RESUMEN
Complete tract excision for complex fistula-in-ano, where the sphincter, is divided is increasingly being followed by immediate sphincter repair. We concluded, by a prospective study conducted on 60 consecutive patients, that this procedure is feasible and safe, and polydioxanone and polyglactin 910 in repair result in a comparable outcome.
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Canal Anal , Fístula Rectal , Humanos , Estudios Prospectivos , Resultado del Tratamiento , Canal Anal/cirugía , Fístula Rectal/cirugíaRESUMEN
Hepatospecific delivery by ligand based receptor targeting is an established strategy to augment therapy associated with liver diseases and disorders. Previously, we have investigated the effect of ligand headgroup on cellular uptake mediated by the asialoglycoprotein receptor by in silico and in vitro approach. In this paper, we report the design of agarose based liposomes for delivery to liver cancer cells and provide a proof of concept of the targeting efficiency against galactose liposomes using an in vivo approach. Sorafenib Tosylate loaded targeting liposomes were developed and optimized using factorial design. Comparative evaluation including cell cytotoxicity, pharmacokinetics and biodistribution and hepatospecific uptake was performed for both the liposomal systems. The formulations possessed a particle size of 150 - 180 nm and a zeta potential of 30 - 60 mV depending on the amount of ligand and drug loading, with more than 90% entrapment efficiency. A two-fold increase in cytotoxicity was observed with agarose-based liposomes as compared to galactose based liposomes. In vivo PK evaluation indicated a reduction in half life of drug when loaded in agarose ligand loaded system, probably due to greater uptake in the liver as evidenced in biodistribution study. Intrahepatic disposition revealed a higher PC/NPC uptake ratio with the targeted systems as compared to conventional liposomes, although the agarose-based system resulted in highest uptake ratio. A biocompatible platform for specific delivery of drugs to hepatocytes was established validating a rational approach to design liver targeting systems.
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Galactosa , Liposomas , Sistemas de Liberación de Medicamentos , Ligandos , Liposomas/farmacocinética , Hígado/metabolismo , Monosacáridos/metabolismo , Monosacáridos/farmacología , Tamaño de la Partícula , Polisacáridos/farmacología , Sefarosa/metabolismo , Sefarosa/farmacología , Sorafenib/farmacología , Distribución TisularRESUMEN
Ligands with the polysaccharide headgroups have been recently reported by our group to possess enhanced interaction with asialoglycoprotein receptor (ASGPR) in silico as compared to ligands having galactose moieties. This enhanced interaction is a result of the polymer's backbone support in anchoring the ligand in a specific orientation within the bilayer. In this paper, we have attempted to provide an in vitro proof of concept by performing a comparative evaluation of polysaccharide and monosaccharide-based ligands. Docking was performed to understand interaction with ASGPR in silico. Agarose and galactose conjugates with behenic acid were synthesized, purified, and characterized to yield biocompatible hepatospecific ligands which were incorporated into nanoliposomes. Cellular internalization of these targeted liposomes was studied using confocal microscopy and flow cytometry. The toxicity potential was assessed in vivo. Results indicated that the polysaccharide-based ligand increased cellular uptake due to better interaction with the receptor as compared to ligand bearing a single galactose group. In addition to developing novel liver targeting ligands, the study also established proof of concept that has been suggested by earlier in silico investigations. The approach can be used to design targeting ligands and develop formulations with improved targeting efficacy.
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MonosacáridosRESUMEN
AIM: To investigate comparative in vitro and in vivo performance of lipid vesicular and particulate systems in escalating oral bioavailability for superior hepatoprotection. MATERIALS AND METHODS: Systems were fabricated using easy to scale up process and novel excipients to deliver Silibinin. In vitro characterization followed by pharmacokinetic and pharmacodynamic evaluation in rats was conducted to establish a correlation. RESULTS: Nanoformulations resulted in 20 fold increase in solubilisation and significant increase in permeation. 2.5 fold increase in bioavailability was evident in vivo. Vesicles demonstrated greatest hepatoprotective potential in efficacy study. CONCLUSION: The findings establish a link between in vitro and in vivo performance to rank order lipid nanoartchitects. Concurrently, a significant potential in therapeutic intervention of hepatotoxicity is envisaged as elucidated.
