DNA-drug interaction measurements using surface plasmon resonance

Formation of the blastocoel in early Xenopus embryos was studied with a novel biotin-permeability assay and newly generated tight junction markers. The blastocoel forms at the first cleavage division since functional tight junctions which excluded biotin and established a segregated intraembryonic compartment were found at the 2-cell and all subsequent developmental stages. Unexpectedly, tight junctions before the 64-cell stage were not at their normal apical positions, but were found deep in the embryos, up to 200 micron from the apical surface. In these positions, the tight junctions left large areas of ion permeable lateral membranes exposed to the extraembryonic environment, explaining why electrophysiological experiments record a decrease in embryonic input resistances concomitant with early cleavage stages. Immunohistochemistry revealed that the recessed tight junctions did not influence the distribution of C-cadherin and Na+,K+ATPase. Both markers were present apical to recessed tight junctions, indicating that the maintenance of polarization of these basolateral markers does not require tight junctions. With further development, tight junctions assumed an increasingly apical location until, by the 2000-cell stage, they occupied their conventional positions between the blastomeres at the apical/lateral membrane boundaries.     

Factors involved in Schistosoma mansoni infection in rural areas of northeast Brazil

Two contiguous villages in Tracunhaém county (State of Pernambuco), endemic for schistosomiasis, were studied: Itapinassu (138 inhabitants) and S?o Joaquim (91 inhabitants). Agriculture predominates in the former region while ceramics is the main activity in the latter. Although no statistical difference was found regarding prevalence, severe infection (> 400 epg) predominated in Itapinassu, probably related to the kind of occupation. No association was found between parasite burden and severity of disease, in spite of the high infection rates for Schistosoma mansoni in both communities (approx. 60%). Typical epidemiological features of schistosomiasis such as age-related prevalences and intensities of infection (high in children, low in adults) were also mutual characteristics. Nutritional status determined through anthropometric evaluation was carried out by measuring specific anthropometric indicators. A deficit of energy intake, as well as vitamin A and riboflavin deficiencies were detected. The prevalence of moderate or severe undernutrition in patients under 18 years old was 21.9% in Itapinassu and 24.1% in S?o Joaquim. In this group an association was found between prevalence of schistosomiasis and chronic undernutrition. Similarly, for patients over 18 year old the prevalence of undernutrition was higher than 20%. However, in this case no association between nutritional status and either prevalence of schistosomiasis or parasite burden could be detected. The two communities had not been treated for eight years.     

Temporal relation of ATP-sensitive potassium-channel activation and contractility before cardioplegia

BACKGROUND: Pharmacologic treatment using potassium-channel openers (PCOs) before cardioplegic arrest has been demonstrated to provide beneficial effects on left ventricular performance with subsequent reperfusion and rewarming. However, the PCO treatment interval necessary to provide protective effects during cardioplegic arrest remains to be defined. The present study was designed to determine the optimum period of PCO treatment that would impart beneficial effects on left ventricular myocyte contractility after simulated cardioplegic arrest. METHODS: Left ventricular porcine myocytes were assigned randomly to three groups: (1) normothermic control = 37 degrees C for 2 hours; (2) cardioplegia = K+ (24 mEq/L) at 4 degrees C for 2 hours followed by reperfusion and rewarming; and (3) PCO and cardioplegia = 1 to 15 minutes of treatment with the PCO aprikalim (100 micromol/L) at 37 degrees C followed by hypothermic (4 degrees C) cardioplegic arrest and subsequent rewarming. Myocyte contractility was measured after rewarming by videomicroscopy. A minimum of 50 myocytes were examined at each treatment and time point. RESULTS: Myocyte velocity of shortening was reduced after cardioplegic arrest and rewarming compared with normothermic controls (63+/-3 microm/s versus 32+/-2 microm/s, respectively; p < 0.05). With 3 minutes of PCO treatment, myocyte velocity of shortening was improved after cardioplegic arrest to values similar to those of normothermic controls (56+/-3 microm/s). Potassium channel opener treatment for less than 3 minutes did not impart a protective effect, and the protective effect was not improved further with more prolonged periods of PCO treatment. CONCLUSIONS: A brief interval of PCO treatment produced beneficial effects on left ventricular myocyte contractile function in a simulated model of cardioplegic arrest and rewarming. These results suggest that a brief period of PCO treatment may provide a strategy for myocardial protection during prolonged cardioplegic arrest in the setting of cardiac operation.     

