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Biomedical subjects

A De Marco

Publications and source records attributed to A De Marco.

At least 19 recordsLinked to original sources

Measuring, modelling and testing ozone exposure, flux and effects on vegetation in southern European conditions--what does not work? A review from Italy.

Ozone (O3) exposure at Italian background sites exceeds UN/ECE concentration-based critical levels (CLe(c)), if expressed in terms of AOT40. Yet the occurrence of adverse effects of O3 on forests and crops is controversial. Possible reasons include (i) ability of response indicators to provide an unbiased estimate of O3 effects, (ii) setting of current CLe(c) in terms of cut-off value and accumulation level, (iii) response functions adopted to infer a critical level, (iv) environmental limitation to O3 uptake and (v) inherent characteristics of Mediterranean vegetation. In particular, the two latter points suggest that critical levels based on accumulated stomatal flux (CLe(f)) can be a better predictor of O3 risk than CLe(c). While this concept is largely acknowledged, a number of factors may limit its applicability for routine monitoring. This paper reviews levels, uptake and vegetation response to O3 in Italy over recent years to discuss value, uncertainty and feasibility of different approaches to risk assessment.

Crops, Agricultural↗

A multi-biomarker analysis of DNA damage in automobile painters.

The genotoxic effects associated with automobile painting were analyzed using a panel of biomarkers. Chromosomal aberrations (CAs), sister chromatid exchange (SCE), and micronuclei were evaluated in 25 car painters (12 smokers, 13 nonsmokers) working in different automobile paint-shops in Italy and in 37 control subjects. The controls were healthy blood donors (14 smokers, 23 non-smokers) that were matched with the experimental population for gender and age. Air samples were analyzed regularly at the work places, and elevated concentrations of benzene and toluene were detected consistently. The exposed group had higher frequencies of CAs (both chromosome- and chromatid-type), micronuclei, and SCE (P < 0.5 - P < 0.001). Furthermore, exposed and control subjects were also genotyped for GSTM1 and GSTT1 polymorphism. No significant associations were detected between the biomarker responses and either the GSTM1 or GSTT1 genotype of the subjects, but the small sample size does not allow definite conclusions on the relationship between the genetic polymorphism and the biomarkers. The results indicate that automobile painters have increased levels of clastogenic and possible aneugenic damage and that smoking may be a confounding factor for the responses.

Adult↗

Lichens as polycyclic aromatic hydrocarbon bioaccumulators used in atmospheric pollution studies.

The aim of this work has been to determine the possibility of using lichens as polycyclic aromatic hydrocarbon (PAH) bioaccumulators for the evaluation of atmospheric pollution in the city of Rieti. A lichen sample collected in a remote unpolluted area was divided into 18 sub-samples. These were collocated in nine different stations in the city of Rieti and every 5 months the PAH concentrations were determined. Only phenanthrene, anthracene, fluoranthene, pyrene and chrysene were found at concentrations over the limit of quantification. In the meantime a continuous increase of their concentrations was observed.

Air Pollutants↗

Influence of a low background radiation environment on biochemical and biological responses in V79 cells.

We present the results of an experiment aimed at comparing the effects of different background radiation environments on metabolism and responses to gamma-rays and cycloheximide of cultured mammalian cells. Chinese hamster V79 cells were maintained in exponential growth in parallel for up to 9 months at the Istituto Superiore di Sanità (ISS) and at the INFN-Gran Sasso underground Laboratory (LNGS) where exposure due to gamma-rays and to radon was reduced by factors of about 70 and 25, respectively. After 9 months the cells grown at the LNGS (cumulative gamma dose about 30 microGy, average radon concentration around 5 Bq/m(3)), compared to the cells grown at the ISS (cumulative gamma-ray dose about 2 mGy, average radon concentration around 120 Bq/m(3)), exhibited i). a significant increase of the cell density at confluence, ii). a significantly higher capacity to scavenge organic and inorganic hydroperoxides but a reduced scavenging capacity towards superoxide anions and iii). an increase in both the basal hprt mutation frequency and sensitivity to the mutagenic effect of gamma-rays. The cells grown at the LNGS also showed a greater apoptotic sensitivity starting at the third month of culture, that was no longer detected after 9 months. Overall, these data suggest a role of background ionizing radiation in determining an adaptive response, although they cannot be considered conclusive.

Air Pollution, Indoor↗

Evaluation of genotoxic and cytotoxic properties of pesticides employed in Italian agricultural practices.

