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Acta cir. bras ; 33(6): 524-532, June 2018. graf
Article in English | LILACS | ID: biblio-949352


Abstract Purpose: To evaluate in vivo animal model of cardiac ischemia/reperfusion the cardioprotective activity of pancreatic lipase inhibitor of the orlistat. Methods: Adult male Wistar rats were anesthetized, placed on mechanical ventilation and underwent surgery to induce cardiac I/R by obstructing left descending coronary artery followed by reperfusion to evaluation of ventricular arrhythmias (VA), atrioventricular block (AVB) and lethality (LET) with pancreatic lipase inhibitor orlistat (ORL). At the end of reperfusion, blood samples were collected for determination of triglycerides (TG), very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase-MB (CK-MB). Results: Treatment with ORL has been able to decrease the incidence of VA, AVB and LET. Besides that, treatment with ORL reduced serum concentrations of CK and LDL, but did not alter the levels of serum concentration of TG, VLDL and HDL. Conclusion: The reduction of ventricular arrhythmias, atrioventricular block, and lethality and serum levels of creatine kinase produced by treatment with orlistat in animal model of cardiac isquemia/reperfusion injury suggest that ORL could be used as an efficient cardioprotective therapeutic strategy to attenuate myocardial damage related to acute myocardial infarction.

Animals , Male , Cardiotonic Agents/pharmacology , Myocardial Reperfusion Injury/prevention & control , Lactones/pharmacology , Myocardial Infarction/prevention & control , Arrhythmias, Cardiac/prevention & control , Triglycerides/blood , Myocardial Reperfusion Injury/blood , Random Allocation , Reproducibility of Results , Risk Factors , Treatment Outcome , Rats, Wistar , Creatine Kinase/blood , Electrocardiography , Atrioventricular Block/prevention & control , L-Lactate Dehydrogenase/blood , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Lipoproteins, VLDL/blood , Myocardial Infarction/blood
J. appl. oral sci ; 26: e20170065, 2018. graf
Article in English | LILACS, BBO | ID: biblio-893689


Abstract Considering oral diseases, antibiofilm compounds can decrease the accumulation of pathogenic species such as Streptococcus mutans at micro-areas of teeth, dental restorations or implant-supported prostheses. Objective To assess the effect of thirteen different novel lactam-based compounds on the inhibition of S. mutans biofilm formation. Material and methods We synthesized compounds based on γ-lactones analogues from rubrolides by a mucochloric acid process and converted them into their corresponding γ-hydroxy-γ-lactams by a reaction with isobutylamine and propylamine. Compounds concentrations ranging from 0.17 up to 87.5 μg mL-1 were tested against S. mutans. We diluted the exponential cultures in TSB and incubated them (37°C) in the presence of different γ-lactones or γ-lactams dilutions. Afterwards, we measured the planktonic growth by optical density at 630 nm and therefore assessed the biofilm density by the crystal violet staining method. Results Twelve compounds were active against biofilm formation, showing no effect on bacterial viability. Only one compound was inactive against both planktonic and biofilm growth. The highest biofilm inhibition (inhibition rate above 60%) was obtained for two compounds while three other compounds revealed an inhibition rate above 40%. Conclusions Twelve of the thirteen compounds revealed effective inhibition of S. mutans biofilm formation, with eight of them showing a specific antibiofilm effect.

Streptococcus mutans/drug effects , Biofilms/drug effects , beta-Lactams/pharmacology , Lactones/pharmacology , Anti-Bacterial Agents/pharmacology , Plankton/growth & development , Plankton/drug effects , Streptococcus mutans/growth & development , Microscopy, Electron, Scanning , Colony Count, Microbial , Microbial Sensitivity Tests , Reproducibility of Results , Analysis of Variance , Biofilms/growth & development , beta-Lactam Resistance/drug effects , beta-Lactams/chemical synthesis , Dose-Response Relationship, Drug , Microbial Viability/drug effects , Gentian Violet , Lactones/chemical synthesis , Anti-Bacterial Agents/chemical synthesis
Rev. biol. trop ; 64(3): 945-954, jul.-sep. 2016. tab, ilus
Article in English | LILACS | ID: biblio-958186


Abstract:The expanded use of macrocyclic lactones (ML) to treat endo- and ectoparasites in cattle in tropical regions, can reduce dung beetle populations, and thus interrupt the dung removal process in cattle pasture ecosystems. During the reproductive period (the rainy season) of two functional groups of dung beetles (paracoprid and telocoprid Scarabaeinae), we compared dung removal amount in ranches where ML are and are not used in Yucatan, Mexico, through exclusion traps baited with 500 g of ML-free cow dung. On each ranch, two transects (separated by 500 m) with six traps each, were set up for 24 hours. After this time, all the dung remnants in each trap were obtained and weighed in order to record the dung removal. Results showed that dung removal amounts were similar in ranches with and without ML use. Dung beetles removed 40.1 % of all cow dung weighed. Paracoprids removed 87.46 % and telocoprids 12.54 % of all the dung that was removed. Our results indicated that the ecological function of dung beetles in the pastures studied, does not seem to be affected by the ML use, and that paracoprid species removed most of the dung. For both types of ranch, further studies that take into account the population dynamics and movement of the most important dung beetle species in the region are required, coupled with laboratory studies evaluating the effect of ML on their reproductive success. This could give some light on the effect of ML on the ecological function of this important insect group in the sustainability of cattle production systems. Rev. Biol. Trop. 64 (3): 945-954. Epub 2016 September 01.

