Experiencing discrimination mediates the relationship between victimization and social withdrawal in patients suffering from a severe mental illness: A cross-sectional study.

Psychiatric patients are often victims of crime and discrimination and are often socially withdrawn. This has negative consequences for their health and recovery. We examined whether such discrimination mediates the association between victimization and social withdrawal, and whether these associations differ between men and women. We also determined the prevalence of social withdrawal and the discrimination experienced by patients suffering from a severe mental illness. This study is embedded in the Victimization in Psychiatric Patients study. Information on discrimination, social withdrawal and victimization was obtained using structured self-report questionnaires (N = 949). We reported the 12-month prevalence of these phenomena and used path analysis to estimate the direct path between personal and property victimization and social withdrawal, and the indirect path through the discrimination experienced. The impact of gender was assessed by testing interaction terms. Social withdrawal was reported by 20.6% (95%CI 18.1-23.2) of participants, and being discriminated against in the past 12 months by 75.3% (95%CI: 72.6-78.0%). While crime victimization had no direct effects on social withdrawal, personal crime victimization (B = 0.47; 95%CI 0.25-0.72; p < 0.001) and property crime victimization (B = 0.65; 95%CI 0.42-0.93; p < 0.001) had significant indirect effects on social withdrawal, which were mediated by the discrimination experienced. In men we found a direct negative effect of property crime on social withdrawal (B = -0.68; 95%CI: -1.21to -0.11, p = 0.014). We conclude that personal and property victimization, for both men and women, was associated with higher levels of social withdrawal, and this was fully mediated by the discrimination experienced.

Grandiose and vulnerable narcissism, identity integration and self-control related to criminal behavior.

BACKGROUND: Although systematic research on narcissism has been conducted for over 100 years, researchers have only recently started to distinguish between grandiose and vulnerable narcissism in relation to criminal behavior. In addition, there is some evidence suggesting that identity integration and self-control may underlie this association. Therefore, the present study aimed to develop a theory-driven hypothetical model that investigates the complex associations between grandiose and vulnerable narcissism, identity integration, self-control, and criminal behavior using structural equation modeling (SEM). METHODS: The total sample (N = 222) included 65 (29.3%) individuals convicted of criminal behavior and 157 (70.7%) participants from the community, with a mean age of 37.71 years (SD = 13.25). Criminal behavior was a grouping variable used as a categorical outcome, whereas self-report questionnaires were used to assess grandiose and vulnerable narcissism, self-control, and identity integration. RESULTS: The overall SEM model yielded good fit indices. Grandiose narcissism negatively predicted criminal behavior above and beyond the influence of identity integration and self-control. In contrast, vulnerable narcissism did not have a direct significant effect on criminal behavior, but it was indirectly and positively associated with criminal behavior via identity integration and self-control. Moreover, grandiose narcissism was positively, whereas vulnerable narcissism was negatively associated with identity integration. However, identity integration did not have a direct significant effect on criminal behavior, but it was indirectly and negatively associated with criminal behavior via self-control. Finally, self-control was, in turn, negatively related to criminal behavior. CONCLUSIONS: We propose that both subtypes of narcissism should be carefully considered in clinical assessment and current intervention practices.

Acylated Ghrelin and The Regulation of Lipid Metabolism in The Intestine.

Acylated ghrelin (AG) is a gastrointestinal (GI) peptide mainly secreted by the stomach that promotes cytosolic lipid droplets (CLD) hypertrophy in adipose tissues and liver. However, the role of AG in the regulation of lipid metabolism in the intestine remains unexplored. This study aimed at determining whether AG influences CLD production and chylomicron (CM) secretion in the intestine. The effects of AG and oleic acid on CLD accumulation and CM secretion were first investigated in cultured Caco-2/15 enterocytes. Intestinal lipid metabolism was also studied in Syrian Golden Hamsters submitted to conventional (CD) or Western (WD) diets for 8 weeks and continuously administered with AG or physiological saline for the ultimate 2 weeks. In cultured Caco-2/15 enterocytes, CLD accumulation influenced CM secretion while AG reduced fatty acid uptake. In WD hamsters, continuous AG treatment amplified chylomicron output while reducing postprandial CLD accumulation in the intestine. The present study supports the intimate relationship between CLD accumulation and CM secretion in the intestine and it underlines the importance of further characterizing the mechanisms through which AG exerts its effects on lipid metabolism in the intestine.

