Melatonin decreases cocaine-induced locomotor activity in pinealectomized rats

Objective: Several studies have shown that the time of day regulates the reinforcing effects of cocaine. Additionally, melatonin and its MT1 and MT2 receptors have been found to participate in modulation of the reinforcing effects of such addictive drugs as cocaine. Loss of the diurnal variation in cocaine-induced locomotor sensitization and cocaine-induced place preference has been identified in pinealectomized mice. In addition, several studies in rodents have shown that administration of melatonin decreased the reinforcing effects of cocaine. The objective of this study was to evaluate the effect of melatonin on cocaine-induced locomotor activity in pinealectomized rats at different times of day (zeitgeber time [ZT]4, ZT10, ZT16, and ZT22). Methods: Naïve, pinealectomized Wistar rats received cocaine at different times of day. Melatonin was administered 30 min before cocaine; luzindole was administered 15 min prior to melatonin and 45 min before cocaine. After administration of each treatment, locomotor activity for each animal was recorded for a total of 30 min. Pinealectomy was confirmed at the end of the experiment through melatonin quantitation by ELISA. Results: Cocaine-induced locomotor activity varied according to the time of day. Continuous lighting and pinealectomy increased cocaine-induced locomotor activity. Melatonin administration decreased cocaine-induced locomotor activity in naïve and pinealectomized rats at different times of day. Luzindole blocked the melatonin-induced reduction in cocaine-induced locomotor activity in pinealectomized rats. Conclusion: Given its ability to mitigate various reinforcing effects of cocaine, melatonin could be a useful therapy for cocaine abuse.

Tapentadol: Can It Kill Two Birds with One Stone without Breaking Windows?

Tapentadol is a novel oral analgesic with a dual mode of action as an agonist of the µ-opioid receptor (MOR), and as a norepinephrine reuptake inhibitor (NRI) all in a single molecule. Immediate release (IR) tapentadol shows its analgesic effect quickly, at around 30 minutes. Its MOR agonistic action produces acute nociceptive pain relief; its role as an NRI brings about chronic neuropathic pain relief. Absorption is rapid, with a mean maximal serum concentration at 1.25-1.5 h after oral intake. It is present primarily in the form of conjugated metabolites after glucuronidation, and excretes rapidly and completely via the kidneys. The most common adverse reactions are nausea, dizziness, vomiting, and somnolence. Constipation is more common in use of the ER formulation. Precautions against concomitant use of central nervous system depressants, including sedatives, hypnotics, tranquilizers, general anesthetics, phenothiazines, other opioids, and alcohol, or use of tapentadol within 14 days of the cessation of monoamine oxidase inhibitors, are advised. The safety and efficacy have not been established for use during pregnancy, labor, and delivery, or for nursing mothers, pediatric patients less than 18 years of age, and cases of severe renal impairment and severe hepatic impairment. The major concerns for tapentadol are abuse, addiction, seeking behavior, withdrawal, and physical dependence. The presumed problem for use of tapentadol is to control the ratio of MOR agonist and NRI. In conclusion, tapentadol produces both nociceptive and neuropathic pain relief, but with worries about abuse and dependence.

Ethanol during adolescence decreased the BDNF levels in the hippocampus in adult male Wistar rats, but did not alter aggressive and anxiety-like behaviors / O etanol durante a adolescência reduziu os níveis de BDNF no hipocampo de ratos Wistar machos adultos, mas não alterou os comportamentos agressivos e a ansiedade

Objective:To investigate the effects of ethanol exposure in adolescent rats during adulthood by assesssing aggression and anxiety-like behaviors and measuring the levels of inflammatory markers.Methods:Groups of male Wistar rats (mean weight 81.4 g, n = 36) were housed in groups of four until postnatal day (PND) 60. From PNDs 30 to 46, rats received one of three treatments: 3 g/kg of ethanol (15% w/v, orally, n = 16), 1.5 g/kg of ethanol (12.5% w/v, PO, n = 12), or water (n = 12) every 48 hours. Animals were assessed for aggressive behavior (resident x intruder test) and anxiety-like behaviors (elevated plus maze) during adulthood.Results:Animals that received low doses of alcohol showed reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus as compared to the control group. No significant difference was found in prefrontal cortex.Conclusions:Intermittent exposure to alcohol during adolescence is associated with lower levels of BDNF in the hippocampus, probably due the episodic administration of alcohol, but alcohol use did not alter the level agression toward a male intruder or anxiety-like behaviors during the adult phase.

