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Small Molecule Drug Candidates for Managing the Clinical Symptoms of COVID-19: a Narrative Review

  • Yun, Chawon;Lee, Hyun Jae;Lee, Choong Jae
    • Biomolecules & Therapeutics
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    • v.29 no.6
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    • pp.571-581
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    • 2021
  • Towards the end of 2019, an atypical acute respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified in Wuhan, China and subsequently named Coronavirus disease 2019 (COVID-19). The rapid dissemination of COVID-19 has provoked a global crisis in public health. COVID-19 has been reported to cause sepsis, severe infections in the respiratory tract, multiple organ failure, and pulmonary fibrosis, all of which might induce mortality. Although several vaccines for COVID-19 are currently being administered worldwide, the COVID-19 pandemic is not yet effectively under control. Therefore, novel therapeutic agents to eradicate the cause of the disease and/or manage the clinical symptoms of COVID-19 should be developed to effectively regulate the current pandemic. In this review, we discuss the possibility of managing the clinical symptoms of COVID-19 using natural products derived from medicinal plants used for controlling pulmonary inflammatory diseases in folk medicine. Diverse natural products have been reported to exert potential antiviral effects in vitro by affecting viral replication, entry into host cells, assembly in host cells, and release. However, the in vivo antiviral effects and clinical antiviral efficacies of these natural products against SARS-CoV-2 have not been successfully proven to date. Thus, these properties need to be elucidated through further investigations, including randomized clinical trials, in order to develop optimal and ideal therapeutic candidates for COVID-19.

Physiological Responses of Starry Flounder Platichthys stellatus during Freshwater Acclimation with Different Speeds in Salinity Change (염분변화 속도를 달리한 담수순화 과정에서 강도다리 Platichthys stellatus의 생리학적 반응)

  • Kim, Young-Soo;Do, Yong-Hyun;Min, Byung-Hwa;Lim, Han-Kyu;Lee, Bok-Kyu;Chang, Young-Jin
    • Journal of Aquaculture
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    • v.22 no.1
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    • pp.28-33
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    • 2009
  • Physiological responses (hematological factors, cortisol, glucose, osmolality, $Na^+$, $K^+$ and $Cl^-$) in starry flounder Platichthys stellatus were investigated during freshwater acclimation in the conditions of different speeds in salinity change with acute-decrease (AD) or stepwise-decrease (SD I and II). In AD of acute-decrease salinity, hematocrit (Ht), red blood cell (RBC) and hemoglobin (Hb) were rapidly increased more than SD I of stepwise-decrease salinity. But in case of SD II, Ht, RBC and Hb were no significant difference from beginning to end of this experiments. In AD, cortisol level significantly increased from $2.1{\pm}1.0{\mu}g/mL$ at the beginning to $13.7{\pm}0.2{\mu}g/mL$ at 6 hours and recovered to the basal levels ($3.1{\mu}g/mL$) at 10 days. In SD I, cortisol level was significantly increased from $2.1{\pm}1.0{\mu}g/mL$ at the beginning to $13.6{\pm}0.6{\mu}g/mL$ at 6 hours and recovered to the basal levels ($3.1{\pm}0.4{\mu}g/mL$) at 10 days. In SD II, cortisol level was a little increased from $2.1{\pm}1.0{\mu}g/mL$ at the beginning to $10.5{\pm}2.5$, $10.8{\pm}5.6{\mu}g/mL$ at 6, 12 hours and recovered to the basal level at 48 hours. Glucose level of AD, SD I, II were no significant difference from beginning to end of this experiments. Osmolality was $286.8{\pm}3.3\;mOsm/kg$ at the beginning. In SD II of stepwise-decrease, osmolality was no significant difference during rearing in freshwater (FW). But AD of stepwise-decrease and SD I of stepwise-decrease, osmolality was a little decreased end of this experiments. In AD of acute-decrease, only $Cl^-$ level was showed no significant difference from beginning to end of experiment and $Na^+$, $K^+$ levels were decreased. In case of SD I, $Cl^-$ level was showed no significant difference from beginning to end of experiment and $Na^+$, $K^+$ levels were decreased.