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Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Excipientes/química , Lípidos/química , Hígado/enzimología , Nanotecnología/métodos , Silibina/química , Administración Oral , Animales , Disponibilidad Biológica , Tetracloruro de Carbono , Liberación de Fármacos , Estabilidad de Medicamentos , Femenino , Técnicas In Vitro , Tamaño de la Partícula , Permeabilidad , Ratas , Silibina/sangre , Silibina/farmacocinética , Silibina/farmacología , Solubilidad , Propiedades de SuperficieRESUMEN
Brown adipose tissue (BAT) has been proposed as a potential target tissue against obesity and its related metabolic complications. Although the molecular and functional characteristics of BAT have been intensively studied in rodents, only a few studies have used human BAT specimens due to the difficulty of sampling human BAT deposits. We established a novel positron emission tomography and computed tomography-guided Bergström needle biopsy technique to acquire human BAT specimens from the supraclavicular area in human subjects. Forty-three biopsies were performed on 23 participants. The procedure was tolerated well by the majority of participants. No major complications were noted. Numbness (9.6%) and hematoma (2.3%) were the two minor complications noted, which fully resolved. Thus, the proposed biopsy technique can be considered safe with only minimal risk of adverse events. Adoption of the proposed method is expected to increase the sampling of the supraclavicular BAT depot for research purposes so as to augment the scientific knowledge of the biology of human BAT.
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Tejido Adiposo Pardo/patología , Biopsia con Aguja Fina/métodos , Obesidad/patología , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Adulto , Frío , Humanos , Masculino , Obesidad/metabolismo , TermogénesisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Pistacia integerrima J.L. Stewart ex Brandis (Family: Anacardiaceae) galls are used in Indian ethnomedicine for its anti-asthmatic, sedative and spasmolytic properties, however, there are no scientific studies demonstrating its spasmolytic activity. The present investigation deals with the evaluation of relaxant and spasmolytic activities of the essential oil isolated from the galls of Pistacia integerrima J.L. Stewart ex Brandis (EOPI). MATERIALS AND METHODS: In vitro pharmacological assays were carried out on rabbit jejunum spontaneous contractions, guinea pig ileum. The present investigation studied the relaxation of basal tone of isolated guinea pig ileum by possible involvement of NO, prostaglandins, membrane Na(+) channels, potassium channel, enteric nervous system, adrenoceptors, Ca(2+) channels. Additional studies were conducted for comparison of the relaxant effects of EOPI on CaCl2 induced contraction in calcium free tyrode solution, effect on nifedipine insensitive component of ACh-induced contraction and on the contractile machinery to intracellular [Ca(2+)] on isolated guinea pig ileum. RESULTS: EOPI at non-relaxing dose potentiated the isoprenaline induced relaxation of rabbit jejunum. EOPI (50 µg/mL) exhibited 28% relaxation of basal tone of 60 mM K(+) induced contraction which is unaltered by preincubation with 0.5 mM hexamethonium, 0.5 µM Tetrodotoxin, 1 µM indomethacin, and 100 µM L-NG-Nitroarginine Methyl Ester (L-NAME). EOPI inhibited Ca(2+) induced contraction of isolated guinea pig ileum in Ca(2+) free medium. EOPI (10 µg/ml) potentiated the reversal of a KCl-induced tonic contraction has been observed in Ca(2+) free medium. CONCLUSION: The present investigation reinforces the use of Pistacia integerrima Stewart ex Brandis as antispasmodic in folk medicine. Moreover, it is demonstrated the involvement of ß- adrenoceptors and calcium channels in this activity, but not the participation of nicotinic receptors, Na(+) channels, prostaglandins or nitric oxide.
