Pluronic F127-modified liposome-containing tacrolimus-cyclodextrin inclusion complexes:improved solubility, cellular uptake and intestinal penetration

Objective The aim of this study was to investigate Pluronic F127-modified liposome-containing cyclodextrin (CD) inclusion complex (FLIC) for improving the solubility, cellular uptake and intestinal penetration of tacrolimus (FK 506) in the gastrointestinal (GI) tract. Methods Molecular modelling was performed to screen the optimal CD for the solubilization of FK 506. FLIC was prepared by thin-lipid film hydration with the inclusion complex solutions followed by membrane extrusion. Dilution tests were conducted in simulated gastric fluids and phosphate-buffered solution of sodium taurocholate to investigate the solubility improvement of FK506. The cellular uptake of nanocarriers was studied in Caco-2 cells, and intestinal mucous membrane penetration in the GI tract was evaluated in Sprague-Dawley rats. Key findings The results showed that β-CD had the strongest binding energy with the guest molecule among the CDs. The prepared FLIC has an average diameter of 180.8 ± 8.1 nm with a spherical shape. The solubility and cellular uptake of FK 506 was greatly improved by the incorporation of CD complexes in the Pluronic F127-modified liposomes. Intestinal mucous membrane penetration was also significantly improved by the preparation of FLIC. Conclusion With improved drug solubility and intestinal mucous membrane penetration, FLIC shows a promising oral delivery system for FK 506. © 2013 Royal Pharmaceutical Society.

Design, synthesis and evaluation of dipeptides as probes for studies of gastro-intestinal tract dipeptide transport

DUE TO COPYRIGHT RESTRICTIONS ONLY AVAILABLE FOR CONSULTATION AT ASTON UNIVERSITY LIBRARY AND INFORMATION SERVICES WITH PRIOR ARRANGEMENT

Seasonal variations of EPG levels in gastro-intestinal parasitic infection in a southeast asian controlled locale:a statistical analysis

We present a data based statistical study on the effects of seasonal variations in the growth rates of the gastro-intestinal (GI) parasitic infection in livestock. The alluded growth rate is estimated through the variation in the number of eggs per gram (EPG) of faeces in animals. In accordance with earlier studies, our analysis too shows that rainfall is the dominant variable in determining EPG infection rates compared to other macro-parameters like temperature and humidity. Our statistical analysis clearly indicates an oscillatory dependence of EPG levels on rainfall fluctuations. Monsoon recorded the highest infection with a comparative increase of at least 2.5 times compared to the next most infected period (summer). A least square fit of the EPG versus rainfall data indicates an approach towards a super diffusive (i. e. root mean square displacement growing faster than the square root of the elapsed time as obtained for simple diffusion) infection growth pattern regime for low rainfall regimes (technically defined as zeroth level dependence) that gets remarkably augmented for large rainfall zones. Our analysis further indicates that for low fluctuations in temperature (true on the bulk data), EPG level saturates beyond a critical value of the rainfall, a threshold that is expected to indicate the onset of the nonlinear regime. The probability density functions (PDFs) of the EPG data show oscillatory behavior in the large rainfall regime (greater than 500 mm), the frequency of oscillation, once again, being determined by the ambient wetness (rainfall, and humidity). Data recorded over three pilot projects spanning three measures of rainfall and humidity bear testimony to the universality of this statistical argument. © 2013 Chattopadhyay and Bandyopadhyay.

Efeito da Olmesartana na resposta inflamatória em modelo de mucosite intestinal em ratos

