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Biomedical subjects

M Guidotti

Publications and source records attributed to M Guidotti.

At least 19 recordsLinked to original sources

Acute encephalopathies.

In daily hospital activity a frequent observation is that of patients in conditions of acute global suffering of the central nervous system due to a primary cause or symptomatic of other diseases. This condition shows an alteration of the state of consciousness, which involves three possible semeiologic manifestations: delirium (acute confusional state), acute confusional state associated with psychomotor underactivity and coma. The possible causes of an acute encephalopathy (AE) are: metabolic, iatrogenic and toxic, infective, primary neurologic, surgery-related and others. Diagnostic-therapeutic routes to be followed by emergency room doctors and neurologists dealing with AE are defined.

Acute Disease↗

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↗

A case of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT). Discussion of clinical features and differential diagnosis.

Chronic short-lasting headaches, in which trigeminal autonomic cephalalgias (TACs) are included, are relatively rare syndromes and not always well recognised. We present a case highly suggestive of short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) and we try to affirm essential points to distinguish the diagnosis from other TACs and chronic short-lasting headaches. We conclude that the qualifying points for differential diagnosis are number and duration of attacks in a day, presence of autonomic features and lack of indomethacin effect.

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↗

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↗

Determination of organic micropollutants in rain water for laboratory screening of air quality in urban environment.

Rain water may collect organic air pollutants, such as polycyclic aromatic hydrocarbons (PAHs), phthalate ester (PEs), pesticides, and polychrorinated biphenyls (PCBs), that could be present in air in consequence of different factors. The determination of these compounds in rain water samples consequently may be interesting for a first screening of air quality in urban and/or industrial areas. For this purpose, 3 areas of the city of Rieti (central Italy) were selected for rain water sampling: a) the city center, densely populated and with high road traffic; b) a suburban residential area; c) the industrial area, about 3 km out of the city center and along the state road. Wet-only precipitation collectors were used for sampling; solid-phase microextraction or liquid-liquid microextraction techniques followed by GC/MS determinations were applied for sample analysis. PCBs and pesticides were never found in the samples collected. On the contrary, some polycyclic aromatic hydrocarbons and phthalates were always found. Significant and seasonal differences in PAH levels were observed in the 3 different sampling areas, with higher values always found in the city center and during the winter period; on the contrary, PEs levels remained unchanged.

Air Pollutants↗

D2AM, a beamline with a high-intensity point-focusing fixed-exit monochromator for multiwavelength anomalous diffraction experiments.

D2AM is a french CRG beamline installed at the ESRF (European Synchrotron Radiation Facility) in Grenoble, with half of the time dedicated to biological macromolecule crystallography and half to materials science studies (diffraction, wide-angle and small-angle scattering). It is constructed at the front-end BM02 of the ESRF storage ring, using the X-ray beam from a 0.8 T bending magnet. D2AM entered into routine operation at the end of 1994, and is used either for single-wavelength or for multiwavelength anomalous diffraction studies. The beam is monochromated by an Si[111] two-crystal monochromator with a resolution of about 2 x 10(-4). The first crystal is water cooled. The X-ray photon energy covers the range between 6.5 keV (lambda approximately 1.9 A) and 17 keV (lambda approximately 0.7 A), a domain of energy with many K or L absorption edges of heavy atoms of interest for biological macromolecules studies and in materials science. The X-ray beam is focused in the vertical plane by two long curved mirrors and in the horizontal plane by the second crystal of the monochromator which is given an adjustable sagittal curvature. A spot size of 0.3 x 0.1 mm (FWHM) is measured at the sample position. Both mirrors are cut out of a 6"-diameter 1.1 m-long Si single crystal, polished and coated with a 400 A Pt thin film. The rugosity is better than 4 A r.m.s. and the longitudinal slope error is better than 5 x 10(-6) rad r.m.s. The first mirror is water cooled, the second is not. The beam intensity on the sample is about 10(11) photon s(-1) on a 0.3 x 0.3 mm focus area at 100 mA in the storage ring of the ESRF. The harmonic rejection ratio obtained with the two mirrors is better than 10(-5) for lambda/3. The combined optical system, mirror/monochromating-crystals/mirror, used on D2AM constitutes altogether a high-intensity point-focusing fixed-exit monochromator, which has the additional property that the energy resolution is not dependent on the beam divergence in use. Its stability and resolution are perfectly adapted to multiwavelength anomalous diffraction studies. The alignment of the mirrors and the monochromator is fully automated, taking 5 min, with the exception of the adjustment of the sagittal focusing. During multiwavelength diffraction experiments the wavelength is changed by a fast single monochromator rotation. Neither realignment of the mirrors nor readjustment of the beam focusing are necessary. The stability and reproducibility of the selected X-ray photon energy is better than 0.5 eV.

Journal Article↗

Inter-laboratory validation of solid-phase microextraction for the determination of triazine herbicides and their degradation products at ng/l level in water samples.

