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Biomedical subjects

G Bruni

Publications and source records attributed to G Bruni.

At least 55 records · Page 3Linked to original sources

Nicergoline in mild to moderate dementia. A multicenter, double-blind, placebo-controlled study.

In view of some controversies still existing about the real efficacy of ergot derivatives in the management of dementia, a double-blind, randomized, parallel group trial extending up to 6 months was carried out to compare the effects of nicergoline, 60 mg daily, and placebo in 315 patients suffering from mild to moderate dementia. Clinical evaluation was performed by the SCAG scale. The trial, which included a 1-month placebo run-in period, showed that both placebo and nicergoline were associated with some degree of improvement. The effect of nicergoline, however, was significantly greater and more sustained, steadily increasing with time. In particular, the difference between nicergoline and placebo in mean total SCAG score was 5.5 at 3 months (95% confidence interval: 3.6-7.4) and increased to 9.8 at 6 months (95% confidence interval: 7.8-11.8). A comparison of nicergoline versus placebo in the frequencies of changes in each item of the SCAG showed also a significant difference at 6 months, the percent of patients displaying an improvement by at least 2 points ranging from 13.5 (bothersome) to 30.2 (disorientation) in nicergoline group, against 4.1 (self-care) to 14.3 (fatigue) in placebo group. The safety of nicergoline, as judged by hemodynamic changes and drug-related adverse reactions, was quite satisfactory.

Aged↗

Antagonism of aminoglutethimide and adrenocorticotropic hormone (ACTH) studied on slices of adrenal glands of the guinea-pig.

Aminoglutethimide at concentrations from 0.1 to 5 nM is able to inhibit the cortisol release elicited by adrenocorticotropic hormone (ACTH) (from 2.5 to 50 ng/ml) in guinea-pig adrenal cortex slices. The antagonism is a non-competitive one (in a Lineweaver-Burk plot), whereas other drugs (morphine, endorphin, indomethacin, etc.) inhibit ACTH competitively. This is in agreement with the known mechanism of action of aminoglutethimide, which inhibits the synthesis of cortisol by blocking reactions of enzymes such as aromatase and desmolase. From the data one can calculate the dissociation constant (Km) of ACTH with its receptor(s) to be 0.27 pg/ml and the inhibiting constant (Kl) of aminoglutethimide to be 49.78 x 10(-10) M. The maximal response of ACTH was 52.9 ng/ml.

Adrenal Glands↗

Kinetics of amiloride in rat following oral and intravenous administration.

The disposition profile of amiloride, a potassium sparing agent, was studied in rats by using an HPLC method coupled to spectrofluorometric detection. Amiloride was administered orally and intravenously at the dose of 10 mg/Kg. The most relevant pharmacokinetic parameters are described for both administration routes.

Administration, Oral↗

Synthesis and antiinflammatory/analgesic activities of N-heterocyclic carboxamides of thiopyrano-1,2-benzothiazine.

We report the synthesis of N-heterocyclic carboxamides of 5-methyl-4-oxo-2,3,4,5-tetrahydrothiopyrano [3,2-c][1,2]benzothiazine 6,6-dioxide, their antiinflammatory and analgesic activities and the attempts to obtain a corresponding sulfoxidate series. Compounds (II c) and (II l) showed a good antiinflammatory activity which is comparable to that of piroxicam. No compound showed any significant analgesic activity.

Animals↗

Relations between sensorimotor attainments and development of language comprehension in retarded children.

Although cognitive precursors of language production have received considerable attention, the relationship between cognitive development and language comprehension is still largely unknown. We report here on an investigation into the relationship between sensorimotor attainments and receptive language skills in normal and retarded infants aged 12-26 months. A major goal of this study was to translate some current notions about onset of representational language and its cognitive prerequisites into some clinically useful procedures both for early diagnosis and treatment of disabled infants. The Uzgiris-Hunt ordinal scales and receptive language tests were administered to 32 infants with motor delay and to 15 normal infants matched for chronological age. Comparison of the resulting scores indicated significant differences in favor of the normal infants on the six Uzgiris-Hunt scales and on the receptive language measures. The cognitive profile of the retarded infants was not homogeneous, some sensorimotor areas (object permanence, vocal and gestural imitation, schemes in relation to objects) showing later onset and slower development than others. Evidence for the parallel emergence of representational ability in language and thought was not as strong as stated by Piagetian theorists. No single stage of sensorimotor functioning prerequisite to language comprehension could be discerned, especially in the retarded infants, who showed considerable gaps between the two domains.

Age Factors↗

Effect of ACTH, beta-endorphin, morphine and naloxone on the release of cortisol by isolated adrenal glands.

The release of cortisol (determined by RIA) from isolated slices of adrenal glands of guinea pigs is stimulated by ACTH, by beta-endorphin, and by morphine in a concentration-dependent way; naloxone gives a small stimulation which is not related to its concentration. Naloxone inhibits the effect of ACTH (1.11 X 10(-11) M) in a competitive manner with an IC50 of about 3.10(-9) M. Also morphine and beta-endorphin inhibit the effect of ACTH, but not in competitive manner. Naloxone (10(-9)-10(-7) M) gives a concentration-related inhibition of the increase of cortisol release produced by morphine (10(-8) M) and by beta-endorphin (1.44 X 10(-10) M). These data suggest a similarity in the conformation of ACTH, beta-endorphin, morphine and naloxone towards the binding sites of ACTH of the guinea pig adrenal glands.

