Immunochromatography screening devices for cannabinoids in oral fluid sample

Abstract Cannabis sativa L. is one of the most consumed drugs in the world and recent studies have associated its use with an increase in the number of traffic accidents in different countries. In many countries, like Brazil, simple and reliable methodologies are still needed for the detection of drugs on site, mainly cannabinoids, considering its prevalence of use and oral fluid (OF) has been proved as an appropriate biological matrix for this purpose. Considering that, this work aims to review previous studies on immunochromatographic devices for on-site detection of cannabinoids in OF, discussing their sensitivity, specificity, cut-offs values and confirmatory methods. This data shows the importance of choosing a screening device and it reinforces the need for its implementation in Brazil. The research was conducted on 5 databases and all original articles, published in the last 10 years, were selected. A total of 32 articles were found, providing data for 17 screening devices of distinct brands. Only 2 screening devices showed satisfactory sensitivity and specificity in the evaluated studies (≥80% and ≥90% respectively). However, it should be considered that the screening devices still have some limitations, such as a higher cut-off than those recommended by international guidelines (cut-off > 2 ng/mL), therefore demonstrating the need for more studies in the area and the importance of confirmatory analysis usually fulfilled by LC-MS/MS, GC-MS/MS or GC-MS. Thus, the screening analyzes should not be evaluated by itself, but in association with confirmatory results and observational traits (behavioral changes), for a better understanding of the traffic scenario

Efficacy of cannabinoids in fibromyalgia: a literature review / Eficacia de los cannabinoides en la fibromialgia: revisión de la literatura

Abstract Fibromyalgia is a chronic disease of unclear etiology, involving a neural oversensitization and impaired pain modulation, in addition to a clinical deficiency of the endocannabinoid system. Fibromyalgia is associated with a number of somatic and psychological disorders and hence multiple pharmacological approaches have been used, including opioids, antidepressants, antiepileptics, and more recently medical cannabis. This narrative review comprises a review of the current literature on the efficacy of cannabinoids in fibromyalgia. The studies describe a possible influence of cannabis on pain control in patients with fibromyalgia, with positive effects on quality of life and sleep. The use of cannabis seems to be beneficial in patients with fibromyalgia; however, more robust studies are still needed to establish is actual efficacy in pain management, quality of life and improvement of associated symptoms.

Resumen La fibromialgia es una enfermedad crónica, cuya etiología no es clara, en la que se involucra una sobresensibilización neural y disminución de la modulación del dolor, así como una deficiencia clínica del sistema endocannabinoide. Está asociada a una variedad de trastornos somáticos y psicológicos, por lo cual se han utilizado múltiples abordajes farmacológicos, entre ellos opioides, antidepresivos, antiepilépticos y, recientemente, cannabis medicinal. En esta revisión narrativa se hace una reseña de la literatura actual relacionada con la eficacia de los cannabinoides en la fibromialgia. Los estudios describen una posible influencia del cannabis sobre el control del dolor en pacientes con fibromialgia, con efectos positivos sobre la calidad de vida y el sueño. El uso del cannabis parece tener beneficios en los pacientes con fibromialgia; sin embargo, aún se requieren estudios más robustos para establecer su verdadera eficacia en el manejo del dolor, calidad de vida y mejoría de los síntomas asociados.

Pharmacology Of Noval Cannabinoids

Cannabis is a plant rich in various compounds that have a variety of impacts on the physiology of humans and the effects of these metabolites have a significant role in managing a variety of clinical diseases. A substantial increase in the use of SC (synthetic cannabinoids) had seen in the last few years especially infrequent cannabis users. The SCs will generate psychoactive effects that were similar to cannabis. However, the composition and pharmacological characteristics of these drugs make them possibly hazardous. Like all drugs, cannabis’ pharmacokinetics depends on the route of administration. Several studies showed that the bioavailability is less in oral administration when compared to inhalation. The main reason for this decrease in oral bioavailability is that cannabinoids undergo the first-pass metabolism before entering into the systemic circulation whereas in inhalation, it enters the circulation directly through the lungs. Cannabis sativa is a psychoactive plant that contains more than 500 components of which 104 cannabinoids had been identified. Of these, 2 components such as Δ9-THC (Δ9-tetrahydrocannabinol) and CBD (cannabidol) were under the scientific investigation. Δ9-THC is the primary cannabinoid which was responsible for the consequences of psychotrophy. The potency of cannabis is assessed based on the THC concentration of a sample that is the main psychoactive cannabinoid in cannabis. The adverse effects are in direct relation to the concentration of THC in the product after regular cannabis use. It can be assumed that several cannabinoids will find their way into the pharmacies from preclinical research within a century.

