Antibiotic activity and synergistic effect of antimicrobial peptide against pathogens from a patient with gallstones

HP (2-20) is a peptide derived from the N-terminus of Helicobacter pylori ribosomal protein L1 that has been shown to have antimicrobial activity against various species of bacteria. When we tested the effects of HP (2-20), we found that this peptide displayed strong activity against pathogens from a patient with gallstones, but it did not have hemolytic activity against human erythrocytes. We also found that HP (2-20) had potent activity against cefazolin sodium-resistant bacterial cell lines, and that HP (2-20) and cefazolin sodium had synergistic effects against cell lines resistant to the latter. To investigate the mechanism of action of HP (2-20), we performed fluorescence activated flow cytometry using pathogens from the patient with gallstones. As determined by propidium iodide (PI) staining, pathogenic bacteria treated with HP (2-20) showed higher fluorescence intensity than untreated cells, similar to melittin-treated cells, and that HP (2-20) acted in an energy- and salt-dependent manner. Scanning electron microscopy showed that HP (2-20) caused significant morphological alterations in the cell surface of pathogens from the patient with gallstones. By determining their 16S rDNA sequences, we found that both the pathogens from the patient with gallstones and the cefazolin sodium-resistant cell lines showed 100% homology with sequences from Pseudomonas aeruginosa. Taken together, these results suggest that HP (2-20) has antibiotic activity and that it may be used as a lead drug for the treatment of acquired pathogens from patients with gallstones and antibiotic-resistant cell lines.     

急性缺血性脑卒中患者血浆Lp-PLA2 的表达及与斑块稳定性及神经功 能缺损的关系

目的：探讨急性缺血性脑卒中患者血浆脂蛋白相关磷脂酶（Lp-PLA2）的表达及与斑块稳定性及神经功能缺损的关系。方法： 按照颈动脉彩超结果将2014 年5 月-2015 年1 月我院收治的80 例急性缺血性脑卒中患者分为斑块稳定组（25 例）、斑块不稳定 组（39 例）和无斑块组（16 例）,并于同期随机抽取120 例健康体检者为对照组。采用散射比浊法测定各组血浆Lp-PLA2,同时采 用美国国立卫生研究所中风量表（NIHSS 评分）对三组的神经功能缺损情况进行评估。结果：斑块稳定组、斑块不稳定组以及无斑 块组血浆Lp-PLA2 高于对照组,斑块稳定组、斑块不稳定组高于无斑块组,斑块不稳定组高于斑块稳定组,差异均有统计学意义 （P<0.05）,患者血浆Lp-PLA2水平与动脉粥样硬化斑块的稳定性呈正相关性（rs=0.638,P<0.05）。神经功能缺损中型组、重型组血 浆Lp-PLA2 高于轻型组,重型组高于中型组,差异有统计学意义（P<0.05）,患者血浆Lp-PLA2 水平与神经功能缺损程度呈正相关 性（rs=0.715,P<0.05）。结论：血浆Lp-PLA2 可作为预测急性缺血性脑卒中患者颈动脉硬化斑块稳定性以及评估患者神经功能缺 损程度的重要指标。     

A community-based study of Helicobacter pylori therapy using the strategy of test, treat, retest, and re-treat initial treatment failures

BACKGROUND: Although eradication of Helicobacter pylori infection can decrease the risk of gastric cancer, the optimal regimen for treating the general population remains unclear. We report the eradication rate (intention-to-treat and per protocol) of a community-based H. pylori therapy using the strategy of test, treat, retest, and re-treat initial treatment failures. MATERIALS AND METHODS: In 2004, a total of 2658 residents were recruited for 13C-urea breath testing. Participants with positive results for infection received a standard 7-day triple therapy (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and clarithromycin 500 mg twice daily), and a 10-day re-treatment (esomeprazole 40 mg once daily, amoxicillin 1 g twice daily, and levofloxacin 500 mg once daily) if the follow-up tests remained positive. Both H. pylori status and side-effects were assessed 6 weeks after treatment. RESULTS: Among 886 valid reporters, eradication rates with initial therapy were 86.9% (95% confidence interval [CI]: 84.7-89.1%) and 88.7% (95%CI: 86.5-90.9%) by intention-to-treat and per protocol analysis, respectively. Re-treatment eradicated infection in 91.4% (95%CI: 86-96.8%) of 105 nonresponders. Adequate compliance was achieved in 798 (90.1%) of 886 subjects receiving the initial treatment and in all 105 re-treated subjects. Mild side-effects occurred in 24% of subjects. Overall intention-to-treat and per protocol eradication rates were 97.7% (95%CI: 96.7-98.7%) and 98.8% (95%CI: 98.5-99.3%), respectively, which were only affected by poor compliance (odds ratio, 3.3; 95%CI, 1.99-5.48; p < .0001). CONCLUSIONS: A comprehensive plan using drugs in which the resistance rate is low in a population combined with the strategy of test, treat, retest, and re-treat of needed can result in virtual eradication of H. pylori from a population. This provides a model for planning country- or region-wide eradication programs.     

