Trends in Pharmaceutical Sciences
Volume:6 Issue: 2, Jun 2020

Dear Editor, On December 2019, new cases of COVID-19 pneumonia were reported from Wuhan city of China that were consequences of 2019-nCoV or SARS-CoV-2 infection (1). Very soon this disease spread around the world and till now over than 3,000,000 person have been infected with this new virus. The most common clinical presentations of these patients were fever, dry cough, malaise, fatigue, myalgia, headache, shortness of breath, chest pain, ageusia, anosmia, gastrointestinal, cerebrovascular and dermatologic presentations (2-4). Since COVID-19 is a new disease, there isn’t any approved treatment regimen. Till now many drugs have been studied under clinical trials projects such as (hydroxyl)chloroquine, azithromycin, ribavirin, lopinavir/ritonavir, atazanavir, umofenovir, favipiravir, remdesivir, interferon alpha, tocilizumab, etc (5). Also many supportive therapies have been considered such as convalescent plasma therapy (6), high dose intravenous vitamin C therapy (7), extracorporeal membrane oxygenation (ECMO), etc. (8). Severe cases of COVID-19, have accompanied tachypnea, shortness of breath, oxygen saturation levels of less than 90%, acute respiratory distress syndrome (ARDS), sepsis, septic shock and multi-organ failure (especially heart, kidney and liver damage).

IL-33 is a type of cytokine and a new member of the IL-1 family labeled as an alarmin, which is released under stressful settings. IL-33 is a biomechanically induced protein and is mainly produced by cardiac fibroblasts and is expressed by various cell types after pro-inflammatory stimulation. Although the physiological role of IL-33 as a nuclear factor is not fully understood, it seems to be involved in transcriptional suppression via binding to nucleosomes and regulating the density of chromatins. It can play different roles, from progression to protection against a disease, depending on the type of the disease. Its signaling happens by means of the sST2 receptor. sST2 is a mechanically induced protein of the cardiac muscle. The IL-33/ST2 axis plays an important role in various illnesses such as cardiovascular diseases and can be a potential target for disease treatment. This review provides an overview of different aspects of IL-33 and its related receptor, sST2 along with the role of IL-33/sST2 axis in different cardiovascular diseases.

Different diseases or xenobiotics could cause cholestasis. The only promising treatment for this disease is the identification of its etiology or liver transplantation in severe cases. Nevertheless, preserving liver function could delay organ injury or help to the treatment of the disease in mild cases. The mechanism of cholestasis-induced liver injury is multifactorial. However, it has been found that hepatocyte mitochondrial function is impaired in this disease. Methylene blue (MB) is a phenothiazine compound. MB is pharmacologically used for a wide range of diseases. It has been found that this compound could significantly improve mitochondrial function and prevent the releases of cell death mediators from this organelle. MB is also well-known for its preventing effect on mitochondria-facilitating reactive oxygen species (ROS) formation. It has been found that mitochondrial function is impaired in the liver tissue in different models of cholestasis. The current study aimed to evaluate the effects of MB administration on mitochondrial indices in cholestatic animals. Rats underwent bile duct ligation (BDL) surgery and treated with MB (0.5 and 1 mg/kg, oral). Significant mitochondrial permeabilization, mitochondrial membrane depolarization, lipid peroxidation, decreased mitochondrial dehydrogenase activity, and depleted ATP content was evident in BDL rats. It was found that mitochondrial indices improved in MB-treated cholestatic animals. Based on the data collected in this study, MB might be useful as a therapeutic agent in cholestasis. The mitochondria protecting properties of this compound could play a major role in its mechanism of action.

Surgery-associated small intestine damage is a clinical complication. It has been found that opening the abdominal cavity during surgery and manipulation of organs, including the intestine, could lead to intestinal barrier disintegrity and the entrance of pathogens to the systemic circulation. Hence, finding agents to protect the intestine during surgical manipulation could have clinical value. Oxidative stress and enterocytes mitochondrial dysfunction and energy (ATP) crisis are the proposed mechanisms for surgery-induced intestinal damage. N-acetylcysteine (NAC) is a thiol reducing agent and radical scavenging molecule which is widely investigated for its pharmacological properties. The current study was designed to evaluate the effects of NAC treatment on the surgery-induced mitochondrial dysfunction in an animal model. Rats were treated with NAC (500 and 1000 mg/kg, oral) and underwent surgical stress. Afterward, the small intestine mitochondria were isolated and assessed. The effects of surgical stress on small intestine mitochondrial was revealed as a significant decrease in mitochondrial dehydrogenase activity, mitochondrial depolarization, decreased mitochondrial ATP levels, and mitochondrial permeabilization. Moreover, the level of alkaline phosphatase secretion from the intestinal brush border was increased. It was found that NAC treatment significantly alleviated ALP levels, and improved mitochondrial indices when this drug was pre-treated (1 week) to rats. Collectively, it could be concluded that NAC treatment might be a therapeutic approach against surgery-induced intestinal damage. The effects of NAC on mitochondrial function seem to has a pivotal role in its protective mechanism of action.

Parkinson’s disease is a disabling neurodegenerative disease which limits many functional activities of the patients. Treatment of the disease by oral formulations is not successful and even applicable in some patients because of difficulty in swallowing. Levodopa is one of the commonly used drugs for Parkinson’s disease which bioavailability of its oral formulations is variable between patients. The aim of the present study was to develop an in-situ gel forming formulation for nasal delivery of levodopa. Poloxamer 407, chitosan and alginate were used as thermosensitive and mucoadhesive polymers for formulating nasal gel. Different concentrations of polymers and drug were tested to optimize the gelation temperature. Based on the gelation temperature, two formulations (PL7 and PAL10) which respectively contained poloxamer 20% and levodopa 0.3% w/v and poloxamer 18%, Alginate 0.4% and levodopa 0.3% w/v presented desirable properties for a nasal gel. The gels showed suitable pH, clarity and strength as well as sustained release profile which is necessary for a formulation designed for retention in the nasal cavity. It seems that thermosensitive nasal gel of levodopa with poloxamer could be a potentially successful formulation for delivery of levodopa to the brain.

