• Journal of Physiology & Pathology in Korean Medicine
• /
• v.16 no.4
• /
• pp.768-773
• /
• 2002

Behcets disease is a systemic inflammatory disorder. The etiology and pathogenesis of Behcets disease has yet been fully elucidated but might involve immune dysfunction. Cytokines involved in the regulation of inflammatory reactions and immune responses may play a role in the pathogenesis of Behcets disease (BD). Onchungeum is an Oriental herbal medication, which has been successfully used in Korea for the treatment of BD. This report describes modulation effects of Onchungeum on cytokine production from phytohaemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMC) of Behcets patients by ELISA. Onchungeum significantly inhibited the production of pro-inflammatory cytokines. TNF-α and IL-1β, compared to absence of Onchungeum (by 52.3 1.4 % inhibition for TNF-α and 113.5 3.3 % for IL-1β, p < 0.001). Onchungeum also inhibited the production of IFN-γ, immunoregulatory Th1 cytokine, by 89.4 0.8 % (p < 0.001). The inhibitory effects of Onchungeum on cytokine production showed dose-dependent manner, and the pre-treatment of 1 mg/ml Onchungeum had better effects than immunosuppressive drug for treatment of BD, cyclosporin A. Our results suggest that Onchungeum treatment for Behcets disease patients may have pharmacologic activities and abilities of regulation of immune and inflammatory responses by cytokine modulation.

• Journal of Yeungnam Medical Science
• /
• v.38 no.1
• /
• pp.27-33
• /
• 2021

The gut is a complex organ that has played an important role in digestion, absorption, endocrine functions, and immunity. The gut mucosal barriers consist of the immunologic barrier and nonimmunologic barrier. During critical illnesses, the gut is susceptible to injury due to the induction of intestinal hyperpermeability. Gut hyperpermeability and barrier dysfunction may lead to systemic inflammatory response syndrome. Additionally, gut microbiota are altered during critical illnesses. The etiology of such microbiome alterations in critical illnesses is multifactorial. The interaction or systemic host defense modulation between distant organs and the gut microbiome is increasingly studied in disease research. No treatment modality exists to significantly enhance the gut epithelial integrity, permeability, or mucus layer in critically ill patients. However, multiple helpful approaches including clinical and preclinical strategies exist. Enteral nutrition is associated with an increased mucosal barrier in animal and human studies. The trophic effects of enteral nutrition might help to maintain the intestinal physiology, prevent atrophy of gut villi, reduce intestinal permeability, and protect against ischemia-reperfusion injury. The microbiome approach such as the use of probiotics, fecal microbial transplantation, and selective decontamination of the digestive tract has been suggested. However, its evidence does not have a high quality. To promote rapid hypertrophy of the small bowel, various factors have been reported, including the epidermal growth factor, membrane permeant inhibitor of myosin light chain kinase, mucus surrogate, pharmacologic vagus nerve agonist, immune-enhancing diet, and glucagon-like peptide-2 as preclinical strategies. However, the evidence remains unclear.

• Journal of Pharmacopuncture
• /
• v.16 no.1
• /
• pp.43-49
• /
• 2013

Objective: Pyungwi-san (PWS) plays a role in a number of physiologic and pharmacologic functions in many organs. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow waves in the gastrointestinal (GI) tract. We aimed to investigate the beneficial effects of PWS in mouse small-intestinal ICCs. Methods: Enzymatic digestion was used to dissociate ICCs from the small intestine of a mouse. The whole-cell patch-clamp configuration was used to record membrane potentials from the cultured ICCs. Results: ICCs generated pacemaker potentials in the GI tract. PWS produced membrane depolarization in the current clamp mode. Pretreatment with a $Ca^{2+}$-free solution and a thapsigargin, a $Ca^{2+}$-ATPase, inhibitor in the endoplasmic reticulum, eliminated the generation of pacemaker potentials. However, only when the thapsigargin was applied in a bath solution, the membrane depolarization was not produced by PWS. Furthermore, the membrane depolarizations due to PWS were inhibited not by U-73122, an active phospholipase C inhibitor, but by chelerythrine and calphostin C, protein kinase C inhibitors. Conclusions: These results suggest that PWS might affect GI motility by modulating the pacemaker activity in the ICCs.

• Biomolecules & Therapeutics
• /
• v.26 no.2
• /
• pp.210-217
• /
• 2018

Neuroinflammation is an immune response within the central nervous system against various proinflammatory stimuli. Abnormal activation of this response contributes to neurodegenerative diseases such as Parkinson disease, Alzheimer's disease, and Huntington disease. Therefore, pharmacologic modulation of abnormal neuroinflammation is thought to be a promising approach to amelioration of neurodegenerative diseases. In this study, we evaluated the synthetic flavone derivative 3',4'-dihydroxyflavone, investigating its anti-neuroinflammatory activity in BV2 microglial cells and in a mouse model. In BV2 microglial cells, 3',4'-dihydroxyflavone successfully inhibited production of chemokines such as nitric oxide and prostaglandin $E_2$ and proinflammatory cytokines such as tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 in BV2 microglia. It also inhibited phosphorylation of mitogen-activated protein kinase (MAPK) and nuclear factor $(NF)-{\kappa}B$ activation. This indicates that the anti-inflammatory activities of 3',4'-dihydroxyflavone might be related to suppression of the proinflammatory MAPK and $NF-{\kappa}B$ signaling pathways. Similar anti-neuroinflammatory activities of the compound were observed in the mouse model. These findings suggest that 3',4'-dihydroxyflavone is a potential drug candidate for the treatment of microglia-related neuroinflammatory diseases.