Hygiene auditing in mass catering: a 4-year study in a university canteen.

OBJECTIVES: The outcomes of hygiene audits carried out two times per year were used to determine the correct execution of the procedures foreseen by the Hazard Analysis and Critical Control Points (HACCP) plan over 4 years (2013-2016) in a university canteen producing about 1200 meals a day. STUDY DESIGN: Critical analysis of hygiene audits. METHODS: Hygiene audits were carried out on the basis of a checklist divided into seven main items and subitems that covered all the production areas of the canteen. For each audit subitem, total percentage of inadequacy was calculated as the total number of negative answers (N) divided by the total number of answers (n = 8) collected in the period 2013-2016. RESULTS: The results showed a discontinuous trend among years. In more detail, the highest percentage of inadequacy was seen for food maintaining temperatures, thus highlighting management issues mainly related to time taken for food preparation. A relatively high level of inadequacy was also recorded for staff clothing and hygiene. CONCLUSIONS: The critical analysis of data emerged from the audits was useful to obtain an overview of improvements and emerging criticalities.

Autochthonous starter cultures and indigenous grape variety for regional wine production.

AIMS: To characterize Oenococcus oeni strains isolated from North-Apulian wines where malic acid degradation is usually achieved by spontaneous fermentations, and to determine the influence of bacterial inoculation time on the malolactic performances in 'Nero di Troia' wine using a complete autochthonous microbial regime. METHODS AND RESULTS: Oenococcus oeni strains from wines produced with the autochthonous (Apulia Region, southern Italy) grape variety 'Uva di Troia' were isolated, selected and characterized. Multilocus sequence typing and variable number tandem repeat analysis were used to investigate intraspecific diversity. Oenococcus oeni strains were tested in co-inoculation and in sequential inoculation, with two autochthonous yeast strains previously isolated from 'Nero di Troia' wine. After a preliminary screening using co-inoculation regime, the O. oeni strains were grouped in reason of the different behaviour in malic acid performances. Results suggested that the efficient degradation of malic acid in co-inoculation is a strain-dependent characteristic. CONCLUSIONS: Autochthonous yeast/bacterium combinations were identified as starter culture, and used in a co-inoculation approach, for vinification of regional wines. SIGNIFICANCE AND IMPACT OF THE STUDY: The 'microbial terroir' of typical fermented food and beverage production represents a dynamic sector of applied research in food microbiology. In this work, we propose the use of autochthonous bacteria and yeast for wine production from an indigenous grape variety.

[Epidemiology of CKD in Italy and prevention strategies]. / Epidemiologia della malattia renale cronica in italia e strategie per la prevenzione.

Although chronic kidney disease (CKD) is a major health problem worldwide; it is not adequately considered in the strategies for the prevention of non-communicable diseases. To plan properly preventive strategies in our country, we need to know what is the prevalence of CKD, the risk factors, the level of awareness for the diagnosis, the referral to specialists nephrologists and the prognosis of patients followed in primary care. The prevalence of CKD, adjusted for age and gender, is 6.3% and the major independent risk factors are represented by old age, arterial hypertension, obesity, diabetes, cardiovascular disease and smoking . The awareness of the diagnosis in our country in 2003 is underestimated and nephrology referral for individuals with glomerular filtration (GF) under 60 ml / min was only 10%. The prognosis of patients, followed exclusively in primary care, worsens progressively for values of GF under 45 ml / min, both as need for substitutive treatment and mortality, compared with patients of stage I and II. To improve the management of CKD, it would be useful to set up an electronic database on our national territory by a network among laboratories, primary care, and nephrologists. An example of this organization is Great Britain that evidences encouraging results in the treatment and prevention of this debilitating disease.

