Interaction of miltefosine with microcavity supported lipid membrane: biophysical insights from electrochemical impedance spectroscopy

Miltefosine an alkylphosphocholine analogue, is the only drug taken orally for the treatment of leishmaniasis-a parasitic disease caused by sandflies. Although it is believed that Miltefosine exerts its activity by acting at the lipid membrane, detailed understanding of the interaction of this drug with eukaryotic membranes is still lacking. Herein, we exploit microcavity pore suspended lipid bilayers (MSLBs) as a biomimetic platform in combination with a highly sensitive label-free electrochemical impedance spectroscopy (EIS) technique to gain biophysical insight into the interaction of Miltefosine with host cell membrane as a function of lipid membranes composition. Four membrane compositions with increasing complexity were evaluated; DOPC, DOPC:Chol (75:25), domain forming DOPC:SM:Chol (40:40:20) and mammalian plasma membrane (MPM) mimetic DOPC:DOPE:Chol:SM:DOPS (32:25:20:15:8) and used to study the interaction of Miltefosine in a concentration-dependent manner using EIS. The membrane resistance changes in response to Miltefosine were modelled by an empirical Langmuir isotherm binding model to provide estimates of binding saturation and equilibrium association constant. Miltefosine was found to have greatest impact on electrochemical properties of the simpler membrane systems; DOPC and DOPC:Chol, where these membranes were found to be more susceptible to membrane thinning, attributed to strong permeation/penetration of the drug whilst, compositions that included both Chol and SM, expected to contain large liquid-ordered domains exhibited weaker changes to membrane resistance but strongest drug association. In contrast, at the MPM membrane, Miltefosine exerts weakest association, which is tentatively attributed to electrostatic effects from the anionic DOPS but some membrane thinning is observed reflected in change in resistance and capacitance values attributed to some weak permeation

Alternative medicine and herbal remedies in the treatment of erectile dysfunction: A systematic review

Objectives: To systematically review and discuss the current evidence from placebo-controlled clinical trials that investigated the use of alternative medicines and herbal remedies in the management of erectile dysfunction (ED). Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)- based systematic review using specific keyword combinations was conducted on the PubMed and Scopus databases. Randomised controlled trials investigating herbal medicine in at least one group and using the International Index of Erectile Function (IIEF) as an outcome in patients primarily diagnosed with ED were included for review. Results: Following the literature search, screening and eligibility analysis, a total of 42 articles were included. The 42 articles were categorised as single herb extractions (n = 14), combination herbal formula (n = 5), combination of herbal formula and non-herbal nutraceuticals (n = 7), non-herbal nutraceuticals (n = 5), acupuncture and moxibustion (n = 2), diet and nutrition (n = 3), exercise (n = 5), and topical treatments (n = 1). Based on the results, Korean ginseng, Pygnogenol and Prelox, Tribulus terrestris, Lepidium meyenii, L-arginine, acupuncture and lifestyle interventions were the more predominantly investigated treatments interventions for ED. Conclusions: Panax ginseng, Pygnogenol, Prelox and Tribulus terrestris have promising evidence as herbal products, alongside L-arginine as a nutritional supplement, for ED based on IIEF outcomes, and warrant further clinical investigation. The mechanisms of action remain unclear, but each of these appears to in part increase nitric oxide synthesis. Importantly, improved diet and exercise should be considered, particularly in patients with obesity or diabetes mellitus

Efficacy of ultrasound guided quadratus lumborum plane-1 block for post operative analgesia at iliac / hypogastric donor sites in patients undergoing reconstructive surgery with graft harvest from dermatomal area t7 - l1 : A prospective randomised controlled study

Background: Ultrasound-guided quadratus lumborum plane-1 (QLP-1) block involves placement of local anesthetic lateral to the quadratus lumborum muscle. It provides better and long-lasting analgesia than transverse abdominis plane block due to the spread of local anesthetic more posteriorly along the thoracolumbar fascial plane, thus involving the L1 dermatomal area. Objectives: We conducted a study to evaluate the efficacy of ultrasound-guided QLP-1 block for postoperative analgesia at iliac/hypogastric donor sites in patients undergoing reconstructive surgery with graft harvest from dermatomal area T7-L1. Materials and Methods: After obtaining approval from the ethical committee, a randomized controlled trial was conducted from February 2018 to November 2018. Eighty patients were randomly allocated into two equal groups, Group A (QLP-1 block) and Group B (control, without any block, and only iv analgesics) based on computer-generated random number techniques. Twenty ml of local anesthetic mixture containing 0.5% bupivacaine and 2% lignocaine with adrenaline and 4 mg of dexamethasone was for QLP-1 block in Group A. Aim was to assess pain scores every second hourly up to 24 h and secondary objective was the requirement of rescue analgesia. SPSS version 19 was used to derive statistical results. The unpaired t-test is used for quantitative analysis. Results: The numerical pain score (NPS) was significantly low in Group A compared to Group B between 6th and 12th h after the block (P < 0.001). The mean time at which first rescue analgesia had to be given was significantly later in group A (15.55 h) compared to Group B (6.25 h). The requirement of double rescue analgesia in the first 24 h after the block was higher in Group B (100%) compared to Group A (0%). Conclusion: Ultrasound-guided QLP-1 block is safe, hemodynamically stable, and provided superior analgesia at iliac/hypogastric donor sites compared to control group in patients undergoing reconstructive surgery with graft harvest from dermatomal area T7-L1. The number of rescue analgesics required in the QLP-1 group is less compared to the control group