Automated postoperative blood pressure control

Abstract  It is very important to maintain the level of mean arterial pressure (MAP) . The MAP control is applied in many clinical situations, including limiting bleeding during cardiac surgery and promoting healing for patient’s post-surgery. This paper presents a fuzzy controller-based multiple-model adaptive control system for postoperative blood pressure management. Multiple-model adaptive control (MMAC) algorithm is used to identify the patient model, and it is a feasible system identification. method even in the presence of large noise. Fuzzy control (FC) method is used to design controller bank. Each fuzzy controller in the controller bank is in fact a nonlinear proportional-integral (PI) controller, whose proportional gain and integral gain are adjusted continuously according to error and rate of change of error of the plant output, resulting in better dynamic and stable control performance than the regular PI controller, especially when a nonlinear process is involved. For demonstration, a nonlinear, pulsatile-flow patient model is used for simulation, and the results show that the adaptive control system can effectively handle the changes in patient’s dynamics and provide satisfactory performance in regulation of blood pressure of hypertension patients.

Blood flow does not limit skeletal muscle force production during incremental isometric contractions

Abstract  It has been suggested that a transient limitation in blood flow during intermittent muscular contractions can contribute to muscle fatigue, and that this limitation is greater as contraction intensity increases. We investigated skeletal muscle blood flow and fatigue in 13 healthy, untrained men (21–27 years) during 16 min of intermittent (4 s contract, 6 s relax) isometric dorsiflexor contractions. Contractions began at 10% of pre-exercise maximal voluntary contraction (MVC) force and increased by 10% every 2 min. Hyperemia (i.e., post-contraction blood flow, measured by venous occlusion plethysmography) and MVC were measured at the end of each stage. Muscle volume measures were obtained using magnetic resonance imaging. After 10 min of exercise, submaximal force and post-contraction hyperemia plateaued. MVC fell from 8 min of exercise onwards (p=0.004), and this onset of fatigue preceded the plateau in submaximal force and hyperemia. Despite a large range in dorsiflexor muscle size (66.3–176.4 cm3) and strength (112.5–421.8 N), neither muscle size nor strength were related to fatigue. The temporal dissociation between changes in blood flow and the onset of fatigue (fall of MVC) suggest that limited blood flow was not a factor in the impaired force production observed during intermittent isometric dorsiflexor contractions in healthy young men. Additionally, post-contraction hyperemia increased linearly with increasing contraction intensity, reflecting a match between blood flow and force production throughout the protocol that was independent of fatigue.

Electroacupuncture Reduces Rectal Distension-Induced Blood Pressure Changes in Conscious Dogs

Abstract  It has been shown that acupuncture relieves symptoms of abdominal pain and bloating in patients with irritable bowel syndrome (IBS). However, the mechanism of beneficial effects of acupuncture still remains unproven. The aim of the present study was to investigate the mechanisms of the antinociceptive effects of acupuncture in conscious dogs. We evaluated the increase in mean arterial blood pressure (MAP) caused by rectal distension as an index of visceral pain. Electroacupuncture (EA; 10 Hz) at ST-36 (lower leg), but not at BL-21 (back), significantly reduced the increase in MAP in response to rectal distension (30 and 40 cm3). The antinociceptive effect of EA at ST-36 was abolished by pretreatment with naloxone (a central and peripheral opioid receptor antagonist) but not by naloxone methiodide (a peripheral opioid receptor antagonist). These results suggest that EA at ST-36 may reduce visceral pain via central opioid pathway. Acupuncture may be useful to treat visceral hypersensitivity in IBS patients.

Nephron endowment and blood pressure: What do we really know?

Abstract  It has been hypothesized that a reduced number of nephrons at birth contributes to the development of essential hypertension. Nephron number in normal human kidneys has been shown to vary up to eightfold. Therefore, a significant proportion of the population appears to be at risk for developing hypertension. Furthermore, nephron deficits might explain why some racial groups have a higher incidence of hypertension and end-stage renal disease than others. Animal studies have demonstrated that maternal limitations in nutrient supply, both gross and nutrient-specific; exposure to elevated levels of hormones or toxins; and genetic factors can lead to permanent deficits in nephron number and, when examined, elevated blood pressure. In this review, maternal and genetic factors influencing nephron endowment and the implications of nephron deficit for hypertension and renal disease in humans are discussed.

Causes of differences in exercise-induced changes of base excess and blood lactate

Abstract  It has been concluded from comparisons of base excess (BE) and lactic acid (La) concentration changes in blood during exercise-induced acidosis that more H+ than La− leave the muscle and enter interstitial fluid and blood. To examine this, we performed incremental cycle tests in 13 untrained males and measured acid–base status and [La] in arterialized blood, plasma, and red cells until 21 min after exhaustion. The decrease of actual BE (−ΔABE) was 2.2 ± 0.5 (SEM) mmol l−1 larger than the increase of [La]blood at exhaustion, and the difference rose to 4.8 ± 0.5 mmol l−1 during the first minutes of recovery. The decrease of standard BE (SBE), a measure of mean BE of interstitial fluid (if) and blood, however, was smaller than the increase of [La] in the corresponding volume (Δ[La]if+blood) during exercise and only slightly larger during recovery. The discrepancy between −ΔABE and Δ[La]blood mainly results from the Donnan effect hindering the rise of [La]erythrocyte to equal values like [La]plasma. The changing Donnan effect during acidosis causes that Cl− from the interstitial fluid enter plasma and erythrocytes in exchange for HCO3−. A corresponding amount of La− remains outside the blood. SBE is not influenced by ion shifts among these compartments and therefore is a rather exact measure of acid movements across tissue cell membranes, but changes have been compared previously to Δ[La]blood instead to Δ[La]if+blood. When performing correct comparisons and considering Cl−/HCO3− exchange between erythrocytes and extracellular fluid, neither the use of ΔABE nor of ΔSBE provides evidence for differences in H+ and La− transport across the tissue cell membranes.

Effects of γ-irradiation on the membrane ATPases of human erythrocytes from transfusional blood concentrates

Abstract  Irradiation of blood derivatives is employed in blood banks to avoid transfusion-associated graft-vs-host disease. As irradiation can damage membranes and membrane proteins by generation of reactive oxygen species, we investigated whether the membrane permeability, Na+,K+–ATPase, and Ca2+–ATPase from red blood cell plasma membranes were altered by γ-irradiation. Whole blood was collected from healthy donors and concentrated to 90% cell fraction. Within 24 h of collection, blood concentrates were irradiated with 25 Gy of γ-radiation. At days 1, 7, 14, and 28 post-irradiation, fractions were removed and centrifuged. Na+,K+–ATPase and Ca2+–ATPase activities from ghost membranes were assessed by γ-32P-ATP hydrolysis. The Na+,K+–ATPase was not immediately affected by irradiation, but it was inhibited by 40% by day 14 and until day 28. The Ca2+–ATPase was unaltered by irradiation. The rate and the maximal 45Ca2+ uptake from re-sealed inside–out vesicles were reduced, and the passive efflux of 45Ca2+ was increased. Thus, irradiation of blood concentrates increased the plasma membrane permeability to monovalent and divalent cations and would change ion homeostasis and cell function. We recommend the use of irradiated blood within a period shorter than 14 days after irradiation.

Pharmacodynamic model of interleukin-21 effects on red blood cells in cynomolgus monkeys

Abstract  Interleukin-21 (IL-21) is a novel cytokine that is currently under clinical investigations as a potential anti-cancer agent. Like many other anti-cancer agents, including other interleukins, IL-21 is seen to produce a broad range of biological effects that may be related to both efficacy and safety of treatment. The present analysis investigates the observed pharmacodynamics effects on red blood cells following various treatment schedules of human IL-21 administrated to cynomolgus monkeys. These effects are described by a novel non-linear mixed-effects model that enabled separation of drug effects and sampling effects, the latter believed to be due partly to blood loss and partly to stress induced haemolysis in connection with blood sampling. Two different studies with a total of 9 different treatment groups of cynomolgus monkeys were used for model development. In conclusion, the model describes the IL-21 induced drop in red blood cells to be (1) caused by removal rather than suppression of production, consistent with increased reticulocyte concentration, and (2) considerably delayed compared to dosing, i.e. not related to the drop in red blood cells observed immediately post dose. It is believed that the structural model presented here can be used for other types of drug induced loss of red blood cells, whereas the mechanism for sampling related blood loss is relevant for investigations of anaemia in all pharmacological studies with smaller animals.

Interferon-gamma production by human cord blood monocyte-derived dendritic cells

Abstract  Interferon (IFN)- is produced by T cells and natural killer cells and activates monocytes and dendritic cells (DCs). Recently, IFN- has been shown to be produced by mouse DCs following stimulation with interleukin (IL)-12, which is markedly augmented by the addition of IL-18. We here analyzed whether human DCs secrete IFN- in response to IL-12 and/or IL-18. Human immature DCs, generated from cord blood CD14+ monocytes by treating with granulocyte–macrophage colony-stimulating factor and IL-4, were incubated with IL-12 and/or IL-18 and assayed for IFN- production. IL-12, but not IL-18, weakly induced IFN- production, while IL-12 together with IL-18 induced high levels of IFN- production. Similar results were obtained with mature DCs, although levels of IFN- production were less than those in immature DCs. Also with mature and immature DCs, IL-12 upregulated the expression of IL-18 receptor (R), and costimulation with IL-12 and IL-18 upregulated CD40 expression. Anti-IL-18R antibody abrogated both the IFN- induction and the CD40 upregulation by IL-12 plus IL-18. These findings suggest that IL-12 upregulates IL-18R expression on human DCs and acts synergistically with IL-18 to induce high levels of IFN-, which subsequently enhances CD40 expression on DCs in an autocrine manner.

Interaction of unmodified and partially silylated nanosilica with red blood cells

Abstract  Interaction of red blood cells (RBCs) with unmodified and partially (50%) silylated fumed silica A-300 (nanosilica)was studied by microscopic, XRD and thermally stimulated depolarisation current (TSDC) methods. Nanosilica at a low concentration C A-300 < 0.01 wt.% in buffered aqueous suspension is characterised by a weak haemolytic effect on RBCs. However, at C A-300 = 1 wt% all RBCs transform into shadow corpuscles because of 100% haemolysis. Partial (one-half) hydrophobization of nanosilica leads to reduction of the haemolytic effect in comparison with unmodified silica at the same concentrations. A certain portion of the TSDC spectra of the buffered suspensions with RBC/A-300 is independent of the amounts of silica. However, significant portions of the low-and high-temperature TSDC bands have a lower intensity at C A-300 = 1 wt% than that for RBCs alone or RBC/A-300 at C A-300 = 0.01 wt.% because of structural changes in RBCs. Results of microscopic and XRD investigations and calculations using the TSDC-and NMR-cryoporometry suggest that the intracellular structures in RBCs (both organic and aqueous components) depend on nanosilica concentration in the suspension.