Intestinal Mucositis is inflammation and/or ulceration of mucosa of the gastrointestinal tract caused by anticancer therapies. Histologically, villous atrophy, damage to enterocytes and infiltration of inflammatory cells. Methotrexate (MTX) is a compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. The aim of this study was to evaluate the effect of Olmesartan (OLM), an angiotensin II receptor antagonist, on an Intestinal Mucositis Model (IMM) induced by MTX in Wistar rats. IMM was induced via intraperitoneal (i.p.) administration of MTX (7 mg/kg) for three consecutive days. The animals were pretreated with oral OLM at 0.5, 1 or 5 mg/kg or with vehicle 30 min prior to exposure to MTX, for three days. Small intestinal (duodenum, jejunum and ileum) homogenates were assayed for levels of the IL-1β, IL-10 and TNF-α cytokines, malondialdehyde and myeloperoxidase activity. Additionally, immunohistochemical analyses of MMP-2, MMP-9, COX-2, RANK/RANKL and SOCS-1 and confocal microscopy analysis of SOCS-1 expression were performed. Treatment with MTX+OLM (5 mg/kg) resulted in a reduction of mucosal inflammatory infiltration, ulcerations, vasodilatation and hemorrhagic areas (p<0.05) as well as reduced concentrations of MPO (p<0.001) and the pro-inflammatory cytokines IL-1β and TNF-α (p<0.01), and increase antiinflammatory cytosine IL-10 (p,0.05). Additionally, the combined treatment reduced expression of MMP-2, MMP-9, COX-2, RANK and RANKL (p<0.05) and increased cytoplasmic expression of SOCS-1 (p<0.05). Our findings confirm the involvement of OLM in reducing the inflammatory response through increased immunosuppressive signaling in an IMM. We also suggest that the beneficial effect of Olmesartan treatment is specifically exerted during the damage through blocking inflammatory cytosines.

Morfometria, variação anual no peso e demografia do Tico-tico-rei-cinza (Lanio pileatus: thraupidae) em dois ambientes de caatinga no nordeste do Brasil

The caatinga is considered the only exclusively Brazilian biome, with a total area of 735.000km². It is estimated that about 59% of this area has already been removed and only 2% are protected in conservations units. The region is characteristic by strong seasonality and heterogeneity in their environments. This paper sets generate information on morphological and population patterns Lanio pilatus in two areas of caatinga of Estação Ecológica do Seridó (ESEC – Seridó), Serra Negra do Norte - RN. Data collection was performed in six phases between July 2012 and December 2014, covering the end of the dry and rainy seasons in the region. The captures were performed with nets and individuals captured were marked with metal rings and measured (weight, wing length, tail, tarsus, culmen and tip of the bill to nostril). Through these measures, we observed that only males of open area range in weight during the dry and rainy season, youngs were significantly lower for all parameters measured, and males were larger than females in three characteristics (weight, wing length and tail) in open area and only one (wing length) in the closed area. The population parameters were generated from the mark-capture-recapture technique by program MARK, using the techniques of robust design and CJS. The survival probability of detection and population estimates varied with time. Only individuals of open area fluctuated in their estimates during the study. Overall, the environment was a great mediator of results which increases the need for more studies on the life history of the species in the region.

Morfometria dos forames mandibular, mentual e infraorbital de Lobo-guará Chrysocyon brachyurus, Illiger, 1815 aplicada a bloqueios anestésicos

CHAPTER II - The Chrysocyon brachyurus is the biggest South American canid which has a high frequency of dental injuries, both in wild and captivity. Thus, veterinary procedures are necessary to preserve the feeding capacity of hundreds of captive specimens worldwide. The aim of this study was to study the mandibular morphometry of maned wolf with emphasis on the establishment of anatomic references to the anesthetic blockage of the inferior alveolar and mental nerves. Therefore, 15 measurements in 22 hemimandibles of C. brachyurus adults were taken. For extra-oral technique of blockage of the inferior alveolar nerve at the level of the mandibular foramen, it is stated that the needle should be advanced, close to the medial surface of the mandibular ramus, by 11.4 mm perpendiculary from the palpable concavity. Alternatively, the needle can be introduced for 30.4 mm from the angular process at 20-25 degrees angle with the ventral margin. For blocking only the mentual nerve, it is recommended the introduction of needle for 10 mm, close to the lateral aspect of the mandibular body, at the level of the lower first premolar. The mandibular foramen showed similars position, size and symmetry in the maned wolfs specimens examined. The comparison of the data with those available for other carnivores reflects the necessity for determining these anatomical references specifically for each species.

Obtención de péptidos alimentarios mediante hidrólisis enzimática con efectos sobre la salud intestinal

