Synthesis, Spectroscopic Characterization, Structural Studies, and in Vitro Antitumor Activities of Pyridine-3-carbaldehyde Thiosemicarbazone Derivatives

Eight new thiosemicarbazone derivatives, 6-(1-trifluoroethoxy)pyridine-3-carbaldehyde thiosemicarbazone (1), 6-(4'-fluorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (2), 5-chloro-pyridine-3-carbaldehyde thiosemicarbazone (3), 2-chloro-5-bromo-pyridine-3-carbaldehyde thiosemicarbazone (4), 6-(3',4'-dimethoxyphenyl)pyridine-3-carbaldehyde thiosemicarbazone (5), 2-chloro-5-fluor-pyridine-3-carbaldehyde thiosemicarbazone, (6), 5-iodo-pyridine-3-carbaldehyde thiosemicarbazone (7), and 6-(3',5'-dichlorophenyl)pyridine-3-carbaldehyde thiosemicarbazone (8) were synthesized, from the reaction of the corresponding pyridine-3-carbaldehyde with thiosemicarbazide. The synthesized compounds were characterized by ESI-Mass, UV-Vis, IR, and NMR (1H, 13C, 19F) spectroscopic techniques. Molar mass values and spectroscopic data are consistent with the proposed structural formulas. The molecular structure of 7 has been also confirmed by single crystal X-ray diffraction. In the solid state 7 exists in the E conformation about the N2-N3 bond; 7 also presents the E conformation in solution, as evidenced by 1H NMR spectroscopy. The in vitro antitumor activity of the synthesized compounds was studied on six human tumor cell lines: H460 (lung large cell carcinoma), HuTu80 (duodenum adenocarcinoma), DU145 (prostate carcinoma), MCF-7 (breast adenocarcinoma), M-14 (amelanotic melanoma), and HT-29 (colon adenocarcinoma). Furthermore, toxicity studies in 3T3 normal cells were carried out for the prepared compounds. The results were expressed as IC50 and the selectivity index (SI) was calculated. Biological studies revealed that 1 (IC50 = 3.36 to 21.35 µM) displayed the highest antiproliferative activity, as compared to the other tested thiosemicarbazones (IC50 = 40.00 to >582.26 µM) against different types of human tumor cell lines. 1 was found to be about twice as cytotoxic (SI = 1.82) than 5-fluorouracile (5-FU) against the M14 cell line, indicating its efficiency in inhibiting the cell growth even at low concentrations. A slightly less efficient activity was shown by 1 towards the HuTu80 and MCF7 tumor cell lines, as compared to that of 5-FU. Therefore, 1 can be considered as a promising candidate to be used as a pharmacological agent, since it presents significant activity and was found to be more innocuous than the 5-FU anticancer drug against the 3T3 mouse embryo fibroblast cells

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Mixoma auricular izquierdo asociado a insuficiencia severa de válvula mitral en paciente de género femenino de 31 años de edad: reporte de caso Left atrial mixoma associated with severe mitral valve insufficiency in a 31 years old female patient: a case report

Se presenta el caso de una paciente de 31 años de edad, sin antecedentes patológicos, con un mixoma auricular izquierdo de 9 cm x 8 cm, el cual se manifestó clínicamente, de manera súbita, con sintomatología de tipo obstructiva, y cuyo diagnóstico requirió ecocardiografía transtorácica. Se realizó cirugía inmediata, en la que se logró la resección completa del tumor y durante la cual se evidenció insuficiencia de la válvula mitral severa que requirió plastia valvular. Fue dada de alta al sexto día post-quirúrgico.<br>We report the case of a 31 years old female patient without pathological antecedents, with a left atrial mixoma that measured 9 cm x 8 cm. It manifested clinically by sudden cardiac obstructive symptoms and was diagnosed by transthoracic echocardiography. Immediate surgery was performed, achieving complete tumor resection. A severe mitral valve insufficiency that required valvuloplasty was evidenced. The patient was discharged on the sixth day after surgery

