ACTA PHYSIOLOGICA, Issue 1 2010
A. J. Bidwell
Abstract Aim:, Fructose intake has increased concurrent with sugar intake and this increase has been implicated in contributing to the development of metabolic syndrome risk factors. Recent evidence suggests a role for uric acid (UA) as a potential mediator via suppression of nitric oxide (NO) bioavailability. The aim of this study was to explore this hypothesis by measuring changes in UA concentration and systemic NO bioavailability as well as endothelial function in response to acute ingestion of a glucose-fructose beverage. Methods:, Ten young (26.80 ± 4.80 years), non-obese (body mass index: 25.1 ± 2.55 kg m,2; percent body fat: 13.5 ± 6.9%) male subjects ingested either a glucose (100 g dextrose in 300 mL) or isocaloric glucose-fructose (glucose : fructose; 45 : 55 g in 300 mL) beverage. Blood was sampled pre- and every 15-min post-ingestion per 90 min and assayed for glucose, lactate, fructose, total nitrate/nitrate, UA and blood lipids. Forearm blood flow and pulse-wave velocity were recorded prior to and at 30 and 45 min time intervals post-ingestion, respectively, while heart rate, systolic and diastolic blood pressure were recorded every 15 min. Results:, The glucose-fructose ingestion was associated with a significant (P < 0.05) increase in plasma lactate concentration and altered free fatty acid levels when compared with glucose-only ingestion. However, UA was not significantly different (P = 0.08) between conditions (AUC: ,1018 ± 1675 vs. 2171 ± 1270 ,mol L,1 per 90 min for glucose and glucose-fructose conditions respectively). Consequently, no significant (P < 0.05) difference in endothelial function or systemic NO bioavailability was observed. Conclusion:, Acute consumption of a fructose-containing beverage was not associated with significantly altered UA concentration, endothelial function or systemic NO bioavailability. [source]

GOOD GIFTS FOR THE COMMON GOOD: Blood and Bioethics in the Market of Genetic Research

CULTURAL ANTHROPOLOGY, Issue 3 2007
DEEPA S. REDDY
This article is based on ethnographic fieldwork conducted with the Indian community in Houston, as part of a NIH,NHGRI-sponsored ethics study and sample collection initiative entitled "Indian and Hindu Perspectives on Genetic Variation Research." At the heart of this research is one central exchange,blood samples donated for genetic research,that draws both the Indian community and a community of researchers into an encounter with bioethics. I consider the meanings that come to be associated with blood donation as it passes through various hands, agendas, and associated ethical filters on its way to the lab bench: how and why blood is solicited, how the giving and taking of blood is rationalized, how blood as material substance is alienated, processed, documented, and made available for the promised ends of basic science research. Examining corporeal substances and asking what sorts of gifts and problems these represent, I argue, sheds some light on two imbricated tensions expressed by a community of Indians, on the one hand, and of geneticists and basic science researchers, on the other hand: that gifts ought to be free (but are not), and that science ought to be pure (but is not). In this article, I explore how experiences of bioethics are variously shaped by the histories and habits of Indic giving, prior sample collection controversies, commitments to "good science" and the common "good of humanity," and negotiations of the sites where research findings circulate. [source]

Cells meeting our immunophenotypic criteria of endothelial cells are large platelets

CYTOMETRY, Issue 2 2007
Michiel H. Strijbos
Abstract Background Circulating endothelial cells (CEC) are shed from damaged vasculature, making them a rational choice to serve as surrogate marker for vascular damage. Currently, various techniques and CEC definitions are in use, and their standardization and validation is needed. A flow cytometric single platform assay defining CEC as forward light scatter (FSC)low-to-intermedate, sideward light scatter (SSC)low, CD45,, CD31++ and CD146+ is a promising approach to enumerate CEC because of its simplicity (Mancuso et al., Blood 2001;97:3658,3661). Here, we set out to confirm the endothelial nature of these cells. Methods We isolated cells with a FSClow-to-intermediate, SSClow, CD31++, CD45dim immunophenotype (termed "cells meeting our immunophenotypic criteria for endothelial cells" [CMOIC]) from healthy donors to study the expression of endothelium-associated markers using several techniques. Special attention was paid to reagents identifying the endothelial cell-specific marker CD146. We compared antigen expression patterns of CMOIC with those of the HUVEC endothelial cell line and lymphocytes. Electron microscopy was used to detect the presence of endothelial cell-specific Weibel,Palade bodies in the sorted cells. Results CD146 expression was negative on CMOIC for all tested CD146 mAbs, but positive on HUVEC cells and a minor subset of T lymphocytes. Using flow cytometry, we found no expression of any endothelium-associated marker except for CD31 and CD34. HUVEC cells were positive for all endothelial markers except for CD34. Evaluation of CMOIC morphology showed a homogenous population of cells with a highly irregular nucleus-like structure and positive endothelial immunohistochemistry. CMOIC contained neither nuclei nor DNA. Electron microscopy revealed the absence of a nucleus, the absence of endothelial specific Weibel,Palade bodies, and revealed CMOIC to be large platelets. Conclusion The vast majority of cells with the immunophenotype FSClow-to-intermediate, SSClow, CD45,, CD31++ do not express CD146 and are large platelets rather than endothelial cells. © 2007 Clinical Cytometry Society. [source]

