Definition of Remission and Disease Activity Assessment in Psoriatic Arthritis: Evidence and Expert-Based Recommendations

ObjectiveWe aimed to reach a consensus on the best instruments to monitor disease activity in patients with psoriatic arthritis (PsA) and to develop a consensus definition of remission.MethodsA modified Delphi approach was used. A scientific committee provided statements addressing the definition of remission and the monitoring of PsA in clinical practice. The questionnaire was evaluated in 2 rounds by rheumatologists with experience in managing PsA patients.ResultsA panel of 77 rheumatologists reached agreement on 62 out of the 86 proposed items (72.0%). The most recommended index for monitoring disease activity was DAPSA (cut-off values: ≤4 for remission and >4–14 for low disease activity ([LDA]), MDA (at least 5/7 criteria). In cases with axial involvement, ASDAS was the preferred index (cut-off values: <1.3 for remission and <2.1 for LDA). BASDAI (cut-off values: ≤2 for remission and ≤4 for LDA) may be used as an alternative. PsAID was the preferred tool to assess disease impact.ConclusionWe propose a definition of remission in PsA as the absence of disease activity evaluated by DAPSA or MDA (ASDAS and/or BASDAI in patients with axial involvement), which would imply absence of signs or symptoms of inflammation, physical well-being, lack of disease impact, and absence of inflammation as measured by biological markers.     

Pharmacological manipulation of anxiety and male rat sexual behavior

Several anxiolytic/anxiogenic treatments were evaluated on male rat sexual behavior. The anxiolytic drug diazepam (1.0 mg/kg) inhibited copulatory behavior as indicated by an increase in the number of mounts preceding ejaculation, prolongation of the ejaculation latency and the postejaculatory interval. These changes were not accompanied by alterations in motor coordination as tested on a treadmill apparatus. A lower dose of diazepam (0.5 mg/kg) did not affect the sexual behavior. The anxiogenic drug Zk 39106 (2 and 4 mg/kg) facilitated the copulatory behavior by reducing the number of intromissions preceding ejaculation. A higher dose of Zk 39106 (8 mg/kg) inhibited sexual behavior. The selective benzodiazepine antagonist, Ro 15-1788 (5 and 10 mg/kg), did not modify male sexual behavior, but effectively antagonized the effects of Zk 39106 and diazepam. The administration of Zk 39106 (2 mg/kg) reversed the inhibitory action of diazepam (1.0 mg/kg) on copulation; however, diazepam did not prevent the facilitory effect of Zk 39106. The data are discussed in terms of the possible relationship existing between anxiety and masculine sexual behavior.     

Necesidades informativas de los pacientes con espondiloartritis sobre su enfermedad

Objective

1. To describe the information provided to, or inquired about, by patients with axial spondyloarthritis and psoriatic arthritis. 2. To analyze improvements.

Efecto de la pérdida de peso en la actividad en artritis psoriásica: una revisión sistemática

Objective

To evaluate the association between weight loss and changes in disease activity in patients with psoriatic arthritis (PsA).

A-ring reduction enhances the antigonadotropic potency of norethisterone

To assess whether structural modifications on the A-ring of norethisterone (NET) could modify its antigonadotropic potency, comparative studies using NET, 5 alpha-dihydro NET (5 alpha-NET) and its 3 beta,5 alpha and 3 alpha,5 alpha tetrahydro derivatives in castrated adult rats were undertaken. The antigonadotropic effect of these compounds was evaluated by measuring the serum and pituitary immunoreactive concentrations of LH and FSH following their chronic sc administration to animals depleted of progesterone receptors. The results demonstrated that 3 beta,5 alpha-NET and 5 alpha-dihydro-NET exhibited a significantly greater gonadotropic inhibiting activity as compared with that of their parent compound. The simultaneous administration of tamoxifen with 3 beta,5 alpha-NET resulted in a significant diminution of its antigonadotropic potency, particularly for LH. These data indicate that the potent antigonadotropic effect of 3 beta,5 alpha-NET metabolite was mediated via oestrogen receptors. The LH inhibitory activity of 5 alpha-dihydro-NET was not suppressed by the non-steroidal antioestrogen administration, thus suggesting that 5 alpha-NET might exert its effect via androgen receptors. The overall data were interpreted as demonstrating that metabolic conversion products of NET exhibit potent antigonadotropic effect. The data are consistent with an A-ring enhancement of the antigonadotropic potency of this synthetic progestin and open an alternate approach to the development of fertility regulating agents.     

