitine levels in asthmatic children. Study group consisted of children with stable asthma and those with acute asthma attacks, while control group included healthy children. Attack severity was determined by the pulmonary score system. Total and free carnitine levels were studied in one blood sample from the control group and stable asthmatics and in two samples from children with acute asthma exacerbation during and after the attack. All the 40 patients in the study group had moderate asthma including 30 with acute attack (13 mild and 17 moderate) and 10 with stable asthma. Carnitine levels were significantly lower in acute attack asthmatics than in the stable asthmatics and controls, while there was no significant difference between the latter two groups. Carnitine levels were not different between asthmatics with mild and moderate attack, and were similar during and after an acute attack. Serum carnitine levels decrease in children with moderate asthma during exacerbation of asthma and shortly thereafter. Further studies are needed to evaluate the effect of carnitine treatment on serum carnitine level.

Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study.

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Buchman, A L; Sohel, M; Brown, M; Jenden, D J; Ahn, C; Roch, M; Brawley, T L

2001-01-01

Previous investigations have demonstrated that choline deficiency, manifested in low plasma-free choline concentration and hepatic injury, may develop in patients who require long-term total parenteral nutrition (TPN). Preliminary studies have suggested lecithin or choline supplementation might lead to improved visual memory in the elderly and reverse abnormal neuropsychological development in children. We sought to determine if choline-supplemented TPN would lead to improvement in neuropsychological test scores in a group of adult, choline-deficient outpatients receiving TPN. Eleven subjects (8 males, 3 females) who received nightly TPN for more than 80% of their nutritional needs for at least 12 weeks before entry in the study were enrolled. Exclusion criteria included active drug abuse, mental retardation, cerebral vascular accident, head trauma, hemodialysis or peritoneal dialysis, (prothrombin time [PT] >2x control), or acquired immune deficiency syndrome (AIDS). Patients were randomly assigned to receive their usual TPN regimen (n = 6, aged 34.0 +/- 12.6 years) over a 12-hour nightly infusion or their usual TPN regimen plus choline chloride (2 g) (n = 5, aged 37.3 +/- 7.3 years). The following neuropsychological tests were administered at baseline and after 24 weeks of choline supplementation (or placebo): Weschler Adult Intelligence Scale-Revised (WAIS-R, intellectual functioning), Weschler Memory Scale-Revised (WMS-R, two subtests, verbal and visual memory), Rey-Osterrieth Complex Figure Test (visuospatial functioning and perceptual organization), Controlled Oral Word Association Test (verbal fluency), Grooved Pegboard (manual dexterity and motor speed), California Verbal Learning Test (CVLT, rote verbal learning ability), and Trail Making Parts A & B (visual scanning, psychomotor speed and set shifting). Scores were reported in terms of standard scores including z scores and percentile ranks. Mean absolute changes in raw scores were compared between groups

Modulation of synergistic cardiotoxicity of doxorubicin and radiation therapy by propionyl l-carnitine

International Nuclear Information System (INIS)

Mansour, H.H.

2002-01-01

Combined radiotherapy and chemotherapy have represented a major advance in the therapeutic management of cancer therapy. However, the combination of Doxorubicin (DOX) and irradiation (IRR) may be more cardiotoxic than either agent. Propionyl-L-carnitine (PLC) is a naturally occurring derivative of L-carnitine that has been considered in the treatment of many forms of cardiomyopathies. In this study, the possible mechanism (S) whereby PLC couls protect against DOX and/or IRR-induced cardiomyopathy were carried out. Administration of DOX as a single dose (5 mg/Kg) or cumulative dose (15 and 25 mg/kg divided into 3 and 5 equal doses 5 mg/kg each, every other day) resulted in significant and dose dependent increase in serum cardiac enzymes (CPK, GOT and LDH) in rat, MDA level and nitric oxide in heart tissue and dose dependent decrease in the antioxidant enzymes (SOD) and GSHPx). Whole body irradiation (2 Gy) induced similar effect to DOX. Combination of DOX and IRR resulted in marked elevation in cardiac enzymes and MDA level and remarkable decrease in the antioxidant enzymes . PLC (250 mg/kg, for 9 days) before DOX and /or IRR induced significant increase in the activity of SOD and GSHPx and significantly decreased the level of MDA and nitric oxide in rat cardiac tissue and the activity of cardiac enzymes in rat serum. Also, DOX-induced dose dependent increase in AC/FC ratio above the normal value (0.4) in serum and heart tissue. Combination of DOX and IRR increased the ratio. Administration of PLC to DOX and/or IRR resulted in partial reversal of DOX induced increase in the AC/FC ratio except for the highest cumulative dose (25 mg/kg) in serum. Dox induced dose-dependent increase in DOX concentration in serum and heart tissue. Administration of PLC decreased DOX concentration in heart with an increase in DOX concentration in serum. IRR did not alter DOX concentration. Worth mentioning os that PLC had no effect on the antitumor activity of DOX and/ or IRR in solid

Parenteral nutrition in short bowel syndrome patients, regardless of its duration, increases serum proinflammatory cytokines.

Science.gov (United States)

Bizari, Letícia; da Silva Santos, Andressa Feijó; Foss, Norma Tiraboschi; Marchini, Júlio Sérgio; Suen, Vivian Marques Miguel

2016-07-01

Short bowel syndrome is a severe malabsorption disorder, and prolonged parenteral nutrition is essential for survival in some cases. Among the undesirable effects of long-term parenteral nutrition is an increase in proinflammatory cytokines. The aim of the present study was to measure the serum levels of interleukin-6, interleukin-10, tumor necrosis factor alpha, and transforming growth factor beta, in patients with short bowel syndrome on cyclic parenteral nutrition and patients who had previously received but no longer require parenteral nutrition. The study was cross-sectional and observational. Three groups were studied as follows: Parenteral nutrition group, 9 patients with short bowel syndrome that receive cyclic parenteral nutrition; Oral nutrition group, 10 patients with the same syndrome who had been weaned off parenteral nutrition for at least 1 year prior to the study; Control group, 13 healthy adults, matched for age and sex to parenteral and oral groups. The following data were collected: age, tobacco use, drug therapies, dietary intake, body weight, height, blood collection. All interleukins were significantly higher in the parenteral group compared with the control group as follows: interleukin-6: 22 ± 19 vs 1.5 ± 1.4 pg/mL, P= .0002; transforming growth factor β: 854 ± 204 vs 607 ± 280 pg/mL, P= .04; interleukin-10: 8 ± 37 vs 0.6 ± 4, P= .03; tumor necrosis factor α: 20 ± 8 vs 8 ± 4 pg/mL, Pparenteral nutrition in short bowel syndrome patients, regardless of its duration, increases serum proinflammatory cytokines. Copyright © 2016 Elsevier Inc. All rights reserved.

L-carnitine is an endogenous HDAC inhibitor selectively inhibiting cancer cell growth in vivo and in vitro.

Science.gov (United States)

Huang, Hongbiao; Liu, Ningning; Guo, Haiping; Liao, Siyan; Li, Xiaofen; Yang, Changshan; Liu, Shouting; Song, Wenbin; Liu, Chunjiao; Guan, Lixia; Li, Bing; Xu, Li; Zhang, Change; Wang, Xuejun; Dou, Q Ping; Liu, Jinbao

2012-01-01

L-carnitine (LC) is generally believed to transport long-chain acyl groups from fatty acids into the mitochondrial matrix for ATP generation via the citric acid cycle. Based on Warburg's theory that most cancer cells mainly depend on glycolysis for ATP generation, we hypothesize that, LC treatment would lead to disturbance of cellular metabolism and cytotoxicity in cancer cells. In this study, Human hepatoma HepG2, SMMC-7721 cell lines, primary cultured thymocytes and mice bearing HepG2 tumor were used. ATP content was detected by HPLC assay. Cell cycle, cell death and cell viability were assayed by flow cytometry and MTS respectively. Gene, mRNA expression and protein level were detected by gene microarray, Real-time PCR and Western blot respectively. HDAC activities and histone acetylation were detected both in test tube and in cultured cells. A molecular docking study was carried out with CDOCKER protocol of Discovery Studio 2.0 to predict the molecular interaction between L-carnitine and HDAC. Here we found that (1) LC treatment selectively inhibited cancer cell growth in vivo and in vitro; (2) LC treatment selectively induces the expression of p21(cip1) gene, mRNA and protein in cancer cells but not p27(kip1); (4) LC increases histone acetylation and induces accumulation of acetylated histones both in normal thymocytes and cancer cells; (5) LC directly inhibits HDAC I/II activities via binding to the active sites of HDAC and induces histone acetylation and lysine-acetylation accumulation in vitro; (6) LC treatment induces accumulation of acetylated histones in chromatin associated with the p21(cip1) gene but not p27(kip1) detected by ChIP assay. These data support that LC, besides transporting acyl group, works as an endogenous HDAC inhibitor in the cell, which would be of physiological and pathological importance.

Comparison of the protective roles of L-carnitine and amifostine against radiation-induced acute ovarian damage by histopathological and biochemical methods

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Vuslat Yurut-Caloglu

2015-01-01

Full Text Available Purpose: The aim of this study was to compare the radioprotective efficacies of L-carnitine (LC and amifostine against radiation-induced acute ovarian damage. Materials and Methods: Forty-five, 3-month-old Wistar albino rats were randomly assigned to six groups. Control (CONT, n = 7; irradiation alone RT: radiation therapy (RT, n = 8; amifostine plus irradiation (AMI + RT, n = 8; LC plus irradiation (LC + RT, n = 8; LC and sham irradiation (LC, n = 7; and amifostine and sham irradiation (AMI, n = 7. The rats in the AMI + RT, LC + RT and RT groups were irradiated with a single dose of 20 Gy to the whole abdomen. LC (300 mg/kg and amifostine (200 mg/kg was given intraperitoneally 30 min before irradiation. Five days after irradiation, both antral follicles and corpus luteum in the right ovaries were counted, and tissue levels of malondialdehyde (MDA and advanced oxidation protein product (AOPP were measured. Results: Irradiation significantly decreased antral follicles and corpus luteum (P: 0.005 and P 0.05. The level of MDA and AOPP significantly increased after irradiation (P = 0.001 and P 0.005. The levels of both MDA and AOPP were also similar when LC + RT is compared with AMI + RT group (P > 0.005. Conclusions: L-carnitine and amifostine have a noteworthy and similar radioprotective effect against radiation-induced acute ovarian toxicity.

ROLE OF PARENTERAL AMINO ACIDS SUPPLEMENATION IN OLIGOHYDRAMNIOS & IUGR COMPLICATED PREGNANCIES

OpenAIRE

Anuradha; Malini; Sumit

2015-01-01

OBJECTIVES: To see whether parenteral nutritional supplementation of women with oligohydramnios/IUGR can improve the amount of liquor and to evaluate the role of pareneral therapy in improving maternal and perinatal outcome and to correlate between the occurrence of oligohydramnios and IUGR among women of different age, parity, education and socioe...

Reversal of growth arrest in adolescents with Crohn's disease after parenteral alimentation.

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Layden, T; Rosenberg, F; Nemchausky, G; Elson, C; Rosenberg, I

1976-06-01

Growth arrest and delayed onset of puberty often complicate childhood onset Crohn's disease of the small bowel (granulomatous enteritis). Nutritional deficits arising from inadequate dietary intake, malabsorption, and increased caloric needs may contribute to growth retardation. To assess whether a sustained high caloric and nitrogen intake could reestablish growth, 4 children with extensive Crohn's disease of the small bowel were studied before and after parenteral alimentation which was instituted for symtomatic disease control. Weight gain, positive nitrogen balance, and improved nutritional status were achieved during parenteral alimentation in each patient. In 2 patients weight gain was sustained using oral nutritional supplements, and a substantial increase in linear skeletal growth continued in the ensuing months. One patient entered puberty within 4 months of parenteral alimentation and another had the onset of menarche and the development of secondary sex characteristics 4 months after parenteral alimentation and resection of diseased bowel. Growth may be reestablished in some growth-arrested children if intake is sufficient to establish a sustained positive caloric and nitrogen balance. Nutritional requirements imposed by the demands of growth and active disease and often compounded by the catabolic effects of corticosteroids may be excessive; growth may occur only if these needs are met orally and/or parenterally.

Enthalpic pairwise self-association of L-carnitine in aqueous solutions of some alkali halides at T = 298.15 K

International Nuclear Information System (INIS)

Wang, Hua-Qin; Cheng, Wei-Na; Zhu, Li-Yuan; Hu, Xin-Gen

2016-01-01

Highlights: • Dilution enthalpies of L-carnitine in aqueous alkali halide solutions by ITC. • The second virial coefficients of enthalpy (h_2) have been calculated. • The values of h_2 increase with increasing molalities of aqueous salt solutions. • The signs of h_2 turn from negative in pure water to positive in salt solutions. • The trends is ascribed to the salt effects on pairwise self-associations. - Abstract: Knowledge of the influence of ions of various nature on intermolecular hydrophilic and hydrophobic interactions in solutions is required in many research fields. In this paper, dilution enthalpies of zwitterion L-carnitine in aqueous NaCl, KCl and NaBr solutions of various molalities (b = 0 to 3.0 mol · kg"−"1) have been determined respectively at T = (298.15 ± 0.01) K and p = (0.100 ± 0.005) MPa by isothermal titration calorimetry (ITC). In light of the MacMillan–Mayer theory, the 2nd virial enthalpic coefficients (h_2) have been calculated. The h_2 coefficients increase gradually with increasing molality (b) of the three aqueous alkali halides solutions, from small negative values in pure water to relatively larger positive values in solution. The trends of h_2 coefficients are ascribed to the salt effects on the balance between hydrophilic and hydrophobic interactions in pairwise self-associations. It is considered that the size of cations and anions exert influences on h_2 coefficients through their surface charge densities and hydration (or dehydration) abilities.

Technetium-99m sestamibi leg scintigraphy for non-invasive assessment of propionyl-l-carnitine induced changes in skeletal muscle metabolism

International Nuclear Information System (INIS)

Cittanti, C.; Colamussi, P.; Giganti, M.; Orlandi, C.; Uccelli, L.; Manfrini, S.; Azzena, G.; Piffanelli, A.

1997-01-01

Carnitine derivatives, such as propionyl-l-carnitine (PLC), have been shown to improve walking distance in patients with obstructive peripheral artery disease (PAOD). The aim of this study was to ascertain whether technetium-99m sestamibi leg scintigraphy may be a useful tool in the evaluation of changes in skeletal muscle metabolism induced by chronic therapy with PLC. Twenty patients with clinical and instrumental evidence of PAOD were randomly assigned to a 3-month period of therapy with either PLC or placebo. Rest 99m Tc-sestamibi leg scintigraphy and echo-Doppler sonography were performed on all subjects immediately before and upon completion of the treatment period. At the end of the protocol the following results were observed in patients who underwent PLC administration: (a) a significant increase in both thigh and calf 99m Tc-sestamibi uptake, in comparison with baseline values (P 99m Tc-sestamibi was demonstrated without any apparent change in regional blood flow. This fact, if proven in further studies, may suggest a role for this tracer as a non-invasive probe of tissue bioenergetics. (orig.). With 4 figs., 4 tabs

Responses of Preterm Pigs to an Oral Fluid Supplement During Parenteral Nutrition

DEFF Research Database (Denmark)

Berding, Kirsten; Makarem, Patty; Hance, Brittany

2016-01-01

Background: Nutrients and electrolytes in amniotic fluid swallowed by fetuses are important for growth and development. Yet, preterm infants requiring parenteral nutrition (PN) receive minimal or no oral inputs. With the limited availability of amniotic fluid, we evaluated the responses of preterm...

Changing to a vegetarian diet reduces the body creatine pool in omnivorous women, but appears not to affect carnitine and carnosine homeostasis: a randomised trial.

Science.gov (United States)

Blancquaert, Laura; Baguet, Audrey; Bex, Tine; Volkaert, Anneke; Everaert, Inge; Delanghe, Joris; Petrovic, Mirko; Vervaet, Chris; De Henauw, Stefaan; Constantin-Teodosiu, Dumitru; Greenhaff, Paul; Derave, Wim

2018-04-01

Balanced vegetarian diets are popular, although they are nearly absent in creatine and carnosine and contain considerably less carnitine than non-vegetarian diets. Few longitudinal intervention studies investigating the effect of a vegetarian diet on the availability of these compounds currently exist. We aimed to investigate the effect of transiently switching omnivores onto a vegetarian diet for 6 months on muscle and plasma creatine, carnitine and carnosine homeostasis. In a 6-month intervention, forty omnivorous women were ascribed to three groups: continued omnivorous diet (control, n 10), vegetarian diet without supplementation (Veg+Pla, n 15) and vegetarian diet combined with daily β-alanine (0·8-0·4 g/d) and creatine supplementation (1 g creatine monohydrate/d) (Veg+Suppl, n 15). Before (0 months; 0M), after 3 months (3M) and 6 months (6M), a fasted venous blood sample and 24-h urine was collected, and muscle carnosine content was determined by proton magnetic resonance spectroscopy (1H-MRS). Muscle biopsies were obtained at 0M and 3M. Plasma creatine and muscle total creatine content declined from 0M to 3M in Veg+Pla (P=0·013 and P=0·009, respectively), whereas plasma creatine increased from 0M in Veg+Suppl (P=0·004). None of the carnitine-related compounds in plasma or muscle showed a significant time×group interaction effect. 1H-MRS-determined muscle carnosine content was unchanged over 6M in control and Veg+Pla, but increased in Veg+Suppl in soleus (Pvegetarian diet in omnivorous women, which was ameliorated when accompanied by low-dose dietary creatine supplementation. Carnitine and carnosine homeostasis was unaffected by a 3- or 6-month vegetarian diet, respectively.

Assessing Selenium, Manganese, and Iodine Status in Pediatric Patients Receiving Parenteral Nutrition.

Science.gov (United States)

Johnsen, Jacob Clarke; Reese, Susan Anne; Mackay, Mark; Anderson, Collin R; Jackson, Daniel; Paul, Irasema Libertad

2017-08-01

Pediatric patients who are receiving parenteral nutrition (PN) unsupplemented with trace minerals can become deficient. Due to shortages in trace mineral products and the 2004 American Society for Parenteral and Enteral Nutrition report stating that individualized trace element supplementation may be warranted, a review was conducted concerning the trace minerals selenium (Se), manganese (Mn), and iodine (I). A retrospective review of pediatric patients receiving PN that contained Se and Mn was conducted to determine if a difference existed between them and patients receiving PN without Se and Mn. Statistical analysis was done to assess a difference between trace mineral levels and the time to deficiency between supplemented and unsupplemented patients. Unsupplemented I patients had urine I levels assessed to determine deficiencies in patients receiving PN. Plasma Se levels were measured at a mean of 20 days for supplemented patients (n = 131) and 19 days for nonsupplemented patients (n = 57) with no difference between groups ( P = .2973). Plasma Mn levels were measured at a mean of 28 days, showing no statistical difference ( P = .721). Of the 177 nonsupplemented I patients, 74% demonstrated I deficiencies without supplementation. Time to the development of a Se, Mn, or I deficiency is important to guide supplementation of exclusive PN in children when trace mineral products are short in supply. Our retrospective experience supports assessment of the trace minerals Se at 21 days and Mn at 30 days. It also suggests that some pediatric patients receiving PN are deficient in I.

Reconciling divergent results of the latest parenteral nutrition studies in the ICU.

Science.gov (United States)

Singer, Pierre; Pichard, Claude

2013-03-01

Recent studies on the optimal modalities to feed patients during the ICU stay show divergent results. The level and the timing of energy provision is a critical issue, associated with the clinical outcome. These results questioned the clinical relevance of the recent guidelines issued by American, Canadian and European academic societies. Four recent prospective randomized studies enrolled critically ill patients who received various nutritional regimens and tested the effect of nutritional support on outcome. The Tight Calorie balance Control Study (TICACOS) targeted on calorie administration according to measured energy expenditure and found increased ICU morbidity but improved hospital mortality. The large EpaNIC study compared 'early' with 'late' (parenteral nutrition) nutrition, mostly in patients after cardiac surgery, and found an increased morbidity associated with early parenteral nutrition. The supplemental parenteral nutrition (SPN) study randomized the patients after 3 days and targeted the calories administered by parenteral nutrition as a complement to unsuccessful enteral nutrition using indirect calorimetry. The SPN resulted in less nosocomial infections and shorter duration of mechanical ventilation. Finally, a recent Australian study enrolled patients unable to be early fed enterally to receive, or not, parenteral nutrition targeted at 1500 kcal. No complications were noted in the parenteral nutrition group. Lessons from all these studies are summarized and should help in designing better studies and guidelines. The critical analysis of recent prospective studies comparing various levels of calorie administration, enteral versus parenteral nutrition and enteral versus SPN confirms the recommendations to avoid underfeeding and overfeeding. Parenteral nutrition, required if enteral feeding is failing, and if adjusted up to a measured optimal level, may improve outcome. More studies on the optimal level of energy and protein administration to

Dietary L-Carnitine and energy and lipid metabolism in African catfish (Clarias gariepinus) juveniles

NARCIS (Netherlands)

A. Ozório, de R.O.

2001-01-01

As the lipid content of the diet increases so does the requirement for certain components involved in lipid metabolism. Carnitine is a normal constituent of animal tissues and plasma, which is required for the transport of long-chain fatty acids (LCFAs) to the site of

Supplementation of diets for weaned piglets withL-Valine and L-Glutamine+ L-Glutamic acid

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Naiara Diedrich Rodrigues

2015-10-01

Full Text Available The objective of this study was to evaluate the effects of supplementation of diets for weaned piglets with L-valine and L-glutamine + L-glutamic acid on performance, frequency of diarrhea, organ weight, digesta pH, intestinal morphology, and economic viability. Seventy-two piglets with a live weight of 7.53 ± 0.84 kg and 24 days of age were used. The animals were submitted to the following four treatments from 24 to 46 days of age: diet not supplemented with amino acids (control diet, CD; diet supplemented with glutamine + glutamic acid (GD; diet supplemented with glutamine + glutamic acid + valine (GVD, and diet supplemented with valine (VD. Two sequential phases (pre-initial I and pre-initial II with a duration of 12 and 11 days, respectively, were established. A completely randomized design, consisting of six repetitions and three pigs per experimental unit, was used. Nine days after weaning, at 32 days of age, a piglet per pen was slaughtered for the evaluation of organ weight, digesta pH and intestinal morphology. All animals received a single diet from days 47 to 65. No effects on performance were observed during the pre-initial phases I and II; however, when the whole study period was considered (24 to 65 days of age, piglets fed GVD consumed less feed and exhibited better feed conversion than animals of the VD group. With respect to morphometric parameters, GD provided a greater ileal crypt depth than CD and VD. There was an economic advantage of diets supplemented with L-valine and L-glutamine + L-glutamic acid, validating their use in diets for weaned piglets until 46 days of age.

Combined enteral and parenteral nutrition.

Science.gov (United States)

Wernerman, Jan

2012-03-01

To review and discuss the evidence and arguments to combine enteral nutrition and parenteral nutrition in the ICU, in particular with reference to the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) study. The EPaNIC study shows an advantage in terms of discharges alive from the ICU when parenteral nutrition is delayed to day 8 as compared with combining enteral nutrition and parenteral nutrition from day 3 of ICU stay. The difference between the guidelines from the European Society of Enteral and Parenteral Nutrition in Europe and American Society for Parenteral and Enteral Nutrition/Society of Critical Care Medicine in North America concerning the combination of enteral nutrition and parenteral nutrition during the initial week of ICU stay was reviewed. The EPaNIC study clearly demonstrates that early parenteral nutrition in the ICU is not in the best interests of most patients. Exactly at what time point the combination of enteral nutrition and parenteral nutrition should be considered is still an open question.

L-Arginine Supplementation and Metabolism in Asthma

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Angela Linderholm

2011-01-01

Full Text Available L-Arginine, the amino acid substrate for nitric oxide synthase, has been tested as a therapeutic intervention in a variety of chronic diseases and is commonly used as a nutritional supplement. In this study, we hypothesized that a subset of moderate to severe persistent asthma patients would benefit from supplementation with L-arginine by transiently increasing nitric oxide levels, resulting in bronchodilation and a reduction in inflammation. The pilot study consisted of a 3 month randomized, double-blind, placebo-controlled trial of L-arginine (0.05 g/kg twice daily in patients with moderate to severe asthma. We measured spirometry, exhaled breath nitric oxide, serum arginine metabolites, questionnaire scores, daily medication use and PEFR with the primary endpoint being the number of minor exacerbations at three months. Interim analysis of the 20 subjects showed no difference in the number of exacerbations, exhaled nitric oxide levels or lung function between groups, though participants in the L-arginine group had higher serum L-arginine at day 60 (2.0 ± 0.6 × 10−3 vs. 1.1 ± 0.2 × 10−3 µmol/L, p < 0.05, ornithine at day 30 (2.4 ± 0.9 vs. 1.2 ± 0.3 µmol/L serum, p < 0.05 and ADMA at day 30 (6.0 ± 1.5 × 10−1 vs. 2.6 ± 0.6 × 10−1 µmol/L serum, p < 0.05 on average compared to the placebo group. The study was terminated prematurely. Supplementing asthma subjects with L-arginine increases plasma levels; whether subgroups might benefit from such supplementation requires further study.

Total parenteral nutrition

Science.gov (United States)

... medlineplus.gov/ency/patientinstructions/000177.htm Total parenteral nutrition To use the sharing features on this page, please enable JavaScript. Total parenteral nutrition (TPN) is a method of feeding that bypasses ...

Parenteral nutrition.

Science.gov (United States)

Inayet, N; Neild, P

2015-03-01

Over the last 50 years, parenteral nutrition has been recognised as an invaluable and potentially lifesaving tool in the physician's arsenal in the management of patients with intestinal failure or inaccessibility; however, it may also be associated with a number of potentially life-threatening complications. A recent NCEPOD report (2010) identified a number of inadequacies in the overall provision and management of parenteral nutrition and recommendations were made with the aim of improving clinical practice in the future. This paper focuses on the practical aspects relating to parenteral nutrition for adults, including important concepts, such as patient selection, as well as general management. We also explore the various pitfalls and potential complications and how these may be minimised.

