Eletriptan in the management of acute migraine. An update on the evidence for efficacy, safety, and consistent response

Migraine is a multifactorial, neurological and disabling disorder, also characterized by several autonomic symptoms. Triptans, selective serotonin 5-HT1B/1D agonists, are the first-line treatment option for moderate-to-severe headache attacks. In this paper, we review the recent data on eletriptan clinical efficacy, safety, and tolerability, and potential clinically relevant interactions with other drugs. Among triptans, eletriptan shows a consistent and significant clinical efficacy and a good tolerability profile in the treatment of migraine, especially for patients with cardiovascular risk factors without coronary artery disease. It shows the most favorable clinical response, together with sumatriptan injections, zolmitriptan and rizatriptan. Additionally, eletriptan shows the most complex pharmacokinetic/dynamic profile compared with the other triptans. It is metabolized primarily by the CYP3A4 hepatic enzyme and therefore the concomitant administration of CYP3A4-potent inhibitors should be carefully evaluated. A relatively low risk of serotonin syndrome is given by the co-administration with serotoninergic drugs. No clinically relevant interaction has been found with drugs used for migraine prophylactic treatment or other acute drugs, with the exception of ergot derivatives that should not be co-administered with eletriptan

Direct C2-H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

A light-driven metal-free protocol for the synthesis of sulfone-containing indoles under mild conditions is reported. Specifically, the process is driven by the photochemical activity of halogen-bonded complexes formed upon complexation of a sacrificial donor, namely 1,4-diazabicyclo[2.2.2]octane (DABCO), with α-iodosulfones. The reaction provides a variety of densely functionalized products in good yields (up to 96% yield). Mechanistic investigations are reported. These studies provide convincing evidences for the photochemical formation of reactive open-shell species

A meta-analysis and systematic review of randomized controlled trials with degarelix versus gonadotropin-releasing hormone agonists for advanced prostate cancer

Our aim was to systematically evaluate the benefits of degarelix as antagonist versus agonists of gonadotropin-releasing hormones (GnRH) for the treatment of advanced prostate cancer (PC). This comparison was performed either in terms of biochemical or oncological or safety profiles. To this end we, carried out a systematic review and meta-analysis of the literature.We selected only studies directly and prospectively analyzing the two treatments in the same population (randomized phase III studies). We followed the Preferred Reporting Items for Systematic Reviews and meta-analyses process for reporting studies.After we eliminated studies according to the exclusion criteria, 9 publications were considered relevant to this review. These articles described 5 clinical trials that were eligible for inclusion. The follow-up duration in all trials did not exceed 364 days. This meta-analysis and review comprised a total of 1719 men, 1061 randomized to degarelix versus 658 to GnRH agonists treatment for advanced PC. Oncological results were evaluated only in 1 trial (CS21:408 cases) and they were not the primary endpoints of the study. Treatment emerging adverse events were reported in 61.4% and 58.8% of patients in the degarelix and GnRH agonists group, respectively (odds ratio, OR = 1.17; 95% confidence interval, 95% CI: 0.78-1.77, P > 0.1). Treatment related severe cardiovascular side effects were reported (trial CS21-30-35) in 1.6% and 3.6% of patients in the degarelix and GnRH agonists group, respectively (OR = 0.55, 95% CI: 0.26-1.14, P > 0.1).Our analysis evidences relevant limitations in particular for the comparative evaluation of the efficacy and the oncological results related to degarelix

Single-isocenter multiple-target stereotactic radiosurgery for multiple brain metastases: dosimetric evaluation of two automated treatment planning systems

Purpose Automated treatment planning systems are available for linear accelerator (linac)-based single-isocenter multi-target (SIMT) stereotactic radiosurgery (SRS) of brain metastases. In this study, we compared plan quality between Brainlab Elements Multiple Brain Metastases (Elements MBM) software which utilizes dynamic conformal arc therapy (DCAT) and Varian HyperArc (HA) software using a volumetric modulated arc therapy (VMAT) technique. Patients and methods Between July 2018 and April 2021, 36 consecutive patients >= 18 years old with 367 metastases who received SIMT SRS at UPMC Hillman Cancer San Pietro Hospital, Rome, were retrospectively evaluated. SRS plans were created using the commercial software Elements MBM SRS (Version 1.5 and 2.0). Median cumulative gross tumor volume (GTV) and planning tumor volume (PTV) were 1.33 cm(3) and 3.42 cm(3), respectively. All patients were replanned using HA automated software. Extracted dosimetric parameters included mean dose (D-mean) to the healthy brain, volumes of the healthy brain receiving more than 5, 8,10, and 12 Gy (V-5Gy, V-8Gy, V-10Gy and V-12Gy), and doses to hippocampi. Results Both techniques resulted in high-quality treatment plans, although Element MBM DCAT plans performed significantly better than HA VMAT plans, especially in cases of more than 10 lesions). Median V-12Gy was 13.6 (range, 1.87-45.9) cm(3) for DCAT plans and 18.5 (2.2-62,3) cm(3) for VMAT plans (p < 0.0001), respectively. Similarly, V-10Gy, V-8Gy, V-5Gy (p < 0.0001) and median dose to the normal brain (p = 0.0001) were favorable for DCAT plans. Conclusions Both Elements MBM and HA systems were able to generate high-quality plans in patients with up to 25 brain metastases. DCAT plans performed better in terms of normal brain sparing, especially in patients with more than ten lesions and limited total tumor volume

