Lipids

This paper presents a new manufacturing method to generate monodisperse microbubble contrast agents with polydispersity index (σ) values of <2% through microfluidic flow-focusing. Micronsized lipid shell-based perfluorocarbon (PFC) gas microbubbles for use as ultrasound contrast agents were produced using this method. The poly(dimethylsiloxane) (PDMS)-based devices feature expanding nozzle geometry with a 7 μm orifice width, and are robust enough for consistent production of microbubbles with runtimes lasting several hours. With high-speed imaging, we characterized relationships between channel geometry, liquid flow rate Q, and gas pressure P in controlling bubble sizes. By a simple optimization of the channel geometry and Q and P, bubbles with a mean diameter of <5 μm can be obtained, ideal for various ultrasonic imaging applications. This method demonstrates the potential of microfluidics as an efficient means for custom-designing ultrasound contrast agents with precise size distributions, different gas compositions and new shell materials for stabilization, and for future targeted imaging and therapeutic applications.

In epidemiological studies, hypopituitary adults show increased mortality compared with population controls. Patients with hypopituitarism caused by a craniopharyngioma (CP) and/or its treatment have a higher mortality than patients with other etiologies, such as a non-functioning pituitary adenoma (NFPA). In order to analyze this difference, we used the KIMS database (Pfizer International Metabolic Database) comparing CP and NFPA patients in terms of baseline characteristics and responses to GH replacement.

Although GH replacement improves the features of GH deficiency (GHD) in adults, it has yet to be established whether cessation of GH at completion of childhood growth results in adverse consequences for the adolescent with GHD. Effects of continuation or cessation of GH on body composition, insulin sensitivity, and lipid levels were studied in 24 adolescents (13 males, 11 females, aged 17.0 ؎ 0.3, yr, mean ؎ SE, puberty stage 4 or 5) in whom height velocity was less than 2 cm/yr. Provocative testing confirmed severe GHD [peak GH < 9 mU/liter (3 g/liter)] in all cases and was followed by a lead-in period of 3 months during which the pediatric dose of GH continued unchanged. Baseline investigations were then performed using dual-energy x-ray absorptiometry (body composition), lipid measurements, and assessment of insulin sensitivity by both homeostasis model assessment and a short insulin tolerance test. Twelve patients remained on GH (0.35 U/kg⅐wk), and 12 patients ceased GH treatment. The groups were followed up in parallel with repeat observations made after 6 and 12 months.

This prospective, randomized study investigated the effect of exercise on leptin, insulin, cortisol and lipid profiles in obese children. A total of 40 obese boys aged 10-12 years with a body mass index (BMI) ≥ 30 kg/m 2 were randomly separated into an exercise group (n = 20) that underwent a 12-week aerobic exercise programme and a non-exercise (control) group (n = 20). The BMI, low-density lipoprotein, cortisol, leptin and insulin levels were significantly lower in the exercise group after 12 weeks compared with baseline values, whereas highdensity lipoprotein levels were significantly higher. In contrast, in the control group, low-density lipoprotein, cortisol and leptin levels were significantly higher after 12 weeks compared with baseline values while high-density lipoprotein levels were significantly lower. These findings indicate the importance of regular exercise in the regulation of body weight and protection against cardiovascular risk factors in obese children.

The aim of this study was to determine the extent of accumulation of lipoprotein(a) [Lp(a)] in human arterial wall and to define its potential role in atherogenesis. Biopsies routinely taken from the ascending aorta of 107 patients undergoing aortocoronary bypass surgery were analyzed for lipid and lipoprotein parameters, which were then correlated to serum values. A significant positive correlation was established between serum Lp(a) and arterial wall apolipoprotein (apo)(a) by enzyme-linked immunosorbent assay. High serum Lp(a) also led to a significant increase of apo B in the arterial wall. No significant correlation was found between apo B in serum and aortic tissue. Apo B was found to be partially linked to apo(a) in the aortic extract. Furthermore, apo(a) was found to be intact, as determined by its molecular weight in sodium dodecyl sulfate electrophoresis. This technique also revealed that the apo(a) isoform pattern of aortic homogenate was comparable to the individual seru...

Mannophosphoinositides appear to be widespread among the Actinomycetales. Besides the well-known mycobacterial source, they are also present in streptomyces, microbispora (Kataoka & Nojima, 1967; Tabaud, Tisnovska & Vilkas, 1971), nocardias (Yano, Furukawa & Kusunose, 1969) and corynebacteria (Brennan & Lehane, 1971) and a related phosphorusfree inannoinositide is prominent in propionibacteria (Prottey & Ballou, r968; Shaw & Dinglinger, I 969). Prompted by the unusual observation of a monomannophosphoinositide in Corynebacterium aquaticirm (Khuller & Brennan, 1972) we have examined in more detail three species of Nocardia, and find that niannophosphoinositides, which are always of the dirnannosyl type, are barely evident in Nocardia polychromogenes, whereas in N. coeliaca, they are among the most obvious phospholipids. Glucose-containing phospholipids and glycolipids are always prominent. Bacteria used were : Nocardia polychromogenes Jensen from the Shinogi Research Laboratorics, Osaka, Japan; N. polychromogenes NRRLB-I 5 I 3 from the Department of Antibiotics, National Institutes of Health, Japan; and N. coeliaca ATCC 131 81. They were grown in a medium containing glucose, polypeptone and yeast extract (Yano et al. 1969). Lipids were

