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Background Conflicting results regarding the impact of left common pulmonary (LCPV) vein on clinical outcome of atrial fibrillation (AF) ablation with cryoballoon technology have been reported. In the present study, we sought to investigate the performance of the 28 mm cryoballoon advance (CB-A) on left common pulmonary vein (LCPV) in terms of post procedural outcome. Methods We systematically searched on PubMed and Cochrane library for the articles that compared the recurrence rate of AF after cryoballoon ablation between patients with four separate and distinct pulmonary vein ostia and with LCPV. Results A total of 5 studies with 1052 patients met our predefined inclusion criteria. Recurrence of AF after CB-A ablation was similar in both groups (Log OR 0.45; 95% CI: −0.03, 0.94; I=48%, p=0.08), Fig 1. Figure 1 Conclusion LCPV doesn't affect clinical outcome of AF ablation with cryoballoon technology.

In the present paper we describe the on-land field operations integrated in the TOMO-ETNA experiment carried out in June-November 2014 at Mt. Etna volcano and surrounding areas. This terrestrial campaign consists in the deployment of 90 short-period portable three-component seismic stations, 17 broadband seismometers and the coordination with 133 permanent seismic station belonging to Italy’s Istituto Nazionale di Geofisica e Vulcanologia (INGV). This temporary seismic network recorded active and passive seismic sources. Active seismic sources were generated by an array of air-guns mounted in the Spanish oceanographic vessel “Sarmiento de Gamboa” with a power capacity of up to 5200 cubic inches. In total more than 26,000 shots were fired and more than 450 local and regional earthquakes were recorded. We describe the whole technical procedure followed to guarantee the success of this complex seismic experiment. We started with the description of the location of the potential safety places to deploy the portable network and the products derived from this search (a large document including full characterization of the sites, owners and indication of how to arrive to them). A full technical description of the seismometers and seismic sources is presented. We show how the portable seismic network was deployed, maintained and recovered in different stages. The large international collaboration of this experiment is reflected in the participation of more than 75 researchers, technicians and students from different institutions and countries in the on-land activities. The main objectives of the experiment were achieved with great success. © 2016 by the Istituto Nazionale di Geofisica e Vulcanologia. All rights reserved.

Synopsis Some cyclic ketals derived from 2-adamantanone were obtained in excellent yields by microwave activation under solvent-free conditions, as a ‘green chemistry’ procedure. A number of experiments were performed to evaluate the most efficient catalytic conditions. The best results were obtained using a simple heterogeneous mixture of reagents and p-toluenesulphonic acid as the catalyst, without any solvent or support. The data are reported and compared with those obtained by other microwave-mediated syntheses or by classical method. In order to check the possible intervention of non-thermal microwave effects, the best experiment in ‘dry media’ was carried out with considerable lower yield by conventional heating, in a thermostated oil bath, under the same conditions as under microwaves (time, temperature and vessel). All the synthesized compounds were tested for their olfactive character and for a potential cosmetic use. The odour evaluation is reported. Resume Des acetals cycliques derives de la 2-adamantanone ont ete obtenus sous irradiation microonde sans solvant avec d'excellents rendements selon un procede de ‘chimie verte’. Un certain nombre d'experiences ont ete realisees pour optimiser les conditions de reaction. Les resultats obtenus par simple melange heterogene des reactifs et de l'acide p-toluenesulphonique 10% (p/p) comme catalyseur ont ete decrits et compares avec ceux obtenus avec les autres procedes, sous irradiation microonde ou par chauffage traditionnel. Dans le but de mettre en evidence l'eventuelle intervention d'effets specifiques (non-purement thermiques) des microondes, la meilleure reaction obtenue en ‘milieu sec’ a ete effectuee, avec des rendements nettement plus faibles, dans les memes conditions (temps et temperature), par chauffage classique. Les proprietes olfactives de tous les produits obtenus ont ete determinees pour evaluer une possible utilization cosmetique.

