Anti-Inflammatory Local Effect of Hydroxytyrosol Combined with Pectin-Alginate and Olive Oil on Trinitrobenzene Sulfonic Acid-Induced Colitis in Wistar Rats.

Purpose: Evaluate the efficacy of hydroxytyrosol in the local treatment of inflammatory colitis. Currently, the existing treatments for inflammatory bowel diseases does not cure the disease and it is associated with high rates of side effects and complications. Hydroxytyrosol is a phenyl-ethyl-alcohol derived from the hydrolysis of oleuropein and present in olive oil, previous studies have demonstrated the anti-inflammatory effect of dietary hydroxytyrosol supplement, with no toxicity. Materials & Methods: Colitis has been induced by using Trinitrobenzene Sulfonic Acid at 40 rats. They were divided into four groups randomly: 10 rats without treatment; 10 rats with pectin/alginate mixture; 10 rats treated with pectin/alginate + olive oil; 10 rats treated with pectin/alginate + olive oil + hydroxytyrosol. Animals were sacrificed 10 days after induction of trinitrobenzene sulfonic acid, receiving 5 days of continuous treatment. Samples of the rectal area were studied and observed under a microscope to determine the damage by Hunter scoring modified, assessing inflammatory infiltration, number of intestinal walls involved, damage to the mucosal architecture, and edema. Results: When the rectum was analyzed in a global way, nonsignificant differences were observed; however, when performing an individualized analysis, statistically significant differences in the inflammatory infiltrate are present in the samples, which were evaluated using the ANOVA and Student-T statistics. Conclusions: Local treatment with the natural antioxidant hydroxytyrosol combined with pectin/alginate and olive oil of inflammatory bowel disease has been shown to be effective against inflammatory infiltration of TNBS-induced colitis.

Dietary oleuropein and its new acyl-derivate attenuate murine lupus nephritis through HO-1/Nrf2 activation and suppressing JAK/STAT, NF-κB, MAPK and NLRP3 inflammasome signaling pathways.

Systemic lupus erythemathosus (SLE) is a chronic inflammatory and autoimmune disease which can affect multiple organ systems, without an effective and safe treatment. Olive leaf extracts are of special interest for their therapeutic effects. Oleuropein (OL) is the most abundant constituents of olive leaf extract and possesses many beneficial properties. In this study, we evaluated the effects of dietary OL and its new derivate, peracetylated oleuropein (Per-OL), in a pristane-induced SLE model. Mice received an injection of pristane or saline solution and were fed with experimental diets: enriched with OL and Per-OL. The levels of proinflammatory cytokines and markers were evaluated by enzyme-linked immunosorbent assay. The protein expressions of inducible nitric oxide synthase, microsomal prostaglandin E synthase 1, heme oxygenase (HO-1), nuclear factor E2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear transcription factor-kappa B (NF-κB) and inflammasome nucleotide-binding domain, leucine-rich repeats-containing family, pyrin domain-containing-3 (NLRP3) pathways activation were determined in kidneys by Western blot. OL and Per-OL significantly reduced renal damage and decreased serum matrix metalloproteinase 3 and prostaglandine E2 kidneys levels. Our findings indicate that Nrf2 and HO-1 antioxidant protein expressions were up-regulated in mice fed with OL and Per-OL diets, whereas the activation of JAK/STAT, MAPK, NF-κB and NLRP3 inflammasome pathways was significantly ameliorated. These results suggest that OL and Per-OL supplementation might provide a new alternative approach as a preventive/palliative treatment of nephritis in SLE management.

New leads for selective inhibitors of alpha-L-fucosidases. Synthesis and glycosidase inhibitory activities of [(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]furan derivatives.

Readily derived from D-glucose, 5-[(2R,3S,4R)-3,4-dihydroxypyrrolidin-2-yl]-2-methyl-3-furoic esters and amides are selective and competitive inhibitors (K(i)> or = 3 microM) of alpha-L-fucosidase from bovine epididymis and from human placenta.

Olive fruit cell wall: degradation of pectic polysaccharides during ripening.