The aim of the present study was to prepare, optimize and characterize ketoprofen proniosomes. The niosomes were prepared using a slurry method followed by in vitro evaluation after embedding the proniosomes-derived niosomes into a carbopol matrix. A central, composite Box-Wilson design was used for the optimization with the total lipid concentration (X 1 ), surfactant loading (X 2 ) and amount of drug (X 3 ) as the independent variables. Prepared proniosomes were characterized for percentage drug entrapment (PDE) and mean volume diameter (MVD). Multiple regression analysis and contour plots were used to relate the dependent and independent variables. Checkpoint batches were also prepared to prove the validity of the evolved mathematical model and contour plots. The optimization model predicted the levels of X 1 , X 2 and X 3 (-1, -0.3 and 0.92, respectively), for a maximized response of PDE with constraints of ≤ 5 μm on MVD. Optimized batch was used to prepare a niosomal gel, which showed significantly higher cumulative amount of drug permeated and steady state transdermal flux compared to plain gel. This work has demonstrated the use of the central composite Box-Wilson design, regression analysis, and contour plots in optimizing ketoprofen proniosomes. Developed niosomal gel formulation has also demonstrated permeation enhancement of ketoprofen compared to plain gel.

Positive effect of thyroid hormone replacement (THR) on lipid profile is well defined. Effectiveness of THR on lipid profile and function among elderly patients with subclinical hypothyroidism (SCH) has not yet been concluded. This is a population-based cross-sectional study. Twenty-six elderly patients with SCH were compared with 31 patients with clinical hypothyroidism (CH). Before the study neither group had received THR therapy. Data on lipid profile, demographic, functional, and cognitive status were obtained at baseline. SCH was defined as an elevated thyroid-stimulating hormone (TSH) level (>4.67 mU/l) and normal serum free thyroxine (FT 4) level. Total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were measured after overnight fast. The level of lower density lipoprotein (LDL) cholesterol was calculated. Both studied groups received levothyroxyne replacement and re-evaluated after 3 months of euthyroidism. Functional and cognitive status were evaluated by the activity of daily living (ADL) and mini mental state evaluation (MMSE), respectively. Participants with SCH did not differ from patients with CH regarding age, gender, cognitive, and functional status, and prevalence of cardiovascular disease (CD) was similar in both groups. Most patients (24/26) with SCH had TSH levels lower than 10 mU/l. Response to THR therapy regarding the improvement of blood levels of TC, LDL, and TG had a non-significant trend, which seemed to be better in patients with SCH than in those with CH. Decreases, TC/HDL and LDL/HDL ratios were greater in patients SCH (p < 0.0001 and p = 0.0004, respectively) than in patients with CH.

Fifty-seven type 2 diabetic patients with metabolic syndrome and on insulin were assessed by a paired analysis before and 6 months after addition of metformin as combination therapy to evaluate the impact of the association on glycemic control, blood pressure, and lipid profile. This was a historical cohort study in which the files of type 2 diabetic patients with metabolic syndrome on insulin were reviewed. The body mass index (BMI), waist circumference, lipid profile, A1C level, fasting blood glucose level, daily dose of NPH insulin, systolic blood pressure, and diastolic blood pressure were assessed in each patient before the start of metformin and 6 months after the initiation of combination therapy. Glycemic control significantly improved (P < 0.001) after the addition of metformin (1404.4 ± 565.5 mg/day), with 14% of the 57 patients reaching A1C levels up to 7%, and 53% reaching values up to 8%. There was a statistically significant reduction (P < 0.05) of total cholesterol (229.0 ± 29.5 to 214.2 ± 25.0 mg/ dL), BMI (30.7 ± 5.4 to 29.0 ± 4.0 kg/m 2), waist circumference (124.6 ± 11.7 to 117.3 ± 9.3 cm), and daily necessity of insulin. The reduction of total cholesterol occurred independently of the reductions of A1C (9.65 ± 1.03 to 8.18 ± 1.01%) and BMI and the reduction of BMI and WC did not interfere with the improvement of A1C. In conclusion, our study showed the efficacy of the administration of metformin and insulin simultaneously without negative effects. No changes were detected in HDL-cholesterol or blood pressure.

