• Title/Summary/Keyword: Biphasic

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The effect of hard-type crosslinked hyaluronic acid with particulate bone substitute on bone regeneration: positive or negative?

  • Yun, Junseob;Lee, Jungwon;Kim, Sungtae;Koo, Ki-Tae;Seol, Yang-Jo;Lee, Yong-Moo
    • Journal of Periodontal and Implant Science
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    • v.52 no.4
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    • pp.312-324
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    • 2022
  • Purpose: The role of hard-type crosslinked hyaluronic acid (HA) with particulate bone substitutes in bone regeneration for combined inlay-onlay grafts has not been fully investigated. We aimed to evaluate the effect of hard-type crosslinked HA used with bone substitute in terms of new bone formation and space maintenance. Methods: A 15-mm-diameter round defect was formed in the calvaria of 30 New Zealand White rabbits. All animals were randomly assigned to 1 of 3 groups: the control group (spontaneous healing without material, n=10), the biphasic calcium phosphate (BCP) graft group (BCP, n=10), and the BCP graft with HA group (BCP/HA, n=10). The animals were evaluated 4 and 12 weeks after surgery. Half of the animals from each group were sacrificed at 4 and 12 weeks after surgery. Samples were evaluated using micro-computed tomography, histology, and histomorphometry. Results: The BCP group showed higher bone volume/tissue volume (BV/TV) values than the control and BCP/HA groups at both 4 and 12 weeks. The BCP and BCP/HA groups showed higher bone surface/tissue volume (BS/TV) values than the control group at both 4 and 12 weeks. The BCP group showed higher BS/TV values than the control and BCP/HA groups at both 4 and 12 weeks. No statistically significant difference in newly formed bone was found among the 3 groups at 4 weeks. The BCP group showed significantly higher new bone formation than the BCP/HA group at 12 weeks. Conclusions: Hard-type crosslinked HA did not show a positive effect on new bone formation and space maintenance. The negative effect of hard-type crosslinked HA may be due to the physical properties of HA that impede osteogenic potential.

Involvement of α1B-adrenoceptors and Rho kinase in contractions of rat aorta and mouse spleen

  • Hadeel A. Alsufyani;James R. Docherty
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.4
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    • pp.325-331
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    • 2023
  • α1-adrenoceptors link via the G-protein Gq/G11 to both Ca2+ entry and release from stores, but may also activate Rho kinase, which causes calcium sensitization. This study aimed to identify the subtype(s) of α1-adrenoceptor involved in Rho kinase-mediated responses in both rat aorta and mouse spleen, tissues in which contractions involve multiple subtypes of α1-adrenoceptor. Tissues were contracted with cumulative concentrations of noradrenaline (NA) in 0.5 log unit increments, before and in the presence of an antagonist or vehicle. Contractions produced by NA in rat aorta are entirely α1-adrenoceptor mediated as they are competitively blocked by prazosin. The α1A-adrenoceptor antagonist RS100329 had low potency in rat aorta. The α1D-adrenoceptor antagonist BMY7378 antagonized contractions in rat aorta in a biphasic manner: low concentrations blocking α1D-adrenoceptors and high concentrations blocking α1B-adrenoceptors. The Rho kinase inhibitor fasudil (10 µM) significantly reduced aortic contractions in terms of maximum response, suggesting inhibition of α1B-adrenoceptor mediated responses. In the mouse spleen, a tissue in which all 3 subtypes of α1-adrenoceptor are involved in contractions to NA, fasudil (3 µM) significantly reduced both early and late components to the NA contraction, the early component involving α1B- and α1D-adrenoceptors, and the late component involving α1B- and α1A-adrenoceptors. This suggests that fasudil inhibits α1B-adrenoceptor mediated responses. It is concluded that α1D- and α1B-adrenoceptors interact in rat aorta and α1D-, α1A- and α1B-adrenoceptors interact in the mouse spleen to produce contractions and these interactions suggest that one of the receptors preferentially activates Rho kinase, most likely the α1B-adrenoceptor.

