The Autoxidized Mixture of (-)-Epicatechin Contains Procyanidins and Shows Antiproliferative and Apoptotic Activity in Breast Cancer Cells.

For this study, procyanidins generated through the autoxidation of (-)-epicatechin (Flavan-3-ol) under mildly acidic conditions (pH = 6.0) were characterized with ultra high-performance liquid chromatography (UHPLC) coupled with tandem mass spectrometry (MS/MS). Two procyanidins (types A and B) and a mix of oligomers were generated through the autoxidation of (-)-epicatechin. The antiproliferative activity of this mixture of procyanidins on MDA-MB-231, MDA-MB-436, and MCF-7 breast cancer cells was evaluated. The results indicate that the procyanidin mixture inhibited the proliferation of breast cancer cells, where the activity of the procyanidin mixture was stronger than that of (-)-epicatechin. Moreover, the mechanism underlying the antiproliferative activity of procyanidins was investigated. The resulting data demonstrate that the procyanidins induced apoptotic cell death in a manner selective to cancerous cells. In particular, they caused the activation of intrinsic and extrinsic apoptotic pathways in the breast cancer cells. The findings obtained in this study demonstrate that the generation of procyanidins in vitro by the autoxidation of (-)-epicatechin has potential for the development of anti-breast cancer agents.

Anticancer Activity of Sargassum fluitans Extracts in Different Cancer Cells.

BACKGROUND: The arrival of large quantities of Sargassum in the Mexican Caribbean Sea has generated major environmental, health and economic problems. Although Sargassum has been used in the generation of some commercial products, few studies have described its possible applications as a source of compounds with anticancer activity. OBJECTIVE: This study aimed to evaluate the antiproliferative effects of different Sargassum extracts on various cancer cell lines. Furthermore, LC/QTOF-MS was used to identify the compounds related to the antiproliferative effect. METHODS: First, determination of the seaweed was performed, and dichloromethane, chloroform and methanol extracts were obtained. The extracts were evaluated for their antiproliferative effects by MTT in breast (MDAMB- 231 and MCF-7), prostate (DU-145), lung (A549) and cervical (SiHa) cancer cell lines. Finally, LC/QTOFMS identified the compounds related to the antiproliferative effect. RESULTS: The authentication showed Sargassum fluitans as the predominant species. The extracts of dichloromethane and chloroform showed an antiproliferative effect. Interestingly, the fractionation of the chloroform extract showed two fractions (FC1 and FC2) with antiproliferative activity in MDA-MB-231, SiHa and A549 cancer cell lines. On the other hand, three fractions of dichloromethane extract (FD1, FD4 and FD5) also showed antiproliferative effects in the MDA-MB-231, MCF-7, SiHa and DU-145 cancer cell lines. Furthermore, LC/QTOF-MS revealed the presence of eight major compounds in FC2. Three compounds with evidence of anticancer activity were identified (D-linalool-3-glucoside, (3R,4S,6E,10Z)-3,4,7,11-tetramethyl-6,10-tridecadienal and alpha-tocotrienol). CONCLUSION: These findings showed that Sargassum fluitans extracts are a possible source of therapeutic agents against cancer and could act as scaffolds for new drug discovery.

Selective TASK-1 Inhibitor with a Defined Structure-Activity Relationship Reduces Cancer Cell Proliferation and Viability.

Chemical structures of selective blockers of TASK channels contain aromatic groups and amide bonds. Using this rationale, we designed and synthesized a series of compounds based on 3-benzamidobenzoic acid. These compounds block TASK-1 channels by binding to the central cavity. The most active compound is 3-benzoylamino-N-(2-ethyl-phenyl)-benzamide or F3, blocking TASK-1 with an IC50 of 148 nM, showing a reduced inhibition of TASK-3 channels and not a significant effect on different K+ channels. We identified putative F3-binding sites in the TASK-1 channel by molecular modeling studies. Mutation of seven residues to A (I118A, L122A, F125A, Q126A, L232A, I235A, and L239A) markedly decreased the F3-induced inhibition of TASK-1 channels, consistent with the molecular modeling predictions. F3 blocks cell proliferation and viability in the MCF-7 cancer cell line but not in TASK-1 knockdown MCF-7 cells, indicating that it is acting in TASK-1 channels. These results indicated that TASK-1 is necessary to drive proliferation in the MCF-7 cancer cell line.

