Eun Shin Lee

Lamotrigine inhibits TRESK regulated by G-protein coupled receptor agonists.

Dorsal root ganglion (DRG) neurons express mRNAs for numerous two-pore domain K(+) (K(2P)) channels and G-protein coupled receptors (GPCR). Recent studies have shown that TRESK is a major background K(+) channel in DRG neurons. Here, we demonstrate the pharmacological properties of TRESK, including GPCR agonist-induced effects on DRG neurons. TRESK mRNA was highly expressed in DRG compared to brain and spinal cord. Similar to cloned TRESK, native TRESK was inhibited by acid and arachidonic acid (AA), but not zinc. Native TRESK was also activated by GPCR agonists such as acetylcholine, glutamate, and histamine. The glutamate-activated TRESK was blocked by lamotrigine in DRG neurons. In COS-7 cells transfected with mouse TRESK, 30 microM lamotrigine inhibited TRESK by approximately 50%. Since TRESK is target of modulation by acid, AA, GPCR agonists, and lamotrigine, it is likely to play an active role in the regulation of excitability in DRG neurons.

Causative factors affecting peripheral neuropathy in burn patients

Peripheral neuropathy in burn patients may be frequently missed in clinical settings. Although its incidence has been reported, little is known regarding the factors that cause burn-related peripheral neuropathy. A retrospective chart review of the demographic and clinical characteristics of patients admitted to a university hospital based burn center was conducted to explore the characteristics of burn-related neuropathy and factors affecting its types or extent. The variables collected were gender, age, length of hospital stay, site and surface area of burn, type of burn, and electrodiagnostic findings. We found that flame injuries, and third degree injuries were the most common in patients with peripheral neuropathy. Axonotmesis was more common than demyelinating injury and polyneuropathy was more common than mononeuropathy. Higher degree and larger area burns were more frequently associated with axonotmesis than with demyelination. Length of hospital stay was significantly longer in patients with axonotmesis. Overall, more severe burns showed a significant association with axonotmesis and a tendency to be related to polyneuropathy.

The Effect of Extracorporeal Shock Wave Therapy on Lower Limb Spasticity in Subacute Stroke Patients

Objective To evaluate the effect of extracorporeal shock wave therapy (ESWT) on lower limb spasticity in subacute stroke patients. Methods We studied thirty hemiplegic subacute stroke patients with ankle plantar flexor spasticity. ESWT was applied for 1 session/week, with a total of 3 sessions at the musculotendinous junction of medial and lateral gastrocnemius muscles. Patients were evaluated both clinically and biomechanically at baseline, after sham stimulation, and at immediately 1 week and 4 weeks after ESWT. For clinical assessment, Modified Ashworth Scale (MAS), clonus score, passive range of motion of ankle, and Fugl-Myer Assessment for the lower extremity were used. A biomechanical assessment of spasticity was conducted by an isokinetic dynamometer. Two parameters, peak eccentric torque (PET) and torque threshold angle (TTA), were analyzed at the velocities of 60°/sec, 180°/sec, and 240°/sec. Results After sham stimulation, there were no significant changes between each assessment. MAS and PET (180°/sec and 240°/sec) were significantly improved immediately and 1 week after ESWT. However, these changes were not significant at 4 weeks after ESWT. PET (60°/sec) and TTA (60°/sec, 180°/sec, and 240°/sec) were significantly improved immediately after ESWT. Yet, these changes were not significant at 1 week and 4 weeks after ESWT as well. Conclusion Lower limb spasticity in subacute stroke patients was significantly improved immediately after ESWT. Although the therapeutic effect of ESWT reduced with time and therefore was not significant at 4 weeks after ESWT, the degree of spasticity was lower than that of the baseline. Future studies with a larger sample of patients are warranted in order to verify the protocols which can optimize the effect of ESWT on spasticity.

