Amyloid β (Aβ) peptides have long been viewed as a potential target for Alzheimer's disease (AD). Aggregation of Aβ peptides in the brain tissue is believed to be an exclusively pathological process. Therefore, blocking the initial stages of Aβ peptide aggregation with small molecules could hold considerable promise as the starting point for the development of new therapies for AD. Recent rapid progresses in our understanding of toxic amyloid assembly provide a fresh impetus for this interesting approach. Here, we discuss the problems, challenges and new concepts in targeting Aβ peptides.

Objectives To evaluate the necessity of multiple salivary pepsin tests within a day when diagnosing laryngopharyngeal reflux. Study Design Prospective cohort study. Setting Tertiary hospitals. Methods A total of 138 patients with signs and/or symptoms associated with laryngopharyngeal reflux were included. Salivary pepsin was detected on the day of 24-hour pH monitoring, and the results of salivary pepsin detected once in the morning and multiple times in 1 day were compared with the results of pH monitoring. Results Among the 138 patients, pH monitoring results were positive in 112. Salivary pepsin was positive in 47 cases in the morning, which was not consistent with the results of pH monitoring (kappa value = 0.117). With the pH monitoring results as the standard, the salivary pepsin detected once in the morning had a sensitivity of 38.4% (43/112) and a specificity of 84.6% (22/26) for the diagnosis of laryngopharyngeal reflux. When salivary pepsin was detected multiple times per day, 102 patients tested positive. The consistency with pH monitoring was moderate (kappa value = 0.587). The sensitivity was 86.6% (97/112), and the specificity was 80.8% (21/26). Of the 97 patients with positive results from pH monitoring and salivary pepsin detected multiple times a day, 54 had negative findings for a single detection in the morning, indicating that 55.7% (54/97) of the true positive cases were missed. Conclusion Although a single detection of salivary pepsin in the morning is more economical, the sensitivity is too low, and it is necessary to detect it multiple times a day.

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Objective: To study the value of multitime point salivary pepsin testing (MTPSPT) for the diagnosis of laryngopharyngeal reflux (LPR).Study Design: Prospective noncontrolled.Methods: For patients who met the enrollment criteria, the reflux symptom index (RSI) and reflux finding score (RFS) were calculated and salivary pepsin testing was performed. The pepsin test was performed every hour from 7:00 a.m. to 6:00 p.m. by collecting fresh saliva samples. A single positive test result was needed for the diagnosis of LPR. The consistency in the diagnosis of LPR between the two methods was compared with the weighted Cohen's kappa statistic.Results: A total of 204 patients were included. The kappa value between the two methods was 0.566 (p = .00). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MTPSPT were 76.43%, 85.94%, 92.24%, and 62.5%, respectively. We also compared a single pepsin measure at 7 a.m. with the screening results based on the RSI and RFS, and found a much lower kappa agreement value (0.223, p = .00). The sensitivity, specificity, PPV, NPV, and false-negative rate of pepsin testing at 7 a.m. (fasting) were 37.86%, 92.18%, 91.38%, 40.41%, and 58.57%, respectively. Conclusion:The use of the result of a single salivary pepsin test in the morning yields a relatively higher rate of missed diagnosis of LPR, and multitime point testing through a day increased the accuracy and sensitivity of detection of LPR twofold compared to a single morning fasting sample.

Although the exact pathogenesis of Alzheimer's disease (AD) remains to be fully defined, several pharmacological strategies for preventing and treating AD are under active investigation. More recently, drug design has targeted molecular events involved in the pathogenesis of AD including b-amyloid (Ab) and neurofibrillary tangle formation. [1][2][3] In in vitro studies, Leveugle 1,4) has shown that heparin oligosaccharides (known as a type of glycosaminoglycans (GAGs)) pass through a blood-brain barrier (BBB) model in a molecular weight-dependent manner and inhibit amyloid b precursor protein processing, suggesting their potential effects against AD.As an analogue of low molecular weight GAGs, acidic oligosaccharide sugar chain (AOSC), an anti-Alzheimer's disease drug candidate, is currently undergoing preclinical evaluation. AOSC bearing rich mannuronate blocks is an acidic marine-derived oligosaccharide extracted from the brown algae Echlonia Kurome Okam by enzymatic depolymerization and has an average molecular weight of about 1300 Da. We have demonstrated that AOSC can alleviate Alzheimer-type behavioral symptoms induced by scopolamine and Ab1-40 in rodent models. The mechanisms of action underlying the cognition-improving activities of AOSC have been illustrated to be attributed to the inhibition of apoptosis, and thus, neurotoxicity via binding to Ab peptide. 5,6) Given that AOSC has a promising therapeutic value for AD, the ability of AOSC to pass through the BBB becomes crucial for understanding its direct central nerve system (CNS) effects.The detection of oligosaccharides has traditionally been performed on TLC, GC, HPLC, and capillary electrophoresis. However, there exist limitations due to the polydisperse and diversiform nature of oligosaccharides, and particularly the interference of endogenous GAGs. Moreover, these analytical methods require many clean up steps and are often time-consuming. Antibody-based methods have been developed as a favorable alternative for either the identification or quantification of oligosaccharides.7) Antibodies are often used in the detection of oligosaccharides in immunoassays for these compounds, 8,9) and enzyme-linked immunosorbent assay (ELISA) is the most commonly used.Recently, the surface plasmon resonance (SPR) biosensor assay has become increasingly recognized to be an accurate method for identifying the interaction between antibody and antigen.10,11) Compared with conventional methods such as ELISA and fluorescence enzyme immunoassay, 12,13) it possesses several inherent advantages. A particular advantage of SPR assay is there is no need to label reactants, allowing 'real-time' detection of biomolecular interactions, which has attracted considerable attention due to its easy and specific recognition of antigen-antibody (antigen-antibody interaction). Other advantages are easy sample preparation, fully automated operation, short-time analysis, and small amount of sample consumption, which are of particular relevance when the interested components are difficult...

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Glucokinase (GK) and fructose-1,6-bisphosphatase (FBPase) play crucial role in glucose metabolism. In the present study, the cDNA encoding GK and FBPase was cloned from the liver of turbot Scophthalmus maximus by rapid amplification of cDNA end technique. Effects of dietary glucose and dextrin on the activities and gene expressions of these two enzymes were also studied. Results showed that the full length of GK cDNA was 2226 bp, consisting of an open reading frame (ORF) of 1434 bp. The full-length cDNA coding FBPase was 1314 bp with a 1014 bp ORF encoding 337 amino acids. Analyses of gene expression of GK and FBPase were conducted in gill, liver, the whole intestine, the whole kidney, heart, the dorsal white muscle and brain. The highest expression of GK was found in liver, followed by muscle. The expression of FBPase was found higher in liver than heart and gill. Both hepatic GK activity and mRNA expression were highly induced in turbot after being fed with dietary carbohydrates (p < 0.05). However, the GK activity and mRNA expression in the group with dietary glucose did not significantly differ from those in the group with dietary dextrin (p > 0.05). Compared with the control group, there were no significant differences in FBPase activity and mRNA expression in the glucose as well as dextrin group (p > 0.05). The increased hepatic GK activity and gene expression indicated that the first step of glycolysis was activated in turbot by dietary carbohydrates.

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