Publications by authors named "In Sun Choi"

46 Publications

Instant, multiscale dry transfer printing by atomic diffusion control at heterogeneous interfaces.

Sci Adv 2021 Jul 9;7(28). Epub 2021 Jul 9.

Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology, Daegu 42988, South Korea.

Transfer printing is a technique that integrates heterogeneous materials by readily retrieving functional elements from a grown substrate and subsequently printing them onto a specific target site. These strategies are broadly exploited to construct heterogeneously integrated electronic devices. A typical wet transfer printing method exhibits limitations related to unwanted displacement and shape distortion of the device due to uncontrollable fluid movement and slow chemical diffusion. In this study, a dry transfer printing technique that allows reliable and instant release of devices by exploiting the thermal expansion mismatch between adjacent materials is demonstrated, and computational studies are conducted to investigate the fundamental mechanisms of the dry transfer printing process. Extensive exemplary demonstrations of multiscale, sequential wet-dry, circuit-level, and biological topography-based transfer printing demonstrate the potential of this technique for many other emerging applications in modern electronics that have not been achieved through conventional wet transfer printing over the past few decades.
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http://dx.doi.org/10.1126/sciadv.abh0040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270493PMC
July 2021

Astrocytes in the Ventrolateral Preoptic Area Promote Sleep.

J Neurosci 2020 11 16;40(47):8994-9011. Epub 2020 Oct 16.

Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea

Although ventrolateral preoptic (VLPO) nucleus is regarded as a center for sleep promotion, the exact mechanisms underlying the sleep regulation are unknown. Here, we used optogenetic tools to identify the key roles of VLPO astrocytes in sleep promotion. Optogenetic stimulation of VLPO astrocytes increased sleep duration in the active phase in naturally sleep-waking adult male rats ( = 6); it also increased the extracellular ATP concentration ( = 3) and c-Fos expression ( = 3-4) in neurons within the VLPO. microdialysis analyses revealed an increase in the activity of VLPO astrocytes and ATP levels during sleep states ( = 4). Moreover, metabolic inhibition of VLPO astrocytes reduced ATP levels ( = 4) and diminished sleep duration ( = 4). We further show that tissue-nonspecific alkaline phosphatase (TNAP), an ATP-degrading enzyme, plays a key role in mediating the somnogenic effects of ATP released from astrocytes ( = 5). An appropriate sample size for all experiments was based on statistical power calculations. Our results, taken together, indicate that astrocyte-derived ATP may be hydrolyzed into adenosine by TNAP, which may in turn act on VLPO neurons to promote sleep. Glia have recently been at the forefront of neuroscience research. Emerging evidence illustrates that astrocytes, the most abundant glial cell type, are the functional determinants for fates of neurons and other glial cells in the central nervous system. In this study, we newly identified the pivotal role of hypothalamic ventrolateral preoptic (VLPO) astrocytes in the sleep regulation, and provide novel insights into the mechanisms underlying the astrocyte-mediated sleep regulation.
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http://dx.doi.org/10.1523/JNEUROSCI.1486-20.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673007PMC
November 2020

Menthol facilitates excitatory and inhibitory synaptic transmission in rat medullary dorsal horn neurons.

Brain Res 2021 01 6;1750:147149. Epub 2020 Oct 6.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 41940, Republic of Korea. Electronic address:

Menthol, which acts as an agonist for transient receptor potential melastatin 8 (TRPM8), has complex effects on nociceptive transmission, including pain relief and hyperalgesia. Here, we addressed the effects of menthol on spontaneous excitatory and inhibitory postsynaptic currents (sEPSCs and sIPSCs, respectively) in medullary dorsal horn neurons, using a whole-cell patch-clamp technique. Menthol significantly increased sEPSC frequency, in a concentration-dependent manner, without affecting current amplitudes. The menthol-induced increase in sEPSC frequency could be completely blocked by AMTB, a TRPM8 antagonist, but was not blocked by HC-030031, a transient receptor potential ankyrin 1 (TRPA1) antagonist. Menthol still increased sEPSC frequency in the presence of Cd, a general voltage-gated Ca channel blocker, suggesting that voltage-gated Ca channels are not involved in the menthol-induced increase in sEPSC frequency. However, menthol failed to increase sEPSC frequency in the absence of extracellular Ca, suggesting that TRPM8 on primary afferent terminals is Ca permeable. On the other hand, menthol also increased sIPSC frequency, without affecting current amplitudes. The menthol-induced increase in sIPSC frequency could be completely blocked by either AMTB or CNQX, an AMPA/KA receptor antagonist, suggesting that the indirect increase in excitability of inhibitory interneurons may lead to the facilitation of spontaneous GABA and/or glycine release. The present results suggested that menthol exerts analgesic effects, via the enhancement of inhibitory synaptic transmission, through central feed-forward neural circuits within the medullary dorsal horn region.
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http://dx.doi.org/10.1016/j.brainres.2020.147149DOI Listing
January 2021

Incremental Treatment Costs Attributable to Overweight and Obesity in Patients with Diabetes: Quantile Regression Approach.

Obesity (Silver Spring) 2018 01 27;26(1):223-232. Epub 2017 Nov 27.

College of Pharmacy, Chung-Ang University, Seoul, South Korea.

Objective: This study aimed to estimate treatment costs attributable to overweight and obesity in patients with diabetes who were less than 65 years of age in the United States.

Methods: This study used data from the Medical Expenditure Panel Survey from 2001 to 2013. Patients with diabetes were identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification code (250), clinical classification codes (049 and 050), or self-reported physician diagnoses. Total treatment costs attributable to overweight and obesity were calculated as the differences in the adjusted costs compared with individuals with diabetes and normal weight. Adjusted costs were estimated by using generalized linear models or unconditional quantile regression models.

Results: The mean annual treatment costs attributable to obesity were $1,852 higher than those attributable to normal weight, while costs attributable to overweight were $133 higher. The unconditional quantile regression results indicated that the impact of obesity on total treatment costs gradually became more significant as treatment costs approached the upper quantile.

Conclusions: Among patients with diabetes who were less than 65 years of age, patients with diabetes and obesity have significantly higher treatment costs than patients with diabetes and normal weight. The economic burden of diabetes to society will continue to increase unless more proactive preventive measures are taken to effectively treat patients with overweight or obesity.
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http://dx.doi.org/10.1002/oby.22080DOI Listing
January 2018

Effects of acidic pH on voltage-gated ion channels in rat trigeminal mesencephalic nucleus neurons.