In a program coordinated by the Italian Ministry of Works, we tested in vitro four pesticides widely employed in a developed agricultural region of central Italy. The four commercial agents were chosen on the basis of their diffusion in agricultural practice, knowledge of their active principle(s), and scant availability of data concerning their toxic and genotoxic activity. The agents were Cirtoxin, Decis, Tramat Combi (TC), and Lasso Micromix (LM). All substances were tested in three in vitro systems: Chinese hamster ovary (CHO) cells, a metabolically competent hamster cell line (Chinese hamster epithelial liver; CHEL), and root tips of Vicia faba (VF). The cytotoxic and genotoxic end points challenged were micronuclei and root tip length (RTL) in VF and mitotic index (MI), proliferation index (PI), cell survival (CS), cell growth (CG), cell cycle length (CCL), sister chromatid exchanges, chromosomal aberrations, and single-cell gel electrophoresis, or comet assay, in CHEL and CHO cells. Tested doses ranged from the field dose up to 200x the field dose to take into account accumulation effects. On the whole, tested agents appear to induce genotoxic damage only at subtoxic or toxic doses, indicating a low clastogenic risk. MI, PI, CS, CG, RTL, and CCL appear to be the less sensitive end points, showing no effects in the presence of a clear positive response in some or all of the other tests. Using cytogenetic tests, we obtained positive results for TC and LM treatments in CHO but not in CHEL cells. These data could be accounted for by postulating a detoxifying activity exerted by this cell line. However, cytogenetic end points appear to be more sensitive than those referring to cytotoxicity.

Agriculture↗

Delta(12)-prostaglandin J(2) is a potent inhibitor of influenza A virus replication.

9-Deoxy-Delta(9),Delta(12)-13,14-dihydro-prostaglandin D(2) (Delta(12)-PGJ(2)), a natural cyclopentenone metabolite of prostaglandin D(2), is shown to possess therapeutic efficacy against influenza A virus A/PR8/34 (H1N1) infection in vitro and in vivo. The results indicate that the antiviral activity is associated with induction of cytoprotective heat shock proteins and suggest novel strategies for treatment of influenza virus infection.

Animals↗

Buthionine sulfoximine prevents the reduction of the genotoxic activity of maleic hydrazide by soil humic substances in Vicia faba seedlings.

A significant reduction of the genotoxic effects caused by herbicide maleic hydrazide (MH) in Vicia faba seedlings was observed to be induced by a growth step in an organic soil as well as by a pretreatment with highly purified humic substances. In addition, such protective activity was resulted quite similar to that observed when the conditioning pretreatment was carried out with metal salts, so suggesting the involvement of the GSH biosynthesis in determining the protective activity observed. In agreement with this hypothesis, a previous exposure to buthionine sulfoximine (BSO), an inhibitor of the phytochelatins production, through the inhibition of GSH synthesis, prevented the reduction of the genotoxic activity of MH. The findings provide evidence for the involvement of the GSH biosynthesis pathway in determining the antigenotoxic activity revealed and suggest a possible involvement of the phytochelatins in this process. However, yet to be clarified is whether the stimulation of GSH production results as a consequence of a nonspecific influence on the protein synthesis by humic substances or of its direct activation due to the presence, as contaminants, of some heavy metals in both organic soil and humic acids extracts.

Antimutagenic Agents↗

Antiviral effect of hyperthermic treatment in rhinovirus infection.

Human rhinoviruses (HRV) are recognized as the major etiologic agents for the common cold. Starting from the observation that local hyperthermic treatment is beneficial in patients with natural and experimental common colds, we have studied the effect of brief hyperthermic treatment (HT) on HRV replication in HeLa cells. We report that a 20-min HT at 45 degrees C is effective in suppressing HRV multiplication by more than 90% when applied at specific stages of the virus replication cycle. Synthesis of virus proteins is not affected by HT, indicating that the target for treatment is a posttranslational event. The antiviral effect is a transient cell-mediated event and is associated with the synthesis of the 70-kDa heat shock protein hsp70. Unlike poliovirus, rhinovirus infection does not inhibit the expression of hsp70 induced by heat. The possibility that hsp70 could play a role in the control of rhinovirus replication is suggested by the fact that a different class of HSP inducers, the cyclopentenone prostaglandins PGA1 and delta 12-PGJ2, were also effective in inhibiting HRV replication in HeLa cells. Inhibition of hsp70 expression by actinomycin D prevented the antiviral activity of prostaglandins in HRV-infected cells. These results indicate that the beneficial effect of respiratory hyperthermia may be mediated by the induction of a cytoprotective heat shock response in rhinovirus-infected cells.

Antiviral Agents↗

Inhibition of HSP70 expression by calcium ionophore A23187 in human cells. An effect independent of the acquisition of DNA-binding activity by the heat shock transcription factor.

