Authenticity study of commercial samples of St. John's wort by paper spray ionization mass spectrometry and chemometric tools

Hypericum perforatum L. (St. John's wort) is one of the world's most consumed medicinal plants for treating depression and psychiatric disorders. Counterfeiting can occur in the medicinal plant trade, either due to the lack of active ingredients or the addition of substances not mentioned on the labels, often without therapeutic value or even harmful to health. Hence, 43 samples of St. John's wort commercially acquired in different Brazilian regions and other countries were analyzed by paper spray ionization mass spectrometry (PS-MS) and modeled by principal component analysis. Hence, samples (plants, capsules, and tablets) were extracted with ethanol in a solid–liquid extraction. For the first time, PS-MS analysis allowed the detection of counterfeit H. perforatum samples containing active principles typical of other plants, such as Ageratum conyzoides and Senna spectabilis. About 52.3% of the samples were considered adulterated for having at least one of these two species in their composition. Furthermore, out of 35 samples produced in Brazil, only 13 were deemed authentic, having only H. perforatum. Therefore, there is a clear need to improve these drugs' quality control in Brazil.     

A Learning Algorithm for Level Sets Weights in Weighted Level-based Averaging Method

The method which we call the Weighted Averaging Based on Levels (WABL) can be used to calculate the average representative of a fuzzy number. It utilizes weight coefficients for the level sets as well as the sides of a fuzzy number. We have developed an algorithm to obtain these coefficients. The most remarkable feature of this algorithm is that it makes use of the decision maker’s (DM) aggregation strategy.     

Drug design with a new transition state analog of the hydrated carbonyl: silicon-based inhibitors of the HIV protease

BACKGROUND: Silicon is the element most similar to carbon, and bioactive organosilanes have therefore been of longstanding interest. Design of bioactive organosilanes has often involved a systematic replacement of a bioactive molecule's stable carbon atoms with silicon. Silanediols, which are best known as unstable precursors of the robust and ubiquitous silicone polymers, have the potential to mimic an unstable carbon, the hydrated carbonyl. As a bioisostere of the tetrahedral intermediate of amide hydrolysis, a silanediol could act as a transition state analog inhibitor of protease enzymes. RESULTS: Silanediol analogs of a carbinol-based inhibitor of the HIV protease were prepared as single enantiomers, with up to six stereogenic centers. As inhibitors of this aspartic protease, the silanediols were nearly equivalent to both their carbinol analogs and indinavir, a current treatment for AIDS, with low nanomolar K(i) values. IC(90) data from a cell culture assay mirrored the K(i) data, demonstrating that the silanediols can also cross cell membranes and deliver their antiviral effects. CONCLUSIONS: In their first evaluation as inhibitors of an aspartic protease, silanediol peptidomimetics have been found to be nearly as potent as currently available pharmaceutical agents, in enzyme and cell protection assays. These neutral, cell-permeable transition state analogs therefore provide a novel foundation for the design of therapeutic agents.     

Effects of angiotensin II receptor blockers in the coronary arteries of hypertensive rats: Analysis of elemental distribution using LEXRF

Hypertension is one of the major public health problems worldwide. It can cause severely alterations in artery structure and function such as vascular remodeling. Angiotensin II (Ang II) has been linked to vascular dysfunction. It has been shown that blockade of the Ang II type 1 receptor with an Ang II receptor blocker (ARBs) may reverse vascular pathology independently of blood pressure lowering. There is therefore a special interest in establishing whether antihypertensive treatment may correct in part or completely the structural and functional alterations of arteries. Several studies have shown regression of structural remodeling or of functional alterations of small arteries in spontaneously hypertensive rats (SHR) treated with ARBs agents. However, its efficiency was not verified at elemental level in the literature. Knowledge of the elemental distribution in tissues has a great importance in the study of diseases, because chemical imbalance can alter biological functions. Elemental semiquantitative microanalysis in the coronary artery of normotensive, SHRs, and SHRs rats treated with ARBs (losartan and olmesartan) was performed using low energy X-ray fluorescence maps acquired on TwinMic X-ray spectromicroscopy station, located at the Elettra synchrotron radiation facility. Morphological changes in coronary samples were also investigated. The results demonstrate that despite the antihypertensive agents used belong to the same class, their capacities to revert chemical and structural changes in the coronary arteries caused by hypertension are different.     

