• Title/Summary/Keyword: $PIP_2$

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Effect of Bevacizumab on Human Tenon's Fibroblasts Cultured from Primary and Recurrent Pterygium

  • Park, Young Min;Kim, Chi Dae;Lee, Jong Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.4
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    • pp.357-363
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    • 2015
  • The purpose of this study was to compare the inhibitory effect of bevacizumab on human Tenon's fibroblasts (HTFs) cultured from primary and recurrent pterygium. Cultured HTFs were exposed to 2.0, 5.0, 7.5, and 15.0 mg/mL concentration of bevacizumab for 24 hours. The 3-[4,5-dimethylthiazol- 2-yl]-2,5-diphenyl tetrazolium bromide and lactate dehydrogenase leakage assays were then performed to assess fibroblast metabolism and viability. The matrix metalloproteinase (MMP), procollagen type I C terminal propeptide (PIP), and laminin immunoassays were performed to examine extracellular matrix production. Changes in cellular morphology were examined by phase-contrast and transmission electron microscopy. Both metabolic activity and viability of primary and recurrent pterygium HTFs were inhibited by bevacizumab in a dose-dependent manner, especially at concentrations greater than 7.5 mg/mL. Both types of HTFs had significant decreases in MMP-1, PIP, and laminin levels. Distinctly, the inhibitory effect of bevacizumab on MMP-1 level related with collagenase in primary pterygium HTFs was significantly higher than that of recurrent pterygium. Significant changes in cellular density and morphology both occurred at bevacizumab concentrations greater than 7.5 mg/mL. Only primary pterygium HTFs had a reduction in cellular density at a bevacizumab concentration of 5.0 mg/mL. Bevacizumab inhibits primary and recurrent pterygium HTFs in a dose-dependent manner, especially at concentrations greater than 7.5 mg/mL. As the primary HTFs produces larger amounts of MMP-1 compared to recurrent HTFs, significant reduction in MMP-1 level in primary pterygium HTFs after exposure to bevacizumab is likely to be related to the faster cellular density changes in primary pterygium HTFs.

Anti-wrinkle and Whitening Effects of Essential Oil from Abies koreana (Abies koreana 유래 정유의 항주름 및 미백 효과)

  • Song, Byeong-Wook;Song, Min-Jeong;Park, Mi-Jin;Choi, Don-Ha;Lee, Sung-Suk;Kim, Myungkil;Hwang, Ki-Chul;Kim, Il-Kwon
    • Journal of Life Science
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    • v.28 no.5
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    • pp.524-531
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    • 2018
  • The essential oil from Abies koreana E.H. Wilson had been developed, however, its efficacy has not yet been studied especially in terms of skin care research. The aim of this study is to investigate the effects of Abies koreana extracts (AKE) on melanogenesis and wrinkle formation in B16F10 melanoma cells (B16F10) and human dermal fibroblast cell line (HDF). The essential oil was extracted by hydrodistillation method and purified by anhydrous sodium sulfate. At a concentration of $10^{-5}$-fold, viability in these cells had been defined by cytotoxicity assays. Anti-melanogenic effects on B16F10 were evaluated using tyrosinase inhibition assay, and real-time PCR for verifying gene expression of tyrosinase, tyrosinase related protein-1 and -2 (TRP-1 and -2). AKEs reduced about 5-fold of tyrosinase inhibitory activity compared to ${\alpha}$-melanocyte-stimulating hormone (${\alpha}$-MSH)-induced group and about 30% reduction compared to Arbutin induced group. The mRNA levels of three melanin-related factors were increased, separately. To investigate the effects of anti-wrinkle, procollagen type I c peptide synthesis assay (PIP) and Western blot were performed. At AKE-treated group, PIP was up-regulated and the expression of collagen type 1 and matrix metalloproteinase (MMP)-1 were improved. Furthermore, AKE presented anti-wrinkle effects by increasing UVB-inhibited collagen type 1 expression, and reducing UVB-induced MMP-1 production at $60mJ/cm^2$ of UVB radiation. Therefore, Abies koreana extracts has potentials as a safe and an effective skin ingredient for whitening and anti-wrinkle.

