Biomedical subjects

M L Scapellato

Publications and source records attributed to M L Scapellato.

12 recordsLinked to original sources

PubMed1993

Interactions between neuropathy target esterase and its inhibitors and the development of polyneuropathy.

This paper combines new and old data in order to offer a modified perspective of the mechanism of organophosphate-induced delayed polyneuropathy. Neuropathy target esterase (NTE) is though to be the molecular target and neuropathy to be initiated with a two-step mechanism: progressive inhibition of NTE and aging of the phosphorylated enzyme. When neuropathic organophosphates modify more than 70% of NTE in this way, neuropathy develops 2 weeks later. Other chemicals producing an inhibited NTE, which is incapable of aging, were thought to be not neuropathic. When given before a challenging dose of a neuropathic organophosphate they protect animals from neuropathy. However, recent evidence indicates that aging may not always be essential in causing neuropathy. In fact, mipafox and methamidophos as well as certain classic protective inhibitors such as carbamate and sulfonyl fluoride form an inhibited NTE which apparently does not age and yet produces neuropathy. We propose that all NTE inhibitors may have the potential to cause neuropathy. In analogy with pharmacological models of drug-receptor interactions, NTE inhibitors might have variable intrinsic activities to initiate neuropathy once attached to the protein. Strong neuropathic chemicals require about 70% inhibition of NTE, others 80-90%, and the least potent almost 100%. These differences have been amplified by means of promotion. Different levels of NTE inhibition as caused by different compounds were promoted by the same dose of phenylmethanesulfonyl fluoride to similar degrees of ataxia. Conversely nearly complete NTE inhibitions obtained in chicks with different chemicals were promoted to varying severities of ataxia. Protection from delayed polyneuropathy by the least neuropathic inhibitors can be explained by their weak intrinsic activity: occupying NTE, they prevent the binding of more neuropathic compounds. Methamidophos represents a particular example because it is protective at lower doses and neuropathic at high doses. Moreover, the levels of NTE inhibited by methamidophos which can be promoted to neuropathy are lower than those required for classic protective chemicals and higher than those of classic neuropathic OPs. This suggests that methamidophos has an intermediate position between the most and the least neuropathic NTE inhibitors.

Animals↗

PubMed1992

Phenylmethanesulfonyl fluoride elicits and intensifies the clinical expression of neuropathic insults.

It has been recently reported that phenylmethanesulfonyl fluoride (PMSF) when given to hens after a neuropathic organophosphate (OP) promotes organophosphate-induced delayed polyneuropathy (OPIDP). Chicks are resistant to OPIDP despite high inhibition/aging of neuropathy target esterase (NTE), the putative target of OPIDP initiation. However, when PMSF (300 mg/kg s.c.) is given to chicks after di-butyl 2,2-dichlorovinyl phosphate (DBDCVP, 1 or 5 mg/kg s.c.), OPIDP is promoted. Inhibition/aging of at least 30% of NTE was thought to be an essential prerequisite for promotion to be elicited in adult hens. However, we observed in hens that when NTE is maximally affected (greater than 90%) by phenyl N-methyl N-benzyl carbamate (40 mg/kg i.v.), a non-ageable inhibitor of NTE, and then PMSF is given (120 mg/kg/day s.c. x 3 days) clinical signs of neuropathy become evident. Methamidophos (50 mg/kg p.o. to hens), which produces in vivo a reactivatable form of inhibited NTE, was shown either to protect from or promote OPIDP caused by DBDCVP (0.45 mg/kg s.c.), depending on the sequence of dosing. Because very high doses of methamidophos cause OPIDP, we considered this effect to be a "self-promoted" OPIDP. We concluded that NTE inhibitors might have different intrinsic activities for producing OPIDP once NTE is affected. Aging might differentiate highly neuropathic OPs, like DBDCVP, from less neuropathic OPs, like methamidophos, or from the least neuropathic carbamates, which require promotion in order for neuropathy to be expressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1991

Chlorpyrifos-induced delayed polyneuropathy.

