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At least 1,171 records · Page 65Linked to original sources
PubMed2005

Dendrimers of citric acid and poly (ethylene glycol) as the new drug-delivery agents.

Citric acid-polyethylene glycol-citric acid (CPEGC) triblock dendrimers as biocompatible compounds containing G(1), G(2) and G(3) were applied as the drug-delivery systems. Some of the small size molecules and drugs are trapped with the above-synthesized dendrimers. The guest molecules, which are hydrophobic when trapped into the suitable sites of dendrimers, are becoming soluble in aqueous solution. The quantity of trapped molecules and drugs such as 5-amino salicylic acid (5-ASA), pyridine, mefenamic acid, and diclofenac was measured. The drug/dendrimer complexes remained in room temperature for about 10 months and after this long time they were stable and the drugs were not released. Also, the controlled release of the above-mentioned molecules and drugs in vitro conditions was investigated. The structure definition and controlled release of the molecules and drugs were carried out using different spectroscopy methods.

Biocompatible Materials↗
PubMed2006

Goat cerebrovascular reactivity to ADP after ischemia-reperfusion. Role of nitric oxide, prostanoids and reactive oxygen species.

To analyze the cerebrovascular effects of ischemia-reperfusion, cerebrovascular reactivity to ADP was studied after inducing 60-min occlusion followed by 60-min reperfusion of the left middle cerebral artery (MCA) in anesthetized goats. In 12 goats, at the end of reperfusion, left MCA resistance was decreased by 19%, and reactive hyperemia to 5- and 10-s occlusions as well as the cerebral vasodilatation to ADP (0.03-0.3 microg) but not to sodium nitroprusside (0.3-3 microg) was decreased. In 28 animals, killed at the end of reperfusion, segments 3-mm long were obtained from the left (ischemic) and right (control) MCA, prepared for isometric tension recording, and precontracted with the thromboxane A2 analogue U46619. The relaxation to ADP (10(-8) to 10(-5) M) but not to sodium nitroprusside (10(-8) to 10(-4) M) was lower in ischemic arteries. L-NAME (inhibitor of nitric oxide synthesis, 10(-4) M), charybdotoxin (10(-7) M)+apamin (10(-6) M) (blockers of KCa), or catalase (1000 U/ml) reduced the relaxation to ADP only in control arteries. Charybdotoxin+apamin further augmented the L-NAME-induced reduction in the relaxation to ADP in control arteries. The inhibitor of cyclooxygenase meclofenamate (10(-5) M) increased the relaxation to ADP only in ischemic arteries. The superoxide dismutase mimetic tiron (10(-2) M) increased the ADP-induced relaxation only in ischemic arteries. Therefore, it is suggested that ischemia-reperfusion produces cerebrovascular endothelial dysfunction, which may be associated with decreased nitric oxide bioavailability, decreased release of an EDHF, and increased production of vasoconstrictor prostanoids. All these alterations may be related in part with an increased production of superoxide anion.

Adenosine Diphosphate↗
PubMed2006

Lipid and lipoprotein dysregulation in insulin resistant states.

Insulin resistant states are commonly associated with an atherogenic dyslipidemia that contributes to significantly higher risk of atherosclerosis and cardiovascular disease. Indeed, disorders of carbohydrate and lipid metabolism co-exist in the majority of subjects with the "metabolic syndrome" and form the basis for the definition and diagnosis of this complex syndrome. The most fundamental defect in these patients is resistance to cellular actions of insulin, particularly resistance to insulin-stimulated glucose uptake. Insulin insensitivity appears to cause hyperinsulinemia, enhanced hepatic gluconeogenesis and glucose output, reduced suppression of lipolysis in adipose tissue leading to a high free fatty acid flux, and increased hepatic very low density lipoprotein (VLDL) secretion causing hypertriglyceridemia and reduced plasma levels of high density lipoprotein (HDL) cholesterol. Although the link between insulin resistance and dysregulation of lipoprotein metabolism is well established, a significant gap of knowledge exists regarding the underlying cellular and molecular mechanisms. Emerging evidence suggests that insulin resistance and its associated metabolic dyslipidemia result from perturbations in key molecules of the insulin signaling pathway, including overexpression of key phosphatases, downregulation and/or activation of key protein kinase cascades, leading to a state of mixed hepatic insulin resistance and sensitivity. These signaling changes in turn cause an increased expression of sterol regulatory element binding protein (SREBP) 1c, induction of de novo lipogensis and higher activity of microsomal triglyceride transfer protein (MTP), which together with high exogenous free fatty acid (FFA) flux collectively stimulate the hepatic production of apolipoprotein B (apoB)-containing VLDL particles. VLDL overproduction underlies the high triglyceride/low HDL-cholesterol lipid profile commonly observed in insulin resistant subjects.

