Natalizumab vs interferon beta 1a in relapsing-remitting multiple sclerosis: a head-to-head retrospective study.

BACKGROUND: No head-to-head study has been performed yet to assess whether natalizumab is more effective than classical immunomodulators in multiple sclerosis (MS). AIM: To retrospectively compare the efficacy of natalizumab vs IFN beta 1a SC (44 µg; Rebif(®) ) on clinical and radiological findings in two matched cohorts of patients with MS. PATIENTS AND METHODS: We retrospectively enrolled two cohorts of 42 patients (F/M: 35/7) with relapsing-remitting multiple sclerosis treated with natalizumab or IFN beta 1a for at least 12 consecutive months. Outcome measures were annualized relapse rate (ARR), changes in expanded disability status scale (EDSS) score, and number of contrast-enhancing lesions (CELs) at magnetic resonance imaging (MRI). RESULTS: In both groups, the ARR in the 12 months of treatment was lower than in the 12 months before therapy (0.24 vs 1.50 in natalizumab-treated group, P < 0.0000; 0.55 vs 1.10 in IFN beta 1a-treated group, P = 0.0006), being the effect of natalizumab significantly stronger (P = 0.0125). EDSS reduction was significantly different between the two groups in favor of natalizumab (P = 0.0018). The frequency and number of CELs per patient were decreased in both groups. In the second year, the treatment affected ARR and EDSS progression in the two groups of patients similarly to the first year, whereas number of CELs decreased more significantly in natalizumab group (P = 0.008). CONCLUSIONS: After 12 and 24 months of therapy, natalizumab was more effective than IFN beta 1a SC on both disease activity and disability progression. Prospective head-to-head studies would be helpful to further evaluate the differences observed in the MRI outcomes.

Insulin-like growth factor (IGF)-I and IGF-binding protein-3 serum levels in relapsing-remitting and secondary progressive multiple sclerosis patients.

BACKGROUND: Insulin-like growth factor (IGF)-I has a role in remyelination, and insulin-like growth factor-binding protein-3 (IGFBP-3) might reduce its bioavailability. A role of IGFBP-3 in multiple sclerosis (MS) progression was hypothesized in patients with primary progressive (PP) MS. OBJECTIVE: To evaluate serum levels of IGF-I and IGFBP-3 in patients with relapsing-remitting (RR) and secondary progressive (SP) MS and their correlations with disease activity and progression. METHODS: Sixty-three (41 RR and 22 SP) 'naive' MS patients and 60 age-matched healthy controls were enrolled. Patients were assessed through clinical [Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Scale (MSSS), number of relapses] and laboratory investigations. IGF-I and IGFBP-3 were measured by ELISA. RESULTS: Levels of IGF-I and IGFBP-3 were similar in the two MS groups. IGFBP-3 levels were higher in patients with MS than in controls (P < 0.001), with a reduction in IGF-I/BP3 ratio (P < 0.001). Patients showing IGFBP-3 levels higher than 2SD of the normal population had a higher EDSS (mean EDSS 3.7 vs. 2.8, P = 0.021). MSSS was not related to IGF-I or IGFBP-3 serum levels. CONCLUSIONS: Our patients showed high IGFBP-3 serum levels respect to controls and higher serum levels were associated with a higher EDSS, despite of comparable disease duration. Therefore, MS and higher disability seem to be associated with a reduction in bioavailability of IGF-I. MSSS score was not related to IGFBP-3 levels, suggesting that IGFBP-3 might not have the pathogenetic role previously suggested for PP MS, in the mechanism of progression in the SP form of disease.

Predictive factors of neutralizing antibodies development in relapsing-remitting multiple sclerosis patients on interferon Beta-1b therapy.

