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In northern Calabria (Italy), the metasedimentary succession of the Lungro–Verbicaro tectonic unit preserves mineral assemblages suggesting underthrusting to depths in excess of 40 km. Internal deformation of these rocks occurred continuously during the following decompression. Index mineral composition associated with progressively younger tectonic fabrics indicates that a substantial part of the structural evolution took place within the blueschist-facies P–T field. Despite their tectonic and metamorphic history, the rocks of the Lungro–Verbicaro Unit preserve significant sedimentary and palaeontological features allowing correlations with successions included in adjacent thrust sheets and the reconstruction of the Mesozoic continental margin architecture. The subduction–exhumation cycle recorded by the Lungro–Verbicaro Unit is entirely of Miocene age. This portion of the Apulia continental palaeomargin was involved in convergence-related deformation not earlier than the Aquitanian. The integration of our results with available constraints on the tectonic evolution of the Apennine–Calabrian Arc system suggests that subduction and most of the subsequent exhumation of the Lungro–Verbicaro Unit occurred, up to Langhian time, at maximum vertical rates in excess of 15 mm a−1. The exhumation process was then completed, at much slower rates (−1) in Late Miocene time, as indicated by both apatite fission-track data and stratigraphic information.

A new structural–stratigraphic synthesis of the Apennine units of northern Calabria is presented. The Meso-Cenozoic successions are grouped into two tectonic units, named Pollino–Ciagola Unit (PCU) and Lungro–Verbicaro Unit (LVU), comprising terrains formerly attributed to five different tectonic units. Fe Mg carpholite and blue amphibole record HP–LT metamorphism in the LVU, followed by progressive decompression leading to final greenschist facies re-equilibration during dominantly extensional deformation. Final tectonic emplacement of the LVU over the PCU post-dated the metamorphism of the LVU and was accompanied by intense ductile deformation along zones of strain localisation in footwall rocks. All of the units were later affected by folding and minor thrusting during subsequent Apennine tectonics. To cite this article: A. Iannace et al., C. R. Geoscience 337 (2005).

The Calabria–Peloritani Arc southern terrane is a stack of crystalline basement nappes, some of them provided with a widely outcropping Alpine sedimentary cover, sealed by clastics of the Stilo–Capo d’Orlando Formation (SCOF). New field observations in the Stilo area lead to define a Pignolo Formation as a sedimentary cycle predating the emplacement of the uppermost nappe (Stilo Unit) of the tectonic pile. It includes the well-known Lithothamnium and larger foraminifers bearing calcarenites, previously interpreted as a basal member of the SCOF. The biostratigraphic revision of both formations, together with recently published data about other preorogenic deposits, point to a stacking of the whole terrane between the Aquitanian and the middle–late Burdigalian. A comparison between the sedimentary cycles characterising the Calabria–Peloritani southern terrane during the Oligocene–Early Miocene and those almost coeval of the Betic–Rifian internal units highlights their quite similar evolution. Thus it is reliable that both the orogenic belts originated from contiguous paleogeographic realms. These considerations confirm that the present western Mediterranean Chains were originally segments of a continuous orogenic belt disrupted by the opening of the Balearic and Tyrrhenian basins.

Ground-based gamma-ray astronomy has had a major breakthrough with the impressive results obtained using systems of imaging atmospheric Cherenkov telescopes. Ground-based gamma-ray astronomy has a huge potential in astrophysics, particle physics and cosmology. CTA is an international initiative to build the next generation instrument, with a factor of 5-10 improvement in sensitivity in the 100 GeV-10 TeV range and the extension to energies well below 100 GeV and above 100 TeV. CTA will consist of two arrays (one in the north, one in the south) for full sky coverage and will be operated as open observatory. The design of CTA is based on currently available technology. This document reports on the status and presents the major design concepts of CTA. © 2011 The Author(s).

A stratigraphic revision of the Paludi Formation, cropping out in Northern Calabria on the north-eastern side of Sila Massif, has confirmed that it has been deposited between two main tectonic phases. Actually the formation is involved only by top to the north-east thrusts, different from those separating the crystalline and ophiolitic nappes of Northern Calabria, and rests unconformably on the Sila Unit, the uppermost nappe of the tectonic stack. In the frame of the interpretation of Northern Calabria as a fragment of the Alps, the Paludi Formation play the role of a deposit post-dating the eo-alpine tectonic phases and pre-dating the Apenninic orogenic transport. Therefore the Aquitanian age of the formation, obtained by nannofloras analyses, can be considered the minimum age to the Apulia-verging orogenic transport, witnessed by top to north-east thrusts. It fairly corresponds to the age referred to the Lucanian ocean closure.