Objetivo: Investigar os efeitos da exposição ao etanol em ratos adolescentes durante a idade adulta sobre os comportamentos agressivos e semelhantes à ansiedade, bem como sobre as medidas de níveis de marcadores inflamatórios.Métodos:Os grupos de ratos Wistar machos (peso médio de 81,4 g; n = 36) foram alojados em grupos de quatro até o dia pós-natal (DPN) 60. Entre os DPNs 30 e 46, os ratos receberam um dos três tratamentos: 3 g/kg de etanol (15% w/v, oralmente, n = 16), 1.5 g/kg de etanol (12,5% w/v, oralmente, n = 12), ou água (n = 12) a cada 48 horas. Os comportamentos agressivos (teste residente-intruso) e semelhantes à ansiedade (labirinto em cruz elevado) foram avaliados durante a idade adulta dos animais.Resultados:Os animais que receberam doses menores de álcool mostraram níveis reduzidos de fator neurotrófico derivado do cérebro (BDNF) no hipocampo quando comparados ao grupo controle. Nenhuma diferença significativa foi verificada no córtex pré-frontal.Conclusões:A exposição intermitente ao álcool durante a adolescência é associada com menores níveis de BDNF no hipocampo, provavelmente divido a administração episódica de álcool, mas o uso não alterou o nível de agressão contra o macho intruso ou os comportamentos semelhantes à ansiedade durante a fase adulta.

A review on alcohol: from the central action mechanism to chemical dependency / Uma revisão sobre o álcool: do mecanismo de ação central à dependência química

SummaryIntroduction:alcohol is a psychotropic depressant of the central nervous system (CNS) that promotes simultaneous changes in several neuronal pathways, exerting a profound neurological impact that leads to various behavioral and biological alterations.Objectives:to describe the effects of alcohol on the CNS, identifying the signaling pathways that are modified and the biological effects resulting from its consumption.Methods:a literature review was conducted and articles published in different languages over the last 15 years were retrieved.Results:the studies reviewed describe the direct effect of alcohol on several neurotransmitter receptors (gamma-aminobutyric acid [GABA], glutamate, endocannabinoids AEA and 2-AG, among others), the indirect effect of alcohol on the limbic and opioid systems, and the effect on calcium and potassium channels and on proteins regulated by GABA in the hippocampus.Discussion and conclusion:the multiple actions of alcohol on the CNS result in a general effect of psychomotor depression, difficulties in information storage and logical reasoning and motor incoordination, in addition to stimulating the reward system, a fact that may explain the development of addiction. Knowledge on the neuronal signaling pathways that are altered by alcohol allows the identification of effectors which could reduce its central action, thus, offering new therapeutic perspectives for the rehabilitation of alcohol addicts.

ResumoIntrodução:o álcool é uma substância psicotrópica depressora do sistema nervoso central (SNC), que promove alteração simultânea de inúmeras vias neuronais, gerando profundo impacto neurológico e traduzindo-se em diversas alterações biológicas e comportamentais.Objetivos:descrever as ações do álcool sobre o SNC, identificando as vias de sinalização modificadas e os efeitos biológicos gerados pelo seu consumo.Métodos:revisão bibliográfica, priorizando trabalhos multilinguísticos publicados nos últimos 15 anos.Resultados:são descritas ação direta do álcool em inúmeros receptores de neurotransmissores (ácido gama-aminobutírico – GABA, glutamato, endocanabinoides AEA e 2-AG, entre outros), ação indireta do álcool no sistema límbico e opioide, ação sobre canais de cálcio, potássio e proteínas reguladas por GABA no hipocampo, além de ações centrais mediadas pela deficiência de vitamina B1.Conclusão:a ação multifocal do álcool sobre o SNC resulta em efeito geral de depressão psicomotora, dificuldades no armazenamento de informações e no raciocínio lógico, incoordenação motora, além da estimulação do sistema de recompensa, o que pode explicar o desenvolvimento da dependência química. O conhecimento das vias de sinalização neuronais alteradas pelo álcool permite reconhecer a descrição de efetores que possam reduzir sua ação central e, assim, vislumbrar novas perspectivas terapêuticas para a reabilitação de adictos a essa substância.