En la presente Tesis Doctoral, se estudió la obtención e identificación de péptidos alimentarios mediante el uso de hidrólisis enzimática y sus efectos sobre la salud gastrointestinal. La secuenciación y cuantificación de los péptidos se realizó mediante cromatografía de líquidos de alta eficacia en fase inversa acoplada a espectrometría de masas en tándem (RP-HPLC-MS/MS). Se analizaron distintos hidrolizados y digeridos gastrointestinales de caseínas, proteínas de suero de leche y lunasina. Inicialmente, se propone la producción de caseinofosfopéptidos (CPPs) mediante la hidrólisis con tripsina de un subproducto de caseína generado durante la fabricación de un ingrediente funcional con actividad antihipertensiva. La identificación y la semi-cuantificación de CPPs revelaron algunos cambios cualitativos y cuantitativos en los CPPs generados en los hidrolizados con distintas condiciones de tiempo de hidrólisis y precipitación selectiva. Una vez realizada la identificación de CPPs en los hidrolizados trípticos, el subproducto también se sometió a un proceso de digestión gastrointestinal simulando las condiciones fisiológicas. La comparación de los péptidos resultantes mostró gran homología en las secuencias de CPPs formados por la hidrólisis con tripsina y la digestión gastrointestinal simulada. Se observó que algunas regiones de αS1-caseína, concretamente las comprendidas entre los residuos (43-59) y (60-74), de la αs1-caseína y los residuos (1-25) y (30-50) de β-caseína, fueron capaces de resistir tanto a la hidrólisis con tripsina como a la digestión gastrointestinal. Por lo tanto, se demuestra que el subproducto industrial puede ser empleado como fuente de CPPs para favorecer la absorción de minerales a nivel intestinal...

Whey protein isolate decreases murine stomach weight and intestinal length and alters the expression of Wnt signalling-associated genes

Acknowledgements K. N. N. was supported by the Teagasc Vision Programme on Obesity (RMIS5974). L. M. was supported by the Teagasc Walsh Fellowship. J. R. S. was supported by a 1000-talents professorship from the Chinese government. The funding bodies had no input on the design of the study or in the interpretation of the data. The authors’ contributions are as follows: L. M., J. R. S., J. F. C. and K. N. N. designed the study; K. N. N. and J. F. C. obtained ethical approval for the study; L. M. performed the experiments; L. M. and J. R. S. analysed the data; L. M. generated the figures. All authors contributed to the drafting of the manuscript. All authors approved the final version for submission. The authors declare that there is no competing interest.

Le rôle du récepteur scavenger B type I, SR-BI, dans l'absorption et le métabolisme du cholestérol au niveau intestinal

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Modulation par l'insuffisance rénale chronique des protéines impliquées dans le transport intestinal des médicaments

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Pro-inflammatory flagellin proteins of prevalent motile commensal bacteria are variably abundant in the intestinal microbiome of elderly humans

Some Eubacterium and Roseburia species are among the most prevalent motile bacteria present in the intestinal microbiota of healthy adults. These flagellate species contribute "cell motility" category genes to the intestinal microbiome and flagellin proteins to the intestinal proteome. We reviewed and revised the annotation of motility genes in the genomes of six Eubacterium and Roseburia species that occur in the human intestinal microbiota and examined their respective locus organization by comparative genomics. Motility gene order was generally conserved across these loci. Five of these species harbored multiple genes for predicted flagellins. Flagellin proteins were isolated from R. inulinivorans strain A2-194 and from E. rectale strains A1-86 and M104/1. The amino-termini sequences of the R. inulinivorans and E. rectale A1-86 proteins were almost identical. These protein preparations stimulated secretion of interleukin-8 (IL-8) from human intestinal epithelial cell lines, suggesting that these flagellins were pro-inflammatory. Flagellins from the other four species were predicted to be pro-inflammatory on the basis of alignment to the consensus sequence of pro-inflammatory flagellins from the beta- and gamma-proteobacteria. Many fliC genes were deduced to be under the control of sigma(28). The relative abundance of the target Eubacterium and Roseburia species varied across shotgun metagenomes from 27 elderly individuals. Genes involved in the flagellum biogenesis pathways of these species were variably abundant in these metagenomes, suggesting that the current depth of coverage used for metagenomic sequencing (3.13-4.79 Gb total sequence in our study) insufficiently captures the functional diversity of genomes present at low (<= 1%) relative abundance. E. rectale and R. inulinivorans thus appear to synthesize complex flagella composed of flagellin proteins that stimulate IL-8 production. A greater depth of sequencing, improved evenness of sequencing and improved metagenome assembly from short reads will be required to facilitate in silico analyses of complete complex biochemical pathways for low-abundance target species from shotgun metagenomes.

Le rôle du récepteur scavenger B type I, SR-BI, dans l'absorption et le métabolisme du cholestérol au niveau intestinal

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Modulation par l'insuffisance rénale chronique des protéines impliquées dans le transport intestinal des médicaments

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.