Multidose Preservative Free Eyedrops by Selective Removal of Benzalkonium Chloride from Ocular Formulations.

PURPOSE: About 70% of eye drops contain benzalkonium chloride (BAK) to maintain sterility. BAK is an effective preservative but it can cause irritation and toxicity. We propose to mitigate ocular toxicity without compromising sterility by incorporating a filter into an eye drop bottle to selectively remove BAK during the process of drop instillation. METHODS: The filter is a packed bed of particles made from poly(2-hydroxyethyl methacrylate) (pHEMA), which is a common ophthalmic material. We showed that pHEMA particle prepared by using ethoxylated trimethylolpropane triacrylate as crosslinker can be incorporated into a modified eyedrop bottle tip to selectively remove the preservative as the formulation is squeezed out of the bottle. Hydraulic permeability of the plug is measured to determine the resistance to eye drop squeezing, and % removal of BAK and drugs are determined. RESULTS: The modified tip has a hydraulic permeability of about 2 Darcy, which allows eyedrops formulations to flow through without excessive resistance. The tip is designed such that the patients can create an eyedrop of solution of 1-10 cP viscosity in 4 s with a nominal pressure. During this short contact time, the packed particles removed nearly 100% of benzalkonium chloride (BAK) from a 15 mL, 0.012% BAK solution but have only minimal impact on the concentration of contained active components. CONCLUSION: Our novel design can eliminate the preservative induced toxicity from eye drops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases like glaucoma and dry eyes.

Hybrid Electrospun Polycaprolactone Mats Consisting of Nanofibers and Microbeads for Extended Release of Dexamethasone.

PURPOSE: We designed electrospun polycaprolactone mats consisting of nanofibers and microbeads for extended delivery of dexamethasone. METHODS: Thin flexible dexamethasone loaded polycaprolactone mats were prepared by electrospinning. The solvents, polymer loading, voltage and tip-to-collector distance were varied to explore the effects on microstructure of the mats. The microstructure was determined by scanning electron microscope imaging; drug transport was measured and modeled, and X-ray diffraction was used to gauge the crystallinity. Drug transport and X-ray diffraction studies were also conducted with a spin cast film for comparison. RESULTS: Thin mats, about 10 µm in thickness, were prepared by electrospinning. By controlling the voltage and tip-to-collector distance, we achieved a hybrid structure comprising of nanorods (nanofibers) and microbeads. The release profiles were fitted to the diffusion equation to obtain the diffusivities in the spheres and the rods. The diffusivity in the electrospun nanofibers was significantly lower compared to the casted films due to increased crystallinity, which was estimated from X-ray diffraction analysis. The electrospun hybrid mats sustained drug release for the desired duration of a month, in spite of the small thickness of about 10 µm. By comparison, a ten-fold thicker cast film sustains release for about the same duration suggesting about 100-fold decrease in diffusivity in the electrospun mats due to increased crystallinity. CONCLUSIONS: Electrospun polycaprolactone mats are optimal for achieving long release durations due to increased crystallinity. Designing a hybrid structure by controlling the electrospinning parameters can be a useful approach to increase the release durations.

Photoprotection and Extended Drug Delivery by UV Blocking Contact Lenses.

PURPOSE: Extended release of photo-unstable drugs from ophthalmic inserts is not useful unless the loaded drug is protected from degradation. Because of the recent interest in extended drug delivery from contact lenses, it is critical to assess whether photo-unstable drugs can be stabilized by loading in lenses. Here, we focus on dexamethasone, which is prone to degradation and has been explored as a candidate for extended release from contact lenses for periods ranging from 10 hours to several days. METHODS: Degradation rates of dexamethasone were measured in phosphate-buffered saline and after loading in contact lenses. The degradation rates were measured in a humidified, constant-temperature (32°C) chamber with controlled UV exposure. Contact lenses with various degrees of UV blocking were used to explore the relationship between degradation rates and UV exposure. It is known that vitamin E absorbs UV radiation; thus, it was loaded into the lenses to explore the feasibility of reducing the degradation rates. RESULTS: About 85% of dexamethasone degraded in 20 hours in non-UV blocking lenses, whereas less than 1% degraded in class 1 UV blocking lenses. Incorporation of vitamin E into the non-UV blocking lenses reduced the fractional degradation to 30%. Degradation rates in phosphate-buffered saline were significantly higher than even in non-UV blocking contact lenses. CONCLUSIONS: The degradation of dexamethasone can be minimized by using a UV blocking contact lens or incorporating vitamin E into a non-UV blocking lens. Vitamin E incorporation has the dual benefits of improving drug stability and release profiles.

