• Title/Summary/Keyword: nNOS

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Cone-beam computed tomography texture analysis can help differentiate odontogenic and non-odontogenic maxillary sinusitis

  • Andre Luiz Ferreira Costa;Karolina Aparecida Castilho Fardim;Isabela Teixeira Ribeiro;Maria Aparecida Neves Jardini;Paulo Henrique Braz-Silva;Kaan Orhan;Sergio Lucio Pereira de Castro Lopes
    • Imaging Science in Dentistry
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    • v.53 no.1
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    • pp.43-51
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    • 2023
  • Purpose: This study aimed to assess texture analysis(TA) of cone-beam computed tomography (CBCT) images as a quantitative tool for the differential diagnosis of odontogenic and non-odontogenic maxillary sinusitis(OS and NOS, respectively). Materials and Methods: CBCT images of 40 patients diagnosed with OS (N=20) and NOS (N=20) were evaluated. The gray level co-occurrence (GLCM) matrix parameters, and gray level run length matrix texture (GLRLM) parameters were extracted using manually placed regions of interest on lesion images. Seven texture parameters were calculated using GLCM and 4 parameters using GLRLM. The Mann-Whitney test was used for comparisons between the groups, and the Levene test was performed to confirm the homogeneity of variance (α=5%). Results: The results showed statistically significant differences(P<0.05) between the OS and NOS patients regarding 3 TA parameters. NOS patients presented higher values for contrast, while OS patients presented higher values for correlation and inverse difference moment. Greater textural homogeneity was observed in the OS patients than in the NOS patients, with statistically significant differences in standard deviations between the groups for correlation, sum of squares, sum of entropy, and entropy. Conclusion: TA enabled quantitative differentiation between OS and NOS on CBCT images by using the parameters of contrast, correlation, and inverse difference moment.

Nitric Oxide: The Pathophysiological Roles and Clinical Implications in Circulatory System (순환계에서 Nitric Oxide의 생리-병리학적 역할과 그 임상적 의의)

  • Lee, K.Y.
    • Journal of Yeungnam Medical Science
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    • v.13 no.2
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    • pp.159-172
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    • 1996
  • 대기오염물질이면서 동시에 생체내 화학반응의 산물이기도 한 nitric oxide(NO)는 그 생체내 분포가 광범위하고 생리적 역할이 다양하여, 최근의 생명과학 분야에서 가장 크게 주목받는 몇가지 연구대상 중 하나이다. 세포에서의 NO 산생은 nitric oxide synthase (NOS)에 의해 촉매되는데, 이들은 brain form (bNOS, neuronal; nNOS, NOS I), inducible form (iNOS), 및 endothelial form(eNOS)로 구분되는데, 이중 bNOS(nNOS)와 eNOS는 inducible form에 대비되는 constitutive form(cNOS)에 해당하므로 각각 ncNOS 와 ecNOS로도 불리운다. NOS는 아미노산인 L-arginine을 산소와 결합시켜 L-citrulline으로 변환시키면서 NO를 유리하고, 이 NO는 세포내의 guanylate cyclase를 활성화하여 cyclic GMP를 생산하거나, superoxide(O2-) 및 수소이온과 차례로 결합하여 반응성이 매우 높은 수산화기(-OH)를 발생시켜 세포독작용을 유발하기도 한다. 정상상태에서 뇌혈관내피세포의 ecNOS로 부터 유리된 NO는 혈관을 확장시켜 신경세포에 대한 산소공급을 원활히 유지해 주지만, 순환장애를 일으켰을 때는 뇌조직내의 iNOS로부터 대량의 NO가 유출되어 신경세포의 손상을 가져온다. 호흡기에서는 NO가 기도평활근을 이완시키고 폐혈류를 개선하므로, 미숙아나 성인의 호흡장애시에 소량의 NO를 흡입시키면 oxygenation을 호전시킬 수 있다. 그러나 대기오염이나 흡연 등으로 대량의 NO를 흡입할 경우 치명적인 폐부종이나 methemoglobin혈종을 일으킬 수 있다. 순환계에서는 cNOS가 혈관을 확장시켜 조직의 혈류를 유지하는데 일익을 담당한다. 세균내 독소(lipopolysaccharide; LPS)나 각종 명역조절물질들이 혈관내피세포와 혈관평활근세포로 부터 과다한 NO를 유리시키면 혈압이 급격히 떨어져 순환허탈상태에 빠지게 된다. 심장에서는 관상혈관 내피세포의 eNOS가 심근의 혈류를 유지해 주지만 허혈이나 세균내독소 또는 면역조절물질 등에 의하여 심근세포나 침윤된 대식세포의 iNOS로 부터 과량의 NO가 유리되면 심근세포의 손상이 초래된다. 신장에서는 내피세포의 cNOS에 의하여 사구체여과가 조절되고 있는데, 세균내독소나 면역 조절물질 등에 의하여 사구체관막세포(mesangial cell)등의 iNOS로 부터 과량의 NO가 유리되면 신조직과 사구체의 손상을 초래한다. 위와 같이 대부분의 장기에서 ecNOS는 조직의 혈류를 유지하는 역할을 하며, iNOS는 애초 세균 등 침입자에 대한 세포독작용이 그 존재 목적이라고 풀이할 수 있겠으나 일종의 부작용으로 자체조직의 손상을 초래하게 되는 것으로 본다. 따라서 NO와 관련된 각종 병변의 치료를 위해서는 NOS의 비선택성 억제제인 arginine 유도체 보다는 iNOS에 대한 선택적 억제제인 S-methylisothiourea(SMT), aminoethylisothiourea(AETU), aminoguanidine (AMG), agmatine, L-canavanine, transforming growth factor b1(TGF-b1) 등의 사용을 검토해 보는 것이 타당할 것으로 사료된다.