Korean J Physiol Pharmacol 2017 Mar 21;21(2):215-223. Epub 2017 Feb 21.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 41940, Korea.; Brain Science & Engineering Institute, Kyungpook National University, Daegu 41940, Korea.

The effects of acidic pH on several voltage-dependent ion channels, such as voltage-dependent K and Ca channels, and hyperpolarization-gated and cyclic nucleotide-activated cation (HCN) channels, were examined using a whole-cell patch clamp technique on mechanically isolated rat mesencephalic trigeminal nucleus neurons. The application of a pH 6.5 solution had no effect on the peak amplitude of voltage-dependent K currents. A pH 6.0 solution slightly, but significantly inhibited the peak amplitude of voltage-dependent K currents. The pH 6.0 also shifted both the current-voltage and conductance-voltage relationships to the depolarization range. The application of a pH 6.5 solution scarcely affected the peak amplitude of membrane currents mediated by HCN channels, which were profoundly inhibited by the general HCN channel blocker Cs (1 mM). However, the pH 6.0 solution slightly, but significantly inhibited the peak amplitude of HCN-mediated currents. Although the pH 6.0 solution showed complex modulation of the current-voltage and conductance-voltage relationships, the midpoint voltages for the activation of HCN channels were not changed by acidic pH. On the other hand, voltage-dependent Ca channels were significantly inhibited by an acidic pH. The application of an acidic pH solution significantly shifted the current-voltage and conductance-voltage relationships to the depolarization range. The modulation of several voltage-dependent ion channels by an acidic pH might affect the excitability of mesencephalic trigeminal nucleus neurons, and thus physiological functions mediated by the mesencephalic trigeminal nucleus could be affected in acidic pH conditions.
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http://dx.doi.org/10.4196/kjpp.2017.21.2.215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5343055PMC
March 2017

Reversible Induction of Pain Hypersensitivity following Optogenetic Stimulation of Spinal Astrocytes.

Cell Rep 2016 12;17(11):3049-3061

Department of Pharmacology, Brain Science & Engineering Institute, BK21 Plus KNU Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu 41944, Republic of Korea. Electronic address:

While glial activation is an integral part of pain pathogenesis, the existence of a causal relationship between glia and pain processing has yet to be demonstrated in vivo. Here, we have investigated whether the activation of spinal astrocytes could directly evoke pain hypersensitivity in vivo via the use of optogenetic techniques. Optogenetic stimulation of channelrhopdopsin-2 (ChR)-expressing spinal astrocytes induced pain hypersensitivity in a reversible and time-dependent manner, which was accompanied by glial activation, NR1 phosphorylation, ATP release, and the production of proalgesic mediators. Photostimulation of ChR2-expressing astrocytes in culture and spinal slices recapitulated in vivo findings, demonstrating the release of proalgesic mediators and electrophysiological disinhibition of spinal projection neurons. These findings deepen our understanding of the role of astrocytes in pain pathogenesis and provide the scientific basis for an astrocyte-oriented pain treatment.
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http://dx.doi.org/10.1016/j.celrep.2016.11.043DOI Listing
December 2016

Acidic pH modulation of Na+ channels in trigeminal mesencephalic nucleus neurons.

Neuroreport 2016 Dec;27(17):1274-1280

aDepartment of Pharmacology, School of Dentistry bBrain Science and Engineering Institute, Kyungpook National University, Daegu, Republic of Korea.

Cell bodies of trigeminal mesencephalic nucleus (Vmes) neurons are located within the central nervous system, and therefore, peripheral as well as central acidosis can modulate the excitability of Vmes neurons. Here, we report the effect of acidic pH on voltage-gated Na channels in acutely isolated rat Vmes neurons using a conventional whole-cell patch clamp technique. Acidic pH (pH 6.0) slightly but significantly shifted both the activation and steady-state fast inactivation relationships toward depolarized potentials. However, acidic pH (pH 6.0) had a minor effect on the inactivation kinetics of voltage-gated Na channels. Less sensitivity of voltage-gated Na channels to acidic pH may allow Vmes neurons to transduce the precise proprioceptive information even under acidic pH conditions.
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http://dx.doi.org/10.1097/WNR.0000000000000692DOI Listing
December 2016

MicroRNA-205-5p is upregulated in myelodysplastic syndromes and induces cell proliferation via PTEN suppression.

Leuk Res 2016 08 16;47:172-7. Epub 2016 Jun 16.

Department of Laboratory Medicine, Chosun University College of Medicine, Gwangju, Republic of Korea. Electronic address:

Micro (mi)RNA dysregulation is implicated in the development of myelodysplastic syndrome (MDS). Chromosomal abnormalities on 1q are frequently detected in Korean patients with MDS; however, how these are related to disease development is unknown. The present study compared the expression profiles of miRNAs encoded by chromosome 1q between 65 MDS patients and 11 controls. We found that miR-205-5p levels were 12.5 fold higher in the former (P=0.001). miR-205-5p level was increased in 44.7% of patients when an arbitrary 2(-ΔCt) cut-off value of 1.25 was used. miR-205-5p expression data were used to generate a receiver operating characteristic (ROC) curve for miR-205-5p, for which the area under the curve (AUC) was 0.825 (95% confidence interval: 0.710-0.941; P=0.001). Moreover, transfection with a miR-205-5p mimic induced cell proliferation by inhibiting the expression of the tumor suppressor protein phosphatase and tensin homolog (PTEN). Our findings suggest that miR-205-5p upregulation contributes to MDS by suppressing PTEN and that miR-205-5p thus acts as an oncogene in hematopoietic cells.
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http://dx.doi.org/10.1016/j.leukres.2016.06.003DOI Listing
August 2016

Development and Evaluation of Species-Specific PCR for Detection of Nine Acinetobacter Species.

Ann Clin Lab Sci 2016 May;46(3):270-8

Department of Laboratory Medicine, Chosun University Medical School, Gwang-Ju, South Korea.

