ABSTRACT
The first European Rhinology Research Forum organized by the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) was held in the Royal Academy of Medicine in Brussels on 17th and 18th November 2016, in collaboration with the European Rhinologic Society (ERS) and the Global Allergy and Asthma European Network (GA2LEN). One hundred and thirty participants (medical doctors from different specialties, researchers, as well as patients and industry representatives) from 27 countries took part in the multiple perspective discussions including brainstorming sessions on care pathways and research needs in rhinitis and rhinosinusitis. The debates started with an overview of the current state of the art, including weaknesses and strengths of the current practices, followed by the identification of essential research needs, thoroughly integrated in the context of Precision Medicine (PM), with personalized care, prediction of success of treatment, participation of the patient and prevention of disease as key principles for improving current clinical practices. This report provides a concise summary of the outcomes of the brainstorming sessions of the European Rhinology Research Forum 2016.
Subject(s)
Asthma/therapy , Hypersensitivity/therapy , Rhinitis/therapy , Sinusitis/therapy , Europe , Humans , Physicians , Precision Medicine , ResearchABSTRACT
A piperidine phospholipid ((+/-)-2-[hydroxy] [1-octadecyloxycarbonylpiperidin-3-yl]methoxy-phosphinyl] oxy]-N,N,N, trimethylethaniminium hydroxide inner salt, SDZ 62-826) has been prepared that exhibited weak direct cytotoxicity and strong macrophage-induced cytotoxicity in vitro against a variety of murine and one human tumor cell lines. This compound was found to be as effective as ET-18-OCH3 and SRI 62-834, phospholipids with both strong direct and macrophage-induced cytotoxicity, in increasing survivors and reducing tumor volume when given either orally or intravenously in the mouse MethA fibrosarcoma model. These findings suggest that the macrophage-induced cytotoxicity exhibited by ET-18-OCH3 and other phospholipids may play an important role in this tumor model.
Subject(s)
Antineoplastic Agents/pharmacology , Phospholipid Ethers/pharmacology , Piperidines/pharmacology , Receptors, Cell Surface , Receptors, G-Protein-Coupled , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/therapeutic use , Binding, Competitive/drug effects , Cell Survival/drug effects , Fibroblasts/drug effects , Fibrosarcoma/drug therapy , Humans , Lethal Dose 50 , Macrophages/drug effects , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Neoplasm Transplantation , Phospholipid Ethers/chemical synthesis , Phospholipid Ethers/therapeutic use , Piperidines/chemical synthesis , Piperidines/therapeutic use , Platelet Activating Factor/metabolism , Platelet Aggregation Inhibitors/pharmacology , Platelet Membrane Glycoproteins/drug effects , Receptors, Platelet-Derived Growth Factor/drug effects , Sarcoma, Experimental/drug therapy , Tumor Cells, CulturedABSTRACT
66 suicide attempters were interviewed with the European Parasuicide Study Interview Schedule (EPSIS) and characteristics of persons under the age of 26 were compared with those over 26.82% of the young suicide attempters gave interpersonal conflicts as reasons for their suicide attempts while most older persons gave psychiatric disorders as reasons. The younger group also had significantly lower scores on the Beck Depression Inventory and the Hopelessness Scale. While younger suicide attempters rarely had sought help from their GP within the month preceding the attempt one third of the older group had done so. It is concluded that in order to understand the reasons why people attempt suicide a differential approach combining the concept of crisis as well as the concept of illness is needed. Helpers should know that young suicide attempters rarely show signs of clear psychiatric disorder but usually attempt suicide because they are unable to cope with interpersonal conflicts.
Subject(s)
Crisis Intervention , Patient Care Team , Suicide, Attempted/psychology , Suicide/psychology , Adolescent , Adult , Female , Humans , Male , Personality Inventory , Risk Factors , Suicide, Attempted/prevention & control , Suicide PreventionABSTRACT
Ether phospholipids have demonstrated both in vitro and in vivo activity against a wide variety of tumor cell lines. The known cyclic ether phospholipid, SRI 62-834, was used as the model to prepare eight novel phospholipids containing a cyclic ether. All of the compounds were as effective as ET-18-OCH3 in their ability to activate macrophage-induced cytotoxicity against the Abelson-8.1 tumor cell line but varied in their direct cytotoxic effects. One of the new compounds, SDZ 62-406, was selected for in vivo studies and showed oral and i.v. activity in the mouse MethA fibrosarcoma model in the same range as ET-18-OCH3. No correlation was found between the direct or macrophage-activated cytotoxicity and the ability of the compounds to inhibit or promote platelet-activating factor (PAF)-induced aggregation of human platelets.
Subject(s)
Antineoplastic Agents , Phospholipid Ethers/pharmacology , Animals , Cell Division/drug effects , Humans , In Vitro Techniques , Macrophages/drug effects , Mice , Molecular Structure , Phospholipid Ethers/chemical synthesis , Phospholipid Ethers/chemistry , Platelet Aggregation/drug effects , Sarcoma, Experimental/drug therapy , Tumor Cells, Cultured/drug effectsSubject(s)
Lung/physiology , Platelet Activating Factor/antagonists & inhibitors , Platelet Membrane Glycoproteins , Quinolinium Compounds/pharmacology , Receptors, G-Protein-Coupled , Animals , Dose-Response Relationship, Drug , Guinea Pigs , Lung/drug effects , Male , Receptors, Cell Surface/drug effects , Structure-Activity RelationshipABSTRACT
We investigated the relationship between the site of airway obstruction and the frequency dependence (FD) of lung acoustic impedance (ZL). The real (RL) and imaginary (XL) parts of ZL were measured by forced random noise in excised left pig lungs, before (base line) and after 1) no airway obstruction (controls, n = 10), 2) insufflation of 1-mm (B1, n = 5) or 2-mm (B2, n = 7) beads, and 3) partial reversible obstruction of lower lobar (LL) and then main-stem (MS) bronchus (n = 4). The beads caused both partial and total obstruction of airways with internal diameters of 2 mm (B1) and 2-6 mm (B2). Compared with base line, a negative FD of RL appeared from 4 to 10 Hz in LL, B1, and B2 obstructions. The FD of XL greater than 20 Hz increased in MS and LL obstruction exclusively and was the ZL feature that most clearly differentiated central from peripheral obstruction. In this experimental model, the anatomic limit distal from which obstruction no longer causes the "central" type of ZL change lies in airways with internal diameters notably greater than 2 mm.
Subject(s)
Airway Obstruction/physiopathology , Airway Resistance , Lung/physiology , Acoustic Impedance Tests , Animals , Disease Models, Animal , In Vitro Techniques , Lung/physiopathology , SwineABSTRACT
SRI 62-834, an analog of the antitumor agent ET-18-OCH3 in which the oxygen atom at carbon atom 2 has been incorporated into a five-membered heterocycle, has been prepared and evaluated as an antitumor agent. The compound exhibited good cytotoxicity in vitro against a variety of tumor cell lines and was as effective as ET-18-OCH3 given orally in the mouse Meth A sarcoma model. SRI 62-834 was shown to be an inhibitor of platelet-derived growth factor (PDGF), possibly at the receptor level, and platelet-activating factor (PAF) at the receptor level.