Decoupling wing-shape effects of wing-swept angle and aspect ratio on a forward-flying butterfly.

The effect of wing shape on a forward-flying butterfly via decoupled factors of the wing-swept angle and the aspect ratio (AR) was investigated numerically. The wing-shape effect is a major concern in the design of a microaerial vehicle (MAV). In nature, the wing of a butterfly consists of partially overlapping forewing and hindwing; when the forewing sweeps forward or backward relative to the hindwing, the wing-swept angle and the AR of the entire wing simultaneously change. The effects of the wing-swept angle and AR on aerodynamics are coupled. To decouple their effects, we established wing-shape models with varied combinations of the wing-swept angle and AR based on the experimental measurement of two butterfly species (Papilio polytes and Kallima inachus) and developed a numerical simulation for analysis. In each model, the forewing and hindwing overlapped partially, constructing a single wing. Across the models, the wing-swept angle and AR of these single wings varied sequentially. The results show that, through our models, the effects of the wing-swept angle and AR were decoupled; both have distinct flow mechanisms and aerodynamic force trends and are consistent in the two butterfly species. For a fixed AR, a backward-swept wing increases lift and drag because of the enhanced attachment of the leading-edge vortex with increased strength of the wingtip vortex and the spanwise flow. For a fixed wing-swept angle, a small AR wing increases lift and decreases drag because of the large region of low pressure downstream and the wake-capture effect. Coupling these effects, the largest lift-to-drag ratio occurs for a forward-swept wing with the smallest AR. These results indicate that, in a flapping forward flight, sweeping a forewing forward relative to a hindwing is suitable for cruising. The flow mechanisms and decoupled and coupled effects of the wing-swept angle and the AR presented in this paper provide insight into the flight of a butterfly and the design of a MAV.

From Stoner to local moment magnetism in atomically thin Cr2Te3.

The field of two-dimensional (2D) ferromagnetism has been proliferating over the past few years, with ongoing interests in basic science and potential applications in spintronic technology. However, a high-resolution spectroscopic study of the 2D ferromagnet is still lacking due to the small size and air sensitivity of the exfoliated nanoflakes. Here, we report a thickness-dependent ferromagnetism in epitaxially grown Cr2Te3 thin films and investigate the evolution of the underlying electronic structure by synergistic angle-resolved photoemission spectroscopy, scanning tunneling microscopy, x-ray absorption spectroscopy, and first-principle calculations. A conspicuous ferromagnetic transition from Stoner to Heisenberg-type is directly observed in the atomically thin limit, indicating that dimensionality is a powerful tuning knob to manipulate the novel properties of 2D magnetism. Monolayer Cr2Te3 retains robust ferromagnetism, but with a suppressed Curie temperature, due to the drastic drop in the density of states near the Fermi level. Our results establish atomically thin Cr2Te3 as an excellent platform to explore the dual nature of localized and itinerant ferromagnetism in 2D magnets.

Systems biology of meridians, acupoints, and chinese herbs in disease.

Meridians, acupoints, and Chinese herbs are important components of traditional Chinese medicine (TCM). They have been used for disease treatment and prevention and as alternative and complementary therapies. Systems biology integrates omics data, such as transcriptional, proteomic, and metabolomics data, in order to obtain a more global and complete picture of biological activity. To further understand the existence and functions of the three components above, we reviewed relevant research in the systems biology literature and found many recent studies that indicate the value of acupuncture and Chinese herbs. Acupuncture is useful in pain moderation and relieves various symptoms arising from acute spinal cord injury and acute ischemic stroke. Moreover, Chinese herbal extracts have been linked to wound repair, the alleviation of postmenopausal osteoporosis severity, and anti-tumor effects, among others. Different acupoints, variations in treatment duration, and herbal extracts can be used to alleviate various symptoms and conditions and to regulate biological pathways by altering gene and protein expression. Our paper demonstrates how systems biology has helped to establish a platform for investigating the efficacy of TCM in treating different diseases and improving treatment strategies.

Cooperative stability renders protein complex formation more robust and controllable.

