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1.
Opt Express ; 31(15): 24045-24053, 2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37475241

ABSTRACT

Image-based deep learning (IBDL) is an advanced technique for predicting the surface irradiation conditions of laser surface processing technology. In pulsed-laser surface processing techniques, the number of superimposed laser shots is one of the fundamental and essential parameters that should be optimized for each material. Our primary research aims to build an adequate dataset using laser-irradiated surface images and to successfully predict the number of superimposed shots using the pre-trained deep convolutional neural network (CNN) models. First, the laser shot experiments were performed on copper targets using a nanosecond YAG laser with a wavelength of 532 nm. Then, the training data were obtained with the different superimposed shots of 1 to 1024 in powers of 2. After that, we used several pre-trained deep CNN models to predict the number of superimposed laser shots. Based on the dataset with 1936 images, VGG16 shows a high validation accuracy, higher sensitivity, and more than 99% precision than other deep CNN models. Utilizing the VGG16 model with high sensitivity could positively impact the industries' time, efficiency, and overall production.

2.
Rev Sci Instrum ; 93(6): 063505, 2022 Jun 01.
Article in English | MEDLINE | ID: mdl-35778032

ABSTRACT

The shock ignition (SI) approach to inertial confinement fusion is a promising scheme for achieving energy production by nuclear fusion. SI relies on using a high intensity laser pulse (≈1016 W/cm2, with a duration of several hundred ps) at the end of the fuel compression stage. However, during laser-plasma interaction (LPI), several parametric instabilities, such as stimulated Raman scattering and two plasmon decay, nonlinearly generate hot electrons (HEs). The whole behavior of HE under SI conditions, including their generation, transport, and final absorption, is still unclear and needs further experimental investigation. This paper focuses on the development of an experimental platform for SI-related experiments, which simultaneously makes use of multiple diagnostics to characterize LPI and HE generation, transport, and energy deposition. Such diagnostics include optical spectrometers, streaked optical shadowgraph, an x-ray pinhole camera, a two-dimensional x-ray imager, a Cu Kα line spectrometer, two hot-electron spectrometers, a hard x-ray (bremsstrahlung) detector, and a streaked optical pyrometer. Diagnostics successfully operated simultaneously in single-shot mode, revealing the features of HEs under SI-relevant conditions.

3.
Phys Rev Lett ; 126(17): 175503, 2021 Apr 30.
Article in English | MEDLINE | ID: mdl-33988455

ABSTRACT

In situ femtosecond x-ray diffraction measurements and ab initio molecular dynamics simulations were performed to study the liquid structure of tantalum shock released from several hundred gigapascals (GPa) on the nanosecond timescale. The results show that the internal negative pressure applied to the liquid tantalum reached -5.6 (0.8) GPa, suggesting the existence of a liquid-gas mixing state due to cavitation. This is the first direct evidence to prove the classical nucleation theory which predicts that liquids with high surface tension can support GPa regime tensile stress.

4.
Rev Sci Instrum ; 83(10): 10E529, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23127036

ABSTRACT

Developments in measuring sound velocity of matter under ultrahigh pressure are described. We employed a time-resolved x-ray shadowgraph technique to measure the sound velocity of shock-compressed diamond and iron foils at around melt. The sound velocity significantly dropped at melting, a behavior that has been difficult to clarify by conventional measurements by subtracting particle velocity from shock velocity (u(s) - u(p)). In addition to sound velocity, other important parameters were also obtained simultaneously.

5.
Rev Sci Instrum ; 81(10): 10D303, 2010 Oct.
Article in English | MEDLINE | ID: mdl-21033829

ABSTRACT

A custom developed (6)Li glass scintillator (APLF80+3Pr) for down-scattered neutron diagnostics in inertial confinement fusion experiments is presented. (6)Li provides an enhanced sensitivity for down-scattered neutrons in DD fusion and its experimentally observed 5-6 ns response time fulfills the requirement for down-scattered neutron detectors. A time-of-flight detector operating in the current mode using the APLF80+3Pr was designed and its feasibility observing down-scattered neutrons was demonstrated. Furthermore, a prototype design for a down-scattered neutron imaging detector was also demonstrated. This material promises viability as a future down-scattered neutron detector for the National Ignition Facility.

