Association of the shuffling of Streptococcus pyogenes clones and the fluctuation of scarlet fever cases between 2000 and 2006 in central Taiwan

<p>Abstract</p> <p>Background</p> <p>The number of scarlet fever occurrences reported between 2000 and 2006 fluctuated considerably in central Taiwan and throughout the nation. Isolates of <it>Streptococcus pyogenes </it>were collected from scarlet fever patients in central Taiwan and were characterized by <it>emm </it>sequencing and a standardized pulsed-field gel electrophoresis (PFGE) method. National weekly report data were collected for investigating epidemiological trends.</p> <p>Results</p> <p>A total of 23 <it>emm </it>types were identified in 1,218 <it>S. pyogenes </it>isolates. The five most prevalent <it>emm </it>types were <it>emm</it>12 (50.4%), <it>emm</it>4 (23.2%), <it>emm</it>1 (16.4%), <it>emm</it>6 (3.8%) and <it>emm</it>22 (3.0%). PFGE analysis with <it>Sma</it>I suggested that, with a few exceptions, strains with a common <it>emm </it>type belonged to the same clone. There were two large <it>emm</it>12 clones, one with DNA resistant to cleavage by <it>Sma</it>I. Each prevalent <it>emm </it>clone had major PFGE strain(s) and many minor strains. Most of the minor strains emerged in the population and disappeared soon after. Even some major strains remained prevalent for only 2–3 years before declining. The large fluctuation of scarlet fever cases between 2000 and 2006 was associated with the shuffling of six prevalent <it>emm </it>clones. In 2003, the dramatic drop in scarlet fever cases in central Taiwan and throughout the whole country was associated with the occurrence of a severe acute respiratory syndrome (SARS) outbreak that occurred between late-February and mid-June in Taiwan.</p> <p>Conclusion</p> <p>The occurrences of scarlet fever in central Taiwan in 2000–2006 were primarily caused by five <it>emm </it>types, which accounted for 96.8% of the isolates collected. Most of the <it>S. pyogenes </it>strains (as defined by PFGE genotypes) emerged and lasted for only a few years. The fluctuation in the number of scarlet fever cases during the seven years can be primarily attributed to the shuffling of six prevalent <it>emm </it>clones and to the SARS outbreak in 2003.</p

Hesperetin-7,3'-O-dimethylether selectively inhibits phosphodiesterase 4 and effectively suppresses ovalbumin-induced airway hyperresponsiveness with a high therapeutic ratio

<p>Abstract</p> <p>Background</p> <p>Hesperetin was reported to selectively inhibit phosphodiesterase 4 (PDE4). While hesperetin-7,3'-<it>O</it>-dimethylether (HDME) is a synthetic liposoluble hesperetin. Therefore, we were interested in investigating its selectivity on PDE4 and binding ability on high-affinity rolipram-binding sites (HARBs) <it>in vitro</it>, and its effects on ovalbumin-induced airway hyperresponsiveness <it>in vivo</it>, and clarifying its potential for treating asthma and chronic obstructive pulmonary disease (COPD).</p> <p>Methods</p> <p>PDE1~5 activities were measured using a two-step procedure. The binding of HDME on high-affinity rolipram-binding sites was determined by replacing 2 nM [³<it>H</it>]-rolipram. AHR was assessed using the FlexiVent system and barometric plethysmography. Inflammatory cells were counted using a hemocytometer. Cytokines were determined using mouse T helper (Th)1/Th2 cytokine CBA kits, and total immunoglobulin (Ig)E or IgG_2alevels were done using ELISA method. Xylazine (10 mg/kg)/ketamine (70 mg/kg)-induced anesthesia was performed.</p> <p>Results</p> <p>HDME revealed selective phosphodiesterase 4 (PDE4) inhibition with a therapeutic (PDE4_H/PDE4_L) ratio of 35.5 <it>in vitro</it>. <it>In vivo</it>, HDME (3~30 μmol/kg, orally (p.o.)) dose-dependently and significantly attenuated the airway resistance (R_L) and increased lung dynamic compliance (C_dyn), and decreased enhanced pause (P_enh) values induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in the numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF) of these mice. In addition, HDME (3~30 μmol/kg, p.o.) dose-dependently and significantly suppressed total and ovalbumin-specific immunoglobulin (Ig)E levels in the BALF and serum, and enhanced IgG_2alevel in the serum of these mice.</p> <p>Conclusions</p> <p>HDME exerted anti-inflammatory effects, including suppression of AHR, and reduced expressions of inflammatory cells and cytokines in this murine model, which appears to be suitable for studying the effects of drugs on atypical asthma and COPD, and for screening those on typical asthma. However, HDME did not influnce xylazine/ketamine-induced anesthesia. Thus HDME may have the potential for use in treating typical and atypical asthma, and COPD.</p

