Ketamine-induced reduction in mGluR5 availability is associated with an antidepressant response: an [11C]ABP688 and PET imaging study in depression.

The mechanisms of action of the rapid antidepressant effects of ketamine, an N-methyl-D-aspartate glutamate receptor antagonist, have not been fully elucidated. This study examined the effects of ketamine on ligand binding to a metabotropic glutamatergic receptor (mGluR5) in individuals with major depressive disorder (MDD) and healthy controls. Thirteen healthy and 13 MDD nonsmokers participated in two [11C]ABP688 positron emission tomography (PET) scans on the same day-before and during intravenous ketamine administration-and a third scan 1 day later. At baseline, significantly lower [11C]ABP688 binding was detected in the MDD as compared with the control group. We observed a significant ketamine-induced reduction in mGluR5 availability (that is, [11C]ABP688 binding) in both MDD and control subjects (average of 14±9% and 19±22%, respectively; P<0.01 for both), which persisted 24 h later. There were no differences in ketamine-induced changes between MDD and control groups at either time point (P=0.8). A significant reduction in depressive symptoms was observed following ketamine administration in the MDD group (P<0.001), which was associated with the change in binding (P<0.04) immediately after ketamine. We hypothesize that glutamate released after ketamine administration moderates mGluR5 availability; this change appears to be related to antidepressant efficacy. The sustained decrease in binding may reflect prolonged mGluR5 internalization in response to the glutamate surge.

Characterization of brain mGluR5 binding in a pilot study of late-life major depressive disorder using positron emission tomography and [¹¹C]ABP688.

The metabotropic glutamate receptor subtype 5 (mGluR5) has been implicated in the pathophysiology of mood and anxiety disorders and is a potential treatment target in major depressive disorder (MDD). This study compared brain mGluR5 binding in elderly patients suffering from MDD with that in elderly healthy volunteers using positron emission tomography (PET) and [(11)C]ABP688. Twenty elderly (mean age: 63.0 ± 6.3) subjects with MDD and twenty-two healthy volunteers in the same age range (mean age: 66.4 ± 7.3) were examined with PET after a single bolus injection of [(11)C]ABP688, with many receiving arterial sampling. PET images were analyzed on a region of interest and a voxel level to compare mGluR5 binding in the brain between the two groups. Differences in [(11)C]ABP688 binding between patients with early- and late-onset depression were also assessed. In contrast to a previously published report in a younger cohort, no significant difference in [(11)C]ABP688 binding was observed between elderly subjects with MDD and healthy volunteers. [(11)C]ABP688 binding was also similar between subgroups with early- or late-onset depression. We believe this is the first study to examine mGluR5 expression in depression in the elderly. Although future work is required, results suggest potential differences in the pathophysiology of elderly depression versus depression earlier in life.

[High dose fibrinogen administration for acute therapy of coagulopathy during massive perioperative transfusion]. / Hochdosierte Fibrinogengabe zur Akuttherapie von Gerinnungsstörungen bei perioperativer Massivtransfusion.

During acute and severe perioperative bleeding a coagulopathy due to depletion, consumption and dilution of clotting factors and thrombocytes may occur. Diagnosis and therapy of such a coagulopathy should take place immediately. We report two cases of acute coagulopathy during perioperative bleeding and massive transfusion, which were treated successfully by administration of high dose fibrinogen concentrate. Diagnosis and treatment control were performed by thrombelastography.

An improved data acquisition method for electrical impedance tomography.

Isaacson, Cheney and Seager have demonstrated that simultaneously applying trigonometric patterns of current to a circular electrode array optimizes the sensitivity of EIT to inner structure. We have found that it is less desirable to measure voltage at an electrode that also applies a current due to variable contact impedance. In order to preserve the optimum sensitivity while minimizing the effect of electrode artefacts, we have devised an approach where we sequentially apply a current between each individual electrode and a separate, fixed ground while measuring voltages at all other electrodes for each consecutive current impulse. By adding weighted sums of both the applied currents and corresponding measured voltages from individual passes, we can synthesize trigonometric patterns of any spatial frequency. Since only one of the electrodes in any given acquired data set is used as a source, this approach significantly dilutes the effect of contact impedance on the resulting voltage measurements. We present simulated data showing the equivalency between the synthesized and actual trigonometric excitation patterns. In addition, we report experimental data, both in vitro and in vivo, that show improved results using this data acquisition technique.