Atrial fibrillation detection using a novel three-vector cardiac implantable monitor: the atrial fibrillation detect study.

Aims Continuous rhythm monitoring is valuable for adequate atrial fibrillation (AF) management in the clinical setting. Subcutaneous leadless implantable cardiac monitors (ICMs) yield an improved AF detection, overcoming the intrinsic limitations of the currently available external recording systems, thus resulting in a more accurate patient treatment. The study purpose was to assess the detection performance of a novel three-vector ICM device equipped with a dedicated AF algorithm. Methods and results Sixty-six patients (86.4% males; mean age 60.4 ± 9.4 years) at risk to present AF episodes, having undergone the novel ICM implant (BioMonitor, Biotronik SE&Co. KG, Berlin, Germany), were enrolled. External 48-h ECG Holter was performed 4 weeks after the device implantation. The automatic ICM AF classification was compared with the manual Holter arrhythmia recordings. Of the overall study population, 63/66 (95.5%) had analysable Holter data, 39/63 (62%) showed at least one true AF episode. All these patients had at least one AF episode stored in the ICM. On Holter monitoring, 24/63 (38%) patients did not show AF episodes, in 16 of them (16/24, 67%), the ICM confirmed the absence of AF. The AF detection sensitivity and positive predictive value for episodes' analysis were 95.4 and 76.3%, respectively. Conclusion Continuous monitoring using this novel device, equipped with a dedicated detection algorithm, yields an accurate and reliable detection of AF episodes. The ICM is a promising tool for tailoring individual AF patient management. Further long-term prospective studies are necessary to confirm these encouraging results

ALIMENTAZIONE, STILI DI VITA E SALUTE

Dopo un breve excursus sulla fisiopatologia della Sindrome Metabolica (SM), viene posta attenzione sul ruolo centrale dell’insulinoresistenza quale fattore eziopatogenetico comune a molte delle componenti della sindrome stessa. Il trattamento nutrizionale diviene il punto cardine dell’approccio terapeutico della SM, per cui viene suggerito dagli AA uno schema idoneo da fornire alla maggior parte dei pazienti e si sottolinea poi, la necessità di promuovere il potenziamento dell’attività fisica che assume oggi un ruolo terapeutico assai rilevante. Gli AA infine, passano in rassegna i fattori di rischio e le comorbilità associate alla SM e concludono sottolineando la necessità di attuare programmi di osservazione epidemiologica e di intervento multifattoriale che si incentrino sulla modificazione dello “stile di vita” oltre che sull’intervento terapeutico farmacologico, riducendo così gran parte dei rischi correlati alla Sindrome Metabolica

Beta-adrenergic receptor changes during tertatolol treatment in healthy volunteers: Relevance for beta-blocking therapy

[No abstract available

Effect of acute and chronic tramadol on [3H]-norepinephrine-uptake in rat cortical synaptosomes.

1 Tramadol hydrochloride is a centrally acting opioid analgesic whose efficacy and potency is only five to ten times lower than that of morphine. Opioid, as well as non-opioid mechanisms, may participate in the analgesic activity of tramadol. 2 [3H]-NE uptake in isolated rat cortical synaptosomes was studied in the presence of tramadol, desipramine, methadone, and morphine. Desipramine and tramadol inhibited synaptosomal [3H]-NE uptake with apparent Kis of 7.3 +/- 0.66 and 1.4 +/- 0.0045 microM, respectively. Methadone was active at a 10-fold higher concentration (Ki: 87 +/- 5.6 microM). In contrast, morphine essentially failed to inhibit [3H]-5-HT uptake (Ki: 0.75 +/- 0.40 M). 3 Methadone, morphine, and tramadol were active in the hot plate test with ED50s of 6.2, 9.3, and 40 mg kg-1, respectively. 4 [3H]-NE uptake was examined in synaptosomes prepared from rats 30 min after receiving a single dose of morphine, methadone or tramadol. Only tramadol (31 mg kg-1, i.p.) decreased uptake of the transmitter, with an ED50 equal to that in the hot plate test. 5 Animals were chronically treated for 15 days with increasing doses of tramadol (20 to 125 mg kg-1, i.p.). Twenty-four hours after the last drug injection, a challenge dose of tramadol (40 mg kg-1, i.p.) was administered. Chronic tramadol was still able to reduce [3H]-NE uptake by 35%. 6 These results further support the hypothesis that [3H]-NE uptake inhibition may contribute to the antinociceptive effects of tramadol. The lack of tolerance in [3H]-NE uptake, together with the absence of behavioural alteration after chronic tramadol treatment proposes that tramadol holds potential over classical opioids in the treatment of pain disorders

Regulation of beta adrenergic receptors on rat mononuclear leukocytes by stress: receptor redistribution and down-regulation are altered with aging.