Inverse Estimation of Viscoplastic Properties of Solder Alloy Using Moir$\acute{e}$ Interferometry and Computer Model Calibration (모아레 간섭계와 모델교정법을 이용한 솔더 합금의 점소성 물성치 역추정)

  • Gang, Jin-Hyuk;Lee, Bong-Hee;Joo, Jin-Won;Choi, Joo-Ho
    • Journal of the Computational Structural Engineering Institute of Korea
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    • v.24 no.1
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    • pp.97-106
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    • 2011
  • In this study, viscoplastic material properties of solder alloy which is used in the electronics packages are inversely estimated. A specimen is fabricated to this end, and an experiment is conducted to examine deformation by Moir$\acute{e}$ interferometry. As a result of the experiment, bending displacement of the specimen and shear strain of the solder are obtained. A viscoplastic finite element analysis procedure is established, and the material parameters are determined to match closely with the experiments. The uncertainties which include inherent experimental error and insufficient data of experiments are addressed by using the method of computer model calibration. As a result, material parameters are identified in the form of confidence interval, and the displacements and strains using these parameters are predicted in the form the prediction interval.

The Pallidal Index in Patients with Acute-on-Chronic Liver Disease: Is It a Predictor of Severe Hepatic Encephalopathy?

  • Lee, Dong Hyun;Lee, Hui Joong;Hahm, Myong Hun
    • Investigative Magnetic Resonance Imaging
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    • v.21 no.3
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    • pp.125-130
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    • 2017
  • Purpose: To evaluate the clinical significance of T1 high signal intensity on the globus pallidus as a predictor of severe hepatic encephalopathy in patients with acute-on-chronic liver failure (ACLF), which is a distinct syndrome characterized by multi-organ dysfunction including cerebral failure. Materials and Methods: From January 2002 to April 2014, we retrospectively reviewed the magnetic resonance imaging (MRI) findings and clinical and magnetic resonance (MR) features of 74 consecutive patients (44 men and 30 women; mean age, 59.5 years) with liver cirrhosis. The chronic liver failure-sequential organ failure assessment score was used to diagnose ACLF. The pallidal index (PI), calculated by dividing the mean signal intensity of the globus pallidus by that of the subcortical frontal white matter were compared according to ACLF. The PI was compared with the Model for End-Stage Liver Disease (MELD) score in predicting the development of ACLF. Results: Fifteen patients who were diagnosed with ACLF had higher hepatic encephalopathy grades (initial, P = 0.024; follow-up, P = 0.002), MELD scores (P < 0.001), and PI (P = 0.048). In the ACLF group, the mean PI in patients with cerebral failure was significantly higher than that in the patients without cerebral failure (1.33 vs. 1.20, P = 0.039). In patients with ACLF, the area under the curve (AUC) for PI was 0.680 (95% confidence intervals [CI], 0.52-0.85), which was significantly lower than that for the MELD score (AUC, 0.88; 95% CI, 0.77-0.99) (P = 0.04). Conclusion: The PI can be an ancillary biomarker for predicting the development of ACLF and severe hepatic encephalopathy.

Effects of Pyengpaetang Extracts on the Acute Pulmonary Edema induced by Oleic acid in dogs (평폐탕(平肺湯)이 Oleic acid로 유발(誘發)된 가견(家犬)의 급성폐수종(急性肺水腫)에 미치는 영향(影響))

  • Chung, Jae-Woo;Han, Sang-Whan;Choe, Sun-Ho
    • The Journal of Internal Korean Medicine
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    • v.11 no.2
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    • pp.1-15
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    • 1990
  • Certain oriental medication have been shown to be effective in decreasing pulmonary vascular resistance and increasing cardiac output in primary pulmonary artery pressure secondary to pulmonary edema. So oleic acid was administered in 14 dogs in order to induce acute lung injury. And we studied the hemodynamics and blood gas changes of Pyengpaetang(50mg, 100mg) with continuous postive pressure was ventilation in pulmonary edema. The pulmonary edema group, arterial oxygenation was improved after 5 and $10cmH_2O$ PEEP(positive end expiratory pressure), but cardiovascular system was depressed. Blood pressure and cardiac output were decreased, and CVP, MP AP, PCWP were increased. In Pyengpaetang(50mg) group, mean aortic pressure was decreased and PCWP(pulmonary capillary wedge pressure) was decreased remarkably, while there was a significant increase in cardiac output. And there was improvement in $PaO_2$ and $PaCO_2$ without hemodynamic changes after applying 5cm $H_2O$ PEEP, but arterial blood gases$(PaO_2,\;PaCO_2)$ were improved, while cardiovascular effects were depressed after cm $H_2O$ PEEP. In Pyengpaetang(100mg) treated group, there was no significant hemodynamic change. But mean pulmonary arterial pressure was significantly increased, and cardiac output was decreased significantly after applying the more degree of PEEP. And blood gases were not changed significantly after applying the more degree of PEEP. The above results suggest that the effects of Pyengpaetang(50mg) group is superior to those of Pyengpaetang(100mg) group on the effects of hemodynamics and gas exchanges in acute lung injury in dogs. So we can conclude that lower degree PEEP 5cm $H_2O$ is more beneficial in Pyengpaetang(50mg) treated group.

