Amapola, lindísima amapola: de los opiáceos y los opioides, utilidad y riesgos / Poppy, beautiful poppy: opiates and opioids, utility and risks

Resumen El opio y sus derivados, y recientemente los opioides, han acompañado a la humanidad desde las civilizaciones más antiguas hasta la actualidad. Sus efectos analgésicos, hipnóticos y placenteros no pasaron desapercibidos para los antiguos, los consideraron de utilidad médica y beneficiosa para el estado de ánimo. Hoy en día no existe otro tipo de medicamentos que puedan tratar el dolor más intenso tan eficientemente como estos potentes analgésicos. Sin embargo, el uso médico y recreativo de los opiáceos y los opioides conlleva riesgos para la salud, como la tolerancia, la hiperalgesia y la adicción. Actualmente, además de ser indiscutiblemente el tratamiento médico más poderoso para mitigar el sufrimiento ocasionado por el dolor, se ha convertido también en un problema de salud pública debido a la alta cantidad de personas con trastorno por uso de opioides y por las muertes ocasionadas por sobredosis. En esta revisión se hará mención de las bondades de los opiáceos y opioides, y también de los efectos no deseados que estos producen.

Abstract Opium and its derivatives, and recently the opioids have accompanied the humankind since the ancient civilizations to the present day. Its analgesic, hypnotic and pleasant effects did not go unnoticed by ancient people, which considered most of these effects of medical utility and noticed that they had remarkable mood benefits. Currently, there are no other kind of drugs that can palliate intense pain as efficiently as these powerful analgesics. However, the medical and recreational use of opiates and opioids may carry health risks such as tolerance, hyperalgesia, and addiction. Nowadays, in addition to being indisputably the most powerful medical treatment to alleviate the suffering caused by pain, it has also become a public health problem due to the high number of people with opioid use disorder that have facilitated deaths caused by opioids overdose. In this review we will discuss the medical benefits of opiates and opioids, as much as the unwanted effects they produce.

Función de la impulsividad en el trastorno por consumo de sustancias / Impulsivity`s role in substance use disorder

Resumen La proporción de usuarios de una sustancia de abuso que desarrolla problemas con su consumo (abuso o dependencia) representa solo una parte de esta población. En México, el 63.8 % de la población consume alcohol, y de ellos, el 15 % desarrolla algún trastorno por consumo de alcohol (TCA). Se ha observado una relación causal entre el trastorno por consumo de sustancias (TCS) y la falta de autocontrol. Es decir, satisfacer necesidades de manera impulsiva, v. gr., consumir una droga sin evaluar las consecuencias. La corteza prefrontal (CPF) es el principal sustrato neuroanatómico del autocontrol y característicamente la CPF alcanza la madurez alrededor de los 30 años, sugieriendo que el autocontrol se alcanza despues de esta edad. Se ha propuesto que todos los grupos etarios que no han consolidado el uso del autocontrol son vulnerables al TCS. Similarmente ocurre con aquellos sujetos que por algún trastorno psiquiátrico tienen como característica una limitada función prefrontal. La CPF coordina una red subcortical cuya interacción depende de distintos sistemas de neurotransmisión, entre ellos, endocanabinoides. En este trabajo se revisó la función de la CPF y del sistema de endocanabinoides (sECB) y su relación con la vulnerabilidad a la adicción y otros trastornos psiquiátricos.

Abstract The proportion of users of a substance of abuse who develop problems with its use (abuse or dependence) represents only a part of this population. In Mexico, 63.8% of the population consumes alcohol and only 15% of them develop an alcohol use disorder (AUD). A causal relation has been observed between substance use disorder (SUD) and the lack of self-control. Which means, satisfying needs in an impulsive way, v.gr. using a drug, without considering the consequences. The prefrontal cortex (PFC) is the main neuroanatomical substrate of self-control and characteristically reaches maturity around the age of 30, suggesting that self-control is reached after this age. We suggest that all age groups that have not consolidated the use of self-control are vulnerable to SUD. The same occurs with those who, due to a psychiatric disorder, have the characteristic of a limited prefrontal function. The PFC coordinates a subcortical network whose interaction depends on different neurotransmission systems among them, the endocannabinoids system (ECBs). In this work we will review the function of the PFC, the ECBs and its relationship with vulnerability to addiction and other psychiatric disorders.