Phenological Patterns and Preferences for Aromatic Compounds by Male Euglossine Bees (Hymenoptera, Apidae) in Two Coastal Ecosystems of the Brazilian Atlantic Forest.

In order to investigate phenological patterns and seasonal and geographic variations in the preference for fragrances of Euglossini males, monthly sampling was carried out from August 2007 to July 2009 in two coastal areas of Atlantic Forest in Ubatuba, northern coast of the state of São Paulo. Fourteen aromatic baits were used, 3 of them in the first year (August 2007 to July 2008) and the other 11 in the second year (August 2008 to July 2009). A total of 1,475 individuals from 22 species were collected. The highest frequency of the individuals of the majority of the sampled species occurred in the hot/super-humid season. However, Eulaema cingulata (Fabricius) showed peaks of abundance in the cold/less-humid season on Anchieta Island. Seasonal variation in fragrance choice by males was not registered. Males of El. cingulata showed preference for ß-ionone on Anchieta Island and for benzyl acetate in the Picinguaba region, characterizing the single example of geographic variation in preference for scent baits we recorded.

Statins in patients with chronic kidney disease: new evidence.

Dyslipidemia represents a common metabolic alteration in chronic kidney disease (CKD). Alterations can be different depending on the stage of the disease and the extent of proteinuria. Despite the high cardiovascular risk in patients with renal impairment, only a small percentage of patients receive adequate cholesterol-lowering therapy. The use of statins, inhibitors of the endogenous synthesis of cholesterol in patients with CKD, represents an efficient therapeutic instrument for reducing cardiovascular risk, at least in the early stage of the disease. Such evidence is currently lacking in dialysis, that is a setting where cardiovascular mortality is not consistently due to classical atherosclerosis. In addition to their efficacy, statins are proved as safe drugs with a high tolerability profile in CKD. In the case of intolerant patients, a new therapeutic perspective is represented by ezetimibe, inhibitor of intestinal absorption of cholesterol, whose effectiveness and tolerability allow its use throughout all stages of the renal disease.

Efficacy of and resistance to anti-IGF-1R therapies in Ewing's sarcoma is dependent on insulin receptor signaling.

Identification of patient selection criteria and understanding of the potential mechanisms involved in the development of resistance are crucial for an appropriate and successful design of clinical trials with anti-insulin-like growth factor (IGF)-1R therapies. Few Ewing's sarcomas are highly sensitive to IGF-1R targeting and understanding the reason why, may hold the secret to improve successful treatments. In this paper, we show that a major mechanism of resistance to highly specific inhibitors of IGF-1R, either antibodies or tyrosine kinase inhibitors may involve enhanced insulin receptor (IR)-A homodimer formation and IGF-2 production. Resistant cells are able to switch from IGF-1/IGF-1R to IGF-2/IR-A dependency to maintain sustained activation of AKT and ERK1/2, proliferation, migration and metastasis. These cells also showed higher proliferative response to insulin, in keeping with a switch towards insulin pathways sustaining proliferation and malignancy, rather than metabolism. Our findings demonstrate a role for IR-A in eliciting intrinsic and adaptive resistance to anti-IGF-1R therapies. Thus, we indicate that tumors with low IGF-1R:IR ratio are unlikely to greatly benefit from anti-IGF-1R therapies and that the efficacy of anti-IGF-1R therapies should be evaluated in relationship to the IR-A:IGF-1R ratio in cancer cells. Moreover, we provide evidences supporting IR-A as an important target in sarcoma therapy.