Effects of carnitine and its congeners on eicosanoid discharge from rat cells: implications for release of TNFα

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Ingrid M. Garrelds

1993-01-01

Full Text Available THE acyl carrier coenzyme A (CoA is involved in fatty acid metabolism. The carnitine/CoA ratio is of particular importance in regulating the transport of long-chain fatty acids into mitochondria for oxidation. Also CoA has a role in the formation and breakdown of products from both the cyclooxygenase and lipoxygenase pathways of the precursor arachidonic acid. In the present study the effect of 4 days feeding of 300 mg/kg/day of L-carnitine, acetyl Lcarnitine and propionyl L-carnitine on the basal and calcium ionophore (A23187 stimulated release of arachidonic acid metabolites from rat carrageenin elicited peritoneal cells was investigated. There were two series of experiments carried out. In the first, the harvested peritoneal cell population consisted of less than 90% macrophages and additional polymorphonuclear (PMN leucocytes. The basal release of prostaglandin E2 (PGE2, 6-ketoprostaglandin F1α (6-keto-PGF1α and leukotriene B4 (LTB4 was stimulated by all treatments. The A23187 stimulated release of 6-keto-PGF1α and LTB4 was increased by all three compounds. The 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 ratios were increased by carnitine treatment. These results suggested that carnitine could modify the macrophage component of an inflammatory site in vivo. In the second series of experiments the harvested cell population was highly purified (>95% macrophages and none of the compounds fed to the rats caused a change of either eicosanoid or TNFα formation. Moreover the 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 ratios were not enhanced by any of the compounds tested. It is conceivable that in the first series the increased ratios 6-keto-PGF1α:TxB2 and 6-keto-PGF1α:LTB4 reflected the effect of carnitine or its congeners on PMN leucocytes rather than on macrophages.

Acute Exercise Stimulates Carnitine Biosynthesis and OCTN2 Expression in Mouse Kidney

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Tom L. Broderick

2017-06-01

Full Text Available Background/Aims: Carnitine is essential for the transport of long-chain FAs (FA into the mitochondria for energy production. During acute exercise, the increased demand for FAs results in a state of free carnitine deficiency in plasma. The role of kidney in carnitine homeostasis after exercise is not known. Methods: Swiss Webster mice were sacrificed immediately after a 1-hour moderate intensity treadmill run, and at 4-hours and 8-hours into recovery. Non-exercising mice served as controls. Plasma was analyzed for carnitine using acetyltransferase and [14C] acetyl-CoA. Kidney was removed for gene and protein expression of butyrobetaine hydroxylase (γ-BBH, organic cation transporter (OCTN2, and peroxisome proliferator-activated receptor (PPARα, a regulator of fatty acid oxidation activated by FAs. Results: Acute exercise caused a decrease in plasma free carnitine levels. Rapid return of free carnitine to control levels during recovery was associated with increased γ-BBH expression. Both mRNA and protein levels of OCTN2 were detected in kidney after exercise and during recovery, suggesting renal transport mechanisms were stimulated. These changes were accompanied with a reciprocal increase in PPARα protein expression. Conclusions: Our results show that the decrease in free carnitine after exercise rapidly activates carnitine biosynthesis and renal transport mechanism in kidney to establish carnitine homeostasis.

Zinc: physiology, deficiency, and parenteral nutrition.

Science.gov (United States)

Livingstone, Callum

2015-06-01

The essential trace element zinc (Zn) has a large number of physiologic roles, in particular being required for growth and functioning of the immune system. Adaptive mechanisms enable the body to maintain normal total body Zn status over a wide range of intakes, but deficiency can occur because of reduced absorption or increased gastrointestinal losses. Deficiency impairs physiologic processes, leading to clinical consequences that include failure to thrive, skin rash, and impaired wound healing. Mild deficiency that is not clinically overt may still cause nonspecific consequences, such as susceptibility to infection and poor growth. The plasma Zn concentration has poor sensitivity and specificity as a test of deficiency. Consequently, diagnosis of deficiency requires a combination of clinical assessment and biochemical tests. Patients receiving parenteral nutrition (PN) are susceptible to Zn deficiency and its consequences. Nutrition support teams should have a strategy for assessing Zn status and optimizing this by appropriate supplementation. Nutrition guidelines recommend generous Zn provision from the start of PN. This review covers the physiology of Zn, the consequences of its deficiency, and the assessment of its status, before discussing its role in PN. © 2015 American Society for Parenteral and Enteral Nutrition.

Differentially expressed genes in Hirudo medicinalis ganglia after acetyl-L-carnitine treatment.

Science.gov (United States)

Federighi, Giuseppe; Macchi, Monica; Bernardi, Rodolfo; Scuri, Rossana; Brunelli, Marcello; Durante, Mauro; Traina, Giovanna

2013-01-01

Acetyl-L-carnitine (ALC) is a naturally occurring substance that, when administered at supra-physiological concentration, is neuroprotective. It is involved in membrane stabilization and in enhancement of mitochondrial functions. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. ALC is known to improve the cognitive capability of aged animals chronically treated with the drug and, recently, it has been reported that it impairs forms of non-associative learning in the leech. In the present study the effects of ALC on gene expression have been analyzed in the leech Hirudo medicinalis. The suppression subtractive hybridisation methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the leech nervous system after ALC treatment. The method detects differentially but also little expressed transcripts of genes whose sequence or identity is still unknown. We report that a single administration of ALC is able to modulate positively the expression of genes coding for functions that reveal a lasting effect of ALC on the invertebrate, and confirm the neuroprotective and neuromodulative role of the substance. In addition an important finding is the modulation of genes of vegetal origin. This might be considered an instance of ectosymbiotic mutualism.

OCTN3 is a mammalian peroxisomal membrane carnitine transporter

International Nuclear Information System (INIS)

Lamhonwah, Anne-Marie; Ackerley, Cameron A.; Tilups, Aina; Edwards, Vernon D.; Wanders, Ronald J.; Tein, Ingrid

2005-01-01

Carnitine is a zwitterion essential for the β-oxidation of fatty acids. The role of the carnitine system is to maintain homeostasis in the acyl-CoA pools of the cell, keeping the acyl-CoA/CoA pool constant even under conditions of very high acyl-CoA turnover, thereby providing cells with a critical source of free CoA. Carnitine derivatives can be moved across intracellular barriers providing a shuttle mechanism between mitochondria, peroxisomes, and microsomes. We now demonstrate expression and colocalization of mOctn3, the intermediate-affinity carnitine transporter (K m 20 μM), and catalase in murine liver peroxisomes by TEM using immunogold labelled anti-mOctn3 and anti-catalase antibodies. We further demonstrate expression of hOCTN3 in control human cultured skin fibroblasts both by Western blotting and immunostaining analysis using our specific anti-mOctn3 antibody. In contrast with two peroxisomal biogenesis disorders, we show reduced expression of hOCTN3 in human PEX 1 deficient Zellweger fibroblasts in which the uptake of peroxisomal matrix enzymes is impaired but the biosynthesis of peroxisomal membrane proteins is normal, versus a complete absence of hOCTN3 in human PEX 19 deficient Zellweger fibroblasts in which both the uptake of peroxisomal matrix enzymes as well as peroxisomal membranes are deficient. This supports the localization of hOCTN3 to the peroxisomal membrane. Given the impermeability of the peroxisomal membrane and the key role of carnitine in the transport of different chain-shortened products out of peroxisomes, there appears to be a critical need for the intermediate-affinity carnitine/organic cation transporter, OCTN3, on peroxisomal membranes now shown to be expressed in both human and murine peroxisomes. This Octn3 localization is in keeping with the essential role of carnitine in peroxisomal lipid metabolism

Correlações entre os níveis de L-carnitina plasmática, o estado nutricional e a função ventilatória de portadores de doença pulmonar obstrutiva crônica Correlations among the levels of plasmatic L-carnitine, the nutritional status, and the ventilatory function in patients with chronic obstructive pulmonary disease

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Audrey Borghi e Silva

2005-06-01

Full Text Available OBJETIVO: Avaliar os níveis de L-carnitina livre no plasma, o estado nutricional, a função pulmonar e a tolerância ao exercício em pacientes com doença pulmonar obstrutiva crônica e verificar as correlações entre a composição corporal e as frações de L-carnitina no plasma. MÉTODOS: Quarenta pacientes entre 66,2±9 anos, com diagnóstico clínico de doença pulmonar obstrutiva crônica, foram divididos em dois grupos: G1, com índice de massa corporal menor que 20kg/m², e G2, com índice de massa corporal maior que 20kg/m². Foram mensurados os parâmetros espirométricos, a tolerância ao exercício no teste de caminhada, a força muscular respiratória, a composição corporal por meio da impedância bioelétrica e as dosagens da L-carnitina plasmática, através de amostras de sangue. RESULTADOS: Foram observados menores valores das variáveis espirométricas (pOBJECTIVE: The objective of this study was to evaluate the levels of free L-carnitine in the plasma, the nutritional condition, the pulmonary function, and the tolerance to exercising in patients with chronic obstructive pulmonary Disease, in order to verify the correlations between body composition and L-carnitine levels in the plasma. METHODS: Forty patients between 66.2±9 years of age, with clinical diagnostics of chronic obstructive pulmonary disease, were divided in two groups: G1, patients with body mass index of less than 20 kg/m², and G2, with Body Mass Index of more than 20 kg/m². There were evaluations of the spirometric variables; the exercise tolerance, through a six-minute walking test; the respiratory muscle strength; the body composition, through the bioelectric impedance; and the free L-carnitine levels in the plasma, through blood exams. RESULTS: The results showed lower values in G1 patients, for the spirometric variables (p<0.01, the respiratory muscle strength, and the L-carnitine levels; however, no difference between the groups was observed

21 CFR 201.323 - Aluminum in large and small volume parenterals used in total parenteral nutrition.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 4 2010-04-01 2010-04-01 false Aluminum in large and small volume parenterals... for Specific Drug Products § 201.323 Aluminum in large and small volume parenterals used in total parenteral nutrition. (a) The aluminum content of large volume parenteral (LVP) drug products used in total...

Safety of parenteral nutrition in newborns: Results from a nationwide prospective cohort study.

Science.gov (United States)

Lapillonne, Alexandre; Berleur, Marie-Pierre; Brasseur, Yvette; Calvez, Sophie

2018-04-01

Limited or delayed availability of parenteral nutrition (PN) solutions, as well as difficulties in ordering are often identified as reasons for non-compliance with international guidelines in newborns. This study aims at assessing the modality of use and safety of premixed standardized PN solutions in a nationwide prospective cohort of newborns treated in clinical practice. Two premixed fixed formulations with respective osmolarity of 715 and 790 mOsm/L specifically designed for neonates were made available throughout the country for clinical use from birth onwards. Descriptive data and modality of use were prospectively collected in a case report form, whereas all related and unrelated adverse events were recorded on a separate adverse event form. A total of 14,167 infants were prospectively included and 16,640 parenteral nutrition periods were analyzed. Mean age was 33 weeks of gestation, and mean weight was 2086 g. The majority of infants (81%) started the parenteral nutrition the first day of life or the day after. The route of parenteral nutrition delivery was peripheral in 47% of the parenteral nutrition periods. During the whole study, a total of 72 adverse events occurring in 68 infants were reported. Of these adverse events, 59 (0.37% of the nutrition periods), among which 19 serious adverse events, were reported as related to the parenteral nutrition solutions. The events related to parenteral nutrition solutions were general disorders and administration site conditions (n = 42 including 9 cases of cutaneous necrosis), and nutrition and metabolism disorders (n = 17). There was no case of thrombophlebitis. Six of the 19 serious events related to the parenteral nutrition solutions (32%) were due to the misuse of the infusion bag. These data support the concept that ready-to-use parenteral nutrition formulations can safely provide parenteral nutrition from birth onwards. They further support that parenteral solutions with an osmolarity up to 800 mOsm/L

Serum levo-carnitine levels and skeletal muscle functions in type 2 diabetes mellitus in rodents

International Nuclear Information System (INIS)

Aleem, S.B.; Hussain, M.M.; Farooq, Y.

2013-01-01

Objective: To study serum levo-carnitine (l-carnitine) levels and isometric contraction, force frequency relationship and fatigue of rodent skeletal muscles in type 2 diabetes mellitus. Study Design: Randomized controlled trial. Place and Duration of Study: Physiology Department, Army Medical College, Rawalpindi, from January 2009 to January 2010. Methodology: Sixty Sprague-Dawley rats were randomly divided into two groups; group I (control), fed on normal diet ad libitum and Group II (diabetic), fed on high fat diet and administered streptozocin to induce type 2 diabetes mellitus (T2DM). At 21st day, plasma glucose and TG/HDL ratio were measured to confirm the development of T2DM in group II. At 28th day, blood was drawn by intracardiac puncture to estimate serum levo-carnitine levels. Contractile functions of skeletal muscles were assessed by using iWorx AHK/214 physiological data acquisition unit. Simple muscle twitches, maximum isometric twitch tension (MITT), time-to-peak twitch tension (TPTT) and time-to-relax to 50% of the peak twitch tension (1/2RT) of extensor digitorum muscles were recorded. Muscles were stimulated at higher frequencies to determine maximum fused tetanic tension (MFTT), maximum fused tetanic tension after fatigue protocol (TTFP) and recovery from fatigue (RF). Results: Serum levo-carnitine level decreased significantly in the diabetic group. Both groups had similar MITT, TPTT and 1/2RT but decline in MFTT, TTFP and RF was significant in the diabetic rats. Conclusion: T2DM adversely affected serum levo-carnitine levels and the contractile functions of rodent skeletal muscle at high frequency stimulation. (author)

Technetium-99m sestamibi leg scintigraphy for non-invasive assessment of propionyl-l-carnitine induced changes in skeletal muscle metabolism

Energy Technology Data Exchange (ETDEWEB)

Cittanti, C. [Department of Nuclear Medicine, University of Ferrara (Italy); Colamussi, P. [Department of Nuclear Medicine, University of Ferrara (Italy); Giganti, M. [Department of Nuclear Medicine, University of Ferrara (Italy); Orlandi, C. [MEDCO Research, Inc., North Carolina (United States); Uccelli, L. [Department of Nuclear Medicine, University of Ferrara (Italy); Manfrini, S. [Surgical Pathology Institute, University of Ferrara (Italy); Azzena, G. [Surgical Pathology Institute, University of Ferrara (Italy); Piffanelli, A. [Department of Nuclear Medicine, University of Ferrara (Italy)

1997-07-01

Carnitine derivatives, such as propionyl-l-carnitine (PLC), have been shown to improve walking distance in patients with obstructive peripheral artery disease (PAOD). The aim of this study was to ascertain whether technetium-99m sestamibi leg scintigraphy may be a useful tool in the evaluation of changes in skeletal muscle metabolism induced by chronic therapy with PLC. Twenty patients with clinical and instrumental evidence of PAOD were randomly assigned to a 3-month period of therapy with either PLC or placebo. Rest {sup 99m}Tc-sestamibi leg scintigraphy and echo-Doppler sonography were performed on all subjects immediately before and upon completion of the treatment period. At the end of the protocol the following results were observed in patients who underwent PLC administration: (a) a significant increase in both thigh and calf {sup 99m}Tc-sestamibi uptake, in comparison with baseline values (P<0.001); (b) the absence of statistically significant modifications of Doppler blood flow indices of the lower limbs. In conclusion, after chronic administration of PLC, a significant increment in skeletal muscle uptake of {sup 99m}Tc-sestamibi was demonstrated without any apparent change in regional blood flow. This fact, if proven in further studies, may suggest a role for this tracer as a non-invasive probe of tissue bioenergetics. (orig.). With 4 figs., 4 tabs.

Carnitine supplementation in high-fat diet-fed rats does not ameliorate lipid-induced skeletal muscle mitochondrial dysfunction in vivo

NARCIS (Netherlands)

Wessels, B.; van den Broek, N.M.A.; Ciapaite, J.; Houten, S.M.; Wanders, R.J.A.; Nicolay, K.; Prompers, J.J.

2015-01-01

Muscle lipid overload and the associated accumulation of lipid intermediates play an important role in the development of insulin resistance. Carnitine insufficiency is a common feature of insulin-resistant states and might lead to incomplete fatty acid oxidation and impaired export of lipid

Commercially marketed supplements for bodybuilding athletes.

Science.gov (United States)

Grunewald, K K; Bailey, R S

1993-02-01

We conducted a survey of 624 commercially available supplements targeted towards bodybuilding athletes. Over 800 performance claims were made for these supplements. Supplements include amino acids, boron, carnitine, choline, chromium, dibencozide, ferulic acid, gamma oryzanol, medium chain triglycerides, weight gain powders, Smilax compounds and yohimbine. Many performance claims advertised were not supported by published research studies. In some instances, we found no research to validate the claims; in other cases, research findings were extrapolated to inappropriate applications. For example, biological functions of some non-essential compounds were interpreted as performance claims for the supplements. Claims for others were based on their ability to enhance hormonal release or activity. We suggest that more research be conducted on this group of athletes and their nutritional needs. Furthermore, the effectiveness and safety of supplements merit further investigation.

Studies concerning chronic and acute effects of L-carnitina in elite athletes.

Science.gov (United States)

Drăgan, I G; Vasiliu, A; Georgescu, E; Eremia, N

1989-01-01

Chronic and acute effects of L-Carnitina (vials of 1 g L-Carnitina endovenous; per orally administered vials of 1 g L-Carnitina; tablets of 1 g L-Carnitina) were recorded in 110 top athletes (rowing, kayak-canoe, swimming, weightlifting medium and long-distance runners), 47 girls and 63 boys, by six double blind placebo trials and cross over. Significant changes were registered after L-Carnitina treatment (both for a single dose or after 3 weeks of treatment) compared to placebo, for FFA, triglycenides, lactic acid after exercise, evoked muscular potential, plasma carnitine (free and acetyl-carnitine), urine carnitine (free carnitine) and others. The authors explain these changes by the increase of free carnitine, which permits a larger quantity of FFA to enter the mitochondria and to be more extensively used as energy source in endurance and strength efforts. Based on these results the authors recommend L-Carnitina as an ergogenic aid in elite athletes, especially in endurance and strength sports.

Parenteral Antibiotics Reduce Bifidobacteria Colonization and Diversity in Neonates

Directory of Open Access Journals (Sweden)

Séamus Hussey

2011-01-01

Full Text Available We investigated the impact of parenteral antibiotic treatment in the early neonatal period on the evolution of bifidobacteria in the newborn. Nine babies treated with intravenous ampicillin/gentamicin in the first week of life and nine controls (no antibiotic treatment were studied. Denaturing gradient gel electrophoresis was used to investigate the composition of Bifidobacterium in stool samples taken at four and eight weeks. Bifidobacteria were detected in all control infants at both four and eight weeks, while only six of nine antibiotic-treated infants had detectable bifidobacteria at four weeks and eight of nine at eight weeks. Moreover, stool samples of controls showed greater diversity of Bifidobacterium spp. compared with antibiotic-treated infants. In conclusion, short-term parenteral antibiotic treatment of neonates causes a disturbance in the expected colonization pattern of bifidobacteria in the first months of life. Further studies are required to probiotic determine if supplementation is necessary in this patient group.

Silent and symptomatic primary carnitine deficiency within the same family due to identical mutations in the organic cation/carnitine transporter OCTN2

NARCIS (Netherlands)

Spiekerkoetter, U.; Huener, G.; Baykal, T.; Demirkol, M.; Duran, M.; Wanders, R.; Nezu, J.; Mayatepek, E.

2003-01-01

A family of Turkish origin with primary systemic carnitine deficiency in the father and his two sons is described. In all three individuals, the same homozygous mutation in the OCTN2 gene (R471H) was present and carnitine uptake in fibroblasts was deficient. Whereas one boy became symptomatic with a

Home parenteral nutrition in children

International Nuclear Information System (INIS)

Kalousova, J.; Rouskova, B.; Styblova, J.

2011-01-01

Parenteral nutrition delivered at home presents a major improvement in the quality of life of children dependent on long term parenteral nutrition. Indications, technical conditions, logistics, complications, prognosis of home parenteral nutrition as well as some health-care issues to be addressed by pediatric practitioner are summarized. (author)

Differentially expressed genes in Hirudo medicinalis ganglia after acetyl-L-carnitine treatment.

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Giuseppe Federighi

Full Text Available Acetyl-L-carnitine (ALC is a naturally occurring substance that, when administered at supra-physiological concentration, is neuroprotective. It is involved in membrane stabilization and in enhancement of mitochondrial functions. It is a molecule of considerable interest for its clinical application in various neural disorders, including Alzheimer's disease and painful neuropathies. ALC is known to improve the cognitive capability of aged animals chronically treated with the drug and, recently, it has been reported that it impairs forms of non-associative learning in the leech. In the present study the effects of ALC on gene expression have been analyzed in the leech Hirudo medicinalis. The suppression subtractive hybridisation methodology was used for the generation of subtracted cDNA libraries and the subsequent identification of differentially expressed transcripts in the leech nervous system after ALC treatment. The method detects differentially but also little expressed transcripts of genes whose sequence or identity is still unknown. We report that a single administration of ALC is able to modulate positively the expression of genes coding for functions that reveal a lasting effect of ALC on the invertebrate, and confirm the neuroprotective and neuromodulative role of the substance. In addition an important finding is the modulation of genes of vegetal origin. This might be considered an instance of ectosymbiotic mutualism.

The effect of carnitine on some biochemical variables in athletes using nuclear technique

International Nuclear Information System (INIS)

Heshmat, H.A.; AbodelAziz, S.M.; El-Arab, A.E.

2003-01-01

Carnitine (3-hydroxy-4-N-trimethylaminobutiric acid) ingestion has a positive effect on work performance and duration as well as delaying muscle fatigue in athletes. Carnitine leas to decrease triglycerides concentration by increasing its rate of oxidation, which decrease atherogenic risk in athletes. On the other hand after exercise, there was an increase in triglyceride level in blood due to increased fat utilization. Also, there was an elevation in lactate concentration after exercise and carnitine ingestion, which is, attributes to aerobic glycolysis. Carnitine. Carnitine ingestion lead also to a slight slight decrease in insulin secretion due to the increasing in glucose uptake by skeletal muscle associated with increasing glucose transport (Glut), however, protein density on the sarcolenma independent of insulin. The data obtained revealed that, was an elevation in cortisol level after exercise and it increased dramatically after carnitine ingestion

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients. Protocol Version 9, 19 February 2007 known as SIGNET (Scottish Intensive care Glutamine or seleNium Evaluative Trial

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Vale Luke D

2007-09-01

Full Text Available Abstract Background Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2–3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. Methods/design 2 × 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrolment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and

Randomised trial of glutamine and selenium supplemented parenteral nutrition for critically ill patients. Protocol Version 9, 19 February 2007 known as SIGNET (Scottish Intensive care Glutamine or seleNium Evaluative Trial).

Science.gov (United States)

Andrews, Peter J D; Avenell, Alison; Noble, David W; Campbell, Marion K; Battison, Claire G; Croal, Bernard L; Simpson, William G; Norrie, John; Vale, Luke D; Cook, Jonathon; de Verteuil, Robyn; Milne, Anne C

2007-09-20

Mortality rates in the Intensive Care Unit and subsequent hospital mortality rates in the UK remain high. Infections in Intensive Care are associated with a 2-3 times increased risk of death. It is thought that under conditions of severe metabolic stress glutamine becomes "conditionally essential". Selenium is an essential trace element that has antioxidant and anti-inflammatory properties. Approximately 23% of patients in Intensive Care require parenteral nutrition and glutamine and selenium are either absent or present in low amounts. Both glutamine and selenium have the potential to influence the immune system through independent biochemical pathways. Systematic reviews suggest that supplementing parenteral nutrition in critical illness with glutamine or selenium may reduce infections and mortality. Pilot data has shown that more than 50% of participants developed infections, typically resistant organisms. We are powered to show definitively whether supplementation of PN with either glutamine or selenium is effective at reducing new infections in critically ill patients. 2 x 2 factorial, pragmatic, multicentre, double-blind, randomised controlled trial. The trial has an enrollment target of 500 patients. Inclusion criteria include: expected to be in critical care for at least 48 hours, aged 16 years or over, patients who require parenteral nutrition and are expected to have at least half their daily nutritional requirements given by that route. Allocation is to one of four iso-caloric, iso-nitrogenous groups: glutamine, selenium, both glutamine & selenium or no additional glutamine or selenium. Trial supplementation is given for up to seven days on the Intensive Care Unit and subsequent wards if practicable. The primary outcomes are episodes of infection in the 14 days after starting trial nutrition and mortality. Secondary outcomes include antibiotic usage, length of hospital stay, quality of life and cost-effectiveness. To date more than 285 patients have been

Enhancement of learning capacity and cholinergic synaptic function by carnitine in aging rats.

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Ando, S; Tadenuma, T; Tanaka, Y; Fukui, F; Kobayashi, S; Ohashi, Y; Kawabata, T

2001-10-15

The effects of a carnitine derivative, acetyl-L-carnitine (ALCAR), on the cognitive and cholinergic activities of aging rats were examined. Rats were given ALCAR (100 mg/kg) per os for 3 months and were subjected to the Hebb-Williams tasks and a new maze task, AKON-1, to assess their learning capacity. The learning capacity of the ALCAR-treated group was superior to that of the control. Cholinergic activities were determined with synaptosomes isolated from the cortices. The high-affinity choline uptake by synaptosomes, acetylcholine synthesis in synaptosomes, and acetylcholine release from synaptosomes on membrane depolarization were all enhanced in the ALCAR group. This study indicates that chronic administration of ALCAR increases cholinergic synaptic transmission and consequently enhances learning capacity as a cognitive function in aging rats. Copyright 2001 Wiley-Liss, Inc.

Primary carnitine deficiency and pivalic acid exposure causing encephalopathy and fatal cardiac events

DEFF Research Database (Denmark)

Rasmussen, Jan; Nielsen, Olav W; Lund, Allan M

2013-01-01

Several episodes of sudden death among young Faroese individuals have been associated with primary carnitine deficiency (PCD). Patients suffering from PCD have low carnitine levels and can present with metabolic and/or cardiac complications. Pivalic acid exposure decreases carnitine levels...

Total parenteral nutrition - infants

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... medlineplus.gov/ency/article/007239.htm Total parenteral nutrition - infants To use the sharing features on this page, please enable JavaScript. Total parenteral nutrition (TPN) is a method of feeding that bypasses ...

Influence of L-citrulline and watermelon supplementation on vascular function and exercise performance.

