Degradation and leaching of the herbicides metolachlor and diuron: a case study in an area of Northern Italy.

In this work the degradation of the herbicides metolachlor, diuron, monuron and of the metabolites 2-ethyl-6-methylaniline (EMA), and 3,4-dichloroaniline (DCA) was assessed in laboratory experiments on microbiologically active and sterilized soils. Their leaching potentials were calculated, using Gustafson's equation, by determining their mobility (as Koc) and persistence (expressed as DT50). Lysimeter experiments were also conducted to assess the actual leaching of the studied herbicides in a cereal crop tillage area vulnerable to groundwater contamination. The data obtained from the field were compared to the laboratory results. Moreover, some compounds of particular concern were searched for in the groundwater located near the experimental area in order to evaluate actual contamination and to test the reliability of the leaching potential. The GUS index, computed on data from microbiologically active soil, shows monuron as a leacher compound, EMA and DCA as non-leachers, metolachlor and diuron as transient ones. The presence of metolachlor in the groundwater monitored, even at concentrations up to 0.1 mug/l, confirms the possibility that transient compounds can be leached if microbial activity has not completely occurred in active surface soil.

Bezafibrate induces a mitochondrial derangement in human cell lines: a PPAR-independent mechanism for a peroxisome proliferator.

Bezafibrate is a hypolipidemic drug that belongs to the group of peroxisome proliferators because it binds to peroxisome proliferator-activated receptors type alpha (PPARs). Peroxisome proliferators produce a myriad of extraperoxisomal effects, which are not necessarily dependent on their interaction with PPARs. An investigation on the peculiar activities of bezafibrate could clarify some of the molecular events and the relationship with the biochemical and pharmacological properties of this class of compounds. In this view, the human acute promyelocytic leukemia HL-60 cell line and human rabdomiosarcoma TE-671 cell line were cultured in media containing bezafibrate and a number of observations such as spectrophotometric analysis of mitochondrial respiratory chain enzymes, NMR metabolite determinations, phosphofructokinase enzymatic analysis, and differentiation assays were carried on. Bezafibrate induced a derangement of NADH cytochrome c reductase activity accompanied by metabolic alterations, mainly a shift to anaerobic glycolysis and an increase of fatty acid oxidation, as shown by NMR analysis of culture supernatants where acetate, lactate, and alanine levels increased. On the whole, the present results suggest a biochemical profile and a therapeutic role of this class of PPARs ligands more complex than those previously proposed.

Assessment of leaching potential of aldicarb and its metabolites using laboratory studies.

The metabolites of pesticides can contaminate groundwater and pose a risk to human health when this water is used for drinking. This paper reports the results of a laboratory study on aldicarb and its main metabolites, aldicarb sulfone and aldicarb sulfoxide. Aldicarb and its metabolites showed Koc values (6-31) which were lower than that of atrazine (55), indicating that they are very mobile in soil. They are less persistent than atrazine (DT50 = 25 days), with DT50 values from less than 1 day and up to 12 days. Aldicarb behaved as a non-leacher, whereas its metabolites clearly showed the characteristics of leachers. Aged residue leaching experiments showed that aldicarb can occur at high concentrations in the leachate, together with its two metabolites. The leachate composition depends on the incubation time of the parent compound. Aldicarb and its metabolites can form various mixtures in groundwater on the basis of the time elapsing between the application of the insecticide and the first significant rainfall. This study confirms the characteristics of contaminants of aldicarb and especially its metabolites, as reported in the literature.

Leaching properties of some degradation products of alachlor and metolachlor.

Once in soil, pesticides undergo degradation processes that give rise to a complex pattern of metabolites. Those presenting a significant percentage of formation, genotoxic and leaching properties may pose a threat to human health associated with the consumption of drinking water. The aim of this study is to assess the hazard potential of some metabolites that may occur in ground water. 2,6-diethylaniline, 2-chloro-2',6'-diethylacetanilide, 2-hydroxy-2',6'-diethylacetanilide, metabolites of alachlor and 2-ethyl-6-methylaniline, metabolite of metolachlor, were chosen for their genotoxic properties. Under laboratory conditions, these metabolites showed DT50 = 1-5 days and Koc = 45-357. Their leaching potential, calculated according to Gustafson, is very low and, therefore, they should not be regarded as contaminants of ground waters. Aged residue leaching studies as well as preliminary studies on well waters seem to confirm these findings.

Bezafibrate as differentiating factor of human myeloid leukemia cells.

