Genetic variants in SLC22A1 are related to serum lipid levels in Mexican women

Dyslipidemia is the main risk factor for coronary artery disease and is characterized by alterations in concentrations of lipids, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triacylglycerols. The participation of several genes in the development of dyslipidemia has been evidenced. Genetic variants in SLC22A1 have been associated with elevated cholesterol and LDL-c levels. The aim of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) in the SLC22A1 gene with atherogenic risk lipid levels in Mexican women. Anthropometric and biochemical measurements were performed, and four SNPs in SLC22A1 were genotyped by real-time polymerase chain reaction. The Hardy–Weinberg equilibrium was verified, and haplotype frequencies were calculated. We found significant differences between the allele frequencies of the SNPs analyzed with those reported in Mexico and in the world, which could be due to differences in the historical admixture of the women studied. Generalized linear models were evaluated to determine the association between genotypes and haplotypes with lipids levels. We identified a significant increase in total cholesterol and LDL-c levels in women who were carriers of the GA and AG genotypes of the polymorphisms rs628031 and rs594709, respectively, significant effect that is also shown in a dominant inheritance model. Interestingly, we identified an important relationship of the AGC-GAT haplotype with the elevation in LDL-c levels and AGA-GAT haplotype with the elevation in HDL-c levels. On the other hand, we found a strong linkage disequilibrium between the polymorphisms studied. Our results show that variants in the SLC22A1 gene influence serum levels of atherogenic risk lipids, suggesting that these variants probably affect the function of organic cation transporter-1 and therefore, on the regulation of lipid metabolism.     

8302A/C and (TTA)n polymorphisms in the HMG-CoA reductase gene may be associated with some plasma lipid metabolic phenotypes in patients with coronary heart disease

HMG-CoA reductase (HMGCR) is a rate-limiting enzyme that participates in cholesterol metabolism. Here we analyzed the 8302A/C and the (TTA)n polymorphisms in the HMGCR gene in 169 Chinese patients with coronary heart disease (CHD) and 161 age-matched controls. Results indicated that the levels of plasma VLDL and TG in patients with the AA genotype of the 8302A/C locus were significantly higher than in patients with other genotypes (P<0.05). In addition, the frequency of allele A4 of the (TTA)n locus was higher (P<0.05) and the frequency of allele A5 was lower (P=0.002) in CHD patients than in the controls. This suggests that both polymorphisms in the HMGCR gene may be associated with lipid and lipoprotein abnormalities in CHD in the Chinese.     

EVALUATION OF A COMPOSITE BASED ON HIGH-DENSITY POLYETHYLENE FILLED WITH SURFACE-TREATED HYDROXYAPATITE

Summary  Composites properties are directly related to the degree of interaction between the plastic matrix and the inorganic filler. In the present work, the improvement of the composite’s properties by means of the addition of surface-treated and untreated hydroxyapatite (STHA and HA, respectively) was studied. An ethylene-acrylic acid copolymer was melt blended with high-density polyethylene and HA (HDPE/HA/EA). A surface treatment was performed using an ethylene-acrylic acid (EA) copolymer for STHA₁ and acrylic acid (AA) for STHA₂. High-density polyethylene (HDPE) was also tested. STHA₁ and STHA₂ composites exhibited Young’s modulus values (556 and 558 MPa, respectively) 22 % higher than that of HDPE/HA (455 MPa) and 8 % higher than that of HDPE/HA/EA (520 MPa). Additionally, STHA composites showed both yield stress and strain (σ_STHA1= 23 MPa; ε_STHA1= 9 %; σ_STHA2= 22 MPa; ε_STHA2= 10 %) having a remarkably different behavior from that of the HA composites, which showed no yielding at all. TEM micrographs showed better filler dispersion when surface treatment was applied to HA. Yet, the presence of EA copolymer exhibited a poorer thermal stability. The crystallinity degree as well as the crystallization and melting temperatures showed no significant variation. Regarding in vitro evaluation, composites with HA and EA copolymer proved to have better cell adhesion at early stages. The results of the STHA composites could be attributed to the electrostatic interactions taking place between the ethylene-acrylic acid copolymer and the polar groups of the HA.     