A Direct Interaction between Cyclodextrins and TASK Channels Decreases the Leak Current in Cerebellar Granule Neurons.

Two pore domain potassium channels (K2P) are strongly expressed in the nervous system (CNS), where they play a central role in excitability. These channels give rise to background K+ currents, also known as IKSO (standing-outward potassium current). We detected the expression in primary cultured cerebellar granule neurons (CGNs) of TWIK-1 (K2P1), TASK-1 (K2P3), TASK-3 (K2P9), and TRESK (K2P18) channels by immunocytochemistry and their association with lipid rafts using the specific lipids raft markers flotillin-2 and caveolin-1. At the functional level, methyl-ß-cyclodextrin (MßCD, 5 mM) reduced IKSO currents by ~40% in CGN cells. To dissect out this effect, we heterologously expressed the human TWIK-1, TASK-1, TASK-3, and TRESK channels in HEK-293 cells. MßCD directly blocked TASK-1 and TASK-3 channels and the covalently concatenated heterodimer TASK-1/TASK-3 currents. Conversely, MßCD did not affect TWIK-1- and TRESK-mediated K+ currents. On the other hand, the cholesterol-depleting agent filipin III did not affect TASK-1/TASK-3 channels. Together, the results suggest that neuronal background K+ channels are associated to lipid raft environments whilst the functional activity is independent of the cholesterol membrane organization.

Síndrome de la mano inútil con astereognosia secundaria a un astrocitoma cervical / Useless hand syndrome with astereognosis secondary to a cervical astrocytoma

Resumen El presente caso es un ejemplo del síndrome de la mano inútil de Oppenheim secundario a un astrocitoma cervical alto. La pérdida sensorial propioceptiva y discriminativa suspendida con conservación de la termoalgesia y el tacto crudo en ambas extremidades superiores es secundaria al daño a la entrada de la raíz dorsal y al núcleo cuneiforme. La torpeza y las dificultades para una prensión precisa con la mano se deben al daño del núcleo proprioespinal en las astas dorsales a nivel C3-C4. Este núcleo integra influencias excitadoras descendentes del tracto corticoespinal e interneuronas inhibitorias controladas por los sistemas descendentes y las aferencias de las extremidades anteriores. Probablemente la pérdida de las aferentes cervicales propioceptivas inhibitorias sea la culpable de las dificultades para agarrar con las manos.

The present case is an example of the useless hand syndrome of Oppenheim secondary to a high cervical astrocytoma. The suspended proprioceptive and discriminative sensory loss with conservation of thermoalgesia and crude touch in both upper extremities is secondary to damage to dorsal root entry and cuneate nucleus. The clumsiness and difficulties in precise grasping with the hand are due to damage of the propriospinal nucleus in the dorsal horns at C3-C4 level. This nucleus integrates descending excitatory influences from corticospinal tract and inhibitory interneurons controlled by descending systems and the forelimb afferents. Probably the loss of the inhibitory proprioceptive cervical afferents is the culprit of the difficulties in grasping by the hands.

Apoptosis Induced by (-)-Epicatechin in Human Breast Cancer Cells is Mediated by Reactive Oxygen Species.

