oalib
Search Results: 1 - 10 of 100 matches for " "
All listed articles are free for downloading (OA Articles)
Page 1 /100
Display every page Item
7. Carnitine: A novel health factor-An overview  [PDF]
C.D. Dayanand,N. Krishnamurthy,S. Ashakiran,K.N. Shashidhar
International Journal of Pharmaceutical and Biomedical Research (IJPBR) , 2011,
Abstract: Carnitine term comprises L-carnitine, acetyl –L-carnitine and Propionyl –L-carnitine. Carnitine in greater amount obtained from animal dietary sources as compared to plant sources. The endogenous synthesis of carnitine takes place in animal tissues like liver, kidney and brain using precursor amino acid lysine and methionine by iron, vitamin C, niacin, pyridoxine dependent pathway. This is the basis of vegans generally depending on carnitine in larger proportion through in vivo synthesis than omnivorous subjects. The concentration of Tri methyl lysine residues and the tissue specificity of Butyro betaine Dehydrogenase will play a significant role in regulating the carnitine biosynthesis. Carnitine transport from the site of synthesis to target tissue occurs via blood. Therefore, the measurement of normal plasma carnitine concentration represents the balance between the rate of synthesis and rate of excretion through specific transporter proteins. The cellular functional role of carnitine depends on the uptake in to cells through carnitine transport proteins and transport in to mitochondrial matrix. The function of carnitine is to traverse Long chain Fatty Acids across inner mitochondrial membrane for β-oxidation for rapid production of ATP. The carnitine level in plasma or tissue is done by spectro photometric, HPLC, or Tandem Mass Spectro photometry methods. Carnitine deficiency results in muscle disorders, there are two types of deficiency states such as primary and secondary deficiency. The primary is of systemic or myopathic, characterized by defect of high affinity organic cation transporter protein present on the plasma membrane of liver and kidney and also due to dysfunction of carnitine reabsorbtion through similar transport proteins in renal tubules. However, secondary carnitine deficiency associated with mitochondrial disorders and also defect of β-oxidation such as CPT-II and acyl CoA Dehydrogenase, several other causes are vitamin c deficiency, valaproate therapy, fancony syndrome, liver dysfunction, and kidney disease. Both these conditions results in recurrent muscle cramp, muscle weakness and fatigue, non ketotic hypoglycemia, encephalopathy, hepatomegaly, muscle necrosis, etc. Therefore, In view of the life threatening events of carnitine deficiency, Food drug administration considered L-carnitine as a drug to treat the primary and secondary carnitine deficiency. In recent times, carnitine has been extensively studied in various research activities to explore the therapeutic benefit. Thus, carnitine justifies as a novel health factor.
Diabetic Cardiovascular Risk and Carnitine Deficiency
—Carnitine Deficiency in Clinical Diabetes Mellitus
 [PDF]

John I. Malone, Michael A. Malone, Anthony D. Morrison
Journal of Diabetes Mellitus (JDM) , 2014, DOI: 10.4236/jdm.2014.43029
Abstract:

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

Fenofibrate Therapy in Carnitine Palmitoyl Transferase Type 2 Deficiency  [PDF]
I. Hamilton-Craig,M. Yudi,L. Johnson,R. Jayasinghe
Case Reports in Medicine , 2012, DOI: 10.1155/2012/163173
Abstract: Bezafibrate therapy has been shown to improve beta-oxidation of fatty acids and to reduce episodes of rhabdomyolysis in patients with carnitine palmitoyltransferase type-2 (CPT2) deficiency. We report the efficacy of fenofibrate in a patient with CPT2 deficiency, in whom beta-oxidation was improved but an episode of rhabdomyolysis nevertheless occurred. This suggests additional methods to avoid rhabdomyolysis in patients with CPT2 deficiency should accompany fibrate therapy, including avoidance of muscular overexertion, dehydration, and heat exposure. 