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

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

Mitochondrial carnitine palmitoyltransferase-Ⅱ dysfunction: A possible novel mechanism for nonalcoholic fatty liver disease in hepatocarcinogenesis

Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world.The complex mechanisms of NAFLD formation are still under identification.Carnitine palmitoyltransferase-Ⅱ(CPT-Ⅱ)on inner mitochondrial membrane(IMM)regulates long chain fatty acidβ-oxidation,and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD.The sequences of its peptide chain and DNA nucleotides have been identified,and the catalytic activity of CPT-Ⅱ is affected on its gene mutations,deficiency,enzymatic thermal instability,circulating carnitine level and so on.Recently,the CPT-Ⅱ dysfunction has been discovered in models of liver lipid accumulation.Meanwhile,the malignant transformation of hepatocyte-related CD44^(+) stem T cell activation,high levels of tumor-related biomarkers(AFP,GPC3)and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology.This review focuses on some of the progress of CPT-Ⅱ inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis.

L-Carnitine拮抗培养心肌细胞缺氧/复氧损伤

目的 探讨L Carnitine对心肌细胞缺氧 /复氧损伤的防护作用及其可能的机制。方法 以原代培养新生鼠心肌细胞建立缺氧 /复氧损伤模型 ,观察不同剂量L Carnitine处理后细胞增殖活性、凋亡细胞百分率及DNA断片化率 ,作为反映L Carnitine对心肌细胞缺氧 /复氧损伤防护作用及其机制的指标。结果 在 5～ 5 0 0 0nmol/L范围内 ,L Carnitine预处理对培养心肌细胞缺氧 /复氧损伤均显示保护效应 ;在 5、5 0及 5 0 0nmol/L时均显著降低DNA断片化率 ;L Carnitine在 5 0nmol/L时与单纯缺氧 /复氧组比较可显著降低凋亡细胞百分率。结论 缺氧 /复氧对心肌细胞的影响之一是可诱导心肌细胞凋亡 ;L Carnitine对培养心肌细胞培养缺氧/复氧损伤具有防护作用 ,其机制可能与抑制缺氧 /复氧诱导细胞凋亡有关。

缺氧复氧对培养仔鼠心肌细胞NRF1和mtTFA表达的影响与L-carnitine保护作用

目的 探讨培养仔鼠心肌细胞缺氧复氧能量代谢损伤的机制及L 肉毒碱 (L carnitine )的保护作用。方法 以原代培养仔鼠心肌细胞建立缺氧复氧损伤模型 ,应用高效液相色谱检测心肌细胞内ATP、ADP、AMP含量 ;应用RT PCR方法检测心肌细胞核呼吸因子 (Nuclearrespiratoryfactor1 ,NRF1 )和线粒体转录因子A(MitochondrialtranscriptionfactorA ,mtTFA)mRNA表达。结果 与正常对照组比较 ,培养的心肌细胞缺氧 2 4h复氧 0、2、4、8h ,心肌细胞ATP、ADP含量均明显下降。与单纯缺氧复氧组比较 ,L carnitine预处理组心肌细胞缺氧复氧后ATP含量明显提升 ;培养的心肌细胞缺氧 2 4h ,NRF1和mtTFAmRNA明显降低 ,复氧 2、4、8h进一步降低。L carnitine预处理使缺氧 2 4h复氧 4h的心肌细胞NRF1和mtTFAmRNA表达分别提升 1 5 %和 2 0 %。结论 心肌细胞缺氧复氧过程中能量代谢明显降低 ,其损伤可能与NRF1和mtTFAmRNA表达下调有关 ;L carnitine对培养仔鼠心肌细胞缺氧复氧能量代谢损伤具有保护作用 ,其机制可能是L carnitine从转录调控水平改善了缺氧复氧过程中心肌细胞的能量代谢。

