Luigi Manzo - Academia.edu (original) (raw)

Papers by Luigi Manzo

PubMed, Mar 1, 2011

Increasing interest in safety evaluation of carbon nanotubes (CNTs) has risen in relation to thei... more Increasing interest in safety evaluation of carbon nanotubes (CNTs) has risen in relation to their wide applications, together with the evidence of their cytotoxic effects. It has been shown that chemical functionalization extends the applications of CNTs, conferring them new functions that cannot otherwise be acquired by pristine CNTs, but also impacts on biological response to CNTs, modifying their toxicological profile. We assessed the onset of pulmonary toxic effects caused by pristine MW-CNTs and functionalized MW-NH₂ or MW-COOH, 16 days after intratracheal instillation (1 mg/kg b.w.); major endpoints tested included (i) histopathology of lung (Haematoxylin/Eosin Staining), (ii) apoptotic/proliferating features examined by TUNEL and PCNA immunostaining, and (iii) presence/distribution of (1) Transforming Growth Factor-beta1 (TGFß1), (2) Interleukin-6 (IL-6) and (3) Collagen (Type I) investigated by immunochemical methods, as markers of lung toxicity, inflammation, and fibrosis, respectively. Lung histopathology from exposed animals showed dark, particulate-laden macrophages, reflecting carbon nanomaterial engulfing, both at alveolar and bronchiolar levels, after treatment with all the tested CNTs. Alteration of lung architecture was also observed in several areas showing collapsed thick-walled alveoli and the presence of micro-haemorrhagic foci. TUNEL and PCNA, indicative of apoptosis and cell proliferation respectively, showed a significant increase of immunopositive cells at bronchiolar, alveolar and macrophagic levels, as expression of an improved cellular turnover. Increased immunoreactivity for pulmonary TGFß1 and IL-6 was observed in treated rats, particularly in bronchiolar areas, collapsed alveoli and at stromal level, while evident changes for collagen were not detected. Taken together these findings demonstrated the general pulmonary toxicity coupled with inflammatory response after in vivo exposure to CNTs, without overt signs of fibrosis and granuloma formation, irrespectively of nanotube functionalization.

Immunopharmacology, 1991

3H-Spiperone binds to dopamine D2 receptors in striatum and, under the assumption that it labels ... more 3H-Spiperone binds to dopamine D2 receptors in striatum and, under the assumption that it labels the same receptors in lymphocytes, this binding site has been suggested as a biological marker for schizophrenia. Recent studies, however, have raised questions about the existence of dopamine receptor changes in drug-free schizophrenic patients, as well as on the presence and/or dopaminergic nature of lymphocytic 3H-spiperone binding sites. In the present study we have conducted an investigation of the binding of 3H-spiperone to rat and human lymphocytes. We found that 3H-spiperone binds in a specific, saturable and reversible manner to a site in lymphocytes; however, its dissociation constant Kd (9 nM) is about 40-fold higher than in striatum. An extensive investigation of the 3H-spiperone sites indicated that their pharmacological profile was not that of a dopamine D2 site, but rather that of sigma receptors, a novel class of non-dopaminergic, non-opioid receptors which bind with high affinity antipsychotic drugs. Sigma receptors were also identified in lymphocytes using the specific ligand 3H-DTG (1,3-di-o-tolyl-guanidine), whose binding characteristics were comparable to those of sigma receptors in rat brain. Receptor density and the pharmacological profile of 3H-spiperone and 3H-DTG were similar. Both compounds also labelled a higher number of sites in B cells than in T cells and a good correlation was found between the lymphocytic binding of both ligands in a group of 58 people. These findings indicate that sigma receptors are present in lymphocytes and suggest that 3H-spiperone binding in these cells occurs to sigma sites and not to dopamine D2 sites.

Journal of Neuroimaging, 2002

brain damage on magnetic resonance imaging after carbon monoxide poisoning.

