Expression of TWEAK and its receptor Fn14 in human subcutaneous adipose tissue. Relationship with other inflammatory cytokines in obesity

TWEAK, a cytokine of the TNF family, has been found to be expressed under different inflammatory conditions but no data is available concerning the expression of this cytokine and its receptor (Fn14) in human obesity. In the present work we have evaluated the expression of many pro-inflammatory TNF system cytokines (TNF-alpha, TWEAK and their respective receptors, TNFR1, TNFR2 and Fn14) in human adipose tissue of 84 subjects some with different degree of obesity and type 2 diabetes, and its relation with inflammation by also measuring the expression of macrophage marker CD68. We detected expression of TWEAK and Fn14 in isolated mature adipocytes and in the stromovascular fraction. Additionally, we found that LPS upregulates the expression of both genes on THP-1 human monocytic cell line. TWEAK was expressed in adipose tissue of all studied subjects with no differences between obesity group, and was associated with Fn14 expression in morbid obese, mainly in women with type 2 diabetes. The data obtained here also showed that TNF-alpha and TNFR2 mRNAs were significantly more expressed in subcutaneous adipose tissue of subjects with morbid obesity compared to obese and non-obese subjects. In contrast, TNFR1 gene expression was negatively associated with BMI. Our results suggest that the expression of TNF-derived pro-inflammatory cytokines are increased in severe obesity, where macrophage infiltrate could modulate the inflammatory environment through activation of its receptors.     

Hatching order and size-dependent mortality in relation to brood sex ratio composition in chinstrap penguins

The differential environmental sensitivity of the sexes hasstrong implications in the evolutionary history of species asit can alter sexual size dimorphism, population sex ratios,and the faculty of parents to manipulate offspring sex in relationto environmental conditions. We studied sexual differences inhatching patterns and evaluated sex- and size-related mortalityin relation to hatching order and brood sex ratios in the chinstrappenguin Pygoscelis antarctica, a moderately size-dimorphic species,with a modal clutch size of 2 eggs. We found that male, second-hatched,and large eggs showed shorter hatching periods than female,first-hatched, and small eggs. We also found a male-biased mortalityof nestlings in the colony. However, male mortality patternsdiffered depending on the brood sex ratio composition. Mortalityof male chicks in all-male broods was higher than in mixed broodsand higher than female mortality in all-female broods. Contrary,females from mixed brood showed higher mortality than theirmale nest mates and higher too than females in all-female broods.Second-hatched chicks also suffered from higher mortality thanfirst-hatched chicks. Our results indicate that both the superiorcompetitive capacity and the higher energy demand of the largersex constitute 2 causal factors explaining patterns of sex-biasedmortality. Both factors occur in the same species and in differentsituations of sibling competition shaped by brood sex ratiocomposition. This study constitutes a good example of how patternsof sex-related mortality can vary depending on nest environmentalcircumstances. Furthermore, our study suggests that hatchingperiod can be a mechanism underlying sexual differences in theembryonic period of birds.     

Apoptotic cell death in the central nervous system of Bufo arenarum tadpoles induced by cypermethrin

Tadpoles of the toad Bufo arenarum treated with cypermethrin (CY) at concentrations above 39 μg CY/L showed dose-dependent apoptotic cell death in immature cells of the central nervous system as demonstrated by morphometric analysis, the TUNEL method, and DNA fragmentation assay. Light-and electron-microscopic studies showed structural alterations in the intermediate and marginal layers of the brain. Immature cerebral tissue showed cellular shrinkage, nuclear fragmentation and increase of intercellular spaces. In this study we demonstrated high toxicity of CY to larval stages of Bufo arenarum. Our results show that doses lower than those used in routine insecticide applications can cause massive apoptosis in the immature cells of the central nervous system. These results coincide with our previous studies in Physalaemus biligonigerus, confirming the severe toxic effects of CY to the central nervous system of anuran species from Argentina. This may increase the mortality index in wild animals and contribute to the loss of biodiversity in our agroecosystems. We postulate that CY induces apoptosis in central nervous system cells of Bufo arenarum tadpoles by specific neurotoxic mechanisms.     

Telomere dysfunction: a new player in radiation sensitivity

Human individuals often exhibit important differences in their sensitivity to ionising radiation. Extensive literature links radiation sensitivity with impaired DNA repair which is due to a lack of correct functioning in many proteins involved in DNA-repair pathways and/or in DNA-damage checkpoint responses. Given that ionising radiation is an important and widespread diagnostic and therapeutic tool, it is important to investigate further those factors and mechanisms that underlie individual radiosensitivity. Recently, evidence is accumulating that telomere function may well be involved in cellular and organism responses to ionising radiation, broadening still further the currently complex and challenging scenario.     