Administration of mesenchymal stem cells and ziprasidone enhanced amelioration of ischemic brain damage in rats

Ziprasidone is a benzisothiazolyl piperazine derivative that was developed from the chemically related antipsychotic drug tiospirone, and it improves neurological functions of the ischemic brain and is effective in treatment of schizophrenia. Mesenchymal stem cells (MSCs) are considered as a leading candidate for neurological regenerative therapy because of their neural differentiation properties in damaged brain. We investigated whether the transplantation of neural progenitor cells (NPCs) derived from adipose mesenchymal stem cells combined with ziprasidone enhances neuroprotective effects in an animal model of focal cerebral ischemia. In combination therapy groups, significant reduction of infarct volume and improvement of neurological functions were observed at 3 days after middle cerebral artery occlusion (MCAO) compared with monotherapy. Co-administration of ziprasidone and NPCs enhanced the anti-apoptotic effect and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with the NPCs alone group at 7 days after MCAO. Ziprasidone or the combination of ziprasidone and NPCs induced the expression of endogenous neurotrophic factor gene brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell-derived neurotrophic factor (GDNF). The immunohistochemical investigation revealed that the ziprasidone and NPCs attenuated the increased intensity of microglial marker (Iba-1) in the infarcted cortical area. Moreover, the number of transplanted NPCs on day 7 with combination therapy was significantly higher than with NPCs alone. These effects might be responsible for improved functional behavior and increased survival of NPCs. Our finding indicates that combination therapy of ziprasidone and NPCs enhances neuroprotection against ischemic brain injury.

Diffusion-Weighted MR Imaging of Unusual White Matter Lesion in a Patient with Menkes Disease

We report here on the diffusion-weighted imaging of unusual white matter lesions in a case of Menkes disease. On the initial MR imaging, the white matter lesions were localized in the deep periventricular white matter in the absence of diffuse cortical atrophy. The lesion showed diffuse high signal on the diffusion-weighted images and diffuse progression and persistent hyperintensity on the follow up imaging. Our case suggests that the white matter lesion may precede diffuse cortical atrophy in a patient with Menkes disease.

Reliability of the Pinch Strength with Digitalized Pinch Dynamometer

Objective To examine the intra-rater, inter-rater, and inter-instrumental reliability of the digitalized pinch muscle strength dynamometer. Method Thirty normal subjects were examined for pinch strength, using both the Preston pinch gauge and the digitalized pinch dynamometer. The participants performed all pinch strength tests in the seated position as recommended by the American Society of Hand Therapists (ASHT). Three successive measurements were taken for each hand. The mean of the three trials was used for data analysis. The pinch strength tests performed used a repeated measure design and measurements were taken by each rater. Results The relationship between the Preston pinch gauge and the digitalized pinch dynamometer in pinch strength was reliable (the ICC were 0.821 and 0.785 in rater 1 and rater 2 respectively). The relationship between the first session and second session in pinch strength using the digitalized pinch dynamometer was reliable (the ICC were 0.872 and 0.886 in rater A and rater B respectively). The relationship between rater A and rater B in pinch strength using the digitalized pinch dynamometer was reliable (the ICC was 0.754). Conclusion The pinch strength measurement using the digitalized pinch dynamometer is reliable within the rater and between raters. Thus, the Preston pinch gauge and the digitalized dynamometer measure grip strength equivalently, and can be used interchangeably.

The Availability of Radiological Measurement of Tibial Torsion: Three-Dimensional Computed Tomography Reconstruction

Objective To assess the intra-rater and inter-rater reliability for measuring tibial torsion measurements by a radiographic method using three-dimensional computed tomography reconstruction (3D-CT) and to compare the physical measures to those of 3D-CT. Method The study included 33 children who presented with intoeing gait. Tibial torsion was measured by 3D-CT. Distal reference point was the bimalleolar axis. Proximal reference points were the transtibial axis and posterior condylar axis. Physical measurements included thigh-foot angle (TFA) and bimalleolar angle (BMA). 3D-CT measurement and physical measurement were performed twice at both lower extremities by each rater. The intra-rater and inter-rater reliability were calculated by intraclass correlation coefficiency (ICC). The relationship between radiological and physical examination was calculated by Spearman correlation coefficient. Results The 3D-CT measures for tibial torsion were reliable within individual raters and between different raters. However, physical measures for tibial torsion were reliable within an individual rater but not reliable between raters. The 3D-CT measures by any proximal reference axis were more reliable within a rater and between raters than physical measurements. There was no significant impact introduced by the selection of the proximal reference axis. The correlation coefficiency between 3D-CT and physical measurement methods was low. Conclusion Because the 3D-CT measurements for tibial torsion are more reliable than physical measurements, we recommend that accurate diagnosis of internal tibial torsion should be detected by using 3D-CT measurements. Also, considering the disadvantages of radiological measurements, physical measurement may be used for short term follow-up by same raters, as intra-rater reliability is relatively good.