L-carnitine对缺氧/复氧新生大鼠心肌细胞能量生成及CPT-Ⅱ mRNA表达的影响

目的 探讨L 肉毒碱 (L carnitine ,L Car)对缺氧 复氧培养新生大鼠心肌细胞能量生成的影响及其机制。方法 以原代培养新生大鼠心肌细胞建立缺氧 复氧损伤模型 ,高效液相色谱检测单纯缺氧 复氧以及L Car预处理缺氧 复氧心肌细胞ATP、ADP、AMP生成改变 ;RT PCR方法检测心肌细胞肉毒碱脂酰基转移酶 Ⅱ (carnitinepalmitoyltransferase Ⅱ ,CPT Ⅱ )mRNA表达。结果 与正常对照组比较 ,培养心肌细胞缺氧 2 4h复氧 0、2、4、8h后 ,心肌细胞ATP、ADP均明显下降。与单纯缺氧 复氧组比较 ,L Car预处理组心肌细胞缺氧 复氧后ATP含量明显增高 ;培养心肌细胞缺氧 2 4h后 ,CPT ⅡmRNA表达除复氧 2h有所上升外 ,复氧 4、8h表达渐次降低。L Car预处理使缺氧 2 4h复氧 4h心肌细胞CPT ⅡmRNA表达呈浓度依赖性增高 ,5 0nmol L处理组CPT ⅡmRNA表达显著高于 0nmol L处理组。结论 心肌细胞缺氧 复氧过程中能量生成明显降低 ,其损伤可能与三羧酸循环中呼吸酶CPT Ⅱ表达降低有关 ;L Car对培养仔鼠心肌细胞缺氧复氧损伤具有显著保护作用 ,其机制可能是与L Car从转录调控水平改善CPT Ⅱ合成有关。

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

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

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

Autism and carnitine: A possible link

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

Enantiomeric Resolution on L-Carnitine Selective Polymers Prepared by Molecular Imprinting

L-carnitine selective polymers were prepared by molecular imprinting using methacrylic acid as the functional monomer. The acid function of the monomer is expected to form hydrogen bond and ionic interactions with the amine function of the target molecule L-carnitine. The imprinted polymers were used as stationary phases in high-performance liquid chromatography (HPLC). It was shown that L-carnitine imprinted polymer exhibited a higher affinity to its template molecule, while the non-imprinted polymer had no affinity to the compounds tested. Racemic carnitine hydrochloride was efficiently resolved on the L-carnitine imprinted polymer, and the separation factor is 1.9.

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

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

Effects of L-carnitine in patients with hepatic encephalopathy

AIM: To evaluate the influence of L-carnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy (HE).METHODS: One hundred and fifty patients (10 patients with alcoholism, 41 patients with hepatitis virus B infection, 78 patients with hepatitis C virus infection,21 patients with cryptogenetic cirrhosis) meeting the inclusion criteria were randomized into group A receiving a 90-d treatment with L-carnitine (2 g twice a day) or into group B receiving placebo in double blind.RESULTS: At the end of the study period, a significant decrease in NH4 fasting serum levels was found in patients with hepatic encephalopathy (P＜0.05) afler the treatment with levocarnitine (LC). Significant differences were also found between symbol digit modalities test and block design in patients with hepatic encephalopathy (P＜0.05).CONCLUSION: Results of our study suggest an important protective effect of L-carnitine against ammonia-precipitated encephalopathy in cirrhotic patients.

Diabetic Cardiovascular Risk and Carnitine Deficiency <br/>—Carnitine Deficiency in Clinical Diabetes Mellitus

Background: Type 1 diabetes mellitus increases the risk of coronary heart disease. The Pittsburgh IDDM morbidity and mortality study reported greater than 10 fold coronary heart disease mortality compared with US national data?[1]. Adults with diabetes have heart disease death rates 2 to 4 times higher than adults without diabetes [2]. Diabetic cardiomyopathy explains much of this survival difference and carnitine deficiency is a cause of cardiomyopathy. Research Design and Methods: Adult subjects (40) with type 1 diabetes mellitus were seen for a routine annual visit having no clinical complaints. Fasting serum samples were collected for annual chemistries and the measurement of carnitine. Results: The mean total (40.8 ± 8.8) [40 - 80 nmol/ml] and free (32.9 ± 7.9) [30 - 60 nmol/ml] carnitine levels for this group included 43% low total and 28% low free carnitine. The mean esterified/free (E/F) carnitine ratio (0.25 ± 0.09) for this group was elevated indicating carnitine insufficiency. Conclusions: Fatty acids are the primary energy source for diabetic heart muscle, and carnitine is essential for intracellular fatty acid transport and ATP production. Therefore, mild carnitine deficiency can compromise fatty acid energy production in a failing heart. Carnitine deficiency in subjects at high risk for cardiovascular failure is a possible unrecognized reason for the 4 fold increased death rate in patients with type 1 diabetes. Supplementation with oral carnitine could reduce that increased risk of heart failure, in patients with type 1 diabetes. Intravenous carnitine may be life saving when managing acute cardiac failure in patients with diabetes mellitus. Normal carnitine levels in patients with type 1 diabetes may provide a biochemical environment that prevents the long recognized idiopathic heart failure that occurs in insulin requiring diabetics as first reported in the 1974 Framingham Study.