Marihuana: legalización y atención médica / Marihuana: Legalization and Medical Care

Resumen A pesar de que el uso de marihuana se considera ilegal en la mayoría de los países del mundo, es una de las drogas más utilizadas. El 8,6% de la población mexicana, entre 12 y 65 años, ha probado la marihuana alguna vez (2017). Este porcentaje ha aumentado significativamente en los últimos años. Casos fatales asociados con el consumo de cannabis no se documentaron durante mucho tiempo; sin embargo, recientemente se ha informado de muertes causada por un síndrome de hiperémesis de cannabis (CHS) y muerte por automutilación. Si bien se ha documentado que la marihuana sintetiza sustancias activas con potenciales propiedades terapéuticas, en la actualidad, el mayor uso de la marihuana en nuestro país y en el mundo es recreativo. Esta revisión analiza las consecuencias del uso recreativo de marihuana, el contexto social y de salud con respecto a la legalización y los posibles usos terapéuticos de compuestos extraídos de la planta, de acuerdo a estudios reportados en la literatura científica. La contribución que hacemos es alertar sobre el impacto negativo en la salud del uso recreativo de marihuana y la urgencia de favorecer la investigación sobre sus efectos en el cerebro. Asimismo, identificar los principios activos que tengan potencial para el uso terapéutico.

Abstract Despite the fact that the use of marihuana is illegal in most countries of the world, it still is one of the most commonly used drugs worldwide. 8.6% of the Mexican population, between 12-65 years old, has smoked marihuana at least once in their lifetime (2017). There has been a significant increase in the number of consumers in the last few years. Fatal cases associated with cannabis use had not been recognized for a long time, however, lately, deaths due to a cannabis hyperemesis syndrome (CHS) and deaths from self-mutilation have been reported. Although marihuana synthesizes several active substances with potential therapeutic properties, nowadays, the greatest use of marihuana in our country and in the world is recreational. This review discusses the consequences of using marihuana for recreational use, the social and health contexts regarding legalization and potential therapeutic uses of compounds isolated from the plant based on the scientific literature. Our contribution is to warn people about the potential negative impact on the health of recreational use marihuana and the urgency of supporting the research of its effects on the brain. Similarly, we aim to identify the active principles with potential therapeutic use.

Monitorización ambulatoria de presión arterial en escolares con antecedente de prematurez extrema / Ambulatory blood pressure monitoring in school children with a history of extreme prematurity

Resumen: Introducción: Los prematuros extremos tienen mayor incidencia de Hipertensión Arterial (HTA) y riesgo de daño renal, secundario a un menor número de glomérulos con la consiguiente hiperfiltración de los remanentes. Objetivo: Evaluar la prevalencia de cifras tensionales alteradas usando monitorización ambulatoria de presión arterial (MAPA) y marcadores de daño renal en escolares con antecedentes de prematurez extrema. Pacientes y Método: Realización medición aislada de presión arterial, MAPA, y evaluación de función renal en el seguimiento de prematuros extremos de edad escolar. Resultados: Se reclutaron 30 pacientes, obteniéndose mediciones válidas de MAPA en 19 casos, de los cuales nueve (47,4%) presentaron alteraciones, principalmente ausencia de diferencia de presión día noche. No hubo alteraciones de la función renal en ellos. Discusión: Nuestro estudio detectó una alta prevalencia de alteraciones en MAPA en escolares con antecedentes de prematurez extrema, principalmente la ausencia de diferencia de presión día noche, que se relaciona con mayor riesgo de progresión a HTA. Se resalta la importancia de realizar MAPA dentro del estudio en pacien tes con factores de riesgo de desarrollar HTA a fin de detectar en forma precoz alteraciones y realizar un manejo y seguimiento estrecho.

