Neutrophil elastase inhibitor (sivelestat) may be a promising therapeutic option for management of acute lung injury/acute respiratory distress syndrome or disseminated intravascular coagulation in COVID-19.

WHAT IS KNOWN AND OBJECTIVE: This article summarizes the effects of sivelestat on acute lung injury/acute respiratory distress syndrome (ALI/ARDS) or ARDS with coagulopathy, both of which are frequently seen in patients with COVID-19. COMMENT: COVID-19 patients are more susceptible to thromboembolic events, including disseminated intravascular coagulation (DIC). Various studies have emphasized the role of neutrophil elastase (NE) in the development of DIC in patients with ARDS and sepsis. It has been shown that NE inhibition by sivelestat mitigates ALI through amelioration of injuries in alveolar epithelium and vascular endothelium, as well as reversing the neutrophil-mediated increased vascular permeability. WHAT IS NEW AND CONCLUSIONS: Sivelestat, a selective NE inhibitor, has not been evaluated for its possible therapeutic effects against SARS-CoV-2 infection. Based on its promising beneficial effects in underlying complications of COVID-19, sivelestat could be considered as a promising modality for better management of COVID-19-induced ALI/ARDS or coagulopathy.

Effects of Nigella sativa Extract on Markers of Cerebral Angiogenesis after Global Ischemia of Brain in Rats.

BACKGROUND: Reduction of permanent or transient cerebral blood flow may lead to some structural and functional changes of the brain, causing high mortality and morbidity. The aim of this experimental study was to investigate the effects of hydroalcoholic extract of Nigella sativa (NS) on markers of cerebral angiogenesis in rats induced by global brain ischemia. METHODS: Thirty-two male Wistar rats (250 ± 20 g) were randomly divided into 4 groups: group 1, control group receiving only normal saline; group 2, sham group undergoing surgery and stroke induction without treatment; and groups 3 and 4 treated with 10 and 20 mg/kg NS, respectively, after induction of stroke. Global ischemia was induced by ligation of the right carotid artery for 20 minutes. RESULTS: According to the results of this study, brain edema and infarct volume were significantly decreased in the group treated with 20 mg/kg NS compared with the group treated with 10 mg/kg NS (P < .05). Global ischemia caused a significant reduction in gene expression of vasoactive endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF) in the sham group compared with the control group (P < .05), but NS groups, in led to a significant increase in gene expression of VEGF and HIF compared with the sham group (P < .05). In addition, the activity level of matrix metallopeptidase-9 was decreased among NS groups compared with the control group (P < .05). CONCLUSIONS: Application of NS extract among rats with brain ischemia is associated with increase of VEGF and HIF as angiogenic markers and inhibition of matrix metallopeptidase-9 activities.

The Potential of Cannabidiol for Acute Respiratory Distress Syndrome in COVID-19.

COVID-19 disease manifests itself in a wide range of signs and symptoms, beginning with mild symptoms, such as fever, cough, and dyspnea, progressing to acute respiratory distress syndrome (ARDS) and death in some cases. The cytokine storm, or an excess of cytokines released locally, is assumed to be the primary cause of ARDS and mortality in COVID-19 patients. To enhance the survival rate of COVID-19 patients, early management of the cytokine storm with immunomodulators is crucial. Although the effectiveness of some immunosuppressants, such as corticosteroids and tocilizumab, has been studied in clinical trials, the administration of these drugs should be exercised cautiously. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid from Cannabis sativa extracts with anti-inflammatory properties. This review is intended to discuss the possible utility of CBD for the management of COVID-19 patients, particularly those with ARDS.

Effect of heart rate control with amiodarone infusion on hemodynamic and clinical outcomes in septic shock patients with tachycardia: a prospective, single-arm clinical study.