Flow cytometric measurement of circulating endothelial cells: The effect of age and peripheral arterial disease on baseline levels of mature and progenitor populations

CYTOMETRY, Issue 2 2006
Rebecca Gusic Shaffer
Abstract Background: Age and cardiovascular disease status appear to alter numbers and function of circulating endothelial progenitor cells (EPCs). Despite no universal phenotypic definition, numerous studies have implicated progenitors with apparent endothelial potential in local responses to vascular injury and with cardiovascular disease in general. To further define the role of this lineage in peripheral artery disease (PAD), we developed a multiparameter flow cytometry assay to analyze multiple phenotypic definitions of progenitor cells (PCs), EPCs, and mature endothelial cells (ECs) and evaluate effects of age and PAD on baseline levels of each subset. Methods: Blood was collected from young healthy subjects (N = 9, mean age 33 ± 8 years), older healthy subjects (N = 13, mean age 66 ± 8 years), and older subjects with PAD (N = 15, mean age 69 ± 8 years). After ammonium chloride lysis, cells were stained and analyzed on a Becton-Dickinson LSR II with a 5-color antibody panel: FITC-anti-CD31, PE-anti-CD146, PE-anti-CD133, PerCP-Cy5.5-anti-CD3,-CD19,-CD33 (lineage panel), PE-Cy7-anti-CD34, and APC-anti-VEGF-R2. Viability was assessed by propidium iodide exclusion, and only viable, low to medium side scatter lineage-negative singlets were analyzed. In some studies, cells were sorted for morphological studies. Subsets were defined as indicated later. Results: Our results, using a comprehensive flow cytometric panel, indicate that CD133+, CD34+, and CD133+/CD34+ PCs are elevated in younger healthy individuals compared to older individuals, both healthy and with PAD. However, the number of EPCs and mature ECs did not significantly differ among the three groups. Assessment of endothelial colony forming units and dual acLDL-lectin staining supported the flow cytometric findings. Conclusions: We describe a comprehensive flow cytometric method to detect circulating mature and progenitor endothelial populations confirmed by conventional morphological and functional assays. Our findings suggest that aging may influence circulating levels of PCs, but not EPCs or ECs; PAD had no effect on baseline levels of any populations investigated. This study provides the basis for evaluating the potential effects of acute stress and therapeutic intervention on circulating progenitor and endothelial populations as a biomarker for cardiovascular status. © 2005 International Society for Analytical Cytology [source]

The clinical presentation of mitochondrial diseases in children with progressive intellectual and neurological deterioration: a national, prospective, population-based study

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 5 2010
CHRISTOPHER M VERITY
Aim, Our aim was to study the clinical presentation, mode of diagnosis, and epidemiology of mitochondrial disorders in children from the UK who have progressive intellectual and neurological deterioration (PIND). Method, Since April 1997, we have identified patients aged 16 years or younger with suspected PIND through the monthly notification card sent to all UK consultant paediatricians by the British Paediatric Surveillance Unit. Clinical details obtained from reporting paediatricians are classified by an Expert Group. Results, By July 2008, 2493 cases of PIND had been reported, among which there were 112 children (69 males, 43 females) with mitochondrial diseases presenting between birth and 14 years 7 months (median 12mo), divided into 13 subgroups. In some instances, clinical features were characteristic of mitochondrial disease, but many children presented non-specifically with combinations of developmental delay, hypotonia, failure to thrive, and seizures; 16 children had multisystem disease at presentation. Mortality was high: 40 children had died. Blood and/or cerebrospinal fluid lactate measurements were abnormal in 87 children, and 47 of 78 brain magnetic resonance images showed increased basal ganglia signal. Definite diagnoses were usually made by muscle enzyme or genetic studies. Interpretation, This is a unique population-based study of the mitochondrial disorders that cause childhood neurodegenerative disease. It provides detailed information about the clinical presentation and investigation of these complex cases. [source]

Decreased activities of mitochondrial respiratory chain complexes in non-mitochondrial respiratory chain diseases

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 2 2006
Joannie Hui MBBS
The aim of this study was to illustrate the difficulties in establishing a diagnosis of mitochondrial respiratory chain (MRC) disorders based on clinical grounds in combination with intermediate activities of the MRC enzyme complexes. We reviewed retrospectively all medical and laboratory records of patients initially considered likely to have MRC disorders on clinical grounds, and subsequently diagnosed with other disorders (n=20; 11 males, 9 females). Data were retrieved from hospital records, referral letters, and results of enzymatic analysis at a reference laboratory. Clinical symptoms included developmental delay, epilepsy, hypotonia, movement disorder, spastic quadriplegia, tetany, microcephaly, visual problems, carpopedal spasms, dysmorphism, hearing loss, muscle weakness and rhabdomyolysis, and fulminant hepatitis. Blood and cerebrospinal fluid lactate levels were elevated in 13/20 and 9/20 respectively. One or more MRC complex activities (expressed as ratios relative to citrate synthase and/or complex II activity) were less than 50% of control mean activity in 11/20 patients (including patients with deficiencies of pyruvate dehydrogenase complex, pantothenate kinase, holocarboxylase synthetase, long-chain hydroxy acyl-CoA dehydrogenase, molybdenum co-factor, and neonatal haemochromatosis). One patient had a pattern suggestive of mitochondrial proliferation. We conclude that intermediate results of MRC enzymes should be interpreted with caution and clinicians should be actively looking for other underlying diagnoses. [source]

