Two patients with history of STEC-HUS, posttransplant recurrence and complement gene mutations.

Hemolytic uremic syndrome (HUS) is a disease of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. About 90% of cases are secondary to infections by Escherichia coli strains producing Shiga-like toxins (STEC-HUS), while 10% are associated with mutations in genes encoding proteins of complement system (aHUS). We describe two patients with a clinical history of STEC-HUS, who developed end-stage renal disease (ESRD) soon after disease onset. They received a kidney transplant but lost the graft for HUS recurrence, a complication more commonly observed in aHUS. Before planning a second renal transplantation, the two patients underwent genetic screening for aHUS-associated mutations that revealed the presence of a heterozygous CFI mutation in patient #1 and a heterozygous MCP mutation in patient #2, and also in her mother who donated the kidney. This finding argues that the two cases originally diagnosed as STEC-HUS had indeed aHUS triggered by STEC infection on a genetic background of impaired complement regulation. Complement gene sequencing should be performed before kidney transplantation in patients who developed ESRD following STEC-HUS since they may be undiagnosed cases of aHUS, at risk of posttransplant recurrence. Furthermore, genetic analysis of donors is mandatory before living-related transplantation to exclude carriers of HUS-predisposing mutations.

[Reactive anxiety crisis: a unique case of work injury]. / Crisi d'ansia reattiva: un caso particolare di infortunio sul lavoro.

The present study aims to describe a unique case in view of the disease diagnosed, the conditions of onset and the management by INAIL (Italian National Institute of Insurance for Injuries at Work and Occupational Diseases). A worker, after a verbal, animated dispute with some collegues, had an acute psychiatric agitation attack and went to the nearest emergency room, where he was investigated. No neuropsychiatric alteration was diagnosed, but based on anamnestic data, the physicians diagnosed an anxiety crisis reactive to work environment. A medical certificate for injury at work was produced and sent to the Insurance Board (INAIL). The worker was off work for 105 days diagnosed with a persistent anxious depressive syndrome, secondary to the traumatic event. INAIL reassessed the case later and confirmed only the first 30 days as due to work accident, while the following period was judged as related to affectivity disturbance due to common disease, not to work environment. Our case opens new perspective for the occupational physician in the assessment of ASD as work injury and of PTSD as professional disease, suggesting to give more attention to psychiatric health of workers.

QSAR study for a novel series of ortho disubstituted phenoxy analogues of alpha1-adrenoceptor antagonist WB4101.

On the basis of the affinities at the alpha1a-, alpha1b- and alpha1d-adrenoceptors and the 5-HT1A receptor of a previous series of sixteen 2-[(2-phenoxyethyl)aminomethyl]-1,4-benzodioxanes ortho monosubstituted at the phenoxy moiety, a number of ortho disubstituted analogues were designed, synthesized in both the enantiomeric forms and tested in binding assays on the same receptors. The affinity values of the new compounds 1-11 were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known alpha1 antagonist WB4101, and of the ortho monosubstituted derivatives, suggesting some distinctive aspects of the interaction of the phenoxy moiety, in particular with the alpha1a-AR and the 5-HT1A receptor, of the monosubstituted and the disubstituted compounds. A classical quantitative structure-activity relationship (Hansch) analysis was applied to the whole set of the S enantiomers of the ortho mono- and disubstituted WB4101 analogues (26 compounds), finding a very good correlation for the alpha1a affinity. For this latter, a significant parabolic relationship was also found with the volume of the two ortho substituents. Diametrically opposite, the same relationships for the 5-HT1A exhibit low or insignificant correlation coefficients.

Respiratory syndrome very similar to extrinsic allergic alveolitis due to Penicillium verrucosum in workers in a cheese factory.

A respiratory syndrome very similar to extrinsic allergic alveolitis due to Penicillium verrucosum was recognized in 4 workers employed in a Gorgonzola cheese factory. A mycogen allergy to P. verrucosum, used as starter in the production, was demonstrated by positive sputum culture and detection of specific antibodies in the blood. Intense and prolonged exposure to inhalation of fungal spores could have lead to the development of this allergic response. The fact that 2 of the subjects are siblings seems to indicate host susceptibility or immunological constitution in the pathogenesis of the respiratory allergy.

