Evaluation of Toxicity and Oxidative Stress of 2-Acetylpyridine-N(4)-orthochlorophenyl Thiosemicarbazone.

Thiosemicarbazones are well known for their broad spectrum of action, including antitumoral and antiparasitic activities. Thiosemicarbazones work as chelating binders, reacting with metal ions. The objective of this work was to investigate the in silico, in vitro, and in vivo toxicity and oxidative stress of 2-acetylpyridine-N(4)-orthochlorophenyl thiosemicarbazone (TSC01). The in silico prediction showed good absorption by biological membranes and no theoretical toxicity. Also, the compound did not show cytotoxicity against Hep-G2 and HT-29 cells. In the acute nonclinical toxicological test, the animals treated with TSC01 showed behavioral changes of stimulus of the central nervous system (CNS) at 300 mg/kg. One hour after administration, a dose of 2000 mg/kg caused depressive signs. All changes disappeared after 24 h, with no deaths, which suggest an estimated LD50 of 5000 mg/kg and GSH 5. The group treated with 2000 mg/kg had an increase of water consumption and weight gain in the second week. The biochemical parameters presented no toxicity relevance, and the analysis of oxidative stress in the liver found an increase of lipid peroxidation and nitric oxide. However, histopathological analysis showed organ integrity was maintained without any changes. In conclusion, the results show the low toxicological potential of thiosemicarbazone derivative, indicating future safe use.

Effect of p-cymene and rosmarinic acid on gastric ulcer healing - Involvement of multiple endogenous curative mechanisms.

BACKGROUND: p-Cymene and rosmarinic acid are secondary metabolites found in several medicinal plants and spices. Previous studies have demonstrated their anti-inflammatory, antioxidant, and cytoprotective effects. PURPOSE: To evaluate their gastroduodenal antiulcer activity, gastric healing and toxicity in experimental models. METHODS: Preventive antiulcer effects were assessed using oral pre-treatment on HCl/ethanol-induced gastric lesions and cysteamine-induced duodenal lesions models. Gastric healing, the underlining mechanisms and toxicity after repeated doses were carried out using the acetic acid-induced gastric ulcer rat model and oral treatment for 14 days. RESULTS: In the HCl/ethanol-induced gastric ulcer and cysteamine-induced duodenal injury, p-cymene and rosmarinic acid (50-200 mg/kg) decreased significantly the ulcer area, and so prevented lesions formation. In the acetic acid-induced ulcer model, both compounds (200 mg/kg) markedly reduced the ulcerative injury. These effects were related to an increase in the levels of reduced glutathione (GSH) and interleukin (IL)-10, and due to a decrease in malondialdehyde (MDA), IL-1ß, tumor necrosis factor (TNF)-α, total and mitochondrial reactive oxygen species (ROS) levels. Downregulation of factor nuclear kappa B (NFκB) and enhanced expression of suppressor of cytokine signaling (SOCS)3 were also demonstrated. Furthermore, positive vascular endothelial growth factor (VEGF), metalloproteinase (MMP)-2, and cyclooxygenase (COX-2)-stained cells were increased in treated groups. Treatment also upregulated the platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-ß and epidermal growth factor receptor (EGFR) in gastric tissues. In isolated gastric epithelial cells this healing effect seems to be linked to a modulation of apoptosis, proliferation, survival and protein phosphorylation, such as the extracellular signal-regulated kinases (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK). Oral toxicity investigation for 14 days revealed no alterations in heart, liver, spleen, and kidneys weight nor the biochemical and hematological assessed parameters. p-Cymene and rosmarinic acid also protected animals from body weight loss maintaining feed and water intake. CONCLUSIONS: Data altogether suggest low toxicity, antiulcer and gastric healing activities of p-cymene and rosmarinic acid. Antioxidant and immunomodulatory properties seem to be involved in the curative effect as well as the induction of different factors linked to tissue repair.

Non-clinical study of the anxiolytic effect of Citrus aurantium L. essential oil in an inclusion complex with 2-hydroxypropyl-ß-cyclodextrin

Anxiety in the world population has increased significantly; the problem has encouraged studies regarding innovative alternatives for treatment. Research with Citrus aurantium L. essential oil (CEO) has revealed positive results with anxiolytic effects in both animals and humans. However, certain limitations affect its storage and preservation, its efficiency in therapy, and determination of adequate posologies. The potential use of cyclodextrins as drug carriers has been successfully explored. This study aims to assess the anxiolytic potential of a CEO/2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex. Preparation of the inclusion complex was performed using the Alpha 1-2 LDplus lyophilizer. To allow formation, and avoid loss of volatiles to the atmosphere, Limonene (LIM), the main compound in CEO, together with HP-ß-CD in a molar ratio of (1: 1M) was dispersed in ethanol for 36 hours using a laboratory shaker at room temperature (25°C). Non-clinical murine pharmacological tests were performed for anxiety assessment in experimental and control groups. To assess anxiety and motor impairment, the animals were evaluated using the elevated plus maze, open field, and rota-rod tests. Satisfactory results of the anxiolytic effect of the OEC complexed in HP-ß-CD were observed, with the indication of an potentiation of the effect with doses lower than 500 mg/kg and 250 mg/kg complexed, suggesting improvement in the anxiolytic properties of the OEC.