Effects of estrogen deficiency combined with chronic alcohol consumption on rat mandibular condyle

Estrogen deficiency and chronic alcohol consumption may have a synergistic and deleterious effect on bone tissue. AIM: To investigate the effects of estrogen deficiency associated with chronic alcohol consumption on the mandibular condyle in rats. METHODS: Fifty-four female rats were first divided equally into two groups: ovariectomized Ovx and simulated ovariectomy Sham. One month after the surgeries, these groups were equally sub-divided according to their dietary treatment: G1: Sham/ad-libitum diet; G2: Sham/alcohol; G3: Sham/isocaloric; G4: Ovx/ad-libitum diet; G5: Ovx/alcohol, G6: Ovx/isocaloric. Eight weeks after starting the diets, all animals were anesthetized and sacrificed. The condyles were analyzed histologically, histomorphometrically, and immunohistochemically using the antibodies for bone sialoprotein BSP, osteocalcin OCC and receptor activator of nuclear factor kappa-B ligand RANKL. RESULTS: Histological analysis of the mandibular condyles showed that Ovx and Sham groups presented almost the same characteristics. The histomorphometric analysis showed that there was a statistically significant difference only between Ovx/isocaloric and Ovx/ad-libitum groups p=0.049. No difference was observed in the intensity of BSP, OCC, and RANKL antibody staining between the Ovx/alcohol and the other groups. CONCLUSIONS: It may be concluded that there was no histomorphometric, histological, or RANKL, BSP, and OCC staining differences between the Ovx/alcohol group and other experimental groups...

Alveolar bone loss induced by chronic ethanol consumption from adolescence to adulthood in Wistar rats.

Though there are literature indicating the bone loss due to alcohol consumption, studies on the association between ethanol consumption and periodontal breakdown in animals are either scarce or have provided conflicting results. Here, we investigated the effects of chronic alcohol exposure from adolescence to adulthood on the alveolar bone in rats. Wistar rats were exposed to ethanol (6.5 g/kg/day) in a solution of 22.5% (w/v) or distilled water (control) by gavage from 35 days of age (adolescent) until 90 days (adulthood). Evaluation of the bone loss was performed using scanning electronic microscopy, in which the distances between the cement-enamel junction and the alveolar bone crest from the palatal side of the first molar mandibular were measured. The measurements obtained were tabulated and analyzed using Student’s t-test. Alcohol-treated group revealed greater bone loss in comparison to the control group. These findings indicate that heavy chronic alcohol exposure from adolescent to adulthood can induce alveolar bone loss in rats associated to absence of periodontitis.

Isolation of compound and CNS depressant activities of Mikania scandens Willd with special emphasis to brain biogenic amines in mice.

Mikania scandens, a twining herb that grows as a weed in India and Bangladesh is used as vegetables and is a good source of vitamin A, C, B complex, mikanin, sesquiterpenes, betasitosterin, stigmasterol and friedelin. The present communication reports CNS depressant activities with special emphasis to brain biogenic amines in mice. Ethanol extract of leaves of M. scandens (EEMS) was prepared by Soxhalation and analyzed chemically. EEMS potentiated sleeping time induced by pentobarbitone, diazepam and meprobamate and showed significant reduction in the number of writhes and stretches. EEMS caused significant protection against pentylene tetrazole-induced convulsion and increased catecholamines and brain amino acids level significantly. Results showed that EEMS produced good CNS depressant effects in mice.

Rutin ameliorates glycemic index, lipid profile and enzymatic activities in serum, heart and liver tissues of rats fed with a combination of hypercaloric diet and chronic ethanol consumption.

Alcoholism and obesity are strongly associated with several disorders including heart and liver diseases. This study evaluated the effects of rutin treatment in serum, heart and liver tissues of rats subjected to a combination of hypercaloric diet (HD) and chronic ethanol consumption. Rats were divided into three groups: Control: rats fed a standard diet and drinking water ad libitum; G1: rats fed the HD and receiving a solution of 10% (v/v) ethanol; and G2: rats fed the HD and ethanol solution, followed by injections of 50 mg/kg-1 rutin as treatment. After 53 days of HD and ethanol exposure, the rutin was administered every three days for nine days. At the end of the experimental period (95 days), biochemical analyses were carried out on sera, cardiac and hepatic tissues. Body weight gain and food consumption were reduced in both the G1 and G2 groups compared to control animals. Rutin effectively reduced the total lipids (TL), triglycerides (TG), total cholesterol (TC), VLDL, LDL-cholesterol and glucose levels, while it increased the HDL-cholesterol in the serum of G2 rats, compared to G1. Although rutin had no effect on total protein, albumin, uric acid and cretinine levels, it was able to restore serum activities of alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) in animals fed HD and receiving ethanol. Glycogen stores were replenished in both hepatic and cardiac tissues after rutin treatment. Moreover, rutin consistently reduced hepatic levels of TG and TC and cardiac AST, ALT and CK activities. Thus, rutin treatment was effective in reducing the risk factors for cardiac and hepatic disease caused by both HD and chronic ethanol consumption.

