1,721,086 research outputs found
Varicella-zoster virus infection in rheumatoid arthritis patients in the anti-tumour necrosis factor era
No full textPatients with rheumatoid arthritis are increasingly being treated with different drugs (both non-biologic and biologic disease-modifying anti-rheumatic drugs - DMARDs) that may have immunomodulatory, cytotoxic, or immunosuppressive effects; in particular, anti-tumour necrosis factor (TNF) agents are raising major concern as regards safety issues. An increased risk of infections has been extensively reported during anti-TNF treatment, owing to the primary role of TNF in host defense and immune responses. Although in clinical practice cases of reactivation of varicella zoster virus (VZV) infections during therapy with TNF inhibitors commonly occur, the knowledge on this topic deriving from randomised clinical trials is limited. In this narrative review we focus on the pathophysiology of VZV infection and the role of TNF, and report the available data about VZV outbreaks recorded on Registries of rheumatic patients treated with anti-TNF agents. Finally, we discuss screening strategies and promising preventive measures against VZV infection
Monitoring extracellular dopamine in the rat nucleus accumbens shell and core during intravenous WIN 55,212-2 SELF-ADMINISTRATION
No full textSafety Profile and Low Risk of Disease Relapse After BNT162b2 mRNA SARS-CoV-2 Vaccination in Patients With Rare Rheumatic Diseases
Full text linkN.A
Differential neurochemical and behavioural effects of response-contingentand response-noncontingent cocaine exposure: Shell/core dopamine responsiveness and sensitization
No full textDifferential alpha2 mediated inhibition of dopamine and noradrenaline release in the parietal and occipital cortex following noradrenaline transporter blockade
No full textParietal and occipital cortices, while densely innervated by noradrenalin 2 (NA) projections, possess a comparatively sparse dopamine 2 (DA) innervation, even sparser than the prefrontal cortex. We previously reported that reboxetine and desipramine, two selective norepinephrine transporter (NET) blockers, at doses that maximally increase DA in the prefrontal cortex, do not increase DA in the parietal and occipital cortices. In the present study, we performed a full dose-response study of the effect of systemic reboxetine and desipramine on DA and NA in dialysates from the parietal and occipital cortices. Seven doses of reboxetine (0.1, 0.25, 0.5, 1.0, 2.5, 5.0 and 10 mg/kg) and four doses of desipramine (0.25, 1.0, 2.5 and 5.0 mg/kg) were tested. Reboxetine and desipramine differentially affected dialysate DA as compared with NA. Reboxetine increased DA maximally by about 100% after doses of 0.25-0.5 mg/kg and showed a bell-shaped dose-response function in both areas; desipramine did not affect DA in the parietal cortex and increased it in the occipital cortex only at 2.5 mg/kg. NA was maximally increased by 275% by 0.5-2.5 mg/kg reboxetine and by about 300% by 5.0 mg/kg desipramine with a more linear dose-response curve. The mechanism of peculiar dose-response function of dialysate DA after reboxetine and desipramine was further investigated by testing the effect of drugs on dialysate DA and NA under alpha(2) receptor blockade. Under local perfusion of the occipital cortex with idazoxan, an otherwise ineffective dose of reboxetine and desipramine (5 mg/kg) became effective in raising extracellular DA. In contrast, the effect of reboxetine on NA was potentiated, while that of desipramine was not affected. These results suggest that, in the parietal and occipital cortices, extracellular NA, raised by NET blockade, exerts a preferential inhibitory influence on DA release by acting on local alpha(2) receptors, thus accounting for the bell-shaped feature of the dose-response function of drugs on dialysate DA in these areas
Selective serotonin reuptake blockade increases extracellular dopamine in noradrenaline-rich isocortical but not prefrontal areas: dependence on serotonin-1A receptors and independence from noradrenergic innervation
No full textThe present study investigated the effects of two serotonin (5-HT) uptake inhibitors, citalopram and paroxetine, and of a non-selective noradrenaline (NA) and 5-HT uptake blocker, imipramine, on extracellular NA and dopamine (DA) in the prefrontal cortex (PfCX), parietal cortex (ParCX) and occipital cortex (OccCX). Citalopram, the most selective 5-HT uptake blocker, increased dialysate DA in the OccCX and ParCX but not in the PfCX and this effect was prevented in the OccCX by WAY-100635, an antagonist of serotonin-1A (5-HT1A) receptors, but not by dorsal noradrenergic bundle (DNAB) lesions that reduced to unmeasurable levels basal dialysate NA but did not affect dialysate DA. Paroxetine, a less selective 5-HT uptake inhibitor than citalopram, at the dose of 5 mg/kg, increased DA in the OccCX but not in the PfCX; however, at doses of 10 mg/kg, which increase PfCX NA, paroxetine increased DA also in this area. Imipramine increased dialysate DA and NA both in the PfCX and in the OccCX and this effect was abolished by DNAB lesions and was reduced but not abolished by WAY-100635. Administration of doses of reboxetine and citalopram that do not increase DA release in the OccCX if given separately, markedly increased DA when combined. These results indicate that endogenous 5-HT, raised by selective blockade of the 5-HT carrier, can increase extracellular DA in the OccCX and in the ParCX by stimulating 5-HT1A receptors independently from the presence of NA terminals, although blockade of 5-HT and NA carrier can strongly interact to raise extracellular DA in this area. These observations are consistent with the existence of DA neurons separate from the NA ones contributing to extracellular DA even in NA-rich/DA poor isocortical areas
Monitoring extracellular dopamine in the rat nucleus accumbens shell and core during acquisition and maintenance of intravenous WIN 55,212-2 self-administration
No full textRationale WIN 55,212-2, a potent cannabinoid receptor 1 agonist, is self-administered by animals to evaluate abuse liability of cannabinoids, but to date no information is yet available about its effects on dopaminergic transmission during active response-contingent administration.