1. Introduction Carnitine palmitoyl transferase type 2 (CPT2) deficiency is a rare autosomal recessive disorder of mitochondrial fatty acid oxidation [1]. It manifests clinically by muscle stiffness, myalgia, exercise intolerance, and episodes of rhabdomyolysis especially after overexertion, heat exposure, viral infection or other intercurrent illness [1]. In 2009, Bonnefont and colleagues found that bezafibrate therapy restored the capacity for normal fatty acid oxidation in muscle cells from patients with CPT2 deficiency by stimulating the expression of the mutated gene [2]. They described a series of six patients with CPT2 deficiency treated with bezafibrate 200?mg three times daily for a period of 6 months. Bezafibrate therapy resulted in 60–284% improvement in skeletal muscle palmitoyl L-carnitine oxidation levels, 20–93% increase in skeletal muscle CPT2 mRNA, and full correction of the initial defective fatty acid oxidation in myoblasts in vitro. The number of episodes of rhabdomyolysis was reduced from 3–24 per patient over a 6-month period before treatment to 0–6 per patient over a 6-month period after treatment. Levels of creatine kinase (CK) were reduced from a mean of 10,900?IU/L before treatment to 4,700?IU/L after treatment, indicating a reduced rate of muscle damage [2]. Unlike gemfibrozil and fenofibrate, bezafibrate is not widely available in many countries, necessitating therapy with the former two agents for patients with dyslipidaemia, the common indication for fibrate use. In this paper we report the case of a patient with CPT2 deficiency who responded to fenofibrate therapy with regard to improvement in plasma acylcarnitine and lipid levels, as well as improvement in muscle symptoms. While on fibrate therapy, he nevertheless experienced an episode of rhabdomyolysis after heat exposure and a viral infection. As in the experience of Bonnefont et al., fibrate therapy did not completely abolish episodes of rhabdomyolysis in this patient in spite of evidence for improved CPT2 activity.
Role of carnitine in disease
Judith L Flanagan, Peter A Simmons, Joseph Vehige, Mark DP Willcox, Qian Garrett
Nutrition & Metabolism , 2010, DOI: 10.1186/1743-7075-7-30
Abstract: Carnitine (β-hydroxy-γ-N-trimethylaminobutyric acid) is widely distributed in food from animals sources but there is limited availability in plants [1]. In humans, 75% of carnitine is obtained from the diet [2]. L-carnitine (the biologically active stereoisomer) is absorbed from foods via both active and passive transport across enterocyte (intestinal cell) membranes [3]. The bioavailability of L-carnitine varies due to dietary composition. Bioavailability of L-carnitine in individuals such as vegetarians who are adapted to low-carnitine diets is higher (66% to 86% of available carnitine) than regular red-meat eaters adapted to high-carnitine diets (54% to 72% of available carnitine) [4]. Carnitine not obtained from food is synthesized endogenously from two essential amino acids, lysine and methionine. This occurs in kidney, liver and brain [5]. Cardiac and skeletal muscle, harboring the highest concentrations, cannot synthesize carnitine and so must acquire carnitine from plasma. Unabsorbed L-carnitine is mostly degraded by microorganisms in the large intestine [3]. Almost all carnitine (99%) is intracellular [5]. Carnitine influences carbohydrate metabolism. Aberrations in carnitine regulation are implicated in complications of diabetes mellitus, hemodialysis, trauma, malnutrition, cardiomyopathy, obesity, fasting, drug interactions, endocrine imbalances and other disorders.The purpose of this review is to summarize the role of carnitine in human nutrition and disease and highlight the major areas of research in this field.Carnitine, a branched non-essential amino acid, is synthesized from the essential amino acids lysine and methionine. Ascorbic acid, ferrous iron, pyroxidine and niacin are also necessary cofactors [1] and deficiencies of any of these can lead to carnitine deficiency. The pathway in mammals is unique using protein-bound lysine that is enzymatically methylated to form trimethyllysine as a post-translational modification of protein synthesis [6]. T
Effect of Acupuncture on Carnitine for Skeletal Muscle Fatigue  [PDF]
Shizuo Toda
Chinese Medicine (CM) , 2012, DOI: 10.4236/cm.2012.31003
Abstract: Skeletal muscle fatigue is a common symptom in various diseases, works and exercises. These were generally induced by neuron, metabolic conditions, overused muscle, and stress. But, there have been few principles about it. Many researchers have reported that acupuncture therapy has been useful to skeletal muscle fatigue on various diseases and conditions. However, it has never been shown why acupuncture therapy has the effect on skeletal muscle fatigue. The deficiency of carnitine induces fatigue, weakness, and disorder of skeletal muscle. It has showed that acupuncture induces the increase of carnitine in skeletal muscle. These findings demonstrated that acupuncture on skeletal muscle fatigue could increase carnitine as a possible affection mechanism.
