[Use of medicinal plants among older people attending a public primary care center]. / Uso de plantas medicinales por adultos mayores en Centros de Atención Primaria de una Comuna de la Región Metropolitana de Chile.

BACKGROUND: The use of medicinal plants is common among a significant part of the elderly population. In addition, at present, the use of medicinal plants has been introduced in Primary Health Care centers, and is becoming increasingly popular, especially in this population. OBJECTIVES: The present study aimed to determine the main medicinal plants consumed by the elderly attending a primary care unit (Puente Alto, Chile), considering main indications for use, preparation, frequency of use, place of obtaining and the possibility of drug interactions. METHODS: Observational, descriptive and cross-sectional study conducted in a primary care unit. The questionnaire on the use of medicinal plants was applied in self-reliant elderly patients. RESULTS: Were interviewed 310 elderly users who attended primary health care centers in Puente Alto (Chile) and met the eligibility criteria. About 83% were women and 17% men. The first 10 most used plants comprise 70% of the total citations and correspond to mint (15.80%), chamomile (7.96%), rue (7.96%), matico (6.98%), plantain (6.85%), boldo (5.99%), lemon balm (5.80%), pennyroyal (5.06%), paico (4.69%), and lemon verbena (2.72%). The reasons for the use of medicinal plants were mainly gastrointestinal, nervous system, dermal, respiratory, metabolic and genitourinary problems. Home-growing was the most cited method and infusion the most popular form of preparation. The main plants mentioned have some possible interaction already described. CONCLUSIONS: The results reinforce the importance of knowing the plant species used by the population and the correct orientation on their rational use, potential benefits, adverse effects and interactions.

Atorvastatin reduces the proadhesive and prothrombotic endothelial cell phenotype induced by cocaine and plasma from cocaine consumers in vitro.

OBJECTIVE: Cocaine consumption is a risk factor for vascular ischemic complications. Although endothelial dysfunction and accelerated atherosclerosis have been observed in cocaine consumers, the mechanisms underlying their pathogenesis are not fully understood. This study aimed at identifying the effects of atorvastatin in relation to a proadhesive and prothrombotic phenotype induced by cocaine and plasma from chronic cocaine users on endothelial cells. APPROACH AND RESULTS: Human umbilical vein endothelial cells were exposed to either cocaine or platelet-free plasma (PFP) from chronic cocaine consumers in the presence or absence of 10 µmol/L of atorvastatin. Atorvastatin significantly reduced the enhanced platelet adhesion that was induced by cocaine and PFP from chronic cocaine consumers, as well as the release of the von Willebrand factor. Atorvastatin also avoided striking alterations on cell monolayer structure triggered by both stimuli and enhanced NO reduction because of cocaine stimulation through disrupting interactions between endothelial nitric oxide synthase (eNOS) and caveolin-1, thus increasing eNOS bioavailability. Cocaine-increased tissue factor-dependent procoagulant activity and reactive oxygen species generation were not counteracted by atorvastatin. Although monocyte chemoattractant protein-1 levels were not significantly higher than controls either under cocaine or PFP stimulation, atorvastatin completely avoided monocyte chemoattractant protein-1 release in both conditions. Platelets stimulated with cocaine or PFP did not express P-selectin, glycoprotein IIb/IIIa, or CD40L and failed to adhere to resting human umbilical vein endothelial cell. CONCLUSIONS: Cocaine and patient plasma equally induced a proadhesive and prothrombotic phenotype in endothelial cells, except for von Willebrand Factor release, which was only induced by PFP from chronic cocaine consumers. Atorvastatin improved endothelial cell function by reducing cocaine-induced and PFP from chronic cocaine consumer-induced effects on platelet adhesion, cell architecture, and NO production.

New NADPH Oxidase 2 Inhibitors Display Potent Activity against Oxidative Stress by Targeting p22phox-p47phox Interactions.