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Figueroa, Arturo; Wong, Alexei; Jaime, Salvador J; Gonzales, Joaquin U

2017-01-01

L-Citrulline, either synthetic or in watermelon, may improve vascular function through increased L-arginine bioavailability and nitric oxide synthesis. This article analyses potential vascular benefits of L-citrulline and watermelon supplementation at rest and during exercise. There is clear evidence that acute L-citrulline ingestion increases plasma L-arginine, the substrate for endothelial nitric oxide synthesis. However, the subsequent acute improvement in nitric oxide production and mediated vasodilation is inconsistent, which likely explains the inability of acute L-citrulline or watermelon to improve exercise tolerance. Recent studies have shown that chronic L-citrulline supplementation increases nitric oxide synthesis, decreases blood pressure, and may increase peripheral blood flow. These changes are paralleled by improvements in skeletal muscle oxygenation and performance during endurance exercise. The antihypertensive effect of L-citrulline/watermelon supplementation is evident in adults with prehypertension or hypertension, but not in normotensives. However, L-citrulline supplementation may attenuate the blood pressure response to exercise in normotensive men. The beneficial vascular effects of L-citrulline/watermelon supplementation may stem from improvements in the L-arginine/nitric oxide pathway. Reductions in resting blood pressure with L-citrulline/watermelon supplementation may have major implications for individuals with prehypertension and hypertension. L-Citrulline supplementation, but not acute ingestion, have shown to improve exercise performance in young healthy adults.

Suplementação enteral e parenteral com glutamina em neonatos pré-termo e com baixo peso ao nascer Enteral and parenteral supplementation with glutamine in preterm and low-birth-weight neonates

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Maria Carolina Borges

2008-03-01

receive only total parenteral nutrition during their first weeks of life, which contains no glutamine. It must be pointed out that these infants present low muscular mass and that therefore, their stock of glutamine is limited. Because PT and BPN neonates are subject to intensive growth periods and numerous physiological stresses, it is possible that glutamine is a conditionally essential nutrient in this stage of life, thus giving foundation for the pursuit of studies aiming at the evaluation of the possible clinical benefits of enteral and parenteral supplementation with glutamine in PT and BPN neonates.

Oxidative stress in response to aerobic and anaerobic power testing: influence of exercise training and carnitine supplementation.

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Bloomer, Richard J; Smith, Webb A

2009-01-01

The purpose of this study is to compare the oxidative stress response to aerobic and anaerobic power testing, and to determine the impact of exercise training with or without glycine propionyl-L-carnitine (GPLC) in attenuating the oxidative stress response. Thirty-two subjects were assigned (double blind) to placebo, GPLC-1 (1g PLC/d), GPLC-3 (3g PLC/d) for 8 weeks, plus aerobic exercise. Aerobic (graded exercise test: GXT) and anaerobic (Wingate cycle) power tests were performed before and following the intervention. Blood was taken before and immediately following exercise tests and analyzed for malondialdehyde (MDA), hydrogen peroxide (H2O2), and xanthine oxidase activity (XO). No interaction effects were noted. MDA was minimally effected by exercise but lower at rest for both GPLC groups following the intervention (p = 0.044). A time main effect was noted for H2O2 (p = 0.05) and XO (p = 0.003), with values increasing from pre- to postexercise. Both aerobic and anaerobic power testing increase oxidative stress to a similar extent. Exercise training plus GPLC can decrease resting MDA, but it has little impact on exercise-induced oxidative stress biomarkers.

Studies with a safflower oil emulsion in total parenteral nutrition.

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Wong, K. H.; Deitel, M.

1981-01-01

The prevention of essential fatty acid deficiency and the provision of adequate amounts of energy are two major concerns in total parenteral nutrition. Since earlier preparations of fat emulsion used to supplement the usual regimen of hypertonic glucose and amino acids have widely varying clinical acceptability, a new product, a safflower oil emulsion available in two concentrations (Liposyn), was evaluated. In four clinical trials the emulsion was used as a supplement to total parenteral nutrition. In five surgical patients 500 ml of the 10% emulsion infused every third day prevented or corrected essential fatty acid deficiency; however, in some cases in infusion every other day may be necessary. In 40 patients in severe catabolic states the emulsion provided 30% to 50% of the energy required daily: 10 patients received the 10% emulsion for 14 to 42 days, 9 patients received each emulsion in turn for 7 days, and 21 patient received the 20% emulsion for 14 to 28 days. All the patients survived and tolerated the lipid well; no adverse clinical effects were attributable to the lipid infusions. Transient mild, apparently clinically insignificant abnormalities in the results of one or more liver function tests and eosinophilia were observed in some patients. Thus, the safflower oil emulsion, at both concentrations, was safe and effective as a source of 30% to 50% of the energy required daily by seriously ill patients. PMID:6799182

Crystal Structure of Rat Carnitine Palmitoyltransferase II (CPT-II)

Energy Technology Data Exchange (ETDEWEB)

Hsiao,Y.; Jogl, G.; Esser, V.; Tong, L.

2006-01-01

Carnitine palmitoyltransferase II (CPT-II) has a crucial role in the {beta}-oxidation of long-chain fatty acids in mitochondria. We report here the crystal structure of rat CPT-II at 1.9 Angstroms resolution. The overall structure shares strong similarity to those of short- and medium-chain carnitine acyltransferases, although detailed structural differences in the active site region have a significant impact on the substrate selectivity of CPT-II. Three aliphatic chains, possibly from a detergent that is used for the crystallization, were found in the structure. Two of them are located in the carnitine and CoA binding sites, respectively. The third aliphatic chain may mimic the long-chain acyl group in the substrate of CPT-II. The binding site for this aliphatic chain does not exist in the short- and medium-chain carnitine acyltransferases, due to conformational differences among the enzymes. A unique insert in CPT-II is positioned on the surface of the enzyme, with a highly hydrophobic surface. It is likely that this surface patch mediates the association of CPT-II with the inner membrane of the mitochondria.

Trace Elements in Parenteral Nutrition: Considerations for the Prescribing Clinician.

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Jin, Jennifer; Mulesa, Leanne; Carrilero Rouillet, Mariana

2017-04-28

Trace elements (TEs) are an essential component of parenteral nutrition (PN). Over the last few decades, there has been increased experience with PN, and with this knowledge more information about the management of trace elements has become available. There is increasing awareness of the effects of deficiencies and toxicities of certain trace elements. Despite this heightened awareness, much is still unknown in terms of trace element monitoring, the accuracy of different assays, and current TE contamination of solutions. The supplementation of TEs is a complex and important part of the PN prescription. Understanding the role of different disease states and the need for reduced or increased doses is essential. Given the heterogeneity of the PN patients, supplementation should be individualized.

Comparison Between Premixed and Compounded Parenteral Nutrition Solutions in Hospitalized Patients Requiring Parenteral Nutrition.

Science.gov (United States)

Beattie, Colleen; Allard, Johane; Raman, Maitreyi

2016-04-01

Parenteral nutrition (PN) may be provided through compounded or premixed solutions. To determine the proportion of stable custom-compounded PN prescriptions that would fit within a 20% deviance of an existing premixed PN solution. A retrospective study design was used. Inpatients who received PN in non-critical care units in the preceding year were screened for eligibility. Results are reported descriptively as means (95% confidence intervals) and proportions. We reviewed 97 PN prescriptions that met inclusion criteria. Stable hospital PN prescriptions compared with the reference premixed prescription provided 1838 (1777-1898) vs 1843 (1781-1905) kcal/d, P = .43; dextrose, 266 (254-277) vs 225 (216-234) g/d, P magnesium, 5.4 (4.8-5.4) vs 7.6 (7.4-7.9) mmol/L. Calories and protein were remarkably similar, but dextrose, lipid, and electrolytes differed between hospital PN and the reference premixed prescription. We believe that there may be a role for premixed solutions in quaternary centers in stable non-critically ill patients. © 2016 American Society for Parenteral and Enteral Nutrition.

Functional analysis of mutant human carnitine acylcarnitine translocases in yeast

NARCIS (Netherlands)

IJlst, L.; van Roermund, C. W.; Iacobazzi, V.; Oostheim, W.; Ruiter, J. P.; Williams, J. C.; Palmieri, F.; Wanders, R. J.

2001-01-01

Long chain fatty acids are translocated as carnitine esters across the mitochondrial inner membrane by carnitine acylcarnitine translocase (CACT). We report functional studies on the mutant CACT proteins from a severe and a mild patient with CACT deficiency. CACT activities in fibroblasts of both

Effects of parenteral gibberellic acid and dietary supplementaion of vitamin D3 on egg quality and physiological characteristics in aged laying hens

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Waleed M. Razuki

2014-12-01

Full Text Available The aim of this study was to determine the effect of parenteral gibberellic acid (GA3 and/or vitamin D3 supplementation in diet on egg quality and blood physiological characteristics in aged laying hens. A total of 270 Lohmann Brown Classic laying hens aging 73-week were randomly assigned to equal three treatment groups (T1, T2 and T3 with equal 3 replicas in each group. The birds of group T1 (control group were injected subcutaneously (SC with sesame oil at 0.2 mL/kg body weight. The birds of group T2 were given with GA3 at 400 µg/kg b.wt., SC, whereas group T3 had diet containing vitamin D3 at 500 IU/kg feed. Relative weight of albumen and egg shell, Haugh unit, shell thickness, serum glucose, serum calcium, serum phosphorous, serum estradiol, and bone calcium absorption were significantly increased in the birds of group T2 and T3. On the other hand, relative weight of yolk, yolk cholesterol, and serum cholesterol were significantly decreased in group T2 and T3 as compared to group T1. However, serum protein and albumen were unaffected in the treatments. In conclusion, the parenteral GA3 and vitamin D3 supplementation in diet could improve egg quality traits and serum blood biochemical perperties in agend laying hens.

Clinical relevance of trace element measurement in patients on initiation of parenteral nutrition.

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Salota, Rashim; Omar, Sohail; Sherwood, Roy A; Raja, Kishor; Vincent, Royce P

2016-11-01

Background and Aims Serum zinc, copper and selenium are measured in patients prior to commencing on parenteral nutrition; however, their interpretation can be difficult due to acute phase reactions. We assessed (i) the relationship of raised C-reactive protein with trace elements and albumin (ii) benefits of measuring trace elements when C-reactive protein is raised in patients requiring short-term parenteral nutrition. Methods Samples were collected for zinc, copper, selenium and albumin at baseline and then every two weeks and correlated with C-reactive protein results in patients on parenteral nutrition. Results were categorized into four groups based on the C-reactive protein concentrations: (i)  0.05), whereas selenium and albumin were lower in the group with C-reactive protein > 40 mg/L ( P parenteral nutrition, measurement of C-reactive protein is essential when interpreting zinc and selenium but not copper results. Routine measurement of trace elements prior to commencing parenteral nutrition has to be considered on an individual basis in patients with inflammation.

Vitamin E and L-carnitine, separately or in combination, in the prevention of radiation-induced oral mucositis and myelosuppression. A controlled study in a rat model

International Nuclear Information System (INIS)

Uecuencue, H.; Ertekin, M.V.; Yoeruek, O.; Sezen, O.; Oezkan, A.; Erdogan, F.; Kiziltunc, A.; Guendogdu, C.

2006-01-01

The aim of this study was to determine the effects of vitamin E (VE) and L-carnitine (LC) supplementation, separately or in combination, on radiation-induced oral mucositis and myelosuppression. Group 1 received no treatment (control). Group 2 received 15 Gray of 60 Co gamma irradiation as a single dose to total cranium (IR). Group 3, 4, and 5 received irradiation plus 40 mg/kg/day VE (IR+VE) or 200 mg/kg day LC (IR+LC) or in combination (IR+VE+LC) respectively. Clinically and histopathologically, assessments of mucosal reactions were performed by two independent experts in Radiation Oncology and Pathology, respectively. Hematologic analyses and antioxidant enzyme evaluations were also performed. Irradiation significantly increased oral mucositis, and decreased thrombocyte and White Blood Cell counts. A significant increase in malondialdehyde (MDA) levels and decrease in superoxide dismutase (SOD) and catalase (CAT) activities in plasma were found in the IR group. VE and LC administration, separately, plus irradiation significantly delayed the starting day, and reduced the severity of, oral mucositis. This administration also reduced a fall in the numbers of thrombocyte and white blood cell (WBC) caused by irradiation, and decreased the MDA level, and increased the activity of SOD and CAT enzymes in the plasma. VE and LC, in combination, plus irradiation did not provide a superior radioprotection against radiation-induced toxicities. (author)

Radiolabeled 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine: Pt. 1

International Nuclear Information System (INIS)

Reed, K.W.; Ueda, C.T.; Murray, W.J.; Augustine, S.C.

1989-01-01

The purpose of this investigation was to synthesize and purify radiolabeled 9- or 10-monoiodostearyl carnitine for potential use as a perfusion and metabolic imaging agent for the heart. Oleic acid was iodinated via a free radical addition reaction of Hl across the double bond to give 9- or 10-monoiodostearic acid which in turn was esterified with carnitine. The identity of 9- or 10-monoiodostearic acid and 9-or 10-monoiodostearyl carnitine was determined using nuclear magnetic resonance (NMR), infrared (i.r.), ultraviolet (u.v.), and mass spectroscopy. The purity of the fatty acid and carnitine ester was established by thin layer chromatography. 9- or 10-Monoiodo[ 125 I]stearic acid and 9- or 10-monoiodo[ 125 I]stearyl carnitine were synthesized via the isotopic exchange of 125 I for cold iodine bonded to 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine. (author)

Composition, disintegrative properties, and labeling compliance of commercially available taurine and carnitine dietary products.

Science.gov (United States)

Bragg, Rebecca R; Freeman, Lisa M; Fascetti, Andrea J; Yu, Zengshou

2009-01-15

To test the quality, disintegration properties, and compliance with labeling regulations for representative commercially available taurine and carnitine dietary products. Evaluation study. 11 commercially available taurine and 10 commercially available carnitine products. For each product, the amount of taurine or carnitine was determined and compared with the label claim. All products were evaluated for concentrations of mercury, arsenic, and selenium. Disintegration properties of 5 taurine and 8 carnitine products were determined in vitro. Labels were evaluated for compliance with FDA guidelines. 10 of 11 taurine and 10 of 10 carnitine products were within 10% of the stated label claim. Three of 11 taurine and 6 of 10 carnitine products were within 5% of the stated label claim. The median percentage difference between laboratory analysis and label claim was -5.7% (range, -26.3% to 2.5%) for taurine and 3.6% (range, -2.6% to 8.8%) for carnitine. No substantial amount of contamination with mercury, arsenic, or selenium was found in any of the products. During disintegration testing, 1 of 5 taurine products and 5 of 8 carnitine products did not disintegrate within 45 minutes during at least 1 test. Disintegration time for those that did disintegrate ranged from 1.7 to 37.0 minutes. All product labels conformed with FDA regulations. Taurine and carnitine products evaluated in this study closely adhered to manufacturer claims and labeling guidelines. However, disintegration testing suggested high variability in some products, possibly limiting uptake and use by animals that receive them.

Effect of Caffeine Co-Ingested with Carnitine on Weight, Body-Fat Percent, Serum Leptin and Lipid Profile Changes in Male Teen Soccer Players: a Randomized Clinical Trial

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Saeed Shirali

2016-10-01

Full Text Available Background: Weight loss and decreasing the Body fat percentage (BF% is motivated to optimize performance. In order to achieve these, many supplements are used by athletes, however the possible negative or synergic effects have not been fully described in the literature, specifically in humans. The present study was conducted to investigate the co-administration effects of two common used supplements in body weight and BF% management to recommend athletes for safe weight and BF% reduction. Materials and Methods: In the present double-blind, randomized, parallel, placebo-controlled study, the effect of six-week co-administration of caffeine and carnitine was determined on changes in body weight (BW, BF%, serum leptin concentration and lipid profile (triglyceride, HDL Cholesterol, LDL Cholesterol and Total Cholesterol, fasting blood glucose (FBG, and free fatty acid (FFA changes. Twenty eight male teen soccer players  from Ahvaz-Iran, were divided in three groups (group CafPlc, caffeine (6 mg/kg/day + dextrose; group CafCar, caffeine (6 mg/kg/day + carnitine (2g; and group Plc, dextrose. Results: Caffeine-carnitine had a lowering effect on BW (P=0.02 and BF% (P=0.03, compared to caffeine alone and placebo in male teen soccer players (mean age of 16.92 ± 0.76 years. TG was significantly decreased in CafCar (P=0.04. FFA levels were increased in CafCar (P=0.04 and there was significant differences between CafCar and Plc groups (P=0.01. FBG was increased in both CafPlc and CafCar (P=0.01 and P=0.02, respectively, with no significant differences between groups. Conclusion: The synergistic effect of caffeine-carnitine might be suggested to decrease the BF% and BW, besides it may prevent the increment of FFA levels; however it should be prescribed cautiously since it increased FBG levels.

Is there a place for nutritional supplements in the treatment of idiopathic male infertility?

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Davide Arcaniolo

2014-09-01

Full Text Available Objective: Infertility affects 15% of couples in fertile age. Male factor is a cause of infertility in almost half of cases, mainly due to oligoasthenoteratozoospermia (OAT. The purpose of this study is to review the effects of nutritional supplements as medical treatment for idiopathic male infertility. Material and methods: A Pub Med and Medline review of the published studies utilizing nutritional supplements for the treatment of male infertility has been performed. Results: Clinical trials on Vitamin E, Vitamin A, Vitamin C. Arginine, Carnitine, N-Acetyl-Carnitine, Glutathione, Coenzyme Q10, Selenium and Zinc were reviewed. Although there is a wide variability in selected population, dose regimen and final outcomes, nutritional supplements both alone and in combination seems to be able to improve semen parameters (sperm count, sperm motility and morphology and pregnancy rate in infertile men. Conclusions: There are rising evidences from published randomized trials and systematic review suggesting that nutritional supplementation may improve semen parameters and the likelihood of pregnancy in men affected by OAT. This improvement, however, is not consistent and there is a wide variation in the treatment regimens used. Well designed and adequately powered RCTs are needed to better clarify the role of nutritional supplements as treatment for male infertility.

Crystal Structures of Murine Carnitine Acetyltransferase in Ternary Complexes with Its Substrates

Energy Technology Data Exchange (ETDEWEB)

Hsiao,Y.; Jogl, G.; Tong, L.

2006-01-01

Carnitine acyltransferases catalyze the reversible exchange of acyl groups between coenzyme A (CoA) and carnitine. They have important roles in many cellular processes, especially the oxidation of long-chain fatty acids in the mitochondria for energy production, and are attractive targets for drug discovery against diabetes and obesity. To help define in molecular detail the catalytic mechanism of these enzymes, we report here the high resolution crystal structure of wild-type murine carnitine acetyltransferase (CrAT) in a ternary complex with its substrates acetyl-CoA and carnitine, and the structure of the S554A/M564G double mutant in a ternary complex with the substrates CoA and hexanoylcarnitine. Detailed analyses suggest that these structures may be good mimics for the Michaelis complexes for the forward and reverse reactions of the enzyme, representing the first time that such complexes of CrAT have been studied in molecular detail. The structural information provides significant new insights into the catalytic mechanism of CrAT and possibly carnitine acyltransferases in general.

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to acetyl-L-carnitine and contribution to normal cognitive function (ID 1432) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

DEFF Research Database (Denmark)

Tetens, Inge

claims in relation to acetyl-L-carnitine and contribution to normal cognitive function. The scientific substantiation is based on the information provided by the Member States in the consolidated list of Article 13 health claims and references that EFSA has received from Member States or directly from......Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... be drawn for the scientific substantiation of the claim. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of acetyl-L-carnitine and contribution to normal cognitive function....

Use of Piggyback Electrolytes for Patients Receiving Individually Prescribed vs Premixed Parenteral Nutrition.

Science.gov (United States)

Busch, Rebecca A; Curtis, Caitlin S; Leverson, Glen E; Kudsk, Kenneth A

2015-07-01

Parenteral nutrition (PN) is available as individualized prescriptions frequently prepared with an automated compounding device or as commercially prepared premixed solutions. Our institution exclusively used individualized PN until an amino acid shortage forced a temporary switch to premixed solutions. In general, premixed solutions contain lower electrolyte levels than individualized formulations prescribed for patients with normal organ function. We aimed to quantify supplemental intravenous piggyback (IVPB) electrolyte use in adult patients receiving individualized and premixed PN and to quantify any effect on difference in the cost of therapy. We compared use of supplemental IVPB electrolytes administered to patients receiving PN during consecutive periods prior to and during the amino acid shortage. Electrolyte IVPBs tabulated were potassium chloride, 10 and 20 mEq; magnesium sulfate, 2 g and 4 g; potassium phosphate, 7.5 and 15 mmol; and sodium phosphate, 7.5 and 15 mmol IVPB. There was no statistical difference in the number of PN formulations administered per day during each period (14.7 ± 3.9 vs 14.0 ± 2.6, individualized vs premixed, respectively). Total IVPB electrolytes prescribed per day increased significantly from the individualized PN period to the premixed PN period (7.03 ± 3.8 vs 13.8 ± 6.8; P Parenteral and Enteral Nutrition.

Impaired exercise performance and skeletal muscle mitochondrial function in rats with secondary carnitine deficiency

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Jamal BOUITBIR

2016-08-01

Full Text Available Purpose: The effects of carnitine depletion upon exercise performance and skeletal muscle mitochondrial function remain largely unexplored. We therefore investigated the effect of N-trimethyl-hydrazine-3-propionate (THP, a carnitine analogue inhibiting carnitine biosynthesis and renal carnitine reabsorption, on physical performance and skeletal muscle mitochondrial function in rats.Methods: Male Sprague Dawley rats were treated daily with water (control rats; n=12 or with 20 mg/100 g body weight THP (n=12 via oral gavage for 3 weeks. Following treatment, half of the animals of each group performed an exercise test until exhaustion.Results: Distance covered and exercise performance were lower in THP-treated compared to control rats. In the oxidative soleus muscle, carnitine depletion caused atrophy (-24% and impaired function of complex II and IV of the mitochondrial electron transport chain. The free radical leak (ROS production relative to oxygen consumption was increased and the cellular glutathione pool decreased. Moreover, mRNA expression of markers of mitochondrial biogenesis and mitochondrial DNA were decreased in THP-treated compared to control rats. In comparison, in the glycolytic gastrocnemius muscle, carnitine depletion was associated with impaired function of complex IV and increased free radical leak, whilst muscle weight and cellular glutathione pool were maintained. Markers of mitochondrial proliferation and mitochondrial DNA were unaffected.Conclusions: Carnitine deficiency is associated with impaired exercise capacity in rats treated with THP. THP-induced carnitine deficiency is associated with impaired function of the electron transport chain in oxidative and glycolytic muscle as well as with atrophy and decreased mitochondrial DNA in oxidative muscle.

Endogenous glutamine production in critically ill patients: the effect of exogenous glutamine supplementation.

Science.gov (United States)

Mori, Maiko; Rooyackers, Olav; Smedberg, Marie; Tjäder, Inga; Norberg, Ake; Wernerman, Jan

2014-04-14

Glutamine rate of appearance (Ra) may be used as an estimate of endogenous glutamine production. Recently a technique employing a bolus injection of isotopically labeled glutamine was introduced, with the potential to allow for multiple assessments of the glutamine Ra over time in critically ill patients, who may not be as metabolically stable as healthy individuals. Here the technique was used to evaluate the endogenous glutamine production in critically ill patients in the fed state with and without exogenous glutamine supplementation intravenously. Mechanically ventilated patients (n = 11) in the intensive care unit (ICU) were studied on two consecutive days during continuous parenteral feeding. To allow the patients to be used as their own controls, they were randomized for the reference measurement during basal feeding without supplementation, before or after the supplementation period. Glutamine Ra was determined by a bolus injection of 13C-glutamine followed by a period of frequent sampling to establish the decay-curve for the glutamine tracer. Exogenous glutamine supplementation was given by intravenous infusion of a glutamine containing dipeptide, L-alanyl-L-glutamine, 0.28 g/kg during 20 hours. A 14% increase of endogenous glutamine Ra was seen at the end of the intravenous supplementation period as compared to the basal measurements (P = 0.009). The bolus injection technique to measure glutamine Ra to estimate the endogenous production of glutamine in critically ill patients was demonstrated to be useful for repetitive measurements. The hypothesized attenuation of endogenous glutamine production during L-alanyl-L-glutamine infusion given as a part of full nutrition was not seen.

Early versus Late Parenteral Nutrition in Critically Ill Children.

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Fivez, Tom; Kerklaan, Dorian; Mesotten, Dieter; Verbruggen, Sascha; Wouters, Pieter J; Vanhorebeek, Ilse; Debaveye, Yves; Vlasselaers, Dirk; Desmet, Lars; Casaer, Michael P; Garcia Guerra, Gonzalo; Hanot, Jan; Joffe, Ari; Tibboel, Dick; Joosten, Koen; Van den Berghe, Greet

2016-03-24

Recent trials have questioned the benefit of early parenteral nutrition in adults. The effect of early parenteral nutrition on clinical outcomes in critically ill children is unclear. We conducted a multicenter, randomized, controlled trial involving 1440 critically ill children to investigate whether withholding parenteral nutrition for 1 week (i.e., providing late parenteral nutrition) in the pediatric intensive care unit (ICU) is clinically superior to providing early parenteral nutrition. Fluid loading was similar in the two groups. The two primary end points were new infection acquired during the ICU stay and the adjusted duration of ICU dependency, as assessed by the number of days in the ICU and as time to discharge alive from ICU. For the 723 patients receiving early parenteral nutrition, parenteral nutrition was initiated within 24 hours after ICU admission, whereas for the 717 patients receiving late parenteral nutrition, parenteral nutrition was not provided until the morning of the 8th day in the ICU. In both groups, enteral nutrition was attempted early and intravenous micronutrients were provided. Although mortality was similar in the two groups, the percentage of patients with a new infection was 10.7% in the group receiving late parenteral nutrition, as compared with 18.5% in the group receiving early parenteral nutrition (adjusted odds ratio, 0.48; 95% confidence interval [CI], 0.35 to 0.66). The mean (±SE) duration of ICU stay was 6.5±0.4 days in the group receiving late parenteral nutrition, as compared with 9.2±0.8 days in the group receiving early parenteral nutrition; there was also a higher likelihood of an earlier live discharge from the ICU at any time in the late-parenteral-nutrition group (adjusted hazard ratio, 1.23; 95% CI, 1.11 to 1.37). Late parenteral nutrition was associated with a shorter duration of mechanical ventilatory support than was early parenteral nutrition (P=0.001), as well as a smaller proportion of patients

The Technical and Financial Effects of Parenteral Supplementation with Selenium and Vitamin E during Late Pregnancy and the Early Lactation Period on the Productivity of Dairy Cattle

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T. Bayril

2015-08-01

Full Text Available This study aimed to determine the effects of parenteral selenium (Se and vitamin E supplementation on economic impact, milk yield, and some reproductive parameters in high-yield dairy cows in the dry period and in those at the beginning of lactation. At the beginning of the dry period, cows (n = 323 were randomly divided into three groups as follows: Treatment 1 (T1, Treatment 2 (T2, and Control (C. Cows in group T1 received this preparation 21 days before calving and on calving day, and cows in group T2 received it only on calving day. The cows in the control group did not receive this preparation. Supplementation with Se increased Se serum levels of cows treated at calving day (p<0.05. Differences in milk yield at all weeks and the electrical conductivity values at the 8th and 12th weeks were significant (p<0.05. Supplementation with Se and Vitamin E decreased the incidence of metritis, the number of services per conception and the service period, but had no effects on the incidence of retained fetal membrane. A partial budgeting analysis indicated that Se supplementation was economically profitable; cows in group T1 averaged 240.6$ per cow, those in group T2 averaged 224.6$ per cow. Supplementation with Se and Vitamin E has been found to increase serum Se levels, milk yield, and has positive effects on udder health by decreasing milk conductivity values and incidence of sub-clinical mastitis.