Synthesis and biological evaluation of some novel furan derivatives

The present work involved cyclization of Schiff bases to azetidine-2-one and thiazolidine 4-one derivatives. The schiff bases [IIIa-j] were obtained upon reaction between electrophillic carbon atom of furfuraldehyde and nucleophillic nitrogen atom of amines. Azetidine-2-one derivatives [IVa-j] were obtained by reaction between imines and monochloro acetyl chloride in the presence of triethyl amine and 1, 4 dioxan. On the other hand, preparations of thiazolidine-4-ones [Va-j] were preceded by nucleophilic attack of sulphur of thioglycolic acid on imine carbon followed by intramolecular cyclization in the presence of SnCl[2]. The structures of the compounds were confirmed by spectral and elemental analysis. The biological evaluation of the compounds like anti-microbial, antioxidant, analgesic, CNS depressant and anti-diabetic activity were determined. From the pharmacological investigation it was found that out of all the compounds IVa, IVb, IVe, IVf, IVh,Va, Vb, Ve, Vf, Vh had shown more potent activity

Host-Microbiome Interactions in Alcoholic Liver Disease

Alcoholic liver disease is a leading cause of morbidity and liver-related death worldwide. Intestinal bacterial overgrowth and dysbiosis induced by ethanol ingestion play an important role in the pathogenesis of alcoholic liver disease. After exposure to alcohol in the lumen, enteric bacteria alter their metabolism and thereby disturb intestinal homeostasis. Disruption of the mucosal barrier results in the translocation of microbial products that contribute to liver disease by inducing hepatic inflammation. In this review, we will discuss the effects of alcohol on the intestinal microbiome, and in particular, its effects on bacterial metabolism, bacterial translocation and ecological balance. A better understanding of the interactions among alcohol, the host and the microbiome will reveal new targets for therapy and lead to new treatments.

Central nervous system activity of Illicium verum fruit extracts

OBJECTIVE@#To research the acute toxicity of Illicium verum (I. verum) fruit extracts and its action on central nervous system.@*METHODS@#The TLC and HPTLC techniques were used as fingerprints to determine the chemical components present in I. verum. Male albino rats and mice were utilized for study. The powdered material was successively extracted with n-hexane, ethyl acetate and methanol using a Soxhlet extractor. Acute toxicity studies were performed as per OECD guidelines. The CNS activity was evaluated on parameters of general behavior, sleeping pattern, locomotor activity, anxiety and myocoordination activity. The animals were trained for seven days prior to experiments and the divided into five groups with six animals in each. The drug was administered by intraperitoneal route according to body weight. The dosing was done as prescribed in each protocol.@*RESULTS@#Toxicity studies reported 2 000 mg/kg as toxicological dose and 1/10 of the same dose was taken as therapeutic dose Intraperitoneal injection of all extracts at dose of 200 mg prolonged phenobarbitone induced sleeping time, produced alteration in general behavior pattern, reduced locomotor activity and produced anxiolytic effects but the extracts do not significantly alter muscles coordination activity. The three extracts of I. verum at the dose of 200 mg, methanol extract was found to produce more prominent effects, then hexane and ethylacetate extracts.@*CONCLUSIONS@#The observation suggested that the extracts of I. verum possess potent CNS depressant action and anxiolytic effect without interfering with motor coordination.

Coma blisters after poisoning caused by central nervous system depressants: case report including histopathological findings / Bolhas do coma pós-intoxicação por depressores do sistema nervoso central: relato de caso incluindo achados histopatológicos

Blister formation and eccrine sweat gland necrosis is a cutaneous manifestation associated with states of impaired consciousness, most frequently reported after overdoses of central nervous system depressants, particularly phenobarbital. The case of a 45-year-old woman who developed "coma blisters" at six distinct anatomic sites after confirmed (laboratory) phenobarbital poisoning, associated with other central nervous system depressants (clonazepam, promethazine, oxcarbazepine and quetiapine), is presented. A biopsy from the left thumb blister taken on day 4 revealed focal necrosis of the epidermis and necrosis of sweat gland epithelial cells; direct immunofluorescence was strongly positive for IgG in superficial blood vessel walls but negative for IgM, IgA, C3 and C1q. The patient was discharged on day 21 with no sequelae.