Characterisation of Lactobacillus helveticus strains producing antihypertensive peptides by RAPD and inverse-PCR of IS elements.

Lactobacillus helveticus is used for the manufacture of cheeses and milk-based products. Although it is not considered a probiotic microorganism, some strains demonstrated beneficial effects through the production of antihypertensive peptides from the hydrolysis of casein during milk fermentation. Strain-specificity of bioactive peptide production by L. helveticus makes the availability of reliable typing methods essential for both legal and good manufacturing processes. Accordingly, RAPD and inverse-PCR of five insertion sequence elements were comparatively evaluated for the molecular characterisation of four L. helveticus dairy cultures producing antihypertensive peptides and fourteen reference strains. Calculation of discriminatory indices and cluster analysis of the DNA fingerprints confirmed the suitability of both approaches for acceptable strain differentiation. Although RAPD was more discriminating, for a few test strains a neat discrimination was only achieved through multiplex inverse-PCR, thus suggesting the suitability of a combined analytical approach for a finer strain discrimination.

Bionomics and sociological aspects of Euglossa fimbriata (Apidae, Euglossini).

The nesting biology and the social structure of Euglossa fimbriata were studied based on two original nests found on the campus of the University of São Paulo, Ribeirão Preto, Brazil. Nest 1 contained two inseminated females, 39 sealed cells, one cell being provisioned, and six old and empty cells. Nest 2 contained three inseminated females, 45 sealed cells, one cell being provisioned, and 27 old and empty cells. The cells of nest 1 were distributed into three clusters from which three new nests were set up in the laboratory and maintained in observation boxes from August 1993 to March 1994 in order to study the behaviors performed by the bees. The males left the nest immediately after emergence and did not return. Some females left the nest within a few days of eclosing, and others stayed in their original nests and began to reactivate them. The E. fimbriata colonies were small, with semi-social and eusocial organization. In these colonies one female becomes the dominant female, usually the oldest female, and the others behave as subordinate females. The subordinate females build their cells, provision and oviposit in them, while the dominant female becomes the major guard bee, and oviposits in cells oviposited in by subordinate females. Oviposition by the dominant female is always preceded by oophagy. Irrespective of the behavior displayed, all the females that we dissected had been inseminated. The behavior displayed by the dominant female is characteristic of brood parasitism and fits the parental parasitism hypothesis developed as an alternative pathway by which insect sociality could have arisen.

Trap-nesting bees (Hymenoptera: Apoidea) in forest fragments of the State of São Paulo, Brazil.

We studied the community ecology of trap-nesting bees in two forest fragments of the state of São Paulo, Brazil, during two years, utilizing bamboo canes and tubes made of black cardboard as trap nests. The traps were inspected once a month with an otoscope. One hundred and fifteen nests were obtained at Estação Ecológica de Paulo de Faria, Paulo de Faria (EEPF). These included nine species belonging to five genera and two families. At Santa Cecília Farm (SCF), 12 species belonging to seven genera and three families built 392 nests. Natural enemies reared from nests of both areas included Hymenoptera, Diptera and Coleoptera. Species richness was similar between the areas but the communities differed considerably in species composition. The higher diversity found at EEPF was due to more even distribution of the species. No difference was observed between the numbers of nests built in each year in each area. Although the species richness was lower in the cool/dry season of both years at SCF, and in the first year at EEPF, the nesting frequencies did not differ between seasons for both the overall community but for each of the most abundant species. No annual fluctuation in the frequencies of nesting was observed. As temperature and precipitation were not found to be significantly different between the two years of study in each area, we concluded that climatic stability resulted in population stability.

PCR-DGGE analysis of lactic acid bacteria and yeast dynamics during the production processes of three varieties of Panettone.