Molecular methods have the potential to improve the speed and accuracy of Acinetobacter species identification in clinical settings. The goal of this study is to develop species-specific PCR assays based on differences in the RNA polymerase beta-subunit gene (rpoB) to detect nine commonly isolated Acinetobacter species including Acinetobacter baumannii, Acinetobacter calcoaceticus, Acinetobacter pittii, Acinetobacter nosocomialis, Acinetobacter lwoffii, Acinetobacter ursingii, Acinetobacter bereziniae, Acinetobacter haemolyticus, and Acinetobacter schindleri. The sensitivity and specificity of these nine assays were measured using genomic DNA templates from 55 reference strains and from 474 Acinetobacter clinical isolates. The sensitivity of A. baumannii-specific PCR assay was 98.9%, and the sensitivity of species-specific PCR assays for all other species was 100%. The specificities of A. lwoffii- and A. schindleri-specific PCR were 97.8 and 98.9%, respectively. The specificity of species-specific PCR for all other tested Acinetobacter species was 100%. The lower limit of detection for the nine species-specific PCR assays developed in this study was 20 or 200 pg of genomic DNA from type strains of each species. The Acinetobacter species-specific PCR assay would be useful to determine the correct species among suggested candidate Acinetobacter species when conventional methods including MALDI-TOF MS identify Acinetobacter only to the genus level. The species-specific assay can be used to screen large numbers of clinical and environmental samples obtained for epidemiologic study of Acinetobacter for the presence of target species.
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May 2016

In Vitro Interactions of Antibiotic Combinations of Colistin, Tigecycline, and Doripenem Against Extensively Drug-Resistant and Multidrug-Resistant Acinetobacter baumannii.

Ann Lab Med 2016 Mar;36(2):124-30

Department of Laboratory Medicine, College of Medicine, Chosun University, Gwangju, Korea.

Background: Acinetobacter baumannii infections are difficult to treat owing to the emergence of various antibiotic resistant isolates. Because treatment options are limited for multidrug-resistant (MDR) A. baumannii infection, the discovery of new therapies, including combination therapy, is required. We evaluated the synergistic activity of colistin, doripenem, and tigecycline combinations against extensively drug-resistant (XDR) A. baumannii and MDR A. baumannii.

Methods: Time-kill assays were performed for 41 XDR and 28 MDR clinical isolates of A. baumannii by using colistin, doripenem, and tigecycline combinations. Concentrations representative of clinically achievable levels (colistin 2 μg/mL, doripenem 8 μg/mL) and achievable tissue levels (tigecycline 2 μg/mL) for each antibiotic were used in this study.

Results: The colistin-doripenem combination displayed the highest rate of synergy (53.6%) and bactericidal activity (75.4%) in 69 clinical isolates of A. baumannii. Among them, the-doripenem-tigecycline combination showed the lowest rate of synergy (14.5%) and bactericidal activity (24.6%). The doripenem-tigecycline combination showed a higher antagonistic interaction (5.8%) compared with the colistin-tigecycline (1.4%) combination. No antagonism was observed for the colistin-doripenem combination.

Conclusions: The colistin-doripenem combination is supported in vitro by the high rate of synergy and bactericidal activity and lack of antagonistic reaction in XDR and MDR A. baumannii. It seems to be necessary to perform synergy tests to determine the appropriate combination therapy considering the antagonistic reaction found in several isolates against the doripenem-tigecycline and colistin-tigecycline combinations. These findings should be further examined in clinical studies.
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http://dx.doi.org/10.3343/alm.2016.36.2.124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4713845PMC
March 2016

Proton-induced currents in substantia gelatinosa neurons of the rat trigeminal subnucleus caudalis.

Eur J Pharmacol 2015 Sep 9;762:18-25. Epub 2015 May 9.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea. Electronic address:

Acid-sensing ion channels (ASICs) are widely expressed in both the peripheral and central nervous system, and contribute to the modulation of central nociceptive transmission under both physiological and pathophysiological conditions. In this study, we characterized the proton-induced membrane currents in acutely isolated rat substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis using the whole cell patch-clamp technique. Exposure to acidic conditions (pH<6.5) induced the inward currents in a pH-dependent manner. Amiloride, a general ASIC antagonist, significantly blocked the proton-induced currents in a non-competitive manner. The pH 6.0-induced membrane current (IpH6.0) was greatly attenuated in the Na(+)-free external solution, and the reversal potential of the proton-induced currents was similar to the theoretical Na(+) equilibrium potential. The IpH6.0 was reciprocally potentiated by a lower extracellular Ca(2+) concentration. The modulation of IpH6.0 by divalent cations and other modulators suggests that the proton-induced currents are mediated by multiple types of ASIC subunits, including ASIC1a and ASIC2a. Multi-cell RT-PCR analysis revealed that SG neurons express these subunits. Exposure to a pH 6.0 solution directly depolarized the membrane potential, and generated a burst of action potentials in a current-clamp mode. This acidic pH-induced depolarization was significantly blocked by amiloride. The present results suggest that ASICs expressed on SG neurons play important roles in the regulation of nociceptive transmission from the orofacial tissues.
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http://dx.doi.org/10.1016/j.ejphar.2015.04.052DOI Listing
September 2015

Contribution of persistent sodium currents to the excitability of tonic firing substantia gelatinosa neurons of the rat.

Neurosci Lett 2015 Mar 19;591:192-196. Epub 2015 Feb 19.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea. Electronic address:

The roles of persistent Na(+) currents (INaP) in intrinsic membrane properties were examined in rat substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis using a conventional whole-cell patch clamp technique. In a voltage-clamp mode, riluzole inhibited the slow voltage ramp-induced INaP but had little effect on the peak amplitude of transient Na(+) currents in SG neurons. In a current-clamp mode, most SG neurons exhibited spontaneous action potentials and tonic firing pattern. Riluzole reduced both spontaneous and elicited action potentials in a concentration-dependent manner. The present results suggest that the riluzole-sensitive INaP plays an important role in the excitability of SG neurons and are thus, likely to contribute to the modulation of nociceptive transmission from the orofacial tissues.
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http://dx.doi.org/10.1016/j.neulet.2015.02.039DOI Listing
March 2015

Enzymatic conversion of ATP to adenosine contributes to ATP-induced inhibition of glutamate release in rat medullary dorsal horn neurons.