Formação de bolhas e necrose de glândula sudoríparas écrinas é uma manifestação cutânea associada com estados de diminuição da consciência, mais frequentemente relatada após superdosagens de depressores do sistema nervoso central, particularmente fenobabital. Relatamos o caso de uma paciente de 45 anos que desenvolveu "bolhas do coma" após tentativa de suicídio por fenobarbital (confirmada laboratorialmente), associada a outros depressores do sistema nervoso central (clonazepam, prometazina, oxcarbazepina e quetiapina). Biópsia da bolha do 1o quirodáctilo esquerdo no 4o dia de internação revelou necrose focal da epiderme e necrose de células epiteliais de glândula sudorípara; a imunofluorescência direta foi fortemente positiva para IgG na parede superficial dos vasos sanguíneos, mas negativa para IgM, IgA, C3 e C1q. A paciente teve alta no 21o dia, sem seqüelas.

Pharmacological evaluation of Antidesma ghaesembilla Gaertn fruits for central nervous system depressant activity / Evaluación farmacológica de frutos de Antidesma ghaesembilla Gaertncomo depresores del sistema nervioso central

The objective of this study is to investigate the anxiolytic and sedative activities of the methanol and chloroform extracts of Antidesma ghaesembilla fruits at the dose of 400 mg/kg bw using rodent behavioral models such as thiopental sodium-induced sleeping time, hole cross method and open field process for sedative and its anxiolytic activity was evaluated using the elevated plus maze (EPM) methods. In case of thiopental sodium-induced sleeping time, both extracts exhibited dose dependent suppression of motor activity, exploratory behavior (in open field and hole cross method) and prolongation of thiopental sodium-induced sleeping time in mice, where maximum effect was shown by the methanol extract. In EPM test, the methanolic extract significantly increased exploration to and time spent by the treated mice in EPM open arms in a way similar to that of diazepam, but the chloroform extract was found to produce moderate activity. These significant results may justify the scientific basis for use of this plant in traditional medicine as a modality for anxiety and related disorders.

El objetivo de este estudio fue la investigación de las actividades ansiolíticas y sedantes de los extractos clorofórmicos y metabólicos de los frutos de Antidesma ghaesembilla a las dosis de 400 mg/kg pp utilizando modelos de comportamiento de roedores, tales como el tiempo de sueño inducido por tiopental sódico, el método de “hole cross” (cruce de un agujero) y el campo abierto para evaluar sedación, y la actividad ansiolítica fue evaluada utilizando el método del laberinto elevado (elevated plus maze, EPM). En el caso del sueño inducido por tiopental sódico, ambos extractos exhibieron una supresión dosis dependiente de la actividad motora, de la actividad exploratoria (en el método de campo abierto y “hole cross”) y prolongación del tiempo de inducción de sueño inducido por tiopental en ratones, con efectos máximos mostrados para el extracto metabólico. En el ensayo de EPM, el extracto metabólico aumentó significativamente el tiempo de exploración y el tiempo consumido en el laberinto de una manera similar al diazepam, pero el extracto clorofórmico se encontró que produjo solo una moderada actividad. Estos resultados significativos pueden justificar una base científica para el uso de plantas en medicina tradicional para tratar la ansiedad y desórdenes relacionados.

Effect of moderate ethanol administration on biochemical indices in streptozotocin-diabetic Wistar rats / Efecto de la administración moderada de etanol sobre los índices bioqumicos en ratas Wistar diabéticas por estreptozotocina

