Background And Objectives: CHF 5993 is an extrafine 'triple therapy' combination of the long-acting muscarinic antagonist glycopyrronium bromide (GB), the long-acting β-agonist formoterol fumarate (FF), and the inhaled corticosteroid beclometasone dipropionate (BDP). It is in development for chronic obstructive pulmonary disease and asthma delivered via pressurised metered-dose inhaler.
Methods: This two-period, open-label, crossover study examined the drug-drug interaction of CHF 5993 and cimetidine.
In experimental cerebral ischemia, melanocortin MC4 receptor agonists induce neuroprotection and neurogenesis with subsequent long-lasting functional recovery. Here we investigated the molecular mechanisms underlying melanocortin-induced neurogenesis. Gerbils were subjected to transient global cerebral ischemia, then they were treated every 12 h, and until sacrifice, with 5-bromo-2'-deoxyuridine (BrdU; to label proliferating cells), and the melanocortin analog [Nle(4),d-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) or saline.
View Article and Find Full Text PDFMelanocortin peptides with the adrenocorticotropin/melanocyte-stimulating hormone (ACTH/MSH) sequences and synthetic analogs have protective and life-saving effects in experimental conditions of circulatory shock, myocardial ischemia, ischemic stroke, traumatic brain injury, respiratory arrest, renal ischemia, intestinal ischemia and testicular ischemia, as well as in experimental heart transplantation. Moreover, melanocortins improve functional recovery and stimulate neurogenesis in experimental models of cerebral ischemia. These beneficial effects of ACTH/MSH-like peptides are mostly mediated by brain melanocortin MC(3)/MC(4) receptors, whose activation triggers protective pathways that counteract the main ischemia/reperfusion-related mechanisms of damage.
View Article and Find Full Text PDFCentrally acting leptin induces the activation of the sympathetic nervous system with a pressor effect in normotensive rats. The purpose of the study was to examine central leptin-evoked action in critical haemorrhagic hypotension. In anaesthetized male Wistar rats subjected for irreversible haemorrhagic shock with mean arterial pressure (MAP) 20-25 mmHg haemodynamic parameters and plasma concentrations of adrenaline and noradrenaline were measured.
View Article and Find Full Text PDFBackground: Melanocortin peptides improve hemodynamic parameters and prevent death during severe hemorrhagic shock. In the present research we determined influences of a synthetic melanocortin 1/4 receptor agonist on the molecular changes that occur in rat liver during hemorrhage.
Methods: Controlled-volume hemorrhage was performed in adult rats under general anesthesia by a stepwise blood withdrawal until mean arterial pressure fell to 40 mmHg.
Objective: Treatment for traumatic brain injury remains elusive despite compelling evidence from animal models for a variety of therapeutic targets. Melanocortins have established neuroprotective effects against experimental ischemic stroke. We investigated whether melanocortin treatment of traumatic brain injury induces neuroprotection and promotes functional recovery.
View Article and Find Full Text PDFIndirect evidence indicates that, in cerebral ischemia, melanocortins have neuroprotective effects likely mediated by MC₄ receptors. To gain direct insight into the role of melanocortin MC₄ receptors in ischemic stroke, we investigated the effects of a highly selective MC₄ receptor agonist. Gerbils were subjected to transient global cerebral ischemia by occluding both common carotid arteries for 10 min.
View Article and Find Full Text PDFMelanocortins produce neuroprotection against ischemic stroke with subsequent long-lasting functional recovery, through melanocortin MC(4) receptor activation. Here we investigated whether the long-lasting beneficial effect of melanocortins in stroke conditions is associated with a stimulation of neurogenesis. Gerbils were subjected to transient global cerebral ischemia by occluding both common carotid arteries for 10 min; then, they were prepared for 5-bromo-2'-deoxyuridine (BrdU) labeling of proliferating cells.
View Article and Find Full Text PDFMelanocortins (MC) trigger a vagus nerve-mediated cholinergic-antiinflammatory pathway projecting to the testis. We tested whether pharmacological activation of brain MC receptors might protect the testis from the damage induced by ischemia-reperfusion. Adult male rats were subjected to 1-h testicular ischemia, followed by 24-h reperfusion [testicular ischemia-reperfusion (TI/R)].
View Article and Find Full Text PDFObjective: Acute pancreatitis is an inflammatory condition that may lead to multisystemic organ failure. Melanocortin peptides have been successfully used in experimental models of organ failure and shock, and their protective effect occurs through the activation of a vagus nerve-mediated cholinergic anti-inflammatory pathway by acting at brain melanocortin 4 receptors. In the light of these observations, we studied the effects of the selective melanocortin 4 receptor agonist RO27-3225 in an experimental model of cerulein-induced pancreatitis.
View Article and Find Full Text PDFBackground And Purpose: Melanocortins reverse circulatory shock and improve survival by counteracting the systemic inflammatory response, and through the activation of the vagus nerve-mediated cholinergic anti-inflammatory pathway. To gain insight into the potential therapeutic value of melanocortins against multiple organ damage following systemic inflammatory response, here we investigated the effects of the melanocortin analogue [Nle⁴ D-Phe⁷]α-MSH (NDP-α-MSH) in a widely used murine model of multiple organ dysfunction syndrome (MODS).
Experimental Approach: MODS was induced in mice by a single intraperitoneal injection of lipopolysaccharide followed, 6 days later (= day 0), by zymosan.
Aims: The aims of this survey were: (i) to examine the pharmacoepidemiology of triptans in a headache centre; (ii) to compare the characteristics of patients who continued to take triptans with those of patients who had discontinued them.
Methods: We enrolled all migraine patients according to ICHD-II criteria, ensuring they were over 18 years of age, consecutively examined during a follow-up visit at the Headache Centre of the University Hospital of Modena from October 2008 to March 2009. Only patients who had used or were using a triptan were included.
Recently we reported that an efferent vagal fibre-mediated cholinergic protective pathway, activated by melanocortins acting at brain melanocortin MC(3) receptors, is operative in a condition of short-term myocardial ischemia/reperfusion associated with a high incidence of severe arrhythmias and death. Here we investigated melanocortin effects, and the role of the vagus nerve-mediated cholinergic protective pathway, in a rat model of prolonged myocardial ischemia/reperfusion associated with marked inflammatory and apoptotic reactions, and a large infarct size. Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30 min.
View Article and Find Full Text PDFThere are a large number of drugs inducing headache as an adverse reaction. Nevertheless, headaches as adverse reactions to drugs have received limited attention. Non-serious adverse reactions, such as headache, are not quantified and described as accurately as serious, life threatening ones.
View Article and Find Full Text PDFBackground: While adult headache patients' satisfaction with treatments has been widely investigated, less attention has been paid to children and adolescent headache patients' opinions and their parents' views.
Objective: The aim of our follow-up survey was to analyze the outcomes of the Headache Centre's intervention and the evolution of headache according to patients until the age of 16 and their parents.
Methods: We studied all outpatients suffering from episodic primary headache according to International Classification of Headache Disorders 2nd edition criteria, seen for the first time in 2005-2006 at the Headache Centre of the University Hospital of Modena (Italy), and at least one of their parents.
We describe the case of a 34 year-old man with diagnosis of migraine with and without aura that developed myopia and acute glaucoma after 7 days of treatment with topiramate. The patient had also been taking citalopram daily for two months. Both topiramate and citalopram have been related to the increase of intraocular pressure and the development of glaucoma.
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