Cyclosporine (CsA), commercially available as iv or oral Sandimrnune, is a potent immunosuppressant which can induce doserelated nephrotoxocity. In addition, the iv product contains a solubilizing agent, Cremophore EL, which in itself is reported to be nephrotoxic and can induce, in sensitized patients, anaphylactic reactions. Solubilization of CsA with liposomes or lipid emulsions could provide a suitable alternative dosage form for iv administration. With this in mind, male New Zealand white rabbits were given iv CsA (10 mglkg) in three different dosage forms: (7) CsA:liposornes; (2) CsA:lntralipid (soybean oil and phospholipids); and (3) the commercially available Sandimmune (cyclosporine). The CsA concentration in whole blood samples was analyzed by HPLC. The terminal disposition half-life of CsA (t,,, p) ranged from 400 to 475 min and was not statistically different among the three groups. However, the distribution characteristics of CsA changed dramatically depending on the dosage form. The volume of distribution of CsA at steady state (Vd,,) in Sandimmune was 2.7 ? 0.2 Ukg and was significantly lower than that of either lntralipid (10.6-+ 2.7 Ukg) or liposomes (7.4-+ 2.3 Ukg). A significantly lower total body clearance (TBC) of CsA also was seen for Sandimmune (1 2.7 f 0.3 rnuminlkg) as compared with that of either lntralipid (24.4 f 8.2 mUminlkg) or liposomes (18.9 5 3.9 mUmin1kg). Since CsA is extensively bound to lipoproteins, it is surprising that both test vehicles showed a different distribution pattern. It is speculated that in addition to the benefit of removing Cremophore EL from the product, the different distribution of CsA:liposomes or CsA:lntralipid may prove useful in altering the nephrotoxocity and immunosuppression of CsA during iv therapy.

Purpose To develop a tumor-targeted drug delivery system based on solid lipid nanoparticles (SLNs) conjugated with the enzymatically cleavable polyethylene glycol (PEG). Methods SLNs loaded with paclitaxel (PTX) were prepared using the film ultrasonication method, followed by conjugation with a PEGylated peptide (Pp) that can specifically interact with matrix metalloproteinases (MMPs) that is over-expressed by tumor cells. The physicochemical characteristics of the Pp-PTX-SLNs were studied and the in vitro drug release, cytotoxicity and cell uptake of the formulations were investigated. Furthermore, using an animal model, the pharmacokinetic properties, biodistribution and anti-tumor activity of this system were evaluated.

Background: 1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH) 3 , in several clinical trials for melanoma, breast, and lung cancer. During early clinical development this mAb was obtained in vivo from mice ascites fluid. Currently, the production process of 1E10 is being transferred from the in vivo to a bioreactor-based method.

The scarcity of sizeable specimens of normal oral mucosa for experimental purposes has hampered research on oral epithelium. Because large specimens of viable human vaginal mucosa are readily available and because vaginal and buccal epithelia are microscopically similar, vaginal mucosa has been used successfully to establish a human cyst model in experimental animals. The ultrastructure and distribution of keratin filaments in these epithelia are also similar, as is their permeability to water and a number of chemical substances. Therefore, if vaginal mucosa could be substituted for buccal mucosa it would expedite research on the epithelium of buccal mucosa. To strengthen further the concept that vaginal epithelium could replace buccal epithelium in certain experimental studies, the thickness of these epithelia, their patterns of surface keratinization, the presence or absence of intercellular lipid lamellae and their lipid contents were now compared. Thirty-three specimens of vaginal mucosa from postmenopausal women and 36 of buccal mucosa were investigated. To compare the thickness of the epithelial layers the number of cell layers in sections of 20 vaginal and 20 buccal mucosal specimens were counted in the three thickest and three thinnest regions of each specimen. Surface keratinization was evaluated on sections stained with the Picro-Mallory method. To demonstrate lipid lamellae two vaginal and two buccal mucosa specimens were examined electron microscopically after normal fixation and postfixation in ruthenium tetroxide. Following solvent extraction of 11 vaginal and 14 buccal epithelia, quantitative lipid analyses were performed using thin-layer chromatography. No statistically significant differences were found between the maximum and minimum number of epithelial cell layers. The patterns of surface keratinization and the distribution and appearance of the lipid lamellae in the intercellular spaces were similar. The lipid composition of the two epithelia corresponded, except for the cholesterol esters and glycosylceramides, which were higher in buccal epithelium. Ceramides for vaginal epithelium and triglycerides for buccal epithelium were not determined. Based on structural similarities, a similar lipid composition and earlier findings, it is concluded that vaginal epithelium can be used as a substitute for buccal epithelium in certain in vitro, and possibly for in vivo, studies.

Fibrinogen IS an important risk factor for atherosclerosis, stroke and cardiovascular heart disease (CHD). This risk is increased when associated with a high serum cholesterol. Furthermore, it is also believed that not only fibrinogen concentration, but also the quality of fibrin networks may bean important risk factor for the development of CHD. CHD and stroke as a result of atherosclerosis, plus the related problems of hyperinsulinaemia,hyperlipidaemia and hypertensionare strongly related to diet. The "western" diet, defined by low fibre and high fat, sucrose and animal protein intakes, appears to be a major factor leading to death. It has been established that the water-soluble dietary fibre, pectin, significantly decrease the concentration of serum cholesterol levels. Evidence is also accumulating that a diet rich in fibre may protect against diseases associated with raised clotting factors. This investigation studied the possible effects of pectin on fibrinogenlevels and fibrin network architecture. Two groups of 10 male hyperlipidaemicvolunteerseach, received a pectin supplement ( 15g/day)or placebo ( 15rg/day) for 4 weeks. Lipid and fibrin network structure variables were measured at baseline and the end of supplementation. Pectin supplementation caused significant decreases in total cholesterol, low-density lipoproteincholesterol, , apolipoproteinA & B and lipoprotein (a). Significant changes in the characteristics of fibrin networks developed in the plasma of the pectin supplemented group indicated that networks were more permeable and had lower tensile strength. These network structures are believed to be less atherogenic. It is suspected that pectin modified network characteristics by a combinationof its effects on metabolism and altered fibrin conversion. This confirms the therapeutic possibilities of dietary intervention. Furthermore, this stud} also showed that changes in plasma fibrinogen need not be present to induce alterations in fibrin network architecture. 01997Elsevier