ResumenLa expansión en el uso de lactonas macrocíclicas (LM) para el tratamiento de endo y ectoparásitos del ganado en las regiones tropicales puede reducir las poblaciones de escarabajos del estiércol, interrumpiendo así el proceso de eliminación de estiércol de ganado en los pastizales. Durante el período reproductivo (época de lluvias) de dos grupos funcionales de escarabajos coprófagos (paracópridos y telecópridos), se comparó la cantidad removida de estiércol usando trampas de exclusión cebadas con 500 g de estiércol de vaca libre de LM en dos ranchos donde se usan y en dos donde no se usan LM, en la península de Yucatán, México. En cada rancho se establecieron dos transectos (separados por 500 m) con seis trampas cada uno, las cuales estuvieron activas durante 24 horas. Después de este tiempo, todos los restos de estiércol en cada trampa se pesaron para registrar la remoción. Los resultados mostraron que las cantidades de remoción fueron similares en ranchos con y sin uso de LM. Los escarabajos estercoleros removieron 40.1 % del peso total del excremento. Los paracópridos removieron 87.46 % y los telecópridos 12.54 % del total de excremento removido. Los resultados indican que la función ecológica de los escarabajos estercoleros en los potreros estudiados no parece verse afectada por el uso de LM y que las especies paracórpidas remueven la mayor parte del excremento. Se requiere hacer más estudios en ambos tipos de ranchos, en los que se tome en cuenta la dinámica poblacional y el movimiento de las especies más importantes de la región, acoplados a estudios de laboratorio que evalúen el efecto de las LM sobre el éxito reproductivo, y de esta manera esclarecer el efecto de las LM sobre la función ecológica de este grupo de insectos tan importante para la sustentabilidad de los sistemas ganaderos.

Animals , Coleoptera/drug effects , Coleoptera/physiology , Macrocyclic Compounds/pharmacology , Lactones/pharmacology , Manure , Antiparasitic Agents/pharmacology , Rain , Seasons , Species Specificity , Time Factors , Cattle , Mexico
J. appl. oral sci ; 24(3): 271-277, graf
Article in English | LILACS, BBO | ID: lil-787548


ABSTRACT Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants used in traditional medicine for the treatment of inflammatory diseases and other ailments. Objective In this study, we evaluated whether budlein A modulates the activation of innate and adaptive immune cells such as neutrophils and lymphocytes. Material and Methods Our research group has investigated several plant species and several compounds have been isolated, identified, and their medical potential evaluated. Budlein A is a SL isolated from the species Aldama buddlejiformis and A. robusta (Asteraceae) and shows anti-inflammatory and anti-nociceptive activities. Advances in understanding how plant-derived substances modulate the activation of innate and adaptive immune cells have led to the development of new therapies for human diseases. Results Budlein A inhibited MPO activity, IL-6, CXCL8, IL-10, and IL-12 production and induces neutrophil apoptosis. In contrast, budlein A inhibited lymphocyte proliferation and IL-2, IL-10, TGF-β, and IFN-γ production, but it did not lead to cell death. Conclusions Collectively, our results indicate that budlein A shows distinct immunomodulatory effects on immune cells.

Humans , Male , Female , Adult , Middle Aged , Sesquiterpenes/pharmacology , T-Lymphocytes/drug effects , Lactones/pharmacology , Anti-Inflammatory Agents/pharmacology , Neutrophils/drug effects , Enzyme-Linked Immunosorbent Assay , Transforming Growth Factors/analysis , Transforming Growth Factors/drug effects , Cells, Cultured , Reproducibility of Results , Analysis of Variance , Interleukin-8/analysis , Interleukin-8/drug effects , Interleukins/analysis , Apoptosis/drug effects , Peroxidase/analysis , Peroxidase/drug effects , Asteraceae/chemistry , Cell Proliferation/drug effects , Flow Cytometry
Rev. latinoam. enferm ; 23(2): 329-336, Feb-Apr/2015. graf
Article in English | LILACS, BDENF | ID: lil-747176


OBJECTIVE: to analyze the socio-familial and community inclusion and social participation of people with disabilities, as well as their inclusion in occupations in daily life. METHOD: qualitative study with data collected through open interviews concerning the participants' life histories and systematic observation. The sample was composed of ten individuals with acquired or congenital disabilities living in the region covered by a Family Health Center. The social conception of disability was the theoretical framework used. Data were analyzed according to an interpretative reconstructive approach based on Habermas' Theory of Communicative Action. RESULTS: the results show that the socio-familial and community inclusion of the study participants is conditioned to the social determinants of health and present high levels of social inequality expressed by difficult access to PHC and rehabilitation services, work and income, education, culture, transportation and social participation. CONCLUSION: there is a need to develop community-centered care programs in cooperation with PHC services aiming to cope with poverty and improve social inclusion. .

OBJETIVO: analisar a inclusão sociofamiliar e comunitária e a participação social de pessoas com deficiência, bem como sua inserção em ocupações na vida cotidiana. MÉTODO: estudo qualitativo, com coleta de dados por meio de entrevistas abertas sobre história de vida e observação sistemática. A amostra foi composta por dez pessoas com deficiência, adquirida ou congênita, moradoras de região adstrita a um Núcleo de Saúde da Família. O referencial teórico foi a concepção social da deficiência. Os dados foram analisados segundo abordagem interpretativa reconstrutiva, fundamentada no referencial da Teoria da Ação Comunicativa de Habermas. RESULTADOS: os resultados evidenciaram que a inclusão sociofamiliar e comunitária dos sujeitos do estudo condiciona-se a determinantes sociais da saúde, apresentando índices de iniquidades sociais, expressos pela dificuldade de acesso a serviços de Atenção Primária à Saúde e de reabilitação, trabalho e renda, educação, cultura, transporte e participação social. CONCLUSÃO: conclui-se a necessidade da elaboração de programas de atenção centrados na comunidade, voltados ao enfrentamento da pobreza e à inclusão social, em articulação com serviços de Atenção Primaria à Saúde. .