In HepG2 cells, coexisting carnitine deficiency masks important indicators of marginal biotin deficiency.

Science.gov (United States)

Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

2015-01-01

A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography-tandem mass spectrometry. Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased by >8-fold. Our findings provide strong

Inhibited Carnitine Synthesis Causes Systemic Alteration of Nutrient Metabolism in Zebrafish.

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Li, Jia-Min; Li, Ling-Yu; Qin, Xuan; Degrace, Pascal; Demizieux, Laurent; Limbu, Samwel M; Wang, Xin; Zhang, Mei-Ling; Li, Dong-Liang; Du, Zhen-Yu

2018-01-01

Impaired mitochondrial fatty acid β-oxidation has been correlated with many metabolic syndromes, and the metabolic characteristics of the mammalian models of mitochondrial dysfunction have also been intensively studied. However, the effects of the impaired mitochondrial fatty acid β-oxidation on systemic metabolism in teleost have never been investigated. In the present study, we established a low-carnitine zebrafish model by feeding fish with mildronate as a specific carnitine synthesis inhibitor [0.05% body weight (BW)/d] for 7 weeks, and the systemically changed nutrient metabolism, including carnitine and triglyceride (TG) concentrations, fatty acid (FA) β-oxidation capability, and other molecular and biochemical assays of lipid, glucose, and protein metabolism, were measured. The results indicated that mildronate markedly decreased hepatic carnitine concentrations while it had no effect in muscle. Liver TG concentrations increased by more than 50% in mildronate-treated fish. Mildronate decreased the efficiency of liver mitochondrial β-oxidation, increased the hepatic mRNA expression of genes related to FA β-oxidation and lipolysis, and decreased the expression of lipogenesis genes. Mildronate decreased whole body glycogen content, increased glucose metabolism rate, and upregulated the expression of glucose uptake and glycolysis genes. Mildronate also increased whole body protein content and hepatic mRNA expression of mechanistic target of rapamycin ( mtor ), and decreased the expression of a protein catabolism-related gene. Liver, rather than muscle, was the primary organ targeted by mildronate. In short, mildronate-induced hepatic inhibited carnitine synthesis in zebrafish caused decreased mitochondrial FA β-oxidation efficiency, greater lipid accumulation, and altered glucose and protein metabolism. This reveals the key roles of mitochondrial fatty acid β-oxidation in nutrient metabolism in fish, and this low-carnitine zebrafish model could also be

Inhibited Carnitine Synthesis Causes Systemic Alteration of Nutrient Metabolism in Zebrafish

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Jia-Min Li

2018-05-01

Full Text Available Impaired mitochondrial fatty acid β-oxidation has been correlated with many metabolic syndromes, and the metabolic characteristics of the mammalian models of mitochondrial dysfunction have also been intensively studied. However, the effects of the impaired mitochondrial fatty acid β-oxidation on systemic metabolism in teleost have never been investigated. In the present study, we established a low-carnitine zebrafish model by feeding fish with mildronate as a specific carnitine synthesis inhibitor [0.05% body weight (BW/d] for 7 weeks, and the systemically changed nutrient metabolism, including carnitine and triglyceride (TG concentrations, fatty acid (FA β-oxidation capability, and other molecular and biochemical assays of lipid, glucose, and protein metabolism, were measured. The results indicated that mildronate markedly decreased hepatic carnitine concentrations while it had no effect in muscle. Liver TG concentrations increased by more than 50% in mildronate-treated fish. Mildronate decreased the efficiency of liver mitochondrial β-oxidation, increased the hepatic mRNA expression of genes related to FA β-oxidation and lipolysis, and decreased the expression of lipogenesis genes. Mildronate decreased whole body glycogen content, increased glucose metabolism rate, and upregulated the expression of glucose uptake and glycolysis genes. Mildronate also increased whole body protein content and hepatic mRNA expression of mechanistic target of rapamycin (mtor, and decreased the expression of a protein catabolism-related gene. Liver, rather than muscle, was the primary organ targeted by mildronate. In short, mildronate-induced hepatic inhibited carnitine synthesis in zebrafish caused decreased mitochondrial FA β-oxidation efficiency, greater lipid accumulation, and altered glucose and protein metabolism. This reveals the key roles of mitochondrial fatty acid β-oxidation in nutrient metabolism in fish, and this low-carnitine zebrafish model

Children at risk of diabetes type 1. Treatment with acetyl-L-carnitine plus nicotinamide - case reports.

Science.gov (United States)

Fernandez, Ivana Cristina; Del Carmen Camberos, María; Passicot, Gisel Anabel; Martucci, Lucía Camila; Cresto, Juan Carlos

2013-01-01

Abstract Objectives: The aim was to evaluate the treatment with acetyl-L-carnitine (50 mg/kg/day) and nicotinamide (25 mg/kg/day) in children at risk of type 1 diabetes. This treatment was effective and harmless in experimental type 1 diabetes in mice. Nine out of seventy healthy participants of the type 1 diabetes risk study were treated. They were typified for diabetes with HLA-DQB1 and positive autoantibodies. Children with a first peak of insulin response ≤48 µU were randomly distributed in control and treated patients. Children evolution was followed with an intravenous glucose tolerance test. Control children were treated when was another risk parameter was added. During their evolution all children were treated. Treatment periods differ (range: 120-16 months) because children began treatment at different times. During the treatment 4 patients recovered their parameters and the medication was suspended; 2 patients continued the treatment with favorable evolution. Two children evolved slowly with normal growth and development. One girl became diabetic because she was treated late. In children at risk, this treatment delays the development or remits the evolution of type 1 diabetes.

Copper and Zinc Deficiency in a Patient Receiving Long-Term Parenteral Nutrition During a Shortage of Parenteral Trace Element Products.

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Palm, Eric; Dotson, Bryan

2015-11-01

Drug shortages in the United States, including parenteral nutrition (PN) components, have been common in recent years and can adversely affect patient care. Here we report a case of copper and zinc deficiency in a patient receiving PN during a shortage of parenteral trace element products. The management of the patient's deficiencies, including the use of an imported parenteral multi-trace element product, is described. © 2014 American Society for Parenteral and Enteral Nutrition.

Delivery of vitamins E and C from parenteral alimentation solution.

Science.gov (United States)

Shenai, J P; Borum, P R; Duke, E A

1982-01-01

We have previously shown that substantial losses of fat-soluble (FS) vitamin A from parenteral alimentation solution occur due to adsorption in the intravenous tubing and photodegradation in the bottle. This study assessed the delivery of other vitamins, viz, FS vitamin E and water-soluble (WS) vitamin C, from parenteral alimentation solution. The solution containing 2.0 ml/L of an aqueous multivitamin infusion was infused at a constant rate of 10 ml/h using a standard intravenous administration set. Multiple aliquots of the solution from the bottle and the effluent obtained sequentially in a 24-h period were analyzed for concentrations of vitamins E and C. Both vitamins remained relatively stable in the bottle. A significant amount (12%) of vitamin E was lost in the intravenous tubing. No losses of vitamin C were incurred in the intravenous tubing. The data suggest that delivery of FS vitamin E from parenteral alimentation solutions is less than optimum because of adsorptive losses. Similar losses are not encountered with WS vitamin C.

Treatment of idiopathic hepatic lipidosis in cats: 11 cases (1986-1987).

Science.gov (United States)

Jacobs, G; Cornelius, L; Allen, S; Greene, C

1989-09-01

Idiopathic hepatic lipidosis was diagnosed in 11 cats. Cats were treated by delivery of balanced nutrients supplemented with L-carnitine via a surgically placed gastrostomy tube. Feeding through the gastrostomy tube was initiated in the hospital and was continued at home in all cats. The mean duration of gastrostomy tube feeding was 48 days (range, 22 to 98 days). Vomiting associated with feeding (3 cats) and localized cellulitis at the gastrostomy site (2 cats) were the most frequent complications. Vomiting was controlled by reducing the volume of food administered at each feeding or by administration of metoclopramide. Cellulitis was treated successfully by parenteral administration of antibiotics and local wound cleansing. Seven of 11 cats (65%) survived and have remained clinically healthy for 15 to 29 months (mean, 20 months) since diagnosis. The other 4 cats died of peritonitis (n = 1), pneumonia (n = 1), hepatic encephalopathy (n = 1), or cardiopulmonary arrest (n = 1) between 0 and 10 days after surgery.

Oral potassium supplementation in surgical patients.

Science.gov (United States)

Hainsworth, Alison J; Gatenby, Piers A

2008-08-01

Hospital inpatients are frequently hypokalaemic. Low plasma potassium levels may cause life threatening complications, such as cardiac arrhythmias. Potassium supplementation may be administered parenterally or enterally. Oral potassium supplements have been associated with oesophageal ulceration, strictures and gastritis. An alternative to potassium salt tablets or solution is dietary modification with potassium rich food stuffs, which has been proven to be a safe and effective method for potassium supplementation. The potassium content of one medium banana is equivalent to a 12 mmol potassium salt tablet. Potassium supplementation by dietary modification has been shown to be equally efficacious to oral potassium salt supplementation and is preferred by the majority of patients. Subsequently, it is our practice to replace potassium using dietary modification, particularly in surgical patients having undergone oesophagogastrectomy or in those with peptic ulcer disease.

Hypothalamic carnitine metabolism integrates nutrient and hormonal feedback to regulate energy homeostasis.

Science.gov (United States)

Stark, Romana; Reichenbach, Alex; Andrews, Zane B

2015-12-15

The maintenance of energy homeostasis requires the hypothalamic integration of nutrient feedback cues, such as glucose, fatty acids, amino acids, and metabolic hormones such as insulin, leptin and ghrelin. Although hypothalamic neurons are critical to maintain energy homeostasis research efforts have focused on feedback mechanisms in isolation, such as glucose alone, fatty acids alone or single hormones. However this seems rather too simplistic considering the range of nutrient and endocrine changes associated with different metabolic states, such as starvation (negative energy balance) or diet-induced obesity (positive energy balance). In order to understand how neurons integrate multiple nutrient or hormonal signals, we need to identify and examine potential intracellular convergence points or common molecular targets that have the ability to sense glucose, fatty acids, amino acids and hormones. In this review, we focus on the role of carnitine metabolism in neurons regulating energy homeostasis. Hypothalamic carnitine metabolism represents a novel means for neurons to facilitate and control both nutrient and hormonal feedback. In terms of nutrient regulation, carnitine metabolism regulates hypothalamic fatty acid sensing through the actions of CPT1 and has an underappreciated role in glucose sensing since carnitine metabolism also buffers mitochondrial matrix levels of acetyl-CoA, an allosteric inhibitor of pyruvate dehydrogenase and hence glucose metabolism. Studies also show that hypothalamic CPT1 activity also controls hormonal feedback. We hypothesis that hypothalamic carnitine metabolism represents a key molecular target that can concurrently integrate nutrient and hormonal information, which is critical to maintain energy homeostasis. We also suggest this is relevant to broader neuroendocrine research as it predicts that hormonal signaling in the brain varies depending on current nutrient status. Indeed, the metabolic action of ghrelin, leptin or insulin

78 FR 28834 - Salton Sea Power L.L.C.; Supplemental Notice That Initial Market-Based Rate Filing Includes...

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2013-05-16

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER13-1272-000] Salton Sea Power L.L.C.; Supplemental Notice That Initial Market- Based Rate Filing Includes Request for Blanket Section 204 Authorization This is a supplemental notice in the above-referenced proceeding of Salton Sea...

Synthesis of carbon-11 labelled (R)-carnitine

International Nuclear Information System (INIS)

Holschbach, M.; Hamkens, W.; Roden, W.; Feinendegen, L.E.

1991-01-01

A route to 11 C-labelled (R)-carnitine, based on the methylation of the dimethyl derivative is described. Furthermore, a five-step synthesis for the enantiomerically pure precursor is outlined. (author)

Advantages of enteral nutrition over parenteral nutrition

OpenAIRE

Seres, David S.; Valcarcel, Monika; Guillaume, Alexandra

2013-01-01

It is a strong and commonly held belief among nutrition clinicians that enteral nutrition is preferable to parenteral nutrition. We provide a narrative review of more recent studies and technical reviews comparing enteral nutrition with parenteral nutrition. Despite significant weaknesses in the existing data, current literature continues to support the use of enteral nutrition in patients requiring nutrition support, over parenteral nutrition.

Parenteral nutrition-associated liver disease and lipid emulsions.

Science.gov (United States)

Zugasti Murillo, Ana; Petrina Jáuregui, Estrella; Elizondo Armendáriz, Javier

2015-01-01

Parenteral nutrition-associated liver disease (PNALD) is a particularly important problem in patients who need this type of nutritional support for a long time. Prevalence of the condition is highly variable depending on the series, and its clinical presentation is different in adults and children. The etiology of PNALD is not well defined, and participation of several factors at the same time has been suggested. When a bilirubin level >2 mg/dl is detected for a long time, other causes of liver disease should be ruled out and risk factors should be minimized. The composition of lipid emulsions used in parenteral nutrition is one of the factors related to PNALD. This article reviews the different types of lipid emulsions and the potential benefits of emulsions enriched with omega-3 fatty acids. Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

Free carnitine and acylcarnitines in obese patients with polycystic ovary syndrome and effects of pioglitazone treatment

DEFF Research Database (Denmark)

Vigerust, Natalya Filipchuk; Bohov, Pavol; Bjørndal, Bodil

2012-01-01

To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS).......To determine fasting and insulin-stimulated levels of carnitine precursors, total and free carnitine, and acylcarnitines, and evaluate the impact of pioglitazone treatment in obese patients with polycystic ovary syndrome (PCOS)....

Home parenteral nutrition in children: the Polish experience.

Science.gov (United States)

Ksiazyk, J; Lyszkowska, M; Kierkus, J; Bogucki, K; Ratyńska, A; Tondys, B; Socha, J

1999-02-01

Home parenteral nutrition has become routine for management of intestinal failure in patients. In Poland the main obstacle to widespread use of home parenteral nutrition is the lack of interest of commercial companies in delivering feedings and ancillaries to patients. Twenty-five home parenteral nutrition patients aged from 4 months to more than 13 years were reviewed. The mother or both parents were trained in home parenteral nutrition techniques for 4 to 6 weeks and compounded the nutrients themselves at home. The mean duration of home parenteral nutrition was 10,117 patient days. Hospital stays of patients receiving parenteral feedings were significantly shorter than the duration of administration of home parenteral nutrition (p rate of catheter occlusion decreased within the observation period, and in 1997 not one case of occlusion was observed. In 1997 only three catheters were removed during 7.8 patient years, and the overall incidence of catheter-related complications was 0.38 per patient year. The overall occurrence of septicemia was one case in 516 days and of catheter infection was one in 459 days. In 1997 a catheter was infected on average of once every 1419 days. There was significant improvement in the z score for weight during therapy. The average monthly cost of nutrients and ancillary items was approximately $1200 (4200 Polish zlotys [PLN]). These costs are 1.6 to 3 times lower than those recorded in other studies. Home parenteral nutrition in children with nutrients mixed by caregivers in the home setting is a safe and appropriate method of treatment that can be used in countries where home parenteral nutrition solutions are not manufactured or where commercial home parenteral nutrition is not economically feasible.

Dietary fat intake, supplements, and weight loss

Science.gov (United States)

Dyck, D. J.

2000-01-01

Although there remains controversy regarding the role of macronutrient balance in the etiology of obesity, the consumption of high-fat diets appears to be strongly implicated in its development. Evidence that fat oxidation does not adjust rapidly to acute increases in dietary fat, as well as a decreased capacity to oxidize fat in the postprandial state in the obese, suggest that diets high in fat may lead to the accumulation of fat stores. Novel data is also presented suggesting that in rodents, high-fat diets may lead to the development of leptin resistance in skeletal muscle and subsequent accumulations of muscle triacylglycerol. Nevertheless, several current fad diets recommend drastically reduced carbohydrate intake, with a concurrent increase in fat content. Such recommendations are based on the underlying assumption that by reducing circulating insulin levels, lipolysis and lipid oxidation will be enhanced and fat storage reduced. Numerous supplements are purported to increase fat oxidation (carnitine, conjugated linoleic acid), increase metabolic rate (ephedrine, pyruvate), or inhibit hepatic lipogenesis (hydroxycitrate). All of these compounds are currently marketed in supplemental form to increase weight loss, but few have actually been shown to be effective in scientific studies. To date, there is little or no evidence supporting that carnitine or hydroxycitrate supplementation are of any value for weight loss in humans. Supplements such as pyruvate have been shown to be effective at high dosages, but there is little mechanistic information to explain its purported effect or data to indicate its effectiveness at lower dosages. Conjugated linoleic acid has been shown to stimulate fat utilization and decrease body fat content in mice but has not been tested in humans. The effects of ephedrine, in conjunction with methylxanthines and aspirin, in humans appears unequivocal but includes various cardiovascular side effects. None of these compounds have been

In HepG2 Cells, Coexisting Carnitine Deficiency Masks Important Indicators of Marginal Biotin Deficiency123

Science.gov (United States)

Bogusiewicz, Anna; Boysen, Gunnar; Mock, Donald M

2015-01-01

Background: A large number of birth defects are related to nutrient deficiencies; concern that biotin deficiency is teratogenic in humans is reasonable. Surprisingly, studies indicate that increased urinary 3-hydroxyisovalerylcarnitine (3HIAc), a previously validated marker of biotin deficiency, is not a valid biomarker in pregnancy. Objective: In this study we hypothesized that coexisting carnitine deficiency can prevent the increase in 3HIAc due to biotin deficiency. Methods: We used a 2-factor nutrient depletion design to induce isolated and combined biotin and carnitine deficiency in HepG2 cells and then repleted cells with carnitine. To elucidate the metabolic pathogenesis, we quantitated intracellular and extracellular free carnitine, acylcarnitines, and acylcarnitine ratios using liquid chromatography–tandem mass spectrometry. Results: Relative to biotin-sufficient, carnitine-sufficient cells, intracellular acetylcarnitine increased by 90%, propionylcarnitine more than doubled, and 3HIAc increased by >10-fold in biotin-deficient, carnitine-sufficient (BDCS) cells, consistent with a defensive mechanism in which biotin-deficient cells transesterify the acyl-coenzyme A (acyl-CoA) substrates of the biotin-dependent carboxylases to the related acylcarnitines. Likewise, in BDCS cells, the ratio of acetylcarnitine to malonylcarnitine and the ratio of propionylcarnitine to methylmalonylcarnitine both more than tripled, and the ratio of 3HIAc to 3-methylglutarylcarnitine (MGc) increased by >10-fold. In biotin-deficient, carnitine-deficient (BDCD) cells, the 3 substrate-derived acylcarnitines changed little, but the substrate:product ratios were masked to a lesser extent. Moreover, carnitine repletion unmasked biotin deficiency in BDCD cells as shown by increases in acetylcarnitine, propionylcarnitine, and 3HIAc (each increased by >50-fold). Likewise, ratios of acetylcarnitine:malonylcarnitine, propionylcarnitine:methylmalonylcarnitine, and 3HIAc:MGc all increased

Amino acids – Guidelines on Parenteral Nutrition, Chapter 4

Directory of Open Access Journals (Sweden)

Working group for developing the guidelines for parenteral nutrition of The German Association for Nutritional Medicine

2009-11-01

Full Text Available Protein catabolism should be reduced and protein synthesis promoted with parenteral nutrion (PN. Amino acid (AA solutions should always be infused with PN. Standard AA solutions are generally used, whereas specially adapted AA solutions may be required in certain conditions such as severe disorders of AA utilisation or in inborn errors of AA metabolism. An AA intake of 0.8 g/kg/day is generally recommended for adult patients with a normal metabolism, which may be increased to 1.2–1.5 g/kg/day, or to 2.0 or 2.5 g/kg/day in exceptional cases. Sufficient non-nitrogen energy sources should be added in order to assure adequate utilisation of AA. A nitrogen calorie ratio of 1:130 to 1:170 (g N/kcal or 1:21 to 1:27 (g AA/kcal is recommended under normal metabolic conditions. In critically ill patients glutamine should be administered parenterally if indicated in the form of peptides, for example 0.3–0.4 g glutamine dipeptide/kg body weight/day (=0.2–0.26 g glutamine/kg body weight/day. No recommendation can be made for glutamine supplementation in PN for patients with acute pancreatitis or after bone marrow transplantation (BMT, and in newborns. The application of arginine is currently not warranted as a supplement in PN in adults. N-acetyl AA are only of limited use as alternative AA sources. There is currently no indication for use of AA solutions with an increased content of glycine, branched-chain AAs (BCAA and ornithine-α-ketoglutarate (OKG in all patients receiving PN. AA solutions with an increased proportion of BCAA are recommended in the treatment of hepatic encephalopathy (III–IV.

21 CFR 862.1055 - Newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

Science.gov (United States)

2010-04-01

..., free carnitine, and acylcarnitines using tandem mass spectrometry. 862.1055 Section 862.1055 Food and... screening test system for amino acids, free carnitine, and acylcarnitines using tandem mass spectrometry. (a) Identification. A newborn screening test system for amino acids, free carnitine, and acylcarnitines using tandem...

Iron Deficiency in Long-Term Parenteral Nutrition Therapy.

Science.gov (United States)

Hwa, Yi L; Rashtak, Shahrooz; Kelly, Darlene G; Murray, Joseph A

2016-08-01

Iron is not routinely added to parenteral nutrition (PN) formulations in the United States because of the risk of anaphylaxis and concerns about incompatibilities. Studies have shown that iron dextran in non-lipid-containing PN solutions is safe. Data are limited on iron status, prevalence of iron deficiency anemia (IDA), and efficacy of intravenous iron infusion in long-term home PN (HPN). We aimed to determine the incidence of IDA and to examine the effectiveness of parenteral iron replacement in patients receiving HPN. Medical records of patients receiving HPN at the Mayo Clinic from 1977 to 2010 were reviewed. Diagnoses, time to IDA development, and hemoglobin, ferritin, and mean corpuscular volume (MCV) values were extracted. Response of iron indices to intravenous iron replacement was investigated. Of 185 patients (122 women), 60 (32.4%) were iron deficient. Five patients were iron deficient, and 18 had unknown iron status before HPN. Of 93 patients who had sufficient iron storage, 37 had IDA development after a mean of 27.2 months (range, 2-149 months) of therapy. Iron was replaced by adding maintenance iron dextran to PN or by therapeutic iron infusion. Patients with both replacement methods had significant improvement in iron status. With intravenous iron replacement, mean ferritin increased from 10.9 to 107.6 mcg/L (P Parenteral and Enteral Nutrition.

[Applied studies of structured triglycerides for parenteral nutrition in severe hemorrhagic shock patients after resuscitation].

Science.gov (United States)

Su, Mao-sheng; He, Lei; Liu, Zhi-wei; Ma, Huan-xian; Zhao, Qing-hua; Zhang, Wen-zhi

2012-03-27

To evaluate the effects of structured triglycerides in parenteral nutrition versus a physical medium-chain triglycerides (MCT)/long-chain triglycerides (LCT) mixture on severe hemorrhagic shock patients after resuscitation. In a randomized trial, we studied 20 critical patients with a total blood loss of over 3000 ml perioperatively and/or intraoperatively. The use of triglycerides started from Day 3 postoperation and parenteral nutrition lasted for no less than 5 days. They were allocated to receive one of two nutrition regiments: structured triglycerides in Group A (n = 10) and MCT/LCT in Group B (n = 10). There were no significant differences of general conditions in two groups. Before the start of parenteral nutrition (d0), d1 d3 and d5 after start of infusion, the following parameters were measured: hemoglobin (Hb), platelet count (Plt), alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), serum triglycerides (TG), prealbumin (PA) and transferrin (TF). And mean artery pressure (MAP), heart rate (HR) and central vein pressure (CVP) were also recorded at the same time-points. Then the post-TG changes of the above data were compared in both groups. After the use of triglycerides, there were no significant differences of MAP, HR, CVP, Hb and Plt in both groups (P > 0.05). At D3 and D5, the serum levels of TG ((2.1 ± 0.4) vs (1.6 ± 0.6) mg/L, (2.3 ± 0.7) vs (1.5 ± 0.3) mg/L) and alanine aminotransferase ((133 ± 58) vs (97 ± 26) U/L; (116 ± 48) vs (77 ± 31) U/L) were significantly higher in Group B versus those receiving structured triglycerides in Group A (P 0.05). The serum levels of such nutrition markers as PA ((195 ± 55) vs (166 ± 55) mg/L,(245 ± 53) vs (195 ± 58) mg/L) and TF ((2.6 ± 0.5) vs (2.5 ± 0.6) g/L, (3.3 ± 0.8) vs (2.9 ± 0.6) g/L)were significantly higher in Group A than those in Group B (P synthesis and hepatocyte protection, structured triglycerides in parenteral nutrition is advantageous to standard MCT

Comparison of plasma, liver, and skeletal muscle carnitine concentrations in cats with idiopathic hepatic lipidosis and in healthy cats.

Science.gov (United States)

Jacobs, G; Cornelius, L; Keene, B; Rakich, P; Shug, A

1990-09-01

Concentrations of total, free, and esterified carnitine were determined in plasma, liver, and skeletal muscle from cats with idiopathic hepatic lipidosis and compared with values from healthy cats. The mean concentrations of plasma, liver, and skeletal muscle total carnitine; plasma and skeletal muscle free carnitine; and plasma and liver esterified carnitine were greater (P less than 0.05) in cats with idiopathic hepatic lipidosis than in control cats. The mean for the ratio of free/total carnitine in plasma and liver was lower (P less than 0.05) in cats with idiopathic hepatic lipidosis than in control cats. These data suggest that carnitine deficiency does not contribute to the pathogenesis of feline idiopathic hepatic lipidosis.

