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1.
Bull Entomol Res ; 107(4): 458-465, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27871340

ABSTRACT

A careful measure of fitness represents a crucial target in crop pest management and becomes fundamental considering extremely prolific insects. In the present paper, we describe a standardized rearing protocol and a bioinformatics tool to calculate aphid fitness indices and invasiveness starting from life table data. We tested the protocol and the bioinformatic tool using six Myzus persicae (Sulzer) asexual lineages in order to investigate if karyotype rearrangements and ecotype could influence their reproductive performances. The tool showed that different karyotypes do not influence adaptive success and put in evidence a marked invasive potential of the M. persicae lineage 64. The presence of a similar fitness rate of 33H and 7GK asexual lineages (both possessing intra-individual karyotype variations) in respect to the asexual lineage 1 (with a standard karyotype) represents an important demonstration of the potentiality of holocentric chromosomes to reduce the effects of chromosome rearrangements.


Subject(s)
Aphids , Computational Biology/methods , Genetic Fitness , Animals , Female
2.
Eur Rev Med Pharmacol Sci ; 5(4): 131-8, 2001.
Article in English | MEDLINE | ID: mdl-12067081

ABSTRACT

Aminoglycosides are effective against Pseudomonas aeruginosa but with intravenous administration there are only very low concentrations achieved in sputum; therefore in order to obtain therapeutic levels in patients with endobronchial infections should be administered high doses with increased likelihood to produce both nephrotoxic and ototoxic effects. Direct aerosol delivery of aminoglycosides to the lower respiratory tract has the advantage to achieve high antibiotic sputum concentrations in the infected area with reduced risk of systemic toxic reactions because of minimal absorption into the circulation. Nowadays, except for patients suffering from cystic fibrosis and bronchiectasis, the administration of antibiotics through inhalers is not very much in use. The aim of this study was to administer nebulized tobramycin in chronic respiratory infections developed during the evolution of Wegener's Granulomatosis in order to obtain data concerning the safety and efficacy of inhaled aminoglycosides. The results obtained underlined an improvement in FEV1, FEF75 and PaO2. The aerosolized tobramycin administered in 300 mg doses three times per day for four weeks, showed itself to be effective and safe, not causing any undesirable clinical or microbiological side-effects. Moreover, a long term treatment has been shown to control the Pseudomonas aeruginosa infection on the bronchial system in Wegener's granulomatosis and reduce the frequency of exacerbations in chronic patients.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Granulomatosis with Polyangiitis/complications , Respiratory Tract Infections/drug therapy , Tobramycin/therapeutic use , Administration, Inhalation , Anti-Bacterial Agents/administration & dosage , Chronic Disease , Female , Humans , Middle Aged , Respiratory Tract Infections/etiology , Tobramycin/administration & dosage
3.
Eur Respir J ; 9(8): 1648-51, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8866588

ABSTRACT

Type I and type III are the most abundant collagens in the lung. The aim of our study was to compare type I and III procollagen peptides in sera of sarcoid patients. Sixty eight patients with sarcoidosis were studied (19 with newly recognized disease, 7 with relapsing disease, 15 with chronic disease, and 27 in stable remission). Thirty healthy volunteers served as controls. The levels of procollagen I and III peptides were determined by radioimmunoassay. Angiotensin-converting enzyme (ACE) level was evaluated by means of a colorimetric assay. In patients with newly recognized sarcoidosis, both serum procollagen I and III peptide levels were increased with respect to controls (p=0.0014 and p<0.00001, respectively). There was a poor correlation between levels of procollagen I and III (r=0.26), whereas there was a closer correlation between procollagen III and ACE (r=0.69). Procollagen I peptide level did not identify patients in roentgenological stage III. In conclusion, in patients with newly recognized sarcoidosis there is a significant increase in the serum level of procollagen I peptide. However, procollagen I peptide is not a marker of sarcoid patients with fibrosis, ie. stage III disease. Its clinical usefulness seems to be weaker than that of procollagen III peptide.


