Book Review

Advances in Chitin and Chitosan Edited by Charles J. Brine, Paul A. Sandford and John P. Zikakis 2135.00, ISBN 1 851 66 8993, Elsevier, UK     

Left ventricular pseudoaneurysm after mitral valve replacement

Development of left ventricular pseudoaneurysm is a rare complication of mitral valve surgery and requires urgent surgical intervention. We describe a case of pseudoaneurysm of membranous septum following repeat mitral valve replacement with the use of multimodality imaging.     

Engineering furfural tolerance in Escherichia coli improves the fermentation of lignocellulosic sugars into renewable chemicals

Pretreatments such as dilute acid at elevated temperature are effective for the hydrolysis of pentose polymers in hemicellulose and also increase the access of enzymes to cellulose fibers. However, the fermentation of resulting syrups is hindered by minor reaction products such as furfural from pentose dehydration. To mitigate this problem, four genetic traits have been identified that increase furfural tolerance in ethanol-producing Escherichia coli LY180 (strain W derivative): increased expression of fucO, ucpA, or pntAB and deletion of yqhD. Plasmids and integrated strains were used to characterize epistatic interactions among traits and to identify the most effective combinations. Furfural resistance traits were subsequently integrated into the chromosome of LY180 to construct strain XW129 (LY180 ΔyqhD ackA::P_yadC′fucO-ucpA) for ethanol. This same combination of traits was also constructed in succinate biocatalysts (Escherichia coli strain C derivatives) and found to increase furfural tolerance. Strains engineered for resistance to furfural were also more resistant to the mixture of inhibitors in hemicellulose hydrolysates, confirming the importance of furfural as an inhibitory component. With resistant biocatalysts, product yields (ethanol and succinate) from hemicellulose syrups were equal to control fermentations in laboratory media without inhibitors. The combination of genetic traits identified for the production of ethanol (strain W derivative) and succinate (strain C derivative) may prove useful for other renewable chemicals from lignocellulosic sugars.     

Role for cytoplasmic nucleotide hydrolysis in hepatic function and protein synthesis

Nucleotide hydrolysis is essential for many aspects of cellular function. In the case of 3′,5′-bisphosphorylated nucleotides, mammals possess two related 3′-nucleotidases, Golgi-resident 3′-phosphoadenosine 5′-phosphate (PAP) phosphatase (gPAPP) and Bisphosphate 3′-nucleotidase 1 (Bpnt1). gPAPP and Bpnt1 localize to distinct subcellular compartments and are members of a conserved family of metal-dependent lithium-sensitive enzymes. Although recent studies have demonstrated the importance of gPAPP for proper skeletal development in mice and humans, the role of Bpnt1 in mammals remains largely unknown. Here we report that mice deficient for Bpnt1 do not exhibit skeletal defects but instead develop severe liver pathologies, including hypoproteinemia, hepatocellular damage, and in severe cases, frank whole-body edema and death. Accompanying these phenotypes, we observed tissue-specific elevations of the substrate PAP, up to 50-fold in liver, repressed translation, and aberrant nucleolar architecture. Remarkably, the phenotypes of the Bpnt1 knockout are rescued by generating a double mutant mouse deficient for both PAP synthesis and hydrolysis, consistent with a mechanism in which PAP accumulation is toxic to tissue function independent of sulfation. Overall, our study defines a role for Bpnt1 in mammalian physiology and provides mechanistic insights into the importance of sulfur assimilation and cytoplasmic PAP hydrolysis to normal liver function.     

Effects of fluticasone on systemic markers of inflammation in chronic obstructive pulmonary disease

