The otoliths of the antarctic teleost Trematomus bernacchii: scanning electron microscopy and X-ray diffraction studies.

The authors studied the otoliths of the Nototheniid Trematomus bernacchii with scanning electron microscopy and X-ray diffraction analysis. Results obtained reveal that three otoliths are present: a large sagitta, a lapillus and a fragile asteriscus. Their sensorial faces appear finely decorated as shown by scanning electron microscopy (SEM). The sagitta and the lapillus are aragonitic while the asteriscus is vateritic, as demonstrated by X-ray diffraction.

In vitro evaluation of the mutagenic and carcinogenic power of high purity zirconia ceramic.

Tetragonal zirconia polycrystal (TZP) is a new interesting ceramic for the manufacture of medical devices. Its wide use in orthopedic and odontoiatric implants was limited till now by the high chemical and radiochemical impurities of the raw materials. Purification processes now available allow to obtain high purity ceramic grade powders suitable for TZP ceramics manufacture, even if their possible mutagenic and transforming effects are still unclear. The aim of this work is to study in vitro the mutagenic and oncogenic effects of a new zirconia ceramic stabilized by yttria (Y-TZP). This ceramic was sintered from high purity powders obtained by a process developed under a project carried out within the Brite EuRam programme. For comparison, ceramics made from unpurified zirconia powder were also tested. Fibroblasts irradiated by a linear accelerator were used as positive control. The results obtained show that Y-TZP ceramic does not elicit either mutagenic or transforming effect on C3H/10T(1/2) (10T(1/2)) cells and demonstrate that ceramic from high purity powders can be considered suitable for biomedical applications from the point of view of the effects of its radioactive impurity content.

Y-TZP ceramics for artificial joint replacements.

Due to their excellent mechanical properties, Yttria-stabilized Tetragonal Zirconia Polycrystal ceramics (Y-TZP) are used in ball heads for Total Hip Replacements. It is known that Y-TZP materials may show strength degradation due to ageing or to hydrothermal treatment. Also high wear of UHMWPE sockets coupled to steam sterilized Y-TZP ball heads after a short implantation period was recently reported. This effect may be related to ball head surface phase transformation, due to corrosive attack. The aim of this study is the evaluation of Y-TZP ceramics stability. Y-TZP made out of Yttria coated powders were aged at 140 degrees C under 0.2 MPa water pressure, in Ringer's solution at 37 degrees C, in NZW rabbits. Samples made out Yttria coated powders show lower strength degradation than samples made out coprecipitated powders, and UHMWPE discs coupled to Y-TZP rings made out coated powders do not show increase in wear after repeated sterilization cycles of the ceramic rings.

Preparation and pharmacological activity of some 1-lupinylbenzimidazoles and 1-lupinylbenzotriazoles.

Twelve new 1-lupinyl-benzimidazole and 1-lupinyl-benzotriazole derivatives were prepared and, together with some previously described analogues, were tested for analgesic (hot plate test), antiinflammatory (against carrageenan edema), diuretic and antihypertensive (in spontaneously hypertensive rats) activities. Several compounds exhibited a good degree of activity in one or in more than one areas.

5-substituted 4-isoxazolecarboxamides with platelet antiaggregating and other activities.

The synthesis of a series of 5-substituted 4-isoxazolecarboxamides by reaction of eight 5-substituted 4-isoxazolecarbonyl chlorides with pyrrolidine, piperidine, morpholine and 4-trifluoromethylaniline is described. Some of these amides showed platelet antiaggregating activity in vitro slightly inferior to that of acetylsalicylic acid, as well weak antiinflammatory, analgesic and antipyretic activities in rats and mice.

Esters of 7-(diphenylmethylene)bicyclo[2.2.1]heptan-2-endo-ol with antiarrhythmic and other activities.

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.

5-[4-(omega-dialkylaminoalkoxy)phenylmethylene] -1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ones with platelet antiaggregating and other activities.

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.

2H-pyrano[3,2-d]-1-benzoxepin derivatives with platelet antiaggregating and other activities.

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.

Benzo[6,7]cyclohepta[1,2-b]pyran derivatives with platelet antiaggregating and other activities.

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.