Isopropyl Caffeate: A Caffeic Acid Derivative-Antioxidant Potential and Toxicity.

Phenolic compounds, among them isopropyl caffeate, possess antioxidant potential, but not without toxicity and/or adverse effects. The present study aimed to evaluate the antioxidant activity and toxicity of isopropyl caffeate through in silico, in vitro and in vivo testing. The results showed that isopropyl caffeate presents no significant theoretical risk of toxicity, with likely moderate bioactivity: GPCR binding, ion channel modulation, nuclear receptor binding, and enzyme inhibition. Isopropyl caffeate induced hemolysis only at the concentrations of 500 and 1000 µg/ml. We observed types A and O erythrocyte protection from osmotic stress, no oxidation of erythrocytes, and even sequestrator and antioxidant behavior. However, moderate toxicity, according to the classification of GHS, was demonstrated through depressant effects on the central nervous system, though there was no influence on water and food consumption or on weight gain, and it did present possible hepatoprotection. We conclude that the effects induced by isopropyl caffeate are due to its antioxidant activity, capable of preventing production of free radicals and oxidative stress, a promising molecule with pharmacological potential.

In Silico Study and Bioprospection of the Antibacterial and Antioxidant Effects of Flavone and Its Hydroxylated Derivatives.

Flavonoid compounds are widely used as natural protective species, which can act as anti-inflammatory, antioxidant, anticoagulant, antihypertensive and antitumor agents. This study set out to investigate the probable pharmacological activities, along with the antibacterial and antioxidant effects, of flavone and its hydroxy derivatives: 3-hydroxyflavone, 5-hydroxyflavone and 6-hydroxyflavone. To do so, we investigated their pharmacological characteristics, using in silico tests that indicate likelihood of activity or inactivity, with the PASS online software, and the antimicrobial potential against Gram positive and Gram negative bacteria was also analyzed, including bacteria of clinical importance. We also tested for oxidant and antioxidant potential in these molecules in the presence of reactive oxygen species (ROS) and phenylhydrazine (Ph). The results revealed the following characteristics: pharmacological activities for the flavonoids as agonists of cell membrane integrity and as permeability inhibitors, as antagonists of anaphylatoxin receptors, as inhibitors of both kinase and peroxidase, and as having both antimutagenic capacity and vaso-protective potential. All of the flavonoids exhibited moderate antibacterial activity against Gram positive and Gram negative strains, with the flavones being bactericidal at 200 µg/mL for the strains of P. aeruginosa ATCC 8027, S. aureus ATCC 25619 and E. coli 104; the other flavonoids revealed bacteriostatic action. The substances did not promote erythrocyte oxidation and behaved as sequestrators and antioxidants of hydrogen peroxide (H2O2) and phenylhydrazine (Ph). It was concluded that the analyzed compounds have various pharmacological activities in accordance with the predictions of PASS online, as their antibacterial and antioxidant activities were confirmed. The study also helps to consolidate the use of computational chemistry in silico tools to guide new drug search and discovery protocols.

Investigação oftalmológica pré-clínica do óleo essencial de Origanum vulgare L. Lamiaceae / Ophthalmological pre-clinical research about essential oil from the Origanum vulgare L. Lamiaceae

RESUMO Objetivo: Avaliar a irritação ocular aguda em coelhos, após a administração tópica de óleo essencial. Métodos: Para tanto, os animais foram divididos em três grupos, cada um com três coelhos, totalizando 6 olhos por grupo, e a diferença entre eles foi a concentração utilizada ( 1, 3 e 9%). Aplicou-se no saco conjuntival, de um dos olhos do animal, uma dose única de 0,1 ml do produto e o olho contralateral foi usado como controle. Analisou-se os efeitos causados pelo óleo essencial na conjuntiva, íris e córnea após 1, 24, 48, 72 horas e no final do sétimo dia após a aplicação tópica. As avaliações oftalmológicas foram feitas com o auxílio de um oftalmoscópio binocular indireto com e sem fluoresceína. As reações observadas foram graduadas segundo a escala de Draize. Foram realizados exames anatomopatológicos em todos os olhos estudados no final do experimento. Resultados: No grupo de animais submetidos à instilação ocular do óleo essencial a 1%, não se observou alterações. O tratamento com o óleo a 3% provocou alteração conjuntival no exame feito em 1 hora, o que foi reduzindo. A administração do óleo essencial a 9% induziu hiperemia conjuntival, não havendo qualquer alteração nos outros tempos de avaliação oftalmológica. Conclusão: A avaliação contribuiu para conhecer as alterações clínicas na superfície ocular. Desta forma, foi possível classificar o óleo a 1% como não irritante e nas concentrações de 3 e 9% como pouco irritante, tornando possível estudos clínicos, a fim de estabelecer o óleo como alternativa terapêutica em conjuntivites bacterianas.

