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Biomedical subjects

A Forni

Publications and source records attributed to A Forni.

At least 55 records · Page 3Linked to original sources

Biological monitoring of cadmium exposure--an Italian experience.

Studies carried out over the last 12 years in northern Italy on a case list of 105 cadmium (Cd) workers showed that blood levels (B-Cd) were influenced not only by current exposure but also by body burden, while urinary levels (U-Cd) were influenced predominantly by body burden. Moreover, no advantages were gained by adjusting U-Cd for creatinine or specific gravity. The urinary beta 2-microglobulin levels were within the reference values when B-Cd and U-Cd were below the current threshold values. However, some indicators of early renal effect appeared to be altered. An increase in chromosome-type aberrations in lymphocytes occurred in workers with a heavy cadmium burden. Studies carried out on more than 600 subjects from the general population showed higher B-Cd levels in smokers than in nonsmokers. B-Cd levels were higher in men and in higher age groups. Identifying reference values for B-Cd through meta-analysis studies seems useful.

Cadmium↗

Reference values for chromosome aberrations in human lymphocytes as indicators of genotoxic effects.

Increased chromosome aberrations (CA) in human cultured lymphocytes are an accepted indicator of early biological effects of exposure to genotoxic agents, which has also been investigated, with conflicting results, in several groups of subjects occupationally exposed to metals known or suspected to be carcinogenic. One of the problems with this indicator is the lack of universally accepted reference values. Difficulty in establishing absolute reference values for CA depends on individual variability in the reference groups (due to several environmental and genetic confounding factors) and on methodological variants at the different stages of the test (culture methods, scoring, classification and reporting of CA). Therefore, at present, CA studies in exposed groups should include proper 'control' groups, matched for the known confounders, investigated in the same laboratory, with the same methods in order to minimize factors of variation. The results of the studies should be statistically compared and evaluated mainly on a group basis.

Carcinogens↗

Chromosomal effects of cadmium exposure in humans.

Cytogenetic studies on subjects occupationally or environmentally exposed to cadmium are reviewed and discussed. After a first report of increased chromosome aberrations in lymphocytes of itai-itai patients from Japan, several studies on workers occupationally exposed to cadmium gave conflicting results. These differences may perhaps be explained by the action of co-factors (e.g., nutritional deficiencies in itai-itai patients; concomitant exposure to other metals in some occupational groups), or by different levels of exposure. In a study on cadmium workers with a wide range of cumulative exposure, as compared with matched controls, an increase in chromosome-type aberrations in lymphocytes, an indicator of cumulative damage, was found only because of the increased rates in the subgroup with the highest cumulative exposure and cadmium burden. As far as environmental exposure is concerned, of two recent reports, one from China is positive for chromosome aberrations and the other, from Japan, is negative for sister chromatid exchanges.

Adult↗

Interactions of nucleic acids with distamycins. Binding of Dst-3 to d(CGTTTAAACG)2 and d(CGTACGTACG)2.

The binding between Distamycin 3 and the palindromic duplexes d(CGTTTAAACG)2 and d(CGTACGTACG)2 was investigated by two independent techniques: UV-Vis absorption in the Job's plot approach and Induced Circular Dichroism. Both decamers bind two molecules of peptide per duplex, with close overall affinities. This result indicates that a row of six A:T base pairs can accommodate two molecules of drug and that the minimal binding site of Distamycin 3 can consist of just two A:T base pairs.

Base Sequence↗

Interactions of nucleic acids with distamycins. The drug monomeric chromophore.

A study of the monomeric chromophore of the oligopeptides netropsin (1), distamycin III (2), and distamycin V (3) by polarization spectroscopy techniques and molecular orbital calculations is reported. Linear dichroism spectra of the monomeric model compounds 1-methyl-2(ethylcarbamoyl)-4-acetamido-pyrrole (4) and 1-methyl-2(ethylcarbamoyl)-pyrrole (5) dissolved and oriented in lyotropic and thermotropic liquid crystals provide, together with the magnetic CD spectra, experimental checks of the theoretical calculations. The polarization directions of the investigated transition obtained by these means in this study allow us to build up in the following paper the exciton states of (1)-(3) and these provide a stereochemical interpretation of the flow linear dichroism spectra of the complexes of DNA with (2) and (3).

DNA↗

Linear dichroism studies of the complexes between CT-DNA and distamycins.

The study of the monomeric chromophore of the distamycins reported in Ref. 1 was used here to build up a description of the electronic states of the whole oligopeptide by the exciton theory. Liquid crystal-linear dichroism (LC-LD) spectra of the distamycins were recorded by using as orienting solvents both thermotropic and lyotropic mesomorphic media. The agreement between the LD spectra and the polarization assignments by the exciton treatment is satisfactory. On this basis the flow-LD spectra of the complex between distamycin V and DNA was interpreted in terms of the preferred relative orientations of the guest and host molecules. A single site location of the distamycin within the minor groove does not perfectly match the experimental order parameters. This orientational distribution function could be too simple to explain the experimental data. It may therefore be assumed that a small fraction of the guest molecules are preferentially aligned more parallel to the host chain axis than the minor groove. Alternatively, and probably more likely, the partial mismatch of the experimental data with the minor groove location may be seen as a manifestation of the well-known stiffening and bending effects at the binding sites, which have already been observed by other techniques.

