Monoaminergic and histaminergic strategies and treatments in brain diseases

The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable strategies for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity), the identification of monoamines in the diseases processes (Parkinson's disease, addiction) and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer's disease, stroke). In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in this review.peer-reviewe

Hypereosinophilic Syndrome and Clonal Eosinophilia: Point-of-Care Diagnostic Algorithm and Treatment Update

Acquired eosinophilia is operationally categorized into secondary, clonal, and idiopathic types. Causes of secondary eosinophilia include parasite infections, allergic or vasculitis conditions, drugs, and lymphoma. Clonal eosinophilia is distinguished from idiopathic eosinophilia by the presence of histologic, cytogenetic, or molecular evidence of an underlying myeloid malignancy. The World Health Organization classification system for hematologic malignancies recognizes 2 distinct subcategories of clonal eosinophilia: chronic eosinophilic leukemia, not otherwise specified and myeloid/lymphoid neoplasms with eosinophilia and mutations involving platelet-derived growth factor receptor α/β or fibroblast growth factor receptor 1. Clonal eosinophilia might also accompany other World Health Organization—defined myeloid malignancies, including chronic myelogenous leukemia, myelodysplastic syndromes, chronic myelomonocytic leukemia, and systemic mastocytosis. Hypereosinophilic syndrome, a subcategory of idiopathic eosinophilia, is defined by the presence of a peripheral blood eosinophil count of 1.5 × 109/L or greater for at least 6 months (a shorter duration is acceptable in the presence of symptoms that require eosinophil-lowering therapy), exclusion of both secondary and clonal eosinophilia, evidence of organ involvement, and absence of phenotypically abnormal and/or clonal T lymphocytes. The presence of the latter defines lymphocytic variant hyper eosinophilia, which is best classified under secondary eosinophilia. In the current review, we provide a simplified algorithm for distinguishing the various causes of clonal and idiopathic eosinophilia and discuss current therapy, including new drugs (imatinib mesylate, alemtuzumab, and mepolizumab)