OBJETIVO: analizar la inclusión social familiar y comunitaria, y la participación social de personas con deficiencia, así como su inserción en ocupaciones en la vida cotidiana. MÉTODO: estudio cualitativo, con recolección de datos por medio de entrevistas abiertas sobre historia de vida y por observación sistemática. La muestra estuvo compuesta por diez personas con deficiencia, adquirida o congénita, habitantes de una región adscrita a un Núcleo de Salud de la Familia. El referencial teórico fue la concepción social de la deficiencia. Los datos fueron analizados según abordaje interpretativo reconstructivo, fundamentado en el referencial de la Teoría de la Acción Comunicativa de Habermas. RESULTADOS: los resultados evidenciaron que la inclusión social familiar y comunitaria de los sujetos del estudio se condiciona a determinantes sociales de la salud, presentando índices de iniquidades sociales, expresados por la dificultad de acceso a servicios de Atención Primaria de la Salud y de rehabilitación, trabajo y renta, educación, cultura, transporte y participación social. CONCLUSIÓN: se concluye que existe la necesidad de elaborar programas de atención centrados en la comunidad, dirigidos al enfrentamiento de la pobreza y a la inclusión social, en articulación con servicios de Atención Primaria a la Salud. .

Humans , Animals , Female , Mice , Antineoplastic Agents/pharmacology , HSP90 Heat-Shock Proteins/metabolism , Lactones/pharmacology , /drug therapy , Oximes/pharmacology , Cell Line, Tumor , Cell Proliferation , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Mice, Nude , Mice, Transgenic , /metabolism , Proteolysis , Transcriptome/drug effects , Xenograft Model Antitumor Assays
Biol. Res ; 48: 1-6, 2015. ilus, graf, tab
Article in English | LILACS | ID: biblio-950821


BACKGROUND: Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the plant kingdom is mainly confined to plant families of Meliaceae and Rutaceae. Owing to their wide range of pharmacological and therapeutic properties, this study was aimed at investigating the potential nitric oxide (NO) and acetylcholinesterase (AChE) inhibitory activity and the cytotoxicity of three limonoids: trichilia lactone D5 (1), rohituka 3 (2) and dregeanin DM4 (3), isolated from Trichilia welwitschii C.DC. RESULTS: Results indicated that the three limonoids had low cytotoxicity towards Vero cells with LC50 values ranging from 89.17 to 75.82 µg/mL. Compounds (2) and (3) had lower cytotoxicity compared to puromycin and doxorubicin used as reference cytotoxic compounds. Compound (1) (LC50 of 23.55 µg/mL) had good antiproliferative activity against RAW 264.7 cancer cells. At the lowest concentration tested (0.5 µg/mL), compound (2) and (3) released the lowest amount of nitric oxide (2.97 and 2.93 µM, respectively). The three limonoids had anti-AChE activity with IC50 values ranged of 19.13 µg/mL for (1), 34.15 µg/mL for (2) and 45.66 µg/mL for (3), compared to galantamine (IC50 of 8.22 µg/mL) used as positive control. CONCLUSION: The limonoid compounds studied in this work inhibited nitric oxide production in LPS-stimulated macrophages and had anti-AChE activity. Trichilia lactone D5 had potential antiproliferative activity against RAW 264.7 cancer cells. The limonoids had low cytotoxicity towards Vero cells lines. This study provided further examples of the importance of limonoids compounds as potential AChE inhibitors and anti-inflammatory agents targeting the inhibition of NO production.

Animals , Mice , Cholinesterase Inhibitors/pharmacology , Meliaceae/chemistry , Limonins/pharmacology , Nitric Oxide/antagonists & inhibitors , Vero Cells , Chlorocebus aethiops , Lipopolysaccharides , Inhibitory Concentration 50 , Limonins/isolation & purification , Limonins/analysis , Cell Proliferation/drug effects , RAW 264.7 Cells , Lactones/analysis , Lactones/pharmacology , Lethal Dose 50 , Macrophages/drug effects , Anti-Inflammatory Agents/pharmacology , Nitric Oxide/analysis
Rev. bras. parasitol. vet ; 23(2): 113-122, 06/2014. tab
Article in English | LILACS | ID: lil-714788


Ticks and the diseases they transmit cause great economic losses to livestock in tropical countries. Non-chemical control alternatives include the use of resistant cattle breeds, biological control and vaccines. However, the most widely used method is the application of different chemical classes of acaricides and macrocyclic lactones. Populations of the cattle tick, Rhipicephalus (Boophilus) microplus, resistant to organophosphates (OP), synthetic pyrethroids (SP), amitraz and fipronil have been reported in Mexico. Macrocyclic lactones are the most sold antiparasitic drug in the Mexican veterinary market. Ivermectin-resistant populations of R. (B.) microplus have been reported in Brazil, Uruguay and especially in Mexico (Veracruz and Yucatan). Although ivermectin resistance levels in R. (B.) microplus from Mexico were generally low in most cases, some field populations of R. (B.) microplus exhibited high levels of ivermectin resistance. The CHPAT population showed a resistance ratio of 10.23 and 79.6 at lethal concentration of 50% and 99%, respectively. Many field populations of R. (B.) microplus are resistant to multiple classes of antiparasitic drugs, including organophosphates (chlorpyrifos, coumaphos and diazinon), pyrethroids (flumethrin, deltamethrin and cypermethrin), amitraz and ivermectin. This paper reports the current status of the resistance of R. (B.) microplus to acaricides, especially ivermectin, in Mexican cattle.