NADPH oxidase (NOX2) is responsible for reactive oxygen species (ROS) production in neutrophils and has been recognized as a key mediator in inflammatory and cardiovascular pathologies. Nevertheless, there is a lack of specific NOX2 pharmacological inhibitors. In medicinal chemistry, heterocyclic compounds are essential scaffolds for drug design, and among them, indole is a very versatile pharmacophore. We tested the hypothesis that indole heteroaryl-acrylonitrile derivatives may serve as NOX2 inhibitors by evaluating the capacity of 19 of these molecules to inhibit NOX2-derived ROS production in human neutrophils (HL-60 cells). Of these compounds, C6 and C14 exhibited concentration-dependent inhibition of NOX2 (IC50~1 µM). These molecules also reduced NOX2-derived oxidative stress in cardiomyocytes and prevented cardiac damage induced by ischemia-reperfusion. Compound C6 significantly reduced the membrane translocation of p47phox, a cytosolic subunit that is required for NOX2 activation. Molecular docking analyses of the binding modes of these molecules with p47phox indicated that C6 and C14 interact with specific residues in the inner part of the groove of p47phox, the binding cavity for p22phox. This combination of methods showed that novel indole heteroaryl acrylonitriles represent interesting lead compounds for developing specific and potent NOX2 inhibitors.

Photophysical characterization of atorvastatin (Lipitor®) ortho-hydroxy metabolite: role of hydroxyl group on the drug photochemistry.

The influence of the phenolic hydroxyl group of ortho-hydroxy atorvastatin metabolite (Ato-OH) on the photochemistry of atorvastatin (Ato) has been evaluated by steady and time-resolved experiments. Direct excitation of Ato and Ato-OH led to phenanthrene-like intermediate formation, being ∼30% for Ato-OH less efficient than that for its parent compound in methanol. Both, Ato and Ato-OH are able to quench benzophenone (E(T)∼69 kcal mol(-1)) and xanthone (E(T)∼74 kcal mol(-1)) triplet excited state with rate constants close to diffusion limit control which suggest energy transfer mechanism is taking place. In fact, lower triplet energies ∼63 kcal mol(-1) and π,π* character, were confirmed by DFT calculations for both compounds. Interestingly, only Ato-OH can act as a hydrogen donor towards triplet benzil excited state (E(T)∼ 54 kcal mol(-1)) due to the presence of the phenolic hydroxyl group. Nevertheless, the presence of this group in Ato-OH does not modify to a significant degree the compound reactivity toward singlet oxygen. The importance of triplet energy transfer in biological systems to form Ato and Ato-OH triplet excited state as well as the hydrogen donor capacity of Ato-OH toward triplet excited state are discussed in the present communication.

Biological evaluation of novel 6-Arylbenzimidazo[1,2-c]quinazoline derivatives as inhibitors of LPS-induced TNF-alpha secretion.

This study describes the effect of novel 6-Arylbenzimidazo[1,2-c]quinazoline derivatives as tumor necrosis factor alpha (TNF-alpha) production inhibitors. The newly synthesized compounds were tested for their in vitro ability to inhibit the lipolysaccharide (LPS) induced TNF-alpha secretion in the human promyelocytic cell line HL-60. The compound 6-Phenyl-benzimidazo[1,2-c]quinazoline, coded as Gl, resulted as the most potent inhibitor and with no significant cytotoxic activity. Thus, 6-Arylbenzimidazo[1,2-c]quinazoline derivatives may have a potential as anti-inflammatory agents.