A novel high-rate anaerobic reactor, called ''Buoyant Filter Bioreactor'' (BFBR), has been developed for treating lipid-rich complex wastewater. The BFBR is able to decouple the biomass and insoluble COD retention time from the hydraulic retention time by means of a granular filter bed made of buoyant polystyrene beads. Filter clogging is prevented by an automatic backwash driven by biogas release, which fluidizes the granular filter bed in a downward direction. During filter backwash, the solids captured in the filter are reintroduced into the reaction zone of the reactor. The reaction zone is provided with a mixing system, which is independent of the hydraulic retention time.

Cereals are an important part of diets for hypercholesterolemic patients. However, some of these patients are allergic to these natural products. The purpose of the current study was to compare oatmeal with equal in nutritional values two allergy-free amaranth meals to determine whether this pseudocereal can be a substitute for allergic to cereals individuals. The total phenols of the samples were determined with the Folin-Chocalteu reagent, anthocyanins, and flavonoids spectrophotometrically. The antioxidant activities were estimated with nitric oxide scavenging radical (NO) and by ␤-carotene bleaching (␤-carotene). It was found that the contents of different protein fractions, antioxidant compounds, and the antioxidant activities of oatmeal were significantly higher than those of the two amaranth samples. The results of kinetic reactions showed that samples differed in their capacities to quench these radicals, and oats have shown more antioxidant activity than amaranth. High correlation was observed between antioxidant activities and phenols (R 2 ϭ 0.99). In the in vivo part of the investigation, 60 male Wistar rats were divided into five diet groups of 12 animals each; these groups were designated as Control, Chol, Chol/Oat, Chol/AmarI, and Chol/AmarII. The rats of the Control group were fed basal diet (BD) only. To the BD of the four other groups were added the following: 1% of cholesterol (Chol), 10% of oat meal and 1% of cholesterol (Chol/Oat), 10% of amaranth I meal, and 1% of cholesterol (Chol/AmarI) and 10% of amaranth II meal and 1% of cholesterol (Chol/AmarII). After 32 days of different feeding, diets supplemented with oat meal and, to lesser degree, with amaranth I and amaranth II hindered the rise in the plasma lipids: a) TC: 3.14 vs. 4.57 mmol/L, Ϫ 31.3%; 3.31 vs. 4.57 mmol/L Ϫ 27.6%; and 3.40 vs. 4.57, Ϫ 25.6%, respectively b) LDL-C: 1.69 vs. 3.31 mmol/L, Ϫ 49.9%; 2.05 vs. 3.31 mmol/L, Ϫ 38.1%; and 2.16 vs. 3.31 mmol/L, Ϫ 34.8%, respectively; c) TG: 0.73 vs. 0.88 mmol/L, Ϫ 17.1%; 0.75 vs. 0.88 mmol/L, Ϫ 14.8%; and 0.79 vs. 0.88 mmol/L, Ϫ10.2%, respectively. The HDL-PH was increased as follows: 0.79 vs. 0.63 mmol/L, Ϫ25.3%; 0.75 vs. 0.63 mmol/L, Ϫ23.0%; and 0.71 vs. 0.63 mmol/L, Ϫ12

Progression of Rheumatoid arthritis (RA) and osteoarthritis (OA) is associated with inflammation and oxidative stress. Previous studies have shown that there was no difference between RA and OA patients regarding the percentages of the different lymphocytes subsets reflecting the abnormalities in T cells and its subsets that may contribute to the pathogenesis of OA as in RA. Therefore, the present study was aimed to analyze that whether disease activity of OA is able to affect a few serological and biochemical parameters in the same way as RA does or differently. The study was done on 36 asymptomatic controls (25 women), 28 patients with OA (20 women), 36 patients with RA (22 women). Patients with OA were screened according to radiological and clinical finding of Kellgren and Lawrence grade and ACR criteria and assessed by VAS and WOMAC score. Patients with RA were selected who were fulfilling 4/5 symptoms of ACR criteria, and their DAS28-CRP, VAS score, and RF positivity were evaluated. Participants of the groups were matched for sex, age, weight, and height (body mass index). The BMI of all three groups was also found to be the same (P > 0.05). The mean level of LDL, Cholesterol, MDA, CRP, and Triglyceride was significantly (P < 0.05 or P < 0.01) higher in both OA and RA as compared to control. The mean level of total lipid, cholesterol, MDA, CRP, and triglyceride was found to be significantly (P < 0.05 or P < 0.01) higher in RA as compared to OA. The pre-treatment CRP level of both groups of patients showed significant and direct relation with total lipid (r = 0.27, P < 0.05) and cholesterol (r = 0.66, P < 0.01). Inverse relation was observed between Uric acid and Creatinine (r = −0.26, P < 0.05) and cholesterol and HDL (r = −0.34, P < 0.01). Our study shows the similar trend in lipid profile and other parameters studied in both patients with OA and patients with RA with more pronounced changes in RA.

