998 resultados para Gastrointestinal Agents


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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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O objetivo deste trabalho foi investigar o efeito da idade das matrizes pesadas sobre o desenvolvimento do trato gastrointestinal (TGI) dos embriões no terço final do período de incubação, bem como a utilização das reservas do saco vitelino nas 24 h pós-eclosão, em pintos alimentados ou em jejum. Foram utilizados ovos férteis da linhagem Cobb 500, oriundos de matrizes pesadas com 30 e 60 semanas de idade. O desenvolvimento do TGI (proventrículo+moela, segmentos do intestino delgado e saco vitelino) foi estudado entre o 17º e 21º dias de incubação (Experimento 1). Nas 24 h pós-eclosão foi pesquisado o efeito da presença ou não de alimento no lúmen intestinal sobre a utilização das reservas do saco vitelino (Experimento 2). Os achados deste trabalho mostraram que, ao contrário do embrião, o desenvolvimento do intestino delgado e o peso do saco vitelino não sofreram influência da idade das matrizes. Na fase pós-eclosão, na ausência de alimento, o desenvolvimento do intestino delgado foi maior nas matrizes com 60 semanas, sendo dependente do crescimento do jejuno. A presença do alimento no lúmen teve influência na utilização das reservas do saco vitelino apenas nas matrizes com 30 semanas de idade. Os resultados deste experimento mostraram que a idade da matriz é importante fator no desenvolvimento do trato gastrointestinal do embrião, sendo fator relevante no crescimento pós-ecloão dos pintos.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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The objective of this experiment was to investigate the effects of different particle sizes, expressed as Geometric Mean Diameter (GMD) of corn (0.336mm, 0.585mm, 0.856mm and 1.12mm) of mash and pelleted broiler chicken diets on the weight of the gizzard, duodenum and jejunum+ileum; on the pH of the gizzard and small intestine and on the characteristics of the duodenal mucous layer (number and height of villi and crypt depth) in 42-day-old broilers. The physical form and the particle size of the diet had no significant effect on gizzard and intestine pH (p > 0.05). A greater gizzard weight was seen in the birds receiving pelleted diet and particle size of 0.336mm (p < 0.008). However, for the particle sizes of 0.856 and 1.12 mm, a greater weight was found in birds that received mash diet (p < 0.039 and p < 0.006, respectively). Also, gizzard weight was greater with increasing corn GMD independent of the physical form of the diet. In the mash diet, the increase in particle size promoted a quadratic response in the weight of duodenum and jejunum + ileum. The pelleted diet promoted a greater number of villi per transverse duodenum cut (p < 0.007) and greater crypt depth (p < 0.05). As the particle size increased, there was a linear increase of villus height and crypt depth in the duodenum, irrespective of the physical form of the diet.

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Resistance to natural infection by gastrointestinal nematodes was compared in 67 female calves of the following genetic groups: Nelore (NX); 1/2 Senepol + 1/2 Nelore (SN); and 1/2 Aberdeen Angus + 1/2 Nelore (AN). The NX (n = 26), SN (n = 23) and AN (n = 18) animals were monitored for 14 months, during which they remained without treatment, allowed to graze in a tropical environment. Eggs per gram of feces (EPG), coprocultures and packed cell volume (PCV) were carried out monthly. No significant effects of the interaction between the genetic groups and month/year of collection and the genetic group on the EPG were found, but there was a significant influence of the month of collection (P < 0.01). The monthly PCV measurements did not differ for the animals of the three genetic groups and there was no association found between the EPG and PCV. The animals of the SN and NX groups showed similar numbers of EPG with results zero, while for the AN group these numbers were significantly lower (P < 0.05). Although the NX group had a large number of EPG with results zero, it also contained many animals with high counts, meaning this group had higher averages during the entire study period. The following nematode genera were found in the coprocultures: Haemonchus, Cooperia, Oesophagostomum and Trichostrongylus, the latter in smallest proportion. There was no significant difference between the genetic groups for averages of all parasites identified, except Cooperia, which were present in higher numbers in the animals of the NX group (P < 0.05). The results obtained in this experiment suggest that the use of Bos taurus x Bos indicus crossbreeds can be a good strategy to reduce the use of chemical control in Brazil. (C) 2009 Elsevier B.V. All rights reserved.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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The Topliss method was used to guide a synthetic path in support of drug discovery efforts toward the identification of potent antimycobacterial agents. Salicylic acid and its derivatives, p-chloro, p-methoxy, and m-chlorosalicylic acid, exemplify a series of synthetic compounds whose minimum inhibitory concentrations for a strain of Mycobacterium were determined and compared to those of the reference drug, p-aminosalicylic acid. Several physicochemical descriptors (including Hammett's sigma constant, ionization constant, dipole moment, Hansch constant, calculated partition coefficient, Sterimol-L and -B-4 and molecular volume) were considered to elucidate structure-activity relationships. Molecular electrostatic potential and molecular dipole moment maps were also calculated using the AM1 semi-empirical method. Among the new derivatives, m-chlorosalicylic acid showed the lowest minimum inhibitory concentration. The overall results suggest that both physicochemical properties and electronic features may influence the biological activity of this series of antimycobacterial agents and thus should be considered in designing new p-aminosalicylic acid analogs.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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With the objective of obtaining slow-acting isoniazid derivatives, of potential use as chemoprophylactics or chemotherapeutics in tuberculosis, the micelle-forming copolymer of poly(ethylene glycol)-poly(aspartic acid) prodrug with isoniazid was synthesized. The derivative obtained was found to be active in Mycobacterium Il(tuberculosis culture, with a minimal inhibitory concentration (MIC) 5.6 times lower than that of the tuberculostatic drug.