Consumo de ácidos grasos trans y riesgo cardiovascular Consumption of trans fatty acids and cardiovascular risk

Los ácidos grasos con configuración trans poco se encuentran en los alimentos de manera natural, sino que se incorporan a éstos como consecuencia de modificaciones principalmente debidas a los procesos industriales de hidrogenación a que se someten los aceites para convertirlos en grasas sólidas. Aún cuando su estructura incluye dobles enlaces, el tipo de configuración permite un comportamiento biológico similar al de los ácidos grasos saturados, con efectos negativos sobre múltiples funciones celulares. La evidencia demuestra que son perjudiciales para la salud, en especial a lo que se refiere a riesgo de enfermedad cardiovascular, razón por la cual es importante disminuir su consumo. Teniendo en consideración la evidencia obtenida de investigaciones sobre las alteraciones del metabolismo producidas por los ácidos grasos trans, es posible plantear una precaución lógica hacia el consumo de dietas ricas en dichos ácidos. Sus efectos deletéreos serían incluso peores en aquellas poblaciones que consumen bajas cantidades de ácidos grasos esenciales. De ahí surge la importancia de iniciar con prontitud políticas sanitarias orientadas a controlar la aterosclerosis en nuestro país. Las mismas deben estar necesariamente sustentadas sobre un conocimiento profundo de las características o condiciones particulares a las que nuestra población se encuentra sometida. Sólo así podrá darse inicio a una intervención efectiva sobre nuestros cuestionados hábitos alimentarios.<br>Trans fatty acids are scarcely found naturally in food; they are incorporated to it as a result of modifications mainly due to hydrogenation industrial processes to which oils are submitted in order to obtain solid fats. Even when its structure includes double bonds, the type of configuration allows a biological behavior similar to that of saturated fatty acids, with negative effects on multiple cellular functions. The evidence shows that they are harmful to health, especially in regard to risk of cardiovascular disease, which is why it is important to reduce its consumption. Given the evidence obtained from research on alterations of metabolism produced by trans fatty acids, it is possible to raise a logical precaution for the consumption of diets rich in these acids. Its deleterious effects would be even worse in those populations that consume low amounts of essential fatty acids. Hence the importance of prompt sanitary policies directed to the control of atherosclerosis in our country. They must be based necessarily on an in-depth knowledge of the characteristics or particular conditions to whiwhich our our population is subjected. Only thus, can initiate an effective intervention questioned about our eating habits

Mixoma auricular izquierdo asociado a insuficiencia severa de válvula mitral en paciente de género femenino de 31 años de edad: reporte de caso

Se presenta el caso de una paciente de 31 años de edad, sin antecedentes patológicos, con un mixoma auricular izquierdo de 9 cm x 8 cm, el cual se manifestó clínicamente, de manera súbita, con sintomatología de tipo obstructiva, y cuyo diagnóstico requirió ecocardiografía transtorácica. Se realizó cirugía inmediata, en la que se logró la resección completa del tumor y durante la cual se evidenció insuficiencia de la válvula mitral severa que requirió plastia valvular. Fue dada de alta al sexto día post-quirúrgico

Colombian guidelines for the diagnosis and treatment of hypertension

La hipertensión arterial es un problema de salud de particular importancia dadas su prevalencia e impacto en la población general. El acercamiento diagnóstico y en especial el tratamiento de la misma, cambian con la aparición de nuevos métodos diagnósticos y nuevos medicamentos, a medida que se reconocen efectos diferentes sobre los órganos blanco, producidos por fármacos de uso corriente. Por la complejidad y la extensión del tema, se hace difícil para muchos médicos tener una idea clara y precisa acerca de la aproximación más recomendable hacia un paciente o situación en particular. Es arduo seguirle la pista a tantas publicaciones que aportan a la resolución de una duda en particular, a veces con resultados contradictorios. Estas guías pretenden ayudar a solucionar esas dificultades.Q4Artículo original187-31