In the human airway, mucus exists to protect the respiratory system as a primary barrier of the innate immune system. However, hyperexpressed mucus limits airflow, resulting in a decrease of lung function. Among more than 20 mucin family members, MUC5AC and MUC5B are major glycoproteins in human airway mucus. The epidermal growth factor receptor (EGFR) signaling pathway is one of the mechanisms of these mucins expression and specificity protein-1 (Sp1) transcription factor is the downstream signal of this pathway, playing pivotal roles in mucin expression. Even though there are some drugs for treating mucus hypersecretion, no drug has proven effects on humans. We found that the flavonoid tilianin regulated MUC5AC expression and also inhibited Sp1 phosphorylation. In this study, we investigated how tilianin would modulate EGFR signaling and regulate mucin production. In conclusion, tilianin inhibited MUC5AC expression mediated via modulating the EGFR-MEK-ERK-Sp1 signaling pathway in NCI-H292 human airway epithelial cells. This study may provide the basis for the novel treatment of mucus hypersecretion.
Kim, Minjee;Nguyen, Dinh-Van;Heo, Yoonki;Park, Ki Hoon;Paik, Hyun-Dong;Kim, Young Bong
Journal of Microbiology and Biotechnology
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v.30
no.2
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pp.172-177
/
2020
Influenza viruses cause respiratory diseases in humans and animals with high morbidity and mortality rates. Conventional anti-influenza drugs are reported to exert side effects and newly emerging viral strains tend to develop resistance to these commonly used agents. Fritillaria thunbergii (FT) is traditionally used as an expectorant for controlling airway inflammatory disorders. Here, we evaluated the therapeutic effects of FT extracts against influenza virus type A (H1N1) infection in vitro, in ovo, and in vivo. In the post-treatment assay, FT extracts showed high CC50 (7,500 ㎍/ml), indicating low toxicity, and exerted moderate antiviral effects compared to oseltamivir (SI 50.6 vs. 222) in vitro. Antiviral activity tests in ovo revealed strong inhibitory effects of both FT extract and oseltamivir against H1N1 replication in embryonated eggs. Notably, at a treatment concentration of 150 mg/kg, only half the group administered oseltamivir survived whereas the FT group showed 100% survival, clearly demonstrating the low toxicity of FT extracts. Consistent with these findings, FT-administered mice showed a higher survival rate with lower body weight reduction relative to the oseltamivir group upon treatment 24 h after viral infection. Our collective results suggest that FT extracts exert antiviral effects against influenza H1N1 virus without inducing toxicity in vitro, in ovo or in vivo, thereby supporting the potential utility of FT extract as a novel candidate therapeutic drug or supplement against influenza.
Ok, Hwoe Gyeong;Kim, Su Young;Lee, Su Jung;Kim, Tae Kyun;Huh, Billy K;Kim, Kyung Hoon
The Korean Journal of Pain
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v.31
no.2
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pp.73-79
/
2018
All drugs have both favorable therapeutic and untoward adverse effects. Conventional opioid analgesics possess both analgesia and adverse reactions, such as nausea, vomiting, and respiratory depression. The opioid ligand binds to ${\mu}$ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the ${\beta}$-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the ${\beta}$-arrestin pathway. Oliceridine (TRV130) has a novel characteristic mechanism on the action of the ${\mu}$ receptor G protein pathway selective (${\mu}$-GPS) modulation. Even though adverse reactions (ADRs) are significantly attenuated, while the analgesic effect is augmented, the some residual ADRs persist. Consequently, a G protein biased ${\mu}$ opioid ligand, oliceridine, improves the therapeutic index owing to increased analgesia with decreased adverse events. This review article provides a brief history, mechanism of action, pharmacokinetics, pharmacodynamics, and ADRs of oliceridine.
Journal of The Korean Society of Clinical Toxicology
/
v.10
no.1
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pp.33-36
/
2012
Opioids are the one of the most commonly used drugs to control cancer pain all over the world. But, we should not overlook the potential risk of opioid intoxication because they have well-known detrimental side effects. The opioid intoxication can be diagnosed thorough various clinical manifestations. The altered mental status, respiratory depression, and miosis is very representative clinical features although these symptoms don't always appear together. Unfortunately the opioid-toxidrome can be varied. A 42 years old man came to our emergency room after taking about 900 mg morphine sulfate per oral. He was nearly alert and his respiration was normal. Even though his symptoms didn't deteriorated clinically, serial arterial blood gas analysis showed increase in PaCO2. So we decided to use intravenous naloxone. Soon, he was fully awaked and his pupils size was increased. After a continuous infusion of intravenous naloxone for 2 hours, PaCO2 decreased to normal range and his pupil size also returned to normal after 12 hours. Though the levels of serum amylase and lipase increased slightly, his pancreas was normal according to the abdominal computed tomography. He had nausea, vomit, and whole body itching after naloxone continuous infusion, but conservatively treated. We stopped the continuos infusion after 1 day because his laboratory results and physical examinations showed normal. As this case shows, it is very important to prescribe naloxone initially. If you suspect opioid intoxication, we recommend the initial use of naloxone even though a patient has atypical clinical features. In addition, we suggest intranasal administration of naloxone as safe and effective alternative and it's necessary to consider nalmefene that has a longer duration for opioid intoxication.