Dietary phospholipid alters biliary lipid composition in formula-fed piglets

Plasma cholesterol, arachidonic acid (AA, 20∶4n−6), and docosahexaenoic acid (DHA, 22∶6n−3) are higher in breast-fed infants than in infants fed formula without cholesterol, AA, or DHA. This study investigated differences in plasma, hepatic, and bile lipids and phospholipid fatty acids, and expression of hepatic proteins involved in sterol metabolism that result from feeding formula with cholesterol with egg phospholipid to provide AA and DHA. For this study, three groups of piglets were evaluated: piglets fed formula with 0.65 mmol/L cholesterol, the same formula with 0.8% AA and 0.2% DHA from egg phospholipid, and piglets fed sow milk. Piglets fed the formula with phospholipid AA and DHA had higher plasma high density lipoprotein, but not apoprotein (apo) B cholesterol or triglyceride; higher bile acid and phospholipid concentrations in bile; and higher liver and bile phospholipid AA and DHA than piglets fed formula without AA and DHA (P<0.05). Hydroxy methylglutaryl (HMG)-CoA reductase and 7-α-hydroxylase, the rate-limiting enzymes of cholesterol and bile acid synthesis, respectively, and low density lipoprotein receptor mRNA levels were not different between piglets fed formula without and with phospholipid AA and DHA, but HMG-CoA reductase and 7α-hydroxylase mRNA were higher, and plasma apo B containing lipoprotein cholesterol was lower in all piglets fed formula than in piglets fed milk. These studies show that supplementing formula with AA and DHA from egg phospholipid alters bile metabolism by increasing the bile AA and DHA, and bile acid and phospholipid.     

Common Variants of <Emphasis Type="Italic">ABCB4</Emphasis> and <Emphasis Type="Italic">ABCB11</Emphasis> and Plasma Lipid Levels: A Study in Sib Pairs with Gallstones,and Controls

Most epidemiological surveys have confirmed the association of low HDL-cholesterol and high triglyceride levels with cholesterol gallstones. Our objective was to analyze the relationship between plasma lipid levels and common polymorphisms of ABCB11 (encoding the bile salt export pump, BSEP) and ABCB4 (encoding the phospholipid transporter into bile, MDR3) genes. Plasma lipids were measured in 108 index patients of sib pairs with gallstones and in 260 controls. Using PCR-based assays with 5′-nuclease and fluorescence detection (TaqMan), the ABCB11 coding SNP p.A444V and four haplotype-tagging SNPs covering the ABCB4 gene (c.504C > T, c.711T > A, p.R652G, rs31653 in intron 26) were genotyped. Plasma lipids were compared in carriers of the common versus rare allele of these polymorphisms using Student’s t test and Pearson’s correlation. BMI and triglyceride levels were higher and HDL-cholesterol levels were lower in affected siblings than in controls. Among cases, triglyceride and cholesterol levels were higher in carriers of the common versus rare (hetero/homozygous carriers) allele of the SNPs p.A444V of ABCB11 and C.504C > T of ABCB4. HDL-cholesterol was lower in carriers of the common allele of rs31653. In controls, significant differences of cholesterol and HDL-cholesterol levels were found in carriers of ABCB4 polymorphisms. Our results do not support the hypothesis of a link between ABCB4 and ABCB11 polymorphisms, lithogenic dyslipidemia, and gallstone risk.     

Pinolenic Acid Downregulates Lipid Anabolic Pathway in HepG2 Cells

Pine nut oil (PNO) was reported to reduce lipid accumulation in the liver. However, the specific effect of pinolenic acid (18:3, all‐cis‐Δ5,9,12), a unique component of PNO, on lipid metabolism has not been studied. We hypothesized that pinolenic acid downregulates the lipid anabolic pathway in HepG2 cells. HepG2 cells were incubated in serum‐free medium supplemented with 50 μM bovine serum albumin (BSA), palmitic acid, oleic acid, γ‐linolenic acid, pinolenic acid, eicosapentaenoic acid (EPA), or α‐linolenic acid for 24 h. Lipid accumulation was determined by Oil Red O (ORO) staining. The mRNA levels of genes related to fatty acid biosynthesis (SREBP1c, FAS, SCD1, and ACC1), fatty acid oxidation (ACC2, PPARα, CPT1A, and ACADL), cholesterol synthesis (SREBP2 and HMGCR), and lipoprotein uptake (LDLr) and of genes that may be involved in the downregulation of the lipogenic pathway (ACSL3, ACSL4, and ACSL5) were determined by qPCR. LDLR protein levels were measured by Western blot analysis. The mRNA levels of SREBP1c, FAS, and SCD1 were significantly downregulated by pinolenic acid treatment compared to BSA control (53, 54, and 38 % lower, respectively). In addition, the mRNA levels of HMGCR, ACSL3, and LDLr were significantly lower (30, 30, and 43 % lower, respectively), and ACSL4 tended to be lower in the pinolenic acid group (20 % lower, P = 0.082) relative to the control group. In conclusion, pinolenic acid downregulated the lipid anabolic pathway in HepG2 cells by reducing expression of genes related to lipid synthesis, lipoprotein uptake, and the regulation of the lipogenic pathway.     

The impact of dietary mono‐ and poly‐unsaturated fatty acids on risk factors for atherosclerosis in humans

The fatty acid composition of the diet has various effects on atherosclerosis risk factors. Dietary saturated fatty acids (SFA) and trans‐unsaturated fatty acids increase the low‐density lipoprotein (LDL)‐/high‐density lipoprotein (HDL)‐cholesterol ratio in serum, while these fats do not have a significant bearing on serum triglyceride levels. By contrast, dietary monounsaturated fatty acids (MUFA), n‐6 polyunsaturated fatty acids (PUFA), and α‐linolenic acid (C18:3n‐3) similarly reduce LDL cholesterol concentrations, while their influence on serum HDL cholesterol and triglycerides is not appreciable. Dietary long‐chain n‐3 PUFA slightly increase serum LDL cholesterol concentrations, but are nevertheless considered salubrious with regard to serum lipids due to the distinct triglyceride‐lowering effects. MUFA‐rich compared to n‐6 PUFA‐rich diets strongly reduce the in vitro oxidizability of LDL. The available studies on this subject also suggest that n‐3 PUFA in the small amounts usually present in the diet are not unduly harmful. These findings are consistent with reports from observational studies: the amount of SFA is positively and the amount of MUFA and n‐6 PUFA in the diet is inversely associated with the risk of cardiovascular disease in most epidemiological studies. The available studies have had an impact on current dietary guidelines, which unanimously recommend that most of the dietary fat should be in the form of MUFA, while the amount of SFA and trans fatty acids in the diet should be as low as possible.     

Adsorptive removal of tetracycline from water using Fe (III)-functionalized carbonized humic acid

Humic acid (HA) was carbonized at 300, 400 and 500 ℃ and then functionalized with 1 wt%-12 wt% Fe(III) respectively [CHA300/400/500-Fe(III)]. Adsorption of such Fe(III)-functionalized carbonized HA as adsorbents to aqueous tetracycline (TC: 25 mg·L^-1) was studied. The adsorption equilibrium time for CHA400-Fe(III) to TC was 6 h faster and the adsorption removal efficiency (R_e) was two times higher than that of HA/CHA. The adsorption R e of CHA400-Fe(III) loaded 10% iron [CHA400-(10%)Fe(III)] to TC could reach 99.8% at 8 h and still kept 80.6% after 8 cycles. The adsorption kinetics were well fitted to the pseudo-second-order equation and the adsorption isotherms could be well delineated via Langmuir equations(R² > 0.99), indicating that the homogeneous chemical adsorption of TC occurred on the adsorbents. The main adsorption mechanisms of TC were complexation Fe(III) and hydrophobic distribution. Electropositive and electronegative repulsion between TC and CHA400-(10%)Fe(III) at lowly pH(2) and highly pH(8-10) respectively, leaded to the relatively low adsorption capacity and more notable influence of ion concentration. When the pH was between 4 and 8, TC mainly existed in neutral molecules (TCH₂), so the influence of ion concentration was not obvious. The dynamic adsorption results showed that the CHA400-(10%)Fe(III) could continuously treat about 2.4 L TC(27 mg·L^-1) wastewater with the effluent concentration as low as 0.068 mg·L^-1. Our study suggested a broad application prospect of a new, effective, lowcost and environment-friendly adsorbent CHA400-(10%)Fe(III) for treatment of low-concentration TC polluted wastewater.     