Single-Channel Recording of TASK-3-like K + Channel and Up- Regulation of TASK-3 mRNA Expression after Spinal Cord Injury in Rat Dorsal Root Ganglion Neurons

Single-channel recordings of TASK-1 and TASK-3, members of two-pore domain K(+) channel family, have not yet been reported in dorsal root ganglion (DRG) neurons, even though their mRNA and activity in whole-cell currents have been detected in these neurons. Here, we report single-channel kinetics of the TASK-3-like K(+) channel in DRG neurons and up-regulation of TASK-3 mRNA expression in tissues isolated from animals with spinal cord injury (SCI). In DRG neurons, the single-channel conductance of TASK-3-like K(+) channel was 33.0+/-0.1 pS at -60 mV, and TASK-3 activity fell by 65+/-5% when the extracellular pH was changed from 7.3 to 6.3, indicating that the DRG K(+) channel is similar to cloned TASK-3 channel. TASK-3 mRNA and protein levels in brain, spinal cord, and DRG were significantly higher in injured animals than in sham-operated ones. These results indicate that TASK-3 channels are expressed and functional in DRG neurons and the expression level is up-regulated following SCI, and suggest that TASK-3 channel could act as a potential background K(+) channel under SCI-induced acidic condition.

Neonatal Late-onset Hypocalcemia: Is There Any Relationship with Maternal Hypovitaminosis D?

Purpose Neonatal late-onset hypocalcemia is defined as hypocalcemia developed after postnatal 3 days and associated with hypoparathyroidism, high phosphate diets and vitamin D deficiency. We experienced the increment of neonatal late onset hypocalcemia over 1 year. We tried to evaluate the relationship between late onset hypocalcemia and maternal hypovitaminosis D. Methods The medical records in the neonates with late-onset hypocalcemia during January 2007 to July 2008 were retrospectively reviewed. Among those patients, 17 paired sera of mothers and neonates had collected. The levels of 25-OH vitamin D (25OHD) and intact parathyroid hormone (iPTH) were measured and were compared with neonate and the mother. Results The mean gestational age was 38+1 weeks, and the mean body weight was 2,980 g. The onset time of hypocalcemia was 5.9 days of age. Most of them (88.2%) were feeding with formula and no one was only breast milk feeding. Of the 17 patients, 13 were born in spring or in winter. The median levels of calcium, phosphorus, alkaline phosphatase, iPTH and 25OHD were 7.0 mg/dL, 8.6 mg/dL, 191.0 U/L, 57.2 pg/mL and 24.0 ng/mL in neonates. The levels of 25OHD of 6 neonates were <20 ng/mL. A total of 16 mothers were considered vitamin D-deficient (<20 ng/mL), and vitamin D insufficient (20<25OHD<30 ng/mL). Conclusion Neonatal late-onset hypocalcemia in our study seems to be influenced by maternal vitamin D deficiency and insufficiency. Sun tanning and vitamin D supplements from winter to spring would be helpful to prevent maternal vitamin D deficiency, one of the causes of neonatal late-onset hypocalcemia.

Lamotrigine increases intracellular Ca2+ levels and Ca2+/calmodulin-dependent kinase II activation in mouse dorsal root ganglion neurones

Lamotrigine is a neuroprotective agent that is used clinically for the treatment of seizures and neuropathic pain. A significant volume of literature has reported that lamotrigine exerts analgesic effect by blocking Ca2+ channels. However, little is known regarding the effect of lamotrigine on the intracellular Ca2+ concentration ([Ca2+]i). The aim of this study was to determine whether lamotrigine modulates [Ca2+]i in sensory neurones.