Inhibition of Osteoclast Differentiation and Promotion of Osteogenic Formation by Wolfiporia extensa Mycelium

  • Tae Hyun Son;Shin-Hye Kim;Hye-Lim Shin;Dongsoo Kim;Jin-Sung Huh;Rhim Ryoo;Yongseok Choi;Sik-Won Choi
    • Journal of Microbiology and Biotechnology
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    • v.33 no.9
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    • pp.1197-1205
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    • 2023
  • Osteoporosis, Greek for "porous bone," is a bone disease characterized by a decrease in bone strength, microarchitectural changes in the bone tissues, and an increased risk of fracture. An imbalance of bone resorption and bone formation may lead to chronic metabolic diseases such as osteoporosis. Wolfiporia extensa, known as "Bokryung" in Korea, is a fungus belonging to the family Polyporaceae and has been used as a therapeutic food against various diseases. Medicinal mushrooms, mycelium and fungi, possess approximately 130 medicinal functions, including antitumor, immunomodulating, antibacterial, hepatoprotective, and antidiabetic effects, and are therefore used to improve human health. In this study, we used osteoclast and osteoblast cell cultures treated with Wolfiporia extensa mycelium water extract (WEMWE) and investigated the effect of the fungus on bone homeostasis. Subsequently, we assessed its capacity to modulate both osteoblast and osteoclast differentiation by performing osteogenic and anti-osteoclastogenic activity assays. We observed that WEMWE increased BMP-2-stimulated osteogenesis by inducing Smad-Runx2 signal pathway axis. In addition, we found that WEMWE decreased RANKL-induced osteoclastogenesis by blocking c-Fos/NFATc1 via the inhibition of ERK and JNK phosphorylation. Our results show that WEMWE can prevent and treat bone metabolic diseases, including osteoporosis, by a biphasic activity that sustains bone homeostasis. Therefore, we suggest that WEMWE can be used as a preventive and therapeutic drug.

The Impact of Right Atrial Size to Predict Success of Direct Current Cardioversion in Patients With Persistent Atrial Fibrillation

  • Christoph Doring;Utz Richter;Stefan Ulbrich;Carsten Wunderlich;Micaela Ebert;Sergio Richter;Axel Linke;Krunoslav Michael Sveric
    • Korean Circulation Journal
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    • v.53 no.5
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    • pp.331-343
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    • 2023
  • Background and Objectives: The prognostic implication of right atrial (RA) and left atrial (LA) size for an immediate success of direct current cardioversion (DCCV) in atrial fibrillation (AF) remains unclear. This study aimed to compare RA and LA size for the prediction of DCCV success. Methods: Between 2012 and 2018, 734 consecutive outpatients were screened for our prospective registry. Each eligible patient received a medical history, blood analysis, and transthoracic echocardiography with a focus on indexed RA (iRA) area and LA volume (iLAV) prior to DCCV with up to three biphasic shocks (200-300-360 J) or additional administration of amiodarone or flecainide to restore sinus rhythm. Results: We enrolled 589 patients, and DCCV was in 89% (n=523) successful. Mean age was 68 ± 10 years, and 40% (n=234) had New York heart association class >II. A prevalence of the male sex (64%, n=376) and of persistent AF (86%, n=505) was observed. Although DCCV success was associated with female sex (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.06-3.65), with absence of coronary heart disease and normal left ventricular function (OR, 2.24; 95% CI, 1.26-4.25), with short AF duration (OR, 1.93; 95% CI, 1.05-4.04) in univariable regression, only iRA area remained a stable and independent predictor of DCCV success (OR, 0.27; 95% CI, 0.12-0.69; area under the curve 0.71), but not iLAV size (OR, 1.16; 95% CI, 1.05-1.56) in multivariable analysis. Conclusions: iRA area is superior to iLAV for the prediction of immediate DCCV success in AF.

