Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.     

A contribution to the kinetics of the polymerization of styrene with CF3SO3H as catalyst

Summary The time dependence of the cationic polymerization of styrene in CH₂Cl₂ with CF₃SO₃H as catalyst can be formally described as being first-order with respect to monomer concentration [M]₀. The reaction rate shows a third-order dependence in catalyst concentration [C]₀. A high polymer and a low polymer polystyrene fraction are found at [M]₀>0.2 mole · l^–. The reaction rate of the high polymer fraction is proportional to [C] ₀ ³ , that of the low polymer fraction probably proportional to [C] ₀ ² . The polymerization active species may thus be triple ions in the first and ion pairs in the second case.     

Iron, folic acid and vitamin B12 deficiencies related to anemia in adolescents from a region with a high incidence of congenital malformations in Venezuela

Since in recent years for certain age groups, the main cause of anemia is not iron deficiency, we intended to study the effect of iron, folic acid and vitamin B12 deficiencies on anemia prevalence in adolescents from Venezuela. One hundred adolescents aged between 12 and 19 years participated in the study. Each subject was interviewed about antecedents and habits and a physical examination and a 24-hour food recall questionnaire were performed. From a blood sample, hemoglobin and hematocrit concentrations were determined and serum was separated for quantification of ferritin, folic acid and vitamin B12 concentrations. Prevalence of anemia was 78% and for iron, folic acid and vitamin B12 deficiencies were 34.66, 90.9 and 18.18%, respectively. From anemic cases, 35.89% presented iron deficiency, while 91.02% presented folic acid deficiency. Only 19.23% of adolescents with anemia presented also vitamin B12 deficiency, but all the cases with vitamin B12 deficiency, were anemic. Simultaneous iron and folic acid deficiencies affected 30.76% of anemic cases. The high prevalence of deficiencies found in this work could be explained by insufficient intake and inadequate food habits. The prevalence of anemia was associated to folic acid deficiency rather than to iron deficiency, due to the high prevalence of folic acid deficiency. The high prevalence of nutritional deficiencies found in this work, especially regarding folic acid deficiency, require immediate interventions.     

Efficient wavelet-based ECG processing for single-lead FHR extraction

This paper describes a novel model for fetal heart rate (FHR) monitoring from single-lead mother?s abdomen ECG (AECG) measurements. This novel method is divided in two stages: the first step consists on a one-step wavelet-based preprocessing for simultaneous baseline and high-frequency noise suppression, while the second stage efficiently detects fetal QRS complexes allowing FHR monitoring. The presented structure has been simplified as much as possible, in order to reduce computational cost and thus enable possible custom hardware implementations. Moreover, the proposed scheme and its fixed-point modeling have been tested using real abdominal ECG signals, which allow the validation of the presented approach and provide high accuracy.     

Preoperative selection for curable renovascular hypertension

Clinical research has defined the criteria for identifying "curable" renovascular hypertension. The prediction is based on the measurement of plasma renin activity in peripheral veins, renal veins, and the aorta. Renin profiles can be examined with the method of Laragh and coworkers (the so-called incremental method), in which values for plasma renin activity are incorporated into formulas to compute indexed parameters. A score is attributed to each index and the prediction is based on the final score. Because the identification of curable renovascular hypertension is made according to numerical rules, the method is easily transformed into a computer-assisted process. The program is written in BASIC, and it is short enough to run on a personal computer.     

Direct-EI in LC-MS: towards a universal detector for small-molecule applications

This review article will give an up-to-date and exhaustive overview on the efficient use of electron ionization (EI) to couple liquid chromatography and mass spectrometry (LC-MS) with an innovative interface called Direct-EI. EI is based on the gas-phase ionization of the analytes, and it is suitable for many applications in a wide range of LC-amenable compounds. In addition, thanks to its operating principles, it prevents unwelcome matrix effects (ME). In fact, although atmospheric pressure ionization (API) methodologies have boosted the use of LC-MS, the related analytical methods are sometime affected by inaccurate quantitative results, due to unavoidable and unpredictable ME. In addition, API's soft ionization spectra always demand for costly and complex tandem mass spectrometry (MS/MS) instruments, which are essential to acquire an "information-rich" spectrum and to obtain accurate quantitative information. In EI a one-stage analyzer is sufficient for a qualitative investigation and MS/MS detection is only used to improve sensitivity and to cut chemical noise. The technology illustrated here provides a robust and straightforward access to classical, well-characterized EI data for a variety of LC applications, and readily interpretable spectra for a wide range of areas of research. The Direct-EI interface can represent the basis for a forthcoming universal LC-MS detector for small molecules.     

Potential Use of Ascorbic Acid–Based Surfactants as Skin Penetration Enhancers

ABSTRACT

6-O-Ascorbic acid alkanoates (ASCn) are amphiphilic molecules having physical-chemical properties that depend on the alkyl chain length. The derivatives of low molecular weight (n < 11) have enough aqueous solubility to produce self-assemblies at room temperature (≈25°C), while those with longer alkyl chains possess a critical micellar temperature (CMT) higher than 30°C. At higher temperatures (T° > CMT), ASCn aqueous suspensions turn into either micellar solutions or gel phases, depending on the length of the hydrophobic chain. On cooling, coagels are produced, which possess a lamellar structure that exhibit sharp X-ray diffraction patterns and optical birefringence. The semisolid consistency of such coagels is an interesting property to formulate dermatological pharmaceutical dosage forms able to solubilize and stabilize different drugs. The objective of the present study was the evaluation of the enhancing permeation effect of ASCn with different chain lengths and to correlate permeability changes with histological effects. With this purpose, ASCn coagels containing anthralin (antipsoriasic drug) or fluorescein isothiocyanate (FITC, hydrophobic fluorescent marker) were assayed on rat skin (ex vivo) and mice skin (in vivo), respectively. Also, histological studies were performed aimed at detecting some possible side effects of ASCn. No inflammatory cellular response was observed in the skin when ASCn coagels were applied, suggesting non-irritating properties. Light microscopy indicated slight disruption and fragmentation of stratum corneum. The penetration of ASCn through rat skin epidermis was very fast and quantitatively significant. The permeation of anthralin was significantly increased when the drug was vehiculized in ASCn coagels, compared to other pharmaceutical systems. The results indicated that ASC12 seems to have the highest enhancing effect on FITC permeation. ASC12 appears to be the compound that possesses the highest capacity to enhance the penetration of the drugs. Furthermore, it has the highest permeation of the serie.