Timing of fetal exposure to stress hormones: Effects on newborn physical and neuromuscular maturation

DEVELOPMENTAL PSYCHOBIOLOGY, Issue 3 2008
Lauren M. Ellman
Abstract The purpose of the study was to determine the specific periods during pregnancy in which human fetal exposure to stress hormones affects newborn physical and neuromuscular maturation. Blood was collected from 158 women at 15, 19, 25, and 31 weeks' gestation. Levels of placental corticotropin-releasing hormone (CRH) and maternal cortisol were determined from plasma. Newborns were evaluated with the New Ballard Maturation Score. Results indicated that increases in maternal cortisol at 15, 19, and 25 weeks and increases in placental CRH at 31 weeks were significantly associated with decreases in infant maturation among males (even after controlling for length of gestation). Results also suggested that increases in maternal cortisol at 31 weeks were associated with increases in infant maturation among females, although these results were not significant after controlling for length of gestation. Findings suggest that stress hormones have effects on human fetal neurodevelopment that are independent of birth outcome. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 232,241, 2008. [source]

Decreased red blood cell aggregation subsequent to improved glycaemic control in Type 2 diabetes mellitus

DIABETIC MEDICINE, Issue 4 2003
B. Chong-Martinez
Abstract Aims Reports of rheological changes following intensification of metabolic control are limited and not concordant. The present study was designed to test the hypothesis that intensification of management of Type 2 diabetes (T2DM) with diet, exercise and insulin improves haemorheological behaviour by reducing red blood cell (RBC) aggregation. Methods Blood was sampled from 55 subjects before and following 14 ± 3 weeks of intensified management. RBC aggregation was measured in vitro for cells in plasma or in an aggregating 70 kD dextran solution. Plasma viscosity and whole blood viscosity were also measured. Results During treatment, fasting glucose fell 27%, HbA1c fell 21%, and serum triglycerides and total cholesterol fell 28% and 12%, respectively (P < 0.0001 for each). The extent and strength of RBC aggregation in plasma fell by 10,13% (P < 0.002). Similar decreases of RBC aggregation were seen for cells suspended in dextran (P < 0.002). Plasma viscosity decreased by 3% (P < 0.02) and high shear blood viscosity by 6,7% (P < 0.0001). Changes of RBC aggregation in plasma and in dextran were significantly correlated, supporting a cellular rather than a plasmatic origin for these changes. However, there were no significant correlations between RBC aggregation changes and changes of fasting glucose, HbA1c, serum triglycerides, serum cholesterol, or plasma fibrinogen. Conclusions Intensified metabolic control results in a reduction of RBC aggregation that appears to be intrinsic to RBC. Since increased RBC aggregation can impair microcirculatory flow, it is possible that haemorheological factors may contribute to the reduction of microvascular complications resulting from improved metabolic control in T2DM. [source]

Characteristic patterns of circadian variation in plasma catecholamine levels, blood pressure and heart rate variability in Type 2 diabetic patients

DIABETIC MEDICINE, Issue 5 2002
K. Kondo
Abstract Aims To investigate whether Type 2 diabetic patients exhibit characteristic patterns of circadian variation in plasma levels of catecholamines, blood pressure (BP) and heart rate variability (HRV). Methods Ten Type 2 diabetic and eight control in-patients were studied. Blood for catecholamine measurement was collected every 4 h, and non-invasive ambulatory BP and heart rate were monitored throughout the day. HRV was determined using frequency domain methods. Results Diabetic patients showed a different pattern of circadian variation in BP and HRV from that of controls, the diurnal-nocturnal differences (D-N) being significantly smaller. The mean 24-h HRV levels were reduced in diabetic subjects. The mean 24-h plasma noradrenaline level of 1.36 ± 0.12 nmol/l in diabetic patients was significantly lower than the 2.03 ± 0.20 nmol/l in controls (P < 0.01). In contrast, no significant difference in adrenaline levels was observed. The mean 24-h plasma noradrenaline level demonstrated a significant positive correlation with D-N in systolic BP (r = 0.49, P = 0.0153). Conclusions The present study demonstrated distinctive patterns of circadian variation in plasma noradrenaline level, BP and HRV in Type 2 diabetic patients, associated with an abnormal circadian pattern of sympathovagal modulation. [source]

Blood and bone marrow pathology: Authors: Sunitha N. Wickramasinghe and Jeffrey McCullough.

