Lipid Solution Research Articles

Evaporation retardation by model tear-lipid films: The roles of film aging, compositions and interfacial rheological properties

A novel methodology for assessing evaporation (up to 48 h) through lipid-nanofilms in vitro was developed. The influence of lipid-mixture compositions on evaporation rates was studied. The evaporative fluxes and rheology of lipid-nanofilms were compared with those of human tear-lipid nanofilms in vitro.A sessile-drop technique with precise drop-volume control was adapted to measure evaporation rates at constant temperature of 36 °C and humidity of 75 %. Model lipid solutions were deposited on the surface of aqueous drops to create nanofilms of 10–100 nm. The measurements of dynamic surface pressure vs. nanofilm-thickness were performed under the same conditions. The lipid-mixtures compositions were chosen to mimic that of human tear lipids. Evaporation through lipid nanofilms decreased with film thickness and aging. Evaporation through 70-nm films was 2.5–3 time slower than through 10-nm-thick films. Nonpolar-lipid mixtures reduced evaporation by approximately 35 %. The optimized model-lipid mixtures containing polar phospholipids reduced evaporation by 70–75 %, matching the evaporation-reduction by human-lipid nanofilms in vitro. These model mixtures exhibited interfacial rheology similar to human tear lipids in vitro.This methodology substantiated that aged lipid-nanofilms significantly reduced evaporation in vitro. These findings contradict to the previous reports suggesting that model lipid and meibum films do not retard evaporation in vitro. Polar phospholipids enhance evaporative resistance close to the level observed for human tear-lipid films in vivo. We hypothesize that unique rheological properties of tear-lipid nanofilms are germane to the specific mono- and bi-layered structures formed by phospholipids at the lipid-air and lipid-aqueous interfaces.

In vitro release studies of ferulic acid in semi-solid formulations with optimized synthetic membrane

Cutaneous release assays are a fast, low-cost procedure, which allows to obtain essential preliminary results for the development of topical formulations containing new active substances. In this sense, this study aimed to obtain and characterize a low-cost and easy-to-reproduce membrane model, based on a biodegradable polymeric cellulose acetate membrane, which had similarity with the lipid composition of skin and then mimicked its barrier function. For this purpose, membranes prepared by impregnation of a lipid solution in a synthetic membrane were tested for ferulic acid (FA) release from semi-solid and stable formulations using Franz diffusion cells. Thermal features of impregnation were investigated by Differential Scanning Calorimetry, while membranes were structurally characterized by Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). Gel and cream-gel formulations containing 0.5% (w/w) FA were submitted to in vitro skin release tests in phosphate-buffered saline + Tween 80, pH 7.4, using either the synthetic membrane or that optimized by Franz diffusion cell testing. AFM demonstrated membrane impregnation through a change in surface roughness, while SEM showed significant reduction of pore size as well as lipid deposition in the polymer network of the synthetic membrane. With the optimized membrane the gel formulation released almost the same FA percentage (52.36%) as the cream-gel one (52.40%), while with the synthetic one the release was slower and less effective, even if the former formulation performed better than the latter (49.55 vs. 46.04%). Whereas with the synthetic membrane the two formulations showed the same release profile, the optimized membrane was more selective for FA diffusion, thus leading to different release profiles. The results of this study suggest that the optimized membrane may be applied in a simple and accessible way to both initial screening of topical formulations and in vitro release tests.

Ambient Formation of Spherulites of Mg-Calcite in an Aqueous Lipid Solution through the Interplay between Multiple Pathways

Nanograins of Mg-containing amorphous calcium carbonate were prepared in an l-α-lecithin solution from which spherulitic crystallites of high-Mg calcite were subsequently formed. The structures of ...

Determination of aluminum concentrations of parenteral nutrition solutions by HPLC.

Aluminum (Al) contamination of parenteral nutrition (PN) solutions has been known for over 30 years. In particular, vascular intake of Al leads to its accumulation in tissues. In this study, 8 all-in-one PN solutions the aluminum concentration was analyzed by high-performance liquid chromatography. The mean Al concentration of the glucose solutions of the PN solutions combinations was 16.36 ± 8.31 µg/L, the mean Al concentration of the amino acid solutions was 4.96 ± 3.73 µg/L, and the mean Al concentration of the lipid solutions was 9.09 ± 11.23 µg/L. The Al concentration of the PN5 glucose and PN2 lipid solutions were above 25 µg/L, which is the limit set by the Food and Drug Administration (FDA). No studies in the literature have examined the Al concentrations of all-in-one PN solutions via HPLC. In two of the analyzed solutions, the Al concentration was found to be higher than the limit set by the FDA.

