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Biomedical subjects

F Fraschini

Publications and source records attributed to F Fraschini.

At least 55 records · Page 3Linked to original sources
PubMed1991

Clinical results with the pineal hormone melatonin in advanced cancer resistant to standard antitumor therapies.

The pineal hormone melatonin (MLT) is able to exert an oncostatic action. Its possible use in the treatment of human tumors, however, has not yet been investigated. The present study was carried out to evaluate the effects of MLT in patients with metastatic solid tumors resistant to conventional therapies. The study included 54 patients, most of them were affected by lung cancer or colorectal carcinoma. MLT was given intramuscularly at a daily dose of 20 mg at 3.00 p.m. for 2 months; this induction phase was followed by a maintenance period at a dose of 10 mg orally in responder patients or in those with an improvement in performance status (PS). The clinical response was as follows: 1 partial response (cancer of pancreas), 2 minor responses (colon cancer and hepatocarcinoma) and 21 with stable disease. The remaining 30 patients rapidly progressed within the first 2 months of therapy. An evident improvement in PS was achieved in 18 of 54 (33%) cases. These results, by showing an apparent control of the neoplastic growth and an improvement in the quality of life in a reasonable number of cancer patients for whom no other standard therapy is available, would justify further clinical trials to better define the impact of MLT therapy on the survival and quality of life of untreatable advanced cancer patients.

Adult↗
PubMed1991

Kinetic profile of miocamycin in middle ear fluid and mucosa.

A group of 18 patients, before undergoing otoplastic surgery, was treated with miocamycin 600 mg in a single dose; middle ear tissue samples were collected at 2, 3, 4 and 6 h. A group of 20 patients suffering from secretory otitis media (SOM) was also treated with 600 mg of miocamycin in a single dose; collections of middle ear fluid (MEF) were performed at 1, 2, 4 and 6 h. Blood withdrawals from all patients occurred at the same time intervals. The miocamycin determination was performed by means of a microbiological method employing Sarcina lutea ATCC 9341. The highest serum levels (1.06 +/- 0.13 mg/l) were found at 2 h in the group from which middle ear mucosa had been withdrawn and at 1 h (2.2 +/- 0.5 mg/l) in the group from which the MEF had been collected; at 6 h miocamycin could be determined in both groups, with values ranging from 0.1 to 0.2 mg/l. In middle ear mucosa the miocamycin concentration was 1.52 +/- 0.27 mg/kg at 2 h and 0.2 +/- 0.09 mg/kg at 6 h. In MEF, the miocamycin concentration was 2.1 +/- 0.27 mg/l at 1 h and 0.24 +/- 0.05 mg/l at 6 h. The miocamycin concentration determined at 1 h in MEF was virtually equal to that in serum at the same time. At the following experimental times of withdrawal, the miocamycin concentration in mucosa specimens, as well as in MEF samples, proved to be markedly higher than values simultaneously found in serum.

Adult↗
PubMed1990

Hormonal circadian rhythms in eating disorders.

The circadian rhythm of several plasma hormones (prolactin, growth hormone, adrenocorticotropic hormone (ACTH), cortisol, and melatonin) was simultaneously evaluated in 23 women with anorexia nervosa (AN), in 27 obese (OB) women, and in gender and age-matched healthy controls. A trend toward similar alterations of the circadian pattern of the different hormones was observed in the two groups of patients, with the exception of plasma growth hormone (GH), which exhibited nutrition-dependent impairments. The timing of the peaks for each hormonal rhythm revealed the existence of an internal desynchronization in both eating disorders.

Adult↗
PubMed1990

T cell subpopulations in vitiligo: a chronobiologic study.

