Dizajniranje i optimizacija mikrokapsula artemetera za maskiranje gorkog okusa

The objective of the present investigation was to reduce the bitterness of artemether (ARM). Microparticles were prepared by the coacervation method using Eudragit E 100 (EE) as polymer and sodium hydroxide solution as nonsolvent for the polymer. A 32 full factorial design was used for optimization wherein the amount of drug (A) and polymer (B) were selected as independent variables and the bitterness score, particle size and drug release at pH, 1.2 and 6.8 were selected as dependent variables. Optimization was carried out using the desirability function. The optimized microparticles batch was characterized by FT-IR and DSC. Multiple linear regression analysis revealed that reduced bitterness of ARM can be obtained by controlling the drug release of microparticles at pH 6.8 and increasing the amount of EE. The increase in the amount of polymer leads to reduction in drug release from microparticles at pH > 5 due to its insolubility and thus reduces bitterness. However, the increase in the amount of polymer results in improved dissolution, suggesting improved availability of ARM in stomach. Optimized microparticles prepared using 0.04 g of ARM and 15 mL of 1% m/V solution of EE showed complete bitter taste masking with improved drug release at pH 1.2.Cilja ovog rada je bio maskirati gorki okus artemetera (ARM) mikrokapsuliranjem. Mikročestice su pripravljene metodom koacervacije pomoću Eudragita E 100 (EE) kao polimerne komponente i natrijevog hidroksida u kojem se polimer ne otapa. 32 faktorijalni dizajn upotrebljen je za optimizaciju. Količine ljekovite tvari (A) i polimera (B) izabrane su kao nezavisne varijable, a intenzitet gorkog okusa, veličina čestica i oslobađanje ljekovite tvari pri pH 1,2 i 6,8 izabrane su kao zavisne varijable. Optimizirane mikročestice karakterizirane su pomoću FT-IR i DSC. Multipla linearna regresijska analiza otkrila je da se smanjenje gorčine artemetera može postići kontroliranjem oslobađanja ljekovite tvari pri pH 6,8 i povećanjem količine EE. Povećanje količine polimera dovodi do smanjenja oslobađanja ljekovite tvari pri pH > 5 pa se smanjuje i gorčina. Međutim, povećanje količine polimera povećava topljivost ljekovite tvari, a time potencijalno i njenu raspoložljivost u želucu. U optimiziranim mikročesticama pripravljenim pomoću 0,04 g ARM i 15 mL 1% m/v otopine EE potpuno se maskirao gorki okus, a oslobađanje ljekovite tvari pri pH 1,2 bilo je poboljšano

Anomalous visual experience is linked to perceptual uncertainty and visual imagery vividness

An imbalance between top-down and bottom-up processing on perception (specifically, over-reliance on top-down processing) can lead to anomalous perception, such as illusions. One factor that may be involved in anomalous perception is visual mental imagery, which is the experience of “seeing” with the mind’s eye. There are vast individual differences in self-reported imagery vividness, and more vivid imagery is linked to a more sensory-like experience. We, therefore, hypothesized that susceptibility to anomalous perception is linked to individual imagery vividness. To investigate this, we adopted a paradigm that is known to elicit the perception of faces in pure visual noise (pareidolia). In four experiments, we explored how imagery vividness contributes to this experience under different response instructions and environments. We found strong evidence that people with more vivid imagery were more likely to see faces in the noise, although removing suggestive instructions weakened this relationship. Analyses from the first two experiments led us to explore confidence as another factor in pareidolia proneness. We, therefore, modulated environment noise and added a confidence rating in a novel design. We found strong evidence that pareidolia proneness is correlated with uncertainty about real percepts. Decreasing perceptual ambiguity abolished the relationship between pareidolia proneness and both imagery vividness and confidence. The results cannot be explained by incidental face-like patterns in the noise, individual variations in response bias, perceptual sensitivity, subjective perceptual thresholds, viewing distance, testing environments, motivation, gender, or prosopagnosia. This indicates a critical role of mental imagery vividness and perceptual uncertainty in anomalous perceptual experience. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00426-020-01364-7) contains supplementary material, which is available to authorized users

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

A review of medicinal uses and pharmacological effects of Mentha piperita

214-221Mentha piperita Linn. emend. Huds. is widely used in food, cosmetics and medicines. It has been proven helpful in symptomatic relief of the common cold. It may also decrease symptoms of irritable bowel syndrome and decrease digestive symptoms such as dyspepsia and nausea, although more research is needed. It is used topically as an analgesic and to treat headaches. Though M. piperita is on the FDA’s GRAS (Generally recognized as safe) list but herb has few side effects. The peppermint oil can cause heartburn or perianal irritation, and is contraindicated in patients with bile duct obstruction, gallbladder inflammation and severe liver damage, and caution should be taken in patients with GI reflux. Menthol products should not be used directly under the nose of small children and infants due to the risk of apnoea

Design, synthesis of novel lipids as chemical permeation enhancers and development of nanoparticle system for transdermal drug delivery.

