Marta Benedetti

Cancer risk associated with residential proximity to industrial sites: a review.

Abstract In this study, the authors sought to review available epidemiologic studies of cancer risk and its association with residence in a neighborhood characterized by industrial sites and to discuss options for future study design. The authors attempted to identify all case-control studies published from January 1980 through July 1997 in which investigators examined exposure resulting from residential proximity to an industrial site neighborhood relative to an increased risk of lung, urinary tract, and lymphohematopoietic malignancies. During these years, some authors reported significant associations between lung cancer risk and residential proximity to (a) smelters, (b) complex industrial areas, and (c) other localized emission sources. There was some evidence that leukemia and lymphomas occurred in the neighborhoods that contained industrial sites.

Ecological studies of cancer incidence in an area interested by dumping waste sites in Campania (Italy)

Cancer incidence was investigated in an area which has been affected by the illegal practices of dumping hazardous waste and setting fire to mismanaged waste. For the 35 municipalities of this area that are served by a Cancer Registry, municipal standardized incidence ratios (SIR) and hierarchical Bayesian estimators (BIR) were computed. Moreover, municipal spatial clustering and a Poisson regression by municipality index of waste-related exposure were performed for 10 cancer types. Increased municipality SIRs were found for some cancer types. The BIRs confirmed the increases for liver cancer in two municipalities. Statistically significant clusters were detected for liver, lung, leukaemia and soft tissue sarcomas. In the regression analysis, testis cancer showed significant trend with the index of waste-related exposure (RR = 1.18).

Comparative influence of calcium blocker and purinergic drugs on epileptiform bursting in rat hippocampal slices

Caffeine (50 microM) increases the amplitude of the basal field potential (BFP) due to orthodromic stimulation of CA1 pyramidal neurons in rat hippocampal slices. This effect is absent if (1) the adenosine agonist L-phenyl-isopropyladenosine (L-PIA) (0.5 microM) is added to the perfusion with caffeine, and (2) low calcium (0.1 mM)-high magnesium (5mM) solutions are used. The calcium blocker verapamil (0.05-0.2 mM) does not modify the caffeine-induced effects. Higher concentrations of caffeine (0.2-0.5 mM) elicit the appearance of an epileptiform bursting, whose duration is inhibited at almost the 50% by 0.5 microM of L-PIA and unaffected by verapamil (0.2 mM) and nifedipine (0.05-0.10 mM). 5 microM of L-PIA, low calcium (0.1 mM)-high magnesium (5 mM) solution and verapamil (0.2 mM) are able to inhibit at almost the 50% the epileptiform bursting duration due to the potassium blocker 4-aminopyridine (4-AP). Nifedipine (0.05-0.1 mM) does not affect the 4-AP effects. L-PIA (0.5-2 microM) but not verapamil (0.2 mM) and nifedipine (0.1 mM) inhibits at almost the 50% the penicillin (1 mM) epileptiform bursting duration. The data indicate a different antagonistic influence of purinergic drugs and verapamil, on different models of epilepsy in rat hippocampal slices. In addition, the lack of antagonism between purinergic drugs and verapamil suggests different sites of action of the drugs.

Behavioural and electroencephalographic effects of excitatory amino acid antagonists and sigma opiate/phencyclidine-like compounds in rats

The present work was a comparative study of the electrocortical and behavioural effects of phencyclidine-like drugs and sigma-opiate drugs and of some excitatory amino acid antagonists. Phencyclidine-like drugs and sigma-opiate drugs elicited three dose-dependent electrocortical patterns: 1. Increase of periods of cortical desynchronization 2. Increase of the amplitude of fast (20-30 Hz) cortical waves; 3. Appearance of typical cortical complexes consisting of slow-wave (0.5-2 Hz) sharp-wave complexes. These effects were accompanied by excitatory motor symptoms, such as stereotyped movements of the neck and limbs. The NMDA competitive antagonist D,L-2-amino-5-phosphonovaleric acid (D,L-AP5), administered intracerebroventricularly (0.25-2 mumol), elicited phencyclidine-like stereotyped behaviour and cortical desynchronization, but failed to elicit/sigma typical cortical complexes. The non-selective amino acid antagonist cis-2,3 piperidine dicarboxilic acid (cis 2,3-PDA), administered intraperitoneally (3.3 mmol) failed to elicit both stereotyped behaviour and typical phencyclidine/sigma cortical complexes. The results strongly suggest the hypothesis that a reduction of excitatory amino acid neurotransmission, utilizing N-methyl-d-aspartate (NMDA)-preferring receptors, may be involved in the genesis of phencyclidine/sigma-induced stereotyped behaviour.