Systemic primary carnitine deficiency: an overview of clinical manifestations, diagnosis, and management  [cached]
Magoulas Pilar L,El-Hattab Ayman W
Orphanet Journal of Rare Diseases , 2012, DOI: 10.1186/1750-1172-7-68
Abstract: Systemic primary carnitine deficiency (CDSP) is an autosomal recessive disorder of carnitine transportation. The clinical manifestations of CDSP can vary widely with respect to age of onset, organ involvement, and severity of symptoms, but are typically characterized by episodes of hypoketotic hypoglycemia, hepatomegaly, elevated transaminases, and hyperammonemia in infants; skeletal myopathy, elevated creatine kinase (CK), and cardiomyopathy in childhood; or cardiomyopathy, arrhythmias, or fatigability in adulthood. The diagnosis can be suspected on newborn screening, but is established by demonstration of low plasma free carnitine concentration (<5 μM, normal 25-50 μM), reduced fibroblast carnitine transport (<10% of controls), and molecular testing of the SLC22A5 gene. The incidence of CDSP varies depending on ethnicity; however the frequency in the United States is estimated to be approximately 1 in 50,000 individuals based on newborn screening data. CDSP is caused by recessive mutations in the SLC22A5 gene. This gene encodes organic cation transporter type 2 (OCTN2) which transport carnitine across cell membranes. Over 100 mutations have been reported in this gene with the c.136C > T (p.P46S) mutation being the most frequent mutation identified. CDSP should be differentiated from secondary causes of carnitine deficiency such as various organic acidemias and fatty acid oxidation defects. CDSP is an autosomal recessive condition; therefore the recurrence risk in each pregnancy is 25%. Carrier screening for at-risk individuals and family members should be obtained by performing targeted mutation analysis of the SLC22A5 gene since plasma carnitine analysis is not a sufficient methodology for determining carrier status. Antenatal diagnosis for pregnancies at increased risk of CDSP is possible by molecular genetic testing of extracted DNA from chorionic villus sampling or amniocentesis if both mutations in SLC22A5 gene are known. Once the diagnosis of CDSP is established in an individual, an echocardiogram, electrocardiogram, CK concentration, liver transaminanses measurement, and pre-prandial blood sugar levels, should be performed for baseline assessment. Primary treatment involves supplementation of oral levocarnitine (L-carnitine) at a dose of 50–400 mg/kg/day divided into three doses. No formal surveillance guidelines for individuals with CDSP have been established to date, however the following screening recommendations are suggested: annual echocardiogram and electrocardiogram, frequent plasma carnitine levels, and CK and liver transamina
Primary Systemic Carnitine Deficiency Presenting as Recurrent Reye-Like Syndrome and Dilated Cardiomyopathy  [PDF]
Jia-Woei Hou
Chang Gung Medical Journal , 2002,
Abstract: Carnitine deficiency syndrome is a rare and potentially fatal but treatable metabolic disorder.I present a 6-year-old girl with primary systemic carnitine deficiency (SCD) provedby very low plasma carnitine level. Her major clinical features included neonatal metabolicacidosis, epilepsy, recurrent infections, acute encephalopathy, and dilated cardiomyopathywith heart failure before 4 years of age. Other features such as hepatomegaly, hypoglycemia,or hyperammonemia were noted around 5 years of age. Her health improved withresolving cardiomyopathy after the use of L-carnitine (50-100 mg/kg/day). Patients withSCD have high morbidity and mortality. If SCD is suggested as a cause of Reye-like syndromeor dilated cardiomyopathy, L-carnitine therapy should be initiated as a diagnostic testimmediately, until the definite diagnosis is confirmed.