Adrenal Glands↗

Effect of morphine and naloxone on the levels of ACTH and beta-endorphin in plasma, brain and pituitary of rats.

The effect of i.p. administration of morphine (25 mg/kg) and of naloxone (50 mg/kg) on the levels of ACTH and beta-endorphin in plasma, in brain and in pituitary has been studied in rats. An opposite effect morphine and naloxone is seen in plasma ACTH with an increase elicited by morphine and a decrease produced by naloxone. Small changes are seen in plasma levels of beta-endorphin as well as in ACTH and in beta-endorphin levels in brain and in pituitary. To every change in ACTH levels in plasma an opposite change in ACTH brain levels is observed.

Adrenocorticotropic Hormone↗

Successful treatment of biliary colic with intravenous ketoprofen or lysine acetylsalicylate.

In a double-blind trial, 60 patients with biliary colic were allocated at random to receive 200 mg ketoprofen, 1.8 g lysine acetylsalicylate or placebo by intravenous bolus. The patients were asked to rate their pain at intervals within 3 hours of injection and to indicate their overall pain experience on a visual analogue scale. Both ketoprofen and lysine acetylsalicylate proved significantly more effective than placebo in relieving pain, with no significant difference between them. A good analgesic response, reflected by complete or almost complete relief of pain within 30 minutes of injection, was recorded in 4, 17, and 16 patients, respectively, in the placebo, ketoprofen, and lysine acetylsalicylate treatment groups. All drugs were well tolerated. It is concluded that the results provide further evidence for a useful therapeutic role of prostaglandin inhibitors in the treatment of biliary colic.

Adult↗

[Contraction of the isolated stomach of the rat as a result of stimulation of postganglionic fibers in the presence of 4-methylesculetol].

It is known that the bioflavonoids as the Ca++ have an enhancing effect on the transmitter release in different cholinergic nerve-endings. For this reason, it is seemed interesting to study the influence of the separately tested 4-methylesculetin or associated with the ascorbic acid and comparatively the Ca++ concentration increase on the isolated rat stomach response by electrical transmural stimulation achieved in presence or absence of hexamethonium. Both the 4-methylesculetin and the ascorbic acid have always increased the response of the preparation submitted to electrical transmural stimulation. The 4-methylesculetin effect resulted particularly strong if the substance was employed with the ascorbic acid. The enhancing effect of the 4-methylesculetin, obtained with or without the ascorbic acid, is resulted comparatively lesser in presence of hexamethonium. On the basis of the evident analogy between the 4-methylesculetin effects and the ones determined by the increased Ca++ concentration, it can be supposed that the bioflavonoid facilitates the transmitter release in the pre- and postganglionic nerve-endings. The results here reported, confirm other previous observations accomplished on different cholinergic nerve-endings and could substain the hypothesis according to which the 4-methylesculetin increase the Ca++ transport through the biological membranes.

Animals↗

Analgesic treatment in acute myocardial infarction: a comparison between indoprofen and morphine by a double-blind randomized pilot study.

On the basis of the results of an earlier study, showing that i.v. indoprofen induced no clinically significant changes in hemodynamic parameters of patients with acute myocardial infarction (AMI), a double-blind randomized trial was carried out in 40 AMI patients to evaluate the analgesic activity of 400 mg i.v. indoprofen in comparison with 10 mg i.m. morphine hydrochloride. Pain severity was recorded before and at several intervals within 24 h after drug administration. The average analgesic response was prompt and progressive up to the 6th hour in both treatment groups, with no significant difference between drugs in various pain descriptors. However, the proportion of responding patients in indoprofen group was greater than in morphine group at all observation times, indicating a significant difference (p less than 0.05) in favor of indoprofen. In view of its good tolerability, i.v. indoprofen is worth considering in early AMI as an alternative to morphine in those patients in whom non-opiate analgesia might be preferable.

Adult↗

Injectable ketoprofen vs. acetylsalicylic acid for the relief of severe cancer pain: a double-blind, crossover trial.

Thirty-six patients suffering from severe pain due to bone involvement from cancer participated in an analgesic study that compared single doses of ketoprofen 100 or 400 mg iv or injectable acetylsalicylic acid 1 g. A double-blind, balanced incomplete block design was adopted, in which each patient received two of the three test treatments, with an interval of 24 hours. Ketoprofen 400 mg proved significantly superior to 100 mg of the same drug, and was superior to 1 g of the acetylsalicylic acid derivative in the patients' assessment of the overall response. This was expressed by a visual analog scale and preferences. No adverse reaction was observed with any treatment.

Adult↗

A double-blind, interpatient comparison of plain and slow-release ketoprofen in osteoarthritis.