Fabrication and Characterization of C/SiC Composite by Electron Beam Curing (전자선 가교 방법을 이용한 탄소/탄화규소 복합재 제조 및 특성)

  • Shin, Jin-Wook;Jeun, Joon-Pyo;Kang, Phil-Hyun
    • Polymer(Korea)
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    • v.33 no.6
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    • pp.575-580
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    • 2009
  • Carbon fabric-reinforced silicon carbide composites (C/SiC) have attracted a considerable attention for high temperature structural application because of their outstanding oxidation resistance property and thermal shock resistance. In this study, we reported on the preparation of C/SiC composites by the polymer impregnation and pyrolysis (PIP) method. For this, polycarbosilane solution was impregnated into the carbon fabric and then cured by electron beam irradiation under argon atmosphere. Afterwards, the cured composite was pyrolyzed at $1300^{\circ}C$ for 1 h under argon atmosphere to produce the C/SiC composite. The porosity and density of the C/SiC composite were 13.5% and $2.44\;g/cm^3$, respectively, when the impregnation of the carbon fabric with the 30 wt% polycarbosilane solution conducted four times. In addition, in the isothermal experiment at $1500\;^{\circ}C$ in air for 5 h, the 95.9 wt% of the C/SiC composite was remained, indicating that the prepared C/SiC composite has a outstanding oxidation resistance.

Volar plate avulsion fracture alone or concomitant with collateral ligament rupture of the proximal interphalangeal joint: A comparison of surgical outcomes

  • Kim, Yong Woo;Roh, Si Young;Kim, Jin Soo;Lee, Dong Chul;Lee, Kyung Jin
    • Archives of Plastic Surgery
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    • v.45 no.5
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    • pp.458-465
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    • 2018
  • Background Volar plate avulsion fracture of the proximal interphalangeal (PIP) joint is one of the most common hand injuries. In this study, we divided patients into two groups: patients with pure volar plate avulsion fracture, and patients with volar plate avulsion fracture concomitant with collateral ligament rupture. The purpose of this study was to compare long-term surgical outcomes between the two groups. As a secondary measure, the Mitek bone anchoring and polydioxanone (PDS) bone suturing techniques were compared. Methods A single-institutional retrospective review of the surgical treatment of volar plate avulsion fracture was performed. The cases were divided into those with pure volar plate avulsion fracture (group A, n=15) and those with volar plate avulsion fracture concomitant with collateral ligament rupture (group B, n=15). Both groups underwent volar plate reattachment using Mitek bone anchoring or PDS bone suturing followed by 2 weeks of immobilization in a dorsal protective splint. Results The average range of motion of the PIP joint and extension lag were significantly more favorable in group A (P<0.05). Differences in age; follow-up period; flexion function; visual analog scale scores; disabilities of the arm, shoulder, and hand scores; and the grip strength ratio between the two groups were non-significant. No significant differences were found in the surgical outcomes of Mitek bone anchoring and PDS bone suturing in group A. Conclusions Overall, the surgical outcomes of volar plate reattachment were successful irrespective of whether the collateral ligaments were torn. However, greater extension lag was observed in cases of collateral ligament injury.

Genetic Transfer of Bacillus pasteurii Urease Gene into Antagonistic Bacillus subtilis YBL-7 against Root Rotting Fungi Fusarium solani (Bacillus parteurii Urease Gene의 생물방제균 Bacillus subtilis YBL-7내에서의 발현)

  • 김용수;김상달
    • Microbiology and Biotechnology Letters
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    • v.19 no.4
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    • pp.356-361
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    • 1991
  • - To investigate the possibility of genetic development for a multi-purpose strain of Bacillus subtilis YBL-7 against Fusat-iurn solani causing root rot of many impotant corps, the plasmid pGU66 inserting urease gene of Bacillus pasteurii had been introduced into Bacillus subtilis YBL-7 by PEG-induced protoplast (PIP) transformation system. Protoplasts of B. subtilis YBL-7 were prepared by treating the cells with lysozyme (200 $\mu g$/ml) in hypertonic buffer (SMMP). The highest transformation frequency was achieved when cells of the strain with lysozyme at $42^{\circ}C$ for 90 minutes. Optimal transformation was obtained using polyethylene glycol (MW 4000) at final concentration of 30% (V/V). The transformation frequency was increased proportionally to 1.2 $\mu g$ of plasmid DNA. At best condition, the transformation frequency (transformants/ regenerants/$\mu g$ of DNA) for pGU66 was appoximately $4 \times 10^{-3}$. Also, the urease gene was strongly expressed in the transformants of B. subtilis YBL-7 and maintained steadily. The antifungal ability of transformant was very similar to that of B. ssubtilis YBL-7.

