Acquired Demyelinating Syndromes of the Central Nervous System in Children: The Importance of Regular Follow-up in the First Year After Onset.

Aim: We reviewed the clinical features of a sample of pediatric acquired demyelinating syndromes with the purpose of determining the appropriate protocol for follow-up after the first episode.

Methods: A multicenter retrospective observational study was conducted on a cohort of 40 children diagnosed with a first episode of acquired demyelinating syndrome over the period 2012-2021. Patients were evaluated with clinical and neuroradiologic assessment after 3, 6, and 12 months, with a median follow-up of 4.

Synthesis and crystallographic analysis of new sulfonamides incorporating NO-donating moieties with potent antiglaucoma action.

Several aromatic/heterocyclic sulfonamide scaffolds have been used to synthesize compounds incorporating NO-donating moieties of the nitrate ester type, which have been investigated for the inhibition of five physiologically relevant human carbonic anhydrase (hCA, EC 4.2.1.

Therapeutic potential of nitrate esters of commonly used drugs.

Organic nitrates, such as nitroglycerin, have been used in clinical practice for more than one century for the treatment of angina, even before the identification of Nitric Oxide (NO) as the so-called Endothelium Derived Relaxing Factor (EDRF). Recently, multiple functions of this molecule in biology and pathophysiology have been discovered and alterations in the NO signalling pathway have often been associated with disease progression in mammals, providing a strong rationale for the use of NO as a potential drug. To have a therapeutic benefit from NO properties, an elegant approach has been designed coupling well-known existing drugs with moieties able to slowly release NO following enzymatic metabolism.

Positional isomerism markedly affects the growth inhibition of colon cancer cells by nitric oxide-donating aspirin in vitro and in vivo.

NO-donating aspirin (NO-ASA), a novel pharmacological agent currently undergoing clinical testing, consists of ASA to which a nitrate group is covalently linked via a spacer molecule. We synthesized the three positional isomers of NO-ASA with respect to the -CH(2)ONO(2) group (ortho, meta, and para) and examined whether this isomerism affects the biological activity of NO-ASA on HT-29 human colon cancer cells. The ortho- and para-isomers showed similar IC(50) values (1-5 microM) for cell growth inhibition over 72 h, whereas the IC(50) of the meta-isomer was 200 to 500 microM.

Synthesis of nitro esters of prednisolone, new compounds combining pharmacological properties of both glucocorticoids and nitric oxide.

Glucocorticoids (GC) are widely used in therapy for their many pharmacological properties including antiinflammatory and immunosuppressive actions. However, their use over long periods is hampered by a number of severe side effects. Given the biological properties of nitric oxide (NO) and previous experience with nonsteroidal antiinflammatory agents, we synthesized new chemical entities combining both NO and GC properties.

Nitric oxide-donating non-steroidal anti-inflammatory drugs: the case of nitroderivatives of aspirin.

Nitric oxide (NO) acts as a key signalling mechanism in a number of cells and tissues in the mammalian organism. Modulation of the biosynthesis of NO has emerged to be relevant to the treatment of a variety of human diseases. In the attempt to reduce the serious side effects of non-steroidal anti-inflammatory drugs (NSAIDs), especially in the gastrointestinal tract, a NO-releasing moiety has been linked to conventional NSAIDs.

New antianginal nitro esters with reduced hypotensive activity. Synthesis and pharmacological evaluation of 3-[(nitrooxy)alkyl]-2H-1,3-benzoxazin-4(3H)-ones.

New nitro ester 3-[(nitrooxy)alkyl]-2H-1,3-benzoxazin-4(3H)-ones show marked inhibitory activity against ischemia-induced electrocardiographic changes, with only limited systemic hemodynamic effects, and are reported in the present study. These new nitro vasodilators are potent inhibitors of the electrocardiographic T-wave and S-T segment elevation induced by intravenous or intracoronary administration of Arg-vasopressin or methacholine in the anesthetized rat. The most active compounds are up to 300- and 600-fold more potent than glyceryl trinitrate or Nicorandil, respectively.

The discovery of a new organic nitrate: an overview.

Organic nitrates have been in therapeutic use for the treatment of angina pectoris for over a century. During the past decade, the search for new organic nitro esters with reduced side effects and improved oral bioavailability has been greatly intensified. We have discovered a new class of organic nitrates characterized by good oral activity and a coronary vascular selectivity greater than that of glyceryl trinitrate.

Intraduodenal absorption in the rabbit of a novel heparin salt.

The intraduodenal absorption of a new low-molecular-weight heparin (LMWH) diamine salt (ITF 1331) was compared with the parent compound ITF 1060 and with sodium LMWH, in anaesthetized rabbits. The administration of either salt, but not of sodium LMWH, resulted in a dose-related increase in plasma anti-Xa activity. In this respect ITF 1331 was slightly superior to ITF 1060, and in acute-toxicity studies the counterion itself (ITF 258) was less toxic than that in ITF 1060 (counterion No.