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Biomedical subjects

R M Silva

Publications and source records attributed to R M Silva.

At least 19 recordsLinked to original sources

Bacterial translocation, microcirculation injury and sepsis.

Sepsis is the result from a complex bacterial-host interaction, which is an often-fatal response when host protective molecular mechanisms designed to fight invading bacteria surpass the beneficial intensity to the point of causing injury to the host. Increasing evidences have implicated the bacterial translocation (BT) as the main source for the induction of sepsis, although the beneficial effect of BT process has been related to the development of the intestinal immune response by physiological interaction between bacteria and host. In this article, we examined evolving concepts concerning to BT and discussed about its potential role in the promotion of microcirculation injury, moreover, its possible participation in the sepsis induction. According to our data obtained from in-vivo BT animal-model, both bacterial overgrowth and bacterial pathogenic determinants seem to be major predisposing factors for the induction of BT. Besides, translocation of luminal bacteria through the lymphatic via elicits the activation of the GALT inflammatory response contributing to microcirculation injuries, and the haematological via of BT was responsible to the systemic bacterial spread. On other hand, the combination of BT process to the pre-existing host systemic infection played a crucial role in the worsening of the clinical outcome. In our understanding, studies concerning to intestinal immune response and the pathophysiology of bacterial-host interaction, under normal and disease conditions, seems to be the key elements to the development of therapeutic approaches towards sepsis.

Animals↗

1,8-cineole (eucalyptol), a monoterpene oxide attenuates the colonic damage in rats on acute TNBS-colitis.

The monoterpene oxide, 1,8-cineole (cineole, eucalyptol) was examined for its possible influence on the acute phase of trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats. The test compound, 1,8-cineole (200 and 400 mg/kg) or vehicle (1 ml, 2% Tween 80) was instilled rectally, 24, and 2 h before (pre-treatment) or 2 and 24 h after (post-treatment) the induction of colitis by intracolonic administration of TNBS (0.25 ml of 25 mg of TNBS in 50% ethanol). Rats were killed 48 h after colitis induction and colonic segments were analysed for gross damage scores, changes in wet weights, myeloperoxidase activity, an indicator of neutrophilic infiltration and glutathione level, a major cellular antioxidant. TNBS induced an extensive inflammation and ulceration in the colon. Colonic damage was associated with an increase in myeloperoxidase activity and by a decrease in glutathione. When compared to vehicle-treated TNBS controls, a marked reduction in gross damage scores and wet weights (mg/cm) of colonic segments were evident in animals pre-treated but not post-treated with 1,8-cineole. Cineole also significantly reduced the myeloperoxidase activity, and caused repletion of glutathione. These results confirm the anti-inflammatory action of 1,8-cineole and suggest its potential value as a dietary flavoring agent in the prevention of gastrointestinal inflammation and ulceration.

Acute Disease↗

Protective effect of Copaifera langsdorffii oleo-resin against acetic acid-induced colitis in rats.

The oleo-resin from Copaifera langsdorffii (Leguminosae) was evaluated in rats on acetic acid-induced colitis. Rats were pretreated orally (15 and 2 h) or rectally (2 h) before the induction of colitis with copaiba oleo-resin (200 and 400 mg/kg) or vehicle (1 ml, 2% Tween 80). Colitis was induced by intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and 24 h later, the colonic mucosal damage was analyzed for the severity of macroscopic colonic damage, myeloperoxidase (MPO) activity, and malondialdehyde levels. A significant reduction in gross damage score and in wet weight/length ratio of colonic tissue were evident in test substance-pretreated animals as compared to vehicle or oleo-resin alone-treated controls. This effect was confirmed biochemically by a reduction in colonic myeloperoxidase activity, the marker of neutrophilic infiltration, and by a marked decrease in malondialdehyde level, an indicator of lipoperoxidation. Furthermore, microscopical examination revealed the diminution of inflammatory cell infiltration, and submucosal edema in the colon segments of rats treated with copaiba oleo-resin. The data indicate the protective effect of copaiba oleo-resin in the animal model of acute colitis possibly through an antioxidant and or anti-lipoperoxidative mechanism.

Acetic Acid↗

Influence of beta-radiation sterilisation in properties of new chitosan/soybean protein isolate membranes for guided bone regeneration.