Heat shock proteins (HSPs) are induced in mammalian cells in a variety of pathophysiological states and have an important role in cytoprotection in vitro and in vivo. In this study, we report that the calcium ionophore A23187, a glucose-regulated protein (GRP) inducer, dramatically inhibits HSP70 synthesis and HSP70 mRNA transcription after induction by heat shock, sodium arsenite, or prostaglandin A1 treatment in human K562 cells. A23187 does not suppress, and it actually prolongs, the DNA-binding activity of the human heat shock transcription factor (HSF), while it alters HSF1 phosphorylation in heat shock-treated cells. To inhibit HSP70 expression, A23187 needs to be present during heat shock, while treatment before or after heat shock does not affect HSP70 mRNA transcription. The GRP inducer thapsigargin, which specifically inhibits the endoplasmic reticulum Ca2+-ATPase, has no effect on heat-induced HSP70 synthesis, indicating that A23187 inhibitory activity is not due to depletion of intracellular calcium stores and is independent of the concomitant induction of GRP genes. Inhibition of HSP70 expression is correlated with alterations in HSF1 phosphorylation in heat-shocked cells, but not in sodium arsenite-treated cells, indicating that different mechanisms may be involved in mediating A23187 inhibitory activity.

Calcimycin↗

Inhibition of HIV-1 replication by cyclopentenone prostaglandins in acutely infected human cells. Evidence for a transcriptional block.

Cyclopentenone prostaglandins (PGs) inhibit virus replication in several DNA and RNA virus models, in vitro and in vivo. In the present report we demonstrate that the cyclopentenone prostaglandins PGA(1) and PGJ(2) at nontoxic concentrations can dramatically suppress HIV-1 replication during acute infection in CEM-SS cells. PGs did not affect HIV-1 adsorption, penetration, reverse transcriptase activity nor viral DNA accumulation in HIV-1 infected cells. A dramatic reduction in HIV-1 mRNA levels was detected up to 48-72 h after infection (p.i.) in PG-treated cells, and HIV-1 protein synthesis was greatly reduced by a single PG-treatment up to 96 h p.i. Repeated PGA(1)-treatments were effective in protecting CEM-SS cells by the cytopathic effect of the virus, and in dramatically reducing HIV-1 RNA levels up to 7 d after infection. The antiviral effect was not mediated by alterations in the expression of alpha-, beta-, or gamma-interferon,TNFalpha, TNFbeta, IL6, and IL10 in HIV-infected CEM-SS cells. The fact that prostaglandins are used clinically in the treatment of several diseases, suggests a potential use of cyclopentenone PGs in the treatment of HIV-infection.

Antiviral Agents↗

Inhibition of poliovirus replication by prostaglandins A and J in human cells.

Cyclopentenone prostaglandins (PGs) inhibit the replication of a wide variety of enveloped DNA and RNA viruses. The antiviral activity is associated with alterations in the synthesis, maturation, and intracellular translocation of viral proteins. In the present report, we describe the effects of cyclopentenone PGs PGA1 and delta 12-PGJ2 on poliovirus (PV) replication in HeLa cells. Both PGs were found to inhibit PV replication dose dependently. Virus yield was significantly reduced at nontoxic concentrations, which did not suppress RNA or protein synthesis in uninfected or PV-infected cells. Both the pattern of PV proteins synthesized and the kinetics of viral protein synthesis and degradation appeared to be similar in PGA1-treated cells and control cells. Antiviral PGs have been shown to selectively inhibit virus protein synthesis during the replication of several viruses, including vesicular stomatitis virus (VSV), and this effect has been recently associated with the induction of a 70-kDa heat shock protein (HSP70). PGA1 and delta 12-PGJ2 were found to induce HSP70 synthesis in uninfected or VSV-infected HeLa cells. PV infection was found to inhibit PG-induced HSP70 synthesis in these cells, suggesting that the lack of ability of cyclopentenone PGs to block PV protein synthesis could be related to an impaired heat shock response in PV-infected cells. The finding that PV protein synthesis was not inhibited by PGs suggests that cyclopentenone PGs could interfere with a late event in the virus replication cycle, such as protein assembly and maturation of PV virions.

Antiviral Agents↗

Effects of single and short-term administration of clonidine on hypothalamic-pituitary somatotropic function of the adult male rat: an in situ hybridization study.