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Effects of Natural Products on the Inhibition of Lipopolysaccharide-Inducible Nitric Oxide Synthase Activity in RAW264.7 Cell Culture System

  • Park, Bong-Joo;Cho, Myung-Haing;Kim, Kyeong-Ho;Lee, Sang-Kook;Lee, Chong-Soon;An, Gil-Hwan;Mar, Woong-Chon
    • Natural Product Sciences
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    • v.5 no.3
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    • pp.113-120
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    • 1999
  • Nitric oxide (NO) is a free radical synthesized from L-arginine by nitric oxide synthase (NOS). It is believed that NO is an important mediator in numerous physiological and inflammatory responses. Particularly, a large amount of NO released from the inducible nitric oxide synthase (iNOS) is mostly associated with inflammatory processes. Overproduction of NO in these processes including sepsis and autoimmune diseases can have deleterious consequences and pathophysiologic relevance. Therefore, for the discovery of new inhibitory agents against iNOS activity, we have evaluated about 100 kinds of natural products after partition into three layers (n-hexane, ethyl acetate and aqueous) from 100% methanol extracts to study inhibitory effects on iNOS activity induced by lipopolysaccharide (LPS) in RAW264.7 cells culture system. As a positive control, curcumin, which is known as an anti-tumor promoter, anti-inflammatory agent as an iNOS inhibitor, was used and showed the dose-dependent inhibitory effect $(IC_{50},\;2.5\;{\mu}g/ml)$. Among tested fractions, the n-hexane fraction of Cimicifuga heracleifolia $(IC_{50}:\;9.65\;{\mu}g/ml)$, Forsythiae fructus $(IC_{50}:\;6.36\;{\mu}g/ml)$, Saposhnikovia divaricata $(IC_{50}:\;5.92\;{\mu}g/ml)$, and the ethyl acetate fraction of Chrysanthemum sibiricum $(IC_{50}:\;2.56\;{\mu}g/ml)$, Gastrodia elata $(IC_{50}:\;3.46\;{\mu}g/ml)$, and the aqueous fraction of Dianthus chinensis $(IC_{50}:\;6.73\;{\mu}g/ml)$, Euonymus alatus $(IC_{50}:\;6.78\;{\mu}g/ml)$, Mechania urticifoloria $(IC_{50}:\;8.01\;{\mu}g/ml)$ showed strong inhibitory activity against LPS-stimulated iNOS. Especially, the ethyl acetate fraction of Chrysanthemum sibiricum $(IC_{50}:\;2.56\;{\mu}g/ml)$, which exhibited the strongest inhibition against iNOS, was fractionated with silica-gel column chromatography. These subfractions exhibited dose-dependent inhibition against iNOS activity in the range of $2.59-5.6\;{\mu}g/ml$ except for fraction No. 3, 4, 5, 6, 8, 9, and 16. Our study shows that Chrysanthemum sibiricum has the strongest inhibitory effect against iNOS activity and has similar effect to curcumin. Therefore, further studies for the identification of active principles from Chrysanthemum sibiricum and investigation for the mechanism of the inhibition of iNOS by active principles will be performed.