Journal of Neurochemistry, 1990

Abstract: σ‐Receptors are nonopioid, nondopaminergic receptors that bind with high affinity sever... more Abstract: σ‐Receptors are nonopioid, nondopaminergic receptors that bind with high affinity several antipsychotic drugs and appear to be involved in regulation of posture and movement. The second messenger system coupled to these receptors is still unknown. Recently, an inhibitory effect of various σ‐compounds on carbachol‐stimulated phosphoinositide metabolism has been reported. We have investigated the effect of six σ‐compounds on carbachol‐ and norepinephrine‐stimulated 3H‐inositol phosphate accumulation in rat cerebral cortex slices. All compounds tested had a dose‐dependent inhibitory effect on both systems, although their order of potency differed between neurotransmitters. Pentazocine and 1,3‐di‐o‐tolylguanidine were the most potent inhibitors of carbachol‐stimulated phosphoinositide turnover (IC50= 31.5 and 45.7 μM, respectively), while haloperidol showed the greatest potency on the norepinephrine‐coupled system (IC50= 3.5 μM). In the presence of IC50 concentrations of these inhibitors, the dose‐response curves for the agonists were shifted to the right and the EC50 values were significantly increased. σ‐Compounds also inhibited the binding of [3H]quinuclidinyl benzilate to muscarinic receptors and of [3H]prazosin to α1‐adrenoceptors in cortical membranes. In the presence of IC50 concentration (11 μM) of 1,3‐di‐o‐tolylguanidine, no differences were found in the maximal number of muscarinic binding sites, whereas the dissociation constant increased approximately fivefold, indicating a decrease of the radioligand's affinity for the receptor. These results indicate that σ‐compounds, at micromolar concentrations, inhibit muscarinic and α1‐adrenergic receptor‐coupled phosphoinositide metabolism, probably through an interaction with the neurotransmitter recognition sites.

Emergency Care Journal, 2008

clinica e terapia emergency care journal Materiale protetto da copyright. Non fotocopiare o distr... more clinica e terapia emergency care journal Materiale protetto da copyright. Non fotocopiare o distribuire elettronicamente senza l'autorizzazione scritta dell'editore.

Archives of Industrial Hygiene and Toxicology, 2007

Contaminants in Fish: Risk-Benefit ConsiderationsFish provide a healthful source of dietary prote... more Contaminants in Fish: Risk-Benefit ConsiderationsFish provide a healthful source of dietary protein and are high in nutrients such as omega-3 fatty acids. There is evidence of beneficial effects of fish consumption in coronary heart disease, stroke, age-related macular degeneration, and growth and development. Yet, benefits may be offset by the presence of contaminants, such as methylmercury (MeHg), dioxins, polychlorinated biphenyls (PCBs) and several other halogenated persistent organic pollutants. MeHg is a known developmental neurotoxicant, as evidenced by several animal studies and episodes of human intoxication in Japan and Iraq. Fish represent the main source of exposure to MeHg for the general population, and large predatory fish (swordfish, tuna) have the highest levels of MeHg contamination. Provisional tolerable weekly intakes of 0.7 μg kg-1 to 1.6 μg kg-1 have been set by regulatory agencies. Concern for contamination of fish with dioxins and dioxin-like PCBs stems from ...

Reviews on Environmental Health, 2003

Mercurials are global environmeniäl ρθ!= lutants deriving from natural processes and anthropogeni... more Mercurials are global environmeniäl ρθ!= lutants deriving from natural processes and anthropogenic activities. Most human exposure to mercury occUFs through the intake of fish, shellfish, and sea mammals contaminäf£t) With methylmercury. Methylmercury is bioaccumulated and biomagnified in the aquatic food chain and reaches its highest levels in top predatory fish. The neurotoxic hazard posed by methylmercury to humans and the unique susceptibility of the developing brain have been well documented following the mass poisonings occurring in Japan and Iraq. Adult cases of methylmercury poisoning are characterized by the delayed onset of symptoms and by the focal degeneration of neurons in selected brain regions (for example, cerebral cortex and cerebellum). Why the fetus displays different neuropathological effects and a higher sensitivity to methylmercury relative to the adult is still unknown. Depending on the degree of Iii utero exposure, methylmercury may result in effects ranging from fetal death to subtle neurodevelopmental delays. On the basis of epidemiological studies performed in populations having moderate chronic methylmercury exposure, no definitive consensus has been reached to date on the safety level of maternal

Toxicology Letters, 1996

Poster Session 3P Toxicokinetic 89 100 and 600 mg/kg. After the administration of a smaller dose ... more Poster Session 3P Toxicokinetic 89 100 and 600 mg/kg. After the administration of a smaller dose (100 mg/kg) the maximum radioactivity in the blood was detected after 4 hours. Decline of 3H tritium in the plasma was bi-phasic, with the half-lives: 4 and 54 hours, respectively. However, after the administration of the higher dose (600 mg/kg), the maximum radioactivity in the plasma and erythrocytes was observed after 12 hours. No decline of tritium was detected throughout the whole time of observation (72 hours), which may suggest durable binding of 1,2-[3H]-dBB to blood elements, and especially to plasma. In the blood, tritium was mostly bound to plasma, irrespectively of the administered dose. The highest concentration of 3H was detected in all examined rat tissues between 4 and 8 hours following the administration. Liver, kidneys, plasma and fat tissue accumulated most of 3H tritium during the first hours after the administration. The level of tritium decreased fastest in the liver, kidneys and spleen. Urine turned out to be the main route of excretion for 3H (about 82%). In faeces about 4% of the administered dose was excreted. In order to identify the isolated metabolites in urine mass spectrometry technique was used. Unchanged compound and the following metabolites were detected: 2,3-dibromophenol, 3,4-dibromopbenol and 2-bromophenol. The obtained data point out that 1,2-dibromobenzene belongs to compounds with a high turnover in the organism, whereas its metabolism consists principally in C-hydroxylation. This study was carried out under KBN Grant No 50%13-011.