Neuropharmacology 2015 Jun 3;93:94-102. Epub 2015 Feb 3.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea. Electronic address:

Purine nucleotides, such as ATP and ADP, activate ionotropic P2X and metabotropic P2Y receptors to regulate neurotransmitter release in the peripheral as well as central nervous system. Here we report another type of ATP-induced presynaptic modulation of glutamate release in rat medullary dorsal horn neurons. Glutamatergic excitatory postsynaptic currents (EPSCs) induced by electrical stimulation of trigeminal tract were recorded from horizontal brain stem slices using a whole-cell patch clamp technique. ATP decreased the amplitude of glutamatergic EPSCs in a reversible and concentration dependent manner and increased the paired-pulse ratio. In addition, ATP reduced the frequency of miniature EPSCs without affecting the current amplitude, suggesting that ATP acts presynaptically to reduce the probability of glutamate release. The ATP-induced decrease in glutamatergic EPSCs was not affected by P2X and P2Y receptor antagonists, but was completely blocked by DPCPX, a selective adenosine A1 receptor antagonist. The ATP-induced decrease in glutamatergic EPSCs was also inhibited by an inhibitor of tissue nonspecific alkaline phosphatase but not by inhibitors of other enzymes such as ecto-nucleoside triphosphate diphosphohydrolases and ecto-5'-nucleotidases. The results suggest that exogenously applied purine nucleotides are rapidly converted to adenosine by specific enzymes, and subsequently act on presynaptic A1 receptors to inhibit glutamate release from primary afferent terminals. This type of modulation mediated by purine nucleotides may play an important role in regulating nociceptive transmission from orofacial tissues.
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http://dx.doi.org/10.1016/j.neuropharm.2015.01.020DOI Listing
June 2015

Cholinergic modulation of primary afferent glutamatergic transmission in rat medullary dorsal horn neurons.

Neuropharmacology 2013 Dec 13;75:295-303. Epub 2013 Aug 13.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea. Electronic address:

Although muscarinic acetylcholine (mACh) receptors are expressed in trigeminal ganglia, it is still unknown whether mACh receptors modulate glutamatergic transmission from primary afferents onto medullary dorsal horn neurons. In this study, we have addressed the cholinergic modulation of primary afferent glutamatergic transmission using a conventional whole cell patch clamp technique. Glutamatergic excitatory postsynaptic currents (EPSCs) were evoked from primary afferents by electrical stimulation of trigeminal tract and monosynaptic EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices. Muscarine and ACh reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, muscarine reduced the frequency of miniature EPSCs without affecting the current amplitude, suggesting that muscarine acts presynaptically to decrease the probability of glutamate release onto medullary dorsal horn neurons. The muscarine-induced decrease of glutamatergic EPSCs was significantly occluded by methoctramine or AF-DX116, M2 receptor antagonists, but not pirenzepine, J104129 and MT-3, selective M1, M3 and M4 receptor antagonists. The muscarine-induced decrease of glutamatergic EPSCs was highly dependent on the extracellular Ca2+ concentration. Physostigmine and clinically available acetylcholinesterase inhibitors, such as rivastigmine and donepezil, significantly shifted the concentration-inhibition relationship of ACh for glutamatergic EPSCs. These results suggest that muscarine acts on presynaptic M2 receptors to inhibit glutamatergic transmission by reducing the Ca2+ influx into primary afferent terminals, and that M2 receptor agonists and acetylcholinesterase inhibitors could be, at least, potential targets to reduce nociceptive transmission from orofacial tissues.
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http://dx.doi.org/10.1016/j.neuropharm.2013.07.030DOI Listing
December 2013

Pregnenolone sulfate modulates glycinergic transmission in rat medullary dorsal horn neurons.

Eur J Pharmacol 2013 Jul 9;712(1-3):30-8. Epub 2013 May 9.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.

The neurosteroid pregnenolone sulfate (PS), a representative excitatory neuromodulator, has a variety of neuropharmacological actions, such as memory enhancement and convulsant effects. In this study, the effects of PS on glycinergic transmission, such as glycinergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs), were investigated in acutely isolated medullary dorsal horn neurons by use of a conventional whole-cell patch-clamp technique. PS significantly increased the frequency but decreased the amplitude of glycinergic mIPSCs in a concentration-dependent manner. PS also accelerated the decay time constant of glycinergic mIPSCs. The PS-induced decrease in mIPSC amplitude was due to the direct postsynaptic inhibition of glycine receptors because PS inhibited the glycine-induced Cl(-) currents in a noncompetitive manner. The PS-induced increase in mIPSC frequency was not due to the activation of α7 nicotinic acetylcholine, NMDA, σ1 receptors and voltage-dependent Ca(2+) channels, which are known to be molecular targets of PS. On the other hand, the PS-induced increase in mIPSC frequency was completely attenuated either in the Ca(2+)-free external solution or in the presence of transient receptor potential (TRP) channel blockers, suggesting that PS elicits an increase in Ca(2+) concentration within glycinergic nerve terminals via the activation of putative TRP channels. The PS-mediated modulation of glycinergic synaptic transmission, such as the enhancement of presynaptic glycine release and direct inhibition of postsynaptic glycine receptors, might have a broad impact on the excitability of medullary dorsal horn neurons and therefore affect the processing of nociceptive transmission from orofacial tissues.
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http://dx.doi.org/10.1016/j.ejphar.2013.04.039DOI Listing
July 2013

5-Hydroxytryptamine 1A receptors inhibit glutamate release in rat medullary dorsal horn neurons.

Neuroreport 2013 May;24(8):399-403

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.

We examined 5-hydroxytryptamine 1A (5-HT1A) receptor-mediated modulation of glutamatergic transmission in rat medullary dorsal horn neurons using a conventional whole-cell patch clamp technique. 5-HT reversibly and concentration dependently decreased the amplitude of glutamatergic excitatory postsynaptic currents and increased the paired-pulse ratio, indicating that 5-HT acts presynaptically to reduce glutamate release from primary afferents. The 5-HT-induced inhibition of excitatory postsynaptic currents was partially occluded by NAN-190, a 5-HT1A receptor antagonist, and mimicked by 8-OH-DPAT, a 5-HT1A receptor agonist. Our results suggest that presynaptic 5-HT1A receptors inhibit glutamate release from trigeminal primary afferents onto medullary dorsal horn neurons, and thus in addition to other 5-HT1 receptor subtypes, 5-HT1A receptors could be a potential target for treatment of pain from orofacial tissues.
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http://dx.doi.org/10.1097/WNR.0b013e3283614cbfDOI Listing
May 2013

TRPA1-like channels enhance glycinergic transmission in medullary dorsal horn neurons.