OBJECTIVE: This study was designed to evaluate the effect of moderate ethanol administration on the biochemical indices in streptozotocin (STZ)-diabetic rats. METHODS: Twenty-four male Wistar rats were divided into four groups of six animals each. Groups one and two contained non-diabetic normal rats and normal rats treated with ethanol, respectively. Group three was untreated STZ-diabetic rats and group four was made up of ethanol-treated STZ-diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (35 mg/kg), while ethanol (10%v/v) was given at a dose 2 g/kg thrice per week for three weeks. After the last dose of ethanol and an overnight fasting, rats were sacrificed by cervical dislocation. Blood was collected by syringe from the heart into plain centrifuge tubes. RESULTS: Moderate ethanol administration to STZ-diabetic rats caused a significant (p < 0. 05) increase in relative weight of liver relative to normal. Ethanol intake in STZ-diabetic rats produced an insignificant (p > 0. 05) effect on the levels of fasting blood glucose (FBG) and HbA1c rrelative to the untreated-diabetic group. Moderately, ethanol administration to STZ-diabetic rats produced a marked and significant (p < 0. 05) increase in the levels of serum total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol and the activities of alanine aminotransferase relative to untreated diabetic rats. Ethanol-treated diabetic rats had significantly (p < 0. 05) lower high-density lipoprotein (HDL)-cholesterol levels, while the activities of lactate dehydrogenase and α-amylase were insignificantly (p > 0. 05) affected. There were no significant (p > 0. 05) differences in all the biochemical indices in normal rats relative to ethanol-treated normal rats. CONCLUSIONS: Moderate ethanol administration did not affect FBG and HbA1c , but altered the lipid profile of STZ-diabetic rats. Moderate ethanol intake may further increase the risk of complications in diabetes.

OBJETIVO: Este estudio se diseñó con el propósito de evaluar el efecto del uso de etanol moderado sobre los índices bioquímicos en ratas Wistar diabéticas por estreptozotocina (STZ). MÉTODOS: Veinticuatro ratas Wistar machos fueron divididas en cuatro grupos de seis animales cada uno. Dos de los grupos tenían ratas normales no diabéticas y ratas normales tratadas con etanol, respectivamente. El tercer grupo estaba formado por ratas diabéticas por STZ no tratadas, y el cuarto por ratas diabéticas por STZ tratadas con etanol. La diabetes fue inducida mediante una inyección intraperitoneal de STZ (35 mg/kg), mientras que el etanol (10% v/v) fue administrado en dosis de 2 g/kg tres veces por semana durante tres semanas. Tras la última dosis de etanol y un ayuno de una noche, las ratas fueron sacrificadas mediante dislocación cervical. La sangre fue recogida del corazón con jeringuillas e introducida en tubos para centrífuga sin graduación. RESULTADOS: La administración moderada de etanol a ratas diabéticas por STZ, causó un aumento significativo (p < 0.05) en el peso relativo del hígado con relación al normal. La ingestión de etanol en ratas diabéticas por STZ tuvo un efecto insignificante (p > 0.05) en los niveles de glucosa en sangre en ayuno (GSA) y HbA1c en relación con grupos diabéticos no tratados. En medida moderada, la administración de etanol a ratas diabéticas por STZ produjo un aumento marcado y significativo (p < 0.05) en los niveles de colesterol total en suero, triglicéridos, el colesterol asociado con las lipoproteínas de baja densidad, o colesterol LDL, y la actividad de la aminotransferasa alanina en relación con las ratas diabéticas no tratadas. Las ratas diabéticas tratadas con etanol tuvieron niveles significativamente disminuidos de colesterol asociado con las lipoproteínas de alta densidad, o colesterol HDL, en tanto que la actividad del lactato deshidrogenasa y la α-amilasa no fue afectada significativamente (p > 0.05). No hubo diferencias significativas (p > 0.05) en todos los índices bioquímicos en las ratas normales con respecto a las ratas normales tratadas con etanol. CONCLUSIONES: El suministro moderado de etanol no afectó el GSA ni el HbA1c , pero alteró el perfil lípido de las ratas diabéticas por STZ. La ingestión moderada de etanol puede aumentar a un más el riesgo de las complicaciones de la diabetes.

Chemical constituents and pharmacological properties of capsule gurmar, a new anti-diabetes formulation of Hamdard laboratories [Waqf] Bangladesh