Genome‐wide association study for pigmentation traits in Chinese Holstein population

With the Illumina BovineSNP50K BeadChip, we performed a genome‐wide association study (GWAS) for two pigmentation traits in a Chinese Holstein population: proportion of black (PB) and teat colour (TC). A case–control design was used. Cases were the cows with PB <0.30 (n = 129) and TC <2 points (n = 140); controls were those with PB >0.90 (n = 58) and TC >4 points (n = 281). The RM test of roadtrips (version 1.2) was applied to detect SNPs for the two traits with 42 883 and 42 741 SNPs respectively. A total of nine and 12 genome‐wide significant (P < 0.05) SNPs associated with PB and TC respectively were identified. Of these, two SNPs for PB were located within the KIT and IGFBP7 genes, and the other four SNPs were 23~212 kb away from the PDGFRA gene on BTA6; nine SNPs associated with TC were located within or 21~78.8 kb away from known genes on chromosomes 4, 11, 22, 23 and 24. By combing through our GWAS results and the biological functions of the genes, we suggest that the KIT, IGFBP7, PDGFRA, MITF, ING3 and WNT16 genes are promising candidates for PB and TC in Holstein cattle, providing a basis for further investigation on the genetic mechanism of pigmentation formation.     

On the permanent hip-stabilizing effect of atmospheric pressure

Hip joint dislocations related to total hip arthroplasty (THA) are a common complication especially in the early postoperative course. The surgical approach, the alignment of the prosthetic components, the range of motion and the muscle tone are known factors influencing the risk of dislocation. A further factor that is discussed until today is atmospheric pressure which is not taken into account in the present THA concepts. The aim of this study was to investigate the impact of atmospheric pressure on hip joint stability.     

Amine substitution of quinazolinones leads to selective nanomolar AChE inhibitors with ‘inverted’ binding mode

Selective and nanomolar acetylcholinesterase inhibitors were obtained by connecting tri- and tetracyclic quinazolinones—previously described as moderately active and unselective cholinesterase (ChE) inhibitors—via a hydroxyl group in para position to an anilinic nitrogen with different amines linked via a three carbon atom spacer. These tri- and tetracyclic quinazolinones containing different alicyclic ring sizes and connected to tertiary amines were docked to a high-resolution hAChE crystal structure to investigate the preferred binding mode in relation to results obtained by experimental structure–activity relationships. While the ‘classical orientation’ locating the heterocycle in the active site was rarely found, an alternative binding mode with the basic aliphatic amine in the active center (‘inverted’ orientation) was obtained for most compounds. Analyses of extended SARs based on this inverted binding mode are able to explain the compounds’ binding affinities at AChE.     

Structure–activity relationship studies on acremomannolipin A,the potent calcium signal modulator with a novel glycolipid structure 2: Role of the alditol side chain stereochemistry

Five alditol analogs 1b–1f of a novel glycolipid acremomannolipin A (1a), the potential Ca²⁺ signal modulator isolated from Acremonium strictum, were synthesized by employing a stereoselective β-mannosylation of appropriately protected mannose with five hexitols with different stereochemistry, and their potential on modulating Ca²⁺ signaling were evaluated. All these analogs were more potent compared to the original compound 1a, and proved that mannitol stereochemistry of 1a was not critical for the potent calcium signal modulating.     

