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Biomedical subjects

A Fietta

Publications and source records attributed to A Fietta.

At least 19 recordsLinked to original sources

Uptake of flurithromycin by human polymorphonuclear phagocytes: partial characterization of the entry mechanism.

The ability of flurithromycin and erythromycin to enter human polymorphonuclear phagocytes were studied and compared by a velocity centrifugation gradient technique. Both macrolides were markedly concentrated by human cells and attained cellular to extracellular concentration ratios (C/E) > or = 10. The incorporation was rapid and essentially complete after 60 min incubation. When PMNs were pretreated with formaldehyde, or incubated at low temperatures (4-25 degrees C) or at low pH, the transport ratios of both molecules were reduced. Sodium fluoride and 2,4-dinitrophenol, which decreased erythromycin uptake, did not affect flurithromycin penetration. Perturbation of cell membrane by phorbol myristate acetate, but not by formyl methionyl leucyl peptide, affected C/E ratios of both antibiotics. The addition of amino acids or nucleosides did not influence their transfer into PMNs.

Adult

Evidence for CD8+ cell increase in long-term PUVA-treated psoriatic patients after PUVA discontinuation.

Long-term PUVA-treated psoriatic patients given maintenance therapy (UVA doses greater than 1,000 J/cm2) have been demonstrated to undergo lymphopenia and a decrease in the total number of circulating CD3+ and CD4+ T cells. The aim of this study was to assess whether the impairment of T cells is detectable also in psoriatic patients after long-lasting PUVA discontinuation. A group of 34 psoriatic patients (25 males, 9 females; mean age 52.7 +/- 12.82 years), who had previously been treated by PUVA therapy (average cumulative dose 1,898.48 +/- 1,207.12 J/cm2), was studied 1 year or more after discontinuation of PUVA therapy. The patients studied failed to show any impairment in CD3+ and CD4+ cells. Nevertheless, a significant increase (p less than 0.05) in circulating CD8+ cells (both in the percentage and the total number) was detectable in PUVA patients as compared to appropriate controls. The significance and implications of this finding are not known and need further investigations.

CD4-CD8 Ratio

Lymphopenia and decrease in the total number of circulating CD3+ and CD4+ T cells during 'long-term' PUVA treatment for psoriasis.

The relationship between high-dose PUVA treatment in psoriatic patients and peripheral T lymphocyte subsets (total number and percentage) has been studied. Of the two groups of patients considered, the first included 19 patients, all affected by chronic, progressively worsening psoriasis; they had never been previously treated by photochemotherapy. The second group included 13 psoriatic patients, who had received an average cumulative dose of 2,007.69 +/- 1,191.05 J/cm2. The 'long-term' PUVA-treated group was assessed while undergoing maintenance therapy. No significant differences were found between untreated patients and healthy controls for any of the parameters considered. A significant reduction (p less than 0.05) in the total number of lymphocytes in long-term PUVA-treated patients both versus untreated patients and controls was found. Furthermore, long-term PUVA-treated patients showed a significant reduction (p less than 0.05) in the percentage of lymphocytes as compared with controls. The reduction in the total number of CD3+ and CD4+ T cells was, moreover, significant (p less than 0.05) as compared with untreated patients. The impairment of circulating CD3+ and CD4+ T cells (total number) was only on the borderline of statistical significance vis-à-vis controls. These findings suggest the usefulness of a careful assessment of circulating T lymphocyte subsets in patients who undergo long-term PUVA therapy.

Adult

Effects of medium-term PUVA therapy on peripheral T-lymphocyte subsets in psoriatic patients.

Three to four months' PUVA treatment is a widely-adopted procedure to induce psoriasis remission and for the purpose of this study is called "medium-term". The 32 psoriatic patients considered revealed a statistically significant baseline decrease in OKT3+ (p less than 0.001), OKT4+ (p less than 0.001) and OKT8+ (p less than 0.001) as compared with 40 healthy controls, while OKT4/OKT8 was normal. Variance analysis within the psoriatic group failed to reveal further significant variation in the immunological parameters during the 3 months under study. Nevertheless, there was a marked trend towards a reduction in OKT4+ cells and OKT4/OKT8 as compared with baseline values after 3 months. These results suggest that "medium-term" PUVA therapy does not statistically restore the pre-existing baseline changes in T-lymphocyte subsets of the psoriatic patients. The non-statistically significant effects as regards OKT4+ may be due to the small number of patients who reached 3 months' treatment (9 patients) but could be regarded as the first step towards the significant changes described here in long-term PUVA-treated psoriatic patients.

Adult

Evaluation of systemic host defense mechanisms in chronic bronchitis.