The circadian rhythms of helper (CD4) and suppressor (CD8) T cells from the peripheral blood of 12 vitiligo patients (seven with active disease, five with static) and 12 healthy control subjects were studied. Patients with active vitiligo had a lower percentage of CD4+ cells than did control subjects at 0000 hours and at 0600 and 1200 hours; there were no differences between these values in patients with static vitiligo and those in control subjects. The percentage of CD8+ cells were lower at 1200 and 1800 hours in both active and static vitiligo patients than in control subjects. Cosinor analysis of the CD4+ cells showed a circadian rhythm in static vitiligo, whereas the rhythmicity was lost in active vitiligo. CD8+ cells did not show any circadian rhythm in either active or static vitiligo. Our data show more striking aberrations for T cell subtypes in active vitiligo than in static vitiligo. They suggest that cell-mediated immunity may play a role in the pathogenesis of the disease.

Adolescent↗
PubMed1990

Pharmacokinetics and tissue distribution of amoxicillin plus clavulanic acid after oral administration in man.

Augmentin (875 amoxicillin and 125 mg potassium clavulanate) was administered orally to patients with chronic bronchitis. Concentrations of amoxicillin and clavulanic acid were measured in serum, sputum and urine. Peak serum levels for amoxicillin of 11.23 +/- 2.61 micrograms/ml were observed at 2 hours and for clavulanic acid of 2.55 +/- 0.54 micrograms/ml at 1 hour. After 9 hours, 50% of the amoxicillin and 39% of the clavulanic acid had been renally excreted. The peak sputum concentration of amoxicillin was 1.31 +/- 0.42 micrograms/ml at 4 hours and of clavulanate was 0.79 +/- 0.23 micrograms/ml at 2 hours. Patients awaiting surgery received an oral dose of augmentin as above. Samples of lung, tonsil, middle ear mucosa and prostate were obtained and tissue concentrations of both compounds measured. Peak levels of amoxicillin ranged from 0.87 micrograms/g (tonsil) to 2.56 micrograms/g (lung) and of clavulanic acid from 0.20 micrograms/g (prostate) to 0.56 micrograms/g (lung) between 3 and 4 hours after dosing.

Administration, Oral↗
PubMed1990

Pathogen-host interaction.

Host defense, as it generally applies to humans, refers to the individual's ability to withstand infections. Human host defense mechanisms are numerous, diversified, complex, and often interdependent. The administration of drugs may influence some phases of immunocompetence mechanisms. The effect of several antimicrobial agents on organic defenses has been studied. The parameters considered were chemotaxis, phagocytosis, intracellular killing, superoxide-anion production, antibody production, lymphocyte subset behavior, and natural killer cell activity. Some antibacterial agents inhibit these parameters, whereas others can enhance some of these immune parameters to differing extents. Some antibacterial agents have a neutral effect on these parameters.

Anti-Bacterial Agents↗
PubMed1990

In-vitro postantibiotic effects of miocamycin and erythromycin on gram-positive cocci.

The capability of miocamycin to induce a postantibiotic effect (PAE) on a Group A Streptococcus beta-haemolyticus clinical isolate and on Staphylococcus aureus ATCC 29213 has been studied. Erythromycin was chosen as a reference molecule. The exposure time to antibiotics was 90 min. The removal technique of the antibiotic agents consisted of a 1:200 dilution in cultural broth. Miocamycin displayed a PAE of 2 h 30 min in relation to the minimum inhibitory concentration (MIC) of Streptococcus and a PAE of 2 h 30 min in relation to the MIC of Staphylococcus. The PAE value lasting longer than the others was of 5 h 40 min towards Streptococcus and of 4 h 18 min towards Staphylococcus at a concentration eightfold the MIC. Erythromycin showed a PAE of 1 h 36 min in relation to the MIC of Streptococcus and a PAE of 1 h 30 min in relation to the MIC of Staphylococcus. The PAE value lasting longer than the others was of 3 h 15 min against Streptococcus and of 2 h 30 min against Staphylococcus at a concentration eightfold the MIC. In some cases a PAE was observed in relation to subinhibitory concentrations (1/2 MIC). Miocamycin therefore proved to possess a more evident capability to induce a PAE against the clinical isolate of Group A Streptococcus beta-haemolyticus and on Staphylococcus aureus ATCC 29213 than did erythromycin.

Adult↗
PubMed1990

Miocamycin distribution in tonsillar and pulmonary tissues after repeated administration.