Determinación y comparación cualitativa de cannabinoides presentes en productos naturales comerciales del departamento del Cauca, Colombia / Determination and qualitative comparison of cannabinoids present in commercial natural products of the Cauca Department-Colombia

RESUMEN Actualmente, hay un creciente interés por el estudio de Cannabis sativa y sus componentes ya que se le atribuye propiedades terapéuticas en el tratamiento de enfermedades. En Colombia y específicamente en el departamento del Cauca se comercializan productos de cannabis tanto para fines no medicinales como terapéuticos. En consecuencia, es necesario el análisis de estos productos de manera que se pueda conocer la composición de los mismos y el posible efecto que pueda tener sobre la salud. El análisis de los componentes de estos productos se llevó a cabo empleando la cromatografía líquida de alta resolución (CLAR) y espectrometría de masas (EM), de tal manera que permitieron la identificación de las principales especies cannabinoides; Δ9-tetra hidrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG). La separación de los analitos se llevó a cabo mediante la implementación de una columna analítica C18 de fase reversa, elución isocrática 1 mL/ min, presión del sistema 800 PSI, una mezcla de acetonitrilo ACN y buffer fosfato (KHPO4) en relación 65/35 como fase móvil, volumen de inyección de 10 µL, un tiempo de análisis de 15 min, y detección a 220 nm.

SUMMARY Cannabis sativa has now experienced an increasing interest in the study of its components since it is attributed therapeutic properties in the treatment of diseases. In Colombia and specifically in the Cauca Department, Cannabis products are marketed both for non-medicinal and therapeutic purposes. Consequently, it is necessary to analyze these products in such a way that the composition of the products and their possible effect on health can be known. The analysis ofthe components of these products was carried out using high performance liquid chromatog-raphy (HPLC) and mass spectrometry (MS), in such a way that they allowed the identification of the main cannabinoid species; Δ9-tetra hydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG). The separation of the analytes was carried out by means of the implementation of a reverse phase C18 analytical column, isocratic elution 1 mL/min, system pressure 800 PSI, a mixture of acetonitrile ACN and phosphate buffer (KHPO4) in relation 65/35 as mobile phase, injection volume of10 µL, analysis time of15 min, and detection at 220 nm.

El megacariocito: una célula muy original / The megakaryocyte: a very original cell

Resumen El megacariocito es la célula más grande de la médula ósea, por lo tanto es relativamente fácil reconocer su presencia al observar un aspirado o una biopsia de este tejido. Difiere de otras células por su tamaño, por ser poliploide y crecer por endomitosis. No hay otra célula humana que crezca así. Además, tiene funciones biológicas muy importantes. La más conocida es el dar origen a las plaquetas, que son indispensables para la hemostasia y la reparación de los vasos sanguíneos dañados, así como para la cicatrización de los tejidos que rodean a las heridas. Sin embargo, en los últimos años, a los megacariocitos también se les han atribuido algunas otras funciones que discutiremos en esta revisión.

Abstract The Megakaryocyte is the biggest cell in the bone marrow; therefore, it is easy to recognize in a bone marrow aspirate. In humans, this cell differs from others because of its size, its polyploidy and because it grows by endomitosis. It is the only human cell that grows this way. In addition, the megakaryocyte has very important biological functions. Its best-known function is being in charge of the production of platelets, which are essential for hemostasis, the repair of damaged blood vessels, and healing the tissues surrounding wounds. However, in recent years, other functions have been attributed to the megakaryocyte, which will be discussed in this review.

Action of ketamine and endocannabinoid system in rapid anti-depression therapy / 上海交通大学学报（医学版）

Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour induced by MDD during its later stage put a heavy burden on society and family. Anti-depression drugs lack efficiency in treating a portion of MDD patients. This is referred to as treatment resistant depression (TRD). A study reported the rapid onset and long lasting anti-depression effect of ketamine, which also come into effect in TRD patients. Δ9-Tetrahydrocannabinol is the active substance of marijuana, which also exerts rapid anti-depression effect via targeting at brain cannabinoid receptors. The two central nerve system stimulants belonging to the tightly controlled psychoactive substances have obvious adverse effects. This article summarizes the action of ketamine and endocannabinoid system in rapid anti-depression therapy in recent researches.

Action of ketamine and endocannabinoid system in rapid anti-depression therapy / 上海交通大学学报（医学版）

Major depression disorder (MDD) is a common but serious affective disorder in modern society. Suicide idea and suicide behaviour induced by MDD during its later stage put a heavy burden on society and family. Anti-depression drugs lack efficiency in treating a portion of MDD patients. This is referred to as treatment resistant depression (TRD). A study reported the rapid onset and long lasting anti-depression effect of ketamine, which also come into effect in TRD patients. △9-Tetrahydrocannabinol is the active substance of marijuana, which also exerts rapid anti-depression effect via targeting at brain cannabinoid receptors. The two central nerve system stimulants belonging to the tightly controlled psychoactive substances have obvious adverse effects. This article summarizes the action of ketamine and endocannabinoid system in rapid anti-depression therapy in recent researches.

Avaliação da presença de cocaína e anfetamina em amostras de sangue post mortem e de indivíduos vivos, utilizando técnica de microextração em fase líquida (HF-LPME) / Amphetamine, cocaine and tetrahydrocannabinol evaluation in blood samples of living people and post mortem blood samples using microextraction technique in liquid phase (HF-LPME)

Estima-se atualmente que mais de 5% da população mundial vem fazendo uso recreativo de algum tipo de substância psicoativa, sendo que o direito a esse uso é tema recorrente da sociedade contemporânea. Por apresentar riscos associados à saúde e a segurança das populações, o uso abusivo dessas substâncias tem instigado a toxicologia social na busca de respostas, com as quais se possa caracterizar, analisar e gerenciar esses riscos. Drogas de grande consumo no Brasil são a anfetamina, cocaína e Cannabis sativa. Esta tese desenvolveu uma nova metodologia para detectar e quantificar anfetamina, cocaína e tetrahidrocanabinol em sangue total, com uso de microextração em fase líquida via fibra de polipropileno (HF-LPME), seguida de cromatografia gasosa acoplada a espectrometria de massa (GC-MS). Trata-se de uma técnica que apresenta vantagens sobre as tradicionais, uma vez que demanda quantidades menores de solvente orgânico, diminuindo riscos e custos de processo. Também propôs um estudo com a aplicação dos métodos em 69 amostras de sangue de vivos e de post mortem, as quais foram obtidas por convênio com a superintendência da polícia técnica científica de São Paulo (SPTC/SP). Os métodos desenvolvidos foram validados de acordo com diretrizes internacionais de interesse forense. Como resultado da validação, os métodos desenvolvidos se mostraram precisos e exatos para anfetamina e cocaína. O limite de detecção da cocaína foi de 5 ng . mL-1 e o limite de quantificação de 10 ng . mL-1. Quanto a anfetamina, os limites de detecção e de quantificação foram de 5 ng . mL-1. A técnica de HF-LPME não foi aplicável ao tetraidrocanabinol (Δ9-THC). Como resultado da análise das amostras, 40% delas apresentaram resultados positivos para cocaína. Desses positivos, 35% foram oriundos das matrizes de sangue de vivos e 64% oriundos de sangue post mortem. Nenhuma delas apresentou resultado quantificável para anfetamina