The effects of the alpha-2 adrenoceptor agonist clonidine (CLO) on the growth hormone (GH) regulatory neuronal systems, growth hormone-releasing hormone (GHRH) and somatostatin (SS), were studied in adult male rats given a single or a short-term administration (1, 3 and 6 days) of the drug. Acute administration of CLO significantly decreased hypothalamic GHRH content [leaving unaltered GHRH messenger RNA (mRNA) levels] and increased plasma GH levels; hypothalamic SS content/mRNA levels and pituitary GH content/mRNA levels remained unchanged. In 1- and 3-day CLO-treated rats, by contrast, decreased hypothalamic GHRH content was coupled with a significant reduction in GHRH mRNA levels. In these rats, pituitary GH content and mRNA levels were also significantly increased, whereas hypothalamic SS content and mRNA levels remained unaltered. In 6-day CLO-treated rats, hypothalamic GHRH content and mRNA levels were still significantly reduced, plasma GH levels were increased, but to a lesser extent than in 1- and 3-day CLO-treated rats, and pituitary GH content and mRNA reverted to control levels. Hypothalamic SS content and mRNA levels remained unaltered. These results indicate that 1) functional activation of alpha-2 adrenergic receptors by CLO increases GHRH release from the hypothalamus, 2) CLO, via GHRH, increases GH secretion and biosynthesis, which in turn feeds back in the hypothalamus to reduce GHRH biosynthesis, and 3) reduction of hypothalamic GH-stimulatory activity tones down the initial pituitary somatotropic hyperfunction. Unaltered hypothalamic SS content and mRNA levels in all CLO-treated rats suggests that the somatostatinergic system is less sensitive than the GHRH system to changes in circulating GH levels.

Adrenergic alpha-2 Receptor Agonists↗

Testosterone maintenance therapy. Effects on vulvar lichen sclerosus treated with clobetasol propionate.

OBJECTIVE: To evaluate the possible effects of topical testosterone as maintenance therapy after clobetasol propionate treatment. STUDY DESIGN: Thirty-two patients with biopsy-proven vulvar lichen sclerosus (LS), after 24 weeks of treatment with 0.05% clobetasol propionate cream, were randomly distributed into two groups of 16 each and treated for a further length of time (24 weeks) with testosterone 2% ointment or a cream-based preparation (placebo). The patients were examined before and after treatment for symptoms, gross aspects and histologic features. RESULTS: With clobetasol propionate all patients had a marked improvement (P < .001) in both clinical and histologic parameters. After clobetasol propionate therapy, the 16 testosterone-treated patients had significant worsening of their symptoms (P < .05%) and no evident changes in gross aspects (P = NS). The placebo-treated group had good symptomatic control of their disease, with no significant changes in symptoms or gross aspects (P = NS). CONCLUSION: After the good results obtained with clobetasol propionate, treatment with testosterone appeared to have a negative effect, while a regularly provided emollient cream was useful in symptom control.

Administration, Cutaneous↗

Influence of soil characteristics on the clastogenic activity of maleic hydrazide in root tips of Vicia faba.

The clastogenic activity of the herbicide maleic hydrazide (MH) in Vicia faba seedlings grown in different soils was studied. In the first series of experiments the seedlings were treated with MH in nine soils of different selected properties. The second experimental protocol provided for a growth step in each of the nine soils under study and then for the treatment of the seedlings with MH in a sandy soil. The results obtained show that less clastogenic damage (induction of micronuclei and aberrant anatelophases) was observed in the seedlings treated in the soils with a high content of organic and clay-type colloids. A growth step carried out in the organic soils, before the treatment with MH, was observed to reduce the genotoxic effects of the herbicide when the seedlings were treated in a sandy soil. These findings suggest that some components of soil organic matter, such as fulvic and humic acids, may be absorbed by the plant roots and so carry out an antimutagenic activity against MH within the plant.

Antimutagenic Agents↗

Idiopathic vulvodynia. Clinical evaluation of the pain threshold with acetic acid solutions.

Idiopathic vulvodynia is vulvar discomfort in which a diagnosis has not yet been established. As in other idiopathic pain syndromes, the involvement of primary afferent fibers (PAFs) has been postulated as playing a role in the pathogenesis and maintenance of idiopathic vulvodynia. Capsaicin induces the release of substance P (SP) by PAFs, producing vasodilation and increasing vascular permeability (neurogenic inflammation). Likewise, it has been shown that acid solutions can stimulate PAFs with the release of SP. To evaluate the pain threshold in women with idiopathic vulvodynia, 10 patients with vulvar pain but without significant vulvar physical changes and 10 asymptomatic controls received topically applied acetic acid solutions with increasing hydrogenionic concentrations (pH 3, 2.5, 2, 1.5, 1.2). Results related to pain threshold and pain time monitoring and intensity were analyzed with Fisher's exact and Wilcoxon's tests, respectively. Our data suggest that in idiopathic vulvodynia the pain threshold for acid solutions is decreased, probably in relation to increased sensitivity of PAFs involved in the transduction of painful signals.