Aims Radiofrequency catheter ablation is effective at terminating ventricular tachycardia, but the overall clinical role of the technique in patients with a prior myocardial infarction is still debated, due to the uncertainties of the long-term reliability of the procedure. The purpose of this study was to prospectively investigate the relationship between acute results obtained by catheter ablation and long-term outcome in a homogeneous population of patients with post-myocardial infarction ventricular tachycardia. Methods and Results One hundred and twenty-four consecutive patients with recurrent, drug-refractory, haemodynamically tolerated ventricular tachycardia were included in the study. This population accounted for 30% of the patients with post-myocardial infarction ventricular tachycardia admitted between April 1992 and September 1997 to the investigating centres. The ablation was successful in eliminating sustained ventricular tachycardia in 91 of them (73%); a partial result was obtained in 21 (17%) and failure in 12 (10%). Low dose amiodarone and/or beta-blockers were maintained in 86% of the patients. Over a median follow-up of 41·5 months (interquartile range 30·5–59·5 months), there were 15 deaths (12%), three of which were sudden (2·4%); the 12 remaining patients died of heart failure. Event-free survival analysis showed a significally lower ventricular tachycardia recurrence rate in patients with a successful procedure as compared to those with failure or a partial result (19% vs 53% at one year and 27% vs 60% at 3 years, P =0·003). A repeat procedure was performed in 15 patients with early recurrences and was followed in all by long-term success. Of those who submitted to a second procedure, 93/124 patients (75%) are free of ventricular tachycardia recurrences. An implantable cardioverter-defibrillator (ICD), following procedure failure, was implanted in 13 patients (11%) of the study population. Conclusions Radiofrequency catheter ablation is effective in a wide population of patients with recurrent tolerated ventricular tachycardia, with very low sudden death and cardiac mortality rates over the long-term. Persistent ventricular tachycardia inducibility after catheter ablation requires an ICD implant and/or repeat ablation.

La domanda di acqua crescerà a causa dell’incremento della popolazione, dell’industrializzazione e dell’urbanizzazione. In rapporto alle riserve d’acqua è stato pertanto introdotto il nuovo concetto di “stress dell’acqua”. Esso misura la proporzione d’acqua prelevata sul totale delle risorse rinnovabili. Poiché tali risorse stanno progressivamente diminuendo, sono necessari nuovi strumenti e nuove misure per ridurre il consumo dell’acqua. L’articolo illustra la ricerca svolta presso la Scuola di Architettura della Oxford Brookes University sulla carenza dell’acqua in alcune aree del mondo e sull’incremento del suo valore economico.

Aim This study reports on the results and safety of a simplified method of trans-septal catheterization for radiofrequency catheter ablation of cardiac arrhythmias. Method and Results Over 5 years, 411 patients underwent trans-septal catheterization for radio frequency catheter ablation: 388 patients had a left-sided accessory pathway, 19 a left-sided focal atrial tachycardia, two atrial fibrillation and two post-infarction ventricular tachycardia. All but one patient with ventricular tachycardia underwent elective trans-septal catheterization. In the absence of a patent foramen ovale, puncture of the atrial septum was performed by using an 8F Mullins sheath and a Brockenbrough needle, according to the simplified method described in this paper. Trans-septal catheterization was accomplished in 383/388 patients (98.7%); in 41 patients a second trans-septal catheterization and radio frequency catheter ablation was performed for initial failure or recurrence. Radiofrequency catheter ablation was successful in 96% of accessory pathway patients, 90% of atrial tachycardia patients, in both patients with atrial fibrillation and in both patients with ventricular tachycardia. No complication related to trans-septal catheterization was observed. Conclusion In experienced hands and according to the method described in this paper, the elective use of transseptal catheterization for radiofrequency catheter ablation in a large cohort of patients with cardiac arrhythmias is feasible, safe and allows successful ablation in the vast majority of the patients.

Low-temperature magnetic force microscopy has been used to visualize spontaneous formation of vortex-antivortex pairs in hybrid ferromagnet/superconductor systems. Vortex-antivortex pairs are induced by the periodic stray field of the ferromagnet. We find general equilibrium conditions for which spontaneous vortex-antivortex pairs are formed during zero-field cooling of the hybrid ferromagnet/superconductor bilayers. Vortices can be generated by the ferromagnet domains in the absence of an external field and they are thermodynamically stable for values of the stray field and the period of the stripe magnetic domains that exceed a certain threshold.

