Comparative effects of trichothecene mycotoxins on bovine platelet function: Acetyl T-2 toxin,a more potent inhibitor than T-2 toxin

The effects of the trichothecene mycotoxins (acetyl T-2 toxin, T-2 toxin, HT-2 toxin, palmityl T-2 toxin, diacetoxyscirpenol (DAS), deoxynivalenol (DON), and T-2 tetraol) on bovine platelet function were examined in homologous plasma stimulated with platelet activating factor (PAF). The mycotoxins inhibited platelet function with the following order of potency: acetyl T-2 toxin > palmityl T-2 toxin = DAS > HT-2 toxin = T-2 toxin. While T-2 tetraol was completely ineffective as an inhibitor, DON exhibited minimal inhibitory activity at concentrations above 10×10^?4M. The stability of the platelet aggregates formed was significantly reduced in all mycotoxin treated platelets compared to that of the untreated PAF controls. It is suggested that the increased sensitivity of PAF stimulated bovine platelets to the more lipophilic mycotoxins may be related to their more efficient partitioning into the platelet membrane compared to the more hydrophilic compounds.     

Influence of the Carbohydrate Moieties on the Immunoreactivity and Digestibility of the Egg Allergen Ovomucoid

Background

Ovomucoid (OM) has two carbohydrate chains on each of the first and second domains and one in the third. The contribution of the covalently bound carbohydrate chains to the overall OM allergenicity is controversial. Another aspect directly related with the immunological properties of OM that has not been studied in depth is the importance of the carbohydrate chains on its digestibility.

Objective

The aim of the study was to assess the involvement of the carbohydrate moieties of OM in its digestibility and allergenic properties.

Methods

IgE-binding and basophil activation by glycosylated and enzymatically deglycosylated OM (dOM) were compared using blood from egg-allergic patients. The peptides obtained after digestion using a physiologically relevant model were identified by RP-HPLC-MS/MS and the IgE-binding of the resulting fragments was evaluated by DOT-Blot.

Results

No structural changes were observed after deglycosylation of OM. 80% of the patients showed lower IgE binding to dOM as compared with OM and, in some patients, IgE reactivity could not be inhibited by pre-incubation with dOM. A subtle reduction in the percentage of activated basophils was observed when incubated with dOM as compared to OM. Following simulated digestion, dOM was more extensively degraded than OM, particularly during the gastric phase and both, OM and dOM, yielded, after the duodenal phase, immunoreactive fragments that were totally or partially coincident with previously described epitopes.

Conclusion

& Clinical Relevance: this work demonstrated an enhanced IgE reactivity towards carbohydrate containing OM in some egg-allergic patients that could be attributed to cross-sensitization or sensitization to the glycosylated components. The carbohydrate chains contributed to an increased resistance to proteolysis, and thus, to its allergenic potency. Evaluation of the products of digestion of OM and dOM revealed the presence of high-frequency IgE-binding epitopes that could remain linked by disulphide bonds.     

Role of Catalase and Superoxide Dismutase Activities on Oxidative Stress in the Brain of a Phenylketonuria Animal Model and the Effect of Lipoic Acid

Phenylketonuria (PKU) is an inherited metabolic disorder caused by deficiency of phenylalanine hydroxylase which leads to accumulation of phenylalanine and its metabolites in tissues of patients with severe neurological involvement. Recently, many studies in animal models or patients have reported the role of oxidative stress in PKU. In the present work we studied the effect of lipoic acid against oxidative stress in rat brain provoked by an animal model of hyperphenylalaninemia (HPA), induced by repetitive injections of phenylalanine and α-methylphenylalanine (a phenylalanine hydroxylase inhibitor) for 7 days, on some oxidative stress parameters. Lipoic acid prevented alterations on catalase (CAT) and superoxide dismutase (SOD), and the oxidative damage of lipids, proteins, and DNA observed in HPA rats. In addition, lipoic acid diminished reactive species generation compared to HPA group which was positively correlated to SOD/CAT ratio. We also observed that in vitro Phe inhibited CAT activity while phenyllactic and phenylacetic acids stimulated superoxide dismutase activity. These results demonstrate the efficacy of lipoic acid to prevent oxidative stress induced by HPA model in rats. The possible benefits of lipoic acid administration to PKU patients should be considered.     

吐鲁番市胃食管反流病发生相关危险因素分析（附280例报道）

目的：探讨280例胃食管反流病（GERD）的分布特点及危险因素。方法：对临床诊断和胃镜确诊的280例GERD患者进行临床和风险因子相关性分析。结果：不论汉族还是维族,男性患者比例均明显高于女性;汉族患者高发年龄段早于维族患者（z=-2．939,P=0．003,）;汉族和维族患者占反流性食管炎和Barrett食管比例分别为42．4％、81_3％及56．5％、18．8％,其中汉族患者Barrett食管比例较高（X2=14．358,P=0．000）;肥胖、习惯性便秘、重体力活动者、饮食习惯不良在维族患者中的比例较高（P〈0．001）。结论：GERD与性别、年龄密切相关,男性多于女性,汉族患者发病年龄高峰旱于维族患者;汉族患者Barrett食管发生比例高于维族患者;肥胖、习惯性便秘、重体力活动、饮食习惯不良可能是GERD尤其是维族人群GERD的危险因素。     

Successful immunotherapy with matrix metalloproteinase-derived peptides in adjuvant arthritis depends on the timing of peptide administration

We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development of such therapies.     

