Tósigos y antídotos en la literatura cervantina: sobre los venenos en la España tardorrenacentista / “Tosigos” and antidotes in Cervantine literature: on the poisons in the late Renaissance Spain

Los textos cervantinos constituyen una interesante fuente para el estudio de la sociedad española tardorrenacentista. Nosotros hemos abordado las obras de Cervantes desde la óptica de la toxicología, analizando el uso de agentes tóxicos y venenosos, fundamentalmente alucinógenos y narcóticos en el ámbito de la práctica de la brujería y hechicería (ungüentos de brujas, filtros de amor, pócimas venenosas, etc.), así como las menciones a las hipotéticas sustancias dotadas de acción alexifármaca, como la verbena (Verbena officinalis), el cuerno de unicornio, las piedras bezoares o el castóreo. Las obras cervantinas en las que se hace referencia a estos preparados son las novelas El Quijote, La Galatea, Viaje del Parnaso y cuatro Novelas Ejemplares (La española inglesa, El licenciado Vidriera, El celoso extremeño y El coloquio de los perros), así como en las comedias Pedro de Urdemalas, La entretenida y El laberinto del amor. Entre los agentes tóxicos de origen herbal citados expresamente por Cervantes en el contexto analizado se encuentran el beleño (Hyoscyamus niger / albus), el tabaco (Nicotiana tabacum), la adelfa (Nerium oleander), el tártago (Euphorbia lathyris), el ruibarbo (Rheum officinale, Rumex alpinus) y, de forma enmascarada, el opio (Papaver somniferum). En relación con el resto de preparados dotados de actividad tóxica, Cervantes no identifica sus ingredientes, aunque, a tenor de la sintomatología descrita por el autor, podrían ser plantas de la familia de las solanáceas, como el beleño, el solano, la datura, la belladona o la mandrágora. Con respecto a los tóxicos minerales, únicamente hay referencias a los efectos del mercurio o azogue. El Dioscórides comentado por Andrés Laguna pudo ser la fuente técnica utilizada por Cervantes para documentarse en esta materia (AU)

Cervantine texts are an interesting source for the study of Spanish late Renaissance society. We have studied the works of Cervantes from the toxicology viewpoint, analyzing the use of toxic and poisonous substances, essentially hallucinogenic and narcotic agents in the field of witchcraft and sorcery practice (witches ointments, love filters, poisonous potions, etc.), as well as references to hypothetical substances endowed with alexipharmic action, as the vervain (Verbena officinalis), unicorn horn, bezoar stones or castoreum. Cervantine works which refers to these preparations are the novels Don Quixote, The Galatea, Voyage to Parnassus and four Exemplary Novels (The Spanish-English Lady, The Licentiate of Glass, The Jealous Extremaduran and The Colloquy of the Dogs), as well as the comedies Pedro de Urdemalas, The Amusing Woman and The Labyrinth of Love. Toxic agents of herbal origin mentioned explicitly by Cervantes in the analyzed context include the henbane (Hyoscyamus niger / albus), tobacco (Nicotiana tabacum), oleander (Nerium oleander), spurge (Euphorbia lathyris), rhubarb (Rheum officinale, Rumex alpinus), and masked way, opium (Papaver somniferum). In relation to the rest of preparations endowed with toxic activity, Cervantes does not identify its ingredients, though, within the meaning of the symptoms described by the author, they could be plants of the Solanaceae family, as the henbane, nightshade, jimsonweed, belladonna or mandrake. Concerning toxic minerals, only there are references to the effects of mercury (“azogue”). The Dioscorides commented by Andrés Laguna could be the technical font used by Cervantes to document in this matter (AU)

An historical view of the pineal gland and mental disorders.