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Silymarin Inhibits Cytokine-Stimulated Pancreatic Beta Cells by Blocking the ERK1/2 Pathway

  • Kim, Eun Jeong;Kim, Jeeho;Lee, Min Young;Sudhanva, Muddenahalli Srinivasa;Devakumar, Sundaravinayagam;Jeon, Young Jin
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.282-287
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    • 2014
  • We show that silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), inhibits cytokine mixture (CM: TNF-${\alpha}$, IFN-${\gamma}$, and IL-$1{\beta}$)-induced production of nitric oxide (NO) in the pancreatic beta cell line MIN6N8a. Immunostaining and Western blot analysis showed that silymarin inhibits iNOS gene expression. RT-PCR showed that silymarin inhibits iNOS gene expression in a dose-dependent manner. We also showed that silymarin inhibits extracellular signal-regulated protein kinase-1 and 2 (ERK1/2) phosphorylation. A MEK1 inhibitor abrogated CM-induced nitrite production, similar to silymarin. Treatment of MIN6N8a cells with silymarin also inhibited CM-stimulated activation of NF-${\kappa}B$, which is important for iNOS transcription. Collectively, we demonstrate that silymarin inhibits NO production in pancreatic beta cells, and silymarin may represent a useful anti-diabetic agent.

Effects of Electroacupuncture of GB30 on Transient Forebrain Ischemia Injury in Rats (일과성(一過性) 전뇌(前腦) 허혈(虛血) 손상(損傷)에 대한 환도(環跳) (GB30) 전침자극(電鍼刺戟)의 효과(效果))

  • Kim Poong-Sik;Kim Jae-Hyo;Choi Dong-Ok;Kim Kyung-Sik;Sohn In-Cheul
    • Korean Journal of Acupuncture
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    • v.19 no.1
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    • pp.35-45
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    • 2002
  • Acupuncture and herbal medicine have been used to prevent and treat the cerebrovascular accident, such as a stroke, and many studies of acupuncture and moxibustion concerning to the stroke have been undertaken in the human and various animals. However, it was not published the protective effect of the electroacupuncture (EA) of Huan-do (GB30) on the transient forebrain ischemia injury. The neuroprotective effects of EA (2 ms, 10 Hz, and 1 - 2 mA) of GB30 on the transient forebrain ischemia injury was investigated by western blot of nNOS and hematoxylin and eosin stain in Sprague-Dawley rats. The transient forebrain ischemia injury resulted in increased expression of nNOS in the brain for 6 hrs after ischemia, and EA decreased significantly expression of nNOS protein in brain increased by transient forebrain ischemia injury. The survived neuronal cell stained with hematoxylin and eosin (H&E) decreased in the hippocampus by the 7 days after ischemia comparing with the normal. Comparing with the normal, the survived neurons seriously decreased cell in the hippocampus after the injury. However, the proportion of survived neurons was increased in EA treatment. These results suggest that EA of GB30 have neuroprotective effects on transient forebrain ischemia injury.