J Neurochem 2012 Aug 27;122(4):691-701. Epub 2012 Jun 27.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.

The effect of icilin, a potent agonist of transient receptor potential ankyrin 1 (TRPA1) and TRPM8, on glycinergic transmission was examined in mechanically isolated rat medullary dorsal horn neurons by use of the conventional whole-cell patch-clamp technique. Icilin increased the frequency of glycinergic spontaneous miniature inhibitory post-synaptic currents (mIPSCs) in a dose-dependent manner. Either allyl isothiocyanate(AITC) or cinnamaldehyde, other TRPA1 agonists, also increased mIPSC frequency, but the extent of facilitation induced by AITC or cinnamaldehyde was less than that induced by icilin. However, menthol, a TRPM8 agonist, had no facilitatory effect on glycinergic mIPSCs. The icilin-induced increase in mIPSC frequency was significantly inhibited by either HC030031, a selective TRPA1 antagonist, or ruthenium red, a non-selective transient receptor potential channel blocker. Icilin failed to increase glycinergic mIPSC frequency in the absence of extracellular Ca(2+), suggesting that the icilin-induced increase in mIPSC frequency is mediated by the Ca(2+) influx from the extracellular space. In contrast, icilin still increased mIPSC frequency either in the Na(+) -free external solution or in the presence of Cd(2+), a general voltage-dependent Ca(2+) channel blocker. The present results suggest that icilin acts on pre-synaptic TRPA1-like ion channels, which are permeable to Ca(2+), to enhance glycinergic transmission onto medullary dorsal horn neurons. The TRPA1-like channel-mediated enhancement of glycinergic transmission in medullary dorsal horn neurons would contribute to the regulation of pain information from the peripheral tissues.
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http://dx.doi.org/10.1111/j.1471-4159.2012.07817.xDOI Listing
August 2012

Effect of amitriptyline on glycinergic transmission in rat medullary dorsal horn neurons.

Brain Res 2012 May 20;1455:10-8. Epub 2012 Mar 20.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.

Amitriptyline, a representative tricyclic antidepressant, has been widely used for the treatment of neuropathic pain, such as post-herpetic and trigeminal neuralgia. In the present study, we investigated the effect of amitriptyline on glycinergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in acutely isolated medullary dorsal horn neurons by use of a conventional whole-cell patch-clamp technique. Amitriptyline (30 μM) significantly increased mIPSC frequency without affecting the current amplitude, suggesting that amitriptyline acts presynaptically to increase the probability of glycine release. Amitriptyline also directly inhibited the glycine receptor-mediated Cl(-) currents induced by lower concentrations of glycine. The amitriptyline-induced increase in mIPSC frequency was not affected either in the Na(+)-free external solutions or in the presence of Cd(2+), a general voltage-dependent Ca(2+) channel blocker, indicating that amitriptyline is unlikely to elicit a presynaptic depolarization. In addition, amitriptyline still increased mIPSC frequency even in the absence of extracellular Ca(2+). In contrast, the depletion of intracellular Ca(2+) stores with thapsigargin significantly reduced the extent of amitriptyline-induced increase in mIPSC frequency. These data suggest that amitriptyline increases spontaneous glycine release onto acutely isolated medullary dorsal neurons by increasing the intraterminal Ca(2+) concentration, which might be mediated by the Ca(2+) release from the Ca(2+) stores rather than the Ca(2+) influx from the extracellular space. The amitriptyline-induced modulation of glycinergic transmission could have a broad impact on the excitability of medullary dorsal neurons, and this mechanism would contribute, at least in part, to the anti-allodynic action of amitriptyline.
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http://dx.doi.org/10.1016/j.brainres.2012.03.030DOI Listing
May 2012

A₁ receptors inhibit glutamate release in rat medullary dorsal horn neurons.

Neuroreport 2011 Oct;22(14):711-5

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.

We have investigated the adenosine-mediated presynaptic inhibition of primary afferent-evoked glutamate release in rat substantia gelatinosa neurons of the trigeminal subnucleus caudalis using a conventional whole-cell patch clamp technique. Adenosine reversibly and concentration dependently decreased the amplitude of glutamatergic excitatory postsynaptic currents and increased the paired-pulse ratio, indicating that adenosine acts presynaptically to reduce glutamate release from primary afferents. The adenosine-induced inhibition of excitatory postsynaptic currents was occluded by a selective A₁ receptor antagonist, DPCPX, and was mimicked by a selective A₁ receptor agonist CPA. The results suggest that presynaptic A₁ receptors decrease action potential-dependent glutamate release from trigeminal primary afferents onto medullary dorsal horn neurons, and thus adenosine A₁ receptors could be a potential target for the treatment of pain of orofacial tissues.
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http://dx.doi.org/10.1097/WNR.0b013e32834ab174DOI Listing
October 2011

Tyramine reduces glycinergic transmission by inhibiting presynaptic Ca(2+) channels in the rat trigeminal subnucleus caudalis.

Eur J Pharmacol 2011 Aug 7;664(1-3):29-35. Epub 2011 May 7.

Department of Pharmacology, Craniofacial Dysfunction Research Center, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.