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Nitroaromatic compounds such as nifuroxazide are used in many human enteropathogenic bacteria infections without causing an increase in the plasmidial antibiotic resistance of the aerobic Gram-negative intestinal Enterobacteriaceae. For these reasons, these compounds have been synthesized using the rational approach of Topliss' decision tree. Generally. this approach allows us to obtain the most active derivative from the series in a few steps. These compounds were tested against Mycobacterium tuberculosis in vitro and the most active of the series identified. A new lead for potential tuberculostatic activity has been predicted and will be used in further QSAR studies. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

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The aim of this study was to develop multiparticulate therapeutic systems of alginate (AL) and chitosan (CS) containing triamcinolone (TC) to colonic drug delivery. Multiparticulate systems of AL-CS, prepared by a complex coacervation/ionotropic gelation method, were characterized for morphological and size aspects, swelling degree, encapsulation content and efficiency, in vitro release profile in different environments simulating the gastrointestinal tract (GIT) and in vivo gastrointestinal transit. The systems showed suitable morphological characteristics with particle diameters of approximately 1.6 mm. In simulated gastric environment, at pH 1.2, the capsules presented low degree of swelling and in vitro release of drug. A higher swelling degree was observed in simulated enteric environment, pH 7.5, followed by erosion. Practically all the drug was released after 6 h of in vitro assay. The in vivo analysis of gastrointestinal transit, carried out in rats, showed that the systems passed practically intact through the stomach and did not show the same profile of swelling observed in the in vitro tests. It was possible to verify the presence of capsules in the colonic region of GIT. The results indicate that AL-CS multiparticulate systems can be used as an adjuvant for the preparation of therapeutic systems to colonic delivery of drugs. (C) 2010 Elsevier Ltd. All rights reserved.

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Drug delivery systems based on natural polysaccharides, such as chitosan (CS) and pectin (PC), rather than on synthetic polymers, have been widely studied. Some reasons for that are low toxicity and costs and high biodegradability of the formers. A multiparticulate system based on CS and PC was developed in our laboratories, including the addition of an enteric polymer, cellulose acetate phtalate (CAP). Such improvement promoted stronger gastric and enteric resistances, as assessed in vitro, making the systems more selective to enzymatic degradation in the colon. Although in vitro dissolution tests can simulate some properties concerning the gastrointestinal transit (GT), collaborating to characterize the systems behavior in the biological fluids, frequently they do not result in satisfactory in vitro/in vivo correlations. The objective of this work was to follow in vivo the GT of the particles developed by means of AC biosusceptometry (ACB), a non-invasive and of low cost methodology. The particles containing ferrite in powder form were prepared by complex coacervation using an ideal 3:1:1 mass ratio for PC:CS:CAP. The magnetic particles were administered to healthy volunteers by oral route. The GT was monitored by using multi-sensor ACB system and the signal acquisition was performed every IS min until the colonic region was reached. By means of ACB technique, it was possible to acquiring images generated by the magnetic particles within the whole gastrointestinal tract including the colonic region. Variable particles transit times were observed among the volunteers, but without interference on the mapping of the particles until the colonic region. The particles were able to produce magnetic field strong enough to generate signals adequate for mapping the particles. The results suggest that integral particles reached the colon, after they resisted against gastric and enteric media. Studies associating transit time and in vivo drug release are in development in order to confirm the efficiency of the systems.

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The smaller volemic state from hypertonic (7.5%) saline (HS) solution administration in hemorrhagic shock can determine lesser systemic oxygen delivery and tissue oxygenation than conventional plasma expanders. In a model of hemorrhagic shock in dogs, we studied the systemic and gastrointestinal oxygenation effects of HS and hyperoncotic (6%) dextran-70 in combination with HS (HSD) solutions in comparison with lactated Ringer's (LR) and (6%) hydroxyethyl starch (HES) solutions. Forty-eight mongrel dogs were anesthetized, mechanically ventilated, and subjected to splenectomy. A gastric air tonometer was placed. in the stomach for intramucosal gastric CO2 (Pgco(2)) determination and for the calculation of intramucosal. pH (pHi):[pHi = pHa - log(Pgco(2)/Paco(2))].The dogs were hemorrhaged (42% of blood volume) to hold mean arterial blood pressure at 40-50 mm Hg over 30 min and were then resuscitated with LR (n = 12) in a 3:1 relation to removed blood volume; HS (n = 12), 6 mL / kg; HSD (n = 12), 6 mL / kg; and HES (mean molecular weight, 200 kDa; degree of substitution, 0.5) (n = 12) in a 1:1 relation to the removed blood volume. Hemodynamic, systemic, and gastric oxygenation variables were measured at baseline, after 30 min of hemorrhage, and 5, 60, and 120 min after intravascular fluid resuscitation. After fluid resuscitation, HS showed significantly lower arterial pH and mixed venous Po-2 and higher systemic oxygen uptake index and systemic oxygenation extraction than LR and HES (P < 0.05), whereas HSD showed significantly lower arterial pH than LR and HES (P < 0.05). Only HS and HSD did not return arterial pH and pHi to control levels (P < 0.05). In conclusion, all solutions improved systemic and gastrointestinal oxygenation after hemorrhagic shock in dogs. However, the HS solution showed the worst response in comparison to LR and HES solutions in relation to systemic oxygenation, whereas HSD showed intermediate values. HS and HSD solutions did not return regional oxygenation to control values.