A hybrid living/organic electrochemical transistor based on the Physarum polycephalum cell endowed with both sensing and memristive properties.

A hybrid bio-organic electrochemical transistor was developed by interfacing an organic semiconductor, poly(3,4-ethylenedioxythiophene) doped with poly(styrene sulfonate), with the Physarum polycephalum cell. The system shows unprecedented performances since it could be operated both as a transistor, in a three-terminal configuration, and as a memristive device in a two terminal configuration mode. This is quite a remarkable achievement since, in the transistor mode, it can be used as a very sensitive bio-sensor directly monitoring biochemical processes occurring in the cell, while, as a memristive device, it represents one of the very first examples of a bio-hybrid system demonstrating such a property. Our system combines memory and sensing in the same system, possibly interfacing unconventional computing. The system was studied by a full electrical characterization using a series of different gate electrodes, namely made of Ag, Au and Pt, which typically show different operation modes in organic electrochemical transistors. Our experiment demonstrates that a remarkable sensing capability could potentially be implemented. We envisage that this system could be classified as a Bio-Organic Sensing/Memristive Device (BOSMD), where the dual functionality allows merging of the sensing and memory properties, paving the way to new and unexplored opportunities in bioelectronics.

Infundibular septal defect with severe aortic regurgitation: a new surgical approach.

Aortic regurgitation associated with prolapse of an aortic cusp and an infundibular septal defect is caused by the lack of anatomical support for the aortic annulus by the conal septum. This fact is taken into consideration in the new surgical approach that we performed in 5 children 3 to 16 years of age with infundibular ventricular septal defect and severe aortic regurgitation. The ventricular septal defect is closed by a patch anchored to another patch through the prolapsed cusp. This second patch is pulled up with the prolapsed cusp and is then fixed in the aortic wall. In all 5 patients, all clinical signs of aortic insufficiency disappeared, and only minimal aortic regurgitation could be demonstrated by color Doppler mapping.

Balloon dilation of postsurgical subaortic obstruction.

Two children aged 10 and 5.5 years underwent balloon dilation for postsurgical subaortic obstruction. The outcome and the role of this procedure are discussed.

[Non-surgical closure of patent ductus arteriosus in children with the Rashkind double disk occluder]. / Chiusura non chirurgica del dotto arterioso pervio in età pediatrica con dispositivo di Rashkind a doppio ombrello.

Since the first clinical application of transcatheter closure technique for patent ductus arteriosus in children and infants in 1977 by Rashkind and Coll., this technique is routinely performed only in a few major Pediatric Cardiology Centers. We report our successful series which is the first of its kind both in Italy and in Southern Europe. The series included 11 children aged 1.6 to 10 years (mean age 4.5 years) all affected with patent ductus arteriosus (PDA). Subaortic stenosis (1) and ventricular septal defect with pulmonary stenosis (1) were associated anomalies. In all of the cases, after the standard percutaneous cardiac catheterization, the Mullins method was attempted to advance and deliver the Rashkind PDA double-disk occluder. Successful closure was accomplished in 10 while almost complete closure was achieved in the 11th. Normal Doppler flow pattern after the procedure confirmed the successful results. No complications occurred. Although our experience is limited, non-surgical PDA closure provided an excellent alternative to surgical procedure.

Evolving concepts in the management of congenital junctional ectopic tachycardia. A multicenter study.

We reviewed the records of 26 infants with congenital junctional ectopic tachycardia (JET) from seven institutions to examine the evolution in the management of this tachycardia that is difficult to treat. JET was defined electrocardiographically as an incessant tachycardia with normal QRS morphology and atrioventricular (AV) dissociation. The ventricular rate ranged from 140 to 370 beats/min (mean, 230 beats/min); 16 of 26 patients had cardiac failure. Treatment success was defined as a stable decrease in the rate of JET, below 150 beats/min; partial success was a significant decrease of JET rate with alleviation of symptoms. All patients received digoxin with no significant effect. Propranolol was given to 16 patients, with two successes and one partial success. Combinations of other conventional agents were used in 11 patients with two successes; 14 patients were treated with amiodarone, which resulted in eight successes and three partial successes; three patients died suddenly on medical treatment (amiodarone, one patient; propranolol, one patient; or amiodarone plus propranolol, one patient); sudden AV block was a possible cause and consequently, two later patients had pacemaker implantation as well as medical treatment. His catheter ablation was successfully performed twice but contributed to death in a newborn; three surgical His ablations were performed for intractable JET with two successes and one death. The overall mortality was 35%. Among survivors, treatment has been stopped without any complications in five patients ranging in age from 10 months to 8 years (mean, 3.5 years). It seems that amiodarone alone is the best drug for treatment of congenital JET; necessity for permanent pacing remains unsettled. His ablation should be reserved only for intractable JET.

Percutaneous balloon valvuloplasty of pulmonary valve stenosis, dysplasia, and residual stenosis after surgical valvotomy for pulmonary atresia with intact ventricular septum: long-term results.