ABSTRACT Objective: To evaluate acute eye irritation in rabbits following topical administration of essential oil. Methods: animals were divided into three groups, each containing three rabbits, with a total of 6 eyes per group. The difference between them was the concentration used (1, 3 and 9%). A single dose of 0.1 ml of the product was applied into the conjunctival sac of one eye of the animal, and the contralateral eye was used as control. The effects caused by the essential oil in the conjunctiva, iris and cornea were analyzed after 1, 24, 48 and 72 hours and at the end of the seventh day after topical application. Ophthalmologic evaluations were performed with the aid of a binocular indirect ophthalmoscope fluorescein and with and without the observed responses, before being graded according to the Draize scale. Pathological examinations were performed on all eyes studied at the end of the experiment. Results: in the group of animals subjected to the ocular instillation of 1% essential oil, there was no change. For treatment with 3% oil, conjunctival changes were found to be decreasing during the examination after 1 hour. Administration of the 9%essential oil induced conjunctival injection, without any change in the other ophthalmologic evaluation times. Conclusion: the evaluation contributed to meet the clinical changes in the ocular surface. Thus, it was possible to classify the oil at 1% as non-irritating and the concentration of 3% and 9 as mildly irritating, making it possible for clinical studies to establish the oil as an alternative therapy in bacterial conjunctivitis.

Iliac artery myointimal hyperplasia in rabbits submitted to angioplasty and treated with Moringa oleifera / Hiperplasia miointimal na artéria ilíaca em coelhos submetidos à angioplastia e tratados com Moringa oleifera

Objective: to assess post-angioplasty myointimal hyperplasia in iliac artery of rabbits treated with extract of Moringa oleifera leaves. Methods : we conducted a randomized trial in laboratory animals for five weeks of follow-up, developed in the Vivarium of Pharmaceutical Technology Laboratory of the Universidade Federal da Paraíba. We used rabbits from the New Zealand breed, subjected to a hypercholesterolemic diet and angioplasty of the external iliac artery, randomized into two groups: M200 Group (n=10) - rabbits treated with 200mg/kg/day of Moringa oleifera leaves extract orally; SF group (n=10) - rabbits treated with 0.9% saline orally. After five weeks, the animals were euthanized and the iliac arteries prepared for histology. Histological sections were analyzed by digital morphometry. Statistical analysis was performed using the Student's t test. The significance level was 0.05. Results : there was no significant difference in myointimal hyperplasia between M200 and SF groups when comparing the iliac arteries submitted to angioplasty. Conclusion : there was no difference of myointimal hyperplasia between groups treated with saline and Moringa oleifera after angioplasty.

Objetivo: determinar a diferença da média de hiperplasia miointimal pós-angioplastia na artéria ilíaca de coelhos tratados e não tratados com extrato das folhas de Moringa oleifera. Métodos: ensaio aleatório em animais de laboratório por cinco semanas de seguimento, desenvolvido no Biotério do Laboratório de Tecnologia Farmacêutica da Universidade Federal da Paraíba. Foram utilizadas coelhas da raça Nova Zelândia, submetidas à dieta hipercolesterolêmica e angioplastia da artéria ilíaca externa, randomizadas em dois grupos: Grupo M200 (n=10), coelhas tratadas com 200mg/kg/dia de extrato de folhas de Moringa oleifera, por via oral; Grupo SF (n=10), coelhas tratadas com soro fisiológico 0,9%, por via oral. Após cinco semanas, os animais foram eutanaziados e as artérias ilíacas preparadas para histologia. Os cortes histológicos foram analisados por morfometria digital. A análise estatística foi realizada com o teste t de Student. O nível de significância foi 0,05. Resultados: comparando as artérias ilíacas submetidas à angioplastia do grupo M200 com as do grupo SF, não houve diferença significativa da hiperplasia miointimal Conclusão: não houve diferença da hiperplasia miointimal nos grupos tratados com soro fisiológico e Moringa oleifera após angioplastia.

Anxiolytic Effect of Citrus aurantium L. on Patients with Chronic Myeloid Leukemia.

The bone marrow aspiration procedure is used in hematological diseases and consists of a painful, invasive procedure causing anxiety-associated symptoms. The present study assessed the effect of Citrus aurantium L. essential oil on the treatment of anxiety, in the moment that precedes the collection of medullary material in patients with chronic myeloid leukemia (CML). Volunteers from both sexes were divided into groups receiving either the C. aurantium essential oil through inhalation, diazepam (10 mg), or the placebo. The evaluation was performed through psychometric scales [State-Trait Anxiety Inventory (STAI)] and physiological measurements (blood pressure and cardiac and respiratory frequency). Inhalation of C. aurantium was associated with a decrease in the STAI-S scores, suggesting an anxiolytic effect. In support of these results, a change in all the physiological measurements was observed in the group exposed to C. aurantium. In the diazepam group, only the diastolic pressure decreased, and no effect was observed in the placebo group. Therefore, the results showed that C. aurantium exhibits an anxiolytic effect and reduces the signs and symptoms associated with anxiety in patients with CML.

Clinical safety evaluation of a tea containing Cissampelos sympodialis in healthy volunteers

ABSTRACTCissampelos sympodialis Eichler, Menispermaceae, is widely used by Indian tribes and folk medicine to treat various inflammatory disorders, including asthma. Clinical toxicological trials were made with the tea of C. sympodialis, a medicinal plant. The study took place at Lauro Wanderley Hospital/UFPB-PB, where seventeen healthy volunteers were chosen, among those six men and eleven women who orally ingested, during four weeks uninterruptedly, 150 ml of the tea, once a day. Before the first ingestion and after the last one, the participants were subjected to clinical and laboratorial tests for their overall conditions in order to analyze the toxicity of the plant. The results demonstrated that the volunteers neither experience clinical nor laboratorial alterations, as well as no significant adverse effects, apart from little change detected in their hematological tests. Nevertheless, none demonstrated any pathological conditions, just alterations of the normal human being physiology. Therefore, it is concluded that these data complement that obtained during pre-clinical studies and confirm a low toxicity of this plant.