The accuracy and precision of solid-phase microextraction (SPME) were validated in an inter-laboratory study including ten laboratories for the analysis of triazine herbicides and their metabolites at ng/l level in aqueous samples. The SPME conditions were optimised in order to obtain maximum sensitivity. Especially, salt addition and choice of the SPME fibre coated with Carbowax-divinylbenzene increased the sensitivity. The average detection limits were in the range from 4 to 24 ng/l for the triazine herbicides, and 20 and 40 ng/l for desisopropylatrazine and desethylatrazine, respectively. The average r2 values of the calibration curves were above 0.99 for all of the analytes. The statistical data treatment was performed in accordance with the International Standardisation Organisation (ISO) standard 5725. Relative repeatability standard deviations between 6 and 14% and relative reproducibility standard deviations between 10 and 17% were found. The determined concentrations of the reference sample compared well to the "true" values, thus proving the good accuracy of the method. It is concluded that SPME is a reliable technique for the quantitative analysis of water samples containing triazine herbicides in concentrations around the European limit of 100 ng/l for individual pesticides in drinking water.

Calibration↗

Determination of pesticide residues in wine by SPME and GC/MS for consumer risk assessment.

An analytical procedure applying solid phase microextraction (SPME) combined with gas chromatography/ mass spectrometry (GC/MS) for the detection of pesticide residues in wine was performed for the determination of 14 of the pesticides most frequently used on grapes (insecticides, fungicides, herbicides). As SPME combines the possibility of a single-step extraction with other advantages (short sampling times, solvent-free procedure, speedy extraction, low cost and simplicity) it could be successfully used either for screening or routine analysis for detecting pesticides of different chemical classes in wines, even at trace levels. The analytical procedure performed showed minimum detectable quantities ranging from 0.10 microgram/l to 6.0 micrograms/l and precision from 9.7% to 18% (as relative standard deviation of 1 microgram/l levels), assuring high sensitivity and precision of analysis. Twenty-one wine samples (10 white wines and 11 red wines) available on the Italian market were analysed with the procedure described and about 57% were positive for one or more pesticides. An approach for consumer risk assessment on the basis of the data obtained was proposed for further assessments of the daily dietary intake of pesticides through wine.

Calibration↗

Determination of the binding of a beta 2-blocker drug, frusemide and ceftriaxone to serum proteins by capillary zone electrophoresis.

A modified Hummel-Dreyer method was used to study the binding of drugs with serum proteins by high performance capillary electrophoresis. The study was carried out to check the possible interaction between serum proteins and a highly selective beta 2-blocker, ICI 118551 (ICI). To prove the suitability of the method the protein binding of frusemide and ceftriaxone, drugs previously investigated, was also studied. The analyses were carried out by injecting a solution of s alpha(1)-acidic glycoprotein (alpha(1)-AGP) or human serum albumin in 70 mM NaH2PO4/Na2HPO4(pH 7.4) buffer into an uncoated fused silica capillary filled with the same buffer. In the capillary, maintained at a working temperature of 35 degrees C, a known amount of the ICI, frusemide or ceftriaxone was added. The method allows the bound drug to be determined directly.

Adrenergic beta-2 Receptor Antagonists↗

Long-term lowering of blood pressure after carotid and vertebrobasilar ischemic stroke.

We followed up 107 patients experiencing a first-ever ischemic stroke after having been affected by essential hypertension for at least one year, in order to analyze the phenomenon of post-stroke blood pressure lowering. Of the 82 patients still surviving after three months of follow-up, 44 (54%) had normal arterial blood pressure values. There were no significant differences between these normotensive patients and the 38 with high blood pressure in terms of cerebrovascular risk factors or disability, but blood pressure normalized in 34 of the 54 patients experiencing a carotid stroke (63%) and in only 10 of the 28 experiencing vertebrobasilar stroke (36%) (p = 0.035). These data may offer a starting point for further studies of the neurogenesis of arterial hypertension.

Adult↗

Progress in the development of oxytocin antagonists for use in preterm labor.

From a targeted screening effort and medicinal chemistry program, L-368,899 was selected as the first orally-active oxytocin (OT) antagonist to enter clinical trials. In animal studies, L-368,899 was shown to be a potent and selective OT antagonist and was orally bioavailable in rats, dogs and chimpanzees. L-368,899 was further shown to be a potent OT antagonist in pregnant rhesus and to inhibit spontaneous nocturnal uterine contractions. In Phase I human studies, L-368,899 was generally well-tolerated given intravenously and showed significant plasma levels after oral administration. In addition, L-368,899 blocked OT-stimulated uterine activity in postpartum women with a potency similar to that in the pregnant rhesus monkey. More recently, another structural series has been pursued, represented by L-371,257 [1-(1-(4-(N-acetyl-4-piperidinyloxy)-2-methoxybenzoyl)pip eridin-4-yl)- 1,2-dihydro-4(H)-3,1-benzoxazin-2-one]. L-371,257 exhibits high affinity (Ki, 4.6 nM) for human uterine OT receptors with high selectivity vs. human vasopressin receptors. In rat tissues in vitro, L-371,257 is a potent and competitive OT antagonist (pA2, 8.4) and, in vivo, blocks OT-stimulated uterine activity given both i.v. and intraduodenally. L-371,257 highlights the promise of this novel structural class.