Prooxidant and antioxidant systems of the blood during experimental bile peritonitis

Abstract  Intensification of lipid peroxidation against the background of exhaustion of the antioxidant protective system was demonstrated in 70 rats with experimental bile peritonitis. Free radical oxidation primarily concerned free lipids and fatty acids in the plasma and to a lesser extent erythrocyte membrane lipids.

The effect of AMPD1 genotype on blood flow response to sprint exercise

Abstract  Inherited deficiency of skeletal muscle myoadenylate deaminase (mAMPD) is a genetic disorder characterized primarily by a 34C>T transition in exon 2 of the AMPD1 gene. mAMPD deficient individuals exhibit alterations in ATP catabolic flow, resulting in greater adenosine accumulation during high intensity exercise that may possibly enhance exercise-induced hyperaemia. This study tested the hypothesis that individuals with diminished mAMPD activity due to mutations in the AMPD1 gene develop a greater and faster blood flow response to high intensity exercise than individuals with two AMPD1 normal alleles (NN). Four 34C>T homozygotes, two compound heterozygotes (34C>T in one allele and a recently identified 404delT mutation in the other AMPD1 allele), collectively termed MM, one 34C>T heterozygote (NM) and eight NN males were studied. They performed a 30 s Wingate cycling test with monitoring of power output and other parameters of exercise performance. Common femoral artery blood flow was measured before and after (up to 25 min) exercise, using ultrasonography. Mean power during Wingate cycling was approximately 10% lower in MM/NM than in NN; p < 0.01. Blood flow response to exercise also differed between MM/NM and NN individuals (ANOVA; p < 0.001). There was also a difference in peak post-exercise blood flow (p < 0.05), and the subsequent fall in blood flow during the recovery phase (T1/2) occurred more than twice as fast in MM/NM compared to NN subjects (7.8 ± 1.1 min vs. 16.1 ± 1.4 min, p < 0.001). These results suggest a better circulatory adaptation to exercise in individuals with diminished mAMPD activity, probably due to an AMPD1 genotype-dependent increase in adenosine formation.

Activation techniques for the determination of stable isotopes of cerium in blood plasma

Abstract  Information on the biokinetics of cerium can be obtained directly from humans by using stable isotopes as tracers. Neutron, photon and proton activation analysis have all been tested as analytical techniques able to quantify different isotopes of the same element in biological fluids. The experimental conditions were optimized for Ce analysis in blood plasma samples. The performances of the different techniques have been explored. The simultaneous determination of two Ce isotopes with the required sensitivity in the order of few ppb is difficult to obtain using a single technique, and, therefore, a combination of techniques can be envisaged.

Organ blood flow and vessels of microcirculatory bed in fish

Abstract  Information on density of fish capillary network and its permeability, peculiarities of geometry, morphology, and ultrastructure of vessels of microcirculation bed—arterioles, venules, capillaries—is presented. A great attention is paid to vasomotor reactions and their participation in redistribution of blood. Nervous and humoral mechanisms of control of tone of the vessel smooth muscle wall and voluminous blood flow are considered. Effects of environmental factors on processes of microcirculation in fish are discussed.

Reproducibility of heart rate variability and blood pressure variability in individuals with spinal cord injury

Abstract  Individuals with spinal cord injury (SCI) are prone to orthostatic intolerance and an increased risk of cardiovascular disease. The use of heart rate variability (HRV) and blood pressure variability (BPV) as indices of cardiovascular regulation would be valuable in this population; however, their reproducibility has yet to be tested in those with SCI. The purpose of this study was to examine the day-to-day reproducibility of resting HRV and BPV in individuals with SCI. Ten individuals (age 35.9±13.2 yrs) with chronic (5.4±7.7 years post injury) SCI (C4-T12; ASIA A-C) participated. On two occasions within a two-week period, 10-minute supine electrocardiogram and Finapres blood pressure recordings were obtained during spontaneous breathing. Computer software calculated frequency domain measures of HRV and BPV (Low frequency (LF) power, High frequency (HF) power, and LF:HF ratio). Intraclass correlations coefficients (R) were used as an index of day-to-day reproducibility, and analyses were conducted on all participants and only those with tetraplegia. For HRV, measures of heart rate, LF, and LF:HF were found to be highly reproducible (R=0.82–0.88); however, the reproducibility of HF was found to be poor (all participants: R=0.53, tetraplegia: R=0.66). Measures of blood pressure as well as systolic BPV also showed high reproducibility (R=0.72–0.93). Measures of diastolic BPV were less reproducible but still acceptable (R=0.71–0.89) with the exception of LF:HFDBP (R=0.51). In conclusion, despite the autonomic dysfunction associated with SCI, measures of HRV and BPV may still be used as reproducible indices of autonomic cardiovascular regulation in this population.

Detection of bacteria and fungi in BacT/Alert standard blood-culture bottles

Abstract  Incubation periods of aerobic (AE) and anaerobic (AN) blood-culture bottles with the BacT/Alert system were assessed in our laboratory. We reviewed the results of 6229 blood-culture sets collected at Kyoto University Hospital from January 1999 to December 2000. Of these sets, 731 (11.7%) were positive for bacteria or yeast. Excluding 87 sets with growth evidence on arrival, of the 644 positive blood-culture sets from 341 patients, a total of 691 organisms were isolated. Of the 691 organisms, 413 (59.8%) were recovered from both bottles, 206 (29.8%) were recovered only from the AE bottle, and 72 (10.4%) were recovered only from the AN bottle. The AE bottle was significantly superior to the AN bottle in terms of both recovery rate and detection time for overall organisms, but there was no significant difference in detection time for facultative anaerobic bacteria between the two bottles. Of the 691 organisms, 530 (76.7%) were classified as usual pathogens. Of the 530 usual pathogens, 501 (94.5%) were recovered in at least one bottle of each set within the first 3 days, and 523 (98.7%) within the first 5 days of incubation. Twenty-nine organisms initially isolated on day 4 or later were recovered from 19 patients. Of these, chart reviews indicated that 21 organisms recovered from 11 patients were considered clinically significant bacteria, and the reviews also revealed that no patient had a treatment plan altered based on the results of positive blood culture. Seven organisms initially isolated on day 6 or later were recovered from 7 patients. Chart reviews revealed that 5 of these organisms from 5 patients were considered to be clinically significant. In conclusion, if the incubation period had been less than 3 days, 11 patients with clinically significant bacteremia or fungemia, (3.2% of all patients with bacteremia or fungemia) would have been undiagnosed. Similarly, with an incubation period of 5 days, 5 such patients (1.5%) would have been undiagnosed.

Quantitative trait loci for peripheral blood cell counts: a study in baboons

Abstract  Increasingly, baseline peripheral blood cell counts are implicated as risk factors for common complex diseases. While genetic influences on these hematologic parameters are firmly established, the genetic architecture of the blood counts is still poorly understood. In this article we used data from 582 healthy pedigreed baboons and variance components methods to localize quantitative trait loci (QTLs) influencing complete blood count variables. Besides performing genome-wide linkage scans for each trait individually, we conducted bivariate linkage analyses for all pairwise trait combinations to also identify pleiotropic QTLs influencing several blood counts. While significant and suggestive QTLs were localized throughout the genome (LOD range: 1.5–3.5), chromosomal regions associated with the expression of various hematologic parameters stand out. In particular, our results provide significant and consistent evidence for a QTL on the orthologous human chromosome 1p that is shared by several blood counts, mainly erythrocyte parameters. In addition, multiple suggestive evidence of linkage was detected on the orthologous human chromosomes 10 (near the q-terminus) and 19 (centromeric section). Future studies should help identify the genes responsible for these QTL and elucidate their role on baseline variation in hematologic indicators of health and disease.

Endothelin1 mediates the mcoholinduced reduction of pancreatic capillary blood flow

Abstract  Increased plasma endothelin-1 (ET-1) levels in rats after alcohol administration and increased endothelin receptor expression in the pancreas in chronic alcoholic pancreatitis have led to the hypothesis that ET-1 may play a critical role in the pathogenesis of ethanol-induced pancreatic injury through impairment of perfusion. To further test the hypothesis that ET-1 mediates an alcohol-induced reduction of pancreatic perfusion, the present study compares the effect of intravenous alcohol and ET-1 on pancreatic capillary blood flow (PCB10 and investigates whether endothelin receptor blockade prevents the alcohol-induced reduction in PCBE Anesthetized rats were randomly assigned to receive one of the following: a 1-hour infusion of 2 g/kg alcohol or the volume equivalent of saline solution plus ET-1 (1.25 γg/kg), a specific endothelin-A receptor antagonist (50 mg/kg), or saline solution (volume equivalent). The pancreas was exposed for intravital microscopy; PCBF was determined at the same location before the test solutions were given, after the infusion, and 1 hour thereafter. Alcohol and ET-1 significantly decreased PCBF from 2.0 hi/rain/cap to 1.7 hi/rain/cap. The reduction in PCBF was even more pronounced when alcohol and ET-1 were combined (1.5 nl/min/cap), whereas the ET receptor antagonist increased PCBF in saline-treated rats to 2.2 nl/min cap and maintained stable PCBF in alcohol-treated animals. The observation that PCBF is reduced by both alcohol and ET1 and that the alcohol-induced reduction of PCBF can be aggravated by ET-1 and prevented by a specific endothelin-1 antagonist supports the hypothesis that ET-1 is the mediator of the alcohol-associated reduction of pancreatic perfusion.

Transfusion of post-operative shed blood: laboratory characteristics and clinical utility

Abstract  Increased awareness of the potential hazards of allogenic blood transfusion, such as incompatibility reactions, metabolic and immunologic disorders, or transmission of viral diseases, has led to an emphasis on allogeneic blood alternatives. For orthopaedic surgery, several autologous transfusion modalities have emerged as alternatives to allogeneic blood transfusion, avoiding its immunomodulatory effects. Among them, transfusion or return of post-operative salvaged shed blood has become popular in major orthopaedic procedures. However, although the effectiveness of this blood-saving method is well documented, several authors have questioned its safety and recommended the use of washed blood. Therefore, this review analyses the haematologic characteristics of unwashed filtered shed blood, including metabolic status and survival of red blood cells, the components of the haemostatic system, the content of fat particles, bacterial and tumour cells and the possibility of their removal, the content of inflammatory mediators, and the effects on the patients immune system. From data reviewed in this paper, it can be concluded that post-operative salvage of blood seems to be an excellent source of functional and viable red cells without many of the transfusion-related risks and with some immuno-stimulatory effects. In addition, from our experience, post-operative re-infusion of unwashed shed blood after major spine procedures has proved to reduce post-operative homologous transfusion requirements and to complement pre-operative autologous blood donation, without any clinically relevant complication.