SYNOPSIS. An age-autolyzed culture of Chroomonas salina, grown under cool-white light with glycerol, produced waxy lipid constituting about 44% of total matter harvested. This lipid was composed of 87% wax ester, 9% triglyceride, 3% polar lipid and 1% hydrocarbon. The major wax ester species were identified by total carbon number as C26(28%), C28(35%), C30(15%). The main fatty acid components of the wax esters were 12:0 (39%), 14:0 (30%), 16:0 (14%), while the main alcohols were 14:0 (53%) and 16:0 (40%). The hydrocarbon fraction showed saturated paraffins ranging from C17 to C33, with odd-numbered chain components predominating. No polyunsaturated components were detected in the wax ester or hydrocarbon fractions. This is the first record of wax ester production by a cryptomonad or a marine phytoplankter.

The majority of reduced calorie fats and fat substitutes avaiable, today, though similar in texture and flavor to natural fats, contain fatty acids that are not usually present in edible oils and fats and thus do not fully match the chemistry and functions of natural fats. For example, such products do not provide nutritionally important essential fatty acids (EFA). In this investigation, we prepared and evaluated a reduced calorie fat, prepared entirely from natural fats, taking advantage of the fact that long-chain saturated fatty acids (LCSFA), such as behenic acid (22∶0), are poorly absorbed. Mustard oil (MO) and sunflower oil (SO) were used as substrates to yield a structured lipid (SL). The product, being derived from a natural vegetable oil, would thus provide EFA, as would a native fat, a feature not provided by the low-calorie fats available in the market. Erucic acid (22∶1) was isolated from MO by a lipase (EC 3.1.1.3)-catalyzed reaction. It was then hydrogenated to behenic acid, the ethyl ester of which was subsequently enzymatically transesterified with SO to yield a plastic fat containing about 30–35% behenic acid. Absorption of this fat was studied in Wistar rats. In a preliminary single oral dose experiment, rats were fed equal amounts (2 mL) of SO and the SL. Plasma triacylglycerol (TAG) levels were estimated after 1, 2, and 3 h of feeding. The significantly lower concentration of plasma TAG in the 2-h sample, observed in the SL-fed group compared to the SO-fed group (Pad libitum group the previous day. Body weights were recorded during the experiment. Calorific value of the SL was estimated by comparing the 21st-d mean body weight gain of the control group with that of the experimental group. Estimated calorific value of the SL was 5.36 kcal/g. Most of the behenic acid fed was excreted, as indicated by the analysis of the fatty acids of plasma and fecal total lipid. A second growth experiment on ad libitum diet was conducted over 21 d on weanling Wistar male rats to compare the absorption behavior of the SL with that of natural oil. SO (10%) was added to the diet of the control group, and SL (10%) was added to the diet of the experimental group. Feed consumption, as well as body weights, was recorded during the experiment. The growth pattern of the experimental group was identical to that of the control group during the period of study. The mean feed intake (9.8 g/d/rat for the control group vs. 9.9 g/d/rat for the experimental group) indicated good palatability of the product. In conclusion, the enzymatically synthesized SL containing EFA and natural antioxidants has nutritional properties almost identical to those of natural fats, and can be used as a reduced calorie fat.

LL-37 is a cationic, amphipathic R-helical antimicrobial peptide found in humans that kills cells by disrupting the cell membrane. To disrupt membranes, antimicrobial peptides such as LL-37 must alter the hydrophobic core of the bilayer. Differential scanning calorimetry and deuterium ( 2 H) NMR experiments on acyl chain perdeuterated lipids demonstrate that LL-37 inserts into the hydrophobic region of the bilayer and alters the chain packing and cooperativity. The results show that hydrophobic interactions between LL-37 and the hydrophobic acyl chains are as important for the ability of this peptide to disrupt lipid bilayers as its electrostatic interactions with the polar headgroups. The 2 H NMR data are consistent with the previously determined surface orientation of LL-37 (Henzler Wildman, K. A., et al. (2003) Biochemistry 42, 6545) with an estimated 5-6 Å depth of penetration of the hydrophobic face of the amphipathic helix into the hydrophobic interior of the bilayer. LL-37 also alters the material properties of lipid bilayers, including the area per lipid, hydrophobic thickness, and coefficient of thermal expansion in a manner that varies with lipid type and temperature. Comparison of the effect of LL-37 on 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC-d 31 ) and 1,2-dimyristoyl-phosphatidylcholine (DMPC-d 54 ) at different temperatures demonstrates the importance of bilayer order in determining the type and extent of disordering and disruption of the hydrophobic core by LL-37. One possible explanation, which accounts for both the 2 H NMR data presented here and the known surface orientation of LL-37 under identical conditions, is that bilayer order influences the depth of insertion of LL-37 into the hydrophobic/hydrophilic interface of the bilayer, altering the balance of electrostatic and hydrophobic interactions between the peptide and the lipids.