DIAGNOSTIC CYTOPATHOLOGY, Issue 1 2005
Churchill Livingstone
No abstract is available for this article. [source]

SDS-PAGE of recombinant and endogenous erythropoietins: benefits and limitations of the method for application in doping control

DRUG TESTING AND ANALYSIS, Issue 1 2009
Christian Reichel
Abstract Doping of athletes with recombinant and genetically modified erythropoietins (EPO) is currently detected by isoelectric focusing (IEF). The application of these drugs leads to a significant change in the isoform profile of endogenous urinary erythropoietin (uhEPO). Dynepo, MIRCERA, biosimilars with variable IEF-profiles as well as active urines and effort urines have made additional testing strategies necessary. The new generation of small molecule EPO-receptor stimulating agents like Hematide will also challenge the analytical concept of detecting the abuse of erythropoiesis stimulating agents (ESA). By determining their apparent molecular masses with SDS-PAGE a clear differentiation between endogenous and exogenous substances also concerning new EPO modifications is possible. Due to the orthogonal character of IEF- and SDS-PAGE both methods complement each other. The additional benefits of SDS-PAGE especially in relation to active and effort urines as well as the detection of Dynepo were investigated. Due to significant differences between the apparent molecular masses of uhEPO/serum EPO (shEPO) and recombinant, genetically or chemically modified erythropoietins the presence of active or effort urines was easily revealed. The characteristic band shape and apparent molecular mass of Dynepo on SDS-PAGE additionally evidenced the presence of this substance in urine. A protocol for the detection of EPO-doping in serum and plasma by SDS-PAGE was developed. Blood appears to be the ideal matrix for detecting all forms ESA-doping in the future. Copyright © 2009 John Wiley & Sons, Ltd. [source]

"My Two-week-old Daughter Is Throwing up Blood"

ACADEMIC EMERGENCY MEDICINE, Issue 8 2005
M.H. Moustafa MD
Abstract Swallowed maternal blood at the time of delivery or from cracked nipples during breastfeeding is the most common cause of suspected gastrointestinal bleeding in the neonate. In this case, the Apt,Downey test is a useful diagnostic tool. The Apt,Downey test can effectively differentiate neonatal from maternal hemoglobin based on the conversion of oxyhemoglobin to alkaline globin hematin when mixed with alkali. [source]

Impact of microcystin containing diets on physiological performance of Nile tilapia (Oreochromis niloticus) concerning stress and growth,

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2010
Andrea Ziková
Abstract Diets containing Microcystis with considerable amounts of the cyanotoxin microcystin-LR (MC-LR) were fed to determine their impact on the physiological performance of the omnivorous Nile tilapia (Oreochromis niloticus) with regard to stress and growth performance. Four different diets were prepared based on a commercial diet (control, MC-5% [containing 5% dried Microcystis biomass], MC-20% [containing 20% dried Microcystis biomass], and Arthrospira-20% [containing 20% dried Arthrospira sp. biomass without toxin]) and fed to female Nile tilapia. Blood and tissue samples were taken after 1, 7, and 28 d, and MC-LR was quantified in gills, muscle, and liver by using high-performance liquid chromatography (HPLC). Only in the liver were moderate concentrations of MC-LR detected. The stress hormone cortisol and glucose were analyzed from plasma, suggesting that all modified diets caused only minor to moderate stress, which was confirmed by analyses of hepatic glycogen. In addition, the effects of the different diets on growth performance were investigated by determining gene expression of hypophyseal growth hormone (GH) and hepatic insulin-like growth factor-I (IGF-I). For all diets, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) demonstrated no significant effect on gene expression of the major endocrine hormones of the growth axis, whereas classical growth data, including growth and feed conversion ratio, displayed slight inhibitory effects of all modified diets independent of their MC-LR content. However, no significant change was found in condition or hepatosomatic index among the various diets, so it seems feasible that dried cyanobacterial biomass might be even used as a component in fish diet for Nile tilapia, which requires further research in more detail. Environ. Toxicol. Chem. 2010;29:561,568. © 2009 SETAC [source]

Disposition of perfluorinated acid isomers in sprague-dawley rats; Part 2: Subchronic dose

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2009
Amila O. De Silva
Abstract Two major industrial synthetic pathways have been used to produce perfluorinated acids (PFAs) or their precursors: Telomerization and electrochemical fluorination (ECF). Products of telomer and ECF origin can be distinguished by structural isomer profiles. A mixture of linear and branched perfluoroalkyl isomers is associated with ECF. Telomer products characteristically consist of a single perfluoroalkyl geometry, typically linear. In biota, it is unclear if the isomer profile is conserved relative to the exposure medium and hence whether PFA isomer profiles in organisms are useful for distinguishing environmental PFA sources. A companion study suggested isomer-specific disposition following a single oral gavage exposure to rats. To confirm these findings under a more realistic subchronic feeding scenario, male and female rats were administered PFA isomers by diet for 12 weeks, followed by a 12-week depuration period. The diet contained 500 ng/g each of ECF perfluorooctanoate (PFOA, ,80% n -PFOA), ECF perfluorooctane sulfonate (PFOS, ,70% n -PFOS), and linear and isopropyl perfluorononanoate (n - and iso -PFNA). Blood sampling during the exposure phase revealed preferential accumulation of n -PFOA and n -PFNA compared to most branched isomers. Female rats depurated all isomers faster than males. Both sexes eliminated most branched perfluorocarboxylate isomers more rapidly than the n -isomer. Elimination rates of the major branched PFOS isomers were not statistically different from n -PFOS. Two minor isomers of ECF PFOA and one branched PFOS isomer had longer elimination half-lives than the n-isomers. Although extrapolation of these pharmacokinetics trends in rats to humans and wildlife requires careful consideration of dosage level and species-specific physiology, cumulative evidence suggests that perfluorocarboxylate isomer profiles in biota may not be suitable for quantifying the relative contributions of telomer and ECF sources. [source]

