Electrospray synthesis of PLGA TIPS microspheres

We successfully demonstrate the synthesis of polymer microspheres using a single electrospray source, and show their physical characterisation. Electrospray has proven to be a versatile method to manufacture particles, giving tight control over size with quasi-monodisperse size distributions. It is a liquid atomisation technique that generates a monodisperse population of highly charged liquid droplets over a broad size range (nanometres to tens of microns). The droplets contain liquid precursors for the in-flight synthesis of particles, and control over the trajectory of these droplets can be precisely manipulated with the use of electric fields to drive them to a grounded substrate. This study reports a method to synthesize poly(lactic-co-glycolic) acid (PLGA) microspheres using the electrospray and thermally induced phase separation (TIPS) techniques, followed by subsequent freeze-drying, for particle production. These microspheres are of interest as vehicles for controlled drug release systems

Effects of ursodeoxycholic acid on synthesis of cholesterol and bile acids in healthy subjects

Background/Aims: Ursodeoxycholic acid ( UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methyl-glutarylcoenzyme A reductase and cholesterol 7alpha-hydroxylase, respectively, in normal subjects during UDCA feeding. Methods: UDCA was given to 8 healthy volunteers ( 5 men, 3 women; age 24-44 years) in a single dose of 10-15 mg/kg body weight for 40 days. Before and during ( days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7alpha-hydroxy-4-cholesten-3-one (7alpha-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman's rank correlation coefficient were used for statistical analysis. Results: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7alpha-HCO serum concentrations from 39.7 +/- 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 +/- 30.4 ng/ml (median 77.5 ng/ml) at days 30-40 of UDCA treatment ( p < 0.05). Conclusions: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy

Synthesis AndCharacterization of 2,3,4-Trihydroxy-5-methyl Xanthone as Antimalarial Compound

Synthesis of xanthone derivatives had been conducted to obtain new antimalaria active compounds. The characterization of the synthesized xanthones was also conducted.Synthesis of xanthone was conducted from the raw material of hydroxybenzoic acid and phenol derivatives using Eaton\u27s reagent via acylation-dehydration reaction by modified Grover, Shah and Shah (GSS) method. The synthesis of 2,3,4-trihydroxy-5-methyl xanthone was carried out using gallic acid, o-cresol and Eaton\u27s reagent.The mixture was heated for 3 h at 80 °C to yield2,3,4-trihydroxy-5-methyl xanthone in 43% yield as dark red viscous liquid. The results of IR, 1H-NMR and 13C-NMR analysis of sampleshowed that the compound2,3,4-trihydroxy-5-methyl xanthonehas successfully synthesized

Searching for Bayesian Network Structures in the Space of Restricted Acyclic Partially Directed Graphs

Although many algorithms have been designed to construct Bayesian network structures using different approaches and principles, they all employ only two methods: those based on independence criteria, and those based on a scoring function and a search procedure (although some methods combine the two). Within the score+search paradigm, the dominant approach uses local search methods in the space of directed acyclic graphs (DAGs), where the usual choices for defining the elementary modifications (local changes) that can be applied are arc addition, arc deletion, and arc reversal. In this paper, we propose a new local search method that uses a different search space, and which takes account of the concept of equivalence between network structures: restricted acyclic partially directed graphs (RPDAGs). In this way, the number of different configurations of the search space is reduced, thus improving efficiency. Moreover, although the final result must necessarily be a local optimum given the nature of the search method, the topology of the new search space, which avoids making early decisions about the directions of the arcs, may help to find better local optima than those obtained by searching in the DAG space. Detailed results of the evaluation of the proposed search method on several test problems, including the well-known Alarm Monitoring System, are also presented

Synthesis and Properties of Ethoxylated Glycerol Monooleate as Palm Oil Based Nonionic Surfactants

Palm oil based nonionic surfactants were synthesized by reacting glycerol monooleate with ethylene oxide at 80 ºC in the prescence of an alkaline catalyst. Purification of the products was conducted by use of acetic acid and black carbon which gave ethoxylated products (EGMO) with a higher level of viscocity and greater solubility in water. Physical and chemical properties of the product such as surface activity, cloud point, acid value, ester value, hydroxyl value, and hydrophilic-lipophilic balance was also determined and results varied depending on the reagent molar ratio. The synthesized EGMO were soluble in water and therefore show potential use as surface active agents in personal care and cosmetic products

Ascorbic acid enhances the inhibitory effect of aspirin on neuronal cyclooxygenase-2-mediated prostaglandin E2 production.