CAD is a major cause of death in worldwide. Both vitamin D (vit D) and Vitamin-D receptor (VDR) gene polymorphisms have been reported to be associated with Coronary artery disease (CAD). Because of high prevalence of vit D deficiency and mortality caused by cardiovascular diseases in our country, Iran, in this study we aimed to determine the frequency of two known VDR gene polymorphisms (BsmI and ApaI) in patients undergoing Percutaneous Coronary Intervention (PCI) in Iranian populations. Blood samples were collected from 150 patients performing elective PCI (102 males and 48 females). VDR genotypes were determined by RFLP method. Serum vit D levels were measured using HPLC method and patients were divided into three groups as follows: subjects with a total vit D concentration 30 ng/ml> were described as normal, 20-30 ng/ml as insufficient and < 20 ng/ml as deficient. Among 150 samples analyzed for ApaI and BsmI polymorphisms the following genotypic frequency was observed: AA 44.67%, AC 44.67%, and CC 10.66% for ApaI and GG 47.33%, GA 37.33%, AA 15.34% for BsmI Levels of active vitamin D could be influenced by both environmental and genetic factors. Our results also revealed that VDR gene polymorphisms (ApaI and BsmI) may vary across different ethnic groups in CAD patients.

The extensive use of antifungal drugs and their resistance against fungal infections have led to develop novel antimicrobial compounds. In this research, 14 new pyranopyrazole compounds (D1-D14) which were synthesized before, screened for antimicrobial activity. These compounds consist of a pyranopyrazole scaffold with a phenyl substitution at the 4-position of the pyran ring. Antimicrobial evaluation of the above compounds were investigated against different species of fungi, gram positive and gram negative bacteria by broth micro dilution methods as recommended by CLSI. The specific binding mode or the binding orientation of the compounds to CYP51 active site, have been also performed by molecular modeling investigations. Our results implies that some of our compounds possess desirable inhibitory activity against the tested microorganisms. Our docking study results also showed that the binding free energy values of the compounds are in agreement with the corresponding experimental activity values. By comparison the relationship between chemical structures and biological activities revealed that the presence of a withdrawing substituent at4-position of phenyl group at para position of the pyran ring enhance the antimicrobial activity.

Proper diagnosis of the corneal ulcer is one the most important efforts in the eyes medical urgencies. The aim of this study was to determine the bacteriological profile and in vitro antibiotic resistance of the bacteria isolated from the eyes of patients with infectious corneal ulcers In this study, 94 patients with corneal ulcer disease participated. After differential diagnosis of potentiated corneal ulcer infection and sampling of the active area of the wounds, the sample was transferred to the laboratory for cultivation in the suitable culture medium and finally incubatedin proper temperature. In cases of positive culture, the type of bacteria and antibiotic sensitivity test of the broth micro-dilution method was performed and evaluated for five antibiotics including ciprofloxacin, levofloxacin, gentamycin, erythromycin, and chloramphenicol. our results indicated that patients consisted of 55% male and 45% female, 51% of whom were positive and the most common bacterium was staphylococcus negative coagulase with 48% prevalence. The isolated bacteria sensitivity for levofloxacin, ciprofloxacin, gentamycin, erythromycin and chloramphenicol was 94%, 79%, 67%, 33%, 27%, respectively.In vitro study for levofloxacin and ciprofloxacin showed ahigher percentage of antibiotic sensitivity in patients with corneal infectious ulcers in comparisonto other antibiotics. However, Erythromycin and chloramphenicol were not suitable for the bacterial corneal ulcer treatment due to the high microbial resistance. Accurate and precise training of physicians in the prescribing of ocular antibiotics as well as the prevention of arbitrary use of these drugs is important for reducing the microbial resistance.

The present study deals with antibacterial and antioxidant screening of ethanolic leaf extract and various fractions of Lonicera nummularifolia, an endemic plant of Caprifoliace family. The ethanolic extract was prepared using soxhlet extraction procedure and fractionation of extract was performed by a continuous liquid-liquid extraction method. Total phenol, flavonoid and triterpenoid were determined in the extract using standard spectrophotometric methods. Antioxidant assays including DPPH and FRAP were conducted in order to evaluate the antioxidant capacity. Antibacterial activity of total ehanolic extract and fractions were evaluated by measuring MIC (Minimum Inhibitory Concentration) and MBC (Minimum Bactericidal Concentration) against four standard bacterial strains, including Escherichia Coli, Staphylococcus ureus, Pseudomonas aeroginosae and Acenitobacter baumannii. using broth micro-dilution method. Total phenol content of hydroalcoholic extract was found to be higher than flavonoid. Results of antioxidant assays indicated that ferric reducing antioxidant power of the extract was promising. Results of antibacterial screening declared the lowest MIC value for ethanol extract and therefore higher bacteriostatic activity against the tested bacterial strains compare to chloroform and ethyl acetate fractions. Ethanolic extract also revealed significant bactericidal activity among all the tested extracts. Overall inspection of the results declared moderate DPPH free radical scavenging, ferric reducing activity and antibacterial properties of L. nummularifolia which is worthy of further thorough investigations. Isolation and characterisation of active substances of the extract are interesting approaches in order to validate antibacterial and ferric reducing properties of the plant.