In the present study, we designed and developed novel lipids that include (Z)-1-(Octadec-9-en-1-yl)-pyrrolidine (Cy5T), 1, 1-Di-((Z)-octadec-9-en-1-yl)pyrrolidin-1-ium iodide (Cy5), (Z)-1-(Octadec-9-en-1-yl)-piperidine (Cy6T), and 1, 1-Di-((Z)-octadec-9-en-1-yl) piperidin-1-ium iodide (Cy6) to enhance the transdermal permeation of some selected drugs. Firstly, we evaluated the transdermal permeation efficacies of these lipids as chemical permeation enhancers in vehicle formulations for melatonin, ß-estradiol, caffeine, α-MSH, and spantide using franz diffusion cells. Among them Cy5 lipid was determined to be the most efficient by increasing the transdermal permeation of melatonin, ß-estradiol, caffeine, α-MSH, and spantide by 1.5 to 3.26-fold more at the epidermal layer and 1.3 to 2.5-fold more at the dermal layer, in comparison to either NMP or OA. Hence we developed a nanoparticle system (cy5 lipid ethanol drug nanoparticles) to evaluate any further improvement in the drug penetration. Cy5 lipid formed uniformly sized nanoparticles ranging from 150-200 nm depending on the type of drug. Further, Cy5 based nanoparticle system significantly (p<0.05) increased the permeation of all the drugs in comparison to the lipid solution and standard permeation enhancers. There were about 1.54 to 22-fold more of drug retained in the dermis for the Cy5 based nanoparticles compared to OA/NMP standard enhancers and 3.87 to 66.67-fold more than lipid solution. In addition, epifluorescent microscopic analysis in rhodamine-PE permeation studies confirmed the superior permeation enhancement of LEDs (detection of fluorescence up to skin depth of 340 μm) more than lipid solution, which revealed fluorescence up to skin depth of only 260 μm. In summary the present findings demonstrate that i) cationic lipid with 5 membered amine heterocyclic ring has higher permeating efficacy than the 6 membered amine hertocyclic ring. ii) The nanoparticle system prepared with Cy5 showed significant (p<0.05) increase in the permeation of the drugs than the control penetration enhancers, oleic acid and NMP

Chemoprevention of Skin Cancer with 1,1-Bis (3′-Indolyl)-1-(Aromatic) Methane Analog through Induction of the Orphan Nuclear Receptor, NR4A2 (Nurr1)

<div><p>Background</p><p>The objective of this study was to demonstrate the anti-skin cancer and chemopreventive potential of 1,1-bis(3′-indolyl)-1-(p-chlorophenyl methane) (DIM-D) using an in vitro model.</p><p>Methods</p><p>In vitro cell cytotoxicity and viability assays were carried out in A431 human epidermoid carcinoma cell line and normal human epidermal keratinocytes (NHEK) respectively by crystal violet staining. Apoptosis induction in A431 cells (DIM-D treated) and NHEK cells pretreated with DIM-D (2 hr) prior to UVB irradiation, were assessed. The accumulation of reactive oxygen species (ROS) in DIM-D pretreated NHEK cells (2 hr) prior to UVB exposure was also determined. Immunocytochemistry and western blot analysis was performed to determine cleaved caspase 3 and DNA damage markers in DIM-D treated A431 cells and in DIM-D pretreated NHEK cells prior to UVB irradiation.</p><p>Results</p><p>The IC50 values of DIM-D were 68.7±7.3, 48.3±10.1 and 11.5±3.1 μM whilst for Epigallocatechin gallate (EGCG) were 419.1±8.3, 186.1±5.2 and 56.7±3.1 μM for 24, 48 and 72 hr treatments respectively. DIM-D exhibited a significantly (p<0.05) greater induction of DNA fragmentation in A431 cells compared to EGCG with percent cell death of 38.9. In addition, DIM-D induced higher expression in A431 cells compared to EGCG of cleaved caspase 3 (3.0-fold vs. 2.4-fold changes), Nurr1 (2.7-fold vs. 1.7-fold changes) and NFκB (1.3-fold vs. 1.1-fold changes). DIM-D also exhibited chemopreventive activity in UVB-irradiated NHEK cells by significantly (p<0.05) reducing UVB-induced ROS formation and apoptosis compared to EGCG. Additionally, DIM-D induced expression of Nurr1 but reduced expression of 8-OHdG significantly in UVB-irradiated NHEK cells compared to EGCG and UV only.</p><p>Conclusion</p><p>Our results suggest that DIM-D exhibits Nurr1-dependent transactivation in the induction of apoptosis in A431 cells and it protects NHEK cells against UVB-induced ROS formation and DNA damage.</p></div