Cloning, mapping and identification of the Aeromonas salmonicida fstA, fepA and irpA genes, encoding the 86, 82 and 74 kDa iron-regulated outer membrane proteins, respectively

Three iromps (iron-regulated outer membrane proteins) of Aeromonas salmonicida were identified by the use of specific antibodies together with Southern hybridization analysis and limited nucleotide sequencing of their genes. The results of these experiments together with a search of the international database for homologous sequences led to their identification as follows: -86 kDa iromp (FstA) as a Vibrio anguillarum Fat A homologue -82 kDa iromp (FepA) as an Escherichia coli FepA homologue -74 kDa iromp (IrpA) as an Escherichia coli Cir homologue.

Mechanism of uptake of the catecholic (7)-α-formamido cephalosporin BRL 41897A by klebsiella pneumoniae

The catecholic cephalosporin BRL 41897 A is resistant to β-lactamases and is taken up by bacteria via the iron transport system. The uptake of this antibiotic in E.coli uses the Fiu and Cir outer membrane proteins, whereas in P. aerugtnosa it enters via the pyochelin transport system. In this thesis mutants of K. pneumoniae resistant to BRL 41897A were isolated using TnphoA mutagenesis and used to study the mechanism of uptake of BRL 41897A by K. pneumoniae. The activity of BRL 41897A towards the parent strain (M10) was increased in iron depleted media, whereas no significant differences in the resistant (KSL) mutants were observed. Three mutants (KSL19, KSL38and KSL59) produced decreased amounts of certain iron-regulated outer membrane proteins. The uptake of 55Fe-BRL 41897A by M10 in iron-deficient medium was higher than in iron-rich medium. This result indicated the involvement of an iron transport system in the uptake of BRL 41897A by K. pneumoniae. Uptake by the KSL mutants in iron-deficient culture was higher than that by M10. This result, supported by analysis of outer membrane and periplasmic proteins of the KSL mutants, indicates that loss of one outer membrane protein can be compensated by over expression of other outer membrane and/or periplasmic proteins. However, the increased uptake of BRL 41897A by the KSL mutants did not reflect increased activity towards these strains, indicating that there are defects in the transport of BRL 41897A resulting in failure to reach the penicillin binding protein target sites in the cytoplasmic membrane. Southern blotting of chromosomal digests and sequencing in one mutant (KSL19) showed that only one copy of TnphoA was inserted into its chromosome. A putative TnphoA inserted gene in KSL19, designated kslA, carrying a signal sequence was identified. Transformation of a fragment containing the kslA gene into KSL19 cells restored the sensitivity to BRL 41897A to that of the parent strain. Data base peptide sequence searches revealed that the kslA gene in the KSL19 has some amino acid homology with the E. coli ExbD protein, which is involved in stabilisation of the TonB protein. 

Editorial : which weight loss diet?

Full editorial: A recent study evaluating the long-term (2 yr) weight reducing efficacy of different types of diets – high or low in carbohydrates (CHOs), protein or fat - confirmed that it is calorie deficit not dietary composition that determines the loss and maintenance of body weight.1 Is there any advantage in following a specific weight loss diet? Short-term use of nutritionally complete commercially available (very) low calorie diets has benefited people with diabetes when  supported by education programmes.2 Initial weight loss has been encouraging with some fad diets eg the Atkins and the South Beach diets, but these diets are difficult to maintain and there are safety issues regarding their short- and long-term use – especially in people with diabetes.3 The types of macronutrients consumed can have a considerable impact on glycaemic control and energy metabolism. Although a low CHO diet additionally enhances initial weight loss by reducing cellular water content, if fat is not proportionally reduced the diet may not benefit the lipid profile for vascular disease risk. High fat and high protein diets – which are simultaneously low in CHOs – increase vulnerability to hypoglycaemia in people taking insulin secretagogues or on insulin therapy, and may promote excess fat metabolism and ketogenesis, particularly in people vulnerable to lack of insulin. Very low protein diets are not recommended as lean body mass tends to be reduced in diabetes. Altering the macronutrient balance has implications for the micronutrient mix: deficiencies are higher if more foods are excluded and conversely specific micronutrient excess can occur with some fad diets. The altered nutrient mix affects intestinal fauna and flora, and gut motility and glycaemic control are influenced by the quantity and type of fibre consumed. Support programmes help individuals achieve long term weight loss and there is mounting evidence that community schemes which educate and promote lifestyle changes may stem the rising tide of obesity and consequent type 2 diabetes.4 Consuming smaller portions of a balanced diet (and adjusting antidiabetic medications accordingly) will create an energy deficit to promote healthy weight loss. Increased movement/exercise will enhance this energy deficit. Knowledge (eg 1g fat has 2.25 times more energy than 1g CHO) allows sensible food choices and compensation for inclusion of small volumes of  ‘naughty but nice’ foods. Ultimately weight control requires self control. References 1. Sacks FM, Bray GA, Carey VJ et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009;360:859–73. 2. Bennett P. Obesity, diabetes and VLCD. Br J Diabetes Vasc Dis 2004;4:328–30. 3. Baldwin EJ. Fad diets in diabetes. Br J Diabetes Vasc DIs 2004;4:333–7. 4. Romon M, Lommoz A, Tafflet M et al. Downward trends in the prevalence of childhood overweight in the setting of 12-year school- and community-based programmes. Public Health Nutr 2008; Dec 28, 1–8 [Epub ahead of print].

