Overview of the potent cyanobacterial neurotoxin β-methylamino-L-alanine (BMAA) and its analytical determination

Blue-green algae are responsible for the production of different types of toxins which can be neurotoxic, hepatotoxic, cytotoxic and dermatotoxic and that can affect both aquatic and terrestrial life. Since its discovery the neurotoxin β-methylamino-L-alanine (BMAA) has been a cause for concern, being associated with the neurodegenerative disease amyotrophic lateral sclerosis/Parkinsonism–dementia complex (ALS/PDC). The initial focus was on Guam where it was observed that a high number of people were affected by the ALS/PDC complex. Subsequently, researchers were surprised to find levels of BMAA in post mortem brains from Canadian patients who also suffered from ALS/PDC. Recent research demonstrates that BMAA has been found at different levels in the aquatic food web in the brackish waters of the Baltic Sea. There is emerging evidence to suggest that sand-borne algae from Qatar can also contain BMAA. Furthermore, there is now concern because BMAA has been found not only in warmer regions of the world but also in temperate regions like Europe. The aim of this review is to focus on the methods of extraction and analysis of the neurotoxic non-protein amino acid BMAA. We also consider the neurotoxicity, aetiology, and diverse sources and routes of exposure to BMAA. In recent years, different methods have been developed for the analysis of BMAA. Some of these use HPLC-FD, UPLC-UV, UPLC-MS and LC-MS/MS using samples that have been derivatised or underivatised. To date the LC-MS/MS approach is the most widely used analytical technique as it is the most selective and sensitive method for BMAA determination.     

Combining strategies to optimize a gel formulation containing miconazole: the influence of modified cyclodextrin on textural properties and drug release

Background: Miconazol, an antimycotic drug, is commonly formulated into semisolid formulations designed to be applied in the oral cavity to treat oral candidiasis. However, given its limited aqueous solubility, permeation through the biological membranes is low and therefore its activity is also limited. Cyclodextrins (CDs) have been widely used to increase the solubility and stability of poorly water-soluble drugs. Aim: The aim of this study is to formulate a gel containing an inclusion complex between a modified CD, methyl-β-cyclodextrin (MβCD), and miconazole (MCZ). The influence of the CD on the textural properties of the prepared gel and the drug release from formulation were evaluated. Methods: The gels were prepared using two polymers, Carbopol 71G and Pluronic F127, which were selected taking into account their bioadhesiveness and thermal-sensitive gelling properties, respectively. Texture profile analyses were performed at two different temperatures to ascertain the influence of the temperature on the gel texture properties. The in vitro MCZ release profiles from the prepared gel and the commercial gel formulations were evaluated and compared using modified Franz diffusion cells. Results: The addition of MβCD to the gel resulted in a decrease of the gel adhesiveness and firmness, and the MCZ release profile through f1 and f2 proved to be similar to the commercial product. Conclusions: A gel comprising miconazol in the form of an inclusion complex with MβCD showed suitable textural properties to be applied to the buccal mucosa. The MβCD enhanced the solubility of the MCZ in the gel formulation resulting in adequate in vitro drug release profiles.     

Anisotropic thermal expansion behaviors of copper matrix in β-eucryptite/copper composite

A β-eucryptite/copper composite was fabricated by spark plasma sintering process. The thermal expansion behaviors of Cu matrix of the composite were studied by in situ X-ray diffraction during heating process. The results show that Cu matrix exhibits anisotropic thermal expansion behaviors for different crystallographic directions, the expansion of Cu{1 1 1} plane is linear in the temperature range from 20 °C to 300 °C and the expansion of Cu{2 0 0} is nonlinear with a inflection at about 180 °C. The microstructures of Cu matrix before and after thermal expansion testing were investigated using transmission electronic microscope. The anisotropic thermal expansion behavior is related to the deformation twinning formed in the matrix during heating process. At the same time, the deformation twinning of Cu matrix makes the average coefficient of thermal expansion of the composite increase.     

β-甲基萘氧化合成维生素K3(1,4-甲萘醌)的研究进展

综述近年来国内外氧化合成1,4-甲萘醌(维生素K3)的研究发展,目的是寻求绿色高效的合成方式。作为目前较热点的过氧化氢的氧化方式,探索最佳的氧化剂/催化剂体系以及反应类型是关键,希望通过综述方法能对1,4-甲萘醌合成的研究起到一定的帮助。     

A novel insight to screen the optimal spray-drying protectants and parameters for manufacturing lactic acid bacteria preparations

Abstract

This study constructed a β-galactosidase (β-gal) liposome model instead of bacterial cells to optimize spray-drying protectants and parameters. The screened protectant combination consisted of 35?g/L monosodium glutamate, 50?g/L sucrose, and 35?g/L maltodextrin. The optimal parameters for spray drying were 130?°C inlet air temperature, 7.5?mL/min feed flow rate, and 150?mL optimal protectant combination. The viability of the five lactic acid bacteria strains spray-dried with the optimized protectant and parameters was over 50%. Lactobacillus helveticus strain LH-9’s mechanism of resistance to spray-dry treatment was investigated in the presence of the optimal protectant combination.     