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

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

L-carnitine protects C2C12 cells against mitochondrial superoxide overproduction and cell death

AIM To identify and characterize the protective effect that L-carnitine exerted against an oxidative stress in C2C12 cells.METHODS Myoblastic C2C12 cells were treated with menadione, a vitamin K analog that engenders oxidative stress, and the protective effect of L-carnitine(a nutrient involved in fatty acid metabolism and the control of the oxidative process), was assessed by monitoring various parameters related to the oxidative stress, autophagy and cell death. RESULTS Associated with its physiological function, a muscle cell metabolism is highly dependent on oxygen and may produce reactive oxygen species(ROS), especially under pathological conditions. High levels of ROS are known to induce injuries in cell structure as they interact at many levels in cell function. In C2C12 cells, a treatment with menadione induced a loss of transmembrane mitochondrial potential, an increase in mitochondrial production of ROS; it also induces autophagy and was able to provoke cell death. Pre-treatment of the cells with L-carnitine reduced ROS production, diminished autophagy and protected C2C12 cells against menadione-induced deleterious effects. CONCLUSION In conclusion, L-carnitine limits the oxidative stress in these cells and prevents cell death.

L-carnitine supplementation improves hematological pattern in patients affected by HCV treated with Peg interferon-α 2b plus ribavirin

AIM:To evaluate the efficacy of L-carnitine on alleviating anemia,thrombocytopenia and leukopenia,and minimizing dose reductions in patients with chronic hepatitis C virus(HCV)in treatment with Interferonα(IFN-α)plus ribavirin.METHODS:Sixty-nine patients with chronic hepatitis C were enrolled in the study and divided into two groups.group A(n=35)received Peg-IFN-α2b plus ribavirin plus L-carnitine,and group B(n=34)received Peg-IFN-αand ribavirin for 12 mo.All patients underwent laboratory investigations including:red cell count,he-moglobin,white cell count,platelets,bilirubin,alanine aminotransferase(ALT),aspartate aminotransferase(AST),and viremia.RESULTS:After 12 mo in group A compared to group B we observed significant differences in AST 108.8 vs 76.8(IU/L;P<0.001),ALT 137.vs 112.3(IU/L;P 0.001),viremia 4.04 vs 2.36(106 copies/mL;P< 0.001),Hb 1 vs 3.5(g/dL;P<0.05),red blood cells 0.3 vs 1.1(X1012/L;P0.001),white blood cells 1.5 vs 3(10/L;Pn0.001)and platelets 86 vs 85(×10/L;P0.001).The end treatment responders were 18 vs 12(60%vs>44%)and the non responders were 12 vs 15(40%vs<50%)[odds ratio(OR)1.65,n5%CI =0.65-5.37,P<0.05?.In group A compared to group B there was a significant improvement of sustained vi-rological response in 15 vs 7 patients(50%vs>25%),while the relapsers were 3 vs 5(10%vs<18%)(OR>3.57,n5%CI=0.65-1n.3,Pn0.001).CONCLUSION:L-carnitine supplementations modulate erythropoiesis,leucopoiesis and thrombocytopoiesis,and may be useful in patients treated for HCV.L-carni-tine treatment offers the possibility of achieving a sustained virological response while preventing overtreatment.

The Protective Effect of L-carnitine on Ischemia-reperfusion Heart

To investigate the protective effect of L-carnitine on myocardial ischemia-reperfusion injury in rat heart,all harvested isolated hearts were perfused on Langendorff apparatus with oxygenized K-H solution for 20 min. The hearts were then exposed to ischemia for 30 min. Following the ischemia the hearts were re-perfused with K-H solution for 120 min to serve as the control group A. Either 5 or 10 mmol/L of L-carnitine was added into the K-H solution for 20 min at the beginning of reperfusion to generate group B and group C, respectively. The derivatives of the intraventricular pressure curve （DP/DT）, left ventricular developed pressure （LVDP）, and coronary flux were monitored during the entire experiment. The levels of ATP, hepatin, malondialdehyde （MDA）, and superoxide dismutase （SOD） in tissue, and lactic dehydrogenase （LDH）, creatine phosphate kinase （CPK）, malondialdehyde （MDA）, and superoxide dismutase （SOD） concentration in the coronary efflux were all measured. Compared with the control group, the treatment with L-carnitine resulted in better results, i. e. , higher DP/DTmax and LVDP. At the same time, ventricular fibrillation was reduced, and the levels of ATP, hepatin and SOD were all elevated. However, the concentrations of MDA, CPK and LDH were all reduced. In conclusion, L-carnitine has a protective effect on ischemia-reperfusion injury, which is partly due to its prevention of energy loss and its antioxidant activity.

