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Biomedical subjects

M Falchi

Publications and source records attributed to M Falchi.

At least 19 recordsLinked to original sources

Expression of interphasic nucleolar organizer regions in normal, dysplastic and neoplastic colorectal mucosa.

Silver-binding nucleolar organizer region (Ag-NOR) expression in interphasic nuclei was studied in normal, dysplastic and neoplastic colorectal mucosa at the light microscope level and by means of an image analyser (IBAS II). Both methods showed a progressive increase in the mean number of Ag-NOR sites per nucleus from mild dysplasia to invasive carcinoma. Ag-NOR counts differed significantly in the various classes of lesions (P less than 0.001), except between moderate and severe dysplasia (P greater than 0.05). Severe dysplasia showed a mean number of NORs lower than that for invasive carcinoma though an overlap in the respective frequency distributions was observed. The mean of the variances of the mean dot areas per cell nucleus (pooled variance) also showed a step-wise increase from normal to neoplastic lesions, indicating a greater variability in NOR size as a characteristic of malignant cells. A similar increase was observed in the percentage of nuclear area occupied by Ag-NORs. The mean area per silver-stained dot was also measured in the different classes of lesions by IBAS II. Data obtained showed no significant differences among the values. In conclusion, the wide overlap between the frequency distributions does not allow consideration of the Ag-NOR count alone to be a reliable marker of malignant transformation in a single cell. It appears that the study of Ag-NOR number needs to be evaluated together with dot anisometry in order to be a useful criterion in distinguishing the biological behaviour of neoplastic lesions in colorectal mucosa.

Colon

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

On the mechanism of cell internalization of chrysotile fibers: an immunocytochemical and ultrastructural study.

Human breast carcinoma cells (CG5) and human laryngeal carcinoma cells (HEp-2) were exposed to 10 and 50 micrograms/ml of small (about 5 microns) chrysotile asbestos fibers. Morphological and ultrastructural changes were evaluated by means of immunocytochemistry and by scanning and transmission electron microscopy. Our attention was focused on the mechanisms of cell internalization and on transport of chrysotile fibers. The fibers appeared to penetrate the cell cytoplasm and to be translocated in proximity of the nucleus. Small chrysotile fibers could also be found inside the nucleus of interphase cells. Involvement of the main cytoskeletal components, i.e., microfilaments, intermediate filaments, and microtubules, in the cytotoxicity of chrysotile fibers was also evaluated. Our findings suggest that after fiber penetration, a rearrangement of the cytoskeletal apparatus occurs. It has also been observed that small fibers remain associated with the cytoskeletal framework, which can thus play a role in asbestos intracytoplasmic translocation in epithelial cells. Furthermore, after the cell has completely recovered its morphology, fiber internalization ultimately seems to lead to the formation of giant multinucleated cells. These data could be indicative of an interaction occurring between asbestos fibers and the normal mitotic process. The disturbance of the cell cytoskeleton and the close morphologic contact between asbestos fibers and the cell's nuclear region may be of importance in explaining the well-known carcinogenic effects of asbestos mineral fibers.

Asbestos

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

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

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

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

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

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

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

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

Mineral fibres and dusts in lungs of subjects living in an urban environment.

We have undertaken a study on 200 autopsy lung samples collected from subjects who lived in the Rome urban area and were not occupationally exposed to mineral dusts. The samples belonged to subjects who died aged between 15 and 65, both male and female. Subjects suffering from diseases and drug addicts were excluded. The purpose of this investigation was to determine whether any correlation existed between subjects' life-style, in particular smoking habits, and the presence of mineral fibres and dusts in their lungs. The data obtained were compared with those on airborne mineral dusts in the environment of the subjects themselves, particularly data on the concentration and types of mineral fibres present in that environment.

Adolescent

Miokamycin penetration into oral cavity tissues and crevicular fluid.

Diffusion of miokamycin into gum, maxillary-mandibular bone and crevicular fluid was studied in human beings. The antibiotic concentrations were determined in specimens at different times after oral administration of 600 mg in a single dose of miokamycin. Peak serum levels (2.32 +/- 0.67 mcg/ml) were found at the first hour after dosage. In healthy gum tissue the highest antibiotic levels (1.44 +/- 0.34 mcg/gr) were observed at the second hour, while in the inflamed gum miokamycin penetrates more rapidly, being, as in serum at the highest levels detectable during the first hour. In the bone of the maxilla or mandible the highest levels of miokamycin (0.88 +/- 0.13 mcg/gr) were detected at the second hour after treatment. In the crevicular fluid miokamycin showed a similar profile as that in serum, since the peak levels were reached at the first hour (2.4 +/- 0.88 mcg/ml, but the decrease of the antibiotic occurred more slowly than in serum. Miokamycin rapidly penetrates into tissues and fluids of oral cavity. A single oral dose of 600 mg guarantees antibacterial levels against susceptible bacteria over six hours.

Administration, Oral

Bactericidal effect of ceftriaxone versus imipenem plus cilastatin in bronchial secretion.

The bactericidal quotient (BQ) assessed in the site of infection represents an essential parameter for evaluating the real bactericidal potency of an antibiotic in vivo. The assessment and knowledge of BQ values allow us to set up a more accurate and appropriate antibacterial therapy. The two drugs--ceftriaxone (Rocephin) and imipenem plus cilastatin (Tienam)--that have been taken into consideration in this study, having a similar antibacterial spectrum though with different kinetics, may have the same BQ values in bronchial secretion versus Haemophilus influenzae, Klebsiella pneumoniae and Streptococcus pneumoniae, when administered at different dosages, i.e. ceftriaxone 1 g (i.v.) every 24 h, imipenem 0.5 g (i.v.) every 8 h.

Aged

Non-interference of xibornol on the theophylline blood levels.

The authors have proposed the evaluation of the possible pharmacokinetic interactions between xibornol and theophylline. This study has been carried out on eight healthy volunteers of both sexes between 19 and 27 years of age. On the first day each subject was treated with 600 mg oral sustained-release formulation of aminophylline at 08h00 and at 20h00. From the 2nd day an oral administration of 500 mg of xibornol every 8 h was added to the treatment of aminophylline. On the 1st, 2nd and 5th day blood samples were taken after 30, 90, 180 and 300 min following drug administration. After serum separation an analysis was performed on them. The results have shown that theophylline levels at the programmed times during the three days tested are just overlapping. In conclusion the administration of xibornol does not introduce any interference with theophylline clearance or lengthening of its plasma half-life.

Adult

Distribution of ceftriaxone in the tissues of the female genital system.

Twenty-nine patients, hospitalized in order to undergo gynaecological surgery involving organ removal, were treated with a single intramuscular administration of 1 g ceftriaxone before surgery. The tissue levels of the drug determined in the organs considered: uterus, ovary, fallopian tubes, vagina, proved to be comparable and to guarantee its satisfactory and uniform penetration into the tissues of the female genital system at a slowly decreasing rate. The high levels observed 12 h and 24 h after administration (2.24 +/- 0.74 mcg/g; 3.58 +/- 0.60 mcg/g; 0.70 +/- 0.45 mcg/g; 1.20 +/- 0.57 mcg/g in the ovaries and myometrium respectively) suggest a possible application of ceftriaxone in presurgical prophylaxis also in cases of female genital surgery.

Adolescent