We have recently reported that tyramine acts on putative presynaptic trace amine receptors to inhibit glycinergic transmission in substantia gelatinosa (SG) neurons of the rat trigeminal subnucleus caudalis. However, it is still unknown how tyramine elicits presynaptic inhibition of glycine release. In the present study, therefore, we investigated cellular mechanisms underlying the tyramine-induced inhibition of glycinergic transmission in SG neurons using a conventional whole-cell patch clamp technique. Tyramine (100 μM) reversibly and repetitively decreased the amplitude of action potential-dependent glycinergic inhibitory postsynaptic currents (IPSCs), and increased the paired-pulse ratio. Pharmacological data suggest that the tyramine-induced decrease in glycinergic IPSCs was not mediated by the modulation of adenylyl cyclase, protein kinase A and C, or G-protein coupled inwardly rectifying K(+) channels. On the other hand, glycinergic IPSCs were mainly mediated by the Ca(2+) influx passing through presynaptic N-type and P/Q-type Ca(2+) channels. The tyramine-induced decrease in glycinergic IPSCs was completely blocked by ω-conotoxin GVIA, an N-type Ca(2+) channel blocker, but not ω-agatoxin IVA, a P/Q-type Ca(2+) channel blocker. The results suggest that tyramine acts presynaptically to decrease action potential-dependent glycine release onto SG neurons via the selective inhibition of presynaptic N-type Ca(2+) channels. This tyramine-induced inhibition of glycinergic transmission in SG neurons might affect the process of orofacial nociceptive signals.
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http://dx.doi.org/10.1016/j.ejphar.2011.04.058DOI Listing
August 2011

Multiple effects of allopregnanolone on GABAergic responses in single hippocampal CA3 pyramidal neurons.

Eur J Pharmacol 2011 Feb 29;652(1-3):46-54. Epub 2010 Nov 29.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea.

3α-Hydroxy, 5α-reduced pregnane steroids, such as allopregnanolone, are potent modulators of GABA(A) receptors and have many biological responses including sedative, anxiolytic, anticonvulsant and anesthetic actions. In the present study, we have investigated the effects of allopregnanolone on GABA(A) receptors in acutely isolated single hippocampal CA3 pyramidal neurons using the whole cell patch-clamp technique. Allopregnanolone induced membrane Cl(-) currents in a concentration-dependent manner, and the allopregnanolone-induced currents (I(AlloP)) were blocked by noncompetitive GABA(A) receptor antagonists. The I(AlloP) was not affected by the intracellular loading of γ-cyclodextrin (γ-CD), which efficiently sequesters several kinds of endogenous neurosteroids including allopregnanolone, suggesting that allopregnanolone accesses extracellular but not intracellular sites to activate GABA(A) receptors. Allopregnanolone prolonged the decay time constant of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs), suggesting that allopregnanolone modulates the desensitization kinetics of postsynaptic GABA(A) receptors. The picrotoxin-sensitive tonic currents (I(tonic)), which were mediated by extrasynaptic GABA(A) receptors, were recorded from CA3 pyramidal neurons. The intracellular loading of γ-CD or allopregnanolone significantly decreased or increased the amplitude of picrotoxin-sensitive I(tonic), respectively, suggesting that endogenous neurosteroids might, at least in part, be involved in the generation of picrotoxin-sensitive I(tonic). Allopregnanolone also increased the frequency of GABAergic sIPSCs, in a manner dependent on the integrity of voltage-dependent Na(+) and Ca(2+) channels, suggesting that allopregnanolone activates presynaptic GABA(A) receptors to depolarize GABAergic nerve terminals. The present results suggest that allopregnanolone exerts its pharmacological and pathophysiological actions via the modulation of multiple types of GABA(A) receptor-mediated responses.
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http://dx.doi.org/10.1016/j.ejphar.2010.10.097DOI Listing
February 2011

P2X7 receptors enhance glutamate release in hippocampal hilar neurons.

Neuroreport 2010 Sep;21(13):865-70

Department of Pharmacology, School of Dentistry, Kyungpook National University, Jung-gu, Daegu, Republic of Korea.

We examined the effect of 2'-3'-O-(4-benzoylbenzoyl)-adenosine-5'-triphosphate (Bz-ATP), a P2X7 receptor agonist, on action potential-independent glutamate release from nerve terminals attached to mechanically isolated immature hilar neurons. Bz-ATP increased spontaneous excitatory postsynaptic current (sEPSC) frequency, and this effect was blocked by Brilliant blue G, a P2X7 receptor antagonist, suggesting that P2X7 receptors mediate the facilitatory action of Bz-ATP on sEPSCs. In most of hilar neurons tested, the Bz-ATP-induced increase in sEPSC frequency was blocked by tetrodotoxin or Cd, suggesting that the activation of P2X7 receptors leads to a presynaptic depolarization. The P2X7 receptor-mediated facilitation of glutamate release would modulate the excitability of hilar neurons, and eventually have a broad impact on the pathophysiological functions mediated by the hippocampus.
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http://dx.doi.org/10.1097/WNR.0b013e32833d9142DOI Listing
September 2010

Dopamine inhibition of glycine release in the rat trigeminal nucleus pars caudalis: possible involvement of trace amine receptors.

J Neurochem 2010 Sep 19;114(6):1639-50. Epub 2010 Aug 19.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.

Dopamine (DA)-induced pre-synaptic inhibition of glycinergic transmission was studied from substantia gelatinosa (SG) neurons of the trigeminal nucleus pars caudalis using a conventional whole-cell patch clamp technique. The action potential-dependent glycinergic inhibitory post-synaptic currents (IPSCs) were recorded from SG neurons in the presence of 3 mM kynurenic acid and 10 μM 6-imino-3-(4-methoxyphenyl)-1(6H)-pyridazinebutanoic acid HBr (SR95531). In these conditions, bath applied DA (100 μM) reduced the amplitude of glycinergic IPSCs and increased the paired-pulse ratio, suggesting that DA acts pre-synaptically to reduce the probability of glycine release. However, the inhibitory action of DA on glycinergic IPSCs was not blocked by SCH23390 (10 μM) and spiperone (1 μM), selective D(1) - and D(2) -like receptor antagonists, respectively. In addition, either SKF38393 (100 μM), a selective D(1) -like receptor agonist, or quinpirole (100 μM), a selective D(2) -like receptor agonist, had no pre-synaptic effect on glycinergic IPSCs. The results suggest that both D(1) - and D(2) -like receptors are not involved in the DA-induced decrease in glycinergic IPSCs. On the other hand, tyramine (100 μM), one of representative trace amines, reduced the amplitude of glycinergic IPSCs and increased the paired-pulse ratio, suggesting that tyramine acts pre-synaptically to reduce the probability of glycine release. Considering that DA can activate trace amine (TA) receptors and that TA receptors are exclusively expressed on the trigeminal nucleus pars caudalis, DA might act on putative pre-synaptic TA receptors, rather than classical DA receptors, to inhibit glycinergic transmission onto SG neurons of the trigeminal nucleus pars caudalis.
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http://dx.doi.org/10.1111/j.1471-4159.2010.06870.xDOI Listing
September 2010

Compound K, a metabolite of ginsenosides, facilitates spontaneous GABA release onto CA3 pyramidal neurons.

