Cytokine modulation (IL-6, IL-8, IL-10) by human breast milk lipids on intestinal epithelial cells (Caco-2)

Human breast milk is the best form of nourishment for infants during the first year of life. It is composed by a complex mixture of carbohydrates, proteins and fats. Breast milk provides nutrients and bioactive factors that themselves modulate maturation and development of the gastrointestinal tract. Many studies have shown that it provides protection against gastrointestinal tract inflammation. In this sense, this study aimed to evaluate the effect of human breast milk lipids on epithelial intestinal cells (Caco-2) cytokine regulation and the fatty acid transporter protein (FATP) involved in this process. Caco-2 cells were cultivated and stimulated with different concentration of human milk lipids from healthy human mothers (18–30-year-olds) or single commercial lipids for 48?h. We measured the concentrations and mRNA levels of IL-6, IL-8 and IL-10 cytokines by immunoassay (ELISA) and quantitative-PCR (qRT-PCR) technique, respectively. We observed a two to three times decrease in pro-inflammatory cytokine levels (p?<?0.01) as well as an increase in anti-inflammatory IL-10 levels in cells stimulated with increasing concentrations of breast milk lipids. These results suggest that human breast milk lipids could have an important role on the cytokine modulation in the newborn bowel.     

Parental Perceptions of Siblings’ Grieving After a Childhood Cancer Death: A Longitudinal Study

We investigated longitudinally parental perceptions of siblings' bereavement after childhood cancer death. Parents were interviewed 6 months (n = 25) and 18 months (n = 15) post-death. Data are analyzed combined and over time. The following themes emerged: (a) expression of grief: missing deceased child (verbally, crying), behavioral problems, difficulty understanding the meaning of death (pre-schoolers), and avoiding talking with parents about feelings (adolescents); (b) what helps siblings grief: moving on, talking about deceased child and social support; (c) relationship with parents improved for most siblings; and (d) bond with deceased sibling: pretend-play (preschoolers), dreaming, and career choices (adolescents). Over time, themes reflected stability and change.     

Chromosomal aneuploidy precedes morphological changes and supports multifocality in head and neck lesions.

OBJECTIVE: To identify chromosome changes associated with the transformation of dysplastic lesions and to verify evidence for multifocality in synchronous premalignant lesions associated with head and neck squamous cell carcinoma (HNSCC). STUDY DESIGN: Chromosomal aneuploidy was evaluated in sections of formalin-fixed, paraffin-embedded tissues from 16 patients with HNSCC, including sites with normal squamous mucosa, dysplasia (low- and high-grade), and invasive tumor. METHODS: A panel of 6 centromeric probes (chromosomes 1, 3, 7, 8, 9, and 17) was analyzed in dual-color fluorescence in situ hybridization assays, using matched hematoxylin-eosin-stained sections for histologic correlation. RESULTS: Imbalances for most of the targets tested were found in 20 of 24 invasive carcinoma sites, mainly represented by gain in copy number per cell. However, cell populations with chromosome losses and gains in multimodal patterns were concomitantly observed in a number of tumors, indicating a high degree of chromosome instability. The detection of chromosomal aneuploidy precedes the malignant transformation as indicated by findings of monosomy and trisomy in normal squamous mucosa, and in low-grade and high-grade dysplasia sites. Loss of chromosomes 3 and 17 prevailed in low-grade dysplasias, and gain of chromosomes 7 and 8 were prevalent in high-grade dysplasias. Synchronous low-grade and high-grade dysplastic lesions displayed discordant molecular signatures, suggesting a multifocal origin. CONCLUSIONS: The interphase fluorescence in-situ hybridization (FISH) assay with centromeric may detect early changes in the progression of dyplastic epithelia to invasive carcinoma and supports the field cancerization theory of multifocality.     