DNA↗

Alveolar and lung fibre levels in non-occupationally exposed subjects.

Mineral fibre concentrations and characteristics were evaluated by the same electron microscope methods in 15 bronchoalveolar lavage samples and in 40 surgical lung tissue samples of subjects with no occupational exposure to asbestos. Both fibre alveolar load and lung burden evaluated by transmission electron microscopy were higher in the groups of industrial workers with no specific asbestos exposure than in the groups of individuals exposed only to general environmental pollution. In both types of samples, the fibre burden consisted of extremely small fibres (mean length less than 2 microns, mean diameter less than 0.1 micron), with a trend towards a further reduction in mean length in the lung tissue as compared with the alveolar load. These data suggest that there is a need for a critical reconsideration of the methods of evaluating environmental fibre pollution and of those for assessing exposure-effect relationships.

Adult↗

Alveolar fiber load in asbestos workers and in subjects with no occupational asbestos exposure: an electron microscopy study.

The alveolar fiber load was evaluated by bronchoalveolar lavage and by scanning and transmission electron microscopy (SEM and TEM) in 50 subjects with or without occupational exposure to asbestos. The concentration of asbestos fibers in bronchoalveolar lavage was significantly higher in the groups of people currently and formerly occupationally exposed, compared to the concentration found in people only exposed environmentally, despite wide interindividual variation within the groups. Nonasbestos inorganic fibers were present in all groups, but the concentrations did not differ significantly. Both in people occupationally exposed and in those only environmentally exposed, the alveolar load consisted mainly of ultrashort and ultrathin fibers, which can be studied only with TEM. In fact, the percentage of fibers greater than 5 micron long was only around 15% in the occupationally exposed and was minimal in those only environmentally exposed. The geometric mean diameters of asbestos fibers retained in the alveoli ranged from 0.05 micron for chrysotile to 0.15 micron for amphiboles.

Asbestos↗

[Talcosis-asbestosis: an unusual risk in a food industry].

In a 37 years-old female worker, who had undergone surgical excision of a segment of the right lower lobe for a chronic aspecific pleuropneumonitis, the histological examination of the excised lung tissue showed asbestos alveolitis with diffuse interstitial fibrosis, and multiple granulomata containing talc particles. An investigation at the work site showed that the worker had been engaged for 22 years in dusting salami with a mixture of rice flour and talc contaminated with chrysotile asbestos. Thirteen work-mates engaged in the same job were studied. In two of them, with chest X-rays negative for pneumoconiosis, a functional ventilatory impairment, restrictive in type, associated with a reduced pulmonary diffusion of gases, was demonstrated. In these two cases, bronchoalveolar lavage showed signs of severe exposure to asbestos (which at TEM evaluation resulted to be amphibolic) talc and other fibres, with presence of iron-laden macrophages, indicators of haemorrhagic alveolitis. Moreover, in one of them, a severe macrophagic-lymphocytic alveolitis, with inverted T helper/T suppressor ratio, was presented, possible expression of a hypersensitivity pulmonary reaction. Taking into consideration the length and modality of work, with exposure to talc powder contaminated with asbestos, for the three cases the diagnosis of "pre-radiologic talcosis-asbestosis" was made. Since the occupational risk was not known in this industry, no ambient and personal preventive and protective measures had been taken; anyway, such type of work has now been stopped. The exposed workers shall be kept under control in the future for surveillance directed towards early diagnosis of possible further asbestos effects.

Adult↗

Epidemiology in protection and prevention against environmental mutagens/carcinogens. Examples from occupational medicine.

Subjects occupationally exposed to potential mutagens/carcinogens represent the most suitable groups for epidemiological studies aimed at assessing the risk for the individual or the offspring. Several cancer risks to humans have been detected by epidemiological studies performed in occupational settings. Cancer epidemiology studies have been able (a) to identify specific occupations or agents associated with the risk; (b) to verify the results of experimental studies; (c) to test the effectiveness of changes in production or preventive measures in decreasing risks. Reproductive epidemiology has suggested a risk of spontaneous abortions or of malformation in the offspring of workers exposed to some chemicals or occupations, but data are often conflicting due to methodological problems. With the aim of early assessment of risk in mind, the epidemiological use of indicators of exposure or of the early effect of exposure to genotoxic agents is increasingly applied to occupational groups. Cytological monitoring of subjects at risk of occupational cancer of lung or bladder is carried out mainly to diagnose precancerous lesions of target tissues. Cytogenetic methods (chromosome aberrations, SCE, micronuclei) in somatic cells provide a means for detecting early effects of occupational exposure to known or potential mutagens/carcinogens in selected groups of individuals, but their significance is widely debated. Monitoring of urinary mutagenicity, as applied in nurses handling cytostatic drugs, is an example of how an indicator of exposure to genotoxins can be used to evaluate the impact of preventive measures. Among the perspectives, biochemical epidemiology seems to be promising in detecting individuals genetically susceptible to cancer.