In the last few decades, combined exposure to methylmercury (MeHg) and polychlorinated biphenyls ... more In the last few decades, combined exposure to methylmercury (MeHg) and polychlorinated biphenyls (PCBs) from fish and seafood, and their potentially interactive effects on neurodevelopment, have been giving increasing cause for concern. We examined the combined effects of MeHg and either a non-dioxin PCB (PCB153) or a dioxin-like PCB (PCB126) congener on the developing brain cholinergic muscarinic receptors (MRs). These receptors are known to play a major role in many central functions including higher cognitive processes and the modulation of extrapyramidal motor activity. MRs in pup rat brains diminished following prenatal and lactational exposure, from gestational day [GD]7 to postnatal day [PND]21, to MeHg (0.5 mg/kg body weight [bw]/day), PCB153 (5 mg/kg bw/day), and PCB126 (100 ng/kg/day), alone or in combination. Total MR density, as well as M1, M2, and M3 receptor subtypes of the weanling and pubertal rats, were affected in a brain-area-, gender-, time-and compound-dependent fashion. MeHg decreased (by 15-20%) the total MR density in a delayed (PND36) manner in the cerebral cortex of both genders, and early (at weaning) in the cerebellum of both genders, with the effect lasting until puberty (in males only). MeHg decreased the ACh M1-and M3-immunopositive neurons in the cerebral cortex and also increased the M2-immunopositive Bergmann glia in the cerebellum. PCB153 also induced a delayed (PND36) decrease (of 20%) in total MR number in the cerebellum of the male offspring and in the cerebral cortex of both genders. The latter effect was coupled with a decrease in ACh M1-and ACh M3-immunopositive neuron populations. PCB126 decreased (by 30-40%) total MR density in a gender-dependent manner, males being more sensitive than females. The effect was evident early (at PND21) and lasted until puberty in the cerebellum, while it was observed later (at PND36) in the cerebral cortex. The M1 and M3 receptors were similarly affected by PCB126. Co-exposure to MeHg and either PCB153 or PCB126 had the same effect on the cerebral MRs as exposure to each compound alone. The results rule out additive or synergistic interactions between MeHg and PCB153 or PCB126 on MRs in the brain areas examined.

Environmental Toxicology and Pharmacology, 2005

Lymphocyte cholinergic muscarinic receptors (MRs) and platelet monoamine oxidase-B (MAO-B) activi... more Lymphocyte cholinergic muscarinic receptors (MRs) and platelet monoamine oxidase-B (MAO-B) activity are considered surrogate markers of the same parameters in the central nervous system. Lymphocyte MR binding and platelet MAO-B activity were measured in a consistent number of healthy human adults and analysed according to gender and age. The mean value ± S.D. of MR binding neither differed between males (12.2 ± 10.0 fmol/10 6 cells, range: 0.5-37.9, n = 86) and females (10.7 ± 9.7 fmol/10 6 cells, range: 0.5-39.7, n = 69) nor among age groups. MAO-B activity was significantly higher in women (geometric mean: 11.3 nmol/mg protein/h, with 65% of values from 7.3 to 17.6; n = 43), than in men (7.7 nmol/mg protein/h, with 65% of values from 4.5 to 13; n = 95). Males aged 56-66 years displayed a higher, though not statistically significant, basal enzyme activity than younger subjects. Altogether these data indicate gender-related differences in MAO activity, but not in MR binding, and inter-individual differences in the basal values of both peripheral blood markers in healthy subjects.