Capsule Gurmar is a new polyherbal Unani formulation developed by the R and D Department of Hamdard Laboratories [Waqf] Bangladesh for management and treatment of diabetes. The chemical constituents and analgesic, antioxidant, cytotoxic, neuropharmacological and hypoglycemic properties of the formulation have been preliminarily investigated using standard methods. We report here the results of these investigations. Phytochemical tests on the methanol extract of the contents of the capsules showed the presence of carbohydrates, glycosides, saponins, steroids, flavonoids, alkaloids and tannins in the formulation. When tested by using Tail-immersion method and acetic acid-induced Writhing test, the extract exhibited significant analgesic activity [comparable to that of the standard drug, Diclofenac-Sodium] and reduction of writhing response [38% at a dose of 400 mg/Kg body weight] in a dose-dependant manner. In the Hole cross and Open-field tests, the extract, at a dose of 400 mg/Kg body weight, displayed significant suppression of locomotor activity and exploratory behaviour of the mice. When subjected to Brine shrimp Lethality Bioassay, the extract was found to be significantly toxic to Brine shrimp nauplii [having LC[50] value of 3.16 micro g/ml]. Glucose Tolerance Test [GTT] demonstrated quite strong hypoglycemic activity of the Formulation, which significantly lowered the blood glucose level of the treated mice at the doses of 100 mg and 200 mg/Kg body weight. The effect was comparable to that of the standard oral hypoglycemic drug, Metformin Hydrochloride. These results indicated that Capsule Gurmar possesses analgesic, antioxidant, cytotoxic, CNS depressant and hypoglycemic properties

Advance of pharmacological studies on Valeriana jatamansi / 中国中药杂志

As a traditional Chinese medicine, Valeriana jatamansi has a long history of application in China. It is widely distributed and commonly adopted by many ethnic groups. In particular, its roots have a wide range of medicinal value. With the increasingly more attention on it from domestic and foreign researchers, there have been more and more studies on its pharmacological activity and mechanism. This essay summarizes domestic and foreign reports on its pharmacological activity and mechanism.

Melatonin in Chagas´ disease: Possible therapeutic value / La melatonina en la enfermedad de Chagas: Su posible valor terapéutico

Chagas' disease is a severe health problem in Latin America, causing approximately 50 000 deaths a year, with approximately 18 million infected people. About 25-30% of the patients infected with Trypanosoma cruzi develop the chronic form of the disease. The protective response against T. cruzi depends on both innate and acquired immunity involving macrophages, natural killer cells, T and B lymphocytes, and the production of proinflammatory Th-1 cytokines. In addition, an increased nitric oxide (NO) production in macrophages leading to effective microbicidal action is needed to control parasitemia. Melatonin is detectable in T. cruzi and may play a role in promoting infection whereas, when administered in high doses during the acute phase of T. cruzi infection, it can decrease parasitemia while reducing NO production. During chronic disease progression, the sustained oxidative stress concomitant to myocardial damage could be reduced by administering melatonin. It is hypothesized that the coordinated administration of a melatonin agonist like the MT1/MT2 agonist ramelteon, that lacks antioxidant activity and may not affect NO production during the acute phase, and of melatonin in doses high enough to decrease oxidative damage, to preserve mitochondrial and to prevent cardiomyopathy during the chronic phase, could be a novel add-on treatment of Chagas´ disease.

La enfermedad de Chagas es un problema grave de salud en América Latina, causando cerca de 50 000 muertes al año y unos 18 millones de infectados. Alrededor del 25-30% de los pacientes infectados con Trypanosoma cruzi desarrollan la forma crónica de la enfermedad. La respuesta de defensa ante el T. cruzi depende de la inmunidad innata y adquirida con la participación de macrófagos, células “natural killer”, linfocitos T y B, y la producción de citoquinas proinflamatorias de tipo Th-1. Además, el aumento en la producción de óxido nítrico (NO) en los macrófagos lleva a una acción microbicida eficaz necesaria para controlar la parasitemia. La melatonina es detectable en T. cruzi y podría desempeñar un papel en la promoción de la infección como lo hace en el paludismo, mientras que, cuando se administra en dosis farmacológicas altas durante la fase aguda de la infección por T. cruzi, disminuye la parasitemia, aun en presencia de una reducción de la producción de NO. Durante la progresión de la enfermedad de Chagas a la cronicidad, el estrés oxidativo aumentado con el concomitante daño miocárdico podría reducirse por la administración de melatonina, de reconocida acción antioxidante. Se propone como un nuevo enfoque complementario en el tratamiento de la enfermedad de Chagas la administración durante la fase aguda de un agonista MT1/MT2 de la melatonina como el ramelteon, que carece de actividad antioxidante y podría no afectar a la producción de NO, y de melatonina durante la fase crónica de en dosis suficientemente altas como para disminuir el daño oxidativo y prevenir la miocardiopatía.