Twenty patients undergoing tonsillectomy were treated with a peroral administration of 600 mg of miocamycin every 12 hours for 4 days. On the 5th day, after a last administration of a dose of 600 mg the ablation of the tonsils was carried out on groups of 4 subjects, each one at the following times after oral intake of the drug: 2, 4, 6, 8, 12 h. Twenty-nine patients, admitted to hospital to undergo lung resection were treated with peroral administration of miocamycin in accordance with the above mentioned dose scheme. The operation was carried out on groups of 5 subjects, each on the fifth day at the following times after the last administration: 2, 3, 4, 6, 8 and 12 h (4 subjects). Simultaneously blood was withdrawn for the determination of miocamycin in serum. Miocamycin was measured by a microbiological procedure using Sarcina lutea ATCC 9341. The highest levels of miocamycin were observed after 2h in tonsils (3.2 +/- 0.82 mg/kg) and serum (1.3 +/- 0.33 mg/l). After 12h miocamycin proved to be still measurable in the tissue (0.12 +/- 0.05 mg/kg), whereas it was not detected in serum. In pulmonary tissue, the highest levels of miocamycin were likewise identified at the 2nd hour (2.82 +/- 0.59 mg/kg), simultaneously with the highest serum levels (2.3 +/- 0.61 mg/l). At the 12th hour miocamycin could still be dosed in 3 tissue samples, with values between 0.1 and 0.2 mg/kg and was found just at dosing limits in only one serum sample.

Adolescent↗
PubMed1990

Serum protein binding and extravascular diffusion of methoxyimino cephalosporins. Time courses of free and total concentrations of cefotaxime and ceftriaxone in serum and pleural exudate.

A new approach to the study of the distribution pharmacokinetics of variably bound beta-lactams is to plot the concentration time course of their free (dialysable) and total (free and bound) forms. In the present study, the 6-h concentration time course was plotted of the total and free concentrations of cefotaxime and ceftriaxone in serum and pleural exudate in 12 patients per group, after iv dosing with 1 g of either cefotaxime or ceftriaxone. Samples were taken at 0.5, 1, 1.5, 2, 3, 4 and 6h after dosing. The results of a study of similar design, but conducted over 24 h in ten patients per group, following iv dosing with either cefotaxime 1 g 12-hourly or ceftriaxone 1 g daily are also reported. Samples were taken at 0.5, 1, 1.5, 2, 4, 6, 8, 12, 14, 16 and 24 h after dosing. Areas under the curve of free cefotaxime in pleural fluid were greater than those of free ceftriaxone, in both the 6 h (+54.6%) and 24 h studies (+29.8% after 12 h and +71.0% after 24 h). The free cefotaxime/free ceftriaxone Cmax ratio was 1.75 in the 6 h study. Cefotaxime was superior to ceftriaxone in terms of the diffusion of the free (antibacterially active) fraction into a typical inflammatory exudate. Assessment of the effects of protein binding must be taken into account in antibiotic pharmacokinetic profiles.

Adult↗
PubMed1990

Alpha-1 adrenoceptor involvement in the control of melatonin secretion in the golden hamster.

The nocturnal peak in pineal and serum melatonin content was reduced following administration of the selective alpha-1 adrenoceptor antagonist prazosin in a dose of 0.25 mg/kg. The effect was pronounced one hour post treatment during the late dark phase of the daily photocycle. These data confirm the reported findings that the hamster pineal sensitivity to adrenergic challenge is confined to the second part of the dark phase and indicate that postsynaptically located alpha-1 adrenoceptors are also involved in the physiological control of melatonin synthesis and/or release in that species.

Animals↗
PubMed1990

Failure of prazosin to mimic the effects of melatonin under in vivo and in vitro conditions.