Matrix effect and optimization of LC-MSn determination of trachylobane-360 in mice blood.

Xylopia langsdorffiana A. St.-Hil. & Tul. (Annonaceae) is popularly known as "pimenteira-da-terra". Various constituents have been isolated from this species, including diterpenes, such as 8(17), 12E, 14-labdatrien-18-oic acid, ent-atisan-7α, 16α-diol (xylodiol), ent-7α-hydroxytrachyloban-18-oic acid (trachylobane-318) and ent-7α-acetoxytrachyloban-18-oic acid, a crystalline solid with a molecular weight of 360 and molecular formula of C22H32O4 (trachylobane-360). When administered intraperitoneally to mice, trachylobane-360 (T-360) significantly inhibits growth of the solid tumor sarcoma 180 transplanted in mice, without causing alterations in biochemical, hematological and histopathological parameters that are frequently associated with the clinical use of antineoplastic. Furthermore, this diterpene blocks voltage-dependent calcium channels (Cav), showing spasmolytic activity. The present study shows that variables such as extraction solvent (methanol, acetonitrile and chloroform), centrifugation force (1000, 7000 and 14,000×g), and centrifugation time (5, 15 and 25min), are important in the liquid-liquid extraction of T-360 from male Swiss mice blood in HPLC-MSn studies. The study confirms matrix influence on recovery and detection of T-360. The recovery for T-360 was 37.02% using chloroform as better extractor solvent, while centrifuged at 14,000×g for 15min demonstrated the importance of the parameters chosen for the extraction/recovery process of analyte. The effect of mice blood matrix for T-360 was -51.23%. This method was optimized by repeating the extraction procedure and acidification of samples. These conditions were essential in increasing recovery (49.47%) by decreasing the matrix effect (-37.60%). The efficiency of the process, after optimization with two extractions and acidification, increased by 14.19% when compared to the initial method, from 18.05% to 32.24%. According to Marchi et al. (2010), the matrix effect does not necessarily need to be reduced or eliminated, but it does need to be identified and quantified. Therefore, these findings are essential for the subsequent evaluation of the pharmacokinetic parameters of this promising natural product.

Medicinal Plants and Other Living Organisms with Antitumor Potential against Lung Cancer.

Lung cancer is a disease with high morbidity and mortality rates. As a result, it is often associated with a significant amount of suffering and a general decrease in the quality of life. Herbal medicines are recognized as an attractive approach to lung cancer therapy with little side effects and are a major source of new drugs. The aim of this work was to review the medicinal plants and other living organisms with antitumor potential against lung cancer. The assays were conducted with animals and humans, and Lewis lung carcinoma was the most used experimental model. China, Japan, South Korea, and Ethiopia were the countries that most published studies of species with antitumor activity. Of the 38 plants evaluated, 27 demonstrated antitumor activity. In addition, six other living organisms were cited for antitumor activity against lung cancer. Mechanisms of action, combination with chemotherapeutic drugs, and new technologies to increase activity and reduce the toxicity of the treatment are discussed. This review was based on the NAPRALERT databank, Web of Science, and Chemical Abstracts. This work shows that natural products from plants continue to be a rich source of herbal medicines or biologically active compounds against cancer.

Relação Papilomavírus (HPV) eTumor Maligno da Cavidade Bucal / Relationship between Papillomavirus (HPV) and Oral Malignant Tumor

Este estudo tem o objetivo de revisar a literaturacientífica sobre o Papilomavírus humano (HPV). Material eMétodos: Foi consultada a base BVS com o descritorPapiloma vírus. Resultados: A literatura situa o HPV comovírus da família Papovaridae, alguns deles responsáveis porverrugas vulgares, anogenitais e ainda papilomas danasofaringe. O vírus possui um genoma de DNA de cadeiadupla combinado com histonas, que formam um complexosemelhante a um cromossoma, contido num capsídeo externode proteína virótica. O Papilomavírus humano (HPV) tem sidorelacionado ao desenvolvimento de tumores malignos emalgumas regiões que ocasionalmente costumam infectar,sendo os locais de maior incidência na mulher, o períneo,vulva, vagina, colo do útero e região anal; no homem afetamprincipalmente o pênis, uretra, saco escrotal e região anal.Além dessas áreas, estudos demonstraram a presença deHPV de alto risco e sua possível associação com ofavorecimento de lesões malignas na região da cavidadebucal e orofaringe. O seu potencial carcinogênico estáprovavelmente relacionado a duas proteínas virais, E6 e E7,as quais são capazes de interagirem com outras proteínasque regulam o ciclo celular. Conclusão: Nesta revisão podeser aferido que à medida que os conhecimentos sobre opapilomavírus humano (HPV) avançam, abrem-se novasperspectivas para entender e tratar adequadamente aslesões induzidas por este vírus. Entre os mais de 100 tiposde HPV já identificados conclui-se que cerca de 24 tiposforam associados com lesões bucais, sendo o HPV 16, omais prevalente tanto em lesões orais como genitais...