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Aceites Volátiles/farmacología , Parasimpatolíticos/farmacología , Pistacia , Acetilcolina/farmacología , Animales , Canales de Calcio/fisiología , Cloruro de Calcio/farmacología , Epinefrina/farmacología , Cobayas , Hexametonio/farmacología , Íleon/efectos de los fármacos , Íleon/fisiología , Técnicas In Vitro , Indometacina/farmacología , Yeyuno/efectos de los fármacos , Yeyuno/fisiología , Masculino , Ratones , Contracción Muscular/efectos de los fármacos , NG-Nitroarginina Metil Éster/farmacología , Nifedipino/farmacología , Aceites Volátiles/toxicidad , Parasimpatolíticos/toxicidad , Potasio/farmacología , Conejos , Receptores Adrenérgicos beta/fisiología , Tetrodotoxina/farmacologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Embelia ribes Burm. f. (Fam. Myrsinaceae) locally known as Vidanga have been used for treating tumors, ascites, bronchitis, jaundice, diseases of the heart and brain in traditional Indian medicine. However, no scientific studies providing new insights in its pharmacological properties with respect to acute respiratory distress syndrome have been investigated. AIM: The present investigation aimed to elucidate the effectiveness of Embelin isolated from Embelia ribes seeds on attenuation of LPS-induced acute respiratory distress syndrome in murine models. METHODS: Embelin (5, 10 and 20 mg/kg/day, i.p.) and Roflumilast (1 mg/kg/day, p.o.) were administered for four days and prior to LPS in rats (i.t.). Four hour after LPS challenge animals were anesthesized and bronchoalveolar lavage was done with ice-cold phosphate buffer. Assessment of BAL fluid was done for albumin, total protein, total cell and neutrophil count, TNF-α levels, nitrosoative stress. Superior lobe of right lung was used for histopathologic evaluation. Inferior lobe of right lung was used to obtain lung edema. Left lung was used for myeloperoxidase estimation. Arterial blood was collected immediately and analyzed for pH, pO2 and pCO2 were estimated. RESULTS: Pretreatment with embelin (5, 10 and 20 mg/kg, i.p.) decreased lung edema, mononucleated cellular infiltration, nitrate/nitrite, total protein, albumin concentrations, TNF-α in the bronchoalveolar lavage fluid and myeloperoxidase activity in lung homogenate. Embelin markedly prevented pO2 down-regulation and pCO2 augmentation. Additionally, it attenuated lung histopathological changes in acute respiratory distress syndrome model. CONCLUSION: The study demonstrates the effectiveness of Embelia ribes Burm. f. (Fam. Myrsinaceae) seeds in acute respiratory distress syndrome possibly related to its anti-inflammatory and protective effect against LPS induced airway inflammation by reducing nitrosative stress, reducing physiological parameters of blood gas change, TNF-α and mononucleated cellular infiltration indicating it as a potential therapeutic agent for acute respiratory distress syndrome.
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Antiinflamatorios/uso terapéutico , Benzoquinonas/uso terapéutico , Embelia , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Benzoquinonas/aislamiento & purificación , Benzoquinonas/farmacología , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Edema/tratamiento farmacológico , Edema/metabolismo , Edema/patología , Femenino , Lipopolisacáridos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Nitratos/metabolismo , Nitritos/metabolismo , Peroxidasa/metabolismo , Fitoterapia , Ratas , Ratas Sprague-Dawley , Síndrome de Dificultad Respiratoria/metabolismo , Síndrome de Dificultad Respiratoria/patología , Semillas , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The inflammatory bowel disease (IBD) is an idiopathic, immune mediated and chronic inflammation of the intestine. The study aimed to elucidate the ameliorative effect of methanolic extract of Dillenia indica (DIME), hexane fraction (HFDI) and chloroform fraction (CFDI) of Dillenia indica in acetic acid induced experimental colitis in mice. Macroscopic score, colon weight, colonic catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), myeloperoxidase (MPO), malondialdehyde (MDA), tumor necrosis factor (TNF-alpha), and histological changes were recorded after the treatment regimen of 7 days. Intra-rectal instillation of acetic acid caused enhanced macroscopic score, colon weight, colonic MPO, MDA, and TNF-alpha level. It caused significant decreased level of CAT, SOD and GSH. DIME (800 mg/kg), HFDI (200 mg/kg) and CFDI (200 mg/kg) treatment exhibited significant effect in lowering macroscopic score, colon weight, MPO, MDA, TNF-alpha levels and elevation of CAT, GSH and SOD levels. The results suggest that D. indica has ameliorating effects on experimental colitis by inhibiting the proinflammatory mediators like TNF-alpha production.