Hesperidin-3′- O

Hesperidin is present in the traditional Chinese medicine, “Chen Pi,” and recently was reported to have anti-inflammatory effects. Therefore, we were interested in comparing the effects of hesperidin and hesperidin-3′-O-methylether on phosphodiesterase inhibition and airway hyperresponsiveness (AHR) in a murine model of asthma. In the present results, hesperidin-3′-O-methylether, but not hesperidin, at 30 μmol/kg (p.o.) significantly attenuated the enhanced pause (Penh) value, suppressed the increases in numbers of total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and BALF, and enhanced the level of total IgG2a in the serum of sensitized and challenged mice, suggesting that hesperidin-3′-O-methylether is more potent than hesperidin in suppression of AHR and immunoregulation. The different potency between them may be due to their aglycons, because these two flavanone glycosides should be hydrolyzed by β-glucosidase after oral administration. Neither influenced xylazine/ketamine-induced anesthesia, suggesting that they may have few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, hesperidin-3′-O-methylether is more potent in phosphodiesterase inhibition and suppression of AHR and has higher therapeutic (PDE4H/PDE4L) ratio than hesperidin. Thus, hesperidin-3′-O-methylether may have more potential for use in treating allergic asthma and chronic obstructive pulmonary disease

Utility of Multilocus Variable-Number Tandem-Repeat Analysis as a Molecular Tool for Phylogenetic Analysis of Shigella sonnei▿

A panel of 916 isolates, including 703 closely related IST1 isolates, were characterized by inter-IS1 spacer typing (IST), pulsed-field gel electrophoresis (PFGE), and multilocus variable-number tandem-repeat (VNTR) analysis (MLVA) to evaluate the utility of MLVA as a molecular tool for the phylogenetic analysis of Shigella sonnei. The global phylogenetic patterns determined by IST, PFGE, and MLVA were concordant. MLVA was carried out using 26 VNTR loci with a range of degrees of variability. MLVA data for the 703 IST1 isolates revealed that diversification among the closely related isolates was attributed mainly to four highly variable loci. The phylogenetic pattern for the closely related isolates determined using MLVA profiles of 8 highly variable loci was in agreement with that determined using the 26-locus profiles. A clustering analysis using the profiles of 18 loci with limited variability established clear phylogenetic relationships among IST clonal groups. Accordingly, MLVA is a useful tool for the phylogenetic analysis of S. sonnei. Combined VNTR loci with higher variability are useful markers for resolving closely related isolates, whereas combined loci with lower variability are suitable for establishing clear phylogenetic relationships between strains or clones that have evolved over a longer timescale

Multilocus variable-number tandem repeat analysis for molecular typing and phylogenetic analysis of <it>Shigella flexneri</it>

Abstract Background Shigella flexneri is one of the causative agents of shigellosis, a major cause of childhood mortality in developing countries. Multilocus variable-number tandem repeat (VNTR) analysis (MLVA) is a prominent subtyping method to resolve closely related bacterial isolates for investigation of disease outbreaks and provide information for establishing phylogenetic patterns among isolates. The present study aimed to develop an MLVA method for S. flexneri and the VNTR loci identified were tested on 242 S. flexneri isolates to evaluate their variability in various serotypes. The isolates were also analyzed by pulsed-field gel electrophoresis (PFGE) to compare the discriminatory power and to evaluate the usefulness of MLVA as a tool for phylogenetic analysis of S. flexneri. Results Thirty-six VNTR loci were identified by exploring the repeat sequence loci in genomic sequences of Shigella species and by testing the loci on nine isolates of different subserotypes. The VNTR loci in different serotype groups differed greatly in their variability. The discriminatory power of an MLVA assay based on four most variable VNTR loci was higher, though not significantly, than PFGE for the total isolates, a panel of 2a isolates, which were relatively diverse, and a panel of 4a/Y isolates, which were closely-related. Phylogenetic groupings based on PFGE patterns and MLVA profiles were considerably concordant. The genetic relationships among the isolates were correlated with serotypes. The phylogenetic trees constructed using PFGE patterns and MLVA profiles presented two distinct clusters for the isolates of serotype 3 and one distinct cluster for each of the serotype groups, 1a/1b/NT, 2a/2b/X/NT, 4a/Y, and 6. Isolates that had different serotypes but had closer genetic relatedness than those with the same serotype were observed between serotype Y and subserotype 4a, serotype X and subserotype 2b, subserotype 1a and 1b, and subserotype 3a and 3b. Conclusions The 36 VNTR loci identified exhibited considerably different degrees of variability among S. flexneri serotype groups. VNTR locus could be highly variable in a serotype but invariable in others. MLVA assay based on four highly variable loci could display a comparable resolving power to PFGE in discriminating isolates. MLVA is also a prominent molecular tool for phylogenetic analysis of S. flexneri; the resulting data are beneficial to establish clear clonal patterns among different serotype groups and to discern clonal groups among isolates within the same serotype. As highly variable VNTR loci could be serotype-specific, a common MLVA protocol that consists of only a small set of loci, for example four to eight loci, and that provides high resolving power to all S. flexneri serotypes may not be obtainable.</p

New Multidrug-Resistant Salmonella enterica Serovar Anatum Clone, Taiwan, 2015–2017

In 2011, a Salmonella enterica serovar Anatum clone emerged in Taiwan. During 2016–2017, infections increased dramatically, strongly associated with emergence and spread of multidrug-resistant strains with a plasmid carrying 11 resistance genes, including blaDHA-1. Because these resistant strains infect humans and food animals, control measures are urgently needed