Uso de plantas medicinales por adultos mayores en Centros de Atención Primaria de una Comuna de la Región Metropolitana de Chile

Background: The use of medicinal plants is common among a significant part of the elderly population. In addition, at present, the use of medicinal plants has been introduced in Primary Health Care centers, and is becoming increasingly popular, especially in this population. Objectives: The present study aimed to determine the main medicinal plants consumed by the elderly attending a primary care unit (Puente Alto, Chile), considering main indications for use, preparation, frequency of use, place of obtaining and the possibility of drug interactions. Methods: Observational, descriptive and cross-sectional study conducted in a primary care unit. The questionnaire on the use of medicinal plants was applied in self-reliant elderly patients. Results: Were interviewed 310 elderly users who attended primary health care centers in Puente Alto (Chile) and met the eligibility criteria. About 83% were women and 17% men. The first 10 most used plants comprise 70% of the total citations and correspond to mint (15.80%), chamomile (7.96%), rue (7.96%), matico (6.98%), plantain (6.85%), boldo (5.99%), lemon balm (5.80%), pennyroyal (5.06%), paico (4.69%), and lemon verbena (2.72%). The reasons for the use of medicinal plants were mainly gastrointestinal, nervous system, dermal, respiratory, metabolic and genitourinary problems. Home-growing was the most cited method and infusion the most popular form of preparation. The main plants mentioned have some possible interaction already described. Conclusions: The results reinforce the importance of knowing the plant species used by the population and the correct orientation on their rational use, potential benefits, adverse effects and interactions.

Nox1-based NADPH oxidase-derived superoxide is required for VSMC activation by advanced glycation end-products.

Vascular diseases are important clinical complications of diabetes. Advanced glycation end-products (AGE) are mediators of vascular dysfunction, but their effects on vascular smooth muscle cell (VSMC) ROS production are unclear. We studied the source and downstream targets of AGE-mediated ROS and reactive nitrogen species production in these cells. Significant increases in superoxide production in AGE-treated VSMC were measured using lucigenin (7650+/-433 vs 4485+/-424 LU/10(6) cells, p<0.001) or coelenterazine (277,907+/-71,295 vs 120,456+/-4140 LU/10(6) cells, p<0.05) and confirmed by ESR spectroscopy. These signals were blocked by the flavin-containing oxidase inhibitor diphenylene iodonium (DPI). AGE-stimulated NF-kappaB activity was abolished by DPI and the superoxide scavenger MnTBAP. AGE differentially regulated VSMC NADPH oxidase catalytic subunits, stimulating the transcription of Nox1 (201+/-12.7%, p<0.0001), while having no effect on Nox4. AGE also increased 3-nitrotyrosine formation, which was inhibited by MnTBAP, DPI, or the NOS inhibitor L-NAME. Regarding the source of NO, AGE stimulated inducible nitric oxide synthase mRNA (1 vs 9.7+/-3.0, p=0.046), which was abolished by a NF-kappaB inhibitor, SOD, catalase, or siRNA against Nox1. This study establishes that AGE activate iNOS in VSMC through a ROS-sensitive, NF-kappaB-dependent mechanism involving ROS generation by a Nox1-based oxidase.

Evaluación de una nueva formulación de compuestos naturales sobre la modificación de los componentes del síndrome metabólico en adultos con sobrepeso

El sobrepeso y la obesidad, condiciones cada vez más frecuentes en Chile y el Mundo, se definen como una enfermedad crónica caracterizada por la acumulación excesiva de grasa corporal que puede ser perjudicial para la salud. El exceso de grasa corporal es el principal factor patogénico para el desarrollo de resistencia a la insulina y síndrome metabólico (SM), este último caracterizado por la agrupación de una serie de anormalidades metabólicas que determinan un mayor riesgo de padecer enfermedades metabólicas y mortalidad cardiovascular. El objetivo de este estudio piloto transversal y observacional fue evaluar una nueva formulación de compuestos naturales, Delphinol®, resveratrol y ácido oleanólico, frente a parámetros asociados al SM en una población joven con exceso de peso, al ingerir durante 22 semanas la nueva formulación. La evaluación fue realizada en base al estado clínico y antropométrico de 20 sujetos voluntarios (ambos sexos, 18 a 30 años e IMC 26 a 42), mediante valoración médica y exámenes de laboratorio clínico para cada componente del SM (obesidad abdominal, triglicéridos, HDL, presión arterial y glicemia en ayunas). De esta manera, se observó que con la ingesta diaria de esta formulación existe una reducción significativa de los niveles de glicemia, índice HOMA-IR, triglicéridos y aumento de HDL-colesterol. Estos resultados preliminares se traducirían en un beneficio sobre el estado de salud de los individuos con sobrepeso y obesidad, lo cual impactaría en reducir los índices de SM y de esta manera enlentecer la progresión hacia enfermedades crónicas como diabetes y dislipidemia, y contribuir también a disminuir el riesgo cardiometabólico asociado.