New studies have been carried out on the Tertiary of the Stilo Unit, the uppermost of the Calabria–Peloritani Arc southern sector, and the Stilo–Capo d'Orlando Formation, sealing the whole nappe stack. The Tertiary terrains linked to the Mesozoic cover of the Stilo Unit consist of the lowermost Oligocene Palizzi Formation and the Late Rupelian–Aquitanian Pignolo Formation. The possibility that they deposited before the emplacement of this unit as the highest tectonic sheet of the sector is suggested. The base of the Stilo–Capo d'Orlando Formation resulted of Burdigalian age in both type areas. This interpretation, together with the existing and new data, allows proposing an age close to the Aquitanian–Burdigalian boundary for the stacking of the whole Calabria–Peloritani Arc southern sector. To cite this article: G. Bonardi et al., C. R. Geoscience 334 (2002) 423–430.

Romeo G, Ceccherini I, Celli J, Priolo M, Betsos N, Bonardi G, Seri M, Yin L, Lerone M, Jasonni V, Martucciello G (University of Genoa Medical School, Genoa, Italy; International Agency for Research on Cancer, Lyon, France). Association of multiple endocrine neoplasia type 2 and Hirschsprung disease (Minisymposium: MEN & VHL). J Intern Med 1998; 243: 515–20. In a few patients with Hirschsprung disease (HSCR) and no clinical symptoms of multiple endocrine neoplasia type 2 (MEN-2A) or medullary thyroid carcinoma (MTC), missense mutations in the cysteine residues 609 and 620 of the Ret gene have been identified. In several pedigrees with either MEN-2A or familial MTC (FMTC) a documented germline mutation in cysteine 618 or 620 follows the segregation of the disease phenotype. The appearance of the HSCR phenotype in such patients and pedigrees cannot be easily reconciled with the gain of function which is associated with the dominant oncogenic effect of MEN-2A mutations. Gastrointestinal manifestations are known to occur also in association with MEN-2B but, to the best of our knowledge, in only very few cases the intestinal phenotype of MEN-2B has been investigated by enzymo-histochemical techniques, as in the present work. We report an extensive molecular study of patients, two with HSCR and FMTC carrying a Cys620Arg or Ser mutation and two with MEN-2B and gastrointestinal symptoms carrying a Met918Thr mutation. One of the latter two patients showed aganglionosis of the last 5 cm of rectum which caused a congenital megacolon leading to the diagnosis and operation for HSCR. The mutation screening of all the exons of Ret in 3 of these patients did not reveal any additional mutation. Therefore these results do not support the hypothesis of additional constitutional Ret mutations in patients showing association of MEN-2 and HSCR, whilst the histochemical and clinical data in one of these patients indicate that MEN-2B can be associated with a true form of short segment HSCR.

A splenic arteriovenous fistula is a situation often presenting with signs of portal hypertension and with a characteristic murmur. Though rare, the possibility of a splenic arteriovenous fistula must be borne in mind in differential diagnosis, since it can be corrected surgically by resolving the portal hypertension.

Absorption, distribution and excretion of [14C]cadralazine in rat after oral and i.v. administration of 3 mg/kg were studied. Plasma levels after oral administration of 10 and 45 mg/kg were also evaluated. A direct relation between dose and plasma levels was demonstrated. The drug was well absorbed, disappeared very rapidly from plasma, and was distributed in all the organs examined, with the highest concentration in liver, kidney, and gastrointestinal tract. For more than 4 days excretion was essentially through the urine (75.6% after i.v. and 80% after oral administration), whereas faecal and biliary excretions were quite low. The total recovery was respectively 77.6% and 83.2% after i.v. and oral administration of 3 mg/kg, with the greatest amount (65-70% of the administered dose) appearing in the first 4 to 7 hours. Placental transfer and excretion of radioactivity with milk were demonstrated. Drug-protein binding was 25.9%. Elimination of 14CO2 was not observed. Plasma levels in dog, after oral and i.v. administration of 1 mg/kg of labelled compound, showed similar behaviour to that observed in the rat. Binding of the radioactivity to erythrocytes was found; the radioactivity values observed up to 24 hours were constant with time and not dependent on the decreasing plasma levels. The total recovery (urine and faeces) in the dog over 4 days was 71.1% and 82.1% after oral and i.v. dose, respectively. Preliminary metabolic approaches in rats showed that cadralazine was essentially excreted as unchanged drug in the presence of minor metabolites.

Summary The present investigation is devoted to the study of the action of 4-prenyl-1,2-diphenyl-3,5-pyrazolidinedione (DA 2370, Fenilprenazone * ), a new anti-inflammatory drug, on the glycosaminoglycan fractions of inflamed rat paws (kaolin oedema) in comparison with the action of phenylbutazone. As a result of the experiments performed it has been shown that DA 2370 and phenylbutazone, administered orally, reduce the increased hyaluronate and dermatan sulphate concentrations in the inflamed tissue.

Summary An experimental hyperuricosuria was induced in the rat by potassium oxonate and the uricosuric action of 4-prenyl-1,2-diphenyl1-3,5-pyrazolidinedione (DA 2370 * ), phenylbutazone (PBZ) and zoxazolamine was verified. DA 2370 revealed a clear activity, however its action is slightly lower than that of PBZ. Both drugs showed a proportional uricosuric activity; zoxazolamine resulted active only at the highest dose.