Synthesis, free solution capillary electrophoresis separation and toxicity of seven potential impurities of dobutamine.

The seven O-methylated analogs of dobutamine [(+/-)-4-[2-[[3-(p-hydroxyphenyl)-1-methylpropyl]amino]ethyl]pyrocatechol, CAS 34368-04-2), a trihydroxy secondary amine, can be considered potential impurities of the latter, the ultimate step of the synthesis of dobutamine being the deprotection of the three phenolic groups. In order to enable the detection and the identification of such a contamination, the di- and the monomethylated derivatives of dobutamine were prepared and their mixture with dobutamine and its trimethoxy precursor completely resolved by Free Solution Capillary Electrophoresis (FSCE). Indeed, the above impurities proved to occur in dobutamine in consequence of improper demethylation conditions and to be significantly more toxic than the latter.

2-Hydroxymethyl-1,4-dioxane: synthesis, resolution and determination of the absolute configurations of the enantiomers.

2-Hydroxymethyl-1,4-dioxane 3 was resolved via salt formation between its hydrogen phthalate and (R)- or (S)-1-phenylethylamine, selective crystallization of the resultant diastereomeric mixtures and subsequent recovery of its enantiomers by saponification. The progress of the resolution was followed by chiral HPLC and the absolute stereochemistry of the two enantiomers determined by comparison of their specific rotations with that of (R)-3 synthesized from enantiomerically pure (R)-1-O-benzylglycerol. The results of the synthesis of 3 and of its resolution are discussed and compared with those previously obtained for 1,2-isopropylidene glycerol evaluating the consequences of replacement of ispropylidene with an ethylene bridge.

3,4 Dichloroaniline-haemoglobin adducts in humans: preliminary data on agricultural workers exposed to propanil.

Propanil is one of the major herbicides used on rice-paddies and is thought to produce adverse health effects through the action of its metabolite 3,4-dichloroaniline (3,4-DCA). T he feasibility of monitoring human exposure to propanil on the basis of 3,4-DCA adducts to haemoglobin (Hb) was investigated. We developed a method based on gas chromatography negative ion chemical ionization-mass spectrometry (NICI-GC-MS) to quantify 3,4-DCA released from human Hb after alkaline hydrolysis of the protein. 3,4-DCA-Hb adducts were identified in agricultural workers exposed to propanil and were detectable even 4 months after the last herbicide application. Urine samples collected at the same time had no measurable level of 3,4-DCA. 3,4-DCA-Hb adducts might be useful for monitoring human exposure to 3,4-DCA from agricultural sources.

[A case of occupational pulmonary siderosis: the pathogenetic and prognostic considerations]. / Un caso di siderosi polmonare professionale: considerazioni patogenetiche e prognostiche.

Pulmonary siderosis is a disease which can be considered with the pneumoconioses of the so-called inert dust (either by deposit or by accumulation) and, from the earliest nosographic descriptions dating back to the thirties and forties, it has been substantially considered a benign form because of the scarce sclerogenic evolution and the preservation of discrete respiratory function. We present a case of pulmonary siderosis characterized on one hand by the importance and clarity of the cytopathological picture and on the other by the presence of changes, although modest, in lung function which confirm the most recent hypotheses in the literature on the potential evolution of pneumosiderotic diseases and their relatively less benign prognosis. From a preventive point of view the case draws attention to the need for greater control of environmental hygiene conditions in small factories. From an insurance and medico-legal point of view siderosis has recently been explicitly added to the occupational diseases which can be declared to the Italian state department dealing with occupational disease and disability payments (I.N.A.I.L.) (DPR of the 13.04.1994, section 47).