Protein complexes are the fundamental units of many biological functions. Despite their many advantages, one major adverse impact of protein complexes is accumulations of unassembled subunits that may disrupt other processes or exert cytotoxic effects. Synthesis of excess subunits can be inhibited via negative feedback control or they can be degraded more efficiently than assembled subunits, with this latter being termed cooperative stability. Whereas controlled synthesis of complex subunits has been investigated extensively, how cooperative stability acts in complex formation remains largely unexplored. To fill this knowledge gap, we have built quantitative models of heteromeric complexes with or without cooperative stability and compared their behaviours in the presence of synthesis rate variations. A system displaying cooperative stability is robust against synthesis rate variations as it retains high dimer/monomer ratios across a broad range of parameter configurations. Moreover, cooperative stability can alleviate the constraint of limited supply of a given subunit and makes complex abundance more responsive to unilateral upregulation of another subunit. We also conducted an in silico experiment to comprehensively characterize and compare four types of circuits that incorporate combinations of negative feedback control and cooperative stability in terms of eight systems characteristics pertaining to optimality, robustness and controllability. Intriguingly, though individual circuits prevailed for distinct characteristics, the system with cooperative stability alone achieved the most balanced performance across all characteristics. Our study provides theoretical justification for the contribution of cooperative stability to natural biological systems and represents a guideline for designing synthetic complex formation systems with desirable characteristics.

Knee-ankle joint line angle: a significant contributor to high-degree knee joint line obliquity in medial opening wedge high tibial osteotomy.

BACKGROUND: Medial opening wedge high tibial osteotomy (MOWHTO) changes the knee joint inclination in the coronal plane, which can be compensated by the ankle joint. Once there is a decompensated knee joint obliquity, it can induce excessive shear force on the articular cartilage. This study aimed to investigate the capacity of the compensation by analyzing the correlation of the knee-ankle joint line angle (KAJA) and the knee joint line obliquity (KJLO). PATIENTS AND METHODS: Ninety-six patients undergoing MOWHTO were included. We measured potential predictors including preoperative or postoperative body mass index (BMI), weight-bearing line (WBL) ratio/correction amount, knee-ankle joint line angle(KAJA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibia angle (MPTA), ankle joint line obliquity (AJLO), mechanical hip-knee-ankle angle (mHKA) and joint line convergence angle (JLCA). The correlations of these predictors and postoperative KJLO were determined using Pearson correlation coefficient. The contribution of significant predictors was further analyzed using multiple linear regression. Finally, the cutoff value of the most contributing factor resulting in decompensated KJLO was derived with receiver operating characteristic (ROC) curve analysis. RESULTS: Preoperative AJLO, JLCA, MPTA, mHKA and KJLO and postoperative KAJA and MPTA correlated with postoperative KJLO. After multiple linear regression, only preoperative AJLO and JLCA and postoperative KAJA still showed significant contribution to postoperative KJLO. Postoperative KAJA made the greatest contribution. The cutoff value of postoperative KAJA was at 9.6° after ROC analysis. The incidence rate of high-grade KJLO was 69.6% when postoperative KAJA exceeded 9.6°. CONCLUSIONS: Postoperative KAJA is a significant contributor to high-grade KJLO after MOWHTO. The incidence was increased at angles greater than 9.6°. The results suggest that KAJA should be carefully assessed during preoperative planning or intraoperative evaluation. Postoperative KAJA < 9.6° can lower the rate of early high-degree KJLO.

A reflective polarizer-free electro-optical switch using dye-doped polymer-stabilized blue phase liquid crystals.

We demonstrate a reflective polarizer-free electro-optical switch using dye-doped polymer-stabilized blue phase liquid crystals (DDPSBP-LC). At the voltage-off state, the dye molecules and liquid crystals form the structure of the double twist cylinders. As a result, the DDPSBP-LC is in dark state due to the combination of Bragg reflection and light absorption. At the voltage-on state, the blue phase structure is unwound locally. The DDPSBP-LC is then in bright state because of the small light absorption only. The applications of such a switch are shutter glass of 3D displays, and electronic papers.

Focal proximal fibular angle: A potential indicator of the tibial mechanical axis in opening-wedge high tibial osteotomy.

