A novel binuclear copper complex incorporating a nalidixic acid derivative displaying a one-dimensional coordination polymeric structure.

The identification of the antibacterial action of nalidixic acid (nx) was central to the development of the quinolone antibacterial compounds. The ability of the nx naphthyridyl ring to interact with and inhibit some proteins has encouraged the investigation of similar structures in the search for more active compounds with less adverse effects. The possibility of structural modification by attachment of other biologically active moieties to the naphthyridyl ring of nx allowed the development of new active antimicrobial molecules. Hydrazone derivatives of nx can be synthesized easily based on the condensation of the hydrazide derivative of nx with the desired aldehyde or ketone. Only a few complexes with nx hydrazone derivatives have been described but for none were the crystal structures elucidated. The synthesis of a new one-dimensional Cu(II) coordination polymer, namely catena-poly[[copper(II)-di-µ-chlorido-copper(II)-{µ-1-ethyl-N'-[(1H-imidazol-4-yl)methylidene]-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazidato}-[dimethanolcopper(II)]-{µ-1-ethyl-N'-[(1H-imidazol-3-yl)methylidene]-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carbohydrazidato}] dichloride methanol tetrasolvate], {[Cu3(C16H15N6O2)2Cl2(CH3OH)2]Cl2·4CH3OH}n, with the (1H-imidazol-4-yl)methylidene carbohydrazide derivative of nalidixic acid (denoted h4imi), is presented and its structure is compared to the density functional theory (DFT) optimized structure of free h4imi. The title structure presents an octahedral Cu(II) ion on an inversion centre alternating along a polymer chain with a square-pyramidal Cu(II) ion, with the two Cu(II) centres bridged by two chloride ligands. Hydrogen bonds involving chloride counter-ions and methanol solvent molecules mediate the three-dimensional packing of the polymer. Comparison of the geometrical results from the structure analysis with those derived from a DFT study of the free ligand reveal the differences that arise upon coordination.

Sequence types and pleuromutilin susceptibility of Brachyspira hyodysenteriae isolates from Italian pigs with swine dysentery: 2003-2012.

Swine dysentery is a mucohaemorrhagic colitis of pigs caused by infection with Brachyspira hyodysenteriae. The disease can be controlled by treatment with antimicrobial agents, with the pleuromutilins tiamulin and valnemulin being widely used. In recent years, the occurrence of B. hyodysenteriae with reduced susceptibility to these drugs has been increasing. The aim of this study was to determine temporal changes in genetic groups and pleuromutilin susceptibility amongst B. hyodysenteriae isolates from Italy. Multilocus sequence typing (MLST) was performed on 108 isolates recovered from 87 farms in different regions of Italy from 2003 to 2012, and their minimum inhibitory concentrations (MICs) for tiamulin and valnemulin were determined. Logistic regression was performed to assess associations between susceptibility to the two antimicrobial agents and genetic group, year and region of isolation. The isolates were allocated to 23 sequence types (STs), with five clonal clusters (Ccs) and seven singletons. More than 50% of isolates were resistant to both pleuromutilins (MIC >2.0 µg/mL for tiamulin and >1.0 µg/mL for valnemulin). All 10 isolates in ST 83 were resistant; these were first isolated in 2011 and came from nine farms, suggesting recent widespread dissemination of a resistant strain. Significant associations were found between the proportion of pleuromutilin susceptible isolates and the genetic group and year of isolation. Although resistant isolates were found in all Ccs, isolates in Ccs 2 and 7 were over five times more likely to be susceptible than those in the other Ccs. A significant trend in the reduction of susceptibility over time also was observed.

Diagnosis of macular pseudoholes and lamellar macular holes: is optical coherence tomography the "gold standard"?

AIM: To assess fundus autofluorescence (AF) for differential diagnosis of macular pseudoholes (MPH) and lamellar macular holes (LMH) evaluated by optical coherence tomography (OCT) as the "gold standard". METHODS: The files on 50 eyes of 46 consecutive patients diagnosed by OCT as having a foveal defect with residual retinal tissue at the bottom were reviewed. Retinal thickness was measured at the foveal centre and 750 microm temporally and nasally to differentiate further MPH and LMH. The corresponding corrected AF images were then evaluated. Eyes with either macular pucker or stage 1a impending macular hole served as controls. RESULTS: OCT measurements allowed the classification of two different profiles: 28 eyes classified with MPH had macular centres and perifoveal retinas that were significantly thicker than the 22 eyes classified with LMH. The corrected value of the foveal AF intensity was not significantly different between the two groups. In addition, the AF did not correlate with the thickness of the retinal tissue at the base of either MPH or LMH eyes. None of the control eyes showed foveal AF. CONCLUSIONS: The findings suggest that OCT data must be interpreted with caution when differentiating between MPH and LMH. In this series, the two groups showed similar foveal AF. AF imaging may add useful information to the differential diagnosis of MPH from LMH: the presence of foveal AF is consistent with a loss of foveal tissue and therefore a diagnosis of LMH.