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Colitis/tratamiento farmacológico , Colon/efectos de los fármacos , Dilleniaceae/química , Extractos Vegetales/farmacología , Sustancias Protectoras/farmacología , Ácido Acético , Animales , Colitis/inducido químicamente , Colon/patología , Femenino , Ratones , Tamaño de los Órganos/efectos de los fármacos , Extractos Vegetales/química , Sustancias Protectoras/químicaRESUMEN
Long-term cardiovascular complications in metabolic syndrome are a major cause of mortality and morbidity in India and forecasted estimates in this domain of research are scarcely reported in the literature. The aim of present investigation is to estimate the cardiovascular events associated with a representative Indian population of patients suffering from metabolic syndrome using United Kingdom Prospective Diabetes Study risk engine. Patient level data was collated from 567 patients suffering from metabolic syndrome through structured interviews and physician records regarding the input variables, which were entered into the United Kingdom Prospective Diabetes Study risk engine. The patients of metabolic syndrome were selected according to guidelines of National Cholesterol Education Program - Adult Treatment Panel III, modified National Cholesterol Education Program - Adult Treatment Panel III and International Diabetes Federation criteria. A projection for 10 simulated years was run on the engine and output was determined. The data for each patient was processed using the United Kingdom Prospective Diabetes Study risk engine to calculate an estimate of the forecasted value for the cardiovascular complications after a period of 10 years. The absolute risk (95% confidence interval) for coronary heart disease, fatal coronary heart disease, stroke and fatal stroke for 10 years was 3.79 (1.5-3.2), 9.6 (6.8-10.7), 7.91 (6.5-9.9) and 3.57 (2.3-4.5), respectively. The relative risk (95% confidence interval) for coronary heart disease, fatal coronary heart disease, stroke and fatal stroke was 17.8 (12.98-19.99), 7 (6.7-7.2), 5.9 (4.0-6.6) and 4.7 (3.2-5.7), respectively. Simulated projections of metabolic syndrome patients predict serious life-threatening cardiovascular consequences in the representative cohort of patients in western India.