The fabrication and characterization of superconducting and ferromagnetic heterostructures is an open field due to the fundamental interest in the physics of the coexistence of these two competing orders and their possible applications in the spintronics industry. In this paper we present structural, electrical and magnetic characterization for the single La(0.7)Ca(0.3)MnO(3) (LCMO) thin layer, La(0.7)Ca(0.3)MnO(3)/YBa(2)Cu(3)O(7-x) (LCMO/YBCO) bilayers and the LCMO/YBCO/LCMO trilayers. In particular, we show a detailed magnetic characterization of the LCMO thin films by means of low temperature magnetic force microscopy. We discuss the different dynamics of the magnetic domains observed, depending on the substrate induced strain and on the film thickness.

We have realized highly epitaxial La0.7Ca0.3MnO3/YBa2Cu3O7−x/La0.7Ca0.3MnO3 (LCMO/YBCO/LCMO) trilayers grown on SrTiO3 (001) oriented single crystal substrates by dc sputtering technique. Transport and magnetic measurements indicate that the superconducting critical temperature is strongly suppressed while the Curie temperature is higher than in a single LCMO film. These results are discussed in terms of interaction between superconductivity and magnetism and strain relaxation of the LCMO layer.

Patients submitted to cardiac surgery for correction of congenital or acquired heart diseases may subsequently experience several types of atrial tachyarrhythmias [1–4]. Most of these are macroreentrant atrial tachycardias strictly related to the presence of scars, prosthetic materials, or conduits and have therefore been named “incisional” or “scar-related” atrial tachycardias. Although their electrocardiographic characteristics may resemble those of atrial flutter, slight differences in P wave morphology and tachycardia cycle length are present and should be identified in order to formulate the correct diagnosis. “Incisional” atrial tachycardia may occur at widely variable times after the operation, most frequently in patients submitted to septal atrial defect repair and Fontan or Mustard procedures for tricuspid atresia or great vessel transposition correction, respectively. The true prevalence of these arrhythmias is unknown; small retrospective series reported a prevalence of 32–57% after the Fontan procedure [4, 6, 7] and about 15% after the Mustard operation [3, 8].

The current goal of radiofrequency catheter ablation of supraventricular tachycardias is to cure a large cohort of patients with a primary success rate close to 100% and a complication and recurrence rate close to 0%. In this setting, the ablation of the atrioventricular (A-V) accessory pathway in the triangle of Koch may still represent a grey area, since the strict anatomical relationship between the bypass tract and the A-V node-His bundle may affect the feasibility and safety of the procedure. Consequently, the only rationale for successful ablation with no complication in this area relies on the assumption that the accessory pathway is more sensitive to radiofrequency energy delivery than the normal A-V conduction system [1]. The risk of damaging the normal A-V conduction pathway and of inducing a complete A-V block requiring a permanent pacemaker has been pointed out by both early [2, 3] and recent [4–6] reports, although successful and safe ablation has been described in limited series of cases [7, 8], even with “para-hissian” accessory pathways [1]. Moreover, in the risk/benefit ratio of ablation of by-pass tracts in the Koch’s triangle one must consider not only failure and the risk of permanent complete A-V block, but also the theoretical possibility of creating an incessant reentrant circuit by partially damaging both the accessory pathway and the A-V node conduction.

In 1997 almost the entire population with arrhythmias related to the presence of an anomalous AV pathway (AP) is treated successfully by radiofrequency catheter ablation (RF-CA) without excessive difficulty, but in some cases a very prolonged procedure or a second session or both are required to obtain a successful outcome [1].

The synthesis of some N,N-disubstituted 1-amino-2-phenyl-3H,12H-naphtho[1,2-b]pyrano[2,3-d]pyran-3-ones 4, by reaction of phenylchloroketene with a series of N,N-disubstituted 3-aminomethylene-2,3-dihydro-4H-naphtho[1,2-b]pyran-4-ones, followed by dehydrochlorination in situ of the primary adducts with DBN, is described. Some compounds 4 showed antiarrhythmic and analgesic activities.