(-)-Epicatechin is a phenolic compound with antioxidant activity that is present in natural food and drinks, such as cocoa and red wine. Evidence suggests that (-)-epicatechin exhibits anticancer activity; however, its mechanism of action is poorly understood. Here, we investigated the anticancer effects of (-)-epicatechin and its mechanism of action in breast cancer cells. We assessed the anticancer activity by cell proliferation assays, apoptosis by DNA fragmentation and flow cytometry. The expression of proteins associated with apoptosis was analyzed by the human apoptosis array. MitoSOXTM Red and biomarkers of oxidative damage were used to measure the effect of (-)-epicatechin on mitochondrial reactive oxygen species (ROS) and cellular damage, respectively. (-)-Epicatechin treatment caused a decreasing in the viability of MDA-MB-231 and MCF-7 cells. This cell death was associated with DNA fragmentation and an apoptotic proteomic profile. Further, (-)-epicatechin in MDA-MB-231 cells upregulated death receptor (DR4/DR5), increased the ROS production, and modulated pro-apoptotic proteins. In MCF-7 cells, (-)-epicatechin did not involve death receptor; however, an increase in ROS and the upregulation of pro-apoptotic proteins (Bad and Bax) were observed. These changes were associated with the apoptosis activation through the intrinsic pathway. In conclusion, this study shows that (-)-epicatechin has anticancer activity in breast cancer cells and provides novel insight into the molecular mechanism of (-)-epicatechin to induce apoptosis.

Trastornos prolongados de conciencia postinjuria cerebral aguda / Prolonged disorders of consciousness after an acute brain injury

Only a fraction of patients in coma secondary to a primary acute brain injury develop a vegetative state (VS). At least 20% of patients show late transitions to a minimally conscious states (MCS). They are particularly common in young adults with traumatic brain injury. The main problems faced by clinicians are the diagnostic accuracy of VS and MCS as well as the usefulness of sophisticated paraclinical investigations. Specific therapies are of limited effectiveness. This population is vulnerable to misdiagnosis and limited access to medical care and rehabilitation, thus generating ethical problems.

[Prolonged disorders of consciousness after an acute brain injury]. / Trastornos prolongados de conciencia postinjuria cerebral aguda.

Only a fraction of patients in coma secondary to a primary acute brain injury develop a vegetative state (VS). At least 20% of patients show late transitions to a minimally conscious states (MCS). They are particularly common in young adults with traumatic brain injury. The main problems faced by clinicians are the diagnostic accuracy of VS and MCS as well as the usefulness of sophisticated paraclinical investigations. Specific therapies are of limited effectiveness. This population is vulnerable to misdiagnosis and limited access to medical care and rehabilitation, thus generating ethical problems.

Latin American algorithm for treatment of relapsing-remitting multiple sclerosis using disease-modifying agents.

OBJECTIVE: It is estimated that circa 50,000 individuals have relapsing-remitting multiple sclerosis in Latin America. European and North-American algorithms for the treatment of multiple sclerosis do not foresee our regional difficulties and the access of patients to treatment. METHODS: The Latin American Multiple Sclerosis Forum is an independent and supra-institutional group of experts that has assessed the latest scientific evidence regarding efficacy and safety of disease-modifying treatments. Accesses to treatment and pharmacovigilance programs for each of the eight countries represented at the Forum were also analyzed. RESULTS: A specific set of guidelines based upon evidence-based recommendations was designed for Latin America. Future perspectives of multiple sclerosis treatment were also discussed. CONCLUSIONS: The present paper translated an effort from representatives of eight countries discussing a matter that cannot be adapted to our region directly from purely European and North-American guidelines for treatment.

Latin American algorithm for treatment of relapsing-remitting multiple sclerosis using disease-modifying agents / Algoritmo latino-americano para tratamento da esclerose múltipla remitente-recorrente utilizando drogas modificadoras da doença

OBJECTIVE: It is estimated that circa 50,000 individuals have relapsing-remitting multiple sclerosis in Latin America. European and North-American algorithms for the treatment of multiple sclerosis do not foresee our regional difficulties and the access of patients to treatment. METHODS: The Latin American Multiple Sclerosis Forum is an independent and supra-institutional group of experts that has assessed the latest scientific evidence regarding efficacy and safety of disease-modifying treatments. Accesses to treatment and pharmacovigilance programs for each of the eight countries represented at the Forum were also analyzed. RESULTS: A specific set of guidelines based upon evidence-based recommendations was designed for Latin America. Future perspectives of multiple sclerosis treatment were also discussed. CONCLUSIONS: The present paper translated an effort from representatives of eight countries discussing a matter that cannot be adapted to our region directly from purely European and North-American guidelines for treatment.