Seventy-six chronic bronchitis patients were studied in order to determine the possible presence of disorders in their systemic defense mechanisms. No significant difference in lymphocyte subsets, in serum immunoglobulin and complement component (C3 and C4) levels was found in chronic bronchitis patients compared to normal adult controls. Skin tests for delayed hypersensitivity revealed a high frequency (39%) of hypoergic patients (with 1-2 positive reactions) in comparison to normal subjects. Altered values of many functional properties of both neutrophils and monocytes were demonstrated. The percentage of patients with intermediate (between 1 and 2 SD below the mean of controls) and defective (lower than 1.96 SD) values of chemotaxis, phagocytosis index and Candida killing was about 50%. Phagocytosis frequency and nitroblue tetrazolium reduction frequency were less frequently impaired.

Aged

Double-blind trial RU 41740 vs. placebo: immunological and clinical effects in a group of patients with chronic bronchitis.

A double-blind trail was performed to investigate the effects of RU 41740, a glycoprotein extract from Klebsiella pneumoniae, on host defenses and its efficacy in reducing the number of exacerbation in 29 evaluable patients with chronic bronchitis, out of 36 patients who entered the study. The drug enhanced the phagocytosis indexes of both polymorphonuclear and mononuclear phagocytes. Increased candidacidal activity of monocytes was also observed. These effects, already detectable after one course of therapy and during the entire period of treatment, were no longer detectable when tested 6 months after the end of treatment. A significantly (p less than 0.05) larger number of patients in the treated group than in the placebo group had no exacerbations during drug administration (0-3 months). Moreover, patients treated with RU 41740 had significantly fewer and shorter episodes of acute exacerbation. The positive decreases in these two parameters persisted throughout the follow-up.

Adjuvants, Immunologic

In vitro and ex vivo enhancement of nonspecific phagocytosis by cefodizime.

The in vitro and ex vivo effects of cefodizime on some functional activities of both human neutrophils and monocytes were studied. In vitro experiments were performed with antibiotic concentrations ranging from 1 to 200 micrograms/ml. For the ex vivo study, 7 adult healthy controls were treated intravenously with 4 g/day of cefodizime for 6 days. We found that the drug modulated phagocytosis frequency and index when nonopsonized zymosan and heat-killed Candida albicans were used as phagocytic challenge both in vitro (from 25 micrograms/ml) and ex vivo 12 h after the last administration of cefodizime. No effect on the other phagocyte functional parameters was shown. The in vitro enhancement of nonspecific phagocytosis was demonstrated both in the presence of cefodizime and when phagocytes and particles were separately incubated with the drug.

Candida albicans

Complement-dependent bactericidal activity for E. coli K12 in serum of preterm newborn infants.

Complement-dependent serum bactericidal activity for E. coli K12 was assessed in 12 term infants and in 16 preterm infants. In both groups of newborns, at birth, bactericidal reaction by the classical pathway of complement activation was impaired with respect to normal controls at less than 0.001 level of significance (as estimated by Student's t-test). The serum bactericidal reaction by the alternative pathway of complement activation was significantly impaired only in preterm newborns, being normal in term infants. At a time corresponding to 40 weeks' gestational age also in preterm newborns alternative pathway mediated bactericidal activity for E. coli K12 was found normal. Classical pathway mediated bactericidal activity became normal only at an age corresponding to 52 weeks' gestational age.

Blood Bactericidal Activity

Does a relationship exist between neutrophil myeloperoxidase deficiency and the occurrence of neoplasms?

36 unrelated individuals with neutrophil MPO deficiency, (10 totally MPO deficient) were found on screening a population of 148,000 subjects. A further 2 subjects with total and 22 with partial MPO deficiency were identified through family studies. The assessment of neutrophil function, i.e., peroxidase activity, superoxide anion generation, microbicidal activity towards fungi and bacteria, and locomotor behaviour, was carried out in 10 subjects with total and 4 with partial MPO deficiency. We found that the enzyme defect is associated with a marked impairment in the killing of both S. aureus and C. albicans, without affecting microbicidal activity against S. faecalis. There appears to be a high incidence of malignancy in patients with complete MPO deficiency, suggesting a relationship between a defective MPO system and neutrophil-mediated tumor cell cytotoxicity.

Adolescent

In vitro and ex vivo influence of rifamycins on human phagocytes.

We studied the effects of rifamycin SV, rifampicin and rifapentine on human phagocyte functions. Rifamycins inhibited in vitro neutrophil chemotaxis in the range of their therapeutic levels, and they significantly affected the survival of a rifamycin-sensitive strain of Staphylococcus aureus inside human monocytes. Both effects were related to the intraphagocytic penetration of these antibiotics. For the ex vivo studies, 600 mg of rifampicin were orally administered to five subjects with defective S. aureus killing. A significant reduction of neutrophil chemotaxis and increased activity against S. aureus were shown 150 and 210 min after administration of the drug.

Chemotaxis, Leukocyte

In vitro activity of macrolides on human phagocytic functions.