The synthesis of nine quaternary ammonium iodides derived from omega-dialkylaminoethyl ethers of 5-(arylmethylene)-1,3, 3-trimethyl-2-oxabicyclo[2.2.2]octan-6-hydroxyimines, as potential cosmetic ingredients, is described. They are routinely prepared starting from cineole aminoethers by reaction with iodoethane and their physics-chemical data are reported. These substances were studied for their UV absorption and three of these compounds were also submitted to microbiological assays on five test organisms. The substances have their UV absorption maxima at 284-321 nm, and one compound is active on Staphylococcus aureus, Streptococcus faecalis and Candida albicans. These preliminary findings seem to indicate that some of these compounds could be considered as potential UV sunscreens; one compound, having a moderate antimicrobial activity, could be considered a potential active compound in cosmetics as deodorants, toothpastes, mouthwashes and other oral care products.

Among patients (pts) with atrioventricular accessory pathway (AP), some cases show wide complex arrhythmias with different QRS morphology. In a subset of these pts, an atrioventricular reentrant tachycardia with left bundle branch block morphology (LBBBM-AVRT) is observed. The aim of this study is: 1) to identify the substrate and the reentrant mechanism underlying the LBBBM-AVRT in pts undergoing radiofrequency catheter ablation (RFCA) of AP; 2) to report the results achieved by RFCA of the identified substrate.From May 1991 to April 1993, among the 168 pts who underwent RFCA for arrhythmias related to an AP, 12 (7.1%) (8M, 4F, mean age 35 +/- 21 yrs, range 8-65) showed LBBBM-AVRT, alone or associated with other arrhythmias. Pts, in whom LBBBM was rate-related during orthodromic AVRT, were excluded from this study. During sinus rhythm, QRS complex was normal in 1 pt, while ventricular preexcitation due to a right-sided Kent bundle (KB) was present in 4 pts; among the other pts without preexcitation, 3 showed left bundle branch block (LBBB) and 4 right bundle branch block. In 2 pts, an Ebstein disease was present, while dilated cardiomyopathy was observed in another. The LBBBM-AVRT was iterative in 3 pts and in 6 pts it was the only arrhythmia observed; the mean tachycardia cycle length was 341 +/- 49 msec (range 250-428). In 1 pt, the LBBBM-AVRT was induced only after successful RFCA of a right-sided AP, responsible for orthodromic AVRT. All pts underwent diagnostic electrophysiologic study and RFCA during the same session.In 6/12 pts one or more KBs were observed, while in the remaining 6 an atrioventricular or atriofascicular "Mahaim like" bundle (MB) was present; the patient population was divided into 4 groups on the basis of the substrate and the reentrant mechanism responsible for LBBBM-AVRT. In Group 1, 3 pts were included: the LBBBM-AVRT was an orthodromic AVRT involving the nodal conduction antegradely (showing LBBB also during sinus rhythm) and a left-sided unidirectional KB, retrogradely. In all the 3 pts, the LBBBM-AVRT was iterative and not controlled by antiarrhythmic agents and RFCA of the KB abolished the arrhythmia. Two further pts were included in Group 2: in these pts with multiple bilateral KBs, the LBBBM-AVRT involved a right-sided KB antegradely and a left-sided one, retrogradely. In these 2 pts both KBs were successfully ablated. In 1 pt, considered in Group 3, the LBBBM-AVRT was sustained by an antidromic circuit involving a right-sided KB antegradely and the nodal conduction retrogradely; in this pt the KB was completely interrupted after two RFCA procedures. The remaining 6 pts with MB were included in Group 4: at least one associated electrophysiologic abnormality was present in all (dual A-V nodal pathway in 4/6 and a right-sided KB in 4/6); Ebstein disease was also observed in 2 of them. In 4/6 pts the LBBBM-AVRT was an antidromic tachycardia involving the nodal conduction retrogradely and the MB antegradely; in 3/4 pts the MB was ablated (along with a nodal reentrant tachycardia in 1 pt), while in the remaining pt in whom the non-sustained LBBBM-AVRT, inducible only after RFCA of a right-sided KB, had not been clinically observed, no further ablation was mandatory. In the remaining 2 pts in Group 4, the LBBBM-AVRT was due to the involvement of MB in other arrhythmias such as an AVRT due to a right-sided KB and a "slow-slow" nodal reentrant tachycardia, respectively; the LBBBM-AVRT were abolished by RFCA of these two underlying arrhythmias. All pts are asymptomatic during a 7.9 +/- 6.9 months follow-up.The LBBBM-AVRT is observed in a minority (7.1%) of the cases referred for RFCA of AP. (ABSTRACT TRUNCATED)

