• The Korean Journal of Physiology and Pharmacology
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• 제14권3호
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• pp.127-132
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• 2010

Reactive oxygen species (ROS), which include hydrogen peroxide ($H_2O_2$), the superoxide anion (${O_2}^-{\cdot}$), and the hydroxyl radical ($OH{\cdot}$), are generated as by-products of oxidative metabolism in cells. The cerebral cortex has been found to be particularly vulnerable to production of ROS associated with conditions such as ischemia-reperfusion, Parkinson's disease, and aging. To investigate the effect of ROS on inhibitory GABAergic synaptic transmission, we examined the electrophysiological mechanisms of the modulatory effect of $H_2O_2$ on GABAergic miniature inhibitory postsynaptic current (mIPSCs) in mechanically isolated rat cerebral cortical neurons retaining intact synaptic boutons. The membrane potential was voltage-clamped at -60 mV and mIPSCs were recorded and analyzed. Superfusion of 1-mM $H_2O_2$ gradually potentiated mIPSCs. This potentiating effect of $H_2O_2$ was blocked by the pretreatment with either 10,000-unit/mL catalase or $300-{\mu}M$ N-acetyl-cysteine. The potentiating effect of $H_2O_2$ was occluded by an adenylate cyclase activator, forskolin, and was blocked by a protein kinase A inhibitor, N -(2-[p-bromocinnamylamino] ethyl)-5-isoquinolinesulfonamide hydrochloride. This study indicates that oxidative stress may potentiate presynaptic GABA release through the mechanism of cAMP-dependent protein kinase A (PKA)-dependent pathways, which may result in the inhibition of the cerebral cortex neuronal activity.

• 미생물학회지
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• 제51권4호
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• pp.444-447
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• 2015

본 연구는 $SeO_2$의 메티실린-내성 S. aureus에 대한 항세균활성을 규명하고자 수행하였다. Disc diffusion method를 이용하여 $SeO_2$의 항세균 활성을 측정한 결과, 그람 양성 세균이 그람 음성 세균과 비교시 우수하였다. 사용한 그람 양성 세균 중 Streptococcus, Staphylococcs 속 세균이 Bacillus 속 간균과 비교시 더 우수하였다. 사용한 모든 MRSA에 항균활성이 나타났다. 항생제의 생육저지환을 측정한 결과, 사용한 모든 항생제에 대해 MRSA의 항균활성이 작게 나타났다. $200-500{\mu}g/disc$ 범위의 $SeO_2$ 적용시 S. aureus 및 S. aureus CCARM (MRSA)에 대한 생육저지환의 직경은 각각 20-32.7 mm 및 13.5-17.9 mm이었다. $SeO_2$의 MRSA에 대한 최소생육억제농도는 $40{\mu}g/ml$이었다. 액체배지에 0.5% 및 1%의 $SeO_2$를 첨가한 결과, MRSA의 생육이 억제 되었다. 본 $SeO_2$의 항균활성 실험 결과는 추후, $SeO_2$의 항균활성 기작의 규명, 병원성 세균 및 항생제-내성 미생물에 적용될 수 있다고 판단된다.

• Journal of Acupuncture Research
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• 제15권2호
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• pp.369-382
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• 1998