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PKC-Independent Stimulation of Cardiac $Na^+/Ca^{2+}$ Exchanger by Staurosporine

  • Kang, Tong-Mook
    • The Korean Journal of Physiology and Pharmacology
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    • v.12 no.5
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    • pp.259-265
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    • 2008
  • $[Ca^{2+}]_i$ transients by reverse mode of cardiac $Na^+/Ca^{2+}$ exchanger (NCX1) were recorded in fura-2 loaded BHK cells with stable expression of NCX1. Repeated stimulation of reverse NCX1 produced a long-lasting decrease of $Ca^{2+}$ transients ('rundown'). Rundown of NCX1 was independent of membrane $PIP_2$ depletion. Although the activation of protein kinase C (PKC) was observed during the $Ca^{2+}$ transients, neither a selective PKC inhibitor (calphostin C) nor a PKC activator (PMA) changed the degrees of rundown. By comparison, a non-specific PKC inhibitor, staurosporine (STS), reversed rundown in a dose-dependent and reversible manner. The action of STS was unaffected by pretreatment of the cells with calphostin C, PMA, or forskolin. Taken together, the results suggest that the stimulation of reverse NCX1 by STS is independent of PKC and/or PKA inhibition.

A Methodology to Integrate Public Processes with Private Processes for B2B e-Commerce (B2B 전자거래를 위한 공개 및 내부 프로세스의 통합 방법론)

  • Lie, Xizuo;Kim, Sun-Ho
    • IE interfaces
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    • v.16 no.4
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    • pp.432-440
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    • 2003
  • The inter-organizational business process is one of the hot issues in B2B e-commerce. In this paper, through the survey of the inter-organizational business process integration and the analysis of B2Bi related standards, e.g., BPML, WSDL, WSCI, and BPSS, we propose a method of linking BPML and BPSS specifications that can be used to integrate private processes with the public processes among enterprises. We also suggest an application example of the method by redefining a PIP of RosettaNet to the BPSS specification. The basic principle of the method is to maintain the independency of the existing BPML and BPSS applications and to construct an intermediary transformation module between the two applications.

The Effect of External PEEP on Work of Breathing in Patients with Auto-PEEP (Auto-PEEP이 존재하는 환자에서 호흡 일에 대한 External PEEP의 효과)