The gonads of male hamsters exposed to short photoperiod (LD, 10:14) or treated with melatonin in the late afternoon under long photoperiod (LD, 14:10) had undergone complete regression by the end of the treatments (8 weeks). Animals treated for the same period of time with prazosin (a putative melatonin analogue) under the same conditions failed to show a difference in their gonadal status as compared to the long photoperiod controls. Prazosin was unable to prevent melatonin-induced gonadal atrophy when injected either in the morning or 30 min before melatonin. Moreover, prazosin was without any effect on (and unable to prevent the melatonin-stimulated) progesterone production by rat adrenals under in vitro conditions. These data demonstrate that prazosin, which reportedly inhibits 2-[125I]iodomelatonin binding in the hamster brain in an affinity-related manner, does not possess properties of a biological melatonin analogue under conditions of two different model systems in two species.

Adrenal Glands↗
PubMed1990

Preliminary studies on melatonin in the treatment of myelodysplastic syndromes following cancer chemotherapy.

Experimental studies have suggested that the pineal hormone melatonin, in addition to its documented antineoplastic action, plays a role in the physiological regulation of blood cell proliferation. Based on these data, we evaluated the clinical effects of melatonin therapy in patients with myelodysplastic syndrome (MDS) secondary to cancer chemotherapy for primary neoplasms. The study was carried out on six patients, and melatonin was given orally at a dose of 20 mg/daily, following a schedule prepared to reproduce the circadian rhythm of the pineal hormone. A transient improvement in platelet and neutrophil count was achieved in two of five patients with thrombocytopenia and in two of four patients with neutropenia before therapy, respectively, while no effect was seen on hemoglobin concentration. Mean survival time was 12.5 months, and a long survival, greater than 30 months, was achieved in two of six patients. These preliminary results seem to suggest that melatonin may have a role in the treatment of MDS induced by previous cancer chemotherapy.

Aged↗
PubMed1990

Comparison of the rat pinealocyte ultrastructure with melatonin concentrations during daytime and at night.

The aim of this study was to investigate the ultrastructure of rat pinealocyte during daytime (1600 h) and at night (0100 h) and to compare these observations with serum melatonin levels in the same animals. In addition, pineal melatonin concentrations were determined in other animals. Both serum and pineal melatonin concentrations were significantly higher at night than during daytime (34 and 21 times, respectively). Sizes of pinealocytes, their nuclei, and nucleoli, as well as cross-sectional areas of mitochondria and granular endoplasmic reticulum were also higher at night than during daytime, whereas areas of lysosomes, Golgi apparatus, and vacuoles containing flocculent material did not differ at the time points studied. In contrast, the number of dense-core vesicles was higher during daytime. The results of the present study show that morphological patterns of higher metabolic activity of the rat pinealocyte at night when compared to those during daytime correlate with melatonin concentrations.

Animals↗
PubMed1990

Immunomodulatory effects of two extracts of Panax ginseng C.A. Meyer.

The effect of Panax ginseng extracts on cell-mediated immune functions in man has been investigated. Three groups, each consisting of twenty healthy volunteers, were treated under conditions of double blindness with capsules containing lactose (Control Group B), with capsules containing 100 mg of aqueous extract of the drug (Group A), and with capsules containing 100 mg of standardized extract of the drug (Group C). All the patients took one capsule every 12 h for 8 weeks. Blood samples were withdrawn before beginning the treatment, at the fourth week and at the eighth week. The immune parameters examined were the following: chemotaxis of PMNs, phagocytosis index (PHI), phagocytosis fraction (PHF), intracellular killing, total lymphocytes (T3), T helper (T4) subset, suppressor cells (T8) subset, blastogenesis of circulating lymphocytes, natural killer-cell activity (NK). Chemotaxis proved to be enhanced (p less than 0.05) already at the fourth week in Group A as well as in Group C; the increase became even more marked (p less than 0.001) at the eight week in subjects belonging to Group C. PHI and PHF proved to be enhanced (p less than 0.05) at the eighth week in subjects of Group A; these increases were found to be higher in subjects of Group C (p less than 0.001) already starting at the fourth week. Intracellular killing was shown to be significantly increased (p less than 0.05) already at the fourth week in Groups A and C; the increase becomes highly significant in both groups (p less than 0.001) at the eighth week; however, a significant increase (p less than 0.05) at the eighth week was also noticed in the placebo group (Group B).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Cefonicid distribution into tonsillar tissue.