Influence of nimodipine and diltiazem, alone and in combination, on phencyclidine-induced effects in rats: an EEG and behavioural study

The influence of nimodipine and/or diltiazem on the EEG and behavioural effects induced by phencyclidine (PCP) was assessed in adult male Wistar rats. Nimodipine (2 and 10 mg/kg i.p.) and diltiazem (25-100 mg/kg i.p.) significantly potentiated both EEG (increase in background activity voltage, incidence of clustered slow waves) and behavioural (ataxia mean intensity) effects of PCP (5 mg/kg i.p.). A synergistic effect between low, ineffective doses of both nimodipine (0.5 mg/kg i.p.) and diltiazem (5 and 10 mg/kg i.p.) was also found. These data confirm the recent finding of a positive allosteric modulation existing between benzothiazepine (diltiazem) and dihydropyridine (nimodipine) binding sites. They also suggest that the modulation of calcium channels may play a pivotal role in the expression of PCP-induced effects.

Pharmacology of calcium-induced long-term potentiation in rat hippocampal slices

A transient increase (10 min) in extracellular calcium concentration (4 mM) causes a long-lasting (greater than 2 hr) enhancement of population spike responses evoked by radiatum fibers to CA1 pyramidal neurons in rat hippocampal slices. This phenomenon is similar to tetanic long-term potentiation (LTP), and is also related to memory processes. The influence of various drugs was investigated on calcium-induced LTP. The NMDA antagonist 2 amino-5-phosphonopentanoic acid (AP5; 100 microM) was able to prevent the calcium-induced LTP, while atropine sulphate (10 microM), propranolol hydrochloride (10 microM) and verapamil hydrochloride (100 microM) were ineffective. The results suggest an involvement of the NMDA receptor in the development of calcium-induced LTP.

Modulatory action of purinergic drugs on high potassium-induced epileptiform bursting in rat hippocampal slices

Increase of the potassium concentration up to 8 mM in the superfused solution of rat hippocampal slices leads to the development of an epileptiform bursting. The derivative agonist L-phenyl isopropyl adenosine (L-PIA) (0.05-0.5 microM) is able to block the potassium induced epileptiform activity. The adenosine antagonist caffeine (100 microM) reverts the antiepileptic effect of L-PIA. Our data show a modulatory action of the purinergic transmission in a model of experimental in vitro epilepsy, and point out about a control of endogenous adenosine in the development of focal epileptiform activity. The relationships between the purinergic influence on the release of neurotransmitters, and the convulsant-anticonvulsant effects of the drugs are discussed.

Incidence of breast, prostate, testicular, and thyroid cancer in italian contaminated sites with presence of substances with endocrine disrupting properties

The aim of the present study was to investigate the incidence of breast (females), prostate, testicular, and thyroid cancer in the Italian National Priority Contaminated Sites (NPCSs), served by cancer registries, where the presence of endocrine disruptors (EDs), reported to be linked to these tumours, was documented. Evidence of carcinogenicity of EDs present in NPCSs was assessed based on evaluation by international scientific institutions and committees. Standardized Incidence Ratios (SIRs) were computed for each NPCS and cancer site between 1996 and 2005. Excess incidence of one or more cancer site studied was found in twelve out of fourteen NPCSs. Significantly increased SIRs were found for breast cancer in eight NPCSs, for prostate cancer in six, for thyroid cancer (both gender) in four, and for testicular cancer in two. Non-significantly increased SIRs were found in five NPCSs for testicular cancer and in two for thyroid cancer (males). In a small number of instances a significant deficit was reported, mainly for thyroid and prostate cancer. Although increased incidence of one or more cancer sites studied were found in several NPCSs, the ecological study design and the multifactorial aetiology of the considered tumours do not permit concluding causal links with environmental contamination. Regarding the observation of some excesses in SIRs, continuing epidemiological surveillance is warranted.

Incidence of Soft Tissue Sarcomas in an Italian Area Affected by Illegal Waste Dumping Sites

The aim of the present study was to investigate the possible association between occurrence of soft tissue sarcomas (STS) and residence in an Italian area affected by illegal practices of dumping and setting fire to both hazardous and solid urban wastes. Standardized incidence ratios (SIRs) were computed separately for STS and some specific STS subtypes. The analysis was performed for the total population and for specific age groups, namely, children, adolescents, and adults. In adults, no significant increase in STS was found other than for gastrointestinal stromal tumors in males. A nonsignificant increase in incidence of STS was observed for male children and female adolescents. The results of the present study do not allow conclusions for a causal association. In the absence of previous epidemiological studies on this issue, further investigations are needed.

Spatial distribution of kidney disease in the contaminated site of Taranto (Italy)

BACKGROUND Exposure to heavy metals has been associated with kidney disease. We investigated the spatial distribution of kidney disease in the industrially contaminated site of Taranto. METHODS Cases were subjects with a first hospital discharge diagnosis of kidney disease. Cases affected by specific comorbidities were excluded. Standardized Hospitalization Ratios (SHRs) were computed for low/high exposure area and for modeled spatial distribution of cadmium and fine particulate matter. RESULT Using the high/low exposure approach, in subjects aged 20-59 years residing in the high exposure area a significant excess of hospitalization was observed in males and a non-significant excess in females. No excesses were observed in subjects aged 60 years and over. The analysis by the modeling approach did not show a significant association with the greatest pollution impact area. CONCLUSION Due to the excesses of hospitalization observed in the high/low exposure approach, a continuing epidemiological surveillance of residents and occupational groups is warranted.