J Neurochem 2010 Aug 26;114(4):1085-96. Epub 2010 May 26.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Jung-gu, Daegu, Korea.

Ginsenoside Rb1, a major ingredient of ginseng saponins, can affect various brain functions, including learning and memory. When ingested orally, ginsenoside Rb1 is not found in plasma as well as urine, but its metabolite compound K (ComK) reaches the systemic circulation in animals and human. Nevertheless, the pharmacological actions of ComK are still poorly known. In the present study, we investigated the effect of ComK on GABAergic spontaneous miniature inhibitory post-synaptic currents (mIPSCs) in acutely isolated rat hippocampal CA3 pyramidal neurons using a conventional whole-cell patch-clamp technique. While ComK significantly increased mIPSC frequency in a concentration-dependent manner, it had no effect on the current amplitude, suggesting that ComK acts pre-synaptically to increase the probability of spontaneous GABA release. ComK still increased mIPSC frequency even in a Ca(2+) -free external solution, suggesting that the ComK-induced increase spontaneous GABA release is not related to Ca(2+) influx from the extracellular space. However, the ComK-induced increase mIPSC frequency was significantly decreased after the blockade of either sarcoplasmic/endoplasmic reticulum Ca(2+) -ATPase or Ca(2+) release channels. These results strongly suggest that ComK enhances spontaneous GABA release by increasing intraterminal Ca(2+) concentration via Ca(2+) release from pre-synaptic Ca(2+) stores. The ComK-induced modulation of inhibitory transmission onto CA3 pyramidal neurons could have a broad impact on the excitability of CA3 pyramidal neurons and affect the physiological functions mediated by the hippocampus.
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http://dx.doi.org/10.1111/j.1471-4159.2010.06833.xDOI Listing
August 2010

Hypoxic ischemia and proteasome dysfunction alter tau isoform ratio by inhibiting exon 10 splicing.

J Neurochem 2010 Jul 3;114(1):160-70. Epub 2010 Apr 3.

Department of Pharmacology, Ajou University School of Medicine, Suwon 442-749, Korea.

Alternative splicing of tau exon 10 influences microtubule assembly and stability during development and in pathological processes of the central nervous system. However, the cellular events that underlie this pre-mRNA splicing remain to be delineated. In this study, we examined the possibility that ischemic injury, known to change the cellular distribution and expression of several RNA splicing factors, alters the splicing of tau exon 10. Transient occlusion of the middle cerebral artery reduced tau exon 10 inclusion in the ischemic cortical area within 12 h, resulting in the induction of three-repeat (3R) tau in cortical neurons. Ubiquitinated protein aggregates and reduced proteasome activity were also observed. Administration of proteasome inhibitors such as MG132, proteasome inhibitor I and lactacystin reduced tau exon 10 splicing in cortical cell cultures. Decreased levels of Tra2beta, an RNA splicing factor responsible for tau exon 10 inclusion, were detected both in cortical cell cultures exposed to MG132 and in cerebral cortex after ischemic injury. Taken together, these findings suggest that transient focal cerebral ischemia reduces tau exon 10 splicing through a mechanism involving proteasome-ubiquitin dysfunction and down-regulation of Tra2beta.
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http://dx.doi.org/10.1111/j.1471-4159.2010.06732.xDOI Listing
July 2010

Association between incidence of acute exacerbation and medication therapy in patients with COPD.

Curr Med Res Opin 2010 Feb;26(2):297-306

Rutgers University School of Pharmacy, 160 Frelinghuysen Road, Piscataway, NJ 08854, USA.

Background: As exacerbations of chronic obstructive pulmonary disease (COPD) significantly worsen patients' health status and increase disease-related mortality, greater control of exacerbations has important implications for improving patients' health and survival. The incremental benefits of pharmacologic therapies in preventing COPD exacerbations remain unclear. The objective of this observational study was to examine the risk of COPD-related exacerbations between groups of patients receiving inhaled corticosteroids (ICS), anticholinergics (AC), long-acting beta(2)-agonists (LABA), or fixed-dose combinations of ICS and LABA.

Methods: A 12-month retrospective cohort analysis of 2923 patients, who were at least 40 years old with the first time COPD in 12 months (i.e., no COPD for 12 months prior to this time) between 2000 and 2004, was conducted using the MarketScan research databases. Patients with at least two prescriptions for ICS, AC, LABA, or ICS + LABA during the observation period were followed from the index prescription date for the duration of the study. COPD-related exacerbations were defined as clinical events in which a primary diagnosis for a respiratory condition had resulted in hospitalization, an emergency room visit, or an outpatient visit followed by a prescription fill of oral corticosteroids or antibiotics within 14 days of the visit. Exacerbation rates were evaluated using a Cox proportional hazard model with adjustment for age, gender, comorbidities, hospitalizations, emergency room visits, and the number of outpatient visits.

Findings: Compared with ICS alone, COPD exacerbation rates were 35% (CI:22-42%) lower with ICS + LABA, 32% (CI:13-43%) lower with LABA, and 28% (CI:15-36%) lower with AC. The hazard ratio of the first observed COPD exacerbation was 13-18% lower with the use of bronchodilators, with or without ICS, than with ICS alone. In addition, patients receiving ICS alone experienced more exacerbations during the 12-month period following initiation of therapy than those patients receiving LABA, AC, or ICS + LABA. Generalizability of the results and randomization of treatments were limited due to nature of the administrative claim databases.

Conclusion: The present study found that use of bronchodilators, with or without ICS, in COPD patients resulted in a lower exacerbation rate when compared with ICS monotherapy. Further research is required to understand the clinical effects of specific pharmacologic therapies on COPD exacerbations, as well as their impact on long-term outcomes and costs.
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http://dx.doi.org/10.1185/03007990903465926DOI Listing
February 2010

Impact of comorbid conditions and race/ethnicity on glycemic control among the US population with type 2 diabetes, 1988-1994 to 1999-2004.

J Diabetes Complications 2010 Nov-Dec;24(6):382-91. Epub 2009 Aug 27.