Carrapatos e as doenças por eles transmitidas causam grandes perdas econômicas ao gado dos países tropicais. Alternativas não-químicas incluem o uso de raças de gado que sejam resistentes, controle biológico e vacinas. No entanto, o método mais utilizado é a aplicação de diferentes classes químicas de acaricidas e lactonas macrocíclicas. Populações de piolhos de gado, Rhipicephalus (Boophilus) microplus, resistentes aos organofosfatos (OP), piretoides sintéticos (SP), amitraz e fipronil, foram descritas no México. Lactonas macrocíclicas são as drogas antiparasitárias mais vendidas no mercado veterinário mexicano. Populações de R. (B.) microplus resistentes à irvemectina foram relatadas no Brasil, Uruguai e especialmente no México (Veracruz e Yucatan). Embora os níveis de resistência à ivermectina no R. (B.) microplus do México tenha sido relativamente baixa, na maioria dos casos, algumas populações campestres de R. (B.) microplus mostraram altos níveis de resistência à ivermectina. A população CHPAT mostrou uma razão de resistência de 10,23 e 79,6 na concentração letal de 50% e 99%, respectivamente. Muitas populações campestres de R. (B.) microplus são resistentes a múltiplas classes de drogas antiparasitárias, incluindo organofosfatos (clorpirifós, coumafos e diazinon), piretoides (flumetrina, deltametrina e cipermetrina), amitraz e ivermectina. Este artigo relata o estado atual de resistência do R. (B.) microplus aos acaricidas, especialmente ivermectina, no gado mexicano.

Animals , Cattle , Acaricides/pharmacology , Antiparasitic Agents/pharmacology , Drug Resistance , Ivermectin/pharmacology , Rhipicephalus/drug effects , Agriculture , Acaricides/therapeutic use , Antiparasitic Agents/therapeutic use , Cattle Diseases/drug therapy , Ivermectin/therapeutic use , Lactones/pharmacology , Lactones/therapeutic use , Mexico , Tick Infestations/drug therapy , Tick Infestations/veterinary
Braz. j. med. biol. res ; 44(6): 562-572, June 2011. ilus, tab
Article in English | LILACS | ID: lil-589981


Inhibition of type-5 phosphodiesterase by sildenafil decreases capacitative Ca2+ entry mediated by transient receptor potential proteins (TRPs) in the pulmonary artery. These families of channels, especially the canonical TRP (TRPC) subfamily, may be involved in the development of bronchial hyperresponsiveness, a hallmark of asthma. In the present study, we evaluated i) the effects of sildenafil on tracheal rings of rats subjected to antigen challenge, ii) whether the extent of TRPC gene expression may be modified by antigen challenge, and iii) whether inhibition of type-5 phosphodiesterase (PDE5) may alter TRPC gene expression after antigen challenge. Sildenafil (0.1 µM to 0.6 mM) fully relaxed carbachol-induced contractions in isolated tracheal rings prepared from naive male Wistar rats (250-300 g) by activating the NO-cGMP-K+ channel pathway. Rats sensitized to antigen by intraperitoneal injections of ovalbumin were subjected to antigen challenge by ovalbumin inhalation, and their tracheal rings were used to study the effects of sildenafil, which more effectively inhibited contractions induced by either carbachol (10 µM) or extracellular Ca2+ restoration after thapsigargin (1 µM) treatment. Antigen challenge increased the expression of the TRPC1 and TRPC4 genes but not the expression of the TRPC5 and TRPC6 genes. Applied before the antigen challenge, sildenafil increased the gene expression, which was evaluated by RT-PCR, of TRPC1 and TRPC6, decreased TRPC5 expression, and was inert against TRPC4. Thus, we conclude that PDE5 inhibition is involved in the development of an airway hyperresponsive phenotype in rats after antigen challenge by altering TRPC gene expression.

Animals , Male , Rats , Calcium Channels/drug effects , Carbachol/pharmacology , Piperazines/pharmacology , Sulfones/pharmacology , TRPC Cation Channels/drug effects , Trachea/drug effects , Vasodilator Agents/pharmacology , Calcium Channels/metabolism , Carbachol/antagonists & inhibitors , Gene Expression , Lactones/pharmacology , Muscle Contraction/drug effects , Muscle Contraction/physiology , Nitric Oxide/metabolism , Ovalbumin/pharmacology , Purines/pharmacology , Rats, Wistar , Sesquiterpenes/pharmacology , TRPC Cation Channels/genetics , TRPC Cation Channels/metabolism , Trachea/metabolism , Trachea/physiopathology
West Indian med. j ; 59(3): 249-252, June 2010. ilus, tab
Article in English | LILACS | ID: lil-672613


OBJECTIVE: The sesquiterpene, mikanolide, was found to possess antibacterial activity. As a result, a structure-activity relationship study was carried out on mikanolide and eleven of its derivatives. METHODS: Mikanolide and two of its derivatives were isolated from organic extract of Mikania micrantha using chromatographic methods. Nine additional derivatives were synthesized and all were investigated for their antibacterial activity against the Gram positive pathogen Staphylococcus aureus and beta haemolytic Streptococcus group A (BHSA) as well as the Gram negative Escherichia coli using the disk diffusion assay. RESULTS: The investigation revealed that only four of the derivatives displayed antibacterial activity and only pathogens Staphylococcus aureus and beta haemolytic Streptococcus group A were susceptible at a concentration of 100 µg per disk. However, there was an increase in activity for three of the derivatives in comparison to mikanolide. CONCLUSION: This study underscores the potential for phytochemicals from locally available plants to be further investigated and developed as antibacterial agents.