Exploring Bacterioplankton Growth and Protein Synthesis to Determine Conversion Factors Across a Gradient of Dissolved Organic Matter

The effect of bacterial specific growth rates of abundance (micro) and protein synthesis (b) on conversion factor (CF) variability was explored in order to provide an alternative approach to the controversial application of just one universal CF to field data. Nine regrowth cultures (RCs) were set up from very diverse aquatic ecosystems, controlling temperature and adding N and P to avoid mineral limitation and force organic carbon limitation. The values of micro varied one order of magnitude from 0.26 to 3.34 d(-1), whereas b values varied two orders of magnitude from 0.28 to 34.87 d(-1). We found no relationships between micro or b values and the dissolved organic carbon (DOC) concentration or the dissolved organic matter (DOM) quality indexes assayed. Abundance and protein synthesis increased exponentially and synchronously in four RCs, leading to balanced growth (micro = b). In contrast, abundance and protein synthesis increased logistically in the other five RCs and b values were significantly higher than g values, leading to unbalanced growth (micro not equal b). CFs ranged from 0.0062 to 0.0576 x 10(18) cells mol leucine(-1) with an average of 0.0305 x 10(18) cells mol leucine(-1). CFs obtained in RCs with balanced growth were generally higher than CFs obtained in RCs with unbalanced growth and were not alike, impeding the establishment of an upper limit for CFs. A positive and significant relationship (n = 8, p < 0.0 1, r2 = 0.71) was found between CFs and DOC concentration (CF (x10(18) cells mol leucine(-1)) = 0.0104 + 0.0094 DOC (mM)) when the value for the most productive system was excluded. This function permits the estimation of site-specific CFs based on DOC concentration instead of the controversial use of a single CF for different systems.     

Characterization of terminal NeuNAcalpha2-3Galbeta1-4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis

Group B and C Neisseria meningitidis are the major cause of meningococcal disease in the United States and in Europe. N . meningitidis lipooligosaccharide (LOS), a major surface antigen, can be divided into 12 immunotypes of which L1 through L8 were found among Group B and C organisms. Groups B and C but not Group A may sialylate their LOSs with N-acetylneuraminic acid (NeuNAc) at the nonreducing end because they synthesize CMP-NeuNAc. Using sialic acid-galactose binding lectins as probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4, L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis leukoagglutinin (MAL), which recognizes NeuNAcalpha2- 3Galbeta1-4GlcNAc/Glc sequence, but not to Sambucus nigra agglutinin, which binds NeuNAcalpha2-6Gal sequence. The combination of SDS-PAGE and MAL-blot analyses revealed that these six LOSs contained only the NeuNAcalpha2-3Galbeta1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS components, which have a common terminal lacto-N-neotetraose (LNnT, Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) structure when nonsialylated as shown by previous studies. The LOS-lectin binding was abolished when the LOSs were treated with Newcastle disease viral neuraminidase which cleaves alpha2-->3 linked sialic acid. Methylation analysis of a representative LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal. Thus, these LOSs structurally mimic certain glycolipids, i.e., paragloboside (LNnT-ceramide) and sialylparagloboside and some glycoproteins in having LNnT and N-acetyllactosamine sequences, respectively, with or without alpha2-->3 linked NeuNAc. The molecular mimicry of the LOSs may play a role in the pathogenesis of N.meningitidis by assisting the organism to evade host immune defenses in man.      

Quantification of the phosphorus released by zooplankton in an oligotrophic lake (La Caldera, Spain): regulating factors and adjustment to theoretical models

Using an in situ approach, we have evaluated the phosphorusinputs from zooplankton in a high-mountain oligotrophic lake.Values of the specific gross release rate (SGRR) fluctuatedbetween 0.2 and 2.9 µg P mg^–1 dry weight h^–1,and were higher when the nauplii of Mixodiaptomus laciniatusdominated the zooplankton community. The rate of P recyclingby the zooplankton was high, reaching 1.6 µg P l^–1day^–1, and showed a highly consistent seasonal patternfrom one year to the next, with maxima in midsummer. Zooplanktonsize accounted for as much as 85% of the variance obtained inthe measurements of the specific rate of P release, while otherfactors, such as the quality or quantity of food, did not significantlyinfluence the SGRR changes. Among the models tested, only theone proposed by Peters (Int, Ver. Theor. Angew. Limnol. Verh.,19, 273–279, 1975) was useful for predictions in thissystem. The stoichiometric model of Hessen and Andersen (Arch.Hydrobiol., 35, 111–120, 1992), applied in this oligotrophicsystem, adequately predicted the phyto- and zooplankton dynamics,whereas the values of P release estimated using this model werefar higher than the excretion rates obtained experimentally.These differences were related to the type of egestion (formationof faecal pellets) of metazooplankton and to the relative importanceof the food resistance to digestion. We believe that in communitieswhere copepods constitute a substantial percentage of the zooplankton,an evaluation of the P release which is readily available [solublereactive phosphate (SRP), total dissolved phosphate (TDP)] toalgae and bacteria would not fit the predictions of generalmodels of mass balance; under these circumstances, assimilationefficiency proves to be the key parameter for predicting thereadily available P (excreted P).     

Roles of the main olfactory and vomeronasal systems in the detection of androstenone in inbred strains of mice

We investigated the role of the main olfactory and accessory olfactory systems (MOS and AOS respectively) in the detection of androstenone. We used the following experimental approaches: behavioral, surgical removal of the vomeronasal organ (VNX) followed by histochemical verification and Fos immunohistochemistry. Using a Y-maze paradigm we estimated sensitivity of NZB/B1NJ and CBA/J mice to androstenone. CBA mice were 2,000-fold more sensitive to androstenone than NZB mice. VNX caused a 4- to 16-fold decre...