Renal replacement therapy in lupus nephritis

The indications and the choice of renal replacement therapy for lupus patients are similar to those for other uremic patients. However, lupus patients can pose some particular problems. First, 10-28% of patients needing dialysis can have a partial renal function recovery. Therefore, the clinician has to decide whether to administer a rescue treatment, risking side-effects, or to reduce immunosuppression precluding a potential recovery. Many patients on regular dialysis show subdued biological and clinical activity. Others can show a hectic disease activity, particularly in the 1st year. In these cases, treatment is difficult, as vigorous immunosuppression can expose uremic patients to severe side-effects. The presence of circulating antiphospholipid antibodies (aPL) can favor thrombosis or stenosis of vascular access (VA). Renal transplantation is the best therapy for most lupus patients with end-stage renal failure. Many, but not all, studies have reported similar patient and graft survival rates in lupus and in non-lupus transplant recipients. The results are much better with living donor transplantation. Patients with aPL, black patients and those on long-term dialysis have a higher graft failure risk. Candidates with active lupus and/or those with significant iatrogenic morbidity should be advised to wait 6-12 months before transplantation. The recurrence risk of lupus nephritis ranged between 2% and 30% in different studies. The histological picture does not usually show severe features. Antiplatelet agents or anticoagulation can be advised for aPL patients.     

Distinct roles of the different ionotropic glutamate receptors within the nucleus accumbens in passive-avoidance learning and memory in mice

Research on the role of the nucleus accumbens in behaviour has been largely focused on the functions of this structure in conditioning to appetitive stimuli. It has been suggested that a network comprising the nucleus accumbens and its convergent inputs might mediate dissociable functions in the acquisition, the consolidation and the retrieval of information. However, findings related to a role of this structure in aversive conditioning are somewhat contradictory, and its involvement in this form of learning is still under debate. Moreover, very little evidence is available on the step of information processing mediated by the accumbens. Thus the purpose of this study was to investigate the effects of the blockade of the AMPA and NMDA glutamate receptors, which have been suggested to mediate the transmission of information from the limbic system to this structure, on a classical aversive conditioning task - the one-trial step through inhibitory avoidance paradigm (24 h interval between training and testing). Intra-accumbens focal injections of AP-5 and DNQX (NMDA and AMPA antagonists, respectively) were performed immediately after training, before training and before testing in mice. The NMDA antagonist (37.5, 75 and 150 ng per side) impaired animal performance only if administered immediately after but not before training or before testing. Conversely, DNQX (0.5, 1.0 and 5.0 ng per side) reduced the step through latencies when administered before training and before testing. These findings suggest that NMDA receptor activation within the accumbens is necessary in formation but not expression of memory for inhibitory avoidance. AMPA receptors, instead, are necessary for the acquisition and the expression but not consolidation of inhibitory avoidance memory.     

Polymorphisms of platelet adhesive receptors: do they play a role in primary intracerebral hemorrhage?

BACKGROUND: Several reports suggested that polymorphisms affecting the structure or level of the main adhesive platelet glycoproteins (GPs) could behave as genetic risk factors for arterial thrombotic disorders. However, very few reports analyzed the significance of these polymorphisms in bleeding disorders. Interestingly, one study suggested a role of the 807 C/T polymorphism of the collagen receptor GP Ia in the severity of the bleeding manifestations in von Willebrand disease. The aim of this study was to evaluate the role of frequent polymorphisms affecting platelet GPs in primary intracerebral hemorrhage (PIH), the third most frequent cause of cerebrovascular disorder. METHODS: We evaluated the role of four putative prothrombotic polymorphisms: GP Ia [807 C/T, and human platelet alloantigen system 5 (HPA-5)], GP Ibalpha (variable number of tandem repeats), and GP IIIa (HPA-1) in 141 Caucasian patients diagnosed of PIH, 141 race-, age-, sex- and risk factor-matched controls, and 446 subjects from the general population. RESULTS: The frequency of genotypes and alleles were similar between patients and controls. CONCLUSIONS: Our results suggest that these polymorphisms play a minor role in PIH.     