Sustainable and Green Production of Nanostructured Cellulose by a 2-Step Mechano-Enzymatic Process

Nanostructured cellulose (NC) represents an emerging sustainable biomaterial for diverse biotechnological applications; however, its production requires hazardous chemicals that render the process ecologically unfriendly. Using commercial plant-derived cellulose, an innovative strategy for NC production based on the combination of mechanical and enzymatic approaches was proposed as a sustainable alternative to conventional chemical procedures. After ball milling, the average length of the fibers was reduced by one order of magnitude (down to 10–20 μm) and the crystallinity index decreased from 0.54 to 0.07–0.18. Moreover, a 60 min ball milling pre-treatment followed by 3 h Cellic Ctec2 enzymatic hydrolysis led to NC production (15% yield). Analysis of the structural features of NC obtained by the mechano-enzymatic process revealed that the diameters of the obtained cellulose fibrils and particles were in the range of 200–500 nm and approximately 50 nm, respectively. Interestingly, the film-forming property on polyethylene (coating ≅ 2 μm thickness) was successfully demonstrated and a significant reduction (18%) of the oxygen transmission rate was obtained. Altogether, these findings demonstrated that nanostructured cellulose could be successfully produced using a novel, cheap, and rapid 2-step physico-enzymatic process that provides a potential green and sustainable route that could be exploitable in future biorefineries

Minorenni vittime di omicidio a Milano (Italia): 1993-2017

This study aims to examine the phenomenon of homicide with victims under 18 years-old in a wide and multiethnic metropolitanarea in the north of Italy. We’re dealing with a type of crime that generates a widespread alarm and a common concern.The data analysis, approached with a multidisciplinary strategy, presented in this paper is based on forensic reports of the Instituteof Legal Medicine of the University of Milan, to provide a detailed framework of the homicides of minors that took place inthe territorial jurisdiction of Milan and Monza Prosecutor’s Office between 1993 and 2017. Quantitative and qualitative analysiswere conducted regarding victims’ socio-demographic characteristics (gender, age, nationality), weapons used, places and modalityof body discovery, murderers, motives of the killing and type of relationship between offenders and victims. Purpose of thispaper is to compare the present set of data with the ones provided by the international literature, as well as make some criminologicalobservations on this matter with a view to preventing the phenomenon. To this end, some representative case studieshave been added, their characteristics and also the relationships between offender and victim have been discussed.Questo studio esamina il fenomeno dell'omicidio con vittime di età inferiore ai 18 anni in una vasta e multietnica area metropolitanadel nord Italia, un tipo di crimine che genera allarme e preoccupazione. L'analisi dei dati, affrontata con una metodologia multidisciplinare,è basata sui verbali autoptici dell'Istituto di Medicina Legale dell'Università di Milano, al fine di fornire un quadro dettagliatodegli omicidi con vittima minorenne che si sono verificati nella giurisdizione territoriale della Procura di Milano e Monzatra il 1993 e il 2017. Sono state condotte analisi quantitative e qualitative sulle vittime, quali le caratteristiche socio-demografiche(genere, età, nazionalità), le armi utilizzate, i luoghi e le modalità di rinvenimento del corpo, le caratteristiche dell’omicida, i motividell'uccisione e il tipo di relazione tra criminale e vittima. Scopo di questo studio è confrontare l'attuale insieme di dati con quelliforniti dalla letteratura internazionale, nonché porre alcune considerazioni di carattere preventivo. A tal fine, sono stati presentatianche alcuni casi studio rappresentativi, discutendone le caratteristiche peculiari e le relazioni tra l'autore del reato e la vittima

Mitochondrial Dysfunction in Cancer and Neurodegenerative Diseases: Spotlight on Fatty Acid Oxidation and Lipoperoxidation Products

In several human diseases, such as cancer and neurodegenerative diseases, the levels of reactive oxygen species (ROS), produced mainly by mitochondrial oxidative phosphorylation, is increased. In cancer cells, the increase of ROS production has been associated with mtDNA mutations that, in turn, seem to be functional in the alterations of the bioenergetics and the biosynthetic state of cancer cells. Moreover, ROS overproduction can enhance the peroxidation of fatty acids in mitochondrial membranes. In particular, the peroxidation of mitochondrial phospholipid cardiolipin leads to the formation of reactive aldehydes, such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), which are able to react with proteins and DNA. Covalent modifications of mitochondrial proteins by the products of lipid peroxidation (LPO) in the course of oxidative cell stress are involved in the mitochondrial dysfunctions observed in cancer and neurodegenerative diseases. Such modifications appear to affect negatively mitochondrial integrity and function, in particular energy metabolism, adenosine triphosphate (ATP) production, antioxidant defenses and stress responses. In neurodegenerative diseases, indirect confirmation for the pathogenetic relevance of LPO-dependent modifications of mitochondrial proteins comes from the disease phenotypes associated with their genetic alterations

Interleukin-1β levels predict long-term mortality and need for heart transplantation in ambulatory patients affected by idiopathic dilated cardiomyopathy

The prognostic stratification of patients with Idiopathic Dilated Cardiomyopathy (iDCM) is a difficult task. Here, we assessed the additive value of the evaluation of biomarkers of inflammasome activation and systemic inflammation for the long-term risk stratification of iDCM patients