An investigation was performed in order to evaluate the presence as polluting agents of chlorinated hydrocarbons in complex cosmetic matrices. Chlorinated pesticides, such as Dieldrin, alpha-Endosulfan, Heptachlor, alpha-Hexachlorocyclohexane (alpha-HCH), Lindane and polychlorinated biphenyls (PCBs) such as Aroclor 1254, were studied in two ingredients and in three finished commercial products. The analytical procedure consists of extraction, extract clean-up, separation of pesticides from PCBs, identification and measurement. Analysis was performed by gas chromatography with electron-capture detector, identity of pesticides and PCBs was assumed from retention times and quantification was based on peak-height measurements.

In some cases undergoing radiofrequency catheter ablation (RFCA) of accessory pathway (AP), a Mahaim-like right-sided atrioventricular AP (M-AP) showing slow and decremental conduction is observed. Among 200 consecutive patients referred to our Institution up to September 1993 for arrhythmias related to an AP and undergoing RFCA, 8 patients (6 males, 2 females; mean age 24 +/- 8 years, range 8-35) showed a M-AP. Seven out of 8 patients have been complaining episodes of palpitation for 13 +/- 7 years (range 1-20), while 1 subject was an asymptomatic young athlete. In 2/8 patients an Ebstein disease (Eb) was present and they had previously undergone right-sided Kent bundle (Kb) ablation elsewhere. During sinus rhythm, QRS was normal in 1 patient, while it showed ventricular preexcitation due to right-sided Kb in 3 patients and right bundle branch block in another 4 patients. A left bundle branch block morphology (LBBBM) reentrant tachycardia (RT) was observed in 7 patients (in 1, only after RFCA of a right-sided Kb); 3 showed also orthodromic RT. In the asymptomatic young athlete, a preexcitation atrial fibrillation with very rapid ventricular response was inducible. All patients underwent diagnostic electrophysiologic (EP) study and RFCA in the same session. In 2/8 patients M-AP was manifest only after right-sided Kb RFCA. In all patients, associated EP abnormalities were noted: in 5/8 patients a dual A-V node pathway was present and in 5/8 patients 6 right-sided Kbs were associated. Patients have been divided in 3 groups, according to the mechanism involving the M-AP in the RT. In the 2 Group I patients showing also Eb, antidromic LBBBM RT and orthodromic RT involving the M-AP anterogradely and retrogradely, respectively, were observed; both arrhythmias were abolished by ablating the M-AP. The 3 Group II patients showed only antidromic LBBBM RT, involving a fast A-V node pathway retrogradely; also in these patients, the M-AP was the target of RFCA. This was performed only in 1 patient, in whom A-V node RT was also observed and ablated after RFCA of M-AP; as to the other 2 patients, in 1 the ablation of M-AP was not considered mandatory, since it was responsible for inducible not sustained LBBBM RT observed only after RFCA of a Kb in the same EP session, while in the other it was not possible because of a prolonged traumatic conduction block through the M-AP.(ABSTRACT TRUNCATED AT 400 WORDS)

In patients with supraventricular tachyarrhythmias refractory to medical therapy, transcatheter ablation (TA) is necessary. From January 1990, in 27 patients with nodal tachycardia and 6 with atrial fibrillation or flutter, referred to our institution for electrophysiologic evaluation, TA by radiofrequency (RF) was performed, respectively for atrioventricular (AV) junction modulation and total AV junction ablation. In all these cases, a total refractoriness to several antiarrhythmic drugs alone or in combination had been observed. The RF current, generated by the Osypka HAT 100 device, was administered through a tripolar USCI 7 F catheter. The ideal site for energy delivery was defined on the basis of a mapping, performed in the AV junction area to find out the most premature retrograde atrial activation. Local atrial activation time was evaluated during nodal tachycardia by delivering a premature ventricular extrastimulus to discover the atrial deflection from the ventricular one. In the selected area, 5 applications (range 1-12) of 20-25 W power RF energy for 5-30 s were delivered on average. A complete prevention of nodal tachycardia was achieved in 26/27 patients (96.2%). Only in 2 patients (7.4%) a total AV block was induced. The pre- and post-procedure values are as follows: AH = pre 71 +/- 18, post 113.2 +/- 53; HV = pre 46.4 +/- 8, post 48 +/- 7; anterograde Wenckebach point = pre 352 +/- 56, post 389 +/- 91; retrograde Wenckebach point = pre 338 +/- 75, post 419 +/- 61. In 13/27 cases the AH interval was normal after RF application. The retrograde conduction was worsened in all patients and totally abolished in 12/27.(ABSTRACT TRUNCATED AT 250 WORDS)