AIMS: To study lactic acid bacteria (LAB) and yeast dynamics during the production processes of sweet-leavened goods manufactured with type I sourdoughs. METHODS AND RESULTS: Fourteen sourdough and dough samples were taken from a baking company in central Italy during the production lines of three varieties of Panettone. The samples underwent pH measurements and plating analysis on three solid media. The microbial DNA was extracted from both the (sour)doughs and the viable LAB and yeast cells collected in bulk, and subjected to PCR-denaturing gradient gel electrophoresis (DGGE) analysis. The molecular fingerprinting of the cultivable plus noncultivable microbial populations provide evidence of the dominance of Lactobacillus sanfranciscensis, Lactobacillus brevis and Candida humilis in the three fermentation processes. The DGGE profiles of the cultivable communities reveal a bacterial shift in the final stages of two of the production processes, suggesting an effect of technological parameters on the selection of the dough microflora. CONCLUSIONS: Our findings confirm the importance of using a combined analytical approach to explore microbial communities that develop during the leavening process of sweet-leavened goods. SIGNIFICANCE AND IMPACT OF THE STUDY: In-depth studies of sourdough biodiversity and population dynamics occurring during sourdough fermentation are fundamental for the control of the leavening process and the manufacture of standardized, high-quality products.

The estrogen receptor alpha:insulin receptor substrate 1 complex in breast cancer: structure-function relationships.

BACKGROUND: Insulin receptor substrate 1 (IRS-1) is a signaling molecule that exerts a key role in mediating cross talk between estrogen receptor alpha (ERalpha) and insulin-like growth factor 1 (IGF-1) in breast cancer cells. Previously, we demonstrated that a fraction of IRS-1 binds ERalpha, translocates to the nucleus, and modulates ERalpha-dependent transcription at estrogen response elements (ERE). Here, we studied structure-function relationships of the ERalpha:IRS-1 complex under IGF-1 and/or estradiol (E2) stimulation. MATERIALS AND METHODS: ERalpha and IRS-1 deletion mutants were used to analyze structural and functional ERalpha/IRS-1 interactions. IRS-1 binding to ERE and IRS-1 role in ERalpha-dependent ERE transcription was examined by chromatin immunoprecipitation and gene reporter analysis, respectively. The requirement for IRS-1 in ERalpha function was tested with RNAi technology. RESULTS: Nuclear translocation of IRS-1 was induced by E2, IGF-1, and a combination of both stimuli. ERalpha/IRS-1 binding was direct and involved the activation function-1 (AF-1)/DNA binding domain (DBD) region of ERalpha and two discrete regions of IRS-1 (the N-terminal pleckstrin homology domain and a region within the C-terminus). IRS-1 knock down abrogated IGF-1-dependent transcriptional activity of unliganded ERalpha, but induced the activity of liganded ERalpha. CONCLUSIONS: ERalpha/IRS-1 interactions are direct and involve the ERalpha AF-1/DBD domain and IRS-1 domains mapping within N- and C-terminus. IRS-1 may act as a repressor of liganded ERalpha and coactivator of unliganded ERalpha.

Asymmetrical regulation of scavenger receptor class B type I by apical and basolateral stimuli using Caco-2 cells.

Cholesterol uptake and the mechanisms that regulate cholesterol translocation from the intestinal lumen into enterocytes remain for the most part unclear. Since scavenger receptor class B type I (SR-BI) has been suggested to play a role in cholesterol absorption, we investigated cellular SR-BI modulation by various potential effectors administered in both apical and basolateral sides of Caco-2 cells. With differentiation, Caco-2 cells increased SR-BI protein expression. Western blot analysis showed the ability of cholesterol and oxysterols in both cell compartments to reduce SR-BI protein expression. Among the n-3, n-6, and n-9 fatty acid families, only eicosapentaenoic acid was able to lower SR-BI protein expression on both sides, whereas apical alpha-linolenic acid decreased SR-BI abundance and basolateral arachidonic acid (AA) raised it. Epidermal growth factor and growth hormone, either in the apical or basolateral medium, diminished SR-BI cellular content, while insulin displayed the same effect only on the basolateral side. In the presence of proinflammatory agents (LPS, TNF-alpha, IFN-gamma), Caco-2 cells exhibited differential behavior. SR-BI was downregulated by lipopolysaccharide on both sides. Finally, WY-14643 fibrate diminished SR-BI protein expression when it was added to the apical medium. Biotinylation studies in response to selected stimuli revealed that regulatory modifications in SR-BI protein expression occurred for the most part at the apical cell surface irrespective of the effector location. Our data indicate that various effectors supplied to the apical and basolateral compartments may impact on SR-BI at the apical membrane, thus suggesting potential regulation of intestinal cholesterol absorption and distribution in various intracellular pools.

