Frataxin participates to the hypoxia-induced response in tumors

Defective expression of frataxin is responsible for the degenerative disease Friedreich's ataxia. Frataxin is a protein required for cell survival since complete knockout is lethal. Frataxin protects tumor cells against oxidative stress and apoptosis but also acts as a tumor suppressor. The molecular bases of this apparent paradox are missing. We therefore sought to investigate the pathways through which frataxin enhances stress resistance in tumor cells. We found that frataxin expression is upregulated in several tumor cell lines in response to hypoxic stress, a condition often associated with tumor progression. Moreover, frataxin upregulation in response to hypoxia is dependent on hypoxia-inducible factors expression and modulates the activation of the tumor-suppressor p53. Importantly, we show for the first time that frataxin is in fact increased in human tumors in vivo. These results show that frataxin participates to the hypoxia-induced stress response in tumors, thus implying that modulation of its expression could have a critical role in tumor cell survival and/or progression

CROWDED HYBRID PANEL MANUFACTURED WITH PEANUT HULLS REINFORCED WITH ITA aBA WOOD PARTICLES

In this paper, it was considered the study of the potential use of peanut hulls and wood particles of ita\ufaba ( Mezilaurus itauba ) species in order to add value to these materials through the manufacture of hybrid particle board in order to compare the physical and mechanical performances as well as durability. For these procedures, it was used the bi-component polyurethane resin based on castor beans (mammon) oil and urea-formaldehyde. The product quality was evaluated based on the requirements of the standards NBR 14.810:2006 APA PRP and 108, through physico-mechanical and microstructural durability. The results indicate that the incorporation of wood particles warrants an increase in physical-mechanical properties of the particleboard manufactured with peanut hulls, the polyurethane resin based on castor oil was effective as a particle adhesive binder and the durability assay indicated that the material should be used under conditions of low exposure to moisture.No presente trabalho, considerou-se o estudo do potencial de utiliza\ue7\ue3o de casca de amendoim e part\uedculas de madeira da esp\ue9cie ita\ufaba ( Mezilaurus itauba ) com o intuito de agregar valor a estes materiais, por meio da fabrica\ue7\ue3o de pain\ue9is de part\uedculas h\uedbridos, a fim de comparar os desempenhos f\uedsicos, mec\ue2nicos e durabilidade. Para esses procedimentos foram utilizadas a resina poliuretana bicomponente \ue0 base de \uf3leo de mamona e a ureia-formalde\ueddo. A qualidade dos produtos foi avaliada com base nas prescri\ue7\uf5es do documento normativo NBR 14.810:2006 e APA PRP 108, por meio de ensaios f\uedsico-mec\ue2nicos, microestruturais e de durabilidade. Com os resultados obtidos foi poss\uedvel verificar que a incorpora\ue7\ue3o de part\uedculas de madeira proporcionou aumento nas propriedades f\uedsico-mec\ue2nicas do painel de part\uedculas com casca de amendoim, a resina poliuretana \ue0 base de \uf3leo de mamona mostrou-se eficiente como adesivo aglomerante das part\uedculas e o ensaio de durabilidade indicou que o material deve ser utilizado em condi\ue7\uf5es de exposi\ue7\ue3o de baixo contato com umidade

Conflict and user involvement in drug misuse treatment decision-making: a qualitative study

<p>Abstract</p> <p>Background</p> <p>This paper examines client/staff conflict and user involvement in drug misuse treatment decision-making.</p> <p>Methods</p> <p>Seventy-nine in-depth interviews were conducted with new treatment clients in two residential and two community drug treatment agencies. Fifty-nine of these clients were interviewed again after twelve weeks. Twenty-seven interviews were also conducted with staff, who were the keyworkers for the interviewed clients.</p> <p>Results</p> <p>Drug users did not expect, desire or prepare for conflict at treatment entry. They reported few actual conflicts within the treatment setting, but routinely discussed latent conflicts – that is, negative experiences and problematic aspects of current or previous treatment that could potentially escalate into overt disputes. Conflict resulted in a number of possible outcomes, including the premature termination of treatment; staff deciding on the appropriate outcome; the client appealing to the governance structure of the agency; brokered compromise; and staff skilfully eliciting client consent for staff decisions.</p> <p>Conclusion</p> <p>Although the implementation of user involvement in drug treatment decision-making has the potential to trigger high levels of staff-client conflict, latent conflict is more common than overt conflict and not all conflict is negative. Drug users generally want to be co-operative at treatment entry and often adopt non-confrontational forms of covert resistance to decisions about which they disagree. Staff sometimes deploy user involvement as a strategy for managing conflict and soliciting client compliance to treatment protocols. Suggestions for minimising and avoiding harmful conflict in treatment settings are given.</p

Activation of Thiazide-Sensitive Co-Transport by Angiotensin II in the cyp1a1-Ren2 Hypertensive Rat

Transgenic rats with inducible expression of the mouse Ren2 gene were used to elucidate mechanisms leading to the development of hypertension and renal injury. Ren2 transgene activation was induced by administration of a naturally occurring aryl hydrocarbon, indole-3-carbinol (100 mg/kg/day by gastric gavage). Blood pressure and renal parameters were recorded in both conscious and anesthetized (butabarbital sodium; 120 mg/kg IP) rats at selected time-points during the development of hypertension. Hypertension was evident by the second day of treatment, being preceded by reduced renal sodium excretion due to activation of the thiazide-sensitive sodium-chloride co-transporter. Renal injury was evident after the first day of transgene induction, being initially limited to the pre-glomerular vasculature. Mircoalbuminuria and tubuloinsterstitial injury developed once hypertension was established. Chronic treatment with either hydrochlorothiazide or an AT1 receptor antagonist normalized sodium reabsorption, significantly blunted hypertension and prevented renal injury. Urinary aldosterone excretion was increased ∼20 fold, but chronic mineralocorticoid receptor antagonism with spironolactone neither restored natriuretic capacity nor prevented hypertension. Spironolactone nevertheless ameliorated vascular damage and prevented albuminuria. This study finds activation of sodium-chloride co-transport to be a key mechanism in angiotensin II-dependent hypertension. Furthermore, renal vascular injury in this setting reflects both barotrauma and pressure-independent pathways associated with direct detrimental effects of angiotensin II and aldosterone

Aquaporins: important but elusive drug targets.

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators