Gastric Acid Suppressive Therapy and Community-Acquired Pneumonia, Etiology and Outcome

Background: Community acquired pneumonia (CAP) is an infection of the pulmonary parenchyma that can be caused by various microbial pathogens. Co-morbidity and medication are related to specific pathogens. Patients on gastric acid suppressive therapy have an increased risk to develop CAP. We aimed to assess whether there are specific pathogens independently associated with gastric acid suppressive therapy and its impact on infection severity. Methods: From December 2007 to January 2010, all subjects consulting the emergency care unit of a general hospital in the south of the Netherlands with a suspected CAP were prospectively registered. Each patient underwent chest radiography. Sputum, urine, nose swabs and blood samples were obtained for microbial culture, antigen detection and polymerase chain reaction techniques, respectively. To study the severity of CAP upon presentation, the validated CURB-65 score was calculated. Furthermore, we assessed hospital or intensive care admission, length of hospitalization and in-hospital mortality. We evaluated the association between use of acid suppressive therapy and microbial aetiology of CAP and severity of illness with logistic regression analysis. Results: The final cohort comprised 463 patients with CAP, defined as presence of infiltrate on chest radiography and/ or microbial aetiology. Overall 136 patients (29%) used acid suppressive therapy, mainly proton pump inhibitors (97%). Patients with acid suppressive therapy more frequently had an infection with Streptococcus pneumoniae (28% vs. 14%) and Haemophilus influenzae (10% vs. 6%), and less frequently with Coxiella burnetii (8% vs. 19%) or H1N1 influenza A virus (2% vs. 7%) in comparison to those without acid suppressive therapy. After adjustment for baseline differences, the risk of proton pump inhibitor users being infected with S. pneumonia was 2.18 times (95%Confidence Interval(CI): 1.2-3.6) higher compared to those not on acid suppressive therapy. Patients using more than one defined daily dose of a PPI had a 1.48-fold increased risk of a S. pneumoniae infection compared with patients using the defined daily dose (95%CI:1.1-2.0). No risk between PPI use and any other microbial pathogen was found. Patients with acid suppressive therapy had on average higher CURB-65 scores, longer hospital stay and subsequently a case fatality rate of 11% vs. 4% compared to those not using acid suppressive therapy. Conclusions. Proton pump inhibitor therapy predisposes with community acquired S. pneumoniae pneumonia, and was associated with higher morbidity

Motion for a Resolution tabled by Mr Barbi, Mr Vergeer, Mr Pedini, Mr Langes, Mr Penders, Mr Marck, Mrs Lenz, Mrs Walz, Mr Alber and Mrs Lentz-Cornette on behalf of the Group of the European People's Party (C-D Group) pursuant to Rule 47 of the Rules of Procedure on Nicaragua, Working Documents 1983-1984, Document 1-237/83, 26 April 1983

Peroxygenases offer an attractive means to address challenges in selective oxyfunctionalization chemistry. Despite this, their application in synthetic chemistry remains challenging due to their facile inactivation by the stoichiometric oxidant H2O2. Often atom-inefficient peroxide generation systems are required, which show little potential for large-scale implementation. Here, we show that visible-light-driven, catalytic water oxidation can be used for in situ generation of H2O2 from water, rendering the peroxygenase catalytically active. In this way, the stereoselective oxyfunctionalization of hydrocarbons can be achieved by simply using the catalytic system, water and visible light.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.BT/BiocatalysisBN/Greg Bokinsky La

Type 2 Endoleak With or Without Intervention and Survival After Endovascular Aneurysm Repair

Objective: The aims of the present study were to examine the impact of type 2 endoleaks (T2EL) on overall survival and to determine the need for secondary intervention after endovascular aneurysm repair (EVAR). Methods: A multicentre retrospective cohort study in the Netherlands was conducted among patients with an infrarenal abdominal aortic aneurysm (AAA) who underwent EVAR between 2007 and 2012. The primary endpoint was overall survival for patients with (T2EL+) or without (T2EL-) a T2EL. Secondary endpoints were sac growth, AAA rupture, and secondary intervention. Kaplan–Meier survival and multivariable Cox regression analysis were used. Results: A total of 2 018 patients were included. The median follow up was 62.1 (range 0.1 – 146.2) months. No difference in overall survival was found between T2EL+ (n = 388) and T2EL- patients (n = 1630) (p =.54). The overall survival estimates at five and 10 years were 73.3%/69.4% and 45.9%/44.1% for T2EL+/T2EL- patients, respectively. Eighty-five of 388 (21.9%) T2EL+ patients underwent a secondary intervention. There was no difference in overall survival between T2EL+ patients who underwent a secondary intervention and those who were treated conservatively (p =.081). Sac growth was observed in 89 T2EL+ patients and 44/89 patients (49.4%) underwent a secondary intervention. In 41/44 cases (93.1%), sac growth was still observed after the intervention, but was left untreated. Aneurysm rupture occurred in 4/388 T2EL patients. In Cox regression analysis, higher age, ASA classification, and maximum iliac diameter were significantly associated with worse overall survival. Conclusion: No difference in overall survival was found between T2EL+ and T2EL- patients. Also, patients who underwent a secondary intervention did not have better survival compared with those who did not undergo a secondary intervention. This study reinforces the need for conservative treatment of an isolated T2EL and the importance of a prospective study to determine possible advantages of the intervention

Vanadium Chloroperoxidases: The Missing Link in the Formation of Chlorinated Compounds and Chloroform in the Terrestrial Environment?

