Stroke: Molecular mechanisms and therapies: Update on recent developments.

Stroke, a neurological disease, is one of the leading causes of death worldwide, resulting in long-term disability in most survivors. Annual stroke costs in the United States alone were estimated at $46 billion recently. Stroke pathophysiology is complex, involving multiple causal factors, among which atherosclerosis, thrombus, and embolus are prevalent. The molecular mechanisms involved in the pathophysiology are essential to understanding targeted drug development. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress, and neuroinflammation. In addition, various modifiable and non-modifiable risk factors increase the chances of stroke manifolds. Once a patient encounters a stroke, complete restoration of motor ability and cognitive skills is often rare. Therefore, shaping therapeutic strategies is paramount for finding a viable therapeutic agent. Apart from tPA, an FDA-approved therapy that is applied in most stroke cases, many other therapeutic strategies have been met with limited success. Stroke therapies often involve a combination of multiple strategies to restore the patient's normal function. Certain drugs like Gamma-aminobutyric receptor agonists (GABA), Glutamate Receptor inhibitors, Sodium, and Calcium channel blockers, and fibrinogen-depleting agents have shown promise in stroke treatment. Recently, a drug, DM199, a recombinant (synthetic) form of a naturally occurring protein called human tissue kallikrein-1 (KLK1), has shown great potential in treating stroke with fewer side effects. Furthermore, DM199 has been found to overcome the limitations presented when using tPA and/or mechanical thrombectomy. Cell-based therapies like Neural Stem Cells, Hematopoietic stem cells (HSCs), and Human umbilical cord blood-derived mesenchymal stem cells (HUCB-MSCs) are also being explored as a treatment of choice for stroke. These therapeutic agents come with merits and demerits, but continuous research and efforts are being made to develop the best therapeutic strategies to minimize the damage post-stroke and restore complete neurological function in stroke patients.

Intravenous Physical Compatibility of Heparin Sodium and Furosemide.

Continuous infusions of heparin and furosemide are often required for hospitalized patients to treat cardiac-related disease states. Concomitant infusion of heparin and furosemide through the same intravenous line minimizes the need for multiple intravenous sites. For concomitant infusions to be administered, knowledge of the physical compatibility for intravenous medications is imperative for patient safety and administering medications to maximize their effectiveness. Currently, heparin and furosemide are listed as Y-site compatible, but precipitation was reported at a large academic medical center, which questions this compatibility. This study investigated the in vitro physical compatibility of heparin sodium premix 25,000 units/250 mL in dextrose 5% water from two different manufacturers with furosemide 40 mg/4 mL at concentrations of 4:1 for heparin sodium and furosemide. The admixtures were prepared in triplicate using aseptic technique, stored at 19°C to 24°C and examined for visual precipitation, turbidity, and pH change at baseline, 1, 5, 8, 24, and 48 hours. Heparin sodium, B. Braun Medical Inc. or Hospira, Inc. solutions, and furosemide admixtures revealed changes over 48 hours. Changes in visual appearance, absorbance, and pH were observed at hour 5 compared to baseline for the B. Braun Medical Inc. admixture. The Hospira, Inc. admixture revealed visual changes by hour 48, but demonstrative changes in absorbance and pH did not occur. Our observations found demonstrative changes in physical compatibility in the admixtures of heparin sodium and furosemide at a ratio of 4:1. The findings suggest that a combination of the solutions in this study be avoided until further research is completed.

Meadowfoam seed oil as a natural dispersing agent for colorants in lipstick.