Abstract: Introduction: Extremely premature children have a higher incidence of High Blood Pressure (HBP) and risk of renal damage due to decreased glomerular count with consequent hyperfiltration of the remnants. Objectives: To assess the prevalence of altered blood pressure values in outpatient measurement and ambulatory blood pressure monitoring (ABPM) in preterm infants ≤ 32 weeks and/ or ≤ 1,500 g birth weight between 5 and 7 years of age, as well as the presence of early renal damage markers. Patients and Methods: An isolated measurement of blood pressure, ABPM and laboratory tests (microalbuminuria/creatininuria ratio in an isolated urine sample, serum creatinine, blood urea nitrogen and urinalysis) were performed. Results: 30 patients were recruited, of whom valid measu rements of ABPM were obtained in 19 cases, of which nine (47,4%) presented some abnormalities, principally nocturnal day/night difference or DIP absent. No abnormal laboratory tests were found. Discussion: Our study detected a high prevalence of abnormalities in ABPM principally DIP absence, which has been related to an increased risk of progression to hypertension. The importance of per forming ABPM in the study is emphasized in patients with risk factors for developing hypertension in order to detect early alterations and close management and follow-up.

Dispositivo de apoyo corporal para atención en medicinas complementarias / Body support device for care in complementary medicines

La salud es una necesidad y preocupación básica del ser humano, ya que un estado bienestar físico, psiquico y social le permite desarrollar su máximo potencial. Hoy la búsqueda de salud por parte de la población ha tendido hacia nuevas prácticas preventivas de enfermedad y atención de salud, para poder contrarrestar los efectos nocivos de las presiones de la vida moderna y el estilo de vida asociado a ella. En la actualidad los gobiernos y autoridades buscan formas de atender los requerimientos sanitarios de la población, incentivar conductas preventivas y ofrecer las nuevas terapias que los pacientes exigen. En ese contexto este proyecto busca intervenir. Basados en una estrategia de la Organización Mundial de la Salud OMS, los países miembros se encuentran generando unidades de Medicina Complementaria Alternativa, MCA para dar el servicio, ampliar la cobertura y educar a la población en el autocuidado y la prevención de enfermedades. El objetivo principal de esta investigación es generar desde el Diseño una propuesta de equipamiento para la óptima implementación de estos espacios de terapia en el Sistema de Salud Público, basado en conceptos extraidos de la intersección entre las bases teóricas y el modo operatorio de las MCA, en orden de intervenir espacialmente el box de atención, para procurar un ambiente armónico y coherente con esta experiencia de salud.

Tormenta simpática paroxística como manifestación de daño axonal difuso postraumatismo encefalocraneano / Paroxysmal sympathetic storm as a manifestation of diffuse axonal damage

Presentamos el caso de un hombre de 24 años que, secundario a un accidente de tránsito, presentó un traumatismo encefalocraneano grave con daño axonal difuso. Luego de un mes de evolución en la unidad de cuidados intensivos comenzó a presentar episodios súbitos de hipertensión, taquicardia, diaforesis, hipertermia, descerebración y dilatación pupilar, todo lo anterior con resolución espontánea en el curso de minutos. Estas crisis se repetían varias veces en el día. Se llegó al diagnóstico de un cuadro denominado Tormenta Simpática Paroxística que puede presentarse muy ocasionalmente como consecuencia de una lesión cerebral grave, especialmente el daño axonal postraumático. En este trastorno prima un desbalance simpático/parasimpático, lo que podría deberse a una pérdida del control cortical. El paciente fue tratado con opiáceos y betabloqueo con una respuesta satisfactoria, logrando disminuir significativamente sus episodios de tormentas simpáticas paroxísticas. En suma, nos parece importante comunicar esta experiencia dado la alta prevalencia de pacientes con trauma cerebral en nuestras Unidades de Pacientes Críticos. A pesar de que ni su diagnóstico ni tratamiento mejoran el pronóstico, su reconocimiento ahorra estudios innecesarios y permite iniciar una terapia sencilla que lleva al control precoz de la sintomatología.