It is well established that the majority of chlorinated organic substances found in the terrestrial environment are produced naturally. The presence of these compounds in soils is not limited to a single ecosystem. Natural chlorination is also a widespread phenomenon in grasslands and agricultural soils typical for unforested areas. These chlorinated compounds are formed from chlorination of natural organic matter consisting of very complex chemical structures, such as lignin. Chlorination of several lignin model compounds results in the intermediate formation of trichloroacetyl-con-taining compounds, which are also found in soils. These decay, in general, through a haloform-type reaction mechanism to CHCl3. Upon release into the atmosphere, CHCl3 will produce chlorine radicals through photolysis, which will, in turn, lead to natural depletion of ozone. There is evidence that fungal chloroperoxidases able to produce HOCl are involved in the chlorination of natural organic matter. The objective of this review is to clarify the role and source of the various chloroperoxidases involved in the natural formation of CHCl

Towards Preparative Chemoenzymatic Oxidative Decarboxylation of Glutamic Acid

The chemoenzymatic oxidative decarboxylation of glutamic acid to the corresponding nitrile using the vanadium chloroperoxidase from Curvularia inaequalis (CiVCPO) as HOBr generation catalysts has been investigated. Product inhibition was identified as major limitation. Nevertheless, 1630000 turnovers and kcat of 75 s−1 were achieved using 100 mM glutamate. The semi-preparative enzymatic oxidative decarboxylation of glutamate was also demonstrated.</p

Chapter 24: Vanadium Chloroperoxidases as Versatile Biocatalysts

In this chapter the catalytic and structural properties of the vanadium chloroperoxidases will be discussed with an emphasis on their superb activity and stability under operational conditions. These properties make these enzymes attractive catalysts in organic synthesis and allow a number of applications. Some of the more recent findings are highlighted, e.g., the use of vanadium chloroperoxidase (VCPO) in the formation of singlet oxygen, halogenation of phenols, alkenes, halocyclisation of ϵ,γ-unsaturated alcohols and the aza-Achmatowicz reaction. Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.BT/Biocatalysi

Cofactor and Substrate Binding to Vanadium Chloroperoxidase Determined by UV-VIS Spectroscopy and Evidence for High Affinity for Pervanadate †

ABSTRACT: The vanadate cofactor in vanadium chloroperoxidase has been studied using UV-VIS absorption spectroscopy. A band is present in the near-UV that is red-shifted as compared to free vanadate and shifts in both position and intensity upon change in pH. Mutation of vanadate binding residues has a clear effect on the spectrum. Substrate-induced spectral effects allow direct measurement of separate kinetics steps for the first time for vanadium haloperoxidases. A peroxo intermediate is formed upon addition of H 2 O 2 , which causes a decrease in the absorption spectrum at 315 nm, as well as an increase at 384 nm. This peroxo form is very stable at pH 8.3, whereas it is less stable at pH 5.0, which is the optimal pH for activity. Upon addition of halides to the peroxo form, the native spectrum is re-formed as a result of halide oxidation. Stopped-flow experiments show that H 2 O 2 binding and Cl -oxidation occur on the millisecond to second time scale. These data suggest that the oxidation of Cl -to HOCl occurs in at least two steps. In the presence of H 2 O 2 , the affinity for the vanadate cofactor was found to be much higher than previously reported for vanadate in the absence of H 2 O 2 . This is attributed to the uptake of pervanadate by the apo-enzyme. Human glucose-6-phosphatase, which is evolutionarily related to vanadium chloroperoxidase, is also likely to have a higher affinity for pervanadate than vanadate. This could explain the enhanced insulin mimetic effect of pervanadate as compared to vanadate

Vanadium K-edge XAS studies on the native and peroxo-forms of vanadium chloroperoxidase from Curvularia inaequalis

Vanadium K-edge X-ray Absorption Spectra have been recorded for the native and peroxo-forms of vanadium chloroperoxidase from Curvularia inaequalis at pH 6.0. The Extended X-ray Absorption Fine Structure (EXAFS) regions provide a refinement of previously reported crystallographic data; one short V = O bond (1.54 Å) is present in both forms. For the native enzyme, the vanadium is coordinated to two other oxygen atoms at 1.69 Å, another oxygen atom at 1.93 Å and the nitrogen of an imidazole group at 2.02 Å. In the peroxo-form, the vanadium is coordinated to two other oxygen atoms at 1.67 Å, another oxygen atom at 1.88 Å and the nitrogen of an imidazole group at 1.93 Å. When combined with the available crystallographic and kinetic data, a likely interpretation of the EXAFS distances is a side-on bound peroxide involving V-O bonds of 1.67 and 1.88 Å; thus, the latter oxygen would be ‘activated’ for transfer. The shorter V-N bond observed in the peroxo-form is in line with the previously reported stronger binding of the cofactor in this form of the enzyme. Reduction of the enzyme with dithionite has a clear influence on the spectrum, showing a change from vanadium(V) to vanadium(IV)