Novel chitosan (cts) and soybean protein isolate (SI) blended membranes were prepared. These membranes were produced by solvent casting. Besides combining the advantages of both materials, cts/SI membranes exhibit a biphasic structure that will eventually originate in situ porous formation, through a two-step degradation mechanism. In this particular work the effect of beta-radiation over the properties of these membranes was evaluated. beta-radiation sterilisation was performed at three different doses (25, 50 and 100 kGy) and eventual surface chemical changes were evaluated by Fourier transformed infrared--with attenuated total reflection and contact angle measurements. Moreover, eventual bulk properties changes due to beta-radiation were assessed by means of mechanical tensile tests and water uptake measurements. In general, no substantial changes were detected on the studied properties, with the exception of the surface energy that was found to be slightly increased for higher applied doses.

Beta Particles↗

Preparation and characterisation in simulated body conditions of glutaraldehyde crosslinked chitosan membranes.

Chitosan membranes, aimed at biomedical applications, were prepared by a solvent casting methodology. Crosslinking was previously performed in acetic acid solution with glutaraldehyde, in order to obtain different degrees of crosslinking. Some membranes were neutralised in a NaOH solution. Mechanical tensile tests comprised quasi-static experiments at constant stress rate and temperature sweep dynamic mechanical analysis tests. This included measurements with the samples immersed in isotonic saline solution at 37 degrees C, in order to simulate physiological conditions, that were performed using a specific liquid container. It was observed that for higher crosslinking levels the membranes become stiffer but their strength decreases; these results are in agreement with swelling tests, also performed at body temperature. All the membranes exhibited similar and significant damping properties in wet conditions, which were stable in a broad temperature range. Weight loss measurements showed that the developed membranes degrade slowly up to 60 days. Cytotoxicity screening, using cell culture tests, showed that eventually such materials could be adequate for use in biomedical applications.

Acetic Acid↗

Effects of nitric oxide synthase inhibitors and melatonin on the hyperglycemic response to streptozotocin in rats.

Recent studies evidence that peroxynitrite is spontaneously formed when nitric oxide (NO) and superoxide coexist and suggest that it is likely to be involved in the destruction of the pancreatic beta cells. We examined whether drugs that inhibit nitric oxide synthase (NOS) or scavenge peroxynitrite could abrogate STZ-induced hyperglycemia in rats. Blood glucose levels were measured before (0 h) and 24, 48, and 72 h following intraperitoneal administration of 60 mg/kg streptozotocin (STZ). The levels of blood sugar in STZ-treated control animals were significantly elevated at all time points of observation with a peak increase at 48 h. The hyperglycemic response of STZ was found to be significantly reduced in animals pretreated with aminoguanidine (50 mg/kg i.p.), an inducible isoform-selective NOS (iNOS) inhibitor with antioxidant property, and by melatonin (6 mg/kg i.p.), an antioxidant that also prevents peroxynitrite formation but not by Nw-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg i.p.), and 7-nitroindazole (7-NI, 50 mg/kg i.p.), the constitutive inhibitors of endothelial and neuronal NOS, respectively. These findings indicate the possible participation of iNOS-derived NO as well as oxygen free radicals in STZ-induced pancreatic beta cell destruction and compounds that act as scavengers of peroxynitrite may offer protection against such a damage.

Analysis of Variance↗

Anti-inflammatory effect of kaurenoic acid, a diterpene from Copaifera langsdorffi on acetic acid-induced colitis in rats.

Kaurenoic acid, a diterpene from Copaifera langsdorffii (Leguminaceae), was evaluated on rat colitis induced by acetic acid. Rats were pretreated orally (15 and 2 h before) or rectally 2 h before induction of colitis with kaurenoic acid (50 and 100 mg/kg) or vehicle (1 ml, 3% DMSO). Colitis was induced by intracolonic instillation of a 2 ml of 4% (v/v) acetic acid solution and, 24 h later, the colonic mucosal damage was analysed macroscopically for the severity of mucosal damage, the myeloperoxidase (MPO) activity and the malondialdehyde (MDA) levels in the colon segments. A marked reduction in gross damage score (52% and 42%) and wet weight of damaged colon tissue (39% and 32%) were observed in rats that received 100 mg/kg kaurenoic acid, respectively, by rectal and oral routes. This effect was confirmed biochemically by a two- to three-fold reduction of colitis associated increase in MPO activity, the marker of neutrophilic infiltration and by a marked decrease in MDA level, an indicator of lipoperoxidation in colon tissue. Furthermore, light microscopy revealed the marked diminution of inflammatory cell infiltration and submucosal edema formation in the colon segments of rats treated with the test compound. These findings indicate the anti-inflammatory potential of kaurenoic acid in acetic acid-induced colitis.