Preparation and characterization of a methyl methacrylate/ethyl acrylate/acrylic acid terpolymer to improve the homogeneity of ethylene–propylene–diene monomer rubber/poly(vinyl chloride) blends

The emulsion terpolymerization of methyl methacrylate (MMA), ethyl acrylate (EA), and acrylic acid (AA) was carried out under a nitrogen atmosphere at 70°C. The final terpolymer conversion was determined gravimetrically. The synthesized MMA–EA–AA terpolymer was characterized with ¹H‐NMR spectroscopy, thermal analysis, and gel permeation chromatography. Glass‐transition temperatures of the MMA–EA–AA terpolymer were determined with a differential scanning calorimeter. Ethylene–propylene–diene monomer rubber (EPDM)/poly(vinyl chloride) (PVC) blends were prepared with different blend ratios (10/90, 20/80, 30/70, 40/60, and 50/50) in the presence and absence of MMA–EA–AA as a compatibilizer. The morphology of those blends was examined with the aid of a scanning electron microscope. The scanning electron micrographs in the presence of the MMA–EA–AA terpolymer illustrated the disappearance of the macroscale phase separation of EPDM/PVC blends as a result of the incorporation of MMA–EA–AA into that blend, indicating an improvement of the homogeneity. The mechanical properties of the EPDM/PVC blend films and the dielectric properties of the melt blends were investigated. The swelling behavior of the cured blends in the brake fluid was also discussed. The results illustrated that the mechanical properties, the weight swelling values, and the dielectric constant values showed linear behavior versus the blend ratios after the incorporation of the terpolymer. However, those values showed deviations from linearity in the absence of the terpolymer. That, in turn, ensured the results obtained with the scanning electron microscope. The results reveal that the MMA–EA–AA terpolymer prepared can be used successfully to improve the homogeneity of EPDM/PVC blends used in hose and oil seal applications. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

n-3 fatty acids and lipoproteins: Comparison of results from human and animal studies

The impact of n-3 fatty acids (FA) on blood lipoprotein levels has been examined in many studies over the last 15 yr in both animals and humans. Studies in humans first demonstrated the potent triglyceride-lowering effect of n-3 FA, and these were followed up with animal studies to unravel the mechanism of action. This paper reviews the reported effects of n-3 FA on blood lipoproteins in 72 placebo-controlled human trials, at least 2 wk in length and providing 7 or less g of n-3 FA/day. Trials in normolipidemic subjects (triglycerides <2.0 mM; 177 mg/dL) were compared to those in hypertriglyceridemic patients (triglycerides ≥2.0 mM). In the healthy subjects, mean triglyceride levels decreased by 25% (P<0.0001), and total cholesterol (C) levels increased by 2% (P<0.009) due to the combined increases in low density lipoprotein (LDL)-C (4%,P<0.02) and high density lipoprotein (HDL)-C (3%,P<0.008). In the patients, triglyceride levels decreased by 28% (P<0.0001), LDL-C rose by 7% (P<0.0001), but neither total C nor HDL-C changed significantly. Although the effect on triglyceride levels is also observed in rats and swine, it is rarely seen in mice, rabbits, monkeys, dogs, and hamsters. Whereas n-3 FA have only a minor impact on lipoprotein C levels in humans, they often markedly lower both total C and HDL-C levels in animals, especially monkeys. These differences are not widely appreciated and must be taken into account when studying the effects of n-3 FA on lipoprotein metabolism.     

Hypoglycemic Effects of Crude Polysaccharide from Purslane

The effects of crude polysaccharide from Purslane (CPP) on body weight (bw), blood glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglyceride (TG) and serum insulin levels were studied in diabetes mellitus mice. CPP treatment (200, 400 mg/kg bw) for 28 days resulted in a significant decrease in the concentrations of fasting blood glucose (FBG), TC and TG. Furthermore, CPP significantly increased the concentration of HDL-c, body weight and serum insulin level in the mice. In addition, according to acute toxicity studies and single cell gel electrophoresis analysis, CPP did not produce any physical or behavioral signs of toxicity. More significantly, our data demonstrated CPP exhibited the best effects at the dose of 400 mg/kg bw. The above results suggest that CPP can control blood glucose and modulate the metabolism of glucose and blood lipids in diabetes mellitus mice, so we conclude that CPP should be evaluated as a candidate for future studies on diabetes mellitus.     

