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Biomedical subjects

A Sala

Publications and source records attributed to A Sala.

At least 199 records · Page 11Linked to original sources

Inhibition by lipoxygenase products of TXA2-like responses of platelets and vascular smooth muscle. 14-Hydroxy from 22:6n-3 is more potent than 12-HETE.

Lipoxygenase products, which are formed in great amounts in platelets during their activation, have been prepared from arachidonic acid (20:4n-6), the main polyunsaturated fatty acid (PUFA) esterified in platelet phospholipids, and from two major PUFAs of fish fat, eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids. These compounds have been synthesized using platelet suspension as enzymic source, purified by high performance liquid chromatography, and their structure were checked by gas chromatography-mass spectrometry. Their effects were investigated in vitro upon human platelet aggregation induced by 11,9-epoxy-methano-analogue of PGH2 (U-46619) and upon thromboxane A2-induced vasoconstriction of rabbit aorta. All hydroxylated fatty acids inhibited U-46619-induced aggregation in a concentration-dependent fashion. Compounds issued from 22:6n-3 were the most potent inhibitors and their IC50 differed significantly from that of 12-hydroxy-eicosatetraenoic acid (12-HETE). Among them, 14-hydroxy-docosahexaenoic acid (14-OH-22:6) was the most effective anti-aggregating molecule (IC50:0.45 microM). 10 microM 12-HETE and 14-OH-22:6 inhibited 60% and 75% of smooth muscle contraction induced by TXA2-like material, respectively. At 1 microM, solely 14-OH-22:6 had an inhibitory effect on adrenaline-, angiotensine- or histamine-induced contraction. Since thromboxane receptors in platelets and vascular smooth muscle cells present strong similarities, it is concluded that hydroxylated fatty acids can antagonize prostanoid action probably by interfering with their receptor sites.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Mediators and allergic inflammation of human airways.

Local antigen challenge in patients with respiratory allergy is associated with histamine and arachidonic acid metabolites release, both in upper and in lower respiratory airways. Raised histamine levels can be detected in nasal secretions 5 min after allergen stimulation. Increased leukotriene C4 and prostaglandin D2 concentrations persist for a longer period (respectively 20 and 30 min). Endobronchial antigen stimulation is also followed by release of histamine, leukotriene C4 and prostaglandin D2, which can be detected in bronchial lavage fluid. Elevated concentrations of these mediators can be found 5 and 15 min after challenge. Moreover, endobronchial antigen stimulation is associated with an increase in the number of bronchial epithelial cells recovered in bronchial lavage fluids.

Adult↗

Subaortic aneurysm of the left ventricle obstructing a coronary artery.

We report a subaortic aneurysm of the left ventricle causing compression of a coronary artery in a 52-year-old white man presenting with angina on effort. Endocarditis seemed to be implicated as the cause of this rare condition. To what extent coronary obstruction influenced the development of myocardial ischaemia was not defined since the patient also had aortic valvular disease. The clinical features, diagnostic studies and successful surgical treatment are described.

Angina Pectoris↗

PGD2 induces pulmonary hyperresponsiveness to acetylcholine in vivo in the guinea-pig.

1 A threshold dose of Prostaglandin D2 (PGD2) (0.5 microgram/kg i.v.), which did not modify the basal values of airway resistance, potentiated the acetylcholine induced bronchospasm in anaesthetized guinea-pigs. 2 beta-adrenoreceptors blockade induced by propranolol enhanced the positive interaction between PGD2 and acetylcholine in the pulmonary dynamics. 3 Active sensitization of guinea-pigs by ovalbumin increased the pulmonary PGD2-acetylcholine interaction and the phenomenon was sustained during the time. 4 The inability of PGD2 to potentiate histamine-induced bronchoconstriction suggests a specificity for the interaction.

Acetylcholine↗

Behavior and clinical relevance of histamine and leukotrienes C4 and B4 in grass pollen-induced rhinitis.

The release kinetics of histamine and leukotrienes C4 (LTC4) and B4 (LTB4) were investigated in nasal secretions of 10 patients with hay fever after antigen challenge. High levels of biologically active histamine were found in nasal washes from asymptomatic allergic and normal subjects. With repeated lavages, the amount of histamine recovered dropped markedly. Grass pollen challenge was followed by a significant (p less than 0.05) dose-dependent and time-limited (5 min) increase in histamine level in 7 of 10 patients; these values, however, were lower than those found in basal conditions. In 8 of 10 patients with hay fever, antigen challenge induced a significant (p less than 0.05) dose-dependent increase in LTC4 level, which persisted for 30 min. The LTC4 generation was well correlated with the appearance of allergic symptoms; LTB4 production was found in 2 patients only. A different pattern of symptoms was observed after in vivo nasal stimulation with histamine and LTC4. Histamine caused sneezing, itching, rhinorrhea, and nasal obstruction; conversely, the main symptom induced by LTC4 was a more pronounced and longer lasting nasal obstruction.