Systemic inflammation is present in chronic obstructive pulmonary disease (COPD), which has been linked to cardiovascular morbidity and mortality. We determined the effects of oral and inhaled corticosteroids on serum markers of inflammation in patients with stable COPD. We recruited 41 patients with mild to moderate COPD. After 4 weeks during which inhaled corticosteroids were discontinued, patients were assigned to fluticasone (500 mcg twice a day), oral prednisone (30 mg/day), or placebo over 2 weeks, followed by 8 weeks of fluticasone at 500 mcg twice a day and another 8 weeks at 1,000 mcg twice a day. Withdrawal of inhaled corticosteroids increased baseline C-reactive protein (CRP) levels by 71% (95% confidence interval [CI], 16-152%). Two weeks with inhaled fluticasone reduced CRP levels by 50% (95% CI, 9-73%); prednisone reduced it by 63% (95% CI, 29-81%). No significant changes were observed with the placebo. An additional 8 weeks of fluticasone were associated with CRP levels that were lower than those at baseline (a 29% reduction; 95% CI, 7-46%). Inhaled and oral corticosteroids are effective in reducing serum CRP levels in patients with COPD and suggest their potential use for improving cardiovascular outcomes in COPD.     

4D In-Situ Microscopy of Aerosol Filtration in a Wall Flow Filter

The transient nature of the internal pore structure of particulate wall flow filters, caused by the continuous deposition of particulate matter, makes studying their flow and filtration characteristics challenging. In this article we present a new methodology and first experimental demonstration of time resolved in-situ synchrotron micro X-ray computed tomography (micro-CT) to study aerosol filtration. We directly imaged in 4D (3D plus time) pore scale deposits of TiO2 nanoparticles (nominal mean primary diameter of 25 nm) with a pixel resolution of 1.6 μm. We obtained 3D tomograms at a rate of ∼1 per minute. The combined spatial and temporal resolution allows us to observe pore blocking and filling phenomena as they occur in the filter’s pore space. We quantified the reduction in filter porosity over time, from an initial porosity of 0.60 to a final porosity of 0.56 after 20 min. Furthermore, the penetration depth of particulate deposits and filtration rate was quantified. This novel image-based method offers valuable and statistically relevant insights into how the pore structure and function evolves during particulate filtration. Our data set will allow validation of simulations of automotive wall flow filters. Evolutions of this experimental design have potential for the study of a wide range of dry aerosol filters and could be directly applied to catalysed automotive wall flow filters.     

Influence of propranolol on the acute thermic effect of feeding in man

The influence of a beta-adrenergic blocker on the thermic effect of feeding (TEF) a meal was investigated in 7 healthy male volunteers. Metabolic rate (MR) was measured before and for 180 min after the consumption of 2.0 MJ 'Ensure' (Abbott Laboratories, Queensborough, Kent, UK); there were 14, 33 and 53% of energy from protein, fat and carbohydrate, respectively. On one occasion propranolol (ICI plc, Macclesfield, Ches., UK) was administered intravenously at 0.1 mg/kg body weight at meal feeding. On the second occasion a similar volume of saline was infused. Serial blood samples (10 ml) were collected before and at 30-min intervals for 180 min after meal feeding. Mean (+/- SD) resting MR was 104 (13) and 116 (11) kJ/kg and MR increased by 12.8% and 10.8% after the test meal with and without propranolol, respectively. These differences were not significant. The postprandial changes in serum glucose and triiodothyronine were similar in the two trials. The magnitude of the rise of serum insulin was similar in the two trials, but the pattern was not. beta-Adrenergenic blockade resulted in an early peak in insulin output at 30 min compared with 60 min for the control trial. We conclude that propranolol had no influence on TEF in this study.     

Physicians' Attitudes and the Use of Oral Anticoagulants: Surveying the Present and Envisioning Future

Atrial fibrillation has the highest prevalence in the elderly. While the elderly are at the highest risk for stroke and would benefit the most from anticoagulation, they are also the least likely to receive anticoagulation. In a pooled analysis of the primary prevention trials, warfarin reduced stroke by 68% compared with placebo, and aspirin reduced stroke by 18%. Age, history of hypertension, diabetes, heart failure or reduced left ventricular function, and previous transient ischemic events and stroke are independent risk factors for stroke in patients with atrial fibrillation. Less than 50% of the elderly who have clear-cut indications and no contraindications for warfarin receive anticoagulant therapy. This low use of warfarin is driven by many factors, but physicians' fear of hemorrhage is among the most important. Better adherence to evidence-driven guidelines, better patient and physician education, point-of-care monitoring of INR and the future development of user friendly anticoagulant drugs are likely to result in higher rates of anticoagulation use.