Organochlorine contaminants in sea turtles: Correlations between whole blood and fat

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2004
Jennifer M. Keller
Abstract Monitoring toxic organochlorine(OC)compounds is an important aspect in wildlife studies, especially in protected species such as sea turtles. The goal of this study was to determine whether blood OC concentrations can predict those in adipose tissue of sea turtles. Blood offers many benefits for monitoring OCs. It can be collected nondestructively from live turtles and can be sampled repeatedly for continuous monitoring. Organochlorine concentrations in blood may better represent the exposure levels of target tissues, but blood concentrations may fluctuate more than those in fatty tissues following recent dietary exposure or lipid mobilization. Paired fat and blood samples were collected from 44 live, juvenile loggerhead sea turtles and 10 juvenile Kemp's ridley sea turtle carcasses. Organochlorines were analyzed using gas chromatography with electron capture detection and mass spectrometry. Lipid-normalized OC concentrations measured in the blood significantly correlated to levels found in the fat samples of both species. This result suggests that sea turtle blood is a suitable alternative to fatty tissues for measuring OCs because blood concentrations reasonably represent those observed in the paired fat samples. However, blood OC concentrations calculated on a wet-mass basis were significantly and inversely correlated to lipid content in the fat samples. Therefore, caution should be used when monitoring spatial or temporal trends, as OC levels may increase in the blood following mobilization of fat stores, such as during long migrations, breeding, or disease events. [source]

Blood,brain barrier damage and brain penetration of antiepileptic drugs: Role of serum proteins and brain edema

EPILEPSIA, Issue 4 2009
Nicola Marchi
Summary Purpose:, Increased blood,brain barrier (BBB) permeability is radiologically detectable in regions affected by drug-resistant epileptogenic lesions. Brain penetration of antiepileptic drugs (AEDs) may be affected by BBB damage. We studied the effects of BBB damage on brain distribution of hydrophilic [deoxy-glucose (DOG) and sucrose] and lipophilic (phenytoin and diazepam) molecules. We tested the hypothesis that lipophilic and hydrophilic drug distribution is differentially affected by BBB damage. Methods:, In vivo BBB disruption (BBBD) was performed in rats by intracarotid injection of hyperosmotic mannitol. Drugs (H3-sucrose, 3H-deoxy-glucose, 14C-phenytoin, and C14-diazepam) or unlabeled phenytoin was measured and correlated to brain water content and protein extravasation. In vitro hippocampal slices were exposed to different osmolarities; drug penetration and water content were assessed by analytic and densitometric methods, respectively. Results:, BBBD resulted in extravasation of serum protein and radiolabeled drugs, but was associated with no significant change in brain water. Large shifts in water content in brain slices in vitro caused a small effect on drug penetration. In both cases, total drug permeability increase was greater for lipophilic than hydrophilic compounds. BBBD reduced the amount of free phenytoin in the brain. Discussion:, After BBBD, drug binding to protein is the main controller of total brain drug accumulation. Osmotic BBBD increased serum protein extravasation and reduced free phenytoin brain levels. These results underlie the importance of brain environment and BBB integrity in determining drug distribution to the brain. If confirmed in drug-resistant models, these mechanisms could contribute to drug brain distribution in refractory epilepsies. [source]

Seizure-Promoting Effect of Blood,Brain Barrier Disruption

EPILEPSIA, Issue 4 2007
Nicola Marchi
Summary:,Purpose: It is generally accepted that blood,brain barrier (BBB) failure occurs as a result of CNS diseases, including epilepsy. However, evidences also suggest that BBB failure may be an etiological factor contributing to the development of seizures. Methods: We monitored the onset of seizures in patients undergoing osmotic disruption of BBB (BBBD) followed by intraarterial chemotherapy (IAC) to treat primary brain lymphomas. Procedures were performed under barbiturate anesthesia. The effect of osmotic BBBD was also evaluated in naive pigs. Results: Focal motor seizures occurred immediately after BBBD in 25% of procedures and originated contralateral to the hemisphere of BBBD. No seizures were observed when BBB was not breached and only IAC was administered. The only predictors of seizures were positive indices of BBBD, namely elevation of serum S100, levels and computed tomography (CT) scans. In a porcine model of BBBD, identical procedures generated an identical result, and sudden behavioral and electrographic (EEG) seizures correlated with successful BBB disruption. The contribution of tumor or chemotherapy to acute seizures was therefore excluded. Conclusion: This is the first study to correlate extent of acute BBB openings and development of seizures in humans and in a large animal model of BBB opening. Acute vascular failure is sufficient to cause seizures in the absence of CNS pathologies or chemotherapy. [source]