It is currently estimated that more than 5% of the world's population has been doing recreational use of some kind of psychoactive substances and the legal right to such use is a recurring theme debated by contemporary society. Due to the risks associated with populations health and safety, the abusive use of these substances has been instigating by social toxicology to search for answers to characterize, analyze and manage these risks. Drugs of great consumption in Brazil are, amphetamine cocaine and marijuana. This thesis proposes to develop a new methodology to detect and quantify psychoactive drugs in whole blood with the use of liquid phase microextraction by polypropylene fiber (HFLPME), followed by gas chromatography coupled to mass spectrometry (GC-MS). It is a technique that presents advantages compared with traditional ones, because of the smaller amounts demands of organic solvent, reducing risks and process costs. It also proposes a study with 69 blood samples taken from living persons and post mortem blood samples, which were obtained by agreement with the Superintendency of São Paulo Scientific Technical Police (SPTC / SP). The methods developed were validated according to international guidelines of forensic interest. As a result of the validation, the methods developed were precise and accurate for amphetamine and cocaine. The limit of cocaine detection was 5 ng . mL-1 and the limit of quantification was 10 ng . mL-1. As for amphetamine, the limits of detection and quantification were 5 ng . mL-1. The HF-LPME technique was not applicable to tetrahydrocannabinol (Δ9-THC). As a result of the sample analysis, 40% of them presented positive results for cocaine. Of these, 35% were from blood samples taken from living persons and 64% from the post mortem blood samples. None of the samples presented quantifiable results for amphetamine

Determination of delta-9-tetrahydrocannabinol content of cannabis seizures in Egypt

OBJECTIVE@#To determine the delta-9-tetrahydrocannabinol (THC) content of cannabis seizures in Egypt.@*METHODS@#Unheated and heated extracts of cannabis seizures were prepared from the dried flowering tops and leaves (marijuana) or from the resin (hashish) and subjected to analysis using high performance liquid chromatography (HPLC).@*RESULTS@#The heated resin extract had the peak of THC in a relative ratio of 31.34%, while extracting the resin directly without heating contained only 18.34% of THC. On the other hand, marijuana showed minimum percentage of THC at 11.188% on heating and 9.55% without heating.@*CONCLUSIONS@#These results indicate the high potency of the abused cannabis plant in the illicit Egyptian market.

Determination of delta-9-tetrahydrocannabinol content of cannabis seizures in Egypt

Objective To determine the delta-9-tetrahydrocannabinol (THC) content of cannabis seizures in Egypt. Methods Unheated and heated extracts of cannabis seizures were prepared from the dried flowering tops and leaves (marijuana) or from the resin (hashish) and subjected to analysis using high performance liquid chromatography (HPLC). Results The heated resin extract had the peak of THC in a relative ratio of 31.34%, while extracting the resin directly without heating contained only 18.34% of THC. On the other hand, marijuana showed minimum percentage of THC at 11.188% on heating and 9.55% without heating. Conclusions These results indicate the high potency of the abused cannabis plant in the illicit Egyptian market.

¿Cuáles son los posibles usos de cannabis en términos medicinales?: síntesis rápida de evidencia / What are the possible medicinal uses of cannabis?: rapid evidence synthesis

ANTECEDENTES Y OBJETIVO Las preparaciones de cannabis (Cannabis sativa) han sido utilizadas con fines medicinales hace miles de años por otras culturas. A lo largo del mundo se ha ido avanzando hacia una legislación que permita el uso medicinal de cannabis como tratamiento para algunas condiciones particulares. Sin embargo, existe una gran heterogeneidad en cuanto a los tipos de preparaciones existentes. El extracto de cannabis contiene Tetrahidrocannabinol (THC) y Canabidiol (CBD) como compuestos. A partir de éstos, las preparaciones existentes se pueden utilizar en forma oral, spray, fumada o inhalada. En este contexto, el Gabinete del Subsecretario de Salud Púbica solicita esta síntesis de evidencia con el objetivo de informar la toma de decisiones respecto de los posibles usos medicinales del cannabis. METODOLOGÍA Se formuló una estrategia de búsqueda para ser utilizada en 5 bases de datos con el objetivo de identificar revisiones sistemáticas del tema. Se seleccionaron preferentemente las realizadas en los últimos 5 años. Se utiliza la metodología sobre la certeza de la evidencia GRADE. Se incluyeron estudios que analizaban el uso medicinal o terapéutico. Se excluyó todo tipo de estudios relacionados con el uso de cannabis y su dependencia. RESULTADOS Se utilizan 15 revisiones sistemáticas -Cannador (extracto THC y CBD oral) tendría algunos efectos sobre el tratamiento de Esclerósis Múltiple (EM), mientras que no sería efectivo en Parkinson. -Dronabinol (cápsulas de THC) probablemente no tenga impacto en EM, sería efectivo en aliviar intensidad del dolor para pacientes con cáncer, aliviaría el dolor crónico, reduciría la pérdida de peso en pacientes con Alzheimer y reduce náuseas y vómitos durante el tratamiento para VIH/SIDA. -Nabiximols (spray oromucoso de THC y CBD) no tendría un impacto significativo en el tratamiento de EM, podría generar efectos adversos en artritis reumatoide y aliviaría el dolor neurológico. -Nabilone (cannabinoide derivado de THC) probablemente no tiene impacto sobre distonías, aliviaría el dolor de fibromialgia y no generaría impacto sobre síntomas de Huntington -Los aceites o extractos con CBD (sin THC) no tienen efectos sobre la esquizofrenia, podrían reducir el dolor neurológico y no generarían impacto sobre el tratamiento del dolor asociado a EM.