P36 Numeta G13% preterm neonatal parenteral nutrition solution – a licensed all-in-one triple chamber, ready to use and terminally sterilised parenteral nutrition for preterm newborn infants

AimsWe aim to evaluate the efficacy and safety of Numeta G13%E preterm neonatal parenteral nutrition (PN) in our neonatal population.In September 2017 a National Patient Safety Alert (NPSA) highlighted the risk of harm to babies when lipid was mistakenly run at the rate intended for the aqueous component resulting in significant lipid overdose.Although we have worked to implement many of the alert’s recommendations, we feel we can avoid this risk further by using an all-in-one PN solution.1Numeta meets current nutritional guidelines as per British Association of Perinatal Medicine (BAPM) but this project allows comparison of outcomes important to both patient and service between those achieved with our current regimen and those with the all-in-one regimen.2MethodsWe carried out a quality improvement project from April 2018 to April 2019. We collected data from 330 babies in our neonatal unit during six months before (154 babies) and after (176 babies) the adoption of the all-in-one solution.Our previous PN regimen consisted of a ‘menu’ of aqueous bags (starter, maintenance, ‘light’ and bespoke) and a separate lipid solution. All of them were suitable for peripheral or central administration. Numeta came with similar choices: starter, maintenance -for central administration only- and ‘lite’ and Numeta peripheral, suitable for peripheral administration. Bespoke bags were also available if clinically indicated. We set out our desired outcomes and measured parameters accordingly:Patient outcomesMetabolic stability: electrolyte, glucose, bilirubin and lipid measurements summarised by the need to change from standard PN regimen and/or requirement for insulin.Fluid balance summarised by the lowest weight during the first two weeks of life and time taken to regain birth weight.Growth summarised by change of standard deviation score of weight and head circumference between birth and discharge or transfer back to local hospital.Liver tolerance of lipid solutions summarised by incidence of cholestasis (>25 μmol/l conjugated fraction of serum bilirubin)Days and type of PNSepsisService outcomesNursing time taken to prepare PNCostWastageAccess to productResultsAlthough we finished collecting the data in April 2019, we are still in the process of analysing it and evaluating the final results. There have been no cases of lipid overdose and our neonates (including the preterm ones) have so far tolerated well the new parenteral nutrition solution. Average nursing time preparing Numeta went down from 18.5 minutes to 8 minutes and comparison of cost came in favour of Numeta. PN wastage was higher with Numeta (4.7% Maintenance, 10% ‘light’, peripheral 50%) especially in the first month during the transition phase. There was no significant increase of bespoke bags when Numeta was introduced.ConclusionsIn summary, so far we have not identified significant clinical differences between the first six months of the project -using our old standardised nutrition regimen- and the last months -on the new all-in-one solution. We have continued with Numeta preterm solution on the basis of assumed safety.ReferencesRisk of severe harm and death from infusing total parenteral nutrition too rapidly in babies. NHS improvement patient safety alert September 2017.The Provision of Parenteral Nutrition within Neonatal Services – A Framework for Practice. British Association of Perinatal Medicine (BAPM) April 2016 www.bapm.org

Determination of free fatty acids in plasma by gas chromatography.

A method was developed for determination of free fatty acids (FFAs) in plasma by gas chromatography. Plasma was extracted with 3vol of methanol. Most cholesterol esters and triacylglycerols did not dissolve in the aqueous methanol. FFAs in the crude lipid solution were directly and selectively methylated with (trimethylsilyl)diazomethane at room temperature. Fatty acid methyl esters (FAMEs) formed were extracted with hexane, and nonreactive phospholipids were washed out with 95% methanol. The partially purified FAME preparation was analyzed by gas chromatography. The composition and amount of plasma FFAs closely approximated those obtained using two different methods.