Since Classical Antiquity numerous authors have linked the origin of some mental disorders to physical and functional changes in the pineal gland because of its attributed role in humans as the connection between the material and the spiritual world. The pineal organ was seen as a valve-like structure that regulated the flow of animal spirits through the ventricular system, a hypothesis that took on more vigour during the Middle Ages and the Renaissance. The framework for this theory was "the three cells of the brain", in which the pineal gland was even called the "appendix of thought". The pineal gland could also be associated with the boom, during this period, of certain legends about the "stone of folly". But the most relevant psychopathological role of this organ arrived with Descartes, who proposed that it was the seat of the human soul and controlled communications between the physical body and its surroundings, including emotions. After a period of decline during which it was considered as a mere vestigial remnant of evolution, the link between the pineal gland and psychiatric disorders was definitively highlighted in the 20th century, first with the use of glandular extracts in patients with mental deficiency, and finally with the discovery of melatonin in 1958. The physiological properties of melatonin reawakened interest in the relationship between the pineal gland and mental disorders, fundamentally the affective and sleep disorders, which culminated in the development of new pharmacological agents acting through melatonergic receptors (ramelteon and agomelatine).

Phytotherapy and psychiatry: bibliometric study of the scientific literature from the last 20 years.

In diverse areas of therapy, including psychiatry, increasing interest in herbal medicine has been shown in recent years. Plants have a wide range of traditional uses, but only a few have been approved therapeutically. Moreover, to our knowledge, no bibliometric analyses on medicinal plants used in psychiatry have been carried out to date. We performed a bibliometric study on scientific publication related to phytotherapy in the psychiatry area during the period 1986-2006. Using the platform Embase.com, including the EMBASE and MEDLINE databases, we selected those documents including the descriptors plant*, herb*, phytotherapy*, phytomedicine*, pharmacognosy*, and psychiatry* (with all diagnostic criteria). The plants' indications were selected according to the PDR for Herbal Medicines. As a bibliometric indicator of the production, Price's Law was applied. Another indicator included was the national participation index (PI) for overall scientific production. A total of 21,409 original documents were obtained. Our data confirm a fulfillment of Price's Law related to scientific production on medicinal plants in Psychiatry. This was observed after we made a linear fit (y=135.08x-466.38; r=0.92) and another fit to an exponential curve (y=132.26e(0.1497x); r=0.99). The plants most widely mentioned in the psychiatric literature were St. John's wort (Hypericum perforatum L.; n=937) and ginkgo (Ginkgo biloba L.; n=694). The countries with the highest percentages of documents were the United States (29.44%), Germany (9.41%) and Japan (8.75%), and those with highest proportional PI were India (IPa=0.935) and China (IPa=0.721). Productivity on medicinal plants in the psychiatry area increased during the period 1986-2006. Nevertheless, documents about therapeutic herbs in this medical field are still relatively few in number.

Abordaje terapéutico de la epilepsia desde la perspectiva nutricional: situación actual del tratamiento dietético / Therapeutic approach to epilepsy from the nutritional view: current status of dietary treatment

Aproximadamente entre un 20-30 % de los pacientes epilépticos no responden adecuadamente al tratamiento farmacológico. En estos pacientes el tratamiento dietético se ha planteado como una alternativa terapéutica o como una herramienta coadyuvante. El objetivo del presente trabajo es realizar una revisión sobre las alternativas dietéticas disponibles en la actualidad en el tratamiento de la epilepsia (dieta cetogénica, dieta de Atkins, etc.). La dieta cetogénica ha sido la más utilizada y estudiada en este trastorno neurológico y por este motivo también es la que más modificaciones ha sufrido y la que más preguntas suscita en relación a su mecanismo de acción, su eficacia, sus efectos adversos, así como al protocolo más adecuado para llevarla a cabo. Son numerosos los estudios observacionales y revisiones que se han planteado sobre este tema y que avalan el efecto beneficioso de la dieta cetogénica. No obstante, son necesarios ensayos clínicos controlados aleatorizados y con mayores muestras poblacionales que confirmen dichos resultados, con el fin de conseguir un tratamiento dietético óptimo e individualizado en la epilepsia refractaria