Enhancing the blood compatibility of ion-selective electrodes

Abstract  In vivo monitoring of various analytes is important for many bioanalytical and biomedical applications. The crucial challenge in this type of applications is the interaction of the sensor with the host environment, which is qualitatively described by the term biocompatibility. This review discusses recent advances in methods and materials used for the improvement of the biocompatibility of ion-selective electrodes especially as it relates to their interaction with blood components.

Blood and urine iodine levels in patients with gastric cancer

Abstract  In this study, we aimed to investigate whether there is any relationship between gastric cancer and iodine concentrations in blood and urine in the northeast Anatolia region, where iodine deficiency is common. A total of 56 patients, diagnosed as gastric cancer and 25 healthy volunteers were included in the study. The methods used were based on the Sandell-Kolthoff reaction. The urine iodine concentration (UIC) and serum protein-bound iodine (PBI) levels were higher in patients with gastric cancer compared with healthy control subjects. The UIC in stage IV was higher than all other stages and the control group. The UIC was higher in stages III and IV compared with stages I and II. However, serum PBI levels in stage III were higher compared with stages I, and II and also control group. The serum PBI level in stage IV was higher than stage II and the control group. In the patient and control groups, there were no significant differences in serum PBI and UIC with regard to age or sex. Our results suggested that urinary and blood iodine concentration might be a useful marker for following the disease.

Quantitative Analysis of Triptolide in Human Whole Blood by LC–APCI-IT-MS-MS

Abstract  In this study, the development and validation of an analytical method for triptolide in whole blood using high-performance liquid chromatography coupled with atmospheric-pressure chemical ionization ion trap tandem mass spectrometry (LC–APCI-IT-MS-MS) is reported. This is the first report of the systematic development and validation of an LC–MS-MS method for the quantitation of triptolide in human whole blood using prednisolone as an internal standard (IS). Prior to LC–MS-MS analysis, liquid–liquid extraction with ethyl acetate was used to isolate them from the biological matrix. Validation parameters such as specificity/selectivity, limit of quantitation (LOQ), linearity, precision, accuracy and stability are evaluated for this method. The calibration curve was linear (r 2 = 0.9973) in the concentration range of 0.5–100.0 ng mL−1 in human whole blood with a lower limit of quantitation of 0.5 ng mL−1. Intra- and inter-day relative standard deviations (RSDs) were less than 8.6 and 11.7%, respectively. Extraction recoveries of triptolide ranged from 81.5 to 88.1%. This assay can be used to determine trace triptolide in human whole blood.

Electronic Mosquito: designing a semi-invasive Microsystem for blood sampling, analysis and drug delivery applications

Abstract  In this study we present an innovative design idea for a semi-invasive blood sampling, analysis and drug delivery device called “Electronic Mosquito” (“e-Mosquito”). The major building blocks of the device are discussed. The principle of operation is described and its feasibility is demonstrated. The integration of the microsystem is outlined and its practical implementation proposed.

Modification of leech behavior following foraging for artificial blood

Abstract  In this study we examined whether the foraging for artificial blood affected the behavioral responsiveness of leeches to electrical stimulation of the body wall. After foraging for artificial blood, electrical stimulation of the posterior end of the leech significantly increased the percentage of stimulation trials that elicited locomotory activity—swimming and crawling—compared to the behaviors elicited when leeches did not forage or foraged for normal saline. On the other hand, shortening always dominated the behavioral profile of the leech to anterior stimulation even after foraging for artificial blood. In intact anterior end-isolated nerve cord preparations, we also found that application of artificial blood to the intact anterior end was sufficient to modify motor responsiveness to DP nerve stimulation. Full strength artificial blood had an overall negative effect on the likelihood of DP nerve stimulation initiating swimming and on the average length of elicited swim episodes compared to when pond water surrounded the anterior end. Application of a 10% solution of artificial blood to the anterior end led to an increase in the likelihood of DP nerve stimulation eliciting swimming.

Computational Approach to Estimating the Effects of Blood Properties on Changes in Intra-stent Flow

Abstract  In this study various blood rheological assumptions are numerically investigated for the hemodynamic properties of intra-stent flow. Non-newtonian blood properties have never been implemented in blood coronary stented flow investigation, although its effects appear essential for a correct estimation and distribution of wall shear stress (WSS) exerted by the fluid on the internal vessel surface. Our numerical model is based on a full 3D stent mesh. Rigid wall and stationary inflow conditions are applied. Newtonian behavior, non-newtonian model based on Carreau-Yasuda relation and a characteristic newtonian value defined with flow representative parameters are introduced in this research. Non-newtonian flow generates an alteration of near wall viscosity norms compared to newtonian. Maximal WSS values are located in the center part of stent pattern structure and minimal values are focused on the proximal stent wire surface. A flow rate increase emphasizes fluid perturbations, and generates a WSS rise except for interstrut area. Nevertheless, a local quantitative analysis discloses an underestimation of WSS for modelisation using a newtonian blood flow, with clinical consequence of overestimate restenosis risk area. Characteristic viscosity introduction appears to present a useful option compared to rheological modelisation based on experimental data, with computer time gain and relevant results for quantitative and qualitative WSS determination.

White blood cell defects: Molecular discoveries and clinical management

Abstract  In this review, we present the most recent discoveries at the molecular level in white blood cell defects, and explain how their identification helped us to understand the underlying pathophysiology and directed our approach in clinical management. These lately discovered genes, relevant to immune disorders of mononuclear phagocytes and neutrophils, include defects in the interferon gamma (IFN?)/interleukin 12 (IL-12) pathway, such as IFN? receptor (IFN?R) defects, IL-12 defect, IL-12 receptor (IL-12R) defect, and signal transducer and activator of transcription 1 (STAT-1) defect. We have also included NF-kappaB essential modifier (NEMO) defects, which lead to X-linked ectodermal dysplasia, with or without lymphedema and osteopetrosis, and a wide range of involvement of the immune system, which can mimic the hyper-IgM phenotype. Neutrophil-specific granule deficiency and neutrophil elastase deficiency are discussed, the latter being the molecular defect in both cyclic neutropenia and in some sporadic cases of severe congenital neutropenia.

Does Aβ 42 Have a Function Related to Blood Homeostasis?

Abstract  In this review, I discuss the possibility that Aβ42 has a physiologic function in blood vessel homeostasis and the consequences that this might have for theories concerning the pathogenesis of Alzheimer’s disease and for treatment.

Sensitivity enhancement for colorimetric glucose assays on whole blood by on-chip beam-guidance

Abstract  In this paper, we present a novel concept for optical beam-guidance to significantly enhance the sensitivity of colorimetric assays by extending the optical path length through the detection cell which linearly impacts the resulting attenuation of a probe beam according to the law of Beer-Lambert. In our setup, the incident probe beam is deflected by 90∘ into the chip plane at monolithically integrated V-grooves to pass a flat detection cell at its full width (i.e., with a path length of 10 mm) instead of its usually much smaller height. Afterwards, the attenuated beam is redirected by another V-groove towards an external detector. The general beam-guidance concept is demonstrated by a glucose assay on human whole blood on a centrifugal microfluidic “lab-on-a-disk” platform made of COC. We achieve an excellent linearity with a correlation coefficient (R 2) of 0.997 paired with a lower limit of detection (200 μM) and a good reproducibility with a coefficient of variation (CV) of 4.0% over nearly three orders of magnitude. With an accelerated sedimentation of cellular constituents by centrifugal forces, the sample of whole blood can be analyzed in a fully integrated fashion within 210 s. This time-to-result can even be improved by the numerical extrapolation of the saturation value. Additionally, the direct assay on whole blood also shows a negligible correlation with the hematocrit of the blood sample.

Integrated siphon-based metering and sedimentation of whole blood on a hydrophilic lab-on-a-disk

Abstract  In this paper, we present a novel and fully integrated centrifugal microfluidic “lab-on-a-disk” for rapid colorimetric assays in human whole blood. All essential steps comprising blood sampling, metering, plasma extraction and the final optical detection are conducted within t = 150 s in passive, globally hydrophilized structures which obviate the need for intricate local hydrophobic surface patterning. Our technology features a plasma extraction structure (V = 500 nL, CV < 5%) where the purified plasma (c RBC < 0.11%) is centrifugally separated, metered by an overflow and subsequently extracted by a siphon-based principle through a hydrophilic extraction channel into the detection chamber.

Segmentation of retinal blood vessels using a novel clustering algorithm (RACAL) with a partial supervision strategy

Abstract  In this paper, segmentation of blood vessels from colour retinal images using a novel clustering algorithm with a partial supervision strategy is proposed. The proposed clustering algorithm, which is a RAdius based Clustering ALgorithm (RACAL), uses a distance based principle to map the distributions of the data by utilising the premise that clusters are determined by a distance parameter, without having to specify the number of clusters. Additionally, the proposed clustering algorithm is enhanced with a partial supervision strategy and it is demonstrated that it is able to segment blood vessels of small diameters and low contrasts. Results are compared with those from the KNN classifier and show that the proposed RACAL performs better than the KNN in case of abnormal images as it succeeds in segmenting small and low contrast blood vessels, while it achieves comparable results for normal images. For automation process, RACAL can be used as a classifier and results show that it performs better than the KNN classifier in both normal and abnormal images.

In vivo whole-field blood velocity measurement techniques

Abstract  In this article a number of whole-field blood velocity measurement techniques are concisely reviewed. We primarily focus on optical measurement techniques for in vivo applications, such as laser Doppler velocimetry (including time varying speckle), laser speckle contrast imaging and particle image velocimetry (including particle tracking). We also briefly describe nuclear magnetic resonance and ultrasound particle image velocimetry, two techniques that do not rely on optical access, but that are of importance to in vivo whole-field blood velocity measurement. Typical applications for whole-field methods are perfusion monitoring, the investigation of instantaneous blood flow patterns, the derivation of endothelial shear stress distributions from velocity fields, and the measurement of blood volume flow rates. These applications require individual treatment in terms of spatial and temporal resolution and number of measured velocity components. The requirements further differ for the investigation of macro-, meso-, and microscale blood flows. In this review we describe and classify those requirements and present techniques that satisfy them.