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ETHNOPHARMACOLOGICAL RELEVANCE: Pistacia integerrima J.L. Stewart ex Brandis locally known as Karkatashringi is an important medicinal plant whose galls are valued in traditional medicine used in India for the treatment of asthma, chronic bronchitis, phthisis, diarrhea, fever, other ailments for the respiratory tract, and as antispasmodic, carminative, antiamoebic and anthelmintic. However, in vitro and in vivo investigations providing new insights into its pharmacological properties have not been thoroughly investigated yet. The present investigation aimed to elucidate the probable mechanism of antiasthmatic action of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls (EOPI). METHODS: EOPI was tested using in vitro studies such as antioxidant activity, mast cell degranulation, angiogenesis, isolated guinea pig ileum preparation and soyabean lipoxidase enzyme activity. In vivo studies included lipopolysaccharide-induced bronchial inflammation in rats and airway hyperresponsiveness in ovalbumin in sensitized guinea pigs using spirometry. RESULTS: EOPI (5-30 µg/ml) inhibits 5-lipoxidase enzyme activity with IC50 of 19.71 µg/ml and DPPH scavenging activity up to 100 µg/ml with maximum inhibition of 44.93 ± 2.53% at 100 µg/ml. Pre-treatment with EOPI inhibited erythropoietin-induced angiogenesis. It showed dose dependent (10, 30 and 100 µg/ml) anti-allergic activity by inhibiting compound 48/80 induced mast cell degranulation to an extent 19.08 ± 0.47%. The finding that essential oil induced inhibition of transient contraction of acetylcholine in calcium free medium, and relaxation of S-(-)-Bay 8644-precontracted isolated guinea pig ileum jointly suggests that the L-subtype Cav channel is involved in spasmolytic action of EOPI. Treatment with EOPI dose dependently (7.5, 15 and 30mg/kg i.p.) inhibited lipopolysaccharide-induced increase in total cell count, neutrophil count, nitrate-nitrite, total protein, albumin levels in bronchoalveolar fluid and myeloperoxidase levels in lung homogenates. Roflumilast was used as a standard. EOPI reduced the respiratory flow due to gasping in ovalbumin sensitized guinea pigs. CONCLUSION: The study demonstrates the effectiveness of essential oil of Pistacia integerrima J.L. Stewart ex Brandis galls in bronchial asthma possibly related to its ability to inhibit L-subtype Cav channel, mast cell stabilization, antioxidant, angiostatic and through inhibition of 5-lipoxygenase enzyme.
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Inhibidores de la Angiogénesis/farmacología , Antiasmáticos/farmacología , Antioxidantes/farmacología , Inhibidores de la Lipooxigenasa/farmacología , Aceites Volátiles/farmacología , Pistacia , Alérgenos , Inhibidores de la Angiogénesis/uso terapéutico , Animales , Antiasmáticos/uso terapéutico , Antioxidantes/uso terapéutico , Araquidonato 5-Lipooxigenasa/metabolismo , Líquido del Lavado Bronquioalveolar/citología , Broncoconstricción/efectos de los fármacos , Recuento de Células , Femenino , Cobayas , Liberación de Histamina/efectos de los fármacos , Íleon/efectos de los fármacos , Íleon/fisiología , Lipopolisacáridos , Inhibidores de la Lipooxigenasa/uso terapéutico , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Pulmón/fisiopatología , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/metabolismo , Ratones , Contracción Muscular/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Aceites Volátiles/uso terapéutico , Ovalbúmina , Peroxidasa/metabolismo , Neumonía/inducido químicamente , Neumonía/tratamiento farmacológico , Neumonía/metabolismo , Neumonía/patología , Ratas Sprague-Dawley , Cigoto/efectos de los fármacos , Cigoto/fisiología , p-Metoxi-N-metilfenetilamina/farmacologíaRESUMEN
The hypothesis that excessive intake of vegetable oil containing polyunsaturated fatty acids and iron load precipitate alcohol-induced liver damage was investigated in a rat model. In order to elucidate the mechanism underlying this synergism, the serum levels of iron, total protein, serum glutamate pyruvate transaminase, liver thiobarbituric acid reactive substances, and activities of antioxidant enzymes superoxide dismutase, catalase in liver of rats treated with alcohol, polyunsaturated fatty acids and iron per se and in combination were examined. Alcohol was fed to the rats at a level of 10-30% (blood alcohol was maintained between 150-350 mg/dl by using head space gas chromatography), polyunsaturated fatty acids at a level of 15% of diet and carbonyl iron 1.5-2% of diet per se and in combination to different groups for 30 days. Hepatotoxicity was assessed by measuring serum glutamate pyruvate transaminase, which was elevated and serum total protein, which was decreased significantly in rats fed with a combination of alcohol, polyunsaturated fatty acids and iron. It was also associated with increased lipid peroxidation and disruption of antioxidant defense in combination fed rats as compared to rats fed with alcohol or polyunsaturated fatty acids or iron. The present study revealed significant exacerbation of the alcohol-induced oxidative stress in presence of polyunsaturated fatty acids and iron.