BACKGROUND: Keeping the heart rate within the normal range has improved the survival of septic shock patients. Amiodarone could target the underlying pathophysiology of sepsis-induced tachycardia. This study aimed to determine whether amiodarone is effective in controlling the heart rate in critically ill patients with septic shock and sustained tachycardia who were receiving vasopressor. METHODS: In this prospective, single-arm cohort study, 46 patients with septic shock and tachycardia were enrolled to receive a loading dose of amiodarone 150 mg, then continuous infusion of 1 mg/min. The primary outcome was the ability of amiodarone in rate control lower than 95 beats per minute (BPM) and maintaining it during 24-h study period. We also recorded the effect of amiodarone on hemodynamic indices as the secondary outcomes. RESULTS: The results of the present study indicated a significant decrease in HR in septic shock patients for amiodarone, from 121.0 (116.5, 140.0) at baseline to 91.5(89.3, 108.0) at the end of the study period (p < 0.001). During the study period, a total of 26 (56.52%) of patients achieved the target heart rate lower than 95 BPM and maintained it during study period. Amiodarone decreased HR by 22.8 ± 13.7. While receiving amiodarone infusion, the values for heart rate, mean arterial pressure, cardiac index, norepinephrine infusion rate, and stroke volume index changed significantly between amiodarone initiation and 24-h follow-up (P < 0.001). Amiodarone was well tolerated, because this anti-arrhythmic agent did not increase the need for vasopressor and none of the patients experienced episodes of refractory hypotension. CONCLUSION: This study showed that amiodarone infusion successfully reduced the heart rate in sepsis-induced tachycardia. The patients had improved hemodynamic state as indicated by an increase in cardiac index and SVI.

The prophylaxis and treatment potential of supplements for COVID-19.

The global impact of the new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infection that caused COVID-19 has been evident in the last few months from the unprecedented socioeconomic disruption to more than 600,000 deaths. The lack of vaccine and effective therapeutic agents for the disease prompted world-wide effort to test those antiviral therapeutics already in use for other diseases. Another interesting approach has been based on the pathological sequel of the disease that involve severe inflammatory reaction (or the cytokine storm) associated with pneumonia in critically ill patients. This article outlines the prophylaxis therapeutic potential of supplements vitamins and micronutrients in COVID-19. By ameliorating the inflammatory and oxidative stress associated with the disease and some direct antiviral effects, the application of these agents as adjuvants and other alternative approaches are discussed. Available clinical trials including those currently registered on these supplements are scrutinized.

Pharmacological treatments of COVID-19.

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and sub-clinical studies are currently undertaken to find a gold-standard therapeutic regimen with high efficacy and low side effect. Based on the published scientific evidence published to date, we summarized herein the effects of different potential therapies and up-to-date clinical trials. The review is intended to help readers aware of potentially effective COVID-19 treatment and provide useful references for future studies.

Acetazolamide and Thyroid-Associated Ophthalmopathy; a Preliminary Tested Hypothesis in a TertiaryReferral Center.

This study evaluated the effect of acetazolamide on thyroid-associated ophthalmopathy (TAO). Patients with a VISA classification index equal to or more than four were enrolled in the study and were randomly assigned into two groups. In both groups, treatment was initiated using prednisolone. Patients in the case group received acetazolamide tablets 250 mg daily in addition to prednisolone. Three months later, the VISA inflammatory score of patients in both groups were determined. Subsequent to intervention with acetazolamide, the VISA inflammatory score of patients in the case group were reduced as follows; orbital pain (57.1% versus 41.7%, P=0.736), eyelid edema (42.8% versus 27.1%, P=0.67), chemosis (53.3% versus 33%, P=0.31), injection of the eyelids (60% versus 41.6%, P=0.342), and conjunctival injection (50% versus 46.13%, P=0.73). However, these reductions were not statistically significant when compared with those observed in the control group (P=0.246). In conclusion, the effect of acetazolamide on all the parameters of the VISA inflammatory score was examined independently. All patients in the case group revealed a reduction in VISA inflammatory score following intervention. However, these reductions were not statistically significant. Further studies with large sample sizes are required.