Eight-six children (aged 20 days to 14 years, 20 under age 1 year) underwent 94 percutaneous balloon valvuloplasty for pulmonary valve stenosis. The patients were divided into three groups: typical pulmonary valve stenosis (71), pulmonary valve dysplasia (9), and residual stenosis after surgical valvotomy for pulmonary atresia with intact ventricular septum (PAIS) (6). Each of the three groups was divided into two subgroups. In the early cases, balloon catheters with diameter 10-20% exceeding pulmonary valve annulus were used and the drop of the gradient was 39.5%. In the later cases, balloon diameters 30-40% greater than the valve anulus or double balloons were used and a drop of 66.7% in the RV-PA pressure gradient was achieved. The dilation in patients with dysplastic valve and residual stenosis after surgical valvotomy for PAIS was less effective. Doppler echocardiography was the technique used to evaluate residual gradient. Six months to 4 years follow-up demonstrated a persistent decrease of the valve gradient.

Univentricular atrioventricular connection to a dominant left ventricle with a concordant ventriculo-arterial connection.

Double inlet left ventricle with concordant ventriculo-arterial connection, first described by Holmes, is an unusual cardiac malformation which includes a right-sided rudimentary right ventricle and, frequently, subpulmonary stenosis. We have now encountered six patients, aged 1 month to 13 years, with this basic combination. In 5 cases, cross-sectional echocardiography, using parasternal, apical and subcostal views was diagnostic. Subpulmonary stenosis was seen in two of them. The sixth case shown to have atresia of the left atrioventricular valve, a concordant ventriculo-arterial connection, a left-sided rudimentary right ventricle, mild subpulmonary stenosis and a right-sided aorta. The combination of the left atrioventricular valve, left-sided rudimentary right ventricle and a concordant ventriculo-arterial connection has not, to our knowledge, been previously reported. Cross-sectional echocardiography always provided the correct morphologic diagnosis.

Percutaneous balloon dilatation of stenotic truncal valve in a newborn.

We describe the use of percutaneous balloon angioplasty of a stenotic truncal valve in a newborn with a common arterial trunk. A 12 mm balloon catheter was chosen, this representing 80% of the diameter of the ventriculo-truncal junction. The peak systolic gradient dropped from 45 to 15 mm Hg. The procedure can avoid, or certainly delay, surgical treatment of the stenotic truncal valve.

Ebstein's malformation of the mitral valve in atrioventricular and ventriculoarterial concordance.

Clinical and pathological data of a full-term male newborn with Ebstein's malformation of the mitral valve are reported. Moderate cyanosis and progressive heart failure were present from birth and he died on the fourth day after birth, with clinical evidence of severe aortic coartaction. Necropsy revealed a severely dysplastic mitral valve, with anatomical features of Ebstein's anomaly, in the absence of corrected transposition but associated with aortic coartaction.

Mechanism of smooth muscle relaxation by tiropramide.

Experiments on rabbit isolated colon show that a carbachol-induced contraction is accompanied by a decrease in cAMP content of the smooth muscle. (+/-)-alpha-(Benzoylamino)-4-[2-(diethylamino)-ethoxy]-NN-di-propylbenzen-propanamid (tiropramide, CR 605), a new tyrosine derivative with antispastic properties, increases cAMP concentrations within the same dose range that produces smooth muscle relaxation with or without carbachol (0.1 microM). These effects are potentiated by 1 mM theophylline, a phosphodiesterase inhibitor. In a purified microsomal preparation from rabbit colon smooth muscle, corresponding to sarcoplasmic reticulum, tiropramide induced a dose-dependent increase Ca2+ binding in the presence of ATP and Mg2+. Tiropramide inhibited phosphodiesterase activity in rabbit colon homogenates in a range of doses about ten times that producing relaxation, cAMP content enhancement and increase Ca2+ binding to sarcoplasmic reticulum. The effects of tiropramide on the carbachol-stimulated rabbit colon in the presence of theophylline, indomethacin of PGE1 are more in agreement with an action of tiropramide as inhibitor of cAMP catabolism than as a result of a prostaglandin-mediated effect. These observations suggest that the smooth muscle relaxant activity of tiropramide arises from drug-induced increase of cAMP concentrations possibly because of inhibition of cAMP catabolism. This effect is accompanied by the binding to the sarcoplasmic reticulum of Ca2+, preventing its interaction with the contractile proteins of the smooth muscle. A direct effect of tiropramide-enhanced cAMP content on contractile proteins in the smooth muscle cannot be excluded.

[ATP effects on eccito-conduction and arterial pressure before and after block of the vagus. Haemodynamic and electrophysiologic study (author's transl)]. / L'azione dell'ATP sull'eccito-conduzione e sulla P.A. prima e dopo blocco del vago. Studio elettrofisiologico ed emodinamico.