In patients with nodal tachycardia refractory to medical therapy, transcatheter or surgical ablation is necessary. From January 1989 to December 1990, in 26/42 patients with nodal tachycardia, referred to our institution for electrophysiologic evaluation, transcatheter ablation by radiofrequency (20 patients) or surgical ablation by perinodal cryo (6 patients) was performed. In all these cases, a total refractoriness to several antiarrhythmic drugs alone or in association had been observed. The radiofrequency current, generated by the Osypka HAT 100 device, was administered through a tripolar USCI 7 F catheter. The ideal site for energy delivery was defined on the basis of a mapping, performed in the A-V junction area. In order to find out the most premature retrograde atrial activation, the following areas were explored: right bundle, atrial His bundle, peri-nodal region, proximal His bundle and coronary sinus ostium. Local atrial activation time was evaluated during nodal tachycardia by delivering a premature ventricular extrastimulus to discover the atrial deflection from the ventricular one. In the selected area, 5 applications (range 1-12) of 20-25 W power radiofrequency energy for 5-30 s were delivered on average. A complete prevention of nodal tachycardia was achieved in 18/20 patients (90%). Only in 2 patients a total A-V block was induced. The pre- and post-procedure values are as follows: AH: pre 71 +/- 19, post 113.6 +/- 50; HV: pre 45.5 +/- 8, post 47 +/- 6; aWP: pre 353 +/- 57, post 391 +/- 87; rWP: pre 322 +/- 58, post 411 +/- 58. In 10/18 cases the AH interval was normal after radiofrequency application.(ABSTRACT TRUNCATED AT 250 WORDS)

The synthesis of 5-[4-(omega-dialkylaminoalkoxy)phenylmethylene]- 1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ones 3 by reaction of some 4-(omega-dialkylaminoalkoxy)benzaldehydes with (+)-1,3,3-trimethyl-2-oxabicyclo [2.2.2]octan-6-one in the presence of sodium methoxide is described. Some aminoethers 3 showed platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as weak antiarrhythmic activity in rats and moderate infiltration anesthesia in mice.

The synthesis of esters derived from 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-endo-ol, obtained by LiAlH4 reduction of 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-one, is described. Some of these esters showed an appreciable antiarrhythmic activity in rats, as well as moderate hypotensive and local anesthetic activities in rats and mice, respectively.

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-pyrano[3,2-d]-1-benzoxepin-2 -ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzoxepin-5(2H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a platelet antiaggregating activity in vitro slightly superior to that of acetylsalicylic acid, as well as weak local anesthetic and antiinflammatory activities in mice and rats, respectively.

The synthesis of some N,N-disubstituted 4-amino-6,7-dihydro-3-phenylbenzo[6,7]cyclohepta[1,2-b]pyran-2(5H) -ones by reaction of phenylchloroketene with a series of N,N-disubstituted 6-aminomethylene-6,7,8,9-tetrahydro-5H-benzocyclohepten-5-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as a weak local anesthetic activity in mice and antiinflammatory activity in rats.

The synthesis of omega-dialkylaminoalkyl ethers 3 by the reaction of some 5-(arylmethylene)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6- hydroxyimines as sodium salts with the appropriate omega-chloroalkyldialkylamine in DMF solution is described. Some aminoethers 3 showed strong platelet antiaggregating activity in vitro superior to that of acetylsalicylic acid, as well as weak antiarrhythmic activity in rats and moderate infiltration anesthesia in mice.