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Role of Angiotensin II and Nitric Oxide in the Rat Paraventricular Nucleus

  • Yang, Eun-Kyoung
    • The Korean Journal of Physiology and Pharmacology
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    • v.5 no.1
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    • pp.41-46
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    • 2001
  • To investigate the mutual relationship between angiotensin II (Ang II) and nitric oxide (NO) in paraventricular nucleus (PVN), Ang II receptor type Ia $(AT_{1A}),$ type Ib $(AT_{1B}),$ endothelial constitutive nitric oxide synthase (ecNOS), and neuronal constitutive nitric oxide synthase (ncNOS) mRNA levels of rat PVN were measured after unilateral carotid artery ligation. $AT_{1A}$ and $AT_{1B}$ mRNA levels were markedly elevated 6 hrs after unilateral carotid artery ligation. Losartan injection $(10\;{\mu}g/0.3\;{\mu}l)$ into the PVN augmented of the increment of $AT_{1A}$ and $AT_{1B}$ mRNAs It also increased ecNOS gene expression. In addition, $AT_{1B}$ mRNA levels increased after N-nitro-L-arginine methyl ester (L-NAME) injection $(50\;{\mu}g/0.3\;{\mu}l)$ into the PVN. These results suggest that Ang II and NO in the rat PVN may interplay, at least in part, through regulation of gene expression of ecNOS and $AT_{1B},$ respectively.

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Antipyretic Effect of Rhizoma Cimicifugae in a Rat Model of LPS-Induced Fever (Lipopolysaccharide에 의해 유발된 발열에 있어서 승마의 해열효과)

  • 권일호;김남권;강학천;임홍진;김진만
    • The Journal of Korean Medicine
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    • v.23 no.4
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    • pp.32-44
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    • 2002
  • Objective: In this study, we investigated the effects of Rhizoma Cimicifugae (RC) on the induction of nitric oxide (NO) in RAW 264.7 murine macrophages treated with lipopolysaccharide (LPS). Methods: We examined whether RC have an antipyretic effect by inhibition of COX and/or NOS in fever that is evoked by an intraperitoneal injection of LPS in rats. Results: 1. RC inhibited NO metabolites produced by activated murine macrophage in a dose-dependent manner. 2. RC had an antipyretic effect in a dose-dependent manner in LPS-induced fever. 3. RC inhibited levels of both COX-2 protein and iNOS protein increased by the treatment of LPS in brain tissues as well as brain blood vessels. 4. There were no changes in proteins of nNOS/COX-1. Conclusions: RC has an antipyretic effect by attenuating the level of iNOS and COX-2 protein.

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The Expressional Changes of Nitric Oxide Synthase in the Rat Brain Following Food Restriction

  • Kang Kyounglan;Huh Youngbuhm;Park Chan;Choue Ryo Won
    • Nutritional Sciences
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    • v.8 no.4
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    • pp.231-236
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    • 2005
  • This study investigated the changes in the neuronal nitric oxide synthase (nNOS) and nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) activities during food restriction in the rat brain such as cerebral cortex, cerebellum, caudate pautamen and hypothalamus. The rats were placed on a restricted feeding schedule consisting of half the ad libitum quantity for 3 days and 1, 2, 4, 6 and 9 weeks, and a free feeding schedule for 4 weeks. The loss of body weight peaked after 1 week of food restriction and persisted during the entire 9-week period of food restriction. The dramatic weight change in the first week ($12\%$) and the reduction in weight changes thereafter suggest that major adaptation changes occur early and body maintenance occurs subsequently. In the hypothalamus, the optical densities of the NADPH-d and nNOS immunoreactivities were found to be significantly higher in the 1-week and lower in the 9-week food restricted group than in the ad libitum fed control rats. In contrast, in the cerebral cortex, the optical densities of the NADPH-d- and nNOS-positive neurons were not changed significantly during the period of food restriction. This study provides the morphological evidence showing that food restriction has a significant effect on the nitric oxide synthesizing system of the hypothalamus.