Animals↗
PubMed2006

The relationship between homeostasis model assessment and cardiovascular risk factors in Iranian subjects with normal fasting glucose and normal glucose tolerance.

BACKGROUND: Insulin resistance is a complex problem which may not always correlate with all its cardiovascular risk factors in various populations. We investigated the relationship between homeostasis model assessment of insulin resistance (HOMA-IR) with cardiovascular risk factors in Iranian subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT). METHODS: Of the 605 subjects aged 25-79 y enrolled in this study, after the oral glucose tolerance test, 366 subjects aged 25-50 y and 135 aged >50 y were classified as NFG and NGT. Insulin resistance was estimated by the HOMA-IR. RESULTS: Women had higher values of body mass index (BMI), insulin and HOMA-IR than men in both age groups. The prevalence of insulin resistance, general and abdominal obesity, low HDL-C and physical inactivity was higher in women than men in the 2 age groups. Men had a higher prevalence of hypertension and hypertriglyceridemia in the group with age 25-50 y. The Pearson correlation controlled for age, BMI, waist circumference and physical activity showed that HOMA-IR had significant correlation with triglyceride and inversely associated with HDL-C in both sexes. In addition, the results of HOMA-IR quartiles demonstrated that the prevalence of hypertension, obesity, and low HDL-C was particular high in women with HOMA-IR >2.39. Multiple regression indicated that log HOMA-IR was independently predicted by BMI, triglyceride and HDL-C in men and BMI, HDL-C and waist-to-hip (WHR) ratio in women. CONCLUSIONS: HOMA-IR is associated with the features of metabolic syndrome with a sex difference in the degree and predictors of HOMA-IR and the frequency of cardiovascular risk factors.

Adult↗
PubMed2004

Improved HPLC methodology for monitoring thiopurine metabolites in patients on thiopurine therapy.

OBJECTIVE: Standardization of thiopurine metabolite testing is currently lacking. This paper presents in-depth methodological analysis and optimization of two currently available HPLC procedures (Lennard-Singleton [J. Chromatogr. 583 (1992) 83] and Dervieux-Boulieu [Clin. Chem. 44 (1998) 551]) to improve precision, turn-around time, ruggedness, and cost effectiveness. DESIGN AND METHODS: Reversed-phase chromatography with UV detection was performed on a Waters HPLC system. The two protocols were improved with regards to internal standardization (IS), chromatographic conditions, as well as reagent preparation, storage, and use. 6-Thioguanine nucleotides (6-TGNs) were analyzed by our optimized techniques in samples from patients on thiopurine therapy (n = 24) and the results were compared. RESULTS: 6-Mercaptopurine (6-MP) was an ideal internal standard in either procedure. Isocratic elution with 5% acetonitrile (ACN) in 20 mmol/l phosphate buffer pH 2.5 allowed for minimal background interference in both protocols. 6-Thioguanine, 6-mercaptopurine, and 6-methylmercaptopurine (6-MMP) eluted at around 4, 5, and 6 min, respectively. Dithiothreitol (DTT) was critical only during the acid hydrolysis step. Less mercury-containing waste was generated in the Lennard-Singleton procedure. With our optimized protocols recovery of 6-TGNs was on average 1.38-fold higher in the Dervieux-Boulieu method over a range of 10-678 pmol/8 x 10(8) RBC and no interfering peaks hindered analysis. Specific extraction of thiopurines before their analysis as per Lennard-Singleton procedure may be redundant. CONCLUSIONS: We improved the quality and cost effectiveness of two known procedures for thiopurine metabolite assay. Through common chromatographic conditions and internal standardization, future comparison studies are now facilitated a great deal. The less tedious Dervieux-Boulieu procedure for routine thiopurine metabolite testing is warranted.

Chromatography, High Pressure Liquid↗
PubMed2004

Challenges of implementing point-of-care testing (POCT) glucose meters in a pediatric acute care setting.

