Ability of hydroxypropyl chitosan nail lacquer to protect against dermatophyte nail infection.

The development of a topical agent that would strengthen the nail, improve the natural barrier, and provide better drug penetration to the nail bed is needed. In this study, we examined the effects of a hydroxypropyl chitosan (HPCH)-based nail solution using a bovine hoof model. Following application of the nail solution, changes in the hardness of the hoof samples were measured using the Vickers method. Tensile and flexural strengths were tested by stretching or punching the samples, respectively. The ultrastructure was examined using scanning electron microscopy (SEM), and samples stained with periodic acid-Schiff (PAS) stain were used to determine the fungal penetration depth. The comparators included 40% urea and 70% isopropyl alcohol solutions. The HPCH nail solution increased hoof sample hardness in comparison to the untreated control sample (mean, 22.3 versus 19.4 Vickers pyramid number [HV]). Similarly, the HPCH solution increased the tensile strength (mean, 33.07 versus 28.42 MPa) and flexural strength (mean, 183.79 versus 181.20 MPa) compared to the untreated control. In contrast, the comparators had adverse effects on hardness and strength. SEM showed that the HPCH solution reduced the area of sample crumbling following abrasion compared to the untreated control (7,418 versus 17,843 pixels), and the PAS-stained images showed that the HPCH solution reduced penetration of the dermatophyte hyphae (e.g., penetration by Trichophyton mentagrophytes was <25 µm at day 9 versus 275 µm in the untreated control). Unlike chemicals normally used in cosmetic treatments, repeated application of the HPCH nail solution may help prevent the establishment of new or recurring fungal nail infection.

Feasibility study of production of radioactive carbon black or carbon nanotubes in cyclotron facilities for nanobioscience applications.

A feasibility study regarding the production of radioactive carbon black and nanotubes has been performed by proton beam irradiation. Experimental and theoretical excitation functions of the nuclear reaction (nat)C(p,x)(7)Be in the proton energy range 24-38 MeV are reported, with an acceptable agreement. We have demonstrated that sufficient activities of (7)Be radioisotope can be produced in carbon black and nanotube that would facilitate studies of their possible impact on human and environment.

Radiolabelling of engineered nanoparticles for in vitro and in vivo tracing applications using cyclotron accelerators.

We present in this article an outline of some cyclotron-based irradiation techniques that can be used to directly radiolabel industrially manufactured nanoparticles, as well as two techniques for synthesis of labelled nanoparticles using cyclotron-generated radioactive precursor materials. These radiolabelled nanoparticles are suitable for a range of different in vitro and in vivo tracing studies of relevance to the field of nanotoxicology. A basic overview is given of the relevant physics of nuclear reactions regarding both ion-beam and neutron production of radioisotopes. The various issues that determine the practicality and usefulness of the different methods are discussed, including radioisotope yield, nuclear reaction kinetics, radiation and thermal damage, and radiolabel stability. Experimental details are presented regarding several techniques applied in our laboratories, including direct light-ion activation of dry nanoparticle samples, neutron activation of nanoparticles and suspensions using an ion-beam driven activator, spark-ignition generation of nanoparticle aerosols using activated electrode materials, and radiochemical synthesis of nanoparticles using cyclotron-produced isotopes. The application of these techniques is illustrated through short descriptions of some selected results thus far achieved. It is shown that these cyclotron-based methods offer a very useful range of options for nanoparticle radiolabelling despite some experimental difficulties associated with their application. For direct nanoparticle radiolabelling, if care is taken in choosing the experimental conditions applied, useful activity levels can be achieved in a wide range of nanoparticle types, without causing substantial thermal or radiation damage to the nanoparticle structure. Nanoparticle synthesis using radioactive precursors presents a different set of issues and offers a complementary and equally valid approach when laboratory generation of the nanoparticles is acceptable for the proposed studies, and where an appropriate radiolabel can be incorporated into the nanoparticles during synthesis.

Acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections in community-acquired pneumonia and exacerbations of COPD or asthma: therapeutic considerations.

Rates of acute Chlamydia pneumoniae and Mycoplasma pneumoniae infections were determined in 115 adults hospitalized for community-acquired pneumonia (CAP), purulent exacerbations of COPD and acute exacerbations of bronchial asthma, by means of serology and molecular methods. Results were compared with those obtained in a matched control group. Common respiratory pathogens were isolated by cultures in 22.5% and 22.2% of CAP and exacerbated COPD patients, respectively. Cultures from exacerbated asthma patients were always negative. Serological and molecular evidence of current C. pneumoniae infection was obtained in 10.0%, 8.9% and 3.3% of CAP, COPD and asthma cases. The corresponding rates of acute M. pneumoniae infection were 17.5%, 6.7% and 3.3%, respectively. Finally, no difference was found between typical and atypical pathogen rates. These findings highlight the importance of taking into account C. pneumoniae and M. pneumoniae infections in guiding the choice of empirical antibacterial treatment for CAP and purulent exacerbations of COPD.