The purpose of this study was finding the pain inhibitory effect of acupuncture at $LI_4$. The pain at dentes incisivi was evoked by noxious electric stimulation and EMG changes based on the interval were measured. To do this, the opioid antagonist was administered intraperitoneally. Following are some of results. 1. The pain inhibitory effect of acupuncture at $LI_4$ was 94.35%, 84.56%, 57.62%, 54.40%, at 10, 20, 30 and 40 minutes respectively. All the data were calculated based on 100% at 0 minute. The effect was very significant at 40 minutes. 2. The continuous effect of acupuncture at $LI_4$ after taking out the needle was 58.58%, 57.62%, 66.22%, 73.18%, 83.70%, 92.68%, at 50, 50, 70, 80, 90 and 100 minutes respectively. The overall continuous effect was shown its maximum 20 minutes after taking out the needle and reached to the initial value at 60 minutes. 3. The pain inhibitory effect following the naloxone administration and acupuncture application at $LI_4$ was 95.96%, 96.04%, 94.86%, 94.92% at 10, 20, 30 and 40 minutes respectively. All values showed similar tendency to the initial data. 4. The continuous effect of acupuncture at $LI_4$ after taking out the needle which was preceded by the naloxone administration was 94.48%, 96.02%, 96.02%, 98.00%, 98.46%, 97.18% at 50, 60, 70, 80, 90 and 100 minutes respectively. This trend was not a significant fluctuation. It was concluded that effect of acupuncture at $LI_4$ was shown in conjunction with secretion of analgesic substance. Therefore it is implied that the acupuncture application will play a major role in treating many diseases with more revelation of scientific acupuncture mechanism. Further studies of acupuncture manipulation are needed in the future based on our study.

• Journal of Acupuncture Research
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• 제15권2호
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• pp.287-300
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• 1998

The purpose of this study was finding the pain inhibitory effect of acupuncture at ST-36. The pain at dentes incisor was evoked by noxious electric stimulation and EMG changes based on time interval were measured. To do this, the opioid antagonist was administered intraperitoneally. Followings are some of the results. 1. The pain inhibitory effect of acupuncture at ST-36 was 93.82%, 87.00%, 75.30%, 69.76% at 10 20, 30 and 40 minutes respectively. All the data were calculated based on 100% at 0 minute. The effect was very significant at 40 minutes. 2. The continuous effect of acupuncture at ST-36 after taking out the needle was 77.46%, 79.66%, 87.60%, 91.50%, 95.14%, 99.48% at 50, 60, 70, 80, 90 and 100 minutes respectively. The overall continuous effect was shown its maximum 20 minutes after taking out the needle and reached to the initial value at 60 minutes. 3. The pain inhibitory effect following the naloxone administration and acupuncture application ST-36 was 93.44%, 94.58%, 90.80%, 88.04% at 10, 20, 30 and 40 minutes respectively. All values showed similar tendency to the initial data. 4. The continuous effect of acupuncture at ST-36 after taking out the needle which was preceded by the naloxone administration was 91.26%, 91.90%, 92.06%, 93.66%, 94.12%, 93.50% at 50, 60, 70, 80, 90 and 100 minutes respectively. This trend was not a significant fluctuation. It Was concluded that effect of acupuncture at ST-36 was shown in conjunction with secretion of analgesic substance. Therefore it is implied that the acupuncture application will play a major role in treating many diseases with more revelation of scientific acupuncture mechanism. Further studies of acupuncture manipulation are needed in the future based on our study.

• IMMUNE NETWORK
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• 제4권2호
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• pp.100-107
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• 2004

Background: The fruit of Rubus coreanus (RC), a perennial herb, has been cultivated for a long time as a popular vegetable. The anti-allergy mechanism of RC is unknown. The purpose of this study is to investigate the inhibitory effect of RC on compound 48/80- or anti-DNP IgE-induced mast cell activation. Methods: For this, influences of RC on the compound 48/80-induced degranulation, histamine release, calcium influx and the change of the intracellular cAMP (cyclic adenosine-3',5' monophosphate) levels of rat peritoneal mast cells (RPMC) and on the anti-DNP IgE-induced histamine release of RPMC were observed. Results: The pretreatment of RC inhibited compound 48/80-induced degranulation, histamine release and intracelluar calcium uptake of RPMC. The anti-DNP IgE-induced histamine release of RPMC was significantly inhibited by pretreatment of RC. The RC increased the level of intracellular cAMP of RPMC, and the pretreatment of RC inhibited compound 48/80-induced decrement of intracellular cAMP of RPMC. Conclusion: These results suggest that RC contains some substances with an activity to inhibit the compound 48/80- or anti-DNP IgE-induced mast cell activitation. The inhibitory effects of RC are likely due to the stabilization of mast cells by blocking the calcium uptake and enhancing the level of intracellular cAMP.