6.
FEMS Microbiol Lett ; 205(2): 349-54, 2001 Dec 18.
Article in English | MEDLINE | ID: mdl-11750826

ABSTRACT

To characterize common sites within the core oligosaccharide of the R-form lipopolysaccharide (LPS), we screened peptides from a phage-displayed heptapeptide library by using the most truncated form of R-LPS, Re-LPS (S. Typhimurium SL1165) as a ligand. After three rounds of biopanning/amplification and subsequent screening by phagemid enzyme-linked immunosorbent assay (ELISA), we selected three distinct clones that bind to the ligand LPS. We characterized the binding sites of the three clones by ELISA and thin-layer chromatography immunostaining and found that the three clones bind the two Re-LPSs (SL1165 and S. Minnesota Re595) and Rb2-LPS. In addition, one of the clones also bound to S-form LPS (S. Enteritidis). Current data show that those clones bind to common carbohydrate structure(s) expressed in the core oligosaccharides of those LPS samples.


Subject(s)
Lipopolysaccharides/metabolism , Oligosaccharides/metabolism , Peptides/metabolism , Ligands , Peptide Library , Peptides/chemistry , Peptides/isolation & purification , Protein Binding
7.
Article in English | MEDLINE | ID: mdl-11102080

ABSTRACT

Kalpha emission of high-Z solid targets irradiated by an intense, short (<100 fs) laser pulse in the 10 keV region is shown to be sensitive to the electron energy cutoff, which is strongly dependent on the density gradient of the plasma corona formed by a long prepulse. The absorption rate of short laser pulses, the hot electron distribution, and x-ray emission from a Cu slab target are studied via a hybrid model, which combines the hydrodynamics, collisional particle-in-cell, and Monte Carlo simulation techniques, and via a direct spectroscopic measurement. An absorption mechanism originating from the interaction of the laser pulse with plasma waves is found to increase the absorption rate by over 30% even for a very short, s-polarized laser pulse. Calculated and measured x-ray spectra are in good agreement, confirming the electron energy cutoff.

8.
Acta Neurochir (Wien) ; 142(9): 1003-12, 2000.
Article in English | MEDLINE | ID: mdl-11086809

ABSTRACT

BACKGROUND: There has been no detailed documentation of the advantages of three-dimensional (3D) wall imaging of cerebral aneurysms. The usefulness of such endoscopic images obtained with modified spiral computed tomography angiography (CTA) was therefore examined in comparison with conventional spiral CTA and digital subtraction angiography (DSA). METHODS: Fifteen of 45 patients who underwent conventional spiral CTA in our department in the past 4 years, were further studied with a technical modification of surface-rendering reconstruction in spiral CT. Endoscopic images were obtained by regulating the lower and higher thresholds of spiral CT scans in processing. Digital subtraction angiography was also performed for 14 of the 15 patients. The 3D wall images of the cerebral aneurysms were assessed in comparison with findings from conventional CTA and DSA. FINDINGS: The true orifice of the aneurysms could be visualized with the endoscopic mode in all of the 15 cases. In paraclinoid aneurysms, particularly below the anterior clinoid process, the relationships to associated vessels and bone structures were more clearly disclosed with this mode. The endoscopic images of aneurysms with rigid clots or neighboring distended veins were not as adversely affected as conventional CTA. In 4 of the 15 the wall imaging precisely located the branches arising from the dome of aneurysms which DSA could not. INTERPRETATION: Wall imaging of complex or small cerebral aneurysms provided valuable information on their relationships to associated arteries and surrounding bony structures. The endoscopic mode, a simple modification of surface rendering, is easily available in commercial CT processing packages.


Subject(s)
Angioscopy , Carotid Arteries/diagnostic imaging , Cerebral Angiography/methods , Cerebral Arteries/diagnostic imaging , Image Processing, Computer-Assisted , Intracranial Aneurysm/diagnostic imaging , Tomography, X-Ray Computed/methods , Adult , Aged , Aged, 80 and over , Angiography, Digital Subtraction , Carotid Arteries/pathology , Cerebral Arteries/pathology , Diagnosis, Differential , Female , Humans , Intracranial Aneurysm/complications , Male , Middle Aged , Predictive Value of Tests , Subarachnoid Hemorrhage/etiology
9.
Neurol Med Chir (Tokyo) ; 40(9): 472-5, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11021080

ABSTRACT

A 77-year-old female presented with a giant aneurysm of the azygos anterior cerebral artery (ACA) manifesting as acute onset of akinetic mutism caused by enlargement of the aneurysm resulting from rapid thrombus formation within the aneurysmal sac. Thrombus removal to obtain decompression of the aneurysmal bulk and tension was performed before parent artery occlusion to prevent thromboembolic events. The aneurysmal neck was completely clipped with preservation of the parent artery and all branches. This strategy for direct neck clipping of a giant thrombosed distal ACA aneurysm can reduce the possibility of ischemic sequelae.


