Altered lipid profile, lipoprotein composition, and oxidant and antioxidant status in pediatric Crohn disease

BACKGROUND: Growing evidence supports a role for peroxidation in the pathogenesis of Crohn disease (CD). The activation of inflammatory cells, the release of their mediators, and the excessive production of free radicals may affect circulating lipids. OBJECTIVE: We examined the lipid profile, lipoprotein composition, and oxidant-antioxidant status of children with CD. DESIGN: We studied 22 pediatric CD patients and 10 healthy control subjects. RESULTS: The proportion of saturated and monounsaturated fatty acids in plasma of CD patients was higher but that of polyunsaturated fatty acids was lower than in control subjects. This resulted in higher ratios in CD patients of palmitoleic acid to linoleic acid (P < 0. 05) and of eicosatrienoic acid to arachidonic acid (P < 0.04), 2 established indexes of essential fatty acid deficiency. Hypocholesterolemia was noted in CD patients as a result of lower LDL-cholesterol concentrations than in control subjects (P < 0.02). Plasma apolipoproteins B (P < 0.02) and A-I (P < 0.02) were also lower in CD patients, whereas plasma triacylglycerols were higher (P < 0.005). Lipoprotein composition was altered in CD patients, with relative triacylglycerol depletion and protein enrichment in VLDL. In contrast, intermediate-density lipoprotein of CD patients was characterized by an increased percentage of triacylglycerol and protein (P < 0.005) and a reduced proportion of phospholipids (P < 0. 01). Additional abnormalities were observed in the chemical distribution of HDL(2) and HDL(3) moieties. Lipid peroxidation was documented by higher plasma malondialdehyde concentrations in CD patients (P < 0.05), accompanied by lower retinol concentrations (P < 0.02). CONCLUSION: Disturbances in the lipid profile, in lipoprotein concentrations and composition, and in oxidant-antioxidant status occur in CD patients.     

Men and reproductive health in rural Pakistan: the case for increased male participation.

OBJECTIVES: In Pakistan, the role of men has always been considered to dominate in the decision-making process pertaining to women's fertility and birth spacing. This study was done to explore men's knowledge, perceptions and behavior on various reproductive health issues. METHODS: A cross-sectional survey was carried out among 180 married adult males in 12 rural districts of Pakistan in 2000. The study was qualitative, utilizing tools such as in-depth and key-informant interviews. RESULTS: The findings pointed out gaps in knowledge and misconceptions among men on a range of reproductive health issues and stress the need for health education. The findings suggest that strategies such as couple counseling, door-to-door campaigns by village-based male family planning workers and small group meetings could be effective. This study indicates a pressing need for incorporating effective intervention strategies, both at the community and the clinic level, backed with efficient counseling, motivation, and provision of services with appropriate education of males in rural areas. CONCLUSION: The findings suggest that investment into promotion of healthy fertility control practices among men will be effective in the near future, as they are interested in acquiring new knowledge and are willing to become partners.     

Erythropoietin and erythropoietin receptor expression in head and neck cancer: relationship to tumor hypoxia.

PURPOSE: Erythropoietin, an oxygen-regulated glycoprotein hormone, is a hematopoietic cytokine that stimulates erythropoiesis by binding to its cellular receptor [erythropoietin receptor (EPOR)]. The recombinant form of human erythropoietin is used to prevent or treat anemia in cancer patients. However, in a recent randomized, placebo-controlled trial involving patients receiving curative radiotherapy for squamous cell carcinoma of the head and neck, erythropoietin treatment was associated with poorer locoregional progression-free survival. The purpose of our study was to determine whether EPOR and its ligand erythropoietin are expressed in primary head and neck cancer. We also investigated the hypothesis that erythropoietin expression in malignant cells may be associated with the presence of tumor hypoxia, an important factor involved in resistance to radiation treatment, tumor aggressiveness, and poor prognosis. EXPERIMENTAL DESIGN: Twenty-one patients received an i.v. infusion of the hypoxia marker pimonidazole hydrochloride before multiple tumor biopsies. Contiguous sections from 74 biopsies were analyzed by immunohistochemistry for EPOR and erythropoietin expression and pimonidazole binding. RESULTS: EPOR expression was present in tumor cells in 97% of the biopsies. Coexpression of erythropoietin was observed in 90% of biopsies. Erythropoietin and pimonidazole adduct staining did not always colocalize within tumors, but there was a significant positive correlation between levels of microregional erythropoietin expression and pimonidazole binding. CONCLUSIONS: The coexpression of erythropoietin and EPOR in tumor cells suggests that erythropoietin may potentially function as an autocrine or paracrine factor in head and neck cancer. The expression of the hypoxia-inducible protein erythropoietin in tumor cells correlates with levels of tumor hypoxia.     

Targeting choline phospholipid metabolism: GDPD5 and GDPD6 silencing decrease breast cancer cell proliferation,migration, and invasion

Abnormal choline phospholipid metabolism is associated with oncogenesis and tumor progression. We have investigated the effects of targeting choline phospholipid metabolism by silencing two glycerophosphodiesterase genes, GDPD5 and GDPD6, using small interfering RNA (siRNA) in two breast cancer cell lines, MCF‐7 and MDA‐MB‐231. Treatment with GDPD5 and GDPD6 siRNA resulted in significant increases in glycerophosphocholine (GPC) levels, and no change in the levels of phosphocholine or free choline, which further supports their role as GPC‐specific regulators in breast cancer. The GPC levels were increased more than twofold during GDPD6 silencing, and marginally increased during GDPD5 silencing. DNA laddering was negative in both cell lines treated with GDPD5 and GDPD6 siRNA, indicating absence of apoptosis. Treatment with GDPD5 siRNA caused a decrease in cell viability in MCF‐7 cells, while GDPD6 siRNA treatment had no effect on cell viability in either cell line. Decreased cell migration and invasion were observed in MDA‐MB‐231 cells treated with GDPD5 or GDPD6 siRNA, where a more pronounced reduction in cell migration and invasion was observed under GDPD5 siRNA treatment as compared with GDPD6 siRNA treatment. In conclusion, GDPD6 silencing increased the GPC levels in breast cancer cells more profoundly than GDPD5 silencing, while the effects of GDPD5 silencing on cell viability/proliferation, migration, and invasion were more severe than those of GDPD6 silencing. Our results suggest that silencing GDPD5 and GDPD6 alone or in combination may have potential as a new molecular targeting strategy for breast cancer treatment. Copyright © 2016 John Wiley & Sons, Ltd.     

Hollow fiber integrated microfluidic platforms for <Emphasis Type="Italic">in vitro</Emphasis> Co-culture of multiple cell types

This study demonstrates a rapid prototyping approach for fabricating and integrating porous hollow fibers (HFs) into microfluidic device. Integration of HF can enhance mass transfer and recapitulate tubular shapes for tissue-engineered environments. We demonstrate the integration of single or multiple HFs, which can give the users the flexibility to control the total surface area for tissue development. We also present three microfluidic designs to enable different co-culture conditions such as the ability to co-culture multiple cell types simultaneously on a flat and tubular surface, or inside the lumen of multiple HFs. Additionally, we introduce a pressurized cell seeding process that can allow the cells to uniformly adhere on the inner surface of HFs without losing their viabilities. Co-cultures of lung epithelial cells and microvascular endothelial cells were demonstrated on the different platforms for at least five days. Overall, these platforms provide new opportunities for co-culturing of multiple cell types in a single device to reconstruct native tissue micro-environment for biomedical and tissue engineering research.