The identification of predictive factors of NAbs development might have a relevant impact on clinical practice. Our objective is to look after predictive factors of NAbs development in MS IFN Beta-1b-treated patients. Database was screened for patients on IFN Beta-1b treatment with an Expanded Disability Status Scale (EDSS) at a baseline between 1 and 3.5, disease duration shorter than 15 years, and NAbs analysis performed every 6 months. The NAbs positive status was analysed in relation to baseline clinical, neuropsychological and brain imaging measures. Forty-nine patients were included. Sixteen patients had become NAbs positive at some point on IFN therapy (35%). NAbs producers differed from not producers for higher incidence of cognitive deficit and higher lesion load (OR = 5.0 and 5.6, respectively). Our study suggests that NAbs development might be a marker of a more aggressive disease and that worse outcome in NAbs producers might be biased by baseline condition.

Frequency, antimicrobial susceptibility and clonal distribution of methicillin-resistant Staphylococcus pseudintermedius in canine clinical samples submitted to a veterinary diagnostic laboratory in Italy: A 3-year retrospective investigation.

In the last decade there has been a rapid global spread of methicillin-resistant Staphylococcus pseudintermedius (MRSP) clones displaying multidrug resistance in dogs. We investigated prevalence, antimicrobial susceptibility and clonal distribution of MRSP isolated from clinical canine samples between during 2011-2014. Following species identification by nuc PCR, MRSP were confirmed by the presence of mecA and characterized by antimicrobial susceptibility testing, Pulsed Field Gel Electrophoresis (PFGE), SCCmec typing, and Multi-Locus Sequence Typing (MLST) of a few isolates having distinct PFGE profiles. Both the MRSP isolation frequency in the 175 samples tested (12%) and the prevalence of methicillin resistance amongst the 63S. pseudintermedius isolates (33%) were high compared to a previous study in Italy. Sequence type (ST)71 carrying SCCmec type II-III, described as the epidemic European MRSP clone, accounted for approximately half of the isolates. The remaining isolates belonged to ST410-SCCmec type II-III, ST258-SCCmec type IV and other three clones associated with SCCmec type IV (ST261, ST290 and ST477). MRSP were consistently resistant to potentiated sulfonamides, and more frequently to clindamycin, ciprofloxacin and doxycycline than methicillin-susceptible isolates. Gentamicin was the only antibiotic showing good in vitro activity on all MRSP with 20 of the 21 isolates being susceptible. Results confirm a high prevalence of MRSP amongst clinical samples in Italy, revealing the emergence of new clones other than ST71, such as ST258, ST410, ST261, ST290 and ST477, here describe for the first time. Implementation of antimicrobial stewardship and surveillance programmes are required to prevent the emergence of new MRSP clones and reducing transmission in small animal practice.

An intensive monitoring campaign of PAHs for assessing the impact of a steel plant.

This study provided a useful approach for assessing the impact of industrial sources on surrounding, especially in a sensitive industrial area as Taranto (South of Italy). Taranto is one of the most industrialized Italian towns, where several emission sources operate simultaneously in proximity to the urban settlement. An intensive monitoring campaign of PAHs was carried out from January 28th to July 30th, 2011, in seven sites located in residential settlement around the industrial area and in the city center. The collected data were integrated with the information about wind direction and speed by means bivariate polarplot in order to characterize and localize the industrial sources. High BaP concentrations were detected especially when Benzene to Toluene ratio (B/T ratio) values excedeed 1 and all receptor sites were downwind to the steel plant. Moreover, in order to discriminate among PAH sources and quantify their contributions, a source apportionment analysis of the collected data was provided by means Principal component Analysis (PCA) and Positive Matrix Factorization (PMF) methods. Finally, the processing of PMF5.0 output by bivariate polar plot, confirmed the impact of steel plant on both industrial sites downwind the steel plant and the city center. B[a]P apportionment was quite similar for industrial and urban sites: the traffic source contributed only 11% and 24% to B[a]P measured at two sites, respectively. Therefore, the proximity of Taranto downtown to industrial pole makes negligible all other source contributions to PAH concentrations.

An integrated approach using high time-resolved tools to study the origin of aerosols.