Subject(s)
Azygos Vein , Intracranial Aneurysm/diagnosis , Aged , Azygos Vein/diagnostic imaging , Azygos Vein/pathology , Azygos Vein/surgery , Cerebral Angiography , Female , Humans , Intracranial Aneurysm/etiology , Intracranial Aneurysm/surgery , Intracranial Thrombosis/complications , Intracranial Thrombosis/diagnosis , Intracranial Thrombosis/surgery , Magnetic Resonance Imaging , Tomography, X-Ray Computed
10.
J Clin Neurosci ; 7 Suppl 1: 33-5, 2000 Sep.
Article in English | MEDLINE | ID: mdl-11013094

ABSTRACT

Complete excision of cerebral arteriovenous malformations (AVMs) is requisite to improving the outcome of patients with AVMs. Five patients with a small or medium cerebral AVM underwent surgery with an intraoperative digital subtraction angiography (DSA) unit. There were no residual AVMs and no complications in the examination of intraoperative DSA. The findings of postoperative angiography were consistent with those of intraoperative DSA. Intraoperative DSA provided the benefits of not only identification of a feeding artery, but also recognition of the complete excision during surgery.


Subject(s)
Angiography, Digital Subtraction , Intracranial Arteriovenous Malformations/surgery , Adolescent , Adult , Aged , Female , Humans , Intracranial Arteriovenous Malformations/diagnostic imaging , Intraoperative Period , Male , Microsurgery , Middle Aged
11.
J Clin Neurosci ; 7(1): 64-6, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10847656

ABSTRACT

A case is reported of a 66 year old woman presenting with perimesencephalic subarachnoid haemorrhage (SAH) which was caused by a spinal dural arteriovenous fistula at the C1 level. The fistula drained into the venous system of the posterior cranial fossa through a perimedullary vein. The bleeding was thought to result from venous hypertension induced by the fistula. This case may support the hypothesis that perimesencephalic non-aneurysmal SAH can be ascribed to venous bleeding and that venous hypertension is the key to its pathology.


Subject(s)
Arteriovenous Fistula/complications , Headache/etiology , Mesencephalon , Spinal Cord/blood supply , Subarachnoid Hemorrhage/etiology , Aged , Arteriovenous Fistula/surgery , Cervical Vertebrae , Exercise , Female , Humans , Mesencephalon/surgery , Spinal Cord/surgery , Subarachnoid Hemorrhage/surgery
12.
J Neurosurg ; 92(2): 278-83, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10659015

ABSTRACT

OBJECT: Patients with subarachnoid hemorrhage (SAH) in whom angiography does not demonstrate diagnostic findings sometimes suffer recurrent disease and actually harbor undetected cerebral aneurysms. The management strategy for such cases remains controversial, but technological advances in spiral computerized tomography (CT) angiography are changing the picture. The purpose of this prospective study was to examine how spiral CT angiography can contribute to the detection of cerebral aneurysms that cannot be visualized on angiography. METHODS: In 134 consecutive patients with SAH, a prospective search for the source of bleeding was performed using digital subtraction (DS) and spiral CT angiography. In 21 patients in whom initial DS angiography yielded no diagnostic findings, spiral CT angiography was performed within 3 days. Patients in whom CT angiography provided no diagnostic results underwent second and third DS angiography sessions after approximately 2 weeks and 6 months, respectively. Six patients with perimesencephalic SAH were included in the 21 cases. Six of the other 15 patients had small cerebral aneurysms detectable by spiral CT angiography, five involving the anterior communicating artery and one the middle cerebral artery. Two patients in whom initial angiograms did not demonstrate diagnostic findings proved to have a ruptured dissecting aneurysm of the vertebral artery; in one case this was revealed at autopsy and in the other during the second DS angiography session. A third DS angiography session revealed no diagnostic results in 13 patients. CONCLUSIONS: Spiral CT angiography was useful in the detection of cerebral aneurysms in patients with SAH in whom angiography revealed no diagnostic findings. Anterior communicating artery aneurysms are generally well hidden in these types of SAH cases. A repeated angiography session was warranted in patients with nonperimesencephalic SAH and in whom initial angiography revealed no diagnostic findings, although a third session was thought to be superfluous.