BACKGROUND: For opening-wedge high tibial osteotomy, correct alignment is essential for a better prognosis. It is difficult to evaluate the mechanical axis of the lower extremity or tibia using a single fluoroscopic image. This study aimed to discuss the use of focal proximal fibular angle (FPFA), which can be assessed by a single fluoroscopic image, as an intraoperative indicator. METHODS: Eligible for analyses were 111 consecutively treated patients; for the final analyses 96 patients were included. The preoperative and postoperative medial proximal tibial angle (MPTA) and FPFA were measured. The relationship between these two angles, correction amount, weight-bearing line ratio and patient characteristics were analyzed. RESULTS: The preoperative FPFA and MPTA were 96.5 ± 3.8° (mean ± standard deviation, SD) and 84.8 ± 3.0°, while the postoperative FPFA and MPTA were 87.6 ± 4.1° and 94.0 ± 3.5°, respectively. The preoperative and postoperative sums of the MPTA and FPFA were constant. The discrepancy was less than 3° in all knees, less than 2° in 92.7% knees and less than 1° in 68.8% knees. It was not correlated with age, sex, weight-bearing line ratio, or correction amount. CONCLUSION: The study findings confirmed the constancy of the sum of the MPTA and FPFA. The FPFA can be easily evaluated on a single fluoroscopic image of the knee. Use of the FPFA as guidance may simplify the procedure of opening-wedge high tibial osteotomy and approximately predict the tibial mechanical axis.

Coulombically-stabilized oxygen hole polarons enable fully reversible oxygen redox.

Stabilizing high-valent redox couples and exotic electronic states necessitate an understanding of the stabilization mechanism. In oxides, whether they are being considered for energy storage or computing, highly oxidized oxide-anion species rehybridize to form short covalent bonds and are related to significant local structural distortions. In intercalation oxide electrodes for batteries, while such reorganization partially stabilizes oxygen redox, it also gives rise to substantial hysteresis. In this work, we investigate oxygen redox in layered Na2-XMn3O7, a positive electrode material with ordered Mn vacancies. We prove that coulombic interactions between oxidized oxideanions and the interlayer Na vacancies can disfavor rehybridization and stabilize hole polarons on oxygen (O-) at 4.2 V vs. Na/Na+. These coulombic interactions provide thermodynamic energy saving as large as O-O covalent bonding and enable ~ 40 mV voltage hysteresis over multiple electrochemical cycles with negligible voltage fade. Our results establish a complete picture of redox energetics by highlighting the role of coulombic interactions across several atomic distances and suggest avenues to stabilize highly oxidized oxygen for applications in energy storage and beyond.

Unveiling the Mechanisms Ruling the Efficient Hydrogen Evolution Reaction with Mitrofanovite Pt3Te4.

By means of electrocatalytic tests, surface-science techniques and density functional theory, we unveil the physicochemical mechanisms ruling the electrocatalytic activity of recently discovered mitrofanovite (Pt3Te4) mineral. Mitrofanovite represents a very promising electrocatalyst candidate for energy-related applications, with a reduction of costs by 47% compared to pure Pt and superior robustness to CO poisoning. We show that Pt3Te4 is a weak topological metal with the Z2 invariant, exhibiting electrical conductivity (∼4 × 106 S/m) comparable with pure Pt. In hydrogen evolution reaction (HER), the electrode based on bulk Pt3Te4 shows a very small overpotential of 46 mV at 10 mA cm-2 and a Tafel slope of 36-49 mV dec-1 associated with the Volmer-Heyrovsky mechanism. The outstanding ambient stability of Pt3Te4 also provides durability of the electrode and long-term stability of its efficient catalytic performances.

A bistable polarizer-free electro-optical switch using a droplet manipulation on a liquid crystal and polymer composite film.

A bistable, polarizer-free, and reflective electro-optical switch based on a droplet manipulation on a liquid crystal and polymer composite film (LCPCF) is demonstrated. A color droplet on LCPCF can be manipulated by a wettability gradient owning to the distribution of LC directors anchored among the polymer grains on LCPCF. The contrast ratio is around 8:1 in a reflective mode. The potential applications of droplet manipulation are electronic papers and reflective displays.

Interfacial polymerization of a thin film on contact lenses for improving lubricity.

HYPOTHESIS: A large number of contact lens wearers drop out each year due to end of day discomfort, which could possibly be reduced by designing lenses with highly lubricious surfaces. We hypothesize that polymerizing a thin film of dimethyl acrylamide (DMA) on the surface of the lenses will improve lubricity. EXPERIMENTS: The thin film is polymerized by loading a commercial contact lens (1-DAY ACUVUE® TruEye®) with N,N,N',N'-Tetramethylethane-1,2-diamine (TEMED) and soaking it in a solution of DMA and ammonium per sulfate (APS). The two components of the redox couple (APS and TEMED) mix near the surface of the lens due to diffusion and react rapidly to form free radicals. The free radicals lead the polymerization of the DMA monomer near the surface resulting in the formation of the thin hydrogel layer that is attached to the lens matrix through activation of unreacted vinyl groups or possibly through formation of entanglements with the lens polymer. FINDINGS: The thickness of the layer is controlled by the polymerization time which is limited to 30 s to create a layer of DMA only at the surface. The presence of the DMA layer is confirmed through measurements of Fourier-transform infrared spectroscopy (FTIR) spectra in total internal reflection mode. The layer is determined to be about 3-5 µm thick with a water content of about 285%. The presence of the layer significantly improves lubricity as is evident through the qualitative rubbing test and quantitative measurement of the friction coefficient. A preliminary one-week safety study in rabbits show that lens wear does not cause any toxicity.

