Biomedical subjects
Publications and source records attributed to F Melani.
Following our previous reports on pyrazolo[4,5-c]quinoline derivatives some isosteric pyrazolo[4,5-c] [1,8]naphthyridines were synthesized and tested for their ability to displace [3H]flunitrazepam from rat brain membranes. The lack of activity of the synthesized compounds and structure-activity relationships for the whole series are discussed.
Some 1-aryl-3-methylpyrazolo[4,5-c]quinolin-4-ones, were prepared and tested for their ability to displace specific [3H]flunitrazepam binding from bovine brain membranes. The 1-meta-aryl derivatives were the compounds that bound with the highest affinity within this class. Our 13C NMR study suggested a correlation between the binding affinity and the chemical shift value of a carbon atom of the tricyclic system.
A series of 1-aryl-3,5-dimethyl-4,5-dihydro-1H-pyrazolo[4,5-c]quinolin-4-ones (2a-e) and 1-aryl-3-methyl-1H-pyrazolo[4,5-c]quinolines (3-7a-e) bearing different substituents at position 4 were prepared and tested for their ability to displace specific [3H]flunitrazepam binding from bovine brain membranes. The 5-N-methyl derivatives 2a-c,e were the compounds that bound with the highest affinity within this class. The replacement of the carbonyl group with other substituents and the resulting aromatization of the pyridine moiety greatly decreased the binding affinity. From a Lineweaver-Burk analysis on the most active compound 2b, it appears that the inhibition is a competitive one.
Some 1,5-diaryl-, 1-aryl-5-(2-nitrobenzyl)-3-methylpyraloze-4-carboxylic acids and some of their 4-morpholino- and 4-N-methylpiperazino amides are prepared and tested as antibacterial agents. None of the tested compounds shows any noteworthy antimicrobial activity. The results are discussed and compared with the previously published results for other similarly structured compounds.
The syntheses of some 2-aryl-3-methyl-4,5-dihydro-2H-pyrazolo [4,3-c] quinolin-4-ones and 1-aryl-3-methyl-4,5-dihydro-1H-pyrazolo-[4,5-c] quinolin-4-ones are reported. Some of the latter have shown a high activity in displacing specific [3H]-flunitrazepam binding from bovine brain membranes.
Concentrations of isoxicam in the plasma and synovial fluid of 7 patients were investigated by means of high-pressure liquid chromatography. The samples were collected after 7 days' treatment with a single 200 mg isoxicam capsule taken each morning. A highly significant correlation was found (r = 0.82; p less than 0.05) between isoxicam concentrations in the plasma and in the synovial fluid. The mean concentration (+/- s.d.) was 25.54 +/- 10.91 micrograms/ml in the plasma and 17.47 +/- 6.54 micrograms/ml in the synovial fluid; the ratio between isoxicam concentrations in the synovial fluid and in the plasma was 71.06% +/- 18.83.
The synthesis of some 3-(pyrazol-1'-yl)indazole derivatives is reported. The synthesized compounds were subjected to in vitro antimicrobial screenings. Only two of the tested compounds showed a mild activity at high concentrations.
The syntheses of all the possible 1-tolyl-3-nitrophenyl-5-methylpyrazole-4-carboxylic acids, 1-tolyl-3-methyl-5-nitrophenylprazole-4-carboxylic acids and of the corresponding carboxylates are reported. Several 1,3- and 1,5-diarylpyrazole derivatives were subjected to in vitro antibacterial screenings. Some acids showed activity against some strains of gram-positive bacteria. The results are discussed on the basis of structure-activity relationships.
The synthesis and the in vitro antimicrobial activity of all the possible 1-chlorophenyl-3-nitrophenyl-5-methylpyrazole-4-carboxylic acids and 1-chlorophenyl-3-methyl-5-nitrophenylpyrazole-4-carboxylic acids are reported. Some acids showed an interesting activity against some strains of gram-positive bacteria. The results are discussed and compared with those of other related compounds.
