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Septic shock, known as the most severe complication of sepsis, is a serious medical condition that can lead to death. Clinical symptoms of sepsis include changes in body temperature in the form of hypothermia or hyperthermia, tachypnea or hyperventilation, tachycardia, leukocytosis or leukopenia, and variations in blood pressure, as well as altered state of consciousness. One of the main problems in septic shock is poor response along with reduced vascular reactivity to vasopressors used to increase blood pressure. Therefore, low vascular response associated with reduced sensitivity or lower number of alpha-1 agonist receptors can result in shock and death. In addition to being the state-of-the-art treatment including volume load and vasopressor, use of alpha-2 agonists e.g. dexmedetomidine (DXM) in septic shock can reduce vasopressors needed to restore adequate blood pressure. They can further moderate massive release of endogenous catecholamine. Therefore, the purpose of this study was to investigate the effect of DXM on outcomes of patients with septic shock, especially their needs for vasopressors and impacts on their hemodynamic status. This single-blind randomized controlled trial was performed on a total number of 66 patients with septic shock admitted to the intensive care unit (ICU) of Imam Khomeini Teaching Hospital in the city of Sari, in northern Iran. To this end, DXM (0.6 µg/kg/h) and normal saline (6 mL/kg/h) were infused for 12 h in the study and control groups, respectively. The results revealed that DXM could increase mean arterial pressure (MAP) (P = 0.021), systolic blood pressure (SBP) (P = 0.002), and reduced heart rate (P < 0.001) but diastolic blood pressure (DBP) (P =0.32) and norepinephrine dose requirement didn’t change statistically in septic shock patients (P = 0.12).

At the end of 2019, Sars-CoV-2 was identified and has since spread in the world. Coronavirus is commonly caused by the upper respiratory tract and severe acute respiratory syndrome in humans. Due to the novel nature of the virus and high mortality among high-risk people, today health care providers used several medications with different mechanisms to overcome this virus. The course of COVID-19 represents three stages that have different symptoms and used different drugs depends on each stage. Ultimately the minority of patients progress to stage III with high mortality. The aim of this study is a comprehensive review of COVID-19 adjuvant therapies. We explained the current study on the use of Glucocorticoids, Interferon, Vitamin C, Tocilizumab, Anakinra, Pentoxifylline, IVIG, Allopurinol, Ivermectin, and Selenium in sepsis, pneumonia, and ARDS and we suggested a new protocol for prescribing each medication currently used in COVID-19 Outbreak. At the end of 2019, Sars-CoV-2 was identified and has since spread in the world. Coronavirus is commonly caused by the upper respiratory tract and severe acute respiratory syndrome in humans. Due to the novel nature of the virus and high mortality among high-risk people, today health care providers used several medications with different mechanisms to overcome this virus. The course of COVID-19 represents three stages that have different symptoms and used different drugs depends on each stage. Ultimately the minority of patients progress to stage III with high mortality. The aim of this study is a comprehensive review of COVID-19 adjuvant therapies. We explained the current study on the use of Glucocorticoids, Interferon, Vitamin C, Tocilizumab, Anakinra, Pentoxifylline, IVIG, Allopurinol, Ivermectin, and Selenium in sepsis, pneumonia, and ARDS and we suggested a new protocol for prescribing each medication currently used in COVID-19 Outbreak.

A new corona virus disease (COVID-19) has affected more than 17 million people worldwide so far, and has become a global pandemic. Since there is no definitive cure for this life threatening disease, many clinical studies are in progress in this regard. Pathogen-associated molecular patterns (PAMP) prompting by coronavirus seems to generate cellular, structural, and functional derangements induced by immune dysregulation as well as many biological abnormalities including cytokine storm. The role of IL-6 in viral pneumonia and also its inhibition impact on the prevention of organ damage are still unknown.IL-6 seems to behave as a double blade evil cytokine, by playing a valuable role in cell to cell natural physiological communication. Tocilizumab, as an inhibitor of interleukin (IL)-6, may interrupt the paracrine system while causing dissemination of bacterial, fungal, and other viral infections, especially COVID-19, who are at a high-risk for development of sepsis and life-threatening superinfection.

Introduction: Prosthetic valve thrombosis is a rare and severe complication of valve replacement, most often encountered with a mechanical prosthesis. The significant morbidity and mortality associated with this condition warrant rapid diagnostic evaluation. Although surgery is the first-line therapy in symptomatic obstructive mechanical valve thrombosis, thrombolytic therapy has been used as an alternative. Case Description: In this case report, we describe a 46-year-old man with a history of the mitral valve and aortic valve replacement 2 years ago. In echocardiography, we detected a mobile mass on the atrial side of the mitral valve prosthesis and a fixed one on the leaflet of the mechanical aortic valve with a high gradient. To save his life, we used double thrombolytic therapy considering the patient’s hemodynamic situation and the risk of bleeding. Although a routine dose of reteplase and streptokinase was considered, we administered these two thrombolytic drugs together within 72 hours. Conclusion: Ultimately we succeeded with this method without any significant or life-threatening adverse effects, and the patient was discharged after an optimal anticoagulation therapy.

The binding of prantschimgin (PRAN) to matrix metalloproteinase 9 (MMP9) was investigated using multiple techniques. Fluorescence spectroscopy showed that PRAN could quench the MMP9 fluorescence spectra. Changes in the UV/vis and Fourier transform infrared (FTIR) spectra were observed upon ligand binding, along with a significant degree of tryptophan fluorescence quenching on complex formation. The interaction of PRAN with MMP9 has also been studied using molecular docking and molecular dynamics (MD) simulation. The binding models demonstrated aspects of PRAN's conformation, active site interaction, important amino acids and hydrogen bonding. Computational mapping of the possible binding site of PRAN revealed that the ligand is bound in a large hydrophobic cavity of MMP9. The MD simulation results suggested that this ligand can interact with the protein, with little affecting the secondary structure. The results not only lead to a better understanding of interactions between PRAN and MMP9, but also provide useful data about the influence of PRAN on the structural conformation. The data provided in this study will be useful for designing a new agonist of MMP9 with the desired activity.

Grandivitin (GRA), a natural coumarin, can inhibit Matrix metalloproteinase 9 (MMP9). Binding characteristics are therefore of interest for pharmacodynamics of GRA and coumarin derivatives. A combination of spectroscopic methods and molecular modeling techniques was used to characterize interaction of GRA with MMP9. Fluorescence spectroscopy showed that GRA could quench the MMP9 fluorescence spectra. Changes in the UV-Vis and FT-IR spectra were observed upon ligand binding along with a significant degree of tryptophan fluorescence quenching on complex formation. Fluorescence studies showed that GRA has an ability to quench the intrinsic fluorescence of MMP9. Molecular modeling analysis showed that GRA to be bound in the large hydrophobic cavity of MMP9. Further investigation of the binding site of GRA within the MMP9 molecule suggested that hydrophobic contacts, hydrogen bond formation and electrostatic interactions account for the binding of GRA. According molecular dynamics (MD) simulation results the ligand can interact with the protein, with affecting the secondary structure of MMP9 and with a modification of its tertiary structure. The biological significance of this work is evident because MMP9 serves as a potential target protein for anticancer agents. The binding study of GRA with MMP9 is of great importance in pharmacy, pharmacology and biochemistry. This work can provide some key data to clinical research and supply the theoretical basis for the new drug candidate designing.