3,5-Diphenyl-1H-pyrazole derivatives. VIII. N-substituted 3-(4-hydroxy-3,5-diphenyl-1H-pyrazol-1-yl)-propanamides, -propanamines and 2-(4-hydroxy-3,5-diphenyl-1H-pyrazol-1-yl)ethanamines with platelet antiaggregating, hypotensive, antiarrhythmic and other activities.

The synthesis of N,N-disubstituted 3-(4-hydroxy-3,5-diphenyl-1H-pyrazol-1-yl)-propanamides and -propanamines, starting from 4-benzoyloxy-3,5-diphenyl-1H-pyrazole, and of N-substituted 2-(4-hydroxy-3,5-diphenyl-1H-pyrazol-1-yl)ethanamines, starting from 4-acetoxy-1-(2-hydroxyethyl)-3,5-diphenyl-1H-pyrazole, is described. Some of the above compounds showed a platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid, as well as moderate hypotensive, antiarrhythmic, local anesthetic, sedative and antiinflammatory activities in rats and mice.

3,3-disubstituted 1-acyl-1-phenylthioureas with platelet antiaggregating and other activities.

This paper describes the synthesis in excellent yields of N-acyl-N-phenyl-1-pyrrolidine-, 1-piperidine-, 4-morpholine-, 1,2,3,4-tetrahydro-1-quinoline-, 1,2,3,4-tetrahydro-2-isoquinoline-, 10-phenothiazine- and 2,2'-dipyridylamine-carbothioamides by reaction of the corresponding 3,3-disubstituted 1-phenylthioureas, prepared in situ from the appropriate secondary amine and phenylisothiocyanate, with aromatic or heterocyclic acyl chlorides in pyridine solution or, in lower yields, in anhydrous dimethylformamide or pyridine solution in the presence of sodium hydride. N-phenyl-1-pyrrolidinecarbothioamide prepared in situ reacted with iodomethane in dimethylformamide solution and in the presence of sodium hydride to give excellent yield of the S-methyl derivative, namely the methyl ester of N-phenyl-1-pyrrolidinethiocarboximidic acid. Some of the above compounds, in particular the phenothiazine acylthioureas, showed platelet antiaggregating activity in vitro superior or comparable to that of acetylsalicylic acid; moreover, some acylthioureas exhibited moderate hypoglycemic activity in rats and competitive antiacetylcholine and H1-antihistaminic effect in vitro inferior to that of atropine and chlorpheniramine, respectively.

omega-Dialkylaminoalkyl ethers of 5-(arylmethylene)-1,3,3-trimethyl-2- oxabicyclo[2.2.2]octan-6-hydroxyimines with platelet antiaggregating and other activities.

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.

2H-pyrano[2,3-f]quinazoline derivatives with platelet antiaggregating and other activities.

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.

[Heart function (angioscintigraphic evaluation) and sympathetic tone in insulin-dependent diabetes mellitus]. / Funzione cardiaca (valutazione angioscintigrafica) e tono simpatico nel diabete mellito insulino-dipendente.

Cardiac failure is a frequent feature in diabetic patients and it often causes their death. But how and when cardiac disease begins in this kind of patient is still debatable. For example, cardiac failure can be present even in the absence of atherosclerotic involvement of coronary arteries in young diabetics. The aims of our study were to evaluate the cardiac function and sympathetic tone of 16 young type 1 diabetic patients (8 M and 8 F, mean age: 27 years, SD +/- 5) in comparison with 10 normal subjects (4 M and 6 F, mean age: 30 years, SD +/- 7). Diabetic patients were choose from a large population because of the following features young age, absence of clinical and instrumental evidence of micro- or macroangiopathy, clinical evidence of diabetic autonomic neuropathy, proteinuria or arterial hypertension. They were in good metabolic control on daily insulin therapy of two or three administrations. Cardiac function was evaluated at rest and during submaximal exercise on a cycloergometer in supine position using radionuclide ventriculography with technetium 99m. Sympathetic tone was checked using the five clinical tests according to Ewing and the plasmatic level of catecholamines at rest was evaluated using high pressure chromatography. The ejection fraction, cardiac output, stroke volume of diabetics were comparable with those of normal subjects even in the presence of comparable systemic vascular resistance. The increase in ejection fraction during effort was normal. Only in one diabetic patient (incidentally the oldest one) did ejection fraction decrease (7%) during effort. The peak ejection and filling rates were significantly higher (p less than 0.001) in diabetic patients compared to those of normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Research on heterocyclic compounds. XXVII. Synthesis and antiinflammatory activity of 2-phenylimidazo[1,2-b]pyridazine-3-carboxylic acids.