The influence of the comonomer in the copolymerization of ethylene with α-olefins using C2H4[ind]2ZrCl2/methylaluminoxane as catalyst system

Copolymers based on ethylene with different incorporations of 1-hexene, 1-octene and 1-decene were obtained. There is not any marked variation of activity when different metallocenes were tested. The type and the concentration of the comonomer in the feed do not have a strong influence on the catalytic activity of the system, but the presence of the comonomer increases the activity compared with that in the absence of it. From ¹³C NMR it was found that below 8% of comonomer incorporated the comonomer units appear isolated between polyethylene blocks, sequences of the type ethylene-comonomer-ethylene-comonomer appear only above 8% of comonomer incorporated for all the systems studied. The reactivity of the comonomers for this particular system shows that the size of the lateral chain influences the percentage of comonomer incorporated, 1-hexene being the highest one incorporated. The crystallinity of the copolymers exerts a linear relation with the amount of comonomer incorporated, and it is independent of lateral chain lengths. The molecular weight of the copolymers obtained was found to be dependent on the comonomer concentration in the feed, showing that there is a transfer reaction with the comonomer. The polydispersity (M̄_w/M̄_n) of the copolymers is rather narrow and dependent on the concentration of the comonomer incorporated.     

Increased collagenase and dipeptidyl peptidase I activity in leucocytes from healthy elderly people.

The incidence of infectious diseases increases with ageing. The enzymatic activity of leucocytes may have a relevant role in the morbidity and mortality due to infections in the elderly. In this study we have compared the activity of enzymes involved in the inflammatory response in leucocytes from young and elderly women. A total of 35 healthy females was studied, 20 volunteers aged 78-98 years (mean 89.1 years) and 15 young controls aged 19-34 years (mean 26 years). All of them were in good clinical condition, without any acute or chronic disease. Intracellular enzyme activity was analysed by flow cytometry in leucocytes from young and elderly women. The enzyme substrates employed were for oxidative burst, L-aminopeptidase, collagenase, cathepsin B, C, D and, G and dipeptidyl peptidase I. The intracellular enzyme activity assessed by flow cytometry in leucocytes from young and elderly women was similar, as far as oxidative burst, L-aminopeptidase, cathepsin B, C, D and G are concerned. An increased collagenase activity was detected in granulocytes from elders. The mean fluorescence channels for this enzyme corresponded to 86 +/- 23 and 60 +/- 15 in cells from elders and controls, respectively (P = 0.01224). An increased dipeptidyl peptidase I activity was detected in lymphocytes from elderly women. The corresponding values for this enzyme in elders and the young were 65.9 +/- 43.3 and 17.3 +/- 5, respectively (P = 0. 0036). The proper functional activity of intracellular enzymes involved in inflammatory responses is likely to be determinant for successful ageing.     

Studies of the slow bidirectional transport of iron and transferrin across the blood-brain barrier

Although iron is involved in brain function, very little is known about the regulation of its concentrations in the central nervous system. We quantitatively measured the entry and exit rates of iron, transferrin (its major transport protein), and albumin in mice. The blood to brain transport of iron greater than transferrin greater than albumin and the brain to blood transport of transferrin greater than albumin greater than iron. The results suggest that iron and transferrin have slow, bidirectional, probably saturable, and to some degree independent transport systems, although iron introduced directly into the brain is not readily available for brain to blood transport.     

Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice

Farnesoid X receptor (FXR) plays an important role in maintaining bile acid and cholesterol homeostasis. Here we demonstrate that FXR also regulates glucose metabolism. Activation of FXR by the synthetic agonist GW4064 or hepatic overexpression of constitutively active FXR by adenovirus-mediated gene transfer significantly lowered blood glucose levels in both diabetic db/db and wild-type mice. Consistent with these data, FXR null mice exhibited glucose intolerance and insulin insensitivity. We further demonstrate that activation of FXR in db/db mice repressed hepatic gluconeogenic genes and increased hepatic glycogen synthesis and glycogen content by a mechanism that involves enhanced insulin sensitivity. In view of its central roles in coordinating regulation of both glucose and lipid metabolism, we propose that FXR agonists are promising therapeutic agents for treatment of diabetes mellitus.