The effects of an L-methionine combination supplement on ...

African Journals Online (AJOL)

Interventions. L-methionine combination supplement (L-methionine, vitamin B6, vitamin B12, folic acid and magnesium) or placebo containing potato starch. Main outcome measures. Incidence of URTS was recorded during the runner's preparation for an ultramarathon race (75 days) and recovery from the same (75 days).

A krill oil supplemented diet suppresses hepatic steatosis in high-fat fed rats.

Science.gov (United States)

Ferramosca, Alessandra; Conte, Annalea; Burri, Lena; Berge, Kjetil; De Nuccio, Francesco; Giudetti, Anna Maria; Zara, Vincenzo

2012-01-01

Krill oil (KO) is a dietary source of n-3 polyunsaturated fatty acids, mainly represented by eicosapentaenoic acid and docosahexaenoic acid bound to phospholipids. The supplementation of a high-fat diet with 2.5% KO efficiently prevented triglyceride and cholesterol accumulation in liver of treated rats. This effect was accompanied by a parallel reduction of the plasma levels of triglycerides and glucose and by the prevention of a plasma insulin increase. The investigation of the molecular mechanisms of KO action in high-fat fed animals revealed a strong decrease in the activities of the mitochondrial citrate carrier and of the cytosolic acetyl-CoA carboxylase and fatty acid synthetase, which are both involved in hepatic de novo lipogenesis. In these animals a significant increase in the activity of carnitine palmitoyl-transferase I and in the levels of carnitine was also observed, suggesting a concomitant stimulation of hepatic fatty acid oxidation. The KO supplemented animals also retained an efficient mitochondrial oxidative phosphorylation, most probably as a consequence of a KO-induced arrest of the uncoupling effects of a high-fat diet. Lastly, the KO supplementation prevented an increase in body weight, as well as oxidative damage of lipids and proteins, which is often found in high-fat fed animals.

Standardized Competencies for Parenteral Nutrition Prescribing: The American Society for Parenteral and Enteral Nutrition Model.

Science.gov (United States)

Guenter, Peggi; Boullata, Joseph I; Ayers, Phil; Gervasio, Jane; Malone, Ainsley; Raymond, Erica; Holcombe, Beverly; Kraft, Michael; Sacks, Gordon; Seres, David

2015-08-01

Parenteral nutrition (PN) provision is complex, as it is a high-alert medication and prone to a variety of potential errors. With changes in clinical practice models and recent federal rulings, the number of PN prescribers may be increasing. Safe prescribing of this therapy requires that competency for prescribers from all disciplines be demonstrated using a standardized process. A standardized model for PN prescribing competency is proposed based on a competency framework, the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.)-published interdisciplinary core competencies, safe practice recommendations, and clinical guidelines. This framework will guide institutions and agencies in developing and maintaining competency for safe PN prescription by their staff. © 2015 American Society for Parenteral and Enteral Nutrition.

L-carnitine contributes to enhancement of neurogenesis from mesenchymal stem cells through Wnt/β-catenin and PKA pathway.

Science.gov (United States)

Fathi, Ezzatollah; Farahzadi, Raheleh; Charoudeh, Hojjatollah Nozad

2017-03-01

The identification of factors capable of enhancing neurogenesis has great potential for cellular therapies in neurodegenerative diseases. Multiple studies have shown the neuroprotective effects of L-carnitine (LC). This study determined whether neuronal differentiation of rat adipose tissue-derived mesenchymal stem cells (ADSCs) can be activated by LC. In this study, protein kinase A (PKA) and Wnt/β-catenin pathways were detected to show if this activation was due to these pathways. The expression of LC-induced neurogenesis markers in ADSCs was characterized using real-time PCR. ELISA was conducted to assess the expression of cyclic adenosine monophosphate (cAMP) and PKA. The expression of β-catenin, reduced dickkopf1 (DKK1), low-density lipoprotein receptor-related protein 5 (LRP5), Wnt1, and Wnt3a genes as Wnt/β-catenin signaling members were used to detect the Wnt/β-catenin pathway. It was observed that LC could promote neurogenesis in ADSCs as well as expression of some neurogenic markers. Moreover, LC causes to increase the cAMP levels and PKA activity. Treatment of ADSCs with H-89 (dihydrochloride hydrate) as PKA inhibitor significantly inhibited the promotion of neurogenic markers, indicating that the PKA signaling pathway could be involved in neurogenesis induction. Analyses of real-time PCR data showed that the mRNA expressions of β-catenin, DKK1, LRP5c-myc, Wnt1, and Wnt3a were increased in the presence of LC. Therefore, the present study showed that LC promotes ADSCs neurogenesis and the LC-induced neurogenic markers could be due to both the PKA and Wnt/β-catenin signaling pathway. Impact statement Neural tissue has long been believed as incapable of regeneration and the identification of cell types and factors capable of neuronal differentiation has generated intense interest. Mesenchymal stem cells (MSCs) are considered as potential targets for stem cell-based therapy. L-carnitin (LC) as an antioxidant may have neuroprotective effects in

21 CFR 310.509 - Parenteral drug products in plastic containers.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Parenteral drug products in plastic containers... Parenteral drug products in plastic containers. (a) Any parenteral drug product packaged in a plastic... parenteral drug product for intravenous use in humans that is packaged in a plastic immediate container on or...

Nutrición parenteral precoz en el neonato grave

Directory of Open Access Journals (Sweden)

Alina González Mustelier

2004-06-01

Full Text Available Se realizó un estudio descriptivo en el Servicio de Terapia Intensiva Neonatal del Hospital Ginecoobstétrico "Ramón González Coro" de Ciudad de La Habana, desde enero del 2000 hasta enero del 2002, con el objetivo de valorar las ventajas del uso de nutrición parenteral (NP precoz en los neonatos críticamente enfermos, durante la primera semana de vida. Se compararon 2 grupos de 23 recién nacidos críticos, uno de ellos recibió alimentación parenteral (grupo I y el otro no (grupo II. Se encontró homogeneidad en ambos grupos en cuanto a peso, edad gestacional, valoración nutricional al nacer, sexo y morbilidad inicial. La nutrición parenteral se caracterizó por su uso precoz (menos de 72 horas, conjuntamente con alimentación enteral mínima. La media del aporte máximo de macronutrientes fue de 16 g/kg/d de dextrosa, 1,2 g/kg/d de lípidos y 2 g/kg/d de proteínas. El desarrollo nutricional fue más favorable en el grupo con NP, porque le disminuyó a la mitad el tanto por ciento de peso perdido en la primera semana de vida, le sostuvo mayor aporte energético durante ese período y recupó 7 días antes su peso del nacimiento en relación con el grupo II. Las complicaciones fueron similares en ambos grupos, para concluir en que estas no estuvieron relacionadas con el uso de NP.A descriptive study was conducted at the Neonatal Intensive Therapy Service of "Ramón Gonzalez Coro" Gynecoobstetric Hospital, in Havana City, from January 2000, to January 2002, aimed at assessing the advantages of the use of early parenteral nutrition in the critically ill neonates during the first week of life. 2 groups of 23 critical newborn infants each were compared. One of them recieved parenteral nutrition (group 1 and the other one did not (group II. Homogeneity was found in both groups as regards weight, gestational age, nutritional assessment at birth and initial morbidity. The parenteral nutrition was characterized by its early use (less than 72

Alteraciones hepáticas inducidas por la nutrición parenteral

OpenAIRE

J Salas Salvado; A Recaséns Garica

1993-01-01

Liver disorders induced by parenteral nutrition Alteraciones hepáticas inducidas por la nutrición parenteral Liver disorders induced by parenteral nutrition Alteraciones hepáticas inducidas por la nutrición parenteral

Metabolic rates of 15N-D- and 15N-L-phenylalanine in an amino acid mixture for parenteral feeding

International Nuclear Information System (INIS)

Wutzke, K.; Heine, W.; Drescher, U.

1982-01-01

15 N investigations on the metabolism of L- and D-phenylalanine under conditions of parenteral feeding with the aminoacid solution Infesol in 6 infants revealed a retention rate of 83.4 +- 3.4 per cent for the L-form and of 36.6 +- 5.2 per cent for the D-form. When the D-isomer was raised from 1:3 to 1:1 in relation to the L-Form, 32.6 per cent of the infused D-phenylalanine were still retained. After continuous 24-hour infusion of the tracers, the maximum of 15 N excretion in the urine was reached between the 24th and the 30th hour. But little incorporation of 15 N-nitrogen was found in the serum and erythrocytes because of the relatively long half-life period of these proteins. Changes in the composition of commercial DL-amino acid mixtures will only be possible after determining the utilization rates of all essential and non-essential D-amino acids being used in such mixtures. (author)

The structure and organization of the human carnitine/acylcarnitine translocase (CACT1) gene2

NARCIS (Netherlands)

Iacobazzi, V.; Naglieri, M. A.; Stanley, C. A.; Wanders, R. J.; Palmieri, F.

1998-01-01

The carnitine/acylcarnitine translocase (CACT) transports acylcarnitines into mitochondria in exchange for free carnitine and it is, therefore, essential for the fatty acid beta-oxidation pathway. We have determined the exon-intron structure of the human CACT gene, which is responsible for a genetic

Standardized Parenteral Nutrition for the Transition Phase in Preterm Infants: A Bag That Fits

Science.gov (United States)

Brennan, Ann-Marie; Fenton, Sarah; Murphy, Brendan P.

2018-01-01

The optimal composition of standardized parenteral nutrition (SPN) is not yet known, contributing to nutrient deficit accrual and growth failure, with the period of parenteral nutrition weaning, i.e., transition (TN) phase, being identified as particularly vulnerable. We created a comprehensive nutrition database, representative of the nutritional course of a diverse range of preterm infants (n = 59, birth weight ≤ 1500 g, gestation nutritional contribution from enteral feeds until target AA intakes were consistently achieved. From the modeling, the AA composition of SPN was determined at 3.5 g/100 mL, which was the maximum to avoid exceeding target intakes at any point in the TN phase. However, in order to consistently achieve target AA intakes, additional nutritional strategies were required, which included increasing the exclusion of enteral feeds in fluid and nutrient calculations from <20 mL/kg/day to <40 mL/kg/day, and earlier fortification of breastmilk at 80 mL/kg/day. This data-driven nutrient modeling process supported the development of an improved SPN regimen for our preterm population in the TN phase. PMID:29393903

L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats.

Science.gov (United States)

de Aguiar Picanço, Etiene; Lopes-Paulo, Francisco; Marques, Ruy G; Diestel, Cristina F; Caetano, Carlos Eduardo R; de Souza, Mônica Vieira Mano; Moscoso, Gabriela Mendes; Pazos, Helena Maria F

2011-05-01

Radiotherapy is widely used for cancer treatment but has harmful effects. This study aimed to assess the effects of L-arginine and glycine supplementation on the colon wall of rats submitted to abdominal irradiation. Forty male Wistar rats were randomly divided into four groups: I-healthy, II-irradiated with no amino acid supplementation, III-irradiated and supplemented with L-arginine, and IV-irradiated and supplemented with glycine. The animals received supplementation for 14 days, with irradiation being applied on the eighth day of the experiment. All animals underwent laparotomy on the 15th day for resection of a colonic segment for stereologic analysis. Parametric and nonparametric tests were used for statistical analysis, with the level of significance set at p ≤0.05. Stereologic analysis showed that irradiation induced a reduction of the total volume of the colon wall of group II and III animals compared to healthy controls, but not of group IV animals supplemented with glycine. The mucosal layer of the irradiated animals of all groups was reduced compared to healthy group I animals, but supplementation with L-arginine and glycine was effective in maintaining the epithelial surface of the mucosal layer. The present results suggest that glycine supplementation had a superior effect on the irradiated colon wall compared to L-arginine supplementation since it was able to maintain the thickness of the wall and the epithelial surface of the mucosa, whereas L-arginine maintained the partial volume of the epithelium and the epithelial surface, but not the total volume of the intestinal wall.

[Intrahepatic cholestasis associated with parenteral nutrition: an experimental study in rats].

Science.gov (United States)

Salas Martínez, J; Morán Penco, J M; Mahedero Ruiz, G; García Gamito, F; Limón Mora, M; Maciá Botejara, E; Vinagre Velasco, L M

1989-01-01

Intrahepatic cholestasis is a condition often observed in patients receiving parenteral nutrition, especially in new born babies who are underweight (taurina. This makes it impossible to achieve a correct conjugation of toxic biliary acids. The access of nutrients to the liver may have an effect on this. An experimental study on rats was performed, administering an oral diet at the expense of lipids (20% Intralipid, 60% of caloric needs) and glucose (40% of caloric needs) in one group, another group received amino acid supplements to this diet (16N) at a proteic rate of 2 gr/kg of weight and day orally, with an identical diet to the above, except that the proteic intake was intraperitoneal. Two control groups were established. We found a microvacuolization in hepatic fat with the help of an electronic microscope in the groups lacking proteins and those with oral or intraperitoneal supplements of amino acids, as well as an increase in plasmatic AST.

Plasma Aluminum Concentrations in Pediatric Patients Receiving Long-Term Parenteral Nutrition.

Science.gov (United States)

Courtney-Martin, Glenda; Kosar, Christina; Campbell, Alison; Avitzur, Yaron; Wales, Paul W; Steinberg, Karen; Harrison, Debra; Chambers, Kathryn

2015-07-01

Patients receiving long-term parenteral nutrition (PN) are at increased risk of aluminium (Al) toxicity because of bypass of the gastrointestinal tract during PN infusion. Complications of Al toxicity include metabolic bone disease (MBD), Al-associated encephalopathy in adults, and impaired neurological development in preterm infants. Unlike the United States, there are no regulations regarding Al content of large- and small-volume parenterals in Canada. We, therefore, aimed to present our data on plasma Al concentration and Al intake from our cohort of pediatric patients receiving long-term PN. Plasma Al concentration was retrospectively gathered from the patient charts of all 27 patients with intestinal failure (IF) receiving long-term PN at The Hospital for Sick Children, Toronto, Canada, and compared with age- and sex-matched controls recruited for comparison. In addition, Al concentration was measured in PN samples collected from 10 randomly selected patients with IF and used to determine their Al intake. The plasma Al concentration of patients with IF receiving long-term PN was significantly higher than that of control participants (1195 ± 710 vs 142 ± 63 nmol/L; P Parenteral and Enteral Nutrition.

Over-expression in Escherichia coli, purification and reconstitution in liposomes of the third member of the OCTN sub-family: The mouse carnitine transporter OCTN3

International Nuclear Information System (INIS)

Scalise, Mariafrancesca; Galluccio, Michele; Pochini, Lorena; Indiveri, Cesare

2012-01-01

Highlights: ► mOCTN3 transport protein has been cloned in pET-21a(+) and over-expressed in Escherichia coli. ► The expressed mOCTN3 has been purified to homogeneity by Ni-chelating chromatography. ► The protein solubilised in Triton X-100 has been reconstituted in liposomes. ► Recombinant mOCTN3 catalyses transport of carnitine by a uniport mode. -- Abstract: pET-21a(+)-mOCTN3-6His was constructed and used for over-expression in Escherichia coli Rosetta(DE3)pLysS. After IPTG induction a protein with apparent molecular mass of 53 kDa was collected in the insoluble fraction of the cell lysate and purified by Ni 2+ -chelating chromatography with a yield of 2 mg/l of cell culture. The over-expressed protein was identified with mOCTN3 by anti-His antibody and reconstitution in liposomes. mOCTN3 required peculiar conditions for optimal expression and reconstitution in liposomes. The protein catalyzed a time dependent [ 3 H]carnitine uptake which was stimulated by intraliposomal ATP and nearly independent of the pH. The K m for carnitine was 36 μM. [ 3 H]carnitine transport was inhibited by carnitine analogues and some Cys and NH 2 reagents. This paper represents the first outcome in over-expressing, in active form, the third member of the OCTN sub-family, mOCTN3, in E. coli.

Identification of two novel mutations in OCTN2 of three patients with systemic carnitine deficiency

NARCIS (Netherlands)

Vaz, F. M.; Scholte, H. R.; Ruiter, J.; Hussaarts-Odijk, L. M.; Pereira, R. R.; Schweitzer, S.; de Klerk, J. B.; Waterham, H. R.; Wanders, R. J.

1999-01-01

Systemic carnitine deficiency is a potentially lethal, autosomal recessive disorder characterized by cardiomyopathy, myopathy, recurrent episodes of hypoketotic hypoglycemia, hyperammonemia, and failure to thrive. This form of carnitine deficiency is caused by a defect in the active cellular uptake

Indicaciones no quirúrgicas de la nutrición parenteral periférica Parenteral periferic nutrition: non surgical indications

OpenAIRE

A. Ayúcar Ruiz de Galarreta; F. Pita Gutiérrez; F. Mosteiro Pereira; L. Cordero Lorenzana; S. Gómez Canosa; C. Seco Vilariño

2011-01-01

Introducción: La Nutrición Parenteral Perif��rica, definida como la mezcla de macronutrientes, vitaminas y minerales con osmolaridad menor de 800 mOsm/L, permite evitar los riesgos del catéter central. Clásicamente ha sido utilizada en postoperados, pero actualmente la patología médica también puede beneficiarse de ella, bien como única fuente de nutrientes, ya que un alto porcentaje de pacientes precisan menor aporte calórico de lo que se creía, o como complementaria. Objetivo: Evaluación de...

“Parenteral Nutrition Supplementation in Biliary Atresia Patients Listed for Liver Transplantation”

Science.gov (United States)

Sullivan, Jillian S; Sundaram, Shikha S; Pan, Zhaoxing; Sokol, Ronald J

2011-01-01

Objective To determine the impact of parenteral nutrition (PN) on outcomes in biliary atresia (BA) patients listed for liver transplantation (LTx). Study Design We retrospectively reviewed charts of all BA patients from 1990 through 2010 at our institution, s/p hepatoportoenterostomy, ≤ 36 months old, and listed for LTx. Initiation of PN was based on clinical indications. Results 25 PN and 22 non-PN subjects (74% female) were studied. Median PN initiation age was 7.7 months, mean duration 86 days, and mean PN energy supplied 77 kcal/kg/day. Prior to PN, triceps skinfold thickness (TSF) and mid-arm circumference (MAC) Z-scores were decreasing. After PN, TSF (p=0.003) and MAC (pnutritional status in malnourished BA patients awaiting LTx, which is associated with post-LTx outcomes comparable to those not requiring PN. PMID:21987426

Parenteral nutrition in malnourished patients

International Nuclear Information System (INIS)

Lichvarova, I.

2011-01-01

Parenteral nutrition became a routine therapeutic option in malnourished patients, if conventional nutritional enteral support is not effective. Cachexia and malnutrition prolong the wound healing, contribute to immunosuppression, increase morbidity and the cost of treatment. Using of a malnutrition protocol as a screening tool is necessary to sort out malnourished patients. Parenteral nutrition is therefore an important part of the multimodal therapy and from the medical and the ethical point of view is a great mistake not to feed a patient. (author)

Standardized Competencies for Parenteral Nutrition Order Review and Parenteral Nutrition Preparation, Including Compounding: The ASPEN Model.

Science.gov (United States)

Boullata, Joseph I; Holcombe, Beverly; Sacks, Gordon; Gervasio, Jane; Adams, Stephen C; Christensen, Michael; Durfee, Sharon; Ayers, Phil; Marshall, Neil; Guenter, Peggi

2016-08-01

Parenteral nutrition (PN) is a high-alert medication with a complex drug use process. Key steps in the process include the review of each PN prescription followed by the preparation of the formulation. The preparation step includes compounding the PN or activating a standardized commercially available PN product. The verification and review, as well as preparation of this complex therapy, require competency that may be determined by using a standardized process for pharmacists and for pharmacy technicians involved with PN. An American Society for Parenteral and Enteral Nutrition (ASPEN) standardized model for PN order review and PN preparation competencies is proposed based on a competency framework, the ASPEN-published interdisciplinary core competencies, safe practice recommendations, and clinical guidelines, and is intended for institutions and agencies to use with their staff. © 2016 American Society for Parenteral and Enteral Nutrition.

Environmental Enteric Dysfunction is Associated with Carnitine Deficiency and Altered Fatty Acid Oxidation

Directory of Open Access Journals (Sweden)

Richard D. Semba

2017-03-01

Interpretation: EED is a syndrome characterized by secondary carnitine deficiency, abnormal fatty acid oxidation, alterations in polyphenol and amino acid metabolites, and metabolic dysregulation of sulfur amino acids, tryptophan, and the urea cycle. Future studies are needed to corroborate the presence of secondary carnitine deficiency among children with EED and to understand how these metabolic derangements may negatively affect the growth and development of young children.

L-acetylcarnitine enhances functional muscle re-innervation.

Science.gov (United States)

Pettorossi, V E; Brunetti, O; Carobi, C; Della Torre, G; Grassi, S

1991-01-01

The efficacy of L-acetylcarnitine and L-carnitine treatment on motor re-innervation was analyzed by evaluating different muscular parameters describing functional muscle recovery after denervation and re-innervation. The results show that L-acetylcarnitine markedly enhances functional muscle re-innervation, which on the contrary is unaffected by L-carnitine. The medial gastrocnemius muscle was denervated by cutting the nerve at the muscle entry point. After 20 days the sectioned nerve was resutured into the medial gastrocnemius muscle, and the extent of re-innervation was monitored 45 days later. L-acetylcarnitine-treated animals show significantly higher twitch and tetanic tensions of re-innervated muscle. Furthermore the results, obtained by analysing the twitch time to peak and tetanic contraction-relaxation times, suggest that L-acetylcarnitine mostly affects the functional re-innervation of slow motor units. The possible mechanisms by which L-acetylcarnitine facilitates such motor and nerve recovery are discussed.

Timing of the initiation of parenteral nutrition in critically ill children.

Science.gov (United States)

Jimenez, Lissette; Mehta, Nilesh M; Duggan, Christopher P

2017-05-01

To review the current literature evaluating clinical outcomes of early and delayed parenteral nutrition initiation among critically ill children. Nutritional management remains an important aspect of care among the critically ill, with enteral nutrition generally preferred. However, inability to advance enteral feeds to caloric goals and contraindications to enteral nutrition often leads to reliance on parenteral nutrition. The timing of parenteral nutrition initiation is varied among critically ill children, and derives from an assessment of nutritional status, energy requirements, and physiologic differences between adults and children, including higher nutrient needs and lower body reserves. A recent randomized control study among critically ill children suggests improved clinical outcomes with avoiding initiation of parenteral nutrition on day 1 of admission to the pediatric ICU. Although there is no consensus on the optimal timing of parenteral nutrition initiation among critically ill children, recent literature does not support the immediate initiation of parenteral nutrition on pediatric ICU admission. A common theme in the reviewed literature highlights the importance of accurate assessment of nutritional status and energy expenditure in deciding when to initiate parenteral nutrition. As with all medical interventions, the initiation of parenteral nutrition should be considered in light of the known benefits of judiciously provided nutritional support with the known risks of artificial, parenteral feeding.

Antiketogenic and hypoglycemic effects of aminocarnitine and acylaminocarnitines

International Nuclear Information System (INIS)

Jenkins, D.L.; Griffith, O.W.

1986-01-01

DL-Aminocarnitine (DL-3-amino-4-trimethyl-aminobutyrate) is a potent, noncovalent inhibitor of carnitine palmitoyltransferase (palmitoyl-CoA:L-carinite O-palmitoyltransferase, EC 2.3.1.21). Here the authors show that decanoyl-DL-aminocarnitine and palmitoyl-DL-aminocarnitine inhibit carnitine palmitoyltransferase in vitro about 7-fold and 100-fold more effectively than does aminocarnitine. Aminocarnitine and its decanoyl and palmitoyl derivatives are active in vivo following oral or parenteral administration and, at doses of 0.3 mmol/kg or less, inhibit the oxidation of [ 14 C]palmitate to 14 CO 2 by 45-70% in mice. Larger doses do not significantly increase the extent of inhibition, a finding suggesting that substantial carnitine palmitoyltransferase-independent long-chain fatty acid oxidation may occur in vivo. Small doses of aminocarnitine and palmitoylaminocarnitine prevent the development of ketoacidemia in fasted, normal mice and reverse the ketoacidemia observed in diabetic mice. Aminocarnitine has a strong hypoglycemic effect in fasted diabetic mice; a single dose (0.3 mmol/kg) normalizes plasma glucose levels within 4-8 hr and remains effective for at least 12 hr

Effects of propionyl-L-carnitine on ischemia-reperfusion injury in hamster cheek pouch microcirculation.

Science.gov (United States)

Lapi, Dominga; Sabatino, Lina; Altobelli, Giovanna Giuseppina; Mondola, Paolo; Cimini, Vincenzo; Colantuoni, Antonio

2010-01-01

Propionyl-l-carnitine (pLc) exerts protective effects in different experimental models of ischemia-reperfusion (I/R). The aim of the present study was to assess the effects of intravenously and topically applied pLc on microvascular permeability increase induced by I/R in the hamster cheek pouch preparation. The hamster cheek pouch microcirculation was visualized by fluorescence microscopy. Microvascular permeability, leukocyte adhesion to venular walls, perfused capillary length, and capillary red blood cell velocity (V(RBC)) were evaluated by computer-assisted methods. E-selectin expression was assessed by in vitro analysis. Lipid peroxidation and reactive oxygen species (ROS) formation were determined by thiobarbituric acid-reactive substances (TBARS) and 2'-7'-dichlorofluorescein (DCF), respectively. In control animals, I/R caused a significant increase in permeability and in the leukocyte adhesion in venules. Capillary perfusion and V(RBC) decreased. TBARS levels and DCF fluorescence significantly increased compared with baseline. Intravenously infused pLc dose-dependently prevented leakage and leukocyte adhesion, preserved capillary perfusion, and induced vasodilation at the end of reperfusion, while ROS concentration decreased. Inhibition of nitric oxide synthase prior to pLc caused vasoconstriction and partially blunted the pLc-induced protective effects; inhibition of the endothelium-derived hyperpolarizing factor (EDHF) abolished pLc effects. Topical application of pLc on cheek pouch membrane produced the same effects as observed with intravenous administration. pLc decreased the E-selectin expression. pLc prevents microvascular changes induced by I/R injury. The reduction of permeability increase could be mainly due to EDHF release induce vasodilatation together with NO. The reduction of E-selectin expression prevents leukocyte adhesion and permeability increase.