The lipid-lowering action of the leaves of the Aleurites moluccana methanol extract was studied in Triton W-1339 and high-fat-diet fed rats. The serum lipids (total cholesterol, LDL-and HDL-cholesterol and triglycerides) and body weight were found to be lowered by A. moluccana (300 mg/kg, b.w.) in rats with Triton-induced hypercholesterolaemia and on a hyperlipaemic diet. The results suggest that the lipid lowering action of this natural product is mediated through inhibition of hepatic cholesterol biosynthesis and reduction of lipid absorption in the intestine.

The physico-chemical properties and in vivo efficacies of two nanoparticulate systems delivering the antiparkinsonian drug bromocriptine (BC) were compared in the present study. Monoolein Aqueous Dispersions (MADs) and Nanostructured Lipid Carriers (NLCs) were produced and characterized. Cryogenic transmission electron microscopy (cryo-TEM) and X-ray diffraction revealed the morphology of MAD and NLC. Dimensional distribution was determined by Photon Correlation Spectroscopy (PCS) and Sedimentation Field Flow Fractionation (SdFFF). In particular, BC was shown to be encapsulated with high entrapment efficiency both in MAD and in NLC, according to SdFFF combined with HPLC. Two behavioral tests specific for akinesia (bar test) or akinesia/bradykinesia (drag test) were used to compare the effects of the different BC formulations on motor disabilities in 6-hydroxydopamine hemilesioned rats in vivo, a model of Parkinson's disease. Both free BC and BC-NLC reduced the immobility time in the bar test and enhanced the number of steps in the drag test, although the effects of encapsulated BC were longer lasting (5 h). Conversely, BC-MAD was ineffective in the bar test and improved stepping activity in the drag test to a much lower degree than those achieved with the other preparations. We conclude that MAD and NLC can encapsulate BC, although only NLC provide long-lasting therapeutic effects possibly extending BC half-life in vivo.

The human body is exposed nowadays to increasing attacks by toxic compounds in polluted air, industrially processed foods, alcohol and drug consumption that increase liver toxicity, leading to more and more severe cases of hepatic disorders. The present paper aims to evaluate the influence of the apitherapy diet in Wistar rats with carbon tetrachloride-induced hepatotoxicity, by analyzing the biochemical determinations (enzymatic, lipid and protein profiles, coagulation parameters, minerals, blood count parameters, bilirubin levels) and histopathological changes at the level of liver, spleen and pancreas. The experiment was carried out on six groups of male Wistar rats. Hepatic lesions were induced by intraperitoneal injection of carbon tetrachloride (dissolved in paraffin oil, 10% solution). Two mL per 100 g were administered, every 2 days, for 2 weeks. Hepatoprotection was achieved with two apitherapy diet formulations containing honey, pollen, propolis, Apilarnil, with/without royal jelly. Biochemical results reveal that the two apitherapy diet formulations have a positive effect on improving the enzymatic, lipid, and protein profiles, coagulation, mineral and blood count parameters and bilirubin levels. The histopathological results demonstrate the benefits of the two apitherapy diet formulations on reducing toxicity at the level of liver, spleen and pancreas in laboratory animals.

To investigate whether autonomic nervous system (ANS) hyperactivity may be a potential cause for the relationship between lower urinary tract symptoms (LUTS) and erectile dysfunction (ED). Twenty-four patients were recruited for this study. Complete physical examinations, urine analysis, uroflowmetry, and postvoid residual urine volume (PVRU) analysis were performed. The potential impact of some factors such as hyperglycemia, obesity, and hyperlipidemia were analyzed. These values were correlated with the various symptom scores. We performed an electromyographic and an electrocardiographic evaluation. The alterations after treatment with 2 different alpha-blockers were also analyzed. The electromyographic and electrocardiographic assessments revealed a minimal increase in ANS activity and it did not change significantly after treatment (P &gt; 0.05). After treatment, maximum flow rate increased and PVRU decreased significantly (P &lt; 0.001 and P &lt; 0.001, respectively); total and...

Venous thromboembolism (VTE) is a significant cause of mortality in patients with lung cancer. Despite the availability of a wide range of anticoagulants to help prevent thrombosis, thromboprophylaxis in ambulatory patients is a challenge due to its associated risk of haemorrhage. As a result, anticoagulation is only recommended in patients with a relatively high risk of VTE. Efforts have been made to develop predictive models for VTE risk assessment in cancer patients, but the availability of a reliable predictive model for ambulate patients with lung cancer is unclear. We have analysed the latest information on this topic, with a focus on the lung cancer-related risk factors for VTE, and risk prediction models developed and validated in this group of patients. The existing risk models, such as the Khorana score, the PROTECHT score and the CONKO score, have shown poor performance in external validations, failing to identify many high-risk individuals. Some of the newly developed an...