A 24-year-old man suffered a traumatic brain injury due to a car accident. After one month of hospitalization in intensive care unit, he experimented episodic crisis of hypertension, tachycardia, hyperhidrosis, hypertermia, extensor posturing and pupil dilatation. This events presented in average 10 times per day. We reached to the diagnosis of Paroxysmal Sympathetic Storm. This is a subtype of dysautonomy which is present occasionally after a brain traumatic injury. The main mechanism of this brain dysfunction is a disassociation between the sympathetic and parasympathetic nervous systems due to cortical control loss. The patient was treated with morphine and labetalol and he experimented an excellent response, reducing his episodes of paroxysmal sympathetic storm by 80 percent. The aim of this review is to communicate this entity because a prompt and accurate diagnosis could minimize unnecessary studies and treatments.

Dependencia de los sistemas de memoria al ciclo luz-oscuridad en la expresión de estrategias adaptativas. Segunda parte

resumen está disponible en el texto completo

Abstract: In the first part of this work we reviewed the hippocampus and striatum anatomy and function in the context of the memory systems. In this second part we describe the anatomic and physiologic basis of the memory systems represented by the amygdala and prefrontal cortex (PFC) and their participation in the expression of strategies for the solution of specific problems. Amygdaloid formation is divided in three principal regions, the baso-lateral nucleus, the superficial nucleus, and the centromedial nucleus. Amygdala is highly connected with several regions of the brain including hippocampus, striatum and PFC. Amygdala has been implicated in the processing, storing and retrieval of emotional information. Another function proposed for the amygdala is to modulate the activity of structures such as the hippocampus, the striatum and the cerebral cortex. The participation of the amygdala has been shown in different tasks such as the Morris water maze, the radial maze, the passive avoidance task, and the freezing behavior among others. In some of these studies it has been shown that the activation of the amygdala enhances the acquisition of the task. When the amygdala is activated pharmacologically it is able to enhance the acquisition of hippocampus or striatum related tasks. In these context, the efficiency of the amygdala activation depends on the synchrony, the precise time, at which it occurs in relation to the event the subject is learning. This is, either immediately before, during or immediately after learning. In support of this enhancing role of the amygdala, some electrophysiological studies have shown that the activation of the amygdala facilitates the development of LTP in the hippocampus while its lesion decreases it. On the other hand, it has also been shown that the amygdala activation increases c-Fos expression in both, the hippocampus and the striatum. In summary, the amygdaloid formation has been proposed as an enhancer of learning, representing the emotional component of the response to the environment. PFC is the other structure involved in the generation of strategies. It has been related with the correct functioning of higher functions such as memory, attention, emotion, anticipation and planning. It has been called the central executor for its fundamental role as a coordinator of past, present information and future performance. It is been proposed as responsible for the so called working memory, that allows to put together different kinds of information at the same time, giving the chance of comparing, selecting and generating a goaloriented behavior. Working memory has been studied with many different techniques, however electrophysiological experiments have shown interesting aspects of its functioning. Recording cells from the PFC of monkeys, Goldman-Rakic showed that these cells remain firing in a short period of time when visual information should be retained to be used in ulterior comparison task. This cell activity suggests that these neurons would be responsible for the maintenance of information in our "mind" a short period of time. These