Expression and inducibility of cytochrome P450 proteins in the liver of chick embryo

 The expression and inducibility of cytochrome P450 proteins in the liver of chick embryo were investigated using substrate probes and/or immunologically using polyclonal antibodies to the mammalian isoforms. Antibodies to CYP1A1 recognised a single protein which was inducible by structurally diverse chemicals, including aminocompounds, and was parallelled by increases in the O-dealkylations of ethoxy- and methoxyresorufin and in the bioactivation of Glu-P-1. When probed with antibodies to CYP2E1 an immunoreacting protein was revealed which was induced by phenobarbital but not acetone; a second protein became apparent following the treatment with phenobarbital. The increase in apoprotein levels was accompanied by similar increases in p-nitrophenol hydroxylase. Antibodies to CYP2C11 recognised two immunorelated proteins, of which one was inducible by phenobarbital. The same inducer, but not dexamethasone, enhanced the N-demethylation of erythromycin but antibodies to rat CYP3A1 failed to detect any proteins. Finally, lauric acid hydroxylation was not detectable in chick embryo and, moreover, no immunoreacting band was visible following probing of microsomes with anti-CYP4A1. It is concluded that proteins immunorelated to the mammalian CYP1 and CYP2 families are expressed in chick embryo but the regulation of the latter family in the embryo by exogenous chemicals differs markedly from that established for mammals. Received: 6 February 1996/Accepted: 3 May 1996     

Aquaporin-7 and glycerol permeability as novel obesity drug-target pathways

Advances in determining the mechanisms that underlie the control of energy balance in mammals have recently been provided by the discovery and characterization of aquaporin-7 (AQP7), a water-glycerol transporter that is present in the plasma membrane of fat-storing cells (adipocytes). Recent studies have shown that the absence of AQP7 expression in fat cells increases glycerol kinase activity, boosting triacylglycerol synthesis and ultimately leading to obesity. Thus, AQP7 operates as a glycerol channel in vivo, whereby adipocyte glycerol permeability has a key role in the regulation of fat accumulation.     

Development and validation of a clinical prediction rule for severe community-acquired pneumonia

RATIONALE: Objective strategies are needed to improve the diagnosis of severe community-acquired pneumonia in the emergency department setting. OBJECTIVES: To develop and validate a clinical prediction rule for identifying patients with severe community-acquired pneumonia, comparing it with other prognostic rules. METHODS: Data collected from clinical information and physical examination of 1,057 patients visiting the emergency department of a hospital were used to derive a clinical prediction rule, which was then validated in two different populations: 719 patients from the same center and 1,121 patients from four other hospitals. MEASUREMENTS AND MAIN RESULTS: In the multivariate analyses, eight independent predictive factors were correlated with severe community-acquired pneumonia: arterial pH < 7.30, systolic blood pressure < 90 mm Hg, respiratory rate > 30 breaths/min, altered mental status, blood urea nitrogen > 30 mg/dl, oxygen arterial pressure < 54 mm Hg or ratio of arterial oxygen tension to fraction of inspired oxygen < 250 mm Hg, age > or = 80 yr, and multilobar/bilateral lung affectation. From the beta parameter obtained in the multivariate model, a score was assigned to each predictive variable. The model shows an area under the curve of 0.92. This rule proved better at identifying patients evolving toward severe community-acquired pneumonia than either the modified American Thoracic Society rule, the British Thoracic Society's CURB-65, or the Pneumonia Severity Index. CONCLUSIONS: A simple score using clinical data available at the time of the emergency department visit provides a practical diagnostic decision aid, and predicts the development of severe community-acquired pneumonia.     

Marine ecosystem health status assessment through integrative biomarker indices: a comparative study after the Prestige oil spill “Mussel Watch”

Five integrative biomarker indices are compared: Bioeffects Assessment Index (BAI), Health Status Index (HSI), integrated biological response (IBR), ecosystem health condition chart (EHCC) and Integrative Biomarker Index (IBI). They were calculated on the basis of selected biomarker data collected in the framework of the Prestige oil spill (POS) Mussel Watch monitoring (2003–2006) carried out in Galicia and the Bay of Biscay. According to the BAI, the health status of mussels was severely affected by POS and signals of recovery were evidenced in Galicia after April-04 and in Biscay Bay after April-05. The HSI (computed by an expert system) revealed high levels of environmental stress in 2003 and a recovery trend from April-04 to April-05. In July-05, the health status of mussels worsened but in October-05 and April-06 healthy condition was again recorded in almost all localities. IBR/n and IBI indicated that mussel health was severely affected in 2003 and improved from 2004 onwards. EHCC reflected a deleterious environmental condition in 2003 and a recovery trend after April-04, although a healthy ecosystem condition was not achieved in April-06 yet. Whereas BAI and HSI provide a basic indication of the ecosystem health status, star plots accompanying IBR/n and IBI provide complementary information concerning the mechanisms of biological response to environmental insult. Overall, although the integrative indices based on biomarkers show different sensitivity, resolution and informative output, all of them provide coherent information, useful to simplify the interpretation of biological effects of pollution in marine pollution monitoring. Each others’ advantages, disadvantages and applicability for ecosystem health assessment are discussed.