Subject(s)
Angiography, Digital Subtraction , Cerebral Angiography , Image Processing, Computer-Assisted , Intracranial Aneurysm/diagnostic imaging , Subarachnoid Hemorrhage/diagnostic imaging , Tomography, X-Ray Computed , Adult , Aged , Female , Humans , Intracranial Aneurysm/surgery , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Prognosis , Prospective Studies , Sensitivity and Specificity , Subarachnoid Hemorrhage/surgery , Surgical Instruments
13.
Neurol Med Chir (Tokyo) ; 39(6): 442-6, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10396119

ABSTRACT

Two rare cases of intracranial dissecting aneurysms of the anterior circulation associated with subarachnoid hemorrhage (SAH) are described. A 56-year-old female presented with a dissecting aneurysm in the proximal segment of the left middle cerebral artery. Proximal occlusion of the affected artery and a superficial temporal artery-middle cerebral artery anastomosis were performed, but the outcome was poor. A 61-year-old male presented with a dissecting aneurysm in the proximal segment of the left anterior cerebral artery. Clipping was enhanced by a piece of fascia lata, allowing patency of the affected artery with a satisfactory outcome. Dissecting aneurysm of the carotid system should be considered in a patient with SAH but no evidence of berry aneurysm.


Subject(s)
Aortic Dissection/diagnosis , Aortic Dissection/surgery , Intracranial Aneurysm/diagnosis , Intracranial Aneurysm/surgery , Subarachnoid Hemorrhage/diagnosis , Anastomosis, Surgical/methods , Cerebral Angiography , Female , Humans , Male , Middle Aged , Treatment Outcome
14.
J Neurosurg ; 90(3): 563-6, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10067931

ABSTRACT

This 62-year-old woman presented with clumsiness in her right hand. Magnetic resonance imaging demonstrated a small lesion mimicking a meningioma, which had arisen from the tentorium and contained notable edema. Full recovery was achieved by total removal of the lesion, which was diagnosed as a lymphoid mass resembling giant lymph node hyperplasia on histological examination. The lack of notable findings on whole-body and laboratory studies was compatible with a rare case of intracranial Castleman's disease of solitary form. The authors document clinical, neuroradiological, and pathological features of this rare disease.


Subject(s)
Brain Diseases/diagnosis , Brain Diseases/surgery , Castleman Disease/diagnosis , Castleman Disease/surgery , Brain Diseases/pathology , Castleman Disease/pathology , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Magnetic Resonance Imaging , Meningeal Neoplasms/diagnosis , Meningioma/diagnosis , Middle Aged
15.
Jpn Heart J ; 33(5): 693-705, 1992 Sep.
Article in English | MEDLINE | ID: mdl-1289599

ABSTRACT

The purpose of this study was to investigate the cellular distribution of carnitine and its acyl derivatives in the normal and ischemic myocardium, and the effects of exogenous 1-carnitine on this distribution and mitochondrial function in the ischemic dog heart. Under non-ischemic conditions, about 93% of the total cellular carnitine was located in the cytosolic compartment and 6.5% in the mitochondrial compartment. Sixty minutes of ischemia induced a decrease in the cytosolic free carnitine content, but caused the accumulation of long-chain acylcarnitine in the cytosolic and mitochondrial compartments. Treatment with 1-carnitine (30 or 100 mg/kg, i.v.) inhibited the mitochondrial accumulation of long-chain acylcarnitine. Free fatty acid (FFA) metabolism in the mitochondria differs from that in the cytosol. So, it is necessary to investigate the changes in FFA metabolism in both of these cellular compartments. Our results suggest that 1-carnitine has a protective effect on the ischemic heart by selectively reducing mitochondrial accumulation of long-chain acylcarnitine.


Subject(s)
Carnitine/metabolism , Carnitine/pharmacology , Myocardial Ischemia/drug therapy , Myocardium/metabolism , Acylation , Animals , Cytosol/metabolism , Dogs , Fatty Acids, Nonesterified/metabolism , Male , Mitochondria, Heart/drug effects , Mitochondria, Heart/physiology , Myocardial Ischemia/metabolism
16.
Digestion ; 49(3): 175-84, 1991.
Article in English | MEDLINE | ID: mdl-1769433

ABSTRACT

The relationship of gastric hypermotility to mucosal hemodynamics, lipid peroxidation and vascular permeability changes was investigated in the pathogenesis of indomethacin-induced gastric lesions in rats. Subcutaneous administration of indomethacin (25 mg/kg) produced an increase in both the amplitude and frequency of stomach contraction from 30 min after treatment, resulting in hemorrhagic damage 2 h later. Gastric mucosal blood flow measured by a Laser flowmetry showed oscillatory fluctuations under hypercontractile states: a decrease during contraction followed by an increase during relaxation. Mucosal lipid peroxidation and vascular permeability were significantly increased with time after indomethacin treatment, and these changes preceded the appearance of hemorrhagic damage. All these events were prevented when gastric hypermotility was inhibited by atropine or 16,16-dimethyl prostaglandin E2. Pretreatment of the animals with allopurinol and hydroxyurea or continuous infusion of superoxide dismutase and dimethyl sulfoxide during a test period also attenuated these functional changes and mucosal lesions induced by indomethacin, without affecting the motility response. We conclude that oxygen free radicals may play a role in the development of mucosal lesions associated with gastric hypermotility in indomethacin-treated rats.


Subject(s)
Gastrointestinal Motility , Indomethacin/toxicity , Lipid Peroxidation , Stomach Ulcer/physiopathology , 16,16-Dimethylprostaglandin E2/pharmacology , Animals , Atropine/pharmacology , Capillary Permeability/drug effects , Free Radicals , Gastric Mucosa/blood supply , Gastric Mucosa/metabolism , Gastrointestinal Motility/drug effects , Lipid Peroxidation/drug effects , Male , Rats , Rats, Inbred Strains , Regional Blood Flow/drug effects , Stomach Ulcer/chemically induced , Stomach Ulcer/metabolism
17.
Yakugaku Zasshi ; 110(3): 225-34, 1990 Mar.
Article in Japanese | MEDLINE | ID: mdl-2374095

ABSTRACT

The effects of levocarnitine chloride [LC-80, (-)-(R)-(3-carboxy-2-hydroxypropyl)-trimethylammonium chloride] on the oxidation of [U-14C]palmitate, [U-14C]glucose and [2-3H]glucose under hypoxic conditions in homogenates from the rat heart were investigated. LC-80 at concentrations of 0.5 and 1.0 mM caused significant and concentration-dependent increases in the depressed 14CO2 production from [U-14C]palmitate or [U-14C]-glucose oxidation under hypoxia up to 50 min after the addition of LC-80. In contrast, a marked increase in 3H2O production from [2-3H]glucose oxidation under hypoxia was observed, and LC-80 at concentrations of 0.5 and 1.0 mM caused further significant and concentration-dependent enhancement of 3H2O production up to 50 min after the addition of LC-80. Moreover, LC-80 at a concentrations of 1.0 mM significantly restored the marked depression of pyruvate dehydrogenase complex activity and mitochondrial respiratory function under hypoxia. These results suggested that LC-80 has an improving effect on myocardial metabolism under ischemia by enhancing fatty acid and glucose metabolisms.


Subject(s)
Carnitine/pharmacology , Fatty Acids/metabolism , Glucose/metabolism , Hypoxia/metabolism , Mitochondria, Heart/metabolism , Myocardium/metabolism , Animals , In Vitro Techniques , Male , Oxidation-Reduction , Oxygen Consumption/drug effects , Rats , Rats, Inbred Strains
18.
Am J Cardiovasc Pathol ; 3(2): 131-42, 1990.
Article in English | MEDLINE | ID: mdl-2264986

ABSTRACT

To elucidate 1-carnitine chloride effects ischemic myocardium for the possibility of a salvage of risk zone around necrosis in myocardial infarcts of dogs, a quantitative evaluation of the extent of myocardial infarcts was done by size detection with use of monastral blue and tissue dehydrogenase histochemistry at 20 hours after coronary ligation. The results show that the ratio of unsalvaged infarct zone to occluded coronary bed is 85.3 +/- 2.9% in the control group, while it is 53.2 +/- 3.6% in the 1-carnitine administered (1 C) group. The difference between these ratios is statistically significant (p less than 0.01). The results also indicate significantly lower serum CPK concentration. Therefore, carnitine may play a role in preventing a size extention of infarcts through improving an altered lipid metabolism, particularly a fatty acid metabolism, of myocardial cells in the risk zone.