1. The concept about Jeok-chwiui(積聚) has been around since before "Hwangje-Naegyeong". Since "Hwangje-Naegyeong(黃帝內經)", Sik-jeok(食積) was made mention of specifically. In "Yu-gyeong(類經)", it is said that Sik-jeok is a combination of our body fluid and blood by bad eating and sleeping habits. 2. In the narrow sense Sik-jeok is indigestion and broadly it is inappropriately stagnant fluids in our body. 3. If studying on Sik-jeok in Dong-ui-bo-gam 1) It is located on the right side, in the epigastric region and between the skin and fascia. 2) The cause of Sik-jeok is indigestion, inappropriate temperature and weak stomach. 3) Symptoms of Sik-jeok are very diverse such as sick ascension, nausea, abdominal pain, headache, fever, etc. The right pulse is big and stressful. 4) Various symptoms related to digestive, respiratory, circulatory and reproductive system are represented by Sik-jeok. - Contemporarily women uterine or ovarian disease and back pain are mostly caused by Sik-jeok 5) Pediatric disease are mostly caused by Sik-jeok. 6) Treatment of Sik-jeok is light eating and if it is serious, you have to induce vomiting or diarrhea. Commonly used drugs are digestive medicine and invigorative medicine 7) To prevent Sik-jeok, you should forbid to eat until you are satisfied and wear warm clothes and continue to do spleen and genital do-in-beop.
Clinical observations were made on 349 cases of acute drug intoxication who were visited to emergency room of Yeungnam University Hospital during recent 7 years from January 1984 to December 1990. The following results were obtained 1) Total number of cases of acute drug intoxication was 349 which was 0.39% of the total patients of the emergency room during the same period. 2) The ratio of male to female was 1.1 : 1. The age incidence was highest in the third decade(26.7%). The monthly incidence was hightest in May. Higher frequency was observed in summer season. 3) The most common drug of the intoxication was pesticides and herbicides(71.9%), the remainders were miscellaneous drugs(11.2%), sedatives(7.7%), rodenticides(6.3%) and unknown drug(3.2%) in orders. 4) The most common cause of drug intoxication was suicide(69.1%) and the others were accident, unknown cause, intention in orders. 5) Main clinical manifestations were the impairment of consciousness, nausea, vomiting and convulsion. Physical examination revealed increased pulses, increased blood pressure, miosis of the pupil and sweating. Above symptoms and signs were more prominent in pesticide intoxication. Leukocytosis, glycosuria and abnormal LFT were common findings in acute intoxications. 6) The complications were developed in 18.3% among 349 cases and the most common complication was respiratory failure, pneumonia, cardiovascular collapse and pulmonary edema in orders. 7) Overall mortality rate was 8.3% of total cases and mortality rate was highest in herbicide intoxication(22.2%).
Purpose: Chloramphenicol and tetracycline are not recommended for treating scrub typhus in pediatric patients because of potential side effects, such as aplastic anemia or tooth discoloration. While clarithromycin has recently been used in adults, few reports have been published on its effects in pediatric patients. We report the clinical profiles of pediatric scrub typhus and the effects of clarithromycin on scrub typhus in children. Methods: We retrospectively analyzed medical records of 56 children with scrub typhus who were admitted between 2004 and 2013 to Chonbuk National University Hospital, Jeonju, Korea. Cases were divided into 3 groups based on the treatment drug (chloramphenicol, azithromycin, and clarithromycin). We compared their clinical manifestations and laboratory findings. Results: All patients exhibited fever and rash. Other common clinical manifestations were eschars (66%), lymphadenopathy (48%), upper respiratory symptoms (42%), abdominal pain (32%), and hepatosplenomegaly (14%). Elevated levels of C-reactive protein, erythrocyte sedimentation rates, aspartate transaminase, and alanine transaminase were detected in 95%, 96%, 84%, and 77% of patients, respectively. Additionally, decreased platelet and white blood cell levels were observed in 43% and 36% of patients, respectively. There were no statistical differences between the treatment groups in mean age (P=0.114) or sex (P=0.507). However, time to defervescence after the treatments differed significantly, being the shortest in the clarithromycin group (P=0.019). All patients recovered without complications related to the disease or drugs. Conclusion: Clarithromycin was as effective as chloramphenicol and azithromycin in pediatric scrub typhus patients and may be used as a first-line treatment drug.