Animals↗

Pathogenetic and prognostic features of lacunar transient ischaemic attack syndromes.

Lacunar ischaemic stroke syndromes are a well defined subgroup of ischaemic strokes. To determine whether a similar subgroup can be identified among patients with transient ischaemic attacks (TIAs) we studied prospectively 102 consecutive patients within 24 hours of their first TIA. Based on their history they were classified as lacunar TIA syndromes (LTIAS; n = 45) if isolated motor or sensory symptoms or their combination had involved at least two of three body parts (face, arm, leg), whereas all other subjects were grouped as non-lacunar TIA syndromes (NLTIAS; n = 57). All patients were investigated according to a standardised protocol and followed up for an average of 51.1 months. Cardiac and arterial sources of thromboembolism were more frequent among NLTIAS (p = 0.0001). Survival curve analysis demonstrated that LTIAS had a significantly lower long term mortality and incidence of major vascular events. In a multivariate regression analysis, the type of TIA (that is, NLTIAS) was an independent predictor of stroke or death. LTIAS share the same distinct pathogenetic and prognostic features of lacunar ischaemic stroke syndromes. These findings have implications for management of TIAs and for studies of their natural history and treatment.

Adult↗

Silent cerebral ischemia in patients with chronic atrial fibrillation--a case-control study.

The cerebral CT-scan results of 72 patients with chronic atrial fibrillation (AF) were compared to those of an age- and sex-matched control group, affected by muscle-tensive headache. None of the patients in the study had any neurologic symptoms. All were normal on neurologic examination. Mean age was 68 years in both groups. Patients with atrial fibrillation had a higher prevalence of hypertension, diabetes and hyperlipidemia, although the differences were not significant. Thirty-two patients (44.4%) with AF showed hypodense lesions on cerebral CT-scan, suggestive of small infarcts, whereas this finding was present only in eight control subjects (11.1%) (p less than 0.05). These results confirm in part the observations reported in literature and suggest a more thorough examination of the problem regarding the prophylaxis of thrombo-embolic risk in patients affected by chronic AF.

Aged↗

Reassessment of the role of splenic leukocyte oxidative activity and macrophage activation in expression of immunity to malaria.

The role of splenic leukocyte oxidative activity and macrophage activation in the development of protective immunity was examined during acute Plasmodium chabaudi adami malaria. Splenic leukocyte oxidative activity was compared in infected BALB/c and P/J mice; the latter are known to suffer from defects in macrophage function. Phorbol myristate acetate-stimulated chemiluminescence and superoxide anion production by splenic leukocytes from infected BALB/c mice were found to be increased dramatically, while the response of splenic leukocytes from infected P/J mice was elevated only minimally. Hydrogen peroxide release was slightly increased in splenic leukocytes from infected BALB/c mice but remained essentially unchanged in those from infected P/J mice. Macrophage function was assessed on the basis of measurements of tumoricidal activity. Splenic macrophages from uninfected BALB/c mice displayed significant tumoricidal activity against L929 target cells. As a result of splenomegaly during infection, tumoricidal activity, when calculated on a per-spleen basis, was increased further in infected BALB/c mice. In contrast, the tumoricidal activity of splenic macrophages from P/J mice was minimal, regardless of infection. Despite these differences, both strains of mice developed malarial infections that resolved within 16 days. Thus, while the production of reactive oxygen radicals by splenic leukocytes and the phenomenon of macrophage activation have traditionally been associated with the resolution of malarial infection, this study failed to establish a correlation between these parameters and the development of protective immunity to blood-stage infection with P. chabaudi adami.

Animals↗

A case-control study of transient global amnesia.

To evaluate risk factors and prognosis of transient global amnesia (TGA), three groups of 30 subjects each affected respectively by: (1) first-ever TGA; (2) first-ever transient ischaemic attack (TIA); (3) depressive neurosis, were compared. Prevalence of cerebrovascular risk factors was similar in patients with TGA and TIA, but significantly lower in the third group. CT showed more hypodense lesions in TIA patients than in those with TGA. In a mean follow-up of 36 months, five TGA patients experienced a TIA and three others had recurrence of TGA, but none suffered stroke or myocardial infarction. In the TIA group, four had recurrence of TIA, two suffered a stroke and two others a myocardial infarction, whereas none had TGA attacks. None of the patients of the third group had any ischaemic event during follow-up. The similar prevalence of risk factors, but the different prognosis between TGA and TIA patients, suggest that TGA is an ischaemic event, probably not triggered by thromboembolism but by a different, possibly vasospastic, mechanism.

Adult↗