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Biomedical subjects

G G Grassi

Publications and source records attributed to G G Grassi.

At least 19 recordsLinked to original sources
PubMed1998

Bombesin, calcium homeostasis and tumour growth.

Bombesin and its analogues are a family of naturally occurring neuropeptides with potent mitogenic activity. The ability of this agent to induce Ca2+ transients is likely to be relevant in this context, but it is not yet clear whether the effect of bombesin on cell growth is directly and exclusively related to its capacity to increase cytoplasmic Ca2+ levels. The present study investigates the affect of bombesin on cytoplasmic Ca2+ concentrations in human tumour cells of different origin: lung adenocarcinoma, lung adenocarcinoma with properties of alveolar epithelial cells (A549 cell line), mesothelioma and uterine carcinoma (HeLa cell line). Furthermore, the ability of bombesin to promote the in vitro growth of the same cells has been analysed. This agent was able to induce a transient rise in cytoplasmic Ca2+ levels in tumour cells from all lines. In lung adenocarcinoma cells, but not in the other tumour cells, bombesin produced Ca2+ transients followed by a moderate but sustained elevation of Ca2+ levels. The effects of bombesin on tumour cell cytoplasmic Ca2+ levels were compared to those of other agents, i.e. adenosine diphosphate (ADP), collagen or thrombin, which have been reported to induce Ca2+ transients in tumour cells. Bombesin and ADP increased cytoplasmic Ca2+ levels in all cell lines, while collagen and thrombin gave rise to higher transients, but were effective only in some tumour cells and not in others. Furthermore, bombesin was able to stimulate in vitro growth of all the tumour cells, except for the A549 cells, in which this agent induced a slightly lower increase in cytoplasmic Ca2+ concentration. These data may aid a better understanding of the complex relationship between the Ca2+ mobilizing and mitogenic activities of bombesin and may be of general interest when considering the biological effects of growth-stimulating factors.

Bombesin↗
PubMed1996

Bombesin enhances monocyte and macrophage activities: possible role in the modulation of local pulmonary defenses in chronic bronchitis.

Increased lung levels of bombesin-related peptides (BRPs) have been described in smokers and in patients with chronic obstructive pulmonary diseases (COPDs). Moreover, previous studies have shown that BRPs are endowed with immunoregulatory activities. The aim of the present study was to assess the in vitro influence of synthetic bombesin on the activity of mononuclear phagocytes obtained from healthy donors and from COPD patients. Bombesin significantly enhanced in vitro phagocytosis of monocytes and alveolar macrophages in both groups of subjects, restoring deficient phagocytosis in a group of COPD patients. Moreover, bombesin stimulated superoxide anion production and interleukin-8 release by peripheral monocytes.

Aged↗
PubMed1994

Comparative clinical efficacy of cefetamet pivoxil in lower respiratory tract infection.

Cefetamet pivoxil, because of its activity against respiratory pathogens and its pharmacokinetic behaviour, is expected to have clinical efficacy in the treatment of lower respiratory tract infection (LRTI). This paper presents an overview of clinical trials conducted worldwide to investigate the efficacy and tolerability of cefetamet pivoxil in the treatment of adults and children with LRTI. A total of 626 adult patients, the majority of whom presented with exacerbations of chronic bronchitis (n = 500), received oral cefetamet pivoxil 500 or 1000mg twice daily for 5 to 10 days (n = 351) or a standard comparator agent (n = 275). The comparator agents were amoxicillin (750mg 3 or 4 times daily, or 1000mg twice daily), amoxicillin/clavulanic acid (625mg 3 times daily), or cefaclor (250 or 500mg 3 times daily) administered for 5 to 12 days. A satisfactory clinical outcome (cure + improvement) was achieved in 79 to 94% of evaluable patients. In 336 children, 240 received cefetamet pivoxil at 2 dosage levels (10 or 20 mg/kg twice daily) for 7 to 12 days and 96 received the standard comparator, cefaclor (10 mg/kg 3 times daily). Cefetamet pivoxil was clinically effective at both dosages, and did not differ significantly compared with cefaclor (clinical cure rates of 97 to 99% with cefetamet pivoxil and 96% with cefaclor). A separate analysis of 305 patients with community-acquired pneumonia showed clinical successes in 80 to 100% of adults, 75 to 78% of elderly patients, and 98% of children treated with cefetamet pivoxil.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Cefepime: overview of activity in vitro and in vivo.