Overweight and obesity, increasingly frequent conditions in Chile and the world, are defined as chronic diseases characterized by the excessive accumulation of body fat, that can be detrimental to health. Excess body fat is the main pathogenic factor for the development of insulin resistance and metabolic syndrome, the latter characterized by a cluster of metabolic abnormalities that increase risk of metabolic diseases and cardiovascular mortality. The objective of this preliminary cross-sectional, observational study was to evaluate a new formulation of natural compounds, Delphinol®, resveratrol and oleanolic acid, against metabolic syndrome components in a young population with excess weight, through the intake during 22 weeks of the new formulation. The evaluation was carried out based on the clinical and anthropometric status of 20 volunteer subjects (both gender, 18 to 30 years and BMI 26 to 42), medical evaluation and laboratory tests using each metabolic syndrome component (abdominal obesity, triglycerides, HDL, blood pressure y fasting glicaemia). It was observed that with the daily intake of this formulation there was a significant reduction in blood glucose levels, HOMA-IR index, triglycerides and an increase in HDL-cholesterol. These preliminary results would translate into a benefit in the health status of overweight and obese individuals, which would impact on reducing rates of metabolic syndrome. Thus, slowing down the progression of chronic diseases such as diabetes and dyslipidemia, and also contributing to decreasing the associated cardiometabolic risk.

Local mechanical response of cells to the controlled rotation of magnetic nanorods.

The mechanical response of the cytoplasm was investigated by the intracellular implantation of magnetic nanorods and exposure to low-frequency rotatory magnetic fields. Nanorods (Pt-Ni, ∼200 nm diameter) fabricated by electrodeposition in templates of porous alumina with lengths of approximately 2 and 5 µm were inserted into NIH/3T3 fibroblasts and manipulated with a rotational magnetic field. Nanorod rotation was observed only for torques greater than 3.0 × 10(-16) Nm, suggesting a Bingham-type behavior of the cytoplasm. Higher torques produced considerable deformation of the intracellular material. The cell nucleus and cell membrane were significantly deformed by nanorods actuated by 4.5 × 10(-15) Nm torques. Our results demonstrate that nanorods under magnetic fields are an effective tool to mechanically probe the intracellular environment. We envision that our findings may contribute to the noninvasive and direct mechanical characterization of the cytoplasm.

Different cell death mechanisms are induced by a hydrophobic flavin in human tumor cells after visible light irradiation.

Riboflavin (RF) is an endogenous cell component and an efficient photosensitizer that can act by both types I and II photochemical mechanisms. Human tumor cells lines cultured in vitro, were used as model to study the effect of a photosensitizer synthesized from riboflavin, the 2',3',4',5'-riboflavin-tetrabutyrate (RTB), to increase the flavin concentration in the human promyelocytic leukemia cell line HL-60 and the human epithelial cervical cancer cell line HeLa. We demonstrate that this compound, alone or with Trp, has a toxic dose-response effect evidenced by abnormal cell morphology and a decrease in the cell proliferation rate. The mechanism of cell death was investigated and the experimental evidence indicates that it proceeds primarily via apoptosis; however, autophagy cannot be discarded. Nuclear fluorescent staining with Hoechst 33258 and transmission electron microscopy of the cells showed condensed chromatin margination at the nuclear periphery and the formation of apoptotic bodies. Furthermore, Caspase-3 activity was demonstrated in both cell lines. In addition, the characteristic apoptotic DNA ladder was observed in HL-60 cells. On the other hand, a high cytoplasmic vacuolization was observed by electron transmission and confocal microscopy. LysoTraker-red localization in the vacuoles was observed by fluorescence microscopy, and a significant decrease in the number of vacuoles and in the cell proliferation rate diminution was observed when irradiation was performed in the presence of the autophagy inhibitor 3-methyladenine. Considering that both cell death mechanisms have a dual role in the killing of tumor cells in vivo, a harmful effect that does not cause inflammation leading to tumor prophylaxis, we conclude that RTB could have potential clinical applications.