• BMB Reports
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• 제31권5호
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• pp.459-467
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• 1998

A new set of functional group interaction energy descriptors relevant to the ACE (Angiotensin-Converting Enzyme) inhibitory peptide, QSAR (Quantitative Structure Activity Relationships), is presented. The functional group interaction energies approximate the charged interactions and distances between functional groups in molecules. The effective energies of the computationally derived geometries are useful parameters for deriving 3D-QSAR models, especially in the absence of experimentally known active site conformation. ACE is a regulatory zinc protease in the renin-angiotensin system. Therapeutic inhibition of this enzyme has proven to be a very effective treatment for the management of hypertension. The non bond interaction energy values among functional groups of six-feature of ACE inhibitory peptides were used as descriptor terms and analyzed for multivariate correlation with ACE inhibition activity. The functional group interaction energy descriptors used in the regression analysis were obtained by a series of inhibitor structures derived from molecular mechanics and semi-empirical calculations. The descriptors calculated using electrostatic and steric fields from the precisely defined functional group were sufficient to explain the biological activity of inhibitor. Application of the descriptors to the inhibition of ACE indicates that the derived QSAR has good predicting ability and provides insight into the mechanism of enzyme inhibition. The method, functional group interaction energy analysis, is expected to be applicable to predict enzyme inhibitory activity of the rationally designed inhibitors.

• 대한의생명과학회지
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• 제24권1호
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• pp.30-34
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• 2018

Silver (Ag) has been widely used in commercial products and medical fields since ancient times because of its antibacterial effect. It is harmless and non-toxic to the human body. For this reason, recent research has actively evaluated antimicrobial activity using silver (Ag). In this study, we investigated the inhibitory effect of a silver-based compound, silver phosphate ($Ag_3PO_4$) on the growth of Staphylococcus aureus and the activation of human immunity. First, the inhibitory effect of $Ag_3PO_4$ on the growth of Staphylococcus aureus was confirmed by a growth curve and a colonyounting method. As a result, the growth inhibitory effect increased as the concentration of $Ag_3PO_4$ increased. Specifically, treatment with $5{\mu}g/mL$ of $Ag_3PO_4$ resulted in no bacteria growth, and the colony-counting method showed a remarkable inhibition. In addition, the expression of cytokine IL-8 by $Ag_3PO_4$ was examined to investigate the cellular immune system activation by $Ag_3PO_4$. After pretreatment of Staphylococcus aureus for 1 hour with $50{\mu}g/mL$ $Ag_3PO_4$, an increased IL-8 mRNA expression resulted. In cells treated with $Ag_3PO_4$, we found that the expression of IL-8 was enhanced in a time-dependent fashion compared to non-treated cells. These results indicate that $Ag_3PO_4$ induces antimicrobial activity against Staphylococcus aureus and activates human immunity. These results are expected to contribute to the future study of the mechanism of silver (Ag) and silver-based compounds in relation to antibacterial activity.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권1호
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• pp.63-71
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• 2020

Purpose: Autoimmune hepatitis (AIH) is a chronic disease that may lead to cirrhosis. The immunopathogenesis of AIH is not fully understood and it mainly involves T-cell mediated mechanism. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that promotes T cell response and its polymorphism may serve as a severity marker of AIH. No previous study has considered investigating MIF polymorphism in children with AIH. Methods: Forty-two children with definite diagnosis of AIH were enrolled along with 100 age and sex matched controls. All participants were tested for polymorphism at -173GC (rs755622) of MIF gene. All patients received the standard protocol of steroid plus azathioprine to achieve remission. Liver biopsy was performed at time of diagnosis for all patients and only 18 of them underwent a second biopsy after treatment. Results: No statistically significant differences in the frequency of the genotypes GG and GC or in allele distribution were found in both patient and control groups (p=0.590, 0.640 respectively). Initial alanine aminotransferase (ALT) levels at the time of presentation was significantly higher in the GC group than GG group (p=0.020). GC genotype significantly correlated with disease relapse (r=0.41, p=0.007). Regression of necroinflammation and the fibrosis score in the second liver biopsy was statistically significant in the GG group (p<0.0001, p=0.010 respectively). Conclusion: MIF -173GC polymorphism is associated with clinically significant markers of pediatric AIH, including increased initial serum ALT levels, may help predict necroinflammatory/fibrosis regression effectively, following immunosuppressive treatment.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7129-7135
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• 2014