Acrylate–vinylidene chloride copolymers derived from corresponding water‐borne latexes: Influence of acrylate units on their potential as heavy‐duty anticorrosive coating materials

A series of aqueous latexes with solid contents of 56%–59% were synthesized by binary emulsion copolymerization of vinylidene chloride (VDC) with an acrylate, namely methyl acrylate (MA), ethyl acrylate (EA), butyl acrylate (BA), hexyl acrylate (HA), or 2‐ethylhexyl acrylate (EHA). Differential scanning calorimetry (DSC) and Fourier‐transform infrared (FTIR) spectroscopy showed that the acrylate units with short ester side‐chains, such as MA and EA, made the copolymers hard and the crystallization tendency of their PVDC segments was reduced. Hydrophobic acrylates with relatively long ester groups, such as HA and EHA, gave flexible copolymers, and favored the crystallization of their PVDC segments. BA endowed the copolymers with medium flexibility and crystallization tendency. As coating materials, the copolymers bearing MA and EA adhered poorly to the tinplate before or after 100 hr of salt‐spray corrosion, whereas those bearing BA, HA, or EHA showed good adhesion to tinplate when they had little or no crystallinity. After 100 hr of salt‐spray corrosion, only BA–VDC80, containing 80% VDC, retained both excellent adhesion to metal and excellent barrier performance. Further study demonstrated that BA–VDC80 could protect tinplate from rusting for at least 250 hr under harsh salt‐spray corrosion. Scanning electron microscopy, FTIR‐attenuated total reflectance spectroscopy and DSC were used to evaluate the corroded BA–VDC80 film. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014 , 131, 40192.     

The effect of different proportions of casein in semipurified diets on the concentration of serum cholesterol and the lipoprotein composition in rabbits

The effect of different proportions of casein in semipurified diets on the concentation of serum cholesterol and the lipoprotein composition was studied in rabbits. Low-casein diets (10% w/w) resulted in serum cholesterol levels and growth rates that were lower than high-casein diets (40%). An intermediate proportion of casein (20%) produced intermediate concentrations ofserum cholesterol, but only minor differences in food intake and weight gain, compared with the high-casein group. In the animals with the highest values of total serum cholesterol (the 40% casein group), most of the serum cholesterol was transported in the very low density lipoproteins, whereas with moderate hypercholesterolemia (the 20% casein group), the low density lipoproteins were the main carriers of cholesterol. Elevation in lipoprotein cholesterol was associated in all groups with an increased ratio of cholesterol to protein, suggesting the formation of particles relatively rich in cholesterol. When the rabbits on the diet containing 10% casein were subsequently transferred to the 40% casein diet, a steep increase in the level of serum cholesterol occurred. Conversely, switching the rabbits on the 40% casein diet to the 10% casein diet resulted in a decrease in the level of serum cholesterol.     

Increase of Serum Cholesterol Levels by Heat-Moisture-Treated High-Amylose Cornstarch in Rats Fed a High-Cholesterol Diet

The effects of four cornstarches containing various contents of resistant starch on serum and liver cholesterol levels in rats fed a high-cholesterol diet were investigated. Male Sprague Dawley rats (aged 4 weeks) were divided into four groups (n = 7) and fed high-cholesterol diets containing 15% of cornstarch (CS), heat-moisture-treated CS (HCS), high-amylose CS (HA), or heat-moisture-treated HA (HHA) for 21 days. The results showed that the serum and hepatic level of total cholesterol, LDL-cholesterol, and triglyceride in rats of the HHA group and their arteriosclerosis index were significantly higher, suggesting that HHA increases the risk of arteriosclerosis under a high-cholesterol dietary condition. No significant between-group differences were noted in the levels of plasma mevalonic acid and hepatic HMG-CoA reductase mRNA, whereas fecal cholesterol excretion was significantly higher in the HHA group, indicating that the elevation of the serum and liver cholesterol levels was not due to the promotion of liver cholesterol synthesis and cholesterol absorption in the intestine.     

Celastrus Orbiculatus Thunb. Reduces Lipid Accumulation by Promoting Reverse Cholesterol Transport in Hyperlipidemic Mice