Objective: This study aims to review the scientific literatureabout the human papillomavirus (HPV). Material and Methods:Searches were carried out in the virtual library in healthdatabase using the descriptor papilloma virus. Results: HPVbelongs to Papovaridae family, whose some members areresponsible for common and anogenital warts, and alsonasopharynx papilloma. This virus has a genome of doublestrandedDNA combined with histones to form a complexsimilar to a chromosome contained in a foreign viral capsidprotein. HPV has been linked to the development of malignanttumors in some regions where infection usually occurs. Thehighest incidence sites in women are: perineum, vulva, vagina,cervix and anus; in men, it affects primarily the penis, urethra,scrotum and anus. In addition to these areas, studies haveshown the presence of high-risk HPV and its possibleassociation with the onset of malignant lesions in the oralcavity and oropharynx. Such potential carcinogenicity isprobably related to two viral proteins, E6 and E7, which arecapable of interacting with other proteins that regulate thecell cycle. Conclusion: This review shows that as theknowledge about the human papillomavirus (HPV) advances,new perspectives are opened to understand and properlyhandle the lesions induced by this virus. Among the morethan 100 types of HPV identified thus far, about 24 typeswere associated with oral lesions, being HPV type 16 themost prevalent one in both oral and genital lesions...

Toxicidade Aguda em Ratos Wistar Tratados com o Extrato Etanólico de Dioclea grandiflora Mart. Ex Benth (Fabaceae) (EEDg) / Acute Toxicity of Dioclea grandiflora Mart. Ex Benth (Fabaceae) Ethanolic Extract in Wistar Rats

Introdução: A Dioclea grandiflora, conhecido como Mucunã de caroço,atua sobre o Sistema Nervoso Central, doenças da próstata e pedrasnos rins. Objetivo: Realizar estudo toxicológico não clínico agudo, emratos, com base na Instrução Normativa nº4, de 18 de junho de 2014da Agência Nacional de Vigilância Sanitária (ANVISA). Material eMétodos: Foram utilizados ratos Wistar, ambos os sexos, dose 2000mg/kg, via oral, do extrato etanólico bruto de Dioclea grandifloraadministrado a um grupo tratado e um grupo controle (veículo). Apósa administração, os parâmetros de comportamento foi observado por30, 60, 90, 120, 180 e 240 minutos, consumo de ração e água,parâmetros hematológicos e bioquímicos. O número de sobreviventescontabilizados para determinar a DL50. Resultados: Houve aumentoestatisticamente significativo no consumo de água (Controle:160,4±5,85; Tratado: 201,3±8,55) e ração das fêmeas (Controle:95,98±3,02; Tratado: 113,1±2,42) e aumento estatisticamentesignificativo no consumo de água (Controle: 236,7±6,43; Tratado:267,5±8,72) e ração dos machos (Controle: 152,4±2,51; Tratado:177,64,15). Aumento estatisticamente significativo na albumina dosmachos (Controle: 3,2±0,08; Tratado: 3,6±0,08), nas fêmeas reduziuestatisticamente significativo a fosfatase alcalina (Controle:198,5±18,81; Tratado: 99,97±16,02) , proteína total (Controle:7,85±0,09; Tratado: 6,85±0,24) e globulinas (Controle: 4,28±0,14;Tratado: 3,27±0,27). Diminuiu estatisticamente significativo o númerode hemácias nas fêmeas (Controle: 10,18±0,28; Tratado: 9,62±0,18).Conclusão: De acordo com os resultados a DL50 foi superior à dosetestada, porém são necessários estudos toxicológicos de longa duraçãopara atestar a segurança de seu uso...

Introduction: Dioclea grandiflora, known as Mucunã de caroço, acts onthe central nervous system, and against prostate disease and kidneystones. Objective: To perform a nonclinical acute toxicology study inrats following the Normative Instruction #4 as of June 18th 2014 of theNational Health Surveillance Agency (ANVISA). Material and Methods:Wistar rats of both sexes were used in the study. A dose of 2000 mg/kg of Dioclea grandiflora ethanolic extract was administered orally tothe test group. A control group using only the vehicle was also included.Then behavioral parameters were monitored for 30, 60, 90, 120, 180,and 240 minutes after feed and water intake, along with hematologicaland biochemical parameters. The number of survivors was recordedto determine the LD50. Results: There was a statistically significantincrease in water (Control: 160.4 ± 5.85; Treated: 201.3 ± 8.55), andfeed intake (Control: 95.98 ± 3.02; Treated: 113.1 ± 2.42) for femalerats; and a statistically significant increase in water (Control: 236.7 ±6.43; Treated: 267.5 ± 8.72) and feed intake (Control: 152.4 ± 2.51;Treated: 177.6 ± 4.15) for males. A statistically significant increase inalbumin levels was observed for males (Control: 3.2 ± 0.08; Treated:3.6 ± 0.08), and a decrease in alkaline phosphatase (Control: 198.5 ±18.81; Treated: 99.97 ± 16.02), total protein (Control: 7.85 ± 0.09;Treated: 6.85 ± 0.24) and globulin (Control: 4.28 ± 0.14; Treated: 3.27± 0.27) was found for females. Also, in females the number of redblood cells was found to be significantly reduced (Control: 10.18 ±0.28; Treated: 9.62 ± 0.18). Conclusion: According to the results, theLD50 value found was higher than that of the tested dose. Howeverlong-term toxicology studies are needed to further prove the safetyof the extract...

