Rheumatoid arthritis (RA) is a systemic inflammatory disease that commonly presents with inflammation and pain in the joints but may also cause extra-articular manifestations affecting different organs, including the central nervous system (CNS). Neurological manifestations have been classically classified in CNS vasculitis, rheumatoid nodules (RNs) and rheumatoid meningitis (RM) [1,2]. RM was first

Mild COVID-19 infection in a patient with multiple sclerosis and severe depletion of T-lymphocyte subsets due to alemtuzumab Dear SirPatients with multiple sclerosis (pwMS) using disease-modifying treatments (DMT) can present a varying degree of immunodeficiency that can translate into an increased risk of infections (Luna et al., 2019). Whether pwMS are at increased risk of COVID-19 or at higher risk of developing severe complications is still unknown. Expert recommendations on the management of pwMS during the COVID-19 pandemic have rapidly emerged, with the Italian Society of Neurology and the Association of British Neurologists releasing the first examples. Overall, both groups consider safe to start or continue treatment with interferons β, glatiramer acetate, teriflunomide, dimethyl fumarate and non-lymphodepleting DMTs such as fingolimod and natalizumab. In relation with the lymphodepleting ocrelizumab and alemtuzumab, the recommendations are less straightforward, focusing on individual factors such as disease activity and lymphocyte count, but suggesting to temporarily delay the start or dosing of alemtuzumab. Nevertheless, such recommendations may be inadequate in pwMS with a highly active form of MS. Alemtuzumab is a humanized monoclonal antibody that depletes circulating lymphocytes by selectively targeting CD52, highly expressed on lymphocytes T and B, and effectively used to treat pwMS. Lymphocyte depletion is followed by a distinct pattern of T-and B-cell repopulation that begins within weeks, with B-cell counts returning to baseline levels within 6 months, whereas T-cell counts rise more slowly, generally approaching the lower limits of normal by 12 months (Li et al., 2018). Many neurologists have stopped prescribing alemtuzumab in pandemic times because of the strong acute post-infusion lymphodepletion.We present a pwMS with mild COVID-19 disease with severe lymphocyte depletion of the major circulating T lymphocytes (CD3 + , CD4 + and CD8 + ) due to alemtuzumab. A 35-year-old man was diagnosed with relapsing remitting multiple sclerosis (RRMS) in November 2018 according to the Mc-Donald criteria. He did not have any other comorbidities. He developed progressive bilateral lower limb numbness and mild motor impairment, followed by diplopia. Magnetic resonance imaging (MRI) at time of diagnosis showed multiple demyelinating lesions in the brain and spinal cord, consistent with multiple sclerosis. In December 2018 he was infused with the first dose of alemtuzumab (12 mg daily IV for five days) and the second dose was infused (12 mg daily IV for three days) at the end of February 2020. Between both doses, he had not experienced clinical deterioration. Neurological examination

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We have studied the effects of chronic therapy with cicaprost (a PGI2 analog), fosinopril (a converting enzyme inhibitor), and the combination of both drugs on the progression of experimental diabetic nephropathy. Uninephrectomized streptozotocin-induced diabetic rats were maintained for 8 months with plasma glucose between 13.7 and 22.0 mmol/L to hasten renal damage. Systemic and renal parameters were measured periodically, and at sacrifice structural and morphometrical renal studies were performed to evaluate diabetic injury. Control rats exhibited characteristic features of this model, such as high blood pressure and plasma creatinine and urinary albumin excretion, together with prominent alterations in the kidney (renal and glomerular hypertrophies, mesangial matrix expansion, and tubular alterations). The three therapies attenuated equivalently the progression of diabetic renal injury, as estimated by lower urinary albumin excretion, renal and glomerular hypertrophies, and a better renal architectural preservation. No synergistic action was appreciated with the combined therapy. However, renal preservation achieved with cicaprost was not linked to reductions in systemic blood pressure, whereas in the groups treated with fosinopril the hypotensive effect of this drug could have contributed to the positive outcome of the therapy. Therefore, nephroprotection exerted by this PGI2 analog in this model seems more related to the derangement of renal local mechanisms than to systemic blood pressure control. Finally, the possibility that an impaired prostacyclin synthesis or bioavailability is involved in the pathogenesis of the diabetic nephropathy in this model underlies our results.

Rapid degradation of prostacyclin (PGI2) inherent to its molecular structure has long been a major limitation in assessing the natriuretic effect of this prostaglandin. The recent availability of the stable PGI2 analogue iloprost now allows for a comparative study with prostaglandin E2 (PGE2). In the present study conducted in six anesthetized dogs, the intrarenal effects of two consecutive doses (1 and 4 ng x kg(-1) x min(-1)) of PGE2 on renal blood flow, glomerular filtration rate, and urinary sodium excretion were compared with the effects of two identical doses of iloprost. The selected doses of PGE2 were those producing a maximal natriuretic and vasodilator response without affecting mean arterial pressure. A washout period was allowed between administration of PGE2 and iloprost. PGE2 infusion significantly increased fractional sodium excretion from 0.69+/-0.1 to 2.79+/-1.1% and 4.27+/-1.2%% (P<.05), respectively. These changes in fractional sodium excretion induced by PGE2 were associated with significant increases in renal blood flow from 151.1+/-62 to 185+/-64.3 and 185.6+/-64.3 mL/min (P<.05), respectively; however, no significant alterations were seen in glomerular filtration rate, from 29.5+/-9.4 to 35.2+/-12.2 and 32.7+/-7.8 mL/min (NS), and mean arterial pressure, from 117.6+/-26 to 113.9+/-24.1 and 112.3+/-24.1 mm Hg (NS) during control and PGE2 infusion. At identical doses, sequential infusion of PGI2 had no effect on renal blood floww and glomerular filtration rate, producing natriuresis only at the highest dose, a fractional sodium excretion from 0.69+/-0.1 to 0.8+/-0.28 mm Hg (NS) and 1.05+/-0.34% (P<.05), respectively. In conclusion, the present study confirms that PGE2 exerts a natriuretic effect during increases in renal blood flow. In contrast, PGI2 had no hemodynamic effect, and the natriuresis was markedly blunted.