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Biomedical subjects

E Pozzi

Publications and source records attributed to E Pozzi.

At least 37 records · Page 2Linked to original sources

[Alveolar macrophage subpopulations and circulating monocytes. Immunophenotypic study in healthy non-smokers].

Peripheral blood monocytes of 10 non-smoker normal subjects and the macrophages of their bronchoalveolar lavage fluid (BAL) were investigated with two commercially available monoclonal antibodies (MAC 387, CD14). Surface membrane monocyte cells show simultaneously both markers. Instead alveolar macrophage (MA) can be divided in three different phenotype groups by the expression of the two markers (MAC 387+/CD14-, MAC 387+/CD14+, MAC 387-/CD14+). Particularly, MA with MAC 387+/CD14+ phenotype are adherent cells and morphologically lack anthracosis. Their alveolar presence in non-smokers can be due to normal turnover of monocytes from blood into alveoli. By contrast MA with MAC 387+/CD14- phenotype are non-adherent cells without anthracosis. At last MA with MAC 387-/CD14+ phenotype are non-adherent cells but different amounts of anthracosis in their cytoplasm can be observed.

Adult

Prostatic cancer--survey of hormonal treatment in Europe.

Prostatic cancer is often locally advanced or metastatic when diagnosed, making surgical removal and radiotherapy ineffective treatments. Alternative therapy involves androgen deprivation because prostatic cancer is known to be androgen-dependent. Orchidectomy has proved effective but other methods of reducing androgen concentrations have also been developed. Oestrogens have proved effective, as have progestogens, and both steriodal and non-steroidal anti-androgens have been extensively studied. Another possible treatment is the use of inhibitors of androgen metabolism (aromatase and 5 alpha-reductase). Luteinizing hormone releasing hormone analogues, which act as antagonists or agonists, have been shown to have efficacies comparable to those of other therapies. Adrenal suppression has provided a useful alternative to adrenalectomy, particularly because of the high morbidity rate of surgery in elderly patients. Complete androgen withdrawal using an anti-androgen in association with surgical or chemical castration may be a more superior treatment. Another possible approach is the use of somatostatin analogues, which have been shown to inhibit the growth of animal prostatic cancer cells.

Estrogens

Alpha 1-antitrypsin variants produced by recombinant DNA: differences in elastase inhibitory activity and resistance to oxidant agents.

Inherited or "acquired" deficiency of alpha 1-antitrypsin (believed to be the cause of pulmonary emphysema) will probably be treated in the future by replacement with alpha 1-antitrypsin purified from human plasma or produced by recombinant DNA, which seems promising because it permits site-specific mutagenesis in the oxidizable active site of the normal human alpha 1-antitrypsin. The aim of this in-vitro study was to investigate the elastase inhibitory activity and the resistance to oxidizing agents of normal human alpha 1-antitrypsin, a recombinant yeast-produced variant (VAL 358) and a recombinant E. coli-produced variant (LEU 358). The inhibitors were exposed to chemical oxidants (NCS, H2O2, xanthine/xanthine oxidase, chloramine-T) and to PMA-activated neutrophils. The elastase inhibitory activity was assayed on porcine pancreatic elastase and neutrophil elastase. Normal alpha 1-antitrypsin and VAL 358 variant were good inhibitors of both elastases. LEU 358 variant was the best inhibitor for neutrophil elastase, but it poorly inhibited the porcine pancreatic elastase. Normal alpha 1-antitrypsin was affected by all oxidants; both variants were almost totally resistant to chemical oxidants and to activated neutrophils. We conclude that recombinant alpha 1-antitrypsin variants differ in their elastase inhibitory activity and offer increased resistance to oxidant agents.

Animals

Familial elevation of serum angiotensin converting enzyme activity.

A clustering of high levels of serum angiotensin converting enzyme (S-ACE) was found in an Italian family. The elevation affected five subjects, two of whom were completely healthy and free from known causes of S-ACE increase. The values of S-ACE in hyperACEmic subjects exceeded the values found in normal relatives severalfold. HyperACEmia seemed to be inherited as an autosomal dominant trait. Immunogenetic studies were performed, but we did not find a genetic marker for this condition. The S-ACE activity was inhibited in vitro by edetic acid (EDTA) and SQ 14,225 (captopril). The S-ACE activity was also determined after 1:8 dilution and dialysis against saline of sera. From these experiments we deduced that Lieberman's intrinsic ACE inhibitor was lacking in the hyperACEmic sera. In the presence of remarkable S-ACE increase, a congenital elevation of S-ACE should be considered and it would be useful to perform a familial investigation.

Female

Studies of MR 889, a new synthetic proteinase inhibitor.

We investigated the proteinase inhibitory activity of MR 889, a thiolactic acid derivative. It is able to in vitro inhibit at low concentration (10(-5),10(-6)M) the activity of porcine pancreatic elastase, human neutrophil elastase and bovine chymotrypsin. In addition, MR 889 is able to inhibit the residual activity of alpha 2-macroglobulin-trapped human neutrophil elastase, paralleling the efficacy of phenylmethylsufonylfluoride. Finally, MR 889 has been shown to in vitro reduce the burden of elastase- and chymotrypsin-like activity found in sputum sol-phases of patients admitted for chronic bronchitis exacerbation.

Chymotrypsin

[Cefotetan in the therapy of respiratory infections. Multicenter research].