Study of the Hormones Controlling Food Intake (Leptin and Agouti Related Protein "AGRP") in Cannabis Smokers.

Background: Leptin is an adipocyte derived hormone which is thought to be a key regulator of food intake and body weight. Agouti-related protein also called Agouti-related peptide (AgRP) is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is one of the most potent and long-lasting of appetite stimulators. The appetite stimulating effects of AgRP are inhibited by the hormone leptin. There is a public perception that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the 'munchies'). This phenomenon needs an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome Aim: This study aimed to find out the food intake style, of subjects smoking cannabis by studing the relationship between the most two popular hormones controlling food intake (leptin hormone, and agouti related protein hormone) compared with healthy subjects. Methods: The study compared two groups of personells; the test group (Group II) included ten males aged 37.40±2.67 years (mean age ±SD) with positive 9-carboxy- Tetrahydrocanabinol (THC) detected in their urine by qualitative analysis using Gas Chromatography-Mass spectrometry. And control group (GroupI) included ten healthy males aged 38.67±2.35 years (mean age ± SD) as volunteers with negative 9-carboxyTetrahydrocanabinol (THC). In both groups, age and body mass index (BMI) were matched, diabetic subjects were excluded. Plasma leptin concentration was measured by quantitative radio immunoassay (RIA). Human plasma AgRP hormone was quantitatively measured by using a kit supplied from Quantikine R&D systems INC. Results: In group I (GI), there was an increase in mean plasma leptin concentrations ±SD (6.39±1.93) ng/ml, than that found, in group II (GII) (4.49±1.40) ng/ml, but it's statistically insignificant (P>0.05). There was an elevation, in mean plasma AgRP concentrations (27.77±2.17) pg/ml in GII, comparing with mean plasma AgRP concentrations (25.84±1.93) pg/ml, in GI but it's statistically insignificant (P>0.05). There was a statistically significant inversely correlation between plasma leptin concentrations and plasma AgRP concentrations in GI (P<0.05). There was a proportionally correlation found between plasma leptin concentrations and plasma AgRP concentrations in (GII), but it's statistically insignificant (P>0.05). Conclusion: The relationship between plasma leptin concentrations and plasma AgRP concentrations affected by smoking cannabis, and that may change the mechanism of food intake in cannabis smokers.

Dependence Potential of the Synthetic Cannabinoids JWH-073, JWH-081, and JWH-210: In Vivo and In Vitro Approaches

Synthetic cannabinoids (CBs) such as the JWH series have caused social problems concerning their abuse liability. Because the JWH series produces euphoric and hallucinogenic effects, they have been distributed illegally under street names such as "Spice" and "Smoke". Many countries including Korea have started to schedule some of the JWH series compounds as controlled substances, but there are a number of JWH series chemicals that remain uncontrolled by law. In this study, three synthetic CBs with different binding affinities to the CB1 receptor (JWH-073, 081, and 210) and Delta9-tetrahydrocannabinol (Delta9-THC) were evaluated for their potential for psychological dependence. The conditioned place preference test (unbiased method) and self-administration test (fixed ratio of 1) using rodents were conducted. Ki values of the three synthetic cannabinoids were calculated as supplementary data using a receptor binding assay and overexpressed CB1 protein membranes to compare dependence potential with CB1 receptor binding affinity. All mice administered JWH-073, 081, or 210 showed significantly increased time spent at unpreferred space in a dose-dependence manner in the conditioned place preference test. In contrast, all tested substances except Delta9-THC showed aversion phenomenon at high doses in the conditioned place preference test. The order of affinity to the CB1 receptor in the receptor binding assay was JWH-210 > JWH-081 >> JWH-073, which was in agreement with the results from the conditioned place preference test. However, no change in self-administration was observed. These findings suggest the possibility to predict dependence potential of synthetic CBs through a receptor binding assay at the screening level.