Fibroblast growth factor-21 (FGF21) administration to early-lactating dairy cows. II. Pharmacokinetics,whole-animal performance,and lipid metabolism

Dairy cows cope with severe energy insufficiency in early lactation by engaging in intense and sustained mobilization of fatty acids from adipose tissue. An unwanted side effect of this adaptation is excessive lipid accumulation in the liver, which in turn impairs hepatic functions. Mice experiencing increased hepatic fatty acid flux are protected from this condition through coordinated actions of the newly described hormone fibroblast growth factor-21 (FGF21) on liver and adipose tissue. The possibility of an analogous role for FGF21 in dairy cows is suggested by its rapid increase in plasma levels around parturition followed by chronically elevated levels in the first few weeks of lactation. To test this hypothesis, dairy cows were randomly assigned on d 12.6 ± 2.2 (± standard error) of lactation to receive either an excipient (control; n = 6) or recombinant human FGF21 (n = 7), first as an FGF21 bolus of 3 mg/kg of body weight (BW) followed 2 d later by a constant i.v. infusion of FGF21 at a rate of 6.3 mg/kg of metabolic BW for 9 consecutive days. After bolus administration, human FGF21 circulated with a half-life of 194 min, and its constant infusion increased total plasma concentration 117-fold over levels in excipient-infused cows. The FGF21 treatment had no effect on voluntary feed intake, milk yield, milk energy output, or net energy balance measured over the 9-d infusion or on final BW. Plasma fatty acids circulated at lower concentrations in the FGF21 group than in the control group for the 8-h period following bolus administration, but this reduction was not significant during the period of constant i.v. infusion. Treatment with FGF21 caused a 50% reduction in triglyceride content in liver biopsies taken at the end of the constant i.v. infusion without altering the mRNA abundance of key genes involved in the transport, acyl coenzyme A activation, or oxidation of fatty acids. In contrast, FGF21 treatment ablated the recovery of plasma insulin-like growth factor-1 seen in control cows during the 9-d i.v. infusion period despite a tendency for higher plasma growth hormone. This effect was associated with increased hepatic mRNA abundance of the intracellular inhibitor of growth hormone receptor trafficking, LEPROT. Overall, these data confirm the ability of FGF21 to reduce lipid accumulation in bovine liver and suggest the possibility that FGF21 does so by attenuating the hepatic influx of adipose tissue-derived fatty acids.     

The X-prolyl dipeptidyl-peptidase PepX of Streptococcus thermophilus initially described as intracellular is also responsible for peptidase extracellular activity

This study addresses the hypothesis that the extracellular cell-associated X-prolyl dipeptidyl-peptidase activity initially described in Streptococcus thermophilus could be attributable to the intracellular X-prolyl dipeptidyl-peptidase PepX. For this purpose, a PepX-negative mutant of S. thermophilus LMD-9 was constructed by interrupting the pepX gene and named LMD-9-ΔpepX. When cultivated, the S. thermophilus LMD-9 wild type strain grew more rapidly than its ΔpepX mutant counterpart. Thus, the growth rate of the LMD-9-ΔpepX strain was reduced by a factor of 1.5 and 1.6 in milk and LM17 medium (M17 medium supplemented with 2% lactose), respectively. The negative effect of the PepX inactivation on the hydrolysis of β-casomorphin-7 was also observed. Indeed, when incubated with this peptide, the LMD-9-ΔpepX mutant cells were unable to hydrolyze it, whereas this peptide was completely degraded by the S. thermophilus LMD-9 wild type cells. This hydrolysis was not due to leakage of intracellular PepX, as no peptide hydrolysis was highlighted in cell-free filtrate of wild type strain. Therefore, based on these results, it can be presumed that though lacking an export signal, the intracellular PepX might have accessed the β-casomorphin-7 externally, perhaps via its galactose-binding domain-like fold, this domain being known to help enzymes bind to several proteins and substrates. Therefore, the identification of novel distinctive features of the proteolytic system of S. thermophilus will further enhance its credibility as a starter in milk fermentation.     

Viscosity reduction of isotonic solutions of the photosensitizer TPCS2a by cyclodextrin complexation

Meso-tetraphenyl chlorin disulphonate (TPCS_2a) is a photosensitizer (PS) particularly developed and patented for use in the technology of photochemical internalization (PCI) against cancer. TPCS_2a is known to aggregate in aqueous media even at low concentrations (≥0.1?µM) and to form a high-viscosity network at clinically relevant concentrations (mM). The aim of this work was to evaluate the effect of two hydroxypropylated cyclodextrin derivatives of beta and gamma type, respectively i.e. HPβCD and HPγCD, on the aggregation and solubilization of TPCS_2a in isotonic solutions. Samples containing micromolar concentrations of TPCS_2a were studied spectrophotometrically, while samples containing a clinical relevant concentration (10?mM?=?9?mg/ml) of TPCS_2a were evaluated by dynamic viscosity measurements. HPβCD was determined to be a more suitable solubilizer of TPCS_2a than HPγCD in aqueous media both in the absence and presence of salt. The complexation stoichiometry between TPCS_2a/HPβCD at micromolar to millimolar concentrations of TPCS_2a was determined to be 1:3 and 1:2 in the absence and presence of isotonic NaCl, respectively. The network of TPCS_2a (10?mM) was broken down in the presence of 3% w/v (=?20?mM) HPβCD, i.e. a 1:2 molar ratio between TPCS_2a and the cyclodextrin. Formation of the inclusion complex resulted in low viscosity samples both in water and in the presence of isotonic NaCl or phosphate buffered saline (PBS) at 25?°C and 37?°C.