Olive fruits at three stages of ripening (green, cherry, and black) have been studied. After cell wall isolation, the compositions of the cell wall and that of the phosphate-soluble polysaccharides were determined. In cell walls, decreases in arabinose, xylose, glucose, and uronic acid levels were observed, together with a slight increase in mannose on ripening. At the beginning of ripening, fragments of pectic polymers were the major constituents of the phosphate-soluble fraction, with the hemicellulosic ones increasing toward the end of the process. The molecular weight of the fragments solubilized was approximately 6 kDa. After cell wall fractionation, the pectic polysaccharides soluble in imidazole and sodium carbonate were also studied. In both fractions, between the green and cherry stages of ripening, a significant loss of homogalacturonans took place. Between the cherry and black stages of ripening, rhamnogalacturonan side chains were also released in addition to homogalacturonans. In any of the pectic fractions, changes in apparent molecular weight were quantified.

Induction of glucose-6-phosphate dehydrogenase by lipopolysaccharide contributes to preventing nitric oxide-mediated glutathione depletion in cultured rat astrocytes.

Treatment of cultured rat astrocytes with lipopolysaccharide (LPS; 1 microg/ml) increased mRNA expression of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting step in the pentose phosphate pathway (PPP), in a time-dependent fashion (0-24 h). This effect was accompanied by an increase in G6PD activity (1.74-fold) and in the rate of glucose oxidation through the PPP (6.32-fold). Inhibition of inducible nitric oxide synthase (iNOS) activity by 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT; 50 microM) did not alter the LPS-mediated enhancement of G6PD mRNA expression or PPP activity. Blockade of nuclear factor-kappaB (NF-kappaB) activation by N-benzyloxycarbonyl-Ile-Glu-(O-tert-butyl)-Ala-leucinal (1 microM) prevented the expression of both iNOS mRNA and G6PD mRNA, suggesting that iNOS and G6PD are co-induced by LPS through a common transcriptional pathway involving NF-kappaB activation. Incubation of cells with LPS for 24 h increased intracellular NADPH concentrations (1.63-fold) as compared with untreated cells, but GSH concentrations were not modified by LPS treatment up to 60 h of incubation. However, inhibition of G6PD activity by dehydroepiandrosterone (DHEA; 100 microM), which prevented LPS-mediated enhancements in PPP activity and NADPH concentrations, caused a 50% decrease in the GSH/GSSG ratio after 24-36 h and in GSH concentrations after 60 h of incubation. Furthermore, the changes in glutathione concentrations caused by DHEA were abolished by AMT, suggesting that nitric oxide and/or its reactive derivatives would be involved in this process. From these results, we conclude that LPS-mediated G6PD expression prevents GSH depletion due to nitric oxide and suggest that this phenomenon may be a contributing factor in the defense mechanisms that protect astrocytes against nitric oxide-mediated cell injury.

Degradation of pectic polysaccharides in pickled green olives.

The changes that occur in the pectic fractions in the cell wall of olives of the Manzanilla variety (Olea europaea pomiformis) during processing (initial treatment at high pH and subsequent lactic fermentation) have been researched. After studying various conditions for fractionating the pectic polysaccharides, the most adequate were chosen, involving sequential extraction with water, imidazole-hydrochloric acid buffer, sodium carbonate, 1 M potassium hydroxide, and 4 M potassium hydroxide. In the unprocessed fruit, the fractions studied consist mainly of high-molecular-weight acidic polysaccharides (70 to 250 kDa): homogalacturonans, rhamnogalacturonans, and branched arabinans. These were found in different proportions depending on the extraction agent used. At the same time, significant amounts of relatively low-molecular-weight (10 to 10.5 kDa) neutral branched arabinans were found in the water-soluble fraction. As a result of the processing, changes occurred in the proportions of the different groups of polysaccharides in accordance with changes in their solubility characteristics. These changes were reflected in the processed fruit by (i) and increase in the neutral branched arabinans in the water-soluble fraction due to the increased presence of such polysaccharides originally found in the carbonate and 4 M KOH-soluble fractions; (ii) an increase in homogalacturonans and rhamnogalacturonans, without significant changes in molecular weights, in the imidazole-soluble fraction as a result of the increased presence of corresponding polysaccharides originally found in the carbonate-soluble and water-soluble fractions; (iii) a substantial increase in uronic acids in the 1 M potassium hydroxide-soluble fraction, preferentially as low-molecular-weight polysaccharides; and (iv) a solubilization of arabinans in the 4 M potassium hydroxide-soluble fraction.