OBJETIVO: Se halló que el sesquiterpene - mikanolida - posee actividad antibacteriana. Como resultado, se llevó a cabo un estudio de la relación estructura-actividad de la mikanolida y once de sus derivados. MÉTODOS: La mikanolida y dos de sus derivados fueron aislados a partir de un extracto orgánico de Mikania micrantha, mediante métodos cromatográficos. Se sintetizaron otros nueve derivados adicionales, y se investigó la actividad antibacteriana de todos sobre el patógeno Gram positivo Staphylococcus aureus y el Streptococcus beta hemolítico grupo A (BHSA) así como Escherichia coli Gram negativo, usando el ensayo de difusión en disco. RESULTADOS: La investigación reveló que sólo cuatro de los derivados mostraban actividad antibacteriana y sólo los patógenos Staphylococcus aureus y Streptococcus beta hemolítico grupo A eran susceptibles a una concentración de 100 µg por disco. Sin embargo, se produjo un aumento en la actividad de tres de los derivados en comparación con la mikanolida. CONCLUSIÓN: Este estudio subraya el potencial que poseen los fotoquímicos a partir de plantas localmente disponibles, para ser objeto de investigación ulterior y ser desarrollados como agentes antibacterianos.

Humans , Lactones/pharmacology , Sesquiterpenes, Germacrane/pharmacology , Anti-Bacterial Agents/pharmacology , Disk Diffusion Antimicrobial Tests , Structure-Activity Relationship , Staphylococcus aureus/drug effects , Streptococcus pyogenes/drug effects
Jordan Journal of Pharmaceutical Sciences. 2010; 3 (2): 69-77
in English | IMEMR | ID: emr-118060


The most practical measure of therapeutic equivalence between two commercially available and generic formulation of a certain drug is to determine their in vivo bioavailability. However, for the oral dosage form that is not intended to be absorbed [e.g. orlistat], in vivo bioavailability studies are irrelevant to the achievement of the product's intended purposes. However, specific requirements for these drug products may be set in a way that they should meet acceptable in vitro standards. For this purpose, a comparative enzymatic inhibition assay of the target enzyme, pancreatic lipase, was developed to demonstrate orlistat products' pharmaceutical and potency equivalence. In this study we compared the pancreatic lipase inhibition that is achieved by two orlistat formulations; a generic product manufactured by local company [Jordan Sweden Medical Company, JOSWE] and the reference one Xenical manufactured by Roche. The inhibition was expressed by the concentration of product which inhibits 50% of the activity of the pancreatic lipase enzyme [IC[50]]. The results of these studies showed that both formulations have equivalent potency that was demonstrated by in vitro studies

Therapeutic Equivalency , Biological Availability , Drugs, Generic , Technology, Pharmaceutical , Lactones/pharmacology , Lipase/drug effects
Rev. biol. trop ; 56(3): 1063-1073, sep. 2008. ilus, graf
Article in Spanish | LILACS | ID: lil-637847


Sesquiterpene lactones of the plants Viguiera sylvatica and Decachaeta thieleana (Asteraceae) modulate nitric oxide production and phagocytosis of macrophages cell line RAW. Different species of the Asteraceae family are a potential source of sesquiterpene lactones with anti-inflammatory properties. Macrophages play a central role in the regulation of immune responses. In the present study, the in vitro effect of two sesquiterpene lactones, a millerenolide and a thieleanin, was assessed by measuring the production of nitric oxide (NO) by cell line RAW (murine macrophages) using the Griess reagent. Additionally, the effect of these sesquiterpene lactones on phagocytic capacity of latex particles and the reduction of nitroblue tetrazolium (NBT) were evaluated microscopically. Treatment of macrophages with >2.5 µg/ml of both sesquiterpene lactones, reduced the production of NO. A decreased number of macrophages able to reduce NBT were observed when these cells were treated with 3 µg/ml of millerenolide or 7.5 µg/ml of thieleanin. Treatment of macrophages with 4 µg/ml of millerenolide or 7.5 µg/ml of thieleanin, reduced the phagocytic capacity of macrophages. Cytotoxic effects on the macrophages were only observed when the concentration was increased to 8 µg/ml of millerenolide or 25 µg/ml of thieleanin. Our results suggest that these sesquiterpene lactones could be useful compounds in the elaboration of anti-inflammatory drugs. Rev. Biol. Trop. 56 (3): 1063-1073. Epub 2008 September 30.