Previously, we found that Celastrus orbiculatus Thunb. (COT) decreases athero‐susceptibility in lipoproteins and the aorta of guinea pigs fed a high‐fat diet, and increases high‐density lipoprotein (HDL). In the present study, we investigated the effect of COT in reducing lipid accumulation and promoting reverse cholesterol transport (RCT) in vivo and vitro. Healthy male mice were treated with high‐fat diet alone, high‐fat diet with COT (10.0 g/kg/d), or general fodder for 6 weeks. Serum levels of total cholesterol (TC), triglyceride (TG), HDL‐C, non‐HDL‐C, and ³H‐cholesterol in plasma, liver, bile, and feces were determined. Pathological changes and the levels of TC and TG in liver were examined. The expression of hepatic genes and protein associated with RCT were analyzed. COT administration reduced lipid accumulation in the liver, ameliorated the pathological changes, and lessened liver injury, the levels of TG, TC, and non‐HDL‐C in plasma were decreased significantly, and COT led to a significant increase in plasma HDL‐C and apolipoprotein A (apoA1). ³H‐cholesterol in plasma, liver, bile, and feces was also significantly increased in COT‐treated mice compared to controls. Both mRNA and protein expression of SRB1, CYP7A1, LDLR, ATP‐binding cassette transporters ABCA1, ABCG5, and LXRα were improved in COT‐treated mice. An in vitro isotope tracing experiment showed that COT and its bioactive ingredients, such as celastrol, ursolic acid, oleanolic acid, and quercetin, significantly increased the efflux of ³H‐cholesterol. They also increased the expression of SRB1, ABCA1, and ABCG1 significantly in macrophages. Our findings provided a positive role of COT in reducing lipid accumulation by promoting RCT. These effects may be achieved by activating the SRB1 and ABC transporter pathway and promoting cholesterol metabolism via the CYP7A1 pathway in vivo. The effective ingredients in vitro are celastrol, ursolic acid, oleanolic acid, and quercetin.     

Adsorptive removal of tetracycline from water using Fe(III)-functionalized carbonized humic acid

Humic acid (HA) was carbonized at 300, 400 and 500 °C and then functionalized with 1 wt%–12 wt% Fe(III) respectively [CHA300/400/500-Fe(III)]. Adsorption of such Fe(III)-functionalized carbonized HA as adsorbents to aqueous tetracycline (TC: 25 mg·L⁻¹) was studied. The adsorption equilibrium time for CHA400-Fe(III) to TC was 6 h faster and the adsorption removal efficiency (R_e) was two times higher than that of HA/CHA. The adsorption R_e of CHA400-Fe(III) loaded 10% iron [CHA400-(10%)Fe(III)] to TC could reach 99.8% at 8 h and still kept 80.6% after 8 cycles. The adsorption kinetics were well fitted to the pseudo-second-order equation and the adsorption isotherms could be well delineated via Langmuir equations(R² > 0.99), indicating that the homogeneous chemical adsorption of TC occurred on the adsorbents. The main adsorption mechanisms of TC were complexation Fe(III) and hydrophobic distribution. Electropositive and electronegative repulsion between TC and CHA400-(10%)Fe(III) at lowly pH(2) and highly pH(8–10) respectively, leaded to the relatively low adsorption capacity and more notable influence of ion concentration. When the pH was between 4 and 8, TC mainly existed in neutral molecules (TCH₂), so the influence of ion concentration was not obvious. The dynamic adsorption results showed that the CHA400-(10%)Fe(III) could continuously treat about 2.4 L TC(27 mg·L⁻¹) wastewater with the effluent concentration as low as 0.068 mg·L⁻¹. Our study suggested a broad application prospect of a new, effective, low-cost and environment-friendly adsorbent CHA400-(10%)Fe(III) for treatment of low-concentration TC polluted wastewater.     

Morphological core/shell structure and dispersion stability of water-dispersible copolyester graft polymerized with acrylic acid and ethyl acrylate

Anionic water-dispersible copolyester was prepared by the polycondensation of dimethyl isophathalate (DMI)/5-sodium sulfo dimethyl isophathalate (DMS) with ethylene glycol (EG)/ diethylene glycol (DEG) to synthesize water-dispersible copolyester-g-AA/EAs by chemical method. In the case of graft polymerization of AA/EA onto DMI/DMS/EG/DEG copolyester does not. This is a result of the core/shell structure that was ascertained by the graft yield and the zeta potential of copolyester-g-AA/EAs. It appears that grafted AA/EA exists at the surface of copolyester-g-AA/EA particles, and the backbone polymer, i.e., DMI/DMS/EG/DEG copolyester, exists in the inner phase of the copolyester, -g-AA/EA particles. The complete solubility of copolyester-g-AA/EAs in 1N NaOH aqueous solution seems to come mainly from the electrostatic repulsion between  COOs that are present at the surface of copolyester-g-AA/EA particles due to AA grafting and  OHs that are present at the dispersion medium due to NaOH decomposition and which cause the hydrolytic breakage and consequently the coagulation of copolyesters in alkaline medium. © 1996 John Wiley & Sons, Inc.     