OBJECTIVE: Green and sustainable trends are growing and with that the demand for naturally derived ingredients is rising. Dispersing agents are essential components of lipsticks due to their ability to wet pigment particles, reduce agglomerates and prevent re-agglomeration by stabilizing pigment particles. In this study, meadowfoam seed oil was evaluated as a pigment-dispersing agent for lipsticks and compared with castor oil and octyldodecanol. METHODS: Dispersions of Red 7 Lake were formulated with 20, 30 and 40% solid content using castor oil, octyldodecanol or meadowfoam seed oil. Particle size, viscosity, spreadability, wetting, oil absorption and colour were measured. Four of the nine dispersions were then formulated into lipsticks, including all the 30% pigment dispersions and the 40% dispersion with meadowfoam seed oil. Lipsticks were tested for hardness, pay-off, friction, rheology, colour and stability for 4 weeks. RESULTS: Average particle size was between 6 and 9 µm across the dispersions. The castor oil dispersions were more viscous, stickier and harder to spread than the other dispersions. The wetting contact angle was very low for all three dispersing agents, indicating that all of the oils wet the pigment well. The lipsticks varied in hardness, as expected, based on differences in the viscosity of the dispersing agents, and oil absorption of the powder. Red 7 Lake absorbed the highest amount of castor oil, which contributed to higher stick hardness. The castor oil lipstick and the meadowfoam seed oil lipstick containing 40% pigment were the hardest and most elastic. The octyldodecanol lipstick was the softest. Friction was the lowest for the meadowfoam seed oil lipstick containing 40% pigment, while pay-off was the highest for the octyldodecanol lipstick. The colour of the lipsticks as a stick and after being spread on paper was very similar. CONCLUSION: While the chemical composition and physicochemical properties of the dispersing agents were different, all three dispersing agents studied formed dispersions and lipsticks with appropriate characteristics. Meadowfoam seed oil's performance was qualitatively and quantitatively similar to castor oil and octyldodecanol. By modifying the amount of pigment and dispersing agent used, lipsticks that have similar characteristics to commercial products can be formulated.

OBJECTIF: Les tendances écologiques et durables sont en hausse, ainsi que la demande en ingrédients d'origine naturelle. Les agents de dispersion sont des composants essentiels des rouges à lèvres en raison de leur capacité à mouiller les particules pigmentaires, à réduire les agglomérats et à prévenir la réagglomération en stabilisant les particules pigmentaires. Dans cette étude, l'huile de graines de limnanthe a été évaluée en tant qu'agent de dispersion pigmentaire pour les rouges à lèvres et comparée à l'huile de ricin et à l'octyldodécanol. MÉTHODES: Les dispersions de Red 7 Lake ont été formulées avec une teneur solide de 20, 30 et 40 % à l'aide d'huile de ricin, d'octyldodécanol ou d'huile de graines de limnanthe. La taille des particules, la viscosité, la facilité d'étalement, le mouillage, l'absorption de l'huile et la couleur ont été mesurés. Quatre des neuf dispersions ont ensuite été formulées dans des rouges à lèvres, y compris toutes les dispersions pigmentaires à 30 % et la dispersion à 40 % avec l'huile de graines de limnanthe. Les rouges à lèvres ont été testés pour la dureté, le résultat, la friction, la rhéologie, la couleur et la stabilité pendant 4 semaines. RÉSULTATS: La taille moyenne des particules était comprise entre 6 et 9 µm dans les dispersions. Les dispersions d'huile de ricin étaient plus visqueuses, plus collantes et plus difficiles à étaler que les autres dispersions. L'angle de contact de mouillage était très faible pour les trois agents de dispersion, indiquant que toutes les huiles humidifient bien le pigment. La dureté des rouges à lèvres variait, comme attendu, en fonction des différences de viscosité des agents dispersants et de l'absorption de l'huile de la poudre. Red 7 Lake absorbe la plus grande quantité d'huile de ricin, ce qui contribue à une dureté du bâton plus élevée. Le rouge à lèvres à base d'huile de ricin et le rouge à lèvres à base d'huile de graines de limnanthe contenant 40 % de pigment étaient les plus durs et les plus élastiques. Le rouge à lèvres à base d'octyldodécanol était le plus mou. La friction était la plus basse pour le rouge à lèvres à base d'huile de graines de limnanthe contenant 40 % de pigment, tandis que le résultat était le plus élevé pour le rouge à lèvres à base d'octyldodécanol. La couleur des rouges à lèvres en bâton et après avoir été étalés sur du papier était très similaire. CONCULSION: Alors que la composition chimique et les propriétés physicochimiques des agents de dispersion étaient différentes, les trois agents de dispersion étudiés ont tous formé des dispersions et des rouges à lèvres ayant des caractéristiques appropriées. Les performances de l'huile de graines de limnanthe étaient qualitativement et quantitativement similaires à celles de l'huile de ricin et de l'octyldodécanol. En modifiant la quantité de pigment et d'agent dispersant utilisée, des rouges à lèvres ayant des caractéristiques similaires aux produits commerciaux peuvent être formulés.