OBJECTIVES: To investigate factors contributing to analytical bias in POCT glucose values generated by the NICU versus the core laboratory. METHODS: The LifeScan Flexx hospital system glucose meters (SureStep) were used in precision and comparison studies between the NICU and laboratory (ABL715 and Vitros 950). RESULTS: Analysis of 40 neonatal blood samples revealed a positive bias between the NICU glucose meters versus either the laboratory glucose meter or instrument (mean difference of 0.28 and 0.21 mmol/L, respectively). Linear regression analysis (R2 = 0.0584) of the difference in glucose results versus time elapsed between measurements indicated that the bias observed between the NICU and laboratory glucose meters was not due to in vitro glycolysis for samples transported on ice. Further analysis indicated that the bias appeared to be mostly operator driven, with different NICU operators exhibiting different mean biases. Increasing the amount of blood applied to the SureStep Pro test strip (e.g., 60 vs. 20 microL), led to higher values for glucose concentration for the same blood. Nearly 50% of all glucose values reported for the NICU were obtained by the SureStep Flexx glucose meters in a 3-month period following the introduction of POCT, yet the number of laboratory-reported glucose results for the same period increased by 21% as compared to the previous year. CONCLUSIONS: Operator error appears to be a source of bias present between the NICU and laboratory, and despite glucose meter utilization in the NICU, the number of glucose measurements by the central laboratory increased after POCT introduction.

Blood Gas Analysis↗
PubMed2005

Analytical performance and workflow evaluation of the Roche E170 modular immunoassay analyzer in a pediatric setting.

OBJECTIVES: To evaluate the analytical performance of the Roche E170 modular analytics immunoassay analyzer and assess its impact on workflow efficiency and ability to consolidate workstations in a pediatric setting. DESIGN AND METHODS: Analytical performance of eleven common immunoassays was assessed. Total imprecision was determined using Roche PreciControl Universal controls, Bio-Rad Lyphochek Immuno Plus, Anemia controls, and a human serum pool. Method comparison was performed with approximately 100 patient specimens. High dose hook effect, sample carryover, and results comparison between the two measuring channels were evaluated. For the workflow study, the time required for sample and reagent handling, instrument preparation, and hands-on time were assessed. RESULTS: Correlation coefficients with existing methods ranged from 0.941 to 0.999. Biases of -19% to 70% were observed. Total imprecision ranged from 1.1 to 7.6%. No sample carryovers were encountered. Results from both measuring channels were comparable. CONCLUSION: E170 is suitable for use in a pediatric setting. The analytical performance is acceptable and gives equivalent results to our existing systems. The precision is comparable and acceptable. Some improvement in efficiency, workflow, cost saving, and consolidation of workstations is possible. Significant workflow improvements can only be realized when integrated with the chemistry modules.

Autoanalysis↗
PubMed2005

Measurement of intracellular vitamin C levels in human lymphocytes by reverse phase high performance liquid chromatography (HPLC).

OBJECTIVES: Vitamin C plays an active role in many important metabolic processes, such as collagen formation and the prevention of bleeding. Although overt scurvy is now rare, there is evidence that subclinical vitamin C deficiency is still quite common. Serum and plasma vitamin C measurements do not correlate well with tissue levels while lymphocyte vitamin C levels provide the most accurate assessment of the true status of vitamin C stores and are not affected acutely by circadian rhythm or dietary changes. We report a specific and reproducible reverse phase high performance liquid chromatographic method (HPLC) for the quantification of vitamin C in lymphocytes. METHODS: Reverse phase HPLC with a UV detection system was used. National Committee for Clinical Laboratory Standards (NCCLS) guidelines were followed for evaluation. Sample stability testing for lymphocyte vitamin C was performed for a period of 24 h at room temperature and 4 degrees C. Lymphocyte vitamin C levels were measured in 51 children. RESULTS: Lymphocyte vitamin C measurement with HPLC revealed very good analytical sensitivity with a 1.42 microg/10(8) lymphocyte lower limit of detection on repeated testing. An external standard curve was used for quantification, which showed a linear range of 1.25-100 microg/10(8) lymphocyte with a correlation coefficient of 0.989. Precision studies showed an inter-assay repeatability coefficient of variance (CV) between 0.25-9.98% and a within-assay coefficient of variance between 1.2-12.49%. The inter-assay CV for a period of 20 days was less than 10% for concentrations equal to or less than 1.42 microg/10(8) lymphocytes and less than 5.5% for concentrations between 5-100 microg/10(8) lymphocytes. Vitamin C was most stable at 4 degrees C, with a 0.31% decrease after 3 h and 2.35% after 4 h. At room temperature, vitamin C loss was more significant, with losses of 8.44% and 15.6% at 3 and 4 h, respectively, at a concentration of 29.9 microg/10(8) lymphocytes. CONCLUSIONS: The proposed HPLC method offers a reliable and reproducible technique for the quantification of intracellular vitamin C. Lymphocyte samples can be rapidly prepared and represent a more homogeneous tissue sample source for intracellular vitamin C measurement as compared to serum. To ensure stability, lymphocyte lysates should be prepared and stored at or below -20 degrees C within 2 h of blood collection.

