For fluoroquinolones, standard media might be insufficient to investigate the impact of PB on bacterial killing. MHB containing 12% albumin seems to be a promising medium in this context. For moxifloxacin and trovafloxacin, PB leads to significant reduction of antimicrobial activity.
We conclude that tariquidar has potent inhibitory effect against certain bacterial efflux pumps in vitro. Their high activity at clinically achievable concentrations might yield this class of drugs promising for future applications in infectious diseases.
Synaptic disturbances may play a key role in the pathophysiology of neuropsychiatric diseases. In this article, we review immunohistological findings of chromogranin peptides in neurodegenerative and neurodevelopmental disorders, with particular emphasis on Alzheimer's disease, the disorder chromogranins have been studied most extensively. Data was collected from existing and new experimental data and medline research. This review focuses on synaptic changes elicited by chromogranin peptides immunoreactivity in Alzheimer's disease, as well in schizophrenia and amyotrophic lateral sclerosis (ALS). An imbalanced availability of chromogranin peptides may be responsible for impaired neurotransmission and a reduced functioning of dense core vesicles. Since chromogranin A was postulated as a potent proinflammatory agent, we focused on chromogranin A in neuroinflammation in Alzheimer's disease and ALS. Further understanding of role and function of chromogranin peptides in neuropathological conditions is still required.
SK2 (KCa2.2) channels are voltage-independent Ca2+-activated K+ channels that regulate neuronal excitability in brain regions important for memory formation. In this study, we investigated the distribution and expression of SK2 channels in human brain by Western blot analysis and immunohistochemistry. Immunoblot analysis of human brain indicated expression of four distinct SK2 channel isoforms: the standard, the long and two short isoforms. Immunohistochemistry in paraffin-embedded post-mortem brain sections was performed in the hippocampal formation, amygdala and neocortex. In hippocampus, SK2-like immunoreactivity could be detected in strata oriens and radiatum of area CA1-CA2 and in the molecular layer. In the amygdala, SK2-like immunoreactivity was highest in the basolateral nuclei, while in neocortex, staining was mainly found enriched in layer V. Activation of SK2 channels is thought to regulate neuronal excitability in brain by contributing to the medium afterhyperpolarization. However, SK2 channels are blocked by apamin with a sensitivity that suggests heteromeric channels. The herein first shown expression of SK2 human isoform b in brain could explain the variability of electrophysiological findings observed with SK2 channels.
The TPPS may prove to be a powerful tool for the estimation of antimicrobial tissue penetration at the bedside in septic patients. This score may allow for adequate individual dose adjustment in septic patients. However, this needs to be verified in subsequent prospective clinical trials.
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