Isoproterenol and angiotensin I-converting enzyme in lung, left ventricle, and plasma during myocardial hypertrophy and fibrosis.

This study investigated whether long-term administration of isoproterenol (ISO) induces differential expression of angiotensin-converting enzyme (ACE) in lung, plasma, and left ventricle (LV) during development of left ventricular hypertrophy (LVH) and myocardial fibrosis. Male Sprague-Dawley rats (n = 7-9 per group) were treated with isoproterenol (ISO) 5 mg/kg per day for 10 days or saline and examined at 1, 15, and 33 days after the last injection. ISO stimulated the development of left ventricular hypertrophy (LVH); relative LV weight (mg LV 100/body weight), LV protein content, and LV beta-myosin heavy chain levels increased at day 1. LVH regressed at days 15 and 33. ISO also increased myocardial fibrosis (assessed by hydroxyproline content and morphometry) at days 15 and 33. There no were changes in arterial blood pressure. Long-term beta-adrenergic stimulation with ISO increased ACE expression in lung, LV, and plasma during development of LVH and myocardial fibrosis. However, time courses were markedly different. ISO stimulated a sustained increase in lung and plasma ACE activities, whereas ISO induced a high LV ACE. Plasma ACE activity paralleled lung ACE activity. LV ACE activity correlated with ACE mRNA levels and paralleled development of LVH. Our data suggest long-term beta-adrenergic stimulation induced a differential temporal expression of LV, lung, and plasma ACE in rat during development of LVH and myocardial fibrosis.

Biological evaluation of novel 6-Arylbenzimidazo [1.2-c] quinazoline derivatives as inhibitors of LPS-induced TNF- alpha secretion

This study describes the effect of novel 6-Arylbenzimidazo [1,2-c] quinazoline derivatives as tumor necrosis factor alpha (TNF-á) production inhibitors. The newly synthesized compounds were tested for their in vitro ability to inhibit the lipolysaccharide (LPS) induced TNF-á secretion in the human promyelocytic cell line HL-60. The compound 6-Phenyl-benzimidazo [1,2-c] quinazoline, coded as Gl, resulted as the most potent inhibitor and with no significant cytotoxic activity. Thus, 6-Arylbenzimidazo [1,2-c] quinazoline derivatives may have a potential as anti-inflammatory agents.

Expresión génica del sistema renina-angiotensina en cardiomiocitos ventriculares de rata adulta / Genic expression of renin-angiotensin system in ventricular cardiomyocites in adult rats

Se ha postulado la existencia de un sistema renina-angiotensina (SRA) intracardíaco funcional que explica las acciones tróficas de la angiotensia II (AII) sobre las distintas poblaciones celulares, así como la acción preventiva y regresiva de distintos fármacos en la hipertrofia ventricular hipertensiva o secundaria al infarto del miocardio. En este estudio hemos determinado la expresión génica de los componentes del SRA en cardiomiocitos ventriculares de corazón de rata adulta, aislados por perfusión retrógrada con proteasas. La expresión de los RNA mensajeros (mRNA) para angiotensinógeno, renina, enzima convertidora (ECA) y receptor subtipo AT-1 para AII (AT-1R), se evaluó a través de la técnica de transcripción reversa asociada a la reacción en cadena de la DNA polimerasa (RT-PCR), usando oligonucleótidos partidores específicos. El procedimiento de aislamiento celular permitió obtener una población enriquecida de cardiomicitos ventriculares viables (> 95 por ciento), los cuales presentaron actividad contráctil espontánea e inmunorreactividad a anticuerpos dirigidos a proteínas específicas del cardiomiocito. En estas células y en tejidos controles (hígado, riñón y pulmón) se detectaron los mRNA para angiotensinógeno, renina, ECA y AT-1R. Se concluye que los cardiomiocitos ventriculares de rata expresan todos los genes esenciales del SRA,confirmando la existencia de este sistema intracardíaco. Igualmente, la implementación de estas metodologías permitirán estudiar in vitro la regulación del SRA local bajo condiciones fisiológicas y patológicas