Effects of propionyl-L-carnitine on ischemia-reperfusion injury in hamster cheek pouch microcirculation.

Directory of Open Access Journals (Sweden)

Dominga Lapi

2010-10-01

Full Text Available Background and Purpose Propionyl-L-carnitine (pLc exerts protective effects in different experimental models of ischemia-reperfusion (I/R. The aim of the present study was to assess the effects of intravenously and topically applied pLc on microvascular permeability increase induced by I/R in the hamster check pouch preparation. Methods The hamster check pouch microcirculation was visualized by fluorescence microscopy. Microvascular permeability, leukocyte adhesion to venular walls, perfused capillary length and capillary red blood cell velocity (VRBC were evaluated by computer-assisted methods. E-selectin expression was assessed by in vitro analysis. Lipid peroxidation and reactive oxygen species (ROS formation were determined by thiobarbituric acid-reactive substances (TBARS and 2’-7’-dichlorofluorescein (DCF, respectively. Results In control animals, I/R caused a significant increase in permeability and in the leukocyte adhesion in venules. Capillary perfusion and VRBC decreased. TBARS levels and DCF fluorescence significantly increased compared with baseline. Intravenously infused pLc dose-dependently prevented leakage and leukocyte adhesion, preserved capillary perfusion and induced vasodilation at the end of reperfusion, while ROS concentration decreased. Inhibition of nitric oxide synthase prior to pLc caused vasoconstriction and partially blunted the pLc-induced protective effects; inhibition of the endothelium-derived hyperpolarizing factor (EDHF abolished pLc effects. Topical application of pLc on check pouch membrane produced the same effects as observed with intravenous administration. pLc decreased the E-selectin expression. Conclusions pLc prevents microvascular changes induced by I/R injury. The reduction of permeability increase could be mainly due to EDHF release induce vasodilatation together with NO. The reduction of E-selectin expression prevents leukocyte adhesion and permeability increase.

Propionyl-L-carnitine improves endothelial function, microcirculation and pain management in critical limb ischemia.

Science.gov (United States)

De Marchi, S; Zecchetto, S; Rigoni, A; Prior, M; Fondrieschi, L; Scuro, A; Rulfo, F; Arosio, E

2012-10-01

Chronic critical limb ischemia (CLI) is a severe condition of hypo-perfusion of lower limbs, which is associated with inflammation and a pro-coagulative state. It is a disease at high risk of amputation and cardiovascular death. Propionyl-L-carnitine (PLC) is efficacious in improving pain free walking distance in peripheral arterial disease with claudication; it also exerts favorable effects on the arterial wall and on endothelial function. The purpose of this study was to evaluate the effects of PLC on microcirculation, endothelial function and pain relief in patients affected by CLI not suitable for surgical intervention. We enrolled 48 patients with CLI. Patients were randomized into two groups: the first group was treated with PLC, the second was treated with saline solution. All of them underwent the following tests: laser Doppler flowmetry at the forefoot at rest and after ischemia, trans cutaneous oxygen partial pressure and carbon dioxide partial pressure at the forefoot at rest and after ischemia, endothelium dependent dilation of the brachial artery. All tests were repeated after treatments. Pain was assessed by visual analog pain scale. Endothelium dependent dilation increased after PLC (9.5 ± 3.2 vs 4.9 ± 1.4 %; p < 0.05). Post-ischemic peak flow with laser-Doppler flow increased after PLC. TcPO2 increased, while TcPCO2 decreased after PLC; CO2 production decreased after PLC. VAS showed a significant reduction in pain perception after active treatment. In CLI patients, PLC can improve microcirculation (post ischemic hyperemia, TcPO2 and TcPCO2 production). PLC also enhances endothelium dependent dilation and reduces analgesic consumption and pain perception.

Evidence-Based Supplements for the Enhancement of Athletic Performance.

Science.gov (United States)

Peeling, Peter; Binnie, Martyn J; Goods, Paul S R; Sim, Marc; Burke, Louise M

2018-03-01

A strong foundation in physical conditioning and sport-specific experience, in addition to a bespoke and periodized training and nutrition program, are essential for athlete development. Once these underpinning factors are accounted for, and the athlete reaches a training maturity and competition level where marginal gains determine success, a role may exist for the use of evidence-based performance supplements. However, it is important that any decisions surrounding performance supplements are made in consideration of robust information that suggests the use of a product is safe, legal, and effective. The following review focuses on the current evidence-base for a number of common (and emerging) performance supplements used in sport. The supplements discussed here are separated into three categories based on the level of evidence supporting their use for enhancing sports performance: (1) established (caffeine, creatine, nitrate, beta-alanine, bicarbonate); (2) equivocal (citrate, phosphate, carnitine); and (3) developing. Within each section, the relevant performance type, the potential mechanisms of action, and the most common protocols used in the supplement dosing schedule are summarized.

Effect of parenteral serum plant sterols on liver enzymes and cholesterol metabolism in a patient with short bowel syndrome.

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Hallikainen, Maarit; Huikko, Laura; Kontra, Kirsi; Nissinen, Markku; Piironen, Vieno; Miettinen, Tatu; Gylling, Helena

2008-01-01

Hepatobiliary complications are common during parenteral nutrition. Lipid moiety in commercially available solutions contains plant sterols. It is not known whether plant sterols in parenteral nutrition interfere with hepatic function in adults. We detected how different amounts of plant sterols in parenteral nutrition solution affected serum plant sterol concentrations and liver enzymes during a 1.5-year follow-up in a patient with short bowel syndrome. Serum lipid, plant sterol, and liver enzyme levels were measured regularly during the transition from Intralipid (100% soy-based intravenous fat emulsion) to ClinOleic (an olive oil-based intravenous fat emulsion with 80% olive oil, 20% soy oil and lower plant sterols); the lipid supply was also gradually increased from 20 to 35 g/d. Plant sterols in parenteral nutrition solution and serum were measured with gas-liquid chromatography. During infusion of soy-based intravenous fat emulsion (30 g/d, total plant sterols 87 mg/d), the concentrations of sitosterol, campesterol, and stigmasterol were 4361, 1387, and 378 microg/dL, respectively, and serum liver enzyme values were >or= 2.5 times above upper limit of normal. After changing to olive oil-based intravenous fat emulsion (20-35 g/d, plant sterols 37-65 mg/d), concentrations decreased to 2148 to 2251 microg/dL for sitosterol, 569-297 microg/dL for campesterol, and 95-55 microg/dL for stigmasterol. Concomitantly, liver enzyme values decreased to 1.4 to 1.8 times above upper limit of normal at the end of follow-up. The nutrition status of the patient improved. The amount of plant sterols in lipid emulsion affects serum liver enzyme levels more than the amount of lipid.

Over-expression in Escherichia coli, purification and reconstitution in liposomes of the third member of the OCTN sub-family: The mouse carnitine transporter OCTN3

Energy Technology Data Exchange (ETDEWEB)

Scalise, Mariafrancesca; Galluccio, Michele; Pochini, Lorena [Department of Cell Biology, University of Calabria, Via P. Bucci 4c, 87036 Arcavacata di Rende (Italy); Indiveri, Cesare, E-mail: indiveri@unical.it [Department of Cell Biology, University of Calabria, Via P. Bucci 4c, 87036 Arcavacata di Rende (Italy)

2012-05-25

Highlights: Black-Right-Pointing-Pointer mOCTN3 transport protein has been cloned in pET-21a(+) and over-expressed in Escherichia coli. Black-Right-Pointing-Pointer The expressed mOCTN3 has been purified to homogeneity by Ni-chelating chromatography. Black-Right-Pointing-Pointer The protein solubilised in Triton X-100 has been reconstituted in liposomes. Black-Right-Pointing-Pointer Recombinant mOCTN3 catalyses transport of carnitine by a uniport mode. -- Abstract: pET-21a(+)-mOCTN3-6His was constructed and used for over-expression in Escherichia coli Rosetta(DE3)pLysS. After IPTG induction a protein with apparent molecular mass of 53 kDa was collected in the insoluble fraction of the cell lysate and purified by Ni{sup 2+}-chelating chromatography with a yield of 2 mg/l of cell culture. The over-expressed protein was identified with mOCTN3 by anti-His antibody and reconstitution in liposomes. mOCTN3 required peculiar conditions for optimal expression and reconstitution in liposomes. The protein catalyzed a time dependent [{sup 3}H]carnitine uptake which was stimulated by intraliposomal ATP and nearly independent of the pH. The K{sub m} for carnitine was 36 {mu}M. [{sup 3}H]carnitine transport was inhibited by carnitine analogues and some Cys and NH{sub 2} reagents. This paper represents the first outcome in over-expressing, in active form, the third member of the OCTN sub-family, mOCTN3, in E. coli.

Total parenteral nutrition - Problems in compatibility and stability

DEFF Research Database (Denmark)

Schroder, A.M.

2008-01-01

Adding calcium, trace elements and vitamins could turn parenteral nutrition into a dangerous product, which could harm the patient. This article focuses on the major pharmaceutical problems of parenteral. nutrition when adding nutritional compounds Udgivelsesdato: 2008...

Managing an outpatient parenteral antibiotic therapy team: challenges and solutions

OpenAIRE

Nguyen, Hien; Halilovic,Jenana; Christensen,Cinda

2014-01-01

Jenana Halilovic,1 Cinda L Christensen,2 Hien H Nguyen31University of the Pacific Thomas J Long School of Pharmacy, Stockton, CA, USA; 2Department of Pharmaceutical Services, University of California, Davis Health System, Sacramento, CA, USA; 3Division of Infectious Diseases, Section of Hospital Medicine, University of California, Davis Health System, Sacramento, CA, USAAbstract: Outpatient parenteral antimicrobial therapy (OPAT) programs should strive to deliver safe, cost effective, and hig...

Identification of two novel mutations in OCTN2 from two Saudi patients with systemic carnitine deficiency

NARCIS (Netherlands)

Rahbeeni, Z.; Vaz, F. M.; Al-Hussein, K.; Bucknall, M. P.; Ruiter, J.; Wanders, R. J.; Rashed, M. S.

2002-01-01

Systemic carnitine deficiency (CDSP) (McKusick 212140) is a rare autosomal recessive disease caused by defective plasma membrane uptake of carnitine. The disease is characterized by Reye syndrome, progressive cardiomyopathy, skeletal myopathy, hypoglycaemia and hyperammonaemia. CDSP is a treatable

Pediatric parenteral nutrition-associated liver disease and cholestasis: Novel advances in pathomechanisms-based prevention and treatment.

Science.gov (United States)

Orso, Giuseppe; Mandato, Claudia; Veropalumbo, Claudio; Cecchi, Nicola; Garzi, Alfredo; Vajro, Pietro

2016-03-01

Parenteral nutrition constitutes a life-saving therapeutic tool in patients unable to ingest/absorb oral or enteral delivered nutrients. Liver function tests abnormalities are a common therapy-related complication, thus configuring the so-called Parenteral Nutrition Associated Liver Disease (PNALD) or cholestasis (PNAC). Although the damage is frequently mild, and resolves after discontinuation of parenteral nutrition, in some cases it progresses into cirrhotic changes, especially in neonates and infants. We present a literature review focusing on the pathogenetic mechanisms-driven prevention and therapies for the cases where parenteral nutrition cannot be discontinued. Ursodeoxycholic acid has been proposed in patients with cholestatic hepatopathy, but its efficacy needs to be better established. Little evidence is available on efficacy of anti-oxidants, antibiotics, probiotics and anti TNFα. Lipid emulsions based on fish oil with a high content of long-chain polyunsaturated fatty acids ω-3 appear effective both in decreasing intrahepatic inflammation and in improving biliary flow. Most recent promising variations such as soybean/MCT/olive/fish oil emulsion [third generation lipid emulsion (SMOFlipid)] are under investigation. In conclusion, we remark the emergence of a number of novel pathomechanisms underlying the severe liver impairment damage (PNALD and PNAC) in patients treated with parenteral nutrition. Only few traditional and innovative therapeutic strategies have hitherto been shown promising. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Parenteral nutrition versus enteral nutrition in severe acute pancreatitis Nutrição parenteral versus enteral em pacientes com pancreatite aguda grave

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Josiel Paiva Vieira

2010-10-01

Full Text Available PURPOSE: To compare the effect of parenteral versus enteral nutritional support in severe acute pancreatitis, with respect to efficacy, safety, morbidity, mortality and length of hospitalization. METHODS: The study was comprised of 31 patients, divided into a parenteral group (n=16 and an enteral group (n=15, who met severity criteria for abdominal tomography (Balthazar classes C, D, and E. The patients were compared by demographics, disease etiology, antibiotic prophylaxis, use or not of somatostatin, nutritional support, complications and disease progression. RESULTS: There was no statistical difference in the average duration of nutritional support, somatostatin, or antibiotics in the two groups. Imipenem was the drug of choice for prophylaxis of pancreatic infections in both groups. More complications occurred in the parenteral group, although the difference was not statistically significant (p=0.10. Infectious complications, such as catheter sepsis and infections of the pancreatic tissue, were significantly more frequent in the parenteral group (p=0.006. There was no difference in average length of hospitalization in the two groups. There were three deaths in the parenteral group and none in the enteral group. CONCLUSION: Enteral nutritional support is associated with fewer septic complications compared to parenteral nutritional support.OBJETIVO: Comparar o efeito do suporte nutricional parenteral versus enteral, em pancreatite aguda grave, com relação à eficácia, à segurança, à morbi-mortalidade e ao tempo de internação. MÉTODOS: Foram estudados 31 pacientes distribuídos em grupo parenteral (n=16, no período de 1995 a 1998 e grupo enteral (n=15, no período de 1999 a 2002, que preencheram os critérios de gravidade pela tomografia de abdome (Balthazar C,D,E. Os pacientes foram comparados quanto aos dados demográficos, etiologia, antibioticoprofilaxia, somatostatina, suporte nutricional, complicações e evolução. RESULTADOS

Delayed onset muscle soreness: No pain, no gain? The truth behind ...

African Journals Online (AJOL)

Delayed onset muscle soreness (DOMS) is muscle pain and stiffness that develops ... limited success in reducing the symptoms.1,4-6 The DOMS phenomenon ... Nutritional supplementation (antioxidants and L-carnitine) shows promise, but ...

The Acetyl Group Buffering Action of Carnitine Acetyltransferase Offsets Macronutrient-Induced Lysine Acetylation of Mitochondrial Proteins

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Michael N. Davies

2016-01-01

Full Text Available Lysine acetylation (AcK, a posttranslational modification wherein a two-carbon acetyl group binds covalently to a lysine residue, occurs prominently on mitochondrial proteins and has been linked to metabolic dysfunction. An emergent theory suggests mitochondrial AcK occurs via mass action rather than targeted catalysis. To test this hypothesis, we performed mass spectrometry-based acetylproteomic analyses of quadriceps muscles from mice with skeletal muscle-specific deficiency of carnitine acetyltransferase (CrAT, an enzyme that buffers the mitochondrial acetyl-CoA pool by converting short-chain acyl-CoAs to their membrane permeant acylcarnitine counterparts. CrAT deficiency increased tissue acetyl-CoA levels and susceptibility to diet-induced AcK of broad-ranging mitochondrial proteins, coincident with diminished whole body glucose control. Sub-compartment acetylproteome analyses of muscles from obese mice and humans showed remarkable overrepresentation of mitochondrial matrix proteins. These findings reveal roles for CrAT and L-carnitine in modulating the muscle acetylproteome and provide strong experimental evidence favoring the nonenzymatic carbon pressure model of mitochondrial AcK.

Early versus Late Parenteral Nutrition in Very Low Birthweight Neonates; A retrospective study from Oman

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Amitha R Aroor

2012-02-01

Full Text Available Objectives: The aim of this study was to compare the biochemical parameters, weight gain, osteopenia and phosphate supplementation in very low birth weight (VLBW neonates receiving early versus late parenteral nutrition (EPN versus LPN. Methods: A retrospective study was undertaken in the level III Neonatal Intensive Care Unit at Sultan Qaboos University Hospital, Oman: from January 2007 to October 2008 (LPN group, n = 47 and from January 2009 to June 2010 (EPN group, n = 44. Demographic data, anthropometric and laboratory parameters were extracted from the electronic record system. Results: The mean age of PN initiation was LPN = 47.3 hours versus EPN = 14.3 hours. Biochemical parameters analysed during the first week of life revealed a reduction in hypernatraemia (12.7% versus 6.8% and non-oliguric hyperkalemia (12.7% versus 6.8% in EPN, with no significant differences in acidosis and urea levels between the two groups. Hyperglycemia >12 mmol/L in <1000g was higher in EPN. Nutritional parameters in 81 babies who survived/stayed in the unit up to a corrected gestational age (CGA of 34 weeks (40 in LPN and 41 in EPN, revealed a reduction in metabolic bone disease (osteopenia of prematurity [OOP], 17.5% versus 7.3% and the need for phosphate supplementation (22.5% versus 7.3% in the EPN group. There was no increase in acidosis or cholestasis. No difference was noted in albumin levels, time to full feeds, time to regain birthweight and mean weight gain per day till 34 weeks corrected CGA. Conclusion: EPN in VLBW newborns is well tolerated and reduces hypernatraemia, non-oliguric hyperkalemia, OOP and the need for phosphate supplementation.

L-carnitine protects against nickel-induced neurotoxicity by maintaining mitochondrial function in Neuro-2a cells

International Nuclear Information System (INIS)

He Mindi; Xu Shangcheng; Lu Yonghui; Li Li; Zhong Min; Zhang Yanwen; Wang Yuan; Li Min; Yang Ju; Zhang Guangbin; Yu Zhengping; Zhou Zhou

2011-01-01

Mitochondrial dysfunction is thought to be a part of the mechanism underlying nickel-induced neurotoxicity. L-carnitine (LC), a quaternary ammonium compound biosynthesized from the amino acids lysine and methionine in all mammalian species, manifests its neuroprotective effects by improving mitochondrial energetics and function. The purpose of this study was to investigate whether LC could efficiently protect against nickel-induced neurotoxicity. Here, we exposed a mouse neuroblastoma cell line (Neuro-2a) to different concentrations of nickel chloride (NiCl 2 ) (0.25, 0.5, 1, and 2 mM) for 24 h, or to 0.5 mM and 1 mM NiCl 2 for various periods (0, 3, 6, 12, or 24 h). We found that nickel significantly increased the cell viability loss and lactate dehydrogenase (LDH) release in Neuro-2a cells. In addition, nickel exposure significantly elevated reactive oxygen species (ROS) and malondialdehyde (MDA) levels, disrupted the mitochondrial membrane potential (ΔΨ m ), reduced adenosine-5'-triphosphate (ATP) concentrations and decreased mitochondrial DNA (mtDNA) copy numbers and mtRNA transcript levels. However, all of the cytotoxicities and mitochondrial dysfunctions that were triggered by nickel were efficiently attenuated by pretreatment with LC. These protective effects of LC may be attributable to its role in maintaining mitochondrial function in nickel-treated cells. Our results suggest that LC may have great pharmacological potential in protecting against the adverse effects of nickel in the nervous system.

Hypophosphatemia occurs with insulin administration during refeeding by total parenteral nutrition in rats.

Science.gov (United States)

Kawamura, Hiromi; Tanaka, Sarasa; Uenami, Yuri; Tani, Mariko; Ishitani, Midori; Morii, Saeko; Sakaue, Motoyoshi; Ito, Mikiko

2018-01-01

Refeeding syndrome (RFS) is characterized by the metabolic and clinical changes that occur following aggressive nutritional supplementation in malnourished patients. Hypophosphatemia is the hallmark of RFS and is key to its prevention and treatment in clinical practice. However, the mechanism of hypophosphatemia during RFS is unclear because of the lack of an animal model. In this study, we developed a rat RFS model as a first step to clarifying the molecular mechanism. After establishing the parenteral route, rats were fasted for 5 days and refeeding was started using total parenteral nutrition. The animals were infused with a high calorie solution with or without insulin administration. Results showed that plasma phosphate levels did not decrease in rats infused with the high calorie solution alone;in contrast, a 20% reduction compared to baseline was observed in rats administered insulin. In addition, rats infused with the high calorie solution containing added phosphate did not present with hypophosphatemia. Thus, we developed a rat RFS model with hypophosphatemia by tube feeding and insulin administration, and demonstrated the importance of phosphate in preventing refeeding hypophosphatemia. J. Med. Invest. 65:50-55, February, 2018.

L-arginine supplementation improves responses to injury and inflammation in dextran sulfate sodium colitis.

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Lori A Coburn

Full Text Available Inflammatory bowel disease (IBD, consisting of Crohn's disease and ulcerative colitis (UC, results in substantial morbidity and is difficult to treat. New strategies for adjunct therapies are needed. One candidate is the semi-essential amino acid, L-arginine (L-Arg, a complementary medicine purported to be an enhancer of immunity and vitality in the lay media. Using dextran sulfate sodium (DSS as a murine colonic injury and repair model with similarities to human UC, we assessed the effect of L-Arg, as DSS induced increases in colonic expression of the y(+ cationic amino acid transporter 2 (CAT2 and L-Arg uptake. L-Arg supplementation improved the clinical parameters of survival, body weight loss, and colon weight, and reduced colonic permeability and the number of myeloperoxidase-positive neutrophils in DSS colitis. Luminex-based multi-analyte profiling demonstrated that there was a marked reduction in proinflammatory cytokine and chemokine expression with L-Arg treatment. Genomic analysis by microarray demonstrated that DSS-treated mice supplemented with L-Arg clustered more closely with mice not exposed to DSS than to those receiving DSS alone, and revealed that multiple genes that were upregulated or downregulated with DSS alone exhibited normalization of expression with L-Arg supplementation. Additionally, L-Arg treatment of mice with DSS colitis resulted in increased ex vivo migration of colonic epithelial cells, suggestive of increased capacity for wound repair. Because CAT2 induction was sustained during L-Arg treatment and inducible nitric oxide (NO synthase (iNOS requires uptake of L-Arg for generation of NO, we tested the effect of L-Arg in iNOS(-/- mice and found that its benefits in DSS colitis were eliminated. These preclinical studies indicate that L-Arg supplementation could be a potential therapy for IBD, and that one mechanism of action may be functional enhancement of iNOS activity.

Biosynthesis of the Essential Fatty Acid Oxidation Cofactor Carnitine Is Stimulated in Heart and Liver after a Single Bout of Exercise in Mice

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Tom L. Broderick

2018-01-01

Full Text Available We determined whether one single bout of exercise stimulates carnitine biosynthesis and carnitine uptake in liver and heart. Free carnitine (FC in plasma was assayed using acetyltransferase and [14C]acetyl-CoA in Swiss Webster mice after 1 hour of moderate-intensity treadmill running or 4 hours and 8 hours into recovery. Liver and heart were removed under the same conditions for measurement of carnitine biosynthesis enzymes (liver butyrobetaine hydroxylase, γ-BBH; heart trimethyllysine dioxygenase, TMLD, organic cation transporter-2 (OCTN2, carnitine transporter, and liver peroxisome proliferator-activated receptor-alpha (PPARα, transcription factor for γ-BBH and OCTN2 synthesis. In exercised mice, FC levels in plasma decreased while heart and liver OCTN2 protein expressed increased, reflecting active uptake of FC. During recovery, the rise in FC to control levels was associated with increased liver γ-BBH expression. Protein expression of PPARα was stimulated in liver after exercise and during recovery. Interestingly, heart TMLD protein was also detected after exercise. Acute exercise stimulates carnitine uptake in liver and heart. The rapid return of FC levels in plasma after exercise indicates carnitine biosynthesis by liver is stimulated to establish carnitine homeostasis. Our results suggest that exercise may benefit patients with carnitine deficiency syndromes.

Feeding filaggrin: effects of L-histidine supplementation in atopic dermatitis

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Tan SP

2017-10-01

Full Text Available Siao Pei Tan,1,2 Simon B Brown,1,2 Christopher EM Griffiths,3 Richard B Weller,1,2 Neil K Gibbs3,4 1MRC Centre for Inflammation Research, 2Department of Dermatology, The University of Edinburgh, Edinburgh, 3Dermatology Centre, Division of Musculoskeletal and Dermatological Sciences, Salford Royal NHS Foundation Trust, University of Manchester, Manchester, 4Curapel, Life Sciences Hub Wales, Cardiff, UK Abstract: Atopic dermatitis (AD, also known as eczema, is one of the most common chronic skin conditions worldwide, affecting up to 16% of children and 10% of adults. It is incurable and has significant psychosocial and economic impacts on the affected individuals. AD etiology has been linked to deficiencies in the skin barrier protein, filaggrin. In mammalian skin, l-histidine is rapidly incorporated into filaggrin. Subsequent filaggrin proteolysis releases l-histidine as an important natural moisturizing factor (NMF. In vitro studies were conducted to investigate the influence of l-histidine on filaggrin processing and barrier function in human skin-equivalent models. Our further aim was to examine the effects of daily oral l-histidine supplementation on disease severity in adult AD patients. We conducted a randomized, double-blind, placebo-controlled, crossover, nutritional supplementation pilot study to explore the effects of oral l-histidine in adult AD patients (n=24. In vitro studies demonstrated that l-histidine significantly increased both filaggrin formation and skin barrier function (P<0.01, respectively. Data from the clinical study indicated that once daily oral l-histidine significantly reduced (P<0.003 AD disease severity by 34% (physician assessment using the SCORingAD tool and 39% (patient self-assessment using the Patient Oriented Eczema Measure tool after 4 weeks of treatment. No improvement was noted with the placebo (P>0.32. The clinical effect of oral l-histidine in AD was similar to that of mid-potency topical corticosteroids

Distinct effects of ketamine and acetyl l-carnitine on the dopamine system in zebrafish

Science.gov (United States)

Robinson, Bonnie L.; Dumas, Melanie; Cuevas, Elvis; Gu, Qiang; Paule, Merle G.; Ali, Syed F.; Kanungo, Jyotshna

2016-01-01

Ketamine, a noncompetitive N-methyl-d-aspartic acid (NMDA) receptor antagonist is commonly used as a pediatric anesthetic. We have previously shown that acetyl L-carnitine (ALCAR) prevents ketamine toxicity in zebrafish embryos. In mammals, ketamine is known to modulate the dopaminergic system. NMDA receptor antagonists are considered as promising anti-depressants, but the exact mechanism of their function is unclear. Here, we measured the levels of dopamine (DA) and its metabolites, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the zebrafish embryos exposed to ketamine in the presence and absence of 0.5 mM ALCAR. Ketamine, at lower doses (0.1–0.3 mM), did not produce significant changes in DA, DOPAC or HVA levels in 52 h post-fertilization embryos treated for 24 h. In these embryos, tyrosine hydroxylase (TH) mRNA expression remained unchanged. However, 2 mM ketamine (internal embryo exposure levels equivalent to human anesthetic plasma concentration) significantly reduced DA level and TH mRNA indicating that DA synthesis was adversely affected. In the presence or absence of 2 mM ketamine, ALCAR showed similar effects on DA level and TH mRNA, but increased DOPAC level compared to control. ALCAR reversed 2 mM ketamine-induced reduction in HVA levels. With ALCAR alone, the expression of genes encoding the DA metabolizing enzymes, MAO (monoamine oxidase) and catechol-O-methyltransferase (COMT), was not affected. However, ketamine altered MAO mRNA expression, except at the 0.1 mM dose. COMT transcripts were reduced in the 2 mM ketamine-treated group. These distinct effects of ketamine and ALCAR on the DA system may shed some light on the mechanism on how ketamine can work as an anti-depressant, especially at sub-anesthetic doses that do not affect DA metabolism and suppress MAO gene expression. PMID:26898327

Phytosterols, Lipid Administration, and Liver Disease During Parenteral Nutrition.