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The effects of exercise training and acute exercise duration on plasma folate and vitamin B12

  • Kim, Young-Nam;Hwang, Ji Hyeon;Cho, Youn-Ok
    • Nutrition Research and Practice
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    • v.10 no.2
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    • pp.161-166
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    • 2016
  • BACKGROUND/OBJECTIVES: Energy production and the rebuilding and repair of muscle tissue by physical activity require folate and vitamin $B_{12}$ as a cofactor. Thus, this study investigated the effects of regular moderate exercise training and durations of acute aerobic exercise on plasma folate and vitamin $B_{12}$ concentrations in moderate exercise trained rats. MATERIALS/METHODS: Fifty rats underwent non-exercise training (NT, n = 25) and regular exercise training (ET, n = 25) for 5 weeks. The ET group performed moderate exercise on a treadmill for 30 min/day, 5 days/week. At the end of week 5, each group was subdivided into 4 groups: non-exercise and 3 exercise groups. The non-exercise group (E0) was sacrificed without exercising and the 3 exercise groups were sacrificed immediately after exercising on a treadmill for 0.5 h (E0.5), 1 h (E1), and 2 h (E2). Blood samples were collected and plasma folate and vitamin $B_{12}$ were analyzed. RESULTS: After exercise training, plasma folate level was significantly lower and vitamin $B_{12}$ concentration was significantly higher in the ET group compared with the NT group (P < 0.05). No significant associations were observed between plasma folate and vitamin $B_{12}$ concentrations. In both the NT and ET groups, plasma folate and vitamin $B_{12}$ were not significantly changed by increasing duration of aerobic exercise. Plasma folate concentration of E0.5 was significantly lower in the ET group compared with that in the NT group. Significantly higher vitamin $B_{12}$ concentrations were observed in the E0 and E0.5 groups of the ET group compared to those of the NT group. CONCLUSION: Regular moderate exercise training decreased plasma folate and increased plasma vitamin $B_{12}$ levels. However, no significant changes in plasma folate and vitamin $B_{12}$ concentrations were observed by increasing duration of acute aerobic exercise.

Results of Protocol-based Perioperative Management in Off-Pump Coronary Artery Bypass Grafting for Patients with Non-dialysis-dependent Chronic Kidney Disease

  • Kim, Jeong-Won;Sim, Hyung Tae;Yoo, Jae Suk;Kim, Dong Jin;Cho, Kwang Ree
    • Journal of Chest Surgery
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    • v.49 no.6
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    • pp.427-434
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    • 2016
  • Background: Recent studies have demonstrated the benefits of off-pump coronary bypass grafting over the on-pump technique in patients with chronic kidney disease (CKD). To further reduce the risk of acute kidney injury and the need for renal replacement therapy, even in patients undergoing off-pump coronary artery bypass grafting, we adopted protocol-based perioperative management for patients with CKD. Methods: From December 2012 to March 2015, 265 patients underwent isolated off-pump coronary artery bypass grafting. To analyze renal function in a stable condition, we excluded 12 dialysis-dependent end stage renal failure and 10 emergency or urgent cases. Among the remaining 243 patients, 208 patients had normal kidney function (normal group), and 35 patients had CKD (CKD group). Minimizing contrast exposure, ensuring adequate hydration, using strict drug dosage adjustment, and optimizing hemodynamic status were key elements of the protocol for the CKD group. Results: The risk of acute kidney injury was about ${\times}3$ higher in the CKD group than in the normal group (p=0.01). Estimated glomerular filtration rates and serum creatinine levels deteriorated until the third postoperative day in the CKD group. However, by adopting protocol-based perioperative management, this transient renal dysfunction recovered to preoperative levels by the fifth postoperative day without requiring renal replacement therapy in all cases. Conclusion: Off-pump coronary bypass surgery combined with this protocol-based perioperative management strategy in patients with non-dialysis-dependent CKD could mostly be performed without renal replacement therapy.