[Burns risk caused by the interaction of NIR at radiofrequency and metal structures at a building site]. / Rischio da ustione dovuto ad interazione tra N.I.R. a radiofrequenza e strutture metalliche di un cantiere edile.

This study pointed out an induced electric field originated from two radio aerials and measured on two cranes being in an neighbour building site. On the basis of the results of the calculations effectuated, it has been showed that the values of the electric field were within the IRPA reference values; although these values, the metallic structures of the two cranes seemed to interfere with the electromagnetic field as well as to create some situations of risk for the workers of the building site. At last, for this reason were suggested some techniques of primary prevention.

Relationships between conformational behaviour and binding affinity towards beta 1 and beta 2 adrenoceptors of some chiral phenoxypropanolamines with bulky N-substituents.

The optical isomers of a series of phenoxypropanolamine compounds with N-substituents bulkier than isopropyl have been synthesized, and their binding affinity towards beta 1 and beta 2-adrenoceptors has been determined. A computational study, including a Molecular Dynamics (MD) simulation and quenching in water and a GRID analysis provided some useful suggestions for possible interpretation patterns for the different affinity exhibited by the compounds studied.

Molecular properties of the WB4101 enantiomers and of its chiral methyl derivatives for alpha 1-adrenoceptor recognition.

The optical isomers of the well known alpha 1-antagonist WB4101 and of its derivatives with a methyl group in the oxyethyl moiety were prepared for the evaluation of their alpha-adrenoceptors binding affinity. By means of a detailed computational analysis, the present work shows that the introduction of a methyl group affects the behaviour of WB4101 in different ways. A limitation of the conformational freedom in certain regions of the torsional subspace of the potential energy function, differences in the reactivity of the protonated species towards a model proton acceptor and the quality of the superposition with the rigid template for alpha 1 antagonists, corynanthine, are examined and discussed in order to select a candidate bioactive form and possible features which act as modulators of the recognition process at the alpha 1-adrenoceptors.

Agonistic activity and charge driven interaction potentiality of PAF derivatives.

Taking into account the contribution of the C2 substituent to the interaction ability of PAF derivatives, an investigation has been undertaken on: i) the role of the presence of two unitary charges of opposite sign in the molecule; ii) the role of the spacing of the same charged moieties. For this purpose, the theoretical analysis of model compounds for newly synthesized and already known compounds has been performed by means of computer-aided modelling, molecular mechanics and semiempirical quantum chemical computational methods. The combination of the results with the available pharmacological data allows a discussion about the stereoelectronic features required for agonist interaction at the PAF receptor.

Chiral PAF agonists: synthesis, theoretical analysis of their stereoelectronic properties and structure activity relationships.

A series of chiral PAF agonists were synthesized. Modifications at the PAF structure were undertaken as far as the C2 substituents and the onium head groups are concerned. In parallel, molecular modelling studies including a MOPAC geometry optimization and the analysis of the electrostatic potential were performed on the newly synthesized and on already known PAF agonists, in order to gain a better insight into the stereoelectronic features required for interaction with the PAF receptor.

[Evaluation of neuropsychological parameters in a group of metal mechanics occupationally exposed to radio frequencies]. / Valutazione di alcuni parametri neuropsicologici in un gruppo di lavoratori metalmeccanici professionalmente esposti a radiofrequenze.

In view of the increasing interest in electromagnetic fields, the effects on behaviour were studied in a group of foundry workers following prolonged exposure to radiofrequencies. The results of behavioural tests revealed significant differences between the exposed and control groups as regards neuropsychological performance. Anxiety and depression tests, however, indicated no pathological alterations, in contrast to previous observations. Nevertheless, the results need to be confirmed by further, more detailed studies.

Cardiovascular and pulmonary activity of platelet-activating factor (PAF-acether) and its derivatives.

Stereoselective synthesis and biological properties of PAF-acether, its enantiomer and some analogues of both are reported. The results clearly indicate that the ONIUM SIZE and SHAPE of the various compounds tested are important in determining guinea-pig bronchoconstriction and human platelet aggregation.