Leptin expression in breast nipple aspirate fluid (NAF) and serum is influenced by body mass index (BMI) but not by the presence of breast cancer.

While obesity is a known risk factor for postmenopausal breast cancer, the molecular mechanisms involved are unclear. Systemic levels of leptin, the product of the ob (obesity) gene, are increased in obese individuals (body mass index, BMI, over 25) and are higher in women than men. Leptin has been found to stimulate the growth of breast cancer cells in vitro. Our goal was to determine whether leptin was 1) present in nipple aspirate fluid (NAF), and 2) whether NAF leptin levels were associated with a) levels in serum, b) obesity, and c) breast cancer. We collected and evaluated NAF specimens from 83 subjects and serum specimens from 49 subjects. NAF leptin was detectable in 16/41 (39 %) of premenopausal and 21/42 (50 %) postmenopausal subjects. NAF leptin was significantly lower (p = 0.042) in premenopausal than postmenopausal women with a BMI < 25, but not in those with a higher BMI. NAF leptin was significantly associated with BMI in premenopausal (p = 0.011) but not in postmenopausal women. Serum leptin was associated with BMI in both premenopausal and postmenopausal women (p = 0.0001 for both). NAF and serum leptin were associated in premenopausal (p = 0.02) but not postmenopausal women. Neither NAF nor serum leptin was associated with premenopausal or postmenopausal breast cancer. Our findings include that 1) leptin is present in the breast and detectable in a subset of NAF samples, 2) NAF leptin in premenopausal but not postmenopausal women parallels serum leptin levels, and 3) neither NAF nor serum levels of leptin were associated with premenopausal or postmenopausal breast cancer.

Expression of the insulin-like growth factor-I receptor in primary breast cancer and lymph node metastases: correlations with estrogen receptors alpha and beta.

Numerous laboratory studies and some epidemiological data have suggested the involvement of the insulin-like growth factor-I receptor (IGF-IR) in breast cancer development and progression. However, data on IGF-IR expression in human tissues, including breast cancer sections, are limited and often inconsistent. We therefore examined by immunohistochemistry the expression of IGF-IR in primary tumors and breast cancer metastases to lymph nodes, and correlated IGF-IR positivity with estrogen receptor (ER) status and selected clinicopathological features. We found that 1) IGF-IR was expressed in primary tumors as well as in lymph node metastases, but the expression in primary tumors was more frequent (56 % vs. 44.4 %); 2) IGF-IR expression in primary tumors was associated with negative node status (p < 0.033); 3) in node-negative primary tumors, IGF-IR positively correlated with ERbeta (p < 0.008; r = 0.538), but not with ERalpha, tumor size or grade; 4) both IGF-IR-positive and IGF-IR-negative primary tumors were found to produce IGF-IR-positive as well as IGF-IR-negative metastases; 5) in metastases, IGF-IR expression did not associate with ERalpha, ERbeta or any of the studied pathobiological markers. The results suggest that IGF-IR could become a viable pharmaceutical target in breast cancer therapy, but such therapy should be based on IGF-IR assessment in primary tumor and metastasis in each potential patient.

Translation initiation factor IF3: two domains, five functions, one mechanism?