The development of cannabidiol as a psychiatric therapeutic: a review of its antipsychotic efficacy and possible underlying pharmacodynamic mechanisms.

Cannabidiol (CBD), a once-considered inert cannabis constituent, is one of two primary constituents of cannabis, alongside delta-9-tetrahydrocannabinol (∆9-THC/THC). In the last 30 years, CBD has become implicated with a range of pharmaceutical mechanisms of great therapeutic interest and utility. This review details the literature speculating CBD’s attenuation of psychotic symptoms, particularly in light of a marked elevation in mean THC concentrations, and a concomitant decline in CBD concentrations in the prevalent U.K street market cannabis derivatives since c. 2000. CBD is purported to exhibit pharmacology akin to established atypical antipsychotics, whilst THC has been implicated with the precipitation of psychosis, and the induction of associated symptoms. The aim of the review was to clarify the conjecture surrounding CBD’s antipsychotic efficacy, before going on to detail prominent theories about its associated pharmacodynamics. Were CBD’s antipsychotic efficacy established, then there is potential for major latent anthropological repercussions to manifest, such as significant elevations in psychosis manifestations in the U.K. The review found a largely affirmative body of evidence asserting CBD’s antipsychotic efficacy. CBD exhibited capacity to attenuate natural and artificially induced psychoses in both animal and human cohorts, the latter of which included individuals considered resistant to conventional treatment. CBD also shows promising potential for use as an antipsychotic drug for Parkinson’s disease (PD) patients with psychosis, owing to its low rate of extra-pyramidal side-effect induction. A range of potential pharmacological mechanisms behind CBD’s neuroleptic pharmacology are outlined, with particular emphasis on its prevention of the hydrolysis and reuptake of the endogenous cannabinoid, anandamide. However, given the nebular aetiological basis for psychoses, explicit conclusions on how CBD attenuates psychotic symptoms remains to be determined.

Usos terapéuticos de sustancias prohibidas: LSD, MDMA, THC, GHB, DMT, psilocybina y mescalina / Therapeutic uses of prohibited substances: LSD, MDMA, THC, GHB, DMT, psilocybin, mescaline

El presente texto hace un breve recorrido sobre los usos terapéuticos que han tenido la LSD, MDMA, THC, GHB, DMT, Psilocybina y Mescalina en la historia, así como también refiere algunos de los beneficios para la salud física y mental que se considera tienen en la actualidad. Esta información científica se contrapone a la normativa internacional en materia de drogas, que las clasifica como sustancias prohibidas en la Lista I, debido a su falta de uso médico aceptado por Estados Unidos y a su alto potencial de abuso. En este trayecto también se intenta comprender a qué hace referencia dicho potencial, así como las motivaciones que podrían existir detrás de la prohibición del uso terapéutico de estas drogas. En este marco, se consideran consecuencias para la salud de la población, las que atentan contra los Derechos Humanos de las personas que podrían requerir alguna de estas sustancias.

This paper makes a brief of the therapeutic uses have had the LSD, MDMA, THC, GHB, DMT, Psilocybin and Mescaline in history, as well as some of the benefits referred to physical and mental health that are considered today. This scientific information seems contrary to international legislation on drugs, which classifies as prohibited substances in Schedule I, due to its lack of acceptance medical use by the United States and its high potential for abuse. In this way also try to understand what makes this potential reference, and the reasons that could be behind the ban on therapeutic use of these drugs. In this framework, we consider health consequences of the population, which violate the human rights of people who may require some of these substances.