results have been replicated in humans by using real time imaging techniques as fMRI and PET. Again, during the periods of retention of the information, the activity on prefrontal areas increase until such information is used. Besides working memory, anticipation is another important function regulated by the PFC. Several studies have shown that the activity of prefrontal cortex increases before the performance, it seems like the prefrontal cortex predicts the actions in the environment and readily generates a strategy to efficiently act in response. PFC is connected reciprocally with the hippocampus, the striatum and the amygdala, the relation between these structures is under heavy investigation. Regarding the hippocampus, some interaction has been observed, and it has been proposed an interaction between these structures for the long term consolidation of memory. As for the striatum, the relationship with PFC has been studied preferentially with the ventral striatum or nucleus accumbens with respect to reinforcement of behavior. We understand poorly the relationship with the dorsal striatum. The relation between amygdala and PFC, on the other hand, has been studied in relation to the expectancy of the reinforcement. This is defined as the representation in the mind of the reinforcement and the association of that representation with the conditions under which it was delivered. In simple words, this is a way to explain how is that a subject prefers a specific reinforcer over another. It has been shown that lesions of the basolateral amygdala as well as PFC interfere with the expectancy of reinforcement. The function of the amygdala in this case is to provide the emotional component related to the presence of the reinforcement. An extensive literature has addressed the question of circadian variations in the release of neurotransmitters. For example, the diurnal variations in the release of acetylcholine in the hippocampus and PFC. The binding for acetylcholine, serotonin and norepinephrine to glutamatergic hippocampal cells is different depending on the light-dark cycle, suggesting that the modulation of the hippocampus by these neurotransmitters is different depending on the presence or absence of light. In this review, we have devoted special interest to the influence of the light dark cycle on these mnemonic systems and on goaloriented behaviors. We analyze selected papers from the available literature on circadian rhythms and memory, emphasizing the hippocampus role. We believe that the study of this relationship (brain/light-dark cycle) could be a useful tool to understand how the environment influences behavior. On this topic, there's evidence that the learning of a task may be different depending on the part of the day when it was learned. For example, it has been shown in humans that when subjects are submitted to explicit or implicit task the performance is different depending on the hour of the day, being better during the light for the explicit memory and better during the dark for the implicit memory. Studies in rats trained in fear conditioning tasks, showed that subjects learn the task easily when they are trained during the light phase of the cycle and the learned behavior showed a higher resistance to extinction. Conclusión. When a subject is confronted with a specific problem, he/she can find the solution by using different strategies. The expression of one of those strategies depends on the interaction of the different memory systems, these systems process and storage different kinds of information, and this information is useful to generate and exhibit a given strategy. The memory systems are constantly under the influence of the environment, one critical component of this environment is the lightdark cycle, which apparently is modulating the activity of these structures. As a result of the influence of the light-dark cycle on these structures, the behavior of the subject would be modulated as well. All these interaction just for the sake of adaptation, survival, and reproduction in this rotating and translating world.

Dependencia de los sistemas de memoria al ciclo luz-oscuridad en la expresión de estrategias adaptativas. Primera parte