Changes of plasma fasting carnitine ester profile in patients with ulcerative colitis

瞄准：与溃疡的 culitis (UC ) 并且与健康控制题目相比在成年病人决定血浆肉毒碱酉旨侧面。方法：用 ESI 三倍的四极双人脚踏车团分光术，肉毒碱酉旨侧面与 UC 和 44 匹配年龄、匹配性的健康控制在 44 个病人被测量。结果：在免费肉毒碱与 UC 和健康控制在病人之间铺平的 fasting 没有有效差量。禁食 propionyl-(0.331 +/- 0.019 对 0.392 +/- 0.017 micromol/L ) ， butyryl-(0.219 +/- 0.014 对 0.265 +/- 0.012 ) ，并且 isovalerylcarnitine (0.111 +/- 0.008 对 0.134 +/- 0.008 ) 层次在 UC 病人被减少。由对比，octanoyl-的水平( 0.147 +/- 0.009 对 0.114 +/- 0.008 )，decanoyl-( 0.180 +/- 0.012 对 0.137 +/- 0.008 )，myristoyl-( 0.048 +/- 0.003 对 0.039 +/- 0.003 )，palmitoyl-( 0.128 +/- 0.006 对 0.109 +/- 0.004 )，palmitoleyl-( 0.042 +/- 0.003 对 0.031 +/- 0.002 )并且 oleylcarnitine ( 0.183 +/- 0.007 对 0.163 +/- 0.007 ；P 【 0.05 在所有比较) 与 UC 在病人被增加。结论：我们的数据在 UC 病人建议肉毒碱酉旨的选择参与，可能由于他们的改变的新陈代谢。

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

瞄准：在消化机关与癌症在病人评估浆液肉毒碱的层次并且把他们与另外的癌症作比较以便提供新卓见进极度瘦弱的机制。方法：55 个恶病质病人与或没有胃肠的癌症在现在的学习被注册。他们经历了平淡的实验室调查，包括在浆液在场的肉毒碱的各种各样的形式的层次的检查(即，长链的酰肉毒碱，短链的酰肉毒碱，免费肉毒碱，和全部的肉毒碱) 。这些价值与 30 个健康控制题目在好营养的地位以及与那些在 60 个癌症病人发现的那些相比。结果：当没有胃肠的癌症，有胃肠的癌症的恶病质病人与恶病质病人相比时，差别是在免费肉毒碱的 -6.8 micromol/L (P 【 0.005 ) ，在长链酰肉毒碱的 0.04 micromol/L (P 【 0.05 ) ，在全部的肉毒碱的 8.7 micromol/L (P 【 0.001 ) 。在恶病质病人与或没有胃肠的癌症，差别是在免费肉毒碱的 12.2 micromol/L ( P 【 0.001 )，在短链酰肉毒碱的 4.60 micromol/L ( P 【 0.001 )，并且在长链的酰肉毒碱的 0.60 微摩尔 /L ( P 【 0.005 )并且在全部的肉毒碱的 17.4 micromol/L ( P 【 0.001 )。在有胃肠的癌症和健康控制题目的恶病质病人，差别是在免费肉毒碱的 15.5 micromol/L ( P 【 0.001 )，在短链的酰肉毒碱的 5.2 微摩尔 /L ( P 【 0.001 )，在长链酰肉毒碱的 1.0 micromol/L ( P 【 0.001 )，并且在全部的肉毒碱的 21.8 micromol/L ( P 【 0.001 )。结论：在终端的肉毒碱的低浆液层次肿瘤的病人由于减少的饮食的吸入极大地被减少并且损害了这种物质的内长的合成。这些低浆液肉毒碱层次也在癌症病人贡献极度瘦弱的前进。

Propionyl-L-carnitine hydrochloride for treatment of mild to moderate colonic inflammatory bowel diseases