Effect of post-prandial lipemia on canine biochemical parameters

Lipemia is one of the main causes of rejection of samples in veterinary clinical laboratories, interfering in biochemical determinations performed through spectrophotometry. However, it is not adequately known whether such interference causes clinical errors of interpretation in routine canine biochemical determinations, which is especially important when considering that lipemia cannot always be avoided in routine veterinary practice. This study assessed postprandial lipemia of healthy dogs fed with commercial feed, as well as the effect of lipemia induced in vitro by the addition of commercial lipid solution. Twenty healthy dogs were selected, for induction of postprandial lipemia, and the peak lipemic time (3 h after feeding) was compared with two non-lipemic times (12 h of fasting), 1 day before and 1 day after the induction of lipemia, respectively. Lipid solution was added to non-lipemic sera simulating triglyceride concentrations similar to the minimum, medium, and maximum values obtained at the lipemic time in vivo. Biochemical analyses were performed in semi-automated spectrophotometer using a set of commercial reagents. Variables were tested for normality and differences between the groups were tested using paired t test or Wilcoxon and ANOVA or Friedman tests. Both in vivo and in vitro lipemia caused significant biochemical changes in routine tests in healthy dogs, varying according to the analyte tested. Results from lipemic samples should be interpreted with caution for some determinations, whereas in some analyses, the need for fasting is dispensable.

Size-Controllable and Scalable Production of Liposomes Using a V-Shaped Mixer Micro-Flow Reactor

The use of microfluidics has been regarded as a promising solution for the costly and complex preparation of liposomes, and the development of controllable and scalable liposome production using simple-structured, readily available, and inexpensive “off-the-shelf” microfluidics remains important pursuit. We have achieved simple and inexpensive production of liposomes using an off-the-shelf V-shaped mixer. The size of liposomes was controlled (50–70 nm diameter, PDI < 0.1) in the desired range (<100 nm) by changing the relative flow rate of the ethanol solution of lipids and the aqueous solution. The developed approach is scalable (12 mL/min), and several representative lipids, including inexpensive Span 60, can be used for the preparation of nanoparticles.

Preparation of Inhalable Salbutamol Proliposome Using Different Core Carriers and Investigate the Impact of Simulated Lung Fluid Use in Evaluation

Objective: Pro-liposomes are free flowing precursor of liposomes. Liposome low stability can overcome by preparation of Pro-liposomes as high stability precursor of liposome produced upon hydration. Salbutamol sulphate is bronchodilator widely used for the treatment of asthma. Because of its high water solubility its penetration through lipid barriers is low. The preparation of water soluble drugs as liposomes improves their solubility across biological membranes. Method: Microparticulate sucrose, mannitol, trehalose, and lactose separately as core carriers were prepared using mini spray dryer. Ethanolic lipid (soya phosphatidylcholine) solution having salbutamol sulphate and micro particulate core carriers at 1:5 w/w phospholipid to carrier ratio was spray dry to find proliposomes. The prepared liposomes were evaluated for particle size distribution, polydispersity, Z.P., entrapment capacity, and morphology. This investigation was undertaken to compare the evaluation results of the produced liposomes that hydrated by simulated lung fluids that mimic human interstitial lung fluid and deionized water. Results: Good proliposomes were obtained with different properties using spray drying. The results show that carrier type has significant effect on the properties of prepared liposome. In addition, there are obvious differences in results between liposomes generated in simulated lung fluid and deionized water. Overall, simulated lung fluid had significant effect on liposomes size, polydispersity, zetapotential, and entrapment efficiency but had minimal effect of liposome morphology. Conclusion: It can be concluded that use of simulated lung fluid is preferable than deionized water in evaluation of prepared liposomes.

MON-184 Disrupted ACTH-Cortisol Temporal Coupling in Healthy Men After an Overnight Fast, and the Modulatory Role of Orally Ingested Macronutrients