Chlorpyrifos [0,0-diethyl 0-(3,5,6-trichloro-pyridyl) phosphorothioate] caused delayed polyneuropathy in man. Contrary to previous studies, we report here that it also causes delayed polyneuropathy in the hen, the animal model for this toxicity. The minimal neuropathic dose was 60-90 mg/kg p.o., corresponding to 4-6 times the estimated LD50. Consequently, pralidoxime (2-PAM) in conjunction with atropine was necessary to reverse acetylcholinesterase (AChE) inhibition and cholinergic toxicity in hens given high enough doses of chlorpyrifos to cause neuropathy. Chlorpyrifos was slowly absorbed after single oral doses and the threshold of inhibition (greater than 70%) of neuropathy target esterase (NTE), the putative target for delayed neuropathy, was reached within 5-6 days. High AChE inhibition (greater than 90%), however, was measured within hours after dosing because of the higher potency of chlorpyrifos to inhibit this enzyme. In vitro studies showed that chlorpyrifos-oxon, the active metabolite of chlorpyrifos, was 10-20 times more active against AChE than against NTE, confirming the clinical observation. No differences were seen between human and hen enzymes in this respect. Hen and human brain homogenates contain A-esterases which hydrolysed chlorpyrifos to about the same extent in both species. In conclusion, chlorpyrifos causes delayed polyneuropathy in the hen, as was reported in man. The reasons for previous negative data in the hen are probably due to the relatively lower doses which were used. Judging from in vitro studies with hen and human enzymes, there are no differences in the two species as far as their relative sensitivity to delayed polyneuropathy. It is likely that delayed polyneuropathy would develop in both species only after severe cholinergic toxicity requiring aggressive antidotal treatment.

Animals↗

PubMedDate not supplied

[Diseases in hospital workers].

Occupational diseases and labour accidents in health care workers (Azienda Ospedaliera di Padova) were evaluated from 1990 to 2000; the information collected is compared with the same data of Regione Veneto and INAIL. 262 occupational diseases were found; nurses are more affected than other health care workers. In both reports (Azienda Ospedaliera di Padova and Osservatorio epidemiologico della Regione Veneto) half of the occupational diseases and injuries are represented by allergic disease. Low back pain is also equally represented in Azienda Ospedaliera and in Osservatorio epidemiologico results (5.3% and 6.6% respectively). Among the labour accidents reported to INAIL from 1994 to 2000, 25% of them were represented by falls and slips, 23% by car accidents, 17% were caused by tools, 17% by movement of goods and persons, 8% by contact with splinters, liquids, dusts, 5% by assaults and 5% by contact with blood or body fluid. The latter result is widely underestimated in the INAIL report, because these events usually produce a temporary inability of less than 3 days; in fact, they represent more than half of the labour accidents treated at the Azienda Ospedaliera di Padova. Medical surveillance (in exposure to aldehydes, anaesthetic gases, chemioterapic drugs) has shown many other occupational health problems that often need specific structural intervention (restructuration and restoration of workplaces in health care environments), and work organization changes.

Accidents, Occupational↗

PubMedDate not supplied

[Occupational exposure to electromagnetic fields in physiotherapy departments].

An assessment of the electromagnetic fields emitted from short and ultrashort wave diathermy sources and from magneto therapy operating at a frequency of 50 Hz was made to evaluate the occupational exposure to the operators. Operators were exposed to electromagnetic fields which rarely exceed the recommended limits of International Commission on Non-Ionizing Radiation Protection (ICNIRP) and American Conference of Governmental Industrial Hygienists (ACGIH). Only a measurement of electromagnetic fields near short wave diathermy equipment operating at a frequency of 27.12 MHz exposed operators to levels above those recommended by ICNIRP at a distance of 1 metre. Magnetic fields of magneto therapy exceeded residential exposition of 1 microtesla, at a distance of 4 metres.

Diathermy↗

PubMedDate not supplied

[Occupational exposure to anesthetic gases at several hospitals].

We considered data of samples collected in the period 1994-2001 in 83 operating rooms of 13 different public and private hospitals in Veneto Region. The anaestetic gases more used in operating rooms were nitrous oxide, isoflurane and, more recently, sevflurane. The mostly polluted positions were those in proximity of anaesthesiologic devices; the gases average concentrations were low in all hospitals examined, although some operating rooms demonstrated concentrations of anasthetic gases exceeding limit values. Lastly, the professional figures had different exposure to the various anaesthetic gases.

Air Pollution, Indoor↗

PubMedDate not supplied

[Pollution by nitrous dioxide during diagnostic laparoscopy interventions].

Here we have outlined the data relative to an environmental survey carried out in a laparoscopy clinic at the hospital of Padua, to determine the environmental concentration of nitrous dioxide (N2O) used for intra-abdominal inflation during diagnostic laparoscopy interventions. The data obtained have revealed cases of considerable N2O environmental pollution. This above all, due to spontaneous loss of gas during the intervention and to the lack of adequate ventilation systems.

Air Pollutants, Occupational↗

PubMedDate not supplied

[Devices for the reduction of N2O pollution during conscious sedation in dentistry].

We considered data of environmental monitoring during three working days in a dentist's office who habitually employs nitrous oxide (N2O): conscious sedation is used to alleviate anxiety and to diminish or eliminate dental pain. Three different nose masks were tested to determine influence on environmental pollution by N2O. The study shows that the levels of N2O always remains low with the use of proper dental procedures, although the chose of the type of nose mask can further diminish air pollution and the exposure of dental personnel.

Air Pollution, Indoor↗

PubMedDate not supplied

[New biomarkers of exposure].