In vitro and in vivo antitumor effect of trachylobane-360, a diterpene from Xylopia langsdorffiana.

Trachylobane-360 (ent-7α-acetoxytrachyloban-18-oic acid) was isolated from Xylopia langsdorffiana. Studies have shown that it has weak cytotoxic activity against tumor and non-tumor cells. This study investigated the in vitro and in vivo antitumor effects of trachylobane-360, as well as its cytotoxicity in mouse erythrocytes. In order to evaluate the in vivo toxicological aspects related to trachylobane-360 administration, hematological, biochemical and histopathological analyses of the treated animals were performed. The compound exhibited a concentration-dependent effect in inducing hemolysis with HC50 of 273.6 µM, and a moderate in vitro concentration-dependent inhibitory effect on the proliferation of sarcoma 180 cells with IC50 values of 150.8 µM and 150.4 µM, evaluated by the trypan blue exclusion test and MTT reduction assay, respectively. The in vivo inhibition rates of sarcoma 180 tumor development were 45.60, 71.99 and 80.06% at doses of 12.5 and 25 mg/kg of trachylobane-360 and 25 mg/kg of 5-FU, respectively. Biochemical parameters were not altered. Leukopenia was observed after 5-FU treatment, but this effect was not seen with trachylobane-360 treatment. The histopathological analysis of liver and kidney showed that both organs were mildly affected by trachylobane-360 treatment. Trachylobane-360 showed no immunosuppressive effect. In conclusion, these data reinforce the anticancer potential of this natural diterpene.

Zumbido e ansiedade: uma revisão da literatura / Tinnitus and anxiety: a literature review

O zumbido, som percebido pelo indivíduo sem que haja estímulo externo, resulta da interação dinâmica de centros do sistema nervoso central, incluindo vias auditivas e não auditivas. O resultado desta interação, especialmente sistema límbico e sistema nervoso autônomo, seria responsável pelo desencadeamento de associações emocionais negativas e reações de incômodo em pacientes com zumbido. A ansiedade, condição fisiológica inerente ao ser humano, quando exacerbada gera um transtorno de humor, comprometendo o pensamento, o comportamento e a atividade psicológica. Se um estímulo interno ou externo for interpretado como perigoso ou ameaçador, desencadeará uma reação emocional caracterizada como estado de ansiedade. Este artigo tem como objetivo realizar uma revisão da literatura sobre a relação do zumbido e da ansiedade. Em se tratando do zumbido, a forma como o som é percebido pode ser alterado pela ansiedade, aguçando assim a sensibilidade para detectar sons que parecem uma ameaça em potencial, pois para muitos o zumbido é sinônimo de enfermidade grave. A etiologia do desenvolvimento da depressão e ansiedade pode estar relacionada ao zumbido. Muitos adquirem esse sintoma por problemas físicos e, consequentemente, desenvolvem a depressão e a ansiedade. Outros com graus diferentes de angústias adquirem o zumbido devido ao comprometimento emocional. Dessa forma, existe um vínculo entre o zumbido e problemas emocionais, mas nem sempre é fácil identificar o precursor. Estudos demonstram que pacientes acometidos pelo zumbido apresentam maior tendência ao suicídio, depressão e ansiedade. Além disso, referem o efeito aditivo da ansiedade e da depressão na qualidade de vida e no zumbido dos indivíduos.

Tinnitus is a sound perceived without external stimulus, and results from the dynamic interaction of the centers in the central nervous system, including non-auditory and auditory ways. The result of this interaction, especially with the limbic system and autonomic nervous system, would be responsible for triggering negative emotional associations and distress in patients with tinnitus. Anxiety, a physiological condition inherent to human beings, when exacerbated, generates a mood disorder, affecting thinking, behavior and physiological activity. If an inner or outer stimulus is interpreted as dangerous or threatening, it may trigger an emotional reaction characterized as a state of anxiety. This work aims to review the relationship between tinnitus and anxiety. The tinnitus sound is perceived can be altered by anxiety, thereby, sharpening the sensitivity in detecting sounds that seem a potential threat, because for many people, tinnitus is synonymous with a serious illness. The etiology for the development of depression and anxiety may be related to tinnitus. Many people acquire this symptom by physical problems and hence develop depression and anxiety. Others with different degrees of distress due to tinnitus acquire emotional problems. Thus, there is a probable link between tinnitus and emotional problems, but it is not always easy to identify which one occurs first. Studies show that patients affected by tinnitus have a greater trend for suicide, depression and anxiety. They also refer to the additive cumulative effects of anxiety and depression on the quality of life of tinnitus sufferers.