To evaluate the efficacies of bimatoprost and travoprost for lowering of intraocular pressure (IOP) for the treatment of glaucoma and ocular hypertension. Methods: Prospective, randomised, investigator-blinded, parallel-group clinical trial. After completing a washout of all glaucoma drugs, patients (n = 157

Aims/hypothesis There has been much focus on the potential role of mitochondria in the aetiology of type 2 diabetes and the metabolic syndrome, and many case–control mitochondrial association studies have been undertaken for these conditions. We tested for a potential association between common mitochondrial variants and a number of quantitative traits related to type 2 diabetes in a large sample of >2,000 healthy Australian adolescent twins and their siblings, many of whom were measured on more than one occasion. Methods To the best of our knowledge, this is the first mitochondrial association study of quantitative traits undertaken using family data. The maternal inheritance pattern of mitochondria means established association methodologies are unsuitable for analysis of mitochondrial data in families. We present a methodology, implemented in the freely available program Sib-Pair for performing such an analysis. Results Despite our study having the power to detect variants with modest effects on these phenotypes, only one significant association was found after correction for multiple testing in any of four age groups. This was for mt14365 with triacylglycerol levels (unadjusted p = 0.0006). This association was not replicated in other age groups. Conclusions/interpretation We find little evidence in our sample to suggest that common European mitochondrial variants contribute to variation in quantitative phenotypes related to diabetes. Only one variant showed a significant association in our sample, and this association will need to be replicated in a larger cohort. Such replication studies or future meta-analyses may reveal more subtle effects that could not be detected here because of limitations of sample size.

The British Petroleum (BP) oil spill has raised several ecological and health concerns. As the first response, BP used a chemical dispersant, Corexit-9500, to disperse the crude oil in the Gulf of Mexico to limit shoreline contamination problems. Nevertheless, portions of this oil/Corexit mixture reached the shoreline and still remain in various Gulf shore environments. The use of Corexit itself has become a significant concern since its impacts on human health and environment is unclear.

Total body turnover of cholesterol was studied in 54 subjects by fitting a three-pool mathematical model to plasma decay curves of 32-49 weeks duration following ['4C]cholesterol injection. Fifteen subjects were normal, 10 hypercholesterolemic, 2 1 hypertriglyceridemic, and 8 had both hypercholesterolemia and hypertriglyceridemia; 2 1 had a familial form of hyperlipidemia. In every subject in this heterogeneous population, the three-pool model gave the best fit for the data.

All, but no tendency to precocious atherosclerosis is present. To elucidate this paradox, the structure of HDL, the potential of serum to promote cholesterol effiux from cultured cells, and the in vivo metabolism of HDL were examined in a 53-year-old Woman with a FED syndrome in association with a markedly decreased lecithin:cholesterol acyltransferase (LCAT) activity in HDL due to a mutation of the LCAT gene (Arglse -~ Cys). HDLs isolated by uitracentrifugation were small and enriched in unesterified cholesterol and phospholipids at the expense of cholesteryl esters and proteins, The apolipoprotein content showed an enrichment in apo E and apo AIV, whereas apo AI and apo All were dramatically reduced. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE} and immunoblotting using specific antibodies showed that the apo E was free or covalently bound to apo All. These particles analyzed by electron microscopy were small and round lipoproteins with a size similar to the smallest fraction of normal HDL3. The potential capacity of the serum to promote efflux from the cells was approximately 40% of control serum levels, but FED HDLs were as efficient as control HDLs in promoting cholesterol efflux from cells. To assess the metabolism of HDL apolipoproteins, in vivo apolipoprotein kinetic studies were performed using endogenous labeling techniques in the patient with FED and three control subjects. All subjects were administered D3-1abeled leucine by primed constant infusion for up to 10 hours. The fractional synthetic rates (FSRs) of apo AI and apo All in the patient were 0.674 and 0,594 per day, clearly higher than in controls, 0.210 +-0.053 and 0.148 +-0.014 per day for apo AI and apo All, respectively. Apo AI and apo All production rates in the patient with FED were normal, 11.32 and 2.62 mgJkg • d, respectively, as compared with those in normal subjects, 11.45 + 1.23 and 2.68 -+ 0.17 mg/kg • d. These data established that hypoalphalipoproteinemia in FED was caused by marked hypercatabolism of apo AI and apo All. This hypercatabolism could be the consequence of structural abnormalities due to the selective LCAT deficiency, in conclusion, two steps of reverse cholesterol transport, cholesterol efflux and apo-HDL metabolism, appeared particularly efficient. This efficiency could participate in the absence of premature atherosclerosis in FED patients as regards the low HDL level.

Long-chain n-3 polyunsaturated fatty acids have variable effects on LDL cholesterol, and the effects of docosahexaenoic acid (DHA) are uncertain. The objective of the study was to determine the effect on blood lipids of a daily intake of 0.7 g DHA as triacylglycerol in middle-aged men and women. Men and women aged 40-65 y (n = 38) underwent a double-blind, randomized, placebo-controlled, crossover trial of treatment with 0.7 g DHA/d for 3 mo. DHA supplementation increased the DHA concentration in plasma by 76% (P &lt; 0.0001) and the proportion in erythrocyte lipids by 58% (P &lt; 0.0001). Values for serum total cholesterol, LDL cholesterol, and plasma apolipoprotein B concentrations were 4.2% (0.22 mmol/L; P = 0.04), 7.1% (0.23 mmol/L; P = 0.004), and 3.4% (P = 0.03) higher, respectively, with DHA treatment than with placebo. In addition, the LDL cholesterol:apolipoprotein B ratio was 3.1% higher with DHA treatment than with placebo (P = 0.04), which suggested an increase in LDL si...