In a controlled multicenter trial 291 patients have been treated with cefotetan. They suffered from acute or chronic exacerbated bronchopulmonary disorders. In 110 patients it was possible to identify the etiological agent: enterobacteria (62), non-fermentative gram-negative bacilli (10), Haemophilus influenzae (8), Branhamella catarrhalis (1), Streptococcus pneumoniae (19), Staphylococcus aureus (12), Streptococcus pyogenes (4). In the exacerbations of chronic bronchitis (203), cefotetan was generally administered at the dose of 1 g/12 h i.m., whereas it was administered at the dose of 2 g/12 h i.v. in acute infection. The mean duration of therapy was 8.8 days. Positive clinical results were obtained in 251 patients (86.2%) with eradication of the pathogen initially isolated in 90.5% of cases. Cefotetan showed good local and general tolerance. The results obtained confirm those of studies concerning limited numbers of patients and show the efficacy of cefotetan both in acute and chronic pathologies, also in patients with serious involvement of their general conditions (concomitant pathologies, high mean age).

Acute Disease

Relationship between changes in alveolar surfactant levels and lung defence mechanisms.

Pulmonary surfactant, besides its mechanical properties, is thought to be involved in lung defence mechanisms. We previously described that: (1) in healthy animals, surfactant synthesis stimulation with ambroxol was accompanied by alveolar macrophage activation and a shift of the alveolar elastase/antielastase balance towards increased antielastase activity, and (2) in bleomycin-treated rats alveolar phospholipidosis was obvious 14 days after drug administration, ambroxol protection reduced the phospholipid peak and the morphological apperance of lung fibrosis at the 14th day of the experiment. The present study found that: (1) in healthy rats, the ambroxol-induced increase of alveolar antielastase activity did not appear due to reactivation of alpha 1-antitrypsin normally oxidized in the alveolar milieu; (2) in bleomycin-induced pulmonary fibrosis, ambroxol protection reduced total long collagen content at day 28, and (3) in paraquat-induced pulmonary fibrosis, alveolar phospholipids were markedly reduced throughout the 21 days of the experiment. On increasing the dose of paraquat, ambroxol protection significantly reduced the animals' death rate.

Ambroxol

Combined measurements of neuron specific enolase and bombesin/gastrin releasing peptide in lung cancer.

Pretreatment serum neuron specific enolase (NSE) and plasma bombesin/gastrin releasing peptide (BN/GRP) were measured in 92 lung cancer patients and 17 controls. The mean level of NSE (p less than 0.001) and BN/GRP (p less than 0.05) was significantly raised in patients with small cell lung cancer (SCLC, n = 62) compared to non-SCLC (n = 30) and controls. The mean concentration of NSE in extensive SCLC was significantly greater (p less than 0.005) than in limited stage but with a substantial overlap of values. Forty-seven out of 62 SCLC patients had at least one of the two markers raised (sensitivity 76%, specificity 83%), 44 had raised NSE (sensitivity 71%, specificity 89%) but only 24 had BN/GRP raised (sensitivity 42%, specificity 91%). At restaging, 16 of 19 patients with SCLC responsive to chemotherapy showed a significant fall of NSE; on the other hand, BN/GRP fell significantly in only 3 patients, remaining unchanged in the majority of responding patients. In conclusion, the combined determination of NSE and BN/GRP in SCLC, at diagnosis and during the follow-up, was not found to be superior to NSE determination alone.

Antineoplastic Combined Chemotherapy Protocols

In vivo studies of rat alveolar macrophage [corrected] microviscosity: influence of pulmonary surfactant synthesis stimulation.

The influence of pharmacological stimulation of pulmonary surfactant synthesis has been studied in rat alveolar spaces. Animals were treated acutely with Ambroxol at a dose of 4 mg/kg b.w./day p.o. and 5 days later the following biochemical and physico-chemical parameters were determined: BAL fluid lecithin content, BAL fluid microviscosity, alveolar macrophage membrane microviscosity, spontaneous generation of superoxide anion by alveolar macrophages, elastase and antielastase activity of BAL fluid. Treatment with Ambroxol significantly increased the lecithin content of BAL fluid and significantly decreased the macrophage plasma membrane microviscosity. A likely consequence of increased lecithin content in alveolar macrophages (an activation of these cells) was suggested by the increase of the spontaneous production of superoxide. Finally, in the BAL fluid of Ambroxol-treated rats the elastase activity was reduced, whereas the elastase inhibitory activity was almost doubled in respect to control rats.

Ambroxol

Role of alveolar phospholipids in bleomycin-induced pulmonary fibrosis in the rat.

The events leading to the onset of the experimental bleomycin-induced pulmonary fibrosis are so far unknown, though recent observations emphasize the crucial role played by lung phospholipids and by alveolar macrophages. In an attempt to verify this point, a series of studies were undertaken by treating rats (CD-COBS) with intratracheal instillation of a single dose of bleomycin (1.5 U). At the same time a group of animals was pretreated with ambroxol (which is known to be a powerful inducer of surfactant production both in fetal and adult type II pneumocytes), 4 mg/kg body weight/day per os, 5 days before the treatment with bleomycin and up to the sacrifice of the animals at the 1st, 3rd, 7th, 14th or 28th day from the instillation. In our experimental model, the 14th day from the treatment with bleomycin seems to be a crucial time since it histologically corresponds to the proliferation of type II pneumocytes; furthermore, an increase of total lecithins in the alveolar spaces was observed, together with an increase of macrophage membrane fluidity. In the ambroxol-pretreated group a partial reduction of the rate of interstitial fibrosis was observed. At the 14th day from treatment the alteration of phospholipid levels was much less pronounced and the microviscosity of alveolar macrophages was similar to that of control animals. These data suggest that the onset of bleomycin-induced pulmonary fibrosis in the rat is characterized by an increase of alveolar lecithins and that this fact could modify the physico-chemical peculiarities of alveolar macrophages. Ambroxol shows a partially protective effect, perhaps by modulating the activity of type II pneumocytes.

Ambroxol