Science.gov (United States)

Zaloga, Gary P

2015-09-01

Phytosterols are plant-derived sterols that are structurally and functionally analogous to cholesterol in vertebrate animals. Phytosterols are found in many foods and are part of the normal human diet. However, absorption of phytosterols from the diet is minimal. Most lipid emulsions used for parenteral nutrition are based on vegetable oils. As a result, phytosterol administration occurs during intravenous administration of lipid. Levels of phytosterols in the blood and tissues may reach high levels during parenteral lipid administration and may be toxic to cells. Phytosterols are not fully metabolized by the human body and must be excreted through the hepatobiliary system. Accumulating scientific evidence suggests that administration of high doses of intravenous lipids that are high in phytosterols contributes to the development of parenteral nutrition-associated liver disease. In this review, mechanisms by which lipids and phytosterols may cause cholestasis are discussed. Human studies of the association of phytosterols with liver disease are reviewed. In addition, clinical studies of lipid/phytosterol reduction for reversing and/or preventing parenteral nutrition associated liver disease are discussed. © 2015 American Society for Parenteral and Enteral Nutrition.

Influence of preoperative peripheral parenteral nutrition with micronutrients after colorectal cancer patients.

Science.gov (United States)

Liu, Ming-Yi; Tang, Hsiu-Chih; Hu, Shu-Hui; Yang, Hui-Lan; Chang, Sue-Joan

2015-01-01

The inflammatory reactions are stronger after surgery of malnourished preoperative patients. Many studies have shown vitamin and trace element deficiencies appear to affect the functioning of immune cells. Enteral nutrition is often inadequate for malnourished patients. Therefore, total parenteral nutrition (TPN) is considered an effective method for providing preoperative nutritional support. TPN needs a central vein catheter, and there are more risks associated with TPN. However, peripheral parenteral nutrition (PPN) often does not provide enough energy or nutrients. This study investigated the inflammatory response and prognosis for patients receiving a modified form of PPN with added fat emulsion infusion, multiple vitamins (MTV), and trace elements (TE) to assess the feasibility of preoperative nutritional support. Methods. A cross-sectional design was used to compare the influence of PPN with or without adding MTV and TE on malnourished abdominal surgery patients. Both preoperative groups received equal calories and protein, but due to the lack of micronutrients, patients in preoperative Group B exhibited higher inflammation, lower serum albumin levels, and higher anastomotic leak rates and also required prolonged hospital stays. Malnourished patients who receive micronutrient supplementation preoperatively have lower postoperative inflammatory responses and better prognoses. PPN with added fat emulsion, MTV, and TE provides valid and effective preoperative nutritional support.

Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: metabolic inhibitors, MPTP, and methamphetamine.

Science.gov (United States)

Virmani, Ashraf; Gaetani, Franco; Binienda, Zbigniew

2005-08-01

A number of strategies using the nutritional approach are emerging for the protection of the brain from damage caused by metabolic toxins, age, or disease. Neural dysfunction and metabolic imbalances underlie many diseases, and the inclusion of metabolic modifiers may provide an alternative and early intervention approach that may prevent further damage. Various models have been developed to study the impact of metabolism on brain function. These have also proven useful in expanding our understanding of neurodegeneration processes. For example, the metabolic compromise induced by inhibitors such as 3-nitropropionic acid (3-NPA), rotenone, and 1-methyl-4-phenylpyridinium (MPP+) can cause neurodegeneration in animal models and these models are thought to simulate the processes that may lead to diseases such as Huntington's and Parkinson's diseases. These inhibitors of metabolism are thought to selectively kill neurons by inhibiting various mitochondrial enzymes. However, the eventual cell death is attributed to oxidative stress damage of selectively vulnerable cells, especially highly differentiated neurons. Various studies indicate that the neurotoxicity resulting from these types of metabolic compromise is related to mitochondrial dysfunction and may be ameliorated by metabolic modifiers such as L-carnitine (L-C), creatine, and coenzyme Q10, as well as by antioxidants such as lipoic acid, vitamin E, and resveratrol. Mitochondrial function and cellular metabolism are also affected by the dietary intake of essential polyunsaturated fatty acids (PUFAs), which may regulate membrane composition and influence cellular processes, especially the inflammatory pathways. Cellular metabolic function may also be ameliorated by caloric restriction diets. L-C is a naturally occurring quaternary ammonium compound that is a vital cofactor for the mitochondrial entry and oxidation of fatty acids. Any factors affecting L-C levels may also affect ATP levels. This endogenous compound

Pharmaceutical Point of View on Parenteral Nutrition

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M. Stawny

2013-01-01

Full Text Available Parenteral nutrition—a form of administering nutrients, electrolytes, trace elements, vitamins, and water—is a widely used mode of therapy applied in many diseases, in patients of different ages both at home and in hospital. The success of nutritional therapy depends chiefly on proper determination of the patient’s energetic and electrolytic needs as well as preparation and administration of a safe nutritional mixture. As a parenterally administered drug, it is expected to be microbiologically and physicochemically stable, with all of the components compatible with each other. It is very difficult to obtain a stable nutritional mixture due to the fact that it is a complex, two-phase drug. Also, the risk of incompatibility between mixture components and packaging should be taken into consideration and possibly eliminated. Since parenteral nutrition is a part of therapy, simultaneous use of drugs may cause pharmacokinetic and pharmacodynamic interactions as well as those with the pharmaceutical phase. The aim of this paper is to discuss such aspects of parenteral nutrition as mixture stability, methodology, and methods for determining the stability of nutritional mixtures and drugs added to them.

Pharmaceutical Point of View on Parenteral Nutrition

Science.gov (United States)

Stawny, M.; Olijarczyk, R.; Jaroszkiewicz, E.; Jelińska, A.

2013-01-01

Parenteral nutrition—a form of administering nutrients, electrolytes, trace elements, vitamins, and water—is a widely used mode of therapy applied in many diseases, in patients of different ages both at home and in hospital. The success of nutritional therapy depends chiefly on proper determination of the patient's energetic and electrolytic needs as well as preparation and administration of a safe nutritional mixture. As a parenterally administered drug, it is expected to be microbiologically and physicochemically stable, with all of the components compatible with each other. It is very difficult to obtain a stable nutritional mixture due to the fact that it is a complex, two-phase drug. Also, the risk of incompatibility between mixture components and packaging should be taken into consideration and possibly eliminated. Since parenteral nutrition is a part of therapy, simultaneous use of drugs may cause pharmacokinetic and pharmacodynamic interactions as well as those with the pharmaceutical phase. The aim of this paper is to discuss such aspects of parenteral nutrition as mixture stability, methodology, and methods for determining the stability of nutritional mixtures and drugs added to them. PMID:24453847

The effect of pumpkin (Cucurbita pepo L) seeds and L-arginine supplementation on serum lipid concentrations in atherogenic rats.

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Abuelgassim, Abuelgassim O; Al-showayman, Showayman I A

2012-01-01

The present study aimed to examine the effect of pumpkin (Cucurbita pepo L.) seeds supplementation on atherogenic diet-induced atherosclerosis. Rat were divided into two main groups , normal control and atherogenic control rats , each group composed of three subgroups one of them supplemented with 2% arginine in drinking water and the other supplemented with pumpkin seeds in diet at a concentration equivalent to 2% arginine. Supplementation continued for 37 days. Atherogenic rats supplemented with pumpkin seeds showed a significant decrease (ppumpkin seeds significantly decreased serum concentrations of TC and LDL-C. Our findings suggest that pumpkin seeds supplementation has a protective effect against atherogenic rats and this protective effect was not attributed to the high arginine concentrations in pumpkin seeds.

Calcium Chloride and Calcium Gluconate in Neonatal Parenteral Nutrition Solutions without Cysteine: Compatibility Studies Using Laser Light Obscuration Methodology

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Robert K. Huston

2018-02-01

Full Text Available There are no compatibility studies for neonatal parenteral nutrition solutions without cysteine containing calcium chloride or calcium gluconate using light obscuration as recommended by the United States Pharmacopeia (USP. The purpose of this study was to do compatibility testing for solutions containing calcium chloride and calcium gluconate without cysteine. Solutions of TrophAmine and Premasol (2.5% amino acids, containing calcium chloride or calcium gluconate were compounded without cysteine. Solutions were analyzed for particle counts using light obscuration. Maximum concentrations tested were 15 mmol/L of calcium and 12.5 mmol/L of phosphate. If the average particle count of three replicates exceeded USP guidelines, the solution was determined to be incompatible. This study found that 12.5 and 10 mmol/L of calcium and phosphate, respectively, are compatible in neonatal parenteral nutrition solutions compounded with 2.5% amino acids of either TrophAmine or Premasol. There did not appear to be significant differences in compatibility for solutions containing TrophAmine or Premasol when solutions were compounded with either CaCl2 or CaGlu-Pl. This study presents data in order to evaluate options for adding calcium and phosphate to neonatal parenteral nutrition solutions during shortages of calcium and cysteine.

Symptomatic acquired zinc deficiency in at-risk premature infants: high dose preventive supplementation is necessary.

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Barbarot, Sébastien; Chantier, Emilie; Kuster, Alice; Hello, Muriel; Roze, Jean-Christophe; Blouin, Eric; Stalder, Jean-François

2010-01-01

Zinc is a cofactor for several enzymes involved in many metabolisms. Zinc deficiency induces various disorders such as acrodermatitis enteropathica, either inherited or acquired. We report three cases of premature infants (24-31 wks gestational age) with low birthweight (650 to 940 g) and enteropathy, two of whom presented with necrotizing enterocolitis. All infants were fed by total parenteral nutrition. At a chronological age ranging from 73 to 80 days, all infants developed a periorificial dermatitis. Before the onset of the first signs, they had received zinc supplementation ranging from 146% to 195% of the recommended dose (400 microg/kg/day). Increased zinc supplementation over a course of 6-18 days induced a complete resolution of symptoms in all cases. No abnormality in the neurologic examination and no recurrence were observed at the end of the zinc treatment. Low birthweight premature infants with enteropathy on total parenteral nutrition are at risk of developing zinc deficiency. The usual recommended zinc supplementation is probably insufficient for those infants. A delay in the diagnosis of zinc deficiency may lead to severe complications.

Hypercalcemia and hypophosphatemia among preterm infants receiving aggressive parenteral nutrition.

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Brener Dik, Pablo H; Galletti, María F; Bacigalupo, Leticia T; Fernández Jonusas, Silvia; L Mariani, Gonzalo

2018-06-01

Aggressive parenteral nutrition is the standard of care among very-low-birth weight preterm infants. However, in recent studies, its impact on short-term outcomes, has been evaluated. The objective was to compare the prevalence of hypercalcemia and hypophosphatemia among preterm infants receiving aggressive or standard parenteral nutrition. Observational, retrospective study comparing a group of preterm infants weighing less than 1250 grams who received aggressive parenteral nutrition with a historical control group. The prevalence of hypercalcemia was estimated and its association with aggressive parenteral nutrition was searched adjusting by confounders. The mean phosphate level was estimated for the control group by linear regression and was compared to the value in the other group. Forty patients per group were included. The prevalence of hypercalcemia was higher in the group who received aggressive parenteral nutrition (87.5% versus 35%, p= 0.001). Aggressive parenteral nutrition was associated with hypercalcemia when adjusting by birth weight, intrauterine growth restriction, amino acid, and calorie intake (adjusted odds ratio: 21.8, 95% confidence interval [CI]: 3.7-128). The mean calcium level was different between both groups (p= 0.002). Infants who received aggressive parenteral nutrition had more sepsis without reaching statistical significance and the mean phosphate level was lower than that estimated for the control group (p= 0.04). The prevalence of hypophosphatemia in this group was 90% (95% CI: 76-97%). Our data show an association between hypercalcemia/hypophosphatemia and aggressive parenteral nutrition. It is recommended to frequently monitor calcium and phosphate levels since they might be associated with adverse clinical outcomes. Sociedad Argentina de Pediatría.

Parenteral nutrition in patients with inborn errors of metabolism - a therapeutic problem.

Science.gov (United States)

Kaluzny, L; Szczepanik, M; Siwinska-Mrozek, Z; Borkowska-Klos, M; Cichy, W; Walkowiak, J

2014-06-01

Parenteral nutrition is now a standard part of supportive treatment in pediatric departments. We describe four cases in which parenteral nutrition was extremely difficult due to coincidence with inborn errors of metabolism. The first two cases was fatty acid beta-oxidation disorders associated with necrotizing enterocolitis and congenital heart disease. Thus, limitations of intravenous lipid intake made it difficult to maintain a good nutritional status. The third case was phenylketonuria associated with a facial region tumour (rhabdomyosarcoma), in which parenteral nutrition was complicated because of a high phenylalanine content in the amino acid formulas for parenteral nutrition. The fourth patient was a child with late-diagnosed tyrosinemia type 1, complicated with encephalopathy - during intensive care treatment the patient needed nutritional support, including parenteral nutrition - we observed amino acid formula problems similar to those in the phenylketonuria patient. Parenteral nutrition in children with inborn errors of metabolism is a rare, but very important therapeutic problem. Total parenteral nutrition formulas are not prepared for this group of diseases.

l-glutamine and l-alanine supplementation increase glutamine-glutathione axis and muscle HSP-27 in rats trained using a progressive high-intensity resistance exercise.

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Leite, Jaqueline Santos Moreira; Raizel, Raquel; Hypólito, Thaís Menezes; Rosa, Thiago Dos Santos; Cruzat, Vinicius Fernandes; Tirapegui, Julio

2016-08-01

In this study we investigated the chronic effects of oral l-glutamine and l-alanine supplementation, either in their free or dipeptide form, on glutamine-glutathione (GLN-GSH) axis and cytoprotection mediated by HSP-27 in rats submitted to resistance exercise (RE). Forty Wistar rats were distributed into 5 groups: sedentary; trained (CTRL); and trained supplemented with l-alanyl-l-glutamine, l-glutamine and l-alanine in their free form (GLN+ALA), or free l-alanine (ALA). All trained animals were submitted to a 6-week ladder-climbing protocol. Supplementations were offered in a 4% drinking water solution for 21 days prior to euthanasia. Plasma glutamine, creatine kinase (CK), myoglobin (MYO), and erythrocyte concentration of reduced GSH and glutathione disulfide (GSSG) were measured. In tibialis anterior skeletal muscle, GLN-GSH axis, thiobarbituric acid reactive substances (TBARS), and the expression of heat shock factor 1 (HSF-1), 27-kDa heat shock protein (HSP-27), and glutamine synthetase were determined. In CRTL animals, high-intensity RE reduced muscle glutamine levels and increased GSSG/GSH rate and TBARS, as well as augmented plasma CK and MYO levels. Conversely, l-glutamine-supplemented animals showed an increase in plasma and muscle levels of glutamine, with a reduction in GSSG/GSH rate, TBARS, and CK. Free l-alanine administration increased plasma glutamine concentration and lowered muscle TBARS. HSF-1 and HSP-27 were high in all supplemented groups when compared with CTRL (p alanine, in both a free or dipeptide form, improve the GLN-GSH axis and promote cytoprotective effects in rats submitted to high-intensity RE training.

n-3 polyunsaturated fatty acids supplementation enhances hippocampal functionality in aged mice

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Debora eCutuli

2014-08-01

Full Text Available As major components of neuronal membranes, omega-3 polyunsaturated acids (n-3 PUFA exhibit a wide range of regulatory functions, modulating from synaptic plasticity to neuroinflammation, from oxidative stress to neuroprotection. Recent human and animal studies indicated the n-3 PUFA neuroprotective properties in aging, with a clear negative correlation between n-3 PUFA levels and hippocampal deficits. The present multidimensional study was aimed at associating cognition, hippocampal neurogenesis, volume, neurodegeneration and metabolic correlates to verify n-3 PUFA neuroprotective effects in aging. To this aim 19 month-old mice were given n-3 PUFA mixture, or olive oil or no dietary supplement for 8 weeks during which hippocampal-dependent mnesic functions were tested. At the end of behavioral testing morphological and metabolic correlates were analyzed. n-3 PUFA supplemented aged mice exhibited better object recognition memory, spatial and localizatory memory, and aversive response retention, without modifications in anxiety levels in comparison to controls. These improved hippocampal cognitive functions occurred in the context of an enhanced cellular plasticity and a reduced neurodegeneration. In fact, n-3 PUFA supplementation increased hippocampal neurogenesis and dendritic arborization of newborn neurons, volume, neuronal density and microglial cell number, while it decreased apoptosis, astrocytosis and lipofuscin accumulation in the hippocampus. The increased levels of some metabolic correlates (blood Acetyl-L-Carnitine and brain n-3 PUFA concentrations found in n-3 PUFA supplemented mice also pointed towards an effective neuroprotection.On the basis of the present results n-3 PUFA supplementation appears to be a useful tool in health promotion and cognitive decline prevention during aging.

Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition in 88 newborn infants

DEFF Research Database (Denmark)

Colding, H; Møller, S; Andersen, G E

1982-01-01

Ampicillin and gentamicin were dissolved once a day in an L-amino acid solution especially prepared for parenteral nutrition of newborn infants and infused continuously to 88 infants in whom septicaemia was suspected or had been proved. The mean dosages were 162 and 5.3 mg/kg per 24 hours...

Potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against tuberculosis: A systematic review

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Farzad Khademi

2018-02-01

Full Text Available Objective(s: Production of effective tuberculosis (TB vaccine is necessity. However, the development of new subunit vaccines is faced with concerns about their weak immunogenicity. To overcome such problems, polymers-based vaccine delivery systems have been proposed to be used via various routes. The purpose of this study was to determine the potential of polymeric particles as future vaccine delivery systems/adjuvants for parenteral and non-parenteral immunization against TB. Materials and Methods: PubMed, Scopus, Science-Direct, and the ISI web of knowledge databases were searched for related keywords. A total of 420 articles, written up to June 25, 2016, were collected on the potential of polymeric particles as TB vaccine delivery systems after parenteral and non-parenteral immunization. Thirty-one relevant articles were selected by applying inclusion and exclusion criteria. Results: It was shown that the immunogenicity of TB vaccines had been improved by using biodegradable and non-biodegradable synthetic polymers as well as natural polymers and they are better able to enhance the humoral and cellular immune responses, compared to TB vaccines alone. The present study revealed that various polymeric particles, after M. tuberculosis challenge in animal models, provide long-lasting protection against TB. PLGA (poly (lactide-co-glycolide and chitosan polymers were widely used as TB vaccine delivery systems/adjuvants. Conclusion: It seems that PLGA and chitosan polymers are well-suited particles for the parenteral and non-parenteral administration of TB vaccines, respectively. Non-biodegradable synthetic polymers in comparison with biodegradable synthetic and natural polymers have been used less frequently. Therefore, further study on this category of polymers is required.

Acetyl-L-carnitine (ALC) administration positively affects reproductive axis in hypogonadotropic women with functional hypothalamic amenorrhea.

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Genazzani, A D; Lanzoni, C; Ricchieri, F; Santagni, S; Rattighieri, E; Chierchia, E; Monteleone, P; Jasonni, V M

2011-04-01

Hypothalamic amenorrhea (HA) is characterized by neuroendocrine impairment that, in turn, negatively modulates endocrine function, mainly within the reproductive axis. HA presents with hypo-LH, hypoestrogenism and, until now, a definite therapeutic strategy has not yet been found. The aim of the following study was to test the efficacy of acetyl-L-carnitine (ALC) administration in HA-affected subjects. Twenty-four patients affected by stress-induced HA were divided into two groups according to LH plasma levels: group A, hypo-LH (LH≤3 mIU/ml; no.=16), and group B, normo-LH (LH>3 mIU/ml; no.=8), were treated with ALC (1 g/day, per os) for 16 weeks. Patients underwent baseline hormonal assessment, pulsatility test (for LH and FSH), naloxone test (for LH, FSH and cortisol) both before and after 16 weeks of treatment. Under ALC administration hypo-LH patients showed a significant increase in LH plasma levels (from 1.4±0.3 to 3.1±0.5 mIU/ml, p<0.01) and in LH pulse amplitude (p<0.001). No changes were observed in the normo-LH group. LH response to naloxone was restored under ALC therapy. Maximal LH response and area under the curve under naloxone were significantly increased (p<0.05 and p<0.01, respectively). No changes were observed in the normo-LH patients. Our data support the hypothesis of a specific role of ALC on counteracting the stress-induced abnormalities in hypo-LH patients affected by hypothalamic amenorrhea.

Glutamine Supplementation in Sick Children: Is It Beneficial?

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Elise Mok

2011-01-01

Full Text Available The purpose of this review is to provide a critical appraisal of the literature on Glutamine (Gln supplementation in various conditions or illnesses that affect children, from neonates to adolescents. First, a general overview of the proposed mechanisms for the beneficial effects of Gln is provided, and subsequently clinical studies are discussed. Despite safety, studies are conflicting, partly due to different effects of enteral and parenteral Gln supplementation. Further insufficient evidence is available on the benefits of Gln supplementation in pediatric patients. This includes premature infants, infants with gastrointestinal disease, children with Crohn's disease, short bowel syndrome, malnutrition/diarrhea, cancer, severe burns/trauma, Duchenne muscular dystrophy, sickle cell anemia, cystic fibrosis, and type 1 diabetes. Moreover, methodological issues have been noted in some studies. Further mechanistic data is needed along with large randomized controlled trials in select populations of sick children, who may eventually benefit from supplemental Gln.

L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m.

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Mansoor, Jim K; Morrissey, Brian M; Walby, William F; Yoneda, Ken Y; Juarez, Maya; Kajekar, Radhika; Severinghaus, John W; Eldridge, Marlowe W; Schelegle, Edward S

2005-01-01

We examined the effect of dietary supplementation with L-arginine on breath condensate VEGF, exhaled nitric oxide (NO), plasma erythropoietin, symptoms of acute mountain sickness, and respiratory related sensations at 4,342 m through the course of 24 h in seven healthy male subjects. Serum L-arginine levels increased in treated subjects at time 0, 8, and 24 h compared with placebo, indicating the effectiveness of our treatment. L-arginine had no significant effect on overall Lake Louise scores compared with placebo. However, there was a significant increase in headache within the L-arginine treatment group at 12 h compared with time 0, a change not seen in the placebo condition between these two time points. There was a trend (p = 0.087) toward greater exhaled NO and significant increases in breath condensate VEGF with L-arginine treatment, but no L-arginine effect on serum EPO. These results suggest that L-arginine supplementation increases HIF-1 stabilization in the lung, possibly through a NO-dependent pathway. In total, our observations indicate that L-arginine supplementation is not beneficial in the prophylactic treatment of AMS.

Acyl/free carnitine ratio is a risk factor for hepatic steatosis after pancreatoduodenectomy and total pancreatectomy.

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Nakamura, Masafumi; Nakata, Kohei; Matsumoto, Hideo; Ohtsuka, Takao; Yoshida, Koji; Tokunaga, Shoji; Hino, Keisuke

Hepatic steatosis, one of the most frequent long-term complications of pancreatectomy, influences not only hepatic function but also survival rate. However, its risk factors and pathogenesis have not been established. The purpose of this study was to clarify the risk factors for hepatic steatosis after pancreatectomy. In this retrospective study of 21 patients who had undergone pancreatectomy (19 cases of pancreatoduodenectomy and 2 cases of total pancreatectomy), serum carnitine concentrations, fractions of carnitine, and hepatic attenuation on computed tomography images were analyzed with the aim of identifying risk factors for hepatic steatosis. Thirteen (61.9%) of the 21 patients were diagnosed as having hypocarnitinemia after pancreatectomy. Average hepatic attenuation was as low as 42.2HU (±21.3 SD). A high ratio of acyl/free carnitine was associated with less pronounced hepatic attenuation according to both univariate (P pancreatectomy in some patients. The statistical analyses suggest that a high ratio of acyl/free carnitine is an independent risk factor for hepatic steatosis after pancreatectomy. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Hidrotórax secundário à nutrição parenteral: relato de caso Hydrothorax due to parenteral nutrition: a case report

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José Henrique Silvah

2011-09-01

Full Text Available Hidrotórax secundário à infusão de nutrição parenteral é uma condição rara, embora se apresente cada vez mais comum. Neste relato de caso, uma paciente com síndrome do intestino curto desenvolveu instabilidade hemodinâmica e insuficiência respiratória algumas horas após o início da infusão de nutrição parenteral. Ressaltamos também as manobras para evitar e tratar tal complicação.Hydrothorax due to parenteral nutrition infusion is a rare, although increasingly common event. This report shows a short bowel patient who developed hemodynamic instability and respiratory failure few hours after parenteral nutrition infusion's start. We also emphasize the maneuvers to avoid and treat such complication.

Use of parenteral testosterone in hypospadias cases

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Vikram Satav

2015-01-01

Full Text Available Objectives: The aim was to evaluate the effect of parenteral testosterone on penile length, preputial hood, vascularity of dartos pedicle in patients with hypospadias. Materials and Methods: A total of 42 patients with hypospadias were included in this study. Injection aquaviron (oily solution each ml containing testosterone propionate 25 mg was given deep intramuscularly in three doses with an interval of 3 weeks before reconstructive surgery at the dose of 2 mg/kg body weight. Preoperatively penile length, transverse preputial width and diameter at the base of the penis were measured. Basal testosterone levels were obtained before the institution of therapy and on the day of operation. Results: Following parenteral testosterone administration, the mean increase in penile length, transverse preputial width and diameter at the base of penis was 1.01 ± 0.25 cm (P < 0.001, 1.250 ± 0.52 cm and 0.61 ± 0.35 cm, respectively, (P < 0.001. Serum testosterone level after injection was well within normal range for that age. Conclusion: Parenteral testosterone increased phallus size, diameter and prepuce hypertrophy without any adverse effects. However, due to lack of a control group we cannot make any inferences. Controlled studies are required to establish the benefits of parenteral testosterone.