Temperature evaluation of UF6 and cluster detection in nozzle expansion using low-resolution infrared absorption spectroscopy

6 and mixtures of UF₆ with argon and nitrogen through a bidimensional nozzle was studied using low-resolution infrared spectroscopy in the ν₃ absorption band region. The experiments were carried out in order to calculate the molecular temperature of the beam and also to verify cluster formation in the expansion. The molecular beam temperature evaluation was based on the measurements of the low-resolution bandwidth, which were compared to simulated spectra results. The temperatures were also evaluated using the measured pressure at the end of the nozzle by a pitot tube. In the conditions where no cluster formation was observed the calculated theoretical temperatures using an equilibrium expansion model are in good agreement with the data obtained through the analysis of the experimental spectra and through the pitot tube pressure measurement. Cluster formation was observed for temperatures below about 120 K. In these conditions the infrared spectra showed shoulders in the region above 630 cm^-1 and a shoulder or band between 616 and 600 cm^-1. Received: 5 January 1998/Accepted: 14 May 1998     

How visual representations participate in algebra classes’ mathematical activity

Our aim is to discuss how a visual display introduced in a classroom activity to represent a specific algebraic procedure is transformed, taking a central role and modifying the ongoing activity. To discuss how visualization comes about in this activity, we describe an illustrative example selected from observations carried out in a 9th grade classroom and analyze the class interaction from a cultural-historical perspective. Our analysis illuminates the tensions that emerge from a difference between the teacher’s way of signifying the algebraic procedure and the students’ overuse of a visual display they associate with it, and how these tensions impel changes in the activity. We further discuss some pros and cons of using visual displays in algebra classes, and we argue that it is very important for the teacher to be aware of them in order to realize the benefits of using such displays.     

Aptamers against Cells Overexpressing Glypican 3 from Expanded Genetic Systems Combined with Cell Engineering and Laboratory Evolution

Laboratory in vitro evolution (LIVE) might deliver DNA aptamers that bind proteins expressed on the surface of cells. In this work, we used cell engineering to place glypican 3 (GPC3), a possible marker for liver cancer theranostics, on the surface of a liver cell line. Libraries were then built from a six‐letter genetic alphabet containing the standard nucleobases and two added nucleobases (2‐amino‐8H‐imidazo[1,2‐a][1,3,5]triazin‐4‐one and 6‐amino‐5‐nitropyridin‐2‐one), Watson–Crick complements from an artificially expanded genetic information system (AEGIS). With counterselection against non‐engineered cells, eight AEGIS‐containing aptamers were recovered. Five bound selectively to GPC3‐overexpressing cells. This selection–counterselection scheme had acceptable statistics, notwithstanding the possibility that cells engineered to overexpress GPC3 might also express different off‐target proteins. This is the first example of such a combination.     

Preformulation and formulation development of a bioactive nitroaromatic compound

The N-(butanoyloxyethyl)-4-(chloromethyl)-3-nitrobenzamide (BNB) is a nitroaromatic derivative with significant antitumor activity. Preformulation, forced degradation (distilled water, acid and base hydrolysis, oxidation, and light), and formulation studies were performed to investigate the chemical behavior of the molecule, the physicochemical properties, and the impact of formulation variables. Pharmacokinetic properties for BNB were estimated in silico. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) containing BNB were developed by a hot melt homogenization method for parenteral administration. Degradation studies demonstrated that this compound is sensitive to hydrolysis. BNB was predicted to have a favorable absorption, distribution, metabolism, and excretion profile. The nanocarriers developed were characterized for particle size (PS?=?61 to 85 nm), polydispersity index (PI?<?0.3), zeta potential (ZP?=???22 to ??34 mV), and encapsulation efficiency (EE?=?66 to 90%) and remained stable for 30 days of storage. These studies indicated that BNB (inhibitory concentration (IC₅₀) 21.8 μM) and BNB-loaded NLC (IC₅₀ 33.7 μM) showed moderate cytotoxicity against breast cancer cell line. Blank formulations did not induce cytotoxicity and BNB-loaded SLN was able to potentiate the action of BNB (lC₅₀ 12.4 μM). BNB is a promising antitumor agent and it is possible to modulate its activity based on the particle size of the formulation.