Treatment of telangiectasia on the cheeks with a compact yellow (585 nm) semiconductor laser and a green (532 nm) KTP laser: a randomized double-blinded split-face trial.

OBJECTIVES: The primary objective of this study was to compare a traditional green KTP laser to a new investigational yellow laser (PhotoLase) in the treatment of facial telangiectasia in terms of the treatment outcomes. The secondary objective was to assess the functionality and reliability of the PhotoLase system from the perspective of the user. STUDY DESIGN/METHODS: The study was a randomized split-face double-blinded study that compared the treatment efficacy of the 532-nm KTP laser and the investigational 585-nm PhotoLase laser. One or two treatments were given based on the response of the first treatment. The improvement of telangiectasia was graded according to a 7-point Telangiectasia Grading Scale (TGS) by the subjects and blinded physicians. The subjects assessed the amount of pain during the treatments using Visual Analogue Scale (VAS), and evaluated adverse effects 2-3 days after the treatment(s) using a self-assessment form. RESULTS: At least 50% improvement was seen in 15/18 subjects after the first PhotoLase treatment, and a similar result was observed for KTP, as assessed by the blinded physicians (P = 0.29). In the subjects' assessment, 7/18 subjects had at least 50% improvement after the first PhotoLase treatment, whereas at least 50% improvement was observed for 10/18 subjects in the KTP side, the difference being significant (P = 0.008). The amount of pain was higher with PhotoLase compared to KTP (67.7 vs. 34.6, P < 0.001). There was no difference in the frequency of erythema, crusting or purpura between the devices, but more blistering and less edema were seen after PhotoLase treatment (P < 0.05). Treatment with PhotoLase was evaluated to be 4.7-fold faster than with KTP and the PhotoLase system was more compact, narrower, lighter, and easier to carry than KTP. CONCLUSIONS: The investigational PhotoLase laser enables significantly faster treatments, but the process is somewhat more painful than with KTP, otherwise providing a similar clinical outcome in the treatment of facial telangiectasia. Treatment Protocol Lasers Surg. Med. 51:223-229, 2019. © Wiley Periodicals, Inc.

1.34 µm VECSEL mode-locked with a GaSb-based SESAM.

Mode locking of a 1.34 µm vertical external cavity surface emitting laser is demonstrated using a GaSb-based semiconductor saturable absorber mirror (SESAM). The SESAM includes six AlGaSb quantum wells (QWs) with an absorption edge at ∼1.37 µm. The proposed approach has two key benefits: the QWs can be grown lattice matched, and only a small number of Bragg reflector layers is required to provide high reflectivity. Pump-probe measurements also reveal that the AlGaSb/GaSb structure exhibits an intrinsically fast absorption recovery on a picosecond timescale. The mode-locked laser pulse train had a fundamental repetition rate of 1.03 GHz, a pulse duration of ∼5 ps, and a peak power of ∼1.67 W. The demonstration paves the way for exploiting GaSb-based SESAMs for mode locking in the 1.3-2 µm wavelength range, which is not sufficiently addressed by GaAs and InP material systems.

Correlation between Ionic Liquid Cytotoxicity and Liposome-Ionic Liquid Interactions.

This study aims at extending the understanding of the toxicity mechanism of ionic liquids (ILs) using various analytical methods and cytotoxicity assays. The cytotoxicity of eight ILs and one zwitterionic compound was determined using mammalian and bacterial cells. The time dependency of the IL toxicity was assessed using human corneal epithelial cells. Hemolysis was performed using human red blood cells and the results were compared with destabilization data of synthetic liposomes upon addition of ILs. The effect of the ILs on the size and zeta potential of liposomes revealed information on changes in the lipid bilayer. Differential scanning calorimetry was used to study the penetration of the ILs into the lipid bilayer. Pulsed field gradient nuclear magnetic resonance spectroscopy was used to determine whether the ILs occurred as unimers, micelles, or if they were bound to liposomes. The results show that the investigated ILs can be divided into three groups based on the cytotoxicity mechanism: cell wall disrupting ILs, ILs exerting toxicity through both cell wall penetration and metabolic alteration, and ILs affecting solely on cell metabolism.

Cholesterol affects the interaction between an ionic liquid and phospholipid vesicles. A study by differential scanning calorimetry and nanoplasmonic sensing.