3,4,5-Trihydroxycinnamic Acid Inhibits LPS-Induced iNOS Expression by Suppressing NF-kappaB Activation in BV2 Microglial Cells

Although various derivatives of caffeic acid have been reported to possess a wide variety of biological activities such as neuronal protection against excitotoxicity and anti-inflammatory property, the biological activity of 3,4,5-trihydroxycinnamic acid (THC), a derivative of hydroxycinnamic acids, has not been clearly examined. The objective of the present study is to evaluate the anti-inflammatory effects of THC on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. THC significantly suppressed LPS-induced excessive production of nitric oxide (NO) and expression of iNOS, which is responsible for the production of iNOS. THC also suppressed LPS-induced overproduction of pro-inflammatory cytokines such as IL-1beta and TNF-alpha in BV2 microgilal cells. Furthermore, THC significantly suppressed LPS-induced degradation of IkappaB, which retains NF-kappaB in the cytoplasm. Therefore, THC attenuated nuclear translocation of NF-kappaB, a major pro-inflammatory transcription factor. Taken together, the present study for the first time demonstrates that THC exhibits anti-inflammatory activity through the suppression of NF-kappaB transcriptional activation in LPS-stimulated BV2 microglial cells.

Hemocyte quantitative changes in Anticarsia gemmatalis (Lepidoptera: Noctuidae) larvae infected by AgMNPV

The initial effects of the infection by AgMNPV in the total and differential counts of the hemocytes in Anticarsia gemmatalis (Lepidoptera: Noctuidae) larvae were studied. The total number of the hemocytes did not decrease in infected larvae, as it occurred in non infected larvae. In infected larvae, the hemocyte types showed the following frequencies: plasmatocytes - 47.8 percent, esferulocytes - 25.9 percent, granulocytes - 15.8 percent, oenocytoids - 7.2 percent, prohemocytes - 2.8 percent, vermicytes - 0,5 percent. Only the percentage of the granulocytes was different among infected and non infected larvae, indicating that these cells responded quickly to the initial viral infection. These results showed the effective role of the hemocytes in the response of the A. gemmatalis to the infection by AgMNPV. The comprehension of the immunological mechanisms of this insect is an important tool to understand its biological control.

Os efeitos iniciais da infecção por AgMNPV nas contagens total e diferencial dos hemócitos em Anticarsia gemmatalis (Lepidoptera: Noctuidae) foram estudados. O número total de hemócitos não diminuiu nas larvas infectadas, como ocorreu nas larvas não infectadas. Nas larvas infectadas, os tipos de hemócitos apresentaram as seguintes freqüências: plasmatócitos - 47,8 por cento, esferulócitos - 25,9 por cento, granulócitos - 15,8 por cento, oenocitóides - 7,2 por cento, prohemócitos - 2,8 por cento, vermiformes - 0,5 por cento. Apenas a porcentagem de granulócitos foi diferente entre larvas infectadas e não infectadas, indicando que estas células responderam rapidamente à infecção viral inicial. Estes resultados mostraram o papel efetivo que dos hemócitos na resposta de A. gemmatalis à infecção por AgMNPV. A compreensão dos mecanismos imunológicos deste inseto é uma ferramenta importante para compreender seu controle biológico.

COX-2 modulates Δ~9-THC-induced inhibition of LTD in CA1 area / 西安交通大学学报(医学版)

Objective To explore the role of cyclooxgense-2 (COX-2) in tetrahydrocannabinol (THC)-induced inhibition of long-term depression (LTD) in CA1 area in vitro. Methods The hippocampal slices were prepared at 24 h after intraperitoneal injection of Δ~9-THC (10 mg/kg) or COX-2 inhibitor NS398 (10 mg/kg). Field excitatory post-synaptic potentials (fEPSP) were recorded in the stratum radiatum of the CA1 area in vitro to observe the effect of NS398, a selective inhibitor of COX-2, on the THC-induced inhibition of LTD and THC's effect on membrane excitability in pyramidal neurons by using the whole-cell patch clamp technique. Results ① Low-frequency stimulation (1 Hz, 15 min) induced-LTD in CA1 area was significantly attenuated by Δ9-THC. ② Δ~9-THC did not affect the basal synaptic transmission and membrane excitability (including membrane resting potentials, input resistance and firing property). ③ THC-induced inhibition of LTD was reversed by NS398. ④ THC-induced inhibition of LTD was robustly impaired in COX-2 knockout mice. Conclusion THC-induced inhibition of LTD in CA1 area was mediated via COX-2.

