, Metal chelation, radical scavenging and inhibition of Aβ 42-fibrillation by food constituents in relation to Alzheimer's disease, Food Chemistry (2015), doi: http://dx.doi.org/10.1016/j.foodchem. 2015.11.118 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 1 These authors contributed equally to this work. Metal chelation, radical scavenging and inhibition of Aβ Abstract Various food constituents have been proposed as disease-modifying agents forAlzheimer's Disease (AD), due to epidemiological evidence of their beneficial effects, and for their ability to ameliorate factors linked to AD pathogenesis, namely by: chelating iron, copper and zinc; scavenging reactive oxygen species; and suppressing the fibrillation of amyloid-beta peptide (Aβ). In this study, nine different food constituents (L-ascorbic acid, caffeic acid, caffeine, curcumin, (−)-epigallocatechin gallate (EGCG), gallic acid, propyl gallate, resveratrol, and α-tocopherol) were investigated for their effects on the above factors, using metal chelation assays, antioxidant assays, and assays of Aβ 42 fibrillation. An assay method was developed using 5-Br-PAPS to examine the complexation of Zn(II) and Cu(II).EGCG, gallic acid, and curcumin were identified as a multifunctional compounds, however their poor brain uptake might limit their therapeutic effects. The antioxidants L-ascorbic acid and α-tocopherol, with better brain uptake, deserve further investigation for specifically addressing oxidative stress within the AD brain.

Abstract:Osmolytes have been proposed as treatments for neurodegenerative proteinopathies including Alzheimer's disease. However, for osmolytes to reach the clinic their efficacy must be improved. In this work, copper(I)-catalyzed azide-alkyne cycloaddition chemistry was used to synthesize glycoclusters bearing six copies of trehalose, lactose, galactose or glucose, with the aim of improving the potency of these osmolytes via multivalency. A trehalose glycocluster was found to be superior to monomeric trehalose in its ability to retard the formation of amyloid-beta peptide 40 (Aβ40) fibrils and protect neurons from Aβ40-induced cell death. Keywords:Alzheimer's disease amyloid beta-peptides click chemistry glycoclusters osmolytes Alzheimer's disease (AD) is the most common neurodegenerative disorder and the leading cause of dementia.1 Currently, only symptomatic treatments are available and there is an urgent need for a disease-modifying drug.2 According to the modified amyloid cascade hypothesis, 3 AD is caused by small, soluble aggregates of amyloidbeta peptide (Aβ) which are highly neurotoxic. 4 It follows that one strategy to combat AD is to minimize the exposure of neurons to these aggregates and approaches to achieve this include: a) inhibiting the production of Aβ; 5,6 b) inhibiting Aβ aggregation; 7 c) promoting off-pathway aggregation that produces non-toxic Aβ aggregates; 8 and d) improving clearance of Aβ. 9,10 Recently, osmolytes have been proposed as treatments for neurodegenerative proteinopathies including AD. 11 Osmolytes are small organic molecules that protect intracellular macromolecules from denaturation caused by environmental stresses such as perturbing solutes, dehydration, desiccation, extreme temperature, and high hydrostatic pressure.12-14 There are three major categories of stabilizing osmolytes: carbohydrates; amino acids; and methylammonium/methylsulfonium compounds. 12,13 Many carbohydrate osmolytes have been found both to inhibit Aβ aggregation and to attenuate Aβ-induced neurotoxicity. Trehalose inhibits Aβ40/42 aggregation, dissociates pre-formed Aβ40/42 aggregates and decreases the toxicity of Aβ40. 15,16 Similarly, polymers carrying trehalose suppress Aβ40/42 fibril formation and reduce Aβ40/42-induced cytotoxicity.17,18 Myo-, scyllo-, and epi-inositol stabilize a nonfibrillar Aβ42 structure and attenuate Aβ42-induced neurotoxicity.19-21 Fructose inhibits fibrillogenesis of Aβ40/42 22 and attenuates Aβ42-induced neurotoxicity. 23 In many of these cases, the carbohydrate osmolytes were active at millimolar concentrations and for them to become viable treatments for AD their effectiveness must be improved. It is well established that weak interactions between proteins and carbohydrates can be amplified by constructing multivalent carbohydrate ligands and this phenomenon is known as the "cluster glycoside effect". 24,25 However, very few studies have investigated whether this phenomenon applies to carbohydrate osmolyte-Aβ interactions and then only for high MW glycopolymers. 17,18 ...

Counterfeit and substandard medicines are recognized as one of serious threats to public health. The product quality of antibacterial medicine will compromise patients’ recovery and increase the chance of antibacterial resistance. The review aims to provide a summary of low quality levofloxacin issues and the risk factors as well as suggesting the aspects of product quality that need to be regulated strictly. Quality of the active ingredient, levofloxacin, has an important role to contribute to successful therapy. The poor quality of raw material, directly and indirectly, causes treatment failure as the presence of insufficient dose, mislabeled content, and poor dissolution characteristics can lead to lower bioavailability. Identifying and reporting these factors can potentially help in improving the quality of drug marketed in various developing countries and may also reduce the incidences of treatment failure. Dissolution test is used for testing the dissolution profiles and the rate of drug release from solid formulation such as oral formulations, thus providing information regarding the in vivo performance of a formulation and its bioequivalence. On the other hand, quality-testing procedures are used for comparing the quality of products.