Angiotensin II activates signal transducer and activators of transcription 3 via Rac1 in atrial myocytes and fibroblasts: implication for the therapeutic effect of statin in atrial structural remodeling.

BACKGROUND: Recently, activation of the local renin-angiotensin system and mitogen-activated protein kinase pathways in atrial myocardium has been found to play an important role in atrial structural remodeling related to atrial fibrillation. Another important mediator of the angiotensin II (Ang II) effect is the Janus kinase/signal transducers and activators of transcription (STAT) pathway, which has never been characterized in the atrium. METHODS AND RESULTS: In cultured atrial myocytes and fibroblasts, Ang II induced tyrosine phosphorylation of STAT3 through a Rac1-dependent mechanism, which was inhibited by dominant-negative Rac1, losartan, and simvastatin. In atrial myocytes, activation of STAT3 by Rac1 was mediated by direct association of Rac1 with STAT3; however, in atrial fibroblasts, it was mediated by an indirect paracrine effect. Constitutively active STAT3 increased protein synthesis, and dominant-negative STAT3 abrogated Ang II-induced protein synthesis in atrial myocytes and fibroblasts. Rats infused long term with Ang II exhibited higher levels of activated Rac1, phospho-STAT3, collagen synthesis, and atrial fibrosis in the atria, all of which were attenuated by oral losartan and simvastatin. In human atrial tissues from patients with atrial fibrillation, Ang II and phospho-STAT3 levels were also elevated. CONCLUSIONS: The Ang II/Rac1/STAT3 pathway is an important signaling pathway in the atrial myocardium to mediate atrial structural remodeling, and losartan and statin may be able to reverse Ang II-induced atrial structural remodeling in atrial fibrillation.

Angiotensin II increases expression of alpha1C subunit of L-type calcium channel through a reactive oxygen species and cAMP response element-binding protein-dependent pathway in HL-1 myocytes.

Angiotensin II (Ang II) is involved in the pathogenesis of atrial fibrillation (AF). L-type calcium channel (LCC) expression is altered in AF remodeling. We investigated whether Ang II modulates LCC current through transcriptional regulation, by using murine atrial HL-1 cells, which have a spontaneous calcium transient, and an in vivo rat model. Ang II increased LCC alpha1C subunit mRNA and protein levels and LCC current density, which resulted in an augmented calcium transient in atrial myocytes. An approximately 2-kb promoter region of LCC alpha1C subunit gene was cloned to the pGL3 luciferase vector. Ang II significantly increased promoter activity in a concentration- and time-dependent manner. Truncation and mutational analysis of the LCC alpha1C subunit gene promoter showed that cAMP response element (CRE) (-1853 to -1845) was an important cis element in Ang II-induced LCC alpha1C subunit gene expression. Transfection of dominant-negative CRE binding protein (CREB) (pCMV-CREBS133A) abolished the Ang II effect. Ang II (1 micromol/L, 2 hours) induced serine 133 phosphorylation of CREB and binding of CREB to CRE and increased LCC alpha1C subunit gene promoter activity through a protein kinase C/NADPH oxidase/reactive oxygen species pathway, which was blocked by the Ang II type 1 receptor blocker losartan and the antioxidant simvastatin. In the rat model, Ang II infusion increased LCC alpha1C subunit expression and serine 133 phosphorylation of CREB, which were attenuated by oral losartan and simvastatin. In summary, Ang II induced LCC alpha1C subunit expression via a protein kinase C-, reactive oxygen species-, and CREB-dependent pathway and was blocked by losartan and simvastatin.

The synergy between RSC, Nap1 and adjacent nucleosome in nucleosome remodeling.