Subject(s)
Bone Morphogenetic Proteins , Metalloendopeptidases/blood , Peptide Fragments/blood , Procollagen/blood , Sarcoidosis/blood , Adult , Analysis of Variance , Bone Morphogenetic Protein 1 , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Sarcoidosis/diagnosis , Sensitivity and Specificity
4.
Eur Respir J ; 9(7): 1482-6, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8836663

ABSTRACT

We investigated whether MR889, a synthetic cyclic thiolic elastase inhibitor, administered for a period of 4 weeks to chronic obstructive pulmonary disease (COPD) patients, is well-tolerated, and whether it modifies biochemical indices of lung destruction. The study was a double-blind, randomized, placebo-controlled clinical trial in COPD patients. Thirty subjects were administered MR889 orally at a dose of 500 mg b.i.d. for 4 weeks, and 30 received placebo following the same schedule. In addition to safety parameters, MR889 efficacy was checked by a pretreatment/postreatment evaluation of levels of plasma elastin-derived peptides and urinary desmosine. There were no statistically significant differences between pretreatment and posttreatment efficacy parameter levels either in the control group or in the treated group. However, in a subset of treated patients with a short disease duration, the level of urinary desmosine dropped significantly with respect to pretreatment values (p = 0.004). We conclude that MR889 is safe to administer to COPD patients for a period of at least 4 weeks. During this time, MR889 does not modify biochemical markers of lung destruction in unselected COPD patients. Nevertheless, a subset of treated patients with fairly short disease duration showed a post-treatment reduction of desmosine urine levels, thus justifying the need for further studies to prove the efficacy of MR889 in modulating indices of lung destruction in COPD.


Subject(s)
Leukocyte Elastase/antagonists & inhibitors , Lung Diseases, Obstructive/drug therapy , Protease Inhibitors/therapeutic use , Thiophenes/therapeutic use , Aged , Desmosine/urine , Double-Blind Method , Drug Administration Schedule , Elastin/blood , Female , Humans , Lung Diseases, Obstructive/metabolism , Male , Protease Inhibitors/administration & dosage , Thiophenes/administration & dosage , Time Factors
5.
Clin Infect Dis ; 22 Suppl 1: S50-4, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8785257

ABSTRACT

This article reviews recent studies conducted outside the United States assessing the efficacy and safety of rifabutin in the treatment of tuberculosis (TB) in HIV-infected patients, in patients with newly diagnosed TB, and in patients with multidrug-resistant TB. A 6-month pilot study of 50 Ugandan patients with TB associated with HIV infection showed that rifabutin and rifampin were similarly effective with regard to conversion of sputum-smear findings (sputum conversion) and in bringing about clinical and radiologic improvement. Compared with rifampin, rifabutin showed potential for reducing the time to sputum conversion for these patients. Multicenter studies in five countries compared two rifabutin dosages (150 mg/d and 300 mg/d) with rifampin as part of a combination regimen for treatment of newly diagnosed TB in 935 patients. Rifabutin compared favorably with rifampin in sputum conversion; administration of 150 mg/d of rifabutin yielded good results and the fewest adverse effects. The use of rifabutin by 270 patients in five countries who had multidrug-resistant TB (approximately 90% of isolates tested were resistant to rifampin and isoniazid) was assessed in another study. For the majority of these patients, signs and symptoms diminished; one-third had bacteriologic conversions.


Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Antibiotics, Antitubercular/therapeutic use , Rifabutin/therapeutic use , Tuberculosis, Pulmonary/drug therapy , Antibiotics, Antitubercular/adverse effects , Clinical Trials as Topic , Humans , Pilot Projects , Rifabutin/adverse effects , Rifampin/pharmacology , Tuberculosis, Multidrug-Resistant/complications , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/complications
6.
Eur Respir J Suppl ; 20: 714s-718s, 1995 Sep.
Article in English | MEDLINE | ID: mdl-8590571

ABSTRACT

Since the late 1960s, tuberculosis has been successfully cured with antibiotics. With the introduction of rifampin, "short course" regimens using isoniazid and rifampin together with either streptomycin, ethambutol or pyrazinamide, for 6-9 months, have been successfully adopted. The spread of drug resistant M. tuberculosis strains in large urban areas has made this armamentarium of drugs insufficient, calling for the development of new drugs. Among rifamycin derivatives, rifabutin is more active than rifampin in vitro and in experimental animals, and allows sputum conversion rats of 95-100%. It is effective in treating multidrug-resistant tuberculosis. Rifapentine is more active than rifampin in vitro and has a longer half-life, but it is not active against rifampin-resistant strains. Fluoroquinolones concentrate within macrophages, are effective against M. tuberculosis and act synergistically with rifampin and isoniazid. Ofloxacin, ciprofloxacin, sparfloxacin and lomefloxacin have been evaluated as antimycobacterial agents, and no cross-resistance with major antituberculous drugs has been found. Several other drugs, including new inhibitors of beta-lactamase and new beta-lactamase-resistant antibiotics, the aminoglycoside antibiotic, paromomycin, and the new nitroimidazole, 2-ethyl-5-intro-2.3-dihydro imidazo-oxazole, have been found to be active in vitro against M. tuberculosis.