Las plantas de la familia Asteraceae son una fuente potencial de lactonas sesquiterpénicas con propiedades antiinflamatorias. Los macrófagos son células que desempeñan una función central en la regulación de la respuesta inmune. Este estudio evaluó el efecto in vitro de dos lactonas sesquiterpénicas, un millerenólido y thieleanina, sobre la producción de óxido nítrico (NO) en una línea celular de macrófagos de ratón (RAW), utilizando el reactivo de Griess. Además, se estudió el efecto sobre la capacidad fagocítica de RAW, evaluando al microscopio la fagocitosis de partículas inertes de látex y la reducción de nitroazul de tetrazolio (NBT). Se observó que los macrófagos tratados con lactona sesquiterpénica (>2.5 µg/ml) disminuyeron la producción de NO. Además, se observó una disminución de la cantidad de macrófagos capaces de reducir NBT, después que fueron tratados con millerenólido (3 µg/ml) o thieleanina (7.5 µg/ ml). Por otro lado, la exposición a 4 µg/ml de millerenólido ó 7.5 µg/ml de thieleanina redujo la cantidad promedio de partículas de látex fagocitadas. No se observaron diferencias entre tratamientos y control en cuanto al porcentaje de células fagocíticas. Sólo se observaron efectos citotóxicos sobre los macrófagos, cuando la concentración de millerenólido se incrementó a 8 µg/ml o la de thieleanina se aumentó a 25 µg/ml. Estos resultados sugieren que el millerenólido y la thieleanina podrían ser compuestos útiles en la elaboración de drogas antiinflamatorias.

Animals , Mice , Asteraceae/chemistry , Lactones/pharmacology , Macrophages/drug effects , Nitric Oxide/biosynthesis , Phagocytosis/drug effects , Sesquiterpenes/pharmacology , Cell Line , Lactones/chemistry , Lactones/isolation & purification , Macrophages/physiology , Sesquiterpenes/chemistry , Sesquiterpenes/isolation & purification
Rev. méd. Chile ; 136(1): 64-72, ene. 2008. ilus, graf
Article in Spanish | LILACS | ID: lil-483221


Background: Natural products are used in the production of therapeutic drugs due to their wide diversity and excellent adaptability to biological structures. Sesquiterpene ¡aciones are the active constituents of several plants from the Asteraceae family. Aim: To assess the in vitro effect of a sesquiterpene lactone (millerenolide). Material and methods: The drug effect was assessed measuring the proliferation of lymphocytes using the 2,3-bis (2-methoxy-4-nitro-5-sulfophenyl)-5-[(phenylamino) carbonylJ-2H-tetrazolium hydroxide (XTT) technique. Changes on the cell cycle were analyzed on a FACSort flow cytometer The effect of millerenolide on the production of nitric oxide (NO) by macrophages was evaluated using the Griess reagent. Additionally, phagocytosis of latex particles and nitroblue tetrazolium (NBT) reduction by macrophages were evaluated microscopically. Results: Treatment of human peripheral blood mononuclear cells (PBMC) with millerenolide decreases the proliferation of lymphocytes, decreases the percentage of cells in S, and G2/Mphases, and increases the proportion of cells in GO/Gl phase. Treatment of macrophages with millerenolide, reduces the production of NO, the phagocytic capacity and the number of cells able to reduce NBT. Cytotoxic effects of the lactone on human PBMC were only observed when the concentration was increased to 6 fig/ml. Conclusions: Millerenolide could be considered as a potential therapeutic agent with immunosuppressiveproperties.

Humans , In Vitro Techniques , Immunosuppressive Agents/pharmacology , Lactones/pharmacology , Leukocytes, Mononuclear/drug effects , Lymphocyte Activation/drug effects , Nitric Oxide/biosynthesis , Sesquiterpenes/pharmacology , Analysis of Variance , Asteraceae/chemistry , Cytotoxicity Tests, Immunologic , Lactones/chemistry , Lactones/toxicity , Leukocytes, Mononuclear/physiology , Lymphocyte Activation/physiology , Phagocytosis/drug effects , Phagocytosis/physiology , Plant Extracts/chemistry , Plant Extracts/toxicity , Sesquiterpenes/chemistry , Sesquiterpenes/toxicity
SPJ-Saudi Pharmaceutical Journal. 2008; 16 (3-4): 203-213
in English | IMEMR | ID: emr-90377


The study was conducted to investigate possible mechanisms of the protective actions of rofecoxib [a selective COX-2 inhibitor] and nitric oxide-releasing aspirin [NO-aspirin] against experimentally induced gastric lesions in rats. The rats were randomly assigned to vehicle [carboxymethylcellulose], rofecoxib [5 mg/Kg] and NO-aspirin [55mg/Kg]-pretreated groups, in addition to the non-stressed control group. Gastric lesions were induced by exposing the rats to 3 hrs cold restraint stress [CRS] and ulcer indices were determined. Gastric juice parameters [pH, free and total acid output, mucin and pepsin concentrations] were determined. The stomachs were used for determination of gastric mucosal level of lipid peroxides as well as total nitrites. Results showed that both rofecoxib and NO-aspirin displayed protective effects against lesions formation. Pretreatment with both drugs significantly lowered gastric acid secretion, mucin and pepsin concentrations as well as mucosal levels of lipid peroxides and total nitrites compared to CRS rats. This protection was possibly mediated through lowering of gastric juice acid secretion and proteolytic activity and increasing mucin concentration as well as free radical scavenging and reduction of the detrimental increase of nitric oxide during CRS

Male , Animals, Laboratory , Lactones/pharmacology , Sulfones/pharmacology , Aspirin/analogs & derivatives , Cyclooxygenase 2 Inhibitors , Stress, Psychological , Rats, Sprague-Dawley , Nitric Oxide
Clinics ; 61(3): 223-230, June 2006. ilus, tab
Article in English | LILACS | ID: lil-430908