Nitric Oxide Prevents the Bovine Cerebral Endothelial Cell Death Induced by Serum-Deprivation

  • Kim, Chul-Hoon;Ahn, Young-Soo
    • The Korean Journal of Physiology and Pharmacology
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    • v.1 no.5
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    • pp.515-521
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    • 1997
  • Endothelial cells play a central role in the inflammatory processes, and activation of nuclear factor kappa B ($NF-_{\kappa}B$) is a key component in that inflammatory processes. Previously, we reported that tumor necrosis factor alpha($TNF{\alpha}$) had protective effect of cell death induced by serum deprivation and this protection was related to $NF-_{\kappa}B$ activation. Inducible nitric oxide synthase (iNOS) is a member of the molecules which transcription is regulated mainly by $NF-_{\kappa}B$. And the role of nitric oxide (NO) generated by iNOS on cell viability is still controversial. To elucidate the mechanism of $TNF{\alpha}$ and $NF-_{\kappa}B$ activation on cell death protection, we investigate the effect of NO on the cell death induced by serum- deprivation in bovine cerebral endothelial cells in this study. Addition of $TNF{\alpha}$, which are inducer of iNOS, prevented serum-deprivation induced cell death. Increased expression of iNOS was confirmed indirectly by nitrite measurement. When selective iNOS inhibitors were treated, the protective effect of $TNF{\alpha}$ on cell death was partially blocked, suggesting that iNOS expression was involved in controlling cell death. Exogenously added NO substrate (L-arginine) and NO donors (sodium nitroprusside and S-nitroso-N-acetylpenicillamine) also inhibited the cell death induced by serum deprivation. These results suggest that NO has protective effect on bovine cerebral endothelial cell death induced by serum-deprivation and that iNOS is one of the possible target molecules by which $NF-_{\kappa}B$ exerts its cytoprotective effect.

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Cedrela sinensis Leaves Suppress Oxidative Stress and Expressions of iNOS and COX-2 via MAPK Signaling Pathways in RAW 264.7 Cells

  • Bak, Min-Ji;Jeong, Jae-Han;Kang, Hye-Sook;Jin, Kyong-Suk;Ok, Seon;Jeong, Woo-Sik
    • Preventive Nutrition and Food Science
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    • v.14 no.4
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    • pp.269-276
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    • 2009
  • Overproduction of reactive oxygen species (ROS), including nitric oxide (NO), could be associated with the pathogenesis of various diseases such as cancer and chronic inflammation. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) are known to play key roles in the development of these diseases. Cedrela sinensis leaves have been used in Asian countries as a traditional remedy for enteritis, dysentery and itching. In the present study, we investigated the anti-inflammatory effects of Cedrela sinensis leaves in lipopolysaccharide (LPS)- stimulated RAW 264.7 macrophages. Powder of C. sinensis leaves was extracted with 95% ethanol and fractionated with a series of organic solvents including n-hexane, dichloromethane, ethyl acetate, n-butanol, and water. The dichloromethane (DCM) fraction strongly inhibited NO production possibly by down-regulating iNOS and COX-2 expression, as determined by Western blotting. Hydrogen peroxide-induced generation of reactive oxygen species (ROS) was also effectively inhibited by the DCM fraction from C. sinensis leaves. In addition, C. sinensis inhibited LPS-mediated p65 activation via the prevention of IκB-$\alpha$ phosphorylation. Furthermore, mitogen-activated protein kinases (MAPKs) such as ERK 1/2 and p38 were found to affect the expression of iNOS and COX-2 in the cells. Taken together, our data suggest that leaves of C. sinensis could be used as a potential source for anti-inflammatory agents.