Gestão de estoque: proposta para umafarmácia diferenciada / Inventory management: a proposal for a differentiatedpharmacy

Diante da competitividade crescente, a gestão de estoques é necessária para evitar os altos custos com os produtos, diminuir o capital total investido pela empresa no estoque, além de evitar a falta de produtos para os clientes. Este trabalho visa a trazer uma abordagem teórico-prática a respeito da gestão de estoque de medicamentos, tendo como exemplo uma farmácia do Serviço de Atenção à Saúde (SAS). A metodologia aplicada consistiu em três partes. A primeira foi uma pesquisa bibliográfica para a construção do modelo teórico; a segunda foi o estudo de caso na farmácia do SAS; e a terceira etapa referiu-se a propostas de melhorias para uma gestão de estoque de qualidade dos medicamentos, com o objetivo de garantir o acesso da população a medicamentos seguros e eficazes. Na farmácia estudada, não havia uma padronização dos procedimentos realizados, desencadeando a falta de critérios técnicos, que impossibilitou a realização dos cálculos necessários para o controle de estoque de qualidade, sendo necessária a realização de uma contagem dos produtos existentes, para servir de ponto de partida do trabalho. Este trabalho indicou duas propostas de gestão de estoque: as fichas de prateleiras, que são ferramentas mais simples e a um custo acessível de serem executadas, e o programa de gerenciamento de materiais. Deve existir regulamentação dos procedimentos operacionais padrões entre estudantes e funcionários e estabelecer-se a divisão de trabalho com as devidas responsabilidades.

In an increasingly competitive market, the management of medication supplies is needed to avoid the high costs of pro-ducts, reduce the total capital invested by the company, and avoid a lack of products to clients. This study aims to bring a practical-theoretical approach regarding the management of medication supplies, having as an example a pharmacy of the Health Care Service (SAS). The methodology consisted in three parts: first a literature search was done to construct the theoretical model, then we did a case study in the SAS pharmacy and in the third stage we examined proposals for improvements in order to reach a quality management of medicine supplies for offering the population access to safe and effective medicines. At the pharmacy studied, there was not procedures standardization, causing a lack of technical crite-ria, which precluded the calculations required for quality inventory control, and this made necessary to count the existing products before beginning the study. This study proposed two proposals for inventory management: the form of shelves, which are more simple tools requiring fewer expenses to be executed, and material management program. There should be rules for standard operating procedures for both students and staff and the establishment of the division of labor with appropriate responsibilities for each.

Atualizações e Perspectivas na Miastenia gravis / Updates and Perspectives on myasthenia gravis

Este estudo teve como objetivo uma buscabibliográfica sobre a Miastenia gravis (MG). Metodologia: Apesquisa bibliográfica foi realizada nas bases de dadoseletrônicos Pubmed, Science Direct, Scielo e Bireme dosúltimos dez anos, além de outros artigos que apresentavamextrema relevância histórica. Resultados: MG é uma doençaauto-imune caracterizada por fraqueza muscular, cujapatogenia está relacionada com a destruição da transmissãoneuromuscular por diferentes mecanismos, como diminuiçãodos receptores nicotínicos de acetilcolina, destruição dasproteínas envolvidas com a formação neuromuscular ou pelaatuação de anticorpos contra uma proteína quinase específicado músculo (MUSK). O tratamento atual da MG se baseia nautilização de inibidores da acetilcolinesterase, corticosteróides,timectomia, imunosupressores, imunoglobulinaintravenosa e plasmaferese. A identificação precoce da MGe de seus fatores precipitantes torna esta patologia maisacessível a novas modalidades de tratamento, comoanticorpos monoclonais, prolactina, tracolimus e crotamina.Conclusão: O melhor conhecimento acerca de seusmecanismos moleculares tem proporcionado o desenvolvimentode novas opções terapêuticas, necessárias paraamenizar crises severas, levando a um prognósticoadequado. Novas descobertas poderão contribuir para aqualidade de vida dos pacientes, ocasionando remissão dadoença e não apenas amenizando os seus sintomas...

This study aimed to a search the literature onmyasthenia gravis (MG). Methodology: Literature search wasconducted in the electronic databases PubMed, ScienceDirect, Scielo and Bireme, in the last ten years, and otherarticles that had extreme historical importance were alsoincluded. Results: MG is an autoimmune diseasecharacterized by muscle weakness, whose pathogenesisis related to the destruction of neuromuscular transmissionby different mechanisms, such as decreased nicotinicacetylcholine receptors, destruction of proteins involved inthe neuromuscular formation or the activity of antibodies ona specific muscle protein kinase (MUSK). The current treatmentof MG is based on the use of acetylcholinesterase inhibitors,corticosteroids, thymectomy, immunosuppressants,intravenous immunoglobulin and plasmapheresis. Earlyidentification of MG and its precipitating factors make thisdisease more accessible to new treatment modalities suchas monoclonal antibodies, prolactin, and tacrolimus crotamine.Conclusion: A better knowledge about molecular mechanismshas provided the development of new therapeutic optionsnecessary to alleviate severe crises, leading to a properprognosis. New findings may contribute to the quality of lifeof patients, resulting in remission of the disease and not justin relieving its symptoms...