Long-range transport of natural and/or anthropogenic particles can contribute significantly to PM10 and PM2.5 concentrations and some European cities often fail to comply with PM daily limit values due to the additional impact of particles from remote sources. For this reason, reliable methodologies to identify long-range transport (LRT) events would be useful to better understand air pollution phenomena and support proper decision-making. This study explores the potential of an integrated and high time-resolved monitoring approach for the identification and characterization of local, regional and long-range transport events of high PM. In particular, the goal of this work was also the identification of time-limited event. For this purpose, a high time-resolved monitoring campaign was carried out at an urban background site in Bari (southern Italy) for about 20 days (1st-20th October 2011). The integration of collected data as the hourly measurements of inorganic ions in PM2.5 and their gas precursors and of the natural radioactivity, in addition to the analyses of aerosol maps and hourly back trajectories (BT), provided useful information for the identification and chemical characterization of local sources and trans-boundary intrusions. Non-sea salt (nss) sulfate levels were found to increase when air masses came from northeastern Europe and higher dispersive conditions of the atmosphere were detected. Instead, higher nitrate and lower nss-sulfate concentrations were registered in correspondence with air mass stagnation and attributed to local traffic source. In some cases, combinations of local and trans-boundary sources were observed. Finally, statistical investigations such as the principal component analysis (PCA) applied on hourly ion concentrations and the cluster analyses, the Potential Source Contribution Function (PSCF) and the Concentration Weighted Trajectory (CWT) models computed on hourly back-trajectories enabled to complete a cognitive framework and confirm the influence of aerosol transported from heavily polluted areas on the receptor site.

DNA polymerases and DNA topoisomerases as targets for the development of anticancer drugs.

Studies of a variety of compounds designed as derivatives of prototype active molecules aphidicolin and doxorubicin are reported. So far none of the aphidicolin simpler analogues is as active as the parental molecule. Ten anthracycline analogues, characterized for their cytotoxicity, antitumor activity and inhibition of the relaxing activity of purified human DNA topoisomerase II can be divided into five groups. The majority of the tested compounds shows properties very similar to those of doxorubicin. Epirubicin shows extremely high inhibitory activity toward the relaxing property of topoisomerase II but its antitumor activity and cytotoxicity are similar to those of the former group. The third group includes a compound with extremely high cytotoxicity. The fourth group is represented by a compound which shows a cytotoxicity. The fourth group is represented by a compound which shows a cytotoxicity. The fourth group is represented by a compound which shows a cytotoxicity typical of anthracyclines and good antitumor activity but which has no specific inhibitory activity on topoisomerase II. A fifth group includes a totally inactive compound. Our results suggest that the inhibition of human DNA topoisomerase II is only partially correlated with antitumor activity.

[Presence of zinc in food and diet in pediatric age]. / Presenza di zinco in alimenti e diete in età pediatrica.

The authors determined the zinc content in the foods of eight diets recommended for different groups of subjects between four and a half months and twelve years. Then the average daily intake was calculated at any age. The highest values were found in meat products, the lowest ones in fruit and vegetables. The average levels of zinc intake were almost always upper than L.A.R.N. in both male and female.

Periodontal disease associated with red complex bacteria in dogs.

OBJECTIVE: Red complex bacteria (Treponema denticola, Tannerella forsythia and Porphyromonas gingivalis) play a major role in the aetiology of periodontal disease in humans. This study was designed to evaluate the association of such bacteria with periodontal disease in dogs. METHODS: Seventy-three subgingival samples taken from dogs ranging from 2 months to 12 years (median age 4 years) were tested for red complex bacteria using a polymerase chain reaction assay. RESULTS: Thirty-six of 73 (49 · 3%) dogs were found to be positive for T. forsythia and P. gingivalis. Dogs with gingivitis or periodontitis were more likely to be infected with T. forsythia and P. gingivalis [odds ratio (OR) 5 · 4 (confidence interval (CI) 1 · 9-15 · 6), P = 0 · 002] than healthy animals. Only 3 (4 · 1%) of 73 samples were positive for red complex bacteria, but the association with periodontal disease was not significant. CONCLUSION AND CLINICAL RELEVANCE: The results indicate that involvement of red complex bacteria in periodontal disease in dogs is similar to that observed in humans. Only the concurrent presence of T. forsythia and P. gingivalis were correlated to periodontal disease in dogs in this study.