Approximately 20%-30% of epilepsy patient do not respond adequately to drug treatment. In this population, a dietary treatment has been posed as a therapeutic alternative or coadjuvant tool. This present work has aimed to carry out a review on the dietary alternatives currently available to treat epilepsy (ketogenic diet, Atkins’ diet, etc.). The ketogenic diet has been used and studied the most in this neurological disorder. That is why it is also the one that has undergone the greatest change. Furthermore, this diet has caused the most controversy about its action mechanism, efficacy and adverse effects as well as about what would be the best protocol to carry it out. Many observational studies and reviews on this subject that support the beneficial effect of the ketogenic diet have been conducted. However, controlled, randomized clinical trials with larger population samples are needed to confirm these results in order to achieve an optimum and individualized dietary treatment in refractory epilepsy

[Therapeutic approach to epilepsy from the nutritional view: current status of dietary treatment]. / Abordaje terapéutico de la epilepsia desde la perspectiva nutricional: situación actual del tratamiento dietético.

Approximately 20%-30% of epilepsy patient do not respond adequately to drug treatment. In this population, a dietary treatment has been posed as a therapeutic alternative or coadjuvant tool. This present work has aimed to carry out a review on the dietary alternatives currently available to treat epilepsy (ketogenic diet, Atkins' diet, etc.). The ketogenic diet has been used and studied the most in this neurological disorder. That is why it is also the one that has undergone the greatest change. Furthermore, this diet has caused the most controversy about its action mechanism, efficacy and adverse effects as well as about what would be the best protocol to carry it out. Many observational studies and reviews on this subject that support the beneficial effect of the ketogenic diet have been conducted. However, controlled, randomized clinical trials with larger population samples are needed to confirm these results in order to achieve an optimum and individualized dietary treatment in refractory epilepsy.

La virtud de aquel precioso bálsamo: aproximación a El Quijote desde la vertiente de la psicofarmacología / The virtude of that precious balsam: approach to Don Quixote from the psychopharmacological perspective

La obra cumbre de la literatura española, El Quijote, constituye una fuente donde habitualmente beben los diferentes especialistas que pretenden conocer con mayor profundidad la sociedad renacentista tardía. Esta obra magistral de Miguel de Cervantes ha sido frecuentemente abordada desde la perspectiva psicopatológica para obtener un diagnóstico psiquiátrico de su principal personaje, Alonso Quijano. También son frecuentes los abordajes clínicos desde la traumatología y desde la terapéutica general (análisis de aceites, ungüentos, bálsamos y demás preparados de botica). Nosotros nos acercamos a El Quijote desde la vertiente de la psicofarmacología, un campo escasamente abordado. En el presente trabajo se estudian los remedios terapéuticos empleados en la época cervantina para el tratamiento de los locos y enajenados (sedantes, como el opio; evacuantes, como el eléboro; tónicos, irritantes y técnicas quirúrgicas, como las sangrías y fuentes) y se analizan las escasas e inespecíficas terapias, fundamentalmente de origen herbal, que Cervantes nos revela en su novela (bálsamos, purgantes y eméticos). Entre ellas cabe mencionar la raíz de ruibarbo (Rumex alpinus), las semillas de tártago (Euphorbia lathyris), la hierba de San Juan (Hypericum perforatum), ingrediente del aceite de Aparicio y el romero (Rosmarinus officinalis), ingrediente del célebre bálsamo de Fierabrás. También se analizan las posibles influencias científicas en que se pudo inspirar Cervantes en este campo, fundamentalmente las obras de Juan Huarte de San Juan Examen de ingenios para las ciencias y de Andrés Laguna Dioscorides, acerca de la materia medicinal y de los venenos mortíferos