IL-18: relationship with anthropometry, body composition parameters, leptin and arterial hypertension.

OBJECTIVE: Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine with potential atherogenic properties whose role in human obesity has been recently suggested. The aim of our study was to analyze the physiologic distribution of IL-18 among sexes and all decades of the adult life in a healthy population randomly selected and to study its relationship with anthropometric, body composition measurements and leptin concentrations. We also studied the relationship of IL-18 with smoking and arterial hypertension, known risk factors implicated in atherogenesis. MATERIALS AND METHODS: One hundred and thirty four men and 127 healthy women were included in the study. Plasma concentrations of IL-18 and leptin were determined in all subjects. Body composition was evaluated by bioelectrical impedanciometry. RESULTS: IL-18 was distributed similarly in men and women and throughout decades. No significant differences were found in IL-18 between obese and normal-weight men and women according to their body mass index and body fat content. Higher IL-18 concentrations were found in subjects with arterial hypertension. In the bivariate correlation analysis only waist to hip ratio correlated weakly with IL-18 in the whole population (r=0.12, p=0.04). In the multiple regression analysis the relationship between IL-18 and waist to hip ratio lost significance after adjusting for age, sex and body mass index. However, IL-18 remained associated with arterial hypertension (adjusted r2=0.25, p=0.023). CONCLUSIONS: The lack of correlation between IL-18 with anthropometric, body composition variables and leptin in our healthy population argues against a role of this cytokine in obesity. Moreover, our findings suggest the implication of this interleukin in the atherogenic process induced by arterial hypertension.     

MLPA: A prenatal diagnostic tool for the study of congenital heart defects?

Congenital heart defects (CHD) represent the most common birth defects, so they are not a rare finding when performing routine ultrasound examinations during pregnancy. Once chromosome abnormalities have been excluded in a fetus with a CHD, chromosome 22q11.2 deletion is usually investigated by FISH, as it is the most frequent microdeletion syndrome and is generally associated with cardiac malformations. If 22q11.2 microdeletion is ruled out, the etiology of the CHD remains generally unexplained, making familial genetic counseling difficult. To evaluate the usefulness of Multiplex Ligation-dependent Probe Amplification (MLPA) kits designed for the study of 22q11.2 and other genomic regions previously associated with syndromic CHD, we performed MLPA in 55 pregnancies with fetuses presenting CHD, normal karyotype and negative FISH results for 22q11.2 microdeletion, which constitutes the largest prenatal series reported. Definitive MLPA results were obtained in 50 pregnancies, and in this setting such MLPA kits did not detect any imbalance. On the other hand, to compare FISH and MLPA techniques for the study of 22q11.2 microdeletions, we performed MLPA in 4 pregnancies known to have 22q11.2 deletions (by FISH). All four 22q11.2 microdeletions were also detected by MLPA, which corroborates that it is a reliable technique for the diagnosis and characterization of 22q11.2 deletions. Finally, we evaluated the possibility of replacing conventional FISH by MLPA for the prenatal diagnosis of CHD, comparing the diagnostic potential, results delivery times, repetition and failure rates and cost of both techniques, and concluded that FISH should still be the technique of choice for the prenatal diagnosis of fetuses with CHD.     

Interaction between head and neck squamous cell carcinoma cells and fibroblasts in the biosynthesis of PGE2

Prostaglandin (PG)E(2) is relevant in tumor biology, and interactions between tumor and stroma cells dramatically influence tumor progression. We tested the hypothesis that cross-talk between head and neck squamous cell carcinoma (HNSCC) cells and fibroblasts could substantially enhance PGE(2) biosynthesis. We observed an enhanced production of PGE(2) in cocultures of HNSCC cell lines and fibroblasts, which was consistent with an upregulation of COX-2 and microsomal PGE-synthase-1 (mPGES-1) in fibroblasts. In cultured endothelial cells, medium from fibroblasts treated with tumor cell-conditioned medium induced in vitro angiogenesis, and in tumor cell induced migration and proliferation, these effects were sensitive to PGs inhibition. Proteomic analysis shows that tumor cells released IL-1, and tumor cell-induced COX-2 and mPGES-1 were suppressed by the IL-1-receptor antagonist. IL-1α levels were higher than those of IL-1β in the tumor cell-conditioning medium and in the secretion from samples obtained from 20 patients with HNSCC. Fractionation of tumor cell-conditioning media indicated that tumor cells secreted mature and unprocessed forms of IL-1. Our results support the concept that tumor-associated fibroblasts are a relevant source of PGE(2) in the tumor mass. Because mPGES-1 seems to be essential for a substantial biosynthesis of PGE(2), these findings also strengthen the concept that mPGES-1 may be \a target for therapeutic intervention in patients with HNSCC.