Ascorbic Acid↗
PubMed2006

Heparin interference in whole blood sodium measurements in a pediatric setting.

OBJECTIVES: In a pediatric setting, the incomplete filling of heparinized syringes is not an uncommon occurrence and has led to reports of falsely low hyponatremia in our institution. Little is known about heparin interference on sodium determination in whole blood, and our study aimed to investigate this interference due to excessive concentrations of heparin in pediatric specimens. DESIGN AND METHODS: Three different types of syringes were filled with various amounts of blood to mimic greater than normal concentrations of heparin. Specimens were analyzed on an ABL 725 blood gas analyzer, and corresponding plasma fractions were analyzed on a VITROS 950 chemistry system. In a separate study, paired patient samples consisting of a capillary tube and microtainer clot were similarly analyzed. RESULTS: The presence of lithium heparin at 100 units/mL in blood caused a significant negative bias of 2-3 mmol/L in sodium concentration with the ABL 725, but no significant bias occurred when the corresponding plasma fraction was analyzed on the VITROS 950. For syringes containing electrolyte-balanced heparin, a similar negative bias was observed for blood but was not significant. Capillary tubes contained high concentrations of heparin (>100 units/mL) even when completely filled. Sodium results from capillary samples averaged 3.4 mmol/L lower than the corresponding serum values. These effects were independent of the sodium concentration across a wide range. CONCLUSIONS: Small blood volumes collected with heparinized sampling devices in pediatric samples lead to excess heparin that may significantly affect sodium determinations and spur false reports of critical hyponatremia.

Child↗
PubMed2006

Gap analysis of pediatric reference intervals for risk biomarkers of cardiovascular disease and the metabolic syndrome.

The childhood obesity epidemic has begun to compromise the health of the pediatric population by promoting premature development of atherosclerosis and the metabolic syndrome (MS), both of which significantly increase the risk of cardiovascular disease (CVD) early in life. As a result, recently, there has been increased recognition of the need to assess and closely monitor children and adolescents for risk factors of CVD and components of the MS. Serum/Plasma biomarkers including total cholesterol, triglycerides, HDL-C, LDL-C, insulin and C-peptide have been used for this purpose for many years. Recently, emerging biomarkers such as apolipoprotein AI, apolipoprotein B, leptin, adiponectin, free fatty acids, and ghrelin have been proposed as tools that provide valuable complementary information to that obtained from traditional biomarkers, if not more powerful predictions of risk. In order for biomarkers to be clinically useful in accurately diagnosing and treating disorders, age-specific reference intervals that account for differences in gender, pubertal stage, and ethnic origin are a necessity. Unfortunately, to date, many critical gaps exist in the reference interval database of most of the biomarkers that have been identified. This review contains a comprehensive gap analysis of the reference intervals for emerging and traditional risk biomarkers of CVD and the MS and discusses the clinical significance and analytical considerations of each biomarker.

Biomarkers↗
PubMed2006

Pediatric reference intervals for lipids and apolipoproteins on the VITROS 5,1 FS Chemistry System.

OBJECTIVES: Lipid biomarkers are integral in the assessment of dyslipidemia and cardiovascular risk, conditions that have become increasingly prevalent in pediatric populations. A comprehensive set of pediatric reference intervals for traditional or recently established lipid analytes is not currently available. DESIGN AND METHODS: 525 outpatient samples from a pediatric population were categorized into five age groups ranging from 0 to 20 years of age. Groups were further partitioned by gender. Serum or plasma samples were analyzed on the VITROS 5,1 FS Chemistry System for cholesterol and triglycerides by dry-film methods, direct HDL-C and LDL-C by selective detergent elimination, and apolipoproteins AI and B by immunoturbidimetry. Reference intervals were established by non-parametric methods at the 2.5th and 97.5th percentiles. RESULTS: Lipid levels show age- and gender-related differences, particularly during the first year of life and in young adults following puberty. Concentrations of total cholesterol, LDL-C, and apo B were lowest in the 12 months after birth and remained relatively constant throughout childhood, but decreased for males in early adulthood. Triglyceride levels increased gradually throughout childhood and adolescence, and along with cholesterol, the upper limits of these intervals exceeded the recommended concentrations of lipid levels in children. For HDL-C and apo AI, no age- or sex-related differences were found until after puberty when values for males decreased slightly. CONCLUSIONS: Our current reference intervals in children and adolescents provide an important update for lipid markers and suggest earlier incidence of hypercholesterolemia when compared to previous ranges. Increased profiling of lipids is anticipated, and these will aid in the early assessment of cardiovascular risk in pediatric populations.