Interactions of Meibum and Tears with Mucomimetic Polymers: A Hint towards the Interplay between the Layers of the Tear Film

Recent clinical findings suggest that mucomimetic polymers (MMP) can alter not only the texture of the aqueous tear but also the spreading and structure of the tear film (TF) lipid layer, thereby allowing for their synchronized performance in vivo. Thus, we aimed to evaluate in vitro (i) the capability of pharmaceutically applicable MMP to ensure the formation of post-evaporative ferning patterns (a characteristic feature of the “healthy” tear colloid) and (ii) the MMP interactions with human meibum films accessed in the course of blink-like deformations via Langmuir surface balance and Brewster angle microscopy (BAM). Four MMP were used- hyaluronic acid (HA), cross-linked hyaluronic acid (CHA), carboxymethyl cellulose (CMC) and gellan gum (GG)- at the concentrations of 0.0001%, 0.001%, 0.01%, 0.05% and 0.1%. Significant differences were observed in the MMP fern formation capability: CHA (≥0.001%) > HA (≥0.01%) = CMC (≥0.01%) > GG (≥0.05%). All MMP affected the spreading of meibum, with BAM micrographs revealing thickening of the films. CHA was particularly efficient, showing concentration-dependent enhancement of tear ferning and of meibomian layer structure, surfactant properties and viscoelasticity. Thus, endogenous and exogenous MMP may play key roles for the concerted action of the TF layers at the ocular surface, revealing novel routes for TF-oriented therapeutic applications.     

Hypolipidemic activity of 6-alkoxycarbonyl-3-aryl-1,3,5-triazabicyclo[3.1.0]hexane-2,4-diones and 2-alkoxycarbonyl-5-aryl-1,3,5-triazine-4,6(1H,5H)-diones in rodents

Significant hypolipidemic activity was demonstrated by 6-ethoxycarbonyl-3-phenyl-1,3,5-triazabicyclo[3.1.0]hexane-2,4-dione, 2-ethoxycarbonyl-5-phenyl-1,3,5-triazine-4,6(1H,5H)-dione and 2-ethoxycarbonyl-5-(4-chlorophenyl)-1,3,5-trizine-4,6(1H,5H)-dione in rodents at 20 mg/kg/day. These agents lowered serum cholesterol and triglyceride levels by approximately 40% in mice after 16 d. Tissue lipids in rat liver, small intestinal mucosa, aortic wall and feces were reduced by treatment with the agents. Very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol levels were reduced in the rat; high density lipoprotein (HDL) cholesterol levels were elevated after 14 d of treatment. The activities of regulatory enzymes,e.g., acetyl-CoA synthetase, acyl-CoA:cholesterol acyltransferase, cholesterol 7α-hydroxylase,sn-glycerol-3-phosphate acyltransferase, phosphatidylate phosphohydrolase and heparin-induced lipoprotein lipase, involved inde novo synthesis of hepatic lipids were affected by the agents. The new compounds may represent another class of potentially useful hypolipidemic agents for the treatment of atherosclerosis since HDL cholesterol levels were increased and VLDL and LDL cholesterol levels were lowered by some of the agents.     

Thermosensitive hydrogels for modified release of ellagic acid obtained from Alchemilla vulgaris L. extract

Stimulus-sensitive hydrogels are used as carriers for modified release of pharmaceuticals. The synthesis of thermosensitive hydrogels poly(N-isopropylacrylamide), p(NIPAM), and poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate), p(NIPAM-HPMet), is performed. The synthesized hydrogels are characterized using FTIR and scanning electron microscope methods and swelling properties, and applied for modified release of ellagic acid (EA). This work presents the selective extraction of EA, as a natural antioxidant, from the aerial parts of Alchemilla vulgaris L. EA and A. vulgaris extract are incorporated into p(NIPAM) and p(NIPAM-HPMet) hydrogels and characterized by FTIR method. The EA content in the extract by the UHPLC–DAD–HESI–MS/MS method is determined (0.64?mg?cm^?3). The total flavonoids content in the A. vulgaris extract was determined by the spectrophotometric method. Antioxidant activity of the A. vulgaris extract and EA is examined using the 2,2-diphenyl-1-picrylhydrazyl assay. The p(NIPAM-HPMet) shows a better incorporation and release at 37°C of EA standard and A. vulgaris extract (98.87 and 96.45% respectively), compared with p(NIPAM).