Surfactant apoprotein A modulates interleukin-8 and monocyte chemotactic peptide-1 production.

Previous studies have shown that surfactant apoprotein A (SP-A) and natural or synthetic surfactant can modulate the release of pro-inflammatory cytokines from alveolar mononuclear phagocytes. The aim of this study was to assess whether SP-A or Surfactant (Surf) from patients with pulmonary alveolar proteinosis (PAP) can affect the release of two chemokines (interleukin (IL)-8 and monocyte chemtactic peptide (MCP)-1) from human monocytes and rat lung type-II cells. In addition IL-8 and MCP-1 levels were assessed in the brochoalveolar lavage fluid (BALF) of seven patients with PAP and compared with those in a group of control subjects (n=5). SP-A, tested over a wide range of concentrations, significantly increased IL-8 and MCP-1 release from monocytes. SP-A retained its activity after collagenase digestion, but was not active after heat treatment. The release of IL-8 by monocytes was also stimulated by Surf. Finally, median BALF IL-8 and MCP-1 levels in PAP patients were significantly higher than in controls (9.50 and 9.51 pg x mL(-1) in controls versus 151.95 and 563.70 pg x mL(-1) in PAP, respectively) and significantly correlated with SP-A concentrations in BALF. Overall the results of this study support the view that the high content of alveolar surfactant apoprotein A may contribute to the upregulation of chemokine release in pulmonary alveolar proteinosis, thus contributing to airway inflammation.

Virulence of Mycobacterium tuberculosis affects interleukin-8, monocyte chemoattractant protein-1 and interleukin-10 production by human mononuclear phagocytes.

Microbial virulence and cytokine-mediated immune responses to Mycobacterium tuberculosis infection are important determinants of the pathogenesis of human tuberculosis. To determine the interrelationship between mycobacterial virulence and cytokine induction, human monocytes and monocyte-derived macrophages were infected with attenuated (H37Ra) and virulent (H37Rv and CH306) strains of M. tuberculosis and the amount of proinflammatory [interleukin (IL)-8 and monocyte chemoattractant protein (MCP)- 1] and inhibitory (IL- 10) cytokines was measured in the culture supernatants by enzyme-linked immunosorbent assay (ELISA). Infection with live bacilli induced de novo synthesis of IL-8, MCP-1 and IL-10, since cytokine release was abolished when cells were preincubated with the protein synthesis inhibitor cycloheximide. A differential production of antiinflammatory and inhibitory cytokines was observed. The amount of IL-8 and MCP-1 release was inversely related to strain virulence, the attenuated H37Ra strain being more prone than virulent strains to induce secretion of chemokines. In contrast, virulent strains induced greater amounts of the inhibitory cytokine IL-10. Efficient upregulation of IL-10 synthesis, but not of chemokines, required infection of cells with live bacilli, since heat killing of organisms or challenge with soluble mycobacterial products completely abrogated the effect. Moreover, cells infected with virulent strains produced IL-10 even at a very low bacillus-to-cell ratio and secreted IL-10 continuously during the 96 h that followed infection. The results suggest that the degree of virulence affects host cell responses to M. tuberculosis infection. Continued production of IL-10 may be one of the means by which M. tuberculosis downregulates acute local inflammatory reactions, favoring the development of tuberculosis.

Some coprophilous fungi from Kenya.

The occurrence of coprophilous fungi on samples of antelope, buffalo, zebra and hippopotamus dung collected from the Marula Estates in Kenya was recorded. A hundred and seventy three fungal isolates representative of 40 genera and 59 species were identified. Among these species, 23 were Ascomycetes (39%), 30 Deuteromycetes (50.8%), 5 Zygomycetes (8.5%) and 1 Basidiomycete (1.7%). Ascobolus immersus, Coprotus niveus, Iodophanus carneus, Lasiobolus lasioboloides, Podospora anserina, P. australis and Sporormiella minima were the dominant species occurring in the dung of these animals. Notes on infrequent or interesting Ascomycetes include Kernia nitida, Saccobolus versicolor, Sordaria fimicola and others. The interdependence of the vegetation of this area with the fungi occurring on the dung of these animals is discussed.

Proteinase/proteinase inhibitor imbalance in sputum sol phases from patients with chronic obstructive pulmonary disease. Suggestions for a key role played by antileukoprotease.