The present work aims at studying the interactions between cholesterol-rich phosphatidylcholine-based lipid vesicles and trioctylmethylphosphonium acetate ([P8881][OAc]), a biomass dissolving ionic liquid (IL). The effect of cholesterol was assayed by using differential scanning calorimetry (DSC) and nanoplasmonic sensing (NPS) measurement techniques. Cholesterol-enriched dipalmitoyl-phosphatidylcholine vesicles were exposed to different concentrations of the IL, and the derived membrane perturbation was monitored by DSC. The calorimetric data could suggest that the binding and infiltration of the IL are delayed in the vesicles containing cholesterol. To clarify our findings, NPS was applied to quantitatively follow the resistance of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine incorporating 0, 10, and 50mol% of cholesterol toward the IL exposure over time. The membrane perturbation induced by different concentrations of IL was found to be a concentration dependent process on cholesterol-free lipid vesicles. Moreover, our results showed that lipid depletion in cholesterol-enriched lipid vesicles is inversely proportional to the increasing amount of cholesterol in the vesicles. These findings support that cholesterol-rich lipid bilayers are less susceptible toward membrane disrupting agents as compared to membranes that do not incorporate any sterols. This probably occurs because cholesterol tightens the phospholipid acyl chain packing of the plasma membranes, increasing their resistance and reducing their permeability.

Monoliths in capillary electrochromatography and capillary liquid chromatography in conjunction with mass spectrometry.

Here, we have reviewed separation studies utilizing monolithic capillary columns for separation of compounds preceding MS analysis. The review is divided in two parts according to the used separation method, namely CEC and capillary LC (cLC). Based on our overview, monolithic CEC-MS technique have been more focused on the syntheses of highly specialized and selective separation phase materials for fast and efficient separation of specific types of analytes. In contrast, monolithic cLC-MS is more widely used and is often employed, for instance, in the analysis of oligonucleotides, metabolites, and peptides and proteins in proteomic studies. While poly(styrene-divinylbenzene)-based and silica-based monolithic capillaries found their place in proteomic analyses, the other laboratory-synthesized monoliths still wait for their wider utilization in routine analyses. The development of new monolithic materials will most likely continue due to the demand of more efficient and rapid separation of increasingly complex samples.

750 nm 1.5 W frequency-doubled semiconductor disk laser with a 44 nm tuning range.

We demonstrate 1.5 W of output power at the wavelength of 750 nm by intracavity frequency doubling a wafer-fused semiconductor disk laser diode-pumped at 980 nm. An optical-to-optical efficiency of 8.3% was achieved using a bismuth borate crystal. The wavelength of the doubled emission could be tuned from 720 to 764 nm with an intracavity birefringent plate. The beam quality parameter M2 of the laser output was measured to be below 1.5 at all pump powers. The laser is a promising tool for biomedical applications that can take advantage of the large penetration depth of light in tissue in the 700-800 nm spectral range.

Quantum dot semiconductor disk laser at 1.3 µm.

We present a semiconductor disk laser (SDL) emitting at the wavelength of 1.3 µm. The active region of the SDL comprises InAs quantum dots (QDs) that are embedded into InGaAs quantum wells (QWs). An output power over 200 mW is obtained at 15°C, which represents the highest output power reported from QD-based SDLs in this wavelength range. The results demonstrate the feasibility of QD-based gain media for fabricating SDLs emitting at 1.3 µm.

A 1.33 µm picosecond pulse generator based on semiconductor disk mode-locked laser and bismuth fiber amplifier.

We demonstrate that a combination of ultrafast wafer bonded semiconductor disk laser and a bismuth-doped fiber amplifier provides an attractive design for high power 1.33 µm tandem hybrid systems. Over 0.5 W of average output power was achieved at a repetition rate of 827 MHz that corresponds to a pulse energy of 0.62 nJ.

High performance wafer-fused semiconductor disk lasers emitting in the 1300 nm waveband.