Introduction: Different variants of haplotype frequencies may lead to various frequencies of the same variants in individuals with drug resistance and disease susceptibility at the population level. Materials and methods: In this study, the haplotype frequencies of 4 STR loci including the D8S1132, D8S1779, D8S514 and D8S1743, and 3 STR loci including D11S1304, D11S1998 and D11S934 were investigated in 563 individuals of four Iranian ethnic groups in the capital city of Iran, Tehran. One hundred thirty subjects had the metabolic syndrome. Haplotype frequencies of all markers were calculated. Results: There were significant differences in the haplotype frequencies in short and long alleles between the metabolic affected subjects and controls. In addition, haplotype frequencies were significant in the four ethnic groups in both chromosomes 8 and 11. Conclusion: Our findings show a relation between the short allele of D8S1743 in all related haplotype frequencies of subjects with metabolic syndrome. These findings may require more studies of some candidate genes, including the lipoprotein lipase gene, in this chromosomal region.

The effect of dietary docosahexaenoic acid (22:6n-3, DHA) on the metabolism of oleic, linoleic, and linolenic acids was investigated in male subjects (n = 6) confined to a metabolic unit and fed diets containing 6.5 or <0.1 g/d of DHA for 90 d. At the end of the diet period, the subjects were fed a mixture of deuterated triglycerides containing 18:1n-9[d6], 18:2n-6[d2], and 18:3n-3[d4]. Blood samples were drawn at 0, 2, 4, 6, 8, 12, 24, 48, and 72 h. Methyl esters of plasma total lipids, triglycerides, phospholipids, and cholesterol esters were analyzed by gas chromatography-mass spectrometry. Chylomicron triglyceride results show that the deuterated fatty acids were equally well absorbed and diet did not influence absorption. Compared to the low-DHA diet (LO-DHA), clearance of the labeled fatty acids from chylomicron triglycerides was modestly higher for subjects fed the high DHA diet (HI-DHA). DHA supplementation significantly reduced the concentrations of most n-6[d2] and n-3[d4] long-chain fatty acid (LCFA) metabolites in plasma lipids. Accumulation of 20:5n-3[d4] and 22:6n-3[d4] was depressed by 76 and 88%, respectively. Accumulations of 20:3n-6[d2] and 20:4n-6[d2] were both decreased by 72%. No effect of diet was observed on acyltransferase selectivity or on uptake and clearance of 18:1n-9[d6], 18:2n-6[d2], and 18:3n-3[d4]. The results indicate that accumulation of n-3 LCFA metabolites synthesized from 18:3n-3 in typical U.S. diets would be reduced from about 120 to 30 mg /d by supplementation with 6.5 g/d of DHA. Accumulation of n-6 LCFA metabolites synthesized from18:2n-6 in U.S. diets is estimated to be reduced from about 800 to 180 mg/d. This decrease is two to three times the amount of n-6 LCFA in a typical U.S. diet. These results support the hypothesis that health benefits associated with DHA supplementation are the combined result of reduced accretion of n-6 LCFA metabolites and an increase in n-3 LCFA levels in tissue lipids.

Introduction: Chronic periodontitis is the inflammatory disease of the periodontium; the tissue that surround and support the teeth. The aim of the study was to estimate and compare some biochemical oxidative stress markers in patients with chronic periodontitis and healthy controls and to assess the effect of nonsurgical periodontal therapy on these parameters.

Aims/hypothesis: Preferential visceral adipose tissue (VAT) accumulation has been clearly associated with insulin resistance. In contrast, the impact of visceral obesity on beta cell function is controversial. Methods: In 62 non-diabetic women and men (age 24-69 years, BMI 21-39 kg/m 2 ), we measured VAT and subcutaneous adipose tissue (SAT) fat mass by magnetic resonance imaging. We also measured insulin secretion and beta cell function by C-peptide deconvolution and physiological modelling of data from a frequently sampled, 75-g, 3-h OGTT, respectively. Results: VAT (range 0.1-3.1 kg) was strongly related to sex, age and BMI; SAT was related to sex and BMI. Controlling for sex, age, BMI and SAT by multivariate analysis, excess VAT was associated with a clinical phenotype comprising higher plasma glucose levels, BP, heart rate and serum transaminases. The corresponding metabolic phenotype consisted of insulin resistance (partial r=−0.38) and hyperinsulinaemia (partial r=0.29). The latter, however, was appropriate for the degree of insulin resistance regardless of obesity and abdominal fat distribution. Moreover, none of the model-derived parameters describing beta cell function (glucose sensitivity, rate sensitivity and potentiation) was independently associated with excess VAT. Conclusions/interpretation: In non-diabetic Caucasian adults of either sex, preferential visceral fat deposition in itself is part of an insulin-resistant phenotype. The insulin secretory response to a physiological challenge is increased to fully compensate for the insulin resistance, but the dynamics of beta cell function (glucose sensitivity, rate sensitivity and potentiation) are largely preserved.