• Biomolecules & Therapeutics
• /
• v.30 no.4
• /
• pp.320-327
• /
• 2022

Neurodevelopmental disorders are complex conditions that pose difficulty in the modulation of proper motor, sensory and cognitive function due to dysregulated neuronal development. Previous studies have reported that an imbalance in the excitation/inhibition (E/I) in the brain regulated by glutamatergic and/or GABAergic neurotransmission can cause neurodevelopmental and neuropsychiatric behavioral deficits such as autism spectrum disorder (ASD). NMDA acts as an agonist at the NMDA receptor and imitates the action of the glutamate on that receptor. NMDA however, unlike glutamate, only binds to and regulates the NMDA receptor subtypes and not the other glutamate receptors. This study seeks to determine whether NMDA administration in mice i.e., over-activation of the NMDA system would result in long-lasting behavioral deficits in the adolescent mice. Both gender mice were treated with NMDA or saline at early postnatal developmental period with significant synaptogenesis and synaptic maturation. On postnatal day 28, various behavioral experiments were conducted to assess and identify behavioral characteristics. NMDA-treated mice show social deficits, and repetitive behavior in both gender mice at adolescent periods. However, only the male mice but not female mice showed increased locomotor activity. This study implies that neonatal exposure to NMDA may illicit behavioral features similar to ASD. This study also confirms the validity of the E/I imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model for ASD. Future studies may explore the mechanism behind the gender difference in locomotor activity as well as the human relevance and therapeutic significance of the present findings.

• The Korean Journal of Nuclear Medicine Technology
• /
• v.14 no.2
• /
• pp.33-37
• /
• 2010

Purpose: In the early stage of using PET/CT, it was used to damper revision but recently shows that CT with MDCT is commonly used and works well for an anatomical diagnosis. This hospital makes the accuracy and convenience more higher in the diagnosis and evaluate of coronary heart disease through concurrently running myocardial perfusion SPECT examination, myocardial PET examination with FDG, and CT coronary artery CT angiography(coronary CTA) used PET/CT with 64-slice. This report shows protocol and image based on results from about 400 coronary heart disease examinations since having 64 channels PET/CT in July 2007. Materials and Methods: An Equipment for this examination is 64-slice CT and Discovery VCT (DVCT) that is consisted of PET with BGO ($Bi_4Ge_3O_{12}$) scintillation crystal by GE health care. First myocardial perfusion SPECT with pharmacologic stress test to reduce waiting time of a patient and get a quick diagnosis and evaluation, and right after it, myocardial FDG PET examination and coronary CTA run without a break. One-stop evaluation protocol of ischemic heart disease is as follows. 1)Myocardial perfusion SPECT with pharmacologic stress: A patient is injected with $^{99m}Tc$-MIBI 10 mCi and does not have any fatty food for myocardial PET examination and drink natural water with ursodeoxcholic acid 100 mg and we get SPECT image in an hour. 2)Myocardial FDG PET: To reduce blood fatty content and to increase uptake of FDG, we used creative oral glucose load using insulin and Acipimox to according to blood acid content. A patient is injected with $^{18}F$-FDG 5 mCi for reduction of his radiation exposure and we get a gated image an hour later and get delay image when we need. 3) Coronary CTA: The most important point is to control heart rate and to get cooperation of patient's breath. In order to reduce a heart rate of him or her below 65 beats, let him or her take beta blocker 50 mg ~ 200 mg after a consultation with a doctor about it and have breath-practices then have the examination. Right before the examination, we spray isosorbide dinitrate 3 to 5 times to lower tension of bessel wall and to extension a blood wall of a patient. It makes to get better the shape of an anatomy. At filming, a patient is injected CT contrast with high pressure and have enough practices before the examination in order to have no problem. For reduction of his radiation exposure, we have to do ECG-triggered X-ray tube modulation exposure. Results: We evaluate coronary artery stenosis through coronary CTA and study correlation (culprit vessel check) of a decline between stenosis and perfusion from the myocardial perfusion SPECT with pharmacologic stress, coronary CTA, and can check viability of infarction or hibernating myocardium by FDG PET. Conclusion: The examination makes us to set up a direction of remedy (drug treatment, PCI, CABG) because we can estimate of effect from remedy, lesion site and severity. In addition, we have an advantage that it takes just 3 hours and one-stop in that all of process of examinations run in succession and at the same time. Therefore it shows that the method is useful in one stop evaluation of ischemic heart disease.