We report for the first time on the performance of 1300 nm waveband semiconductor disc lasers (SDLs) with wafer fused gain mirrors that implement intracavity diamond and flip-chip heat dissipation schemes based on the same gain material. With a new type of gain mirror structure, maximum output power values reach 7.1 W with intracavity diamond gain mirrors and 5.6 W with flip-chip gain mirrors, using a pump spot diameter of 300 µm, exhibiting a beam quality factor M(2)< 1.25 in the full operation range. These results confirm previously published theoretical modeling of these types of SDLs.

High-power flip-chip semiconductor disk laser in the 1.3 µm wavelength band.

We present 6.1 W of output power from a flip-chip semiconductor disk laser (SDL) emitting in the 1.3 µm wavelength region. This is the first demonstration of a flip-chip SDL in this wavelength range with output powers that are comparable to those obtained with intracavity diamond heat spreaders. The flip-chip configuration circumvents the optical distortions and losses that the intracavity diamond heat spreaders can introduce into the laser cavity. This is essential for several key applications of SDLs.

Antievaporative mechanism of wax esters: implications for the function of tear fluid.

The tear film lipid layer (TFLL) is considered to act as an evaporation barrier and to maintain the tear film intact between blinks. In vitro methods have, however, failed to reproduce this evaporation-retarding effect. Wax esters (WEs) are a major component of the TFLL. Close to their bulk melting temperature, WEs have been found to retard the evaporation of water, but the nature of this mechanism has remained unclear. We studied the interfacial organization of WE films by measuring their isochors and isotherms and evaporation-retarding effect, and we imaged these films by Brewster angle microscopy (BAM). Behenyl palmitoleate (BP) was used as a representative WE because it resembles the WEs found in meibum. At low temperatures, BP forms solid monolayer crystals in which the molecules are organized in a bulk-like extended conformation. Within approximately 3 °C below the bulk melting temperature, these solid monolayer domains coexist with a fluid monolayer film. At temperatures above the bulk melting temperature, BP forms a completely fluid monolayer in which the molecules are in a hairpin conformation. A fluid hairpin monolayer of BP does not significantly retard evaporation, whereas a solid monolayer decreases evaporation by >50%. The results provide a molecular-level rationale for the evaporation-retarding properties of WEs close to their melting temperature.

1.56 µm 1 watt single frequency semiconductor disk laser.

A single frequency wafer-fused semiconductor disk laser at 1.56 µm with 1 watt of output power and a coherence length over 5 km in fiber is demonstrated. The result represents the highest output power reported for a narrow-line semiconductor disk laser operating at this spectral range. The study shows the promising potential of the wafer fusion technique for power scaling of single frequency vertical-cavity lasers emitting in the 1.3-1.6 µm range.

1 W at 785 nm from a frequency-doubled wafer-fused semiconductor disk laser.

We demonstrate an optically pumped semiconductor disk laser operating at 1580 nm with 4.6 W of output power, which represents the highest output power reported from this type of laser. 1 W of output power at 785 nm with nearly diffraction-limited beam has been achieved from this laser through intracavity frequency doubling, which offers an attractive alternative to Ti:sapphire lasers and laser diodes in a number of applications, e.g., in spectroscopy, atomic cooling and biophotonics.

Molecular organization of the tear fluid lipid layer.

The tear fluid protects the corneal epithelium from drying out as well as from invasion by pathogens. It also provides cell nutrients. Similarly to lung surfactant, it is composed of an aqueous phase covered by a lipid layer. Here we describe the molecular organization of the anterior lipid layer of the tear film. Artificial tear fluid lipid layers (ATFLLs) composed of egg yolk phosphatidylcholine (60 mol %), free fatty acids (20 mol %), cholesteryl oleate (10 mol %), and triglycerides (10 mol %) were deposited on the air-water interface and their physico-chemical behavior was compared to egg-yolk phosphatidylcholine monolayers by using Langmuir-film balance techniques, x-ray diffraction, and imaging techniques as well as in silico molecular level simulations. At low surface pressures, ATFLLs were organized at the air-water interface as heterogeneous monomolecular films. Upon compression the ATFLLs collapsed toward the air phase and formed hemispherelike lipid aggregates. This transition was reversible upon relaxation. These results were confirmed by molecular-level simulations of ATFLL, which further provided molecular-scale insight into the molecular distributions inside and dynamics of the tear film. Similar type of behavior is observed in lung surfactant but the folding takes place toward the aqueous phase. The results provide novel information of the function of lipids in the tear fluid.