Neurologic complications in the immediate postoperative period after cardiac surgery. Role of brain magnetic resonance imaging

INTRODUCTION AND OBJECTIVES: Neurologic complications still cause significant morbidity and mortality in the immediate postoperative period following cardiac surgery. Our understanding of the pathogenesis, prevention, and management of these lesions is constantly developing. MATERIAL AND METHOD: We describe neurologic complications and their course in a cardiac surgery cohort and analyze the value of brain magnetic resonance imaging (MRI), using T1-weighted, T2-weighted, and FLAIR sequences, in patients with postoperative stroke or encephalopathy in whom CT scanning revealed no abnormalities explaining their clinical condition. RESULTS: In 688 patients studied postoperatively, we observed 57 neurologic complications (8.3%): 25 strokes, 24 encephalopathies, 5 seizure disorders, 2 brain deaths, and 1 intracranial hemorrhage. Initial CT scanning failed to show significant findings in 70%. 18 patients underwent brain MRI. In all but 1 of the 11 with stroke, MRI showed areas of acute or subacute infarction (i.e., hyperintensity in FLAIR or T2-weighted sequences) in different locations, mainly in a watershed distribution. In 3 of the 4 patients with mild-to-moderate encephalopathy, MRI showed lesions similar to those previously described for stroke. In the remaining 3 patients, who had severe encephalopathy, MRI showed diffuse cortical necrosis. CONCLUSIONS: The incidence of neurologic complications in the postoperative period following cardiac surgery is significant. In a high percentage of patients, brain CT scanning may not show pathologic findings. In selected patients, MRI could help identify areas of infarction not detected by CT. These images could improve clinicians' understanding of the pathogenic, pathophysiologic, clinical, and prognostic characteristics of such neurologic complications.     

Pharmacological preconditioning by diazoxide downregulates cardiac L-type Ca2+ channels

BACKGROUND AND PURPOSE

Pharmacological preconditioning (PPC) with mitochondrial ATP-sensitive K⁺ (mitoK_ATP) channel openers such as diazoxide, leads to cardioprotection against ischaemia. However, effects on Ca²⁺ homeostasis during PPC, particularly changes in Ca²⁺ channel activity, are poorly understood. We investigated the effects of PPC on cardiac L-type Ca²⁺ channels.

EXPERIMENTAL APPROACH

PPC was induced in isolated hearts and enzymatically dissociated cardiomyocytes from adult rats by preincubation with diazoxide. We measured reactive oxygen species (ROS) production and Ca²⁺ signals associated with action potentials using fluorescent probes, and L-type currents using a whole-cell patch-clamp technique. Levels of the α_1c subunit of L-type channels in the cellular membrane were measured by Western blot.

KEY RESULTS

PPC was accompanied by a 50% reduction in α_1c subunit levels, and by a reversible fall in L-type current amplitude and Ca²⁺ transients. These effects were prevented by the ROS scavenger N-acetyl-L-cysteine (NAC), or by the mitoK_ATP channel blocker 5-hydroxydecanoate (5-HD). PPC signficantly reduced infarct size, an effect blocked by NAC and 5-HD. Nifedipine also conferred protection against infarction when applied during the reperfusion period. Downregulation of the α_1c subunit and Ca²⁺ channel function were prevented in part by the protease inhibitor leupeptin.

CONCLUSIONS AND IMPLICATIONS

PPC downregulated the α_1c subunit, possibly through ROS. Downregulation involved increased degradation of the Ca²⁺ channel, which in turn reduced Ca²⁺ influx, which may attenuate Ca²⁺ overload during reperfusion.