The most outstanding novel of the Spanish literature, Don Quixote, represents the source to which the different specialists who intend to deepen their knowledge of the late Renaissance society usually address. This masterpiece of Miguel de Cervantes has been frequently approached from the psychopathological perspective to obtain a psychiatric diagnosis of its main character, Alonso Quijano. Also, other clinical approaches from the traumatological and general therapeutical view (oils, ointments, balms and other pharmacy preparations) have been frequent. We have tackled Don Quixote from the psychopharmacological perspective, a barely explored field. In this work, we intend to study the therapeutical cures used during the Cervantine time for the treatment of insane and mentally disturbed people (sedatives like opium, laxatives like hellebore, tonics, irritants and surgical techniques like bloodlettings and «fuentes») and we analyze the limited and unspecific therapies, mainly of herbal origin (balms, purgatives and emetics), which Cervantes reveals to us in his novel. Among them, rhubarb root (Rumex alpinus), seeds of spurge (Euphorbia lathyris), St. John's Wort (Hypericum perforatum), main ingredient of Aparicio's oil, and rosemary (Rosmarinus officinalis), primary component of the famous balsam of Fierabras, should be highlighted. We have also examined the possible scientific influences which might have inspired Cervantes in this field, mainly the works of Juan Huarte de San Juan The examination of men's wits and the one of Andres Laguna Dioscorides' materia medica

[The virtue of that precious balsam...: approach to Don Quixote from the psychopharmacological perspective]. / La virtud de aquel precioso bálsamo...: aproximación a El Quijote desde la vertiente de la psicofarmacología.

The most outstanding novel of the Spanish literature, Don Quixote, represents the source to which the different specialists who intend to deepen their knowledge of the late Renaissance society usually address. This masterpiece of Miguel de Cervantes has been frequently approached from the psychopathological perspective to obtain a psychiatric diagnosis of its main character, Alonso Quijano. Also, other clinical approaches from the traumatological and general therapeutical view (oils, ointments, balms and other pharmacy preparations) have been frequent. We have tackled Don Quixote from the psychopharmacological perspective, a barely explored field. In this work, we intend to study the therapeutical cures used during the Cervantine time for the treatment of insane and mentally disturbed people (sedatives like opium, laxatives like hellebore, tonics, irritants and surgical techniques like bloodlettings and <>) and we analyze the limited and unspecific therapies, mainly of herbal origin (balms, purgatives and emetics), which Cervantes reveals to us in his novel. Among them, rhubarb root (Rumex alpinus), seeds of spurge (Euphorbia lathyris), St. John's Wort (Hypericum perforatum), main ingredient of Aparicio's oil, and rosemary (Rosmarinus officinalis), primary component of the famous balsam of Fierabras, should be highlighted. We have also examined the possible scientific influences which might have inspired Cervantes in this field, mainly the works of Juan Huarte de San Juan The examination of men's wits and the one of Andres Laguna Dioscorides' materia medica.

Evaluation of the antinociceptive effect of Rosmarinus officinalis L. using three different experimental models in rodents.

The rationale of this investigation was to examine the antinociceptive effect of an ethanol extract of Rosmarinus officinalis (RO) aerial parts, using three different experimental models: acetic acid-induced writhing test and formalin test in mice; and a model of arthritic pain: "pain-induced functional impairment model in the rat (PIFIR model)". The antinociceptive efficacies were evaluated using several dose-response curves and time courses. The antinociceptive effects from RO extract were compared with the antinociceptive effect of either tramadol (TR: 3.16-50 mg/kg, i.p. in mice, and 1.0-31.62 mg/kg, i.p. in rats) or acetylsalicylic acid (AA: 31.62-562.32 mg/kg, p.o.). RO extract (10-300 mg/kg, p.o.) significantly (P < 0.001) reduced the number of writhing movement induced by the i.p. administration of acetic acid solution in a dose-dependent way (ED50 = 108.84 mg/kg, whereas, TR showed an ED50 = 12.38 mg/kg). In addition, RO extract (30-300 mg/kg) significantly (P < 0.001) inhibited licking and shaking behaviours in both early (neurogenic pain) and in the late (inflammatory pain) phases of the formalin test. These effects were like those produced by TR. Concerning the results using the PIFIR model, RO extract (30-3000 mg/kg, p.o.) like either TR or AA, produced a significant (P < 0.001) and dose-dependent antinociceptive response in rats (RO: ED50 = 222.78 mg/kg versus TR: ED50 = 11.06 mg/kg and AA: ED50 = 206.13 mg/kg). These results strongly suggest that aerial parts of RO possess antinociceptive and anti-inflammatory activity, and reinforce the use of this plant in folk medicine.