The aim of this study was to examine the in vitro activity of erythromycin, josamycin, flurithromycin, miocamycin and roxithromycin on some leukocyte functional parameters. All tested macrolides did not interfere with the frequency and index of phagocytosis, nitroblue tetrazolium reduction to formazan deposits and candidacidal activity of human polymorphonuclear leukocytes (p greater than 0.05). Among macrolide antibiotics, only flurithromycin significantly inhibited neutrophil chemotaxis at a high concentration (greater than or equal to 50 micrograms/ml). All macrolides, at 10 and 50 micrograms/ml, reduced the survival of a susceptible strain of Staphylococcus aureus ingested by human monocytes.

Anti-Bacterial Agents

The effect of teicoplanin on leukocytic activity and intraleukocytic micro-organisms.

The interference of teicoplanin with certain phagocyte activities was investigated in comparison with that of vancomycin. Neither teicoplanin nor vancomycin interfered with chemotaxis, adherence, phagocytosis or nitroblue tetrazolium reduction of human neutrophils. Teicoplanin, but not vancomycin, enhanced intracellular killing by neutrophils from normal donors and from a patient with chronic granulomatous disease. Human monocytes in the absence of fresh human serum did not significantly kill Staphylococcus aureus but when pre-treated with teicoplanin 90% of phagocytozed bacteria were killed during 4 h incubation.

Anti-Bacterial Agents

Evaluation of the host defense system in asthmatic patients.

The efficiency of some components of the host defense system has been evaluated in 32 atopic patients with rhinitis, asthma or asthma and rhinitis. No alterations in components of complement (C3 and C4), serum immunoglobulins (IgG, IgA, and IgM) and neutrophil functional parameters were found. As expected, serum IgE values were higher than in controls. A decreased percentage of total circulating T lymphocytes, an increased percentage of Ia1-positive cells, but normal values of OKT4- and OKT8-positive T lymphocytes were demonstrated. However, a greater heterogeneity in the distribution of the suppressor-cytotoxic subset was shown in atopic patients.

Adolescent

In vitro activity of flurithromycin, a novel macrolide antibiotic.

Flurithromycin is an (8,S)-8-fluoroerythromycin isolated from the fermentation broth of Streptomyces erythraeus ATCC 31772, a blocked mutant of a strain producer of erythromycin. Its in vitro antibacterial activity has been determined on recent clinical isolates of respiratory pathogens. The range of MIC for Streptococcus pneumoniae and Streptococcus beta-haemolyticus group A is from 0.0015 to 0.006 microgram/ml, for Haemophilus influenzae from 0.012 to 0.4 microgram/ml, for Staphylococcus aureus from 0.1 to 3.1 micrograms/ml. Its action is bacteriostatic and increases at alkaline pH. Among anaerobes Clostridium perfringens, Bacteroides fragilis, other species of Bacteroides and Peptostreptococcus are particularly susceptible. Flurithromycin also showed some activity on Mycobacterium bovis, M. scrofulaceum and M. phley. The determination of killing curves indicated that in most cases a killing effect was obtained at 4 X MIC. A combination of flurithromycin with ampicillin or doxycycline sometimes was synergic, but more often additive and never antagonistic. The possible interference of flurithromycin on some parameters of the natural system of defense was determined. At concentrations equal to therapeutic levels in blood and tissues, flurithromycin did not influence chemotaxis, phagocytosis, metabolic activation and the killing activity of neutrophils.

Ampicillin

[Morphological, ultrastructural, cytochemical and functional analysis of neutrophils deficient in myeloperoxidase].

Eighteen patients with established hereditary myeloperoxidase deficiency underwent morphological, ultrastructural, cytochemical and functional analysis in order to correlate the lack of peroxidase from phagocytes with other leucocyte activities. Cytochemical and ultrastructural findings only confirmed the peroxidase defect in neutrophil and monocyte population, whereas normal peroxidase activity was detected in eosinophil granulocytes ("Alius-Grignaschi anomaly"). Morphological analysis, as determined by both ligh and electron microscopy, showed in two patients with total MPO-deficiency a large number of neutrophils (50-60%) with nuclear abnormalities very similar to Pelger-Huet's heterozygous form (two lobed neutrophils having a typical pince-nez appearance and a nuclear chromatin coarser than that of normal PMNL). Other 2 cases displayed a 50-60% five-lobed neutrophils, as occur in congenital nuclear hypersegmentation of PMNL. These findings suggest that Alius-Grignaschi anomaly and Pelger-Huet syndrome can be found associated in the same individuals, since both these abnormalities have a genetic origin. Finally, since an impaired bactericidal and fungicidal activity was observed, no patients displayed particular susceptibility to persistent or severe infections, thus confirming the presence of MPO-independent enzymatic systems.

Blood Bactericidal Activity