Bezafibrate belongs to the class of fibric acid derivatives usually used as antihyperlipidemia agents. From the biochemical point of view, these drugs show intriguing properties which leads one to think they may promote a differentiation process in tumour cells. This new pharmacological activity of fibrates could partially depend on the induction of an oxidative stress. To test this hypothesis, the effect of bezafibrate, as well as of clofibric acid and gemfibrozil, on growth, functional and cytochemical characteristics of human leukaemia-derived cell lines HL-60, U-937 and K-562 has been studied in some details. The results show that bezafibrate, gemfibrozil and clofibric acid, do induce differentiation in human myeloid leukaemia cell lines as indicated by several differentiation markers. Moreover fibrates, in dose dependent manner, significantly alter the cell cycle distributions, mainly leading to G0/G1 phase increment and G2/M phase reduction. The differentiating activity of fibrates could have significant implications both for the pharmacotoxicological profile of this class of compounds and for the pathophysiology of neoplastic disease.

Impaired reactive oxygen metabolism of phagocytic leukocytes in NIDDM patients. A role for non-enzymatic glycosylation of collagen.

Non-enzymatic glycosylation (NEG) of collagen has been previously shown to significantly influence the reactive oxygen metabolism (ROM) of phagocytic cells in healthy subjects. Considering the role of NEG in the pathophysiology of diabetes, we have further analysed the oxidative metabolism of polymorphonuclear cells (PMNs) and monocytes in 23 patients with non-insulin dependent diabetes mellitus in order to better elucidate a possible pathogenic role of NEG of the extracellular matrix in long-term complications of diabetes. Experiments were performed in triplicate on native-collagen and glycated-collagen coated vials, using a chemiluminescence (CL) assay. Results show that PMNs from diabetic patients display a significant increased basal and zymosan-induced CL activity with respect to controls that are not related to the glycation state of the substrate. Conversely, the CL activity of monocytes induced by zymosan shows a decrease in diabetic patients with respect to healthy volunteers (p < 0.05). Moreover, monocyte CL was reduced by the glycated matrix, both in healthy volunteers and in diabetic subjects (p < 0.05 and p < 0.01, respectively). These data highlight a complex role of phagocytic leukocytes in the pathophysiology of extracellular matrix alterations secondary to NEG that are typically present in clinical conditions such as diabetes or ageing.

[Transient cerebral ischemia and the risk factors]. / Ischemia cerebrale transitoria e fattori di rischio.

A retrospective study was carried out in a general medicine ward of 100 male patients suffering from their first transient ischemic attack (TIA) in order to evaluate the incidence of different cerebrovascular risk factors. The results were then compared with those from another group of 100 patients suffering from initial cerebral ischemic softening (CIS) in order to identify a cerebrovascular risk population taking into account clinical similarities and common and divergent features. The study revealed that age is the prime risk factor in the genesis of TIA, followed by arterial hypertension and hypercholesterolemia. From a comparison with the group of patients affected by initial CIS it was clear that TIA is typical of senility and is more closer correlated to age than other risk factors; therefore, che TIA population is an expression of those who have "survived" cerebrovascular death due to the lesser exposure to risk factors.

Criteria for evaluating the impact of pesticides on groundwater quality.

A lot of data and information are available regarding the presence of pesticides in ground-waters or their tendency to contaminate them. Despite this, for a very large number of pesticides these data and information are almost completely lacking. Many theoretical methods have been proposed to predict the leaching potential of pesticides. Persistence (expressed by DT50) and mobility (expressed by Koc) are key parameters that seem to be particularly representative of the overall leaching potential of nonionic compounds and they are widely used in these methods. Nevertheless, these parameters may vary greatly causing sharp differences in ranking the leaching potential of pesticides. Indeed, when the GUS Index is calculated using the available published values of Koc and DT50 in combinations representing the minimum, medium and maximum leaching potential of herbicides, very different results can be obtained. Many of these compounds can be classified as contaminants or non contaminants, depending on the type of combination used.

Quality problems in waters used for drinking purposes in Italy.

With a grant from the Italian Ministry of the Environment, the National Institute of Health (Istituto Superiore di Sanità) promoted and coordinated some activities aimed at determining the extent and the intensity of contamination of waters used for human consumption by some chemical agents, and describing causes and modalities of contamination and human health implications. The chemical agents examined were herbicides, nitrates, trihalomethanes, asbestos, manganese and fluoride. In this paper a first nationwide picture of these problems is reported.