Tetrahedral recording of 3-D BAEPs: evidence for the centered dipole model.

Three-dimensional brain-stem auditory evoked potentials (3-D BAEPs) were recorded from 12 normal subjects using a new tetrahedral montage, as well as two other bipolar montages previously described for 3-channel Lissajous' trajectories (3-CLTs). Mean responses, as well as between-subject and within-subject variability were described. A mathematical transformation was applied to the recorded trajectories to render them in a common canonical form to test the assumption that the BAEP conforms to a centrally generated dipolar field. Apex, segment, and plane orientations were measured for each trajectory, and discrepancies between montages were evaluated to judge the adequacy of the centered dipole model. For the vector means of apices, segments, and planes, median angles of discrepancy between montages ranged from 10 to 23 degrees. These results support the validity of a centered dipole model for the BAEP and affirm the rationale for employing the 3-channel recording technique. Among the montages studied, the tetrahedron provided maximum economy by using fewer electrodes, avoided certain problematic recording sites, and produced less variable data.

Stress-induced gastroduodenal lesions and total parenteral nutrition in critically ill patients: frequency, complications, and the value of prophylactic treatment. A prospective, randomized study.

OBJECTIVE: To assess the frequency, complications, and value of prophylactic treatment of stress-induced gastroduodenal lesions. DESIGNS: Patients were prospectively randomized to treatment with total parenteral nutrition, either alone, with sucralfate, or with ranitidine. SETTING: A multidisciplinary ICU from a tertiary care referral center. PATIENTS: Ninety-seven patients submitted to prolonged mechanical ventilation, with normal hepatic and renal function, in metabolic stress, and receiving total parenteral nutrition. INTERVENTIONS: On admission, we determined the Acute Physiology and Chronic Health Evaluation II score and the catabolic index score. We also performed an endoscopic examination on day 3, every 7 days subsequently, and whenever needed. Thirty patients received total parenteral nutrition alone. Twenty-four patients received total parenteral nutrition and sucralfate (1 g by nasogastric tube every 4 hrs). Nineteen patients received total parenteral nutrition and ranitidine (50 mg iv every 6 hrs). MAIN RESULTS: The overall occurrence rate of gastroduodenal mucosal damage was 29.6%. The overall frequency rate for stress ulcerations was 15.6% and was 6.2% for stress hemorrhage. There were no deaths secondary to stress hemorrhage. The difference in the frequency of stress-induced mucosal lesions and stress hemorrhage between the studied groups was not statistically significant. CONCLUSIONS: Additional prophylaxis to total parenteral nutrition in the form of sucralfate and ranitidine to prevent acute upper gastrointestinal bleeding is not required in this group of ICU patients.

Adipsia-polydipsia induced by simultaneous lesion of the medioventral septum and anteroventral third ventricle area in the rat.

The medioventral septal area (MVS) and also the tissue surrounding the periventricular preoptic-hypothalamic region (AV3V) of male rats, were destroyed by mean of electrolytic lesions. Before and after the lesions, daily water and food intakes, diuresis, body weight, urine osmolarity, and sodium and potassium excretion were determined. Rats with simultaneous AV3V-MVS lesions showed a biphasic pattern of drinking behavior characterized by a first period of adipsia followed by another period of polydipsia. During the first period of adipsia and except for the first two days, postlesion rats were able to reduce total urine volume but failed to produce an appropriate concentrated urine. During the polydipsia period, on the contrary, rats increased urine output and decreased urine osmolarity in a parallel fashion. Immediately after the lesion, food intake was decreased but recovered to pre-lesion levels gradually. By contrast, body weight was decreased during the entire period of the experiment. Sodium but not potassium excretion showed a significant increase from the 9th to the 20th day postlesion. The results suggest that the AV3V and MVS are part of a circuitry subserving the control of water intake and electrolyte balance.