Cefepime is a novel methoxyimino-aminothiazolyl cephalosporin with a quaternized N-methyl-pyrrolidine moiety at the 3' position conferring zwitterionic properties. Because of this the molecule penetrates the outer cell membrane of Gram-negative bacteria rapidly. In addition it is resistant to degradation by several plasmid and chromosomally-mediated beta-lactamases, for which it also shows very low affinity and no inducing capacity. It has good affinity for PBPs 2 and 3 of Escherichia coli and for PBP 3 of Pseudomonas aeruginosa. Its broad-spectrum of activity includes Gram-positive and Gram-negative pathogens. It is more active than cefotaxime or ceftazidime, against Enterobacteriaceae. The MIC90 for P. aeruginosa is higher than that of ceftazidime, but lower than those of cefpirome, cefoperazone and latamoxef. Other Gram-negative organisms, Haemophilus influenzae, Neiserria meningitidis, Neiserria gonorrhoeae, Moraxella catarrhalis are highly susceptible to cefepime. Among Gram-positive species methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, whether beta-lactamase producers or not, Streptococcus pneumoniae and Streptococcus pyogenes are susceptible. Cefepime is active against cefotaxime- and/or ceftazidime-resistant Enterobacteriaceae. Only strains of P. aeruginosa producing large amounts of beta-lactamase may be resistant to both ceftazidime and cefepime. In experimental infections such as meningitis, induced with various bacterial species in neonatal rats and chronic staphylococcal osteomyelitis in rabbits, cefepime has shown good efficacy.

Animals↗
PubMed1993

Bioavailability of isoniazid, rifampicin and pyrazinamide (in free combination or fixed-triple formulation) in intermittent antituberculous chemotherapy.

A study was carried out in six human volunteers, to assess the blood kinetics of isoniazid, rifampicin and pyrazinamide, administered in a fixed-triple combination intended for use in intermittent chemotherapy of tuberculosis. The formulation employed contained 125 mg of isoniazid (H), 100 mg of rifampicin (R) and 375 mg of pyrazinamide (Z) per tablet; six tablets were administered to every subject, giving a total dosage of 750 mg of isoniazid, 600 mg of rifampicin and 2,250 mg of pyrazinamide. In each subject, the same dose of each drug was administered individually in separate sessions and the results compared. The results indicated that, at the level of dose of the intermittent tablet, no negative interactions between the drugs were observed.

Adult↗
PubMed1991

Antibiotics and their interaction with the host defense system in vivo.

The Authors review their own data on the in-vitro effect of a wide number of chemotherapeutic agents on phagocyte functions (chemotaxis, phagocytosis, phagocytosis-dependent metabolic activation, microbicidal activity). Aminoglycosides affected some leukocyte functions only at concentrations higher than those achieved in therapy. Macrolides, glycopeptides and fluoroquinolones showed no toxic effect on phagocytic activities. Beta-lactams, generally, did not influence phagocytic activities. However, ceftriaxone and cefoperazone irreversibly inhibited neutrophil chemotaxis. Cefodizime, on the other hand, enhanced phagocytosis of both neutrophils and monocytes, when non-opsonized particles were used as phagocytic challenge. Rifamycins inhibited neutrophil chemotaxis and enhanced the intracellular killing of S. aureus. These interactions with phagocyte function were tested ex vivo on cells of normal volunteers treated with these antibiotics. While no effect on chemotaxis in subjects treated with ceftriaxone and cefoperazone could be demonstrated, both cefodizime and rifampicin maintained their in-vitro activity in ex-vivo experiences. These findings seem to indicate that, so far, no definite conclusion can be drawn on the in-vivo significance of in-vitro findings.

Anti-Bacterial Agents↗
PubMed1990

Cefodizime in clinical use: a review of the clinical trial reports.

The clinical efficacy of cefodizime has been tested in several open and comparative studies, above all in lower respiratory tract infections (LRTI) and uncomplicated urinary tract infections (UTI), performed in 151 centres in Europe, Latin America, South-Eastern Asia and South Africa. Of 3791 patients, 2260 could be evaluated for efficacy and safety. Comparative studies in LRTI were carried out vs cefotaxime and cefuroxime (301 vs 299 patients); both clinical and bacteriological results were superimposable (range of satisfactory clinical outcomes from 86% to 95%; bacteriological eradication 95% to 100%). In open studies (533 evaluable patients) the percentage of clinical successes ranged from 79.1% to 91.8% and the bacteriological eradication from about 87% to 90%, according to the type of infections. Comparative studies (cefodizime vs cefuroxime or ceftizoxime) in UTI again demonstrated the equivalence of treatment. In open studies (374 evaluable patients) the percentage of satisfactory clinical outcomes ranged from 84.6% in complicated upper UTI to 95.9% in lower uncomplicated UTI, with overall bacteriological eradication of 92.7%. Side effects could be evaluated in 5801 patients (Western and Japanese clinical studies); 3.79% of patients showed side effects (1.99% gastrointestinal disturbances, 0.9% rash or urticaria, 0.9% other effects); 1.13% of patients required discontinuation of treatment. No relevant changes in laboratory parameters were observed. Cefodizime has been shown to be an effective and safe agent in the treatment of LRTI and UTI caused by susceptible pathogens. A dosage regimen of 1 g every 12 h seems to be the most suitable schedule for the treatment of LRTI while 1 g every 12 h or 2 g every 24 h can equally well be adopted for treatment of UTI.