Modeling of biological and medical systems: a systemic strategy.

A strategy in the frame of General System Theory is proposed for the study of biological systems for medical purposes. Its definition and use requires in each experiment the collaboration between physician and system scientists and hence the definition of a common language, by which the real system under study is described. The strategy is based on three intermingled steps: first an ingenuous model is proposed, gathering all the medical knowledge about the studied system, organized within an informal frame derived from the state space approach. Next, a functional model is derived, enlightening the organization of the relations in the medical model. Finally, this organization is formalized by the most suitable algebraic tools, which are thereafter translated into APL programs. This last version is used for simulation, which is exploited not only as a tool to describe and make provisions on the dynamics of the models, but also to deepen and improve the knowledge about the observed system.

[Cerebral ischemic disease in women. Notes on a CT-documented case series]. / La malattia ischemica cerebrale nella donna. Considerazioni su casistica TAC documentata.

Risk factors in a group of 50 women affected by CT-documented stroke have been analysed. Arterial hypertension, hypercholesterolaemia and hyperglycaemia proved the most frequent.

[A case of lipoma of the small intestine]. / Su un caso di lipoma del piccolo intestino.

A case of small bowel lipoma with few evident symptoms is reported. Radiological diagnosis was confirmed at surgery. The comparative rarity of this type of benign intestinal neoformation is pointed out.

[Cerebral ischemic malacia. A retrospective study of CAT scan-documented cases]. / Il rammollimento ischemico cerebrale. Studio retrospettivo su casistica TAC documentata.

One hundred male patients affected by ischaemic stroke were studied with the use of CT scans. A clinical-biohumoral pattern was traced for every patient, with particular regard to the incidence of risk factors for stroke of which systolic arterial hypertension, appear to be the most frequent. It would be useful to extend this research to female patients as well in order to discover any significant differences between sexes.

[Clinical definition of asymptomatic abdominal masses]. / Definizione clinica di masse addominali asintomatiche.

Five patients with asymptomatic abdominal masses (abdominal leiomyosarcoma, giant hydronephrosis, renal cell carcinoma, squamous cell carcinoma of the lung metastatic to the adrenal gland, retroperitoneal non-Hodgkin's lymphoma) are reported. Non invasive investigations such as Echography and Computed Tomography, are very advantageous for the quick diagnosis of asymptomatic abdominal masses and for subsequent therapy.

[Asymptomatic electrocardiographic abnormalities during antiblastic chemotherapy]. / Anomalie elettrocardiografiche asintomatiche in corso di chemioterapia antiblastica.

In patients under antiblastic treatment electrocardiographic abnormalities without subjective symptomatology were observed. The genesis of these abnormalities is discussed in the light of wath is known from the literature. Periodical electrocardiographic control of patients treated with antiblastic drugs is highly recommended.

[Cardiac damage during radiotherapy of the mediastinum]. / Cardiolesività in corso di radioterapia sul mediastino.

Two cases of patients with neoplasias who were given radiotherapy on the mediastinum are reported. Serious and fully documented ECG alterations were observed in these patients, but the cause is not easy to ascertain, since the results were neither identical nor clinically attributable to a common pathogenetic factor.

[Evaluation of erythrocyte deformability in subjects with essential arterial hypertension]. / Valutazione della deformabilità eritrocitaria in soggetti con ipertensione arteriosa essenziale.

Red blood cell filtration rate was studied in patients with essential hypertension selected according to the homogeneity of parameters which could interfere with such a test. An increase of filtration time in control subjects was put in evidence both in patients without vascular complications and in patients with cerebrovascular diseases; no significant difference was seen between the two groups. The red cell filterability behavior can be correlated to hypertension and is an expression of red cell deformability alterations. The variation of this hemorheological parameter could be better defined by an improvement of the red cell filterability test and by further studies on the membrane function in essential hypertension.

[Hemorrhagic rectocolitis. Attempt at programmed therapy]. / Retto colite emorragica. Tentativo di terapia programmata.

Planned treatment of 30 cases of haemorrhagic colitis is reported. Its protocol included salazopyrine and benzodiazepine per os, salazopyrine and prednisone per rectum, and parenteral ACTH depot. Administration for 60 days brought good results in cases of slight or average severity. Recurrences, albeit less severe, were not prevented, however. Attention is drawn to the need to follow up this group of patients for a longer period. Even so, it is felt that the effect of this form of treatment is primarily symptomatic.