El papel de la medicina herbal ayurvédica en el descubrimiento de las propiedades neurolepticas de la reserpina: a propósito de la Rauwolfia serpentina y los orígenes de la era antipsicótica / The role of the ayurvedic herbal medicine in the discovering of neuroleptic properties of reserpine: Rauwolfia serpentina and the origins of antipsychotic era

En el presente trabajo se revisa el papel de la planta Rauwolfia serpentina en el origen de la denominada "era psicofarmacológica". Para ello, se ha sumarizado su empleo en la tradicional medicina ayurvédica, fundamentalmente en los trastornos mentales. En el clásico tratado hindú Charaka Samhita ya se hablaba de una forma de psicosis denominada Ounmaad, uno de cuyos remedios terapéuticos era la "planta de raíz de serpiente". La medicina científica se ocupó del estudio, durante la primera mitad del siglo XX, de las actividades farmacológicas de esta planta, destacando las propiedades sedantes e hipotensivas. Finalmente, se analiza el proceso de aislamiento de los alcaloides de la raíz de Rauwolfia, iniciado en la India, y que concluyó con el descubrimiento de la reserpina en los laboratorios suizos de Ciba. Con la reserpina, el arsenal farmacológico para el tratamiento de la esquizofrenia, sustentado únicamente en la clorpromazina, se vio sustancialmente implementado; permitiendo un gran avance en el manejo de los trastornos psiquiátricos (AU)

Abordaje farmacológico de las recaídas en las adicciones / Pharmacological therapy of the reapses in the opiate addiction

La adicción es una enfermedad crónica, que requiere tratamiento durante la mayor parte de la vida del paciente y como tal, las recaídas y el incumplimiento terapéutico son hechos habituales. En las dos últimas décadas se ha avanzado notablemente en el conocimiento de las bases neuropsicobiológicas y farmacológicas de las adicciones, lo que ha permitido concluir que estamos ante una patología tratable. En la actualidad, se acepta que la fase más importante en la farmacoterapia de la dependencia es la que la que corresponde a la prevención de las recaídas. En este sentido, los antagonistas de los receptores opiáceos, en especial la naltrexona, constituye el avance más importante en esta fase preventiva. Su utilidad se ha demostrado en la prevención de la recaída a opiáceos y, más recientemente, en pacientes alcohólicos. De hecho, la naltrexona reduce en un 50 por ciento la tasa de recaídas y los individuos permanecen más tiempo abstinentes. Otros agentes utilizados en este campo son el acamprosato y los fármacos moduladores de la transmisión serotoninérgica, como la buspirona o los inhibidores selectivos de la recaptación de serotonina, fluoxetina y citalopram. Desafortunadamente, para otras dependencias (cocaína, cánnabis, anfetaminas, éxtasis, etc.) no existe un abordaje farmacológico específico, si bien se han empleado algunos de los fármacos comentados, así como antagonistas dopaminérgicos, con resultados poco significativos (AU)

Usefulness of the pain-induced functional impairment model to relate plasma levels of analgesics to their efficacy in rats.

In this work we show that the pain-induced functional impairment model (PIFIR) can be used with cannulated rats as a useful procedure for pharmacokinetic/pharmacodynamic modelling. This model evaluates analgesia by measuring motor impairment of the right limb after intra-articular administration of uric acid. Time of contact with a rotating cylinder is referred to the control limb. We studied the pharmacokinetic and pharmacodynamics of naproxen after six peroral doses to Wistar rats, and we examined the adjuvant action of caffeine with naproxen. Surgery and blood sampling did not produce any difference on functional impairment either in rats without uric acid or in the dysfunction produced by uric acid. The relation between naproxen plasma concentration and the analgesic effect was obtained with few rats. Caffeine alone did not produce any significant modification in functional impairment but the co-administration significantly increased the effect of naproxen. Plasma levels of naproxen did not change when caffeine was co-administered. The PIFIR model with blood sampling is a suitable method for pharmacokinetic/pharmacodynamic relationship studies and is specially useful to characterize drug-drug interactions.