Objective This study monitored the changes of extracellular dopamine (DA) in the nucleus accumbens (NAc) shell and core during active intravenous WIN 55,212-2 self-administration (SA).
Methods Rats, implanted with a jugular catheter and bilateral intracerebral chronic cannulae, were trained for 3 weeks to self-administer WIN 55,212-2 (12.5 mu g/kg) in single daily 1-h sessions under a fixed ratio 1 (FR 1) schedule, than switched to FR 2 for a further week. During SA sessions, microdialysis assays were performed every 3rd day, and then daily starting from the 13th session. Dialysate DA from the NAc shell and core was monitored before, during, and for 30 min after SA.
Results Dialysate DA increased during WIN 55,212-2 SA starting from the 1st week in the NAc shell and on the 2nd week in the core. The increase of dialysate DA in the NAc shell was larger than that in the core on all weeks. Dialysate DA did not change during extinction sessions in spite of active nose poking.
Conclusions Response-contingent WIN 55,212-2 SA preferentially increases the NAc shell DA output as compared to that of the core independently from the duration of the WIN 55,212-2 exposure. Increase in NAc DA is strictly related to WIN 55,212-2 actions because it is not observed during extinction despite active responding
Differential neurochemical and behavioral responses induced by contingent and non-contingent heroin administration
No full textIn naive rats, passive administration of drugs of abuse preferentially increases extracellular dopamine (DA) levels in the nucleus accumbens (NAc) shell as compared to the core. Repeated exposure to the same drugs results in the induction of behavioral and biochemical sensitization characterized by stereotyped activity and by reduction of the DA shell/core response ratio. To date, no information is available on the within subject evolution of the response of DA transmission across the daily sessions of heroin drug SA. This study was aimed to investigate the changes of extracellular DA in the NAc shell and core of rats, along with the behavioral responses, during response-contingent and non-contingent intravenous heroin administration. Rats were implanted with a catheter in the right jugular vein and bilaterally with intracerebral chronic cannulae aimed at the NAc shell and core. After recovery, rats were trained to self-administer heroin in single daily 1h-session for four weeks (5 days/weeks). Nose-pokes in the active hole resulted in intravenous injection of heroin (0.05 mg/kg) to master (response contingent) and yoked (non-contingent administration) rats. Dialysate DA was monitored for 90-min after each session from the NAc shell and core starting on the first exposure to the drug. Behavioral effects of contingent and non-contingent drug exposure, distinguished into non-stereotyped and stereotyped activity was recorded. No differences were found in basal extracellular DA in the NAc shell and core. DA levels elicited by heroin in the NAc of master rats were greater in the shell compared to the core, whereas, in yoked rats the DA shell and core responsiveness was similar during the first week and became higher in the core compared to the shell from the second week until the end of heroin paired-administered. Moreover, yoked rats showed a progressive and faster increase of stereotyped behaviors than master rats. Non-stereotyped behavior followed the reverse trend. Response-non-contingent heroin administration is particularly prone, compared to response-contingent administration, to induce behavioral and neurochemical sensitization
Extracellular dopamine in the nucleus accumbens shell and core: differences between response contingent and response-non-contingent drug exposure.
No full textPredictors of long-term clinical remission in rheumatoid arthritis
No full textAim: Little is known about possible predictors of long-term survival on biologic disease-modifying antirheumatic drugs (bDMARD) after achievement of deep clinical remission in rheumatoid arthritis (RA) patients. We aimed at assessing factors associated with drug persistence of the first bDMARD in RA patients who achieved Simplified Disease Activity Index (SDAI) remission. Methods: The clinical charts of RA patients beginning a first bDMARD were retrospectively reviewed, and those who achieved SDAI-based remission were selected for this analysis. Drug retention rate and mean survival time (MST) were estimated using Kaplan-Meier curves, and hazard ratios (HRs) of discontinuing bDMARD were estimated by multivariate Cox-regression models. Results: Eight-six patients were on SDAI remission, and the survival rate of bDMARDs since ‘baseline-time’ was 82.6% (MST = 77.8 (95% CI: 69-86) months). Once on remission, patients not taking concomitant glucocorticoids had significantly higher survival rate (90.7%, MST = 86.3 (95% CI: 78-95) months) than patients who continued to intake low dose of glucocorticoids (68.8%, MST = 56.9 (95% CI: 45-69) months; P =.008). On the contrary, those patients assuming methotrexate (MTX) had significantly higher survival (87.7% (MST = 81.8 (95% CI: 73-91) months) than patients who were not taking MTX (66.7% (MST = 55.3 (95% CI: 40-71) months) (log-rank 4.72, P =.03). After the achievement of disease remission, stopping glucocorticoids (HR 0.31, 95% CI: 0.10-0.93) and methotrexate co-therapy (HR 0.34, 95% CI: 0.12-0.98) were independently associated with a lower risk of bDMARD discontinuation. Conclusions: Among RA patients on clinical remission with a first bDMARD, those stopping glucocorticoids and continuing MTX had much longer survival on bDMARD
- …