In this paper we have defined the new biomarkers of exposure (NBE) as those biomarkers discovered in the last five years and, among previously validated biomarkers, also those applied in different ranges of doses or those determined in biological matrices which differ from matrices originally considered. We examined the results from the surveys carried out by the main Italian research units involved in biological monitoring, i.e. those from the Universities of Brescia, Milan, Naples, Padua, Parma, Pavia, Turin and Verona. The data were collected using a standardized model and included the following: type of element or organic compound, type of biomarker, analytical technique and method, their relationship with environmental monitoring data, their relationship with effect indicators or effects in general, improvement with respect to old biomarkers, reference values. Twenty two NBEs were identified: 14 elements and chemical compounds as such or as metabolites, 4 examples of mixtures, 3 of new matrices, one of speciation. Among the others, aspects such as interest in requiring NBE, quality assurance, availability, cost-benefit ratio were discussed. We conclude that development of this specific field of research appears to be a crucial point for future improvement in risk assessment and health surveillance procedures.

Animals↗

PubMedDate not supplied

[Tannin and gallic acid as marker of exposure to hardwood dust].

The total tannin concentration was determined, using two different SPF methods, in 35 dust powdered wood species, both hard and softwood. Using direct reading-method (280 nm) the concentration varied from 2485 mg/g for Swedish pine to 35,843 mg/g for European oak (quercus robur, hardwood). The data obtained with the second method (Folin-Chocalteau) were well correlated (y = 0.9885x + 4.3373; r = 0.84; n=35) with the data obtained with the first method. The measured concentrations are usually higher in hardwood than softwood tested. Finally, a simple HPLC-DAD method was tested for gallic acid (GA), recently proposed as a marker for oak dust.

Air Pollutants, Occupational↗

PubMedDate not supplied

[Validation of PM10 and PM2.5 personal samplers: comparison between PEM and CEN-ARPAV selectors].

In order to validate specific personal selectors for the collection of fine particles, 65 double measurements of PM10 and PM2.5 were carried out at the same collection site; thus allowing a comparison between two different methods of sampling. The first method was that normally used by ARPAV in order to sample the above-mentioned granulometric fractions in outdoor environment. The second method was chosen by us for personal sampling (PEM working at 2 l/min and at 4 l/min). In both cases the filters gravimetric analysis conformed to the expectations of D.M. 60 of 2/4/2002. The comparison between the two methods showed a good correlation in both the granulometric fractions: correlation coefficients r for the PM2.5 are equal to 0.96 and 0.99 for the PEM working at 2 l/min and at 4 l/min respectively; r for the PM10 are equal to 0.98 and 0.99 for the PEM working at 2 l/min and at 4 l/min respectively. The analysis of results in terms of fine particles concentration and difference between methods against their mean, shows a slight overestimate of the particles concentration with PEM working at 2 l/min, compared to those working at 4 l/min. Nevertheless, considering the good results obtained even with a flow of 2 l/min, we believe that using PEM working at 2 l/min to monitoring 24 hours-personal exposure assures an improved capacity in the battery-operated pumps.

Air Pollutants↗

PubMedDate not supplied

Neurobehavioral functions in operating theatre personnel: a multicenter study.

The study was conducted to evaluate neuropsychological symptoms, subjective stress and response speed functions in subjects occupationally exposed to low levels of anesthetic gases. A group of 112 operating theatre personnel exposed to anesthetic gases (nitrous oxide and isoflurane), and 135 non exposed hospital workers from 10 hospitals in Northern Italy were examined before and after the shift on the first and the last day of the working week. Three different tasks were administered: a complex reaction time test (the Stroop Color Word); a questionnaire for neuropsychological symptoms (EURO-QUEST); the block design subtest (WAIS). Biological and atmospheric indicators of exposure were measured. In the exposed group, the geometric mean of urinary nitrous oxide at the end of the shift was 7.1 micrograms/l (95th percentile 12.4, range 1.5-43) on the first and 7.8 micrograms/l (95th percentile 21.5, range 1.0-73.3) on the last day of the working week. On the same days, end of shift urinary isoflurane was 0.7 microgram/l (95th percentile 2.6, range 0-4.7) on the first day and 0.8 microgram/l (95th percentile 2.0, range 0-5.6) on the last. The exposed and control subjects were comparable for both basic intellectual abilities and subjective stress levels. No statistical differences were observed between exposed and control subjects for neuropsychological tests and symptoms. No dose-effect relationships were observed between the exposure indicators and the test results. In conclusion, no early behavioral effect on the central nervous system was detectable at the exposure levels measured. The biological exposure limits of 13 micrograms/l for nitrous oxide and 1.8 micrograms/l for isoflurane corresponding respectively to the atmospheric concentrations of 25 ppm and 0.5 ppm seem to be adequately protective for the integrity of workers' neurobehavioral functions, as measured with the tests used.

Adolescent↗