Update: Role of the angiotensin type-2 (AT2) receptor in blood pressure regulation

Abstract  In the past, virtually all of the physiologic actions of angiotensin II (ANG II) were thought to be mediated by the type-1 ANG II receptor. However, there is now a compelling body of evidence suggesting that the type-2 (AT2) receptor is an important regulator of renal function and blood pressure (BP). The AT2 receptor stimulates a bradykinin (BK)-nitric oxide (NO)-cyclic GMP vasodilator cascade in blood vessels and in the kidney. Recent studies have shown that absence of the AT2 receptor lends to pressor and natriuretic hypersensitivity to ANG II. Furthermore, there is now excellent evidence that the AT2 receptor mediates pressure natriuresis. The AT2 receptor also stimulates the conversion of prostaglandin E2 (PGE2) to PGF2. In addition, it is now apparent that the therapeutic reduction in BP with AT1 receptor blockade (eg, losartan, valsartan, candesartan) is mediated by ANG II stimulation of the AT2 receptor, leading to increased levels of BK, NO, and cGMP. Current evidence predicts that AT2 receptor agonists would be beneficial in the treatment of hypertension.

Methylation of the INK4A/ARF locus in blood mononuclear cells

Abstract  In the detection of DNA hypermethylation as a tumor-specific epigenetic change in blood mononuclear cell fraction in patients with lymphoid and hematopoetic disorders, circulating tumor cells originating from the lymph nodes or bone marrow can be identified. However, it is still not clear whether methylation in mononuclear cells is disease specific. In the present study, we investigated whether methylation of the inhibitor of cyclin-dependent kinase (INK) 4A/alternative reading frame (ARF) locus is present in a disease-specific manner in the blood mononuclear cell fraction of patients with lymphoma, multiple myeloma, or leukemia. To increase the sensitivity of detection, a two-step methylation-specific PCR approach was used to analyze the methylation status of the promoter/exon 1 regions of both p14ARF and p16INK4A genes. Our findings indicate that although INK4A/ARF locus methylation is present in mononuclear cells, this event is not disease-specific since normal subjects also display methylated DNA in their mononuclear cells. In 85.1% of the patients and in 89% of the controls, p16INK4A gene was methylated, while the methylation rates for the p14ARF gene was 32.6 and 36.5%, respectively. The presence of methylated CpG sites in DNA in samples from normal subjects was confirmed by bisulfite genomic sequencing. The difference in the methylation rate between p16INK4A and p14ARF genes among the patients was highly significant (p<0.001). Our results demonstrate that methylation of the INK4A/ARF locus is not a disease-specific molecular change in mononuclear cell fraction and that the p14ARF and p16INK4A genes are differentially methylated.

Lymphocyte subsets in peripheral blood of patients with moderate-to-severe versus mild plaque psoriasis

Abstract  In several studies peripheral blood T-cells have been quantified, yet few data are available on lymphocyte subsets in moderate-to-severe psoriasis (in terms of extent and activity of lesions) versus mild psoriasis. The objective is to compare lymphocyte subsets in peripheral blood of patients with moderate-to-severe disease (PASI-score ≥12) to patients with mild disease (PASI-score <12) and to healthy subjects. By means of flow cytometry method, lymphocytes in peripheral blood of 27 patients with psoriasis and 10 healthy controls were characterized. The absolute number of total lymphocytes was markedly decreased in patients with moderate-to-severe psoriasis as compared to patients with mild disease and normal subjects. Cellcounts of all analysed subsets were found to be increased in more severe psoriasis, except for CD8+CD45RO+ cells. The under-representation of CD8+CD45RO+ cells is compatible with the dynamics of acquired immunity, which requires a time log after the relapse of the lesions to differentiate from CD45RA+ naive cells.

Impact of female hormones on blood pressure: Review of potential mechanisms and clinical studies

Abstract  In recent studies, it has been found that postmenopausal hormonal therapy is associated with an increased incidence of cardiovascular disease. Experimental studies suggest several potential mechanisms by which estrogens might decrease blood pressures, and estrogen administration attenuates hypertension in several animal models. In humans, although oral contraceptive agents are frequently associated with increases in blood pressure, blood pressure was not increased or was minimally increased in prospective clinical trials of hormone therapy in postmenopausal women. These observations suggest that the excess rates of cardiovascular disease are not caused by increased blood pressure.

Blood Pressure and Contractile Function of Heart Ventricles at the Early Stages of Hypertonic Process

Abstract  In rabbits, arterial hypertension was characterized by progressive elevation of systolic and diastolic blood pressure. The contractile function of the left ventricle augmented, but its potential working capacity decreased. Opposite changes were observed in the right ventricle. It was hypothesized that the compensatory mechanisms in the right ventricle during arterial hypertension are triggered at the very onset of the pathology, while in the left ventricle they develop later.

Selenium supplementation and blood rheological improvement in Japanese adults

Abstract  In order to study the prevention effect of selenium in the development of cardiovascular disease, we investigated the effects of selenium supplementation on the blood rheological properties. Eleven healthy adults were administered with 200 μg of selenium in the form of selenium yeast per day for 1 wk. Before and after the supplementation, serum selenium concentration, glutathione peroxidase (GPx) activity, biochemical indices, and the blood fluidity of the subjects were measured. The blood fluidity was measured using a (microchannel array flow analyzer) by the passage time of 100 μL of heparinized whole blood through the microchannel array. The selenium supplementation significantly (p=0.001) shortened the mean blood passage time from 44.0±5.7 to 37.5±2.8 s. Serum selenium concentration significantly (p=0.008) increased from 109.8±10.2 to 124.5±16.7 μg/L. Meanwhile, the GPx activity did not increased significantly (p=0.058). The mean GPx activity of the subjects before supplementation was 171.0±16.1 Δmmol NADPH/min/L and 180.9±17.8 Δmmol NADPH/min/L after supplementation. Factor analysis of the passage time and biochemical indices of the subjects showed that blood fluidity improvement was related to the metabolic modification of lipoproteins during the selenium supplementation. These results showed that selenium supplementation improved the blood fluidity, without increasing the GPx activity of the subjects.

Key parameters affecting the initial leaky effect of hemoglobin-loaded nanoparticles as blood substitutes

Abstract  In order to realize long-term carrying/delivering oxygen and minimize the adverse effects of free hemoglobin (Hb) in vivo, Hb is desired to be confined in Hb-loaded nanoparticles (HbP), a novel blood substitute with potential clinical applications, and thus functions as the native red blood cells (RBCs). However, the initial burst release of Hb (“leaky effect”) greatly underscores the significance of this work. The study described here wants to disclose the key preparative parameters, including polymer, excipients in the inner aqueous phase and solvent profile, affecting the Hb release behavior (the initial 24 h) from HbP fabricated by commonly used solvent diffusion/evaporation double emulsion technique. The results demonstrate that PEGlytated polymers, regardless of two- or tri-block copolymers show slower release compared with the corresponding non-PEGlytated ones. The higher polymer concentration yields lower initial release. PEG200, added as excipient facilitates Hb burst effect to about 38.4%, almost 17% increase compared to the control (∼21%), whereas, PVA and Poloxamer188, due to amphiphilic nature, can effectively attenuate this leakage to about 13.0 and 5.1%, respectively. The diffusion/extraction rate from oil phase and the subsequent evaporation rate from the aqueous continuous phase of solvents impose different influences on Hb release. To reduce the burst effect, the initial diffusion/extraction rate should be slow, whereas, the concomitant evaporation rate should be as fast as possible. The results obtained here will be guidance’s for the future tailored design of more desirable polymersome nanoparticle blood substitutes.

Prediction of blood glucose level of type 1 diabetics using response surface methodology and data mining

Abstract  In order to improve the accuracy of predicting blood glucose levels, it is necessary to obtain details about the lifestyle and to optimize the input variables dependent on diabetics. In this study, using four subjects who are type 1 diabetics, the fasting blood glucose level (FBG), metabolic rate, food intake, and physical condition are recorded for more than 5 months as a preliminary study. Then, using data mining, an estimation model of FBG is obtained, and subsequently, the trend in fluctuations in the next morning’s glucose level is predicted. The subject’s physical condition is self-assessed on a scale from positive (1) to negative (5), and the values are set as the physical condition variable. By adding the physical condition variable to the input variables for the data mining, the accuracy of the FBG prediction is improved. In order to determine more appropriate input variables from the biological information reflecting on the subject’s glucose metabolism, response surface methodology (RSM) is employed. As a result, using the variables exhibiting positive correlations with the FBG in the RSM, the accuracy of the FBG prediction improved. Conditions could be found such that the accuracy of the predicting trends in fluctuations in blood glucose level reached around 80%. The prediction method of the trend in fluctuations in the next morning’s glucose levels might be useful to improve the quality of life of type 1 diabetics through insulin treatment, and to prevent hypoglycemia.

Nonlinear dynamics of the blood flow studied by Lyapunov exponents

Abstract  In order to gain an insight into the dynamics of the cardiovascular system throughout which the blood circulates, the signals measured from peripheral blood flow in humans were analyzed by calculating the Lyapunov exponents. Over a wide range of algorithm parameters, paired values of both the global and the local Lyapunov exponents were obtained, and at least one exponent equaled zero within the calculation error. This may be an indication of the deterministic nature and finite number of degrees of freedom of the cardiovascular system governing the blood-flow dynamics on a time scale of minutes. A difference was observed in the Lyapunov dimension of controls and athletes.

Prevalence and intensity of blood apicomplexan infections in reptiles from Romania

Abstract  In order to evaluate prevalence and intensity of apicomplexan hemoparasites in free-ranging reptiles from Romania, blood smears were collected from European pond turtles (Emys orbicularis), sand lizards (Lacerta agilis), and spur-thighed tortoises (Testudo graeca). All three host species were positive for blood parasites, with prevalence of infected individuals between 60.71% and 100% and variable intensity. Similarities and differences with other epidemiological data are discussed.

The mechanism of the dextran-induced red blood cell aggregation

Abstract  In order to clarify the mechanism of dextran-induced aggregation, the effect of the ionic strength (I) on the minimal shear stress (τ c ) required to rupture RBC doublets was studied for suspensions with the external media containing 76 and 298 kDa dextrans. At low and high ionic strengths, τ c increases with increasing I, whereas at intermediate I values, τ c versus I dependencies reveal a plateau step. The non-monotonous shape of these curves disagrees with the depletion model of RBC aggregation and is consistent with the predictions of the bridging mechanism. Literature reports point out that elastic behavior of dextran molecules in low and high I regions is fairly typical of Hookean springs and hence predict an increase in τ c with increasing I. A plateau step is accounted for by the enthalpic component of the dextran elasticity due to the shear-induced chair–boat transition of the dextran’s glucopyranose rings. A longer plateau step for suspensions with a higher molecular weight dextran is explained by a larger contribution of the enthalpic component to the dextran elasticity. Thus, the results reported in this study provide evidence that RBC aggregation is caused by the formation of dextran bridges between the cells.