OBJETIVO: Comparar os efeitos do uso de antiinflamatórios não-esteróides tradicionais (AINES) e AINES que são inibidores seletivos da ciclooxigenase-2 (COX-2), no processo de regeneração óssea em ratos. MATERIAL E MÉTODO: Quarenta e quatro ratos da linhagem Wistar submetidos a osteotomia do femur direito e divididos em três grupos, conforme o medicamento que receberam (diclofenaco, rofecoxib e placebo). Cada grupo foi dividido em dois subgrupos, conforme o tempo até o sacrifício, após a cirurgia. Os animais do subgrupo 1 foram sacrificados duas semanas após a cirurgia e os do subgrupo 2, quatro semanas após a cirurgia. Foram analisados exames radiográficos e a histomorfometria do calo ósseo. RESULTADOS: Não foram encontradas diferenças estatísticas na área do calo ósseo 2 e 4 semanas após a cirurgia. No que se refere à área de neoformação óssea dentro do calo, observou-se diferença estatisticamente significante apenas dentro do grupo do diclofenaco, que apresentou menos tecido. CONCLUSÕES: A consolidação da fratura em ratos Wistar ocorre dentro de 2 semanas e o uso de antiinflamatórios não-esteróides não influi de forma significante neste processo.

Animals , Rats , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Bone Regeneration/drug effects , Bony Callus/surgery , /pharmacology , Diclofenac/pharmacology , Lactones/pharmacology , Sulfones/pharmacology , Bony Callus/pathology , Bony Callus , Osteotomy , Rats, Wistar , Time Factors
Arq. bras. endocrinol. metab ; 50(2): 368-376, abr. 2006. ilus, tab
Article in English, Portuguese | SES-SP, LILACS, SES-SP | ID: lil-435164


Weight loss improves metabolic abnormalities and reduces cardiovascular risk in obese hypertensive patients. To evaluate the impact of a sustained weight loss on coronary risk, 181 hypertensive patients with metabolic syndrome underwent to orlistat therapy, 120 mg, t.i.d., plus diet for 36 weeks. During therapy, Framingham risk scores (FRS) were calculated for determination of coronary heart disease risk in ten years. Body mass index decreased from 35.0 ± 4.2 to 32.6 ± 4.5 kg/m² (p< 0.0001) and waist circumference from 108.1 ± 10.1 to 100.5 ± 11.1 cm (p< 0.0001), at the end of the study period (week 36). Systolic and diastolic blood pressure showed reductions after the two first weeks, which were maintained up to the end of the study. A clear shift to the left in FRS distribution curve occurred at the end of the study, compared to baseline, indicating a reduction in coronary risk. Over all patients at risk, 49.2 percent moved to a lower risk category. A weight loss > 5 percent occurred in 64.6 percent of all patients, associated with improvement in glucose metabolism. Among those with abnormal glucose metabolism, 38 out 53 patients (71.7 percent) improved their glucose tolerance (p< 0.0005). In conclusion, long-term orlistat therapy helps to reduce and maintain a lower body weight, decreasing risk of coronary disease and improving glucose metabolism, thus protecting against type 2 diabetes.

A perda de peso melhora as anormalidades metabólicas e reduz o risco cardiovascular em pacientes obesos hipertensos. Com o objetivo de avaliar o impacto da perda de peso mantida sobre o risco coronariano, submetemos 181 pacientes hipertensos com síndrome metabólica à terapia com orlistat, 120 mg, três vezes ao dia, mais dieta, por um período de 36 semanas. Durante a terapia, foram calculados os scores de risco de Framingham (FRS) para a determinação do risco de doença cardíaca coronariana em dez anos. Ao final do período de estudo (semana 36), o índice de massa corpóreo diminuiu de 35,0 ± 4,2 para 32,6 ± 4,5 kg/m² (p< 0,0001) e a circunferência da cintura de 108,1 ± 10,1 para 100,5 ± 11,1 cm (p< 0,0001). As pressões sistólica e diastólica mostraram reduções após as primeiras duas semanas, que se mantiveram até o final do estudo. Um deslocamento evidente para a esquerda na curva de distribuição do FRS ocorreu no final do estudo, em comparação com os valores basais, indicando redução no risco coronariano. Do total de pacientes em risco, 49,2 por cento passou para uma categoria de risco menor. Ocorreu perda de peso > 5 por cento em 64,6 por cento de todos os pacientes, associada com melhora no metabolismo da glicose. Entre os 53 pacientes com metabolismo de glicose anormal, 38 (71,7 por cento) melhoraram sua tolerância à glicose (p< 0,0005). Em conclusão, terapia de longa duração com orlistat auxilia a reduzir e manter mais baixo o peso corpóreo, reduzindo o risco de doença coronária e melhorando o metabolismo da glicose e protegendo, dessa maneira, contra o diabetes tipo 2.