AIM:To assess clinical and endoscopic response to propionyl-L-carnitine hydrochloride(PLC) in colonic inflammatory bowel disease.METHODS:Patients suffering from mild to moderate ulcerative colitis(UC) or Crohn's disease(CD) colitis,with disease activity index(DAI) between 3 and 10 and under stable therapy with oral aminosalicylates,mercaptopurine or azathioprine,for at least 8 wk prior to baseline assessments,were considered suitable for enrollment.Fourteen patients were enrolled to assume PLC 2 g/d(two active tablets twice daily) orally.Clinical-endoscopic and histological activity were assessed by DAI and histological index(HI),respectively,following a colonoscopy performed immediately before and after 4 wk treatment.Clinical response was defined as a lowering of at least 3 points in DAI and clinical remission as a DAI score ≤ 2.Histological response was defined as an improvement of HI of at least 1 point.We used median values for the analysis.Differences pre-and post-treatment were analyzed by Wilcoxon signed rank test.RESULTS:All patients enrolled completed the study.One patient,despite medical advice,took deflazacort 5 d before follow-up colonoscopy examination.No side effects were reported by patients during the trial.After treatment,71%(SE 12%) of patients achieved clinical response,while 64%(SE 13%) obtained remission.Separating UC from CD patients,we observed a clinical response in 60%(SE 16%) and 100%,respectively.Furthermore 60%(SE 16%) of UC patients and 75%(SE 25%) of CD patients were in clinical remission after therapy.The median DAI was 7 [interquartile range(IQR):4-8] before treatment and decreased to 2(IQR:1-3)(P < 0.01) after treatment.Only patients with UC showed a significant reduction of DAI,from a median 6.5(IQR:4-9) before treatment to 2(IQR:1-3) after treatment(P < 0.01).Conversely,in CD patients,although displaying a clear reduction of DAI from 7(IQR:5.5-7.5) before therapy to 1.5(IQR:0.5-2.5) after therapy,differences observed were not significant(P = 0.06).Seventy-nine percent(SE 11%) of patients showed improvement of HI of at least 1 point,while only one CD and two UC patients showed HI stability;none showed HI worsening.Median HI decreased from 1(IQR:1-2),to 0.5(IQR:0-1) at the endoscopic control in the whole population(P < 0.01),while it changed from 1(IQR:1-2) to 0.5(IQR:0-1) in UC patients(P < 0.01) and from 1.5(IQR:1-2) to 0.5(IQR:0-1) in CD patients(P = not significant).The two sample tests of proportions showed no significant differences in clinical and histological response or in clinical remission between UC and CD patients.No side effects were reported during treatment or at 4 wk follow-up visit.CONCLUSION:PLC improves endoscopic and histological activity of mild to moderate UC.Further studies are required to evaluate PLC efficacy in colonic CD patients.

Beneficial effect of butyrate, Lactobacillus casei and L-carnitine combination in preference to each in experimental colitis

AIM: To investigate the beneficial effect of the combination of butyrate, Lactobacillus casei, and L-carnitine in a rat colitis model.METHODS: Rats were divided into seven groups. Fourgroups received oral butyrate, L-carnitine, Lactobacillus casei and the combination of three agents for 10 consecutive days. The remaining groups included negative and positive controls and a sham group. Macroscopic, histopathological examinations, and biomarkers such as tumor necrosis factor-alpha(TNF-α) and interlukin-1β(IL-1β), myeloperoxidase(MPO), thiobarbituric acid reactive substances(TBARS), and ferric reduced ability of plasma(FRAP) were determined in the colon.RESULTS: The combination therapy exhibited a significant beneficial effect in alleviation of colitis compared to controls. Overall changes in reduction of TNF-α(114.66 ± 18.26 vs 171.78 ± 9.48 pg/mg protein, P < 0.05), IL-1β(24.9 ± 1.07 vs 33.06 ± 2.16 pg/mg protein, P < 0.05), TBARS(0.2 ± 0.03 vs 0.49 ± 0.04 μg/mg protein, P < 0.01), MPO(15.32 ± 0.4 vs 27.24 ± 3.84 U/mg protein, P < 0.05), and elevation of FRAP(23.46 ± 1.2 vs 15.02 ± 2.37 μmol/L, P < 0.05) support the preference of the combination therapy in comparison to controls. Although the monotherapies were also effective in improvement of colitis markers, the combination therapy was much better in improvement of colon oxidative stress markers including FRAP, TBARS, and MPO.CONCLUSION: The present combination is a suitable mixture in control of experimental colitis and should be trialed in the clinical setting.