In order to characterize the imbalance between proteinases and proteinase inhibitors in sputum sol phases, we studied 25 patients (mean age, 59 +/- 11 yr) with exacerbated chronic obstructive pulmonary disease (COPD). An aliquot of sputum was used for bacteriologic determinations, and the remainder was centrifuged in order to obtain gel and sol phases. On the basis of the bacteriologic data, patients were divided into colonized patients (14) and noncolonized patients (11). All of the major inhibitors were immunologically detectable in sol phases without a significant difference between colonized and noncolonized patients (alpha 1-proteinase inhibitor [alpha 1-PI], 2.56 microM +/- 0.53 microM and 2.39 microM +/- 0.72 microM; alpha 2-macroglobulin [alpha 2-MG], 0.21 microM +/- 0.07 microM and 0.16 microM +/- 0.05 microM; antileukoprotease (ALP), 1.78 microM +/- 0.57 microM and 1.53 microM +/- 0.6 microM, respectively [mean +/- SE]). With regard to proteinase activities, both free elastase-like and free chymotrypsin-like activities were detectable in the majority of patients (15/25) (0.59 microM +/- 0.15 microM and 0.74 microM +/- 0.15 microM for elastase-like activity [ELA], and 0.010 microM +/- 0.003 microM and 0.017 microM +/- 0.007 microM for chymotrypsin-like activity [CLA], respectively [mean +/- SE]). The inhibitory profile of proteinase activities, performed by means of a panel of inhibitors, allowed us to assign specific activities mainly to neutrophil elastase and cathepsin G (Cat G). Next we looked at the relationships between inhibitors and proteinase activities. We found a significant negative correlation between neutrophil elastase activity and ALP (r = -0.58; p < 0.01). In confirmation of this suggestion, sol phases were divided into samples (15) with detectable ELA (> 0.50 microM) and samples (10) with no detectable ELA (< 0.18 microM). Levels of alpha 1-PI and alpha 2-MG did not differ significantly between the two groups, whereas ALP values were higher in the group with no detectable ELA (3.12 microM +/- 0.69 microM) than in the other group (0.58 microM +/- 0.21 microM; p < 0.001). We conclude that most sputum sol phases from patients with exacerbated COPD have a high burden of free neutrophil elastase and Cat G. Antileukoprotease seems to be the major naturally occurring inhibitor effective in the modulation of proteinase activities in bronchial secretions under these conditions.

Study of functional and biochemical indicators of subclinical lung damage in bleomycin-treated patients.

In 30 patients affected by testicular non-seminomatous cancer we evaluated pulmonary function tests before and after bleomycin-including combination chemotherapy. We paid particular attention to changes in diffusing lung capacity (DCO) and its two components, namely diffusing capacity of the alveolar-capillary membrane (Dm) and pulmonary capillary blood volume (Vc). In the same patients we also evaluated the behaviour of serum procollagen III aminopeptide (sP-III-P), assumed to be a biochemical equivalent to Dm, and of serum angiotensin converting enzyme (S-ACE), assumed to be a biochemical equivalent to Vc. We found that, after chemotherapy, patients showed a significant decline in several pulmonary function parameters, namely VC, TLC, and FEV1 (P < 0.0001, P = 0.0351, P = 0.0004, respectively), when compared to pre-treatment values. DCO was significantly impaired after chemotherapy (P < 0.0001), but with regard to its components, Vc values showed a significant decline (P = 0.0002), whereas Dm values were unchanged. Values of sP-III-P raised significantly after chemotherapy (P = 0.003), whereas S-ACE activity did not show any significant variation. When we looked at relationships between functional and biochemical parameter variations, the only significant correlation we found was between DCO and S-ACE (r2 = 0.112; P < 0.02). We conclude that in asymptomatic patients treated by bleomycin-including combination chemotherapy, DCO impairment is likely to occur because of a subclinical injury to pulmonary vessels, as suggested by Vc decline. Although the occurrence of pulmonary interstitial fibrosis after chemotherapy was excluded by chest X-ray examination and by stable values of Dm, sP-III-P elevation would suggest an accelerated type III collagen turnover in interstitial fibroblasts activated by bleomycin.

Protease-antiprotease imbalance: local evaluation with bronchoalveolar lavage.

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.

Some properties of the alkaline proteinase from Aspergillus melleus.

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.

Elevated serum procollagen III aminopeptide levels in sarcoidosis.