Adult↗

Synthesis and antibacterial properties of 7-[2-(3-substituted-5-isoxazolyl)-2-methoxyiminoacetamido]cep halospora nic acid derivatives.

The synthesis of new 2-(3-substituted-5-isoxazolyl)-2-methoxyiminoacetic acids and their condensation derivatives with a suitable cephalosporanic nucleus, is reported. Their antibacterial properties were tested in vivo and in vitro also against beta-lactamase producer microorganisms; particularly the oral bioavailability of some of these new derivatives was studied.

Animals↗

3-(1-Iminoethyl)-4,5-cycloalkylpyridine-2,6-diol derivatives. A novel class of benzodiazepine receptor antagonists and partial agonists.

A series of 3-(1-iminoethyl)-4,5-cycloalkylpyridine-2,6-diol derivatives have been prepared from isoxazolo [5,4-b] pyridones. Some of these compounds had affinity for the benzodiazepine receptors in vitro and in vivo radioligand displacement assays. These compounds did not have any anticonvulsant properties and were not active in pharmacological tests predictive of antianxiety activity, but antagonised the anticonvulsant and muscle-relaxant effects of diazepam and had proconvulsant properties.

Animals↗

Study of mediators of anaphylaxis in nasal wash fluids after aspirin and sodium metabisulfite nasal provocation in intolerant rhinitic patients.

Nasal histamine (H), leukotriene C4 (I-LTC4) and SRS-A activity were studied in seven aspirin-(ASA)-intolerant patients (AIR) with rhinitis and in five ASA-tolerant control patients with chronic rhinitis after nasal provocation (NP) with a lysine acetylsalicylate solution. The same parameters were also studied after metabisulfite (MBS) NP in four sulfite-intolerant patients with rhinitis and in six control patients with chronic rhinitis. In six ASA-intolerant subjects and in four controls, we studied the PGD2 levels in nasal washes after ASA NP 0.2 mL of lysine acetylsalicylate solution (10 mg/mL) was sprayed intranasally in ASA-intolerant patients and controls and a 25-mg/mL MBS solution in sulfite intolerant patients and controls. Nasal wash fluids were obtained using 5 mL of 0.15 M saline before and 7 1/2, 15, 30, and 60 minutes after nasal provocation. The nasal provocation with ASA induced itching and sneezing in four out of seven intolerant subjects. In this subgroup histamine values in nasal wash fluids were significantly higher versus the remaining ASA-intolerant patients at 30 and 60 minutes (P less than .05 and P less than .01, respectively) and versus controls at 60 minutes (P less than .01). We found significantly higher I-LTC4 (P less than .01) and SRS-A levels in nasal washes collected from ASA-intolerant subjects versus controls at 60 minutes after nasal provocation. There was no significant increase in the mean PGD2 values in either the ASA-intolerant or control groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aspirin↗

Synthesis, in vitro [3H]prazosin displacement, and in vivo activity of 3-aryl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridines, a new class of antihypertensive agents.

A series of new 3-aryl-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridines was synthesized and screened for in vitro [3H]prazosin displacement activity. The results correlated well with their antihypertensive activity in spontaneous hypertensive rats. 1-Benzyl-3-(4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[4,3-c]pyrid ine (50, L 16052) was selected for further pharmacological evaluations of its potency when administered orally to conscious renal hypertensive dogs.

Animals↗

Maximal anaerobic (lactic) capacity and power of the horse.

Blood lactate concentrations were determined in 16 horses (three Thoroughbreds, seven Standardbreds and six polo ponies) before and 5 mins after they galloped over distances of 200, 300 and 400 m at maximal speed. The highest net lactate concentration (delta Lamax) of 14 to 15 mmol/litre was attained by the polo ponies and the highest speed by the Thoroughbreds. The maximal rate of lactate production (delta Låmax) was about 35 mmol/litre X min for the polo ponies and 20 to 25 mmol/litre X min for the Standardbreds and the Thoroughbreds. Values for delta Lamax and delta Låmax were similar to those measured in human athletes after exhaustive work. delta Låmax increases with the speed (v) and can be described by the equation delta Lå = a (v-v1), where a is a proportionality constant representing the amount of lactate needed to cover a unit distance and v1 the theoretical speed at which delta Lå = 0 X v1 was highest for the Thoroughbreds and lowest for the polo ponies; this difference could be caused by the effect of training and/or to genetic differences among the different breeds of horses X v1 could be a useful index of the fitness of a horse following a training programme.

Anaerobiosis↗