Carcinogens↗

Chromosomal aberrations in monitoring exposure to mutagens-carcinogens.

Determination of chromosomal aberration rates in cultured lymphocytes is an established method of monitoring populations occupationally or environmentally exposed to known or suspected mutagenic-carcinogenic agents. Subjects and controls for chromosome studies should be properly selected. Methods of culturing lymphocytes should be standardized, to minimize technical factors which might affect the yield of aberrations. Types of aberrations, their significance, criteria for scoring, reporting and statistical analysis are discussed. From the available experience, the following points must be taken into consideration: Several factors may create confounding, due to nonspecificity of chromosomal aberrations. Persistence of aberrations for years and decades in long-lived lymphocytes makes them an indicator of past damage, but limits the value of the test in monitoring present low-level exposures in subjects with past exposure(s). No clear-cut dose-response relationships have so far been demonstrated, but there is evidence that the method might not be sensitive enough for monitoring very low-level chronic exposures. Results should be evaluated mainly on a group basis. The method is time-consuming, and therefore expensive. Chromosomal damage indicates a biological effect on the genome, the implications of which for carcinogenesis and mutagenesis are still unknown. It is generally believed that increased rates of chromosomal aberration in a population may indicate an increased cancer risk for the group, but not for the single individual presenting excess damage.

Carcinogens↗

Chromosomal effects of lead: A critical review.

The available data on the possible effects of lead on mammalian chromosomes are reviewed. Several studies of cultured lymphocytes of man and non-human mammals exposed to excess lead show increased rates of chromatid and chromosome aberrations, while other studies are negative. In vitro exposure of lymphocytes to lead acetate also give conflicting results. The reviewed data are commented, and the possible technical factors influencing the results are discussed. On the basis of the prevalent types of aberrations observed, it is suggested that the increased rates of aberrations found in cultured lymphocytes of lead-poisoned or lead-exposed subjects might be mainly culture-borne changes, not repaired in the presence of lead or of some lead-induced metabolite.

Adult↗

Chromosome changes and benzene exposure. A review.

Benzene exposure can induce chromosome aberrations in somatic cells (lymphocytes and bone marrow cells) of man and of experimental animals in vivo, as well as in some in vitro systems. Numerical and structural chromosome changes in bone marrow cells have been described in subjects with benzene haemopathy. Increased rates of structural chromosomal aberrations both of the "unstable" and of the "stable" type in cultured peripheral blood lymphocytes have been observed not only in subjects with chronic benzene poisoning, but also in individuals with past benzene haemopathy and in subjects with past benzene exposure without signs of poisoning; these findings persisted for years or decades after cessation of exposure. In some cases of benzene-induced leukaemias the cytogenetic pattern was variable, as it is true also for the "spontaneous" acute leukaemias. The possible implications of the finding of chromosome damage from benzene to bone marrow cells for the occurence of leukaemias are discussed. The possibilities and limitations of cytogenetic studies in the biological monitoring of subjects exposed to benzene are commented on.

Adult↗

Significance of ascitic fluid and peritoneal washing cytology in ovarian tumor diagnosis.

The results of the cytological test on 179 ascitic fluids and 88 peritoneal washes of patients suspected to have ovarian tumors are critically reviewed to illustrate the difficulties, limitations and future possibilities of this technique. Tissue correlation was available in all cases. The data was evaluated in order to obtain information as to the accuracy, sensitivity and specificity of cytological examination, both in ascitic fluids and in peritoneal washings. A correct diagnosis as to the ovarian tumor histotype was obtained in more than 80 per cent of the cases.

Adult↗

Effect of pinealectomy on arterial blood pressure and food and water intake in the rat.

Pinealectomy in the rat induces a significant increase of the arterial blood pressure within 15 days from the surgical procedure; this hypertension is still present 30 and 60 days after pinealectomy while after 90 days it returns to the normal range. Histological examination of the kidneys of pinealectomized hypertensive rats shows wall thickening and lumen narrowing of the arterioles, adventitial and periadventitial fibrosis, dense glomeruli. The vascular lesions are not diffuse but patchily distributed. Body weight is higher in pinealectomized rats compared with normal and sham-operated animals: this difference becomes significant about 40 days after pinealectomy and gradually decreases until it disappears at the end of the third month. Food and water intake is higher in pinealectomized rats up to the 7th week; during the 8th week they return to the normal range.

Animals↗