Rapid Local Recurrence of Breast Myoepithelial Carcinoma Arising in Adenomyoepithelioma: A Case Report (빠른 국소 재발을 보인 유방의 선근상피종에서 발생한 근상피암: 증례 보고)

  • Mo In Ha;Bo Kyoung Seo;Jung Woo Choi
    • Journal of the Korean Society of Radiology
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    • v.81 no.1
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    • pp.207-212
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    • 2020
  • Adenomyoepithelioma (AME) is a rare breast neoplasm composed of both epithelial and myoepithelial cells with biphasic proliferation. Although most AMEs are benign, malignant transformation of either or both cellular components may occur. This report describes an unusual rapid local tumor recurrence a month after excision of the myoepithelial carcinoma arising in an AME. Ultrasound and MRI showed small recurrent masses in the superficial part of a hematoma. This report suggests the benefit of immediate postoperative breast imaging in patients with malignant AME with potential for local recurrence, such as those with narrow resection margins or high mitotic activity.

Integrated Effect of Non-Invasive Neuromodulation on Bladder Capacity in Traumatic Spinal Cord Injury Patient: Single Case Report

  • Priyanka Dangi;Narkeesh Arumugam;Dinesh Suman
    • Physical Therapy Rehabilitation Science
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    • v.13 no.1
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    • pp.86-94
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    • 2024
  • Objective: To evaluate the changes in bladder capacity and storage through non-invasive neuromodulation by application of repetitive Trans magnetic stimulation (rTMS) and genital nerve stimulation (GNS) in traumatic spinal cord survivors. Design: A Single Case Study. Method: The Patient was registered in trail with the clinical trial registry of India (CTRI/2022/05/042431). The Patient was interposed with rTMS on lumbar area, from T11-L4 vertebrae with 1 Hz and the intensity was 20% below that elicited local paraspinal muscular contraction for 13 minutes. GNS was placed over dorsum of the penis with the cathode at the base and anode 2 cm distally at 20 Hz, 200 microseconds, Continuous and biphasic current was delivered and amplitude of stimulation necessary to elicit the genito-anal reflex. For assessment, Neurological examination was done for peri-anal sensation (PAS), voluntary anal contraction (VAC) and bulbocavernous reflex (BCR), deep anal pressure (DAP), and American Spinal Injury Association Impairment Scale (ASIA scale). Outcome assessment was done using Urodynamics, Spinal Cord Independence Measure Scale Version-III (SCIM-III), American Spinal Injury Association Impairment Score (ASIA Score), Beck's Depression Inventory Scale (BDI). The baseline evaluation was taken on Day 0 and on Day 30. Results: The pre-and post-data were collected through ASIA score, SCIM-III, BDI and Urodynamics test which showed significant improvement in bladder capacity and storage outcomes in the urodynamics study across the span of 4 weeks. Conclusion: rTMS along with GNS showed improvement in bladder capacity & storage, on sensory-motor score, in functional independence of individual after SCI.

Effects of Cyclobuxine E on Two Distinct Types of Potassium-Activated Calcium Channels in an Intestinal Smooth Muscle (흰쥐 장관에 있어 칼륨에 의해 활성화되는 칼슘 채널에 대한 Cyclobuxine E의 영향)