Subject(s)
Antitubercular Agents/therapeutic use , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , Animals , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Therapy, Combination , Humans , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Rats
9.
Monaldi Arch Chest Dis ; 48(3): 205-9, 1993.
Article in English | MEDLINE | ID: mdl-8369784

ABSTRACT

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.


Subject(s)
Isoniazid/pharmacokinetics , Isoniazid/therapeutic use , Pyrazinamide/pharmacokinetics , Pyrazinamide/therapeutic use , Rifampin/pharmacokinetics , Rifampin/therapeutic use , Adult , Biological Availability , Capsules , Drug Administration Schedule , Drug Combinations , Half-Life , Humans , Isoniazid/administration & dosage , Isoniazid/blood , Male , Pyrazinamide/administration & dosage , Pyrazinamide/blood , Rifampin/administration & dosage , Rifampin/blood , Tablets , Tuberculosis, Pulmonary/drug therapy
10.
Respiration ; 59 Suppl 1: 24-7, 1992.
Article in English | MEDLINE | ID: mdl-1579728

ABSTRACT

The protease-antiprotease imbalance is thought to be involved in a variety of destructive lung diseases: pulmonary emphysema, chronic bronchitis, cystic fibrosis and adult respiratory distress syndrome. Bronchoalveolar lavage allowed the investigators to assess the protease-antiprotease shift in such conditions but sometimes gave conflicting results. The role of bronchoalveolar lavage as a research and diagnostic tool in diseases characterised by protease-antiprotease imbalance is reviewed, as well as its potential usefulness in the near future.


Subject(s)
Bronchoalveolar Lavage Fluid/enzymology , Lung Diseases, Obstructive/enzymology , alpha 1-Antitrypsin/metabolism , Bronchitis/enzymology , Chronic Disease , Endopeptidases/metabolism , Humans , Pulmonary Emphysema/enzymology , Respiratory Distress Syndrome/enzymology , Smoking/metabolism , alpha 1-Antitrypsin Deficiency
13.
Int J Tissue React ; 13(4): 187-92, 1991.
Article in English | MEDLINE | ID: mdl-1821412

ABSTRACT

Seaprose is a semi-alkaline proteinase produced by Aspergillus melleus. The aim of our study was to further characterize the properties of this enzyme, particularly looking at its interaction with alpha 1-proteinase inhibitor, the major human plasma proteinase inhibitor. We studied the cleavage of three synthetic peptide substrates induced by seaprose and the inhibitory profile of the enzyme by means of a panel of inhibitors, including alpha 1-proteinase inhibitor. The interaction between seaprose and alpha 1-proteinase inhibitor was also studied with SDS-PAGE. Finally, the elastolytic activity of seaprose was checked by means of bovine elastin solubilization. We found that seaprose cleaves preferentially the substrate containing a Phe residue in the P1 position. The inhibitory profile showed that seaprose is a serine-proteinase that cannot be inhibited by alpha 1-proteinase inhibitor. The SDS-PAGE revealed that alpha 1-proteinase inhibitor, after incubation with seaprose, underwent a limited proteolysis. Finally, seaprose 10(-2) M and 10(-3) M was able to solubilize bovine elastin. We conclude that seaprose is a serine-proteinase able to inactivate human alpha 1-proteinase inhibitor with limited proteolysis at (or near) the active site and that it has mild elastinolytic capacity.


Subject(s)
Aspergillus/enzymology , Peptide Hydrolases/metabolism , Serine Endopeptidases , alpha 1-Antitrypsin/metabolism , Amino Acid Sequence , Elastin/metabolism , Electrophoresis, Polyacrylamide Gel , Hydrolysis , Molecular Sequence Data , Solubility
14.
Eur Respir J ; 3(4): 441-6, 1990 Apr.
Article in English | MEDLINE | ID: mdl-2163879

ABSTRACT

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.


Subject(s)
Peptidyl-Dipeptidase A/blood , Female , Humans , Italy , Lung Diseases/drug therapy , Lung Diseases/genetics , Male , Middle Aged , Pedigree , Peptidyl-Dipeptidase A/genetics , Prednisone/administration & dosage , Prednisone/therapeutic use
15.
Am J Respir Cell Mol Biol ; 2(3): 297-9, 1990 Mar.
Article in English | MEDLINE | ID: mdl-1968751

ABSTRACT

The etiology of chronic obstructive pulmonary disease (COPD) is still unknown, and both genetic and environmental factors may play a role. Some clinical aspects of COPD occur similarly in cystic fibrosis (CF), particularly in adult patients. A DNA polymorphic marker in strong linkage disequilibrium with the CF locus has been used to check the hypothesis that mutations of this locus might be involved in COPD. Its allele frequencies have been found to be in equilibrium in COPD patients as well as in appropriate control subjects. The determinants possibly involved in genetic predisposition to COPD therefore do not seem to comprise CF gene mutations.