Background: In this study, we aimed to evaluate the growth inhibitory effect of the combination of ethaselen (BBSKE) and low fixed dose of selenite against A549 human non-small cell lung cancer cells in vitro. Materials and Methods: Growth inhibitory effects against A549 cells were determined by SRB assay. Combination index (CI) values were calculated based on Chou-Talalay median-effect analyses. Dose reduction index (DRI) values were applied to calculate dose reduction of selenite. Contents of free thiols and GSH were determined by DTNB assay and intracellular ROS levels by DCFH-DA fluorescence labeling. Results: Compared with BBSKE or selenite single treatment, the combined application of ethaselen and a low fixed dose of selenite shortened the onset time of sodium selenite, reduced $IC_{50}$ values, and increased the maximum inhibition rates, suggesting a possible molecular mechanism of the synergism. Obvious synergistic effects were observed after different times of combination treatment, especially after 24 h. Compared with selenite single treatment, dosage of selenite could be remarkably reduced in combination therapy to gain the same inhibitory effect on cell proliferation. Compared with BBSKE single treatment, the content of free thiols and GSH were significantly reduced and ROS levels greatly elevated in the combination group. For the combination treatment, cell viability increased as greater concentrations of GSH were added. Conclusions: All these results indicate that the combination treatment of BBSKE and selenite showed synergism to inhibit A549 cell proliferation in vitro, and also reduced the selenite dosage to mitigate its toxicity which is very meaningful for combination chemotherapy of lung cancer. The synergism was probably caused by the accelerated exhaustion of intracellular reductive substances, such as free thiols and GSH, which ultimately leads to enhanced oxidative stress and apoptosis.

• Journal of Microbiology and Biotechnology
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• 제9권3호
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• pp.235-242
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• 1999

We investigated the growth-inhibitory mechanism of Helicobacter pylori by omeprazole (OMP) and its activated sulfenamide (OAS). Using dithiothreitol (DTT) and 5,5'-dithio-bis[2-nitrobenzoic acid] (DTNB; Ellman's reagent), we first determined the relationship between the binding capacity of these compounds to H. pylori membrane and its significance to membrane P-type ATPase activity. After incubation of the intact H. pylori cells with either OMP or OAS, the residual quantity of free SH-groups on the cell membrane was measured, and, the resulting values were plotted as a function of time. From this experiment, we found that there was a considerable difference in the membrane-binding rates between OMP and OAS. At neutral pH, the disulfide bond formation on H. pylori membrane was completed within 2 min of incubation of the intact cells with OAS. By OMP, however, it was gradually formed, exceeding 10 min of incubation for completion, whereby, the extent of P-type ATPase inhibition appeared to be proportional to the disulfide forming rate. From this data, it was suggested that the disulfide formation might directly affect enzyme activity. Since OMP per se cannot yield a disulfide bond with cysteine, it is predicted that the enzyme inactivation must be caused by the OAS form. Accordingly, we postulated that, under the neutral pH, OMP could be converted to OAS in the course of transport. By extrapolating the inhibitory slopes, we could evaluate K₁ values, relating to their minimal inhibitory concentrations (MICs) for H. pylori growth. In these MIC ranges, H. pylori uptake or vesicular export of nutrients such as peptides were totally prohibited, but their effect in Escherichia coli were negligible. From these observations, we strongly suggest that the P-type ATPase activity is essential for the survival of H. pylori cells in particular.