Parâmetros bioquímicos e hematológicos de ratos wistar e camundongos swiss do biotério professor Thomas George / Biochemical and hematological parameters of wistar rats and swiss mice in the professor Thomas George animal laboratory

Objetivo: Este trabalho teve como objetivo estabelecer valores de referência de parâmetros bioquímicos e hematológicos de roedores provenientes do Biotério Professor Thomas George do Laboratório de Tecnologia Farmacêutica (LTF) da Universidade Federal da Paraíba(UFPB). Metodologia: Avaliaram-se o perfil hematológico,hemograma, contagem de plaquetas, e a determinação bioquímica de vários constituintes plasmáticos: glicose, uréia,creatinina, colesterol total, triglicerídeos, ácido úrico,proteínas totais e frações, fosfatase alcalina, transaminases,sódio, potássio, cálcio e magnésio. Foram utilizados ratos Wistar albinos e camundongos Swiss, adultos, pesando 150a 350g e 15 a 35g, respectivamente, totalizando 40 para cada espécie animal (20 machos e 20 fêmeas). Resultados:Algumas variações foram detectadas entre os valores obtidos nos animais investigados e os parâmetros da literatura. Nos ratos, observaram-se valores inferiores para leucócitos e eosinófilos, e para camundongos obtiveram-se valores elevados para plaquetas, AST, ALT, fosfatase alcalina, globulina, íons cálcio e magnésio, em comparação com dados na literatura. Conclusão: Portanto, é importante oconhecimento e a divulgação dos valores de parâmetros fisiológicos dos animais de experimentação, considerando que podem exibir variações influenciadas por vários fatores que devem ser levados em consideração nas pesquisas experimentais, como sexo, linhagem e genótipo.

Objective: The objective of the present study was to establish reference values for the biochemical and hematological parameters of rodents from the Professor Thomas George animal laboratory of the Pharmaceutical Technology Laboratory, Federal University of Paraíba. Methodology: The parameters evaluated consisted of hematological profile withfull blood and platelet counts, as well as serum components including glucose, urea, creatinine, total cholesterol, triglycerides, uric acid, total protein and protein fractions, alkaline phosphatase, transaminases, sodium, potassium, calcium and magnesium. Adult albino Wistar rats and Swissmice (20 males and 20 females of each species), weighing150-350 grams and 15-35 grams, respectively, were used inthe study. Results: Variations were detected between values obtained in the animals and parameters established in theliterature. In rats, leukocyte and eosinophile counts werelower, while in mice, platelet counts, AST, ALT, alkalinephosphatase, globulin, calcium and magnesium levels werehigher compared to data published in the literature. Conclusion: In conclusion, the physiological parameters of experimental animals should be well established and made available in view of the variations that may exist as a result of various factors such as sex, lineage and geno type of the rodents that must be taken into consideration in experimental studies.

Azaphenanthrene alkaloids with antitumoral activity from Anaxagorea dolichocarpa Sprague & Sandwith (Annonaceae).

Phytochemical investigation of Anaxagorea dolichocarpa Sprague & Sandwith led to isolation of three azaphenanthrene alkaloids: eupolauramine, sampangine and imbiline 1. Their chemical structures were established on the basis of spectroscopic data from IR, HR-ESI-MS, NMR (including 2D experiments) and comparison with the literature. Sampangine and imbiline 1 are being described in the Anaxagorea genus for the first time. Eupolauramine and sampangine show concentration-dependent antitumoral activity in leukemic cells K562 with IC(50) of 18.97 and 10.95 µg/mL, respectively.

Analgesic effect of hydroalcoholic extract of Cissampelos sympodialis Eichl leaves / Efecto analgésico del extracto hidroalcoholico de las hojas de Cissampelos sympodialis Eichl

Cissampelos sympodialis Eichl is a species of the family Meniespermaceae known as “Milona”, which extracts showed low toxicity and several pharmacological activities as anti-inflammatory, anti-allergic or anti-depressive. In the present study two classic analgesia models in mice were used to evaluate the hydroalcoholic extract of C. sympodialis leaves (HAECs) at doses of 50, 100 and 200 mg/kg, i.p. In the test of writhing by acetic acid HAECs- treatment induced a significant reduction in the number of abdominal contortions in a dose-dependent manner (p <0,05). In the formalin test, HAECs-200 mg/kg induced a significant inhibition of the second phase (15-30 minutes) (p <0,05). Results suggest that the HAECs presented outlying antinociceptive peripheral activity probably related with the alleged anti-inflammatory proprieties of extracts of this plant.

Existen varios estudios que evidencian que la Cissampelos sympodialis posee atividad anti-inflamatoria, antialérgica, antidepresiva y de baja toxicidad. Este estudio evaluó los efectos de la administración intraperitoneal, del extracto hidroalcohólico de hojas de cissampelos sympodialis (EHACS), en las dosis de 50, 100 y 200 mg/Kg, en modelos de analgesia en camumdongos. En el modelo de las contracciones inducidas por el ácido acético (0,85 por ciento) fue encontrada una reducción en el número de contracciones proporcional a las dosis usadas (p<0,05). En el test de la reacción al formaldeído las dosis utilizadas no presentaron efecto significante en la primera fase del test (0-5 minutos). Sin embargo, la dosis de 200mg/Kg presentó una significante inhibición en la segunda fase (15 – 30 minutos) del test (p<0,05). Los resultados mostraron que el EHACS presentó una actividad antinociceptiva periférica probablemente relacionada con la alegada actividad anti-inflamatoria.