Potential of Pandanus odoratissimus as a CNS depressant in Swiss albino mice / Potencial de Pandanus odoratissimus como um depressor do sistema nervoso central em camundongos Swiss albinos

In this study, several neuropharmacological effects of methanolic leaf extract of Pandanus odoratissimus (PO) (family; Pandanaceae) were studied in albino mice using various experimental models. The effect of PO on the CNS was studied by using different neuropharmacological paradigms including spontaneous motor activity, rota-rod performance and potentiation of Pentobarbital sodium sleeping time in albino mice. Preliminary phytochemical evaluation and acute toxicity studies were also carried out where LD50 >2000 mg/kg was considered non-toxic through acute exposure in rats by the oral route. The methanolic leaf extract (50,100 and 200 mg/kg i. p.) produced a reduction in spontaneous motor activity, motor coordination and prolonged Pentobarbital sodium sleeping time. Preliminary qualitative chemical studies indicated the presence of steroids, saponins, terpinoids, glycosides, tannins, flavonoids and phenolics in the extract. These observations suggest that the leaf of Pandanus odoratissimus contains some active principles which possess potential CNS-depressant action.

Estudaram-se alguns efeitos neurofarmacológicos do extrato metanólico de Pandanus odoratissimus (PO) (família Pandanaceae) em camundongos albinos, usando vários modelos experimentais. O efeito do PO no SNC foi estudado por meio de diferentes paradigmas neurofarmacológicos, como atividade motora espontânea, desempenho na haste rotatória e a potenciação do tempo de sono em camundongos albinos pelo pentobarbital sódico. A avaliação fitoquímica preliminar e os estudos de toxicidade aguda foram realizados e a DL50 >2000 mg/kg é considerada não tóxica, por meio da exposição aguda, por via oral, em ratos. O extrato metanólico de folha (50,100 e 200 mg/kg i. p.) produziu redução da atividade motora espontânea, da coordenação motora e tempo prolongado de sono pelo pentobarbital sódico. Estudos químicos qualitativos preliminares indicaram a presença de esteróide, saponinas, terpenóides, glicosídios, taninos, flavonóides e fenólicos no extrato. As observações sugerem que a folha de Pandanus odoratissimus contém alguns princípios ativos com atividade potencial como depressores do SNC.

Prenatal exposure to tobacco and alcohol are associated with chronic daily headaches at childhood: A population-based study / Tabagismo e ingestão alcoólica pré-natal estão associados à cefaleia crônica diária na infância: um estudo de base populacional

The influence of prenatal events on the development of headaches at childhood has not been investigated and is the scope of our study. Of 2,173 children identified as the target sample, consents and analyzable data were provided by 1,440 (77 percent). Parents responded to a standardized questionnaire with a validated headache module and specific questions about prenatal exposures. Odds of chronic daily headache (CDH) were significantly higher when maternal tabagism was reported. When active and passive smoking were reported, odds ratio (OR) of CDH were 2.29 [95 percent confidence intervals (CI)=1.6 vs. 3.6)]; for active tabagism, OR=4.2 (95 percent CI=2.1-8.5). Alcohol use more than doubled the chance of CDH (24 percent vs. 11 percent, OR=2.3, 95 percent CI=1.2-4.7). In multivariate analyses, adjustments did not substantially change the smoking/CDH association. Prenatal exposure to tobacco and alcohol are associated with increased rates of CDH onset in preadolescent children.

A influência de eventos pré-natais na fisiopatogenia das cefaleias na infância ainda não foi investigada e é o objetivo desse estudo. Da amostra-alvo de 2.173 crianças, um consentimento pós-informado e dados suficientes para as análises foram obtidos de 1.440 (77 por cento). Os pais responderam a um questionário padrão com um módulo de cefaleia validado na população brasileira e questões específicas sobre antecedentes pré-natais. O risco de cefaleia crônica diária (CCD) foi significativamente maior nas crianças cujas mães fumaram durante a gestação. Quando presentes tabagismo ativo e passivo, o risco (OR) de CCD foi de 2,29 [intervalo de confiança (IC) de 95 por cento=1,6-3,6)]; para tabagismo ativo, OR=4,2 (IC 95 por cento=2,1-8,5). O uso de álcool durante a gestação dobrou o risco de CCD (24 por cento vs. 11 por cento, OR=2,3, IC 95 por cento=1,2-4,7). Nas análises multivariadas, os ajustes não modificaram, substancialmente a associação entre tabagismo materno durante a gestação e CCD. A exposição pré-natal ao tabaco e ao álcool encontra-se associada à CCD de início na infância.