  • Chin, Jae-Yong;Lim, Chae-Man;Koh, Youn-Suck;Park, Pyung-Whan;Choi, Jong-Moo;Lee, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.201-209
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    • 1996
  • Background : Auto-PEEP which develops when expiratory lung emptying is not finished until the beginning of next inspiration is frequently found in patients on mechanical ventilation. Its presence imposes increased risk of barotrauma and hypotension, as well as increased work of breathing (WOB) by adding inspiratory threshold load and/or adversely affecting to inspiratory trigger sensitivity. The aim of this study is to evaluate the relationship of auto-PEEP with WOB and to evaluate the effect of PEEP applied by ventilator (external PEEP) on WOB in patients with auto-PEEP. Method : 15 patients, who required mechanical ventilation for management of acute respiratory failure, were studied. First, the differences in WOB and other indices of respiratory mechanics were examined between 7 patients with auto-PEEP and 8 patients without auto-PEEP. Then, we applied the 3 cm $H_2O$ of external PEEP to patients with auto-PEEP and evaluated its effects on lung mechanics as well as WOB. Indices of respiratory mechanics including tidal volume ($V_T$), repiratory rate, minute ventilation ($V_E$), peak inspiratory flow rate (PIFR), peak expiratory flow rate (PEFR), peak inspiratory pressure (PIP), $T_I/T_{TOT}$, auto-PEEP, dynamic compliance of lung (Cdyn), expiratory airway resistance (RAWe), mean airway resistance (RAWm), $p_{0.1}$, work of breathing performed by patient (WOB), and pressure-time product (PTP) were obtained by CP-100 Pulmonary Monitor (Bicore, USA). The values were expressed as mean $\pm$ SEM (standard error of mean). Results : 1) Comparison of WOB and other indices of respiratory mechanics in patients with and without auto-PEEP : There was significant increase in WOB ($l.71{\pm}0.24$ vs $0.50{\pm}0.19\;J/L$, p=0.007), PTP ($317{\pm}70$ vs $98{\pm}36\;cm$ $H_2O{\cdot}sec/min$, p=0.023), RAWe ($35.6{\pm}5.7$ vs $18.2{\pm}2.3\;cm$ H2O/L/sec, p=0.023), RAWm ($28.8{\pm}2.5$ vs $11.9{\pm}2.0cm$ H2O/L/sec, p=0.001) and $P_{0.1}$ ($6.2{\pm}1.0$ vs 2.9+0.6 cm H2O, p=0.021) in patients with auto-PEEP compared to patients without auto-PEEP. The differences of other indices including $V_T$, PEFR, $V_E$ and $T_I/T_{TOT}$ showed no significance. 2) Effect of 3 cm $H_2O$ external PEEP on respiratory mechanics in patients with auto-PEEP : When 3 cm $H_2O$ of external PEEP was applied, there were significant decrease in WOB ($1.71{\pm}0.24$ vs $1.20{\pm}0.21\;J/L$, p=0.021) and PTP ($317{\pm}70$ vs $231{\pm}55\;cm$ $H_2O{\cdot}sec/min$, p=0.038). RAWm showed a tendency to decrease ($28.8{\pm}2.5$ vs $23.9{\pm}2.1\;cm$ $H_2O$, p=0.051). But PIP was increased with application of 3 cm $H_2O$ of external PEEP ($16{\pm}2$ vs $22{\pm}3\;cm$ $H_2O$, p=0.008). $V_T$, $V_E$, PEFR, $T_I/T_{TOT}$ and Cdyn did not change significantly. Conclusion : The presence of auto-PEEP in mechanically ventilated patients was accompanied with increased WOB performed by patient, and this WOB was decreased by 3 cm $H_2O$ of externally applied PEEP. But, with 3 cm $H_2O$ of external PEEP, increased PIP was noted, implying the importance of close monitoring of the airway pressure during application of external PEEP.

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G Protein-Coupled Receptor Signaling in Gastrointestinal Smooth Muscle

  • Sohn, Uy-Dong;Kim, Dong-Seok;Murthy, Karnam S.
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.4
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    • pp.287-297
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    • 2001
  • Contraction of smooth muscle is initiated by an increase in cytosolic $Ca^{2+}$ leading to activation of $Ca^{2+}$/ calmodulin-dependnet myosin light chain (MLC) kinase and phosphorylation of MLC. The types of contraction and signaling mechanisms mediating contraction differ depending on the region. The involvement of these different mechanisms varies depending on the source of $Ca^{2+}$ and the kinetic of $Ca^{2+}$ mobilization. $Ca^{2+}$ mobilizing agonists stimulate different phospholipases $(PLC-{\beta},\;PLD\;and\;PLA_2)$ to generate one or more $Ca^{2+}$ mobilizing messengers $(IP_3\;and\;AA),$ and diacylglycerol (DAG), an activator of protein kinase C (PKC). The relative contributions of $PLC-{\beta},\;PLA_2$ and PLD to generate second messengers vary greatly between cells and types of contraction. In smooth muscle cell derived form the circular muscle layer of the intestine, preferential hydrolysis of $PIP_2$ and generation of $IP_3$ and $IP_3-dependent\;Ca^{2+}$ release initiate the contraction. In smooth muscle cells derived from longitudinal muscle layer of the intestine, preferential hydrolysis of PC by PLA2, generation of AA and AA-mediated $Ca^{2+}$ influx, cADP ribose formation and $Ca^{2+}-induced\;Ca^{2+}$ release initiate the contraction. Sustained contraction, however, in both cell types is mediated by $Ca^{2+}-independent$ mechanism involving activation of $PKC-{\varepsilon}$ by DAG derived form PLD. A functional linkage between $G_{13},$ RhoA, ROCK, $PKC-{\varepsilon},$ CPI-17 and MLC phosphorylation in sustained contraction has been implicated. Contraction of normal esophageal circular muscle (ESO) in response to acetylcholine (ACh) is linked to $M_2$ muscarinic receptors activating at least three intracellular phospholipases, i.e. phosphatidylcholine-specific phospholipase C (PC-PLC), phospholipase D (PLD) and the high molecular weight (85 kDa) cytosolic phospholipase $A_2\;(cPLA_2)$ to induce phosphatidylcholine (PC) metabolism, production of diacylglycerol (DAG) and arachidonic acid (AA), resulting in activation of a protein kinase C (PKC)-dependent pathway. In contrast, lower esophageal sphincter (LES) contraction induced by maximally effective doses of ACh is mediated by muscarinic $M_3$ receptors, linked to pertussis toxin-insensitive GTP-binding proteins of the $G_{q/11}$ type. They activate phospholipase C, which hydrolyzes phosphatidylinositol bisphosphate $(PIP_2),$ producing inositol 1, 4, 5-trisphosphate $(IP_3)$ and DAG. $IP_3$ causes release of intracellular $Ca^{2+}$ and formation of a $Ca^{2+}$-calmodulin complex, resulting in activation of myosin light chain kinase and contraction through a calmodulin-dependent pathway.