Rutgers University School of Pharmacy, Piscataway, NJ 08854, USA.

Objective: To measure trends in glycemic control in type 2 diabetes in the United States from 1988-1994 to 1999-2004 and to identify factors influencing glycemic control, including the presence of comorbid conditions and race/ethnicity.

Methods: Participants in the National Health and Nutrition Examination Surveys (1988-1994 and 1999-2004) aged ≥30 years with diagnosed type 2 diabetes were identified. Outcome measures included glycemic control [glycosylated hemoglobin (A1C) <7%] and pharmacologic treatment rate. Comorbid conditions assessed included obesity, hyperlipidemia, and hypertension.

Results: Prevalence of type 2 diabetes increased from 5.8% in 1988-1994 to 7.1% in 1999-2004. Rates of treatment for type 2 diabetes improved, from 72.3% to 82.2%. The proportion of patients who achieved A1C <7% did not change significantly (44.4% to 50.1%, P=.06); however, blood pressure and cholesterol level both improved. During 1999-2004, only 14% of persons treated for type 2 diabetes did not have an additional comorbid condition; 21% had all three comorbid conditions. During 1999-2004, among treated patients, non-Hispanic blacks were 0.43 times as likely (95% CI 0.29-0.63), and Mexican Americans were 0.47 times as likely (95% CI 0.32-0.68), to have A1C <7% compared to non-Hispanic whites.

Conclusions: Despite improved treatment rates, one in two individuals with type 2 diabetes has A1C of ≥7%. Most type 2 diabetic subjects also suffer from hypertension, hyperlipidemia, and/or obesity, and glycemic control rates were lowest for those with all three conditions. Non-Hispanic blacks and Mexican Americans are less likely to achieve glycemic control as compared to non-Hispanic whites.
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http://dx.doi.org/10.1016/j.jdiacomp.2009.07.001DOI Listing
February 2011

Cyclic AMP-mediated long-term facilitation of glycinergic transmission in developing spinal dorsal horn neurons.

J Neurochem 2009 Sep 8;110(5):1695-706. Epub 2009 Jul 8.

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.

cAMP is known to regulate neurotransmitter release via protein kinase A (PKA)-dependent and/or PKA-independent signal transduction pathways at a variety of central synapses. Here we report the cAMP-mediated long-lasting enhancement of glycinergic transmission in developing rat spinal substantia gelatinosa neurons. Forskolin, an adenylyl cyclase activator, elicited a long-lasting increase in the amplitude of nerve-evoked glycinergic inhibitory postsynaptic currents (IPSCs), accompanied by a long-lasting decrease in the paired-pulse ratio in immature substantia gelatinosa neurons, and this forskolin-induced increase in glycinergic IPSCs decreased with postnatal development. Forskolin also decreased the failure rate of glycinergic IPSCs evoked by minimal stimulation, and increased the frequency of glycinergic miniature IPSCs. All of these data suggest that forskolin induces the long-lasting enhancement of glycinergic transmission by increasing in the presynaptic release probability. This pre-synaptic action of forskolin was mediated by hyperpolarization and cyclic nucleotide-activated cation channels and an increase in intraterminal Ca(2+) concentration but independent of PKA. The present results suggest that cAMP-dependent signal transduction pathways represent a dynamic mechanism by which glycinergic IPSCs could potentially be modulated during postnatal development.
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http://dx.doi.org/10.1111/j.1471-4159.2009.06275.xDOI Listing
September 2009

Differential pharmacological properties of GABAA receptors in axon terminals and soma of dentate gyrus granule cells.

J Neurochem 2009 May 30;109(4):995-1007. Epub 2009 Mar 30.

Department of Oral Surgery, School of Dentistry, Kyungpook National University, Daegu, Korea.

Although it has been well established that GABA(A) receptors are molecular targets of a variety of allosteric modulators, such as benzodiazepines, the pharmacological properties of presynaptic GABA(A) receptors are poorly understood. In this study, the effects of diazepam and Zn(2+) on presynaptic GABA(A) receptors have been investigated by measuring the GABA(A) receptor-mediated facilitation of spontaneous glutamate release in mechanically dissociated rat CA3 pyramidal neurons. Diazepam significantly enhanced the muscimol-induced facilitation (particularly at submicromolar concentrations) of spontaneous glutamate release and shifted the concentration-response relationship for muscimol toward the left, whereas Zn(2+) (
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http://dx.doi.org/10.1111/j.1471-4159.2009.06018.xDOI Listing
May 2009

Trends in blood pressure control and treatment among type 2 diabetes with comorbid hypertension in the United States: 1988-2004.

J Hypertens 2009 Sep;27(9):1908-16

Rutgers University, Piscataway, New Jersey 08854, USA.

Objectives: The objectives of this study were to examine the trends in the prevalence of type 2 diabetic patients with comorbid hypertension and blood pressure (BP) control rates in the United States and determine factors associated with these outcomes.

Methods: We used data from National Health and Nutrition Examination Surveys (NHANES) III (1988-1994) and NHANES 1999-2004, a cross-sectional sample of the noninstitutionalized US populations. Type 2 diabetic patients were identified as patients at least 30 years of age with physician-diagnosed diabetes who were taking insulin or oral antidiabetic drugs to manage the condition. A diagnosis of hypertension was based on physician diagnosis, treatment with antihypertensive medications, or BP at least 140/90 mmHg. BP control was defined as diabetic patients who maintained BP <130/80 mmHg. Logistic regression was used to estimate risks of high BP, and odds of high BP treatment and control rates, after adjusting for demographic and clinical risk factors.

Results: The age-adjusted prevalence of diabetic patients and those with hypertension increased significantly from 5.8 to 7.1% and 3.9 to 4.7%, respectively, from NHANES III to NHANES 1999-2004. Among diabetic patients with hypertension, patients who were treated with medication or lifestyle or behavioral modification therapy have increased significantly from 76.5 to 87.8% during the observation period. The proportion of patients who controlled BP increased from 15.9 to 29.6%, but 70% of patients still did not meet the target BP goal.

Conclusion: Aggressive public health efforts are needed to improve BP control in type 2 diabetic patients with hypertension.
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http://dx.doi.org/10.1097/HJH.0b013e32832d4aeeDOI Listing
September 2009
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