Pharmacology & Toxicology, 1992

Ahstrart: Central and peripheral a,-adrenoceptors, including those of the gastrointestinal tract,... more Ahstrart: Central and peripheral a,-adrenoceptors, including those of the gastrointestinal tract, have been indicated as a toxicity target of formamidine pesticides in mammals. In this study, the inhibitory effect of chlordimeform on twitch contractions from electrically-stimulated longitudinal muscle-myenteric plexus preparations (LMMPs) of the guinea-pig ileum was found to be resistant to the action of the a+drenoceptor antagonist idazoxan. This drug was also ineffective on chlordimeform-induced inhibition of peristalsis recorded in whole ileal segments. As expected, idazoxan antagonized the inhibitory effect of the a,-adrenoceptor agonist clonidine on twitch contractions and peristaltic activity. Chlordimel'orm reduced the amplitude of direct mechanical responses to a variety of spasmogens such as acetylcholine. histamine and substance P, suggesting a muscular site of action. Moreover, in Ca2+-free, K+-depolarized LMMPs. chlordimeform inhibited submaximal contractions caused by addition of exogenous calcium, through an action apparently similar to that of the Ca'+ entry blocker nifedipine. Both chlordimeform-and nifedipine-induced inhibition of calcium contractions were reversed by the calcium channel activator BAY K 8644. This compound also partially prevented the inhibitory action ol' chlordimeform on peristaltic activity. On the whole, these results indicate that chlordimeform-induced depression of motor activity in the guinea-pig ileum is, at least in part, related to inhibition of transmembrane Ca'+ fluxes responsible for smooth muscle contraction. Chlordimeform, [N'-(4-chloro-o-tolyI)-N,N-dimethylformamidine], is a formamidine pesticide of widespread use in agriculture and veterinary medicine as insecticide/acaricide (Hollingworth 1976), though it has been recently withdrawn from the US market due to its suspected carcinogenicity. Pcsticidal action of formamidines in invertebrates is thought to be related to interaction with octopamine receptors (Hollingworth & Murdock 1980) and to the activation of an octopamine-dependent adenylate cyclase (Evans & Gee 1980; Nathanson 1985). In mammals, several adverse effects of formamidines, including inhibition of monoamine oxidase (MAO) (Beeman & Matsumura 1973; Benezet et d. 1978), inhibition of oxidative phosphorylation (Abo-Khatwa & Hollingworth 1974), blockade of neuromuscular transmission (Wang et al. 1975), inhibition of prostaglandin biosynthesis (Yim et 01. 1978) and local anaesthetic properties (Chinn ef al. 1977; Pfister er al. 1978), have been reported. Recently, however, the a,-adrenoceptor system has also been indicated as a major target site for formamidine action in mammals. In fact, most of the adverse effects

Environmental Health Perspectives, 1999

We thank P. Baiardi (Medical Informatics, S. Maugeri Foundation) for statistical analysis and D. ... more We thank P. Baiardi (Medical Informatics, S. Maugeri Foundation) for statistical analysis and D. Acerbi for expert technical assistance. We are also indebted to E. Faustman for insightful comments and suggestions. This study was supported by grants fronm the European Commission (grant ENV4-CT96-0173) and the Italian Ministry of Health.

Regulatory Toxicology and Pharmacology, 2008

Methylmercury (MeHg) is a widespread environmental and food toxicant which has long been known to... more Methylmercury (MeHg) is a widespread environmental and food toxicant which has long been known to affect neurodevelopment in both humans and experimental animals. Risk assessment for MeHg is mainly based on human data coming from the massive episodes of poisoning in Japan and Iraq, as well as from large scale epidemiological studies concerning childhood development and neurotoxicity in relation to in utero exposure in various fish eating communities around the world. Despite the extensive literature and research, the threshold dose for MeHg neurotoxic effects is still unclear, in particular when it comes to subtle effects on neurobehaviour. In this article clinical and epidemiological findings concerning the neurodevelopmental toxicity of MeHg are reviewed. Much attention is focussed on the potential impact of factors, such as diet and nutrition, gender, pattern of exposure and co-exposure to other neurotoxic pollutants, which may modulate MeHg toxic effects. These factors, together with the notion that some symptoms may ensue or exacerbate with aging, contribute to the difficulties in the definition of safe levels for developmental exposure.

Muscle & Nerve, 2000

Ciguatera poisoning causes mainly gastrointestinal and neurological effects of variable severity.... more Ciguatera poisoning causes mainly gastrointestinal and neurological effects of variable severity. However, symptoms of peripheral neuropathy with paresthesias and paradoxical disturbance of thermal sensation are the hallmark. Electrophysiological studies are often normal, except in severe cases. We report four people who developed mild ciguatera poisoning after barracuda ingestion. Electrophysiological studies documented normocalcemic latent tetany. These findings are consistent with ciguatoxin&amp;amp;amp;#39;s mechanism of toxicity, which involves inactivation of voltage-gated Na(+) channels and eventually increases nerve membrane excitability.