RESUMEN
An analytical method based on high-performance liquid chromatography with ultraviolet detection (245 nm) was developed for the determination of actarit in human plasma. Coumarin was used as an internal standard. Chromatographic separation was achieved with a C8 column using a mobile phase of methanol: 1% acetic acid (50-50, v/v) with a flow rate of 1.0 ml/min. The calibration curve was linear over the range of 0.1-4.0 µg/ml (r(2) > 0.99) and the lower limit of quantification was 0.1 µg/ml. The method was validated for sensitivity, accuracy, precision, recovery and stability. The method was used to determine the concentration-time profiles of actarit in the plasma following oral administration of 100 mg actarit tablets.
RESUMEN
N-methyl-D-aspartate (NMDA) receptor and nitricoxide syntheses are the emerging target sites for development of novel drug molecules because their modulation affects the long term potentiation (LTP) process. NMDA receptor antagonists and nitric oxide synthase inhibitors induce amnesia in animals and therefore have been employed for evaluation of efficacy of several novel antiamnesic agents.Bacopa monniera Linn (syn. Brahmi) is commonly used in the ancient Indian medical system for improvement of memory deficit.We have earlier described the involvement of GABAergic and cholinergic system to account for the antiamnesic effects of B. monniera on diazepam- and scopolamine-induced amnesia.In extension to our previous study this study was designed to investigate the downstream mechanism of B. monniera by evaluation of its effect on MK-801 (an NMDA receptor antagonist) and N(w)-nitro-L-arginine (L-NNA) (a nitric oxide inhibitor)induced memory deficit. We used a Morris water maze scale and compared the degree of reversal of amnesia induced by the two agents. Male Swiss albino mice were subjected to a Rotarod muscle incoordination test followed by water maze tasks.Our data revealed that L-NNA and MK-801 produced anterograde and retrograde amnesia and B. monniera significantly attenuated the L-NNA-induced anterograde amnesia, partially reversing L-NNA-induced retrograde amnesia. On the other hand, B. monniera neither attenuated the MK-801-induced anterograde amnesia nor improved retrograde amnesia caused by it.
Asunto(s)
Amnesia/inducido químicamente , Amnesia/tratamiento farmacológico , Bacopa , Fitoterapia , Preparaciones de Plantas/uso terapéutico , Amnesia Anterógrada/inducido químicamente , Amnesia Anterógrada/tratamiento farmacológico , Amnesia Retrógrada/inducido químicamente , Amnesia Retrógrada/tratamiento farmacológico , Análisis de Varianza , Animales , Maleato de Dizocilpina , Excipientes/uso terapéutico , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Ratones , Actividad Motora/efectos de los fármacos , Nitroarginina , Polisorbatos/uso terapéuticoRESUMEN
The petroleum ether soluble fraction (SIPE) of the root extract of S. indicum was evaluated for the vasorelaxant activity using isolated rat aorta. SIPE up to 180 microg/ml concentration significantly inhibited phenylephrine- and KCl-induced contraction to the extent of 98.13 +/- 6.37 and 70.19 +/- 3.43% respectively in isolated rat aorta in a concentration dependent manner. The vasorelaxant activity was not blocked by propranolol (10 microM), atropine (1 microM) indomethacin (10 microM) and glibenclamide (10 microM). Influence of SIPE on phenylephrine-induced contractions in aortic preparations in absence of functional endothelium and on pre-incubating the tissue with L-NAME (300 microM) or methylene blue (10 microM) was also studied. SIPE at 180 microg/ml concentration could elicit partial relaxation in presence of L-NAME or methylene blue to the extent of 34.26 +/- 6.13 and 25.66 +/- 10.95% respectively. However, in absence of functional endothelium, SIPE exhibited little relaxation to the extent of 6.70 +/- 4.87%. These studies revealed that the vasorelaxant activity of SIPE was chiefly mediated through endothelium-dependent pathway.
