Search PubMedSearch

Biomedical subjects

F Fraschini

Publications and source records attributed to F Fraschini.

At least 37 records · Page 2Linked to original sources

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

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

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

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

[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

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

Endocrine and immune effects of melatonin therapy in metastatic cancer patients.

Melatonin, the most important indole hormone produced by the pineal gland, appears to inhibit tumor growth; moreover, altered melatonin secretion has been reported in cancer patients. Despite these data, the possible use of melatonin in human neoplasms remains to be established. The aim of this clinical trial was to evaluate the therapeutic, immunological and endocrine effects of melatonin in patients with metastatic solid tumor, who did not respond to standard therapies. The study was carried out on 14 cancer patients (colon, six; lung, three; pancreas, two; liver, two; stomach, one). Melatonin was given intramuscularly at a daily dose of 20 mg at 3.00 p.m., followed by a maintenance period in an oral dose of 10 mg daily in patients who had a remission, stable disease or an improvement in PS. Before and after the first 2 months of therapy, GH, somatomedin-C, beta-endorphin, melatonin blood levels and lymphocyte subpopulations were evaluated. A partial response was achieved in one case with cancer of the pancreas, with a duration of 18+ months; moreover, six patients had stable disease, while the other eight progressed. An evident improvement in PS was obtained in 8/14 patients. In patients who did not progress, T4/T8 mean ratio was significantly higher after than before melatonin therapy, while it decreased in patients who progressed. On the contrary, hormonal levels were not affected by melatonin administration. This study would suggest that melatonin may be of value in untreatable metastatic cancer patients, particularly in improving their PS and quality of life; moreover, based on its effects on the immune system, melatonin could be tested in association with other antitumor treatments.

Adenocarcinoma

In-vivo and in-vitro interference of antibiotics with antigen-specific antibody responses: effect of josamycin.

The effects of josamycin on the antigen-specific primary antibody responses of human peripheral blood cells have been studied by the method of haemolytic colonies in soft agar. The tests were performed before and after the oral administration of 1 g of josamycin or by adding the drug directly to cultures of cells from untreated donors. The results demonstrate that josamycin, added in vitro or administered in vivo significantly depresses the primary antibody responses. The mechanism by which josamycin exerts its activity on antibody production has been partially elucidated. The immunodepression depends on the stimulation of hydrogen peroxide production by monocytes and requires the actual presence of josamycin during the immune response. The stimulation of the respiratory burst of the phagocytic cell is a common feature of macrolide antibiotics and suggests the need for more extensive clinical and preclinical trials on antibacterial antibiotics that alter the human immune responses.

Adult

Melatonin and pituitary-gonadal function in disorders of eating behavior.

In order to study the possible relationships between melatonin secretion and pituitary-gonadal function, the circadian rhythm of plasma melatonin, the basal levels of estradiol-17beta and testosterone and the luteinizing hormone (LH) and follicle-stimulating hormone (FSH) response to luteinizing hormone-releasing hormone (LH-RH) stimulation were evaluated in normally cycling healthy women and in two groups of women with menstrual dysfunctions related to eating disorders (19 patients with anorexia nervosa and 16 with primary obesity). The circadian rhythm of plasma melatonin reached statistical significance in anorectic patients but not in obese patients. The mean 24 h melatonin level was significantly higher in anorectic than in obese patients and in control subjects. However, both groups of patients shared some abnormalities of melatonin circadian pattern, such as increased ratio between day and night melatonin levels, abnormal secretory peaks during the light hours and great interindividual variability for timing, amplitude, and duration of melatonin nocturnal peak. A selective impairment of LH secretion was observed in both anorectic and obese patients. By considering together the two groups of patients and controls, a linear inverse correlation between the circadian mesor of plasma melatonin and the basal and LH-RH stimulated LH levels was found. The persistence of a certain melatonin secretion during the light hours in both anorectic and obese patients could play an inhibitory role on the pituitary gonadal function in these subjects.

Adolescent

Study on the relationship between pharmacokinetics and antibacterial activity: comparison between ceftriaxone and cefotaxime within the respiratory tract.

The aim of this research was to collect precise data on the antibacterial activity of ceftriaxone and cefotaxime in the respiratory tract. The diffusion into pulmonary tissue and bronchial secretion and the antibacterial activity of the two antibiotics were evaluated in vivo by means of the inhibitory quotient. Ceftriaxone administered at a dosage of 1 g (i.m.) every 24 h resulted in antibacterial levels against the sensitive pathogens over a period of 24 h after each dose. The antibacterial protection afforded by cefotaxime, given at the dosage of 1 g (i.m.) every 12 h, was not as marked and did not extend over the interval between two administrations.

Aged

Miokamycin and leukocyte activity in man.

The effects of miokamycin on the immune system were studied in healthy volunteers by means of the following assays: phagocytosis, intracellular killing and natural killer activity. The tests were performed before, 2 and 6 h after oral administration of 600 mg of miokamycin. The findings suggest that miokamycin stimulates phagocytosis and intracellular killing. These effects could be clearly shown 2 h after drug intake and disappeared at the 6th hour. On the contrary, the natural killer activity was not significantly stimulated by miokamycin.

Adult

Cytosolic androgen receptors in the neuroendocrine tissues of the golden hamster: influence of photoperiod and melatonin treatment.