Effects of recombinant IL-4δ2 on human peripheral blood mononuclears

Abstract  In human cells, expression of IL-4 gene involves alternative mRNA splicing. IL-4δ2 splice variant is an antagonist of full-length IL-4 protein and blocks its effect on the functional activity of immunocompetent cells. The effect of recombinant IL-4δ2 on cytokine-producing activity of human peripheral blood mononuclear cells is shown for the first time.

Changes of physiological and biochemical characteristics of rat erythrocytes after blood loss

Abstract  In experiments on Wistar male rats, changes are studied of erythrocyte hematological, biochemical (activities of transport ATPases), and rheological properties (capability for aggregation and deformability) 7 days after bloodletting of 12–15% of the total blood mass. It has been shown that alongside with an elevation of erythrocyte volume and of the number of immature cells—reticulocytes, there was a statistically significant increase of Na,K-ATPase and Ca-ATPase activities in the whole erythrocytes and in their membrane preparations—ghosts, the increment of activity in the case of Na,K-ATPase being essentially higher in the whole cells. This indicates the appearance of an enzyme activator inside the erythrocytes. There are also revealed a decrease of firmness of erythrocyte aggregates, a deceleration of spontaneous aggregation, and an increase of index of erythrocyte deformability. The conclusion is made that changes of erythrocyte rheological properties are interconnected with changes of the Na,K-ATPase activity and are aimed at optimization of blood circulation in large vessels and capillary network.

Circadian variation of blood clotting time and circulating vitamin K in the athletic horse

Abstract  In equine sport medicine, blood clotting and fibrinolysis variations are well investigated, given the practical implications of several pathophysiological conditions affecting the athlete horse such as exercise-induced pulmonary haemorrhage (EIPH) and other bleeding disorders whose etiology and pathogenesis mechanisms are not yet clearly understood. The purpose of the present investigation was to gain evidence of a daily rhythm of several blood clotting indices such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), plasma fibrinogen concentration and serum vitamin K concentration in the athletic horses. Blood samples from five thoroughbred mares were collected at 4-h intervals for 48 h (starting at 08:00 h on day 1 and finishing at 4:00 on day 2 via an intravenous catheter inserted into the jugular vein. Prothrombin time, activated partial thromboplastin time, thrombin time and plasma fibrinogen concentration were assessed by means of a Seac Clot 2 coagulometer (SEAC, Italy), while serum vitamin K concentration was measured by HPLC. Data analysis was conducted by one-way repeated analysis of variance (ANOVA) and by the single cosinor method. ANOVA showed a significant influence of time on all parameters investigated, in all horses, on either day. Cosinor analysis defined the periodic parameters and their acrophases (expressed in hours) during the 2 days of monitoring. PT showed a nocturnal acrophase, whereas serum vitamin K concentration acrophase occurred during the evening. The results of this study reflect the physiological peculiarities of the horse that is subjected to a number of exogenous (environmental, nutritional, physical) and endogenous stimuli capable of entraining the circadian rhythm specifically and thus producing time-dependent variations not always comparable with those observed in humans or laboratory animals.

Pre dialysis of blood prime in continuous hemodialysis normalizes pH and electrolytes

Abstract  In critically ill children weighing <10 kg, it is necessary to use blood as a priming solution for the extracorporeal continuous renal replacement therapy (CRRT) circuit before initiating CRRT to prevent hemodilution and maintain adequate oxygenation. However, blood bank blood usually contains supra-physiological electrolyte concentrations and a non-physiological acid-base balance that may exacerbate the patients condition. The objective of this trial was to develop a simple protocol to pre-treat blood bank-derived blood to yield a more physiological blood priming solution. Expired human blood in a recirculating in vitro CRRT circuit was dialyzed prior to the initiation of CRRT using a physiological dialysate solution. Serial blood samples were assessed for electrolyte and pH content. Regimens using maximal blood flow rates (180–200 ml/min) and aggressive dialysate flow rates (33–42 ml/min) were able to correct severely hyperkalemic and acidemic blood within 7.5 min. Initially elevated blood potassium concentrations >20 mEq/l were normalized to below 5 mEq/l within 7.5 min of dialysis in all cases. Blood bank-derived blood can be conditioned quickly to physiological pH and electrolyte concentrations using these simple pre-dialysis regimens. Unlike some blood preparation regimens that have been published, the technique used in this trial requires no special equipment or added medications that are not already used in CRRT.

Prediction method for decreases in blood pressure during hemocatharsis therapy by arteriolar blood flow measurement

Abstract  In clinical practice, the prediction of changes in blood pressure during hemocatharsis therapy depends on invasive monitoring, the physician's experience, or blood pressure measurement when patients ask for it. It is extremely difficult to predict blood pressure variation in patients under general anesthesia or with disturbance of consciousness. Therefore, the prediction of blood pressure variation during hemocatharsis therapy is an important issue. To address this issue, we invented a new noninvasive continuous blood flow monitor using arteriolar blood flow measurement by laser Doppler flowmetry. Then we examined and determined some extremely important phenomena, including the relationship between rapid blood pressure change and arteriolar blood flow, and failures of the cerebral blood flow autoregulatory mechanism, through measurements in clinical practice of hemodialysis, specific hemocatharsis therapy, and drug monitoring. The results suggest that blood pressure variation during hemocatharsis therapy is highly predictable by arteriolar blood flow measurement. Therefore, this new method for arteriolar blood flow measurement might be widely useful for patients under anesthesia, anesthesia monitoring in neonatal infants and animals (no conversation ability), as well as for hemocatharsis therapy.

Apoptosis of lymphocytes in peripheral blood of patients with melanoma

Abstract  In cancer, spontaneous apoptosis of circulating peripheral blood lymphocytes (PBLs) is a general phenomenon. In this study we aimed to determine whether spontaneous apoptosis of circulating PBLs of patients with malignant melanoma occurs. Pathologically proven 45 patients with malignant melanoma and 19 healthy controls were included in this study. Samples were obtained both on first admission before treatment, either adjuvant or metastatic, and follow-up period of patients. Human active caspase-3 immunoassay (R&D Systems, Inc. MN, USA) employs the quantitative sandwich enzyme immunoassay technique. A monoclonal specific for caspase-3 has been used. The spontaneously apoptotic PBLs in melanoma patients were not significantly different from those obtained for normal controls (p=0.25). None of the clinical characteristics were significantly correlated with spontaneous apoptosis (p>0.05). Likewise, we found that apoptosis in PBLs was not a prognostic factor in melanoma patients (p=0.79). In conclusion, we did not observe accelerated apoptosis of PBLs in patients with melanoma. Further studies are necessary to determine the potential prognostic importance of this observation.

Dopexamine maintains mesenteric blood flow during systemic hypoxemia in the neonatal piglet

Abstract  In adults, dopexamine is a specific dopaminergic and β2-adrenergic agonist; its effects in neonates are unknown. Ultrasonic flow probes were placed around the ascending and descending aorta and cranial mesenteric artery of 0- to 2-day-old and 2-week-old piglets. Animals of each age group (9 to 14 per group) were subjected to (1) dopexamine infusion (5 μg/kg/min); (2) 30 minutes of hypoxia (inspired oxygen content 0.12) followed by 30 minutes of reoxygenation; and (3) dopexamine infusion during hypoxia and reoxygenation. In both age groups dopexamine alone increased ascending aorta blood flow (cardiac output minus coronary artery blood flow), mildly decreased mean arterial pressure, and increased cranial mesenteric artery blood flow. Compared to baseline values, 30 minutes of hypoxia produced significant (P<0.05, analysis of variance) decreases in cranial mesenteric artery blood flow in 0- to 2-day-old (58±13 ml/min vs. 30±8 ml/min) and 2-week-old (125±18 ml/min vs. 60±11 ml/min) piglets. In all cases blood flow returned to baseline values after reoxygenation. In both animal groups treated with dopexamine before hypoxia, the decreases in cranial mesenteric artery blood flow were eliminated (47±5 ml/min vs. 44±6 ml/min in 0-to 2-day-old piglets; 140±27 ml/min vs. 117±18 ml/min in 2-week-old piglets). Dopexamine may prove to be of clinical benefit when neonates are threatened by hypoxemia-induced decreases in intestinal blood flow.

Isolation of Commensal Bacteria from Umbilical Cord Blood of Healthy Neonates Born by Cesarean Section

Abstract  In a previous study, lactic acid bacteria were isolated from meconium obtained from healthy neonates born by cesarean section. Such a finding suggested that term fetuses are not completely sterile, and that a mother-to-child efflux of commensal bacteria may exist. Therefore, presence of such bacteria in umbilical cord blood of healthy neonates born by elective cesarean section was investigated. The blood samples were submitted to an enrichment step and then inoculated onto agar plates. All the identified isolates belonged to the genus Enterococcus, Streptococcus, Staphylococcus, or Propionibacterium. Later, a group of pregnant mice were orally inoculated with a genetically labeled E. faecium strain previously isolated from breast milk of a healthy woman. The labeled strain could be isolated and polymerase chain reaction detected from the amniotic fluid of the inoculated animals. In contrast, it could not be detected in the samples obtained from a noninoculated control group.

Resolution of Beh?et’s disease after HLA-mismatched unrelated cord blood transplantation for myelodysplastic syndrome

Abstract  In 1991, a 27-year-old woman who presented with recurrent oral and genital ulcers, fever, and erythema nodosum was diagnosed with Behçets disease (BD). Her symptoms were refractory to conventional therapy. In 1999, pancytopenia was noticed in this patient for the first time, and in 2000, her white blood cell count decreased to 0.94×109/l with 1% myeloblasts and 24% neutrophils. Bone marrow examination showed mild hypocellularity with 8% myeloblasts and 6% mature neutrophils with dysplastic features. A diagnosis of myelodysplastic syndrome (MDS)-refractory anemia with excess blasts was made. Despite marked neutropenia, the BD symptoms continued. Since her neutropenia worsened to 0.24×109/l with 21% neutrophils, the patient underwent cord blood transplantation (CBT) from an unrelated donor in July 2001. Myeloid engraftment was documented on day 26. Grade I acute graft-versus-host disease occurred, but resolved spontaneously. Cyclosporin treatment was reduced gradually and discontinued 6 months after CBT. Twenty-three months after CBT, the patient is doing well and has no signs or symptoms of BD or MDS. These observations suggest that allogeneic hematopoietic stem cell transplantation, which encompasses CBT, may be an effective therapy in patients with high-risk aggressive BD.