A group of ethyl esters of 2-phenylimidazo[1,2-b]pyridazine-3-carboxylic acids 3 were obtained by reaction in anhydrous ethanol of some substituted 3-aminopyridazines 1 with ethyl 2-benzoyl-2-bromoacetate 2. The acids 4 obtained via alkaline hydrolysis were tested in vivo for their antiinflammatory, analgesic and ulcerogenic actions and in vitro for their ability to inhibit the prostaglandin biosynthesis. Almost all of the new compounds showed high analgesic activity, whereas the activities exhibited in the other tests were sharply lower. These results are discussed in terms of mechanism of action.

omega-Dialkylaminoalkyl ethers of 5-endo-dialkylamino-1,3,3-trimethyl-2-oxabicyclo [2.2.2]octan-6-hydroxyimines with platelet antiaggregating, antiarrhythmic and local anesthetic activities.

The synthesis of 1,3,3-trhimethyl-5-endo-(1-piperidinyl)- and -5-endo-(4-morpholinyl)-2- oxabicyclo [2.2.2]octan-6-hydroxyimine 3 and 4 starting from 5-endo-bromo-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-hydroxyimine+ ++ and excess piperidine or morpholine is described. Compounds 3 and 4 gave a series of omega-dialkylaminoalkyl ethers 5 by reaction as sodium salts with omega-chloroalkyldialkylamines in DMF solution. Some of aminoethers 5 showed in mice an appreciable antiarrhythmic and local anesthetic activity, as well as a platelet antiaggregating activity in vitro comparable to that of acetylsalicylic acid.

3,5-Diphenyl-1H-pyrazole derivatives. VI--Esters and 2-dialkylaminoethyl ethers of 1(2-hydroxy-2-phenylethyl)-3,5-diphenyl-1H-pyrazole and N,N-disubstituted 1-(2-amino-2-phenylethyl)-3,5-diphenyl-1H-pyrazoles with depressant and platelet antiaggregating activities.

The syntheses of 1-(2-hydroxy-2-phenylethyl)-3,5-diphenyl-1H-pyrazole 1 by reaction of 2-hydrazino-1-phenylethanol with dibenzoylmethane, of esters 2 and 2-dialkylaminoethyl ethers 3 starting from 1 as sodium salt and acyl chlorides or 2-chloroethyldialkylamines, respectively, as well as of N,N-disubstituted 1-(2-amino-2-phenylethyl)-3,5-diphenyl-1H-pyrazoles 5 by reaction of secondary amines with the tosylate of 1, are described. Some of the above compounds showed a considerable sedative effect in mice and a remarkable platelet antiaggregating activity in vitro, as well as moderate local anesthetic, analgesic and antiinflammatory activities in mice and rats.

3,5-Diphenyl-1H-pyrazole derivatives. VII--Esters, 2-dialkylaminoethyl ethers and N-substituted carbamates of 1-(2-hydroxy-3-phenoxypropyl)-3,5-diphenyl-1H-pyrazole with depressant and platelet antiaggregating activities.

The syntheses of 1-(2-hydroxy-3-phenoxypropyl)-3,5-diphenyl-1H-pyrazole 2 by reaction of 1-hydrazino-3-phenoxy-2-propranolol with dibenzoylmethane, of esters 3 and 2-dialkylaminoethyl ethers 4 starting from 2 as sodium salt and acyl chlorides or 2-chloroethyldialkylamines, respectively, as well as of N-aryl carbamates 5 by reaction of 2 with aryl isocyanates, are described. Some of the above compounds showed a considerable sedative effect in mice and a remarkable platelet antiaggregating activity in vitro, as well as moderate local anesthetic, analgesic and antiinflammatory activities in mice and rats.