The proteome microenvironment determines the protective effect of preconditioning in cisplatin-induced acute kidney injury

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Kinetics of isoflurane and sevoflurane in a unidirectional displacement flow and the relevance to anesthetic gas exposure by operating room personnel

International guidelines recommend the use of ventilation systems in operating rooms to reduce the concentration of potentially hazardous substances such as anesthetic gases. The exhaust air grilles of these systems are typically located in the lower corners of the operating room and pick up two-thirds of the air volume, whereas the final third is taken from near the ceiling, which guarantees an optimal perfusion of the operating room with a sterile filtered air supply. However, this setup is also employed because anesthetic gases have a higher molecular weight than the components of air and should pool on the floor if movement is kept to a minimum and if a ventilation system with a unidirectional displacement flow is employed. However, this anticipated pooling of volatile anesthetics at the floor level has never been proven. Thus, we herein investigated the flow behaviors of isoflurane, sevoflurane, and carbon dioxide (for comparison) in a measuring chamber sized 2.46?×?1.85?×?5.40 m with a velocity of 0.3 m/sec and a degree of turbulence <20%. Gas concentrations were measured at 1,728 measuring positions throughout the measuring chamber, and the flow behaviors of isoflurane and sevoflurane were found to be similar, with an overlap of 90%. The largest spread of both gases was 55?cm at 5.4 m from the emission source. Interestingly, neither isoflurane nor sevoflurane was detected at floor level, but a continuous cone-like spreading was observed due to gravity. In contrast, carbon dioxide accumulated at floor level in the form of a gas cloud. Thus, floor level exhaust ventilation systems are likely unsuitable for the collection and removal of anesthetic gases from operating rooms.     

Age-specific norms and validation of the German SDQ parent version based on a nationally representative sample (KiGGS)

European Child & Adolescent Psychiatry - The Strengths and Difficulties Questionnaire (SDQ) is the most widely used mental health screening instrument for children and adolescents. It is a...     

A population of descending tyraminergic/octopaminergic projection neurons of the insect deutocerebrum

In this study, we describe a cluster of tyraminergic/octopaminergic neurons in the lateral dorsal deutocerebrum of desert locusts (Schistocerca gregaria) with descending axons to the abdominal ganglia. In the locust, these neurons synthesize octopamine from tyramine stress-dependently. Electrophysiological recordings in locusts reveal that they respond to mechanosensory touch stimuli delivered to various parts of the body including the antennae. A similar cluster of tyraminergic/octopaminergic neurons was also identified in the American cockroach (Periplaneta americana) and the pink winged stick insect (Sipyloidea sipylus). It is suggested that these neurons release octopamine in the ventral nerve cord ganglia and, most likely, convey information on arousal and/or stressful stimuli to neuronal circuits thus contributing to the many actions of octopamine in the central nervous system.     

Characterization of Aptamer BC 007 Substance and Product Using Circular Dichroism and Nuclear Magnetic Resonance Spectroscopy

Possible unwanted folding of biopharmaceuticals during manufacturing and storage has resulted in analysis schemes compared to small molecules that include bioanalytical characterization besides chemical characterization. Whether bioanalytical characterization is required for nucleotide-based drugs, may be decided on a case-by-case basis. Nucleotide-based pharmaceuticals, if chemically synthesized, occupy an intermediate position between small-molecule drugs and biologics. Here, we tested whether a physicochemical characterization of a nucleotide-based drug substance, BC 007, was adequate, using circular dichroism (CD) spectroscopy. Nuclear magnetic resonance confirmed CD data in one experimental setup. BC 007 forms a quadruplex structure under specific external conditions, which was characterized for its stability and structural appearance also after denaturation using CD and nuclear magnetic resonance. The amount of the free energy (ΔG⁰) involved in quadruplex formation of BC 007 was estimated at +8.7 kJ/mol when dissolved in water and +1.4 kJ/mol in 154 mM NaCl, indicating structural instability under these conditions. However, dissolution of the substance in 5 mM of KCl reduced the ΔG⁰ to ?5.6 kJ/mol due to the stabilizing effect of cations. These results show that positive ΔG⁰ of quadruplex structure formation in water and aqueous NaCl prevents BC 007 from preforming stable 3-dimensional structures, which could potentially affect drug function.     

Consequences of dosing and timing on the antibacterial effects of ADEP antibiotics

Antibiotic acyldepsipeptides (ADEPs) exert potent antibacterial activity in rodent models of bacterial infection and exceptional efficacy against persister cells of methicillin-resistant Staphylococcus aureus (MRSA). The mechanism of ADEP action is unusual in that the antibiotic releases the destructive capacity of over-activated ClpP, the proteolytic core of the bacterial Clp protease. The essential bacterial cell division protein FtsZ had emerged in a previous study as a preferred protein substrate of ADEP-activated ClpP but it is definitely not the only cellular substrate.In the current study, we set out to follow the morphological changes that lead to ADEP-mediated bacterial death in S. aureus and Bacillus subtilis, differentiating between antibacterial effects at low and high ADEP concentrations. Here, fluorescence and time-lapse microscopy data show that cells adopt a characteristic phenotype of cell division inhibition at ADEP levels close to the MIC, but retain the capacity to form viable daughter cells for a substantial period of time when transferred to ADEP-free growth medium. After extended exposure to low ADEP concentrations, nucleoids of B. subtilis started to disorganize and upon compound removal many cells failed to re-organize nucleoids, re-initiate cytokinesis and consequently died. Survival versus cell death of filamentous cells attempting recovery depended on the timing of completion of new septa in relation to the loss of cell envelope integrity. We show that the potential to recover after ADEP removal depends on the antibiotic concentration as well as the treatment duration. When exposed to ADEP at concentrations well above the MIC, biomass production ceased rapidly as did the potential to recover. In time-kill studies both long-time exposure to low ADEP levels as well as short-time exposure to high concentrations proved highly effective, while intermittent concentrations and time frames were not. We here provide new insights into the antimicrobial activity of ADEP antibiotics and the consequences of dosing and timing for bacterial physiology which should be considered in view of a potential therapeutic application of ADEPs.