Evaluation of an in-clinic assay for the diagnosis of canine parvovirus.

The results of a study designed to evaluate the performance of an in-clinic test for the detection of canine parvovirus (CPV) are reported. A total of 150 faecal samples collected from dogs with acute diarrhoea were tested using the in-clinic test, a haemagglutination assay (HA) and a real-time PCR assay for CPV detection, quantification and characterisation. CPV was detected in 66, 73, and 101 faecal samples by in-clinic, HA and PCR testing, respectively. The relative sensitivity and specificity of the in-clinic test were 86.3% and 96.1%, respectively, when the test was compared to HA, and 65.3% and 100%, respectively, when compared to real-time PCR. The sample distribution according to the virus type was CPV-2a, n=44; CPV-2b, n=11; CPV-2c, n=44, CPV-2, n=2, as determined by minor groove binder probe assays and/or sequence analysis. The percentage of positive in-clinic tests was 70.5% for CPV-2a, 72.7% for CPV-2b and 75.0% for CPV-2c (P>0.05). Using real-time PCR as the reference standard for CPV detection, the in-clinic test was more specific than HA and had comparable sensitivity to HA, demonstrating detection rates similar to those previously observed for other rapid in-clinic tests. The in-clinic test was also able to detect all CPV types at equivalent rates.

Characterization of a self-associating glycoprotein from bovine ligamentum nuchae exhibiting dual amine oxidase activity.

A homogeneous preparation of glycoprotein (apparent molecular weight 34,000) has been isolated from bovine ligamentum nuchae by treatment of the tissue with 5 M guanidine HCl and 2-mercaptoethanol. The preparation exhibits amine oxidase activity which is only marginally inhibited by beta-aminopropionitrile.

Characterization of a structural glycoprotein from bovine ligamentum nuchae exhibiting dual amine oxidase activity.

A structural glycoprotein has been extracted from bovine ligamentum nuchae by using 5 M guanidine hydrochloride containing a disulfide bond reducing agent and purified by preparative gel electrophoresis. The isolated material appeared to be monodisperse, with a molecular weight of approximately 34000, as shown by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by analytical ultracentrifugation. It contains 10% carbohydrate comprising mannose, N-acetylglucosamine, galactose, and sialic acid in a 6:5:3:3 molar ratio. The glycoprotein has been assayed for peptidyl-lysine oxidase activity by using [3H]lysine-aortic elastin, prepared from 15- to 17-day-old chick embryos, as a substrate. In the absence of free lysine, the specific activity of the preparation over a 2-h incubation was approximately 60 X 10(4) dpm/mg of purified protein. Addition of 10 mM lysine resulted in an approximately 50% decrease in the specific activity. Free lysine was shown to act as a substrate for the glycoprotein preparation as indicated by control experiments using [3H]lysine in place of the aortic substrate. These results demonstrate that the glycoprotein exhibits a dual amine oxidase activity. In the presence of 0.27 mM beta-aminopropionitrile fumarate, a concentration which completely inhibits peptidyl-lysine oxidase activity in other lysyl oxidases, the glycoprotein preparation was inhibited by approximately 14%. In the absence of 5 M guanidine hydrochloride and reducing agent, the glycoprotein undergoes aggregation which in the presences of copper ions results in the formation of cylindrical tactoids, the diameter of which (11 nm) corresponds closely to that of the fibrils which in the majority of connective tissue matrices constitute the microfibrillar component mainly associated with elastic fibers.