OBJETIVO: Estima-se que haja aproximadamente 50.000 pessoas com a forma remitente-recorrente da esclerose múltipla na América Latina. Os algoritmos de tratamento norte-americanos e europeus não levam em consideração nossas peculiaridades regionais, nem a dificuldade no acesso ao tratamento por parte dos pacientes. MÉTODOS: O Fórum Latino-americano de Esclerose Múltipla é um grupo de especialistas independente e suprainstitucional, que avaliou as mais recentes evidências científicas sobre a eficácia e a segurança das drogas modificadoras do curso da doença. Foram avaliados também o acesso ao tratamento e os programas de farmacovigilância de cada um dos oito países representados no Fórum. RESULTADOS: Uma lista específica de recomendações baseadas em evidências científicas foi estabelecida para a América Latina. Também foram discutidas perspectivas de futuros tratamentos para esclerose múltipla. CONCLUSÕES: O presente estudo representou um esforço dos representantes de oito países latino-americanos em discutir um assunto que não pode ser adaptado para uso em nossa região diretamente a partir de recomendações de tratamento europeias ou norte-americanas.

Hemorragia uterina disfuncional: su comportamiento en la provincia de Villa Clara / Uterine dysfunctional hemorrhage: its behavior in Villa Clara province

La hemorragia uterina disfuncional (HUD) es uno de los problemas ginecológicos más comunes de la adolescencia. En este trabajo se analizó el comportamiento de dicha entidad en 13 pacientes adolescentes, durante cuatro años de evolución en la provincia de Villa Clara. Se analizó la respuesta al tratamiento clínico hormonal, dividiendo a las pacientes en HUD por inmadurez del eje hipot lamo-hipofiso-gonadal (HHG), o por causas orgánicas endocrinas. Tambi,n se estudió la incidencia de los trastornos cualitativos de las plaquetas en las pacientes con HUD. En 7 de 13 pacientes la HUD correspondió a inmadurez del eje HHG; dos de las pacientes con causa orgánica endocrina respondieron a un probable hiperandrogenismo funcional, y 2 de 13 presentaron trastornos cualitativos de plaquetas (TCP). El tratamiento hormonal cíclico con progesterona es útil para suprimir la HUD, mientras que el tratamiento con antifibrinolíticos funciona en pacientes con TCP. La causa orgánica endocrina o asociada a ,sta en pacientes con HUD es más probable en quienes recidivan con la menorragia.

Diabetes mellitus insulinodependiente / Insulin dependent diabetes mellitus

Se comentan de forma práctia y actualizada los aspectos concernientes a la diabetes mellitus insulinodependiente o tipo 1, que afecta mayormente a la población infantil y juvenil. Se detallan el concepto, la epidemiología, la etiopatogenia, la fisiopatología, el diagnóstico, el tratamiento y los criterios de buen control de esta entidad, así como las complicaciones más frecuentes de la misma, abordando la conducta terapéutica actual ante la cetoacidosis diabética y la hipoglucemia del diabético.

Síndrome de baja talla / Low size syndrome

En el siguiente trabajo hacemos una revisión del síndrome de baja talla. Se describen diferentes tipos de clasificaciones (etiológicas y diagnósticas). Una forma rápida, eficaz y económica de acceder al diagnóstico utilizando la semiología y algunos complementarios. Se destaca el valor de la radiografía de edad ósea, la velocidad de crecimiento anual para el diagnóstico, y se plantea la conducta ante cada una de las causas y su pronóstico.