HDAC inhibitor L-carnitine and proteasome inhibitor bortezomib synergistically exert anti-tumor activity in vitro and in vivo.

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Hongbiao Huang

Full Text Available Combinations of proteasome inhibitors and histone deacetylases (HDAC inhibitors appear to be the most potent to produce synergistic cytotoxicity in preclinical trials. We have recently confirmed that L-carnitine (LC is an endogenous HDAC inhibitor. In the current study, the anti-tumor effect of LC plus proteasome inhibitor bortezomib (velcade, Vel was investigated both in cultured hepatoma cancer cells and in Balb/c mice bearing HepG2 tumor. Cell death and cell viability were assayed by flow cytometry and MTS, respectively. Gene, mRNA expression and protein levels were detected by gene microarray, quantitative real-time PCR and Western blot, respectively. The effect of Vel on the acetylation of histone H3 associated with the p21(cip1 gene promoter was examined by using ChIP assay and proteasome peptidase activity was detected by cell-based chymotrypsin-like (CT-like activity assay. Here we report that (i the combination of LC and Vel synergistically induces cytotoxicity in vitro; (ii the combination also synergistically inhibits tumor growth in vivo; (iii two major pathways are involved in the synergistical effects of the combinational treatment: increased p21(cip1 expression and histone acetylation in vitro and in vivo and enhanced Vel-induced proteasome inhibition by LC. The synergistic effect of LC and Vel in cancer therapy should have great potential in the future clinical trials.

Effects of DHA-enriched hen egg yolk and L-cysteine supplementation on quality of cryopreserved boar semen.

Science.gov (United States)

Chanapiwat, Panida; Kaeoket, Kampon; Tummaruk, Padet

2009-09-01

The objective of the present study was to determine the effects of docosahexaenoic acid (DHA)-enriched hen egg yolks and L-cysteine supplementation on the qualities of the cryopreserved boar semen. A total of 15 ejaculates from 5 Pietrain boars were divided into 4 groups according to the compositions of the freezing extenders used, that is, normal hen egg yolk (group I), DHA-enriched hen egg yolk (group II), normal hen egg yolk with 5 mmol L(-1) of cysteine supplementation (group III) and DHA-enriched hen egg yolk with 5 mmol L(-1) of cysteine supplementation (group IV). The semen was cryopreserved using controlled rate freezer and was thawed at 50 degrees C for 12 s. Progressive motility, sperm viability, acrosome integrity and functional integrity of sperm plasma membrane of the post-thawed semen were evaluated. The supplementation of L-cysteine in the freezing extender alone (group III) improved progressive motility (P semen qualities (P > 0.05). In conclusion, the supplementation of antioxidant L-cysteine alone or in combination with DHA-enriched hen egg yolk significantly improved the post-thawed semen qualities, especially progressive motility and acrosome integrity.

Orlistat interaction with sibutramine and carnitine. A physicochemical and theoretical study

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Nicolás-Vázquez, Inés; Hinojosa Torres, Jaime; Cruz Borbolla, Julián; Miranda Ruvalcaba, René; Aceves-Hernández, Juan Manuel

2014-03-01

Chemical degradation of orlistat, (ORT) after melting and reaction of decomposition byproducts with sibutramine, SIB was studied. Interactions between the active pharmaceutical ingredients by using thermal analysis, TA, methods and other experimental techniques such as PXRD, IR and UV-vis spectroscopies were carried out to investigate chemical reactions between components. It was found that orlistat melts with decomposition and byproducts quickly affect sibutramine molecule and then reacting also with carnitine, CRN when the three active pharmaceutical ingredients (API's) are mixed. However ORT byproducts do not react when ORT is mixed only with carnitine. It was found that compounds containing chlorine atoms react easily with orlistat when the temperature increases up to its melting point. Some reaction mechanisms of orlistat decomposition are proposed, the fragments in the mechanisms were found in the corresponding mass spectra. Results obtained indicate that special studies should be carried out in the formulation stage before the final composition of a poly-pill could be established. Similar results are commonly found for compounds very prone to react in presence of water, light and/or temperature. In order to explain the reactivity of orlistat with sibutramine and carnitine, theoretical calculations were carried out and the results are in agreement with the experimental results.

Parenteral nutrition in intestinal failure

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Kurkchubasche AG

2015-01-01

Full Text Available Arlet G Kurkchubasche,1 Thomas J Herron,2 Marion F Winkler31Department of Surgery and Pediatrics, 2Department of Surgery, Alpert Medical School of Brown University, 3Department of Surgery/Nutritional Support Service, Rhode Island Hospital, Providence, RI, USAAbstract: Intestinal failure is a consequence of extensive surgical resection resulting in anatomic loss and/or functional impairment in motility or absorptive capacity. The condition is clinically characterized by the inability to maintain fluid, energy, protein, electrolyte, or micronutrient balance when on a conventionally accepted, normal diet. Parenteral nutrition (PN is the cornerstone of management until intestinal adaptation returns the patient to a PN-independent state. Intestinal length, residual anatomic segments and motility determine the need for and duration of parenteral support. The goals of therapy are to provide sufficient nutrients to enable normal growth and development in children, and support a healthy functional status in adults. This review addresses indications for PN, the formulation of the PN solution, patient monitoring, and considerations for prevention of PN-associated complications. With the ultimate goal of achieving enteral autonomy, the important role of diet, pharmacologic interventions, and surgery is discussed.Keywords: intestinal failure, short-bowel syndrome, parenteral nutrition, home nutrition support, intestinal rehabilitation

Ovlivnění anticholinesterázové aktivity 7-methoxytacrinu a galantaminu L-karnitinem

OpenAIRE

Novotná, Petra

2012-01-01

Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of biological and medical sciences Candidate: Mgr. Petra Novotná Consultant: doc. MUDr. J. Herink, DrSc. Title of Thesis: The influencing of anticholinesterase activity of 7-methoxytacrine and galantamine by L-carnitine The aim of this work was to test the ability of L-carnitine (KAR) to increase the permeation of indirect parasympatomimetic 7-methoxytacrine (MEOTA) and galantamine (GAL) through the blood-brain barr...

Total parenteral nutrition in diabetic rats

International Nuclear Information System (INIS)

Norcross, E.D.; Stein, T.P.

1986-01-01

Parenteral Nutrition with hypertonic glucose is frequently given to diabetic patients. Large amounts of insulin can be required. The purpose of this investigation was to develop a totally parenterally nourished diabetic rat model. 200 g Female Sprague Dawley rats were made diabetic by i.v. injection of streptozotocin (50 mg/kg). Rats were then allowed to recover for at least 1 week before undergoing surgical insertion of a central venous catheter for parenteral feeding. TPN was begun 3 days after surgery. Prior to this they were allowed unlimited access to food and water. Control (non-streptozotocin treated) rats were run at the same time. Protein turnover was investigated by using 15 N glycine. Preliminary results: diabetic rats given mostly fat as a calorie source survived well in the absence of exogenous insulin whereas those that were given glucose only as their non-protein calorie source showed poor survival even with exogenous insulin. N balance and protein turnover in the lipid treated diabetic rats were comparable to the non-diabetic control rats

Plasma fatty acyl-carnitines during 8 Weeks of overfeeding: relation to diet energy expenditure and body composition: the PROOF study.

Science.gov (United States)

Bray, George A; Redman, Leanne M; de Jonge, Lilian; Rood, Jennifer; Sutton, Elizabeth F; Smith, Steven R

2018-01-24

Overfeeding is a strategy for evaluating the effects of excess energy intake. In this secondary analysis we tested the possibility that different levels of dietary protein might differentially modify the response of fatty acyl-carnitines to overfeeding. Twenty-three healthy adult men and women were overfed by 40% for 8 weeks while in-patients with diets containing 5% (LPD), 15% (NPD) or 25% (HPD) protein. Plasma fatty acyl-carnitines were measured by gas chromatography/mass spectrometry (GC/MS) at baseline and after 8 weeks of overfeeding. Measurements included: body composition by DXA, energy expenditure by ventilated hood and doubly-labeled water, fat cell size from subcutaneous fat biopsies, and fat distribution by CT scan. Analysis was done on 5 groups of fatty acyl-carnitines identified by principal components analysis and 6 individual short-chain fatty acyl carnitines. Higher protein intake was associated with significantly lower 8 week levels of medium chain fatty acids and C2, C4-OH and C 6:1, but higher values of C3 and C5:1 acyl-carnitines derived from essential amino acids. In contrast energy and fat intake were only weakly related to changes in fatty acyl-carnitines. A decease or smaller rise in 8 week medium chain acyl-carnitines was associated with an increase in sleeping energy expenditure (P = 0.0004), and fat free mass (P < 0.0001) and a decrease in free fatty acid concentrations (FFA) (P = 0.0067). In contrast changes in short-chain fatty acyl-carnitines were related to changes in resting energy expenditure (P = 0.0026), and fat free mass (P = 0.0007), and C4-OH was positively related to FFA (P = 0006). Protein intake was the major factor influencing changes in fatty acyl carnitines during overfeeding with higher values of most acyl-fatty acids on the low protein diet. The association of dietary protein and fat intake may explain the changes in energy expenditure and metabolic variables resulting in the observed

Protective role of carnitine synergized with vitamin E against ...

African Journals Online (AJOL)

Group III: Rats were injected with vitamin E (100 IU/kg bw, i.p) daily. Group IV: Rats were given carnitine (20 mg/kg bw, i.p) daily .Group V: Rats were injected with ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT · DOWNLOAD FULL TEXT ...

Standardized Parenteral Nutrition for the Transition Phase in Preterm Infants: A Bag That Fits.

LENUS (Irish Health Repository)

Brennan, Ann-Marie

2018-02-02

The optimal composition of standardized parenteral nutrition (SPN) is not yet known, contributing to nutrient deficit accrual and growth failure, with the period of parenteral nutrition weaning, i.e., transition (TN) phase, being identified as particularly vulnerable. We created a comprehensive nutrition database, representative of the nutritional course of a diverse range of preterm infants (n = 59, birth weight ≤ 1500 g, gestation < 34 weeks) by collecting hourly macronutrient intake data as part of a prospective, observational study over 19 months. Using a nutrient modeling technique for the TN phase, various amino acid (AA) concentrations of SPN were tested within the database, whilst acknowledging the nutritional contribution from enteral feeds until target AA intakes were consistently achieved. From the modeling, the AA composition of SPN was determined at 3.5 g\\/100 mL, which was the maximum to avoid exceeding target intakes at any point in the TN phase. However, in order to consistently achieve target AA intakes, additional nutritional strategies were required, which included increasing the exclusion of enteral feeds in fluid and nutrient calculations from <20 mL\\/kg\\/day to <40 mL\\/kg\\/day, and earlier fortification of breastmilk at 80 mL\\/kg\\/day. This data-driven nutrient modeling process supported the development of an improved SPN regimen for our preterm population in the TN phase.

Standardized Parenteral Nutrition for the Transition Phase in Preterm Infants: A Bag That Fits

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Ann-Marie Brennan

2018-02-01

Full Text Available The optimal composition of standardized parenteral nutrition (SPN is not yet known, contributing to nutrient deficit accrual and growth failure, with the period of parenteral nutrition weaning, i.e., transition (TN phase, being identified as particularly vulnerable. We created a comprehensive nutrition database, representative of the nutritional course of a diverse range of preterm infants (n = 59, birth weight ≤ 1500 g, gestation < 34 weeks by collecting hourly macronutrient intake data as part of a prospective, observational study over 19 months. Using a nutrient modeling technique for the TN phase, various amino acid (AA concentrations of SPN were tested within the database, whilst acknowledging the nutritional contribution from enteral feeds until target AA intakes were consistently achieved. From the modeling, the AA composition of SPN was determined at 3.5 g/100 mL, which was the maximum to avoid exceeding target intakes at any point in the TN phase. However, in order to consistently achieve target AA intakes, additional nutritional strategies were required, which included increasing the exclusion of enteral feeds in fluid and nutrient calculations from <20 mL/kg/day to <40 mL/kg/day, and earlier fortification of breastmilk at 80 mL/kg/day. This data-driven nutrient modeling process supported the development of an improved SPN regimen for our preterm population in the TN phase.

Results of home parenteral nutrition in patients with severe inflammatory bowel disease - an alternative for surgery of malnourished patients.

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Turkot, Maryla; Sobocki, Jacek

2017-10-31

In the world, the inflammatory bowel disease affects an increasing number of younger and younger patients, and in some of them parenteral nutrition is an alternative to high-risk surgical intervention due to advancement of the disease and malnutrition. The aim of the study was to assess the results of home parenteral nutrition in patients with severe bowel inflammatory disease, in whom surgical treatment is associated with high risk of complications. A retrospective analysis was conducted on 46 patients, who received home parenteral nutrition instead of another surgical intervention. The inclusion criteria included home parenteral nutrition and diagnosis of Crohn's disease or ulcerative colitis. Mean number of complications requiring hospital admission per patient was 1.76, the BMI increased by 4.3 on average [kg/m2]. During parenteral nutrition, the percentage of patients, in whom anti-inflammatory or immunosuppressant drugs were completely discontinued, was 17.4%. In the whole group, at least one immunosuppressive drug was discontinued in onefifth of patients. Mean albumin level increased by 2.4 g/L, lymphocyte count dropped by 474 lymphocytes/mm3, and leukocyte count increased by 747.6/mm3. The patients described their condition as good in 87%, and 7.4% of patients were able to work. Home parenteral nutrition positively affects patient's general condition by increasing BMI and normalizing biochemical test results. The results indicate the need to consider this method as an alternative to surgical intervention in severe bowel inflammatory disease with high perioperative risk, which could reduce the complication rate.

EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA); Scientific Opinion on the substantiation of health claims related to L-carnitine and faster recovery from muscle fatigue after exercise (ID 738, 1492, 1493), skeletal muscle tissue repair (ID 738, 1492, 1493), increase in endurance

DEFF Research Database (Denmark)

Tetens, Inge

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006. This opinion addresses the scientific substantiation of health...... claims in relation to L-carnitine and faster recovery from muscle fatigue after exercise, skeletal muscle tissue repair, increase in endurance capacity, maintenance of normal blood LDL-cholesterol concentrations, contribution to normal spermatogenesis, “energy metabolism”, and increasing L...

Parenteral nutrition in radiation injuries

International Nuclear Information System (INIS)

Glants, R.M.

1985-01-01

Basing on the results of experiments on mice and rats and their clinical use in oncological patients treatment recommendations are given on use of parenteral nutrition in treatment of radiation disease

Parenteral nutrition in the elderly cancer patient.

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Orrevall, Ylva

2015-04-01

Parenteral nutrition may be considered when oral intake and/or enteral nutrition are not sufficient to maintain nutritional status and the patient is likely to die sooner from starvation than from the cancer. A detailed assessment should be made prior to the decision about whether parenteral nutrition should be started. A follow up plan should be documented with objective and patient centred treatment goals as well as specific time points for evaluation. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of L-arginine supplementation on immune responsiveness in patients with sickle cell disease.

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Scavella, Arnette; Leiva, Lily; Monjure, Hanh; Zea, Arnold H; Gardner, Renee V

2010-08-01

L-arginine (L-Arg) is deficient in sickle cell disease (SSD) during vasoocclusion. We investigated possible causal relationship between L-Arg deficiency and immune dysfunction in SSD in steady-state. Fifteen patients with SSD in steady-state and 13 controls were studied. Plasma L-Arg levels were measured using liquid chromatography. T cell subsets and CD3zeta (CD3zeta) chain expression were analyzed using flow cytometry. Lymphocyte proliferative response to phytohemagglutinin (PHA) and production of IL-6 and interferon-gamma (IFN-gamma) were evaluated with and without L-Arg. SSD patients had significantly lower L-Arg levels than controls. CD3 and CD19 cell populations were comparable for both groups, but SSD patients had above normal numbers of natural killer cells (P = 0.06). Patients and controls exhibited significantly increased lymphocyte blastogenesis to PHA after introduction of L-Arg to cultures; response of patients was significantly greater than values for control individuals. Proliferative response to candida in SSD patients was significantly lower than in controls; L-Arg supplementation did not increase this response. L-Arg had no effect on blastogenic response to PPD and candida albicans. No effect was likewise seen in production of IL-6 and IFN-gamma after addition of L-Arg. CD3zeta chain expression increased after addition of L-Arg in both groups; differences were insignificant. L-Arg levels in steady-state SSD are significantly lower than in controls. L-Arg supplementation enhanced lymphocyte blastogenesis to PHA for both controls and patients, but not in response to antigen. There were no significant differences in CD3zeta chain expression although upregulation of expression occurred after L-Arg supplementation for both groups. (c) 2010 Wiley-Liss, Inc.

L-Carnitine halts apoptosis and myelosuppression induced by carboplatin in rat bone marrow cell cultures (BMC).

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Abd-Allah, Adel R A; Al-Majed, Abdulhakeem A; Al-Yahya, Abdulaziz A; Fouda, Soliman I; Al-Shabana, Othman A

2005-07-01

Carboplatin (CP), a second generation platinum compound, is effective against various types of cancers, producing less nephrotoxicity and ototoxicity but more myelotoxicity than cisplatinum. CP-myelosuppression is the rate-limiting step of its clinical use. Prevention of CP-myelosuppression is a major target in the field of chemotherapy. Therefore, the present study investigates the use of L-carnitine (LCR)-an antioxidant, cardioprotective, neuroprotective, and immunostimulant nontoxic natural compound-to protect against CP-induced myelosuppression. The viability of BMC was studied using a trypan blue exclusion technique following incubation with CP and/or LCR as a function of time and concentration. Apoptosis was tested for by detecting the amount of DNA fragmentation and the visualization of DNA ladders upon gel electrophoresis. Bone marrow progenitor cell function was examined by colony forming unit assay. Cellular contents of glutathione (GSH) and malondialdehyde (MDA) were also estimated. Results revealed that LC50 of CP is 4.7 mM and the highest safe concentration of LCR is 5 mM. Co-exposure of LCR+CP rescued BMC viability by 37% compared to the CP-treated cultures. The LCR halts CP-induced apoptosis and it significantly improves the function of the bone marrow progenitors by increasing the number of colony-forming units as a response to granulocyte/macrophage colony stimulating factors. Finally, LCR restores CP-induced GSH depletion and prevents MDA elevation in BMC. In summary, the results suggest that LCR is able to protect against CP-induced myelosuppression, which suggests its use as an adjuvant therapy. This finding merits further investigation into the mechanism(s) of such protection as well as its interaction with CP antitumor activity.

Oxidative stress in erythrocytes: a study on the effect of antioxidant mixtures during intermittent exposures to high altitude

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Vani, R.; Shiva Shankar Reddy, C. S.; Asha Devi, S.

2010-09-01

The aim of our study was to compare and assess the effectiveness of antioxidant mixtures on the erythrocytes (RBC) of adult male albino rats (Wister) subjected to simulated intermittent high altitudes—5,100 m (AL1) and 6,700 m (AL2)—to induce oxidative stress (OS). To achieve our objective, we pre-supplemented four sets of animals with different antioxidant mixtures [vitamin E (vit.E; 50 IU/kg BW), vitamin C (vit.C; 400 mg/kg) and l-carnitine (400 mg/kg)] in different combinations [M1 (vit.E+vit.C), M2 (vit.C+carnitine), M3 (vit.E+carnitine) and M4 (vit.C+vit.E+carnitine)] for 30 days prior to as well during exposure to intermittent hypobaric hypoxia (IHH). Membrane instability, in terms of osmotic fragility and hemolysis, decreased in RBCs of supplemented animals. There was a significant increase in the activity of glutathione peroxidase in the RBCs of supplemented animals. We confirmed OS imposed by IHH with assays relating to lipid [thiobarbituric acid reactive substances (TBARS) and lipofuscin (LF)] and protein (carbonyl, PrC) oxidation, and found a positive correlation between PrC and hemolysis, with a decrease in both upon supplementation with M3 and M4 mixtures. Fluorescence microscopic observation showed a maximum decrease in the LF content in rats administered M4 and M1 compared to those on M2 and M3 mixtures at both altitudes. We suggest that multiple antioxidant fortifications are effective in overcoming increased OS experienced by RBCs at high altitudes.

l-Leucine Supplementation Worsens the Adiposity of Already Obese Rats by Promoting a Hypothalamic Pattern of Gene Expression that Favors Fat Accumulation

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Thais T. Zampieri

2014-04-01

Full Text Available Several studies showed that l-leucine supplementation reduces adiposity when provided before the onset of obesity. We studied rats that were exposed to a high-fat diet (HFD for 10 weeks before they started to receive l-leucine supplementation. Fat mass was increased in l-leucine-supplemented rats consuming the HFD. Accordingly, l-leucine produced a hypothalamic pattern of gene expression that favors fat accumulation. In conclusion, l-leucine supplementation worsened the adiposity of rats previously exposed to HFD possibly by central mechanisms.

Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis.

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Liu, Xiaoqian; Machado, Gustavo C; Eyles, Jillian P; Ravi, Varshini; Hunter, David J

2018-02-01

To investigate the efficacy and safety of dietary supplements for patients with osteoarthritis. An intervention systematic review with random effects meta-analysis and meta-regression. MEDLINE, EMBASE, Cochrane Register of Controlled Trials, Allied and Complementary Medicine and Cumulative Index to Nursing and Allied Health Literature were searched from inception to April 2017. Randomised controlled trials comparing oral supplements with placebo for hand, hip or knee osteoarthritis. Of 20 supplements investigated in 69 eligible studies, 7 (collagen hydrolysate, passion fruit peel extract, Curcuma longa extract, Boswellia serrata extract, curcumin, pycnogenol and L-carnitine) demonstrated large (effect size >0.80) and clinically important effects for pain reduction at short term. Another six (undenatured type II collagen, avocado soybean unsaponifiables, methylsulfonylmethane, diacerein, glucosamine and chondroitin) revealed statistically significant improvements on pain, but were of unclear clinical importance. Only green-lipped mussel extract and undenatured type II collagen had clinically important effects on pain at medium term. No supplements were identified with clinically important effects on pain reduction at long term. Similar results were found for physical function. Chondroitin demonstrated statistically significant, but not clinically important structural improvement (effect size -0.30, -0.42 to -0.17). There were no differences between supplements and placebo for safety outcomes, except for diacerein. The Grading of Recommendations Assessment, Development and Evaluation suggested a wide range of quality evidence from very low to high. The overall analysis including all trials showed that supplements provided moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip or knee osteoarthritis at short term, although the quality of evidence was very low. Some supplements with a limited number of studies and

Tratamento da endometrite puerperal com antibioticoterapia parenteral exclusiva Treatment of puerperal endometritis using a regimen with exclusive parenteral antibiotics

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Geraldo Duarte

2005-08-01

Full Text Available OBJETIVO: analisar a efetividade e segurança da antibioticoterapia parenteral hospitalar exclusiva para tratamento da endometrite puerperal, em população de baixo nível socioeconômico. MÉTODOS: estudo clínico prospectivo, que avaliou 21 puérperas com diagnóstico de endometrite puerperal, cujas gestações foram resolvidas em hospital universitário por cesárea (52,4% ou parto normal (47,6. A amostra caracterizou-se por baixo nível socioeconômico e de escolaridade. Foram submetidas ao regime de antibioticoterapia parenteral exclusiva, apenas durante o período de internação (grupo ATP-EX. Os resultados foram comparados com aqueles obtidos de série histórica do mesmo serviço (20 casos submetidas a antibioticoterapia parenteral hospitalar, complementada por terapia via oral ambulatorial (grupo ATP+VO. As pacientes foram avaliadas clinicamente em retornos periódicos visando identificar casos de recidivas e complicações infecciosas. RESULTADOS: uma paciente do grupo ATP+VO necessitou de reinternação no 6º dia após a alta por recrudescência da endometrite. Não foi observada nenhuma complicação entre as pacientes do grupo ATP-EX. CONCLUSÃO: para o tratamento de endometrite puerperal, não foi observado benefício adicional com a adição da antibioticoterapia oral complementar após a alta. Os resultados com o uso da antibioticoterapia parenteral exclusiva durante a internação indicam que esse esquema pode ser utilizado com segurança em população de baixo nível socioeconômico.PURPOSE: to analyze the effectiveness and safety of exclusive hospital parenteral antibiotic therapy to treat puerperal endometritis in a population of low socioeconomic level. METHODS: a prospective clinical trial evaluated 21 puerperae with a diagnosis of postpartum endometritis, whose deliveries occurred at a university hospital by cesarean section (52.4% or normal delivery (47.6%. The sample was characterized by low socioeconomic and

Dietary supplementation of tiger nut alters biochemical parameters relevant to erectile function in l-NAME treated rats.

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Olabiyi, Ayodeji A; Carvalho, Fabiano B; Bottari, Nathieli B; Lopes, Thauan F; da Costa, Pauline; Stefanelo, Naiara; Morsch, Vera M; Akindahunsi, Afolabi A; Oboh, Ganiyu; Schetinger, Maria Rosa

2018-07-01

Tiger nut tubers have been reportedly used for the treatment of erectile dysfunction (ED) in folk medicine without scientific basis. Hence, this study evaluated the effect of tiger nut on erectile dysfunction by assessing biochemical parameters relevant to ED in male rats by nitric oxide synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME) treatment. Rats were divided into five groups (n = 10) each: Control group; l-NAME plus basal diet; l-NAME plus Sildenafil citrate; diet supplemented processed tiger nut (20%) plus l-NAME;diet supplemented raw tiger nut (20%) plus l-NAME. l-NAME pre-treatment (40 mg/kg/day) lasted for 14 days. Arginase, acetycholinesterase (AChE) and adenosine deaminase (ADA) activities as well as nitric oxide levels (NO) in serum, brain and penile tissue were measured. l-NAME increased the activity of arginase, AChE and ADA and reduced NO levels. However, dietary supplementation with tiger nut caused a reduction on the activities of the above enzymes and up regulated nitric oxide levels when compared to the control group. The effect of tiger nut supplemented diet may be said to prevent alterations of the activities of the enzymes relevant in erectile function. Quercetin was revealed to be the most active component of tiger nut tuber by HPLC finger printing. Copyright © 2018. Published by Elsevier Ltd.