The kinetic profile in tonsils of cefonicid has been studied in 30 patients who underwent tonsillectomy after administration of a single intramuscular dose of 1 g. Blood and tissue samples were withdrawn 1, 2, 3, 6, 12 and 24 h after administration of the drug. The analytical determination was performed employing a microbiological method. Peak serum levels appeared at the first hour (94.2 +/- 9.83 mg/l), while peak tissue values were determined in samples collected at the third hour (11.9 +/- 3.68 mg/kg). Serum levels at the 24th hour were 3.82 +/- 1.25 mg/l. Levels in the tonsils were 7.54 +/- 2.96 mg/kg at the sixth hour, 3.34 +/- 1.42 mg/kg at the twelfth hour and 0.40 +/- 0.31 mg/kg at the 24th hour.

Adolescent↗
PubMed1990

[Pulmonary and tonsillar distribution of ceftriaxone and cefonicid and the resultant bactericidal activity of the organ].

The therapeutic efficacy of Ceftriaxone and Cefonicid 1 g I.M. single-dose against S. Pneumoniae, H. Influenzae and K. Pneumoniae in tonsil and lung infections was studied using bactericidal quotient (BQ). Samples of lung tissue and serum were obtained from two groups of surgical patients, treated with Ceftriaxone or Cefonicid 1 g I.M., 2-8-16 and 24 hours before surgery. From two other groups of 10 surgical patients, treated as above, samples of tonsil tissue and serum were obtained. In lung tissue the higher levels of Ceftriaxone and Cefonicid appeared at the second hour (11.54 +/- 1.59 mcg/g and 11.4 +/- 2.49 mcg/g respectively); the lower values were observed at the 24th hour (2.18 +/- 0.47 mcg/g for Ceftriaxone and 0.64 +/- 0.21 mcg/g for Cefonicid). Higher Ceftriaxone and Cefonicid levels also appeared in tonsil tissue at the 2nd hour (11.12 +/- 2.42 mcg/g and 9.22 +/- 3.12 mcg/g respectively); the lower values were observed at the 24th hour (1.54 +/- 0.46 mcg/g for Ceftriaxone and 0.42 +/- 0.23 mcg/g for Cefonicid). BQ values were estimated using the ratio between the mean concentrations of Ceftriaxone and Cefonicid in tissue samples and the MBC mean values determined for the above mentioned pathogens, isolated in hospital. Ceftriaxone always showed BQ values greater than 1 during 24 hours versus levels observed for the three reported pathogens. Cefonicid showed BQ values greater than 1 during 24 hours against S. Pneumoniae and BQ values less than 1 for 6-8 hours against H. Influenzae and for 1-4 hours against K. Pneumoniae.

Adolescent↗
PubMed1989

Analysis of pirprofen in cerebrospinal fluid, plasma, and synovial fluid by high-performance liquid chromatography with electrochemical detection.

We describe a high-performance liquid chromatographic method, using electrochemical detection, for the determination of pirprofen in cerebrospinal fluid (CSF), plasma, and synovial fluid (SF). A C-18 column with a mobile phase containing acetonitrile acetate:phosphate buffer (pH 3.0) was employed. Samples were added with phosphoric acid, then extracted into dichloromethane, evaporated, and injected into the chromatograph. A detection potential of +0.85 V was applied on the basis of current-potential curves. Good linearity was found for each fluid in the expected range of therapeutic concentrations. The detection limit was 0.1 ng/mL for CSF, and 1 ng/mL for plasma and SF, with a recovery greater than 96% and intraday coefficient of variation less than 5% in all cases. The main advantages of this method include high specificity and sensitivity which allow the analysis of CSF and the use of small volumes of plasma and SF. The application of the method for the analysis of plasma and SF samples and the kinetic profile in CSF are shown.

Anti-Inflammatory Agents, Non-Steroidal↗