Avances en el tratamiento del síndrome de Tourette / Advances in the treatment of Tourette's syndrome

Tics are the hallmarks of a Tourette syndrome (TS). Dopamine receptor antagonists are the approved treatment, although neuroleptic treatment is often unsatisfactory due to side effects. Therefore, there is expanding interest in new therapeutic strategies. From anecdotal reports it has been suggested that Cannabis sativa L. might reduce tics. Two controlled studies in a small number of TS patients demonstrated that delta-9- tetrahydrocannabinol (THC), the most psychoactive ingredient of cannabis, is effective in the treatment of tics without causing serious adverse effects. In addition, no impairment in neuropsychological performance was observed. Therefore, THC should be added to the list of those drugs that are suitable to reduce tics. We recommend THC treatment in TS patients who did not respond to well-established drugs or develop significant side effects. So far, it is unclear, whether herbal cannabis, other natural or synthetic cannabinoid receptor agonists, or agents that interfere with the inactivation of endocannabinoids may have the best adverse effect profile in the treatment of tics. Available data suggest that the endogenous central cannabinoid CB1 receptor system might regulate motor activity in the basal ganglia. It, therefore, can be speculated that the CB1 receptor system might be involved in the pathophysiology of TS

Los tics son el sello distintivo del síndrome de Gilles de la Tourette (ST). Los antagonistas dopaminérgicos constituyen el tratamiento de elección aunque los neurolépticos frecuentemente presentan efectos colaterales poco satisfactorios. Por tanto, existe un creciente interés en obtener nuevos enfoques terapéuticos. Algunos informes anecdóticos sugirieron que Cannabis sativa podría disminuir los tics. Dos estudios controlados en un número pequeño de pacientes demostraron que el delta-9- tetrahidrocannabinol (THC) ­el ingrediente más psicoactivo de la marihuana­ fue efectivo para controlar los tics sin inducir efectos adversos serios. Además, no se observaron alteraciones del desempeño neuropsicológico. Por lo tanto, el THC debiera incorporarse al listado de fármacos útiles para el tratamiento de los tics. Nosotros recomendamos la utilización de esta molécula en los pacientes con ST que no respondieron al tratamiento con las drogas de referencia o presentaron efectos adversos significativos. Hasta el momento, no queda claro si la planta de cannabis, los agonistas naturales o sintéticos de los receptores cannabinoides o los agentes que interfieren con la inactivación de los endocannabinoides poseen el mejor perfil de efectos adversos en el tratamiento de los tics. Los datos disponibles sugieren que el sistema del receptor cannabinoide central endógeno CB1 podría regular la actividad motora de los ganglios de la base. Por lo tanto, se puede especular que este sistema de receptores podría estar relacionado con la fisiopatología del ST

COX-2 modulates ?~9-THC-induced inhibition of LTD in CA1 area / 西安交通大学学报(医学版)

Objective To explore the role of cyclooxgense-2(COX-2) in tetrahydrocannabinol(THC)-induced inhibition of long-term depression(LTD) in CA1 area in vitro.Methods The hippocampal slices were prepared at 24 h after intraperitoneal injection of ?9-THC(10 mg/kg) or COX-2 inhibitor NS398(10 mg/kg).Field excitatory post-synaptic potentials(fEPSP) were recorded in the stratum radiatum of the CA1 area in vitro to observe the effect of NS398,a selective inhibitor of COX-2,on the THC-induced inhibition of LTD and THC's effect on membrane excitability in pyramidal neurons by using the whole-cell patch clamp technique. Results ① Low-frequency stimulation(1 Hz,15 min) induced-LTD in CA1 area was significantly attenuated by ?9-THC.② ?9-THC did not affect the basal synaptic transmission and membrane excitability(including membrane resting potentials,input resistance and firing property).③ THC-induced inhibition of LTD was reversed by NS398.④ THC-induced inhibition of LTD was robustly impaired in COX-2 knockout mice.Conclusion THC-induced inhibition of LTD in CA1 area was mediated via COX-2.