Evaluating the impact of institutional logic on the corporate Internet reporting by Egyptian listed companies

This study explores the institutional logic(s) governing the Corporate Internet Reporting (CIR) by Egyptian listed companies. In doing so, a mixed methods approach was followed. The qualitative part seeks to understand the perceptions, believes, values, norms, that are commonly shared by Egyptian companies which engaged in these practices. Consequently, seven cases of large listed Egyptian companies operating in different industries have been examined. Other stakeholders and stockholders have been interviewed in conjunction with these cases. The quantitative part consists of two studies. The first one is descriptive aiming to specify whether the induced logic(s) from the seven cases are commonly embraced by other Egyptian companies. The second study is explanatory aiming to investigate the impact of several institutional and economic factors on the extent of CIR, types of the online information, quality of the websites as well as the Internet facilities. Drawing on prior CIR literature, four potential types of logics could be inferred: efficiency, legitimacy, technical and marketing based logics. In Egypt, legitimacy logic was initially embraced in the earlier years after the Internet inception. latter, companies confronted radical challenges in their internal and external environments which impelled them to raise their websites potentialities to defend their competitive position; either domestically or internationally. Thus, two new logics emphasizing marketing and technical perspectives have emerged, in response. Strikingly, efficiency based logic is not the most prevalent logic driving CIR practices in Egypt as in the developed countries. The empirical results support this observation and show that almost half of Egyptian listed companies 115 as on December 2010 possessed an active website, half of them 62 disclosed part of their financial and accounting information, during December 2010 to February 2011. Less than half of the websites 52 offered latest annual financial statements. Fewer 33(29%) websites provided shareholders and stock information or included a separate section for corporate governance 25 (22%) compared to 50 (44%) possessing a section for news or press releases. Additionally, the variations in CIR practices, as well as timeliness and credibility were also evident even at industrial level. After controlling for firm size, profitability, leverage, liquidity, competition and growth, it was realized that industrial companies and those facing little competition tend to disclose less. In contrast, management size, foreign investors, foreign listing, dispersion of shareholders and firm size provided significant and positive impact individually or collectively. In contrast, neither audit firm, nor most of performance indicators (i.e. profitability, leverage, and liquidity) did exert an influence on the CIR practices. Thus, it is suggested that CIR practices are loosely institutionalised in Egypt, which necessitates issuing several regulative and processional rules to raise the quality attributes of Egyptian websites, especially, timeliness and credibility. Beside, this study highlights the potency of assessing the impact of institutional logic on CIR practices and suggests paying equal attention to the institutional and economic factors when comparing the CIR practices over time or across different institutional environments in the future.

An examination of the comprehensiveness of corporate Internet reporting provided by London-listed companies

Recent changes in the regulatory environment of the London Stock Exchange are aimed at prohibiting selective disclosure and enhancing the credibility of reporting. Using an innovative 143-item disclosure checklist, we examine corporate Internet reporting (CIR) comprehensiveness and its determinants within this new regulatory environment. We also extend the literature linking corporate governance measures to CIR. Our findings indicate that despite this new regulatory environment, there is considerable room for improvement in CIR by London-listed companies. For example, our sample companies provide only 58 percent and 70 percent, respectively, of the credibility and usability items assessed by our comprehensiveness index. After controlling for size, profitability, industry, and high growth/ intangibles, we find the CIR comprehensiveness of London-listed companies is associated with analyst following, director holding, director independence, and CEO duality. Because prior research indicates the U.K. leads Europe in Internet reporting, our results may shed light on how CIR will evolve throughout Europe.

Excipient characterization and particle engineering to develop directly compressed orally disintegrating tablets