Cholesterol mobilization and regression of atheroma in cholesterol-fed rabbits induced by large unilamellar vesicles

The antiatherogenic properties of repeated injections of egg phosphatidylcholine large unilamellar vesicles (LUVs) of 100 nm diameter were tested in an experimental model for atherosclerosis. Forty eight rabbits were divided into two diet groups fed standard rabbit chow or fed a cholesterol-enriched diet (0.5% by weight) to induce the formation of atherosclerotic lesions. Prior to the initiation of LUV therapy, the cholesterol diet was ceased and all animals were returned to standard rabbit chow. The treatment protocol consisted of a total of 10 bolus injections of vesicles, at a phospholipid dose of 300 mg/kg body weight or the equivalent volume of saline, with one injection given to each animal every 10 days. LUV injections brought about a large movement of cholesterol into the blood pool and resulted in a significant reduction in the cholesterol content as well as the degree of surface plaque involvement of aortic tissue in atherosclerotic animals. Most notably, the thoracic aorta of LUV-treated animals exhibited a 48% reduction in tissue cholesterol content per gram of protein compared to saline-treated controls. Histochemical analyses revealed that aortas from animals receiving the repeated injections of LUVs displayed less cholesterol deposits in lesions, and a moderate reduction in intimal-to-medial thickness. This regression of atheroma, induced by LUV therapy, was observed even though animals possessed persistent elevated plasma cholesterol levels after the cholesterol-enriched diet was ceased. These results suggest that repeated injections of LUVs, working with endogenous HDL, may be a useful therapy in the management of atherosclerosis.     

An efficient chromatographic system for lipoprotein fractionation using whole plasma

We have validated a semi-automatic procedure for the efficient isolation of plasma lipoproteins from 300 microl of whole plasma (actual injection volume 200 microl) by Fast Phase Liquid Chromatography (FPLC). Modified enzymatic assays were established to allow the determination of low concentrations (1-20 mg/dl) of triglycerides and cholesterol using the Beckman CX-5 Autoanalyzer. The sum of the cholesterol contents in the fractions corresponding to low density (LDL) and high density lipoprotein (HDL) can be demonstrated to be highly correlated to values obtained with dextran sulfate/MgCl2 precipitation for HDLc (slope = 0.98, r2 = 0.997) and ultracentrifugation (beta-quant) for LDLc (slope = 1.03, r2 = 0.988). Using pure lipoprotein fractions isolated by ultracentrifugation, linear ranges of detection for HDLc and HDL apoA-I were performed at 18-95 mg/dl and 59-262 mg/dl, respectively. The ranges for LDLc were 41-435 mg/dl and 21-280 mg/dl for LDL apoB. The mean (range) fractional standard deviations for quadruplicate runs for 15 individual plasma samples ranging widely in lipoprotein concentrations were 0.97 (0.29-2.86%) for LDLc (range: 101.5-258.5 mg/dl), 3.67 (0.62-14.11%) for HDLc (range: 27.1-85.1 mg/dl) and 2.19 (0.16-6.56%) for VLDL-TG (range: 6.1-515.0 mg/dl).     

Texas Medication Algorithm Project: definitions, rationale, and methods to develop medication algorithms

BACKGROUND: The Texas Medication Algorithm Project (TMAP), a public-academic collaborative effort, is a 3-phase project to develop, implement, and evaluate medication treatment algorithms for public sector patients with schizophrenia, major depressive disorders, or bipolar disorders. DISCUSSION: This paper, the first in a series describing the activities of the TMAP, focuses on the various definitions and reasons why guidelines have gained popularity. Also discussed are their strengths, the limitations of the various methods used to develop them, and potential barriers to their implementation.     

THz Properties of Nematic Liquid Crystals

We systematically study the terahertz (THz) properties of a set of nematic liquid crystals. We use THz time domain spectroscopy to obtain data between 0.2 THz up to 2.5 THz. Such a broadband set of terahertz data has not yet been reported. From the measured data, we extract macroscopic data, such as the birefringence, the refractive indices and the absorption coefficients for ordinary and extraordinary polarization. The impact of different side chains and core structures on the terahertz anisotropy are discussed. This paper will serve as a data base and can be very useful for the design of new terahertz liquid crystal material.     

THz Spectroscopy of Liquid Crystals from the CB Family

Liquid crystals represent a very interesting material system but their properties in the THz range have not been extensively investigated yet. In this paper we investigate the THz properties of four liquid crystals from the CB family (5CB, 6CB, 7CB and 8CB). In addition to absolute refractive indices and absorption coefficients we present accurate birefringence measurements for different electric fields and temperatures.