Forty-two evaluable patients with advanced non-small cell lung cancer were treated with teniposide at doses ranging from 120 to 180 mg/m2 on Days 1, 3, and 5 every 3 weeks. Thirty-four patients had received no prior chemotherapy. Seven partial responses (16.6%) were obtained (21% in chemotherapy-unexposed patients). Marrow toxicity was the main side effect: life-threatening thrombocytopenia occurred in 9% of patients, and 54.5% experienced severe leukopenia. Teniposide, at the doses and schedule employed, has moderate activity in non-small cell lung cancer.

A synergistic effect between alpha-Interferon and Bleomycin has been recently shown in in vitro and in vivo experimental systems. Although active, Bleomycin and other antineoplastic drugs give low response rates in non-small cell lung cancer, but, like the other antineoplastic agents, responses are short-lived. We treated 13 patients with advanced non-small cell lung cancer with the combination Bleomycin 15 mg/m2 i.v. at hour 0 and alpha-Interferon 9 X 10(6) U i.m. given at hours 6, 30 and 54. Major side effects were pyrexia, astenia and anorexia; only one case of moderate leukopenia was observed. No major responses were obtained and stable disease lasted a median of 5 months. Further study of this combination is not warranted in patients with pretreated non-small cell lung cancer.

1. Serum levels of DL-gamma-amino-beta-hydroxybutyric acid-1-14C (DL-GABOB-1-14C) in the rat (50 mg/kg) were quite similar after single i.v. and p.o. doses. Also the disappearance from the serum was similar with both administration routes. Within 6 days after p.o. treatment with the same single dose, about 26.5% and 1.6% of the dose were excreted in the urine and the faeces, respectively, and after i.v. administration excretion was 10.15% in urine and 1.75% in faeces. The results show that the compound is well absorbed and retained by the organism. After repeated oral doses (200 mg/kg three times daily for 4 days) the serum levels tended to become constant. 2. Urinary excretion after repeated administration increased progressively every day. Investigations on bile-cannulated rats showed that about 0.4% of the p.o. dose was excreted in 24 h. 3. After single (50 mg/kg) or multiple p.o. doses (200 mg/kg) of GABOB-1-14C, there was no unusual localisation of radioactivity in the organs the highest concentrations being present in the liver and the kidneys. Brain radioactivity was not related to serum levels or to administration route. Radioactivity concentration in other organs, for example the liver, was a function of serum levels. 4. Investigations performed to identify the radioactive products in the brain showed that the radioactivity was mainly ascribable to the unchanged DL-GABOB-1-14C.

Oral absorption of flurithromycin, a new fluorinated macrolide, has been evaluated on eight healthy volunteers on fasting and after a standard meal. Serum levels from 0 to 8 hours, peak serum concentrations, times to peak and areas under the curves were compared using a balanced sequence cross-over design. The highest mean concentration was reached after 3 h from administration on fasting (1.36 +/- 0.31 mcg/ml) and after 1 h following a meal (1.36 +/- 0.30 mcg/ml). All the pharmacokinetic parameters considered showed no statistical change. Therefore a meal does not reduce or delay the absorption of flurithromycin, while in the presence of food other macrolides may behave differently. Moreover the tolerability to the drug was good, lacking any report of side-effects, either on fasting or after the food.

The action of feprazone, compared with other NSAD's, was studied on “in vitro” human platelet aggregation induced by ADP and by collagen. The drugs exhibited inhibitory effects both on ADP-induction and on collagen-induction. Feprazone displayed equivalent action to that of phenylbutazone (lesser than indomethacin and aspirin, greater than salicylic acid) on collagen-induced platelet aggregation.

The effect of the antihypertensive vasodilator, cadralazine, on renal function in the conscious dog was compared to that of hydralazine using inulin and paraaminohippurate clearances. Both drugs were administered as intravenous bolus, at the dose of 1 mg/kg. As expected, hydralazine rapidly decreased mean blood pressure (from 110 to 89 mmHg), significantly increased heart rate (from 109 to 190 beats/min), markedly decreased urine volume (from 0.90 to 0.47 ml/min) and sodium excretion (from 101 to 45 μEq/min), and increased potassium excretion (from 28 to 53 μEq/min). Cadralazine displayed a similar activity on blood pressure and on heart rate, but differently from hydralazine, these effects appeared more slowly and were not accompanied by sodium and water retention. Hydralazine, but not cadralazine, caused a quick and transient decrease in glomerular filtration rate (from 55 to 40 ml/min), whereas both compounds increased renal plasma flow and reduced renal vascular resistance, renal extraction of para-aminohippurate and filtration fraction. Moreover, cadralazine increased plasma renin activity to a lesser extent than hydralazine, and this could explain the different effect on water and sodium excretion after acute administration of the two drugs.

The synthesis of new 1,4-dihydropyridines having an alkoxyimino group in position 3 is described. Pharmacological evaluation included calcium antagonistic activity in the guinea pig Taenia coli test, acute toxicity and oral antihypertensive activity in SHR. The compounds had a remarkable calcium antagonistic activity in vitro and low toxicity, but no antihypertensive activity in vivo, probably due to an unfavourable pharmacokinetic profile.