ODTs have emerged as a novel oral dosage form with a potential to deliver a wide range of drug candidates to paediatric and geriatric patients. Compression of excipients offers a costeffective and translatable methodology for the manufacture of ODTs. Though, technical challenges prevail such as difficulty to achieve suitable tablet mechanical strength while ensuring rapid disintegration in the mouth, poor compressibility of preferred ODT diluent Dmannitol, and limited use for modified drug-release. The work investigates excipients’ functionality in ODTs and proposes new methodologies for enhancing material characteristics via process and particle engineering. It also aims to expand ODT applications for modified drug-release. Preformulation and formulation studies employed a plethora of techniques/tests including AFM, SEM, DSC, XRD, TGA, HSM, FTIR, hardness, disintegration time, friability, stress/strain and Heckel analysis. Tableting of D-mannitol and cellulosic excipients utilised various compression forces, material concentrations and grades. Engineered D-mannitol particles were made by spray drying mannitol with pore former NH4HCO3. Coated microparticles of model API omeprazole were prepared using water-based film forming polymers. The results of nanoscopic investigations elucidated the compression profiles of ODT excipients. Strong densification of MCC (Py is 625 MPa) occurs due to conglomeration of physicomechanical factors whereas D-mannitol fragments under pressure leading to poor compacts. Addition of cellulosic excipients (L-HPC and HPMC) and granular mannitol to powder mannitol was required to mechanically strengthen the dosage form (hardness >60 N, friability <1%) and to maintain rapid disintegration (<30 sec). Similarly, functionality was integrated into D-mannitol by fabrication of porous, yet, resilient particles which resulted in upto 150% increase in the hardness of compacts. The formulated particles provided resistance to fracture under pressure due to inherent elasticity while promoted tablet disintegration (50-77% reduction in disintegration time) due to porous nature. Additionally, coated microparticles provided an ODT-appropriate modified-release coating strategy by preventing drug (omeprazole) release.

A pragmatic approach for engineering porous mannitol and mechanistic evaluation of particle performance

The importance of mannitol has increased recently as an emerging diluent for orodispersible dosage forms. The study aims to prepare spray dried mannitol retaining high porosity and mechanical strength for the development of orally disintegrating tablets (ODTs). Aqueous feed of d-mannitol (10% w/v) comprising ammonium bicarbonate, NH4HCO3 (5% w/v) as pore former was spray dried at inlet temperature of 110-170°C. Compacts were prepared at 151MPa and characterized for porosity, hardness and disintegration time. Particle morphology and drying mechanisms were studied using thermal (HSM, DSC and TGA) and polymorphic (XRD) methods. Tablet porosity increased from 0.20±0.002 for pure mannitol to 0.53±0.03 using fabricated porous mannitol. Disintegration time dropped by 50-77% from 135±5.29s for pure mannitol to 75.33±2.52-31.67±1.53s for mannitol 110-170°C. Hardness increased by 150% at 110°C (258.67±28.89N) and 30% at 150°C (152.70±10.58N) compared to pure mannitol tablets (104.17±1.70N). Increasing inlet temperature resulted in reducing tablet hardness due to generation of 'micro-sponge'-like particles exhibiting significant elastic recovery. Impact of mannitol polymorphism on plasticity/elasticity cannot be ruled out as a mixture of α and β polymorphs formed upon spray drying.

Free to publish - free to read

Full Text: August 2001 saw the birth of the British Journal of Diabetes & Vascular Disease (Figure 1): an open-access peer review journal.1 Free to publish and free to read. The founding editorial board and publisher (MediNews Diabetes) aimed to deliver a free journal to the diabetes team and vascular professionals with a special interest in diabetes. Despite the shifting sands of time and a change of publisher (SAGE) the journal has remained true to its founding philosophy - publication is on merit, not on ability to pay and free online access remains available worldwide (www.bjdvd.com) plus an extensive – mainly UK - print circulation. Evolution- The journal attracted much attention and was soon receiving good quality experimental and clinical science manuscripts. However it was felt that these articles, especially experimental and pre-clinical studies, were not within the focus of the British Journal of Diabetes & Vascular Disease, thus Diabetes & Vascular Disease Research was conceived –and is now also a SAGE journal and has an impact factor of 2.59. Over the years the organisation of topics has changed, for example the Healthcare management, The diabetes care team and Trans-cultural medicine sections have been absorbed into the Achieving Best Practice and Current Topics sections which better reflect the broader-based content of submitted material. Landmark Studies was a regular highly popular section – but how many truly Landmark Studies are undertaken? Not enough to warrant special attention 6 times a year for 12 years. Interestingly one of the studies reviewed is consistently amongst the top ten of our most read online articles.2 The British Journal of Diabetes & Vascular Disease has also challenged convention with the production of two Jubilee issues.3,4 The celebrations for the golden and diamond jubilees of Her Majesty Queen Elizabeth II afforded opportunities to reflect on changes in the understanding and treatment of diabetes during her reign. Most of the articles in these issues were written by authors who had first hand experience of the changing face of diabetes and vascular disease care. The increased costs of print and post – both financially and environmentally mean that digital communications are likely to become more popular (assuming that these approaches have a smaller ecological footprint). The British Journal of Diabetes & Vascular Disease is pleased to be able to celebrate its 12th birthday as an original open-access journal, with an ongoing commitment to support authors to publish free of charge whilst providing free reader access. As for what the future holds: tomorrow is another day. References 1.British Journal of Diabetes & Vascular Disease 2001; 1: 1-92. 2.Levy J. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. Br J Diabetes Vasc Dis 2002; 2: 278-80. 3.British Journal of Diabetes & Vascular Disease. (Golden Jubilee Issue) 2002; 2: 415-480. 4.British Journal of Diabetes & Vascular Disease. (Diamond Jubilee Issue) 2012; 12: 266-380.