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  • Dunn Fogh posted an update 2 weeks ago

    10% along with long operation stability over 1500 h under continuous light illumination. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Structural analysis of modern pharmaceutical practices allows for the identification of two rapidly growing trends the introduction of tailor-made amino acids and the exploitation of fluorinated motifs. Quite curiously, the former represents one of the most ubiquitous classes of naturally occurring compounds while the latter is the most xenobiotic, comprised virtually entirely of man-made derivatives. In this review, we profile 39 selected compounds featuring both of these traits in the same molecule. We discuss the total synthesis, source of the corresponding amino acids and fluorinated residues, and provide a brief discussion of the medicinal chemistry aspects and biological properties of the molecules. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Organophosphate (OP) compounds constitute a class of highly toxic molecules, characterized by irreversible cholinesterase (ChE) inhibition. Being either pesticides or chemical warfare agents, they present a major health issue in some countries, as well as a terrorist or military threat. Prompted by the need for suitable animal models to test novel medical countermeasures, we developed a new convulsive mouse model of OP poisoning using diisopropylfluorophosphate (DFP). Using electrocorticography (ECoG), we analyzed seizure and status epilepticus (SE) occurrences, as well as relative power of ECoG frequency band modifications after DFP injection in male Swiss mice. Next, we investigated DFP effect on ChE inhibition. Histological changes on neuronal activity and neuronal damage were examined by c-Fos immunolabeling and Fluoro-Jade C staining. We showed that mice exposed to DFP presented electrocorticographic seizures that rapidly progressed to SE within 20 minutes. Lasting >8 hours, DFP-induced SE was associated with major power spectrum modifications in seizing DFP animals compared to control animals. Seizures and SE development were concomitant with profound ChE inhibition and induced massive neuronal degeneration. Presenting all hallmarks of convulsive OP poisoning, we showed that our mouse model is valuable for studying pathophysiological mechanisms and preclinical testing of newly available therapeutic molecules. © 2020 International League Against Epilepsy.BACKGROUND The clinical presentation of primary antiphospholipid syndrome (PAPS) can vary, often mimicking many other medical conditions. Therefore, it is difficult to diagnose at the first presentation because of the absence of classical symptoms. We described an unusual presentation of PAPS mimicking livedoid vasculopathy (LV), where the only diagnostic clue at the initial presentation was skin lesions in both lower legs. METHODS A 75-year-old Han Chinese woman presented with features mimicking LV, without clinically significant antiphospholipid syndrome (APS). After many relevant laboratory examinations and histopathological examination, the patient was finally diagnosed as having PAPS. RESULTS LV should not be treated as an independent disease, but as a skin manifestation. A high degree of suspicion of antiphospholipid syndrome (APS) is needed in patients presenting or diagnosed with LV. CONCLUSIONS Early interventions are necessary to prevent and reduce the risk of thrombosis. This case presents a rare clinical manifestation and provides significant information on PAPS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.The Mn4 CaO5 cluster of Photosystem II (PSII) advances sequentially through five oxidation states (S0 to S4 ). Under the enzyme cycle, two water molecules are oxidized, O2 is generated and four protons are released into the lumen. Umena et al. (2011) have proposed that, with other charged amino acids, the R323 residue of the D1 protein could contribute to regulate a proton egress pathway from the Mn4 CaO5 cluster and TyrZ via a proton channel identified from the 3D structure. L-NMMA cell line To test this suggestion, a PsbA3/R323E site-directed mutant has been constructed and the properties of its PSII have been compared to those of the PsbA3-PSII by using EPR spectroscopy, polarography, thermoluminescence and time-resolved UV-visible absorption spectroscopy. Neither the oscillations with a period four nor the kinetics and S-state-dependent stoichiometry of the proton release were affected. However, several differences have been found i) the P680 + decay in the hundreds of ns time domain was much slower in the mutant, ii) the S2 QA – /DCMU and S3 QA – /DCMU radiative charge recombination occurred at higher temperatures and iii) the S0 TyrZ • , S1 TyrZ • , S2 TyrZ • split EPR signals induced at 4.2 K by visible light from the S0 TyrZ , S1 TyrZ , S2 TyrZ , respectively, and the (S2 TyrZ • )’ induced by NIR illumination at 4.2 K of the S3 TyrZ state differed. It is proposed that the R323 residue of the D1 protein interacts with TyrZ likely via the H-bond network previously proposed to be a proton channel. Therefore, rather than participating in the egress of protons to the lumen, this channel could be involved in the relaxations of the H-bonds around TyrZ by interacting with the bulk, thus tuning the driving force required for TyrZ oxidation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.In patients with persistent left superior vena cava (PLSVC), transvenous device implantation for cardiac resynchronization therapy (CRT) may be challenging. We present a complex case with successful, high-density electroanatomic mapping (EAM) guided corrective His bundle pacing (CHBP) following failed CRT upgrade in a patient with PLSVC, congenital heart disease and pacing-associated heart failure. CHBP restored physiological conduction in left bundle branch block with complete conduction block leading to clinical improvement and cardiac remodeling. The presented case supports the growing evidence that EAM guided CHBP may be considered a feasible alternative to conventional CRT when venous anatomy is not favorable for left ventricular lead implantation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.