Unanticipated subcutaneous ICD end-of-service due to premature battery depletion and occurrence of lead fracture: A single centre experience.

The use of subcutaneous ICDs (S-ICD) is growing over years despite increasing alerts on premature battery depletion (PBD) and lead fractures leading to unanticipated device replacements. In our single-centre study including 192 patients, per year analysis demonstrated that incidence of PBD is higher than previously reported with overall greatest battery replacement requirements around the fifth year of follow-up. The underlying issue appears to be limited to old series devices, but only a longer follow-up will clarify the real impact of this phenomenon on patient outcomes. PBD is an underestimated S-ICDs issue and if the hereby demonstrated trend were to be confirmed in latest device series, this would bring significant concerns to patient safety and huge economic expense to health system.

Integration among hospital pharmacists and infectious diseases physicians in the outpatient management of HIV infection.

Permanent monitoring of adherence to combination antiretroviral therapy (cART), together with the assessment and management of related adverse events, plays a key role for optimised management of HIV infection. In our HIV outpatient clinic a dedicated pharmacist provides direct drug distribution and accountability, and gives information on administration mode, possible side effects and drug interactions. A survey card regarding cART adherence and adverse drug reactions (ADRs) is administered to all patients. All figures are recorded in an electronic database. In an ad interim analysis 659 consecutive patients' data were evaluated, of whom 74% were fully adherent to cART. A lower adherence rate was found to be correlated with the presence of concurrent medications, and with the increasing number of daily cART tablets/capsules. A significant impact of cART adherence on a favourable course of the main laboratory surrogate markers of HIV disease progression (CD4+ T-lymphocyte count and HIV viral load) was also observed. Darunavir-containing cART was related to a lower incidence of early gastrointestinal and neuropsychiatric disturbances and also a reduced perception of morphological/physical changes. A multidisciplinary approach based on strict interaction between pharmacists and infectious diseases physicians may significantly improve cART adherence and the monitoring of adverse events, making a considerable contribution to the better management of HIV-infected patients.

Excitotoxic lesion of the perirhinal cortex impairs spatial working memory in a delayed-alternation task.

The perirhinal cortex (PRh) is strategically located between the neocortex and memory-related structures such as the entorhinal cortex and the hippocampal formation. The pattern of strong reciprocal connections between these areas, together with experimental evidence that PRh damage induces specific memory deficits, has placed this cortical region at the center of a growing interest for its role in learning and memory mechanisms. The aim of the present study is to clarify the involvement of PRh in learning and retention in a novel experimental model of spatial working memory, the water T-maze. The data show that pre-acquisition neurotoxic PRh lesions caused task-learning deficits. This impairment was observed during the acquisition phase as well as the retrieval phase. On the other hand, a post-acquisition PRh neurotoxic lesion failed to impair the acquisition and the retrieval of the water T-maze task performed 32 day after lesion. These results suggest a possible key role of PRh in the acquisition but not in the retention of a working memory task. Furthermore, these results show that the water T-maze may be a suitable learning paradigm to study different components of learning and memory.

Olanzapine counteracts stress-induced anxiety-like behavior in rats.

Atypical antipsychotics, such as olanzapine, have been reported to display anxiolytic properties as shown in several preclinical and clinical studies. Furthermore, several experimental evidences have shown that olanzapine reduces fear and anxiety in activated anxiety-like behavior test such as Geller-Seifter test, ultrasonic vocalization test and stress-induced EtOH consumption. Here, we hypothesized that the anxiolytic action of olanzapine might be due to via an indirect activation of the gamma-amino butyric acid (GABA)-ergic system through 3alpha-hydroxy-5alpha-pregnan-20-one [allopregnanolone (ALLO)], a potent neuroactive steroid that positively modulates the benzodiazepine-gamma-aminobutyric acid type A (GABA(A))/benzodiazepine receptors complex. To address this question, we used a preclinical animal test to screen for novel anxiolytic compounds - the elevated plus-maze (EPM) - in basal condition and after 45 min restrain stress after acute or repeated (21 days) administration of olanzapine (0.5mg/kg, i.p.). In this condition, we therefore study the effect of the 5-alpha-reductase inhibitor finasteride (FIN) (50mg/kg) after co-administration with olanzapine. FIN is an inhibitor of steroidogenic enzymes which acts by inhibiting type II 5-alpha reductase, the enzyme that converts into 5-alpha-reduced metabolites like the GABA(A) positive neuroactive steroid ALLO. Results showed an anxiolytic effect of the acute, but not of the chronic, treatment with olanzapine only in stressed rats. This anxiolytic effect was counteracted by the co-administration with FIN. These evidences suggest that the anxiolytic effects of olanzapine might be due to possible action of olanzapine on steroid function via activation of GABA system.

Water T-maze, an improved method to assess spatial working memory in rats: Pharmacological validation.

The present study was performed to validate a spatial working memory task using pharmacological manipulations. The water escape T-maze combines the advantages of the Morris water maze and the T-maze while minimizing the disadvantages. Scopolamine (1mg/kg), a drug that affects cognitive function in spatial working memory tasks, significantly decreased the rats' performance in the present delayed alternation task. Glutamate neurotransmission plays an important role in the maintenance of working memory; rats treated with dizocilpine (MK-801; 0.125-0.25mg/kg), a N-methyl-d-aspartate (NMDA) receptor antagonist, were impaired in this task. In agreement with evidence showing a functional interaction between ionotropic and metabotropic glutamatergic receptors, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), a mGlu(5) receptor antagonist, at a dose (1mg/kg) which by itself had no significant effects, enhanced MK-801-induced impairments of spatial working memory. These evidences suggest that the water escape T-maze might be a valid method to assess spatial working memory, sensitive to pharmacological manipulations.

An ionotropic but not a metabotropic glutamate agonist potentiates the pharmacological effects of olanzapine in the rat.

This study aimed to evaluate the possible potentiating action of ionotropic or metabotropic (metabotropic glutamate receptor type 5) glutamate agonists on pharmacological effects induced in rats by the atypical antipsychotic olanzapine. The administration of doses of olanzapine, which did not affect spontaneous motility, inhibited behaviors induced by the selective stimulation of 5HT(2A) and D(2) receptors. In particular, 0.03 or 0.06 mg/kg of olanzapine was sufficient to reduce, respectively, head shakes induced by the 5HT(2A) agonist 1-2,5-dimethoxy-4-iodophenyl-2-aminopropane (1 mg/kg) or hypermotility elicited by the D(2) stimulant quinpirole (0.15 mg/kg). Behavioral responses to a D(1)/D(2) agonist (apomorphine-induced stereotypies) were inhibited by doses of olanzapine that also influenced spontaneous behavior. The concomitant administration of D-cycloserine, an agonist at the glycine site on the N-methyl-D-aspartate receptor complex, given at a dose (3 mg/kg) that did not affect behavior, increased the inhibitory effect of olanzapine on the responses produced by 5HT2A, D(2) and D(1)/D(2) receptor stimulation. The concomitant administration of 2-chloro-5-hydroxyphenylglycine, an agonist of metabotropic glutamate receptor type 5, increased the inhibitory effect of olanzapine on the behaviors induced by the stimulation of D(2), but not 5HT2A or D(1)/D(2) receptors. As the effect on the serotonergic system seems important for the unusual pharmacological profile of atypical antipsychotics, the present results suggest that N-methyl-D-aspartate, but not metabotropic glutamate receptor type 5 agonists could be seen as promising therapeutic agents for increasing the pharmacological effects of olanzapine.