Vitamin A and inflammatory bowel diseases: from cellular studies and animal models to human disease.

INTRODUCTION: Vitamin A (VA) and metabolites such as Retinoic Acid (RA) and all-trans-RA (at-RA) are crucial in the modulation of the immune system and may be determinative in the balance of the immune responses. Inflammatory bowel diseases (IBD) consist of chronic relapsing and heterogeneous disorders with not well-known etiology. Due to its role in inflammatory processes, VA may be helpful in the treatment of IBD. Area covered: As VA plays a significant role in the inflammatory processes, this review aims to show the potential role of this vitamin in IBD, searching for cellular studies, animal models, and studies with humans. Expert commentary: Many studies have described the importance of alternative therapeutic approaches for IBD. Due to its role in the immune system, VA may also exert an indispensable role in the IBD. Nevertheless, some authors have shown that these compounds could stimulate the release of pro-inflammatory cytokines. For these reasons, more studies should be performed to establish the precise mechanisms of VA and its metabolites in systemic and intestinal inflammation.

Evaluation of pancreatin stability through enzyme activity determination.

Pancreatin is a biotechnological product containing an enzyme complex, obtained from porcine pancreas, that is employed in treating pancreatic diseases. Experiments regarding the stability of the pharmaceutical formulation containing pancreatin were performed using standard binary mixtures with 6 excipients in a 1:1 ratio (m/m) and a commercial formulation. To accomplish these goals, samples were stored for 1, 3 and 6 months at 40 ± 1 °C and 75 ± 5 % relative humidity (RH) and 40 ± 1 °C and 0 % RH. Stress testing was also performed. All samples were analyzed to evaluate the α-amylase, lipase and protease activities through UV/Vis spectrophotometry. The results revealed that the excipient proprieties and the storage conditions affected enzyme stability. Humidity was a strong influencing factor in the reduction of α-amylase and protease activities. Stress testing indicated that pH 9.0 and UV light did not induce substantial alterations in enzyme activity.

Simultaneous synthesis of mixtures of lactulose and galacto-oligosaccharides and their selective fermentation.

Lactulose and galacto-oligosaccharides (GOS) are well recognized prebiotics derived from lactose. In the synthesis of lactulose with ß-galactosidases GOS are also produced, but the ratio of lactulose and GOS in the product can be tuned at will, depending on the operation conditions, so to obtain an optimal product distribution in terms of prebiotic potential. The selectivity of fermentation of each carbohydrate alone as well as mixtures of both was determined using pH-controlled anaerobic batch cultures with faecal inoculum. Within the experimental range considered, lactulose/GOS molar ratio of 4 resulted in the highest selectivity for Bifidobacterium and Lactobacillus/Enterococcus, so this ratio was selected as the target for the synthesis of lactulose from fructose and lactose with Aspergillus oryzae ß-galactosidase. Synthesis was optimized using response surface methodology, considering temperature, initial concentrations of acceptor sugars and fructose/lactose molar ratio as key variables, with the aim of maximizing lactulose yield at the optimal product distribution in terms of prebiotic potential (lactulose/GOS molar ratio of 4). Under optimal conditions (50°C, 50%w/w total initial concentrations of sugars and fructose/lactose molar ratio of 6.44), lactulose yield of 0.26g of lactulose produced per g of initial lactose was obtained at the optimal product distribution.

Treatment of Crohn's disease in pregnant women: drug and multidisciplinary approaches.

Inflammatory bowel disease affects a substantial number of women in their reproductive years. Pregnancy presents a number of challenges for clinicians and patients; the health of the baby needs to be balanced with the need to maintain remission in the mother. Historically, treatments for Crohn's disease (CD) were often discontinued during the pregnancy, or nursing period, due to concerns about teratogenicity. Fortunately, observational data has reported the relative safety of many agents used to treat CD, including 5-aminosalicylic acid, thiopurines, and tumor necrosis factor. Data on the long-term development outcomes of children exposed to these therapies in utero are still limited. It is most important that physicians educate the patient regarding the optimal time to conceive, discuss the possible risks, and together decide on the best management strategy.

Action of phosphorylated mannanoligosaccharides on immune and hematological responses and fecal consistency of dogs experimentally infected with enteropathogenic Escherichia coli strains.