In order to investigate the cardiovascular effects of ATP (15-30 mg) i.v. administration, 12 normal subjects, aged 27-55 yrs, were studied, during Arterial Pressure Monitoring and His Bundle Electrogram recording, using Sherlag's technique. ATP cardiovascular response was divided in the following four phases: Latency phase, Progressive Bra dyarrhythmic-Hypotensive, Maximal Inhibitor Phase, Tachyarrhytthmic Hypotensive Reflex Phase. Atropine (0.02-0.04 mg/Kg) i.v. injection did not significantly prevent ATP effects. Increasing dosage of atropine (0,06, pointed out a moderate competitive antagonism with ATP. These data suggest a possible direct action of ATP (purinergic receptors or direct membrane effect) but don't exclude an interaction with Parasympathetic system (probable purinergic neuromodulation).

Effects of antigastrin drugs on the interaction of 125I-human gastrin with rat gastric mucosa membranes.

A method for studying the interaction of 125I-human gastrin with a rat gastric mucosal membrane fraction is described, and the saturability, high affinity and reversibility of the preparations, as well as the correlation of pharmacological responses to antigastrin-drugs with the observed binding are discussed. Proglumide and other antigastrin drugs inhibit gastrin binding in a dose-dependent way, and their activities in such a system are well correlated with the "in vivo" antisecretory activities of these drugs.

HBsAg uptake by macrophages in vitro: an immunofluorescence study.

The uptake of HBsAg by in vitro cultured macrophages was studied by immunofluorescence method. Intracytoplasmic fluorescent particles appeared 3 h after the contact with HBsAg-positive serum, while after 24-48 h only a few cells contained these particles, which are probably destroyed within the cytoplasm.

The influence of some metabolic inhibitors on phagocytic activity of mouse macrophages in vitro.

The action of different metabolic inhibitors on phagocytosis by macrophages from mouse peritoneal exudate cultured in vitro was studied. The following metabolic inhibitors were tested: sodium iodoacetate, sodium fluoride, sodium fluoroacetate, sodium malonate, 2-4-dinitrophenol, sodium azide, ouabain and cycloheximide, all at the concentration of 10(-3) M. Iodoacetate caused a strong inhibitory effect on phagocytosis; this observation confirms that glycolysis is the main source of energy for the phagocytic process. On the contrary, fluoride, although it is an effective inhibitor of glycolysis, did not exert any effect. This difference may be explained by the fact that sodium fluoride blocks anaerobic glycolysis only in vitro at an unphysiological temperature (0 degrees C). Fluoroacetate and malonate, two compounds which interfere with the Krebs cycle, did not inhibit phagocytosis, but it is known that the Krebs cycle activity is poorly developed in the macrophagic cells. Sodium azide and 2-4-dinitrophenol, two inhibitors of oxidative phosphorylation, showed an effect on phagocytosis only after 3 h of contact with the cell cultures. Ouabain blocks Na+ and K+ transport across the plasma membrane and, probably, it inhibited phagocytosis by interfering with the movements of the cell membrane. Finally, the mode of action of cycloheximide on phagocytosis is uncertain. This compound inhibits the protein synthesis and, perhaps, it can act by preventing the renewal of the cell membrane.

Studies on the mechanism of action of protacine (CR 604), a new non-steroidal anti-inflammatory agent.

3'-(4-[2-(1-P-Chlorobenzoyl-5-methoxy-2-methyl-indol-3-yl-acetoxy)-ethyl]-piperazin-1-yl)propyl-4-benzamido-N,N-dipropyl-glutaramate(+/-)dimaleate (protacine, CR 604), a new non-steroidal compound active on experimental inflammation, in vitro inhibits prostaglandin synthesis from arachidonic acid and platelet aggregation. When administered p.o., it prevents ex vivo platelet aggregation and in vivo arachidonate-induced thrombosis in rabbits. The cAMP levels of rat leucocytes are significantly reduced after treatment in vivo with protacine, even under maximum PGE-mediated stimulation. These effects, the inhibition of the proteolytic activity of trypsin and the fibrinolytic properties evidenced on recalcified plasma clots, contribute to explain the anti-inflammatory activity of protacine.

Phagocytosis and cellular metabolism (a study on mouse and human macrophages in culture).

The uptake of foreign particles by mouse and human macrophages influenced by various metabolic inhibitors was examined in order to obtain further informations about the energy-dependent mechanisms which are involved in the phagocytic process. The inhibitors employed were iodoacetate, fluoroacetate, fluoride, malonate, sodium azide, 2-4-dinitrophenol, cycloheximide and ouabain. These substances were tested on monolayer cultures and the phagocytosis assay was performed by using zymosan suspension in the nutrient media. The quantitation of phagocytosis was obtained by the direct count of intracellular zymosan particles (immersion microscopy, 100x) and the results were evaluated and compared by biometrical analysis. The effects of these inhibitors on phagocytosis and their relation with the metabolic intracellular pathways are discussed.