The utility of point of care serum lactate in predicting serious adverse outcomes among critically ill adult patients at urban emergency departments of tertiary hospitals in Tanzania.

Background: Elevated serum lactate levels have been shown in numerous studies to be associated with serious adverse events, including mortality. Point of care lactate level is increasingly available in resource-limited emergency department (ED) settings. However, little is known about the predictive ability of for serious adverse events.

Anti-inflammatory effects of minocycline are mediated by retinoid signaling.

Background: Minocycline is a lipophilic tetracycline of increasing appeal in neuroscience as it inhibits microglial activation, a mechanism involved in numerous neuropsychiatric disorders. Own data point towards retinoid-mediated effects of minocycline in murine brain and skin, and towards a vicious cycle of neuroinflammation which is driven by microglial activation-induced breakdown of local retinoids such as retinoic acid (RA). We therefore sought to study minocycline's anti-inflammatory effects on human microglial-like monocyte-derived cells in the context of retinoid signaling.

Retinoic Acid Enhances Apolipoprotein E Synthesis in Human Macrophages.

Apolipoprotein E (ApoE) represents a pivotal target in Alzheimer's disease (AD) and is modulated through retinoic acid (RA), an endogenous neuroprotective and anti-inflammatory compound. A major source of ApoE are microglia, which are pathologically activated in AD. Activated microglia are known to block RA signaling.

Clozapine-induced agranulocytosis: Evidence for an immune-mediated mechanism from a patient-specific in-vitro approach.

Use of the atypical antipsychotic clozapine (CZP) is compromised by the risk of potentially fatal agranulocytosis/granulocytopenia (CIAG). To address this, we have established a simple, personalized cell culture-based strategy to identify CIAG-susceptible patients, hypothesizing that an immunogenic and possibly haptene-based mechanism underlies CIAG pathophysiology. To detect a putative haptene-induced response to CZP in vitro exposure, a traditional lymphocyte stimulation assay was adapted and applied to patient-specific peripheral blood-derived mononuclear cells (PBMC).

Inhibition of brain retinoic acid catabolism: a mechanism for minocycline's pleiotropic actions?

Objectives: Minocycline is a tetracycline antibiotic increasingly recognized in psychiatry for its pleiotropic anti-inflammatory and neuroprotective potential. While underlying mechanisms are still incompletely understood, several lines of evidence suggest a relevant functional overlap with retinoic acid (RA), a highly potent small molecule exhibiting a great variety of anti-inflammatory and neuroprotective properties in the adult central nervous system (CNS). RA homeostasis in the adult CNS is tightly controlled through local RA synthesis and cytochrome P450 (CYP450)-mediated inactivation of RA.