Acetic Acid↗

Studies on the antidiarrhoeal effect of dragon's blood from Croton urucurana.

The red sap obtained by slashing the bark of Croton urucurana Baill. (Euphorbiaceae), also known as dragon's blood, was screened for a possible antidiarrhoeal activity on castor oil-induced diarrhoea in rats, cholera toxin-induced intestinal secretion in mice and on small intestinal transit in mice. Dragon's blood at an oral dose of 600 mg/kg caused in marked inhibition of the diarrhoeal response following castor oil administration as well as the intestinal fluid accumulation promoted by cholera toxin. At a similar dose the red sap significantly inhibited the small intestinal transit which was, however, found to be independent of the opioid mechanism. These results suggest a potential usefulness of the red sap from Croton urucurana Baill. in the control of secretory diarrhoea associated pathologies.

Animals↗

Blood glucose- and triglyceride-lowering effect of trans-dehydrocrotonin, a diterpene from Croton cajucara Benth., in rats.

AIM: The objective of this study was to assess in rats the antidiabetic effects (i.e. reduction of hyperglycaemia and hypertriglyceridaemia) of trans-dehydrocrotonin (t-DCTN), a bioactive diterpene isolated from the popular medicinal plant Croton cajucara. METHODS: Hyperglycaemia was induced by intraperitoneal injection of streptozotocin (STZ) and hypertriglyceridaemia by oral administration of ethanol in rats. The blood glucose levels were measured by the glucose oxidase method using commercially available enzyme kits. RESULTS: Treating rats with t-DCTN (50 mg/kg) significantly reduced STZ-induced increases in blood glucose levels as well as ethanol-induced increases in blood triglycerides. CONCLUSION: The results suggest that t-DCTN has an antidiabetic potential that warrants further research on its mechanism and clinical significance.

Animals↗

Effect of trans-dehydrocrotonin, a 19-nor-clerodane diterpene from Croton cajucara on experimental hypertriglyceridaemia and hypercholesterolaemia induced by Triton WR 1339 (tyloxapol) in mice.

The effect of trans-dehydrocrotonin (t-DCTN) from Croton cajucara Benth. was investigated in mice on Triton WR 1339 (tyloxapol)-induced hypercholesterolaemia and hypertriglyceridaemia. Mice treated with single application of tyloxapol (400 mg/kg, i.p.) demonstrated significantly increased blood levels of total cholesterol and triglycerides at 24 h and 48 h after its injection, compared to normal controls. These increases were found to be markedly suppressed in animals treated orally with 25 and 50 mg/kg t-DCTN or 100 mg/kg gemfibrozil, an established antihypercholesterolaemic drug. These results suggest that t-DCTN may be a suitable candidate for combating pathologies associated with hyperlipaemia.

Animals↗

1,8-cineole protects against liver failure in an in-vivo murine model of endotoxemic shock.

The effects of 1,8-cineole on D-galactosamine/lipopolysaccharide (GalN/LPS)-induced shock model of liver injury was investigated in mice. The co-administration of GalN (700 mg kg(-1), i.p.) and LPS (5 microg kg(-1), i.p.) greatly elevated serum concentrations of tumour necrosis factor-alpha (TNF-alpha), alanine aminotransferase and aspartate aminotransferase, and induced massive hepatic necrosis and lethality in 100% of control mice. Pretreatment with 1,8-cineole (400 mg kg(-1), p.o.) and dexamethasone (1 mg kg(-1), s.c.), 60 min before GalN/LPS, offered complete protection (100%) against the lethal shock and acute elevation in serum TNF-alpha and serum transaminases. Hepatic necrosis induced by GalN/LPS was also greatly reduced by both 1,8-cineole and dexamethasone treatment. The results indicate that 1,8-cineole protects mice against GalN/LPS-induced liver injury through the inhibition of TNF-alpha production, and suggest that 1,8-cineole may be a promising agent to combat septic-shock-associated pathologies.

Animals↗