Emergency Trephination Site of Acute Subdural Hematoma (급성 경막하 혈종에서 응급 두개골 천공의 위치)

  • Moon, Soo-Hyeon;Kim, Geun-Hoe;Kwon, Taek-Hyun;Park, Youn-Kwan;Chung, Hung-Seob;Suh, Jung-Keun
    • Journal of Korean Neurosurgical Society
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    • v.29 no.5
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    • pp.659-663
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    • 2000
  • The motality rate of acute subdural hematoma(ASDH) associated with closed head injury is high in spite of recent advances in neurosurgery. Many variables in regard to outcome of ASDH have been assessed. But among them, intracranial pressure(ICP) control and the time interval between injury and operative evacuation are the only things that can be affected by doctor. We introduced a simple method to the management of ASDH for reducing the time interval between injury and operation. When the immediate decompressive operation of ASDH was impossible by any causes, we made a burr hole at the center of hematoma, usually on 2-3cm above temporal squama and 1-2cm behind coronal suture under local anesthesia before main operation. Partial hematoma evacuation was achieved through the burr hole and it was effective in preventing further worsening of patients neurological status before main operation. Prompt hematoma evacuation through the burr hole seemed to be effective in delaying secondary ischemic brain damage and made easy to closing the dura opening and replacement of the bone flap at the end of main decompressive operation. This easy method may reduce the time interval between injury and operation. We represent surgical technique with two cases of ASDH managed with this simple method.

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Overview of Pediatric Continuous Renal Replacement Therapy in Acute Kidney Injury (급성 신손상을 가진 소아의 지속적 신대체 요법)

  • Park, Se-Jin;Shin, Jae-Il
    • Childhood Kidney Diseases
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    • v.15 no.2
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    • pp.107-115
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    • 2011
  • Acute kidney injury (AKI) is associated with mortality and may lead to increased medical expense. A modified criteria (pediatric RIFLE [pRIFLE]: Risk, Injury, Failure, Loss, and End-stage renal disease) has been proposed to standardize the definition of AKI. The common causes of AKI are renal ischemia, nephrotoxic medications, and sepsis. A majority of critically ill children develop AKI by the pRIFLE criteria and need to receive intensive care early in the course of AKI. Factors influencing patient survival (pediatric intensive care unit discharge) are known to be low blood pressure at the onset of renal replacement therapy (RRT), the use of vasoactive pressors during RRT, and the degrees of fluid overload at the initiation of RRT. Early intervention of continuous RRT (CRRT) has been introduced to reduce mortality and fluid overload that affects poor prognosis in patients with AKI. Here, we briefly review the practical prescription of pediatric CRRT and literatures on the outcomes of patients with AKI receiving CRRT and associations among AKI, fluid overload, and CRRT. In conclusion, we suggest that an increased emphasis should be placed on the early initiation of CRRT and fluid overload in the management of pediatric AKI.

A Human Case Infected by the Larva of Terranova type A in Korea (Terrunoua type A 유촉에 의한 인체감염 1예)

  • 서병설;채종일이순형홍성함
    • Parasites, Hosts and Diseases
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    • v.22 no.2
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    • pp.248-252
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    • 1984
  • A human case infected with Terranova type A larva was found in Korea. The patient was a 23-year old soldier of the Korean Army and the chief complaint was acute abdominal pain. The pain was chiefly at right lower quadrant. Appendectomy was performed under the clinical impression of acute appendicitis. However, during the surgery, a nematode larva was found moving on the serosal surface of terminal ileum. The worm was 25.76mm long and O. 66mm -wide, and had the intestinal cecum reaching to anterior one-third level of ventriculus and a mucron at posterior end. Therefore, it was diagnosed as Terranova type A larva. This is the first human case of Terranova type A larva infection in Korea.

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