  • Lee, Jong-Hwoa;Kwon, Jun-Tack;Cho, Byung-Heon;Choi, Kyu-Hong;Kim, Yu-Jae;Kim, Jong-Bae;Kim, Chun-Sook;Cha, Young-Deog;Kim, Young-Suk
    • The Korean Journal of Pharmacology
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    • v.25 no.1
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    • pp.53-58
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    • 1989
  • For several years, we investigated the pharmacological action of several substances isolated from Buxus microphylla var koreana Nakai, which had been used as folk remedies of malaria and venereal disease. Cyclobuxine $D(C_{25}H_{42}ON_2)$, a steroidal alkaloid, exerted an antiinflammatory action, hypotensive and bradycardic effects in rats. In the present study, we isolated alkaloid from the acetone-insoluble fraction of the strong bases of this plants. This alkaloid $(C_{25}H_{38}ON_2)$ was identified as a steroidal alkaloid contained a cyclopropane ring by physical and chemical methods. It is a derivative of cyclobuxine D and named cyclobuxine E. We examined the effect of cyclobuxine E on the contractile response induced by acetylcholine and two distinct types of potassium-activated calcium channels in an intestinal smooth muscle of the rat. Cyclobuxine E inhibited significantly the Ach-induced contraction. The isolated longitudinal muscle from the rat duodenum was immersed calcium-depleted potassium depolarizing solution. Ten minutes after, 1.8 mM $CaCl_2$ was added to muscle bath and elicited a biphasic increase in muscle tension. Cyclobuxine E produced an appreciable inhibition of both components of the mechanical response. In addition, Cyclobuxine E introduced at a point when the tonic response had reached its maximum level, caused the muscle to exhibit a rapid loss of tension. Based on these experimental results, we proposed the possibility that the inhibitory action of cyclobuxine E on the isolated rat duodenum may be due to inhibiting the transmembrane fluxes of calcium ion in potassium-activated calcium channels.

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Effects of Cyclobuxine D on Drug-Induced Contractions of the Isolated Rat Uterine Muscle and Potassium-Activated Calcium Channels in an Intestinal Smooth Muscle (흰쥐 적출 자궁의 수축 작용과 흰쥐 장관에 있어 칼륨에 의해 활성화되는 칼슘 채널에 대한 Cyclobuxine D의 영향)

  • Kwon, Jun-Tack;Lee, Jong-Hwoa;Park, Young-Hyun;Cho, Byung-Heon;Choi, Kyu-Hong;Kim, Yu-Jae;Kim, Jong-Bae;Kim, Chung-Mok;Kim, Chun-Sook;Cha, Young-Deog;Kim, Young-Suk
    • The Korean Journal of Pharmacology
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    • v.24 no.1
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    • pp.103-109
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    • 1988
  • Cyclobuxine D, extracted from Buxus microphylla var. koreana Nakai, is a steroidal alkaloid. Many pharmacological effects of cyclobuxine D were examined in our Lab. Cyclobuxine D showed a significant bradycardic effect in the rat heart and an inhibitory action on acetylcholine and $Ba^{++}-induced$ contraction of the longitudinal muscle isolated from the rabbit jejunum. In this study, we investigated the effect of cyclobuxine D on the contractile response-elicited by acetylcholine, oxytocin and $Ba^{++}$ in rat uterine. In order to analyse the inhibitory action of cyclobuxine D on the smooth muscle, we examined the inhibitory action of cyclobuxine D against the contractile response of the high potassium-depolarized rat ileum to calcium. Concentration-dependent decrease in the peak tension and duration of the acetylcholine, oxytocin and $Ba^{++}-induced$ contraction in the isolated rat uterus was observed when cyclobuxine D was added to the organ bath. The isolated longitudinal muscle from the rat ileum was immersed calcium-depleted potassium-depolarizing solution. Ten minutes after, 1.8 mM $CaCl_2$ was added to muscle bath and elicited a biphasic increase in muscle tension. Cyclobuxine D $(6.2{\times}10^{-5}\;M)$ produced an appreciable inhibition of both components of the mechanical response. In addition, $3.1{\times}10^{-4}\;M$ cyclobuxine D, introduced at a point when the tonic response had reached its maximum level, caused the muscle to exhibit a rapid lose of tension. Based on these experimental results, we propose the possibility that the inhibitory action of cyclobuxine D on the acetylcholine, oxytocin and $Ba^{++}-induced$ contraction in the isolated rat uterus may be due to blocking potassium-activated calcium channels, voltage-sensitive calcium channels.