A population of 8 children aged 7 to 13 and radiologically and/or endoscopically diagnosed of duodenal ulcer is compared with another made up of 12 normal children of similar ages and weights. In both groups gastric secretion, basal and after pentagastrin stimulation, and serum levels of gastrin and pepsinogen I, basal and after pentagastrin stimulation, and serum levels of gastrin and pepsinogen pepsinogen basal and after pentagastrin stimulation, and serum levels of gastrin and pepsinogen I, basal and after proteic meal, were studied. BAO, MAO and PAO were significantly higher in ulcer patients. Gastrinemia, both basal and stimulated, were rather similar in both groups. Serum pepsinogen I was always higher in ulcer patients in the basal state than in their healthy counterparts (greater than ng/ml vs. 30-50 ng/ml), but was not modified by proteic meal in either group. The fact that all ulcer children had a familial history and a basal pepsinogen I elevated, aside with the secretory response to stimulation, suggests that ulcer can be result either of an increased mass or of a higher sensitivity of gastric parietal cells that could be related to genetic factors.
A rapid, sensitive, and specific determination of ketoprofen in human and animal deproteinized body fluids by reversed-phase high-pressure liquid chromatography is presented. The acid is detectable in amounts as low as 0.1 microgram/ml. Limits of error are in the range of +/- 5.1% of the sample mean.
The effect of glucagon on the inhibition of the insulin response to glucose induced by somatostatin was investigated in humans and in the isolated perfused rat pancreas. Both in vivo and in vitro somatostatin suppressed glucose-induced insulin release. This inhibitory effect of somatostatin was overcome by glucagon. Similar results have been observed in vitro by the infusion of theophylline or cyclic adenosine monophosphate.
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The role of insulin secretion in the diurnal variation of glucose tolerance has been investigated. In ten healthy subjects, at 08.00 and at 18.00 after 10 hrs of fasting, a combination test of glucose and glucagon was performed. 1 mg glucagon was injected intravenously 40 min after the intravenous infusion of glucose (0.5 g/kg b.w.). Samples for blood sugar (BS) and serum immunoreactive insulin (IRI) were taken before and 2-5 min following the glucose and glucagon loads, and thereafter at 10 min intervals up to 85 min. In the afternoon test, the mean blood sugar values were higher, the differences in the 20-85 min values being statistically significant: the IRI values were statistically lower after glucose, while after glucagon, the increase of serum IRI was apparently similar in both morning and afternoon tests. However, the insulin/glucose ratio (I/G) was significantly lower at 18.00 at 55-85 men. Corresponding results were obtained in six additional healthy subjects when only glucagon (1 mg i.v.) was injected. In this case also, the mean insulin levels were lower in the afternoon after 5 min, while the BS values during the maximal insulin release (2-30 min) were comparable in both the morning and afternoon tests. In the 40-60 min interval, the BS levels were significantly higher in the afternoon. The existence of a diurnal variation in the blood sugar after intravenous glucose load, as well as after glucagon, seems to be correlated to a simultaneous diurnal variation in the insulin response, suggesting decreased pancreatic beta-cell activity in the afternoon.
In agreement with data previously reported (Yalow and Berson 1973), after gel filtration of acid-ethanol extracts of islet cell adenomas (performed in 3 M acetic acid) 1.4% to 1.8% of total immunoreactive insulin (IRI) eluted ahead of proinsulin. The high-molecular IRI (HM-IRI) was, however, found to be heterogenous in size and consisted of at least three components, the major one having an estimated molecular weight of about 50,000. Under certain conditions, HM-IRI was partially dissociated into proinsulin- and insulin-like components. We conclude that HM-IRI does not represent a precursor of proinsulin and insulin, but probably a self-association product of the peptides or an association of insulin and proinsulin to other proteins extracted from tumor tissue.
Insulin release in the perfused isolated rat pancreas was measured after stimulation with 16.5 mM glucose with and without somatostatin (cycle form, 100 ng/ml) in the medium. A complete blockage of the typical biphasic pattern of insulin release ocurred with somatostatin in the medium. Such blockage was abolished when cAMP (2.5 mM) and a 0.5 ml solution of glucagon (1 mg/ml) were continuously perfused for 20-minute periods and for 30-second periods correspondently. It did not take place when glibenclamide (HB-419) was perfused for a 20-minute period at a rate of 10 mug/ml. The results suggest that the adenylcyclase dependent mechanisms of glucose-induced insulin release are involved in the inhibition of the glucose-induced insulin secretion by somatostatin.