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Biomedical subjects

E Pozzi

Publications and source records attributed to E Pozzi.

At least 55 records · Page 3Linked to original sources

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

Ambroxol and pulmonary toxicity induced by antineoplastic drugs.

The authors describe the potential effects of ambroxol on the pulmonary disorders induced by antineoplastic agents (in particular, bleomycin and the nitrosureas). An experimental stage focussed attention on the early modifications occurring in the alveolar surfactant and in the afflux of inflammatory and immune-effector cells following bleomycin-induced lung fibrosis in the rat (by intratracheal instillation). The ambroxol-protected rats showed a slower drop of alveolar lecithins in the first few hours after bleomycin administration and a lower afflux of neutrophils, macrophages and lymphocytes. In the clinical stage, respiratory function was studied in two groups of cancer patients treated with nitrosureas or bleomycin. Preliminary findings indicate a rapid worsening of some functional parameters--maximal expiratory flow at 25% vital capacity, diffusing capacity for carbon monoxide and diffusing capacity/ventilation--in controls, while no such changes occurred in the ambroxol-protected subjects. The possible pathogenetic implications of these results and perspective for future investigations are discussed.

Ambroxol

Endocrine-paracrine cells in prostatic carcinoma and clinical course of the disease.

The occurrence of endocrine-paracrine (argyrophil and argentaffin) cells in normal and hyperplastic human epithelia has long been recognized. 40 consecutive prostatic carcinomas were studied histochemically and ultrastructurally. The authors consider only clinically evaluable cases and discuss the clinical significance of the presence of endocrine-paracrine cells on the basis of their personal experience.

Adenocarcinoma

Pharmacokinetic studies on antituberculosis regimens in humans. I. Absorption and metabolism of the compounds used in the initial intensive phase of the short-course regimens: single administration study.

The absorption and metabolism of streptomycin, isoniazid, rifampicin, and pyrazinamide were evaluated after administration of each drug alone and in combination. In the combination sessions, isoniazid, rifampicin, and pyrazinamide were administered orally, either individually or in a single fixed-ratio triple preparation. The results have shown that the pattern of absorption and metabolism (acetyl-isoniazid, desacetyl-rifampicin, and pyrazinoic acid) found after administration of each drug alone did not differ from that found after administration of the drugs in free and fixed combination. The 3 orally administered drugs given in a fixed combination resulted in a reduction of the order of 50% of the total number of tablets to be ingested.

Absorption

Interstitial pneumopathy and low-dosage amiodarone.

In a 61-year-old man receiving chronic low-dosage amiodarone an interstitial pneumopathy was observed. In the absence of other causes, we suspected an adverse reaction to amiodarone, not least because of the similarity with histologic findings of cases previously reported. Drug withdrawal and cortisone administration led to resolution of the disease.

Amiodarone