Eighty patients with osteoarthritis of various localization completed a double-blind, parallel-group trial of 2 weeks' duration comparing the efficacy and tolerance of ketoprofen slow-release capsules (150 mg) given either as a morning or a midday or an evening dose with that of ketoprofen conventional capsules (50 mg) 3X daily. All regimens were associated with a statistically significant improvement in pain at rest, pain on active motion, quality of sleep, and spine flexion, but there was no difference between treatments. The tolerance of ketoprofen was also similar in all groups. In view of the alleged better compliance of patients with once-daily medications, the new slow-release formulation of ketoprofen appears to be a useful alternative to the conventional capsules.

Adult↗

Intravenous ketoprofen in renal colic: a placebo-controlled pilot study.

In a double-blind trial 30 patients with renal colic were allocated at random to receive 200 mg of ketoprofen, 1 gm of lysine acetylsalicylate, or placebo by intravenous bolus injection. The patients were asked to rate their pain at intervals within three hours of injection and to indicate on a visual analogue scale the overall pain relief obtained. Both ketoprofen and lysine acetylsalicylate proved significantly more effective than placebo, with no apparent difference between them. Complete relief of pain was obtained in seven of ten patients in each of the active treatment groups compared with only one of ten patients given placebo. No untoward events were observed in any patient.

Adult↗

Inhibition of aminoacid decarboxylases by non-steroidal antiinflammatory drugs.

Several non-steroidal antiinflammatory drugs (NSAID) were shown to inhibit to various extents the decarboxylases of ornithine, lysine, histidine, arginine, and tyrosine. The most sensitive enzyme was ornithine decarboxylase, for which piroxicam, benoxaprofen and aminophenazone showed an IC50 of 0.007 mM; ibuprofen competitively inhibits the lysine decarboxylase. The most effective NSAID's in inhibiting histidine decarboxylase were mefenamic acid, ibuprofen and flufenamic acid. Arginine and tyrosine decarboxylase were inhibited by NSAID's only at high concentrations. None of the decarboxylase inhibitions were reversed by pyridoxal phosphate. Subplantar injection of the 5 amines formed by these aminoacid decarboxylases elicited a paw oedema in rat which was not antagonized by the various NSAID's. Some of the NSAID's stimulated all the decarboxylases and did not antagonize the carrageenin-induced paw oedema. With one exception, all the NSAID's tested in vivo inhibited the elimination of 14CO2 from labeled ornithine and lysine. The inhibition of certain aminoacid decarboxylases, particularly ornithine and lysine decarboxylase, appears to be a noteworthy mechanism of action for certain NSAID's.

Animals↗

Indomethacin and sulindac inhibition of ACTH stimulated cortisol release from adrenal glands in vitro.

In slices of adrenal glands of guinea pig added ACTH (from femtograms to picograms levels) stimulates cortisol synthesis and release. This effect is antagonized in a non-linear competitive way by indomethacin (KE = 1.3 .10(-7)) and by sulindac (KI = 6.9 .10(-10)); indoprofen is a very weak antagonist. A number of other non-steroid antiinflammatory drug are ineffective as antagonists of ACTH.

Adrenal Glands↗

Dose-response study with indoprofen i.v. as an analgesic in postoperative pain.

A double-blind, placebo-controlled parallel-group study was carried out in 100 patients with postoperative pain. The analgesic activity of indoprofen given in a single dose as an i.v. bolus followed by a 2-h infusion, at total doses of 100, 200, and 400 mg was investigated. The highest dose of 400 mg was given additionally as an i.v. bolus alone. Intensity of pain was assessed before, and 30 min, 1, 2, 4, 6 and 8 h after treatment on a 0-4 point scale. An overall assessment was made at the end of treatment by the investigator and the patient using a 0-4 point scale and a visual analogue scale. Statistical analyses according to a multiple regression model on rating scale scores at fixed times and on overall assessments showed: (i) indoprofen was always more active than placebo in providing pain relief; (ii) there was a significant dose--response relationship; and (iii) there was no difference between the two schedules of administration of the largest dose.

Abdomen↗

Effect of i.v. indoprofen on cancer pain and serum prolactin and growth hormone levels--a controlled pharmacologic study vs i. m. morphine and placebo.

Single doses of indoprofen (400 mg, i.v.), morphine hydrochloride (10 mg, i.m.), and placebo were given to 12 women with moderate to severe tumor pain, mainly due to bone involvement, according to a Latin square design. Analgesic response, along with serum prolactin (PRL) and growth hormone (GH) levels, were measured after each treatment under double-blind conditions. Indoprofen and morphine were not significantly different as regards pain relief, but both were significantly more effective than placebo. Unlike morphine, however, indoprofen did not raise PRL. GH levels did not change following any treatment. In a second study indoprofen (400 mg, i.v., three times daily for 7 days) did not modify the PRL response to thyrotropin-releasing hormone nor serum GH levels. On the basis of the above findings it is suggested that indoprofen may be a safe alternative to opiates for relief of moderate to severe pain in women with breast tumors suspected of being prolactin-dependent.

Adult↗