Eukaryotes have evolved a specific strategy to package DNA. The nucleosome is a 147-base-pair DNA segment wrapped around histone core proteins that plays important roles regulating DNA-dependent biosynthesis and gene expression. Chromatin remodeling complexes (RSC, Remodel the Structure of Chromatin) hydrolyze ATP to perturb DNA-histone contacts, leading to nucleosome sliding and ejection. Here, we utilized tethered particle motion (TPM) experiments to investigate the mechanism of RSC-mediated nucleosome remodeling in detail. We observed ATP-dependent RSC-mediated DNA looping and nucleosome ejection along individual mononucleosomes and dinucleosomes. We found that nucleosome assembly protein 1 (Nap1) enhanced RSC-mediated nucleosome ejection in a two-step disassembly manner from dinucleosomes but not from mononucleosomes. Based on this work, we provide an entire reaction scheme for the RSC-mediated nucleosome remodeling process that includes DNA looping, nucleosome ejection, the influence of adjacent nucleosomes, and the coordinated action between Nap1 and RSC.

Renin-angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation.

OBJECTIVES: Local atrial tissue angiotensin II (AngII) level is elevated in atrial fibrillation (AF), but the mechanism is unknown. We hypothesized that atrial myocytes express all components of the renin-angiotensin system (RAS) and investigated whether rapid depolarization alone is sufficient to increase paracrine AngII production by up-regulating RAS component expression. METHODS: In the HL-1 atrial cell line, rapid depolarization was induced by rapid field electrical stimulation (RES) at 1.0 V/cm and 600/min (10 Hz) in atrial HL-1 cells. In a pig model of AF, AF was induced by atrial pacing at 600/min in 10 adult pigs and 10 sham-operated pigs for comparison. RESULTS: In atrial myocytes, RES induced a sustained elevation of intracellular calcium, and up-regulation of angiotensin-converting enzyme (ACE), chymase and angiotensinogen, resulting in increased AngII production. RES-induced AngII production was attenuated by enalapril [ACE inhibitor (ACEI)] and chymostatin (chymase inhibitor). Conditioned medium from RES-stimulated atrial myocytes increased [3H]leucine uptake and atrial natriuretic peptide expression in atrial myocytes, and [3H]proline uptake and collagen type 1 alpha 1 expression in atrial fibroblasts. Both were attenuated by co-incubation with the AngII type 1 receptor blocker (ARB) losartan. In the porcine model, significant structural changes and a similar pattern of changes of RAS components were noted in AF pigs. CONCLUSIONS: Atrial cells expressed all components of RAS and rapid depolarization alone was sufficient to up-regulate RAS components, increase paracrine AngII production and induce atrial structural changes, which are attenuated by ACEI, ARB and chymase inhibitor.

Amiodarone-related pneumonitis.

Amiodarone-related pneumonitis is a potentially limiting factor for amiodarone usage. However, it is believed that amiodarone-related pneumonitis is unlikely to occur during low-dose and short courses of therapy. We report three patients who received low-dose amiodarone, 200 mg/day, for an average of 6.6 months and who developed amiodarone-related pneumonitis. All patients were male with age of 75, 93 and 85, respectively, and had the habit of cigarette smoking. The initial presentation was dyspnea without symptoms and signs of heart failure. Their chest radiographs showed diffuse interstitial pneumonitis pattern and chest computed tomography scan also confirmed interstitial pneumonitis. Treatment included cessation of amiodarone and corticosteroid usage. All patients improved symptomatically by early detection and early treatment. This case report implies that old age and possible pre-existing pulmonary abnormalities caused by smoking could be associated with amiodarone-related pulmonary toxicity. Clinicians must remain alert to detect amiodarone-related pneumonitis even under low dosage and short duration of amiodarone usage. Immediate withdrawal of amiodarone and prompt steroid therapy will ensure full recovery.

Composition, in vitro Anti-inflammatory, Antioxidant and Antimicrobial Activities of the Leaf Essential Oil of Machilus konishii from Taiwan.

The chemical composition and in vitro anti-inflammatory, antioxidant and antimicrobial activities of the leaf essential oil of Machils konishii has been investigated. The essential oil was isolated using hydrodistillation in a Clevenger-type apparatus, and characterized by GC-FID and GC-MS. Sixty-six compounds were identified, representing 100% of the oil. The main components identified were a-pinene (33.9%), α-pinene (13.9%), and thymol (12.0%); The leaf oil was able to reduce nitric oxide production by lipopolysaccharide-activated murine macrophages RAW 264.7 without reducing the cell viability. In addition, the leaf oil showed strong antioxidant and antimicrobial activities. The major ingredient of the oil that was responsible for the anti-inflammatory, antioxidant and antimicrobial activities was thymol.