While long term fasting is reported to augment the corticotropic function, effect of short term (overnight) fasting on ACTH-cortisol coordinated release pattern and potential effect(s) of nutrient intake is not fully defined. Eleven healthy men (age: 33-70 yrs, BMI 20.4-31.5 kg-m2) were studied after overnight fast on 4 separate days, involving oral ingestion of 300 ml of either water, dextrose, protein, or lipid solutions. Test meals were isocaloric (400 kcal). Sessions were 6.5 h long, starting at 0800-0900 hrs. Blood was collected at 10-min intervals for ACTH (pg per mL), and cortisol (µg per dL) measurements. Linear regression, cross-correlation, deconvolution, and ApEn were used for data analyses. ACTH and cortisol concentration time series during short-term fast (water day) were found not to be chronologically coupled per linear regression (r2= 0.0014, P=0.82), and cross-correlation (r= - 0.156, lag=150 min) statistics. Oral intake of the 3 macronutrients improved the temporal relationship between ACTH and cortisol concentrations, verified by linear regression (r2:P- dextrose 0.54:0.0001, protein 0.65: 0.0001, lipid 0.42:0.0001), and cross-correlation (r:lag in min- dextrose 0.8:10, protein 0.77:10, lipid 0.78:20). Oral ingestion of either macronutrient did not significantly alter mean ACTH and cortisol concentrations and their respective secretion pattern (total, pulsatile, basal) over the period of 6.5 hr. However compared to the control (water) session, dextrose ingestion evoked less frequent and larger ACTH secretory bursts, and more regular ACTH and cortisol secretory patterns. In this study, we have observed lack of concordance between ACTH and cortisol after overnight fasting, which is restored with oral intake of macronutrients. This effect appears to be uniform among the 3 macronutrients, except for less frequent and lager ACTH bursts and more regular ACTH and cortisol release events after dextrose intake. These findings and the specific role of nutrients being direct or via physiologic nutrient-induced hormonal adaptation warrants future investigation.

Effect of Electrical Parameters and Cholesterol Concentration on Giant Unilamellar Vesicles Electroformation.

Giant unilamellar vesicles (GUVs) are used extensively as models that mimic cell membranes. The cholesterol (Chol) content in the fiber cell plasma membranes of the eye lens is extremely high, exceeding the solubility threshold in the lenses of old humans. Thus, a methodological paper pertaining to preparations of model lipid bilayer membranes with high Chol content would significantly help the study of properties of these membranes. Lipid solutions containing 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and Chol were fluorescently labeled with phospholipid analog 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiIC18(3)) and spin-coated to produce thin lipid films. GUVs were formed from these films using the electroformation method and the results were obtained using fluorescent microscopy. Electroformation outcomes were examined for different electrical parameters and different Chol concentrations. A wide range of field frequency-field strength (ff-fs) combinations was explored: 10-10,000 Hz and 0.625-9.375 V/mm peak-to-peak. Optimal values for GUVs preparation were found to be 10-100 Hz and 1.25-6.25 V/mm, with largest vesicles occurring for 10 Hz and 3.75 V/mm. Chol:POPC mixing ratios (expressed as a molar ratio) ranged from 0 to 3.5. We show that increasing the Chol concentration decreases the GUVs size, but this effect can be reduced by choosing the appropriate ff-fs combination.

Mechanism of Bile Acid Reabsorption in the Biliopancreatic Limb After Duodenal-Jejunal Bypass in Rats.

Bile acids (BAs) are important in the metabolic effects of bariatric surgery. Most BAs are reabsorbed in the ileum and recycled back to the liver. We have reported that this enterohepatic circulation was shortened by duodenal-jejunal bypass (DJB), and the biliopancreatic (BP)-limb plays an important role in reabsorption of BAs. However, the mechanism of BA reabsorption in BP-limb remains uncertain. We aimed to investigate the mechanisms of BA reabsorption after DJB, especially focusing on carrier-mediated transport of BAs and the impact of the presence or absence of lipids on BA reabsorption. Otsuka-Long-Evans-Tokushima fatty rats or Sprague-Dawley rats were assigned to a control group and DJB group. BA levels in the divided small intestine were quantified with liquid chromatography-mass spectrometry. Labeled BA was injected and perfused with BA transporter inhibitors or mixture of lipids in the isolated BP-limb, and bile was sampled and analyzed. Conjugated BA levels in the BP-limb were significantly higher than that of the control group. BA absorption tended to decrease by the apical sodium-dependent BA transporter inhibitor and was significantly decreased by the organic anion-transporting peptide (OATP) inhibitor. BA absorption tended to increase in the absence of lipid solutions compared with that in the presence of lipid solutions. We attributed the increased BA reabsorption in the BP-limb to lack of food in the BP-limb, which contains concentrated BAs and no lipids. OATP played an important role in BA reabsorption in the BP-limb. Therefore, BAs would be reabsorbed in different manners after DJB.