Adolescent↗
PubMed2005

Management of low birth weight infants with congenital heart disease.

Low birth weight infants with congenital heart disease (CHD) have a higher mortality risk and likely a higher morbidity risk than their preterm or appropriate for gestational age counterparts without CHD and term counterparts with CHD. As our understanding of the pathophysiology and treatment of the diseases associated with prematurity and growth restriction improves, the outcomes for these infants should continue to improve. In addition, as more of these infants survive and are referred for surgery, operative techniques and strategies are likely to continue to improve. At this time, there is no adequate evidence that mortality is improved by delaying surgery for weight gain or performing palliative operations initially. Given the challenging physiology in this population, optimal management includes early referral to a tertiary or quaternary facility and a multidisciplinary team approach consisting of cardiologists, neonatologists, surgeons, nurses, perfusionists, and anesthesiologists.

Cardiac Surgical Procedures↗
PubMed2005

Delivery room and early postnatal management of neonates who have prenatally diagnosed congenital heart disease.

Advances in fetal echocardiography are providing highly accurate diagnoses of congenital heart disease prior to delivery, making it possible to plan the delivery-room management of these newborns. Knowledge of the expected transitional circulation occurring with birth and the pathophysiologic implications of congenital heart disease increases the likelihood of providing efficient and effective therapies. The majority of neonates who have congenital heart disease will not require delivery room resuscitation in excess of routine care; however, a small number of prenatally diagnosed cardiac lesions are more likely to require urgent postnatal intervention immediately following delivery. These cardiac lesions include transposition of the great arteries with intact ventricular septum and restrictive atrial septum, hypoplastic left heart syndrome with intact atrial septum, obstructed total anomalous pulmonary venous return, and complete congenital heart block. Prenatal diagnosis allows for coordination of care surrounding delivery and during the early postnatal hours.

Delivery Rooms↗
PubMed2004

Proteolysis: Adaptor, adaptor, catch me a catch.

The ClpXP protease of bacteria can degrade a wide variety of proteins while maintaining remarkable substrate selectivity. New work in Escherichia coli implicates adaptor proteins in enhancing substrate selectivity and regulating the flow of substrates to cellular proteases.

Carrier Proteins↗
PubMed2004

Age-related differences in metabolic adaptations following resistance training in women.

The purpose of this study was to determine whether aging alters changes in resting metabolic rate, body composition and insulin sensitivity in response to resistance training (RT) in women. The impact of a 6-month controlled RT program on fat-free mass (FFM), resting energy expenditure (REE), and glucose disposal was examined in 19 younger (27.8+/-3.5 yr; range 18-35) and 12 older (66.6+/-4.9 yr, range 55-70) non-obese caucasian women. For younger women, the RT program increased body weight (59.1+/-6.2 to 60.8+/-6.1 kg, p<0.05) due to an increase in FFM (39.2+/-3.7-40.4+/-3.2 kg, p<0.05). REE increased from 1379+/-114 to 1451+/-140 kcal day(-1), p<0.0001), and glucose disposal (from 364.1+/-91.1 to 402.1+/-87.8 mg min(-1), p<0.05). Neither fat mass nor VO2max changed significantly. On the other hand, older women lost fat mass (24.0+/-4.6-23.2+/-5.4 kg, p<0.05) and tended to gain FFM (from 37.3+/-4.0-38.0+/-4.3 kg, +1.9%; p=0.057), whereas no change occurred in body weight, REE, VO(2)max or glucose disposal. Thus, younger women showed greater metabolic changes in body composition, REE and insulin sensitivity in response to RT than older women. These results suggest an age-related alteration in metabolic changes in response to a 6-month RT program in previously untrained women.

Adaptation, Physiological↗
PubMed2006

The multi-dimensional neighbourhood and health: a cross-sectional analysis of the Scottish Household Survey, 2001.

Neighbourhoods may influence the health of individual residents in different ways: via the social and physical environment, as well as through facilities and services. Not all factors may be equally important for all population subgroups. A cross-sectional analysis of the Scottish Household Survey 2001 examined a range of neighbourhood factors for links with three health outcomes and two health-related behaviours. The results support the hypothesis that the neighbourhood has a multi-dimensional impact on health. There was also some evidence that the relationship between neighbourhood factors and health varied according to the population subgroup, although not in a consistent manner.

Cross-Sectional Studies↗