Subject(s)
Cystic Fibrosis/genetics , Genes , Lung Diseases, Obstructive/genetics , Adult , Aged , Alleles , DNA/genetics , Female , Genetic Markers , Humans , Linkage Disequilibrium , Male , Middle Aged , Mutation , Polymorphism, Restriction Fragment Length
16.
Int J Tissue React ; 12(6): 363-8, 1990.
Article in English | MEDLINE | ID: mdl-2102901

ABSTRACT

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.


Subject(s)
Chloramines/pharmacology , DNA, Recombinant , Genetic Variation/genetics , Hydrogen Peroxide/pharmacology , Pancreatic Elastase/antagonists & inhibitors , Xanthine Oxidase/pharmacology , alpha 1-Antitrypsin/genetics , Animals , Drug Resistance , Oxidation-Reduction , Pancreatic Elastase/metabolism , alpha 1-Antitrypsin/metabolism , alpha 1-Antitrypsin/pharmacology
17.
Biochem Biophys Res Commun ; 165(2): 568-73, 1989 Dec 15.
Article in English | MEDLINE | ID: mdl-2597145

ABSTRACT

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.


Subject(s)
Protease Inhibitors/pharmacology , Thiophenes/pharmacology , Chymotrypsin/antagonists & inhibitors , Humans , Kinetics , Pancreatic Elastase/antagonists & inhibitors , Sputum/enzymology
18.
Am J Cardiol ; 61(5): 53C-54C, 1988 Feb 10.
Article in English | MEDLINE | ID: mdl-2893534

ABSTRACT

In 10 patients with bronchial asthma but normal ventilatory function, celiprolol, a cardioselective beta-adrenoreceptor antagonist, did not significantly affect forced expiratory volume in 1 second (FEV1) or airways resistance (Raw). In contrast, metoprolol substantially reduced FEV1 and increased Raw. In addition, compared with metoprolol, celiprolol induced a greater recovery of FEV1 and Raw after methacholine-induced bronchoconstriction.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Asthma/drug therapy , Bronchi/physiopathology , Propanolamines/therapeutic use , Adult , Airway Resistance/drug effects , Asthma/physiopathology , Bronchi/drug effects , Celiprolol , Clinical Trials as Topic , Double-Blind Method , Female , Forced Expiratory Volume , Humans , Male , Middle Aged , Random Allocation
19.
Chemioterapia ; 5(3): 177-84, 1986 Jun.
Article in English | MEDLINE | ID: mdl-3487389

ABSTRACT

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.


Subject(s)
Erythromycin/analogs & derivatives , Ampicillin/pharmacology , Blood Bactericidal Activity/drug effects , Clindamycin/pharmacology , Doxycycline/pharmacology , Drug Synergism , Erythromycin/pharmacology , Haemophilus influenzae/drug effects , Humans , Hydrogen-Ion Concentration , In Vitro Techniques , Leucomycins/pharmacology , Microbial Sensitivity Tests , Neutrophils/drug effects , Neutrophils/immunology , Phagocytosis/drug effects , Staphylococcus aureus/drug effects , Streptococcus/drug effects , Streptomyces/analysis
20.
Int J Clin Pharmacol Res ; 6(2): 129-36, 1986.
Article in English | MEDLINE | ID: mdl-2424848

ABSTRACT

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.


Subject(s)
Ambroxol/therapeutic use , Antineoplastic Agents/adverse effects , Bromhexine/analogs & derivatives , Lung Diseases/chemically induced , Animals , Bleomycin/adverse effects , Busulfan/adverse effects , Cyclophosphamide/adverse effects , Humans , Lung Diseases/prevention & control , Lymphocytes/immunology , Macrophages/immunology , Methotrexate/adverse effects , Middle Aged , Neutrophils/immunology , Nitrosourea Compounds/adverse effects , Phosphatidylcholines/analysis , Procarbazine/adverse effects , Pulmonary Alveoli/analysis , Pulmonary Fibrosis/chemically induced , Rats , Respiratory Function Tests
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