resumen está disponible en el texto completo

Abstract: The ability to abstract, store and recover information from the environment in order to generate new strategies to solve problems is one of the most important qualities of the human brain. We mean by strategy, the sophisticated way to solve a problem. A strategy represents in essence the refinement of a given behavior to solve a problem. A strategy could be generalized to solve different problems. The generation of strategies is subjected to the correct functioning of the brain, meaning, alertness, attention, memory among others brain processes in good stand. In this work we focus on the role of memory in the generation of strategies. In this context, we focus on the literature concerning to memory systems, to show that different memory systems process and store different kinds of information. Therefore, the generation of a given strategy would require the participation of one system instead of other, or at least, one system would be commanding over the others. A memory system is defined as neural network consisting on a central structure communicated through afferences and efferences with others. The ones conveying information to this central structure would provide information from the internal or external environment to be interpreted and stored; while the ones that receive information from the central structure would execute its commands. Curiously, the role of central structure can be played by one structure "A" that in other conditions was under the control of a structure "B". In this condition, "B" is under the control of "A". In this review we sought to describe the anatomic and physiologic basis of the memory systems and their participation in the expression of strategies for the solution of specific problems. In this first part, we review the literature concerning to the hippocampus and striatum. Our endeavor was to make a synthesis of the main components of the functional neuroanatomy of memory and of its specific participation in the generation and expression of strategies, and also of the influence of the light-dark cycle on the strategies resulting from the interaction of these structures. In this review we focus mainly on the basic description of memory systems and on the data obtained from intact rats and of others with lesions and subject to electrophysiological experiments. Many studies reviewed on this first part confront subjects to situations where different solutions can be performed; basically this studies are conducted on mazes were the subject can use different kinds of information for spatial orientation. Depending on the nature of the information available or selected by the subject, investigators may infer the kind of strategy the subject is using to solve the problem. From this background, concepts such as stimulus-stimulus strategy and stimulus-response strategy have been generated. The first one consists of making associations between neutral stimuli, to make a conceptual map that guides the subject toward his/her objective. It has been related with the hippocampus function and it has been classically related to the processing, interpretation, and storage of contexts and events as well as to spatial navigation. We center our attention on studies carried out in mazes, showing that lesions or temporal inactivation of the hippocampus disturb the capacity of orientation by using spatial cues. We also review studies where the expression of spatial strategies is correlated with preferential activation of hippocampus detected with different techniques such as immuno-histochemistry and mycrodialisis in vivo. The stimulus-response strategy, on the other hand, consists on making associations between a particular stimulus and the immediate consequence of its presence. This kind of strategy has been related with the striatum, particularly with its dorsolateral region. For this section we discuss studies where lesions or inactivation of the dorsolateral striatum were performed, on rats submitted to tasks where the solution could be achieved by using stimu-lus-stimulus or stimulus-response strategy. In subjects with striatal dysfunction the ability to perform using a stimulus-response strategy was disrupted but not the ability to use a stimulus-stimu-lus strategy. In addition, we revise studies where the expression of the stimulus-response strategy is correlated with a preferential activation of the striatum over hippocampus. We additionally discuss the interaction hippocampus-striatum to solve a spatial task. We make special emphasis in describing the hippocampal and the striatal systems as independent systems that process and store different kinds of information; therefore, they seem to alternate their activity depending on the demand of the environment. This means that if a stimulus-stimulus strategy is required, the hippocampus will govern the response of the subject, increasing its activity that will be over the activity of the striatum. The opposite will occur if a stimulus-response strategy is required. Studies in humans and rats have been performed to understand the interaction between hippocampus and striatum with similar results. Apparently hippocampus appears more active during the first stages of learning, leading behavior and being expressed as stimulus-stimulus strategy. Later, in learning, the hippocampus decreases in activity and the striatum increases, thus becoming the leader structure. This later activation of stria-tum has been related with the phase of learning when the task is mastered and is starting to become a habit. Finally, we devoted special interest to describe the influence of the light dark cycle over these systems and over the goal-oriented behavior. And as we will see on the second part of this review, the functioning of these structures may be regulated by the light-dark cycle. We will review the influence of the presence or absence of light on neurotransmitters release. We will give evidence indicating that the neurochemical modulation depends greatly on the influence of the light-dark cycle and that it results obviously in a different activity of these structures and hence the behavior. In conclusion, when a subject is confronted with a specific problem, he/she can find the solution by using different strategies. At present, we can not say which are the mechanisms responsible for the selection of a particular strategy at a given mo-ment, but we can say that the expression of any strategy depends on the activity of structures such as the hippocampus and the striatum. In theory each structure represents a memory system or a fundamental part of a memory system. The interaction of the different memory systems, produce a scenario were each system provides, processes, and stores different information about the environment, and this information is useful to generate and exhibit a given strategy. On the second part of this review we will focus on the func-tioning and participation of the amygdala and prefrontal cortex, and the influence of the environment on the memory systems.