Procollagen III aminopeptide (P-III-P), a peptide released during the conversion of type III procollagen to type III collagen, is considered a potential marker of fibroblast activity in a variety of pulmonary and extrapulmonary diseases. The aim of the present article was to investigate the levels of P-III-P in serum samples (sP-III-P) from a large number of sarcoid patients, in particular looking at its relationship with other markers of disease activity and its presumed role as a marker of pulmonary fibrosis. sP-III-P has been radioimmunoassayed in an overall series of 57 patients and the levels were higher (19.18 +/- 9.17 ng/ml) than in 25 age- and sex-matched controls (11.32 +/- 2.15 ng/ml; p less than 0.001). The elevation was neither sex-related nor related to obvious liver sarcoid localization. Although sP-III-P levels were slightly higher in patients with stage II, there was no significant difference in patients with stage I or III. We found a positive relationship with serum angiotensin-converting enzyme (S-ACE) levels (p less than 0.04), but not with other markers of disease activity (67Ga uptake, bronchoalveolar lavage [BAL] lymphocyte percent, vital capacity, and lung diffusing capacity). The relationship with S-ACE was confirmed in a longitudinal follow-up study, where sP-III-P strictly paralleled the S-ACE behavior. Finally, the initial sP-III-P levels did not predict cases either with disease relapse or resistance to corticosteroid treatment. We conclude that, in our study, sP-III-P levels failed to characterize sarcoid patients with radiologic fibrotic pattern (stage III), and, in addition, were unable to predict which patients would have a poor prognosis. Rather, they reflect a metabolic activity of sarcoid granuloma cells. Thus, the usefulness of sP-III-P in the treatment of patients with sarcoid may be considered similar to that of S-ACE.

[Health status of goldsmiths of the USSL 71 in Valenza]. / Indagine sullo stato di salute dei lavoratori orafi dell'USSL 71 di Valenza.

The article verifies health's state and style of life of the goldsmith people of the USSL n. 71-Valenza Po. The study, executed in the 1989 year, consisted in the distribution of a autowriting questionnaire to 565 goldsmith who are working for the majority in small factory. Questionnaire's analysis showed the young age of workers and the big experience in specific duty. The diseases of locomotor district are represented with great differences respect data of italian population. These data are plausibility induced with the postural vices during working activity. Other pathologies relevant are contact dermatitis, chronic bronchitis, bronchial asthma and optic disturb. The results of the study had induced the Authors to organize new and over deepened epidemiological studies to investigate disturbs of visus and locomotor district.

Dual ligand binding of pyridylalkanamides to microsomal cytochrome P-450.

Twelve homologous and regioisomeric pyridylalkanamides were examined spectrally for their binding affinity to cytochrome P-450 in phenobarbital- and 3-methylcholanthrene-induced rat liver microsomes. The pKs values were calculated by the Lineweaver-Burk method and by non-linear analysis using both a one ligand-one acceptor and a one ligand-two acceptor model. The latter model best fits most of the data, confirming that two pKs values exist for most derivatives in the 3-pyridyl and 4-pyridyl series. Structure-binding relationships are discussed. The two binding constants are hypothesized to arise from a dual mode of binding to the ferric ion. At low ligand concentrations, binding to hexacoordinated cytochrome P-450 occurs and involves displacement of an endogenous 6th ligand; at higher concentrations, the ligands bind to the pentacoordinated P-450, resulting in a high-to-low spin shift.

[Radiotherapy of oral cancer. Late results (author's transl)]. / La radioterapia dei carcinomi del cavo orale. Risultati a distanza.

Radiotherapy of the primary site was employed between 1959 and 1965 in the treatment of 335 unselected cases of mouth cancer. The series is examined with regard to the long-term results and gross survival is evaluated in accordance with an actuarial method. Differences dependent on sex and age, and on the type of cancer involved and the treatment modalities are illustrated and discussed.

[Cobalt therapy in the treatment of carcinoma of the oropharynx]. / Risultati della telecobaltoterapia nel trattamento dei carcinoma dell'orofaringe

A clinical retrospective evaluation of 177 cases of carcinoma of the oropharynx treated with Cobalt therapy from 1959 to 1965 has been made. The analysis of long term results has shown that Cobalt therapy alone does not satisfactorily control carcinomas of oropharynx. In fact, less than 30% of the patients is still alive after 3 years. Survival is directly affected by the local extent of disease since, while the 5-year survival of T1 and T2 cases is respectively 26.8% and 21.5%, only 6.5% of patients with T3 carcinomas is still alive after 5 years. Particularly disappointing is the survival rate in cases with mono- or bilateral involvement of neck nodes, since none of these cases are alive 2 years after the initial therapy. In 69.4% of the cases, treatment failure has to be attributed to minimal response or early recurrence of primary tumor, while lymph node relapses have been observed in more than 25% of the cases. To allow a detailed clinical evaluation of the results, the different regions of the oropharynx should be considered separately, since differences in clinical evolution of various carcinomas would call for a different therapeutic approach. The results of this study in oropharyngeal carcinomas, indicate that improvement of long term results may only be obtained through a multidisciplinary therapeutic approach.