Acetates↗

[Use of a GnRH analogue in the treatment of certain forms of endometrial hyperplasia associated with menometrorrhagia].

Hyperestrogenism is a powerful factor inducing the development of endometrial hyperplasia that in its turn may represent the first step in the natural history of endometrial carcinoma. During menopause it is possible to have a condition to relative hyperestrogenism induced by a residual hormonal activity and by aromatisation of androgens in the adipose tissue. Therapeutical approach in this pathology aims to control hyperplastic development of the endometrial mucosa and to exclude menometrorrhagia. This study has been performed according to an open uncontrolled design in 14 women (4 menopausal women) with abnormal uterine bleeding and hysteroscopic endometrial cystic or adenomatous hyperplasia. At the beginning and at the end of treatment all patients underwent routine biohumoral blood-tests, hysteroscopy and diagnostic curretage. The GnRH analogue (tryptorelin) 3.75 mg 1 ampoule i.m. every 28 days was administered during a 6-month treatment cycle. At the end of therapy bleeding had disappeared in all menopausal women; in the premenopausal group 8 patients have shown a normal menstrual cycle while 2 are still amenorrhoic. The final hysteroscopic evaluation displayed atrophic endometrium in 9 patients and simple proliferative endometrium in 5 cases. Safety was excellent: 3 cases of slight increase of systolic blood pressure and 1 case of slight increase of weight took place. Our results demonstrate therapeutic efficacy of GnRH analogues in the treatment of endometrial hyperplasia with menometrorrhagia either in premenopausal or menopausal women.

Aged↗

Modifications of the Poggendorff effect as a function of random dot textures between the verticals.

In the present research, we investigated the modification of the strength of the Poggendorff illusion as a function of different densities of random dot textures filling the space between the verticals. The results of Experiment 1 show that the illusory effect is a nonlinear function of the texture parameter r, the ratio of black pixels to white and black pixels, with a minimum for r = 0.5, approximately, and a maximum for r = 0 and r = 1. The results may be interpreted by an analytical model of perceptual space dynamics, in which the effect depends on the amount of interaction between points of different light intensity. A computer simulation performed by applying the analytical model to different values of r shows a good agreement between the predictions and the experimental data. To test the hypothesis underlying the model, a second experiment was carried out to measure the magnitude of the expansion of the space between the verticals as a function of the parameter r. The results are consistent with the hypothesis of the model. The overall data are discussed in terms of their implications on various theories proposed for the Poggendorff illusion.

Adult↗

Antiproliferative activity of cyclopentenone prostaglandins in early HTLV-1 infection is independent of IL-2 and is associated with HSP70 induction.

Cyclopentenone prostaglandins PGA1 and PGJ2 can inhibit the growth of HTLV-1 infected cord blood-derived human mononuclear cells (CBMC), both after acute infection and in chronically infected, immortalized cells. When CBMC were exposed to HTLV-1 infection by coculturing with lethally irradiated, virus-donor allogeneic MT-2 cells, they underwent a proliferative response, that peaked within the first week and then declined. PG treatment did not inhibit the initial proliferation (day 4) of cocultured CBMC, while multiple treatments with PGA1 and more efficiently with PGJ2, suppressed the late cell proliferation (from day 8 onward). The pharmacological effects of PGA1 and PGJ2 were reversible and therefore multiple treatments were required to maintain their antiproliferative activity. Increasing concentrations (20, 40, 80 IU/ml) of recombinant IL-2 did not affect the virus-associated proliferative response of CBMC, and exogenous IL-2 did not revert the antiproliferative effect of both PGs. Arrest of proliferation in cocultured CBMC occurred concomitantly with expression of high levels of HSP70 in the cells. In fact, though HSP70 expression was induced early (day 5) after exposure to HTLV-1, its expression was further increased after multiple PG treatments and high levels were found when the antiproliferative effect of PGs became manifest. Since HSP70 protein family is involved in the control of cell cycle as well as in antigen processing and presentation during the immune response against tumor cells and pathogens, the persistent expression of this protein in PG-treated cocultures suggested that, beside inhibiting the growth of virus-infected cells, HSP70 expression might play a role in modulating the immune function of CBMC. However, unlike in most virus infection models, in which cyclopentenone PGs exert clear antiviral effects by inhibiting the synthesis and maturation of virus proteins, no antiviral activity was found in this model of infection. This strongly suggests that the main effect of these PGs against HTLV-1 infected cells consists in inhibiting proliferation in vitro without affecting viral expression.

Antiviral Agents↗