Chronic hyperammonemia alters the circadian rhythms of corticosteroid hormone levels and of motor activity in rats

Patients with liver cirrhosis may present hepatic encephalopathy with a wide range of neurological disturbances and alterations in sleep quality and in the sleep‐wake circadian rhythm. Hyperammonemia is a main contributor to the neurological alterations in hepatic encephalopathy. We have assessed, in an animal model of chronic hyperammonemia without liver failure, the effects of hyperammonemia per se on the circadian rhythms of motor activity, temperature, and plasma levels of adrenal corticosteroid hormones. Chronic hyperammonemia alters the circadian rhythms of locomotor activity and of cortisol and corticosterone levels in blood. Different types of motor activity are affected differentially. Hyperammonemia significantly alters the rhythm of spontaneous ambulatory activity, reducing strongly ambulatory counts and slightly average velocity during the night (the active phase) but not during the day, resulting in altered circadian rhythms. In contrast, hyperammonemia did not affect wheel running at all, indicating that it affects spontaneous but not voluntary activity. Vertical activity was affected only very slightly, indicating that hyperammonemia does not induce anxiety. Hyperammonemia abolished completely the circadian rhythm of corticosteroid hormones in plasma, completely eliminating the peaks of cortisol and corticosterone present in control rats at the start of the dark period. The data reported show that chronic hyperammonemia, similar to that present in patients with liver cirrhosis, alters the circadian rhythms of corticosteroid hormones and of motor activity. This suggests that hyperammonemia would be a relevant contributor to the alterations in corticosteroid hormones and in circadian rhythms in patients with liver cirrhosis. © 2009 Wiley‐Liss, Inc.     

Alterations in Bacterial Metabolism Contribute to the Lifespan Extension Exerted by Guarana in Caenorhabditis elegans

Guarana (Paullinia cupana) is a widely consumed nutraceutical with various health benefits supported by scientific evidence. However, its indirect health impacts through the gut microbiota have not been studied. Caenorhabditis elegans is a useful model to study both the direct and indirect effects of nutraceuticals, as the intimate association of the worm with the metabolites produced by Escherichia coli is a prototypic simplified model of our gut microbiota. We prepared an ethanoic extract of guarana seeds and assessed its antioxidant capacity in vitro, with a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and in vivo, utilizing C. elegans. Additionally, we studied the impact of this extract on C. elegans lifespan, utilizing both viable and non-viable E. coli, and assessed the impact of guarana on E. coli folate production. The extract showed high antioxidant capacity, and it extended worm lifespan. However, the antioxidant and life-extending effects did not correlate in terms of the extract concentration. The extract-induced life extension was also less significant when utilizing dead E. coli, which may indicate that the effects of guarana on the worms work partly through modifications on E. coli metabolism. Following this observation, guarana was found to decrease E. coli folate production, revealing one possible route for its beneficial effects.     

Impact of biofilm formation and azoles' susceptibility in Scedosporium/Lomentospora species using an in vitro model that mimics the cystic fibrosis patients' airway environment

BackgroundScedosporium species are the second most isolated filamentous fungi from cystic fibrosis (CF) patients; however, little is known about their virulence aspects in a CF environment. In this context, the current study aimed to evaluate the (i) antifungal susceptibility profiles, (ii) ability to form biofilm and (iii) impact of biofilm formation on the susceptibility to azoles in 21 clinical isolates of Scedosporium recovered from CF patients.MethodsScedosporium apiospermum (n=6), S. aurantiacum (n=6), S. minutisporum (n=3) and Lomentospora prolificans (n=6) were firstly used to compare the antifungal susceptibility profile using a standard culture broth (RPMI-1640) and a mucin (M)-containing synthetic CF sputum medium (SCFM). The ability to form biofilms was investigated in polystyrene microtiter plates containing Sabouraud-dextrose (a classical medium), SCFM and SCFM+M. Mature biofilms were tested for their susceptibility to azoles by microdilution assay.ResultsOur results showed that the minimum inhibitory concentrations (MICs) for planktonic conidia ranged from 0.25 to >16.0 mg/L for voriconazole and 1.0 to >16.0 mg/L for posaconazole. Overall, the MICs for azoles increased from 2- to 8-folds when the susceptibility tests were performed using SCFM+M compared to RPMI-1640. All fungi formed robust biofilms on polystyrene surface at 72 h, with a significant increase in the MICs (ranging from 128- to 1024-times) against both azoles compared to the planktonic cells.ConclusionThese findings confirm the challenge of antifungal treatment of CF patients infected with Scedosporium/Lomentospora and also demonstrated a strong biofilm formation, with extensive increase in antifungal resistance, triggered underconditions mimicking the CF patient airway.     

MVP expression in the prediction of clinical outcome of locally advanced oral squamous cell carcinoma patients treated with radiotherapy

ABSTRACT: OBJECTIVE: Explore the role of Major Vault Protein (MVP) in oral cavity squamous cell carcinoma patients.Subjects and Methods131 consecutive patients suffering from oral cavity squamous cell carcinoma were included in the study. In the whole series, the mean follow-up for survivors was 123.11 [PLUS-MINUS SIGN] 40.36 months. Patients in tumour stages I and II were referred to surgery; patients in stage III-IV to postoperative radiotherapy (mean dose = 62.13 [PLUS-MINUS SIGN] 7.74 Gy in 1.8--2 Gy/fraction). MVP expression was studied by immunohistochemistry in paraffin-embedded tumour tissue. RESULTS: MVP expression was positive in 112 patients (85.5 %) and no relation was found with clinic pathological variables. MVP overexpression (those tumours with moderate or strong expression of the protein) was related to insulin-like growth factor receptor-1 (IGF-1R) expression (P = 0.014). Tumour stage of the disease was the most important prognostic factor related to survival. Tumours overexpressing MVP and IGF-1R were strongly related to poor disease-free survival (P = 0.008, Exp(B) = 2.730, CI95% (1.302-5.724)) and cause-specific survival (P = 0.014, Exp(B) = 2.570, CI95% (1.215-5.437)) in patients achieving tumour stages III-IV, in multivariate analysis. CONCLUSIONS: MVP and IGF-1R expression were related in oral squamous cell carcinoma and conferred reduced long-term survival in patients suffering from advanced stages of the disease.     

Changing policies, changing patterns of care: Danish and Swedish home care at the crossroads

Despite pursuing the policy of ageing in place, the two Nordic countries of Denmark and Sweden have taken diverse roads in regard to the provision of formal, public tax-financed home care for older people. Whilst Sweden has cut down home care and targeted services for the most needy, Denmark has continued the generous provision of home care. This article focuses on the implication of such diverse policies for the provision and combination of formal and informal care resources for older people. Using data from Level of Living surveys (based on interviews with a total of 1,158 individuals aged 67–87 in need of practical help), the article investigates the consequences of the two policy approaches for older people of different needs and socio-economic backgrounds and evaluates how the development corresponds with ideals of universalism in the Nordic welfare model. Our findings show that in both countries tax-funded home care is used across social groups but targeting of resources at the most needy in Sweden creates other inequalities: Older people with shorter education are left with no one to resort to but the family, whilst those with higher education purchase help from market providers. Not only does this leave some older people more at risk, it also questions the degree of de-familialisation which is otherwise often proclaimed to be a main characteristic of the Nordic welfare model.