3 W of 650 nm red emission by frequency doubling of wafer-fused semiconductor disk laser.

3 W at genuine red wavelength of 650 nm has been achieved from a semiconductor disk laser by frequency doubling. An InP based active medium was fused with a GaAs/AlGaAs distributed Bragg reflector resulting in an integrated monolithic gain mirror. 6.6 W of output power at the fundamental wavelength of 1.3 µm represents the best achievement reported to date for this type of lasers.

Immobilization of natural lipid biomembranes and their interactions with choline carboxylates. A nanoplasmonic sensing study.

The cell membrane is mainly composed of lipid bilayers with inserted proteins and carbohydrates. Lipid bilayers made of purified or synthetic lipids are widely used for estimating the effect of target compounds on cell membranes. However, the composition of such biomimetic membranes is much simpler than the composition of biological membranes. Interactions between compounds and simple composition biomimetic membranes might not demonstrate the effect of target compounds as precisely as membranes with compositions close to real organisms. Therefore, the aim of our study is to construct biomimetic membrane closely mimicking the state of natural membranes. Liposomes were prepared from lipids extracted from L-α-phosphatidylcholine, Escherichia coli, yeast (Saccharomyces cerevisiae) and bovine liver cells through agitation and sonication. They were immobilized onto silicon dioxide (SiO2) sensor surfaces using N-(2-hydroxyethyl)piperazine-N'-2-ethanesulfonic acid buffer with calcium chloride. The biomimetic membranes were successfully immobilized onto the SiO2 sensor surface and detected by nanoplasmonic sensing. The immobilized membranes were exposed to choline carboxylates. The membrane disruption effect was, as expected, more pronounced with increasing carbohydrate chain length of the carboxylates. The results correlated with the toxicity values determined using Vibrio fischeri bacteria. The yeast extracted lipid membranes had the strongest response to introduction of choline laurate while the bovine liver lipid extracted liposomes were the most sensitive towards the shorter choline carboxylates. This implies that the composition of the cell membrane plays a crucial role upon interaction with choline carboxylates, and underlines the necessity of testing membrane systems of different origin to obtain an overall image of such interactions.

Interactions of Ionic Liquids and Spirocyclic Compounds with Liposome Model Membranes. A Steady-State Fluorescence Anisotropy Study.

Understanding the toxicity of ionic liquids (ILs) is crucial in the search of greener chemicals. By comparing in vivo toxicity and in vitro interactions determined between compounds and biomimetic lipid membranes, more detailed toxicity vs. structure relation can be obtained. However, determining the interactions between non-surface-active compounds and liposomes has been a challenging task. Organisational changes induced by ILs and IL-like spirocyclic compounds within 1,6-diphenyl-1,3,5-hexatriene-doped biomimetic liposomes was studied by steady-state fluorescence anisotropy technique. The extent of organisational changes detected within the liposome bilayers were compared to the toxicity of the compounds determined using Vibrio Fischeri bacteria. Four liposome compositions made of pure 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocoline (POPC) and mixtures of POPC, 1-palmitoyl-2-oleyl-sn-glycero-3-phosphoserine (POPS), and cholesterol (Chol) were tested as biomimetic models. Changes observed within the POPC/POPS/Chol 55:20:25 bilayers correlated the best with the toxicity results: ten out of twelve compounds followed the trend of increasing bilayer disorder - increasing toxicity. The study suggests that the toxicity of non-surface-active compounds is dependent on their ability to diffuse into the bilayers. The extent of bilayer's organisational changes correlates rather well with the toxicity of the compounds. Highly sensitive technique, such as fluorescence anisotropy measurements, is needed for detecting subtle changes within the bilayer structures.

The Effect of Phospholipids on Tear Film Lipid Layer Surface Activity.

Purpose: We illustrate the importance of small quantities (<10 mol%) of polar phospholipids on the surface-active behavior of meibum-like lipid compositions. Methods: Artificial meibum-like lipid mixture containing cholesteryl and wax esters was mixed with differing amounts of phosphatidylcholine (PC). The surface activity of these mixtures was investigated at the air-water interface by recording surface pressure created by the lipid layer as a function of molecular area at 37°C. The PC proportion in the mixtures was 0, 2.5, 5, 7.5, or 10 mol%, and the remaining proportion in the mixture was 50:50 (mol/mol) of cholesteryl oleate (CO) and behenyl oleate (BO). Also, the effect of temperature was investigated. Results: The surface activity of the mixtures increased in a very predictable and consistent fashion as a function of the PC proportion. The lipid mixture containing only CO and BO showed miniscule surface activity. However, already 2.5% PC mixed with the nonpolar CO and BO generated considerable increase in surface pressure. At small surface areas, the behavior of 7.5% and 10% PC compositions started to approach that of a pure PC monolayer. The temperature did not have a considerable impact on the surface-active behavior of the PC-containing compositions. Conclusions: The polar phospholipids have a considerable effect on the surface-active properties of artificial tear film lipid layer (TFLL) compositions. Surprisingly, this takes place already at very low and physiologically relevant PC proportions. The effect is more dependent on the actual amount of the phospholipids at the air-tear interface than on the relative amount of these lipids in TFLL.

Impact of Surface-Active Guanidinium-, Tetramethylguanidinium-, and Cholinium-Based Ionic Liquids on Vibrio Fischeri Cells and Dipalmitoylphosphatidylcholine Liposomes.

We investigated the toxicological effect of seven novel cholinium, guanidinium, and tetramethylguanidinium carboxylate ionic liquids (ILs) from an ecotoxicological point of view. The emphasis was on the potential structure-toxicity dependency of these surface-active ILs in aqueous environment. The median effective concentrations (EC50) were defined for each IL using Vibrio (Aliivibrio) fischeri marine bacteria. Dipalmitoylphosphatidylcholine (DPPC) liposomes were used as biomimetic lipid membranes to study the interactions between the surface-active ILs and the liposomes. The interactions were investigated by following the change in the DPPC phase transition behaviour using differential scanning calorimetry (DSC). Critical micelle concentrations for the ILs were determined to clarify the analysis of the toxicity and the interaction results. Increasing anion alkyl chain length increased the toxicity, whereas branching of the chain decreased the toxicity of the ILs. The toxicity of the ILs in this study was mainly determined by the surface-active anions, while cations induced a minor impact on the toxicity. In the DSC experiments the same trend was observed for all the studied anions, whereas the cations seemed to induce more variable impact on the phase transition behaviour. Toxicity measurements combined with liposome interaction studies can provide a valuable tool for assessing the mechanism of toxicity.

Pure Glaucoma Drugs Are Toxic to Immortalized Human Corneal Epithelial Cells, but They Do Not Destabilize Lipid Membranes.

PURPOSE: Most pure glaucoma drugs (pGDs) are hydrophobic substances intended to reduce elevated intraocular pressure. The aims of our study were to determine the toxicity of pGDs (brimonidine tartrate, brinzolamide, latanoprost, timolol maleate, and pilocarpine hydrochloride) on ocular surface cells and to establish whether their toxicity is subsequent to cellular membrane destabilization. METHODS: The toxicity of clinically efficient doses of pGDs was measured at different time points in a cell culture of human corneal epithelial cells using a redox indicator. pGD interaction with the plasma membrane was analyzed using a hemolysis assay and liposome electrokinetic chromatography. The capacity of pGDs to induce endoplasmic reticulum stress was investigated by immunoblotting. RESULTS: The toxicity assay showed that all pGDs decrease the viability of the epithelial cells to variable degrees. Early toxicity was measured for 4% pilocarpine and 0.15% brimonidine with 60% cell death at 4 hours, whereas 2% pilocarpine and 0.005% latanoprost showed almost 100% toxicity but only after 16 hours. The hemolysis assay and liposome electrokinetic chromatography experiments suggested that interaction between pGDs and lipid membranes is weak and cannot explain cell death through lysis. Immunoblotting revealed that the drugs activate endoplasmic reticulum stress and, with the exception of pilocarpine, have the capacity to induce apoptosis through upregulation of C/EBP homologous protein. CONCLUSIONS: Our study indicates that all studied pGDs decrease the viability of the corneal epithelial cells, but none of the tested compounds were able to destabilize cellular membranes. The pGDs seem to be internalized and can induce apoptosis through C/EBP homologous protein recruitment.