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The Role of Poly(ADP-ribose) Polymerase-1 in Ventilator-Induced Lung Injury (기계환기로 인한 급성 폐손상에서 poly(ADP-ribose) polymerase-1의 역할)

  • Kim, Je-Hyeong;Yoon, Dae Wui;Hur, Gyu Young;Jung, Ki Hwan;Lee, Sung Yong;Lee, Sang Yeub;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Yoo, Se Hwa;Kang, Kyung Ho
    • Tuberculosis and Respiratory Diseases
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    • v.60 no.4
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    • pp.451-463
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    • 2006
  • Background : Reactive oxygen species (ROS) take center stage as executers in ventilator-induced lung injury (VILI). The protein with DNA-damage scanning activity, poly (ADP-ribose) polymerase-1 (PARP1), signals DNA rupture and participates in base-excision repair. Paradoxically,overactivation of PARP1 in response to massive genotoxic injury such as ROS can induce cell death through ${\beta}$ -nicotinamide adenine dinucleotide ($NAD^+$) depletion, resulting in inflammation. The purpose of this study is to investigate the role of PARP1 and the effect of its inhibitor in VILI. Methods : Forty-eight male C57BL/6 mice were divided into sham, lung protective ventilation(LPV), VILI, and PARP1 inhibitor (PJ34)+VILI (PJ34+VILI) groups. Mechanical ventilator setting for the LPV group was $PIP\;15cmH_2O$ + $PEEP\;3cmH_2O$ + RR 90/min + 2 hours. The VILI and PJ34+VILI groups were ventilated on a setting of $PIP\;40cmH_2O$ + $PEEP\;0cmH_2O$ + RR 90/min + 2 hours. As a PARP1 inhibitor for the PJ34+VILI group, 20 mg/Kg of PJ34 was treated intraperitoneally 2 hours before mechanical ventilation. Wet-to-dry weight ratio and acute lung injury (ALI) score were measured to determine the degree of VILI. PARP1 activity was evaluated by using an immunohistochemical method utilizing biotinylated NAD. Myeloperoxidase (MPO) activity and the concentration of inflammatory cytokines such as tumor necrosis factor $(TNF)-{\alpha}$, interleukin $(IL)-1{\beta}$, and IL-6 were measured in bronchoalveolar lavage fluid (BALF). Results : In the PJ34+VILI group, PJ34 pretreatment significantly reduced the degree of lung injury, compared with the VILI group (p<0.05). The number of cells expressing PARP1 activity was significantly increased in the VILI group, but significantly decreased in the PJ34+VILI group (p=0.001). In BALF, MPO activity, $TNF-{\alpha}$, $IL-1{\beta}$, and IL-6 were also significantly lower in the PJ34+VILI group (all, p<0.05). Conclusion : PARP1 overactivation plays a major role in the mechanism of VILI. PARP1 inhibitor prevents VILI, and decreases MPO activity and inflammatory cytokines.