Blue light protection, part II-Ingredients and performance testing methods.

BACKGROUND: There are numerous cosmetic ingredients that have been identified to have blue light protection benefits. The urge to learn more about blue light protection claims has led to several substantiation test methods that can be utilized by companies to prove product efficacy. AIMS: Part II of this article provides up-to-date information on cosmetic ingredients that can provide protection from blue light, and methods companies can use to substantiate blue light protection claims. METHODS: An Internet search was completed using the Google Scholar database and a cosmetic ingredient supplier database (UL Prospector) for ingredients and relevant literature. RESULTS: Multiple ingredient categories, for example, algae-derived ingredients, UV filters, botanical extracts, antioxidants, and vitamins, are available on the market to fight against blue light-induced skin damage. There is not a formal standardized method to test for blue light protection; however, spectrophotometers, imaging devices, measuring oxidative stress, and visual evaluations are some of the methods being used today. CONCLUSIONS: The number of ingredients launched for blue light protection and new methods developed to test products for blue light protection claims is expected to increase in the near future as we are learning more about the mechanism of damage that occurs in the skin upon blue light exposure.

Blue Light Protection, Part I-Effects of blue light on the skin.

BACKGROUND: Blue light is emitted visible light between the wavelengths of 400 to 500 nm. The main source of blue light is sunlight, but digital screens, light-emitting diodes (LEDs), and fluorescent lighting serve as additional sources. Concerns about the negative effects of blue light on the skin have rapidly increased over the past 15 years, and consequently, the urge to learn more about this topic is increasing as well. AIMS: Part I of this article provides up-to-date information on the definition of blue light and the negative and positive effects of blue light on the skin. METHODS: An Internet search was completed using the Google scholar database for relevant literature. RESULTS: Blue light can be both harmful and beneficial to the skin, depending on intensity and wavelength. Short-term safety information is more readily available from clinical studies; however, the biological effects of repeated and/or longer-term exposure are not fully understood yet. CONCLUSIONS: Low-energy and low exposure times to high-energy blue light can help prevent skin diseases, while studies have revealed that longer exposure to high-energy blue light can increase the amount of DNA damage, cell and tissue death, and injury, eye damage, skin barrier damage, and photoaging.

Evaluation of alkenones, a renewably sourced, plant-derived wax as a structuring agent for lipsticks.

OBJECTIVE: Waxes are used as structuring agents in lipsticks. There are a variety of waxes combined in a single lipstick to provide good stability, pleasant texture and good pay-off. Due to a significant growth for natural, green and sustainable products, there is a constant search for alternatives to animal-derived and petroleum-derived ingredients. In this study, a green, non-animalderived wax, namely long-chain ketones (referred to as alkenones), sourced from marine microalgae was formulated into lipsticks and evaluated as a structuring agent. METHODS: Alkenones were used as a substitute for microcrystalline wax, ozokerite and candelilla wax, typical structuring agents. In total, 384 lipsticks were formulated: L1 (control, no alkenones), L2 (alkenones as a substitute for ozokerite), L3 (alkenones as a substitute for microcrystalline wax) and L4 (alkenones as a substitute for candelilla wax). Products were tested for hardness (bending force), stiffness, firmness (needle penetration), pay-off (using a texture analyser and a consumer panel), friction, melting point and stability for 12 weeks at 25 and 45°C. RESULTS: Alkenones influenced each characteristic evaluated. In general, lipsticks with alkenones (L2-L4) became softer and easier to bend compared to the control (L1). In terms of firmness, lipsticks were similar to the control, except for L4, which was significantly (P < 0.05) firmer. The effect on pay-off was not consistent. L2 and L3 had higher pay-off to skin and fabric than L1. In addition, L4 had the lowest amount transferred, but it still had the highest colour intensity on skin. Alkenones influenced friction (glide) positively; the average friction decreased for L2-L4. The lowest friction (i.e. best glide) was shown in L4. Melting point of the lipsticks was lower when alkenones were present. Overall, L4, containing 7% of 4 alkenones in combination with microcrystalline wax, ozokerite and carnauba wax, was found to have the most desirable attributes, including ease of bending, high level of firmness, low pay-off in terms of amount, high colour intensity on skin and low friction (i.e. better glide). Consumers preferred L4 the most overall. CONCLUSION: Results of this study indicate that alkenones offer a sustainable, non-animal and non-petroleum-derived choice as a structuring agent for lipsticks.