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Fitoterapia , Extractos Vegetales/farmacología , Sesamum , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Aorta Torácica/efectos de los fármacos , Femenino , Técnicas In Vitro , Masculino , Extractos Vegetales/química , Raíces de Plantas , RatasRESUMEN
Benzodiazepines are known to produce amnesia by involvement of GABAergic system and by interference of long term potentiation (LTP). In this study, we examined effect of Bacopa monniera on downstream molecules of LTP after diazepam-induced amnesia in mice. We used a Morris water maze scale for evaluating the effect of Bacopa monniera after screening for muscle coordination by rota rod. The index of acquisition and retrieval was recorded as escape latency time (ELT). Behavioral results showed that Bacopa monniera (120 mg kg(-1) oral) significantly reversed diazepam- (1.75 mg kg(-1) i.p.) induced amnesia in Morris water maze task. The molecular studies revealed that diazepam upregulated mitogen activated protein kinase (MAP kinase), phosphorylated CREB (pCREB) and inducible nitric oxide synthase (iNOS), while it downregulated nitrite, nitrate, total nitrite, cAMP response element binding protein (CREB) expression, phosphodiesterase, cyclic adenosine monophosphate (cAMP) without affecting calmodulin levels. Bacopa monniera suppressed the diazepam induced upregulation of MAP kinase, pCREB and iNOS and attenuated the downregulation of nitrite. It did not affect the cAMP, PDE, nitrate, total nitrite, total CREB level. These behavioral findings displayed the reversal of diazepam-induced amnesia by Bacopa monniera without qualifying the molecular details although some downstream molecules of LTP may be involved.
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Amnesia Anterógrada/inducido químicamente , Amnesia Anterógrada/tratamiento farmacológico , Bacopa , Diazepam/farmacología , Aprendizaje por Laberinto/efectos de los fármacos , Preparaciones de Plantas/farmacología , Amnesia Anterógrada/metabolismo , Animales , Ansiolíticos/farmacología , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Calmodulina/metabolismo , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Interacciones Farmacológicas , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/fisiología , Ratones , Nitratos/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Nitritos/metabolismo , FitoterapiaRESUMEN
A simple, rapid and selective method was developed. The method was validated and found to be linear in the range of 100-4000 ng/ml. Chromatographic peaks were separated by means of a 5 mum, C18 silica column using acetonitrile and phosphate buffer (0.05 M) in proportion of 40:60 (pH 4.0) as a mobile phase. The retention time of torsemide was 5.00+/-0.20 min. The chromatograms showed good resolution and no interference from plasma. The mean recovery from human plasma was found to be above 82%. Both inter-day and intra-day accuracy and precision data showed good reproducibility. This method was applied to a single dose bioequivalence study. Log transformed values were compared by ANOVA followed by classical 90% confidence interval. Confidence limits for C(max), AUC(0-t) and AUC(0-inf) ranged from 98.6 to 102.8, 101.8 to 105.3 and 102.4 to 105.5 respectively. These results suggested that the analytical method was linear, precise and accurate. Test and reference product were found to be bioequivalent.
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The effect of chloroform soluble fraction (F-A) of twigs of Sarcostemma brevistigma on contractions induced by KCl, histamine, and acetylcholine in the isolated guinea pig ileum and taenia coli smooth muscles has been evaluated. F-A (19.5 microg/ml) significantly inhibited the contraction induced by 40 mM KCl to the extent of 87.6% in the isolated guinea pig ileum. In the isolated guinea pig ileum, F-A (64.3 and 59.2 microg/ml) significantly inhibited the contractions induced by acetylcholine and histamine to the extent of 85 and 83% respectively. In the isolated guinea pig taenia coli, F-A (65.2 microg/ml) significantly inhibited the contraction induced by 40 mM KCl to the extent of 96.0%. The inhibitory effect of F-A (40 microg/ml) on the isolated guinea pig taenia coli was reduced by Bay K 8644 (10(-6) M) to the extent of 61.6 from 73.6%. These results suggest that the F-A may exhibit smooth muscle relaxant activity by blocking the Ca2+ channels.