Seroimmunity to poliomyelitis in an Albanian immigrant population.

The immunity against poliomyelitis in a representative sample of the Albanian population recently immigrant to Italy was evaluated. A significant number of the subjects examined lacked protective antibodies against one or more polioviruses. The most prevalent seronegativity related to poliovirus type 3 (41.3%), followed by poliovirus type 1 (21.5%). This result was more consistent in the younger age groups. Our data suggest the hypothesis that this problem arises from the use of a vaccine of discontinuous efficacy caused by defective preservation. A poliovaccine booster dose for all emigree subjects aged less than 15 years is suggested.

Yeast-derived hepatitis B vaccine in dental students. A three-year follow-up study.

Sixty health adults (56 dental students and four post-graduates of the Dental Faculty in Milan; mean age 26.4 years, range 22-42 years) were vaccinated with a recombinant DNA vaccine (Engerix B, Smith Kline and French; 20 micrograms given i.m. at time 0, 1 and 6 months). One month after the third injection, 98.3% (59/60) vaccinees showed anti-HBs at levels higher than 10 mIU ml-1 (geometric mean titre 734.8 mIU ml-1). One year after the beginning of vaccination (i.e. 6 months after the third injection of vaccine), 46 vaccinees showed anti-HBs titre higher than 100 mIU ml-1 (24 between 100 and 1000 mIU ml-1 and 22 higher than 1000 mIU ml-1) and 14 vaccinees had anti-HBs below 100 mIU ml-1 (12 between 10 and 99 mIU ml-1 and 2 below 10 mIU ml-1). Since duration of antibody is directly related to the height of the initial response, the 14 vaccinees with lower anti-HBs titres were given a fourth dose of vaccine. All boosted vaccinees showed a vigorous anti-HBs response and the post-booster anti-HBs GMT increased to 1570 mIU ml-1 compared with 47.8 mIU ml-1 attained before the boosting injection. At three years from the beginning of vaccination, all vaccinees who showed anti-HBs titres higher than 100 mIU ml-1 after the primary vaccination and all but one of the boosted vaccinees were still anti-HBs positive.(ABSTRACT TRUNCATED AT 250 WORDS)

The Italian Cooperative Multiple Sclerosis case-control study: preliminary results on viral antibodies.

Viral antibodies to measles, HSV-1, HSV-2, EBV and HTLB-III have been tested in 120 sera and 90 CFS of 78 MS patients, 21 other neurological diseases and 21 non neurological disease controls included in the Italian Multicenter MS case-control study. A significantly higher frequency of HSV-2 antibodies was found in the MS cases than in the two control groups. Moreover the HSV-2 and the RBV-VCA cantibody levels were higher in the MS patients than in those with non neurological diseases. A clear or weak antibody response to the HTLV-III proteins was shown, using the Western Immunoblotting method, in 10.3% of the MS sera or CSF:8.6% of the sera and 1.8% of the CSF were positive. The significance of these findings in relation to the design of the multicenter case-control study is discussed.

Subacute sclerosing panencephalitis: detection of measles antibody in serum and cerebrospinal fluid by enzyme-linked immunosorbent assay, complement fixation and hemagglutination inhibition.

Subacute sclerosing panencephalitis (SSPE), a slowly progressive central nervous system disease, is related to the measles virus. Because laboratory immunoassays are important in the diagnosis of the disease, we compared enzyme-linked immunosorbent assay (ELISA), complement fixation (CF), and hemagglutination inhibition (HI) for the detection of measles antibody in the serum and cerebrospinal fluid of patients with SSPE and in controls. Differences in the sensitivity of the three methods were not observed in the serum and cerebrospinal fluid from patients because all specimens were positive, but ELISA and CF were more sensitive that HI for both serum and cerebrospinal fluid from controls. ELISA also distinguished between subacute sclerosing panencephalitis cases and controls with high measles antibody levels (acute measles). Thus, it appears that ELISA for measles antibody is superior to CF and HI in the laboratory diagnosis of SSPE and is the preferred method.

Immunogenicity of yeast-derived hepatitis B vaccines in young adults.

A study of the safety and immunogenicity of two different recombinant DNA yeast-derived hepatitis B vaccines was conducted in 90 young adults according to a 0-, 1-, and 6-month vaccination schedule. Preliminary results using the 20 micrograms SmithKline Biologicals or 10 micrograms Merck Sharp & Dohme recombinant yeast-derived hepatitis B vaccines indicate that both vaccines are clinically safe and immunogenic. Only minor side effects have thus far been reported. Seroconversion rates among vaccine recipients were 80% or greater after the first two injections with either vaccine, and 100% after the third dose of the SmithKline Biologicals recombinant DNA hepatitis B vaccine.

