[Tetanus risk prophylaxis: experience at work]. / Rischio tetano: esperienza di profilassi in una realtà aziendale.

As widely known Italian legislation makes the injection against tetanus compulsory for some units of workers. This isn't often easily organized and accepted. The aim of our work is to bring forward our experience with a group of workers servicing in the airport where tests have been carried out to establish the correct antibody cover through periodic controls. Only 46 workers, out of the 294 tested, have shown immunity deficiency. The vaccination programme has therefore been focused only on this group, realising a considerable organization and economic saving and a better acceptance from the workers side. Programmes have been drawn up for a future vaccinal programme taking into consideration the antibody cover results.

[Interaction between occupational health service and National Health Service. Appeals against duty ability judgements]. / Interazione tra un Servizio di Medicina del Lavoro Aziendale e i Servizi di Medicina del Lavoro Pubblici. Ricorsi avverso il giudizio di idoneità alla mansione.

The main purpose of the medical surveillance, in conformity with the Italian D.L. 626/94, is the formulation of ability judgements. The above-mentioned D.L. 626/94 gives the workers the possibility to file a petition versus the judgement itself addressing it to the ASL concerned. The aim of the present work is to report experiences made with the occupational health service as for versus appeals. About 2000 examinations a year are carried out at our occupational health service and the concerned judgements are pronounced. 29 versus appeal have been forwarded between 2002 and half 2007. The ASL decision has been favourable to the "competent" doctor judgement in 21 cases, and adverse in 8. Most appeals concerned osteoarticular problems. Finally some remarks are made about the necessity of improving the cooperation between "competent" physicians and supervision national health services.

Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II suggested by cryogenic X-ray diffraction.

The three-dimensional structure of a possible intermediate in the hydration reaction of cyanamide to urea catalyzed by human carbonic anhydrase II (hCAII) has been determined by cryocrystallographic techniques. The crystal structure shows that two different adducts are formed under the experimental conditions and that they have different occupancy in the crystal. The high occupancy form consists of a binary hCAII-cyanamide complex where the substrate has replaced the zinc-bound hydroxide anion present in the native enzyme, maintaining the tetrahedral geometry around the metal ion. The second, low-occupancy form consists of a hCAII-cyanamide-water ternary complex where the catalytic zinc ion, still being bound to cyanamide, is approached by a water molecule in a five-coordinate adduct. While the first form can be considered a nonproductive complex, the second form may represent an intermediate state of the catalyzed reaction where the water molecule is about to perform a nucleophilic attack on the zinc-activated cyanamide substrate. The structural evidence is consistent with the kinetic data previously reported about this recently described hydrolytic reaction catalyzed by hCAII, and indicates that a different mechanism with respect to that generally accepted for the physiologic carbon dioxide hydration reaction may be adopted by the enzyme, depending on the substrate chemical properties.

Visualisation of extensive water ribbons and networks in a DNA minor-groove drug complex.

The crystal structure is reported of a complex between an ethyl derivative of the minor-groove drug furamidine and the dodecanucleotide duplex d(CGCGAATTCGCG)2, which has been refined to 1.85 A resolution and an R factor of 16.6% for data collected at -173 degreesC. An exceptionally large number (220) of water molecules have been located. The majority of these occur in the first coordination shell of solvation. There are extensive networks of connected waters, both in the major and minor grooves. In particular, there are 21 water molecules associated with the minor-groove drug, via hydrogen bonds from the four charged nitrogen atoms. One cluster of four waters is situated in the groove itself; the majority are on the outer edge of the groove, and serve to bridge between the outward-directed drug nitrogen atoms and backbone phosphate oxygen atoms. These bridges are both intra- and inter-strand, with the net effect that the outer edge of the drug molecule is covered by ribbons of water molecules.

Cytotoxic effects of gold(III) complexes on established human tumor cell lines sensitive and resistant to cisplatin.

Gold(III) complexes, isostructural and isoelectronic with platinum(II) complexes, are potentially attractive as anticancer agents. We have synthesized a group of square planar gold(III) complexes, all containing at least two gold-chloride bonds in cis-position, and tested their in vitro cytotoxicity on a panel of established human tumor cell lines. Remarkably, all these compounds showed significant cytotoxic effects. In particular, the complexes containing the salycilaldiminate ligand induced tumor cell growth inhibitory effects comparable to or even greater than cisplatin. All gold(III) complexes substantially retained their antitumor potency against two cisplatin-resistant tumor cell lines (CCRF-CEM/R leukemia and A2780/R ovarian carcinoma); only minimal cross-resistance with cisplatin was observed. When considering the mechanism of action, it is reasonable to assume that the cytotoxicity of these gold(III) complexes derives from DNA binding. Preliminary spectroscopic results are consistent with this hypothesis; indeed, circular dichroism experiments show that both the salycilaldiminate- and the pyridine-containing gold(III) complexes bind calf thymus DNA in vitro and alter reversibly its B-type solution conformation. These results, however, must be treated with caution; solution studies indicate that gold(III) compounds are poorly stable under physiological conditions, possibly implying that, when injected, only a small amount will reach, unchanged, the DNA target. The results of our investigations are discussed in the perspective of future work on the cytotoxic and antitumor properties of gold(III) compounds.

Biological properties of two gold(III) complexes: AuCl3(Hpm) and AuCl2(pm).

The reactivity in solution of two recently characterized gold(III) complexes, AuCl3(Hpm) and AuCl2(pm), has been investigated in view of their potential use as anti-cancer agents. In water, both compounds undergo relatively fast hydrolysis of the bound chlorides without loss of the heterocycle ligand; the process is much faster within a physiological buffer. When the two gold(III) complexes react with proteins like albumin or transferrin, reduction of gold(III) to gold(I) and/or hydrolysis is observed. On the other hand, both complexes bind rapidly and tightly to either polynucleotides or calf thymus DNA, with gold remaining in the +3 oxidation state. Circular dichroism investigations reveal a large perturbation of DNA conformation upon gold(III) binding; preferential binding to GC sequences is shown. Cytotoxicity studies on a number of tumor cell lines demonstrate a good activity of these gold(III) complexes compared to cisplatin. However, quick hydrolysis and/or reduction of these compounds under physiological conditions may represent a severe limitation to their use.