Background: Various pain treatments have been administered to relieve patients suffering from postoperative pain. Among these, epidural or intravenous opiate administration is by far the most widly applied treatment in recent times. However it was our objective to device a more effective and safe means of postoperative analgesia. Methods: We studied 110 healthy pregnant women scheduled for delivery by elective cesarean section. EPI(epidural)-group is administered morphine 1.5 mg and 0.25% bupivacaine 8 ml as bolus dose, then, a mixture of morphine 6 mg and 0.125% bupivacaine 95 ml as continuous dose via epidural route. IV(intravenous)-group is administered nalbuphine 6~7 mg as bolus dose and nalbuphine 60~70 mg with 0.9% normal saline 90 ml as continuous dose via intravenous route, at the rate of 2 ml/hr for 2 days. We compared the analgesic efficacy and side effects of these two groups using VAS pain score and time duration of constant pain level. Results: VAS pain score was similar between the two groups, but pain duration was significantly shorter in EPI-group. Incidence of pruritus was significantly lower with the IV-group, of nausea and vomiting were similar for both groups, no respiratory depression for either groups. Conclusions: Although the EPI-group had better analgesic efficacy, the IV-group had lower incidence of side effects, and simplicity and safety methods of operation. Therefore, We propose further research and consideration of administering the kinds and doses of those medications prescribe to the IV group in conjunction with other drugs for safer and better efficacy of postoperative analgesia.
Etifoxine (etafenoxine, $Stresam^{(R)}$) is a non-benzodiazepine anxiolytic with an anticonvulsant effect. It was developed in the 1960s for anxiety disorders and is currently being studied for its ability to promote peripheral nerve healing and to treat chemotherapy-induced pain. In addition to being mediated by $GABA_A{\alpha}2$ receptors like benzodiazepines, etifoxine appears to produce anxiolytic effects directly by binding to ${\beta}2$ or ${\beta}3$ subunits of the $GABA_A$ receptor complex. It also modulates $GABA_A$ receptors indirectly via stimulation of neurosteroid production after etifoxine binds to the 18 kDa translocator protein (TSPO) of the outer mitochondrial membrane in the central and peripheral nervous systems, previously known as the peripheral benzodiazepine receptor (PBR). Therefore, the effects of etifoxine are not completely reversed by the benzodiazepine antagonist flumazenil. Etifoxine is used for various emotional and bodily reactions followed by anxiety. It is contraindicated in situations such as shock, severely impaired liver or kidney function, and severe respiratory failure. The average dosage is 150 mg per day for no more than 12 weeks. The most common adverse effect is drowsiness at the initial stage. It does not usually cause any withdrawal syndromes. In conclusion, etifoxine shows less adverse effects of anterograde amnesia, sedation, impaired psychomotor performance, and withdrawal syndromes than those of benzodiazepines. It potentiates $GABA_A$ receptor-function by a direct allosteric effect and by an indirect mechanism involving the activation of TSPO. It seems promising that non-benzodiazepine anxiolytics including etifoxine will replenish shortcomings of benzodiazepines and selective serotonin reuptake inhibitors according to animated studies related to TSPO.
Mun, Jong Gu;Moon, Jeong Mi;Lee, Mi Jin;Chun, Byeong Jo
Journal of The Korean Society of Clinical Toxicology
/
v.16
no.1
/
pp.1-8
/
2018
Purpose: Extremely hazardous pesticides are classified as World Health Organization (WHO) hazard class Ia. However, data describing the clinical course of WHO class Ia OP (organophosphate) poisonings in humans are very scarce. Here, we compare the clinical features of patients who ingested hazard class Ia OPs. Methods: This retrospective observational case study included 75 patients with a history of ingesting ethyl p-nitrophenol thio-benzene phosphonate (EPN), phosphamidon, or terbufos. The patients were divided according to the chemical formulation of the ingested OP. Data regarding mortality and the development of complications were collected and compared among groups. Results: There were no differences in the baseline characteristics and severity scores at presentation between the three groups. No fatalities were observed in the terbufos group. The fatality rates in the EPN and phosphamidon groups were 11.8% and 28.6%, respectively. Patients poisoned with EPN developed respiratory failure later than those poisoned with phosphamidon and also tended to require longer mechanical ventilatory support than phosphamidon patients. The main cause of death was pneumonia in the EPN group and hypotensive shock in the phosphamidon group. Death occurred later in the EPN group than in the phosphamidon group. Conclusion: Even though all three drugs are classified as WHO class Ia OPs (extremely hazardous pesticides), their clinical courses and the related causes of death in humans varied. Their treatment protocols and predicted outcomes should therefore also be different based on the chemical formulation of the OP.
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