Preparation of nanoliposomes by microfluidic mixing in herring-bone channel and the role of membrane fluidity in liposomes formation

Introduction of microfluidic mixing technique opens a new door for preparation of the liposomes and lipid-based nanoparticles by on-chip technologies that are applicable in a laboratory and industrial scale. This study demonstrates the role of phospholipid bilayer fragment as the key intermediate in the mechanism of liposome formation by microfluidic mixing in the channel with “herring-bone” geometry used with the instrument NanoAssemblr. The fluidity of the lipid bilayer expressed as fluorescence anisotropy of the probe N,N,N-Trimethyl-4-(6-phenyl-1,3,5-hexatrien-1-yl) was found to be the basic parameter affecting the final size of formed liposomes prepared by microfluidic mixing of an ethanol solution of lipids and water phase. Both saturated and unsaturated lipids together with various content of cholesterol were used for liposome preparation and it was demonstrated, that an increase in fluidity results in a decrease of liposome size as analyzed by DLS. Gadolinium chelating lipids were used to visualize the fine structure of liposomes and bilayer fragments by CryoTEM. Experimental data and theoretical calculations are in good accordance with the theory of lipid disc micelle vesiculation.

Effect of calcium chloride on the protein encapsulation and stability of proliposomal granules

The purpose of this study was to develop oral proliposomal granules incorporating CaCl2 in order to enhance the encapsulation efficiency (EE) of protein model drug after reconstitution. Proliposomal granules were prepared by a granulation process with a solid carrier, protein model drug, and lipid solution. The proliposomal granules were characterized in terms of particle size, EE, and loading capacity. Protein structure analysis and cellular viability were also examined. CaCl2, ranged 0.125–6.0% w/w, was successfully incorporated into the dried granules during the wet binding process of granulation. Reconstituted proliposomes with 1% w/w CaCl2 showed the highest EE among those examined. Different reconstituted diluents did not alter the EE, but had an impact on particle size and charge. The α-helical content (%), calculated from the mean molar ellipticity, was similar between protein drug alone and that with addition of CaCl2, indicating the preservation of structural integrity, as also confirmed by electrophoresis. CaCl2–incorporated proliposomes were non-toxic to cells at the dose used. In conclusion, inclusion of CaCl2 into proliposomal granules enhanced the EE of protein drug showing optimal effects at 1% w/w with good preservation of protein integrity and cellular viability.

Development of a facile fluorophosphonate-functionalised titanium surface for potential orthopaedic applications

sBackgroundAseptic loosening of total joint replacements (TJRs) continues to be the main cause of implant failures. The socioeconomic impact of surgical revisions is hugely significant; in the United Kingdom alone, it is estimated that £137 m is spent annually on revision arthroplasties. Enhancing the longevity of titanium implants will help reduce the incidence and overall cost of failed devices.MethodsIn realising the development of a superior titanium technology, we exploited the natural affinity of titanium for phosphonic acids and developed a facile means of coating the metal with (3S)1-fluoro-3-hydroxy-4-(oleoyloxy)butyl-1-phosphonate (FHBP), a phosphatase-resistant analogue of lysophosphatidic acid (LPA). Importantly LPA and selected LPA analogues like FHBP synergistically cooperate with calcitriol to promote human osteoblast formation and maturation.ResultsHerein, we provide evidence that simply immersing titanium in aqueous solutions of FHBP afforded a surface that was superior to unmodified metal at enhancing osteoblast maturation. Importantly, FHBP-functionalised titanium remained stable to 2 years of ambient storage, resisted ∼35 kGy of gamma irradiation and survived implantation into a bone substitute (Sawbone™) and irrigation.ConclusionThe facile step we have taken to modify titanium and the robustness of the final surface finish are appealing properties that are likely to attract the attention of implant manufacturers in the future.The translational potential of this articleWe have generated a functionalised titanium (Ti) surface by simply immersing Ti in aqueous solutions of a bioactive lipid. As a facile procedure it will have greater appeal to implant manufacturers compared to onerous and costly developmental processes.

