Hexose transport properties of myoblasts isolated from a patient with suspected muscle carnitine deficiency

The human primary carnitine deficiency syndromes are potentially fatal disorders affecting children and adults. The molecular etiologies of these syndromes have not been fully determined. Muscle carnitine deficiency syndrome is characterized by mild to severe muscle weakness, lipid accumulation in muscle, and reduced muscle carnitine concentration. In the present investigation, the hexose transport properties of muscle cells isolated from a patient with suspected muscle carnitine deficiency (MCD) were examined. We have previously shown that myoblasts from normal human subjects possessed at least two hexose transport systems, the low (LAHT) and the high (HAHT) affinity hexose transport systems. Their preferred substrates were 3-O-methyl-D-glucose and 2-deoxyglucose (dGlc), respectively; HAHT, but not LAHT, was sensitive to inhibition by carbonyl cyanide m-chlorophenylhydrazone (CCCP). Here we show that the kinetic properties of HAHT in the MCD myoblasts differ significantly from those of normal myoblasts and that the rates of dGlc transport by MCD myoblasts are restored to normal by growth in 40 μM L-carnitine. We also demonstrate that the kinetic properties of LAHT are quite similar in both normal and MCD myoblasts. It can be inferred from these findings that HAHT and LAHT may be coded or regulated by different genes. Based on the finding that the dGlc transport system in L-carnitine grown cells is no longer sensitive to inhibition by CCCP, it is thought that L-carnitine may play a regulatory role in HAHT, viz., by maintaining the HAHT transporter in a functional state, even in energy-uncoupled cells. While MCD myoblasts exhibit normal rates of L-carnitine influx, their L-carnitine efflux rates are significantly faster than those of normal myoblasts, thus resulting in significantly reduced intracellular level of L-carnitine in the MCD myoblasts. This reduced intracellular L-carnitine level would then explain the relatively reduced HAHT activity and its subsequent restoration to normal activity following growth in L-carnitine.Key words: hexose transport, human myoblasts, muscle carnitine deficiency, myopathy, human genetic variants, myoblasts, transport regulation, β-oxidation, L-carnitine.

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Familial hypertrophic cardiomyopathy and muscle carnitine deficiency

Muscle & Nerve ◽

10.1002/mus.880130303 ◽

1990 ◽

Vol 13 (3) ◽

pp. 192-194 ◽

Cited By ~ 8

Author(s):

J. Bautista ◽

E. Rafel ◽

A. Martinez ◽

I. Sainz ◽

J. Herrera ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Carnitine Deficiency ◽

Familial Hypertrophic Cardiomyopathy ◽

Muscle Carnitine Deficiency

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Transport Phenomena and Properties in Treelike Networks

Applied Mechanics Reviews ◽

10.1115/1.4033966 ◽

2016 ◽

Vol 68 (4) ◽

Cited By ~ 47

Author(s):

Peng Xu ◽

Agus Pulung Sasmito ◽

Boming Yu ◽

Arun Sadashiv Mujumdar

Keyword(s):

Transport Properties ◽

Scaling Laws ◽

Transport Phenomena ◽

Transport Processes ◽

Research Progress ◽

Transport Systems ◽

Transport Mechanisms ◽

Branching Structures ◽

Flow And Heat Transfer ◽

Flow Heat

Treelike structures abound in natural as well as man-made transport systems, which have fascinated multidisciplinary researchers to study the transport phenomena and properties and understand the transport mechanisms of treelike structures for decades. The fluid flow and heat transfer in treelike networks have received an increasing attention over the past decade as the highly efficient transport processes observed in natural treelike structures can provide useful hints for optimal solutions to many engineering and industrial problems. This review paper attempts to present the background and research progress made in recent years on the transport phenomenon in treelike networks as well as technological applications of treelike structures. The subtopics included are optimization of branching structures, scaling laws of treelike networks, and transport properties for laminar flow, turbulent flow, heat conduction, and heat convection in treelike networks. Analytical expressions for the effective transport properties have been derived based on deterministic treelike networks, and the effect of branching parameters on the transport properties of treelike networks has also been discussed. Furthermore, numerical simulation results for treelike microchannel networks are presented as well. The proposed transport properties may be beneficial to understand the transport mechanisms of branching structures and promote the applications of treelike networks in engineering and industry.