Bacterial Infections↗
PubMed1988

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↗
PubMed1988

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↗
PubMed1986

A multicenter study on clinical efficacy of ofloxacin in respiratory and urinary tract infections.

A multicenter trial on the efficacy and tolerability of ofloxacin in upper and lower respiratory tract infections and urinary tract infections was carried out on 1,436 patients (926 males and 510 females; mean age 55.9 +/- 18.4 years). Three dosage regimens were randomly applied: 200 mg, 300 mg and 400 mg ofloxacin b.i.d. by the oral route. The overall clinical outcome expressed as the ratio of the number of patients cured and improved to the number of patients treated was 279/324 (86%) in upper respiratory tract infections; 612/667 (91.8%) in lower respiratory tract infections and 418/445 (93.9%) in urinary tract infections. Out of 872 bacterial strains isolated in 802 patients, 742 (85.1%) were eradicated. Side effects not requiring interruption of therapy were observed in 65 patients (4.5%), while interruption was necessary in 23 patients (1.6%). The most frequent side effects were gastrointestinal disturbances. In conclusion ofloxacin showed a good clinical efficacy and tolerability in the treatment of respiratory and urinary tract infections.

Adult↗
PubMed1986

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↗
PubMed1985

Respiratory infections: established therapy and its limitations.

Factors influencing the selection of an antibiotic include the findings of susceptibility tests, the relative ability of various agents to reach the site of infection, and the difficulties of treating resistant microorganisms. After a brief review of these factors and the characteristics of piperacillin, established therapies for acute bronchitis, chronic bronchitis, bacterial pneumonias, pleurisy and empyema, bronchiectasis, lung abscess, and cystic fibrosis are outlined. New therapies for various lower respiratory tract infections, aspiration or decubitus pneumonia, and infections in patients with cystic fibrosis, and in immunocompromised patients are discussed, as are the advantages and disadvantages of aerosol administration or endotracheal instillation of antibiotics.

Aged↗
PubMed1983

In-vitro antibacterial activity of cefotetan.

The in-vitro activity of cefotetan, a recently developed cephamycin, was investigated under various experimental conditions. The compound showed moderate activity against Staphylococcus aureus and Streptococcus pyogenes, no activity against Pseudomonas aeruginosa and Streptococcus faecalis, but a high activity against Enterobacteriaceae, including beta-lactamase-producing strains. Haemophilus influenzae also was fairly susceptible. The MBC was usually equal to or two- or fourfold higher than MIC. Medium composition, pH and inoculum size had minimal influence on its activity. About 50% of recent clinical isolates of Bacteroides fragilis were susceptible to cefotetan, but some were highly resistant. Killing curves of cefotetan against different bacterial strains indicated that it was rapidly bactericidal at concentrations equal to MIC or two- to fourfold higher. However, some strains showed regrowth after initial inhibition. Combination of cefotetan with aminoglycosides, or with cefazolin, cefotaxime, moxalactam or piperacillin resulted either in synergy, addition or indifference according to the bacterial strain and the nature of the combination. Antagonism was never observed. Human serum protein binding varied from 75 to 86% according to the assay method. Binding with horse serum protein was about 28%.

Aminoglycosides↗
PubMed1983

Effect of beta-lactam antibiotics on migration and bactericidal activity of human phagocytes.

The effect of beta-lactam antibiotics upon some functions of human phagocytes was examined. Penicillins (carbenicillin and piperacillin), thienamycin, and cephalosporins (cefotetan, ceftazidime, and moxalactam) had no effect on either the random or directional migration or on the bactericidal activity of neutrophils and monocytes against Staphylococcus aureus. On the contrary, cefoperazone at therapeutic levels was shown to inhibit neutrophil chemotaxis.

Anti-Bacterial Agents↗