Humans , Male , Female , Middle Aged , Anti-Obesity Agents/therapeutic use , Lactones/therapeutic use , Obesity/drug therapy , Weight Loss/drug effects , Anti-Obesity Agents/pharmacology , Blood Pressure , Body Mass Index , Follow-Up Studies , Hypertension/complications , Lactones/pharmacology , Metabolic Syndrome , Obesity/diet therapy , Waist-Hip Ratio
Indian J Exp Biol ; 2006 Feb; 44(2): 128-32
Article in English | IMSEAR | ID: sea-63446


The present study was aimed to assess the combined effects of cyclooxygenase and 5-lipoxygenase (COX/5-LOX) inhibitors in different animal models of nociception. Naproxen, nimesulide and rofecoxib are well-established antinociceptive agents acting via COX inhibition. AKBA (acetyl-keto-beta-boswellic acid) is a 5-LOX inhibitor. AKBA (50-200 mg/kg) produced a dose dependent and significant antinociceptive effect in different animal models of nociception. Based on the earlier reports from our laboratory, sub effective doses of all the three COX Inhibitors were selected and they were administered (naproxen, 5 mg/kg; nimesulide, 1 mg/kg; and rofecoxib, 1 mg/kg) with AKBA (100 mg/kg). This produced a more significant antinociceptive effect as compared to per se effect observed in all the three models of nociception. However, the effect of combination of nimesulide with AKBA was more pronounced as compared to naproxen and rofecoxib and their combination with AKBA. The present finding provided an evidence for the potentiation of antinociceptive effect of NSAIDs with AKBA. Such a combination may help to reduce the therapeutic doses of conventional NSAIDs and also reduce side effects (gastric, cardiac and renal) that are popularly associated with the NSAIDs.

Analgesics/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arachidonate 5-Lipoxygenase/antagonists & inhibitors , Cyclooxygenase Inhibitors/pharmacology , Dose-Response Relationship, Drug , Lactones/pharmacology , Lipoxygenase Inhibitors/pharmacology , Mice , Naproxen/pharmacology , Pain Measurement , Prostaglandin-Endoperoxide Synthases/metabolism , Sulfonamides/pharmacology , Sulfones/pharmacology , Triterpenes/pharmacology
Mem. Inst. Oswaldo Cruz ; 101(1): 55-56, Feb. 2006. ilus, tab
Article in English | LILACS | ID: lil-430840


New alternative insecticides are necessary for the chemical control of head lice. In this study the fumigant knockdown time 50 percent (KT50) and repellency index (RI) of three aliphatic lactones was compared with two essential oils and DDVP, against permethrin-resistance Pediculus humanus capitis from Argentina. In the fumigant assay, none of the lactones were effective compared to the highest activity of eucalyptus (KT50 15.53 m). In the repellency test, the three lactones were equally or more effective (RI ranging from 60.50 to 76.68) than the positive control (piperonal). These lactones are promising as head lice repellents.

Humans , Animals , Child , Eucalyptus , Fumigation , Insect Repellents/pharmacology , Insecticides/pharmacology , Lactones/pharmacology , Oils, Volatile , Pediculus/drug effects , Benzaldehydes/pharmacology , Dichlorvos/pharmacology , Monoterpenes/pharmacology , Oils, Volatile/pharmacology
Biocell ; 27(2): 163-172, Aug. 2003.
Article in English | LILACS | ID: lil-384247


The purpose of this review, based on studies from our laboratory as well as from others, is to summarize salient features of mast cell immunobiology and to describe their associations with gastrointestinal mucosal defense. Gastrointestinal mast cells are involved in many pathologic effects, such as food hypersensitivity. On the other hand, they also play a protective role in defense against parasitic and microbial infections. Thus, they have both positive and negative effects, but presently the mechanisms that control the balance of these various effects are poorly known. It has been suggested that stabilization of mast cells may be a key mechanism to protect the gastrointestinal tract from injury. Few molecules are known to possess both mast cell stabilizing and gastrointestinal cytoprotective activity. These include zinc compounds, sodium cromoglycate, FPL 52694, ketotifen, aloe vera, certain flavonoids such as quercetin, some sulfated proteoglycans such as chondroitin sulfate and dehydroleucodine. Dehydroleucodine, a sesquiterpene lactone isolated from Artemisia douglasiana Besser, exhibits anti-inflammatory and gastrointestinal cytoprotective action. The lactone stimulates mucus production, and inhibits histamine and serotonin release from intestinal mast cells. The lactone could act as a selective mast cell stabilizer by releasing cytoprotective factors and inhibiting pro-inflammatory mast cell mediators.

Humans , Digestive System , Mast Cells/cytology , Mast Cells/immunology , Anti-Inflammatory Agents , Immunity, Mucosal/immunology , Inflammation/drug therapy , Inflammation/immunology , Inflammation/physiopathology , Lactones/pharmacology , Lactones/therapeutic use , Mast Cells/drug effects , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/metabolism , Gastric Mucosa/cytology , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Intestinal Mucosa/cytology , Intestinal Mucosa/drug effects , Intestinal Mucosa/immunology , Sesquiterpenes/pharmacology , Sesquiterpenes/therapeutic use
Article in English | IMSEAR | ID: sea-33058


A study on efficacy and effectiveness of artemisinin (total dose of 60 mg/kg) and artesunate (total dose of 12 mg/kg over five days) in treatment of uncomplicated malaria was conducted in highly malaria transmitted areas in Vietnam. 126 uncomplicated malaria cases finished 14 day follow-up. 100% cure rate achieved at day 14 in patients of the efficacy groups received either artemisinin or artesunate, while it was 83% and 93% in patients treated respectively with artemisinin and artesunate of the effectiveness groups. Compliance of the treatment regimens was discussed.

Adolescent , Adult , Antimalarials/pharmacology , Artemisinins , Child , Drug Monitoring/methods , Female , Fever/parasitology , Follow-Up Studies , Humans , Lactones/pharmacology , Malaria, Falciparum/blood , Male , Sesquiterpenes/pharmacology , Treatment Outcome , Vietnam