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Kinematic and Kinetic Comparison of Fresh Frozen and Thiel-Embalmed Human Feet for Suitability for Biomechanical Educational and Research Settings

Journal of the American Podiatric Medical Association ◽

10.7547/16-130 ◽

2019 ◽

Vol 109 (2) ◽

pp. 113-121 ◽

Cited By ~ 1

Author(s):

Alfred Gatt ◽

Pierre Schembri-Wismayer ◽

Nachiappan Chockalingam ◽

Cynthia Formosa

Keyword(s):

Human Subjects ◽

Biomechanical Testing ◽

Biomechanical Properties ◽

Kinetic Properties ◽

Foot Pressure ◽

Human Foot ◽

Observational Study Design ◽

Fresh Frozen ◽

Research And Education

Background: In vitro biomechanical testing of the human foot often involves the use of fresh frozen cadaveric specimens to investigate interventions that would be detrimental to human subjects. The Thiel method is an alternative embalming technique that maintains soft-tissue consistency similar to that of living tissue. However, its suitability for biomechanical testing is unknown. Thus, the aim of this study was to determine whether Thiel-embalmed foot specimens exhibit kinematic and kinetic biomechanical properties similar to those of fresh frozen specimens. Methods: An observational study design was conducted at a university biomechanics laboratory. Three cadavers had both limbs amputated, with one being fresh frozen and the other preserved by Thiel's embalming. Each foot was tested while undergoing plantarflexion and dorsiflexion in three states: unloaded and under loads of 10 and 20 kg. Their segment kinematics and foot pressure mapping were assessed simultaneously. Results: No statistically significant differences were detected between fresh frozen and Thiel-embalmed sample pairs regarding kinematics and kinetics. Conclusions: These findings highlight similar kinematic and kinetic properties between fresh frozen and Thiel-embalmed foot specimens, thus possibly enabling these specimens to be interchanged due to the latter specimens' advantage of delayed decomposition. This can open innovative opportunities for the use of these specimens in applications related to the investigation of dynamic foot function in research and education.

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Carnitine insufficiency in children with inborn errors of metabolism: prevalence and treatment efficacy

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2015-0193 ◽

2015 ◽

Vol 28 (11-12) ◽

Cited By ~ 7

Author(s):

Ilgar Mamedov ◽

Irina Zolkina ◽

Ekaterina Nikolaeva ◽

Pavel Glagovsky ◽

Vladimir Sukhorukov

Keyword(s):

Fatty Acids ◽

Plasma Level ◽

Psychomotor Retardation ◽

Carnitine Deficiency ◽

Free Carnitine ◽

Hereditary Diseases ◽

Inborn Errors ◽

Carnitine Level ◽

Subsequent Investigation ◽

Systemic Carnitine Deficiency

AbstractCarnitine is necessary for the transfer of long-chain fatty acids from the cytosol into mitochondria for subsequent β-oxidation. A carnitine deficiency results in impaired energy production from fatty acids.We reviewed the plasma level of total carnitine, free carnitine, and acylcarnitines in 1270 children with psychomotor retardation, low growth, and weight parameters. Tandem mass spectrometry (MS/MS) was applied. Low free carnitine level in plasma was used as a marker of carnitine deficiency.A total of 102 (8%) children had free carnitine level <19 μmol/L (norm 19–60 μmol/L). As a result of the subsequent investigation, hereditary diseases were diagnosed in 76 (¾) children and out of that 19 had very low free carnitine plasma level (<10 μmol/L). Fanconi syndrome, fat oxidation defects, primary systemic carnitine deficiency, mitochondrial encephalomyopathy, and Noonan syndrome were revealed in these 19 children.Efficacy of levocarnitine treatment in children with very low free carnitine level differs according to pathogenesis of diseases. The highest efficacy was observed in primary systemic carnitine deficiency.

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Muscle carnitine deficiency in patients with severe peripheral vascular disease.

Circulation ◽

10.1161/01.cir.84.4.1490 ◽

1991 ◽

Vol 84 (4) ◽

pp. 1490-1495 ◽

Cited By ~ 56

Author(s):

G Brevetti ◽

C Angelini ◽

M Rosa ◽

R Carrozzo ◽

S Perna ◽

...