Multicenter trial on the efficacy of HBIG and vaccine in preventing perinatal hepatitis B. Final report.

In an attempt to interrupt perinatal transmission of hepatitis B, 92 infants born to HBsAg carrier mothers (49 to HBeAg-positive mothers, 30 to anti-HBe-positive with abnormally elevated ALT levels, and 13 to HBeAg/anti-HBe-negative mothers) received 0.5 ml/kg BW of HBIG at birth and at 1 month of age. Three IM injections of hepatitis B vaccine were given at 3, 4, and 9 months of life. All babies who were given the three doses of vaccine developed an active anti-HBs response: of these, 53 (62.3%) had antibody titers higher than 1,000 mIU/ml, 29 (34.2%) had levels between 100 and 1,000 mIU/ml, and the other three (3.5%) were below 100 mIU/ml. At the end of the 2-year follow-up, these three poor responders became anti-HBs negative, whereas the others still had antibody. All but three babies were protected by HBIG plus vaccine treatment. Two chronic HBV infections occurred within 6 months of life presumably because the babies were already infected when prophylaxis started. The third baby became an HBsAg carrier at 9 months of age in spite of a previous response to the vaccine. Simultaneous presence of HBsAg of y specificity and anti-HBs (anti-a) was still detectable at 24 months of age. The vaccine was well tolerated. Passive plus active immunization is an effective procedure for preventing perinatally transmitted HBV infection.

Screening of pregnant women and hepatitis B prophylaxis in newborns.

Prevention of perinatal hepatitis B includes: (1) screening of pregnant women for hepatitis B surface antigen, and (2) immunoprophylaxis of babies at risk. HBIG treatment seems to be of some efficacy in preventing the HBsAg carrier state while it permits passive active immunization to occur. The disadvantage of HBIG is that it confers only temporary immunity. Therefore, if infection does not occur, babies will still be susceptible to the virus when passively administered anti-HBs will no longer be circulating. On the other hand, vaccine provides a long term but not immediate protection. Therefore the ideal approach in post-exposure prophylaxis is a combination of passive plus active immunization. The aim is to provide an immediate protection, with the HBIG, and a long term immunity, with the vaccine, to babies born to HBsAg carrier mothers.

Posterior polymorphous dystrophy of the cornea. An ultrastructural study.

A corneal button excised from a 2-month-old infant with congenital posterior polymorphous dystrophy of the cornea, a rare disease affecting Descemet's membrane and endothelium, was examined by electron microscopy. We observed irregularly arranged, sometimes multilayered cells with marked epithelial features, lining the posterior surface of the cornea in place of the endothelium, and Descemet's membrane with focal alterations sometimes involving all of its layers. We interpreted these abnormal cells as epithelial-like cells. As these findings were in a very young patient, which is unusual, we concluded that the onset of the disease may take place in the early period of intrauterine life, corresponding to the beginning of Descemet's membrane production.

Immune response to hepatitis B vaccine in staff and patients in renal dialysis units.

Anti-HBs response was detected in 96 per cent of staff members in three haemodialysis units after three 20 microgram doses of hepatitis B vaccine and in 82 per cent of adult patients treated with three 40 microgram doses. The percentage of responders and levels of antibody remained unchanged at 12 months from the beginning of the trial. Three out of six children injected with three 20 microgram doses in a paediatric haemodialysis unit remained free from markers of HBV infection and had high levels of anti-HBs after the second dose of vaccine. The other three children who developed serological markers of HBV infection seroconverted to anti-HBc within six months from the first dose and, in one of them, antigenaemia at three and four months was detected.

[Subacute sclerosing panencephalitis (SSPE); clinical and epidemiological observations of 56 cases studied from 1956 to 1978]. / Panencefalite sclerosante subacuta (PESS); osservazioni cliniche ed epidemiologiche su 56 casi studiati dal 1956 al 1978.

Epidemiological observations on 56 cases of SSPE studied at the Institute of Virology of the University of Milan between 1956 and 1978 and the clinical features of 47 of them, all hospitalized at the Neurologic Institute "C. Besta" of Milan, are reported. The criteria adopted for the diagnosis of the cases, the symptoms at onset and the signs of involvement of CNS eventually present before SSPE and illustrated. Age at onset of SSPE was between 2 and 25 years, average 9,4 years; survival varied from 2 months to 2 years in 20 cases, from 25 months to 7 years in 9 patients while 3 children are still living after 9--11 years. In 1 case a substantial long remission of clinical symptomatology has been observed. As to the distribution of cases, both in the Lombardy region and in the Milan province a low incidence has been noted in the first 10 years, followed by a first increase in the successive decade (1965-1974) and by an abrupt increase from 1975 on. In the Milan province, to be pointed out a lack of cases in the period 1958-1962 and in some of the subsequent years, while since 1971 one or more cases have been observed each year with a maximum of 4-5 subjects from 1975 on. This last figure for an average resident population of 4 millions, averages an SSPE yearly rate of 1-1,15 cases/10(6) inhabitants. Similar to that of other reports are the higher prevalence among males than among females (ratio M/F = 1,4 : 1), and an average distance of 5,6 years from measles. It is also evident an association of SSPE with measles at early age although recent patients seem to have had their infection later in life.