Carnitine Deficiency and Oxidative Stress Provoke Cardiotoxicity in an Ifosfamide-Induced Fanconi Syndrome Rat Model  [PDF]
Mohamed M. Sayed-Ahmed,Amal Q. Darweesh,Amal J. Fatani
Oxidative Medicine and Cellular Longevity , 2010, DOI: 10.4161/oxim.3.4.12859
Abstract: In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC) could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day) combined with mildronate (MD, 200 mg/kg/day) and PLC (250 mg/kg/day), respectively, for 10 successive days. The 4th, 5th and 6th groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day). IFO significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS) in cardiac tissues and significantly decreased adenosine triphosphate (ATP) and total carnitine and reduced glutathione (GSH) content in cardiac tissues. In carnitine-depleted rats, IFO induced dramatic increase in serum creatinine, BUN, CK-MB, LDH, carnitine clearance and intramitochondrial acetyl-CoA/CoA-SH, as well as progressive reduction in total carnitine and ATP in cardiac tissues. Interestingly, PLC supplementation completely reversed the biochemical changes-induced by IFO to the control values. In conclusion, data from the present study suggest that: Carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, constitute risk factors and should be viewed as mechanisms during development of IFO-induced cardiotoxicity. Carnitine supplementation, using PLC, prevents the development of IFO-induced cardiotoxicity through antioxidant signalling and improving mitochondrial function.
Carnitine Deficiency and Oxidative Stress Provoke Cardiotoxicity in an Ifosfamide-Induced Fanconi Syndrome Rat Model  [PDF]
Mohamed M. Sayed-Ahmed,Amal Q. Darweesh,Amal J. Fatani
Oxidative Medicine and Cellular Longevity , 2010, DOI: 10.4161/oxim.3.4.12859
Abstract: In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO) therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC) could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day) combined with mildronate (MD, 200 mg/kg/day) and PLC (250 mg/kg/day), respectively, for 10 successive days. The 4th, 5th and 6th groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day). IFO significantly increased serum creatinine, blood urea nitrogen (BUN), urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS) in cardiac tissues and significantly decreased adenosine triphosphate (ATP) and total carnitine and reduced glutathione (GSH) content in cardiac tissues. In carnitine-depleted rats, IFO induced dramatic increase in serum creatinine, BUN, CK-MB, LDH, carnitine clearance and intramitochondrial acetyl-CoA/CoA-SH, as well as progressive reduction in total carnitine and ATP in cardiac tissues. Interestingly, PLC supplementation completely reversed the biochemical changes-induced by IFO to the control values. In conclusion, data from the present study suggest that: Carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, constitute risk factors and should be viewed as mechanisms during development of IFO-induced cardiotoxicity. Carnitine supplementation,
Effects of zinc deficiency/zinc supplementation on ammonia metabolism in patients with decompensated liver cirrhosis.
Yoshida Y,Higashi T,Nouso K,Nakatsukasa H
Acta Medica Okayama , 2001,
Abstract: Hepatic encephalopathy is one of the major complications in decompensated liver cirrhosis. The current study was conducted to clarify the mechanisms of zinc deficiency in liver cirrhosis and its involvement in hepatic encephalopathy via ammonia metabolism. Ten patients each with compensated or decompensated liver cirrhosis and 11 healthy volunteers were enrolled in the study. Serum zinc levels and its daily urinary excretion were measured, an oral zinc-tolerance test was performed to examine zinc malabsorption, and the effects of diuretics on zinc excretion and of zinc supplementation on ammonia metabolism in the skeletal muscle were studied. The mean serum zinc levels in patients with decompensated liver cirrhosis were found to be significantly lower than the levels in controls and patients with compensated liver cirrhosis. The serum zinc levels were inversely correlated with blood ammonia in the fasting state. In the oral zinc-tolerance test, the percent increase in serum zinc levels 120 and 180 min after ingestion was less in cirrhotic patients than in controls. A diuretic administration resulted in a significant reduction in serum zinc levels. An increased uptake of ammonia by and an increased release of glutamine from leg skeletal muscle after oral supplementation of zinc sulfate were evident. Taken together, zinc deficiency in decompensated cirrhotic patients appears to be due to low absorption and to high urinary excretion, for which excessive diuretic administration is, in part, responsible, and zinc supplementation might play an important role in the prevention of hepatic encephalopathy by activating glutamine synthetase.
Page 1 /100
Display every page Item


Home
Copyright © 2008-2017 Open Access Library. All rights reserved.