Transient human cortical responses during the observation of simple finger movements: a high-resolution EEG study

High-resolution event-related potentials (ERPs) were used to model the hemispherical representation of the transient cortical responses relating to the observation of movement during execution (right or left aimless finger extension). Subjects were seated in front of the observed person and looked at both their own and the observer's hand to receive similar visual feedback during the two conditions. In a visual control condition, a diode light moved at the observed person's hand. A first potential accompanying the movement execution peaked at about +110 msec over the contralateral somatomotor areas. It was followed by a potential (P300) peaking at about +350 msec over the central midline. In contrast, the potentials accompanying the movement observation peaked later over parietal-occipital other than somatomotor areas (N200 peak, +200 msec; P300 peak, +400 msec). Notably, the N200 was maximum in left parietal area whereas the P300 was maximum in right parietal area regardless the side of the movement. They markedly differed by the potentials following the displacement of the diode light. These results suggest a rapid time evolution (approximately 200-400 msec) of the cortical responses characterizing the observation of aimless movements (as opposite to grasping or handling). The execution of these movements would mainly involve somatomotor cortical responses and would be scarcely founded on the visual feedback. In contrast, the observation of the same movements carried out by others would require dynamical responses of somatomotor and parietal-occipital areas (especially of the right hemisphere), possibly for a stringent visuospatial analysis of the motor event.     

Cation-chloride co-transporters in neuronal communication,development and trauma

Electrical signaling in neurons is based on the operation of plasmalemmal ion pumps and carriers that establish transmembrane ion gradients, and on the operation of ion channels that generate current and voltage responses by dissipating these gradients. Although both voltage- and ligand-gated channels are being extensively studied, the central role of ion pumps and carriers is largely ignored in current neuroscience. Such an information gap is particularly evident with regard to neuronal Cl- regulation, despite its immense importance in the generation of inhibitory synaptic responses by GABA- and glycine-gated anion channels. The cation-chloride co-transporters (CCCs) have been identified as important regulators of neuronal Cl- concentration, and recent work indicates that CCCs play a key role in shaping GABA- and glycine-mediated signaling, influencing not only fast cell-to-cell communication but also various aspects of neuronal development, plasticity and trauma.     

High-dose ropinirole in advanced Parkinson's disease with severe dyskinesias

Levodopa (LD) is the gold standard of therapy for Parkinson's disease, but it is commonly associated with motor fluctuations and dyskinesias. Dopamine agonists are often used as adjuncts to LD in an attempt to reduce these complications. In this open-label study the authors investigated the effects of high doses of adjunctive ropinirole in 36 patients with advanced Parkinson's disease and normal cognitive status. The daily dose of ropinirole was increased from 18.4 +/- 3.5 mg to 34.7 +/- 5.5 mg, generally in four separate doses. The daily LD dose was decreased from 734.1 +/- 254.8 mg to 502.8 +/- 228.4 mg. After 12 months 25 patients were still on high doses of ropinirole whereas 11 patients had, after either the emergence of side effects or a worsening of their clinical conditions, decreased or interrupted ropinirole. At 12 months, the daily doses of LD and ropinirole were 489 +/- 243 mg and 34.6 +/- 4.6 mg respectively. There was a significant reduction in the Dyskinesia Rating Scale scores during both ON and OFF periods, indicating a reduction in dyskinesias during ON periods and a reduction in dystonias during OFF periods (p < 0.001). Both the intensity and the hours spent during OFF periods were reduced significantly (p < 0.001). Even though these results need to be confirmed through extended controlled studies, the high-dose dopamine agonist strategy is safe for patients with advanced PD in whom a marked motor response to LD (even at very low doses) is associated with severe dyskinesias, and may be used as a means of delaying surgery or as an alternative to continuous apomorphine infusion.