Inhibition of neuronal cyclooxygenase-2 (COX-2) and hence prostaglandin E2 (PGE2) synthesis by non-steroidal anti-inflammatory drugs has been suggested to protect neuronal cells in a variety of pathophysiological situations including Alzheimer's disease and ischemic stroke. Ascorbic acid (vitamin C) has also been shown to protect cerebral tissue in a variety of experimental conditions, which has been attributed to its antioxidant capacity. In the present study, we show that ascorbic acid dose-dependently inhibited interleukin-1beta (IL-1beta)-mediated PGE2 synthesis in the human neuronal cell line, SK-N-SH. Furthermore, in combination with aspirin, ascorbic acid augmented the inhibitory effect of aspirin on PGE2 synthesis. However, ascorbic acid had no synergistic effect along with other COX inhibitors (SC-58125 and indomethacin). The inhibition of IL-1beta-mediated PGE2 synthesis by ascorbic acid was not due to the inhibition of the expression of COX-2 or microsomal prostaglandin E synthase (mPGES-1). Rather, ascorbic acid dose-dependently (0.1-100 microM) produced a significant reduction in IL-1beta-mediated production of 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a reliable indicator of free radical formation, suggesting that the effects of ascorbic acid on COX-2-mediated PGE2 biosynthesis may be the result of the maintenance of the neuronal redox status since COX activity is known to be enhanced by oxidative stress. Our results provide in vitro evidence that the neuroprotective effects of ascorbic acid may depend, at least in part, on its ability to reduce neuronal COX-2 activity and PGE2 synthesis, owing to its antioxidant properties. Further, these experiments suggest that a combination of aspirin with ascorbic acid constitutes a novel approach to render COX-2 more sensitive to inhibition by aspirin, allowing an anti-inflammatory therapy with lower doses of aspirin, thereby avoiding the side effects of the usually high dose aspirin treatment

Research of influence of technological processing parameters of protein-fat base for supply of sportsmen on activity of protease inhibitors

The object of research is the biological value of the protein-fat base for athletes, workers of heavy physical labor, military personnel, depending on the conditions of its preliminary processing. A technological audit, the purpose of which was to determine the change in the content of amino acids after enzymatic hydrolysis in samples of the protein-fat base, that had undergone pretreatment by microwave radiation, was conducted. The effectiveness of the protein-fat base pretreatment by microwave radiation was evaluated on the amount of α-amino nitrogen after enzymatic hydrolysis. Based on the analysis of the obtained data, the optimal conditions of the protein-fat base pretreatment were established: 250–350 seconds of microwave treatment time and its hydration to the 12–14 % of moisture content. Such processing will increase the biological value of the protein-fat base, namely, increase the degree of digestion and digestibility of proteins in the gastrointestinal tract

Remodeling Of The Bone Tissue Of Rats Of Different Lines After Melatonin Effect

The markers of remodeling of bone tissue (BT) were studied after the impact of pharmacologic dose of melatonin (5 mg/kg of the animal body weight) during 28 days for 3-months rats-males of Wistar and SHR lines. The studies were carried out in autumn. The aim of our work was to study the indices of bone tissue remodeling of rats of Wistar and SHR lines after introduction of pharmacologic dose of exogenous melatonin.Biochemical and immune-enzyme methods of analysis were used in the study. In rats of Wistar line was revealed a reliable increase of activity of alkaline phosphatase (ALP) by 43,9% (Р&lt;0,05), hyaluronidase activity (HA) by 15,4% and free thyroxin concentration (fТ4) by 30%. There was also registered the decrease of pyridinoline (PYD) concentration by 48% and glycosaminoglycan (GAG) by 46,7%. In rats of SHR line under the same conditions the results essentially differed. The activity of acid phosphatase (ACP) has a tendency to increase by 11,6%, and PYD concentration decreased by 25%. The concentrations of free triiodothyronine (fТ3) and fТ4 reliably increased by 51,3% and 31,1% respectively.In the result of research we revealed that melatonin plays the main role among several main factors of regulation of bone tissue remodeling. It has stimulating influence on bone tissue and hormones of thyroid gland

Synthesis of hippuric acid in liver homogenate

The synthesis of hippuric acid from benaoic acid and glycine resembles in several respects the synthesis of a peptide bond. A CONH group is formed, it is a to a carboxyl group, and the free energy of its formation is of the same order of magnitude. The synthesis was demonstrated in liver and kidney slices of a number of animals; it is inhibited by 0.001 M KCN, which is in accord with the view that the necessary free energy is derived from an oxidation.(1