Stocktaking of local anesthetics 2020

For decades local anesthetics have proven to be safe and effective drugs in the clinical practice, crucially promoting the enormous achievements in regional anesthesia. Meanwhile, it is awell-known fact that local anesthetics are much more than just "simple" sodium channel blockers. They also interact with numerous other ion channels and subcellular structures, enhancing nerve blockade and resulting in systemic "alternative" effects, which can sometimes even be clinically used. By the simultaneous administration of various adjuvants (e.g., opioids, corticosteroids and α2-receptor agonists) attempts are made to prolong the time of action of local anesthetics after a single administration in order to achieve the best possible improvement in postoperative analgesia. In this context, ultralong-acting local anesthetics, such as liposomal bupivacaine, which at least theoretically can provide a sensory nerve block for several days, have been developed and clinically introduced. The coming years will show whether these approaches will develop into genuine alternatives to the personnel and cost-intensive continuous nerve blockades.Local anesthetic-induced systemic toxicity is meanwhile rare but still a potentially life-threatening event, frequently resulting from accidental intravascular injection or extensive systemic resorption. Consequently, slow and fractional application of these agents with intermittent aspiration helps to prevent toxic sequelae. If toxic symptoms occur, however, the intravenous infusion of 20% lipid solutions in addition to basic treatment measures can enhance the success of treatment.

Lipid Bilayers Influenced by Taurin and Betain

We studied the influence of natural osmolytes Taurin and Betain on the stability and fluidity of lipid model membranes. They components of daily products aim at our well-being, such as energy drinks or baby creams. We used a combination of simultaneous SAXS/WAXS/DSC measurements, being able to identify the structures, their dimensions and the phase transition temperatures. Thermal scans show morphologies similar to aqueous solution of the pure lipids, although with different dimensions and transition temperatures. In POPE, we observe structures with high curvature, and upon temperature cycling, the induction of possible cubic phases. Fully hydrated POPE hydrated with solutions of such osmolytes surprisingly lacks anomalous diffraction patterns over a wide temperature range on cooling from the hexagonal phase. The diffraction peaks in the last patterns are much less intense than at the beginning of the scan. The DSC shows a higher phase transition temperature on heating than for pure aqueous POPE, while during cooling this is not seen. DSC of POPE in on these samples shows a transition at a different temperature than purely hydrated POPE. The SAXS scan indicates a less organized stack of bilayers and the hexagonal phase, normally following the lamellar upon heating, could not be clearly seen up to 85oC. Moreover, no well-organized structure was formed during cooling. On combining SAXS/WAXS and DSC results obtained from dispersions of POPE in either aqueous solution of Taurin and Betain, one can see their effect from a structural perspective, that is, their influence on the macro organization of the self-assembled mesogenic units. Both osmolytes seem to require high temperatures (weaker interactions between headgroups of neighbouring lipids) to effectively interact with the POPE (headgroups) and influence the dispersion.

Probing Thermotropic Phase Behavior of Dipalmitoylphosphatidylcholine Bilayers from Electrical and Topographic Data in a Horizontal Black Lipid Membrane Model.

Here, a homemade device allowed preparing horizontal lipid bilayer membranes (hBLMs) for recording electrical and topographical data simultaneously and in real-time, under temperature (T)-controlled conditions along a cooling process of dipalmitoylphosphatidylcholine (DPPC) bilayers. Electrical parameters (ionic current intensity, I, and transmembrane resistance, R = ΔV/I) plotted against T exhibited discontinuities at the main transition (TPβ'→Lα) and pretransition (TLβ→Pβ') temperatures of DPPC. The T-dependent sensitivity to ΔV-induced electrostriction was revealed by capacitance measurements. The patterns of I fluctuation described long-range correlations reflected by 1/f-type noise in the ripple phase (Pβ') and Brownian-type fluctuations in the liquid-crystalline (Lα) phase at voltage intensities lower than a voltage threshold (ΔVth = ±160 mV), indicating that autocorrelations arise from an underlying structural connectivity that takes place within ordered phases. At |V| ≥ Vth, the fluctuation dynamics exhibited a 1/f behavior over the whole temperature range analyzed, suggesting that upon a certain intensity of external electrical perturbation, the membrane system evolves toward a voltage-induced percolated-pore state. At T > TPβ'→Lα, differential interference contrast micrographs showed droplet-like structures, probably containing solvent traces of the lipid solution, which were reverted upon cooling. However, droplets did not interfere with the thermotropic equilibrium of the bilayer phase. This suggested that the temperature-induced changes in the electrical properties of the bilayer, as well as in the complexity of the fluctuation patterns (emergency of long- and short-range correlations), were strongly associated with the characteristic thermotropic behavior of DPPC, without significant deviations induced by the presence of residual n-decane in the bilayer. Our hBLM model membrane proved useful for correlating thermotropic phase changes with electro-biophysical and topographical information.