Initiation factor IF3 contains two domains separated by a flexible linker. While the isolated N-domain displayed neither affinity for ribosomes nor a detectable function, the isolated C-domain, added in amounts compensating for its reduced affinity for 30S subunits, performed all activities of intact IF3, namely: (i) dissociation of 70S ribosomes; (ii) shift of 30S-bound mRNA from 'stand-by' to 'P-decoding' site; (iii) dissociation of 30S-poly(U)-NacPhe-tRNA pseudo- initiation complexes; (iv) dissociation of fMet-tRNA from initiation complexes containing mRNA with the non-canonical initiation triplet AUU (AUUmRNA); (v) stimulation of mRNA translation regardless of its start codon and inhibition of AUUmRNA translation at high IF3C/ribosome ratios. These results indicate that while IF3 performs all its functions through a C-domain-30S interaction, the N-domain function is to provide additional binding energy so that its fluctuating interaction with the 30S subunit can modulate the thermodynamic stability of the 30S-IF3 complex and IF3 recycling. The localization of IF3C far away from the decoding site and anticodon stem-loop of P-site-bound tRNA indicates that the IF3 fidelity function does not entail its direct contact with these structures.

Modulation of intestinal and liver fatty acid-binding proteins in Caco-2 cells by lipids, hormones and cytokines.

Intestinal and liver fatty acid binding proteins (I- and L-FABP) are thought to play a role in enterocyte fatty acid (FA) trafficking. Their modulation by cell differentiation and various potential effectors was investigated in the human Caco-2 cell line. With the acquisition of enterocytic features, Caco-2 cells seeded on plastic progressively increased L-FABP quantities, whereas I-FABP was not detectable even very late in the maturation process. On permeable filters that improved differentiation markers (sucrase, alkaline phosphatase, transepithelial resistance), Caco-2 cells furthered their L-FABP content and expressed I-FABP. Western blot analysis showed a significant increase in I- and L-FABP expression following an 8-hour incubation period with butyric acid, oleic acid, and phosphatidylcholine. However, in all cases, I-FABP levels were higher than L-FABP concentrations regardless of the lipid substrates added. Similarly, hydrocortisone and insulin enhanced the cellular content of I- and L-FABP whereas leptin triggered I-FABP expression only after an 8-hour incubation. Finally, tumor necrosis factor-alpha was more effective in increasing the cytosolic amount of I-FABP levels. In conclusion, our data demonstrate that I-FABP expression is limited to fully differentiated Caco-2 cells and can be more easily regulated than L-FABP by lipids, hormones, and cytokines.

Immunolocalization, ontogeny, and regulation of microsomal triglyceride transfer protein in human fetal intestine.

To examine the multiple stages of lipoprotein packaging during development, we studied localization, ontogeny, and regulation of microsomal transfer protein (MTP), a crucial protein for lipid transport. With the use of immunofluorescence, MTP was identified in villus and crypt epithelial cells in different regions of human fetal intestine, including colon. Staining was detected as early as the 13th wk of gestation in all gut segments and was almost entirely confined to the columnar epithelial cells of the jejunum and colon. Unlike immunofluorescence, which provides qualitative but not quantitative information on MTP signal, enzymatic assays revealed a decreasing gradient from proximal small intestine to distal, as confirmed by immunoblot. Activity of MTP in small intestinal explants cultured for different incubation periods (0, 4, 8, and 24 h) peaked at 4 h but remained insensitive to different concentrations of oleic acid. Also, a trend toward increasing MTP activity was observed at 20-22 wk of gestation. Finally, in strong contrast to jejunal efficiency, colonic explants displayed impaired lipid production, apolipoprotein biogenesis, and lipoprotein assembly, in association with poor expression of MTP. These findings provide the first evidence that human fetal gut is able to express MTP and emphasize the distinct regional distribution, regulation by oleic acid, and ontogeny of MTP.