Effects of acupuncture on skin and muscle blood flow in healthy subjects

Abstract  In 14 healthy female subjects, the effects of needle stimulation (acupuncture) on skin and muscle blood flow were investigated using a non-invasive custom-designed probe and photoplethysmography (PPG). In randomised order, 2–7 days apart, three modes of needle stimulation were performed on the anterior aspect of the tibia: superficial insertion (SF), insertion into the anterior tibial muscle (Mu), and insertion into the muscle including manipulation of the needle in order to elicit a distinct sensation of distension, heaviness or numbness (DeQi). Before intervention, the subjects rested for 30 min. After the intervention, the needle was left in situ for 20 min. Blood flow recordings were performed intermittently from 10 min prior to the intervention to the end of the trial. In a fourth session, serving as control, corresponding measurements were performed without any needle stimulation. Area under curve was calculated for 5-min periods prior to and after stimulation, respectively, and for the remaining 15-min period after stimulation. Compared to the control situation, muscle blood flow increased following both Mu and DeQi for 20 min, with the latter being more pronounced for the initial 5 min. Skin blood flow increased for 5 min following DeQi. However, no increase was found following SF. The DeQi stimulation was preceded by higher visual analogue scale ratings of anxiety prior to stimulation, which might have influenced skin blood flow to some extent. The results indicate that the intensity of the needling is of importance, the DeQi stimulation resulting in the most pronounced increase in both skin and muscle blood flow.

Mechanisms of leukocyte migration across the blood–retina barrier

Abstract  Immune-mediated inflammation in the retina is regulated by a combination of anatomical, physiological and immuno-regulatory mechanisms, referred to as the blood–retina barrier (BRB). The BRB is thought to be part of the specialised ocular microenvironment that confers protection or “immune privilege” by deviating or suppressing destructive inflammation. The barrier between the blood circulation and the retina is maintained at two separate anatomical sites. These are the endothelial cells of the inner retinal vasculature and the retinal pigment epithelial cells on Bruch’s membrane between the fenestrated choroidal vessels and the outer retina. The structure and regulation of the tight junctions forming the physical barrier are described. For leukocyte migration across the BRB to occur, changes are needed in both the leukocytes themselves and the cells forming the barrier. We review how the blood–retina barrier is compromised in various inflammatory diseases and discuss the mechanisms controlling leukocyte subset migration into the retina in uveoretinitis in more detail. In particular, we examine the relative roles of selectins and integrins in leukocyte interactions with the vascular endothelium and the pivotal role of chemokines in selective recruitment of leukocyte subsets, triggering adhesion, diapedesis and migration of inflammatory cells into the retinal tissue.

Abstract  Immune stimulation is a promising prospect in cancer therapy. Immunotherapy may be local or systemic, aspecific or targeted and may use monoclonal antibodies or vaccines. The aim of using vaccines is to stimulate the body to produce its own antibodies. Autologous tumor-cell vaccination has no contraindications or side-effects, since the patients own materials (lymphocytes, tumor cells) are used. We describe a method for producing an autologous cancer vaccine. The material to be injected as a vaccine derives from a mixed culture of autologous lymphocytes cocultured with autologous cancer cells. Peripheral blood lymphocytes are obtained by lymphocytapheresis. Cancer cells may be obtained from tissue biopsies or biological fluids, or from long-term cultures from the patient who is to be vaccinated. The culture medium (RPMI 1640) is free of fetal calf serum (FCS). The coculture is mixed with autologous plasma in a 1:1 ratio with the addition of 200 IU of recombinant human interleukin-2/mL, and is incubated at 37°C in a humidified 5% CO2-enriched atmosphere for 48 h. The cocultured material is frozen, thawed to lyse cells, aliquoted and stored at −20°C.

Blood biologic markers of stroke: Improved management, reduced cost?

Abstract  Identifying blood biomarkers may be of particular value in neurologic disorders such as stroke because of the difficulty in directly studying the brain and its blood vessels. Markers of brain injury, inflammation, excitotoxicity, and oxidative damage have been evaluated for their value in stroke diagnosis, treatment, and management, but none have proved to be sensitive or specific enough for routine clinical use. However, new cellular and molecular profiling approaches using the peripheral blood offer the potential for identifying panels of genes and proteins by increasing specificity while maintaining sensitivity. Furthermore, the first biomarker for predicting stroke risk associated with atherosclerosis (lipoprotein-associated phospholipase A2) was recently approved by the United States Food and Drug Administration. The ultimate aim for stroke biomarkers is to develop rapid, easy to use, widely available, and inexpensive diagnostic tests that can be used in the clinic and in clinical trials.

Blood biologic markers of stroke: Improved management, reduced cost?

Abstract  Identifying blood biomarkers may be of particular value in neurologic disorders such as stroke because of the difficulty in directly studying the brain and its blood vessels. Markers of brain injury, inflammation, excitotoxicity, and oxidative damage have been evaluated for their value in stroke diagnosis, treatment, and management, but none has proved to be sensitive or specific enough for routine clinical use. However, new cellular and molecular profiling approaches using the peripheral blood offer the potential for identifying panels of genes and proteins by increasing specificity while maintaining sensitivity. Furthermore, the first biomarker for predicting stroke risk associated with atherosclerosis (lipoprotein-associated phospholipase A2) was recently approved by the United States Food and Drug Administration. The ultimate aim for stroke biomarkers is to develop rapid, easy to use, widely available, and inexpensive diagnostic tests that can be used in the clinic and in clinical trials.

Influence of hyperthermia on carotid blood flow using 99mTc-HMPAO

Abstract  Hyperthermia can be the result of many causes such as environmental conditions, brain tumors and infectious diseases. Since hyperthermia is very common, its role in causing stroke through a decrease in cerebral blood flow needed further emphasis. The aim of this study was to record cerebral blood flow in vitro by using isolated rabbit carotid artery strips and in-vivo using radioactive isotope scanning during temperature elevation. The recording of isometric tension in rabbit carotid artery strips in organ baths, and the scintigraphic cerebral imaging of technetium-99m-hexamethyl-propyleneamineoxime (99mTc-HMPAO) using Gamma camera, were acquired at control and higher body temperature by 4°C. Blood pressure was measured through femoral artery and cerebral blood flow was measured through carotid artery. Elevating temperature by 4°C induced reproducible contraction. During hyperthermia, the carotid artery contraction leads to a decrease in cerebral blood flow although the blood pressure did not decrease. The uptake of 99mTc-HMPAO in the brain was significantly reduced. This decrease in cerebral perfusion is regionally dependent, which is more in the frontal area, the cerebral hemispheres than the cerebellum. The decrease was 36 ± 3, 37 ± 2, 22 ± 2%, respectively. Hyperthermia causes carotid artery contraction leading to decrease in cerebral blood flow, which was confirmed by 99mTc-HMPAO images. The decrease is regionally dependent. Since the blood pressure did not decrease by heating, the reduction in cerebral perfusion is mainly due to carotid contraction. The applied neck cooling may be considered as a promising therapeutic strategy for the hyperthermic patient to avoid brain damage. This can be achieved by external application of an ice-water-perfused neck collar.

Are low target blood pressure goals justified in persons with diabetes mellitus?

Abstract  Hypertension is common in patients with diabetes and is a major risk factor for development and progression of the macro- and microvascular complications seen in diabetes. The Joint National Committee VI recommendation for goal blood pressure is less than 130/85 mm Hg in diabetics—a more aggressive target than in nondiabetic patients. Data over the past decade support these aggressive goals, especially for cardiovascular and renal outcomes and overall mortality. In addition, in diabetics, blood pressure appears to be a continuous risk factor for these outcomes without evidence of a J-point effect. While these goals are rarely obtained in diabetic patients, studies demonstrate that they are achievable with attention to detail and use of multiple antihypertensive agents.

Increased blood pressure later in life may be associated with perinatal n?3 fatty acid deficiency

Abstract  Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Previous work in both animals and humans with high blood pressure has demonstrated the antihypertensive effects of n−3 polyunsaturated fatty acids (PUFA), although it is not known whether these nutrients are effective in preventing hypertension. The predominant n−3 PUFA in the mammalian nervous system, docosahexaenoic acid (DHA), is deposited into synaptic membranes at a high rate during the perinatal period, and recent observations indicate that the perinatal environment is important for the normal development of blood pressure control. This study investigated the importance of perinatal n−3 PUFA supply in the control of blood pressure in adult Sprague-Dawley rats. Pregnant rat dams were fed semisynthetic diets that were either deficient in (DEF) or supplemented with (CON) n−3 PUFA. Offspring were fed the same diets as their mothers until 9 wk; then, half of the rats from each group were crossed over to the opposite diet, creating four groups, i.e., CON-CON; CON-DEF; DEF-DEF, DEF-CON. Mean arterial blood pressures (MAP) were measured directly, at 33 wk of age, by cannulation of the femoral artery. The phospholipid fatty acid profile of the hypothalamic region was determined by capillary gas-liquid chromatography. The tissue phospholipid fatty acid profile reflected the diet that the rats were consuming at the time of testing. Both groups receiving DEF after 9 wk of age (i.e., DEF-DEF and CON-DEF) had similar profiles with a reduction in DHA levels of 30%, compared with rats receiving CON (i.e., CON-CON and DEF-CON). DEF-DEF rats had significantly raised MAP compared with all other groups, with differences as great as 17 mm Hg. DEF-CON rats had raised MAP compared with CON-CON rats, and DEF-DEF rats had higher MAP than CON-DEF rats, despite the fact that their respective fatty acid profiles were not different. These findings indicate that inadequate levels of DHA in the perinatal period are associated with altered blood pressure control in later life. The way in which these long-term effects are produced remains to be elucidated.

Effects of hormone replacement therapy on the sympathetic nervous system and blood pressure

Abstract  Hypertension is a major health problem that significantly contributes to heart disease and stroke. While most studies of hypertension have focused on men, women also experience significant hypertension-related morbidity and mortality. However, the incidence of hypertension and cardiovascular disease is significantly lower in premenopausal women compared with men until the onset of menopause, at which time cardiovascular disease incidence increases dramatically in women and eventually approaches that in men. These observations indicate that the loss of estrogen contributes to menopause-related increases in blood pressure and cardiovascular disease, and suggest that the use of estrogen hormone replacement therapy could decrease the incidence of cardiovascular disease in postmenopausal women. However, new findings from the Women’s Health Initiative study suggest that estrogen therapy has few positive benefits and some significant negative effects on the health of postmenopausal women, and these data have caused many to abandon long-term estrogen replacement therapy. Conversely, numerous clinical and basic research studies indicate that estrogen replacement therapy beneficially reduces blood pressure, thereby decreasing the incidence of hypertension and cardiovascular disease. Further, several of these studies suggest that one means by which estrogen lowers blood pressure is by decreasing sympathetic nervous system activity. This review examines the evidence supporting estrogen’s ability to modulate sympathetic nervous system tone and thereby decrease arterial pressure.