Population-based survival analyses of central nervous system tumors from 1994 to 2008. An up-dated study in the temozolomide-era

The present population-based study describes the survival of malignant central nervous system (CNS) tumors diagnosed during 15 years. Also, we obtained individual data regarding the use of temozolomide to analyze the impact of this drug on the survival of patients diagnosed with glioblastoma. From 1994 to 2008, a total of 679 incident cases of primary CNS tumors were reported by the Girona Cancer Registry after excluding 39 cases diagnosed by death certificate only. Number of cases and the corresponding proportion for each CNS histological subtype in the study population were: 25 oligodendroglial and oligoastrocytics (3.7%), 22 ependymal tumors (3.2%), 24 embryonal (3.5%), 372 astrocytic (54.8%), 1 choroid plexus (0.1%) and 235 without histological confirmation (34.6%). Observed survival after 5 years since diagnosis for the histological subtype were: 58.8%; 47.5%; 37.0%; 14.5% and 6.5%, respectively (p < 0.001). Survival of patients diagnosed with glioblastoma according to temozolomide treatment (yes/no) was 60.8% vs. 13.6% and 5.9% vs. 2.5% after 1 and 5 years since diagnosis, respectively. Short-term survival was higher for patients diagnosed with glioblastoma and treated with temozolomide than patients not treated with temozolomide.     

Dipeptide interactions with Zn(II)–cyclen artificial model for molecular recognition

The Zn(II)–cyclen–dipeptide ternary systems (where cyclen is abbreviated as L and dipeptide is glycylglycine (HL¹) or glycyl‐(S)‐alanine (HL²)) were investigated by potentiometry applying both “out‐of‐cell” and direct titrations and by ¹H NMR spectroscopy. Especially, the ¹H NMR study was found to be very efficient to estimate speciation in the systems. The results obtained under full equilibria indicated two main species, [Zn(L)(HL^1,2)]²⁺ and [Zn(L)(L^1,2)]⁺, in both the systems. In the [Zn(L)(HL^1,2)]²⁺ complex, presence of carbonyl‐carboxylate chelate was confirmed, and in the [Zn(L)(L^1,2)]⁺ species, the peptide coordination is re‐organized to carbonyl‐amine chelate or only terminal amino group is coordinated. Equilibrium constants describing [Zn(L)]²⁺–dipeptide interaction are relatively low, log K = 3.4 for Gly‐Gly and 4.1 for Gly‐(S)‐Ala, respectively. Nevertheless, the values are slightly higher than stability constants for interaction of Zn(II) with the dipeptides (i.e. [Zn(L^1,2)]⁺ species) where a chelate formation is expected. It indicates that interaction between Zn(II) ion in [Zn(L)]²⁺ and the dipeptides should be supported by some additional interactions. Potentiometry carried out under non‐equilibrum condition showed different species where these additional stabilizing forces play more important role. Copyright © 2015 John Wiley & Sons, Ltd.     

Early warning signals as indicators of cyclostationarity in three-species hierarchies

Predicting stability from current ecosystem performance is theoretically difficult, but early statistical warning signals (EWS) may enable the anticipation of regime shifts. However, little is known regarding the behavior of EWS in shifts with cyclic dynamics. In this study, we use indicators to assess the stability of a three-species system in a competitive loop similar to a rock–paper–scissors (RPS) hierarchy. In two scenarios, the RPS is simulated using a 3-D automaton whose input matrix combines probabilities of pair-wise dominance with differential reaction frequencies. The first scenario uses the data of a microbial experiment in which the RPS hierarchy is characterized by incomplete dominance within species pairs and differences in reaction frequency between species pairs. The input of the second model was chosen to generate a contrasting scenario: a symmetric RPS interaction gradually subjected to a stressor. The reaction frequency of one species pair was modeled to decay linearly over time. The relative species abundances are monitored spatiotemporally. In the first scenario, abundances oscillate stably despite initial large swings, whereas in the second scenario, one species gradually dominates, eventually resulting in transitivity. In both scenarios, species cluster spatially in patches of single species. In scenario 1, the average patch size remains constant throughout the iterations and possibly contributes to the overall stability; however, in the second scenario, a further homogenization takes place. In the first scenario, EWS reflected the system's stability with species abundances settling into a stable basin. In scenario 1 only one of the EWS indicators detected consistently the loss of resilience. Sensitivity analysis revealed excessive variability in dominance resulted in immediate loss of the RPS hierarchy.