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Apocynaceae , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Parasimpatolíticos/farmacología , Extractos Vegetales/farmacología , Acetilcolina/farmacología , Animales , Apocynaceae/química , Relación Dosis-Respuesta a Droga , Cobayas , Histamina/farmacología , Íleon/efectos de los fármacos , Masculino , Extractos Vegetales/química , Cloruro de Potasio/farmacología , Verapamilo/farmacologíaRESUMEN
The sesquiterpene lactone fraction of Saussurea lappa roots was evaluated for its effect on the transudative, exudative and proliferative phases of inflammation using the cotton pellet granuloma assay in rats. The fraction (25-100 mg/kg, p.o.) showed significant dose-dependent inhibition of the increase in wet weight of the cotton pellet at 3 h (transudative phase), leakage of dye from the bloodstream around granuloma at 24 h (exudative phase) and increase in dry weight of the cotton pellet on day 6 (proliferative phase). It significantly lowered the elevated biochemical parameters such as alkaline phosphatase, acid phosphatase, gamma-glutamyltranspeptidase and significantly elevated the lowered albumin concentration in serum. The studies suggest that the antiinflammatory activity of the sesquiterpene lactone fraction of S. lappa may, in part, be due to stabilization of lysosomal membranes and an antiproliferative effect.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Granuloma de Cuerpo Extraño/prevención & control , Fitoterapia , Extractos Vegetales/farmacología , Saussurea , Fosfatasa Ácida/efectos de los fármacos , Administración Oral , Fosfatasa Alcalina/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Exudados y Transudados/efectos de los fármacos , Lactonas/administración & dosificación , Lactonas/farmacología , Lactonas/uso terapéutico , Extractos Vegetales/administración & dosificación , Extractos Vegetales/uso terapéutico , Raíces de Plantas , Ratas , Ratas Wistar , Albúmina Sérica/efectos de los fármacos , Sesquiterpenos/administración & dosificación , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéutico , gamma-Glutamiltransferasa/efectos de los fármacosRESUMEN
The flavonoid fraction of Tephrosia purpurea (FFTP) was studied for its effect on cellular and humoral functions and on macrophage phagocytosis in mice. Oral administration of FFTP (10-40 mg/kg) significantly inhibited sheep red blood cells (SRBC)-induced delayed-type hypersensitivity reactions. It also produced a significant, dose-related decrease in sheep erythrocyte-specific haemagglutination antibody titre. However, the fraction failed to show a significant change in the macrophage phagocytic activity. The results obtained indicate the ability of the flavonoidal fraction of T. purpurea to modulate both the cell-mediated and the humoral components of the immune system.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Flavonoides/farmacología , Hipersensibilidad Tardía/inmunología , Fagocitosis/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacología , Tephrosia , Adyuvantes Inmunológicos/administración & dosificación , Administración Oral , Animales , Relación Dosis-Respuesta a Droga , Eritrocitos/inmunología , Femenino , Flavonoides/administración & dosificación , Humanos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Masculino , Ratones , Extractos Vegetales/administración & dosificación , OvinosRESUMEN
The objective of the present study was to investigate the immunomodulatory activity of Argyreia speciosa on cellular and humoral immunity. Oral administration of the ethanolic extract of A. speciosa root (ASEE), at the doses of 50, 100 and 200 mg/kg in mice, dose-dependently potentiated the delayed-type hypersensitivity reaction induced both by sheep red blood cells (SRBC) and oxazolone. It significantly enhanced the production of circulating antibody titre in mice in response to SRBC. ASEE failed to show any effect on macrophage phagocytosis. Chronic administration of ASEE significantly ameliorated the total white blood cell count and also restored the myelosuppressive effects induced by cyclophosphamide. The present investigation reveals that ASEE possesses immunomodulatory activity.