Conducta espectativa ante el bocio eutiroideo puberal / Spectative conduct before the puberal euthyroid goiter

Se siguió espectativamente a 25 niños con bocio eutiroideo en época puberal (23 hembras y 5 varones), mediante la realización de un estudio clínico bioquímico (TSH) semestral durante 1 año, con el objetivo de valorar la eficacia de esta conducta. No se encontraron afectaciones de la talla y la progresión de los estadios puberales de Tanner en estos pacientes sin tratamiento medicamentoso. No existió variación en tamaño del bocio, ni en el valor de la TSH que siempre fue bajo (<20 Mu/L) en los pacientes que no hicieron hipotiroidismo. En el seguimiento se detecto hipotiroidismo subclínico en 3 pacientes, lo cual sugiere que esta conducta sea útil, por cuanto permite captar el hipotiroidismo subclínico cuando la TSH sea mayor e igual 10 Mu/L y así comenzar tratamiento en estos pacientes, evitando un tratamiento innecesario y prolongado con hormonas tiroideas a todo paciente con bocio eutiroideo

Epilepsia mioclónica juvenil: consideraciones clínicas y electroencefalográficas / Juvenile myoclonic epilepsy clinical and electroencephalographic considerations

Se describen 21 pacientes adultos con Epilepsia Mioclónica Juvenil (EMJ) sin diagnóstico previo del síndrome. Todos los pacientes tenían crisis mioclónicas del despertar (MD), 20 (95%) tenían convulsiones tónico-clónicas generalizadas (TCG) y 5 (23%) tenían ausencias (AU). El promedio de edad de comienzo de los distintos tipos de crisis convulsivas fue el siguiente: 15,5 años para la MD y 14 años para la crisis TCG y AU. El examen neurológico fue normal en todos los pacientes y el nivel de inteligencia fue considerado como normal en 18. Doce pacientes comunicaron la ocurrencia de convulsiones generalizadas entre sus familiares. 16 pacientes (76%) presentaron complejos de poliespiga-onda lenta de más de 3,5 Hz. en los electroencefalogramas. La monoterapia con ácido valproico logró controlar todos los tipos de crisis en los 18 pacientes tratados con la droga

Infarto agudo del miocardio: comportamiento de la fase aguda en la unidad de terapia intensiva / Acute myocardium infarct: behavior of the acute phase in an Intensive therapy unit

Se presentan los resultados de 3 años de trabajo en la Unidad de Terapia Intensiva (UTI), Sección de Coronarios de nuestro Hospital. Se estudian 629 pacientes ingresados por infarto agudo del miocardio. La mortalidad fue de un 17,48 porciento y sufre una grave limitante en su descenso, debido al fallo de bomba y a las complicaciones mecánicas. Se comparan resultados con periodos anteriores y con otras unidades del país

Hemicorea secundario a cavernoma del nucleo caudado / Hemichorea secondary to a caudate cavernoma

Se presenta un paciente con hemicorea derecho secundario a un cavernoma del núcleo caudado izquierdo. Esta es la primera comunicación en la literatura de tal asociación. Se plantea una breve discusión de aspectos clínicos, diagnósticos e histopatológicos

Conducta interictal en epilepsia psicomotora / Interictal behavior in psychomotor epilepsy

Ha sido comunicado por Bear y Fedio que el análisis de una serie de rasgos de personalidad inter-ictal es capaz de diferenciar pacientes con epilepsia del lóbulo temporal de controles no epilépticos. Siguiendo una metodología similar hemos aplicado esta escala a 24 sujetos controless sanos, 23 sujetos con epilepsia Grand mal, 30 sujetos con epilepsia del lóbulo temporal y 25 pacientes con diagnóstico de enfermedad psiquiátrica menor. La aplicación de la escala de Bear y Fedio con un análisis de varianza mostró diferencia en alguno de los ítems de los 4 grupos un análisis discriminante permitió diferenciar los pacientes de los cuatro grupos. En conclusión, nuestros hallazgos validan la utilización de la escala propuesta por Bear y Fedio para identificar los sujetos de los cuatro grupos estudiados