OBJECTIF: Les cires sont utilisées comme agents de structuration dans les rouges à lèvres. Un rouge à lèvres contient plusieurs cires, afin d'obtenir une bonne stabilité, une texture agréable et un bon transfert de matière. En raison d'une croissance significative de la demande en produits naturels, écologiques et durables, les chercheurs s'efforcent constamment de trouver des alternatives aux ingrédients d'origine animale et dérivés du pétrole. Dans cette étude, les cétones à longue chaîne (appelés alkénones), une cire verte qui n'est pas d'origine animale, mais provenant de microalgues marines, a été formulée pour les rouges à lèvres et évaluée comme agent de structuration. MÉTHODES: Les alkénones ont été utilisés comme substitut pour la cire microcristalline, l'ozokérite et la cire de candelilla, des agents de structuration courants. Au total, 384 rouges à lèvres ont été formulés : L1 (contrôle, sans alkénone), L2 (alkénones comme substitut de l'ozokérite), L3 (alkénones comme substitut de la cire microcristalline) et L4 (alkénones comme substitut de la cire de candelilla). Des tests ont été réalisés sur les produits pour évaluer la dureté (force de flexion), la rigidité, la fermeté (pénétration de l'aiguille), le transfert de matière (à l'aide d'un analyseur de texture et d'un panel de consommateurs), la friction, le point de fusion et la stabilité pendant 12 semaines à 25 et 45 °C. RÉSULTATS: Les alkénones ont eu une influence sur chacune des caractéristiques évaluées. En général, les rouges à lèvres contenant des alkénones (L2 à L4) sont devenus plus mous et ont présenté une flexion plus facile que dans le cas du contrôle (L1). En termes de fermeté, les rouges à lèvres étaient similaires au contrôle, à l'exception de L4, qui était significativement (P < 0,05) plus ferme. L'effet sur le transfert de matière a été variable. L2 et L3 ont présenté un transfert de matière sur la peau et le tissu supérieur à celui de L1. En outre, dans le cas de L4, la quantité transférée était la plus faible, mais l'intensité de la couleur sur la peau était toujours la plus élevée. Les alkénones ont eu un effet positif sur la friction (glissement) ; la friction moyenne a diminué pour L2 à L4. La friction la plus basse (c.-à-d. le meilleur glissement) a été observée dans le cas de L4. Le point de fusion des rouges à lèvres était plus bas lorsque des alkénones étaient présents. Dans l'ensemble, L4, contenant 7 % d'alkénones en combinaison avec de la cire microcristalline, de l'ozokérite et de la cire de carnauba, s'est révélée avoir les caractéristiques les plus souhaitables, notamment une facilité de flexion, une fermeté élevée, un faible transfert de matière en termes de quantité, une intensité de couleur élevée sur la peau et une faible friction (c.-à-d. un meilleur glissement). En général, les consommateurs ont préféré L4. CONCLUSION: Les résultats de cette étude indiquent que les alkénones offrent un choix durable, non issu de l'animal et non dérivé du pétrole comme agent de structuration pour les rouges à lèvres.