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3,8-diphenyl-2H-pyrano[2,3-f]quinazolin- 2-ones by the reaction of phenylchloroketene with a series of N,N-disubstituted (E)-6-aminomethylene-7,8-dihydro-2-phenylquinazolin-5(6H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. The methylbenzylamino and diphenylamino derivatives showed platelet antiaggregating activity in vitro superior to that of acetylsalicylic acid. The 1-pyrrolidinyl derivative showed appreciable local anesthetic activity in mice, whereas the whole series of compounds exhibited weak antiinflammatory activity in rats.

The synthesis of some N,N-disubstituted 4-amino-3-phenyl-2H,5H-[1]benzothiopyrano [4,3-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted 3-aminomethylene-2,3-dihydro-4H-1-benzothiopyran-4-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. Some of these compounds showed a strong platelet antiaggregating activity in vitro, superior to that of acetylsalicylic acid.

The synthesis of some N,N-disubstituted 4-amino-5,6-dihydro-3-phenyl-2H-[1]benzothiepino [5,4-b]pyran-2-ones by reaction of phenylchloroketene with a series of N,N-disubstituted (E)-4-aminomethylene-3,4-dihydro-1-benzothiepin-5(2H)-ones, followed by dehydrochlorination of the primary adducts with DBN, is described. The 4-methylphenylamino derivative showed a local anesthetic activity in mice superior to that of lidocaine and the 4-morpholino derivative showed an antiarrhythmic activity in rats comparable to that of quinidine.

A series of N,N-dialkyl 5-trans-carbamoyloxy-1,2,3,3-tetramethyl-2-azabicyclo [2,2,2]octanes was prepared by reaction of 1,2,3,3-tetramethyl-2-azabicyclo [2,2,2]octan-5-trans-ol with phosgene, followed by aminolysis of the resulting chlorocarbonate with aliphatic secondary amines. 5-Chloro-1,2,3,3-tetramethyl-2-azabicyclo [2,2,2] octane (cis/trans mixture) was isolated as by-product of the reaction. A number of urethanes showed antiarrhythmic activity in guinea pigs and mice, as well as surface anesthesia in rabbits and infiltration anesthesia in mice, superior or similar to lidocaine. The circulatory, cardiac and respiratory effects in dogs and hens are also described.

The synthesis of a series of amides derived from benzonorbornen-2-endo-amine is described. Some compounds showed a remarkable infiltration anesthesia in mice and a moderate hypotensive activity in rats. Antiarrhythmic activity in mice is also reported.

By reaction of secondary amines with 3-hydroxymethylene-exo-5,6-trimethylenenorbornan-2-one, synthesized from exo-5,6-trimethylenenorbornan-2-one and sodium/ethyl formate, a series of N,N-disubstituted 3-aminomethylene-exo-5,6-trimethylenenorbornan-2-ones has been obtained. These compounds gave N,N-disubstituted 3-aminomethyl-exo-5,6-trimethylenenorbornan-2-ones by LiAlH4 or catalytic reduction. Starting from the same alpha-hydroxymethyleneketone, pyrazole derivatives (V) and (VI) have been also synthesized; the former showed anticonvulsant activity in mice.

A new series of aliphatic and aromatic esters of 1,2,3,3-tetramethyl-2-azabicyclo[2.2.2]octan-5-trans-ol is described. A number of these compounds showed antiarrhythmic activity in guinea pigs and mice, as well as surface anesthesia in rabbits and infiltration anesthesia in mice, superior or similar to that of lidocaine. The circulatory, cardiac and respiratory effects in dogs and hens are also described.

Reaction of N,N-disubstituted 2-carboxyamido-2,6,6-trimethyltetrahydropyran-5-carboxylic acids with diphenyl phosphorazide in the presence of triethylamine and benzyl alcohol gave N,N-disubstituted 5-benzyloxycarbonylamino-2-carboxyamido-2,6,6-trimethyltetrahydr-pyrans, which in turn yielded N,-disubstituted 2-aminomethyl-5-methylamino-2,6,6-trimethyltetrahydropyrans by LiA1H4 reduction. 5-Benzyloxycarbonylamino-2-carboxypyrrolidino-2,6,6-trimethyltetrahydropyran gave 5-amino-2,6,6-trimethyl-2--pyrrolidinomethyltetrahydropyran by hydrogenolysis followed by LiA1H4 reduction. Among the amides prepared from the latter, the diphenylacetic acid amide showed antiarrhythmic and local-anesthetic activity.