The therapeutic action of phosphorylated mannanoligosaccharides (MOS) was investigated regarding its prebiotic activity on enteropathogenic Escherichia coli (EPEC). Diarrhea was induced in dogs by experimental infection with EPEC strains. Then MOS was supplied once a day, in water for 20 days. Immunological (IgA and IgG), hematological (lymphocytes, neutrophils and monocytes) and bacteriological variables (PCR detection of the eae gene of EPEC recovered from stool culture), as well as occurrence of diarrhea were evaluated. All strains caused diarrhea at 24, 48 and 72 h after infection. PCR results indicated that E. coli isolated from stool culture of all infected animals had the eae gene. There was no significant difference among groups as to number of blood cells in the hemogram and IgA and IgG production. MOS was effective in recovering of EPEC-infected dogs since prebiotic-treated animals recovered more rapidly from infection than untreated ones (p < 0.05). This is an important finding since diarrhea causes intense dehydration and nutrient loss. The use of prebiotics for humans and other animals with diarrhea can be an alternative for the treatment and prophylaxis of EPEC infections.

Action of phosphorylated mannanoligosaccharides on immune and hematological responses and fecal consistency of dogs experimentally infected with enteropathogenic Escherichia coli strains

The therapeutic action of phosphorylated mannanoligosaccharides (MOS) was investigated regarding its prebiotic activity on enteropathogenic Escherichia coli (EPEC). Diarrhea was induced in dogs by experimental infection with EPEC strains. Then MOS was supplied once a day, in water for 20 days. Immunological (IgA and IgG), hematological (lymphocytes, neutrophils and monocytes) and bacteriological variables (PCR detection of the eae gene of EPEC recovered from stool culture), as well as occurrence of diarrhea were evaluated. All strains caused diarrhea at 24, 48 and 72 h after infection. PCR results indicated that E. coli isolated from stool culture of all infected animals had the eae gene. There was no significant difference among groups as to number of blood cells in the hemogram and IgA and IgG production. MOS was effective in recovering of EPEC-infected dogs since prebiotic-treated animals recovered more rapidly from infection than untreated ones (p < 0.05). This is an important finding since diarrhea causes intense dehydration and nutrient loss. The use of prebiotics for humans and other animals with diarrhea can be an alternative for the treatment and prophylaxis of EPEC infections.

BDNF and PDE4, but not the GRPR, regulate viability of human medulloblastoma cells.

Medulloblastoma is the most common brain tumor of childhood. Emerging molecular targets in medulloblastoma include neurotrophin and neuropeptide receptors. In the present study, we have examined the influence of brain-derived neurotrophic factor (BDNF)/TrkB receptor- and gastrin-releasing peptide receptor (GRPR)-mediated signaling on the viability of human medulloblastoma cells. The expression of TrkB and GRPR was confirmed by immunohistochemistry and mRNA for both BDNF and GRPR was detected by reverse transcriptase polymerase chain reaction in Daoy, D283, and ONS76 cells. Treatment with BDNF significantly inhibited the viability of Daoy and D283, but not ONS76 cells, measured with the MTT assay. Neither the GRPR agonists GRP and bombesin nor the GRPR antagonist RC-3095 affected cell viability. Because previous findings have indicated that the viability of glioma cells might be enhanced by GRP when combined with the cAMP phosphodiesterase-4 (PDE4) inhibitor rolipram, we also examined the effects of rolipram alone or combined with GRP on cell viability. Rolipram significantly reduced the viability of all three cell lines, and the inhibitory effect of rolipram in Daoy cells was not modified by cotreatment with GRP. The results suggest that BDNF/TrkB and PDE4, but not the GRPR, regulate the viability of medulloblastoma cells.

Metabolic handling of different fatty acids during rehabilitation from childhood malnutrition

The gastrointestinal handling and post absorptive metabolism of [1, 1, 1-13 C] triolein (TO) and [1, 1, 13 C] tripalmitin (TP) were studied in two groups of eight severely malnourished children (5-0 months): on admission (Phase 1), during rapid-catch up growth (Phase 2) and when weight for height had reached 90 percent of the reference (Phase 3). Total excretion of 13 C label in stool (over 3 days) and breath as 13 CO 2 (over 24 hours) were analysed by isotope radio mass spectrometry. Stool 13 C excretion at admission was approximately 10 percent of the administered dose for both trials but varied markedly between subjects, was significantly reduced during rehabilitation in the TO trial (Phase 2:0.5 +or- 1.0; Phase 3: 1.3 +or- 0.9; p<0.05) and tended to decline on the P trial. ANOVA analysis of the magnitude and time course of 13 C excretion in breath (from area under the curve), excretion tended to decrease during rehabilitation in the TO trial but remained unchanged on the TP trial. These results suggest that the efficiency with which dietary triacylglycerol is handled within the gastrointestinal tract is generally impaired in severely malnourished children at admission but improves during rehabilitation.(Au)