Naunyn-Schmiedeberg's archives of pharmacology
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Naunyn Schmiedebergs Arch. Pharmacol. · Feb 2019
Observational StudyAfter standard dosage of piperacillin plasma concentrations of drug are subtherapeutic in burn patients.
Infections are a major problem in patients with burn diseases. Mortality is high despite antibiotic therapy as studies are controversial concerning drug underdosing. The aims of this prospective, observational study were to monitor plasma concentrations of piperacillin during standard piperacillin/tazobactam treatment in 20 burn patients and 16 controls from the intensive care unit (ICU) and to optimize doses by in silico analyses. ⋯ Standard dosage regimens for piperacillin/tazobactam resulted in subtherapeutic piperacillin concentrations in burn and ICU patients. Dose adjustments via in silico analyses can help to optimize antibiotic therapy and to predict respective concentrations in vivo. Trial registration: NCT03335137, registered 07.11.2017, retrospectively.
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Naunyn Schmiedebergs Arch. Pharmacol. · Sep 2018
Cardioprotective and functional effects of levosimendan and milrinone in mice with cecal ligation and puncture-induced sepsis.
Levosimendan and milrinone may be used in place of dobutamine to increase cardiac output in septic patients with a low cardiac output due to impaired cardiac function. The effects of the two inotropic agents on cardiac inflammation and left ventricular (LV) performance were examined in mice with cecal ligation and puncture (CLP)-induced sepsis. CLP mice displayed significant cardiac inflammation, as indicated by highly increased pro-inflammatory cytokines and neutrophil infiltration in myocardial tissues. ⋯ A lesser effect of levosimendan on LV performance after CLP was also found in spontaneously beating Langendorff-perfused hearts. In ventricular myocytes isolated from control and CLP mice, levosimendan, but not milrinone, caused a large increase in the L-type calcium current. This study represents that levosimendan and milrinone have cardioprotective properties but provide different advantages and drawbacks to cardiac inflammation/dysfunction in sepsis.
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Naunyn Schmiedebergs Arch. Pharmacol. · Jul 2018
Scutellarin suppresses neuroinflammation via the inhibition of the AKT/NF-κB and p38/JNK pathway in LPS-induced BV-2 microglial cells.
In vitro and in vivo studies indicate that scutellarin (SCU) exerts anti-inflammatory effects in the central nervous system (CNS) and inhibits microglia activation. This study investigated the anti-neuroinflammation molecular mechanisms exerted by scutellarin in LPS-induced BV-2 cells. ⋯ Consistent with the inhibition of NF-κB, scutellarin inhibited the phosphorylation of p38, JNK, and AKT without affecting phosphorylation of ERK1/2 or PI3K in LPS-induced BV-2 cells. Overall, the present study suggests that scutellarin inhibits the production of pro-inflammatory mediators via inhibition of the IKK-dependent NF-κB and p38/JNK signaling pathway, which inhibits microglia activation and exerts anti-inflammation, indicating its potential therapeutic effect for neurodegenerative and cerebrovascular diseases.
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Naunyn Schmiedebergs Arch. Pharmacol. · Apr 2018
Microglial IL-1β progressively increases with duration of alcohol consumption.
Chronic alcohol abuse leads to severe brain damage. Although the underlying neuropathological processes are largely unknown, recent studies show that chronic alcohol consumption leads to neuroinflammation and may result in neurodegeneration and impaired neuronal connectivity. Long-term alcohol consumption promotes the production of pro-inflammatory cytokines, such as TNF-α and IL-1β, and activates microglia cells in the brain. ⋯ However, we did not find changes in the neuronal density or cortical volume after long-term alcohol consumption. These data show that 12 months of alcohol drinking leads to a pro-inflammatory activation of microglia, which may contribute to impaired neuronal connectivity in the cortex. Anti-inflammatory drug treatment during or after chronic alcohol consumption may thus provide a strategy for restoring brain homeostasis.
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Naunyn Schmiedebergs Arch. Pharmacol. · Jan 2018
ReviewMigraine with prolonged aura: phenotype and treatment.
We review the published literature on migraine with prolonged aura (PA), specifically with regards to the phenotype and treatment options. PA is not uncommon. A recent study found that about 17% of migraine auras are prolonged and that 26% of patients with migraine with aura have experienced at least one PA. ⋯ The only randomised, blinded, controlled trial to date has been of nasal ketamine showing some reduction in aura severity but not duration. A small open-labelled pilot study of amiloride was also promising. Larger randomised, controlled trials are needed to establish whether any of the existing or novel compounds mentioned are significantly effective and safe.