SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (−) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity.
Intravenous paracetamol is effective in treating patients presenting with renal colic to the emergency department. CLINICAL TRIALS REGISTRATION NO: ClinicalTrials.gov ID number NCT01318187.
Intravenous paracetamol and dexketoprofen appear to produce equivalent pain relief for migraine in the emergency department. CLINICALTRIALS.GOV NO: NCT01730326.
Background/Aim: A novel human coronavirus, named SARS-COV-2, has recently caused thousands of deaths all around the world. Endoplasmic reticulum (ER) stress plays an important role in the development of diseases. Patients and Methods: We aimed to to investigate the relationship between ER stress markers in patients infected with SARS-COV-2 and patients with pneumonia. A total of 9 patients (4 patients diagnosed with pneumonia and 5 patients diagnosed with SARS-COV-2 infection) who admitted to the emergency Department with symptoms of pneumonia and SARS-COV-2 were included in the study. A total of 18 healthy individuals without any known chronic or acute disease and drug use were included as the healthy control group. Serum human glucose regulated protein 78 (GRP78), serum human C/EBP homologous protein (CHOP) and serum human phospho extracellular signal regulated kinase (PERK) levels were measured using enzyme-linked immunosorbent assay (ELISA). Results: GRP78 levels were found to be significantly higher in SARS-COV-2 positive cases compared to individuals in other groups. Serum GRP-78 level median value was statistically significantly higher in SARS-COV-2-positive group compared to the other groups (p=0.0003). Serum PERK level was statistically significantly higher in SARS-COV-2-positive pneumonia cases (p=0.046). Conclusion: An association was shown between GRP78 and SARS-COV-2 infection.Although a small number of patients was investigated, these results will be important and guide future treatments of SARS-COV-2.Coronaviruses are spherical or pleomorphic in shape with a mean diameter of 80-120 nm. They have heavily glycosylated trimeric spike (S) proteins on their surface (1). Coronavirus infection starts with receptor binding via the S protein. The interaction between the host cell surface receptor and the S1 subunit is the major determinant of the tropism of coronaviruses (2, 3). Upon receptor binding of S1, a conformational change is triggered in the S2 subunit, exposing its hidden fusion peptide for insertion into the cellular membrane.Endoplasmic reticulum (ER) is the organelle where the synthesis, folding, maturation and transport of proteins, calcium storage and lipid biosynthesis of the cell processes take place. ER stress is defined as the result of ER protein folding capacity, resulting in wrongly folded or unfolded protein accumulation (4). Excessive synthesis of secretion proteins, mutations in proteins involved in protein folding, abnormal changes in the amount of Ca +2 in ER and viral infections are some of the factors that cause protein accumulation in ER (5,6). The cell activates three mechanisms to eliminate ER stress caused by an imbalance between the amount of unfolded proteins in ER and the capacity of the cellular mechanism that handles this amount. Firstly, protein synthesis and translocation of proteins to ER are decreased, and the amount of protein entering ER is reduced with a temporary adaptation. Secondly; unfolded protein response (UPR) is activated. Therefore, an increase in the ca...
This study sought to determine the frequency and types of violence that occurred during the previous year against health care workers in emergency departments in Denizli, Turkey, and to discern the views of workers on the prevention of such aggressive behavior. This study was conducted from March 1 to April 15, 2003, and included a group of 79 health care workers from the emergency departments of 3 hospitals in Denizli, namely, the Hospital of Pamukkale University Medical Faculty, the City Hospital of Denizli, and the Hospital of the Social Insurance Foundation. Data were collected from a self-administered questionnaire. In all, 88.6% of participants had been subjected to or had witnessed verbal violence, and 49.4% of them had been subjected to or had witnessed physical violence during the previous year. The most frequent reason (31.4%) for violence was abuse of alcohol and drugs by perpetrators. The second most frequent reason (24.7%) was the long waiting times typical of emergency departments. The most common type of violence was loud shouting; swearing, threatening, and hitting were the next most frequent violent behaviors. In all, 36.1% of subjects who had experienced violence reported that they developed psychological problems after the incident. Most participants commented on the insufficiency of currently available security systems within emergency departments and on the need for further training about violence. All health care personnel within emergency departments should be aware of the risk of violence and should be prepared for unpredictable conditions and events; in addition, security systems should be updated so that violence within emergency departments can be prevented.
Objectives:To analyze descriptive data and characteristics of work-related eye injuries (WREI) admitted into the emergency department (ED) and obtain information to utilize in planning measures to prevent WREI.Materials and Methods:This prospective study recruited patients with WREI admitted to the center in the two-year study period. Only the casualties occurred at the workplace and while working constituted the sample. The data were collected via face-to-face contact in the ED.Results:Males comprised the majority of the sample (95.3%, n = 778) and mean age of the patients was 28.1 ± 6.5 (range: 15-54) with the biggest percentage in between 25 and 34 years of age (46.2%, n = 377). Most patients were working in the metal and machinery sectors (66.4%, n = 542). Nearly half of the patients had less than 1 year of experience (50.4%, n = 411). The most common mechanism of WREI was noted to be exposures to welding light (26.9%, n = 219), followed by drilling/cutting injuries (21.1%, n = 172). “Carelessness” and “hurrying up” were the most commonly reported causes of WREIs among ‘worker-related causes’ (21.4% and 16.1%, respectively). Lack of protective measures ranked the highest among workplace-related causes (18.7%, n = 207).Conclusions:Programs to increase awareness on workplace safety and sound preventive strategies for both parties-employers and employees are to be pursued. Occupational safety efforts should include training on workplace eye safety and campaigns to raise knowledgeability on this disease among workers.
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