Can we justify goal blood pressure of <140/90 mm hg in most hypertensives?

Abstract  Hypertension is a common disorder with well-recognized consequences on the heart, brain, and kidney as target organs. Guidelines espouse a treatment goal of blood pressure reduction to <140 mm Hg for the systolic pressure and <90 mm Hg for the diastolic pressure in most hypertensive patients. In this review, the basis for these recommendations, the practical achievement of these goals in various practice settings, and the risk versus the benefit of achieving such goals in most hypertensive patients are examined.

Statins and blood pressure regulation

Abstract  Hypertension and high serum cholesterol levels are two of the most relevant risk factors for cardiovascular diseases. A combined increase in both risk factors has been reported in a significant proportion of patients with coronary artery disease. Statins are the most widely used drugs to treat hypercholesterolemia, and they interact with blood pressure control in different populations of hypertensive patients. A significant reduction in blood pressure associated with the use of statins has been described in patients with untreated hypertension and in patients treated with antihypertensive drugs, particularly angiotensin converting enzyme inhibitors and calcium channel blockers. The effect of statins on blood pressure control has also been reported in diabetic patients. The mechanisms responsible for the hypotensive effect seem to be largely independent of the effect of statins on lipid profile, and are probably related to their interaction with endothelial function or angiotensin II receptors. The capacity of statins to improve blood pressure control could be a useful consideration for an integrated approach to better prevention of cardiovascular diseases.

Effects of blood pressure and glucose on endothelial function

Abstract  Hypertension and diabetes mellitus are associated with accelerated atherosclerosis and an increased prevalence of cardiovascular disease. Loss of the modulatory role of the endothelium can be considered the link between these conditions and cardiovascular disease. Substantial evidence suggests that vasodilation mediated by endothelium-derived nitric oxide (NO) is impaired in animal models and in patients with hypertension and diabetes mellitus. NO is a principal factor involved in the anti-atherosclerotic properties of the endothelium. Therefore, the pathogenesis of hypertensive and diabetic vascular disease may involve a reduced bioavailability of endothelium-derived NO. Inactivation of NO by reactive oxygen species is an important common mechanism by which endothelial dysfunction may occur. This review summarizes experimental and clinical evidence for impaired NO-mediated vasodilation in the presence of high blood pressure and hyperglycemia. A better understanding of the mechanisms leading to endothelial dysfunction may unmask new preventive strategies to reduce cardiovascular morbility and mortality in these conditions.

Blood pressure control—Effects on diabetic nephropathy progression: How low does blood pressure have to be?

Abstract  Hypertension and diabetes are independent risk factors for both cardiovascular disease and renal complications. Coexistence of these comorbid conditions predisposes the patient to a much greater risk of progression to end-stage renal disease. Combined with the increased cardiovascular mortality, this has led to recent Joint National Committee-VI recommendations for the initiation of antihypertensive therapy for people with diabetes at a blood pressure of 130/85 mm Hg, a level lower than that recommended for the nondiabetic population. Results of a review of recently published investigations on the effects of blood pressure on diabetic nephropathy progression are presented in this article. This review finds evidence to support reducing the mean arterial blood pressure to levels below 95 mm Hg, a level that is even lower than the blood pressure of 130/80 mm Hg (mean arterial pressure of 97 mm Hg) recommended by the American Diabetes Association and National Kidney Foundation. The effect of blood pressure on renal disease progression is linear and appears to have no lower threshold for the benefits of blood pressure reduction on limiting nephropathy progression. The answer to the question of how low does blood pressure have to be to minimize the effects of blood pressure on diabetic nephropathy progression might be "the lower, the better."

Effect of indomethacin on cerebral blood flow and development of oxygen convulsions

Abstract  Hyperbaric oxygenation modulates cerebral blood flow affecting the development of oxygen convulsions. Before hyperbaric oxygenation-induced convulsions in rats the initial decrease in blood flow gave place to hyperemia, Po2 increased. In rats receiving cyclooxygenase inhibitor indomethacin no convulsions were observed, blood flow and Po2 were lower than in controls. Our results indicate that indomethacin prevents hyperemia and alleviates oxygen convulsions under conditions of hyperbaric oxygenation.

A study of blood flow in microvessels using biospeckle dynamics

Abstract  Hydrodynamic properties of blood flows in small microvessels and the patterns of scattering of focused laser beams in such flows were studied. The processes of formation of dynamic biospeckles are considered. The relationship between the optical parameters and hydrodynamic characteristics of blood microflow are analyzed. A new method is proposed for measureming the plasma rate in small microvessels with the use of in vivo microscopy in combination with speckle microscopy.

Mouse models of blood pressure regulation and hypertension

Abstract  Human essential hypertension is recognized as a multifactorial disease involving many genes, but the causative genes have not yet been identified. For many years hypertension was studied primarily in the rat, but more recently several candidate genes for hypertension have been used to produce transgenic mice for gain of function and gene-targeted mice for loss of function studies. These genetically engineered mouse strains with hypertension or hypotension are providing insights into the mechanisms of blood pressure regulation. However, genetically engineered mice are used to study one gene at a time, and another complementary approach is needed for polygenic inheritance and gene interaction. The phenotype-driven approach to hypertension studies uses the natural variation among inbred strains and crosses to find quantitative trait loci. The four mouse crosses carried out so far have found several quantitative trait loci that are concordant with hypertension loci found in rats and humans.

The impact of mode of delivery and gestational age on cord blood hematopoietic stem/progenitor cells

Abstract  Human cord blood has been successfully used as an alternative source of hematopoietic stem cells suitable for transplantation. The aim of this study was to assess the impact of gestational age and the mode of delivery on cord blood hematopoietic stem/progenitor cell characteristics. The mode of delivery does not seem to affect either the replating capacity of hematopoietic progenitors colony-forming unit-granulocyte-macrophage or the cord blood content in CD34+ cells. The higher percentage of CD34+ cells in cord blood from preterm deliveries compared to full-term ones indicates that hematopoietic progenitors from preterm cord blood may be suitable for transplantation. These findings should be taken into consideration when selection of cord blood units is required for potential use in transplantation.

The value of home blood pressure monitoring

Abstract  Home blood pressure (BP) monitoring has become popular and acceptable. The value of home BP monitoring has been recognized, because it has some potential advantages over office BP. Home BP monitoring is more accurate and reproducible, has a better prognostic value, and increases patients’ compliance with treatment. Home BP monitoring should be performed with an adequate device, following a standardized procedure. The automated arm-cuff-oscillometric devices are recommended currently, and home BP should be measured at least twice daily, in the morning and in the evening. Home BP monitoring has revealed the phenomena ofldwhite-coat hypertension, “masked hypertension,” and “morning hypertension,” and it is useful for their management. In the future, home BP monitoring will be an essential aspect of clinical practice.

Preservation of nucleic acid integrity in guanidine thiocyanate lysates of whole blood

Abstract  High-molecular-mass RNA and DNA have been shown to retain their integrity for three days at room temperature, no less than two weeks at +4°C, and more than a year at −20°C when whole blood samples are stored as lysates containing 4 M guanidine thiocyanate. Storage time at room temperature can be prolonged at least up to 14 days if nucleic acids were precipitated by two volumes of isopropanol. This preservation technique allows storage and transportation of samples at ambient temperature and is completely compatible with the procedure of subsequent isolation of nucleic acids.

Blood leukocyte subsets and cytokine profile after autologous peripheral blood stem cell transplantation

Abstract  High-dose chemotherapy with autologous peripheral blood stem cell transplantation (PBSCT) includes the risk of infectious complications due to neutropenia and therapy-induced immune deviation. In order to understand early immune recovery in this situation, we analyzed the distribution of cell subsets by flow cytometry and we measured cytokine production in a whole blood assay stimulated with lipopolysaccharide (LPS) in order to induce monocyte (MO) activation in 43 patients with solid tumors or lymphoma treated with two cycles of high-dose chemotherapy and PBSCT. Blood was collected at the following time points: before start of mobilization chemotherapy, before and after high-dose chemotherapy, and 10 and 30 days after PBSCT. In the lymphocyte compartment, we found a depletion of B cells and naive T cells and a transitory reduction of natural killer (NK) cells, whereas MO and neutrophils recovered rapidly. However, during early recovery, HLA-DR expression on MO and the percentage of CD16+ MO was considerably reduced. Production of proinflammatory cytokines interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-alpha upon LPS stimulation was severely impaired directly after chemotherapy and unexpectedly remained low during early recovery of myeloid cells, whereas production of IL-1RA was enhanced, indicating a shift of immune competent cells to an anti-inflammatory or anergic state early after PBSCT.

Secondary prevention of stroke by blood pressure-lowering treatment

Abstract  High blood pressure is the most important modiflable risk factor for stroke, accounting for more than 50% of the population-attributable fraction for stroke. There is now strong evidence from randomized trials that blood pressure-lowering treatment is one of the most effective and generalizable strategies for secondary prevention of stroke. Once the patient with stroke has stabilized, all patients should receive blood pressure-lowering therapy, irrespective of their blood pressure levels. Combination therapy with an angiotensin-converting enzyme (ACE) inhibitor plus a diuretic is an established regimen, but an angiotensin II-receptor blocker may provide an alternative regimen in patients who do not tolerate an ACE inhibitor, especially in combination with a diuretic. For patients with previous stroke, goal blood pressures of < 130/80 mm Hg in hypertensive subjects and < 120/80 mm Hg in normotensive (or “prehypertensive”) subjects should be achieved using combination blood pressure-lowering therapy.

The DASH diet and blood pressure

Abstract  High blood pressure (also called hypertension) is one of the most important and common risk factors for atherosclerotic cardiovascular disease (CVD) and other chronic diseases. National guidelines recommend that all individuals with blood pressure readings of 120/80 mm Hg or higher adopt healthy lifestyle habits, including the Dietary Approaches to Stop Hypertension (DASH) diet, to manage their blood pressure. The DASH diet, which is high in fruits, vegetables, and low-fat dairy products and reduced in fat, has been shown in large, randomized, controlled trials to reduce blood pressure significantly. The DASH diet also has been shown to reduce blood cholesterol and homocysteine levels and to enhance the benefits of antihypertensive drug therapy. The DASH diet should be promoted, along with maintaining healthy weight, reducing sodium intake, increasing regular physical activity, and limiting alcohol intake, for lowering blood pressure and reducing the risk of CVD.