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Development of Pharmaceutical Dosage Forms with Biphasic Drug Release using Double-Melt Extrusion Technology (이중 고온용융 압출 성형된 이중 방출능을 가지는 제형의 개발)

  • Kim, Dong-Wook;Kang, Chin-Yang;Kang, Changmin;Park, Jun-Bom
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.17 no.9
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    • pp.228-234
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    • 2016
  • The aim of this study was to develop pharmaceutical dosage forms with a bi-phasic drug using a double extrusion approach. Hot melt extrusion was performed using a co-rotating twin-screw extruder. The. 1st melt extrusion was performed using polymer with a relatively higher Tg, such as HPMC and the 2nd melt extrudate was obtained using the 1st extrudate and polymers with a lower Tg, such as HPMC-AS and PEO. In addition, the formulation with all the content in the same proportion as the double extudate was produced using single extrusion for comparison. Physical characterization was performed on the formulations employing differential scanning calorimetry (DSC). In vitro release tests were studied using a USP Type-I apparatus at $37{\pm}0.5^{\circ}C$ and 100 rpm. The similarity factor (f2) was also used to check the difference statistically. The DSC results indicated that the crystallinity of ibuprofen was changed to an amorphous state after extrusion in both double and single melt extrusion. Double melt extrudate with ibuprofen showed the desired release in acidic media (pH 1.2) in the first two hours and basic (pH 6.8) during six hours. Double melt extrudate with glimepiride showed faster release in 60 min of over 80%, whereas the single extrudate with glimepiride showed retarded release due to the interaction with HPMC. The similarity factor(f2) value was 28.5, which demonstrates that there were different drug release behavior between the double and single extrusion. Consequently, the double melt extrudated formulation was robust and gave the desired drug release pattern.

Magnaporthe oryzae Effector AVR-Pii Helps to Establish Compatibility by Inhibition of the Rice NADP-Malic Enzyme Resulting in Disruption of Oxidative Burst and Host Innate Immunity

  • Singh, Raksha;Dangol, Sarmina;Chen, Yafei;Choi, Jihyun;Cho, Yoon-Seong;Lee, Jea-Eun;Choi, Mi-Ok;Jwa, Nam-Soo
    • Molecules and Cells
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    • v.39 no.5
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    • pp.426-438
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    • 2016
  • Plant disease resistance occurs as a hypersensitive response (HR) at the site of attempted pathogen invasion. This specific event is initiated in response to recognition of pathogen-associated molecular pattern (PAMP) and subsequent PAMP-triggered immunity (PTI) and effector-triggered immunity (ETI). Both PTI and ETI mechanisms are tightly connected with reactive oxygen species (ROS) production and disease resistance that involves distinct biphasic ROS production as one of its pivotal plant immune responses. This unique oxidative burst is strongly dependent on the resistant cultivars because a monophasic ROS burst is a hallmark of the susceptible cultivars. However, the cause of the differential ROS burst remains unknown. In the study here, we revealed the plausible underlying mechanism of the differential ROS burst through functional understanding of the Magnaporthe oryzae (M. oryzae) AVR effector, AVR-Pii. We performed yeast two-hybrid (Y2H) screening using AVR-Pii as bait and isolated rice NADP-malic enzyme2 (Os-NADP-ME2) as the rice target protein. To our surprise, deletion of the rice Os-NADP-ME2 gene in a resistant rice cultivar disrupted innate immunity against the rice blast fungus. Malic enzyme activity and inhibition studies demonstrated that AVR-Pii proteins specifically inhibit in vitro NADP-ME activity. Overall, we demonstrate that rice blast fungus, M. oryzae attenuates the host ROS burst via AVR-Pii-mediated inhibition of Os-NADP-ME2, which is indispensable in ROS metabolism for the innate immunity of rice. This characterization of the regulation of the host oxidative burst will help to elucidate how the products of AVR genes function associated with virulence of the pathogen.