ABSTRACT
AIMS: The aim of this study is to determine the ability of two bioactive compounds, namely, eugenol and linalool, purified from leaves of Ocimum tenuiflorum for eradication of biofilm produced by Pseudomonas aeruginosa. METHODS AND RESULTS: The phytoextract of O. tenuiflorum (KT), a common ethno-botanical plant of India, was purified through high-performance liquid chromatography and was analysed using ultraviolet (UV) spectroscopy and gas chromatography-mass spectrometry (GC-MS). Eugenol and linalool were found to be the most active amongst all phytocompounds present in phytoextract and showed a significant reduction in the viability of sessile cells of P. aeruginosa and the minimum revival after withdrawal of phyto-challenge. They could bring about notable reduction in the protein and carbohydrate content of exopolysaccharide of biofilm. Eugenol and linalool could affect the synthesis of quorum sensing (QS) proteins like LasA and LasB as well as virulence factors such as pyocyanin, and rhamnolipids, which seriously hamper the formation of biofilm. The biofilm framework was extremely affected by the phytocompounds through the reduction of protein and carbohydrate content of extracellular polymeric substance (EPS). Another interesting found out was that they brought about maximum inhibition to the genomic DNA and RNA content. The studies were supported by in silico interaction between eugenol and linalool with the QS proteins. The antibiofilm efficacies of eugenol, linalool and phytoextract (KT) were further confirmed by microscopic studies with scanning electron microscopy (SEM), atomic force microscopy and fluorescence confocal microscopy microscopic studies. CONCLUSIONS: The phytocompounds are proved to be more effective than conventional antibiotics in inhibiting the biofilm forming sessile cells and can be used as a replacement for antibiotic. SIGNIFICANCE AND IMPACT OF THE STUDY: Pure eugenol extracted from common basil leaves can be used as a safe substitute for common antibiotic for treatment of chronic infections caused by P. aeruginosa. It will be cost effective, devoid of notable side effects and will not generate antibiotic resistance in host body.
Subject(s)
Pseudomonas aeruginosa , Quorum Sensing , Acyclic Monoterpenes , Anti-Bacterial Agents/pharmacology , Biofilms , Eugenol/pharmacology , Extracellular Polymeric Substance Matrix , Ocimum sanctum , Virulence FactorsABSTRACT
BACKGROUND: Twenty one amide compounds possessing phenoxy/benzyloxy/pyridinyl groups have been synthesized by benzoylation of respective amines in presence of base with moderate to encouraging yields. Upon confirmation of structure, compounds were subjected for p38 kinase inhibitory, anti-inflammatory, antimicrobial and antitubercular activities. METHOD: Anti-inflammatory activity was determined using carrageenan induced rat paw edema model while p38 kinase inhibitory activity was studied using ELISA method and serial dilution method was employed to determine MICs. Two compounds 4g and 4n showed over 30% p38 kinase inhibitory activity at 10 µM and best anti-inflammatory activity was found for compounds 4g, 4i, 4n and 4o which exhibited to reduce paw edema over 70%. Compound 4b was observed to be the most potent against gram +ve organisms with MIC value of 1.6 µG/mL and compound 4u displayed potent antibacterial activity against gram negative organisms. CONCLUSION: Most encouraging antitubercular activity was noticed for compounds 4u, 4r and 4k with 6.25, 12.5 and 12.5 µG/mL Further, in order to know the binding site interactions, a docking simulations of compounds was performed. These preliminary results will certainly show fruitful directions to improve the activities of compounds.
Subject(s)
Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antifungal Agents/pharmacology , Benzamides/pharmacology , Edema/drug therapy , Protein Kinase Inhibitors/pharmacology , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Animals , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Antifungal Agents/chemical synthesis , Antifungal Agents/chemistry , Benzamides/chemical synthesis , Benzamides/chemistry , Carrageenan , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Design , Drug Evaluation, Preclinical , Edema/chemically induced , Fungi/drug effects , Gram-Negative Bacteria/drug effects , Humans , Microbial Sensitivity Tests , Molecular Docking Simulation , Molecular Structure , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Rats , Structure-Activity Relationship , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
PURPOSE: To present experience with percutaneous balloon-assisted aspiration thrombectomy (BAT) for the treatment of patients with clotted hemodialysis access grafts. MATERIALS AND METHODS: BAT was performed with use of 7-F intravascular sheaths and a Fogarty balloon catheter. It was tested with an in vitro flow-circuit model. Twenty consecutive BAT procedures were performed in 15 patients with clotted grafts. The balloon catheter was advanced through the sheath to the arterial anastomosis. The balloon was inflated and withdrawn while suction was applied from the sideport to recover thrombus. The procedure was repeated for the venous limb. BAT was used alone in 12 procedures and in combination with urokinase in eight procedures. RESULTS: Almost complete thrombectomy was achieved in all tubes (in vitro), with very low venous and arterial embolic fractions. Technical success (restored graft thrill and almost complete thrombectomy) was achieved in 18 cases (90%). Clinical success (patency after 1 week of dialysis) was achieved in 17 cases (85%). CONCLUSION: Percutaneous BAT is feasible in recently clotted dialysis grafts.