Genomics of Brain and Blood: Progress and Pitfalls

EPILEPSIA, Issue 10 2006
Frank R Sharp
Summary:, Gene expression profiles in brain and blood of animals and humans can be useful for diagnosis, prognosis, and treatment of epilepsy. This article reviews recent progress and prospects for the future. [source]

Prolactin Levels in Sudden Unexpected Death in Epilepsy

EPILEPSIA, Issue 1 2000
K. Opeskin
Summary: Purpose: To assess serum prolactin levels in sudden unexpected death in epilepsy (SUDEP) and control groups to test the hypothesis that if seizures occur routinely as a terminal event in SUDEP, then raised prolactin levels may be an indicator of terminal seizure. Methods: Blood was taken for measurement of prolactin levels from subjects with SUDEP and three control groups. The control groups were those with epilepsy dying from causes other than epilepsy (e.g., ischemic heart disease or injuries), physiologically stressed individuals without epilepsy (they were admitted to the hospital after an acute illness and died after several hours to 3 days), and nonepileptic rapid deaths (these people collapsed suddenly and died at the scene). In the SUDEP group, evidence for terminal seizure was considered to be at least one of the following: body found half on, half off the bed, or urinary incontinence at the scene, or bitten lips or tongue at autopsy. Results: There was evidence for terminal seizure at the scene or at autopsy in four of the 10 SUDEP cases. Serum prolactin levels were not significantly increased in the SUDEP group compared with the controls. None of the SUDEP subjects, including those with clinical evidence of a terminal seizure, had high prolactin levels characteristic of those observed after seizures in living subjects. Conclusions: Prolactin levels are not raised in SUDEP, even if there is evidence of terminal seizure. As prolactin takes 15,20 min to peak after a seizure in life, there may be insufficient time for a prolactin increase to occur in SUDEP. Thus prolactin levels cannot be used to determine if a deceased individual with epilepsy had a seizure or to answer the broad question whether SUDEP is always associated with a terminal seizure. [source]

Application of a constant blood withdrawal method in equine exercise physiology studies

EQUINE VETERINARY JOURNAL, Issue 6 2001
P. BARAGLI
Summary The aim of the present study was to test a constant blood withdrawal method (CBWM) to collect blood samples from horses during treadmill exercise. CBWM was performed in 4 Standardbreds and 5 Haflinger horses. A peristaltic pump was used to control blood aspiration from an i.v. catheter via an extension line. Blood was collected using an automatic fractions collector, with a constant delay time between the drawing of blood and sample collection. Blood withdrawal using CBWM was made during a treadmill standardised exercise test (SET). A blood flow of 12 ml/min was used and samples collected every 60 s during the entire period of exercise. The volume of blood collected in each sample tube was 12.1 ± 0.2 ml, with a delay time of mean ± s.d. 25.3 ± 0.8 s. Plasma lactate kinetics based on measurement of lactate in each fraction showed an exponential increase during the first 13 min of exercise (10.5 min of SET and 2.5 min recovery). The peak plasma lactate concentration was observed between 2.5 and 5.5 min after the end of SET. CBWM permits the kinetics of lactate and other blood-borne variables to be studied over time. This method could be a valuable aid for use in studying equine exercise physiology. [source]

Effects of phlebotomy on haemodynamic characteristics during exercise in Standardbred trotters with red cell hypervolaemia

EQUINE VETERINARY JOURNAL, Issue 4 2001
P. FUNKQUIST
Summary Five Standardbred trotters with red cell hypervolaemia (RCHV) were compared before and after removal of approximately 22% (36 ml/kg bwt) of the total blood volume in order to evaluate the haemodynamic responses, haemorheological alterations and oxygen transport during exercise to fatigue. Data were recorded during submaximal exercise at 4 different speeds on a treadmill and then during continued running at the highest speed step until fatigue. Oxygen uptake (V,O2), pulmonary artery pressure (PAP), systemic artery pressure (SAP), heart rate (HR), haematocrit and haemoglobin concentrations (Hb) were measured. Arteriovenous O2 content difference (C(a-v,)O2), pulmonary vascular resistance (PVR) and total systemic resistance (TSR) were calculated. Whole blood and plasma viscosity and erythrocyte aggregation tendency were determined with a rotational viscometer. Endoscopy was performed after exercise. ANOVA was used for statistical analysis. Phlebotomy resulted in a decrease in haematocrit and Hb during the course of exercise. Blood and plasma viscosity were lower and erythrocyte aggregation tendency was higher after phlebotomy. Throughout exercise, including submaximal work and continued running to fatigue, PAP, SAP, PVR, TSR and C(a-v,)O2 were lower after phlebotomy. HR was higher after phlebotomy during submaximal exercise. Oxygen delivery and VO2 were lower after phlebotomy in the period from submaximal exercise to fatigue. Run time to fatigue was shorter after phlebotomy. Four horses showed exercise-induced pulmonary haemorrhage (EIPH) before phlebotomy and the degree of bleeding was diminished but not abolished after phlebotomy. The reductions in PVR, TSR, PAP and SAP after phlebotomy were probably a result of reduced blood viscosity. In conclusion, although a 22% reduction in blood volume improved the haemodynamic and haemorheological parameters and the degree of EIPH, it was found that RCHV trotters have to rely on high oxygen delivery to the working muscles for maintenance of maximal performance. [source]