Hamsters exposed for eight weeks to short photoperiod (LD 10:14) or treated with melatonin in the late afternoon under long photoperiod (LD 14:10) had significantly higher number of cytosolic androgen receptors in the pituitaries, hypothalami and harderian glands, as compared to the long photoperiod (LD 14:10) exposed controls. The numerical value of the apparent Kd was two to three times lower in the hypothalami and pituitaries, but not in the harderian glands of the animals from these groups. These results indicate that alterations in receptor numbers and affinity constants may be responsible for the dramatic changes in the sensitivity of the hypothalamo-pituitary axis to the negative feedback actions of the gonadal steroids, observed under inhibitory photoperiods and that this effect could be duplicated by late afternoon melatonin treatment.

Animals

Cortical and medullary kidney tissue levels of cefonicid in human beings.

Cefonicid concentration has been determined microbiologically in cortical and medullary tissue in 30 patient undergoing surgery because of neoplastic disease localized within the kidney. Each subject received 1 g of cefonicid intramuscularly in a single administration. The patients were divided into six groups, from which samples of blood and tissue were collected 2, 4, 6, 8, 12, 24 h respectively after treatment with the drug. The mean peak serum levels appeared at the second hour (74.96 +/- 8.14 mcg/ml) and the decay shows a monoexponential behaviour, reaching a minimum value of 5.4 +/- 2.33 mcg/ml at the 24th hour. In the cortical tissue of the kidney the peak levels appeared at the fourth hour (26.22 +/- 8.87 mcg/g), while at the 24th hour levels were about 3.08 +/- 0.81 mcg/g. A very similar behaviour could also be observed in the medullary tissue of the kidney with peak levels at the fourth hour (25.82 +/- 10.06 mcg/g) and levels of 3.48 +/- 0.85 mcg/g at the 24th hour. A delay in the decay of tissue levels in comparison with the decay of blood levels could be observed from the eighth hour.

Adult

Pharmacokinetics of dactimicin in rats.

Dactimicin is a new pseudo-disaccharidic aminoglycosidic antibiotic produced by Dactylosporangium matsuzakiense. The aim of the present research was to evaluate the pharmacokinetics of dactimicin intramuscularly administered, at the dosage of 20 mg/kg, in male Sprague-Dawley rats with an average b.w. of 200-220 g. Dactimicin levels were assessed by using a microbiological method (agar diffusion) employing Bacillus subtilis ATCC 6633 as test organism. Samples were collected immediately before and 0.25, 0.50, 1, 1.15 and 2 h after drug administration. The mean peak serum level, reached after 15 min, was 33.6 micrograms/ml (range 30.3-40 micrograms/ml); T1/2 beta was 0.42 h; extrapolated AUC was 26.8 mg h/l.

Aminoglycosides

Efficacy and safety of enoxacin in the treatment of respiratory infections.

The present report concerns an open clinical trial aimed to investigate the efficacy and safety of enoxacin (Zami 8401), a new quinolone drug, in bacterial infections of the lower respiratory tract. A total of 30 hospital in patients, 25 males and 5 females, of a mean age of 67 years (range 39-84 years), suffering from bronchopneumonia, or acute exacerbation of chronic bronchitis, were treated. Enoxacin was administered at the dose of 800 mg twice daily by the oral route. As a rule the patients received the drug for ten days. Efficacy was assessed on the basis of radiological, bacteriological and clinical changes. Tolerance was monitored by the daily recording of any sign or symptom possibly related with the drug as well as by laboratory tests performed before, during and after the treatment. Efficacy was excellent in 80%, good in 17%, poor in 3% of the patients. Tolerance was excellent in all except one patient. Enoxacin appears a very effective and safe drug in the treatment of the infections of the lower respiratory tract.

Adult

Cefroxadine in the treatment of children affected by respiratory and ENT diseases. A multicentre study involving 1072 in-patients.

In this multicentre trial, 1072 hospitalized children, 573 boys and 499 girls (847 of whom were aged less than 6 years), affected by respiratory tract (376 patients) or ENT (696 patients) infections were treated for 10 days with cefroxadine per os, at an average dose of 650 mg/day (325 mg every 12 h corresponding to 25 mg/kg b.w.). Most patients (1047; 97.7%) completed the trial, while 25 patients were withdrawn from the study (20 patients for viral diseases and 5 for side-effects). Of the patients affected by respiratory tract infections, 361 completed the trial and 342 of them (94.7%) were cured in 6.0 days on average. Of the patients affected by ENT infections, 686 completed the trial and 649 of them (94.6%) were also cured in an average of 6.0 days. In the two groups the signs and symptoms of the disease significantly (p less than 0.001) decreased by the end of the study. Some patients (80; 7.6%) complained of side-effects, mainly gastric discomfort (4.9%), skin rash (2.2%) and glossitis (0.5%). In conclusion, cefroxadine exerts a satisfactory antibacterial action with only a few days of treatment, and it appears to be very well tolerated.

Bacterial Infections

Pharmacokinetics of buflomedil after various dosage forms.

The pharmacokinetic disposition of buflomedil was compared in humans after oral administration of solution, tablets and film tablets. Six healthy male volunteers received a single oral dose of the three different dosage formulations. Blood and urine samples were taken before dosing and at selected times over 24 h and 72 h, resp., after dosing. The concentration of the drug in samples was measured by gas-chromatography with nitrogen detector. The absorption of buflomedil was faster after solution administration, while other plasma parameters did not show any major differences. Also the amount of drug excreted in urines was higher with solution dosing.

Adult