Prevalence of HBeAg, anti-HBe and Dane particle-associated DNA polymerase activity in asymptomatic carriers of HBsAg.

HBeAg/anti-HBe and Dane particle-associated DNA polymerase activity were detected in serum samples from 358 HBsAg asymptomatic carriers found during normal routine screening of 11,200 blood donors (HBsAg prevalence 3.1%). Since virus specific DNA polymerase activity and HBeAg seem to be associated in some way with hepatitis B virus infectivity and liver damage, 5% of the HBsAg carriers examined, as detected by the presence of HBeAg, and 9.5%, as shown by DNA polymerase activity, can be expected to have liver damage and a potential risk of transmitting hepatitis B to contacts. On the other hand, 48% of subjects were theoretically healthy and non-infective because of the presence of anti-HBe in their blood. The differentiation of groups of asymptomatic HBsAg carriers, on the basis of these serological markers, may have important clinical and epidemiological implications.

Slow virus E malattie croniche del sistema nervoso centrale.

The purpose of this report was to detect whether some subacute or chronic human neurological diseases are significantly associated with traditional virus like papovavirus and paramixovirus and non conventional agents (scrapie-like) or non classified (multiple sclerosis associated agent or MSAA). In this connection for M.S. the data concerning the ethiological factors paramixovirus or MSSA are presented and discussed and it is hypothesized the virus mechanism in the pathogenesis of M.S.

Transplacental acquisition of cytomegalovirus antibody. Observations with two different CMV strains.

Titrations of complement fixing antibody (c.f.a.) were done in paired sera of 127 women at delivery and cord blood of their babies using two different cytomegalovirus strains both of which had undergone many passages in WI-38 cells, With High strain 74% of the mother and 41% of the babies were negative at the serum dilution 1:4. With Towne strain the incidence of negative was 5% both among the mother and the newborns. Worth of mention is the study of correlation of the titers in the matched pairs of sera according to the strain. With High strain 23 of the babies had c.f.a. titers significantly higher than their mothers and 14 of them were from negative women. This situation could be suggestive of an active placental transfer of IgG globulins. No such disparities were found using Towne strain as antigen. 48 pairs of sera were then tested with both strains by indirect hemagglutination, indirect immunofluorescence and gel precipitin test. Results are discussed in relation to the possible differences in the antigenic composition of the two cytomegalovirus strains.

[Clinical control, study of viral shedding and evaluation of circulating and local antibody response after administration of live and attenuated "Alice" strain influenza vaccine]. / Controllo clinico, studio dell'escrezoine virale e valutazione della risposta in anticorpi circolanti e locali dopo somministrazioned di vaccino influenzale vivente ed attenuato contenente il ceppo "Alice"

Thirty-four young adults were inoculated intranasally by nose drops with two doses, two weeks apart, of inhibitor resistant "Alice" vaccine strain of A/England/42/72 (H3N2). By the rate of volunteers with clinical reactions, always mild and short-lasting, the vaccine showed a low degree of reactogenicity. Viral shedding was evidenced only the day after the first dose and was limited to two vaccinees. Two weeks after the first dose homologous serum h.i.a. appeared in all the 15 volunteers lacking prevaccination antibody and significant titer rises occurred in a substantial number of vaccine recipients with low titers. The incidence of subjects with h.i.a at titers considered to be protective (larger than or equal to 1:40), which was 26% before vaccination, rose to 93% in fully vaccinated volunteers. Very likely because of the presence of n.i.a. in the prevaccinal serum of all the volunteers, the n.i.a. response was less satisfactory. The vaccine induced h.i.a. to A/Port Chalmers/73 e A Scotland/74 (H3N2) variants, although in a lower titer than to the homologous strain. Serum h.i. and n.i. antibody response appeared not to be significantly increased by a second dose. H.i.a., never present in the first sample, were found in the nasal washings taken two weeks after the second dose from 9 out of 16 vaccinees examined. Antibody was detected more frequently in the specimens with relatively high levels of protein and IgA. Secretory n.i.a., already demonstrable in 7 volunteers before vaccination, were acquired by all but one at the end of the experience.