Several studies reveal that diabetes doubles the odds of comorbid depression with evidence of a pro-inflammatory state underlying its vascular complications. Indeed, little information is available about vascular effects of antidepressant drugs in diabetes. Method: We investigated the effect of chronic administration of fluoxetine “FLU” and imipramine “IMIP” on behavioral, metabolic and vascular abnormalities in diabetic and non-diabetic rats exposed to chronic restraint stress (CRS). Results: Both diabetes and CRS induced depressive-like behavior which was more prominent in diabetic/depressed rats; this was reversed by chronic treatment with FLU and IMIP in a comparable manner. Diabetic and non-diabetic rats exposed to CRS exhibited abnormalities in glucose homeostasis, lipid profile and vascular function, manifested by decreased endothelium-dependent relaxation, increased systolic blood pressure and histopathological atherosclerotic changes. Vascular and metabolic dysfunctions were associated with significant increase in aortic expression of TLR-4, and pro-inflammatory cytokines (TNF-α and IL-1ß). FLU ameliorated these metabolic, vascular and inflammatory abnormalities, while IMIP induced either no change or even worsening of some parameters. Conclusion: FLU has favorable effect over IMIP on metabolic, vascular and inflammatory aberrations associated with DM and CRS in Wistar rats, clarifying the preference of FLU over IMIP in management of comorbid depression in diabetic subjects.

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Tranexamic acid (TXA) is widely utilized to control perioperative bleeding. TXA is considered a safe drug with few serious adverse effects, but many studies report TXA‐associated seizures, especially with cardiac surgeries. Usually, TXA‐associated seizures persist for a few minutes with no progression into status epilepticus. Here, we report, for the first time, a case of refractory status epilepticus after IV injection of TXA in a paediatric non‐cardiac surgery. This case report and literature review aim to increase awareness about TXA‐associated seizures and to provide mechanistic‐based prevention and treatment recommendations. During adenotonsillectomy for a 4‐year‐old male child, TXA infusion started after induction of anaesthesia for surgical bleeding prophylaxis. During recovery from anaesthesia, the patient developed tonic–clonic convulsions which did not improve after two IV doses of midazolam but showed an improvement after a dose of propofol. The patient did not regain consciousness and was transferred to the ICU. He had recurrent treatment‐resistant attacks of tonic–clonic convulsions. The patient developed acute kidney injury and died after 18 hours. In high‐risk patients, using the lowest effective dose with early termination of TXA infusion and prolongation of administration of anaesthetics may prevent seizures. General anaesthetics (propofol and halogenated inhaled anaesthetics) are considered the first line for prevention/treatment of TXA‐associated seizures.

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Depression is the disease of the modern era. The lack of response to the available antidepressants, which were developed on the basis of the monoaminergic deficit hypothesis of depression, has encouraged scientists to think about new mechanisms explaining the pathogenesis of depression. In this context, the inflammatory theory has emerged to clarify many aspects of depression that the previous theories have failed to explain. Toll-like receptor-4 (TLR-4) has a regulatory role in the brain's immune response to stress, and its activation is suggested to play a pivotal role in the pathophysiology of depression. In this study, we tested eritoran (ERI), a TLR-4 receptor-4 antagonist, as a potential antidepressant. We investigated the effect of long-term administration of ERI in three different doses on behavioral changes, hippocampal and prefrontal cortex (PFC) neurogenesis, and γ-aminobutyric acid (GABA)/glutamate balance in male Wistar rats exposed to chronic restraint stress (CRS). Long-term administration of ERI ameliorated CRS-induced depressive-like symptoms and hypothalamic-pituitary-adrenal axis hyperactivity alongside reducing levels of hippocampal and PFC inflammatory cytokines, restoring GABA and glutamate balance, and enhancing PFC and hippocampal neurogenesis, by increasing BDNF gene and protein expression in a dose-dependent manner. The results demonstrate an antidepressant-like activity of ERI in Wistar rats exposed to CRS, which may be largely mediated by its ability to reduce neuroinflammation, increase BDNF, and restore GABA/glutamate balance in prefrontal cortex and hippocampus. Nonetheless, further studies are needed to characterize the mechanism of the antidepressant effect of ERI.