Growth hormone axis in chronic kidney disease

Chronic kidney disease (CKD) in children is associated with dramatic changes in the growth hormone (GH) and insulin-like growth factor (IGF-1) axis, resulting in growth retardation. Moderate-to-severe growth retardation in CKD is associated with increased morbidity and mortality. Renal failure is a state of GH resistance and not GH deficiency. Some mechanisms of GH resistance are: reduced density of GH receptors in target organs, impaired GH-activated post-receptor Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, and reduced levels of free IGF-1 due to increased inhibitory IGF-binding proteins (IGFBPs). Treatment with recombinant human growth hormone (rhGH) has been proven to be safe and efficacious in children with CKD. Even though rhGH has been shown to improve catch-up growth and to allow the child to achieve normal adult height, the final adult height is still significantly below the genetic target. Growth retardation may persist after renal transplantation due to multiple factors, such as steroid use, decreased renal function and an abnormal GH–IGF1 axis. Those below age 6 years are the ones to benefit most from transplantation in demonstrating acceleration in linear growth. Newer treatment modalities targeting the GH resistance with recombinant human IGF-1 (rhIGF-1), recombinant human IGFBP3 (rhIGFBP3) and IGFBP displacers are under investigation and may prove to be more effective in treating growth failure in CKD

Gene expression changes induced by the tumorigenic pyrrolizidine alkaloid riddelliine in liver of Big Blue rats

<p>Abstract</p> <p>Background</p> <p>Pyrrolizidine alkaloids (PAs) are probably the most common plant constituents that poison livestock, wildlife, and humans worldwide. Riddelliine is isolated from plants grown in the western United States and is a prototype of genotoxic PAs. Riddelliine was used to investigate the genotoxic effects of PAs via analysis of gene expression in the target tissue of rats in this study. Previously we observed that the mutant frequency in the liver of rats gavaged with riddelliine was 3-fold higher than that in the control group. Molecular analysis of the mutants indicated that there was a statistically significant difference between the mutational spectra from riddelliine-treated and control rats.</p> <p>Results</p> <p>Riddelliine-induced gene expression profiles in livers of Big Blue transgenic rats were determined. The female rats were gavaged with riddelliine at a dose of 1 mg/kg body weight 5 days a week for 12 weeks. Rat whole genome microarray was used to perform genome-wide gene expression studies. When a cutoff value of a two-fold change and a <it>P</it>-value less than 0.01 were used as gene selection criteria, 919 genes were identified as differentially expressed in riddelliine-treated rats compared to the control animals. By analysis with the Ingenuity Pathway Analysis Network, we found that these significantly changed genes were mainly involved in cancer, cell death, tissue development, cellular movement, tissue morphology, cell-to-cell signaling and interaction, and cellular growth and proliferation. We further analyzed the genes involved in metabolism, injury of endothelial cells, liver abnormalities, and cancer development in detail.</p> <p>Conclusion</p> <p>The alterations in gene expression were directly related to the pathological outcomes reported previously. These results provided further insight into the mechanisms involved in toxicity and carcinogenesis after exposure to riddelliine, and permitted us to investigate the interaction of gene products inside the signaling networks.</p

Designing ionic liquids: the chemical structure role in the toxicity

Ionic liquids (ILs) are a novel class of solvents with interesting physicochemical properties. Many different applications have been reported for ILs as alternatives to organic solvents in chemical and bioprocesses. Despite the argued advantage of having low vapor pressure, even the most hydrophobic ILs show some degree of solubility in water, allowing their dispersion into aquatic systems and raising concerns on its pollutant potential. Moreover, nowadays most widespread notion concerning the ILs toxicity is that there is a direct relationship with their hydrophobicity/lipophilicity. This work aims at enlarging the currently limited knowledge on ILs toxicity by addressing negative impacts in aquatic ecosystems and investigating the possibility of designing hydrophobic ILs of low ecotoxicity, by the manipulation of their chemical structures. The impact of aromaticity on the toxicity of different cations (pyridinium, piperidinium, pyrrolidinium and imidazolium) and hydrophobic anions (bis(trifluoromethylsulfonyl)imide [NTf2] and hexafluorophosphate [PF6]) was analysed. Concomitantly, several imidazolium-based ILs of the type [C (n) C (m) C (j) im][NTf2] were also studied to evaluate the effects of the position of the alkyl chain on the ILs' toxicity. For that purpose, standard assays were performed using organisms of different trophic levels, Vibrio fischeri, Pseudokirchneriella subcapitata and Daphnia magna, allowing to evaluate the consistency of the structure-activity relationships across different biological targets. The results here reported suggest the possibility of designing ILs with an enhanced hydrophobic character and lower toxicity, by elimination of their aromatic nature

Prevention of HIV infection among migrant population groups in Northeast Brazil O papel da migração na prevenção da infecção pelo HIV no Nordeste Brasileiro

HIV infection is spreading among the poor, women, and migrant communities in the interior of Northeast Brazil. The research focused on different configurations, beliefs, representations, and forms of social organization of behavior thought to be associated with the population's capacity to efficiently follow AIDS prevention measures. Participants located in neighborhoods known for having large migrant populations were identified by Family Health Program Workers in Fortaleza and Teresina. The study adopted a qualitative methodology. Several belief-system concepts and values, as well as the social organization of sexuality revealed in the study, represent obstacles both to AIDS prevention and condom use. Hunger, lack of prospects, and fear are associated with a social situation of poverty, exclusion, prejudice, and total absence of basic human rights When examined together, these elements define different configurations in the migrants' increased vulnerability to HIV/AIDS. The groups' increased vulnerability relates to the socioeconomic complexity that must be considered in HIV/AIDS control and prevention programs.<br>A infecção pelo HIV entre pobres, mulheres e populações migrantes do interior do Nordeste Brasileiro vem crescendo. As diferentes configurações, crenças e representações e formas de organização do comportamento, associadas à capacidade de seguir adequadamente medidas de prevenção, foram o foco desta investigação. Os participantes foram localizados em bairros com altas taxas de migração através do Programa Saúde da Família em Fortaleza e Teresina. Empregou-se a metodologia qualitativa nesta investigação. Vários sistemas de crenças, valores e organização social da sexualidade desta população representam obstáculos à prevenção da AIDS e inibem o uso do preservativo. Pobreza, falta de perspectiva e medo estão associados à situação de pobreza, exclusão social e preconceito e à total ausência de direitos humanos. Quando examinados conjuntamente, estes fatores definem diferentes configurações dos migrantes com uma elevada vulnerabilidade ao HIV/AIDS. A alta vulnerabilidade destes grupos, relacionada à complexidade sócio-econômica, deve ser considerada nos programas de prevenção e controle da AIDS