Hexylresorcinol Induces Chromosome Aberrations in Mouse Peripheral Blood Cells

Abstract  Hexylresorcinol has been demonstrated to induce chromosome aberrations in eukaryotic cells at doses of 0.5, 0.05, and 0.005 mg/g body weight. The metabolic transformation of hexylresorcinol in mice decreases its genotoxic effect. The mutagenic effect is retained for three days only after the administration of the highest dose of hexylresorcinol (0.5 mg/g); during the first two days, lower doses are also genotoxic. Therefore, hexylresorcinol doses lower than 0.5 mg/g body weight are metabolized within two days to the extent precluding the expression of the cytotoxic effect. After a single administration to mice, exogenous hexylresorcinol is transformed at a rate of 0.0025–0.025 mg/day.

Regulation of the blood–biliary barrier: interaction between gap and tight junctions in hepatocytes

Abstract  Hepatocytes tightly connect with each other by intercellular junctions to form liver cell plates. The junctions composed of gap, tight, and adherens junctions and desmosomes concentrate around bile canaliculi. In particular, tight junctions serve as a barrier to keep bile in bile canaliculi away from the blood circulation. Thus, it is very reasonable to call tight junctions of hepatocytes the blood–biliary barrier. On the other hand, gap junctions of hepatocytes are considered to enable ordered contraction of bile canaculi from centrizonal to periportal hepatocytes by their function of intercellular communication. Gap and tight junctions may thus play a crucial role in bile secretion, one of the most differentiated functions of the liver. In intrahepatic cholestasis, a common pathological condition of the liver, downregulation of gap and tight junctional functions is seen, which results in impaired intercellular communication and in leaky tight junctions. Although the changes in gap and tight junctions had been considered to be independent of each other, recent findings that the tight junction-associated proteins ZO-1 and occludin bind to connexins indicate the possibility of either coordinate or reciprocal regulation of macromolecular complexes containing gap- and tight-junction proteins. In this review, we introduce the interaction and regulation between gap and tight junctions of hepatocytes in vitro and discuss the regulatory mechanisms of the blood–biliary barrier to study the molecular pathogenesis of cholestasis.

Role of hepatocyte nuclear factor 4α in control of blood coagulation factor gene expression

Abstract  Hepatocyte nuclear factor 4α (HNF4α) plays an important role in the maintenance of many liver-specific functions. Liver-specific HNF4α-null mice were used to determine whether hepatic HNF4α regulates blood coagulation in vivo. These mice exhibited reduced expression of hepatic coagulation factors V, IX, XI, XII, and XIIIB and a prolonged activated partial thromboplastin time but not prothrombin time. Promoter analysis of the mouse FXII and FXIIIB genes was performed to determine whether HNF4α directly regulates the genes encoding these coagulation factors. Sequence analysis revealed the presence of one and two HNF4α binding sites in the mouse FXII and FXIIIB genes, respectively. Using transient transfection and electrophoretic mobility shift analyses with the mouse FXII and FXIIIB promoters, it was established that the high levels of promoter activity were dependent on HNF4α binding sites and the expression of HNF4α. In conclusion, HNF4α has a critical role in blood coagulation homeostasis by directing transcription of the FXII and XIIIB genes.

Fluid–structure Interaction Modeling of Aneurysmal Conditions with High and Normal Blood Pressures

Abstract  Hemodynamic factors like the wall shear stress play an important role in cardiovascular diseases. To investigate the influence of hemodynamic factors in blood vessels, the authors have developed a numerical fluid–structure interaction (FSI) analysis technique. The objective is to use numerical simulation as an effective tool to predict phenomena in a living human body. We applied the technique to a patient-specific arterial model, and with that we showed the effect of wall deformation on the WSS distribution. In this paper, we compute the interaction between the blood flow and the arterial wall for a patient-specific cerebral aneurysm with various hemodynamic conditions, such as hypertension. We particularly focus on the effects of hypertensive blood pressure on the interaction and the WSS, because hypertension is reported to be a risk factor in rupture of aneurysms. We also aim to show the possibility of FSI computations with hemodynamic conditions representing those risk factors in cardiovascular disease. The simulations show that the transient behavior of the interaction under hypertensive blood pressure is significantly different from the interaction under normal blood pressure. The transient behavior of the blood-flow velocity, and the resulting WSS and the mechanical stress in the aneurysmal wall, are significantly affected by hypertension. The results imply that hypertension affects the growth of an aneurysm and the damage in arterial tissues.

Blood and urine values of free-living European wildcats in Slovenia

Abstract  Hematological, serum biochemistry, and urinalysis values were determined for nine (two females and seven males) adult, free-living European wildcats (Felis silvestris) in the Kocevje Forests of the southern Slovenia. Samples were collected from August 1999 to March 2001. Cats were anesthetized with ketamine and medetomidine. Blood samples were taken by jugular venipuncture and urine samples by bladder puncture. A control group of domestic cats (F. silvestris catus) was assembled to determine if differences exist among blood and urine values between free-living European wildcats and domestic cats. Hematological, biochemical, and urine parameters were similar to those of the control group. Values of glucose, blood urea nitrogen, albumin, mean corpuscular value, basophile count, and alanine aminotransferase were significantly higher than values of the control group. All urine samples contained white blood cells and proteins, and seven of them contained red blood cells.

Age-dependent increase in green autofluorescence of blood erythrocytes

Abstract  Green auto-fluorescence (GAF) of different age groups of mouse blood erythrocytes was determined by using a double in vivo biotinylation (DIB) technique that enables delineation of circulating erythrocytes of different age groups. A significant increase in GAF was seen for erythrocytes of old age group (age in circulation >40 days) as compared to young erythrocytes (age <15 days). Erythrocytes are removed from blood circulation by macrophages in the reticulo-endothelial system and depletion of macrophages results in an increased proportion of aged erythrocytes in the blood. When mice were depleted of macrophages for 7 days by administration of clodronate loaded liposomes, the overall GAF of erythrocytes increased significantly and this increase could be ascribed to an increase in GAF of the oldest population of erythrocytes. Using the DIB technique, the GAF of a cohort of blood erythrocyte generated during a 5 day window was tracked in vivo. GAF of the defined cohort of erythrocytes remained low till 40 days of age in circulation and then increased steeply till the end of the life span of erythrocytes. Taken together our results provide evidence for an age dependent increase in the GAF of blood erythrocytes that is accentuated by depletion of macrophages. Kinetics of changes in GAF of circulating erythrocytes with age has also been defined.

Glycated haemoglobin (HbG) as a stable indicator of blood glucose status in ostrich

Abstract  Glycated haemoglobin (HbG) concentration is a retrospective measure of mean blood glucose level and is not affected by recent stresses, food ingestion or exercise. HbG has been determined in various wild and domestic animals such as kestrels, mankhor, mouflon, aoudad, deer, goat, sheep, dog, camel and horse. But there is no information regarding HbG in ostrich and its relation to blood glucose. The purposes of this study were to determine the normal values of HbG in ostriches and to investigate its relation to fasting plasma glucose. Blood samples were collected from jugular veins of 30 clinically healthy ostriches after 12 h of fasting. After separation and washing of red blood cells, haemolysate was prepared and subjected to weak cation exchange chromatography for determination of HbG. Glucose was measured in plasma samples. Fasting plasma glucose and HbG were 11.23 ± 0.80 mmol/l and 1.20 ± 0.2% of total haemoglobin, respectively. It was shown that HbG percent and fasting plasma glucose were correlated (P < 0.05; r = 0.93). To determine if low HbG percent in ostrich is related to low permeability of erythrocytes to blood glucose, haemolysates incubated with glucose (11.21 mmol/l final glucose concentrations) were subjected to chromatography under the same conditions. It was shown that HbG was significantly increased in glycosylated haemolysates. It was concluded that low HbG percent in ostrich is related to low glucose permeability of erythrocytes.

Decreased blood activity of glucose-6-phosphate dehydrogenase associates with increased risk for diabetes mellitus

Abstract  Glucose-6-phosphate dehydrogenase (G6PD) deficiency predisposes affected individuals highly susceptible to oxidative stress, which is one of the risk factors for diabetes. To evaluate the relationship between blood level of G6PD activity and diabetes in Taiwan, blood G6PD activity was analyzed among 237 patients with diabetes and 656 healthy subjects. A significant difference in the distribution of G6PD activities as grouped by an increment of 100 U/1012 red blood cells (RBCs) was observed between diabetic patients and healthy subjects. The odds ratio for diabetes was 1.46 (95% confidence interval=1.11−1.92) for every decrement of 100 U/1012 RBC G6PD activities in these subjects. The data indicate that low G6PD activity is another risk factor for diabetes.

Interactions of glucagon-like peptide-1 (GLP-1) with the blood-brain barrier

Abstract  Glucagon-like peptide-1 (GLP-1) reduces insulin requirement in diabetes mellitus and promotes satiety. GLP-1 in the periphery (outside the CNS) has been shown to act on the brain to reduce food ingestion. As GLP-1 is readily degraded in blood, we focused on the interactions of [Ser8]GLP-1, an analog with similar biological effects and greater stability, with the blood-brain barrier (BBB). The influx of radiolabeled [Ser8]GLP-1 into brain has several distinctive characteristics: 1.  A rapid influx rate of 8.867±0.798 × 104 mL/g-min as measured by multiple-time regression analysis after iv injection in mice. 2.  Lack of self-inhibition by excess doses of the unlabeled [Ser8]GLP-1 either iv or by in situ brain perfusion, indicating the absence of a saturable transport system at the BBB. 3.  Lack of modulation by short-term fasting and some other ingestive peptides that may interact with GLP-1, including leptin, glucagon, insulin, neuropeptide Y, and melanin-concentrating hormone. 4.  No inhibition of influx by the selective GLP-1 receptor antagonist exendin(9–39), suggesting that the GLP-1 receptor is not involved in the rapid entry into brain. Similarly, there was no efflux system for [Ser8]GLP-1 to exit the brain other than following the reabsorption of cerebrospinal fluid (CSF). The fast influx was not associated with high lipid solubility. Upon reaching the brain compartment, substantial amounts of [Ser8]GLP-1 entered the brain parenchyma, but a large proportion was loosely associated with the vasculature at the BBB. Finally, the influx rate of [Ser8]GLP-1 was compared with that of GLP-1 in a blood-free brain perfusion system; radiolabeled GLP-1 had a more rapid influx than its analog and neither peptide showed the self-inhibition indicative of a saturable transport system. Therefore, we conclude that [Ser8]GLP-1 and the endogenous peptide GLP-1 can gain access to the brain from the periphery by simple diffusion and thus contribute to the regulation of feeding.