Information on local anesthetics and toxicity for doctors in surgical department of Karadeniz Technical University Medical Faculty Hospital

Aim: Local anesthetics are commonly used in surgical interventions and anesthesia applications. The aim of this study was to increase the sensitivity of local anesthetic toxicity to the presence of symptoms, precautions to be taken and the use of 20% lipid infusion for treatment. Material and Methods: The questionnaire was applied on 160 of 205 physicians who were prescribed local anesthetics.Results: Of the 160 participants included in the study, 108 (67.5%) were research assistants, 47 (29.4%) were faculty members and the remaining 5 (3.1%) were expert medical practitioners. 63 of the participants (39.4%) had been working in the medical profession for more than 5 years. While 42.5% of the participants administered local anesthetics every day, 33.1% had not received any training in the area. On the basis of their training status, it was the anesthetists among specialist doctors who were the most trained in anesthetics with a statistically high rate of 86.3%. Thirty-three of the surveyed physicians (20.6%) who responded stated that they had experienced a case of local anesthetic toxicity previously. The most frequent answer to the question in early findings concerning local anesthetic toxicity was anaphylaxis (74.4%). 38.1% of the participants had not heard the use of 20% lipid solution in local anesthetic toxicity. Although there was 20% lipid solution in the university hospital where the research was conducted, 31.9% of the participants knew this.Conclusion: Although local anesthetic toxicity is rare, it frequently occurs in clinical practice. Therefore, physicians should have general knowledge regarding local anesthetic drugs, maximum doses, side effects, toxicity symptoms and the required treatment in the case of toxicity. We also think local anesthetic toxicity should be included in annual training programs and practical applications by other clinical branches that apply local anesthetic drugs as we currently do at our Clinic and physicians should be given appropriate guidance.

A review on the recent application of ketamine in management of anesthesia, pain, and health care.

Ketamine is considered as a promising drug for many clinical applications even after five decades since its discovery. Ketamine is a dissociative anesthetic agent with a variety of pharmacological effects from anesthetic induction and maintenance to analgesic and sedative depending on the consuming dose. It can be used solely or in combination with other co-adjuvant drugs, increasing their efficacy. Many therapeutic properties of ketamine have been attributed to its antagonism mechanism to N-Methyl-D-aspartate receptor. Identifying new properties of ketamine such as neuroprotective, antiinflammatory, and antitumor effects, on one hand, and taking advantage of subanesthetic regimens of ketamine, on the other hand, have resulted in a widespread use of ketamine in various clinical applications. Ketamine is solvable in aqueous and lipid solutions, providing convenient administration via multiple routes, including oral, nasal, rectal, intravenous, intramuscular, subcutaneous, transdermal, sublingual, and intraosseous administration. Application of ketamine has some advantages over other sedative and anesthetic agents. It produces bronchodilation status, allowing for most secure induction of anesthesia in patients with life-threatening asthma and intense acute bronchial constriction. Ketamine has an excellent hemodynamic profile, makes it the agent of choice for patients with unstable hemodynamics, such as shocked or hypotensive patients. Ketamine usage has been associated with a lower risk of respiratory depression and relatively more conserved airway reflexes. Although being an anesthetic agent, ketamine has been increasingly used in subanesthetic doses for acute and chronic pain as well as depression. Using ketamine in pre and postoperative pain management is well established. However, the studies on ketamine performance in pain management demonstrated contradicting results. On the other hand, various side effects along with no confirmatory data on long-term treatment demand great caution when using ketamine for treating complex chronic pains. The present study aimed to provide a general review on the recent applications of ketamine in anesthesia, pain management, and critical care.