Subject(s)
Carnitine/therapeutic use , Myocardial Infarction/drug therapy , Myocardium/pathology , Animals , Creatine Kinase/blood , Dogs , Electrocardiography , Fatty Acids, Nonesterified/blood , Female , Male , Microscopy, Electron , Myocardial Infarction/blood , Myocardial Infarction/pathology
19.
Res Commun Chem Pathol Pharmacol ; 66(2): 179-90, 1989 Nov.
Article in English | MEDLINE | ID: mdl-2602654

ABSTRACT

We examined in isolated superfused guinea-pig papillary muscle whether palmitoylcarnitine caused electrophysiological derangements similar to those caused by anoxia, and whether l-carnitine was similarly effective in improving membrane potential characteristics in both cases. Superfusion with Krebs-Henseleit solution containing 3 x 10(-4) M palmitoylcarnitine for 30 min caused gradual reduction of resting membrane potential and amplitude of action potential, and marked shortenings of the duration of action potential and absolute refractory period. On the other hand, aeration with 95%N2-5%CO2 for 30 min caused the same electrophysiological changes as those caused by palmitoylcarnitine. In both deteriorated preparations with palmitoylcarnitine superfusion and with 95%N2-5%CO2 aeration, l-carnitine (3 x 10(-3) M) prevented the papillary muscle from these derangements and restored the membrane potential at 10(-2) and 3 x 10(-2) M. It is concluded from these results that acylcarnitines such as palmitoylcarnitine, the accumulation of which has been thought to inhibit oxidative phosphorylation in ischemic heart, induce electrophysiological derangements quite similar to those found under anoxia, and that the application of l-carnitine is an effective solution to improve the electrophysiological derangements.


Subject(s)
Carnitine/analogs & derivatives , Carnitine/pharmacology , Cell Hypoxia/physiology , Heart/physiology , Palmitoylcarnitine/pharmacology , Animals , Electrophysiology , Guinea Pigs , In Vitro Techniques , Male , Membrane Potentials/drug effects , Papillary Muscles/drug effects , Papillary Muscles/physiology
20.
Nihon Yakurigaku Zasshi ; 93(5): 305-14, 1989 May.
Article in Japanese | MEDLINE | ID: mdl-2744657

ABSTRACT

The beneficial effect of LC-80 in the therapy for organic acidemias, especially propionic acidemia and methylmalonic acidemia, was compared with those of its optical isomers, d-carnitine chloride (d-isomer) and dl-carnitine chloride (dl-isomer) in rat liver mitochondria. LC-80 at concentrations of 5 and 10 mM did not inhibit the mitochondrial function, while the d-isomer at a concentration of 5 mM significantly reduced the respiratory control ratio (RCR) of mitochondria. In addition, the dl-isomer at concentrations of 10 and 20 mM also significantly reduced RCR in a concentration-dependent manner. Thus, it seems likely that the d-isomer inhibits the mitochondrial function. On the other hand, the inhibition of mitochondrial function induced by a preincubation with propionate (4.76 mM) was significantly reversed by LC-80 (5 and 10 mM) in a concentration-dependent manner, while the d-isomer (5 mM) had no effect on the inhibitory effect of propionate. Moreover, although the dl-isomer (10 and 20 mM) significantly reversed the inhibitory effect of propionate as compared with the d-isomer, its effect was significantly weaker as compared with the effect of LC-80. The substrate specificity of rat liver mitochondrial carnitine acetyltransferase (CAT) was more potent with propionyl CoA than with acetyl CoA. Kinetic studies indicate that the d-isomer is a competitive inhibitor of CAT. These results suggest that LC-80 is useful in the clinical treatment of organic acidemias, whereas the d-isomer has a harmful effect in clinical application.


Subject(s)
Amino Acid Metabolism, Inborn Errors/drug therapy , Carnitine/therapeutic use , Malonates/blood , Methylmalonic Acid/blood , Mitochondria, Liver/physiology , Oxygen Consumption/drug effects , Propionates/blood , Animals , Carnitine/pharmacology , Drug Evaluation, Preclinical , Isomerism , Rats , Rats, Inbred Strains , Structure-Activity Relationship
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