Keyword(s):

Vascular Disease ◽

Peripheral Vascular Disease ◽

Carnitine Deficiency ◽

Peripheral Vascular ◽

Muscle Carnitine Deficiency

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Association of Carnitine Deficiency in Indian Continuous Ambulatory Peritoneal Dialysis Patients with Anemia, Erythropoietin Use, Residual Renal Function, and Diabetes Mellitus

Peritoneal Dialysis International ◽

10.1177/089686080702702s40 ◽

2007 ◽

Vol 27 (2_suppl) ◽

pp. 235-238

Author(s):

S. Ramalakshmi ◽

Bjoe Baben ◽

Ben S. Ashok ◽

V. Jayanthi ◽

Nancy Leslie ◽

...

Keyword(s):

Renal Function ◽

Peritoneal Dialysis ◽

Residual Renal Function ◽

Carnitine Deficiency ◽

Free Carnitine ◽

Dialysis Patients ◽

Carnitine Level ◽

Daily Urine ◽

The Mean ◽

Daily Urine Output

♦ In the present study, we aimed to determine levels of free carnitine in hemodialysis (HD) and peritoneal dialysis (PD) patients in India and to correlate carnitine deficiency with various clinical parameters. ♦ Patients on HD and PD at two tertiary care centers were selected for the study. Baseline data were obtained, and a free carnitine analysis was performed. Carnitine deficiency was defined as a free carnitine level of less than 40 μmol/L. ♦ The total number of study patients was 96 (77 on HD, 19 on PD). In the PD group, the mean age was 56 years, with 26.3% of the patients being vegan, 47.4% having diabetes, and 57.9% having a daily urine output of <500 mL. The mean carnitine level in that group was 38.9 μmol/L, and 68.4% of the patients had a carnitine deficiency. A Pearson correlation test failed to show any association of carnitine level with parameters such as anemia, use of erythropoietin, non-vegetarian diet, diabetes, and hypertension. In the HD group, the mean age was 45 years, with 22% of the patients being vegan, 23% having diabetes, and 45.5% having a daily urine output of <500 mL. The mean carnitine level in the group was 38.2 μmol/L, and 64.3% of the patients had a carnitine deficiency. Residual renal function and duration of dialysis were different in HD patients with and without carnitine deficiency. Carnitine levels in the HD group correlated positively and statistically significantly with the presence of diabetes and hypertension. ♦ Conclusion This study is the first demonstration that Indian dialysis patients have carnitine deficiency.

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Prevalence of Carnitine Deficiency and Decreased Carnitine Levels in Patients on Hemodialysis

Blood Purification ◽

10.1159/000496720 ◽

2019 ◽

Vol 47 (Suppl. 2) ◽

pp. 38-44 ◽

Cited By ~ 4

Author(s):

Yoshinari Hatanaka ◽

Terumi Higuchi ◽

Yurie Akiya ◽

Tomomi Horikami ◽

Ritsukou Tei ◽

...

Keyword(s):

At Risk ◽

High Risk ◽

Multivariate Regression ◽

Reduction Rate ◽

Carnitine Deficiency ◽

Free Carnitine ◽

Prevalence Rates ◽

Carnitine Level ◽

Serum Free ◽

Free Serum

Background: Patients on hemodialysis (HD) are known to be at risk of carnitine deficiency. The aims of this study were to investigate the prevalence of carnitine deficiency in patients on dialysis and to compare the likelihood of a reduction in the serum carnitine level on HD with that on hemodiafiltration (HDF). Methods: The prevalence of carnitine deficiency, defined as a serum free carnitine level < 20 μmol/L, and that of carnitine insufficiency, defined as an acyl/free carnitine ratio > 0.4, was investigated in 150 patients on dialysis. The reduction rate of serum carnitine was then compared between HD and HDF. Results: The prevalence of carnitine deficiency and that of carnitine insufficiency was 25.3 and 86.7%, respectively. Patients at high risk of carnitine deficiency accounted for 64.7%. Multivariate regression identified an association of duration of dialysis with the free serum carnitine level. The reduction rates of serum free carnitine in HD and HDF were 64 ± 4 and 75 ± 7%, respectively (p < 0.0001). Conclusion: The prevalence rates of carnitine deficiency and carnitine insufficiency were high in patients on dialysis. The serum carnitine reduction rate was greater with HDF than with HD.

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