Agmatine produces an antidepressant-like effect when assessed in the forced swimming test (FST) and in the tail suspension test (TST) in mice (dose range 0.01-50 mg/kg, i.p.), without accompanying changes in ambulation in an open-field. I.c.v. injection of agmatine (1-100 nmol/site) also reduced the immobility time in the FST. Agmatine significantly enhanced the anti-immobility effect of imipramine, but did not affect that of MK-801. The anti-immobility effect of agmatine assessed in the FST was not affected by pre-treatment with prazosin. In contrast, agmatine's antidepressant-like effect was completely prevented by pre-treatment of animals with yohimbine, GMP or L-arginine. Taken together these data demonstrate that agmatine elicited a significant antidepressant-like effect through a mechanism that seems to involve an interaction with NMDA receptors, the L-arginine-nitric oxide pathway and alpha2-adrenoceptors.

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Summary Purpose:  To investigate the cerebral metabolic differences between patients with juvenile myoclonic epilepsy (JME) and normal controls and to evaluate to what extent these metabolic alterations reflect involvement of an epileptic network. Methods:  Sixty patients with JME were submitted to multi‐voxel proton spectroscopy (1H‐MRS) at 1.5 T over medial prefrontal cortex (MPC), primary motor cortex (PMC), thalamus, striatum, posterior cingulate gyrus (PCG), and insular, parietal, and occipital cortices. We determined ratios for integral values of N‐acetyl‐aspartate (NAA) and glutamate‐glutamine (GLX) over creatine‐phosphocreatine (Cr). The control group (CTL) consisted of 30 age‐ and sex‐matched healthy volunteers. Results:  The NAA/Cr ratio, a measure of neuronal injury, was reduced in PMC, MPC, and thalamus among patients. In addition, they had an altered GLX/Cr ratio, which is involved in excitatory activity, on PMC, MPC, and PCG, where it was reduced, whereas it was increased on insula and striatum. Multiple regression analysis revealed the strongest correlation between thalamus and MPC, but the thalamus was also correlated with insula, occipital cortex, and striatum among patients. Lower NAA/Cr was observed with advancing age and duration of epilepsy, regardless of frequency of seizures and antiepileptic drug therapy in thalamus and frontal cortex. Discussion:  The identification of a specific network of neurochemical dysfunction in patients with JME, with diverse involvement of particular structures within the thalamocortical circuitry, suggests that cortical hyperexcitability in JME is not necessarily diffuse, supporting the knowledge that the focal/generalized distinction of epileptogenesis should be reconsidered. Furthermore, evidence is provided toward progressive neuronal dysfunction in JME.

Our aim was to assess the association between obesity and the risk of unfavourable outcomes (composite of severe disease and mortality) in inpatients with COVID-19. We conducted a systematic search of databases between December 2019 and 28th June 2020. Studies were included if they reported or allowed estimation of an odds ratio (OR) for unfavourable outcome in obese compared to non-obese patients hospitalised for COVID-19. Twenty cohort studies of 28 355 hospitalised patients with COVID-19 infection were included. Meta-analysis estimated a pooled OR of 2.02 (1.41–2.89, p<0.001) for an unfavourable outcome in obese versus non-obese patients when adjusted for age, sex and co-morbidities. When unadjusted for confounders, the OR for unfavourable outcomes was 1.25 (CI 1.07–1.45, p=0.005). An increased adjusted OR was also seen for death (OR 1.51; CI 1.13–2.21, p=0.006) and severe illness (OR 2.26; CI 1.47–3.48, p<0.001). Compared to a normal BMI, the risk of an unfavourable outcome was increased even in overweight patients, with severe obesity having an escalated risk.Obesity is independently associated with an unfavourable outcome of COVID-19 illness, with obese patients having twice the risk of a composite outcome of severe disease or mortality, and a 50% increased risk of death.