In vitro incubation of mononuclear leukocytes (MNL) with catecholamines desensitizes beta adrenergic receptors, meaning isoproterenol-stimulated cyclic AMP accumulation decreases. This desensitization is accompanied by two patterns of receptor changes: first, reduction of surface receptors (defined as binding of [3H]dihydroalprenolol inhibited by 1 microM CGP 12177 [4-3-tertiarybutylamino-2-hydroxypropoxy)-benzimidazole- 2-on-hydrochloride]) without any change in the total number of [3H] dihydroalprenolol binding sites inhibited by 1 microM propranolol (receptor redistribution); then reduction of the total number of receptors (receptor down-regulation). In the present study we investigated receptor redistribution and down-regulation under physiological conditions by raising endogenous catecholamines in the rat by stress. In young rats a single immobilization stress induced MNL beta adrenergic receptor redistribution: the number of surface receptors was reduced by about 50% but the total number remained the same. Receptor redistribution was prevented completely in rats pretreated with beta-blocking nadolol. Repeated stress down-regulated the MNL beta adrenergic receptors as shown by a reduction in the total number of sites. We also investigated the regulation of beta adrenergic receptors in three age-groups. After 60 min of immobilization stress the number of MNL surface receptors was reduced in young (4-month-old) rats but not in mature (12-month-old) or aged (26-month-old) rats. Using an alternative stress procedure, after single or repeated open-field sessions, we found receptor redistribution and down-regulation, respectively, in young rats. None of these adaptive receptor response was observed in 26-month-old rats

Lack of anticonvulsant tolerance and benzodiazepine receptor down regulation with imidazenil in rats.

1. Development of anticonvulsant tolerance and benzodiazepine (BZD) receptor down-regulation has been reported to occur upon chronic administration of conventional BZDs. We compared the effect of chronic treatment with imidazenil, a new BZD partial agonist, and diazepam in rats. 2. After acute administration, imidazenil was more potent though less effective than diazepam in protecting from bicuculline-induced seizure. The time-course analysis of two peak equieffective doses of imidazenil (2.5 mumol kg-1 p.o.) and diazepam (35 mumol kg-1, p.o.) showed a longer lasting action of the former drug. 3. The anticonvulsant efficacy of diazepam (35 mumol kg-1, p.o.) was reduced in rats given chronic diazepam (35 mumol kg-1 p.o., 3 times a day for 8-15 days). No tolerance to imidazenil (2.5 mumol kg-1, p.o.) was apparent after 130-day administration with imidazenil (2.5 mumol kg-1, p.o., 3 times a day). 4. Plasma levels of imidazenil and diazepam, assessed 30 min after administration, were not changed in chronically treated animals. 5. In rats made tolerant to diazepam, the maximum number of [3H]-flumazenil binding sites were reduced in both cerebral cortex (-36%) and cerebellum (-42%). No changes in [3H]-flumazenil binding were found in chronic imidazenil-treated rats. 6. Specific [3H]-flumazenil binding in vivo was decreased in the forebrain of chronic diazepam- but not of chronic imidazenil-treated animals. 7. These data indicate that imidazenil possesses a very low tolerance potential to its anticonvulsant activity and does not affect BZD receptor density even after prolonged administration

Abecarnil enhances recovery from diazepam tolerance.

Treatment with diazepam (25 mg/kg; p.o., twice-daily for 17 days) induced tolerance to the anticonvulsant effect of diazepam against bicuculline-induced convulsions in mice. Cross-tolerance was observed to the anticonvulsant action of clonazepam, imidazenil but not abecarnil. While substitution of clonazepam (12 mg/kg; p.o., twice-daily for 15 days) for diazepam did not affect tolerance to diazepam, substitution of imidazenil (17 mg/kg; p.o., twice-daily for 15 days) for diazepam significantly increased sensitivity to the anticonvulsant effect of diazepam, although tolerance was not abolished. Tolerance to diazepam progressively decreased either after suspension of diazepam administration or replacement treatment with abecarnil (20 mg/kg; p.o., twice-daily). Complete recovery of diazepam efficacy was detected after 8 and 15 days of administration of abecarnil and vehicle, respectively. Binding experiments using [H-3]-flumazenil showed that K-d values did not differ among treatment groups. A significant decrease in B-max (-42%) was observed in the cortex of diazepam-tolerant mice whether or not also treated with imidazenil and clonazepam. Conversely, chronically diazepam-treated mice, that further received abecarnil for either 8 or 15 days or vehicle for 15 days showed B-max values similar to those of vehicle-treated mice never exposed to diazepam. Results suggest that repeated abecarnil administration to diazepam-tolerant mice can facilitate re-adaptation of receptors to the diazepam-free state. It is proposed that replacement therapy with abecarnil after long-term treatment with conventional benzodiazepines (BDZs) may provide a novel approach for reducing tolerance to their anticonvulsant effects. (C) 1999 Elsevier Science Ltd. All rights reserved

Agonist-induced beta-adrenergic receptor internalization on intact human mononuclear leukocytes: effect of temperature of mononuclear leukocyte separation.

The hydrophilic ligand 3H-CGP 12177 was used to measure beta-adrenergic receptors on intact human mononuclear leukocytes (MNLs). A single homogeneous class of receptor sites was found, with KD value of 0.71 +/- 0.04 nmol/L and Bmax of 3.0 +/- 0.4 fmol/10(6) cells (mean +/- SEM; n = 12). The receptor affinity (KD) and density (Bmax) were similar when measured on MNLs, purified lymphocytes, and a T-lymphocyte-enriched population from the same individual. Preincubation of intact MNLs with 1 mumol/L isoproterenol at 37 degrees C for 20 minutes reduced the number of surface receptors, measured by 3H-CGP 12177 binding at 4 degrees C for 20 hours, by approximately 70% (receptor internalization) without affecting KD. This effect was reversible, and surface receptors completely reappeared when binding was investigated at 37 degrees C for 40 minutes. Receptor internalization was similar when either isolated MNLs or whole blood was incubated with isoproterenol. Agonist-induced receptor internalization was stable during MNL isolation from whole blood at 4 degrees C but was partially or completely lost from MNLs prepared at 20 degrees C