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The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, we have selected indications, where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, to provide first-line options for therapeutic repurposing. These indications are as follows: acute ischaemic stroke; traumatic brain injury; septic shock; acute pancreatitis; and severe asthma and severe acute lung injury. In addition, chronic, devastating diseases, where alternative therapeutic options cannot halt disease development (e.g. Parkinson's disease, progressive multiple sclerosis or severe fibrotic diseases), should also be considered. We present a preclinical and clinical action plan for the repurposing of PARP inhibitors.Linked articlesThis article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

The recent clinical availability of the PARP inhibitor olaparib (Lynparza) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, we have selected indications, where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, to provide first-line options for therapeutic repurposing. These indications are as follows: acute ischaemic stroke; traumatic brain injury; septic shock; acute pancreatitis; and severe asthma and severe acute lung injury. In addition, chronic, devastating diseases, where alternative therapeutic options cannot halt disease development (e.g. Parkinson's disease, progressive multiple sclerosis or severe fibrotic diseases), should also be considered. We present a preclinical and clinical action plan for the repurposing of PARP inhibitors.This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

Background Neuroleptic malignant syndrome (NMS) is a rare side effect of antipsychotic therapy characterized by fever, muscular rigidity, altered mental status, increased level of serum creatinine phosphokinase, and increased number of white blood cells. The mortality rate of patients with NMS remains elevated. Methods We examined the clinical records of patients diagnosed with severe NMS admitted to the Clinical Toxicology Unit, Florence University Hospital, between 1990 and 2004. Results Eight patients presented with this neurological disorder. All were treated with supportive therapy, which included dantrolene, levodopa/benserazide, benzodiazepines, metamizole and/or paracetamol, and antibiotics. Five survived and three died. Of the three deceased, two had large hemorrhages in the gastrointestinal tract, and one had massive liver damage and diffuse hemorrhages throughout the body. Conclusion Our results suggest that gastrointestinal bleeding is a frequent cause of death in NMS patients. Bleeding may occur as a consequence of commonly accepted medical treatments (especially the use of cyclooxygenase inhibitors as antipyretic agents) and NMS-induced changes in blood coagulation status. To increase the survival rate of these patients, it is necessary to avoid using drugs that may facilitate gastrointestinal lesions and to utilize procedures known to decrease the risk of bleeding.

Moroni Flavio. Principi di funzionamento e aspetti progettuali di un sistema con macrofite radicate a flusso sub-superficiale per il trattamento di reflui civili. In: Le Journal de botanique, n°1, 1997. pp. 57-59.