Disminución de receptores cardíacos para el factor de crecimiento análogo a la insulina tipo I en la hipertrofia ventricular hipertensiva experimental / Decrease of type I insulin-like growth factor cardiac receptors of the hypertensive experimental ventricular hypertrophy

La hipertrofia ventricular es una respuesta celular a la sobrecarga de presión. Se ha sugerido que el factor de crecimiento análogo a la insulina, tipo I (IGF-I), un polipéptido con mecánismo de acción paracrino y/o endocrino, puede participar como estímulo para el crecimiento celular cardiaco. Usando RIA determinamos los niveles séricos de IGF-I en ratas hipertensas por el mecánismo de Goldblatt de 2 riñones-1 clamp, 9 semanas después de la operación. La hipertrofia ventricular fue evaluada por peso ventricular en relación a peso corporal y por la relación de peso del ventrículo izquierdo al ventrículo derecho. El número de receptores cardiacos de IGF-I de alta afinidad fue determinado por la unión de 125-I IGF-I a las membranas ventriculares a las 3, 6 y 9 semanas siguientes a la cirugía. En relación a los controles, se observó una significativa (p< 0,05) hipertensión sistólica en cada punto: 184 vs 136, 196 vs 131 y 197 vs 136 mmHg, respectivamente. Se documentó hipertrofia ventricular izquierda (relación de peso con VD): 4,8 vs 3,7, 4,6 vs 3,6 y 4,4 vs 3,7. El número de receptores de IGF-I (fmol/mg protein) en los mismos periodos fue 1,6 vs 4,1, 2,3 vs 7,5 y no detectable vs 3,0. Los niveles séricos de IGF-I fueron determinados sólo a las 9 semanas y fueron similares en los animales tratados que en los controles (452 vs 469). Los errores estándar de todos los valores dados fueron menores de 5 por ciento del promedio. La progresiva disminución de los receptores cardiacos de IGF-I puede reflejar un aumento de los niveles tisulares de IGF-I, más aún cuando el nivel sérico de IGF-I no difirió entre los animales tratados y los controles

Mecanismos moleculares en la remodelación cardíaca patológica por estrés mecánico experimental / Molecular mechanisms on the pathological cardiac remodeling induced by mechanical stress

Recientes estudios han establecido que las fuerzas mecánicas producen efectos importantes en la estructura y función de los distintos tipos celulares del sistema cardiovascular. El estrés mecánico no sólo afecta las propiedades mecánicas de los cardiomiocitos sino que también a la homeostasis de otras células cardíacas y a la composición y estructura de la matriz extracelular. La estimulación mecánica crónica, clínicamente representada por la hípertensión arterial, produce el desarrollo de hipertrofia y fibrosis, procesos celulares centrales de la remodelación cardíaca patológica, ya sea en forma directa o a través de la liberación y/o producción de diversas substancias neuroendocrinas y factores de crecimiento locales. Aunque no se han identificado y caracterizado del todo aquellos elementos que sensan y transducen molecularmente dichos cambios mecánicos, en esta revisión se recopilan los últimos avances en la mecanotransducción cardíaca y su relación con el proceso de remodelación cardíaca patológica, los cuales abren nuevas expectivas farmacoterapéuticas