• The Korean Journal of Nuclear Medicine
• /
• v.38 no.2
• /
• pp.180-189
• /
• 2004

Although the outcome of cancer patients after cytotoxic chemotherapy is related diverse mechanisms, multidrug resistance (MDR) for chemotherapeutic drugs due to cellular P-glycoprotein (Pgp) or multidrug-resistance associated protein (MRP) is most important factor in the chemotherapy failure to cancer. A large number of pharmacologic compounds, including verapamil, quinidine, tamoxifen, cyclosporin A and quinolone derivatives have been reported to overcome MDR. Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are available for the detection of Pgp and MRP-mediated transporter. $^{99m}Tc$-MIBI and other $^{99m}Tc$-radiopharmaceuticals are substrates for Pgp and MRP, and have been used in clinical studies for tumor imaging, and to visualize blockade of PgP-mediated transport after modulation of Pgp pump. Colchicine, verapamil and daunorubicin labeled with $^{11}C$ have been evaluated for the quantification of Pgp-mediated transport with PET in vivo and reported to be feasible substrates with which to image Pgp function in tumors. Leukotrienes are specific substrates for MRP and $N-[^{11}C]acetyl-leukotriene$ E4 provides an opportunity to study MRP function non-invasively in vivo. SPECT and PET pharmaceuticals have successfully used to evaluate pharmacologic effects of MDR modulators. Imaging of MDR and reversal of MDR with bioluminescence in a living animal is also evaluated for future clinical trial. We have described recent advances in molecular imaging of MDR and reviewed recent publications regarding feasibility of SPECT and PET imaging to study the functionality of MDR transporters in vivo.

• Journal of Ginseng Research
• /
• v.40 no.2
• /
• pp.160-168
• /
• 2016

Background: Ginseng (Panax ginseng Meyer) is a well-characterized medicinal herb listed in the classic oriental herbal dictionary as "Shin-nong-bon-cho-kyung." Ginseng has diverse pharmacologic and therapeutic properties. Black ginseng (BG, Ginseng Radix nigra) is produced by repeatedly steaming fresh ginseng nine times. Studies of BG have shown that prolonged heat treatment enhances the antioxidant activity with increased radical scavenging activity. Several recent studies have showed the effects of BG on increased lipid profiles in mice. In this study report the effects of water and ethanol extracts of BG on hypercholesterolemia in rats. To our knowledge, this is the first time such an effect has been reported. Methods: Experiments were conducted on male Sprague Dawley rats fed with a high-cholesterol diet supplemented with the water and ethanol extracts of BG (200 mg/kg). Their blood cholesterol levels, serum white blood cell levels, and cholesterol-metabolizing marker genes messenger RNA (mRNA) expression were determined. Liver and adipose tissues were histologically analyzed. Results: We found that BG extracts efficiently reduced the total serum cholesterol levels, low-density lipoprotein (LDL) levels with increased food efficiency ratio and increased number of neutrophil cells. It also attenuated the key genes responsible for lipogenesis, that is, acetyl-coenzyme A (CoA) acetyltransferase 2, 3-hydroxy-3-methyl-glutaryl-CoA reductase, and sterol regulatory element-binding protein 2, at the mRNA level inside liver cells. Furthermore, the BG extract also reduced the accumulation of fat in adipose tissues, and inhibited the neutral fat content in liver cells stained with hematoxylin and eosin and oil red O. Conclusion: Administration of BG extracts to Sprague Dawley rats fed with high-cholesterol diet ameliorated hypercholesterolemia, which was mediated via modulation of cholesterol-metabolizing marker genes. This data throw a light on BG's cardioprotective effects.

• Investigative Magnetic Resonance Imaging
• /
• v.16 no.2
• /
• pp.136-141
• /
• 2012

Purpose : To investigate the pharmacologic modulation of motor task-dependent physiologic responses by antiplatelet agent, clopidogrel, during hand motor tasks in healthy subjects. Materials and Methods: Ten healthy, right-handed subjects underwent three functional magnetic resonance (fMRI) sessions: one before drug administration, one after high dose drug administration and one after reaching drug steady state. For the motor task fMRI, finger flexion-extension movements were performed. Blood oxygenation level dependent (BOLD) contrast was collected for each subject using a 3.0 T VHi (GE Healthcare, Milwaukee, USA) scanner. $T2^*$-weighted echo planar imaging was used for fMRI acquisition. The fMRI data processing and statistical analyses were carried out using SPM2. Results: Second-level analysis revealed significant increases in the extent of activation in the contralateral motor cortex including primary motor area (M1) after drug administration. The number of activated voxels in motor cortex was 173 without drug administration and the number increased to 1049 for high dose condition and 673 for steady-state condition respectively. However, there was no significant difference in the magnitude of BOLD signal change in terms of peak T value. Conclusion: The current results suggest that cerebral motor activity can be modulated by clopidogrel in healthy subjects and that fMRI is highly senstive to evidence such changes.