BNP and N-terminal proBNP are both extracted in the normal kidney

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 1 2006
J. P. Goetze
Abstract Background, Increased plasma concentrations of cardiac-derived B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (proBNP) are both associated with left ventricular dysfunction. Information on the regional elimination of the peptides is, however, still scarce. We therefore examined the renal and peripheral extraction of N-terminal proBNP and BNP. Materials and methods, The study comprised 18 patients with essential arterial hypertension, 51 with cirrhosis, and 18 control patients without kidney or liver disease. All patients underwent a haemodynamic investigation with catheterization of the femoral artery and femoral and renal veins. Blood sampling from the catheters allowed determination of the arteriovenous extraction ratio of N-terminal proBNP and BNP. Results, Neither the peripheral N-terminal proBNP (13, 11, 19 pmol L,1, NS) nor the BNP plasma concentrations (4, 12, 9 pmol L,1, NS) differed between the patient groups. In addition, similar renal extractions were observed in the groups. The renal extraction of N-terminal proBNP (0·16) was not different from that of BNP (0·16). In contrast, the N-terminal proBNP extraction in the lower extremity was markedly lower compared with BNP (0·00 vs. 0·125, P = 0·007). Conclusions, A comparable renal elimination of N-terminal proBNP and BNP is contrasted by a selective extraction of BNP in the lower extremity. Our results suggest a different elimination mechanism in the renal and peripheral circulation, which partly may explain the higher N-terminal proBNP compared with BNP concentrations in normal plasma. [source]

Haematological reference values in Spanish adolescents: the AVENA study

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2009
Javier Romeo
Abstract Objectives:, To provide reference values for haematological indices in Spanish adolescents according to age and gender. Methods:, A cross sectional study conducted in five Spanish cities was performed. Blood was drawn from a representative sample of 581 adolescents with age ranging from 13 to 17,18.5 yr. Age- and gender-specific means, standard deviations and percentiles were determined for the following parameters: total red blood cell counts (RBC), haemoglobin concentration (Hb), haematocrit percentage (Hct), mean corpuscular volume (MCV), mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red cell distribution width and total white blood cell (WBC) counts as well as counts and percentage of neutrophils, lymphocytes, monocytes, eosinophils and basophils; platelet count (PLT), mean platelet volume and plateletcrit percentage. Results:, Younger male subjects presented lower RBC, Hb, Hct and MCV means that their older counterpart. By contrast these differences were not observed in female subjects. As expected, RBC, Hb and Hct mean values in males were found significantly higher than in girls for all studied age groups. No significant differences were observed in WBC by age and gender. PLT values gradually decreased with age, except for females aged 17,18.5 yr. Conclusion:, The present study provides reference data on the distribution of haematological indices of Spanish adolescents. These data can be useful biomarkers of the nutritional status in adolescents. [source]

Efficacy of single-agent bortezomib vs. single-agent thalidomide in patients with relapsed or refractory multiple myeloma: a systematic comparison

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2007
H. Miles Prince
Abstract Objective:, To conduct a systematic review of the efficacy of single-agent bortezomib vs. single-agent thalidomide in patients with relapsed/refractory multiple. Methods:, Publications in English from 1966 to June 2005 (MEDLINE, EMBASE, Cochrane library), publication reference lists, Janssen-Cilag data-on-file and abstracts from recent multiple myeloma conferences were reviewed. Prospective studies containing at least a single arm of either treatment group with n,30 were included. Studies adding dexamethasone for non-responders were excluded. Statistical pooling was performed for response rate and overallsurvival. Results:, One bortezomib study (n = 333, NEJM 2005, 352; 2487,98) and 15 thalidomide (n = 1007) studies met these criteria and were included. Patient baseline characteristics including age, gender, IgG : IgA, disease duration and beta-2 microglobulin were well matched except that 48% of bortezomib patients had received prior thalidomide. Response rate, defined as serum M-protein reduction ,50%, was 53% for patients receiving bortezomib vs. 32% for thalidomide (P < 0.001, n = 10 studies). Response rate determined by European Group for Blood and Marrow Transplantation (EBMT) criteria was 41% for patients receiving bortezomib vs. 22% for thalidomide (P < 0.001, n = 4 studies). Conclusion:, Bortezomib was associated with a significantly higher response rate and complete remission rate using both M-protein and EBMT criteria. [source]

Micropatterning: Patterned Hydrogels for Controlled Platelet Adhesion from Whole Blood and Plasma (Adv. Funct.

