Down-Regulation of Platelet Imidazoline-1-Binding Sites after Bupropion Treatment

An elevation of I1 (imidazoline-1)-binding sites on platelets may be a state marker for depression. Herein, platelet I1 sites were compared in two groups of unipolar depressed patients given different regimens of bupropion treatment : Regimen 1 (n=13 titrated up to 300 mg}d by week 4 and held constant until week 6) ; Regimen 2 (n=15 titrated up to 300 mg}d by week 2, to 450 mg}d by week 6, and held constant until week 8). Platelet I1 sites were quantified by p-[125I]iodoclonidine binding (0.5–15 nm) and displaced by moxonidine under a saturating concentration of norepinephrine to mask α2-adrenoceptors. I1 Bmax values were confirmed to be high at pretreatment in depressed patients (n=28) compared to healthy control subjects (n=18 ; p=0.02). Highest Bmax values at pretreatment were found in patients who responded worst to treatment. More than two-thirds of patients recovered from depression (69 and 80% in Regimens 1 and 2, respectively) after treatment. Dose and/or time of exposure to bupropion were relevant variables since (1) only Regimen 2 led to platelet I1 down-regulation and (2) the extent of down-regulation correlated with plasma concentrations of bupropion. The data suggest a dissociation exists between I1 down-regulation and therapeutic response, or else platelet I1 down-regulation lags behind clinical antidepressant response before becoming measurable

Further characterization of agmatine binding to mitochondrial membranes: involvement of imidazoline I2 receptor.

Agmatine, a divalent diamine with two positive charges at physiological pH, is transported into the matrix of liver mitochondria by an energy-dependent mechanism, the driving force of which is the electrical membrane potential. Its binding to mitochondrial membranes is studied by applying a thermodynamic treatment of ligand-receptor interactions on the analyses of Scatchard and Hill. The presence of two mono-coordinated binding sites S(1) and S(2), with a negative influence of S(2) on S(1), has been demonstrated. The calculated binding energy is characteristic for weak interactions. S(1) exhibits a lower binding capacity and higher binding affinity both of about two orders of magnitude than S(2). Experiments with idazoxan, a ligand of the mitochondrial imidazoline receptor I(2), demonstrate that S(1) site is localized on this receptor while S(2) is localized on the transport system. S(1) would act as a sensor of exogenous agmatine concentration, thus modulating the transport of the amine by its binding to S(2)

Clinical Phenotypes and Comorbidity in European Sleep Apnoea Patients

Background Clinical presentation phenotypes of obstructive sleep apnoea (OSA) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure (CPAP) treatment have not been established. Methods A prospective follow-up cohort of adult patients with OSA (apnoea-hypopnoea index (AHI) of 655/h) from 17 European countries and Israel (n = 6,555) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness ("EDS") and nocturnal sleep problems other than OSA (labelled as "insomnia"): 1) EDS (daytime+/nighttime-), 2) EDS/insomnia (daytime+/nighttime+), 3) non-EDS/noninsomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype. Results The EDS phenotype comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/ insomnia type 23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only 5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%, p<0.001) despite more severe OSA in the EDS group (AHI 35.0\ub125.5/h vs. 27.9\ub122.5/h, p<0.001, respectively). Psychiatric comorbidity was associated with insomnia like OSA phenotypes independent of age, gender and body mass index (HR 1.5 (1.188-1.905), p<0.001). The EDS phenotype tended to associate with higher CPAP usage (22.7 min/d, p = 0.069) when controlled for age, gender, BMI and sleep apnoea severity. Conclusions Phenotypes with insomnia symptoms comprised more than half of OSA patients and were more frequently linked with comorbidity than those with EDS, despite less severe OSA. CPAP usage was slightly higher in phenotypes with EDS