ADVANCED FUNCTIONAL MATERIALS, Issue 15 2010
Mater.
Poly(ethylene glycol)-based hydrogel coatings patterned with selected proteins can be utilized to control and study the adhesion of human blood platelets with excellent precision, as presented by B. Liedberg et al. on page 2396. This frontispiece shows how imaging surface plasmon resonance is used in combination with fluorescence microscopy to investigate the platelet adhesion process in undiluted blood plasma. [source]

Patterned Hydrogels for Controlled Platelet Adhesion from Whole Blood and Plasma

ADVANCED FUNCTIONAL MATERIALS, Issue 15 2010
Tobias Ekblad
Abstract This work describes the preparation and properties of hydrogel surface chemistries enabling controlled and well-defined cell adhesion. The hydrogels may be prepared directly on plastic substrates, such as polystyrene slides or dishes, using a quick and experimentally simple photopolymerization process, compatible with photolithographic and microfluidic patterning methods. The intended application for these materials is as substrates for diagnostic cell adhesion assays, particularly for the analysis of human platelet function. The non-specific adsorption of fibrinogen, a platelet adhesion promoting protein, is shown to be completely inhibited by the hydrogel, provided that the film thickness is sufficient (>5,nm). This allows the hydrogel to be used as a matrix for presenting selected bioactive ligands without risking interference from non-specifically adsorbed platelet adhesion factors, even in undiluted whole blood and blood plasma. This concept is demonstrated by preparing patterns of proteins on hydrogel surfaces, resulting in highly controlled platelet adhesion. Further insights into the protein immobilization and platelet adhesion processes are provided by studies using imaging surface plasmon resonance. The hydrogel surfaces used in this work appear to provide an ideal platform for cell adhesion studies of platelets, and potentially also for other cell types. [source]

Pharmacokinetics of alizapride in children receiving chemotherapy for solid tumour

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2001
Elisabeth Rey
The purpose of the present study was to determine the pharmacokinetics of alizapride to optimize its use in children aged 1 month to 15 years old who were receiving chemotherapy. Seventeen children were given a single 4 mg/kg alizapride infusion prior to the administration of cytostatic drugs. Blood and urine samples were collected within 10 h after onset of the infusion. Kinetic parameters were calculated and showed a decrease in plasma clearance expressed per unit of body weight with age. The current data suggest that dosage expressed per unit of body weight should be higher in children than in adults and higher in infants than in children. [source]

The impact of joint bleeding and synovitis on physical ability and joint function in a murine model of haemophilic synovitis

HAEMOPHILIA, Issue 1 2008
C. MEJIA-CARVAJAL
Summary., Haemophilia is a congenital disorder that commonly results in musculoskeletal bleeding and orthopaedic complications. After an acute joint haemorrhage, an increase in intra-articular pressure and inflammation cause pain, swelling and limited motion. Blood in the joint space provokes a proliferative disorder known as haemophilic synovitis. Overgrowth of the synovial membrane causes mechanical dysfunction. Eventually, there is destruction of the articular surface and underlying bone. The aim of this project was to test the hypothesis that a minimum number of haemarthroses negatively impacts on joint function and that this would be reflected by decreased physical performance of experimental animals. Mice deficient in factor VIII coagulant activity were trained to ambulate on a rotating rod then injured three times at weekly intervals. Their ability to walk was then compared to a group of uninjured mice. Cohorts of mice were killed after 1, 2 or 3 months and the knee joints examined by gross and histological methods. The results supported the following conclusions: (i) haemophilic mice can be trained to ambulate on a rotating rod; (ii) acute hemarthrosis temporarily impairs their ability to ambulate and (iii) following recovery from acute injury, mice developing synovitis demonstrated inferior physical ability compared to mice not developing synovitis. This is the first description of a quantitative assay to monitor joint function in experimental animals and should be useful to evaluate the efficacy of new therapies developed to prevent and treat bleeding and to test strategies to counter the devastating effects of synovitis. [source]

COX-2 polymorphisms and the risk for head and neck cancer in white patients

HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 7 2009
Wilbert H. M. Peters PhD
Abstract Background. Cyclooxygenase-2 (COX-2) is an enzyme involved in the synthesis of prostaglandins and thromboxanes, which are regulators of processes such as inflammation, cell proliferation, and angiogenesis, all relevant for cancer development. We investigated whether functional genetic polymorphisms in COX-2 may have a risk-modifying effect on head and neck carcinogenesis. Methods. Blood from 431 white patients with oral, pharyngeal, or laryngeal carcinoma and 438 white healthy controls was investigated for the presence of 2 functional promoter region polymorphisms (,1195A,G and ,765G,C) in COX-2. Results. Logistic regression analysis did not show differences in COX-2 genotype distributions between patients and controls. Also no differences were found when stratified according to tumor localization, sex, or tobacco consumption. Conclusion. In contrast to earlier reports on the role of these COX-2 polymorphisms in mediating susceptibility to squamous esophageal carcinoma in a Chinese population, we could not demonstrate a risk-modifying effect in head and neck carcinogenesis in whites. © 2009 Wiley Periodicals, Inc. Head Neck, 2009 [source]